Endoscopic therapy and beta-blockers for secondary prevention in adults with cirrhosis and oesophageal varices

DEFF Research Database (Denmark)

Gluud, Lise Lotte; Morgan, Marsha Y.

2017-01-01

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To evaluate the beneficial and harmful effects of endoscopic therapy and beta-blockers used as a combination therapy versus monotherapy with either endoscopic therapy or beta-blockers for secondary prevention...

Impact of beta-blocker treatment on the prognostic value of currently used risk predictors in congestive heart failure.

Science.gov (United States)

Zugck, Christian; Haunstetter, Armin; Krüger, Carsten; Kell, Robert; Schellberg, Dieter; Kübler, Wolfgang; Haass, Markus

2002-05-15

This prospective study tested the impact of beta-blocker treatment on currently used risk predictors in congestive heart failure (CHF). Given the survival benefit obtained by beta-blockade, risk stratification by factors established in the "pre-beta-blocker era" may be questioned. The study included 408 patients who had CHF with left ventricular ejection fraction (LVEF) 2.24 nmol/l (18% vs. 40%) and NT-proBNP >364 pmol/l (27% vs. 45%), although patients with beta-blocker treatment received only 37 +/- 21% of the maximal recommended beta-blocker dosages. The prognostic value of variables used for risk stratification of patients with CHF is markedly influenced by beta-blocker treatment. Therefore, in the beta-blocker era, a re-evaluation of the selection criteria for heart transplantation is warranted.

Non-selective vs. selective beta-blocker treatment and the risk of thrombo-embolic events in patients with heart failure

NARCIS (Netherlands)

de Peuter, Olav R.; Souverein, Patrick C.; Klungel, Olaf H.; Büller, Harry R.; de Boer, Anthonius; Kamphuisen, Pieter W.

2011-01-01

Aims Heart failure (HF) is associated with a prothrombotic state, resulting in an increased risk for thrombo-embolic events. Studies suggest a reduced prothrombotic state when non-selective beta-blockers relative to selective beta-blockers are given. We studied the influence of non-selective

Pharmacogenetics of β-Blockers

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Shin, Jaekyu; Johnson, Julie A.

2009-01-01

β-Blockers are an important cardiovascular drug class, recommended as first-line treatment of numerous diseases such as heart failure, hypertension, and angina, as well as treatment after myocardial infarction. However, responses to a β-blocker are variable among patients. Results of numerous studies now suggest that genetic polymorphisms may contribute to variability in responses to β-blockers. This review summarizes the pharmacogenetic data for β-blockers in patients with various diseases and discusses the potential implications of β-blocker pharmacogenetics in clinical practice. PMID:17542770

Beta blockers and chronic heart failure patients: prognostic impact of a dose targeted beta blocker therapy vs. heart rate targeted strategy.

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Corletto, Anna; Fröhlich, Hanna; Täger, Tobias; Hochadel, Matthias; Zahn, Ralf; Kilkowski, Caroline; Winkler, Ralph; Senges, Jochen; Katus, Hugo A; Frankenstein, Lutz

2018-05-17

Beta blockers improve survival in patients with chronic systolic heart failure (CHF). Whether physicians should aim for target dose, target heart rate (HR), or both is still under debate. We identified 1,669 patients with systolic CHF due to ischemic heart disease or idiopathic dilated cardiomyopathy from the University Hospital Heidelberg and the Clinic of Ludwigshafen, Germany. All patients were treated with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker and had a history of CHF known for at least 6 months. Target dose was defined as treatment with ≥ 95% of the respective published guideline-recommended dose. Target HR was defined as 51-69 bpm. All-cause mortality during the median follow-up of 42.8 months was analysed with respect to beta blocker dosing and resting HR. 201 (12%) patients met the dose target (group A), 285 (17.1%) met the HR target (group B), 627 (37.6%) met no target (group C), and 556 (33.3%) did not receive beta blockers (Group D). 5-year mortality was 23.7, 22.7, 37.6, and 55.6% for group A, B, C, and D, respectively (p <  0.001). Survival for group A patients with a HR ≥ 70 bpm was 28.8% but 14.8% if HR was 50-70 bpm (p = 0.054). Achieving guidelines recommended beta blocker dose or to HR control has a similar positive impact on survival. When on target dose, supplemental HR control additionally improves survival.

Effects of beta-blockers on heart failure with preserved ejection fraction: a meta-analysis.

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Feng Liu

Full Text Available BACKGROUND: Effects of beta-blockers on the prognosis of the heart failure patients with preserved ejection fraction (HFpEF remain controversial. The aim of this meta-analysis was to determine the impact of beta-blockers on mortality and hospitalization in the patients with HFpEF. METHODS: A search of MEDLINE, EMBASE, and the Cochrane Library databases from 2005 to June 2013 was conducted. Clinical studies reporting outcomes of mortality and/or hospitalization for patients with HFpEF (EF ≥ 40%, being assigned to beta-blockers treatment and non-beta-blockers control group were included. RESULTS: A total of 12 clinical studies (2 randomized controlled trials and 10 observational studies involving 21,206 HFpEF patients were included for this meta-analysis. The pooled analysis demonstrated that beta-blocker exposure was associated with a 9% reduction in relative risk for all-cause mortality in patients with HFpEF (95% CI: 0.87 - 0.95; P < 0.001. Whereas, the all-cause hospitalization, HF hospitalization and composite outcomes (mortality and hospitalization were not affected by this treatment (P=0.26, P=0.97, and P=0.88 respectively. CONCLUSIONS: The beta-blockers treatment for the patients with HFpEF was associated with a lower risk of all-cause mortality, but not with a lower risk of hospitalization. These finding were mainly obtained from observational studies, and further investigations are needed to make an assertion.

How should we manage heart failure developing in patients already treated with angiotensin-converting enzyme inhibitors and beta-blockers for hypertension, diabetes or coronary disease?

DEFF Research Database (Denmark)

Gustafsson, Finn; Segura, Julian; Ruilope, Luis M

2010-01-01

An increasing number of patients in the community are being treated with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and beta-blockers for hypertension, coronary disease or diabetic renal and vascular complications. Some of these patients will develop heart...... failure despite such treatment. Based on data from hypertension trials it can be estimated that approximately 5% of treated patients will develop heart failure over 5 years. It is unclear whether patients developing heart failure on and off ACE-inhibitors or beta-blockers, respectively, at the time...

A self-controlled case series to assess the effectiveness of beta blockers for heart failure in reducing hospitalisations in the elderly

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Pratt Nicole L

2011-07-01

Full Text Available Abstract Background To determine the suitability of using the self-controlled case series design to assess improvements in health outcomes using the effectiveness of beta blockers for heart failure in reducing hospitalisations as the example. Methods The Australian Government Department of Veterans' Affairs administrative claims database was used to undertake a self-controlled case-series in elderly patients aged 65 years or over to compare the risk of a heart failure hospitalisation during periods of being exposed and unexposed to a beta blocker. Two studies, the first using a one year period and the second using a four year period were undertaken to determine if the estimates varied due to changes in severity of heart failure over time. Results In the one year period, 3,450 patients and in the four year period, 12, 682 patients had at least one hospitalisation for heart failure. The one year period showed a non-significant decrease in hospitalisations for heart failure 4-8 months after starting beta-blockers, (RR, 0.76; 95% CI (0.57-1.02 and a significant decrease in the 8-12 months post-initiation of a beta blocker for heart failure (RR, 0.62; 95% CI (0.39, 0.99. For the four year study there was an increased risk of hospitalisation less than eight months post-initiation and significant but smaller decrease in the 8-12 month window (RR, 0.90; 95% CI (0.82, 0.98. Conclusions The results of the one year observation period are similar to those observed in randomised clinical trials indicating that the self-controlled case-series method can be successfully applied to assess health outcomes. However, the result appears sensitive to the study periods used and further research to understand the appropriate applications of this method in pharmacoepidemiology is still required. The results also illustrate the benefits of extending beta blocker utilisation to the older age group of heart failure patients in which their use is common but the evidence is

Antihypertensive treatment and risk of atrial fibrillation

DEFF Research Database (Denmark)

Marott, Sarah C W; Nielsen, Sune F; Benn, Marianne

2014-01-01

AIMS: To examine the associations between antihypertensive treatment with angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs), β-blockers, diuretics, or calcium-antagonists, and risk of atrial fibrillation. We examined these associations using the entire Danish...... population from 1995 through 2010. METHODS AND RESULTS: Excluding medication used in atrial fibrillation, we matched individuals on ACEi monotherapy 1:1 with individuals on β-blocker (n = 48 658), diuretic (n = 69 630), calcium-antagonist (n = 57 646), and ARB monotherapy (n = 20 158). Likewise, individuals...... on ARB monotherapy were matched 1:1 with individuals on β-blocker (n = 20 566), diuretic (n = 20 832), calcium-antagonist (n = 20 232), and ACEi monotherapy (n = 20 158). All were free of atrial fibrillation and of predisposing diseases like heart failure, ischaemic heart disease, diabetes mellitus...

Comparative effect of angiotensin II type I receptor blockers and calcium channel blockers on laboratory parameters in hypertensive patients with type 2 diabetes

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Nishida Yayoi

2012-05-01

Full Text Available Abstract Background Both angiotensin II type I receptor blockers (ARBs and calcium channel blockers (CCBs are widely used antihypertensive drugs. Many clinical studies have demonstrated and compared the organ-protection effects and adverse events of these drugs. However, few large-scale studies have focused on the effect of these drugs as monotherapy on laboratory parameters. We evaluated and compared the effects of ARB and CCB monotherapy on clinical laboratory parameters in patients with concomitant hypertension and type 2 diabetes mellitus. Methods We used data from the Clinical Data Warehouse of Nihon University School of Medicine obtained between Nov 1, 2004 and July 31, 2011, to identify cohorts of new ARB users (n = 601 and propensity-score matched new CCB users (n = 601, with concomitant mild to moderate hypertension and type 2 diabetes mellitus. We used a multivariate-adjusted regression model to adjust for differences between ARB and CCB users, and compared laboratory parameters including serum levels of triglyceride (TG, total cholesterol (TC, non-fasting blood glucose, hemoglobin A1c (HbA1c, sodium, potassium, creatinine, alanine aminotransferase (ALT, aspartate aminotransferase (AST, gamma-glutamyltransferase (GGT, hemoglobin and hematocrit, and white blood cell (WBC, red blood cell (RBC and platelet (PLT counts up to 12 months after the start of ARB or CCB monotherapy. Results We found a significant reduction of serum TC, HbA1c, hemoglobin and hematocrit and RBC count and a significant increase of serum potassium in ARB users, and a reduction of serum TC and hemoglobin in CCB users, from the baseline period to the exposure period. The reductions of RBC count, hemoglobin and hematocrit in ARB users were significantly greater than those in CCB users. The increase of serum potassium in ARB users was significantly greater than that in CCB users. Conclusions Our study suggested that hematological adverse effects and

Treatment with beta-blockers in nurse-led heart failure clinics

DEFF Research Database (Denmark)

Gustafsson, Finn; Schou, Morten; Videbaek, Lars

2007-01-01

BACKGROUND: Beta-blockers (BBs) are a cornerstone in the treatment of chronic heart failure (HF), but several surveys have documented that many patients are not offered treatment or are not titrated to target doses. In part to address this problem, specialized, nurse-led HF clinics have been......% of the patients were being treated with a BB. Mean dose (relative to target dose) was 63 (+/-35)% in patients receiving a BB and target dose was reached by 21%. Patients who were not on BBs were more often female, elderly and in NYHA class III-IV. In a multivariable model only lower age predicted BB use at three...... months (PElderly patients appear to be less likely to receive treatment....

Beta-Blockers and Outcome in Heart Failure and Atrial Fibrillation A Meta-Analysis : a meta-analysis

NARCIS (Netherlands)

Rienstra, Michiel; Damman, Kevin; Mulder, Bart A.; Van Gelder, Isabelle C.; McMurray, John J. V.; Van Veldhuisen, Dirk J.

Objectives The purpose of this study was to analyze the effect of beta blockade on outcome in patients with heart failure (HF) and atrial fibrillation (AF). Background Beta-blockers are widely used in patients with HF and AF. Recommendation in current HF guidelines, however, is based on populations

Factors associated with β-blocker initiation and discontinuation in a population-based cohort of seniors newly diagnosed with heart failure

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Girouard C

2016-09-01

Full Text Available Catherine Girouard,1–3 Jean-Pierre Grégoire,1–3 Paul Poirier,2,4 Jocelyne Moisan1–3 1Chair on Adherence to Treatments, Université Laval, 2Faculty of Pharmacy, Université Laval, 3Population Health and Optimal Health Practices Research Unit, CHU de Québec Research Center, 4Quebec Heart and Lung Institute-Université Laval, Quebec City, QC, Canada Purpose: β-Blockers (bisoprolol, carvedilol, and metoprolol are the cornerstone of heart failure (HF management. The incidence rate of β-blocker initiation and discontinuation and their associated factors among seniors with a first HF diagnosis were assessed.Methods: A population-based inception cohort study that included all individuals aged ≥65 years with a first HF diagnosis in Quebec was conducted. β-Blockers initiation among 91,131 patients who were not using β-blockers at the time of HF diagnosis and discontinuation among those who initiated a β-blocker after HF diagnosis were assessed. Stepwise Cox regression analyses were used to calculate hazard ratios (HR and to identify factors associated with β-blocker initiation and discontinuation.Results: After HF diagnosis, 32,989 (36.2% individuals initiated a β-blocker. Of these, 15,408 (46.7% discontinued their β-blocker during the follow-up. Individuals more likely to initiate a β-blocker were those diagnosed in a recent calendar year (2009: HR, 2.11; 95% confidence interval [CI], 2.00–2.23 and diagnosed by a cardiologist (HR, 1.38; 95% CI, 1.34–1.42. Individuals less likely to initiate were those aged ≥90 years (HR, 0.65; 95% CI, 0.61–0.68 and those with chronic obstructive pulmonary disease (HR, 0.66; 95% CI, 0.64–0.68. Individuals more likely to discontinue were those with more than nine medical consultations (HR, 1.14; 95% CI, 1.10–1.18 and those with dementia (HR, 1.13; 95% CI, 1.01–1.27. Individuals less likely to discontinue were those diagnosed in a recent calendar year (2009: HR 0.74; 95% CI, 0.65–0.82 and

Barriers to Beta-Blocker Use and Up-Titration Among Patients with Heart Failure with Reduced Ejection Fraction.

Science.gov (United States)

Levitan, Emily B; Van Dyke, Melissa K; Loop, Matthew Shane; O'Beirne, Ronan; Safford, Monika M

2017-12-01

For patients with heart failure with reduced ejection fraction (HFrEF), guidelines recommend use of beta-blockers with gradual up-titration. However, many patients with HFrEF do not use beta-blockers and up-titration is rare. Our purpose was to identify and rank barriers to beta-blocker use and up-titration from the perspective of primary care physicians. We conducted 4 moderated, structured group discussions among 19 primary care physicians using the nominal group technique; 16 participants also completed a survey. Participants generated lists of barriers to beta-blocker use and up-titration among patients with HFrEF. Each participant had six votes with three votes assigned to the item ranked most important, two to the second most important item, and one to the third most important item. Investigators characterized items into themes. The percentage of available votes was calculated for each theme. Fifteen of 16 participating primary care physicians who completed the survey reported that management of beta-blockers was their responsibility. Treatment/side effects, particularly hypotension, were identified as the most important barrier for beta-blocker use (72% of available votes) followed by polypharmacy (11%), healthcare system barriers (10%), and comorbidities (6%). Barriers to up-titration included treatment/side effects (49% of available votes), patient communication/buy-in (21%), polypharmacy (13%), and healthcare system barriers (8%). Many barriers to guideline concordant use of beta-blockers among patients with HFrEF identified by primary care providers are not readily modifiable. Addressing these barriers may require development, testing, and dissemination of protocols for beta-blocker initiation and up-titration that are safe and appropriate in primary care.

Calcium channel blockers, angiotensin receptor blockers, and angiotensin-converting enzyme inhibitors: Effectiveness in combination with diuretics or β-blockers for treating hypertension

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John D Bisognano

2007-11-01

Full Text Available John D Bisognano1, Trent McLaughlin2, Craig S Roberts3, Simon SK Tang31Internal Medicine Department, Cardiology Division, the University of Rochester Medical Center, Rochester, NY, USA; 2NDC Health, Phoenix, Arizona, USA; 3Pfizer Inc, New York, NY, USAAbstract: This retrospective database analysis compared the effectiveness of dihydropyridine calcium channel blockers (DHPs, angiotensin-converting enzyme (ACE inhibitors, and angiotensin receptor blockers (ARBs added to diuretics or β-blockers. Adults with hypertension treated with diuretic or β-blocker monotherapy between 1998 and 2001 were identified from a large US electronic medical records database of primary care practices. Patients were required to have a baseline blood pressure (BP ≥140/90 mmHg (≥130/80 mmHg for diabetes mellitus and recorded BP measurements within 6 months before and 1–12 months following index date. Patients were matched 1:1:1 by propensity score to correct for differences in baseline characteristics. 1875 patients met study criteria and 660 (220 in each cohort were matched based on propensity scores. Matched cohorts had no significant differences in baseline characteristics. Mean changes in systolic/diastolic BP were –17.5/–8.8, –15.7/–6.3, and –13.0/–8.0 mmHg with DHPs, ACE inhibitors, and ARBs, respectively. Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High BP 6/7 goal attainment for each regimen was 47.3%, 40.0%, and 32.2%, respectively. DHPs, ACE inhibitors, and ARBs improved BP when added to patients’ β-blocker or diuretic therapy. The greatest benefits were observed with DHPs, followed by ACE inhibitors, then ARBs.Keywords: hypertension, amlodipine besylate, lisinopril, valsartan, Joint National Committee (JNC 6 and 7

Search for HRV-parameters that detect a sympathetic shift in heart failure patients on beta-blocker treatment

NARCIS (Netherlands)

Zhang, Yanru; de Peuter, Olav R.; Kamphuisen, Pieter W.; Karemaker, John M.

2013-01-01

Background: A sympathetic shift in heart rate variability (HRV) from high to lower frequencies may be an early signal of deterioration in a monitored patient. Most chronic heart failure (CHF) patients receive (3-blockers. This tends to obscure HRV observation by increasing the fast variations. We

Guideline-recommended therapy, including beta-blocker utilization, in patients with chronic heart failure: results from a Canadian community hospital heart function clinic

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Heffernan M

2016-06-01

Full Text Available Michael Heffernan Division of Cardiology, Oakville Trafalgar Memorial Hospital, Oakville, ON, Canada Abstract: A comprehensive analysis of beta-blocker utilization and other guideline-recommended therapies for the treatment of chronic heart failure in a Canadian community hospital heart function clinic has not been undertaken and was, therefore, the focus of this study. The proportion of patients who would be potential candidates for ivabridine and sacubitril–valsartan therapy as a result of fulfilling the criteria for enrollment in either the Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT study (left-ventricular ejection fraction [LVEF] >35%, sinus rhythm, New York Heart Association II–IV or the Prospective Comparison of angiotensin receptor-neprilysin inhibitor (ARNI with angiotensin-converting enzyme inhibitor (ACEI to determine impact on global Mortality and Morbidity in Heart Failure (PARADIGM-HF study (LVEF <40%, New York Heart Association II–IV, glomerular filtration rate >30 mL/min, was also assessed. A retrospective cross-sectional analysis was carried out in all 371 patients treated in this community heart function clinic for at least a 12-month period. The patients were elderly (mean age 74±13.3 years and predominately male (61.5% with symptomatic (82.5% moderate left-ventricular dysfunction (LVEF 45.4%±15.6%. A substantial proportion of the patients also had a diagnosis of atrial fibrillation (52.8%. The total use of beta blockers exceeded 87%, while 100% of patients without a documented contraindication or intolerance to a beta blocker received therapy. Adherence to other guideline-recommended pharmacotherapies specifically for heart failure with reduced left ventricular ejection was high: 86.1% of the eligible patients were treated with an ACEI/angiotensin receptor blocker and 61.9% received a mineralcorticoid receptor antagonist. We determined that 13.7% of the complement of this heart

Importance of beta-blocker dose in prevention of ventricular tachyarrhythmias, heart failure hospitalizations, and death in primary prevention implantable cardioverter-defibrillator recipients

DEFF Research Database (Denmark)

Ruwald, A C; Gislason, G H; Vinther, M

2018-01-01

Aims: There is a paucity of studies investigating a dose-dependent association between beta-blocker therapy and risk of outcome. In a nationwide cohort of primary prevention implantable cardioverter-defibrillator (ICD) patients, we aimed to investigate the dose-dependent association between beta-blocker...... therapy and risk of ventricular tachyarrhythmias (VT/VF), heart failure (HF) hospitalizations, and death. Methods and results: Information on ICD implantation, endpoints, comorbidities, beta-blocker usage, type, and dose were obtained through Danish nationwide registers. The two major beta-blockers...... carvedilol and metoprolol were examined in three dose levels; low (metoprolol ≤ 25 mg; carvedilol ≤ 12.5 mg), intermediate (metoprolol 26-199 mg; carvedilol 12.6-49.9 mg), and high (metoprolol ≥ 200 mg; carvedilol ≥ 50 mg). Time to events was investigated utilizing multivariate Cox models with beta-blocker...

Absent Lung Deflation Because of Blockade Using an Endobronchial Blocker.

Science.gov (United States)

Garg, Rakesh; Pandit, Anuja

2017-06-01

One-lung ventilation is required for various thoracic procedures. In addition, various strategies such as the use of double-lumen tube, uninvent tubes, and endobronchial blocker have been used for performing one-lung ventilation. Each of these techniques has its advantages and limitations. Certain factors for failure of endobronchial blocker to provide lung deflation has been described in literature. We report a different aetiology of failure of lung deflation, although the endobronchial blocker was appropriately placed.

Add-on Therapy With the α-Blockers Tamsulosin and Naftopidil Improves Voiding Function by Enhancing Neuronal Activity in Prostatic Hyperplasia Rats.

Science.gov (United States)

Ko, Il-Gyu; Hwang, Lakkyong; Jin, Jun-Jang; Kim, Sang-Hoon; Han, Jin Hee; Jeon, Jung Won; Cho, Sung Tae

2018-03-01

Benign prostatic hyperplasia (BPH) impacts quality of life in men by causing lower urinary tract symptoms. α1-Adrenoceptor (α1-AR) blockers improve lower urinary tract symptoms. We investigated the efficacy of add-on therapy with α1-AR blockers on BPH rats. Rats in the drug-treated groups were orally administered each drug once a day for 30 days after orchiectomy. To induce BPH, rats were castrated and testosterone (20 mg/kg) was injected subcutaneously once per day for 30 days. Cystometry was conducted to measure voiding contraction pressure and the interval contraction time, immunohistochemistry was performed to measure c-Fos and nerve growth factor (NGF) expression in the neuronal voiding centers, and nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry was used to measure nitric oxide synthase (NOS) expression. Orchiectomy and testosterone injection decreased voiding contraction pressure and the interval contraction time, suggesting BPH symptoms. Voiding contraction pressure and the interval contraction time were greater in the group that received the combination treatment (tamsulosin with naftopidil) than in the tamsulosin monotherapy or naftopidil monotherapy groups. c-Fos, NGF, and NOS expression in the neuronal voiding centers was enhanced by BPH induction. c-Fos, NGF, and NOS expression was suppressed by the combination treatment (tamsulosin with naftopidil) to a greater extent than was the case for tamsulosin monotherapy or naftopidil monotherapy. Combination therapy of tamsulosin and naftopidil showed greater efficacy for the treatment of BPH than tamsulosin monotherapy or naftopidil monotherapy; therefore, combination therapy can be considered as a novel therapeutic method for BPH.

Calcium channel blocker poisoning

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Miran Brvar

2005-04-01

Full Text Available Background: Calcium channel blockers act at L-type calcium channels in cardiac and vascular smooth muscles by preventing calcium influx into cells with resultant decrease in vascular tone and cardiac inotropy, chronotropy and dromotropy. Poisoning with calcium channel blockers results in reduced cardiac output, bradycardia, atrioventricular block, hypotension and shock. The findings of hypotension and bradycardia should suggest poisoning with calcium channel blockers.Conclusions: Treatment includes immediate gastric lavage and whole-bowel irrigation in case of ingestion of sustainedrelease products. All patients should receive an activated charcoal orally. Specific treatment includes calcium, glucagone and insulin, which proved especially useful in shocked patients. Supportive care including the use of catecholamines is not always effective. In the setting of failure of pharmacological therapy transvenous pacing, balloon pump and cardiopulmonary by-pass may be necessary.

CYP2D6 Genetic Variation and Beta-Blocker Maintenance Dose in Patients with Heart Failure.

Science.gov (United States)

Luzum, Jasmine A; Sweet, Kevin M; Binkley, Philip F; Schmidlen, Tara J; Jarvis, Joseph P; Christman, Michael F; Sadee, Wolfgang; Kitzmiller, Joseph P

2017-08-01

This study examined whether a CYP2D6 polymorphism (CYP2D6*4) was related to beta-blocker maintenance dose in patients with heart failure. Logistic regression modeling was utilized in a retrospective chart-review analysis of heart-failure patients (60% Male, 90% of European descent) to assess whether CYP2D6*4 (non-functional CYP2D6 allele present in 1 of 5 individuals of European descent) is associated with maintenance dose of carvedilol (n = 65) or metoprolol (n = 33). CYP2D6*4 was associated with lower maintenance dose of metoprolol (OR 0.13 [95% CI 0.02-0.75] p = 0.023), and a trend was observed between CYP2D6*4 and higher maintenance dose of carvedilol (OR 2.94 [95% CI 0.84-10.30] p = 0.093). None of the patients that carried CYP2D6*4 achieved the recommended target dose of metoprolol (200 mg/day). Consistent with the role of CYP2D6 in the metabolism of metoprolol, the tolerated maintenance dose of metoprolol was lower in CYP2D6*4 carriers compared to non-carriers. Consistent with the role of CYP2D6 in activation of carvedilol, tolerated maintenance dose of carvedilol was higher in CYP2D6*4 carriers compared to non-carriers. Further investigation is warranted to ascertain the potential of CYP2D6 as a potential predictive biomarker of beta-blocker maintenance dose in heart failure patients.

Impact of β-blocker selectivity on long-term outcomes in congestive heart failure patients with chronic obstructive pulmonary disease

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Kubota Y

2015-03-01

Full Text Available Yoshiaki Kubota, Kuniya Asai, Erito Furuse, Shunichi Nakamura, Koji Murai, Yayoi Tetsuou Tsukada, Wataru Shimizu Department of Medicine (Division of Cardiology, Nippon Medical School, Bunkyo-ku, Tokyo, Japan Background: Chronic obstructive pulmonary disease (COPD is present in approximately one-third of all congestive heart failure (CHF patients, and is a key cause of underprescription and underdosing of β-blockers, largely owing to concerns about precipitating respiratory deterioration. For these reasons, the aim of this study was to evaluate the impact of β-blockers on the long-term outcomes in CHF patients with COPD. In addition, we compared the effects of two different β-blockers, carvedilol and bisoprolol. Methods: The study was a retrospective, non-randomized, single center trial. Acute decompensated HF patients with COPD were classified according to the oral drug used at discharge into β-blocker (n=86; carvedilol [n=52] or bisoprolol [n=34] and non-β-blocker groups (n=46. The primary endpoint was all-cause mortality between the β-blocker and non-β-blocker groups during a mean clinical follow-up of 33.9 months. The secondary endpoints were the differences in all-cause mortality and the hospitalization rates for CHF and/or COPD exacerbation between patients receiving carvedilol and bisoprolol. Results: The mortality rate was higher in patients without β-blockers compared with those taking β-blockers (log-rank P=0.039, and univariate analyses revealed that the use of β-blockers was the only factor significantly correlated with the mortality rate (hazard ratio: 0.41; 95% confidence interval: 0.17–0.99; P=0.047. Moreover, the rate of CHF and/or COPD exacerbation was higher in patients treated with carvedilol compared with bisoprolol (log-rank P=0.033. In the multivariate analysis, only a past history of COPD exacerbation significantly increased the risk of re-hospitalization due to CHF and/or COPD exacerbation (adjusted hazard

Cardiac metaiodobenzylguanidine activity can predict the long-term efficacy of angiotensin-converting enzyme inhibitors and/or beta-adrenoceptor blockers in patients with heart failure

Energy Technology Data Exchange (ETDEWEB)

Nakata, Tomoaki; Wakabayashi, Takeru; Kyuma, Michifumi; Takahashi, Toru; Tsuchihashi, Kazufumi; Shimamoto, Kazuaki [Sapporo Medical University School of Medicine, Second Department of Internal Medicine (Cardiology), Sapporo (Japan)

2005-02-01

Although the benefits of treatment with angiotensin-converting enzyme (ACE) inhibitors and beta-blockers are well known, no method has as yet been established to predict the efficacy of drug therapy. This study tested whether cardiac{sup 123}I-metaiodobenzylguanidine (MIBG) activity is of prognostic value and can predict the improvement in heart failure patients resulting from treatment with ACE inhibitors and/or beta-blockers. Following quantification of the heart-to-mediastinum ratio (HMR) of MIBG activity, 88 patients with heart failure who were treated with ACE inhibitors and/or beta-blockers (treated group) and 79 patients with heart failure who were treated conventionally without the aforementioned agents, and who served as controls, were followed up for 43 months with a primary endpoint of cardiac death. The treated group had a significantly lower prevalence of cardiac death and a significantly lower mortality at 5 years compared with the control group (15% vs 37% and 21% vs 42%, p<0.05, respectively). Multivariate analysis revealed that significant predictors were HMR, age, nitrate use and ventricular tachycardia for the treated group, and HMR, nitrate use and NYHA class for the control group. The drug treatment significantly reduced mortality from 36% to 12% when HMR was 1.53 or more and from 53% to 37% when HMR was less than 1.53. The reduction in risk of mortality within 5 years in patients without a severe MIBG defect (67%) was twice that in patients with such a defect (32%) (p<0.05). The reduction in mortality risk achieved by using ACE inhibitors and/or beta-blockers is associated with the severity of impairment of cardiac MIBG uptake. Cardiac MIBG activity can consequently be of long-term prognostic value in predicting the effectiveness of such treatment in patients with heart failure. (orig.)

Cardiac metaiodobenzylguanidine activity can predict the long-term efficacy of angiotensin-converting enzyme inhibitors and/or beta-adrenoceptor blockers in patients with heart failure

International Nuclear Information System (INIS)

Nakata, Tomoaki; Wakabayashi, Takeru; Kyuma, Michifumi; Takahashi, Toru; Tsuchihashi, Kazufumi; Shimamoto, Kazuaki

2005-01-01

Although the benefits of treatment with angiotensin-converting enzyme (ACE) inhibitors and beta-blockers are well known, no method has as yet been established to predict the efficacy of drug therapy. This study tested whether cardiac 123 I-metaiodobenzylguanidine (MIBG) activity is of prognostic value and can predict the improvement in heart failure patients resulting from treatment with ACE inhibitors and/or beta-blockers. Following quantification of the heart-to-mediastinum ratio (HMR) of MIBG activity, 88 patients with heart failure who were treated with ACE inhibitors and/or beta-blockers (treated group) and 79 patients with heart failure who were treated conventionally without the aforementioned agents, and who served as controls, were followed up for 43 months with a primary endpoint of cardiac death. The treated group had a significantly lower prevalence of cardiac death and a significantly lower mortality at 5 years compared with the control group (15% vs 37% and 21% vs 42%, p<0.05, respectively). Multivariate analysis revealed that significant predictors were HMR, age, nitrate use and ventricular tachycardia for the treated group, and HMR, nitrate use and NYHA class for the control group. The drug treatment significantly reduced mortality from 36% to 12% when HMR was 1.53 or more and from 53% to 37% when HMR was less than 1.53. The reduction in risk of mortality within 5 years in patients without a severe MIBG defect (67%) was twice that in patients with such a defect (32%) (p<0.05). The reduction in mortality risk achieved by using ACE inhibitors and/or beta-blockers is associated with the severity of impairment of cardiac MIBG uptake. Cardiac MIBG activity can consequently be of long-term prognostic value in predicting the effectiveness of such treatment in patients with heart failure. (orig.)

Association between spironolactone added to beta-blockers and ACE inhibition and survival in heart failure patients with reduced ejection fraction: a propensity score-matched cohort study.

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Frankenstein, L; Katus, H A; Grundtvig, M; Hole, T; de Blois, J; Schellberg, D; Atar, D; Zugck, C; Agewall, S

2013-10-01

Heart failure (CHF) guidelines recommend mineralocorticoid receptor antagonists for all symptomatic patients treated with a combination of ACE inhibitors/angiotensin receptor blockers (ARBs) and beta-blockers. As opposed to both eplerenone trials, patients in RALES (spironolactone) received almost no beta-blockers. Since pharmacological properties differ between eplerenone and spironolactone, the prognostic benefit of spironolactone added to this baseline combination therapy needs clarification. We included 4,832 CHF patients with chronic systolic dysfunction from the Norwegian Heart Failure Registry and the heart failure outpatients' clinic of the University of Heidelberg. Propensity scores for spironolactone receipt were calculated for each patient and used for matching to patients without spironolactone. During a total follow-up of 17,869 patient-years, 881 patients (27.0 %) died in the non-spironolactone group and 445 (28.4 %) in the spironolactone group. Spironolactone was not associated with improved survival, neither in the complete sample (HR 0.82; 95 % CI 0.64-1.07; HR 1.03; 95 % CI 0.88-1.20; multivariate and propensity score adjusted respectively), nor in the propensity-matched cohort (HR 0.98; 95 % CI 0.82-1.18). In CHF outpatients we were unable to observe an association between the use of spironolactone and improved survival when administered in addition to a combination of ACE/ARB and beta-blockers.

Feasibility and Association of Neurohumoral Blocker Up-titration After Cardiac Resynchronization Therapy.

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Martens, Pieter; Verbrugge, Frederik H; Nijst, Petra; Bertrand, Philippe B; Dupont, Matthias; Tang, Wilson H; Mullens, Wilfried

2017-08-01

Cardiac resynchronization therapy (CRT) improves mortality and morbidity on top of optimal medical therapy in heart failure with reduced ejection fraction (HFrEF). This study aimed to elucidate the association between neurohumoral blocker up-titration after CRT implantation and clinical outcomes. Doses of angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and beta-blockers were retrospectively evaluated in 650 consecutive CRT patients implanted from October 2008 to August 2015 and followed in a tertiary multidisciplinary CRT clinic. All 650 CRT patients were on a maximal tolerable dose of ACE-I/ARB and beta-blocker at the time of CRT implantation. However, further up-titration was successful in 45.4% for ACE-I/ARB and in 56.8% for beta-blocker after CRT-implantation. During a mean follow-up of 37 ± 22 months, a total of 139 events occurred for the combined end point of heart failure admission and all-cause mortality. Successful, versus unsuccessful, up-titration was associated with adjusted hazard ratios of 0.537 (95% confidence interval 0.316-0.913; P = .022) for ACE-I/ARB and 0.633 (0.406-0.988; P = .044) for beta-blocker on the combined end point heart failure admission and all-cause mortality. Patients in the up-titration group exhibited a similar risk for death or heart failure admission as patients treated with the maximal dose (ACE-I/ARB: P = .133; beta-blockers: P = .709). After CRT, a majority of patients are capable of tolerating higher dosages of neurohumoral blockers. Up-titration of neurohumoral blockers after CRT implantation is associated with improved clinical outcomes, similarly to patients treated with the guideline-recommended target dose at the time of CRT implantation. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficacy of monotherapies and artesunate-based combination therapies in children with uncomplicated malaria in Somalia.

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Warsame, Marian; Atta, Hoda; Klena, John D; Waqar, Butt Ahmed; Elmi, Hussein Haji; Jibril, Ali Mohamed; Hassan, Hassan Mohamed; Hassan, Abdullahi Mohamed

2009-02-01

In order to guide the antimalarial treatment policy of Somalia, we conducted therapeutic efficacy studies of routinely used antimalarial monotherapies as well as artemisinin-based combination therapies (ACTs) for uncomplicated malaria in three sentinel sites during 2003-2006. Therapeutic efficacy of chloroquine (CQ), amodiaquine (AQ) and sulfadoxine/pyrimetahmine (SP) monotherapies, and artesunate plus SP (AS+SP) or AQ (AS+AQ) were evaluated in children 6 months to 10 years old with uncomplicated malaria. For the assessment of the monotherapies, 2003 WHO protocol with 14-day follow-up was used while the 2005 WHO protocol with 28-day follow-up was used for testing the ACTs. Of the monotherapies, CQ performed very poorly with treatment failures varying from 76.5% to 88% between the sites. AQ treatment failure was low except for Janale site with treatment failure of 23.4% compared to 2.8% and 8% in Jamame and Jowhar, respectively. For SP, treatment failures from 7.8% to 12.2% were observed. A 28-day test of artemisinin-based combinations, AS+SP and AS+AQ, proved to be highly efficacious with cure rates of 98-100% supporting the choice of AS+SP combination as first line treatment for uncomplicated malaria for Somalia.

Thirty Years of Evidence on the Efficacy of Drug Treatments for Chronic Heart Failure With Reduced Ejection Fraction: A Network Meta-Analysis.

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Burnett, Heather; Earley, Amy; Voors, Adriaan A; Senni, Michele; McMurray, John J V; Deschaseaux, Celine; Cope, Shannon

2017-01-01

Treatments that reduce mortality and morbidity in patients with heart failure with reduced ejection fraction, including angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), β-blockers (BB), mineralocorticoid receptor antagonists (MRA), and angiotensin receptor-neprilysin inhibitors (ARNI), have not been studied in a head-to-head fashion. This network meta-analysis aimed to compare the efficacy of these drugs and their combinations regarding all-cause mortality in patients with heart failure with reduced ejection fraction. A systematic literature review identified 57 randomized controlled trials published between 1987 and 2015, which were compared in terms of study and patient characteristics, baseline risk, outcome definitions, and the observed treatment effects. Despite differences identified in terms of study duration, New York Heart Association class, ejection fraction, and use of background digoxin, a network meta-analysis was considered feasible and all trials were analyzed simultaneously. The random-effects network meta-analysis suggested that the combination of ACEI+BB+MRA was associated with a 56% reduction in mortality versus placebo (hazard ratio 0.44, 95% credible interval 0.26-0.66); ARNI+BB+MRA was associated with the greatest reduction in all-cause mortality versus placebo (hazard ratio 0.37, 95% credible interval 0.19-0.65). A sensitivity analysis that did not account for background therapy suggested that ARNI monotherapy is more efficacious than ACEI or ARB monotherapy. The network meta-analysis showed that treatment with ACEI, ARB, BB, MRA, and ARNI and their combinations were better than the treatment with placebo in reducing all-cause mortality, with the exception of ARB monotherapy and ARB plus ACEI. The combination of ARNI+BB+MRA resulted in the greatest mortality reduction. © 2017 The Authors.

Use of β-Blockers in Pulmonary Hypertension.

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Perros, Frédéric; de Man, Frances S; Bogaard, Harm J; Antigny, Fabrice; Simonneau, Gérald; Bonnet, Sébastien; Provencher, Steeve; Galiè, Nazzareno; Humbert, Marc

2017-04-01

Contrasting with the major attention that left heart failure has received, right heart failure remains understudied both at the preclinical and clinical levels. However, right ventricle failure is a major predictor of outcomes in patients with precapillary pulmonary hypertension because of pulmonary arterial hypertension, and in patients with postcapillary pulmonary hypertension because of left heart disease. In pulmonary hypertension, the status of the right ventricle is one of the most important predictors of both morbidity and mortality. Paradoxically, there are currently no approved therapies targeting the right ventricle in pulmonary hypertension. By analogy with the key role of β-blockers in the management of left heart failure, some authors have proposed to use these agents to support the right ventricle function in pulmonary hypertension. In this review, we summarize the current knowledge on the use of β-blockers in pulmonary hypertension. © 2017 American Heart Association, Inc.

Successful Treatment of Mild Pediatric Kasabach-Merritt Phenomenon with Propranolol Monotherapy

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Worawut Choeyprasert

2014-01-01

Full Text Available Kasabach-Merritt phenomenon (KMP is relatively rare in childhood and adolescents with high mortality rate because of its hemorrhagic complications and unresponsiveness to treatments such as corticosteroids, vincristine, intravascular embolization, and/or surgery. Propranolol, a β-adrenergic receptor blocker, has a promising efficacy against vascular tumors such as infantile hemangiomas. But limited and variable data has been reported regarding the role of propranolol in treatment of KMP. We herein reported the successful treatment of mild pediatric KMP with propranolol monotherapy in a case of a five-week-old child with kaposiform hemangioendothelioma with successful treatment of both clinical and hematologic responses. After eight months of follow-up, patient still had stable cutaneous lesion while receiving propranolol monotherapy. Regular hematologic monitoring was done in order to detect any late relapse of the disease. Six months after discontinuation of propranolol, patient has still remained free of hematologic relapse, and primary cutaneous lesion has become a pale pink, 1 cm sized skin lesion.

Effect of early treatment with ivabradine combined with beta-blockers versus beta-blockers alone in patients hospitalised with heart failure and reduced left ventricular ejection fraction (ETHIC-AHF): A randomised study.

Science.gov (United States)

Hidalgo, Francisco J; Anguita, Manuel; Castillo, Juan C; Rodríguez, Sara; Pardo, Laura; Durán, Enrique; Sánchez, José J; Ferreiro, Carlos; Pan, Manuel; Mesa, Dolores; Delgado, Mónica; Ruiz, Martín

2016-08-15

To analyse the effect of the early coadministration of ivabradine and beta-blockers (intervention group) versus beta-blockers alone (control group) in patients hospitalised with heart failure and reduced left ventricular ejection fraction (HFrEF). A comparative, randomised study was performed to compare the treatment strategies of beta-blockers alone versus ivabradine and beta-blockers starting 24hours after hospital admission, for acute HF in patients with an left ventricular ejection fraction (EF)70bpm. A total of 71 patients were examined, 33 in the intervention group and 38 in the control group. No differences were observed with respect to their baseline characteristics or standard treatment at discharge. HR at 28days (64.3±7.5 vs. 70.3±9.3bpm, p=0.01) and at 4months (60.6±7.5 vs. 67.8±8bpm, p=0.004) after discharge were significantly lower in the intervention group. Significant differences were found with respect to the EF and brain natriuretic peptide levels at 4months. No differences in clinical events (rehospitalisation/death) were reported at 4months. No severe side effects attributable to the early administration of ivabradine were observed. The early coadministration of ivabradine and beta-blockers during hospital admission for acute HFrEF is feasible and safe, and it produces a significant decrease in HR at 28days and at 4months after hospital discharge. It also seemed to improve systolic function and functional and clinical parameters of HF patients at short-term. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Current role of beta-blockers in the treatment of hypertension.

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Aronow, Wilbert S

2010-11-01

It is important to know which patients with hypertension will benefit from beta-blocker therapy and which beta-blockers should be used in the treatment of hypertension to reduce cardiovascular events and mortality. Studies between 1981 and 2009 using a Medline search are reported. Beta-blockers should be used to treat hypertension in patients with previous myocardial infarction, acute coronary syndromes, angina pectoris, congestive heart failure, ventricular arrhythmias, supraventricular tachyarrhythmias, diabetes mellitus, after coronary artery bypass graft surgery, and in patients who are pregnant, have thyrotoxicosis, glaucoma, migraine, essential tremor, perioperative hypertension, or an excessive blood pressure response after exercise. The use of beta-blockers as first-line therapy in patients with primary hypertension has been controversial. However, the 2009 guidelines of the European Society of Hypertension state that large-scale meta-analyses of available data confirm that diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and calcium channel blockers do not significantly differ in their ability to lower blood pressure and to exert cardiovascular protection both in elderly and in younger patients. The key message of this paper is that atenolol should not be used as an antihypertensive drug and that the degree of reduction of mortality, myocardial infarction, stroke and congestive heart failure by antihypertensive therapy is dependent on the degree of lowering of aortic blood pressure. Newer vasodilator beta-blockers such as carvedilol and nebivolol may be more effective in reducing cardiovascular events than traditional beta-blockers, but this needs to be investigated by controlled clinical trials.

Race and Beta-Blocker Survival Benefit in Patients With Heart Failure: An Investigation of Self-Reported Race and Proportion of African Genetic Ancestry.

Science.gov (United States)

Luzum, Jasmine A; Peterson, Edward; Li, Jia; She, Ruicong; Gui, Hongsheng; Liu, Bin; Spertus, John A; Pinto, Yigal M; Williams, L Keoki; Sabbah, Hani N; Lanfear, David E

2018-05-08

It remains unclear whether beta-blockade is similarly effective in black patients with heart failure and reduced ejection fraction as in white patients, but self-reported race is a complex social construct with both biological and environmental components. The objective of this study was to compare the reduction in mortality associated with beta-blocker exposure in heart failure and reduced ejection fraction patients by both self-reported race and by proportion African genetic ancestry. Insured patients with heart failure and reduced ejection fraction (n=1122) were included in a prospective registry at Henry Ford Health System. This included 575 self-reported blacks (129 deaths, 22%) and 547 self-reported whites (126 deaths, 23%) followed for a median 3.0 years. Beta-blocker exposure (BBexp) was calculated from pharmacy claims, and the proportion of African genetic ancestry was determined from genome-wide array data. Time-dependent Cox proportional hazards regression was used to separately test the association of BBexp with all-cause mortality by self-reported race or by proportion of African genetic ancestry. Both sets of models were evaluated unadjusted and then adjusted for baseline risk factors and beta-blocker propensity score. BBexp effect estimates were protective and of similar magnitude both by self-reported race and by African genetic ancestry (adjusted hazard ratio=0.56 in blacks and adjusted hazard ratio=0.48 in whites). The tests for interactions with BBexp for both self-reported race and for African genetic ancestry were not statistically significant in any model ( P >0.1 for all). Among black and white patients with heart failure and reduced ejection fraction, reduction in all-cause mortality associated with BBexp was similar, regardless of self-reported race or proportion African genetic ancestry. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Antiandrogen monotherapy

DEFF Research Database (Denmark)

Kolvenbag, G J; Iversen, P; Newling, D W

2001-01-01

%) and gynecomastia (49%) are the most common adverse events seen during monotherapy with this drug. In summary, the availability of bicalutamide 150-mg monotherapy broadens treatment options for men with locally advanced prostate cancer, offering a viable and attractive alternative to castration in this patient......Nonsteroidal antiandrogens are generally used in conjunction with castration as combined androgen blockade. However, the changing profile of patients with prostate cancer has made monotherapy with a nonsteroidal antiandrogen an attractive alternative therapeutic approach, offering potential quality...

β-Blockers on Discharge From Acute Atrial Fibrillation Are Associated With Decreased Mortality and Lower Cerebrovascular Accidents in Patients With Heart Failure and Reduced Ejection Fraction.

Science.gov (United States)

Abi Khalil, Charbel; Zubaid, Mohammad; Asaad, Nidal; Rashed, Wafa A; Hamad, Adel Khalifa; Singh, Rajvir; Al Suwaidi, Jassim

2018-04-01

The benefits of β-blockers in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and atrial fibrillation (AF) are controversial. The Gulf Survey of Atrial Fibrillation Events was a prospective, multinational, observational registry of consecutive patients with AF recruited from the emergency department (ED). We studied the incidence of 6- and 12-month mortality, hospitalization for HF or AF, and stroke/transient ischemic attacks (TIAs) in patients with HFrEF, in relation to β-blockers on discharge from the ED or the subsequent hospital stay. Of the 344 patients with HFrEF and AF in the GULF-SAFE, 177 patients (53%) were discharged on β-blockers. Mortality was lower in those patients compared with the non-β-blockers group at 6 and 12 months (odds ratios [ORs] 0.31, 95% CI [0.16-0.61]; OR 0.30, 95% CI [0.16-0.55]; P = .001 for both, respectively), so was the risk of stroke/TIAs. However, hospitalizations for AF increased in the β-blockers group. Even after adjustment for several risk variables in 2 different models, the beneficial effect of β-blockers on mortality persisted, at the cost of more hospitalization for AF.

Reassessing guidelines for heart failure

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Helmut Drexler

2004-03-01

Full Text Available Significant progress has been made in the last few years in the management of heart failure. In particular several trials have given significant results. It has become apparent that heart failure may be prevented in some patients by treatment of risk factors such as coronary artery disease. Experience with angiotensin-converting enzyme (ACE inhibitors has shown that the survival and symptomatic benefits do last in the long term, and confirm that they are the first-line treatment in heart failure. The results of a number of trials using the angiotensin receptor blockers (ARBs candesartan, valsartan and losartan are presented and discussed. There is also some experience now in the use of candesartan for patients with heart failure and preserved left ventricular systolic function. The COMET trial compared the β-blockers carvedilol and metoprolol tartrate, and suggests that there may be differences in clinical effect between β-blockers. The selective aldosterone receptor blocker eplerenone was evaluated in the EPHESUS trial in post-MI patients with signs of heart failure. Based on these clinical trials, heart failure guidelines are now being updated.

Ramelteon combined with an ?1-blocker decreases nocturia in men with benign prostatic hyperplasia

OpenAIRE

Kawahara, Takashi; Morita, Satoshi; Ito, Hiroki; Terao, Hideyuki; Sakata, Ryoko; Ishiguro, Hitoshi; Tanaka, Katsuyuki; Miyamoto, Hiroshi; Matsuzaki, Junichi; Kubota, Yoshinobu; Uemura, Hiroji

2013-01-01

Background Nocturia is defined as waking one or more times during the night due to the urge to void. Recently, the effectiveness of several sedatives and analgesics for nocturia has been reported. We herein investigated the effects of ramelteon, an antioxidant and sleep inducer, on nocturia unresponsive to ?1-blocker monotherapy in males with lower urinary tract symptoms (LUTS) as a pilot study. Methods Subjects were 19 patients who had LUTS suggestive of benign prostate hyperplasia, received...

Treatment of febrile neutropenia with cefepime monotherapy.

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Jándula, B M; Martino, R; Gurgi, M; Manteiga, R; Sierra, J

2001-01-01

The empirical administration of a broad-spectrum beta-lactam antibiotic, either as monotherapy or in combination with an aminoglycoside, is an essential component of the initial management of patients with fever and severe neutropenia. Multiple antibiotics have been tested for this indication. Cefepime is a fourth-generation cephalosporin with in vitro activity against most gram-negative and many gram-positive bacteria. We have studied the use of this agent as monotherapy in this indication. One hundred and twenty-six episodes of febrile neutropenia in 98 adults with hematological malignancies were treated with cefepime monotherapy. Cefepime was given at a dose of 2 g every 8 h i.v. Most episodes (49%) were fever of unexplained origin, while a microbiologically documented and clinically documented infection occurred in 25% episodes each. Seventy-six (61%) episodes occurred after conventional chemotherapy, while 51 (41%) after a hematopoietic stem cell transplantation. Twelve episodes (10%) were not evaluable for response. Among the 114 evaluable episodes, 69 (55% of the initial sample and 61% of those evaluable) responded to cefepime monotherapy, while therapy failed in 45 cases (36% of the initial sample and 39% of those evaluable), including 14 cases who developed breakthrough bacteremia during therapy. There were no deaths due to bacterial infection. At the end of all antibiotic therapy (final outcome) 69 episodes were cured only with monotherapy, 47 were cured with modification of therapy and 10 patients died from an unrelated cause. The only variable that appeared to correlate with response to therapy was the duration of neutropenia, which was longer among patients who failed or developed breakthrough bacteremia than among those who responded to monotherapy. Initial empirical antibiotic therapy with cefepime as a single agent in patients with febrile neutropenia and a hematological malignancy is effective, but patients with prolonged neutropenia appear to be

Multiple treatment comparisons in epilepsy monotherapy trials

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Chadwick David W

2007-11-01

Full Text Available Abstract Background The choice of antiepileptic drug for an individual should be based upon the highest quality evidence regarding potential benefits and harms of the available treatments. Systematic reviews and meta-analysis of randomised controlled trials should be a major source of evidence supporting this decision making process. We summarise all available individual patient data evidence from randomised controlled trials that compared at least two out of eight antiepileptic drugs given as monotherapy. Methods Multiple treatment comparisons from epilepsy monotherapy trials were synthesized in a single stratified Cox regression model adjusted for treatment by epilepsy type interactions and making use of direct and indirect evidence. Primary outcomes were time to treatment failure and time to 12 month remission from seizures. A secondary outcome was time to first seizure. Results Individual patient data for 6418 patients from 20 randomised trials comparing eight antiepileptic drugs were synthesized. For partial onset seizures (4628 (72% patients, lamotrigine, carbamazepine and oxcarbazepine provide the best combination of seizure control and treatment failure. Lamotrigine is clinically superior to all other drugs for treatment failure but estimates suggest a disadvantage compared to carbamazepine for time to 12 month remission [Hazard Ratio (95% Confidence Interval = 0.87(0.73 to 1.04] and time to first seizure [1.29(1.13 to 1.48]. Phenobarbitone may delay time to first seizure [0.77(0.61 to 0.96] but at the expense of increased treatment failure [1.60(1.22 to 2.10]. For generalized onset tonic clonic seizures (1790 (28% patients estimates suggest valproate or phenytoin may provide the best combination of seizure control and treatment failure but some uncertainty remains about the relative effectiveness of other drugs. Conclusion For patients with partial onset seizures, results favour carbamazepine, oxcarbazepine and lamotrigine. For

Effect of selective and nonselective beta-blockers on resting energy production rate and total body substrate utilization in chronic heart failure.

Science.gov (United States)

Podbregar, Matej; Voga, Gorazd

2002-12-01

In chronic heart failure (CHF) beta-blockers reduce myocardial oxygen consumption and improve myocardial efficiency by shifting myocardial substrate utilization from increased free fatty acid oxidation to increased glucose oxidation. The effect of selective and nonselective beta-blockers on total body resting energy production rate (EPR) and substrate utilization is not known. Twenty-six noncachectic patients with moderately severe heart failure (New York Heart Association class II or III, left ventricular ejection fraction < 0.40) were treated with carvedilol (37.5 +/- 13.5 mg/12 h) or bisoprolol (5.4 +/- 3.0 mg/d) for 6 months. Indirect calorimetry was performed before and after 6 months of treatment. Resting EPR was decreased in carvedilol (5.021 +/- 0.803 to 4.552 +/- 0.615 kJ/min, P <.001) and bisoprolol group (5.230 +/- 0.828 to 4.978 +/- 0.640 kJ/min, P <.05; nonsignificant difference between groups). Lipid oxidation rate decreased in carvedilol and remained unchanged in bisoprolol group (2.4 +/- 1.4 to 1.5 +/- 0.9 mg m(2)/kg min versus 2.7 +/- 1.1 to 2.5 +/- 1.1 mg m(2)/kg min, P <.05). Glucose oxidation rate was increased only in carvedilol (2.6 +/- 1.4 to 4.4 +/- 1.6 mg m(2)/kg min, P <.05), but did not change in bisoprolol group. Both selective and nonselective beta-blockers reduce total body resting EPR in noncachectic CHF patients. Carvedilol compared to bisoprolol shifts total body substrate utilization from lipid to glucose oxidation.

[Effect of benazepril on cardiac function in Chinese patients with chronic heart failure: a meta-analysis of randomized controlled trials].

Science.gov (United States)

Yan, Xiaowei; Xu, Dingli; Huang, Jun

2014-10-14

To evaluate the efficacy and tolerability of benazepril in Chinese patients with chronic systolic heart failure. We searched the databases of Cochrane, PubMed, EMbase, CBM and CNKI from January 1989 to November 2010 for the relevant studies. Two investigators identified randomized controlled trials (RCTs) independently according to the predefined inclusion and exclusion criteria. Statistical data analysis was performed with the Stata 11 software. A total of 15 studies with 1 355 Chinese patients of chronic systolic heart failure fulfilled the inclusion criteria. Among them, 546 received benazepril monotherapy. The dose range of benazepril was 5 to 40 mg daily. And it was similar to angiotensin II receptor blockers (ARBs) in improving left ventricular ejection fraction (LVEF)(P = 0.674), reducing LVEDD (P = 0.511) and improving cardiac output (P = 0.363). The combination therapy of benazepril and ARB was superior to ARB monotherapy in reducing left ventricular end-diastolic diameter (LVEDD) (P = 0.001). However, LVEF was comparable between patients with ACEI/ARB combination therapy and those with ARB monotherapy (P = 0.105). Compared with blank control, benazepril treatment was associated with a significant improvement in LVEF from baseline to follow-up (WMD = 6.5%; 95% CI: 0.9%, 12.0%; P = 0.022). Compared with baseline, benazepril treatment significantly increased LVEF (WMD = 10.4%; 95% confidence interval [CI]:7.1%, 13.8%; P benazepril group. As the most common side effect after benazepril treatment, cough had a prevalence of 11.6%. Other side effects were rare. Benazepril is both efficacious and safe in the management of Chinese patients with chronic heart failure.

DOGMAS AND UPDATES ON THE USE OF BETA-BLOCKERS IN SECONDARY PREVENTION. FIRST PART.

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Alberto Morales Salinas

2011-08-01

Full Text Available There is consensus on clinical guidelines that beta-blockers (BB provide unquestionable benefits in several environments of secondary prevention, such as heart failure and myocardial infarction. However, in everyday practice they are underused in contexts where they are not contraindicated. Such is the case of heart failure with ejection fraction. This article presents an analysis on the available evidence of beta blockers’ effectiveness in heart failure with ejection fraction. It is concluded that overwhelming evidence favours the use of beta-blockers in chronic heart failure with ejection fraction, whereas in episodes of acute decompensated heart failure, their suspension should be avoided whenever it is possible.

Bisoprolol for congestive heart failure

DEFF Research Database (Denmark)

Rosenberg, J.; Gustafsson, F.

2008-01-01

Background: beta-Blockers are a cornerstone in the treatment of systolic heart failure treatment, but not all beta-blockers are effective or in this setting. Objective: To define the role of bisoprolol, a highly selective beta(1)-antagonist in congestive heart failure due to systolic dysfunction....... Methods: Using the keywords 'bisoprolol' and 'heart failure' PubMed and BIOSIS databases were searched for information regarding pharmacology and relevant randomised clinical trials. Supplementary publications were acquired by scrutinising reference lists of relevant papers. Additional information...... was obtained from the FDA website. Conclusion: Bisoprolol is an effective and well-tolerated first-line beta-blocker for patients with systolic heart failure. The knowledge is primarily based on study patients with moderate-to-severe heart failure from the three CIBIS trials Udgivelsesdato: 2008/2...

Beta-Adrenergic Receptor Blockers in Hypertension: Alive and Well.

Science.gov (United States)

Frishman, William H

Beta-adrenergic receptor blockers (β-blockers) are an appropriate treatment for patients having systemic hypertension (HTN) who have concomitant ischemic heart disease (IHD), heart failure, obstructive cardiomyopathy, aortic dissection or certain cardiac arrhythmias. β-Blockers can be used in combination with other antiHTN drugs to achieve maximal blood pressure control. Labetalol can be used in HTN emergencies and urgencies. β-Blockers may be useful in HTN patients having a hyperkinetic circulation (palpitations, tachycardia, HTN, and anxiety), migraine headache, and essential tremor. β-Blockers are highly heterogeneous with respect to various pharmacologic properties: degree of intrinsic sympathomimetic activity, membrane stabilizing activity, β 1 selectivity, α 1 -adrenergic blocking effects, tissue solubility, routes of systemic elimination, potencies and duration of action, and specific properties may be important in the selection of a drug for clinical use. β-Blocker usage to reduce perioperative myocardial ischemia and cardiovascular (CV) complications may not benefit as many patients as was once hoped, and may actually cause harm in some individuals. Currently the best evidence supports perioperative β-blocker use in two patient groups: patients undergoing vascular surgery with known IHD or multiple risk factors for it, and for those patients already receiving β-blockers for known CV conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

Dolutegravir as maintenance monotherapy for HIV (DOMONO): a phase 2, randomised non-inferiority trial.

Science.gov (United States)

Wijting, Ingeborg; Rokx, Casper; Boucher, Charles; van Kampen, Jeroen; Pas, Suzan; de Vries-Sluijs, Theodora; Schurink, Carolina; Bax, Hannelore; Derksen, Maarten; Andrinopoulou, Eleni-Rosalina; van der Ende, Marchina; van Gorp, Eric; Nouwen, Jan; Verbon, Annelies; Bierman, Wouter; Rijnders, Bart

2017-12-01

The high genetic barrier to resistance of dolutegravir might allow for its use as maintenance monotherapy in patients with HIV. We investigated whether dolutegravir monotherapy was non-inferior to combination antiretroviral therapy (ART) for maintaining virological suppression in patients with HIV-1 infection successfully treated with combination ART. We did this open-label, phase 2, randomised non-inferiority trial at two medical centres in the Netherlands. Eligible patients (aged ≥18 years) were on combination ART, had been virologically suppressed (HIV RNA <50 copies per mL) for at least 6 months, and had CD4 nadirs of 200 cells per μL or higher, HIV RNA zeniths of 100 000 copies per mL or less, and no history of virological failure. Patients were randomly assigned (1:1), via a web-based block randomisation method (variable block sizes of 4 and 6), to switch to dolutegravir monotherapy (50 mg once a day) either immediately or after a delay of 24 weeks of continued combination ART. Randomisation was stratified by HIV RNA zenith (<50 000 copies per mL vs 50 000-99 999 copies per mL). Investigators and patients were not masked to group allocation. The primary endpoint was the proportion of patients with plasma HIV RNA viral loads of less than 200 copies per mL at week 24, with a non-inferiority margin of 12%. We did analyses in the on-treatment and intention-to-treat populations. This trial is registered with ClinicalTrials.gov, NCT02401828. Between March 10, 2015, and Feb 4, 2016, we randomly assigned 51 patients to the immediate switch group and 53 patients to the delayed switch group. One patient who received immediate monotherapy discontinued treatment at week 12 because of disturbed sleep. At week 24, dolutegravir monotherapy was non-inferior to combination ART, with plasma HIV RNA loads of 200 copies per mL or higher observed in 2% (1/50) of patients in the immediate switch group and in no patients in the delayed switch group (difference 2%, 95% CI

Additive effects of cilnidipine, an L-/N-type calcium channel blocker, and an angiotensin II receptor blocker on reducing cardiorenal damage in Otsuka Long-Evans Tokushima Fatty rats with type 2 diabetes mellitus

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Mori Y

2014-06-01

Full Text Available Yutaka Mori,1,2 Shizuka Aritomi,3 Kazumi Niinuma,3 Tarou Nakamura,3 Kenichi Matsuura,1 Junichi Yokoyama,1 Kazunori Utsunomiya1 1Division of Diabetes and Endocrinology, Department of Internal Medicine, The Jikei University School of Medicine, Minato-ku, Japan; 2Department of Clinical Research, National Hospital Organization, Utsunomiya National Hospital, Utsunomiya, Japan; 3Research Center, Ajinomoto Pharmaceuticals Co, Ltd, Kanagawa, Japan Abstract: Cilnidipine (Cil, which is an L-/N-type calcium channel blocker (CCB, has been known to provide renal protection by decreasing the activity of the sympathetic nervous system (SNS and the renin–angiotensin system. In this study, we compared the effects of the combination of Cil and amlodipine (Aml, which is an L-type CCB, with an angiotensin (Ang II receptor blocker on diabetic cardiorenal damage in spontaneously type 2 diabetic rats. Seventeen-week-old Otsuka Long-Evans Tokushima Fatty rats were randomly assigned to receive Cil, Aml, valsartan (Val, Cil + Val, Aml + Val, or a vehicle (eight rats per group for 22 weeks. Antihypertensive potencies were nearly equal among the CCB monotherapy groups and the combination therapy groups. The lowering of blood pressure by either treatment did not significantly affect the glycemic variables. However, exacerbations of renal and heart failure were significantly suppressed in rats administered Cil or Val, and additional suppression was observed in those administered Cil + Val. Although Val increased the renin–Ang system, Aml + Val treatment resulted in additional increases in these parameters, while Cil + Val did not show such effects. Furthermore, Cil increased the ratio of Ang-(1–7 to Ang-I, despite the fact that Val and Aml + Val decreased the Ang-(1–7 levels. These actions of Cil + Val might be due to their synergistic inhibitory effect on the activity of the SNS, and on aldosterone secretion through N-type calcium channel antagonism and Ang II

Beta-blockers influence the short-term and long-term prognostic information of natriuretic peptides and catecholamines in chronic heart failure independent from specific agents.

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Frankenstein, Lutz; Nelles, Manfred; Slavutsky, Maxim; Schellberg, Dieter; Doesch, Andreas; Katus, Hugo; Remppis, Andrew; Zugck, Christian

2007-10-01

In chronic heart failure (CHF), the physiologic effects of natriuretic peptides and catecholamines are interdependent. Furthermore, reports state an agent-dependent effect of individual beta-blockers on biomarkers. Data on the short-term and long-term predictive power comparing these biomarkers as well as accounting for the influence of beta-blocker treatment both on the marker or the resultant prognostic information are scarce. We included 513 consecutive patients with systolic CHF, measured atrial natriuretic peptide (ANP), N-terminal prohormone brain natriuretic peptide (NTproBNP), noradrenaline, and adrenaline, and monitored them for 90 +/- 25 months. Death or the combination of death and cardiac transplantation at 1 year, 5 years, and overall follow-up were considered end points. Compared with patients not taking beta-blockers, patients taking beta-blockers had significantly lower levels of catecholamines but not natriuretic peptides. Only for adrenaline was the amount of this effect related to the specific beta-blocker chosen. Receiver operating characteristic curves demonstrated superior prognostic accuracy for NTproBNP both at the 1- and 5-year follow-up compared with ANP, noradrenaline, and adrenaline. In multivariate analysis including established risk markers (New York Heart Association functional class, left ventricular ejection fraction, peak oxygen uptake, and 6-minute walk test), of all neurohumoral parameters, only NTproBNP remained an independent predictor for both end points. Long-term beta-blocker therapy is associated with decreased levels of plasma catecholamines but not natriuretic peptides. This effect is independent from the actual beta-blocker chosen for natriuretic peptides and noradrenaline. In multivariate analysis, both for short-term and long-term prediction of mortality or the combined end point of death and cardiac transplantation, only NTproBNP remained independent from established clinical risk markers.

The less familiar side of heart failure: symptomatic diastolic dysfunction.

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Morris, Spencer A; Van Swol, Mark; Udani, Bela

2005-06-01

Arrange for echocardiography or radionuclide angiography within 72 hours of a heart failure exacerbation. An ejection fraction >50% in the presence of signs and symptoms of heart failure makes the diagnosis of diastolic heart failure probable. To treat associated hypertension, use angiotensin receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, calcium channel blockers, or diuretics to achieve a blood pressure goal of <130/80 mm Hg. When using beta-blockers to control heart rate, titrate doses more aggressively than would be done for systolic failure, to reach a goal of 60 to 70 bpm. Use ACE inhibitors/ARBs to decrease hospitalizations, decrease symptoms, and prevent left ventricular remodeling.

H2 blockers

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Peptic ulcer disease - H2 blockers; PUD - H2 blockers; Gastroesophageal reflux - H2 blockers; GERD - H2 blockers ... H2 blockers are used to: Relieve symptoms of acid reflux, or gastroesophageal reflux disease (GERD). This is a ...

Effect on Intraocular Pressure of Switching from Latanoprost and Travoprost Monotherapy to Timolol Fixed Combinations in Patients with Normal-Tension Glaucoma

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Ryoko Igarashi

2014-01-01

Full Text Available Purpose. To evaluate the effect on intraocular pressure (IOP of switching from latanoprost and travoprost monotherapy to timolol fixed combinations in Japanese patients with normal-tension glaucoma (NTG. Methods. 27 NTG patients (54 eyes were compared IOP, superficial punctuate keratitis (SPK scores, and conjunctival injection scores in eyes treated with prostaglandin (PG or PG analog/beta-blocker (PG/b fixed-combination 6 months after the change in therapy. Results. The mean baseline intraocular pressure was 17.4±1.59 mmHg in eyes receiving PG therapy only and 17.4±1.69 mmHg in eyes switched to PG/b. Switching to fixed combination therapy from PG monotherapy, the mean IOP was 13.1±1.79 mmHg (P<0.001  (-24.71% reduction from baseline at 6 months. The mean conjunctival injection score was 0.69 for eyes on PG monotherapy and 0.56 for eyes on fixed combination therapy (P=0.028. The mean SPK scores were 0.46 and 0.53. This difference was not statistically significant (P=0.463. Conclusions. Switching from PG monotherapy to PG/b fixed combination therapy for NTG resulted in a greater intraocular pressure reduction than PG alone without increasing the number of instillations.

Beta-blockers for preventing aortic dissection in Marfan syndrome.

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Koo, Hyun-Kyoung; Lawrence, Kendra Ak; Musini, Vijaya M

2017-11-07

Marfan syndrome is a hereditary disorder affecting the connective tissue and is caused by a mutation of the fibrillin-1 (FBN1) gene. It affects multiple systems of the body, most notably the cardiovascular, ocular, skeletal, dural and pulmonary systems. Aortic root dilatation is the most frequent cardiovascular manifestation and its complications, including aortic regurgitation, dissection and rupture are the main cause of morbidity and mortality. To assess the long-term efficacy and safety of beta-blocker therapy as compared to placebo, no treatment or surveillance only in people with Marfan syndrome. We searched the following databases on 28 June 2017; CENTRAL, MEDLINE, Embase, Science Citation Index Expanded and the Conference Proceeding Citation Index - Science in the Web of Science Core Collection. We also searched the Online Metabolic and Molecular Bases of Inherited Disease (OMMBID), ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 30 June 2017. We did not impose any restriction on language of publication. All randomised controlled trials (RCTs) of at least one year in duration assessing the effects of beta-blocker monotherapy compared with placebo, no treatment or surveillance only, in people of all ages with a confirmed diagnosis of Marfan syndrome were eligible for inclusion. Two review authors independently screened titles and abstracts for inclusion, extracted data and assessed trial quality. Trial authors were contacted to obtain missing data. Dichotomous outcomes will be reported as relative risk and continuous outcomes as mean differences with 95% confidence intervals. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. One open-label, randomised, single-centre trial including 70 participants with Marfan syndrome (aged 12 to 50 years old) met the inclusion criteria. Participants were randomly assigned to

Clinical usefulness of a dual L/N-type Ca2+ channel blocker, cilnidipine, in patients with chronic heart failure. Assessment with 123I-MIBG myocardial scintigraphy

International Nuclear Information System (INIS)

Ito, Kazuki; Nishikawa, Susumu; Adachi, Yoshihiko; Kato, Shuuji; Azuma, Akihiro; Matsubara, Hiroaki

2003-01-01

Sympathetic nerve system is activated as a compensatory mechanism in heart failure. However excessive activation of sympathetic nerve system deteriorates disease state. Sympathetic nerve system can be suppressed with N-type Ca 2+ channel blocker. An antihypertensive drug, cilnidipine, is a dual L/N-type Ca 2+ channel blocker. We studies usefulness of cilnidipine in treating with chronic heart failure with 123 I-MIBG myocardial scintigraphy. We enrolled 24 patients with stable chronic heart failure. Twelve patients were treated with angiotensin converting enzyme (ACE)-inhibitors, diuretics and cardiotonics (control group), and the other 12 patients were treated with ACE-inhibitors, diuretics, cardiotonics and cilnidipine (cilnidipine group). We examined blood pressure, heart rate, norepinephrine level, brain natriuretic peptide (BNP) level, cardiothoracic ratio on chest X-ray, ejection fraction of left ventricle on two-dimensional echocardiography, count rate of heart to mediastinum (H/M) and washout rate (WOR) on 123 I-MIBG myocardial scintigraphy before and six months after medication. Symptom was improved in 8 patients in the control group and 10 patients in the cilnidipine group after medication. And another parameters were also improved in the both groups after medication. However the degree of change in blood pressure (mmHg) was 21.2±8.0 in the cilnidipine group and 10.8±9.1 in the control group, that in heart rate (/min) was 24.1±6.8 and 16.2±11.0, that in BNP level (pg/ml) was 65.2±12.0 and 42.8±11.1, that in H/M was 0.30±0.08 and 0.19±0.09, that in WOR was 19.4±5.6 and 12.2±7.0, respectively. And the degree of these changes were larger in the cilnidipine group (p 2+ channel blocker, might be useful in treating with chronic heart failure. (author)

Use of angiotensin II receptor blockers alone and in combination with other drugs: a large clinical experience trial

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Matthew R Weir

2001-03-01

Full Text Available Angiotensin II (Ang II receptor blockers are the newest class of antihypertensive drugs to be developed. No large-scale clinical trials have been performed to evaluate their efficacy alone, or in combination with other drugs. A large-scale, eight week, open-label, non-placebo-controlled, single-arm trial evaluated the efficacy, tolerability and dose-response of candesartan cilexetil, 16—32 mg once-daily, either as monotherapy or as part of combination therapy, in a diverse hypertensive population in actual practice settings. 6465 patients with high blood pressure, of whom 52% were female and 16% African American, with a mean age of 58 years, were included. 5446 patients had essential hypertension and 1014 patients had isolated systolic hypertension. In order to be included in this study, patients had either untreated or uncontrolled hypertension (systolic blood pressure (SBP 140—179 mmHg and/or diastolic blood pressure (DBP 90—109 mmHg inclusive at baseline, despite a variety of other antihypertensive drugs. Of the 5156 patients with essential hypertension and at least one post baseline efficacy measurement, the mean pretreatment blood pressure (BP was 156/97 mmHg. Candesartan cilexetil monotherapy reduced mean SBP/DBP by 18.0/12.2 mmHg. Similarly, in the 964 patients with isolated systolic hypertension and at least one post baseline efficacy measurement, candesartan cilexetil monotherapy reduced SBP/DBP from 158/81 by 16.5/4.5 mmHg. Candesartan cilexetil was similarly effective when employed as add-on therapy. When added to baseline antihypertensive medication in 51% of the patients with essential hypertension not achieving BP control, additional reduction in BP was achieved regardless of the background therapy, including diuretics (17.8/11.7 mmHg calcium antagonists (16.6/11.2 mmHg, beta-blockers (16.5/10.4 mmHg, angiotensin-converting enzyme inhibitors (ACE-I (15.3/10.0 mmHg, and alpha blockers (16.4/10.4 mmHg. Likewise, when

[Focus on beta-blockers for vascular specialists in 2012].

Science.gov (United States)

Mairesse, S; Blacher, J; Safar, M-E

2011-12-01

Since they were launched on the market in 1964, cardiovascular indications for beta-blockers have been validated and accepted worldwide. Numerous studies and meta-analysis have confirmed their benefits. They reduce mortality in post infarction and acute coronary syndrome populations and also in people with stable coronary heart disease. Moreover, heart failure with systolic left ventricular dysfunction is a major indication for this therapeutic class, providing a 30% decrease in mortality. In patients with permanent atrial fibrillation, beta-blockers are recommended for rate control. In hypertension patients, first-line drug treatment with beta-blockers is currently discussed. Indeed, several studies have shown that patients randomized in the beta-blocker arms experienced more coronary heart and cerebrovascular diseases than comparators. Their lesser effect on central blood pressure decrease could partially explain those results. Nevertheless, beta-blockers are still considered as first-line drugs for hypertension in the French and European guidelines. Long-term comparative studies focusing on central blood pressure are needed. Concerning the other indications for beta-blockers in vascular diseases, their use perioperatively to reduce surgical cardiovascular risk raised much hope, but the most recent results are disappointed and even suggest possible higher mortality. Finally, except for patients with critical ischemia of the lower limbs, presence of peripheral artery disease should probably be considered as a condition favoring their prescription. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Beta-blockers

DEFF Research Database (Denmark)

Arboe, Bente; Ulrik, Charlotte Suppli

2013-01-01

Recently, β-blockers have been suggested as a potential maintenance treatment option for asthma. The aim of this review is to provide an overview of the current knowledge of the potential benefits and risks of β-blocker therapy for asthma.......Recently, β-blockers have been suggested as a potential maintenance treatment option for asthma. The aim of this review is to provide an overview of the current knowledge of the potential benefits and risks of β-blocker therapy for asthma....

Effectiveness of Ritonavir-Boosted Protease Inhibitor Monotherapy in Clinical Practice Even with Previous Virological Failures to Protease Inhibitor-Based Regimens.

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Luis F López-Cortés

Full Text Available Significant controversy still exists about ritonavir-boosted protease inhibitor monotherapy (mtPI/rtv as a simplification strategy that is used up to now to treat patients that have not experienced previous virological failure (VF while on protease inhibitor (PI -based regimens. We have evaluated the effectiveness of two mtPI/rtv regimens in an actual clinical practice setting, including patients that had experienced previous VF with PI-based regimens.This retrospective study analyzed 1060 HIV-infected patients with undetectable viremia that were switched to lopinavir/ritonavir or darunavir/ritonavir monotherapy. In cases in which the patient had previously experienced VF while on a PI-based regimen, the lack of major HIV protease resistance mutations to lopinavir or darunavir, respectively, was mandatory. The primary endpoint of this study was the percentage of participants with virological suppression after 96 weeks according to intention-to-treat analysis (non-complete/missing = failure.A total of 1060 patients were analyzed, including 205 with previous VF while on PI-based regimens, 90 of whom were on complex therapies due to extensive resistance. The rates of treatment effectiveness (intention-to-treat analysis and virological efficacy (on-treatment analysis at week 96 were 79.3% (CI95, 76.8-81.8 and 91.5% (CI95, 89.6-93.4, respectively. No relationships were found between VF and earlier VF while on PI-based regimens, the presence of major or minor protease resistance mutations, the previous time on viral suppression, CD4+ T-cell nadir, and HCV-coinfection. Genotypic resistance tests were available in 49 out of the 74 patients with VFs and only four patients presented new major protease resistance mutations.Switching to mtPI/rtv achieves sustained virological control in most patients, even in those with previous VF on PI-based regimens as long as no major resistance mutations are present for the administered drug.

Calcium channel blockers, more than diuretics, enhance vascular protective effects of angiotensin receptor blockers in salt-loaded hypertensive rats.

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Eiichiro Yamamoto

Full Text Available The combination therapy of an angiotensin receptor blocker (ARB with a calcium channel blocker (CCB or with a diuretic is favorably recommended for the treatment of hypertension. However, the difference between these two combination therapies is unclear. The present work was undertaken to examine the possible difference between the two combination therapies in vascular protection. Salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP were divided into 6 groups, and they were orally administered (1 vehicle, (2 olmesartan, an ARB, (3 azelnidipine, a CCB, (4 hydrochlorothiazide, a diuretic, (5 olmesartan combined with azelnidipine, or (6 olmesartan combined with hydrochlorothiazide. Olmesartan combined with either azelnidipine or hydrochlorothiazide ameliorated vascular endothelial dysfunction and remodeling in SHRSP more than did monotherapy with either agent. However, despite a comparable blood pressure lowering effect between the two treatments, azelnidipine enhanced the amelioration of vascular endothelial dysfunction and remodeling by olmesartan to a greater extent than did hydrochlorothiazide in salt-loaded SHRSP. The increased enhancement by azelnidipine of olmesartan-induced vascular protection than by hydrochlorothiazide was associated with a greater amelioration of vascular nicotinamide adenine dinucleotide phosphate (NADPH oxidase activation, superoxide, mitogen-activated protein kinase activation, and with a greater activation of the Akt/endothelial nitric oxide synthase (eNOS pathway. These results provided the first evidence that a CCB potentiates the vascular protective effects of an ARB in salt-sensitive hypertension, compared with a diuretic, and provided a novel rationale explaining the benefit of the combination therapy with an ARB and a CCB.

Ramelteon combined with an α1-blocker decreases nocturia in men with benign prostatic hyperplasia.

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Kawahara, Takashi; Morita, Satoshi; Ito, Hiroki; Terao, Hideyuki; Sakata, Ryoko; Ishiguro, Hitoshi; Tanaka, Katsuyuki; Miyamoto, Hiroshi; Matsuzaki, Junichi; Kubota, Yoshinobu; Uemura, Hiroji

2013-06-12

Nocturia is defined as waking one or more times during the night due to the urge to void. Recently, the effectiveness of several sedatives and analgesics for nocturia has been reported. We herein investigated the effects of ramelteon, an antioxidant and sleep inducer, on nocturia unresponsive to α1-blocker monotherapy in males with lower urinary tract symptoms (LUTS) as a pilot study. Subjects were 19 patients who had LUTS suggestive of benign prostate hyperplasia, received α1-blockers (tamsulosin, silodosin, or naftopidil), and continued to have two or more episodes of nocturia per night before starting ramelteon. Ramelteon at 8 mg once daily for one month was added to the α1-blocker. A self-administered questionnaire including the International Prostate Symptom Score (IPSS), quality of life (QoL) index, Overactive Bladder Symptom Score (OABSS), and Nocturia Quality-of-Life Questionnaire (N-QOL) were assessed before and one month after starting ramelteon. The mean score on IPSS question 7 (nocturia) decreased significantly from 2.88 before starting ramelteon to 2.41 one month after starting the medication (P = 0.03). The mean total OABSS decreased significantly from 6.31 to 5.38 (P = 0.03), and the mean for OABSS question 2 (nighttime frequency of nocturia) also significantly decreased from 2.63 to 2.13 (P = 0.01). The mean total N-QOL score did not change significantly. Two patients had dizziness; the remaining patients had no adverse drug-related events. Ramelteon in combination with an α1-blocker could be a treatment option for reducing nocturia in men with BPH.

Antiandrogen monotherapy: indications and results

DEFF Research Database (Denmark)

Iversen, Peter

2002-01-01

monotherapy is generally well tolerated, with a predictable side-effect profile. The most common side effects are male breast pain and gynecomastia. Emerging evidence also supports the use of bicalutamide 150 mg, both as immediate monotherapy and as adjuvant therapy in early stage (localized or locally...

Prostate-Specific Antigen Bounce After High-Dose-Rate Monotherapy for Prostate Cancer

International Nuclear Information System (INIS)

Mehta, Niraj H.; Kamrava, Mitchell; Wang, Pin-Chieh; Steinberg, Michael; Demanes, Jeffrey

2013-01-01

Purpose: To characterize the magnitude and kinetics of prostate-specific antigen (PSA) bounces after high-dose-rate (HDR) monotherapy and determine relationships between certain clinical factors and PSA bounce. Methods and Materials: Longitudinal PSA data and various clinical parameters were examined in 157 consecutive patients treated with HDR monotherapy between 1996 and 2005. We used the following definition for PSA bounce: rise in PSA ≥threshold, after which it returns to the prior level or lower. Prostate-specific antigen failure was defined per the Phoenix definition (nadir +2 ng/mL). Results: A PSA bounce was noted in 67 patients (43%). The number of bounces per patient was 1 in 45 cases (67%), 2 in 19 (28%), 3 in 2 (3%), 4 in 0, and 5 in 1 (1%). The median time to maximum PSA bounce was 1.3 years, its median magnitude was 0.7, and its median duration was 0.75 years. Three patients (2%) were noted to have PSA failure. None of the 3 patients who experienced biochemical failure exhibited PSA bounce. In the fully adjusted model for predicting each bounce, patients aged <55 years had a statistically significant higher likelihood of experiencing a bounce (odds ratio 2.22, 95% confidence interval 1.38-3.57, P=.001). There was also a statistically significant higher probability of experiencing a bounce for every unit decrease in Gleason score (odds ratio 1.52, 95% confidence interval 1.01-2.04, P=.045). Conclusions: A PSA bounce occurs in a significant percentage of patients treated with HDR monotherapy, with magnitudes varying from <1 in 28% of cases to ≥1 in 15%. The median duration of bounce is <1 year. More bounces were identified in patients with lower Gleason score and age <55 years. Further investigation using a model to correlate magnitude and frequency of bounces with clinical variables are under way

Beta-blocker withdrawal among patients presenting for surgery from home

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Schonberger, Robert B.; Lukens, Carrie L.; Turkoglu, O. Dicle; Feinleib, Jessica L.; Haspel, Kenneth L.; Burg, Matthew M.

2012-01-01

Structured Abstract Objective This study sought to measure the incidence of perioperative beta-blocker non-compliance by patients who were prescribed chronic beta blocker therapy and presented for surgery from home. The effect of patient non-compliance on day of surgery presenting heart rate was also examined. Design Prospective observational study with outcome data obtained from review of the medical record. Setting The preoperative clinic and operating rooms of a Veterans Administration hospital. Participants Patients on chronic beta blocker therapy who presented from home for surgery. Interventions None. Measurements and Main Results Demographic and comorbidity data as well as data on self-reported compliance to beta-blocker therapy, initial day of surgery vital signs, and recent ambulatory vital signs were collected. Ten out of fifty subjects (20%; 95% CI = 9-31%) reported not taking their day of surgery beta-blocker. These self-reported non-adherers demonstrated a higher presenting heart rate on the day of surgery vs. adherent subjects (median of 78 beats per minute vs. 65 beats per minute, p=0.02 by Wilcoxon Rank-Sum Test). The difference-in-difference between baseline primary care and day of surgery heart rate was also statistically significant between compliant and non-compliant subjects (-7 beats per minute vs. +12.5 beats per minute, p<0.00001). Conclusions Patient self-report and physiologic data documented failure to take beta-blockers and possible beta-blocker withdrawal in 20% of patients who presented for surgery from home. If these findings are confirmed in larger studies, improved patient understanding of and compliance with medication instructions during preoperative visits should be a focus of future quality improvement initiatives. PMID:22418043

Maitake mushroom (Grifola frondosa) extract induces ovulation in patients with polycystic ovary syndrome: a possible monotherapy and a combination therapy after failure with first-line clomiphene citrate.

Science.gov (United States)

Chen, Jui-Tung; Tominaga, Kunihiko; Sato, Yoshiaki; Anzai, Hideo; Matsuoka, Ryo

2010-12-01

Insulin resistance is a prominent feature of polycystic ovary syndrome (PCOS), and insulin-sensitizing drugs are used to induce ovulation. Recently, it was reported that an extract from Maitake mushroom (Grifola frondosa) improves insulin resistance. The objective was to explore the effects of Maitake extract (SX-fraction: MSX) to induce ovulation in patients with PCOS in comparison with and in combination with clomiphene citrate (CC). We conducted an open trial with 80 patients with PCOS at three clinics in Japan. Seventy-two (72) new patients were randomly assigned to receive MSX or CC monotherapy for up to 12 weeks. Eighteen (18) patients who did not respond to MSX or CC were subjected to combination therapy of MSX and CC for up to 16 weeks. Eight (8) patients with documented history of failure to CC received combination therapy from the beginning. Ovulation was assessed by ultrasonography. Twenty-six (26) patients in the MSX group and 31 in the CC group were evaluated for ovulation. The ovulation rates for MSX and CC were as follows: 76.9% (20/26) and 93.5% (29/31), respectively by the patients (NS), and 41.7% (30/72) and 69.9% (58/83), respectively, by the cycles (p = 0.0006). In the combination therapy, 7 of 7 patients who failed in MSX monotherapy and 6 of 8 patients who failed in CC monotherapy showed ovulation. The present study suggests that MSX alone may induce ovulation in PCOS patients and may be useful as an adjunct therapy for patients who failed first-line CC treatment.

Alpha Blockers

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... quickly, but their effects last only a few hours. Long-acting medications take longer to work, but their effects last longer. Which alpha blocker is best for you depends on your health and the condition being treated. Alpha blockers are ...

Rationale for combination therapy in hypertension management: focus on angiotensin receptor blockers and thiazide diuretics.

Science.gov (United States)

Nash, David T

2007-04-01

Despite recognition that hypertension is a major risk factor for cardiovascular events and mortality, blood pressure control rates remain low in the US population. Reflecting clinical trial results, hypertension management guidelines assert the clinical benefit of achieving current blood pressure goals and indicate that most patients will require 2 or more drugs to reach goal. Well-designed drug combinations counter hypertension via complementary mechanisms that increase antihypertensive efficacy, potentially with lower rates of adverse events than higher dose monotherapy regimens. Lower adverse event rates, in turn, may contribute to greater adherence with treatment. The combination of a low-dose diuretic with agents that block the effects of the renin-angiotensin system (RAS), such as angiotensin receptor blockers, has been found in numerous clinical trials to be highly effective for lowering blood pressure in patients with uncomplicated as well as high-risk hypertension, with a comparable favorable side effect profile compared with monotherapy. Moreover, agents that block the RAS are associated with a lower risk of new-onset diabetes mellitus than other antihypertensive classes. Complementary combinations of antihypertensive agents provide an efficient and effective approach to hypertension management.

Efficacy and safety of a therapeutic interchange from high-dose calcium channel blockers to a fixed-dose combination of amlodipine/benazepril in patients with moderate-to-severe hypertension.

Science.gov (United States)

Hilleman, D E; Reyes, A P; Wurdeman, R L; Faulkner, M

2001-08-01

Recent hypertension trials have demonstrated the importance of achieving goal blood pressures to reduce the risk of target organ damage. In patients with moderate to severe hypertension, the use of high-dose monotherapy and/or combinations of drugs are necessary to achieve these goals. Fixed-dose combination products may be useful in these patients by reducing the number of daily doses required to control blood pressure. The objective of the present study was to evaluate the efficacy and safety of a therapeutic interchange between high-dose calcium channel blocker therapy and a fixed-dose combination of amlodipine/ benazepril (Lotrel; Novartis Pharmaceuticals, USA) in patients with moderate to severe hypertension. A total of 75 patients were switched from amlodipine (n = 25), felodipine (n = 25), and nifedipine-GITS (n = 25) to amlodipine/benazepril. Twenty-eight of the 75 patients (37%) were taking either a beta-blocker or a diuretic in addition to the high-dose calcium channel blocker prior to the switch. Blood pressure control, side effects and the cost of the therapeutic interchange were evaluated in the year following the therapeutic interchange. Sixty-six of the 75 (88%) patients were successfully switched with maintenance of blood pressure control and without the development of new dose-limiting side effects. Reasons for treatment failure after the therapeutic interchange included loss of blood pressure control in five patients and the development of new dose-limiting side effects in four patients. These side effects included cough in three patients and rash in one patient. After accounting for differences in drug acquisition cost and costs related to the switch (clinic and emergency room and laboratory tests), a cost savings of $16030 for all 75 patients was realised in the first year. The per patient-per year cost savings was $214. Our data indicate that a therapeutic interchange from selected high-dose calcium channel blockers to a fixed-dose combination

HIV-1 resistance dynamics in patients failing dolutegravir maintenance monotherapy.

Science.gov (United States)

Wijting, Ingeborg E A; Lungu, Cynthia; Rijnders, Bart J A; van der Ende, Marchina E; Pham, Hanh T; Mesplede, Thibault; Pas, Suzan D; Voermans, Jolanda J C; Schuurman, Rob; van de Vijver, David A M C; Boers, Patrick H M; Gruters, Rob A; Boucher, Charles A B; van Kampen, Jeroen J A

2018-03-29

A high genetic resistance barrier to the integrase-strand-transfer-inhibitor (INSTI) dolutegravir has been reported in vitro and in vivo. We describe the dynamics of INSTI-resistance-associated-mutations (INSTI-RAMs) and mutations in the 3'-polypurine tract (3'-PPT) in relation to virological failure (VF) observed in the randomized dolutegravir maintenance monotherapy study (DOMONO, NCT02401828). From ten patients with VF plasma samples prior to start cART and during VF were used to generate Sanger sequences of integrase, the 5' terminal bases of the 3'- LTR, and the 3'-PPT. Median HIV-RNA (IQR) at VF was 3,490 (1,440-4,990) c/mL. INSTI-RAMs were detected in 4/10 patients (S230R, R263K, N155H, E92Q+N155H) and in 4/10 patients no INSTI-RAMs were detected (2/10 patients integrase sequencing was unsuccessful). The time-to-VF ranged from 4 weeks to 72 weeks. In one patient, mutations developed in the highly conserved 3'-PPT. No changes in the terminal bases of the 3'-LTR were observed. The genetic barrier to resistance is too low to justify dolutegravir maintenance monotherapy as single INSTI-RAMs are sufficient to cause VF. The large variation in time-to-VF suggests that stochastic reactivation of a pre-existing provirus containing a single INSTI-RAM is the mechanism for failure. Changes in the 3'-PPT point to a new dolutegravir resistance mechanism in vivo.

Low-dose β-blocker in combination with milrinone safely improves cardiac function and eliminates pulsus alternans in patients with acute decompensated heart failure.

Science.gov (United States)

Kobayashi, Shigeki; Susa, Takehisa; Tanaka, Takeo; Murakami, Wakako; Fukuta, Seiko; Okuda, Shinichi; Doi, Masahiro; Wada, Yasuaki; Nao, Tomoko; Yamada, Jutaro; Okamura, Takayuki; Yano, Masafumi; Matsuzaki, Masunori

2012-01-01

The purpose of this study was to determine whether a low-dose β-blocker, in combination with milrinone, improves cardiac function in acute decompensated heart failure (ADHF) with tachycardia. Twenty ADHF patients (New York Heart Association classification III, n=1, and IV, n=19; heart rate [HR], 107±12 beats/min; left ventricular ejection fraction, 24±7%; cardiac index [CI], 2.2±0.6 L·min(-1)·m(-2); pulmonary capillary wedge pressure [PCWP], 26±8 mmHg) were enrolled in this study. The patients first underwent conventional therapy with milrinone, vasodilators and diuretics; landiolol (1.5-6.0 µg·kg(-1)·min(-1); i.v.), which is an ultra-short-acting β(1)-selective blocker, was then added to the treatment regimen to study its effect on hemodynamics. Low-dose landiolol (1.5 µg·kg(-1)·min(-1)) significantly reduced HR by 11% without changing blood pressure (BP) and CI, whereas higher doses (≥3.0 µg·kg(-1)·min(-1)) tended to decrease BP and CI while increasing PCWP and systemic vascular resistance. After treatment with landiolol (1.5 µg·kg(-1)·min(-1)), hemodynamic parameters such as PCWP, stroke volume index, SvO(2), rate pressure product, filling time/RR, E/e', and Tei index were significantly improved. A low-dose β-blocker in combination with milrinone improved cardiac function in ADHF patients with tachycardia; therefore, it may be considered as an adjunct therapy for use when standard therapy with milrinone is not effective at slowing HR.

Bisoprolol for congestive heart failure

DEFF Research Database (Denmark)

Rosenberg, J.; Gustafsson, F.

2008-01-01

was obtained from the FDA website. Conclusion: Bisoprolol is an effective and well-tolerated first-line beta-blocker for patients with systolic heart failure. The knowledge is primarily based on study patients with moderate-to-severe heart failure from the three CIBIS trials Udgivelsesdato: 2008/2...

The S230R Integrase Substitution Associated with Viral Rebound during DTG Monotherapy Confers Low Levels INSTI Drug Resistance.

Science.gov (United States)

Pham, Hanh T; Labrie, Lydia; Wijting, Ingeborg E A; Hassounah, Said; Lok, Ka Yee; Portna, Inna; Goring, Mark; Han, Yingshan; Lungu, Cynthia; van der Ende, Marchina E; Brenner, Bluma G; Boucher, Charles A; Rijnders, Bart J A; van Kampen, Jeroen J A; Mesplède, Thibault; Wainberg, Mark A

2018-03-29

Dolutegravir (DTG) is an integrase strand-transfer inhibitor (INSTI) used for treatment of HIV-infected individuals. Due to its high genetic barrier to resistance, DTG has been clinically investigated as maintenance monotherapy to maintain viral suppression and to reduce complication and healthcare costs. Our study aims to explain the underlying mechanism related to the emergence of a S230R substitution in patients who experienced virological failure while using DTG monotherapy. We evaluated the effect of S230R substitution in regard to IN enzyme activity, viral infectivity, replicative capacity and susceptibility to different INSTIs by biochemical and cell-based assays. S230R substitution conferred 63% reduction in enzyme efficiency. The S230R virus was 1.29-fold less infectious than wildtype (WT), but could replicate in PM1 cells without significant delay. Resistance levels against DTG, CAB, RAL and EVG in tissue culture were 3.85-, 3.72-, 1.52-, and 1.21-fold, respectively. Our data indicate that the S230R substitution is comparable to the previously reported R263K in some respects. Virological failure under DTG monotherapy can occur through the development of such S230R or R263K mutations without the need for high levels DTG resistance.

Differential clinical profile of candesartan compared to other angiotensin receptor blockers

Directory of Open Access Journals (Sweden)

Zimlichman R

2011-12-01

Full Text Available Relu Cernes1,2, Margarita Mashavi1,3, Reuven Zimlichman1,31The Brunner Institute for Cardiovascular Research, Wolfson Medical Center and Tel Aviv University, Tel Aviv, Israel; 2Department of Nephrology, Wolfson Medical Center, Holon, Israel; 3Department of Medicine, Wolfson Medical Center, Holon, IsraelAbstract: The advantages of blood pressure (BP control on the risks of heart failure and stroke are well established. The renin-angiotensin system plays an important role in volume homeostasis and BP regulation and is a target for several groups of antihypertensive drugs. Angiotensin II receptor blockers represent a major class of antihypertensive compounds. Candesartan cilexetil is an angiotensin II type 1 (AT[1] receptor antagonist (angiotensin receptor blocker [ARB] that inhibits the actions of angiotensin II on the renin-angiotensin-aldosterone system. Oral candesartan 8–32 mg once daily is recommended for the treatment of adult patients with hypertension. Clinical trials have demonstrated that candesartan cilexetil is an effective agent in reducing the risk of cardiovascular mortality, stroke, heart failure, arterial stiffness, renal failure, retinopathy, and migraine in different populations of adult patients including patients with coexisting type 2 diabetes, metabolic syndrome, or kidney impairment. Clinical evidence confirmed that candesartan cilexetil provides better antihypertensive efficacy than losartan and is at least as effective as telmisartan and valsartan. Candesartan cilexetil, one of the current market leaders in BP treatment, is a highly selective compound with high potency, a long duration of action, and a tolerability profile similar to placebo. The most important and recent data from clinical trials regarding candesartan cilexetil will be reviewed in this article.Keywords: angiotensin receptor blockers, candesartan, candesartan cilexetil, clinical trials, efficacy studies, safety, blood pressure

Modeling the Effects of β1-Adrenergic Receptor Blockers and Polymorphisms on Cardiac Myocyte Ca2+ Handling

Science.gov (United States)

Amanfu, Robert K.

2014-01-01

β-Adrenergic receptor blockers (β-blockers) are commonly used to treat heart failure, but the biologic mechanisms governing their efficacy are still poorly understood. The complexity of β-adrenergic signaling coupled with the influence of receptor polymorphisms makes it difficult to intuit the effect of β-blockers on cardiac physiology. While some studies indicate that β-blockers are efficacious by inhibiting β-adrenergic signaling, other studies suggest that they work by maintaining β-adrenergic responsiveness. Here, we use a systems pharmacology approach to test the hypothesis that in ventricular myocytes, these two apparently conflicting mechanisms for β-blocker efficacy can occur concurrently. We extended a computational model of the β1-adrenergic pathway and excitation-contraction coupling to include detailed receptor interactions for 19 ligands. Model predictions, validated with Ca2+ and Förster resonance energy transfer imaging of adult rat ventricular myocytes, surprisingly suggest that β-blockers can both inhibit and maintain signaling depending on the magnitude of receptor stimulation. The balance of inhibition and maintenance of β1-adrenergic signaling is predicted to depend on the specific β-blocker (with greater responsiveness for metoprolol than carvedilol) and β1-adrenergic receptor Arg389Gly polymorphisms. PMID:24867460

Ribavirin monotherapy for chronic hepatitis C

DEFF Research Database (Denmark)

Brok, J; Gluud, L L; Gluud, C

2005-01-01

Hepatitis C is a major cause of liver-related morbidity and mortality. The disease progresses without symptoms for several decades. Ribavirin monotherapy may represent a treatment for some patients.......Hepatitis C is a major cause of liver-related morbidity and mortality. The disease progresses without symptoms for several decades. Ribavirin monotherapy may represent a treatment for some patients....

Ribavirin monotherapy for chronic hepatitis C infection

DEFF Research Database (Denmark)

Brok, Jesper; Gluud, Lise L; Gluud, Christian

2006-01-01

Adding ribavirin to interferon improves treatment response for patients with chronic hepatitis C, but the effects of ribavirin monotherapy are unclear. We conducted a systematic review to assess the benefits and harms of ribavirin monotherapy for patients with chronic hepatitis C....

Derivation and validation of a simple clinical risk-model in heart failure based on 6 minute walk test performance and NT-proBNP status--do we need specificity for sex and beta-blockers?

Science.gov (United States)

Frankenstein, L; Goode, K; Ingle, L; Remppis, A; Schellberg, D; Nelles, M; Katus, H A; Clark, A L; Cleland, J G F; Zugck, C

2011-02-17

It is unclear whether risk prediction strategies in chronic heart failure (CHF) need to be specific for sex or beta-blockers. We examined this problem and developed and validated the consequent risk models based on 6-minute-walk-test and NT-proBNP. The derivation cohort comprised 636 German patients with systolic dysfunction. They were validated against 676 British patients with similar aetiology. ROC-curves for 1-year mortality identified cut-off values separately for specificity (none, sex, beta-blocker, both). Patients were grouped according to number of cut-offs met (group I/II/III - 0/1/2 cut-offs). Widest separation between groups was achieved with sex- and beta-blocker-specific cut offs. In the derivation population, 1-year mortality was 0%, 8%, 31% for group I, II and III, respectively. In the validation population, 1-year rates in the three risk groups were 2%, 7%, 14%, respectively, after application of the same cut-offs. Risk stratification for CHF should perhaps take sex and beta-blocker usage into account. We derived and independently validated relevant risk models based on 6-minute-walk-tests and NT-proBNP. Specifying sex and use of beta-blockers identified three distinct sub-groups with widely differing prognosis. In clinical practice, it may be appropriate to tailor the intensity of follow-up and/or the treatment strategy according to the risk-group. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Defining the optimal biological monotherapy in rheumatoid arthritis

DEFF Research Database (Denmark)

Tarp, Simon; Furst, Daniel E; Dossing, Anna

2017-01-01

Objectives To summarize and compare the benefits and harms of biological agents used as monotherapy for rheumatoid arthritis (RA) in order to inform decisions for patients who are intolerant to conventional DMARD therapy. Methods We searched MEDLINE, EMBASE, CENTRAL, and other sources for randomi...... treatment with biological monotherapy. However, given our limited confidence in the estimates including possibility of bias, it is appropriate to strongly weight patients׳ preferences and values in the final treatment choice.......Objectives To summarize and compare the benefits and harms of biological agents used as monotherapy for rheumatoid arthritis (RA) in order to inform decisions for patients who are intolerant to conventional DMARD therapy. Methods We searched MEDLINE, EMBASE, CENTRAL, and other sources...... for randomised trials that compared biological monotherapy with methotrexate, placebo, or other biological monotherapies. Primary outcomes were ACR50 and the number of patients who discontinued due to adverse events. Our network meta-analysis was based on mixed-effects logistic regression, including both direct...

Declining risk of sudden death in heart failure

DEFF Research Database (Denmark)

Shen, Li; Jhund, Pardeep S.; Petrie, Mark C.

2017-01-01

BACKGROUND The risk of sudden death has changed over time among patients with symptomatic heart failure and reduced ejection fraction with the sequential introduction of medications including angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, and mineralocorti......BACKGROUND The risk of sudden death has changed over time among patients with symptomatic heart failure and reduced ejection fraction with the sequential introduction of medications including angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, beta...... cardioverter-defibrillator at the time of trial enrollment were excluded. Weighted multivariable regression was used to examine trends in rates of sudden death over time. Adjusted hazard ratios for sudden death in each trial group were calculated with the use of Cox regression models. The cumulative incidence...... rates of sudden death were assessed at different time points after randomization and according to the length of time between the diagnosis of heart failure and randomization. RESULTS Sudden death was reported in 3583 patients. Such patients were older and were more often male, with an ischemic cause...

Beta-blocker therapy in patients with left ventricular systolic dysfunction and chronic obstructive lung disease in an ambulatory care setting

Directory of Open Access Journals (Sweden)

Billups SJ

2009-12-01

Full Text Available Objective: To evaluate beta blocker persistence six months after beta-blocker initiation or dose titration in heart failure (HF patients with COPD compared to those without COPD. Secondary objectives included comparison of beta-blocker dose achieved, changes in left ventricular ejection fraction (LVEF and incidence of hospitalizations or emergency department (ED visits during follow-up.Methods: We conducted a matched, retrospective, cohort study including 86 patients with COPD plus concomitant HF (LVEF ≤40% and 137 patients with HF alone. All patients were followed in an outpatient HF clinic. Eligible patients had a documented LVEF ≤40% and were initiated or titrated on a beta-blocker in the HF clinic. Patients were matched based on LVEF (categorized as ≤ 20% or 21-40%, gender, and age (> or ≤70 years. The primary outcome was beta blocker persistence at 6 months. Secondary outcomes were dose achieved, LVEF, and incidence of hospitalizations or ED visits. Results: There were no differences between the COPD and non-COPD groups in beta-blocker persistence at six-month follow-up (94.2% vs. 93.4% respectively, adjusted p=0.842. The proportion of patients who achieved a daily metoprolol dose equivalent of at least 100 mg was similar between the groups (adjusted p=0.188. The percent of patients with at least one ED visit or hospitalization in the six-month post-titration period was substantial but similar between the groups (53.5% and 48.2% for COPD and non-COPD patients, respectively, adjusted p=0.169. Conclusion: Our results support the use of beta-blockers in the population of heart failure patients with COPD and without reactive airway disease.

Nebivolol in chronic heart failure : current evidence and future perspectives

NARCIS (Netherlands)

Lipsic, Erik; van Veldhuisen, Dirk J.

Areas covered in the review: We describe the role of the sympathetic nervous system, beta-blockers and specifically nebivolol in chronic heart failure. What the reader will gain: Nebivolol is a third-generation beta-blocker, with high beta(1)/beta(2) selectivity. Moreover, it has important

Calcium channel blocker overdose

Science.gov (United States)

... this page: //medlineplus.gov/ency/article/002580.htm Calcium-channel blocker overdose To use the sharing features on this page, please enable JavaScript. Calcium-channel blockers are a type of medicine used ...

Efficacy of carvedilol in pediatric heart failure

DEFF Research Database (Denmark)

Christensen, Alex Hørby; Fatkin, Diane

2013-01-01

Evaluation of: Huang M, Zhang X, Chen S et al. The effect of carvedilol treatment on chronic heart failure in pediatric patients with dilated cardiomyopathy: a prospective, randomized-controlled study. Pediatr. Cardiol. 34, 680-685 (2013). A role for β-blockers in children with heart failure has...

Intravenous Milrinone in Treatment of Advanced Congestive Heart Failure

Science.gov (United States)

Zewail, Aly M.; Nawar, Mohammad; Vrtovec, Bojan; Eastwood, Cathy; Kar, Biswajit; Delgado, Reynolds M.

2003-01-01

Phosphodiesterase inhibitors such as milrinone can relieve symptoms and improve hemodynamics in patients with advanced congestive heart failure. We retrospectively evaluated the hemodynamic and clinical outcomes of long-term combination therapy with intravenous milrinone and oral β-blockers in 65 patients with severe congestive heart failure (New York Heart Association class IV function and ejection fraction milrinone. Oral medical therapy was maximized when possible. The mean duration of milrinone treatment in this combination-treatment group was 269 days (range, 14–1,026 days). Functional class improved from IV to II–III with milrinone therapy. Twenty-four such patients tolerated β-blocker up-titration and were successfully weaned from milrinone. Sixteen patients (31%) died while receiving combination therapy; one died of sudden cardiac death (on treatment day 116); the other 15 died of progressive heart failure or other complications. Hospital admissions during the previous 6 months and admissions within 6 months after milrinone initiation stayed the same. Meanwhile, the total number of hospital days decreased from 450 to 380 (a 15.6% reduction), and the mean length of stay decreased by 1.4 days (a 14.7% reduction). We conclude that 1) milrinone plus β-blocker combination therapy is an effective treatment for heart failure even with β-blocker up-titration, 2) weaning from milrinone may be possible once medications are maximized, 3) patients' functional status improves on the combination regimen, and 4) treatment-related sudden death is relatively infrequent during the combination regimen. (Tex Heart Inst J 2003;30:109–13) PMID:12809251

Designing clinical trials to assess antiepileptic drugs as monotherapy : difficulties and solutions.

Science.gov (United States)

Perucca, Emilio

2008-01-01

Designing monotherapy trials in epilepsy is fraught with many hurdles, including diagnostic and classification difficulties, sparse information regarding the natural history of the disorder, and ethical objections to the use of placebo or a suboptimal comparator in a condition where the consequences of therapeutic failure can be serious. These issues are further complicated by regulatory differences between the US and the EU.In the US, the FDA considers that evidence of efficacy requires demonstration of superiority to a comparator. Because available antiepileptic drugs possess relatively high efficacy, in most settings it is unrealistic to expect that a new treatment will be superior to a standard treatment used at optimized dosages. To circumvent this problem, trial designs have been developed whereby patients in the control group are assigned to receive a suboptimal comparator and are required to exit from the trial if seizure deterioration occurs. This allows demonstration of a between-group difference in efficacy endpoints, such as time to exit or time to first seizure. Although these trials have come under increasing criticism because of ethical concerns, extensive information is now available on the outcome of patients with chronic epilepsy randomized to suboptimal treatment in similarly designed conversion to monotherapy trials. This has allowed the construction of a dataset of historical controls against which response to a fully active treatment can be compared. A number of studies using this novel approach are now in progress.In the EU, in addition to requiring data on conversion to monotherapy in refractory patients, the European Medicines Agency stipulates that a monotherapy indication in newly diagnosed epilepsy can only be granted if a candidate drug has shown at least a similar benefit/risk balance compared with an acknowledged standard at its optimal use during an assessment period of no less than 1 year. This has led to the implementation of

Adherence to the ESC Heart Failure Treatment Guidelines in Spain: ESC Heart Failure Long-term Registry.

Science.gov (United States)

Crespo-Leiro, María G; Segovia-Cubero, Javier; González-Costello, José; Bayes-Genis, Antoni; López-Fernández, Silvia; Roig, Eulàlia; Sanz-Julve, Marisa; Fernández-Vivancos, Carla; de Mora-Martín, Manuel; García-Pinilla, José Manuel; Varela-Román, Alfonso; Almenar-Bonet, Luis; Lara-Padrón, Antonio; de la Fuente-Galán, Luis; Delgado-Jiménez, Juan

2015-09-01

To estimate the percentage of heart failure patients in Spain that received the European Society of Cardiology recommended treatments, and in those that did not, to determine the reasons why. The study included 2834 consecutive ambulatory patients with heart failure from 27 Spanish hospitals. We recorded general information, the treatment indicated, and the reasons why it was not prescribed in some cases. In patients who met the criteria to receive a certain drug, true undertreatment was defined as the percentage of patients who, without justification, did not receive the drug. In total, 92.6% of ambulatory patients with low ejection fraction received angiotensin converting enzyme inhibitors or angiotensin receptor blockers, 93.3% beta-blockers, and 74.5% mineralocorticoid receptor antagonists. The true undertreatment rates were 3.4%, 1.8%, and 19.0%, respectively. Target doses were reached in 16.2% of patients receiving angiotensin converting enzyme inhibitors, 23.3% of those with angiotensin receptor blockers, 13.2% of those prescribed beta-blockers, and 23.5% of those with mineralocorticoid receptor antagonists. Among patients who could benefit from ivabradine, 29.1% received this drug. In total, 36% of patients met the criteria for defibrillator implantation and 90% of them had received the device or were scheduled for implantation, whereas 19.6% fulfilled the criteria for resynchronization therapy and 88.0% already had or would soon have the device. In patients who met the criteria, but did not undergo device implantation, the reasons were not cost-related. When justified reasons for not administering heart failure drugs were taken into account, adherence to the guideline recommendations was excellent. Exclusive use of the percentage of treated patients is a poor indicator of the quality of healthcare in heart failure. Measures should be taken to improve the attainment of optimal dosing in each patient. Copyright © 2015 Sociedad Española de Cardiolog

The Sacubitril/Valsartan, a First-in-Class, Angiotensin Receptor Neprilysin Inhibitor (ARNI): Potential Uses in Hypertension, Heart Failure, and Beyond.

Science.gov (United States)

Kario, Kazuomi

2018-01-27

Sacubitril/valsartan (LCZ696) is a first-in-class, novel-acting, angiotensin receptor neprilysin inhibitor (ARNI) that provides inhibition of neprilysin and the angiotensin (AT 1 ) receptor. A recent clinical trial PRARDIGM-HF demonstrated that this drug is superior to angiotensin-converting enzyme (ACE) inhibitors for improving the prognosis in the patients with heart failure, and this has resulted in the drug being included in clinical practice guidelines for the management of heart failure with reduced ejection fraction (EF). In addition, sacubitril/valsartan has been developed for the management of hypertension, because it has unique anti-aging properties. However, the clinical evidence of mechanism has not been well validated. A recent mechanistic study PARAMETER demonstrated that sacubitril/valsartan (LCZ696) is superior to angiotensin receptor blocker (ARB) monotherapy for reducing central aortic systolic pressure (primary endpoint) as well as for central aortic pulse pressure (secondary endpoint) and nocturnal BP preferentially. Considering these results, sacubitril/valsartan may be an attractive therapeutic agent to treat the elderly with age-related hypertension phenotypes, such as drug-uncontrolled (resistant) hypertension characterized as systolic (central) hypertension (structural hypertension) and/or nocturnal hypertension (salt-sensitive hypertension). These are the high-risk hypertension phenotypes which are prone to develop heart failure with preserved EF and chronic kidney disease. Sacubitril/valsartan may be effective to suppress the age-related continuum from hypertension to heart failure, and it could be clinically useful not only for secondary prevention, but also as primary prevention of heart failure in uncontrolled elderly hypertensive patients.

Comparison of patient-reported acute urinary and sexual toxicity scores in a 6- versus 2-fraction course of high-dose-rate prostate brachytherapy monotherapy

International Nuclear Information System (INIS)

Ragab, Omar; Park, Sang-June; Zhang, Mingle; Wang, Jason; Velez, Maria; Demanes, David J.; Banerjee, Robyn; Patel, Shyamal; Kamrave, Mitchell

2018-01-01

To identify differences in acute urinary and sexual toxicity between a 6-fraction and 2-fraction high-dose-rate brachytherapy monotherapy regimen and correlate dosimetric constraints to short-term toxicity. A single institution retrospective study of 116 men with prostate cancer treated with HDR monotherapy from 2010 to 2015 was conducted. Eighty-one men had 7.25 Gy × 6-fractions and 35 men had 13.5 Gy × 2-fractions. Patients had two CT-planned implants spaced 1–2 weeks apart. Patient baseline characteristics, International Prostate Symptom Scores (IPSS) and Sexual Health Inventory for Men (SHIM) scores were collected pre-treatment and 3, 6 and 12 months post-implantation. Mixed effect modelling was undertaken to compare baseline, 1–6 month and 7–12 month scores between groups. Poisson regression analysis was performed to correlate dosimetric constraints with acute toxicity. There was no difference between baseline and post-implantation IPSS scores between 6-fraction and 2-fraction groups. SHIM scores for men treated with 6-fractions had a steeper decline at 1–6 months, but resolved at 7–12 months. Pre-treatment alpha-blocker use correlated with worse short-term acute urinary toxicity. Worsened SHIM score correlated with increasing age, diabetes mellitus and androgen-deprivation therapy. In a dosimetric analysis of outcomes, prostate V150 dose and bladder wall (D01.cc, D1cc, D2cc) dose correlated with increased IPSS score. No increased acute genitourinary or sexual dysfunction has been observed in men when transitioning from 6-fraction to 2-fraction HDR monotherapy. A dosimetric correlation was found between the V150 and bladder wall doses for acute urinary toxicity. Future research should continue to standardize and validate dose constraints for prostate HDR monotherapy patients.

Platelet Arachidonic Acid Deficiency May Contribute to Abnormal Platelet Function During Parenteral Fish Oil Monotherapy in a Piglet Model.

Science.gov (United States)

Turner, Justine M; Field, Catherine J; Goruk, Sue; Wizzard, Pamela; Dicken, Bryan J; Bruce, Aisha; Wales, Paul W

2016-05-01

Fish oil monotherapy has been an advance for treating intestinal failure-associated liver disease (IFALD). However, such patients are at risk of bleeding complications from liver disease and because fish oil can inhibit thrombosis. We have previously reported abnormal platelet function in neonatal piglets given fish oil monotherapy during parenteral nutrition (PN). The purpose of this study was to determine if abnormal fatty acid composition of the platelets could explain the prior observed antiplatelet effect. Neonatal piglets were assigned to 2 treatments: PN with fish oil monotherapy (FO; n = 4) or PN with soy oil (SO; n = 5). On day 14, plasma was collected and platelets isolated by centrifuging. The fatty acid content in plasma and platelet plug were measured using gas liquid chromatography and compared with controls (CON; n = 5). The arachidonic acid (AA) content in the FO group was on average half that of the SO group, in both the platelets (FO, 3.5% vs SO, 7.6%; P = .021; CON, 4.5%-11%) and the plasma (FO, 3.8% vs SO, 9.2%; P = .002; CON, 6.1%-9.5%). No bleeding complications were observed for any piglets during PN treatment. Using platelet mapping, we have previously shown that neonatal piglets given fish oil monotherapy have abnormal platelet function in the AA pathway. This report demonstrates that such an abnormality can be explained by platelet AA deficiency. Platelet mapping and platelet fatty acid analysis should be undertaken in human infants treated with fish oil monotherapy during PN. © 2015 American Society for Parenteral and Enteral Nutrition.

α-blockers, antibiotics and anti-inflammatories have a role in the management of chronic prostatitis/chronic pelvic pain syndrome.

Science.gov (United States)

Thakkinstian, Ammarin; Attia, John; Anothaisintawee, Thunyarat; Nickel, J Curtis

2012-10-01

antibiotics (risk ratio 1.2, 95% CI 0.7-1.9; P= 0.527). α-blockers, antibiotics and/or anti-inflammatory/immune modulation therapy appear to be beneficial for some patients with CP/CPPS. • The magnitude of effect and the disconnect between mean CPSI decrease and response rates compared with placebo suggest that directed multimodal therapy, rather than mono-therapy, with these agents should be considered for optimal management of CP/CPPS. © 2012 BJU INTERNATIONAL.

Feasibility and early outcome of high-dose-rate Ir-192 brachytherapy as monotherapy in two fractions within 1 day for high-/very high-risk prostate cancer.

Science.gov (United States)

Ashida, Shingo; Yamasaki, Ichiro; Tamura, Kenji; Shimamoto, Tsutomu; Inoue, Keiji; Kariya, Shinji; Kobayashi, Kana; Yamagami, Takuji; Shuin, Taro

2016-05-01

The aim of the present study was to evaluate the feasibility and preliminary outcomes of high-dose-rate (HDR)-brachytherapy as a monotherapy in two fractions within 1 day for localized prostate cancer, including high-/very high-risk cases. Among the 68 patients treated with HDR monotherapy between July 2011 and December 2014, 65 had a minimal follow-up of 12 months without adjuvant androgen deprivation therapy and were enrolled in the present study [42/65 (64.6%) exhibited high-/very high-risk diseases]. HDR monotherapy was performed in two fractions with a minimal interval of 6 h and the prescribed dose was 13.5 Gy (×2). Adverse events (AEs) were assessed using Common Terminology Criteria for Adverse Events (version 4; http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40), and biochemical failure was assessed by the Phoenix definition. The median follow-up time was 30.1 months. The majority of patients had Grade 0-1 acute AEs. Four patients (6.2%) exhibited urinary retention, requiring a Foley catheter. Grade 3 acute AEs occurred at a frequency of 3.1% and hematuria at 1.5%. The majority of patients also exhibited Grade 0-1 chronic AEs. Grade 3 chronic AEs occurred at a frequency of 1.5% and urethral stricture at 1.5%, for which endoscopic treatment was indicated. Acute and chronic gastrointestinal AEs were uncommon, and no Grade 3 or above AEs developed. Biochemical failure occurred in 4 patients who all exhibited high-/very high-risk diseases. Kaplan-Meier estimated that 3 year biochemical failure-free survival was 91.6% overall and 88.0% in high-/very high-risk cases. The present two-fraction 1 day HDR monotherapy is feasible with minimal AEs and achieved acceptable biochemical control of localized prostate cancer, including high-/very high-risk cases, although long-term follow-up is required.

Perioperative beta-blockers for preventing surgery-related mortality and morbidity.

Science.gov (United States)

Blessberger, Hermann; Kammler, Juergen; Domanovits, Hans; Schlager, Oliver; Wildner, Brigitte; Azar, Danyel; Schillinger, Martin; Wiesbauer, Franz; Steinwender, Clemens

2018-03-13

), whereas in the remaining trials, some form of bias was present or could not be definitively excluded (studies with overall unclear or high risk of bias). Outcomes were evaluated separately for cardiac and non-cardiac surgery.CARDIAC SURGERY (53 trials)We found no clear evidence of an effect of beta-blockers on the following outcomes.• All-cause mortality: RR 0.73, 95% CI 0.35 to 1.52, 3783 participants, moderate quality evidence.• Acute myocardial infarction (AMI): RR 1.04, 95% CI 0.71 to 1.51, 3553 participants, moderate quality evidence.• Myocardial ischaemia: RR 0.51, 95% CI 0.25 to 1.05, 166 participants, low quality evidence.• Cerebrovascular events: RR 1.52, 95% CI 0.58 to 4.02, 1400 participants, low quality evidence.• Hypotension: RR 1.54, 95% CI 0.67 to 3.51, 558 participants, low quality evidence.• Bradycardia: RR 1.61, 95% CI 0.97 to 2.66, 660 participants, low quality evidence.• Congestive heart failure: RR 0.22, 95% CI 0.04 to 1.34, 311 participants, low quality evidence.Beta-blockers significantly reduced the occurrence of the following endpoints.• Ventricular arrhythmias: RR 0.37, 95% CI 0.24 to 0.58, number needed to treat for an additional beneficial outcome (NNTB) 29, 2292 participants, moderate quality evidence.• Supraventricular arrhythmias: RR 0.44, 95% CI 0.36 to 0.53, NNTB five, 6420 participants, high quality evidence.• On average, beta-blockers reduced length of hospital stay by 0.54 days (95% CI -0.90 to -0.19, 2450 participants, low quality evidence).NON-CARDIAC SURGERY (35 trials)Beta-blockers significantly increased the occurrence of the following adverse events.• All-cause mortality: RR 1.25, 95% CI 1.00 to 1.57, 11,413 participants, low quality of evidence, number needed to treat for an additional harmful outcome (NNTH) 167.• Hypotension: RR 1.50, 95% CI 1.38 to 1.64, NNTH 16, 10,947 participants, high quality evidence.• Bradycardia: RR 2.23, 95% CI 1.48 to 3.36, NNTH 21, 11,033 participants, moderate quality

Detecting Anti Ad-blockers in the Wild

Directory of Open Access Journals (Sweden)

Mughees Muhammad Haris

2017-07-01

Full Text Available The rise of ad-blockers is viewed as an economic threat by online publishers who primarily rely on online advertising to monetize their services. To address this threat, publishers have started to retaliate by employing anti ad-blockers, which scout for ad-block users and react to them by pushing users to whitelist the website or disable ad-blockers altogether. The clash between ad-blockers and anti ad-blockers has resulted in a new arms race on the Web. In this paper, we present an automated machine learning based approach to identify anti ad-blockers that detect and react to ad-block users. The approach is promising with precision of 94.8% and recall of 93.1%. Our automated approach allows us to conduct a large-scale measurement study of anti ad-blockers on Alexa top-100K websites. We identify 686 websites that make visible changes to their page content in response to ad-block detection. We characterize the spectrum of different strategies used by anti ad-blockers. We find that a majority of publishers use fairly simple first-party anti ad-block scripts. However, we also note the use of third-party anti ad-block services that use more sophisticated tactics to detect and respond to ad-blockers.

Quetiapine monotherapy for bipolar depression

Directory of Open Access Journals (Sweden)

Michael E Thase

2008-03-01

Full Text Available Michael E ThaseDepartments of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; the Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA; and the University of Pittsburgh Medical Center, Pittsburgh, PA, USAAbstract: Bipolar depression is more common, disabling, and difficult-to-treat than the manic and hypomanic phases that define bipolar disorder. Unlike the treatment of so-called “unipolar” depressions, antidepressants generally are not indicated as monotherapies for bipolar depressions and recent studies suggest that - even when used in combination with traditional mood stabilizers – antidepressants may have questionable value for bipolar depression. The current practice is that mood stabilizers are initiated first as monotherapies; however, the antidepressant efficacy of lithium and valproate is modest at best. Within this context the role of atypical antipsychotics is being evaluated. The combination of olanzapine and the antidepressant fluoxetine was the first treatment to receive regulatory approval in the US specifically for bipolar I depression. Quetiapine was the second medication to be approved for this indication, largely as the result of two pivotal trials known by the acronyms of BOLDER (BipOLar DEpRession I and II. Both studies demonstrated that two doses of quetiapine (300 mg and 600 mg given once daily at bedtime were significantly more effective than placebo, with no increased risk of patients switching into mania. Pooling the two studies, quetiapine was effective for both bipolar I and bipolar II depressions and for patients with (and without a history of rapid cycling. The two doses were comparably effective in both studies. Although the efficacy of quetiapine monotherapy has been established, much additional research is necessary. Further studies are needed to more fully investigate dose-response relationships and comparing quetiapine monotherapy to other mood stabilizers

Consensus statement on management of chronic heart failure in India

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Sandeep Seth

2015-01-01

Full Text Available Summary of the Consensus Statement: This statement has been prepared keeping Indian heart failure patients in mind. Optimal management of CHF improves quality of life, reduces hospitalization rates and prolongs survival for people with this condition. Echocardiography is the single most useful test in the evaluation of heart failure, and is necessary to confirm the diagnosis. Plasma B-natriuretic peptide (BNP measurements may be useful in excluding CHF but not mandatory in India. Educate people with CHF about lifestyle changes (e.g., increase physical activity levels, reduce salt intake and manage weight. Educate people with CHF about CHF symptoms and how to manage fluid load. Avoid prescribing drugs that exacerbate CHF. Prescribe angiotensin-converting enzyme inhibitors (ACEI at effective doses for people with all grades of systolic heart failure, and titrate to the highest recommended dose tolerated. Angiotensin II receptor antagonists (ARA may be used as alternatives in people who cannot tolerate ACEIs. Mineralocorticoid receptor antagonists (MRAs should also be used. For people with stabilised systolic heart failure, prescribe beta-blockers that have been shown to improve outcome in heart failure (e.g., bisoprolol, carvedilol, extended release metoprolol or nebivolol. Titrate to the highest recommended dose tolerated. Prescribe diuretics, digoxin and nitrates for people already using ACEIs and beta-blockers to manage symptoms as indicated. For people who have systolic heart failure (New York Heart Association (NYHA Class II-IV despite appropriate doses of ACEIs and diuretics, consider prescribing spironolactone. Eplerenone can be considered in certain setting especially post myocardial infarction though it is more expensive. Consider direct sinus node inhibition with ivabradine for people with CHF who have impaired systolic function, have had a recent heart failure hospitalisation and are in sinus rhythm with a heart rate >70 bpm despite

Lamivudine monotherapy in children and adolescents: The devil is ...

African Journals Online (AJOL)

We also propose guidance for using lamivudine monotherapy, suggesting clinical and immunological criteria for its use. Close monitoring and adherence support are required with this approach. Given many new emerging ART drugs and strategies, lamivudine monotherapy should be administered temporarily, while efforts ...

S-1 monotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck after progression on platinum-based chemotherapy

International Nuclear Information System (INIS)

Yokota, Tomoya; Onozawa, Yusuke; Boku, Narikazu

2011-01-01

Platinum compounds play pivotal roles in treatment for squamous cell carcinoma of the head and neck. The objective was to evaluate the efficacy of S-1 monotherapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after failure of platinum-based chemotherapy. We retrospectively analyzed 39 consecutive patients with recurrent or metastatic squamous cell carcinoma of the head and neck who received S-1 monotherapy after failure of platinum-based chemotherapy or chemoradiotherapy at the Shizuoka Cancer Center between August 2003 and October 2010. S-1 was given orally twice daily (80 mg/m 2 /day) for 28 days followed by a 14-day rest. The median follow-up period in survivors was 31.5 months. Among 38 patients with measurable lesions, 9 (24%) showed partial response and 15 (39%) showed stable disease. The median progression-free survival was 4.9 months and the median overall survival was 13.2 months. The median progression-free survival for oropharyngeal cancer (n=7) was significantly longer than for other cancers (n=32) (14.9 vs. 4.7 months, P=0.035). The response rate in patients with a recurrence-free interval since the last platinum administration >6.0 months was significantly better than with a recurrence-free interval 6.0 months also showed a significantly better progression-free survival (6.0 vs. 2.6 months, P=0.045). The frequency of Grade 3/4 toxicities was less than 10%. S-1 monotherapy shows promising signs of efficacy and tolerability in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after failure of platinum-based chemotherapy in this retrospective cohort and warrants further investigation in this population. (author)

Patterns and predictors of evidence-based medication continuation among hospitalized heart failure patients (from Get With the Guidelines-Heart Failure).

Science.gov (United States)

Krantz, Mori J; Ambardekar, Amrut V; Kaltenbach, Lisa; Hernandez, Adrian F; Heidenreich, Paul A; Fonarow, Gregg C

2011-06-15

Hospitalized patients with heart failure and decreased ejection fraction are at substantial risk for mortality and rehospitalization, yet no acute therapies are proven to decrease this risk. Therefore, in-hospital use of medications proved to decrease long-term mortality is a critical strategy to improve outcomes. Although endorsed in guidelines, predictors of initiation and continuation of angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs), β blockers, and aldosterone antagonists have not been well studied. We assessed noncontraindicated use patterns for the 3 medications using the Get With the Guidelines-Heart Failure (GWTG-HF) registry from February 2009 through March 2010. Medication continuation was defined as treatment on admission and discharge. Multivariable logistic regression using generalized estimating equations was used to determine factors associated with discharge use. In total 9,474 patients were enrolled during the study period. Of those treated before hospitalization, overall continuation rates were 88.5% for ACE inhibitors/ARBs, 91.6% for β blockers, and 71.9% for aldosterone-antagonists. Of patients untreated before admission, 87.4% had ACE inhibitors/ARBs and 90.1% had β blocker initiated during hospitalization or at discharge, whereas only 25.2% were started on an aldosterone antagonist. In multivariate analysis, admission therapy was most strongly associated with discharge use (adjusted odds ratios 7.4, 6.0, and 20.9 for ACE inhibitors/ARBs, β blockers, and aldosterone antagonists, respectively). Western region, younger age, and academic affiliation were also associated with higher discharge use. Although ACE inhibitor/ARB and β-blocker continuation rates were high, aldosterone antagonist use was lower despite potential eligibility. In conclusion, being admitted on evidence-based medications is the most powerful, independent predictor of discharge use. Copyright © 2011 Elsevier Inc. All rights reserved.

Shifting brachytherapy monotherapy case mix toward intermediate-risk prostate cancer.

Science.gov (United States)

Muralidhar, Vinayak; Mahal, Brandon A; Ziehr, David R; Chen, Yu-Wei; Nezolosky, Michelle D; Viswanathan, Vidya B; Beard, Clair J; Devlin, Phillip M; Martin, Neil E; Orio, Peter F; Nguyen, Paul L

2015-01-01

The relative use of brachytherapy (BT) for prostate cancer has declined in recent years. In this setting, we sought to determine whether the case mix of BT monotherapy-treated men has changed over time in terms of risk group composition. The Surveillance, Epidemiology, and End Results database was used to identify 30,939 patients diagnosed with prostate adenocarcinoma between 2004 and 2011 who received BT monotherapy. The case mix of BT monotherapy patients was calculated by patient risk group and year of diagnosis. Between 2004 and 2011, the use of BT monotherapy declined overall. The relative percentage of men undergoing BT with low-risk disease declined by 4.5%, whereas the relative percentage of patients with intermediate-risk disease increased by 4.7%. Non-white patients and those from poorer counties did not show shifts in the risk group makeup of BT monotherapy patients, whereas white patients and those from wealthier counties did. Although fewer patients with prostate cancer are undergoing BT monotherapy, men with intermediate-risk disease comprised a significantly larger portion of the BT case mix in 2011 compared with 2004. Future research efforts by brachytherapists should be directed toward improving BT technique, optimizing radiation doses, and obtaining long-term followup data for patients with intermediate-risk prostate cancer. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Misperceptions About β-Blockers and Diuretics

Science.gov (United States)

Ubel, Peter A; Jepson, Christopher; Asch, David A

2003-01-01

BACKGROUND Based on a series of clinical trials showing no difference in the effectiveness or tolerability of most major classes of antihypertensive medications, the Joint National Commission on High Blood Pressure Treatment recommends that physicians prescribe β-blockers or diuretics as initial hypertensive therapy unless there are compelling indications for another type of medication. Nevertheless, many physicians continue to favor more expensive medications like angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers as first line agents. The persistent use of these agents raises questions as to whether physicians perceive ACE inhibitors and calcium channel blockers to be better than β-blockers and diuretics. METHODS We surveyed 1,200 primary care physicians in 1997, and another 500 primary care physicians in 2000, and asked them to estimate the relative effectiveness and side effects of 4 classes of medication in treating a hypothetical patient with uncomplicated hypertension: ACE inhibitors, β-blockers, calcium channel blockers, and diuretics. In addition, we asked them to indicate whether they ever provided free samples of hypertension medications to their patients. RESULTS Perceptions of the relative effectiveness and side effects of the 4 classes of hypertension medications did not significantly change over the 3 years, nor did prescription recommendations. Physicians perceive that diuretics are less effective at lowering blood pressure than the other 3 classes (P diuretics were less effective and β-blockers were less tolerated than other medications. Moreover, their prescription practices were associated with their provision of free samples provided by pharmaceutical representatives, even after adjusting for other demographic characteristics. Efforts to increase physicians' prescribing of β-blockers and diuretics may need to be directed at overcoming misunderstandings about the effectiveness and tolerability of these medicines

Adverse CNS-effects of beta-adrenoceptor blockers.

Science.gov (United States)

Gleiter, C H; Deckert, J

1996-11-01

In 1962 propranolol, the first beta adrenoceptor antagonist (beta blocker), was brought on to the market. There is now a host of different beta blockers available, and these compounds are among the most commonly prescribed groups of drugs. The efficacy of beta blockers has been proven predominantly for the treatment of cardiovascular diseases. Beta blockers are also used for certain types of CNS disorders, such as anxiety disorders, essential tremor and migraine. While low toxicity means that they have a favorable risk-benefit ratio, given the high intensity of use, it is essential to have a comprehensive knowledge of adverse events. Adverse events of beta blockers that can be related to the CNS are quite often neglected, even in textbooks of clinical pharmacology or review articles, and thus often misdiagnosed. The following article, therefore, after summarizing the use of beta blockers for CNS indications, critically reviews the literature on centrally mediated adverse events. General pharmacological features of beta blockers and their molecular basis of action will briefly be addressed to the extent that they are or may become relevant for central nervous pharmacotherapy and side-effects.

NI-60RECURRENT PATTERNS OF BEVACIZUMAB MONOTHERAPY FOR RECURRENT PRIMARY GLIOBLASTOMA AND PERSPECTIVES ON BEVACIZUMAB-BASED THERAPIES

Science.gov (United States)

Nagane, Motoo; Kobayashi, Keiichi; Saito, Kuniaki; Shiokawa, Yoshiaki

2014-01-01

BACKGROUND. Prognosis of patients with recurrent glioblastoma (GBM) remains dismal, their median overall survival (mOS) ranging from 7 to 10 months. Currently, bevacizumab (BEV), a monoclonal antibody against VEGF, has been widely used since it prolonged progression-free survival (PFS) accompanied with symptom relief in BEV trials. However, improvement of OS seems modest at most, and issues regarding short survival after BEV failure, invasive relapse, and difficulty in determining true progression remain unsolved. Here we examined the patterns of radiological BEV failure in relationship with survival of several post-treatment periods. METHODS. Twenty-five patients with primary GBM who were treated with BEV monotherapy at recurrence in Kyorin University hospital since August 2009 were included in this study. Mean age was 53 yo, 13 males/12 females, median KPS was 60 (30-100), and mOS from the initial surgery was 23.2 months. MRI patterns at BEV progression were determined using modified classification by Nowosielsky et al. (Neurology 2014) as follows: 1) T2-diffuse, 2) cT1-flare up, 3) Primary non-responders, 4) T2-circumscribed, and 5) Remote metastasis. RESULTS. mPFS and mOS of BEV monotherapy were 3.4 and 7.6 months, respectively, and post-BEV mOS was 4.7 months. Frequency and BEV-PFS/post-BEV OS were 1) 20%, 3.8/0.8 months; 2) 40%, 3.4/7.1 months, 3) 24%, 0.9/3.3 months, 4) 8%, 3.7/3.9 months, 5) 8%, 2.0/4.2 months. The cT1-flare up recurrent pattern was found most frequently with relatively better survivals, whereas the T2-diffuse recurrence included fatal brain stem invasion in two cases, resulting in poorer prognosis. CONCLUSIONS. BEV monotherapy showed limited survival benefit and the clinical course after BEV failure may differ by patterns of relapse. Although RANO criteria have been a standard method to determine progression, measurement of T2/FLAIR hyperintensity remains critically controversial. Efforts to improve BEV-based therapy for recurrent GBM

Topical beta-blockers and mortality

NARCIS (Netherlands)

Müskens, Rogier P. H. M.; Wolfs, Roger C. W.; Witteman, Jacqueline C. M.; Hofman, Albert; de Jong, Paulus T. V. M.; Stricker, Bruno H. C.; Jansonius, Nomdo M.

2008-01-01

To study the associations between long-term and short-term use of topical beta-blockers and mortality. Prospective population-based cohort study. To examine long-term effects, 3842 participants aged 55 years and older were recruited. To examine short-term effects, 484 incident beta-blocker users and

Efficacy and Safety of Metronidazole Monotherapy versus Vancomycin Monotherapy or Combination Therapy in Patients with Clostridium difficile Infection: A Systematic Review and Meta-Analysis.

Directory of Open Access Journals (Sweden)

Rui Li

Full Text Available Clostridium difficile infection (CDI has become a global epidemiological problem for both hospitalized patients and outpatients. The most commonly used drugs to treat CDI are metronidazole and vancomycin. The aim of this study was to compare the efficacy and safety of metronidazole monotherapy with vancomycin monotherapy and combination therapy in CDI patients.A comprehensive search without publication status or other restrictions was conducted. Studies comparing metronidazole monotherapy with vancomycin monotherapy or combination therapy in patients with CDI were considered eligible. Meta-analysis was performed using the Mantel-Haenszel fixed-effects model, and odds ratios (ORs with 95% confidence intervals (95% CIs were calculated and reported.Of the 1910 records identified, seventeen studies from thirteen articles (n = 2501 patients were included. No statistically significant difference in the rate of clinical cure was found between metronidazole and vancomycin for mild CDI (OR = 0.67, 95% CI (0.45, 1.00, p = 0.05 or between either monotherapy and combination therapy for CDI (OR = 1.07, 95% CI (0.58, 1.96, p = 0.83; however, the rate of clinical cure was lower for metronidazole than for vancomycin for severe CDI (OR = 0.46, 95% CI (0.26, 0.80, p = 0.006. No statistically significant difference in the rate of CDI recurrence was found between metronidazole and vancomycin for mild CDI (OR = 0.99, 95% CI (0.40, 2.45, p = 0.98 or severe CDI (OR = 0.98, 95% CI (0.63, 1.53, p = 0.94 or between either monotherapy and combination therapy for CDI (OR = 0.91, 95% CI (0.66, 1.26, p = 0.56. In addition, there was no significant difference in the rate of adverse events (AEs between metronidazole and vancomycin (OR = 1.18, 95% CI (0.80, 1.74, p = 0.41. In contrast, the rate of AEs was significantly lower for either monotherapy than for combination therapy (OR = 0.30, 95% CI (0.17, 0.51, p < 0.0001.Metronidazole and vancomycin are equally effective for the

Blood pressure effects of high-dose amlodipine-benazepril combination in Black and White hypertensive patients not controlled on monotherapy.

Science.gov (United States)

Chrysant, Steven G

2012-06-01

Black hypertensive patients are more resistant to angiotensin-converting enzyme (ACE) inhibitor monotherapy than White patients. This resistance can be overcome with the combination of ACE inhibitors with diuretics or calcium-channel blockers (CCBs). The objective of this clinical investigation was to evaluate the antihypertensive effectiveness of monotherapy with the ACE inhibitor benazepril or the CCB amlodipine and their combination in Black and White hypertensive patients in two separate studies. This was a post hoc analysis of data from two separate studies, pooled because of their similarities, to increase the sample size. Outpatient Black and White hypertensive patients were selected for these studies. In study H2303, 201 patients of both sexes and races, whose mean seated diastolic blood pressure (MSDBP) was ≥95 mmHg after 4 weeks of single-blind treatment with benazepril 40 mg/day, were randomized into two groups. Group 1 received benazepril 40 mg/day and group 2 received amlodipine/benazepril 5/40 mg/day, which was uptitrated to amlodipine/benazepril 10/40 mg/day at week 4 of the study. In study H2304, 812 similar patients, whose MSDBP was ≥95 mmHg after 4 weeks of single-blind treatment with amlodipine 10 mg/day, were randomized into three groups. Group 1 received amlodipine/benazepril 10/20 mg/day, uptitrated to amlodipine/benazepril 10/40 mg/day after 2 weeks. Group 2 received amlodipine/benazepril 10/20 mg/day. Group 3 received amlodipine 10 mg/day. All three groups were followed up for 6 additional weeks. This report presents the results of post hoc analysis of pooled data from two separate but similar studies. Combination therapy resulted in greater lowering of MSDBP and mean seated systolic blood pressure (MSSBP) than monotherapy with either benazepril or amlodipine (p benazepril 10/20 mg/day resulted in greater blood pressure (BP) reductions in White patients than in Black patients (p benazepril 10/40�

Weight gain in children on oxcarbazepine monotherapy.

Science.gov (United States)

Garoufi, Anastasia; Vartzelis, George; Tsentidis, Charalambos; Attilakos, Achilleas; Koemtzidou, Evangelia; Kossiva, Lydia; Katsarou, Eustathia; Soldatou, Alexandra

2016-05-01

Studies of the effect of oxcarbazepine (OXC) on body growth of children with epilepsy are rare and their results are controversial. To the contrary, many studies have shown significant weight gain following valproate (VPA) treatment. To prospectively evaluate the effect of OXC monotherapy on growth patterns of children with epilepsy and compare it with the effect of VPA monotherapy. Fifty-nine otherwise healthy children, aged 3.7-15.9 years, with primary generalized, partial or partial with secondary generalization seizure disorder, were included in the study. Twenty six children were placed on OXC and thirty three on VPA monotherapy. Body weight (BW), height and body mass index (BMI) as well as their standard deviation scores (SDS), were evaluated prior to as well as 8 months post initiation of OXC or VPA therapy. Eight months post OXC-treatment, BW, SDS-BW, BMI and SDS-BMI increased significantly. The increase was similar to that observed in the VPA group. An additional 15.4% of children in the OXC group and 21.2% in the VPA group became overweight or obese. The effect of both OXC and VPA therapy on linear growth did not reach statistical significance. Similarly to VPA, OXC monotherapy resulted in a significant weight gain in children with epilepsy. Careful monitoring for excess weight gain along with counseling on adapting a healthy lifestyle should be offered to children on OXC therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Beta Blockers

Science.gov (United States)

... may not work as effectively for people of African heritage and older people, especially when taken without ... conditions/high-blood-pressure/in-depth/beta-blockers/ART-20044522 . Mayo Clinic Footer Legal Conditions and Terms ...

Effectiveness of maintenance therapy of lithium vs other mood stabilizers in monotherapy and in combinations

DEFF Research Database (Denmark)

Kessing, Lars Vedel; Bauer, Michael; Nolen, Willem A.

2018-01-01

Objectives: For the first time to present a systematic review of observational studies on the efficiency of lithium monotherapy in comparison with other maintenance mood stabilizers in monotherapy and in combination. Methods: As part of the International Society for Bipolar Disorders (ISBD) Task...... Force on Lithium Treatment, we undertook a systematic literature search of non-randomized controlled observational studies on (i) lithium monotherapy vs treatment with another maintenance mood stabilizer in monotherapy and (ii) lithium in combination with other mood stabilizers vs monotherapy. Results......: In eight out of nine identified studies including a total of lithium monotherapy was associated with improved outcome compared with another mood stabilizer in monotherapy, including valproate, lamotrigine, olanzapine, quetiapine, unspecified anticonvulsants, carbamazepine...

Treatment with non-selective beta blockers is associated with reduced severity of systemic inflammation and improved survival of patients with acute-on-chronic liver failure

DEFF Research Database (Denmark)

Mookerjee, Rajeshwar P; Pavesi, Marco; Thomsen, Karen Louise

2016-01-01

BACKGROUND & AIMS: Non-selective beta blockers (NSBBs) have been shown to have deleterious outcomes in patients with refractory ascites, alcoholic hepatitis and spontaneous bacterial peritonitis leading many physicians to stop the drug in these cases. Acute-on-chronic liver failure (ACLF......) is characterized by systemic inflammation and high mortality. As NSBBs may have beneficial effects on gut motility and permeability and, systemic inflammation, the aims of this prospective, observational study were to determine whether ongoing use of NSBBs reduced 28-day mortality in ACLF patients. METHODS...... at enrollment significantly associated with treatment and mortality were taken into account as potential confounders to adjust for treatment effect. A logistic regression model was fitted. RESULTS: 164 (47%) ACLF patients received NSBBs whereas 185 patients did not. Although the CLIF-C ACLF scores were similar...

Model tests of a once-through steam generator for land-blocker assessment and THEDA code verification. Final report

International Nuclear Information System (INIS)

Carter, H.R.; Childerson, M.T.; Moskal, T.E.

1983-06-01

The Babcock and Wilcox Company (B and W) operating Once-Through Steam Generators (OTSGs) have experienced leaking tubes in a region adjacent to the untubed inspection lane. The tube leaks have been attributed to an environmentally-assisted fatigue mechanism with moisture transported up the inspection lane being a major factor in the tube-failure process. B and W has developed a hardware modification (lane blockers) to mitigate the detrimental effects of inspection lane moisture. A 30-tube Laboratory Once-through Steam Generator (Designated OTSGC) was designed, fabricated, and tested. Tests were performed with and without five flat-plate lane blockers installed on tube-support plates (TSPs) 10, 11, 12, 13, and 14. The test results were utilized to determine the effectiveness of lane blockers for eliminating moisture transport to the upper tubesheet in the inspection lanes and to benchmark the predictive capabilities of a three-dimensional steam-generator computer code, THEDA

Patient's adherence on pharmacological therapy for benign prostatic hyperplasia (BPH)-associated lower urinary tract symptoms (LUTS) is different: is combination therapy better than monotherapy?

Science.gov (United States)

Cindolo, Luca; Pirozzi, Luisella; Sountoulides, Petros; Fanizza, Caterina; Romero, Marilena; Castellan, Pietro; Antonelli, Alessandro; Simeone, Claudio; Tubaro, Andrea; de Nunzio, Cosimo; Schips, Luigi

2015-09-21

Recent studies showed that the non-adherence to the pharmacological therapy of patients affected by BPH-associated LUTS increased the risk of clinical progression of BPH. We examined the patients adherence to pharmacological therapy and its clinical consequences in men with BPH-associated LUTS looking at the differences between drug classes comparing mono vs combination therapy. A retrospective, population-based cohort study, using prescription administrative database and hospital discharge codes from a total of 1.5 million Italian men. Patients ≥ 40 years, administered alpha-blockers (AB) and 5alpha-reductase inhibitors (5ARIs), alone or in combination (CT), for BPH-associated LUTS were analyzed. The 1-year and long term adherence together with the analyses of hospitalization rates for BPH and BPH-related surgery were examined using multivariable Cox proportional hazards regression model and Pearson chi square test. Patients exposed to at least 6 months of therapy had a 1-year overall adherence of 29 % (monotherapy AB 35 %, monotherapy 5ARI 18 %, CT 9 %). Patient adherence progressively declined to 15 %, 8 % and 3 % for AB, 5ARI, and CT, respectively at the fifth year of follow up. Patients on CT had a higher discontinuation rate along all the follow-up compared to those under monotherapy with ABs or 5ARIs (all p BPH-related surgery (HR 0.94; p BPH-associated LUTS is low and varies depending on drugs class. Patients under CT have a higher likelihood of discontinuing treatment for a number of reasons that should be better investigated. Our study suggests that new strategies aiming to increase patient's adherence to the prescribed treatment are necessary in order to prevent BPH progression.

Beta-blockers: friend or foe in asthma?

Directory of Open Access Journals (Sweden)

Arboe B

2013-07-01

Full Text Available Bente Arboe, Charlotte Suppli UlrikDepartment of Pulmonary Medicine, Hvidovre Hospital and University of Copenhagen, Hvidovre, DenmarkBackground and aim: Recently, β-blockers have been suggested as a potential maintenance treatment option for asthma. The aim of this review is to provide an overview of the current knowledge of the potential benefits and risks of β-blocker therapy for asthma.Method: Systematic literature review.Results: No significant increase in the number of patients requiring rescue oral corticosteroid for an exacerbation of asthma has been observed after initiation of β-blocker treatment. Patients with mild to moderate reactive airway disease, probably both asthma and chronic obstructive pulmonary disease, may have a limited fall in forced expiratory volume in 1 second (FEV1 following single-dose administration of β-blocker, whereas no change in FEV1 has been reported following long-term administration. In a murine model of asthma, long-term administration of β-blockers resulted in a decrease in airway hyperresponsiveness, suggesting an anti-inflammatory effect. In keeping with this, long-term administration of a nonselective β-blocker to steroid-naïve asthma patients has shown a dose-dependent improvement in airway hyperresponsiveness, and either an asymptomatic fall in FEV1 or no significant change in FEV1. Furthermore, available studies show that bronchoconstriction induced by inhaled methacholine is reversed by salbutamol in patients on regular therapy with a β-blocker. On the other hand, a recent placebo-controlled trial of propranolol and tiotropium bromide added to inhaled corticosteroids revealed no effect on airway hyperresponsiveness and a small, not statistically significant, fall in FEV1 in patients classified as having mild to moderate asthma.Conclusion: The available, although limited, evidence suggests that a dose-escalating model of β-blocker therapy to patients with asthma is well tolerated, does not

Management of hypertension: Insights into prescribing behavior with focus on angiotensin receptor blockers

Directory of Open Access Journals (Sweden)

S Ramakrishnan

2017-01-01

Full Text Available Introduction: Angiotensin receptor blockers (ARBs are emerging as an attractive first choice antihypertensive as recommended by various guidelines. However, choice among the first-line antihypertensive classes and among ARBs differs between practicing physicians. Aims: This survey aimed to understand the usage preferences of ARBs and its place in for treating hypertension (HTN among physicians from various clinical settings in India. Methods: A cross-sectional survey was conducted with a prevalidated survey questionnaire consisting of 25 questions for HTN management. Practicing general physicians and cardiologists were approached for seeking their perception, opinions, and prescribing behavior. Results: Responses of 594 physicians and cardiologists were received. As opined by 90.1% of physicians, newly diagnosed HTN represented more than 10% of their overall patient load. As a monotherapy, 59.9% of the physicians preferred ARB as the first choice in newly diagnosed HTN patients, followed by calcium channel blocker (12.3% and angiotensin-converting-enzyme inhibitor (8.1%. Of all ARBs, telmisartan is preferred by 73% of physicians. Most physicians prefer telmisartan among all ARBs for 24 h blood pressure (BP control, including morning BP surge (76.4% and for prevention of cardiovascular morbidity and mortality (78.8% followed by olmesartan and losartan. Predominantly, majority of physicians (89.1% agreed for the beneficial role of telmisartan in preventing onset of microalbuminuria and nephropathy. Conclusion: Indian physicians prefer ARBs as the first choice in most hypertensive patients, which shows agreement with the guideline recommendations followed globally. Telmisartan has emerged as the most preferred ARB among all, for most of the HTN patients including those with comorbidities.

The influence of carvedilol vs. metoprolol on sympathetic activity and hemostasis in patients with heart failure

NARCIS (Netherlands)

De Peuter, O.R.; Kok, W. E.; Verberne, H.J.; Van Den Bogaard, B.; Truijen, J.; Schaap, M.C.; Nieuwland, R.; Meijers, J.C.; Verheul, J.A.; De Groot, C.A.; Bakx, A.D.; Somsen, G.A.; Brewster, L.M.; Buller, H.R.; Kamphuisen, P.W.

2011-01-01

Background: Carvedilol, a non-selective beta-blocker, may be more effective in reducing the risk of thromboembolic events in heart failure, compared to metoprolol, a selective beta-blocker (De Peuter et al., Eur J Heart Fail, in press/ISTH 2009). We hypothesized that carvedilol lowers this risk

Erythema multiforme associated with gemfibrozil monotherapy.

Science.gov (United States)

Yaçsar, Hamiyet Yilmaz; Ertuğrul, Ozden; Deniz, Coçskun

2010-01-01

A case of erythema multiforme associated with gemfibrozil monotherapy. A 46-year-old man with hyperlipidemia was treated with 600 mg gemfibrozil twice a day. On the fifth day of treatment, skin lesions consistent with erythema multiforme appeared. With the discontinuation of the treatment and start of a topical steroid treatment, the lesions recovered after 4 weeks. After 6 months, when gemfibrozil therapy was restarted, lesions reappeared on the fourth day of therapy. Lesions recovered again following the previous treatment strategies after 4 weeks. An objective casualty assessment suggests that erythema multiforme was probably related to gemfibrozil monotherapy. Patients starting gemfibrozil therapy should be warned about the occurrence of erythema multiforme in addition to previous reported and established side effects.

Ribavirin monotherapy for chronic hepatitis C

DEFF Research Database (Denmark)

Brok, Jesper; Gluud, Lise Lotte; Gluud, Christian

2009-01-01

BACKGROUND: Hepatitis C is a major cause of liver-related morbidity and mortality. A high proportion of patients never experience symptoms. Peginterferon plus ribavirin is the recommended treatment for chronic hepatitis C. However, ribavirin monotherapy may be considered for some patients....... OBJECTIVES: To assess the beneficial and harmful effects of ribavirin monotherapy for patients with chronic hepatitis C. SEARCH STRATEGY: We identified trials through electronic databases, manual searches of bibliographies and journals, authors of trials, and pharmaceutical companies until March 2009....... SELECTION CRITERIA: We included all randomised trials irrespective of blinding, language, or publication status comparing ribavirin versus no intervention, placebo, or interferon for chronic hepatitis C. DATA COLLECTION AND ANALYSIS: The primary outcome measures were serum sustained virological response...

Efficacy and tolerability of micafungin monotherapy for candidemia and deep-seated candidiasis in adults with cancer.

Science.gov (United States)

Farmakiotis, Dimitrios; Tarrand, Jeffrey J; Kontoyiannis, Dimitrios P

2014-06-01

The response rate among 58 patients with cancer and candidemia or deep-seated candidiasis treated with micafungin monotherapy was 81%. Intensive care unit (ICU) stay, concomitant nonfungal infections, and acute kidney injury were significantly associated with the 30-day crude mortality rate. Severe neutropenia was an independent predictor of micafungin failure. The efficacy and safety of micafungin in cancer patients with invasive candidiasis were comparable to those reported for patients without malignancy and for cancer patients treated with caspofungin. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Efficacy and Safety of Initial Combination Treatment of an Alpha Blocker with an Anticholinergic Medication in Benign Prostatic Hyperplasia Patients with Lower Urinary Tract Symptoms: Updated Meta-Analysis.

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Hyun Jung Kim

Full Text Available There is still controversy as to whether initial combination treatment is superior to serial addition of anticholinergics after maintenance or induction of alpha blockers in benign prostatic hyperplasia (BPH/lower urinary tract symptoms (LUTS.The objective of this study was to determine the benefits and safety of initial combination treatment of an alpha blocker with anticholinergic medication in BPH/LUTS through a systematic review and meta-analysis.We conducted a meta-analysis of improvement in LUTS using International Prostate Symptom Score (IPSS, maximal urinary flow rate (Qmax, post-voided residual volume (PVR, and quality of life (QoL.In total, 16 studies were included in our analysis, with a total sample size of 3,548 subjects (2,195 experimental subjects and 1,353 controls. The mean change in total IPSS improvement from baseline in the combination group versus the alpha blocker monotherapy group was -0.03 (95% CI: -0.14-0.08. The pooled overall SMD change of storage IPSS improvement from baseline was -0.28 (95% CI: -0.40 - -0.17. The pooled overall SMD changes of QoL, Qmax, and PVR were -0.29 (95% CI: -0.50 - -0.07, 0.00 (95% CI: -0.08-0.08, and 0.56 (95% CI: 0.23-0.89, respectively. There was no significant difference in the number of acute urinary retention (AUR events or PVR.Initial combination treatment of an alpha blocker with anticholinergic medication is efficacious for in BPH/ LUTS with improved measures such as storage symptoms and QoL without causing significant deterioration of voiding function.

Antipsychotic monotherapy and polypharmacy in the naturalistic treatment of schizophrenia with atypical antipsychotics

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Correll Christoph

2005-05-01

Full Text Available Abstract Background Antipsychotic monotherapy is recognized as the treatment of choice for patients with schizophrenia. Simultaneous treatment with multiple antipsychotics (polypharmacy is suggested by some expert consensus guidelines as the last resort after exhausting monotherapy alternatives. This study assessed the annual rate and duration of antipsychotic monotherapy and its inverse, antipsychotic polypharmacy, among schizophrenia patients initiated on commonly used atypical antipsychotic medications. Methods Data were drawn from a large prospective naturalistic study of patients treated for schizophrenia-spectrum disorders, conducted 7/1997–9/2003. Analyses focused on patients (N = 796 who were initiated during the study on olanzapine (N = 405, quetiapine (N = 115, or risperidone (N = 276. The percentage of patients with monotherapy on the index antipsychotic over the 1-year post initiation, and the cumulative number of days on monotherapy were calculated for all patients and for each of the 3 atypical antipsychotic treatment groups. Analyses employed repeated measures generalized linear models and non-parametric bootstrap re-sampling, controlling for patient characteristics. Results During the 1-year period, only a third (35.7% of the patients were treated predominately with monotherapy (>300 days. Most patients (57.7% had at least one prolonged period of antipsychotic polypharmacy (>60 consecutive days. Patients averaged 195.5 days on monotherapy, 155.7 days on polypharmacy, and 13.9 days without antipsychotic therapy. Olanzapine-initiated patients were significantly more likely to be on monotherapy with the initiating antipsychotic during the 1-year post initiation compared to risperidone (p = .043 or quetiapine (p = .002. The number of monotherapy days was significantly greater for olanzapine than quetiapine (p Conclusion Despite guidelines recommending the use of polypharmacy only as a last resort, the use of antipsychotic

Effect of aliskiren and valsartan combination versus aliskiren monotherapy on hemostatic biomarkers in hypertensive diabetics: Aliskiren and Valsartan Impact in Diabetics pilot trial.

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Serebruany, Victor L; Pokov, Alex N; Aradi, Daniel; Can, Mehmet; DiNicolantonio, James; Kipshidze, Nodar; Atar, Dan

2014-01-01

Valsartan is known to inhibit platelet activity in both in vitro and ex vivo clinical setting, whereas aliskiren in vitro modulates antithrombin-III in plasma. The authors tested how aliskiren and valsartan combination versus aliskiren monotherapy will affect hemostatic biomarkers in mild-to-moderate hypertensive diabetics in the frame of the Aliskiren and Valsartan Impact in Diabetics (AVID) trial. A total of 52 patients with type 2 diabetes and mild-to-moderate hypertension were equally randomized to aliskiren (150-300 mg/d) and valsartan (160 mg/d) versus aliskiren (150-300 mg/d) alone for 4 weeks. A total of 25 biomarkers were serially measured, of which 16 are related to platelet function, 6 to coagulation, and 3 to fibrinolysis. Aliskiren monotherapy has no significant impact on any of the assessed biomarkers. In contrast, valsartan on top of aliskiren provided significant inhibition of ADP-induced platelet aggregation (P=0.032), decreased shear-induced activation measured with PFA-100 analyzer (P=0.041), and diminished expression of GP IIb/IIIa activity (P=0.027) measured by PAC-1 antibody, GP Ib (CD42b, P=0.033), vitronectin receptor (CD51/61, P=0.046), P-selectin (CD62p, P=0.026), lysosome-associated membrane protein (CD107a, P=0.042), and CD40-ligand (CD154, P=0.048). In AVID trial, valsartan in combination with aliskiren mildly but significantly inhibited platelets, confirming previous observations. In contrast, aliskiren monotherapy does not enhance antithrombin activity, suggesting that previous data probably represent a laboratory artifact. Importantly, these randomized data were generated on top of low-dose daily aspirin, supporting extra benefit for combination use of angiotensin receptor blockers and renin inhibitors in high-risk diabetic population.

Calcium Channel Blockers

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... Certain calcium channel blockers interact with grapefruit products. Kaplan NM, et al. Treatment of hypertension: Drug therapy. In: Kaplan's Clinical Hypertension. 11th ed. Philadelphia, Pa.: Wolters Kluwer ...

Current concepts in combination therapy for the treatment of hypertension: combined calcium channel blockers and RAAS inhibitors

Directory of Open Access Journals (Sweden)

Alberto F Rubio-Guerra

2009-11-01

Full Text Available Alberto F Rubio-Guerra1, David Castro-Serna2, Cesar I Elizalde Barrera2, Luz M Ramos-Brizuela21Metabolic and Research Clinic, 2Internal Medicine Department, Hospital General de Ticomán SS DF, MéxicoAbstract: Recent guidelines for the management of hypertension recommend target blood pressures <140/90 mmHg in hypertensive patients, or <130/80 mmHg in subjects with diabetes, chronic kidney disease, or coronary artery disease. Despite the availability and efficacy of antihypertensive drugs, most hypertensive patients do not reach the recommended treatment targets with monotherapy, making combination therapy necessary to achieve the therapeutic goal. Combination therapy with 2 or more agents is the most effective method for achieving strict blood pressure goals. Fixed-dose combination simplifies treatment, reduces costs, and improves adherence. There are many drug choices for combination therapy, but few data are available about the efficacy and safety of some specific combinations. Combination therapy of calcium antagonists and inhibitors of the renin-angiotensin-aldosterone system (RAAS are efficacious and safe, and have been considered rational by both the JNC 7 and the 2007 European Society of Hypertension – European Society of Cardiology guidelines for the management of arterial hypertension. The aim of this review is to discuss some relevant issues about the use of combinations with calcium channel blockers and RAAS inhibitors in the treatment of hypertension.Keywords: hypertension, calcium channel blockers, renin-angiotensin-aldosterone system inhibitors, fixed-dose combination, adherence

Benazepril combined with either amlodipine or hydrochlorothiazide is more effective than monotherapy for blood pressure control and prevention of end-organ injury in hypertensive Dahl rats.

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Zhou, Ming-Sheng; Jaimes, Edgar A; Raij, Leopoldo

2006-07-01

We studied the effect of hydrochlorothiazide (HCTZ), the angiotensin-converting enzyme inhibitor benazepril, the calcium channel blocker amlodipine, or a combination of benazepril/amlodipine or benazepril/HCTZ on systolic blood pressure (BP) and end-organ injury (left ventricular hypertrophy, proteinuria, and endothelium-dependent relaxation to acetylcholine) in hypertensive Dahl salt-sensitive rats fed either a normal-salt (0.5% NaCl) or high-salt (4% NaCl) diet for 6 weeks. Rats fed a high-salt diet developed hypertension and significant end-organ injury. Monotherapy with HCTZ (75 mg/L in drinking water) or amlodipine (10 mg/kg/day by gavage) reduced systolic BP and proteinuria; benazepril (40 mg/kg/day by gavage) decreased proteinuria without significantly lowering systolic BP. In rats receiving a high-salt diet, only HCTZ reduced left ventricular hypertrophy, whereas endothelium-dependent relaxation was improved by amlodipine and benazepril but not by HCTZ. Combining benazepril with either amlodipine or HCTZ dramatically reduced systolic BP and end-organ injury. These data clearly support clinical studies suggesting that combination therapy is more effective than monotherapy for systolic BP control and prevention of end-organ injury. Complementary mechanisms of action of agents from different antihypertensive classes appear to facilitate the greater benefit on BP and end-organ injury.

Medication adherence and Medicare expenditure among beneficiaries with heart failure.

Science.gov (United States)

Lopert, Ruth; Shoemaker, J Samantha; Davidoff, Amy; Shaffer, Thomas; Abdulhalim, Abdulla M; Lloyd, Jennifer; Stuart, Bruce

2012-09-01

To (1) measure utilization of and adherence to heart failure medications and (2) assess whether better adherence is associated with lower Medicare spending. Pooled cross-sectional design using six 3-year cohorts of Medicare beneficiaries with congestive heart failure (CHF) from 1997 through 2005 (N = 2204). Adherence to treatment was measured using average daily pill counts. Bivariate and multivariate methods were used to examine the relationship between medication adherence and Medicare spending. Multivariate analyses included extensive variables to control for confounding, including healthy adherer bias. Approximately 58% of the cohort were taking an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB), 72% a diuretic, 37% a beta-blocker, and 34% a cardiac glycoside. Unadjusted results showed that a 10% increase in average daily pill count for ACE inhibitors or ARBs, beta-blockers, diuretics, or cardiac glycosides was associated with reductions in Medicare spending of $508 (not significant [NS]), $608 (NS), $250 (NS), and $1244 (P <.05), respectively. Estimated adjusted marginal effects of a 10% increase in daily pill counts for beta-blockers and cardiac glycosides were reductions in cumulative 3-year Medicare spending of $510 to $561 and $750 to $923, respectively (P <.05). Higher levels of medication adherence among Medicare beneficiaries with CHF were associated with lower cumulative Medicare spending over 3 years, with savings generally exceeding the costs of the drugs in question.

Formulary considerations in selection of beta-blockers.

Science.gov (United States)

Yedinak, K C

1993-08-01

Selection of beta-adrenergic blockers for formulary addition can be a difficult task, especially with the increasing availability of new beta-blockers, as well as the numerous differences in pharmacodynamic and pharmacokinetic properties of currently available agents. Nevertheless, appropriate evaluation of the important characteristics of beta-blockers should allow selection of the most cost-effective agents for formulary addition. Most importantly, differences in efficacy, product formulation and cost should be carefully considered when making formulary decisions. Notably, evidence from clinical trials indicates differences in efficacy among beta-blockers for post-myocardial infarction prophylaxis, situational anxiety, essential tremor, thyrotoxicosis, migraine prophylaxis and prevention of bleeding associated with oesophageal varices. For many clinical situations, it is also important to select an effective agent that is available in both an oral and intravenous formulation, especially for cardioprotection after acute myocardial infarction and for use in supraventricular arrhythmias. In addition, availability of sustained release products and generic formulations should be considered for their potential to increase compliance and decrease cost, respectively. Comparative drug costs, as well as costs associated with decreased compliance, should also be carefully evaluated. Differences in beta-receptor selectivity, duration of action and presence of intrinsic sympathomimetic activity (ISA) are also important considerations in the selection of beta-blockers for formulary consideration. Although degree of selectivity is relative, beta 1-selective agents may be less likely to induce bronchospasm in patients with chronic obstructive pulmonary disease (COPD) and may be less likely to affect glucose homeostasis in patients with diabetes mellitus. Duration of action of a beta-blocker is an important consideration for evaluation of efficacy throughout the recommended

Prognosis in heart failure and the value of {beta}-blockers are altered by the use of antidepressants and depend on the type of antidepressants used

DEFF Research Database (Denmark)

Fosbøl, Emil Loldrup; Gislason, Gunnar H; Poulsen, Henrik Enghusen

2009-01-01

to cardiovascular causes (median follow-up, 1.9 years; 5, 95% fractiles, 0.04 to 7.06 years). Use of beta-blockers was associated with decreased risk of cardiovascular death (hazard ratio [HR], 0.77; 95% CI, 0.75 to 0.79). Antidepressants were prescribed to 19 411 patients, and both TCA and SSRI were associated...... with increased risk of overall and cardiovascular death (TCA: HR, 1.33; CI, 1.26 to 1.40; and HR, 1.25; CI, 1.17 to 1.32; SSRI: HR, 1.37; CI, 1.34 to 1.40; and HR, 1.34; CI, 1.30 to 1.38, respectively). Coadministration of SSRI and beta-blockers was associated with a higher risk of overall and cardiovascular...... death compared with coadministration of beta-blockers and TCA (P for interaction beta-blockers was associated with increased risk of overall death and cardiovascular death...

EFFECTIVENESS AND SAFETY OF THE «DE ALEX» BIO COMPLEX AS MONOTHERAPY AND IN COMBINATION WITH TAMSULOSIN IN PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA

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P. A. Scheplev

2017-01-01

proved to be an effective and safe supplement with fast effect. Considering the above, we can recommend the "De Alex" bio complex at dose 1 tablet 2 times a day for 3 months (1–2 courses a year as an effective and safe preparation that can be used as monotherapy or in combination with alpha-blockers to manage LUTS. 

Beta-blockers in cirrhosis and refractory ascites

DEFF Research Database (Denmark)

Kimer, Nina; Feineis, Martin; Møller, Søren

2015-01-01

OBJECTIVE: It is currently discussed if beta-blockers exert harmful effects and increase mortality in patients with cirrhosis and refractory ascites. In this study, we provide an overview of the available literature in this field in combination with a retrospective analysis of 61 patients...... trials (9 trials on propranolol, 1 case-control study and 4 retrospective analyses) were identified. One trial suggested an increased mortality in patients treated with beta-blockers and refractory ascites. The results of the remaining trials were inconclusive. No increase in mortality among beta-blocker......-treated patients was found in the present retrospective analysis. CONCLUSIONS: Treatment with beta-blockers may increase mortality in patients with cirrhosis and refractory ascites. However, the current evidence is sparse and high-quality studies are warranted to clarify the matter....

Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis

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Zheng, Sean Lee; Chan, Fiona T; Nabeebaccus, Adam A; Shah, Ajay M; McDonagh, Theresa; Okonko, Darlington O; Ayis, Salma

2018-01-01

Background Clinical drug trials in patients with heart failure and preserved ejection fraction have failed to demonstrate improvements in mortality. Methods We systematically searched Medline, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCT) assessing pharmacological treatments in patients with heart failure with left ventricular (LV) ejection fraction≥40% from January 1996 to May 2016. The primary efficacy outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, heart failure hospitalisation, exercise capacity (6-min walk distance, exercise duration, VO2 max), quality of life and biomarkers (B-type natriuretic peptide, N-terminal pro-B-type natriuretic peptide). Random-effects models were used to estimate pooled relative risks (RR) for the binary outcomes, and weighted mean differences for continuous outcomes, with 95% CI. Results We included data from 25 RCTs comprising data for 18101 patients. All-cause mortality was reduced with beta-blocker therapy compared with placebo (RR: 0.78, 95%CI 0.65 to 0.94, p=0.008). There was no effect seen with ACE inhibitors, aldosterone receptor blockers, mineralocorticoid receptor antagonists and other drug classes, compared with placebo. Similar results were observed for cardiovascular mortality. No single drug class reduced heart failure hospitalisation compared with placebo. Conclusion The efficacy of treatments in patients with heart failure and an LV ejection fraction≥40% differ depending on the type of therapy, with beta-blockers demonstrating reductions in all-cause and cardiovascular mortality. Further trials are warranted to confirm treatment effects of beta-blockers in this patient group. PMID:28780577

Clinical and economic aspects of the use of nebivolol in the treatment of elderly patients with heart failure

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Donatella Del Sindaco

2010-12-01

Full Text Available Donatella Del Sindaco1, Maria Denitza Tinti2, Luca Monzo2, Giovanni Pulignano2,1Heart Failure Unit, Division of Cardiology, INRCA Institute of Care and Research for Elderly, Rome, Italy; 2Heart Failure Clinic, Division of Cardiology/CCU, San Camillo Hospital, Rome, ItalyAbstract: Heart failure is a common and disabling condition with morbidity and mortality that increase dramatically with advancing age. Large observational studies, retrospective subgroup analyses and meta-analyses of clinical trials in systolic heart failure, and recently published randomized studies have provided data supporting the use of beta-blockers as a baseline therapy in heart failure in the elderly. Despite the available evidence about beta-blockers, this therapy is still less frequently used in elderly compared to younger patients. Nebivolol is a third-generation cardioselective beta-blocker with L-arginine/nitric oxide-induced vasodilatory properties, approved in Europe and several other countries for the treatment of essential hypertension, and in Europe for the treatment of stable, mild, or moderate chronic heart failure, in addition to standard therapies in elderly patients aged 70 years old or older. The effects of nebivolol on left ventricular function in elderly patients with chronic heart failure (ENECA and the study of effects of nebivolol intervention on outcomes and rehospitalization in seniors with heart failure (SENIORS have been specifically aimed to assess the efficacy of beta-blockade in elderly heart failure patients. The results of these two trials demonstrate that nebivolol is well tolerated and effective in reducing mortality and morbidity in older patients, and that the beneficial clinical effect is present also in patients with mildly reduced ejection fraction. Moreover, nebivolol appears to be significantly cost-effective when prescribed in these patients. However, further targeted studies are needed to better define the efficacy as well as

Use of beta-blockers and risk of serious upper gastrointestinal bleeding

DEFF Research Database (Denmark)

Reilev, Mette; Damkier, Per; Rasmussen, Lotte

2017-01-01

Background: Some studies indicate a reduced risk of serious upper gastrointestinal bleeding (UGIB) for users of beta-blockers, but the association remains to be confirmed in larger studies and characterized with respect to differences among beta-blockers. We aimed to assess whether beta-blocker use...... and adjusted odds ratios (ORs) of the association between current beta-blocker use and the risk of UGIB by using conditional logistic regression and further stratified by selective and non-selective beta-blockers, respectively. Results: We identified 3571 UGIB cases and 35,582 controls. Use of beta-blockers...... was not found to be associated with a decreased risk of UGIB (adjusted OR 1.10; 95% CI: 1.00-1.21). The association remained neutral after stratification by selective and non-selective beta-blockers, and by single beta-blocker substances. Similarly, we found no association between current beta-blocker use...

β1-Adrenoceptor blocker aggravated ventricular arrhythmia.

Science.gov (United States)

Wang, Yan; Patel, Dimpi; Wang, Dao Wu; Yan, Jiang Tao; Hsia, Henry H; Liu, Hao; Zhao, Chun Xia; Zuo, Hou Juan; Wang, Dao Wen

2013-11-01

To assess the impact of β1 -adrenoceptor blockers (β1 -blocker) and isoprenaline on the incidence of idiopathic repetitive ventricular arrhythmia that apparently decreases with preprocedural anxiety. From January 2010 to July 2012, six patients were identified who had idiopathic ventricular arrhythmias that apparently decreased (by greater than 90%) with preprocedural anxiety. The number of ectopic ventricular beats per hour (VPH) was calculated from Holter or telemetry monitoring to assess the ectopic burden. The mean VPH of 24 hours from Holter before admission (VPH-m) was used as baseline (100%) for normalization. β1 -Blockers, isoprenaline, and/or aminophylline were administrated successively on the ward and catheter lab to evaluate their effects on the ventricular arrhythmias. Among 97 consecutive patients with idiopathic ventricular arrhythmias, six had reduction in normalized VPHs in the hour before the scheduled procedure time from (104.6 ± 4.6%) to (2.8 ± 1.6%) possibly due to preprocedural anxiety (P < 0.05), then increased to (97.9 ± 9.7%) during β1 -blocker administration (P < 0.05), then quickly reduced to (1.6 ± 1.0%) during subsequent isoprenaline infusion. Repeated β1 -blocker quickly counteracted the inhibitory effect of isoprenaline, and VPHs increased to (120.9 ± 2.4%) from (1.6 ± 1.0%; P < 0.05). Isoprenaline and β1 -blocker showed similar effects on the arrhythmias in catheter lab. In some patients with structurally normal heart and ventricular arrhythmias there is a marked reduction of arrhythmias associated with preprocedural anxiety. These patients exhibit a reproducible sequence of β1 -blocker aggravation and catecholamine inhibition of ventricular arrhythmias, including both repetitive ventricular premature beats and monomorphic ventricular tachycardia. ©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.

Is 30-Day Mortality after Admission for Heart Failure an Appropriate Metric for Quality?

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Faillace, Robert T; Yost, Gregory W; Chugh, Yashasvi; Adams, Jeffrey; Verma, Beni R; Said, Zaid; Sayed, Ibrahim Ismail; Honushefsky, Ashley; Doddamani, Sanjay; Berger, Peter B

2018-02-01

The Centers for Medicare and Medicaid Services (CMS) model for publicly reporting national 30-day-risk-adjusted mortality rates for patients admitted with heart failure fails to include clinical variables known to impact total mortality or take into consideration the culture of end-of-life care. We sought to determine if those variables were related to the 30-day mortality of heart failure patients at Geisinger Medical Center. Electronic records were searched for patients with a diagnosis of heart failure who died from any cause during hospitalization or within 30 days of admission. There were 646 heart-failure-related admissions among 530 patients (1.2 admissions/patient). Sixty-seven of the 530 (13%) patients died: 35 (52%) died during their hospitalization and 32 (48%) died after discharge but within 30 days of admission; of these, 27 (40%) had been transferred in for higher-acuity care. Fifty-one (76%) died from heart failure, and 16 (24%) from other causes. Fifty-five (82%) patients were classified as American Heart Association Stage D, 58 (87%) as New York Heart Association Class IV, and 30 (45%) had right-ventricular systolic dysfunction. None of the 32 patients who died after discharge met recommendations for beta-blockers. Criteria for prescribing angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor blockers were not met by 33 of the 34 patients (97%) with heart failure with reduced ejection fraction not on one of those drugs. Fifty-seven patients (85%) had a do-not-resuscitate (DNR) status. A majority of heart failure-related mortality was among patients who opted for a DNR status with end-stage heart failure, limiting the appropriateness of administering evidence-based therapies. No care gaps were identified that contributed to mortality at our institution. The CMS 30-day model fails to take important variables into consideration. Copyright © 2018 Elsevier Inc. All rights reserved.

Variation in hospital performance for heart failure management in the National Heart Failure Audit for England and Wales.

Science.gov (United States)

Emdin, Connor A; Conrad, Nathalie; Kiran, Amit; Salimi-Khorshidi, Gholamreza; Woodward, Mark; Anderson, Simon G; Mohseni, Hamid; Dargie, Henry J; Hardman, Suzanna M C; McDonagh, Theresa; McMurray, John J V; Cleland, John G F; Rahimi, Kazem

2017-01-01

Investigation of variations in provider performance and its determinants may help inform strategies for improving patient outcomes. We used the National Heart Failure Audit comprising 68 772 patients with heart failure with reduced left ventricular ejection fraction (HFREF), admitted to 185 hospitals in England and Wales (2007-2013). We investigated hospital adherence to three recommended key performance measures (KPMs) for inhospital care (ACE inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) on discharge, β-blockers on discharge and referral to specialist follow-up) individually and as a composite performance score. Hierarchical regression models were used to investigate hospital-level variation. Hospital-level variation in adherence to composite KPM ranged from 50% to 97% (median 79%), but after adjustments for patient characteristics and year of admission, only 8% (95% CI 7% to 10%) of this variation was attributable to variations in hospital features. Similarly, hospital prescription rates for ACE-I/ARB and β-blocker showed low adjusted hospital-attributable variations (7% CI 6% to 9% and 6% CI 5% to 8%, for ACE-I/ARB and β-blocker, respectively). Referral to specialist follow-up, however, showed larger variations (median 81%; range; 20%, 100%) with 26% of this being attributable to hospital-level differences (CI 22% to 31%). Only a small proportion of hospital variation in medication prescription after discharge was attributable to hospital-level features. This suggests that differences in hospital practices are not a major determinant of observed variations in prescription of investigated medications and outcomes. Future healthcare delivery efforts should consider evaluation and improvement of more ambitious KPMs. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Systematic review of use of β-blockers in sepsis

Directory of Open Access Journals (Sweden)

Cyril Jacob Chacko

2015-01-01

Conclusion: There is insufficient evidence to justify the routine use of β-blockers in sepsis. A large adequately powered multi-centered randomized controlled clinical trial is required to address the question on the efficacy of β-blocker usage in sepsis. This trial should also consider a number of important questions including the choice of β-blocker used, optimal dosing, timing of intervention, duration of intervention and discontinuation of the drug. Until such time based on the available evidence, there is no place for the use of β-blockers in sepsis in current clinical practice.

Sulfonylurea monotherapy and emergency room utilization among elderly patients with type 2 diabetes.

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Rajpathak, Swapnil N; Fu, Chunmay; Brodovicz, Kimberley; Engel, Samuel S; Heaton, Pamela C

2015-09-01

In elderly Americans with type 2 diabetes, use of insulin and oral antidiabetic drugs (OADs) accounts for almost one-fourth of drug adverse event-related hospitalizations. It is not clear, however, if sulfonylureas (SUs), frequently prescribed OADs known to cause hypoglycemia, increase the risk of emergency room (ER) visits compared to other OADs. The aim of this study was to compare the emergency room utilization between US elderly patients with diabetes on SU monotherapy vs. other non-SU monotherapies. This retrospective cohort study was conducted using MarketScan(®) database (2009-10) and aimed to evaluate the association between use of SU and ER visits. The analysis included 28,533 patients (aged ≥65 years) receiving SU monotherapy at baseline and 1:1 propensity score (PS)-matched group receiving monotherapy with other OADs. ER utilization was determined during a 1-year follow-up period. The SU and non-SU groups were overall well balanced after PS matching. The mean (SD) number of ER visits during the follow-up was 0.56 among users of SU users compared to 0.49 (Pmetformin users. Elderly patients with type 2 diabetes on SU monotherapy were more likely to use ER than those on other monotherapies. Further studies are needed to confirm our findings and evaluate other factors associated with ER visits. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Usefulness of {sup 123}I-MIBG scintigraphy for prediction of effect of {beta}-blocker therapy in dilated cardiomyopathy

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Tawarahara, Kei; Sugiyama, Tsuyoshi; Nakano, Tomoyasu; Matou, Fumitaka [Hamamatsu Red Cross Hospital, Shizuoka (Japan); Kurata, Chinori; Wakabayashi, Yasushi; Shouda, Sakae; Mikami, Tadashi

1998-07-01

To determine whether {sup 123}I-MIBG (MIBG) scintigraphy is useful for predicting the effect of {beta}-blocker therapy in patients with dilated cardiomyopathy (DCM), we studied MIBG scintigraphy in 11 controls and 9 patients with DCM before starting {beta}-blocker therapy. First, initial and delayed heart-to-mediastinum ratios (H/M ratio) of MIBG activity in patients with DCM were significantly lower than those in 11 controls, respectively (initial H/M; 1.8{+-}0.3 vs. 2.1{+-}0.3, p<0.02, delayed H/M; 1.6{+-}0.3 vs. 2.4{+-}0.2, p<0.0001), and MIBG washout rate from the heart was significantly higher in patients than in controls (washout rate; 33{+-}7% vs. 22{+-}4%, p<0.0005). Second, {beta}-blocker therapy improved LVEF in 7 patients (improved group), while it resulted in deterioration of heart failure, followed by death in 2 patients (deteriorated group). Although initial and delayed H/M ratios in the improved group were not significantly different from those in the deteriorated group, respectively, MIBG washout rate was significantly higher in the deteriorated group than in the improved group (45{+-}8% vs. 30{+-}3%, p=0.04). Our study suggests that DCM patients with markedly rapid MIBG clearance may be deteriorated by {beta}-blocker therapy. In contrast, there were no differences in LVEF and plasma norepinephrine between improved and deteriorated groups. In conclusion, {sup 123}I-MIBG scintigraphy is useful for predicting the effects of {beta}-blocker therapy in patients with DCM. (author)

Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis.

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Zheng, Sean Lee; Chan, Fiona T; Nabeebaccus, Adam A; Shah, Ajay M; McDonagh, Theresa; Okonko, Darlington O; Ayis, Salma

2018-03-01

Clinical drug trials in patients with heart failure and preserved ejection fraction have failed to demonstrate improvements in mortality. We systematically searched Medline, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCT) assessing pharmacological treatments in patients with heart failure with left ventricular (LV) ejection fraction≥40% from January 1996 to May 2016. The primary efficacy outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, heart failure hospitalisation, exercise capacity (6-min walk distance, exercise duration, VO 2 max), quality of life and biomarkers (B-type natriuretic peptide, N-terminal pro-B-type natriuretic peptide). Random-effects models were used to estimate pooled relative risks (RR) for the binary outcomes, and weighted mean differences for continuous outcomes, with 95% CI. We included data from 25 RCTs comprising data for 18101 patients. All-cause mortality was reduced with beta-blocker therapy compared with placebo (RR: 0.78, 95%CI 0.65 to 0.94, p=0.008). There was no effect seen with ACE inhibitors, aldosterone receptor blockers, mineralocorticoid receptor antagonists and other drug classes, compared with placebo. Similar results were observed for cardiovascular mortality. No single drug class reduced heart failure hospitalisation compared with placebo. The efficacy of treatments in patients with heart failure and an LV ejection fraction≥40% differ depending on the type of therapy, with beta-blockers demonstrating reductions in all-cause and cardiovascular mortality. Further trials are warranted to confirm treatment effects of beta-blockers in this patient group. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Impact of Tamsulosin, Tolterodine and drug-combination on the ...

African Journals Online (AJOL)

Objectives: To compare the role of alpha-blocker (Tamsulosin) monotherapy, anticholinergic (Tolterodine) monotherapy or combination of both drugs versus analgesics in improving post-ureteroscopy (URS) lower urinary tract symptoms related to double-J ureteral stent. Patients and methods: Between January 2009 and ...

Systematic review of use of β-blockers in sepsis.

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Chacko, Cyril Jacob; Gopal, Shameer

2015-01-01

We proposed a review of present literature and systematic analysis of present literature to summarize the evidence on the use of β-blockers on the outcome of a patient with severe sepsis and septic shock. Medline, EMBASE, Cochrane Library were searched from 1946 to December 2013. The bibliography of all relevant articles was hand searched. Full-text search of the grey literature was done through the medical institution database. The database search identified a total of 1241 possible studies. The citation list was hand searched by both the authors. A total of 9 studies were identified. Most studies found a benefit from β-blocker administration in sepsis. This included improved heart rate (HR) control, decreased mortality and improvement in acid-base parameters. Chronic β-blocker usage in sepsis was also associated with improved mortality. The administration of β-blockers during sepsis was associated with better control of HR. The methodological quality of all the included studies, however, was poor. There is insufficient evidence to justify the routine use of β-blockers in sepsis. A large adequately powered multi-centered randomized controlled clinical trial is required to address the question on the efficacy of β-blocker usage in sepsis. This trial should also consider a number of important questions including the choice of β-blocker used, optimal dosing, timing of intervention, duration of intervention and discontinuation of the drug. Until such time based on the available evidence, there is no place for the use of β-blockers in sepsis in current clinical practice.

Beta-Blockers for Exams Identify Students at High Risk of Psychiatric Morbidity.

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Butt, Jawad H; Dalsgaard, Søren; Torp-Pedersen, Christian; Køber, Lars; Gislason, Gunnar H; Kruuse, Christina; Fosbøl, Emil L

2017-04-01

Beta-blockers relieve the autonomic symptoms of exam-related anxiety and may be beneficial in exam-related and performance anxiety, but knowledge on related psychiatric outcomes is unknown. We hypothesized that beta-blocker therapy for exam-related anxiety identifies young students at risk of later psychiatric events. Using Danish nationwide administrative registries, we studied healthy students aged 14-30 years (1996-2012) with a first-time claimed prescription for a beta-blocker during the exam period (May-June); students who were prescribed a beta-blocker for medical reasons were excluded. We matched these students on age, sex, and time of year to healthy and study active controls with no use of beta-blockers. Risk of incident use of antidepressants, incident use of other psychotropic medications, and suicide attempts was examined by cumulative incidence curves for unadjusted associations and multivariable cause-specific Cox proportional hazard analyses for adjusted hazard ratios (HRs). We identified 12,147 healthy students with exam-related beta-blocker use and 12,147 matched healthy students with no current or prior use of beta-blockers (median age, 19 years; 80.3% women). Among all healthy students, 0.14% had a first-time prescription for a beta-blocker during the exam period with the highest proportion among students aged 19 years (0.39%). Eighty-one percent of the students filled only that single prescription for a beta-blocker during follow-up. During follow-up, 2225 (18.3%) beta-blocker users and 1400 (11.5%) nonbeta-blocker users were prescribed an antidepressant (p beta-blocker users and 658 (5.4%) nonbeta-blocker users were prescribed a psychotropic drug (p beta-blocker users and 6 (0.05%) nonbeta-blocker users attempted suicide (p = 0.03). Exam-related beta-blocker use was associated with an increased risk of antidepressant use (adjusted HRs, 1.68 [95% confidence intervals (CIs), 1.57-1.79], p beta-blockers during the exam period was

The burden of chronic obstructive pulmonary disease associated with maintenance monotherapy in the UK

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Edwards SC

2016-11-01

Full Text Available Susan C Edwards,1 Sian E Fairbrother,2 Anna Scowcroft,3 Gavin Chiu,4 Andrew Ternouth,3 Brian J Lipworth5 1Department of Market Access Pricing & Outcomes Research, 2Department of Medical Affairs - Respiratory, 3Department of Market Access, 4Department of Prescription Medicine - Respiratory, Boehringer Ingelheim, Bracknell, UK; 5Asthma and Allergy Research Group, Division of Cardiovascular and Diabetes Medicine, Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK Background: This study characterized a cohort of chronic obstructive pulmonary disease (COPD patients on maintenance bronchodilator monotherapy for ≥6 months to establish their disease burden, measured by health care utilization.Methods: Data were extracted from the UK Clinical Practice Research Datalink and linked to Hospital Episode Statistics. The monotherapy period spanned the first prescription of a long-acting β2-adrenergic agonist or a long-acting muscarinic antagonist until the end of the study (December 31, 2013 or until step up to dual/triple therapy, for example, addition of another long-acting bronchodilator, an inhaled corticosteroid, or both. A minimum of four consecutive prescriptions and 6 months on continuous monotherapy were required. Patients <50 years old at first COPD diagnosis or with another significant respiratory disease before starting monotherapy were excluded. Disease burden was evaluated by measuring patients’ rate of face-to-face interactions with a health care professional (HCP, COPD-related exacerbations, hospitalizations, and referrals.Results: A cohort of 8,811 COPD patients (95% Global initiative for chronic Obstructive Lung Disease stage A/B on maintenance monotherapy was identified between 2002 and 2013; 45% of these patients were still on monotherapy by the end of the study. Median time from first COPD diagnosis to first monotherapy prescription was 56 days, while the median time on

Direct renin inhibition in addition to or as an alternative to angiotensin converting enzyme inhibition in patients with chronic systolic heart failure: rationale and design of the Aliskiren Trial to Minimize OutcomeS in Patients with HEart failuRE (ATMOSPHERE) study

DEFF Research Database (Denmark)

Krum, Henry; Massie, Barry; Abraham, William T

2011-01-01

S for Patients with HEart failuRE (ATMOSPHERE) study is to evaluate the effect of both aliskiren and enalapril monotherapy and aliskiren/enalapril combination therapy on cardiovascular death and HF hospitalization in patients with chronic systolic HF, NYHA functional class II-IV symptoms, and elevated plasma......-inferior to enalapril monotherapy on this endpoint. Perspective The ATMOSPHERE study will definitively determine the role of a DRI strategy additional to or as an alternative to conventional RAAS blockade in patients with chronic systolic HF....

Real-life indications to ivabradine treatment for heart rate optimization in patients with chronic systolic heart failure.

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Tondi, Lara; Fragasso, Gabriele; Spoladore, Roberto; Pinto, Giuseppe; Gemma, Marco; Slavich, Massimo; Godino, Cosmo; Salerno, Anna; Montanaro, Claudia; Margonato, Alberto

2018-05-11

: Ivabradine is a selective and specific inhibitor of If current. With its pure negative chronotropic action, it is recommended by European Society of Cardiology and American College of Cardiology/American Heart Association guidelines in symptomatic heart failure patients (NYHA ≥ 2) with ejection fraction 35% or less, sinus rhythm and heart rate (HR) at least 70 bpm, despite maximally titrated β-blocker therapy. Data supporting this indication mainly derive from the SHIFT study, in which ivabradine reduced the combined endpoint of mortality and hospitalization, despite the fact that only 26% of patients enrolled were on optimal β-blocker doses. The aim of the present analysis is to establish the real-life eligibility for ivabradine in a population of patients with systolic heart failure, regularly attending a single heart failure clinic and treated according to guideline-directed medical therapy (GDMT). The clinical cards of 308 patients with heart failure with reduced ejection fraction (HFrEF) through a 68-month period of observation were retrospectively analyzed. GDMT, including β-blocker up-titration to maximal tolerated dose, was implemented during consecutive visits at variable intervals. Demographic, clinical and echocardiographic data were collected at each visit, together with 12-leads ECG and N-terminal pro-B-type natriuretic peptide levels. Out of 308 analyzed HFrEF patients, 220 (71%) were on effective β-blocker therapy, up-titrated to effective/maximal tolerated dose (55 ± 28% of maximal dose) (HR 67 ± 10 bpm). Among the remaining 88 patients, 10 (3.2%) were on maximally tolerated β blocker and ivabradine; 21 patients (6.8%), despite being on maximal tolerated β-blocker dose, had still HR ≥70 bpm, ejection fraction 35% or less and were symptomatic NYHA ≥2, being therefore eligible for ivabradine treatment. The remaining 57 (18%) patients were not on β blocker due to either intolerance or major contraindications. Among

Validity, prognostic value and optimal cutoff of respiratory muscle strength in patients with chronic heart failure changes with beta-blocker treatment.

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Frankenstein, Lutz; Nelles, Manfred; Meyer, F Joachim; Sigg, Caroline; Schellberg, Dieter; Remppis, B Andrew; Katus, Hugo A; Zugck, Christian

2009-08-01

Training studies frequently use maximum inspiratory mouth occlusion pressure (PImax) as a therapeutic target and surrogate marker. For patients on beta-blocker (BBL), prognostic data allowing this extrapolation do not exist. Furthermore, the effects of BBL, mainstay of modern chronic heart failure therapy, on respiratory muscle function remain controversial. Finally, no proper separate cutoff according to treatment exists. Prospective, observational inclusion of patients with stable systolic chronic heart failure and recording of 1 year and all-time mortality for endpoint analysis. In 686 patients, 81% men, 494 patients on BBL, PImax was measured along with clinical evaluation. The median follow-up was 50 months (interquartile range: 26-75 months). Patients with or without BBL did not differ significantly for PImax, percentage of predicted PImax or other marker of disease severity. PImax was a significant (hazard ratio: 0.925; 95% confidence interval: 0.879-0.975; chi(2): 8.62) marker of adverse outcome, independent of BBL-status or aetiology. Percentage of predicted PImax was not independent of PImax. The cutoff identified through receiver-operated characteristics for 1-year mortality was 4.14 kPa for patients on BBL and 7.29 kPa for patients not on BBL. When separated accordingly, 1-year mortality was 8.5 versus 21.4%, P=0.02, for patients not on BBL and 4.3 versus 16.2%, P<0.001, for patients on BBL. This study fills the gap between trials targeting respiratory muscle on a functional basis and the resultant prognostic information with regard to BBL. BBL lowered the optimal PImax cutoff values for risk stratification without changing the measured values of PImax. This should be considered at inclusion and evaluation of trials and interpretation of exercise parameters.

Boosted protease inhibitor monotherapy versus boosted protease inhibitor plus lamivudine dual therapy as second-line maintenance treatment for HIV-1-infected patients in sub-Saharan Africa (ANRS12 286/MOBIDIP): a multicentre, randomised, parallel, open-label, superiority trial.

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Ciaffi, Laura; Koulla-Shiro, Sinata; Sawadogo, Adrien Bruno; Ndour, Cheik Tidiane; Eymard-Duvernay, Sabrina; Mbouyap, Pretty Rosereine; Ayangma, Liliane; Zoungrana, Jacques; Gueye, Ndeye Fatou Ngom; Diallo, Mohamadou; Izard, Suzanne; Bado, Guillaume; Kane, Coumba Toure; Aghokeng, Avelin Fobang; Peeters, Martine; Girard, Pierre Marie; Le Moing, Vincent; Reynes, Jacques; Delaporte, Eric

2017-09-01

Despite satisfactory efficacy of WHO-recommended second-line antiretroviral treatment for patients with HIV in low-income countries, the need for simplified, low-cost, and less-toxic maintenance strategies remains high. We compared boosted protease inhibitor monotherapy with dual therapy with boosted protease inhibitor plus lamivudine in patients on second-line antiretrovial therapy (ART). We did a multicentre, randomised, parallel, open-label, superiority, trial in the HIV services of five hospitals in sub-Saharan Africa (Yaoundé, Cameroon; Dakar, Senegal; and Bobo Dioulasso, Burkina Faso). We recruited patients from the long-term, post-trial cohort of the ANRS 12169/2LADY study that compared the efficacy of three second-line combinations based on boosted protease inhibitors. Participants for our study were HIV-1 infected with multiple mutations including M184V, at first-line failure, aged 18 years and older, on boosted protease inhibitor plus two nucleoside reverse transcriptase inhibitors (NRTI) for at least 48 weeks with at least 48 weeks follow-up in the 2LADY trial, with two viral load measurements of less than 200 copies per mL in the previous 6 months, CD4 counts of more than 100 cells per μL, adherence of at least 90%, and no change to ART in the past 3 months. We randomly assigned participants (1:1) to receive either monotherapy with their boosted protease inhibitor (once-daily darunavir 800 mg [two 400 mg tablets] boosted with ritonavir 100 mg [one tablet] or coformulation of lopinavir 200 mg with ritonavir 50 mg [two tablets taken twice per day]) or to boosted protease inhibitor plus once-daily lamivudine 300 mg (one 300 mg tablet or two 150 mg tablets). Computer-generated randomisation was stratified by study site and viral load at screening (treatment allocation was not masked from clinicians or patients]. Patients had follow-up visits at weeks 4 and 12, and every 3 months until 96 weeks; if viral load exceeded 500 copies per mL at any visit, NRTI

Topical antibiotic monotherapy prescribing practices in acne vulgaris.

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Hoover, William D; Davis, Scott A; Fleischer, Alan B; Feldman, Steven R

2014-04-01

The aim of this study is to evaluate the frequency of dosing topical antibiotics as monotherapy in the treatment of acne vulgaris, and physician specialty prescribing these medications. This study is a retrospective review of all visits with a sole diagnosis of acne vulgaris (ICD-9-CM code 706.1) found on the National Ambulatory Medical Care Survey (NAMCS) in 1993-2010. We recorded the number of visits surveyed where acne vulgaris was the sole diagnosis, number of visits where topical antibiotics were the only treatment prescribed, and the specialty of physician in each encounter. Topical erythromycin or clindamycin were the sole medication prescribed in 0.81% of the visits recorded, with 60% of these prescriptions arising from dermatologists and 40% from non-dermatologists. The trend of prescribing topical antibiotic monotherapy is declining (p acnes to topical antibiotic regimens has led to the need to re-evaluate the use of topical antibiotics in the treatment of acne vulgaris. While the rate of topical antibiotic monotherapy is declining, their use should be reserved for situations where the direct need for antibiotics arises. If a clinician feels that antibiotics are a necessary component to acne therapy, they should be used as part of a combination regimen.

Calcium channel blockers and Alzheimer's disease★

Science.gov (United States)

Tan, Yi; Deng, Yulin; Qing, Hong

2012-01-01

Alzheimer's disease is characterized by two pathological hallmarks: amyloid plaques and neurofibrillary tangles. In addition, calcium homeostasis is disrupted in the course of human aging. Recent research shows that dense plaques can cause functional alteration of calcium signals in mice with Alzheimer's disease. Calcium channel blockers are effective therapeutics for treating Alzheimer's disease. This review provides an overview of the current research of calcium channel blockers involved in Alzheimer's disease therapy. PMID:25767489

The Effects of Topical Antiglaucoma Drugs as Monotherapy on the Ocular Surface: A Prospective Study

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Sevda Aydin Kurna

2014-01-01

Full Text Available Purpose. The aim was to compare the effects of antiglaucoma eye drops on the tear functions and ocular surface. Method. Eighty-five eyes of 43 patients with glaucoma were included into this randomized prospective study. Timolol without preservative (1, timolol with benzododecinium bromide (2, latanoprost (3, bimatoprost (4, travoprost with benzalkonium chloride (5, and brimonidine with purite (6 were given to 6 groups. Schirmer I, tear film breakup time (TBUT, staining scores, and impression cytology samples were evaluated before and during 12-month-follow-up period. Results. At the end of 12 months, there was no detected change in Schirmer I and TBUT tests indicating dry eye. Corneal staining scores were higher in groups 1 and 2, while conjunctival staining scores were higher in group 6. Goblet cell count decreased in groups 1 and 5 in superior and inferior, group 2 in superior, and groups 3 and 6 in inferior conjunctiva. Squamous metaplasia grades showed a significant increase in groups 1 and 2 at 3rd, 6th, and 12th month controls (P<0.05. Conclusion. We observed nonserious impact on tear functions and ocular surface with antiglaucoma monotherapy. Beta blockers induced more damage on the ocular surface suggesting the role of the dosing and active substances beside preservatives.

The Hriday Card: A checklist for heart failure

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Sandeep Seth

2017-01-01

Full Text Available Use of a simple checklist can drastically lower the likelihood of heart failure patient readmission and improve quality of life. The Hriday Card is a simple 4 page booklet which combines patient education material teaching the patient about heart failure, how to tackle daily emergencies, how to look after their fluid balance with appropriate use of diuretics. It also contains medication and daily weight charts for the patient and a heart failure checklist for the heart failure nurse or doctor which covers points like vaccination, presence of LBBB or Atrial fibrillation and use or lack of use of ACE inhibitors and beta blockers and many other points related to heart failure. This checklist can be filled in less than a minute. It is a simple tool to enhance heart failure care and medication adherence.

Managing first-line failure.

Science.gov (United States)

Cooper, David A

2014-01-01

WHO standard of care for failure of a first regimen, usually 2N(t)RTI's and an NNRTI, consists of a ritonavir-boosted protease inhibitor with a change in N(t)RTI's. Until recently, there was no evidence to support these recommendations which were based on expert opinion. Two large randomized clinical trials, SECOND LINE and EARNEST both showed excellent response rates (>80%) for the WHO standard of care and indicated that a novel regimen of a boosted protease inhibitor with an integrase inhibitor had equal efficacy with no difference in toxicity. In EARNEST, a third arm consisting of induction with the combined protease and integrase inhibitor followed by protease inhibitor monotherapy maintenance was inferior and led to substantial (20%) protease inhibitor resistance. These studies confirm the validity of the current recommendations of WHO and point to a novel public health approach of using two new classes for second line when standard first-line therapy has failed, which avoids resistance genotyping. Notwithstanding, adherence must be stressed in those failing first-line treatments. Protease inhibitor monotherapy is not suitable for a public health approach in low- and middle-income countries.

Frequency of Anti-Toxoplasma IgM and IgG Antibodies in Leukemic Patients

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M.J. Gharavi

2015-11-01

Full Text Available Aim: the efficacy and safety of combined therapy with anticholinergics and alpha blockers in comparison with alpha blockers monotherapy among patients with BPH. Methods: We conducted a single blinded RCT and 80 patients with BPH who referred to Ali-ebn-abitaleb, Zahedan were included. One group received 0.4 mg/d Tamsulosin in addition to Tolterodine and the other group received the same doses of Tamsulosin in addition to placebo. Both groups were evaluated before and 6 months after treatment with special attention to clinical symptoms, life quality improvement and treatment satisfaction. SPSS was applied for data analysis. Results: There is no significant difference between these two groups of patients’ demographics and basic indices such as PVR, PSA and the volume of prostate. IPSS was significantly improved among patients who received Toltrodine (p=0.0008 whereas both groups showed same score before treatment. Conclusion: It seems that combined therapy with anticholinergics and alpha blockers is a safe and efficient regimen among patients with BPH, either as primary or alternative treatment after the failure of conventional treatments.

Is There Any Benefit Adding Anticholinergics to Drug Regime of Patients with Benign Prostate Hyperplasia?

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A. Mortazavi

2015-08-01

Full Text Available Aim: the efficacy and safety of combined therapy with anticholinergics and alpha blockers in comparison with alpha blockers monotherapy among patients with BPH. Methods: We conducted a single blinded RCT and 80 patients with BPH who referred to Ali-ebn-abitaleb, Zahedan were included. One group received 0.4 mg/d Tamsulosin in addition to Tolterodine and the other group received the same doses of Tamsulosin in addition to placebo. Both groups were evaluated before and 6 months after treatment with special attention to clinical symptoms, life quality improvement and treatment satisfaction. SPSS was applied for data analysis. Results: There is no significant difference between these two groups of patients’ demographics and basic indices such as PVR, PSA and the volume of prostate. IPSS was significantly improved among patients who received Toltrodine (p=0.0008 whereas both groups showed same score before treatment. Conclusion: It seems that combined therapy with anticholinergics and alpha blockers is a safe and efficient regimen among patients with BPH, either as primary or alternative treatment after the failure of conventional treatments.

Overview of clinical use and side effect profile of valsartan in Chinese hypertensive patients

Science.gov (United States)

Huang, Qi-Fang; Li, Yan; Wang, Ji-Guang

2014-01-01

We reviewed the Chinese and English literature for the efficacy and safety data of valsartan monotherapy or combination therapy in Chinese hypertensive patients. According to the data of ten randomized controlled trials, valsartan monotherapy was as efficacious as another angiotensin receptor blocker or other classes of antihypertensive drugs, excepting the slightly inferior diastolic blood pressure-lowering effect in comparison with calcium channel blockers. According to the data of six randomized controlled trials, valsartan combination, with hydrochlorothiazide, amlodipine, or nifedipine gastrointestinal therapeutic system, was more efficacious than monotherapy of valsartan, amlodipine, or nifedipine gastrointestinal therapeutic system. According to these trials, valsartan had an acceptable tolerability, regardless of whether it was used as monotherapy or in combination therapy. Nonetheless, several rare side effects have been reported, indicating that it should still be used with caution. This is of particular importance given that there are millions of hypertensive patients, worldwide, currently exposed to the drug. PMID:24403822

Severe iatrogenic bradycardia related to the combined use of beta-blocking agents and sodium channel blockers

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Kawabata M

2015-02-01

Full Text Available Mihoko Kawabata,1 Yasuhiro Yokoyama,1 Takeshi Sasaki,1 Susumu Tao,1 Kensuke Ihara,1 Yasuhiro Shirai,1 Tetsuo Sasano,2 Masahiko Goya,1 Tetsushi Furukawa,3 Mitsuaki Isobe,4 Kenzo Hirao1 1Heart Rhythm Center, Tokyo Medical and Dental University, Tokyo, Japan; 2Department of Biofunctional Informatics, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan; 3Department of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan; 4Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan Purpose: Drug-induced bradycardia is common during antiarrhythmic therapy; the major culprits are beta-blockers. However, whether other antiarrhythmic drugs are also a significant cause of this, alone or in combination with beta-blockers, is not well known. Methods: We retrospectively investigated the records of all patients hospitalized at our institution for drug-related bradycardia from the years 2004 to 2012. Patients with cardiac disease and electrolytic or hormonal abnormalities that could cause bradyarrhythmias were excluded. Results: Eight patients were identified (mean age, 79±5 years; range, 71–85 years; 6 women. Three patients were taking only beta-blockers (hereafter referred to as the BB group, while five patients were on both beta-blockers and Na channel blockers (hereafter referred to as the BB + Na group. Heart rates ranged from 20~49 beats/minute on arrival. The initial electrocardiogram showed sinus bradycardia (n=6 or sinus arrest with escape beats (n=2. QRS duration was 80–100 ms. The clinical presentation of the BB + Na group was considerably worse than that of the BB group, and included cardiogenic shock and heart failure. Four of the BB + Na patients had been on their medications for over 300 days. The BB group recovered solely with drug discontinuation, while 4 of the 5 patients in the BB + Na group needed additional

Acrolein-mediated conduction loss is partially restored by K+ channel blockers

Science.gov (United States)

Yan, Rui; Page, Jessica C.

2015-01-01

Acrolein-mediated myelin damage is thought to be a critical mechanism leading to conduction failure following neurotrauma and neurodegenerative diseases. The exposure and activation of juxtaparanodal voltage-gated K+ channels due to myelin damage leads to conduction block, and K+ channel blockers have long been studied as a means for restoring axonal conduction in spinal cord injury (SCI) and multiple sclerosis (MS). In this study, we have found that 100 μM K+ channel blockers 4-aminopyridine-3-methanol (4-AP-3-MeOH), and to a lesser degree 4-aminopyridine (4-AP), can significantly restore compound action potential (CAP) conduction in spinal cord tissue following acrolein-mediated myelin damage using a well-established ex vivo SCI model. In addition, 4-AP-3-MeOH can effectively restore CAP conduction in acrolein-damaged axons with a range of concentrations from 0.1 to 100 μM. We have also shown that while both compounds at 100 μM showed no preference of small- and large-caliber axons when restoring CAP conduction, 4-AP-3-MeOH, unlike 4-AP, is able to augment CAP amplitude while causing little change in axonal responsiveness measured in refractory periods and response to repetitive stimuli. In a prior study, we show that 4-AP-3-MeOH was able to functionally rescue mechanically injured axons. In this investigation, we conclude that 4-AP-3-MeOH is an effective K+ channel blocker in restoring axonal conduction following both primary (physical) and secondary (chemical) insults. These findings also suggest that 4-AP-3-MeOH is a viable alternative of 4-AP for treating myelin damage and improving function following central nervous system trauma and neurodegenerative diseases. PMID:26581866

The review of identification and assay methods of β-blockers

Directory of Open Access Journals (Sweden)

Ольга Олександрівна Віслоус

2015-10-01

Full Text Available Every year the number of β-blockers on the pharmaceutical market is increasing, requiring systematization of their standardization methods.Aim of research. The aim of our research is to study literature data about identification and assay methods of β-blockers with different direction of action – selective (praktolol, metoprolol, atenolol, acebutolol, betaxolol, bevantolol, bisoprolol, celiprolol, esmolol, epanolol, esatenolol, nebivolol, Talinolol, non-selective (alprenolol, Oxprenololum, pindolol, propranolol, timolol, sotalol, nadolol, mepindolol, karteol, tertatolol, bopindolol, bupranolol, penbutolol, kloranolol and combined (labetalol, carvedilol.Methods. The analytical review of literature sources about β-blockers analysis by physical, chemical, and physicochemical methods.Results. After literature sources’ analyzing it was found that physical and physicochemical constants are basically used for β-blockers pharmacopoeial analysis; both physicochemical values and chemical reactions are used in forensic analysis, resulting in the article.It was founded that titration methods, mostly acid-base titration method, are used for β-blockers assay in the analysis of substances. For β-blockers detection in biological fluids and dosage forms, active pharmaceutical ingredients and metabolites mixture separation one should prefer physicochemical methods, such as gas chromatography and liquid chromatography, absorption UV-Visible spectroscopy, fluorometry, etc.Conclusion. The results have shown can be used for the further search of the identification and assay optimal methods of β-blockers both pure and mixed with other active substances and excipients

STUDY OF PHARMACO THERAPEUTIC CONSIDERATIONS IN THE MANAGEMENT OF HEART FAILURE

Directory of Open Access Journals (Sweden)

Souris Kondaveti

2015-02-01

Full Text Available BACKGROUND AND OBJECTIVES: Congestive heart failure (CHF continues to be a major clinical and public health problem. Conflicting data exists about its rate of occurrence in general population, relative frequencies of predisposing heart diseases and the prognosis of the patient. In the present study, gender aspects, age wise distribution, drug distribution pattern were assessed in these patients. MATERIALS AND METHODS: A total number of 100 patients from the medical outpatient department of medicine, M.G.M. Hospital Warangal were en rolled into the study. All male and female patients between 30 to 85 years of age, diagnosed with heart failure falling into the category of functional New York Heart Association (NYHA class II or III with left ventricular ejection fraction (LVEF ≤35% we re included in the study. RESULTS: Of the 100 subjects studied 55 (40 - 75 yr were male and 45 (35 - 73 yr were female. 94 patients presented with ischemic heart failure compared to only 6 patients with non - ischemic heart failure. Out of total subjects enrol led, 61 were put on Digoxin, 71 on Diuretics, 47 on ACEI, 20 on Beta Blocker (Carvedilol, 30 on Nitrates, 64 on Anticoagulants, 19 on Statins. CONCLUSION: The incidence of heart failure was more in advanced age groups and slightly more common in males. Is chemic heart disease accounted for heart failure in majority of patients in our study we found that Digoxin, Diuretics, ACEI and Anticoagulants followed by Nitrates, Beta blockers and Statins were the most prescribed medications in the management of heart failure

Association of beta-adrenergic receptor polymorphisms and mortality in carvedilol-treated chronic heart-failure patients

DEFF Research Database (Denmark)

Petersen, Morten; Andersen, Jon T; Hjelvang, Brian R

2011-01-01

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Chronic heart failure (HF) is a syndrome with increasing prevalence. Though mortality is still high, the introduction of ß-adrenoceptor blockers for its treatment has improved survival considerably. • As is the case for all medical treatment, not all...... patients benefit from ß-adrenoceptor blocker treatment, and stratifying patients to different ß-adrenoceptor blockers by the use of pharmacogenomics might be of great value in improving HF therapy. • Previous studies have shown that the two single nucleotide polymorphisms (SNPs) ADRB1 Arg389Gly and ADRB2...... Gln27Glu interact with the ß-adrenoceptor blockers metoprolol and carvedilol, respectively. These interactions have led to stratified responses with regard to surrogate parameters, e.g. left ventricular ejection fraction (LVEF), pulse and blood pressure. • Several studies have failed to show...

Direct renin inhibition in addition to or as an alternative to angiotensin converting enzyme inhibition in patients with chronic systolic heart failure: rationale and design of the Aliskiren Trial to Minimize OutcomeS in Patients with HEart failuRE (ATMOSPHERE) study

DEFF Research Database (Denmark)

Krum, Henry; Massie, Barry; Abraham, William T

2011-01-01

AIMS: The renin-angiotensin-aldosterone system (RAAS) represents a key therapeutic target in heart failure (HF) management. However, conventional agents that block this system induce a reflex increase in plasma renin activity (PRA), which may lead to RAAS 'escape'. Direct renin inhibitors (DRIs......S for Patients with HEart failuRE (ATMOSPHERE) study is to evaluate the effect of both aliskiren and enalapril monotherapy and aliskiren/enalapril combination therapy on cardiovascular death and HF hospitalization in patients with chronic systolic HF, NYHA functional class II-IV symptoms, and elevated plasma...... levels of BNP. Methods Patients tolerant to at least 10 mg or equivalent of enalapril will undergo an open-label run-in period where they receive enalapril then aliskiren. Approximately 7000 patients tolerating this run-in period will then be randomized 1:1:1 to aliskiren monotherapy, enalapril...

Fracture risk in perimenopausal women treated with beta-blockers

DEFF Research Database (Denmark)

Rejnmark, Lars; Vestergaard, Peter; Kassem, M.

2004-01-01

beta2-Adrenergic receptors have been identified on human osteoblastic and osteoclastic cells, raising the question of a sympathetic regulation of bone metabolism. We investigated effects of treatment with beta-adrenergic receptor antagonists (beta-blockers) on bone turnover, bone mineral density...... (BMD), and fracture risk. Within the Danish Osteoporosis Prevention Study (DOPS) a population based, comprehensive cohort study of 2016 perimenopausal women, associations between treatment with beta-blockers and bone turnover and BMD were assessed in a cross-sectional design at the start of study....... Moreover, in a nested case-control design, fracture risk during the subsequent 5 years was assessed in relation to treatment with beta-blockers at baseline. Multiple regression- and logistic regression-analyses were performed. Treatment with beta-blockers was associated with a threefold increased fracture...

Pioglitazone and the risk of cardiovascular events in patients with Type 2 diabetes receiving concomitant treatment with nitrates, renin-angiotensin system blockers, or insulin: results from the PROactive study (PROactive 20).

Science.gov (United States)

Erdmann, Erland; Spanheimer, Robert; Charbonnel, Bernard

2010-09-01

Patients with Type 2 diabetes mellitus (T2DM) are often treated with multiple glucose-lowering and cardiovascular agents. The concomitant use of nitrates, renin-angiotensin system (RAS) blockers, or insulin has been linked to a potential increase in myocardial ischemic risk with rosiglitazone. The PROactive database provides an opportunity to investigate the effects of these medications on the potential macrovascular benefits reported with pioglitazone. The PROactive study was a randomized double-blind prospective trial that evaluated mortality and cardiovascular morbidity in 5238 patients with T2DM and macrovascular disease. Patients received pioglitazone or placebo in addition to their baseline glucose-lowering and cardiovascular medications. The effect of pioglitazone on composite endpoints was evaluated, including all-cause death, myocardial infarction (MI), and stroke, as well as safety events of edema and serious heart failure, in subgroups using nitrates, RAS blockers, or insulin at baseline. The risk of all-cause death, MI, and stroke for pioglitazone versus placebo was similar regardless of the baseline use of nitrates, RAS blockers, or insulin, with hazard ratios ranging from 0.81 to 0.87. Similar results were obtained for the other composite endpoints analyzed. There were no significant interactions between baseline medication subgroups and treatment. The increased risk of edema and serious heart failure was consistent across the baseline medication subgroups. This post hoc analysis did not reveal an increased risk of macrovascular events with pioglitazone in patients receiving nitrates, RAS blockers, or insulin. Rather, all patients realized the same trend towards benefit with pioglitazone, and adverse events of edema and heart failure were predictable. © 2010 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.

Success of electromagnetic shock wave lithotripter as monotherapy ...

African Journals Online (AJOL)

K.S. Meitei

Objectives: To evaluate the success of shock wave lithotripsy (SWL) as monotherapy for solitary .... history of previous renal surgery on the affected side were excluded .... energy. Twelve (63.2%) of the steinstrasse cases were managed con-.

Sacubitril/Valsartan: The Newest Addition to the Toolbox for Guideline-Directed Medical Therapy of Heart Failure.

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Rodgers, Jo E

2017-06-01

Sacubitril/valsartan combines a neprilysin inhibitor with an angiotensin receptor blocker. As an inhibitor of neprilysin, an enzyme that degrades biologically active natriuretic peptides, this first-in-class therapy increases levels of circulating natriuretic peptides, resulting in natriuretic, diuretic, and vasodilatory effects. In patients with chronic New York Heart Association class II-IV heart failure with reduced ejection fraction, the PARADIGM-HF trial demonstrated that sacubitril/valsartan significantly reduced the primary endpoint of cardiovascular mortality and heart failure hospitalization, compared with enalapril. The rate of all-cause mortality was also significantly reduced. Subsequently, the American College of Cardiology/American Heart Association/Heart Failure Society of America recently updated guideline recommendations for Stage C patients with heart failure with reduced ejection fraction to recommend angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or sacubitril/valsartan in conjunction with other evidence-based therapies to reduce morbidity and mortality. Several analyses have suggested the cost-effectiveness of this new therapy. To ensure tolerability, initiating the lower dosage form of sacubitril/valsartan is warranted in patients with severe renal impairment, moderate hepatic impairment, and low blood pressure, and close monitoring is warranted in such patients. A 36-hour washout period is recommended when switching patients from an angiotensin-converting enzyme inhibitor to sacubitril/valsartan. Similarly, sacubitril/valsartan is contraindicated in patients receiving concomitant angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and those with a history of angioedema. Copyright © 2017 Elsevier Inc. All rights reserved.

Long-term Outcome of Irish Wolfhound Dogs with Preclinical Cardiomyopathy, Atrial Fibrillation, or Both Treated with Pimobendan, Benazepril Hydrochloride, or Methyldigoxin Monotherapy.

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Vollmar, A C; Fox, P R

2016-01-01

Dilated cardiomyopathy (DCM) is a common cause of morbidity and mortality in the Irish Wolfhound (IW). However, the benefit of medical treatment in IW dogs with preclinical DCM, atrial fibrillation (AF), or both has not been demonstrated. Compare the time to develop congestive heart failure (CHF) or sudden death in IW dogs with preclinical DCM, AF, or both receiving monotherapy with pimobendan, methyldigoxin, or benazepril hydrochloride. Seventy-five client-owned IW dogs. Irish Wolfhound dogs were prospectively randomized to receive pimobendan (Vetmedin®), benazepril HCl (Fortekor®), or methyldigoxin (Lanitop®) monotherapy in a 1:1:1 ratio in a blinded clinical trial. The prospectively defined composite primary endpoint was onset of CHF or sudden death. To assure stringent evaluation of treatment effect, data from dogs complying with the study protocol were analyzed. Sixty-six IW fulfilling the study protocol included 39 males, 27 females; median (interquartile range) age, 4.0 years (3.0-5.0 years) and weight, 70.0 kg (63.0-75.0 kg). Primary endpoint was reached in 5 of 23 (21.7%) IW receiving pimobendan, 11 of 22 (50.0%) receiving benazepril HCl, and 9 of 21 (42.9%) receiving methyldigoxin. Median time to primary endpoint was significantly longer for pimobendan (1,991 days; 65.4 months) compared to methyldigoxin (1,263 days; 41.5 months; P = .031) or benazepril HCl-(997 days; 32.8 months; P = .008) treated dogs. In IW dogs with preclinical DCM, AF or both, pimobendan monotherapy significantly prolonged time to onset of CHF or sudden death than did monotherapy with benazepril HCl or methyldigoxin. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Adherence to the European Society of Cardiology guidelines for the treatment of chronic heart failure

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Sitepu, A.; Hamdani, K.

2018-03-01

Heart failure is a tremendous health problem with significant morbidity and mortality. The treatment of heart failure should be applied appropriately to improve the successful management of patients. This study aims to evaluate the adherence to European Society of Cardiology (ESC) guidelines for the treatment of chronic heart failure and to determine factors associated with guideline adherence. This study is an observational study comprising 97 patients with chronic heart failure with reduced ejection fraction. The guideline adherence was assessed the by the use of guideline adherence indicator (GAI), which consider GAI-3 or GAI-5, by calculating the proportion of recommended drugs was prescribed divided by a number of drugs indicated according to the ESC guidelines, in the absence of contraindications. The results showed the use of each indicated drugs were angiotensin- converting enzyme inhibitors or angiotensin receptor blockers (78.4%), beta-blockers (61.9%), mineralocorticoid receptor antagonists (61.9%), diuretics (89.7%), and digitalis (26.8%). Furthermore, the predominant categories of GAI-3 and GAI-5 were moderate. This study demonstrates that the adherence to ESC guidelines for the treatment of chronic heart failure still needs to be improved compared to recent studies. Also, age, etiology of heart failure and comorbidity were associated factors that influence the implementation of ESC guidelines.

Comparison of the efficacy of dihydropyridine calcium channel blockers in African American patients with hypertension. ISHIB Investigators Group. International Society on Hypertension in Blacks.

Science.gov (United States)

Hall, W D; Reed, J W; Flack, J M; Yunis, C; Preisser, J

1998-10-12

Hypertension is a prevalent disease among African Americans, and successful treatment rates are low. Since calcium channel blockers are well-tolerated and efficacious in African Americans, we undertook this study to compare the efficacy, safety, and tolerability of 3 commonly prescribed calcium channel blockers: amlodipine besylate (Norvasc), nifedipine coat core (CC) (Adalat CC), and nifedipine gastrointestinal therapeutic system (GITS) (Procardia XL). One hundred ninety-two hypertensive patients across 10 study centers were randomly assigned to double-blind monotherapy with amlodipine besylate (5 mg/d), nifedipine CC (30 mg/d), or nifedipine GITS (30 mg/d) for 8 weeks. Patients not achieving therapeutic response after 4 weeks had their dose doubled for the next 4 weeks. The primary end point was a comparison of the average reduction (week 8 minus baseline) in 24-hour ambulatory diastolic blood pressure (DBP). Secondary end points included a comparison of average 24-hour ambulatory systolic blood pressure (SBP), office SBP or DBP reduction, responder rates, safety, and tolerability. One hundred sixty-three patients were evaluable for efficacy after 8 weeks. There was no significant difference in the average 24-hour ambulatory DBP (-8.5, -9.0, and -6.1 mm Hg, respectively) or SBP (-14.3, -15.7, and -11.8 mm Hg, respectively) reduction. Average office SBP and DBP were reduced to a comparable degree (19-22 mm Hg [P =.50] and 12-14 mm Hg [P =.51], respectively). Responder rates (DBP or = 10 mm Hg) were similar (P = .38). Discontinuation rates and adverse event frequency were distributed similarly across the 3 treatment groups. The efficacy, safety, and tolerability of the 3 dihydropyridine calcium channel blockers are equivalent in African Americans with stages 1 and 2 hypertension.

Photochemical fate of beta-blockers in NOM enriched waters

International Nuclear Information System (INIS)

Wang, Ling; Xu, Haomin; Cooper, William J.; Song, Weihua

2012-01-01

Beta-blockers, prescribed for the treatment of high blood pressure and for long-term use after a heart attack, have been detected in surface and ground waters. This study examines the photochemical fate of three beta-blockers, atenolol, metoprolol, and nadolol. Hydrolysis accounted for minor losses of these beta-blockers in the pH range 4–10. The rate of direct photolysis at pH 7 in a solar simulator varied from 6.1 to 8.9 h −1 at pH 7. However, the addition of a natural organic matter (NOM) isolate enhanced the photochemical loss of all three compounds. Indirect photochemical fate, generally described by reactions with hydroxyl radical (·OH) and singlet oxygen ( 1 ΔO 2 ), and, the direct reaction with the triplet excited state, 3 NOM ⁎ , also varied but collectively appeared to be the major loss factor. Bimolecular reaction rate constants of the three beta-blockers with 1 ΔO 2 and ·OH were measured and accounted for 0.02–0.04% and 7.2–38.9% of their loss, respectively. These data suggest that the 3 NOM ⁎ contributed 50.6–85.4%. Experiments with various 3 NOM ⁎ quenchers supported the hypothesis that it was singly the most important reaction. Atenolol was chosen for more detailed investigation, with the photoproducts identified by LC–MS analysis. The results suggested that electron-transfer could be an important mechanism in photochemical fate of beta-blockers in the presence of NOM. - Highlights: ► Photochemical degradation of beta-blockers in the simulated natural waters. ► Reactive Oxygen Species play a minor role in the indirect photodegradation. ► The loss of beta-blockers results from direct reaction with 3 DOM ⁎ .

Beta-Blockers and Nitrates: Pharmacotherapy and Indications.

Science.gov (United States)

Facchini, Emanuela; Degiovanni, Anna; Cavallino, Chiara; Lupi, Alessandro; Rognoni, Andrea; Bongo, Angelo S

2015-01-01

Many clinically important differences exist between beta blockers. B1-selectivity is of clinical interest because at clinically used doses, b1- selective agents block cardiac b-receptors while having minor effects on bronchial and vascular b-receptors. Beta-adrenergic blocking agents significantly decrease the frequency and duration of angina pectoris, instead the prognostic benefit of beta-blockers in stable angina has been extrapolated from studies of post myocardial infarction but has not yet been documented without left ventricular disfunction or previous myocardial infarction. Organic nitrates are among the oldest drugs, but they still remain a widely used adjuvant in the treatment of symptomatic coronary artery disease. While their efficacy in relieving angina pectoris symptoms in acute settings and in preventing angina before physical or emotional stress is undisputed, the chronic use of nitrates has been associated with potentially important side effects such as tolerance and endothelial dysfunction. B-blockers are the firstline anti-anginal therapy in stable stable angina patients without contraindications, while nitrates are the secondline anti-anginal therapy. Despite 150 years of clinical practice, they remain fascinating drugs, which in a chronic setting still deserve investigation. This review evaluated pharmacotherapy and indications of Beta-blockers and nitrates in stable angina.

Beta-blockers and depression in elderly hypertension patients in primary care

DEFF Research Database (Denmark)

Ringoir, Lianne; Pedersen, Susanne S.; Widdershoven, Jos W M G

2014-01-01

BACKGROUND AND OBJECTIVES: Previous findings regarding a possible association between beta-blocker use and depression are mixed. To our knowledge there have been no studies investigating the association of beta-blockers with depression in primary care hypertension patients without previous...... myocardial infarction. The aim of this study was to determine the relation between lipophilic beta-blocker use and depression in elderly primary care patients with hypertension. METHODS: This was a cross-sectional study in primary care practices located in the South of The Netherlands. Primary care...... for potential confounders. CONCLUSIONS: Our findings show that primary care hypertension patients who use a lipophilic beta-blocker are more likely to have higher depression scores than those who do not use a lipophilic beta-blocker....

USE OF DRUGS AND PATIENT’S QUALITY OF LIFE IN HEART FAILURE CLINIC

Directory of Open Access Journals (Sweden)

Mitja Lainščak

2003-05-01

Full Text Available Background. Heart failure is associated with poor quality of life and frequent hospitalizations. Implementation of the clinical trials results, especially prescription of adequate daily doses, is regarded as insufficient. In Slovenia there is no data on quality of life in patients treated in heart failure clinic.Aim. This study assessed the effects of heart failure clinic on patients pharmacological treatment, number of hospitalisations and quality of life.Methods. Patients with established heart failure were enrolled on a basis of the European Society of Cardiology guidelines.Results. During seven months 48 patients (28 men and 20 women, aged 68.4 ± 11.9 years were included. Half of the patients referred after heart failure hospitalisation. After mean of 3.8 ± 1.5 visits in mean time of 2.9 ± 2.6 months more patients received angiotenzin converting enzyme inhibitors and beta adrenergic blockers (90 vs. 100%, p < 0.05 and 42% vs. 88%, p < 0.001, respectively. There was also an increase in mean daily dose of both drugs: from 60% to 86% for angiotenzin converting enzyme inhibitors and from 26% to 44% for beta adrenergic blockers (p < 0.001 for both. Hospital admissions were reduced by 79%. Quality of life, health, MLHFQ result and NYHA class all significantly improved (p < 0.001.Conclusions. Heart failure clinic can significantly improve patient’s quality of life and pharmacological treatment as well as reduce number of admissions due to heart failure.

[Assessment of medical management of heart failure at National Hospital Blaise COMPAORE].

Science.gov (United States)

Kambiré, Y; Konaté, L; Diallo, I; Millogo, G R C; Kologo, K J; Tougouma, J B; Samadoulougou, A K; Zabsonré, P

2018-05-09

The aim of this study was to assess the quality of medical management of heart failure at the National Hospital Blaise Compaoré according to the international guidelines. A retrospective study was performed including consecutive patients admitted for heart failure documented sonographically from October 2012 to March 2015 in the Medicine and Medical Specialties Department of National Hospital Blaise Compaore with a minimum follow-up of six weeks. Data analysis was made by the SPSS 20.0 software. Eighty-four patients, mean age of 57.61±18.24 years, were included. It was an acute heart failure in 84.5% of patients with systolic left ventricular function impaired (77.4%). The rate of prescription of different drugs in heart failure any type was 88.1% for loop diuretics; 77.1% for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and 65.5% for betablockers. In patients with systolic dysfunction, 84.62% of patients were received the combination of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and 75.38% for betablockers. Exercise rehabilitation was undergoing in 10.7% of patients. The death rate was 16.7% and hospital readmission rate of 16.7%. The prescription rate of major heart failure drugs is satisfactory. Cardiac rehabilitation should be developed. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Biologic and oral disease-modifying antirheumatic drug monotherapy in rheumatoid arthritis

Science.gov (United States)

Emery, Paul; Sebba, Anthony; Huizinga, Tom W J

2013-01-01

Clinical evidence demonstrates coadministration of tumour necrosis factor inhibitor (TNFi) agents and methotrexate (MTX) is more efficacious than administration of TNFi agents alone in patients with rheumatoid arthritis, leading to the perception that coadministration of MTX with all biologic agents or oral disease-modifying antirheumatic drugs is necessary for maximum efficacy. Real-life registry data reveal approximately one-third of patients taking biologic agents use them as monotherapy. Additionally, an analysis of healthcare claims data showed that when MTX was prescribed in conjunction with a biologic agent, as many as 58% of patients did not collect the MTX prescription. Given this discrepancy between perception and real life, we conducted a review of the peer-reviewed literature and rheumatology medical congress abstracts to determine whether data support biologic monotherapy as a treatment option for patients with rheumatoid arthritis. Our analysis suggests only for tocilizumab is there evidence that the efficacy of biologic monotherapy is comparable with combination therapy with MTX. PMID:23918035

PATIENT WITH CHRONIC HEART FAILURE. RATIONAL CHOICE OF THERAPY

Directory of Open Access Journals (Sweden)

O. M. Drapkina

2017-01-01

Full Text Available The theory of chronic hyperactivation of neurohormonal systems, in particular, sympathoadrenal and renin-angiotensin-aldosterone, is the basis of modern concepts of the pathogenesis of heart failure. The medicinal blocking of these two systems has proved to be effective in the treatment of heart failure with reduced ejection fraction (<40%. Antagonists of mineralocorticoid receptors, along with angiotensin-converting enzyme inhibitors and beta-blockers, are neurohumoral modulators. They are used to treat patients with heart failure with reduced ejection fraction. The prescription of mineralocorticoid receptor antagonists in clinical practice remains insufficient despite their high efficacy. Demonstration of the site of mineralocorticoid receptor antagonists in the complex treatment of a patient with chronic heart failure and diabetes type 2 is the goal of this article.

Hinge-deleted IgG4 blocker therapy for acetylcholine receptor myasthenia gravis in rhesus monkeys.

Science.gov (United States)

Losen, Mario; Labrijn, Aran F; van Kranen-Mastenbroek, Vivianne H; Janmaat, Maarten L; Haanstra, Krista G; Beurskens, Frank J; Vink, Tom; Jonker, Margreet; 't Hart, Bert A; Mané-Damas, Marina; Molenaar, Peter C; Martinez-Martinez, Pilar; van der Esch, Eline; Schuurman, Janine; de Baets, Marc H; Parren, Paul W H I

2017-04-20

Autoantibodies against ion channels are the cause of numerous neurologic autoimmune disorders. Frequently, such pathogenic autoantibodies have a restricted epitope-specificity. In such cases, competing antibody formats devoid of pathogenic effector functions (blocker antibodies) have the potential to treat disease by displacing autoantibodies from their target. Here, we have used a model of the neuromuscular autoimmune disease myasthenia gravis in rhesus monkeys (Macaca mulatta) to test the therapeutic potential of a new blocker antibody: MG was induced by passive transfer of pathogenic acetylcholine receptor-specific monoclonal antibody IgG1-637. The effect of the blocker antibody (IgG4Δhinge-637, the hinge-deleted IgG4 version of IgG1-637) was assessed using decrement measurements and single-fiber electromyography. Three daily doses of 1.7 mg/kg IgG1-637 (cumulative dose 5 mg/kg) induced impairment of neuromuscular transmission, as demonstrated by significantly increased jitter, synaptic transmission failures (blockings) and a decrease in the amplitude of the compound muscle action potentials during repeated stimulations (decrement), without showing overt symptoms of muscle weakness. Treatment with three daily doses of 10 mg/kg IgG4Δhinge-637 significantly reduced the IgG1-637-induced increase in jitter, blockings and decrement. Together, these results represent proof-of principle data for therapy of acetylcholine receptor-myasthenia gravis with a monovalent antibody format that blocks binding of pathogenic autoantibodies.

New Medications for Heart Failure

Science.gov (United States)

Gordin, Jonathan S.; Fonarow, Gregg C.

2016-01-01

Heart failure is common and results in substantial morbidity and mortality. Current guideline-based therapies for heart failure with reduced ejection fraction, including beta-blockers, angiotensin converting enzyme (ACE) inhibitors, and aldosterone antagonists aim to interrupt deleterious neurohormonal pathways and have shown significant success in reducing morbidity and mortality associated with heart failure. Continued efforts to further improve outcomes in patients with heart failure with reduced ejection fraction have led to the first new-in-class medications approved for heart failure since 2005, ivabradine and sacubitril/valsartan. Ivabradine targets the If channels in the sinoatrial node of the heart, decreasing heart rate. Sacubitril/valsartan combines a neprilysin inhibitor that increases levels of beneficial vasodilatory peptides with an angiotensin receptor antagonist. On a background of previously approved, guideline-directed medical therapies for heart failure, these medications have shown improved clinical outcomes ranging from decreased hospitalizations in a select group of patients to a reduction in all-cause mortality across all pre-specified subgroups. In this review, we will discuss the previously established guideline-directed medical therapies for heart failure with reduced ejection fraction, the translational research that led to the development of these new therapies, and the results from the major clinical trials of ivabradine and sacubitril/valsartan. PMID:27038558

Prognostic Impact of Loop Diuretics in Patients With Chronic Heart Failure　- Effects of Addition of Renin-Angiotensin-Aldosterone System Inhibitors and β-Blockers.

Science.gov (United States)

Miura, Masanobu; Sugimura, Koichiro; Sakata, Yasuhiko; Miyata, Satoshi; Tadaki, Soichiro; Yamauchi, Takeshi; Onose, Takeo; Tsuji, Kanako; Abe, Ruri; Oikawa, Takuya; Kasahara, Shintaro; Nochioka, Kotaro; Takahashi, Jun; Shimokawa, Hiroaki

2016-05-25

It remains to be elucidated whether addition of renin-angiotensin-aldosterone system (RAAS) inhibitors and/or β-blockers to loop diuretics has a beneficial prognostic impact on chronic heart failure (CHF) patients. From the Chronic Heart failure Analysis and Registry in the Tohoku district 2 (CHART-2) Study (n=10,219), we enrolled 4,134 consecutive patients with symptomatic stage C/D CHF (mean age, 69.3 years, 67.7% male). We constructed Cox models for composite of death, myocardial infarction, stroke and HF admission. On multivariate inverse probability of treatment weighted (IPTW) Cox modeling, loop diuretics use was associated with worse prognosis with hazard ratio (HR) 1.28 (Pdiuretics were associated with worse prognosis with HR 1.32 and 1.56, respectively (both Pdiuretics. Chronic use of loop diuretics is significantly associated with worse prognosis in CHF patients in a dose-dependent manner, whereas the triple combination of RAAS inhibitor(s), MRA, and β-blocker(s) is associated with better prognosis when combined with low-dose loop diuretics. (Circ J 2016; 80: 1396-1403).

Rhabdomyolysis Associated with Fenofibrate Monotherapy in a Patient with Chronic Myelogenous Leukemia

Directory of Open Access Journals (Sweden)

Kazuya Kato

2011-08-01

Full Text Available Rhabdomyolysis associated with fenofibrate monotherapy is extremely rare. Here, we report a rare case of rhabdomyolysis of the psoas muscle in an 82-year-old man with chronic myelogenous leukemia (CML. He was prescribed fenofibrate because of a hypertriglyceridemia. The patient reported generalized muscle pain and right abdominal pain while receiving fenofibrate monotherapy. An abdominal computed tomography scan and an abdominal ultrasound showed a large and low attenuation and high echogenicity, respectively, in the right middle abdominal area. Laboratory values included a serum creatine concentration of 4.1 mg/dl and a creatinine phosphokinase concentration of 5,882 IU/l. During laparotomy, a large hematoma and necrotic mass was identified in the right psoas muscle. Histological examination revealed that the resected specimens were of the psoas muscle with irregular fiber sizes, degenerating fibers surrounding the inflammatory reaction, and fiber necrosis that is typical for polymyositis. Based on these findings and the clinical history, a diagnosis of fenofibrate-induced rhabdomyolysis was made. To the best of our knowledge, no patient has ever been diagnosed with fulminant psoas rhabdomyolysis due to a fenofibrate monotherapy. This report details the rare case of rhabdomyolysis in a patient with CML associated with fenofibrate monotherapy and offers a review of the literature.

ESC guidelines adherence is associated with improved survival in patients from the Norwegian Heart Failure Registry.

Science.gov (United States)

De Blois, Jonathan; Fagerland, Morten Wang; Grundtvig, Morten; Semb, Anne Grete; Gullestad, Lars; Westheim, Arne; Hole, Torstein; Atar, Dan; Agewall, Stefan

2015-01-01

To assess the adherence to heart failure (HF) guidelines for angiotensin-converting enzyme-I (ACE-I), angiotensin II receptor blockers (ARB), and β-blockers and the possible association of ACE-I or ARB, β-blockers, and statins with survival in the large contemporary Norwegian Heart Failure Registry. The study included 5761 outpatients who were diagnosed with HF of any aetiology (mean left ventricular ejection fraction 32% ± 11%) from January 2000 to January 2010 and followed up until death or February 2010. Adherence to treatment according to the guidelines was high. Cox regression analysis to identify risk factors for all-cause mortality, after adjustment for many factors, showed that ACE-I ≥ 50% of target dose, use of beta-blockers, and statins were significantly related to improved survival (P = 0.003, P < 0.001, and P < 0.001, respectively). Propensity scoring showed the same benefit for these variables. Both multivariable and propensity scoring analyses showed survival benefits with β-blockers, statins, and adequate doses of ACE-I in this contemporary HF cohort. This study stresses the importance of guidelines adherence, even in the context of high levels of adherence to guidelines. Moreover, respecting the recommended target doses of ACE-I appears to have a crucial role in survival improvement and, in the multivariate Cox regression analysis, ARB treatment was not significantly associated with a lower all-cause mortality. Published on behalf of the European Society of Cardiology. All rights reserved. ©The Author 2015. For permissions please email: journals.permissions@oup.com.

Beta-blocker use and fall risk in older individuals

NARCIS (Netherlands)

Ham, Annelies C.; Dijk, van S.C.; Swart, Karin M.A.; Enneman, Anke W.; Zwaluw, van der Nikita L.; Brouwer-Brolsma, Elske M.; Schoor, van Natasja M.; Zillikens, M.C.; Lips, Paul; Groot, de Lisette C.P.G.M.; Hofman, Albert; Witkamp, Renger F.; Uitterlinden, André G.; Stricker, Bruno H.; Velde, van der Nathalie

2017-01-01

Aims: To investigate the association between use of β-blockers and β-blocker characteristics - selectivity, lipid solubility, intrinsic sympathetic activity (ISA) and CYP2D6 enzyme metabolism - and fall risk. Methods: Data from two prospective studies were used, including community-dwelling

Beta-blocker therapy for tremor in Parkinson's disease.

Science.gov (United States)

Crosby, N J; Deane, K H O; Clarke, C E

2003-01-01

The tremor of Parkinson's disease can cause considerable disability for the individual concerned. Traditional antiparkinsonian therapies such as levodopa have only a minor effect on tremor. Beta-blockers are used to attenuate other forms of tremor such as Essential Tremor or the tremor associated with anxiety. It is thought that beta-blockers may be of use in controlling the tremor of Parkinson's disease. To compare the efficacy and safety of adjuvant beta-blocker therapy against placebo for the treatment of tremor in patients with Parkinson's disease. Electronic searches of MEDLINE, EMBASE, SCISEARCH, BIOSIS, GEROLIT, OLDMEDLINE, LILACS, MedCarib, PASCAL, JICST-EPLUS, RUSSMED, DISSERTATION ABSTRACTS, SIGLE, ISI-ISTP, Aslib Index to Theses, The Cochrane Controlled Trials Register, Clinicaltrials.gov, metaRegister of Controlled Trials, NIDRR, NRR and CENTRAL were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of beta-blockers were contacted. Randomised controlled trials of adjuvant beta-blocker therapy versus placebo in patients with a clinical diagnosis of idiopathic Parkinson's disease. Data was abstracted independently by two of the authors onto standardised forms and disagreements were resolved by discussion. Four randomised controlled trials were found comparing beta-blocker therapy with placebo in patients with idiopathic Parkinson's disease. These were double-blind cross-over studies involving a total of 72 patients. Three studies did not present data from the first arm, instead presenting results as combined data from both treatment arms and both placebo arms. The risk of a carry-over effect into the second arm meant that these results were not analysed. The fourth study presented data from each arm. This was in the form of a mean total score for tremor for each group. Details of the baseline scores, the numbers of patients in each group and standard deviations were not

Asthma Severity in patients initiating controller monotherapy versus combination therapy.

Science.gov (United States)

Diette, Gregory B; Fuhlbrigge, Anne L; Allen-Ramey, Felicia; Hopper, April; Sajjan, Shiva G; Markson, Leona E

2011-04-01

Asthma treatment guidelines recommend medications based on the level of asthma control. To evaluate differences in asthma control between patients who initiated asthma controller monotherapy versus combination therapy. Children (5-16 years; n = 488) and adults (17-80 years; n = 530) with asthma and no controller therapy in the prior 6 months were included. Telephone surveys were conducted within 5 days of filling a new asthma controller prescription with either the caregiver of children or the adult patient. Demographics, asthma control before therapy, and asthma-related resource use were assessed for patients initiating monotherapy (filling one asthma controller prescription) and combination therapy (filling more than one controller medication or a fixed-dose combination). Mean pediatric age was 10 years; 53% were male. Mean adult age was 47 years; 25% were male. There were no significant differences in asthma control score between patients receiving monotherapy and combination therapy. Children on combination therapy did not have more nighttime awakening or short-acting β-agonist use but were more likely to have been hospitalized due to asthma attack (p = .05) and have more unscheduled (p = .0374) and scheduled (p = .009) physician visits. Adults on combination therapy were more likely to have been hospitalized due to asthma attack (p asthma (p asthma control scores in the 4 weeks before index medication suggests that asthma severity during a treatment-free period did not differ significantly for patients initiating controller monotherapy versus combination therapy. From these findings, it appears that although physicians may not focus on asthma control when choosing the intensity of initial controller therapy, the intensity of health-care encounters may be an influence.

Postmeal exercise blunts postprandial glucose excursions in people on metformin monotherapy.

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Erickson, Melissa L; Little, Jonathan P; Gay, Jennifer L; McCully, Kevin K; Jenkins, Nathan T

2017-08-01

Metformin is used clinically to reduce fasting glucose with minimal effects on postprandial glucose. Postmeal exercise reduces postprandial glucose and may offer additional glucose-lowering benefit beyond that of metformin alone, yet controversy exists surrounding exercise and metformin interactions. It is currently unknown how postmeal exercise and metformin monotherapy in combination will affect postprandial glucose. Thus, we examined the independent and combined effects of postmeal exercise and metformin monotherapy on postprandial glucose. A randomized crossover design was used to assess the influence of postmeal exercise on postprandial glucose excursions in 10 people treated with metformin monotherapy (57 ± 10 yr, HbA 1C  = 6.3 ± 0.6%). Each participant completed the following four conditions: sedentary and postmeal exercise (5 × 10-min bouts of treadmill walking at 60% V̇o 2max ) with metformin and sedentary and postmeal exercise without metformin. Peak postprandial glucose within a 2-h time window and 2-h total area under the curve was assessed after a standardized breakfast meal, using continuous glucose monitoring. Postmeal exercise significantly blunted 2-h peak ( P = 0.001) and 2-h area under the curve ( P = 0.006), with the lowest peak postprandial glucose excursion observed with postmeal exercise and metformin combined ( P exercise: 9.7 ± 2.3, washout/sedentary: 13.3 ± 3.2, washout/exercise: 11.1 ± 3.4 mmol/l). Postmeal exercise and metformin in combination resulted in the lowest peak postprandial glucose excursion compared with either treatment modality alone. Exercise timed to the postprandial phase may be important for optimizing glucose control during metformin monotherapy. NEW & NOTEWORTHY The interactive effects of metformin and exercise on key physiological outcomes remain an area of controversy. Findings from this study show that the combination of metformin monotherapy and moderate-intensity postmeal exercise led to

A combined role of calcium channel blockers and angiotensin receptor blockers in stroke prevention

Directory of Open Access Journals (Sweden)

Ji-Guang Wang

2009-07-01

Full Text Available Ji-Guang WangCentre for Epidemiological Studies and Clinical Trials, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaAbstract: Stroke is a leading cause of death and disability worldwide. The importance of lowering blood pressure for reducing the risk of stroke is well established. However, not all the benefits of antihypertensive treatments in stroke can be accounted for by reductions in BP and there may be differences between antihypertensive classes as to which provides optimal protection. Dihydropyridine calcium channel blockers, such as amlodipine, and angiotensin receptor blockers, such as valsartan, represent the two antihypertensive drug classes with the strongest supportive data for the prevention of stroke. Therefore, when combination therapy is required, a combination of these two antihypertensive classes represents a logical approach.Keywords: stroke, angiotensin, calcium channel, cerebrovascular, hypertension, blood pressure

Photochemical fate of beta-blockers in NOM enriched waters

Energy Technology Data Exchange (ETDEWEB)

Wang, Ling; Xu, Haomin; Cooper, William J. [Urban Water Research Center, Department of Civil and Environmental Engineering, University of California, Irvine, Irvine, CA 92697-2175 (United States); Song, Weihua, E-mail: wsong@fudan.edu.cn [Department of Environmental Science and Engineering, Fudan University, Shanghai 200433 (China)

2012-06-01

Beta-blockers, prescribed for the treatment of high blood pressure and for long-term use after a heart attack, have been detected in surface and ground waters. This study examines the photochemical fate of three beta-blockers, atenolol, metoprolol, and nadolol. Hydrolysis accounted for minor losses of these beta-blockers in the pH range 4-10. The rate of direct photolysis at pH 7 in a solar simulator varied from 6.1 to 8.9 h{sup -1} at pH 7. However, the addition of a natural organic matter (NOM) isolate enhanced the photochemical loss of all three compounds. Indirect photochemical fate, generally described by reactions with hydroxyl radical ({center_dot}OH) and singlet oxygen ({sup 1}{Delta}O{sub 2}), and, the direct reaction with the triplet excited state, {sup 3}NOM{sup Low-Asterisk }, also varied but collectively appeared to be the major loss factor. Bimolecular reaction rate constants of the three beta-blockers with {sup 1}{Delta}O{sub 2} and {center_dot}OH were measured and accounted for 0.02-0.04% and 7.2-38.9% of their loss, respectively. These data suggest that the {sup 3}NOM{sup Low-Asterisk} contributed 50.6-85.4%. Experiments with various {sup 3}NOM{sup Low-Asterisk} quenchers supported the hypothesis that it was singly the most important reaction. Atenolol was chosen for more detailed investigation, with the photoproducts identified by LC-MS analysis. The results suggested that electron-transfer could be an important mechanism in photochemical fate of beta-blockers in the presence of NOM. - Highlights: Black-Right-Pointing-Pointer Photochemical degradation of beta-blockers in the simulated natural waters. Black-Right-Pointing-Pointer Reactive Oxygen Species play a minor role in the indirect photodegradation. Black-Right-Pointing-Pointer The loss of beta-blockers results from direct reaction with {sup 3}DOM{sup Low-Asterisk }.

Short‑term Effect of Tamsulosin and Finasteride Monotherapy and ...

African Journals Online (AJOL)

2017-05-18

May 18, 2017 ... and finasteride monotherapies, and their combination in men with benign prostatic ... single‑blind randomized study of ninety men with BPH who were managed ..... United State of America: Blackwell Publishing Company;.

A randomized controlled study of the efficacy of tamsulosin monotherapy and its combination with mirabegron for overactive bladder induced by benign prostatic obstruction.

Science.gov (United States)

Ichihara, Koji; Masumori, Naoya; Fukuta, Fumimasa; Tsukamoto, Taiji; Iwasawa, Akihiko; Tanaka, Yoshinori

2015-03-01

We evaluated the efficacy and safety of add-on treatment with a β3-adrenoceptor agonist (mirabegron) for overactive bladder symptoms remaining after α1-blocker (tamsulosin) treatment in men with benign prostatic obstruction. Patients with benign prostatic obstruction with urinary urgency at least once per week and a total OABSS of 3 or more points after 8 or more weeks of treatment with tamsulosin were enrolled in the study. They were randomly allocated to receive 0.2 mg tamsulosin daily or 0.2 mg tamsulosin and 50 mg mirabegron daily for 8 weeks. The primary end point was change in total OABSS. Safety assessments included change in post-void residual urine volume and adverse events. From January 2012 through September 2013 a total of 94 patients were randomized. Of these patients 76 completed the protocol treatment. In the full analysis set the change in total OABSS during the treatment period was significantly greater in the combination group than in the monotherapy group (-2.21 vs -0.87, p=0.012). The changes in scores for urinary urgency, daytime frequency, International Prostate Symptom Score storage symptom subscore and quality of life index at 8 weeks were significantly greater in the combination group. The change in post-void residual urine volume was significantly greater in the combination group. Although 6 patients experienced adverse events in the combination group, urinary retention was observed in only 1 patient. Combined tamsulosin and mirabegron treatment is effective and safe for patients with benign prostatic obstruction who have overactive bladder symptoms after tamsulosin monotherapy. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Therapeutical considerations in associated atrial fibrillation and heart failure.

Science.gov (United States)

Mitu, O; Mitu, F; Constantin, S; Cojocaru, Elena; Leon, Maria-Magdalena

2014-01-01

Atrial fibrillation is a supraventricular tachyarrhythmia very common in medical practice, often associated with heart failure. Pathophysiological relationship between atrial fibrillation and heart failure is in the attention of numerous case studies, being incomplete elucidated. We made a retrospective study on patients with both diseases, hospitalized in Cardiovascular Rehabilitation Hospital, Iasi, during 01.01.2013 - 31.12.2013. The obtained data allowed the classification of patients according to gender distribution, age groups, area of origin, clinical aspects, and association with other diseases, instituted treatment and appreciation of CHADS2 score. Data interpretation was performed with appropriate statistical methods. We found a higher frequency of the disease among male patients, male: female ratio being 2:1; the most of the patients lived in urban area. The pick of diseases incidence was in patients over 65 years with a total percentage of 70.84% of cases. We noted that the most common symptoms were exertional dyspnea (in all patients), palpitations, dizziness, headache, fatigue, asthenia, dyspnea at rest and pain/chest pressure. In our study, the majority of patients received the beta-blocker--digoxin combination (46 patients, 40 patients respectively). The coexistence of the two disorders could be explained by identifying common risk factors. Beta blockers should be the first therapeutic option in patients with chronic heart failure and atrial fibrillation because they have the effect of controlling heart rate and improve survival in patients with these disorders. Meanwhile, digoxin is a drug, only certain conditions of high accuracy monitoring; whose major clinical indications are heart failure and atrial rhythm disturbances.

Comparative Long-Term Effectiveness of a Monotherapy with Five Antiepileptic Drugs for Focal Epilepsy in Adult Patients: A Prospective Cohort Study

Science.gov (United States)

Zhu, Pan; He, Ru-Qian; Bao, Yi-Xin; Zheng, Rong-Yuan; Xu, Hui-Qin

2015-01-01

Objective To evaluate and compare long-term effectiveness of five antiepileptic drugs (AEDs) for monotherapy of adult patients with focal epilepsy in routine clinical practice. Methods Adult patients with focal epilepsy, who were prescribed with carbamazepine (CBZ), valproate (VPA), lamotrigine (LTG), topiramate (TPM), or oxcarbazepine (OXC) as monotherapy, during the period from January 2004 to June 2012 registered in Wenzhou Epilepsy Follow Up Registry Database (WEFURD), were included in the study. Prospective long-term follow-up was conducted until June 2013. The endpoints were time to treatment failure, time to seizure remission, and time to first seizure. Results This study included 654 patients: CBZ (n=125), VPA (n=151), LTG (n=135), TPM (n=76), and OXC (n=167). The retention rates of CBZ, VPA, LTG, TPM, and OXC at the third year were 36.1%, 32.4%, 57.6%, 37.9%, and 41.8%, respectively. For time to treatment failure, LTG was significantly better than CBZ and VPA (LTG vs. CBZ, hazard ratio, [HR] 0.80 [95% confidence interval: 0.67-0.96], LTG vs. VPA, 0.53 [0.37-0.74]); TPM was worse than LTG (TPM vs. LTG, 1.77 [1.15-2.74]), and OXC was better than VPA (0.86 [0.78-0.96]). After initial target doses, the seizure remission rates of CBZ, VPA, LTG, TPM, and OXC were 63.0%, 77.0%, 83.6%, 67.9%, and 75.3%, respectively. LTG was significantly better than CBZ (1.44 [1.15-1.82]) and OXC (LTG vs. OXC, 0.76 [0.63-0.93]); OXC was less effective than LTG in preventing the first seizure (1.20 [1.02-1.40]). Conclusion LTG was the best, OXC was better than VPA only, while VPA was the worst. The others were equivalent for comparisons between five AEDs regarding the long-term treatment outcomes of monotherapy for adult patients with focal epilepsy in a clinical practice. For selecting AEDs for these patients among the first-line drugs, LTG is an appropriate first choice; others are reservation in the first-line but VPA is not. PMID:26147937

Comparative Long-Term Effectiveness of a Monotherapy with Five Antiepileptic Drugs for Focal Epilepsy in Adult Patients: A Prospective Cohort Study.

Directory of Open Access Journals (Sweden)

Qing-Yi Zeng

Full Text Available To evaluate and compare long-term effectiveness of five antiepileptic drugs (AEDs for monotherapy of adult patients with focal epilepsy in routine clinical practice.Adult patients with focal epilepsy, who were prescribed with carbamazepine (CBZ, valproate (VPA, lamotrigine (LTG, topiramate (TPM, or oxcarbazepine (OXC as monotherapy, during the period from January 2004 to June 2012 registered in Wenzhou Epilepsy Follow Up Registry Database (WEFURD, were included in the study. Prospective long-term follow-up was conducted until June 2013. The endpoints were time to treatment failure, time to seizure remission, and time to first seizure.This study included 654 patients: CBZ (n=125, VPA (n=151, LTG (n=135, TPM (n=76, and OXC (n=167. The retention rates of CBZ, VPA, LTG, TPM, and OXC at the third year were 36.1%, 32.4%, 57.6%, 37.9%, and 41.8%, respectively. For time to treatment failure, LTG was significantly better than CBZ and VPA (LTG vs. CBZ, hazard ratio, [HR] 0.80 [95% confidence interval: 0.67-0.96], LTG vs. VPA, 0.53 [0.37-0.74]; TPM was worse than LTG (TPM vs. LTG, 1.77 [1.15-2.74], and OXC was better than VPA (0.86 [0.78-0.96]. After initial target doses, the seizure remission rates of CBZ, VPA, LTG, TPM, and OXC were 63.0%, 77.0%, 83.6%, 67.9%, and 75.3%, respectively. LTG was significantly better than CBZ (1.44 [1.15-1.82] and OXC (LTG vs. OXC, 0.76 [0.63-0.93]; OXC was less effective than LTG in preventing the first seizure (1.20 [1.02-1.40].LTG was the best, OXC was better than VPA only, while VPA was the worst. The others were equivalent for comparisons between five AEDs regarding the long-term treatment outcomes of monotherapy for adult patients with focal epilepsy in a clinical practice. For selecting AEDs for these patients among the first-line drugs, LTG is an appropriate first choice; others are reservation in the first-line but VPA is not.

Fluvoxamine monotherapy for psychotic depression: the potential role of sigma-1 receptors

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Hashimoto Kenji

2009-12-01

Full Text Available Abstract Background Psychotic depression is a clinical subtype of major depressive disorder. A number of clinical studies have demonstrated the efficacy of the combination of an antidepressant (for example, a tricyclic antidepressant or selective serotonin reuptake inhibitor (SSRI and an atypical antipsychotic or electroconvulsive therapy in treating psychotic depression. In some cases, the clinician or patient may prefer to avoid antipsychotic drugs altogether because of the risk of extrapyramidal side effects (EPS in patients with psychotic depression treated with these drugs. Methods We report five cases where fluvoxamine monotherapy was effective in the patients with psychotic depression. Results The scores on the Hamilton Depression (HAM-D scale and the Brief Psychiatric Rating Scale (BPRS in the five patients with psychotic depression were reduced after fluvoxamine monotherapy. Conclusion Doctors should consider fluvoxamine monotherapy as an alternative approach in treating psychotic depression because it avoids the risk of EPS from antipsychotic drugs.

A novel hypothesis for the binding mode of HERG channel blockers

International Nuclear Information System (INIS)

Choe, Han; Nah, Kwang Hoon; Lee, Soo Nam; Lee, Han Sam; Lee, Hui Sun; Jo, Su Hyun; Leem, Chae Hun; Jang, Yeon Jin

2006-01-01

We present a new docking model for HERG channel blockade. Our new model suggests three key interactions such that (1) a protonated nitrogen of the channel blocker forms a hydrogen bond with the carbonyl oxygen of HERG residue T623; (2) an aromatic moiety of the channel blocker makes a π-π interaction with the aromatic ring of HERG residue Y652; and (3) a hydrophobic group of the channel blocker forms a hydrophobic interaction with the benzene ring of HERG residue F656. The previous model assumes two interactions such that (1) a protonated nitrogen of the channel blocker forms a cation-π interaction with the aromatic ring of HERG residue Y652; and (2) a hydrophobic group of the channel blocker forms a hydrophobic interaction with the benzene ring of HERG residue F656. To test these models, we classified 69 known HERG channel blockers into eight binding types based on their plausible binding modes, and further categorized them into two groups based on the number of interactions our model would predict with the HERG channel (two or three). We then compared the pIC 5 value distributions between these two groups. If the old hypothesis is correct, the distributions should not differ between the two groups (i.e., both groups show only two binding interactions). If our novel hypothesis is correct, the distributions should differ between Groups 1 and 2. Consistent with our hypothesis, the two groups differed with regard to pIC 5 , and the group having more predicted interactions with the HERG channel had a higher mean pIC 5 value. Although additional work will be required to further validate our hypothesis, this improved understanding of the HERG channel blocker binding mode may help promote the development of in silico predictions methods for identifying potential HERG channel blockers

Comparative effectiveness of everolimus-based therapy versus endocrine monotherapy among postmenopausal women with HR+/HER2- metastatic breast cancer: a retrospective chart review in community oncology practices in the US.

Science.gov (United States)

Xie, Jipan; Hao, Yanni; Li, Nanxin; Lin, Peggy L; Ohashi, Erika; Koo, Valerie; Signorovitch, James E; Wu, Eric Q; Yardley, Denise A

2015-06-01

Everolimus-based therapy and endocrine monotherapy are used among postmenopausal women with hormone receptor-positive human epidermal growth factor receptor-2 negative (HR+/HER2-) metastatic breast cancer (mBC) whose disease progressed or recurred on a non-steroidal aromatase inhibitor (NSAI). However, limited evidence exists regarding the real-world comparative effectiveness of these agents. This retrospective chart review examined postmenopausal HR+/HER2- mBC patients in community-based oncology practices who received everolimus-based therapy or endocrine monotherapy (index therapy) as any line of therapy for mBC between 1 July 2012 and 15 April 2013 after NSAI failure. Time on treatment (TOT), progression-free survival (PFS), and time to chemotherapy (TTC) from index therapy initiation were compared using Kaplan-Meier analyses and Cox proportional hazards models adjusting for baseline characteristics. A total of 243 and 270 patients received everolimus-based therapy or endocrine monotherapy in a quota-based sample. Patients treated with everolimus-based therapy had a higher proportion of visceral metastases, high tumor burden, and use of prior chemotherapies for mBC. After adjusting for baseline characteristics, everolimus-based therapy was associated with significantly longer TOT (HR = 0.67, 95% CI: 0.51-0.87) and PFS (HR = 0.75, 95% CI: 0.57-0.98) than endocrine monotherapy. No significant difference was found between everolimus-based therapy and endocrine monotherapy in TTC (HR = 0.81, 95% CI: 0.52-1.27). Results stratified by line of therapy were generally consistent with the overall results. Limitations include recall and information bias with potentially absent or erroneous chart data, unobserved factors due to non-randomization, inability to measure outcome assessments paired with measuring outcomes prior to exposures, and potential patient selection bias associated with chart review. Among a nationwide sample of postmenopausal HR+/HER2- m

Perioperative beta blockers in patients having non-cardiac surgery

DEFF Research Database (Denmark)

Bangalore, Sripal; Wetterslev, Jørn; Pranesh, Shruthi

2008-01-01

American College of Cardiology and American Heart Association (ACC/AHA) guidelines on perioperative assessment recommend perioperative beta blockers for non-cardiac surgery, although results of some clinical trials seem not to support this recommendation. We aimed to critically review the evidence...... to assess the use of perioperative beta blockers in patients having non-cardiac surgery....

Role of triple fixed combination valsartan, amlodipine and hydrochlorothiazide in controlling blood pressure

Directory of Open Access Journals (Sweden)

Monica Doménech

2010-04-01

Full Text Available Monica Doménech, Antonio CocaHypertension Unit, Department of Internal Medicine, Institute of Internal Medicine and Dermatology, Hospital Clinic (IDIBAPS, University of Barcelona, SpainAbstract: Hypertension is one of the main risk factors for the development of cardiovascular diseases and the search for new therapeutic strategies aimed at optimizing its control remains an ongoing research and clinical challenge. In recent years, there has been a marked increase in the use of combinations of antihypertensive drugs with complementary mechanisms of action, with the aims of reducing blood pressure levels more rapidly and vigorously than strategies employing monotherapy and improving treatment compliance and adhesion. Therefore, as recommended by the 2009 reappraisal of the European Society of Hypertension/European Society of Cardiology Guidelines, the use of a triple combination that combines a calcium channel blocker, an angiotensin II receptor blocker and a thiazide diuretic seems a reasonable and efficacious combination for the management of hypertensive patients with moderate, high or very high risk. This article reviews the clinical trials carried out with the fixed combination of amlodipine/valsartan/hydrochlorothiazide at the doses recommended for each drug in monotherapy. The data show that this combination achieved greater reductions in mean sitting diastolic and systolic blood pressure than amlodipine, valsartan or hydrochlorothiazide in monotherapy, with favorable pharmacodynamic and pharmacokinetic profiles. The triple combination at high single doses should be used with caution in elderly patients and those with renal or liver failure. Although the tolerability and safety of the triple combination are good, the mostfrequently reported adverse effects were peripheral edema, headache and dizziness. Analytical alterations were consistent with the already-known biochemical effects of amlodipine, valsartan or hydrochlorothiazide in

Using supply side evidence to inform oral artemisinin monotherapy replacement in Myanmar: a case study.

Science.gov (United States)

Khin, Hnin Su Su; Aung, Tin; Aung, Moe; Thi, Aung; Boxshall, Matt; White, Chris

2016-08-18

In 2012, alarmingly high rates of oral artemisinin monotherapy availability and use were detected along Eastern Myanmar, threatening efforts to halt the spread of artemisinin resistance in the Greater Mekong Subregion (GMS), and globally. The aim of this paper is to exemplify how the use of supply side evidence generated through the ACTwatch project shaped the artemisinin monotherapy replacement malaria (AMTR) project's design and interventions to rapidly displace oral artemisinin monotherapy with subsidized, quality-assured ACT in the private sector. The AMTR project was implemented as part of the Myanmar artemisinin resistance containment (MARC) framework along Eastern Myanmar. Guided by outlet survey and supply chain evidence, the project implemented a high-level subsidy, including negotiations with a main anti-malarial distributor, with the aim of squeezing oral artemisinin monotherapy out of the market through price competition and increased availability of quality-assured artemisinin-based combinations. This was complemented with a plethora of demand-creation activities targeting anti-malarial providers and consumers. Priority outlet types responsible for the distribution of oral artemisinin monotherapy were identified by the outlet survey, and this evidence was used to target the AMTR project's supporting interventions. The widespread availability and use of oral artemisinin monotherapy in Myanmar has been a serious threat to malaria control and elimination in the country and across the region. Practical anti-malarial market evidence was rapidly generated and used to inform private sector approaches to address these threats. The program design approach outlined in this paper is illustrative of the type of evidence generation and use that will be required to ensure effective containment of artemisinin drug resistance and progress toward regional and global malaria elimination goals.

TNFα blockers and infectious risk in rheumatoid arthritis

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S. Todesco

2011-06-01

Full Text Available Patients suffering from rheumatoid arthritis have increased risk of infections when compared with general population. The risk depends directly from disease activity and severity. Furthermore, risk increases with aging, immunosuppressive agents and comorbidities such as diabetes, pulmonary and cardiac diseases. In particular corticosteroids, even at low doses, are a major risk factor. Due to disease related risk it is difficult to separate the risk deriving from the use of TNF alpha blockers. Data from clinical trials, meta-analysis and national registers are somewhat contradictory. In patients with rheumatoid arthritis on routine follow-up, treatment with TNF alpha blockers seems to carry an increased risk of infections compared to traditional DMARDs but not associated with increased risk of overall serious infection. Physicians should carefully monitor for signs of infection when using TNF alpha blockers, particularly shortly after treatment initiation.

Combined therapy in gastro-esophageal reflux disease of term neonates resistant to conservative therapy and monotherapy: a clinical trial

Directory of Open Access Journals (Sweden)

Peymaneh Alizadeh Taheri

2018-05-01

Full Text Available Background: Gastroesophageal reflux disease (GERD is one of the most common problems in neonates. The main clinical manifestations of neonatal GERD are frequent regurgitation or vomiting associated with irritability, crying, anorexia or feeding refusal, failure to thrive, arching of the back and sleep disturbance.Aims: As no study has compared metoclopramide plus ranitidine with metoclopramide plus omeprazole in the management of neonatal GERD resistant to conservative and monotherapy, this study was carried out.Study design: This study was a randomized clinical trial of term neonates with GERD resistant to conservative and monotherapy admitted to the neonatal ward of Bahrami Children Hospital during 2013-2015. Totally, 116 term neonates (mean age 10.53 ± 8.17 days; girls 50.9% were randomly assigned to a double blind trial with either oral omeprazole plus metoclopramide (group A or oral ranitidine plus metoclopramide (group B. The changes of the symptoms and signs were recorded after one week and one month.Results: There was no significant difference in demographic and baseline characteristics between the two groups. The response rate of “omeprazole plus metoclopramide” was significantly higher than “ranitidine plus metoclopramide” (93.74% ± 7.28% vs. 75.43% ± 23.24%, p = 0.028. All clinical manifestations recovered significantly in group A while the response rate of irritability and wheezing was not significant in group B (primary outcome. There were no side effects in either group after one week and one month of treatment (secondary outcome.Conclusions: The response rate was > 70% in each group, but it was significantly higher in group A (> 90%. Combination of each acid suppressant with metoclopramide led to higher response rate in comparison with monotherapy used before intervention.

Long-term changes of renal function in relation to ace inhibitor/angiotensin receptor blocker dosing in patients with heart failure and chronic kidney disease.

Science.gov (United States)

Fröhlich, Hanna; Nelges, Christoph; Täger, Tobias; Schwenger, Vedat; Cebola, Rita; Schnorbach, Johannes; Goode, Kevin M; Kazmi, Syed; Katus, Hugo A; Cleland, John G F; Clark, Andrew L; Frankenstein, Lutz

2016-08-01

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have become cornerstones of therapy for chronic heart failure (CHF). Guidelines advise high target doses for ACEIs/ARBs, but fear of worsening renal function may limit dose titration in patients with concomitant chronic kidney disease (CKD). In this retrospective observational study, we identified 722 consecutive patients with systolic CHF, stable CKD stage III/IV (estimated glomerular filtration rate [eGFR] 15-60 mL min(-1) 1.73 m(-2)) and chronic ACEI/ARB treatment from the outpatient heart failure clinics at the Universities of Hull, UK, and Heidelberg, Germany. Change of renal function, worsening CHF, and hyperkalemia at 12-month follow-up were analyzed as a function of both baseline ACEI/ARB dose and dose change from baseline. ΔeGFR was not related to baseline dose of ACEI/ARB (P = .58), or to relative (P = .18) or absolute change of ACEI/ARB dose (P = .21) during follow-up. Expressing change of renal function as a categorical variable (improved/stable/decreased) as well as subgroup analyses with respect to age, sex, New York Heart Association functional class, left ventricular ejection fraction, diabetes, concomitant aldosterone antagonists, CKD stage, hypertension, ACEI vs ARB, and congestion status yielded similar results. There was no association of dose/dose change with incidence of either worsening CHF or hyperkalemia. In patients with systolic CHF and stable CKD stage III/IV, neither continuation of high doses of ACEI/ARB nor up-titration was related to adverse changes in longer-term renal function. Conversely, down-titration was not associated with improvement in eGFR. Use of high doses of ACEI/ARB and their up-titration in patients with CHF and CKD III/IV may be appropriate provided that the patient is adequately monitored. Copyright © 2016 Elsevier Inc. All rights reserved.

Beta blockers and their combinations in the management of ...

African Journals Online (AJOL)

Review Article: Beta blockers and their combinations in the management of hypertension. 409. Vol 54 No 5. S Afr Fam Pract 2012. Introduction. Beta blockers have been prescribed for the treatment of primary hypertension for a very long time. Currently, it is doubtful whether this is still a good idea. In fact, many are of the ...

MBST-exposure opportunities as a monotherapy of chronic dorsalgia

Directory of Open Access Journals (Sweden)

Levchenko КК

2017-09-01

Full Text Available The aim: to analyze the clinical effect of MBST-exposure monotherapy, a magnetic resonance method, on the pain syndrome caused by degenerative dystrophic changes of vertebral column structures. Material and Methods. 132 patients both male and female with cervical and lumbar dorsopathy were enrolled into the study. Treatment course included 9 sessions of 60 min. daily. MRI-results of corresponding spine regions and visual analogue pain intensity scale were used as assessment tools for treatment efficiency before, immediately after, 3, 6 and 12 months after MBST-treatment. Results. The objective results of structural transformation of pathological formations in vertebral motional segments correlated with significant decrease of pain syndrome at all stages of control tests. Conclusion. MBST-exposure is an effective method of non-invasive, notouch monotherapy for patients with chronic dorsalgia caused by degenerative dorsopathy.

Assessing the impact of heart failure specialist services on patient populations

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Lyratzopoulos Georgios

2004-05-01

Full Text Available Abstract Background The assessment of the impact of healthcare interventions may help commissioners of healthcare services to make optimal decisions. This can be particularly the case if the impact assessment relates to specific patient populations and uses timely local data. We examined the potential impact on readmissions and mortality of specialist heart failure services capable of delivering treatments such as b-blockers and Nurse-Led Educational Intervention (N-LEI. Methods Statistical modelling of prevented or postponed events among previously hospitalised patients, using estimates of: treatment uptake and contraindications (based on local audit data; treatment effectiveness and intolerance (based on literature; and annual number of hospitalization per patient and annual risk of death (based on routine data. Results Optimal treatment uptake among eligible but untreated patients would over one year prevent or postpone 11% of all expected readmissions and 18% of all expected deaths for spironolactone, 13% of all expected readmisisons and 22% of all expected deaths for b-blockers (carvedilol and 20% of all expected readmissions and an uncertain number of deaths for N-LEI. Optimal combined treatment uptake for all three interventions during one year among all eligible but untreated patients would prevent or postpone 37% of all expected readmissions and a minimum of 36% of all expected deaths. Conclusion In a population of previously hospitalised patients with low previous uptake of b-blockers and no uptake of N-LEI, optimal combined uptake of interventions through specialist heart failure services can potentially help prevent or postpone approximately four times as many readmissions and a minimum of twice as many deaths compared with simply optimising uptake of spironolactone (not necessarily requiring specialist services. Examination of the impact of different heart failure interventions can inform rational planning of relevant healthcare

Assessing the impact of heart failure specialist services on patient populations.

Science.gov (United States)

Lyratzopoulos, Georgios; Cook, Gary A; McElduff, Patrick; Havely, Daniel; Edwards, Richard; Heller, Richard F

2004-05-24

The assessment of the impact of healthcare interventions may help commissioners of healthcare services to make optimal decisions. This can be particularly the case if the impact assessment relates to specific patient populations and uses timely local data. We examined the potential impact on readmissions and mortality of specialist heart failure services capable of delivering treatments such as b-blockers and Nurse-Led Educational Intervention (N-LEI). Statistical modelling of prevented or postponed events among previously hospitalised patients, using estimates of: treatment uptake and contraindications (based on local audit data); treatment effectiveness and intolerance (based on literature); and annual number of hospitalization per patient and annual risk of death (based on routine data). Optimal treatment uptake among eligible but untreated patients would over one year prevent or postpone 11% of all expected readmissions and 18% of all expected deaths for spironolactone, 13% of all expected readmisisons and 22% of all expected deaths for b-blockers (carvedilol) and 20% of all expected readmissions and an uncertain number of deaths for N-LEI. Optimal combined treatment uptake for all three interventions during one year among all eligible but untreated patients would prevent or postpone 37% of all expected readmissions and a minimum of 36% of all expected deaths. In a population of previously hospitalised patients with low previous uptake of b-blockers and no uptake of N-LEI, optimal combined uptake of interventions through specialist heart failure services can potentially help prevent or postpone approximately four times as many readmissions and a minimum of twice as many deaths compared with simply optimising uptake of spironolactone (not necessarily requiring specialist services). Examination of the impact of different heart failure interventions can inform rational planning of relevant healthcare services.

Optimal medical therapy in chronic heart failure-an audit

International Nuclear Information System (INIS)

Hussain, S.; Kayani, A.M.; Munir, R.

2013-01-01

Objective: Systolic heart failure is a chronic condition with significant morbidity and mortality. Evidence based optimal medical therapy (OMT) has been shown to reduce mortality. Underuse of OMT due to multiple reasons has been a consistent problem. The study objective was to audit the use of OMT in patients with heart Failure. Study Design: Descriptive study. Place and Duration of study: This audit was carried out in AFIC-NIHD from April 2011- February 2012. Material and Methods: Seventy consecutive stage D heart failure patients were included in the study. The patients were assessed clinically by a cardiologist and all previous documentations, referral letters, prescriptions, and purchase receipts were reviewed. To identify any other medication patients might have been taking (which did not appear on the prescriptions) patients were asked to identify common medicine packs. The patients underwent a detailed clinical evaluation including history, physical examination. Relevant investigations were done. ACCF/AHA (American College of Cardiology Foundation / American Heart Association) and ESC (European Society of Cardiology) guidelines for the diagnosis and treatment of acute and chronic heart failure were taken as standard of care. Results: In our audit we found that a large proportion of patients who were at high risk as per the Seattle Heart Failure Model (SHFM) were not on OMT, only 4.3% of the patients were on beta blockers that have been shown to improve mortality in the large randomized clinical trials, 64.3% were not taking any beta blockers where as 55.7% were not on ACE inhibitors and adding the OMT greatly reduced their mortality risk. Conclusions: We concluded that a large proportion of patients were not on OMT despite not having any contraindication to such therapy. This deprives them of significant survival benefit. (author)

Beta-blockers for exams identify students at high risk of psychiatric morbidity

DEFF Research Database (Denmark)

Butt, Jawad H.; Dalsgaard, Søren; Torp-Pedersen, Christian

2017-01-01

Objectives: Beta-blockers relieve the autonomic symptoms of exam-related anxiety and may be beneficial in exam-related and performance anxiety, but knowledge on related psychiatric outcomes is unknown. We hypothesized that beta-blocker therapy for exam-related anxiety identifies young students...... at risk of later psychiatric events. Methods: Using Danish nationwide administrative registries, we studied healthy students aged 14-30 years (1996-2012) with a first-time claimed prescription for a beta-blocker during the exam period (May-June); students who were prescribed a beta-blocker for medical...... reasons were excluded. We matched these students on age, sex, and time of year to healthy and study active controls with no use of beta-blockers. Risk of incident use of antidepressants, incident use of other psychotropic medications, and suicide attempts was examined by cumulative incidence curves...

Safety and effectiveness of olanzapine in monotherapy: a multivariate analysis of a naturalistic study.

Science.gov (United States)

Ciudad, Antonio; Gutiérrez, Miguel; Cañas, Fernando; Gibert, Juan; Gascón, Josep; Carrasco, José-Luis; Bobes, Julio; Gómez, Juan-Carlos; Alvarez, Enrique

2005-07-01

This study investigated safety and effectiveness of olanzapine in monotherapy compared with conventional antipsychotics in treatment of acute inpatients with schizophrenia. This was a prospective, comparative, nonrandomized, open-label, multisite, observational study of Spanish inpatients with an acute episode of schizophrenia. Data included safety assessments with an extrapyramidal symptoms (EPS) questionnaire and the report of spontaneous adverse events, plus clinical assessments with the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impressions-Severity of Illness (CGI-S). A multivariate methodology was used to more adequately determine which factors can influence safety and effectiveness of olanzapine in monotherapy. 339 patients treated with olanzapine in monotherapy (OGm) and 385 patients treated with conventional antipsychotics (CG) were included in the analysis. Treatment-emergent EPS were significantly higher in the CG (pOGm (p=0.005). Logistic regression analyses revealed that the only variable significantly correlated with treatment-emergent EPS and clinical response was treatment strategy, with patients in OGm having 1.5 times the probability of obtaining a clinical response and patients in CG having 5 times the risk of developing EPS. In this naturalistic study olanzapine in monotherapy was better-tolerated and at least as effective as conventional antipsychotics.

β-Blocker treatment during pregnancy and adverse pregnancy outcomes

DEFF Research Database (Denmark)

Petersen, Kasper Meidahl; Jimenez-Solem, Espen; Andersen, Jon Traerup

2012-01-01

To investigate the association between exposure to β-blockers during pregnancy and the risk of being born small for gestational age (SGA), preterm birth and perinatal mortality in a nationwide cohort.......To investigate the association between exposure to β-blockers during pregnancy and the risk of being born small for gestational age (SGA), preterm birth and perinatal mortality in a nationwide cohort....

Evidence to support the use of vildagliptin monotherapy in the treatment of type 2 diabetes mellitus

Directory of Open Access Journals (Sweden)

Dejager S

2012-05-01

Full Text Available Sylvie Dejager,1 Anja Schweizer,2 James E Foley31Novartis Pharma SAS, Rueil Malmaison, France; 2Novartis Pharma AG, Basel, Switzerland; 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, USAAbstract: The efficacy and safety of the dipeptidyl peptidase-4 inhibitor, vildagliptin, as monotherapy have been widely confirmed in a large body of clinical studies of up to 2 years’ duration in various populations with type 2 diabetes mellitus. This paper reviews the data supporting the use of vildagliptin in monotherapy. Consideration based on baseline glycated hemoglobin levels and age is given to patient segments where metformin is not appropriate. In addition, although prediabetes is not an indication, this manuscript briefly reviews some of the existing data showing that the mechanisms at work in diabetic populations are active in patients currently classified as prediabetic, with impaired glucose tolerance or impaired fasting glucose. Finally, the rationale for vildagliptin dosing frequency in monotherapy is discussed. In summary, this review aims to define where in community practice the use of vildagliptin as monotherapy is most desirable, focusing on segments of the population with type 2 diabetes mellitus that might receive the greatest benefit from vildagliptin in the management of their disease.Keywords: vildagliptin, type 2 diabetes, dipeptidyl peptidase-4 inhibitors, monotherapy, elderly

Cognitive and psychosocial effects of oxcarbazepine monotherapy in newly diagnosed partial epilepsy.

Science.gov (United States)

Kim, Daeyoung; Seo, Ji-Hye; Joo, Eun Yeon; Lee, Hyang Woon; Shin, Won Chul; Hong, Seung Bong

2014-01-01

The aim of this study was to assess the effects of oxcarbazepine (OXC) on cognition and psychosocial difficulties in patients with new-onset partial epilepsy. Cognitive and psychosocial assessments were performed before and after 6 to 12 months of OXC monotherapy in 52 drug-naive patients (25 women; mean age, 31.1 years; SD, 12.1 years). Cognitive functions were evaluated with well-structured and validated tools. Mood, psychological distress, subjective handicap, and quality of life were also evaluated. Differences between baseline and after-treatment evaluation were compared and adjusted for possible confounders such as age, sex, seizure control, duration of epilepsy, assessment interval, and epileptogenic region. Mean assessment interval was 231.8 (range, 182-348) days, and mean (SD) OXC dose at retest was 693.8 (208.9) mg. The OXC was found to have no significant adverse effect on cognition. Furthermore, OXC monotherapy was not found to affect psychosocial difficulties, including psychological distress and subjective handicap. The results suggest that OXC monotherapy could be used to treat newly diagnosed partial epilepsy without adversely affecting cognitive and psychosocial functions.

Topical beta-Blockers and Mortality

NARCIS (Netherlands)

Muskens, Rogier P. H. M.; Wolfs, Roger C. W.; Wittenian, Jacqueline C. M.; Hofman, Albert; de Jong, Paulus T. V. M.; Stricker, Bruno H. C.; Jansonius, Nomdo M.

Purpose: To study the associations between long-term and short-term use of topical beta-blockers and mortality. Design: Prospective population-based cohort study. Participants: To examine long-term effects, 3842 participants aged 55 years and older were recruited. To examine short-term effects, 484

Bisoprolol in the treatment of chronic heart failure

OpenAIRE

Pascal de Groote; Pierre-Vladimir Ennezat; Fréderic Mouquet

2007-01-01

Pascal de Groote1, Pierre-Vladimir Ennezat2, Fréderic Mouquet11Service de Cardiologie C, 2Service des soins intensifs cardiologiques, Hôpital Cardiologique, Centre Hospitalier Régional et Universitaire de Lille, FranceAbstract: Bisoprolol fumarate is a highly selective beta-1 receptor blocker. Bisoprolol has been extensively studied in three large mortality trials in stable chronic heart failure (CHF) patients. The CIBIS trial enrolled 641 patients and demonstrated the goo...

Pre-injury beta blocker use does not affect the hyperdynamic response in older trauma patients

Directory of Open Access Journals (Sweden)

David C Evans

2014-01-01

Full Text Available Purpose: Trauma dogma dictates that the physiologic response to injury is blunted by beta-blockers and other cardiac medications. We sought to determine how the pre-injury cardiac medication profile influences admission physiology and post-injury outcomes. Materials and Methods: Trauma patients older than 45 evaluated at our center were retrospectively studied. Pre-injury medication profiles were evaluated for angiotensin-converting enzyme inhibitors / angiotensin receptor blockers (ACE-I/ARB, beta-blockers, calcium channel blockers, amiodarone, or a combination of the above mentioned agents. Multivariable logistic regression or linear regression analyses were used to identify relationships between pre-injury medications, vital signs on presentation, post-injury complications, length of hospital stay, and mortality. Results: Records of 645 patients were reviewed (mean age 62.9 years, Injury Severity Score >10, 23%. Our analysis demonstrated no effect on systolic and diastolic blood pressures from beta-blocker, ACE-I/ARB, calcium channel blocker, and amiodarone use. The triple therapy (combined beta-blocker, calcium channel blocker, and ACE-I/ARB patient group had significantly lower heart rate than the no cardiac medication group. No other groups were statistically different for heart rate, systolic, and diastolic blood pressure. Conclusions: Pre-injury use of cardiac medication lowered heart rate in the triple-agent group (beta-blocker, calcium channel blocker, and ACEi/ARB when compared the no cardiac medication group. While most combinations of cardiac medications do not blunt the hyperdynamic response in trauma cases, patients on combined beta-blocker, calcium channel blocker, and ACE-I/ARB therapy had higher mortality and more in-hospital complications despite only mild attenuation of the hyperdynamic response.

[Sacubitril/valsartan, a new and effective treatment for heart failure with reduced ejection fraction].

Science.gov (United States)

Senni, Michele; Trimarco, Bruno; Emdin, Michele; De Biase, Luciano

2017-01-01

Despite significant therapeutic advances, patients with chronic heart failure and reduced ejection fraction (HFrEF) remain at high risk for heart failure progression and death. The PARADIGM-HF study, the largest outcome trial in HFrEF, has shown improved cardiovascular outcomes with sacubitril/valsartan (Entresto®, Novartis), previously known as LCZ696, compared with angiotensin-converting enzyme (ACE) inhibitor therapy, possibly leading us to a new era for heart failure treatment. Sacubitril/valsartan represents a first-in-class drug acting through inhibition of angiotensin receptor and neprilysin, thus modulating the renin-angiotensin-aldosterone system and vasoactive substances such as natriuretic peptides. This approach can be considered a "paradigm shift" from neurohumoral inhibition to neurohumoral modulation. Based on the PARADIGM-HF results, the European Society of Cardiology and the American Heart Association/American College of Cardiology guidelines proposed a substitution of ACE-inhibitor/angiotensin receptor blocker therapy rather than an "add-on" strategy in HFrEF. Sacubitril/valsartan can be considered a milestone in cardiovascular therapy, like aspirin, statins, beta-blockers. Of course there are many questions that arise spontaneously from this trial, three recognized experts can help us to answer them.

Protection against death and renal failure by renin-angiotensin system blockers in patients with diabetes and kidney disease.

Science.gov (United States)

Shen, Jian; Huang, Yan-Mei; Song, Xin-Nan; Hong, Xue-Zhi; Wang, Min; Ling, Wei; Zhang, Xiao-Xi; Zhao, Hai-Lu

2016-07-01

Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are widely used to block the renin-angiotensin system (RAS). Yet it remains uncertain whether these drugs are equally effective and safe. Systematic reviews and meta-analyses of ACEis/ARBs in diabetes and kidney disease published in PubMed, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases were searched for clinical outcomes including all-cause mortality, end-stage renal disease (ESRD), hyperkalemia and cough. Eight meta-analyses included 2177-61,264 patients with follow-up of 6-108 months. RAS blockers reduced mortality (relative risk ratio (RR), 0.90, 95% confidence interval (CI), 0.86-0.95) without heterogeneity. The death protection was significant specifically with ACEis (RR, 0.85, 95% CI, 0.79-0.91), but not with ARBs. Protection against ESRD was homogenously evident by ARBs (RR, 0.79, 95% CI, 0.73-0.87), ACEis (RR, 0.79, 95% , 0.64-0.94), and both (RR, 0.79, 95% CI, 0.73-0.87). Significant side effects were hyperkalemia by ARBs (RR, 2.44, 95% CI, 1.13-5.26), and cough by ACEis (RR, 2.38, 95% CI, 1.75-3.22) CONCLUSIONS: In patients with diabetes and kidney disease, ACEis and ARBs are consistently protective for the development of ESRD. Use of ACEis alone additionally reduces deaths and increases the risk for cough. Use of ARBs alone increases the risk for hyperkalemia without additional benefit of death protection. © The Author(s) 2016.

Levetiracetam Monotherapy in Children with Epilepsy : A Systematic Review

NARCIS (Netherlands)

Weijenberg, Amerins; Brouwer, Oebele F.; Callenbach, Petra M. C.

Background Levetiracetam, a second-generation anti-epileptic drug (AED) with a good efficacy and safety profile, is licensed as monotherapy for adults and children older than 16 years with focal seizures with or without secondary generalization. However, it is increasingly being used off-label in

Prevalence of major depressive disorder in patients receiving beta-blocker therapy versus other medications.

Science.gov (United States)

Carney, R M; Rich, M W; teVelde, A; Saini, J; Clark, K; Freedland, K E

1987-08-01

Depression is believed to be a common side effect in patients receiving beta-blocker therapy. However, diagnoses of depression defined by current diagnostic criteria may not be more common in patients receiving beta-blockers than in patients with the same medical disorder receiving other medications. Seventy-seven patients undergoing elective cardiac catheterization for evaluation of chest pain received a semi-structured diagnostic psychiatric interview. Twenty-one percent of the patients receiving beta-blockers and 33 percent of the patients receiving medications other than beta-blockers met the current American Psychiatric Association criteria for major depressive disorder (DSM-III) (p = NS). The mean heart rate and state anxiety scores for patients taking beta-blockers were significantly lower than those measured in patients taking medications other than beta-blockers. No other medical or demographic differences were observed between the two groups. Despite the methodologic limitations of the study, there does not appear to be a difference in the point prevalence of depression between patients receiving beta-blockers and those receiving other medications.

Banding ligation versus beta-blockers as primary prophylaxis in esophageal varices

DEFF Research Database (Denmark)

Gluud, Lise L; Klingenberg, Sarah; Nikolova, Dimitrinka

2007-01-01

To compare banding ligation versus beta-blockers as primary prophylaxis in patients with esophageal varices and no previous bleeding.......To compare banding ligation versus beta-blockers as primary prophylaxis in patients with esophageal varices and no previous bleeding....

Angiotensin Converting-Enzyme Inhibitors, Angiotensin Receptor Blockers, and Calcium Channel Blockers Are Associated with Prolonged Vascular Access Patency in Uremic Patients Undergoing Hemodialysis.

Directory of Open Access Journals (Sweden)

Fu-An Chen

Full Text Available Vascular access failure is a huge burden for patients undergoing hemodialysis. Many efforts have been made to maintain vascular access patency, including pharmacotherapy. Angiotensin converting enzyme inhibitor (ACE-I, angiotensin receptor blocker (ARB, and calcium channel blocker (CCB are known for their antihypertensive and cardio-protective effects, however, their effects on long-term vascular access patency are still inconclusive.We retrospectively enrolled patients commencing maintenance hemodialysis between January 1, 2000, and December 31, 2006 by using National Health Insurance Research Database in Taiwan. Primary patency was defined as the date of first arteriovenous fistula (AVF or arteriovenous graft (AVG creation to the time of access thrombosis or any intervention aimed to maintain or re-establish vascular access patency. Cox proportional hazards models were used to adjust the influences of patient characteristics, co-morbidities and medications.Total 42244 patients were enrolled in this study, 37771 (89.4% used AVF, 4473 (10.6% used AVG as their first long term dialysis access. ACE-I, ARB, and CCB use were all associated with prolonged primary patency of AVF [hazard ratio (HR 0.586, 95% confidence interval (CI 0.557-0.616 for ACE-I use; HR 0.532, CI 0.508-0.556 for ARB use; HR 0.485, CI 0.470-0.501 for CCB use] and AVG (HR 0.557, CI 0.482-0.643 for ACE-I use, HR 0.536, CI 0.467-0.614 for ARB use, HR 0.482, CI 0.442-0.526 for CCB use.In our analysis, ACE-I, ARB, and CCB were strongly associated with prolonged primary patency of both AVF and AVG. Further prospective randomized studies are still warranted to prove the causality.

Beta-blocker use and COPD mortality: a systematic review and meta-analysis

Directory of Open Access Journals (Sweden)

Etminan Mahyar

2012-09-01

Full Text Available Abstract Background Despite the benefits of beta-blockers in patients with established or sub-clinical coronary artery disease, their use in patients with chronic obstructive pulmonary disease (COPD has been controversial. Currently, no systematic review has examined the impact of beta-blockers on mortality in COPD. Methods We systematically searched electronic bibliographic databases including MEDLINE, EMBASE and Cochrane Library for clinical studies that examine the association between beta-blocker use and all cause mortality in patients with COPD. Risk ratios across studies were pooled using random effects models to estimate a pooled relative risk across studies. Publication bias was assessed using a funnel plot. Results Our search identified nine retrospective cohort studies that met the study inclusion criteria. The pooled relative risk of COPD related mortality secondary to beta-blocker use was 0.69 (95% CI: 0.62-0.78; I2=82%. Conclusion The results of this review are consistent with a protective effect of beta-blockers with respect to all cause mortality. Due to the observational nature of the included studies, the possibility of confounding that may have affected these results cannot be excluded. The hypothesis that beta blocker therapy might be of benefit in COPD needs to be evaluated in randomised controlled trials.

Risk of Cardiovascular Events in Patients With Diabetes Mellitus on β-Blockers.

Science.gov (United States)

Tsujimoto, Tetsuro; Sugiyama, Takehiro; Shapiro, Martin F; Noda, Mitsuhiko; Kajio, Hiroshi

2017-07-01

Although the use of β-blockers may help in achieving maximum effects of intensive glycemic control because of a decrease in the adverse effects after severe hypoglycemia, they pose a potential risk for the occurrence of severe hypoglycemia. This study aimed to evaluate whether the use of β-blockers is effective in patients with diabetes mellitus and whether its use is associated with the occurrence of severe hypoglycemia. Using the ACCORD trial (Action to Control Cardiovascular Risk in Diabetes) data, we performed Cox proportional hazards analyses with a propensity score adjustment. The primary outcome was the first occurrence of a cardiovascular event during the study period, which included nonfatal myocardial infarction, unstable angina, nonfatal stroke, and cardiovascular death. The mean follow-up periods (±SD) were 4.6±1.6 years in patients on β-blockers (n=2527) and 4.7±1.6 years in those not on β-blockers (n=2527). The cardiovascular event rate was significantly higher in patients on β-blockers than in those not on β-blockers (hazard ratio, 1.46; 95% confidence interval, 1.24-1.72; P diabetes mellitus was associated with an increased risk for cardiovascular events. © 2017 The Authors.

[Diuretics in monotherapy and in combination with other diuretics and nondiuretics in the treatment of hypertension].

Science.gov (United States)

Spinar, J; Spinarová, L; Vítovec, J

2013-06-01

Diuretics belong to the basic group of medicines for the treatment of hypertension and heart failure. In the case of hypertension treatment, their main indication is higher age and isolated systolic hypertension. In the case of heart failure they are used for the treatment of swellings and shortness of breath. The most frequently prescribed group of diuretics is thiazides and similar products. In patients with renal insufficiency, loop diuretics are administered. In the case of hypertension, diuretics are mainly used in the combination treatment. The most frequently used diuretic in combination is again hydrochlorothiazide, which is combined with reninangiotensin system blockers. It is mainly the combination of an ACE inhibitor + indapamide that seems to be modern and promising, and it is, on the basis of large clinical trials, recommended also for diabetics (ADVANCE) or for secondary prevention following a cerebrovascular accident (PROGRESS) or for the elderly (HYVET). Also a combination of two diuretics is popular -  mainly hydrochlorothiazide + amiloride. A combination of a betablocker and diuretic is less suitable.

Effect of beta-blockers on exacerbation rate and lung function in chronic obstructive pulmonary disease (COPD).

Science.gov (United States)

Duffy, Sean; Marron, Robert; Voelker, Helen; Albert, Richard; Connett, John; Bailey, William; Casaburi, Richard; Cooper, J Allen; Curtis, Jeffrey L; Dransfield, Mark; Han, MeiLan K; Make, Barry; Marchetti, Nathaniel; Martinez, Fernando; Lazarus, Stephen; Niewoehner, Dennis; Scanlon, Paul D; Sciurba, Frank; Scharf, Steven; Reed, Robert M; Washko, George; Woodruff, Prescott; McEvoy, Charlene; Aaron, Shawn; Sin, Don; Criner, Gerard J

2017-06-19

Beta-blockers are commonly prescribed for patients with cardiovascular disease. Providers have been wary of treating chronic obstructive pulmonary disease (COPD) patients with beta-blockers due to concern for bronchospasm, but retrospective studies have shown that cardio-selective beta-blockers are safe in COPD and possibly beneficial. However, these benefits may reflect symptom improvements due to the cardiac effects of the medication. The purpose of this study is to evaluate associations between beta-blocker use and both exacerbation rates and longitudinal measures of lung function in two well-characterized COPD cohorts. We retrospectively analyzed 1219 participants with over 180 days of follow up from the STATCOPE trial, which excluded most cardiac comorbidities, and from the placebo arm of the MACRO trial. Primary endpoints were exacerbation rates per person-year and change in spirometry over time in association with beta blocker use. Overall 13.9% (170/1219) of participants reported taking beta-blockers at enrollment. We found no statistically significant differences in exacerbation rates with respect to beta-blocker use regardless of the prevalence of cardiac comorbidities. In the MACRO cohort, patients taking beta-blockers had an exacerbation rate of 1.72/person-year versus a rate of 1.71/person-year in patients not taking beta-blockers. In the STATCOPE cohort, patients taking beta-blockers had an exacerbation rate of 1.14/person-year. Patients without beta-blockers had an exacerbation rate of 1.34/person-year. We found no detrimental effect of beta blockers with respect to change in lung function over time. We found no evidence that beta-blocker use was unsafe or associated with worse pulmonary outcomes in study participants with moderate to severe COPD.

Associations of serumpotassiumlevels with mortality in chronic heart failure patients

DEFF Research Database (Denmark)

Aldahl, Mette; Caroline Jensen, Anne Sofie; Davidsen, Line

2017-01-01

Aims Medication prescribed to patients suffering from chronic heart failure carries an increased risk of impaired potassium homeostasis. We examined the relation between different levels of serum potassium and mortality among patients with chronic heart failure. Methods and results From Danish...... National registries, we identified 19 549 patients with a chronic heart failure diagnosis who had a measurement of potassium within minimum 90 days after initiated medical treatment with loop diuretics and angiotensin converting enzyme inhibitors or angiotensin-II receptor blockers. All-cause mortality......-cause mortality. Conclusion Levels within the lower and upper levels of the normal serum potassium range (3.5-4.1 mmol/L and 4.8-5.0 mmol/ L, respectively) were associated with a significant increased short-term risk of death in chronic heart failure patients. Likewise, potassium below 3.5 mmol/L and above 5...

Short‑term Effect of Tamsulosin and Finasteride Monotherapy and ...

African Journals Online (AJOL)

Objective: The objective of this study was to assess the efficacy of tamsulosin and finasteride monotherapies, and their combination in men with benign prostatic hyperplasia (BPH). Materials and Methods: This is a prospective single‑blind randomized study of ninety men with BPH who were managed using drugs.

Beta-blockers and depression in elderly hypertension patients in primary care

NARCIS (Netherlands)

Ringoir, Lianne; Pedersen, Susanne S.; Widdershoven, Jos W. M. G.; Pouwer, Francois; Keyzer, Josephine M. L.; Romeijnders, Arnold C.; Pop, Victor J. M.

2014-01-01

Background and Objectives: Previous findings regarding a possible association between beta-blocker use and depression are mixed. To our knowledge there have been no studies investigating the association of beta-blockers with depression in primary care hypertension patients without previous

Influence of beta blockers on survival in dogs with severe subaortic stenosis.

Science.gov (United States)

Eason, B D; Fine, D M; Leeder, D; Stauthammer, C; Lamb, K; Tobias, A H

2014-01-01

Subaortic stenosis (SAS) is one of the most common congenital cardiac defects in dogs. Severe SAS frequently is treated with a beta adrenergic receptor blocker (beta blocker), but this approach largely is empirical. To determine the influence of beta blocker treatment on survival time in dogs with severe SAS. Retrospective review of medical records of dogs diagnosed with severe, uncomplicated SAS (pressure gradient [PG] ≥80 mmHg) between 1999 and 2011. Fifty dogs met the inclusion criteria. Twenty-seven dogs were treated with a beta blocker and 23 received no treatment. Median age at diagnosis was significantly greater in the untreated group (1.2 versus 0.6 years, respectively; P = .03). Median PG at diagnosis did not differ between the treated and untreated groups (127 versus 121 mmHg, respectively; P = .2). Cox proportional hazards regression was used to identify the influence of PG at diagnosis, age at diagnosis, and beta blocker treatment on survival. In the all-cause multivariate mortality analysis, only age at diagnosis (P = .02) and PG at diagnosis (P = .03) affected survival time. In the cardiac mortality analysis, only PG influenced survival time (P = .03). Treatment with a beta blocker did not influence survival time in either the all-cause (P = .93) or cardiac-cause (P = .97) mortality analyses. Beta blocker treatment did not influence survival in dogs with severe SAS in our study, and a higher PG at diagnosis was associated with increased risk of death. Copyright © 2014 by the American College of Veterinary Internal Medicine.

Beta-blockers and depression after myocardial infarction - A multicenter prospective study

NARCIS (Netherlands)

van Melle, Joost P.; Verbeek, Danielle E. P.; van den Berg, Maarten P.; Ormel, Johan; van der Linde, Marcel R.; de Jonge, Peter

2006-01-01

OBJECTIVES The purpose of this research was to explore the prospective relationship between the use of beta-blockers and depression in myocardial infarction (MI) patients. BACKGROUND Beta-blocker use has been reported to be associated with the development of depression, but the methodological

β-Blocker-Associated Risks in Patients With Uncomplicated Hypertension Undergoing Noncardiac Surgery

DEFF Research Database (Denmark)

Jørgensen, Mads E; Hlatky, Mark A; Køber, Lars Valeur

2015-01-01

IMPORTANCE: Perioperative β-blocker strategies are important to reduce risks of adverse events. Effectiveness and safety may differ according to patients' baseline risk. OBJECTIVE: To determine the risk of major adverse cardiovascular events (MACEs) associated with long-term β-blocker therapy...... antihypertensive drugs (β-blockers, thiazides, calcium antagonists, or renin-angiotensin system [RAS] inhibitors) undergoing noncardiac surgery between 2005 and 2011. INTERVENTIONS: Various antihypertensive treatment regimens, chosen as part of usual care. MAIN OUTCOMES AND MEASURES: Thirty-day risk of MACEs...... (cardiovascular death, nonfatal ischemic stroke, nonfatal myocardial infarction) and all-cause mortality, assessed using multivariable logistic regression models and adjusted numbers needed to harm (NNH). RESULTS: The baseline characteristics of the 14,644 patients who received β-blockers (65% female, mean [SD...

Beta-blocker use and clinical outcomes after primary vascular surgery

DEFF Research Database (Denmark)

Høgh, A.; Lindholt, J.S.; Nielsen, Henrik

2013-01-01

To explore the associations between beta-blocker use and clinical outcomes (death, hospitalisation with myocardial infarction (MI) or stroke, major amputation and recurrent vascular surgery) after primary vascular reconstruction.......To explore the associations between beta-blocker use and clinical outcomes (death, hospitalisation with myocardial infarction (MI) or stroke, major amputation and recurrent vascular surgery) after primary vascular reconstruction....

Is there a role for antiandrogen monotherapy in patients with metastatic prostate cancer?

DEFF Research Database (Denmark)

Kaisary, A V; Iversen, P; Tyrrell, C J

2001-01-01

with a prostate specific antigen (PSA) level 400 ng/ml) may decide that quality of life and symptomatic benefits outweigh the slight survival disadvantage seen in clinical trials and opt for bicalutamide monotherapy as an alternative to castration.Prostate Cancer and Prostatic Diseases (2001) 4, 196-203.......Castration is the most widely used form of androgen ablation employed in the treatment of metastatic (M1) prostate cancer. Non-steroidal antiandrogen monotherapy is a potential alternative treatment option for men for whom castration is unacceptable or not indicated. Of the three non...

Evidence to support the use of vildagliptin monotherapy in the treatment of type 2 diabetes mellitus

Science.gov (United States)

Dejager, Sylvie; Schweizer, Anja; Foley, James E

2012-01-01

The efficacy and safety of the dipeptidyl peptidase-4 inhibitor, vildagliptin, as monotherapy have been widely confirmed in a large body of clinical studies of up to 2 years’ duration in various populations with type 2 diabetes mellitus. This paper reviews the data supporting the use of vildagliptin in monotherapy. Consideration based on baseline glycated hemoglobin levels and age is given to patient segments where metformin is not appropriate. In addition, although prediabetes is not an indication, this manuscript briefly reviews some of the existing data showing that the mechanisms at work in diabetic populations are active in patients currently classified as prediabetic, with impaired glucose tolerance or impaired fasting glucose. Finally, the rationale for vildagliptin dosing frequency in monotherapy is discussed. In summary, this review aims to define where in community practice the use of vildagliptin as monotherapy is most desirable, focusing on segments of the population with type 2 diabetes mellitus that might receive the greatest benefit from vildagliptin in the management of their disease. PMID:22661900

Pre-stroke use of beta-blockers does not affect ischaemic stroke severity and outcome

NARCIS (Netherlands)

De Raedt, S.; Haentjens, P.; De Smedt, A.; Brouns, R.; Uyttenboogaart, Maarten; Luijckx, G. J.; De Keyser, J.

Background and purpose: It is unclear whether pre-stroke beta-blockers use may influence stroke outcome. This study evaluates the independent effect of pre-stroke use of beta-blockers on ischaemic stroke severity and 3 months functional outcome. Methods: Pre-stroke use of beta-blockers was

Beta-Blocker Use in Pregnancy and Risk of Specific Congenital Anomalies

DEFF Research Database (Denmark)

Bergman, Jorieke E H; Lutke, L Renée; Gans, Rijk O B

2018-01-01

INTRODUCTION: The prevalence of chronic hypertension is increasing in pregnant women. Beta-blockers are among the most prevalent anti-hypertensive agents used in early pregnancy. OBJECTIVE: The objective of this study was to investigate whether first-trimester use of beta-blockers increases the r...

Nurse-coordinated collaborative disease management improves the quality of guideline-recommended heart failure therapy, patient-reported outcomes, and left ventricular remodelling.

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Güder, Gülmisal; Störk, Stefan; Gelbrich, Goetz; Brenner, Susanne; Deubner, Nikolas; Morbach, Caroline; Wallenborn, Julia; Berliner, Dominik; Ertl, Georg; Angermann, Christiane E

2015-04-01

Heart failure (HF) pharmacotherapy is often not prescribed according to guidelines. This longitudinal study investigated prescription rates and dosages of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB), beta-blockers, and mineralocorticoid receptor antagonists (MRA), and concomitant changes of symptoms, echocardiographic parameters of left ventricular (LV) function and morphology and results of the Short Form-36 (SF-36) Health Survey in participants of the Interdisciplinary Network Heart Failure (INH) programme. The INH study evaluated a nurse-coordinated management, HeartNetCare-HF(TM) (HNC), against Usual Care (UC) in patients hospitalized for decompensated HF [LV ejection fraction (LVEF) ≤40% before discharge). A total of 706 subjects surviving >18 months (363 UC, 343 HNC) were examined 6-monthly. At baseline, 92% received ACEi/ARB, (HNC/UC 91/93%, P = 0.28), 86% received beta-blockers (86/86%, P = 0.83), and 44% received MRA (42/47%, P = 0.07). After 18 months, beta-blocker use had increased only in HNC (+7.6%, P change +17/+14%, P = 0.010), LV end-diastolic diameter (59 ± 9 vs. 61 ± 9.6 mm, P = 0.024, change -2.3/-1.4 mm, P = 0.13), New York Heart Association class (1.9 ± 0.7 vs. 2.1 ± 0.7, P = 0.001, change -0.44/-0.25, P = 0.002) and SF-36 physical component summary score (41.6 ± 11.2 vs. 38.5 ± 11.8, P = 0.004, change +3.3 vs. +1.1 score points, P changes after 18 months. © 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.

Effects of beta-blockers and nicardipine on oxotremorine-induced tremor in common marmosets.

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Mitsuda, M; Nomoto, M; Iwata, S

1999-10-01

Effects of beta-blockers (propranolol, arotinolol and nipradilol) and a Ca2+ channel blocker (nicardipine) on oxotremorine-induced tremor were studied in common marmosets. Generalized tremor was elicited by an intraperitoneal administration of 0.25 mg/kg oxotremorine. Intensity of the tremor was classified into 7 degrees, and it was evaluated every 10 min. The total intensity of oxotremorine-induced tremor for each drug was expressed as "points", which were the sum of tremor intensity scores evaluated every 10 min up to 190 min following the administration of oxotremorine. Beta-blockers significantly suppressed the tremor. On the other hand, the Ca2+ channel blocker exacerbated the tremor.

Predictors of antipsychotic monotherapy with olanzapine during a 1-year naturalistic study of schizophrenia patients in Japan

Directory of Open Access Journals (Sweden)

Ye W

2012-01-01

Full Text Available Wenyu Ye1, Haya Ascher-Svanum2, Jennifer A Flynn3, Yuka Tanji3, Michihiro Takahashi3,41Lilly Suzhou Pharmaceutical Co, Shanghai, People's Republic of China; 2Eli Lilly and Company, Indianapolis, IN, USA; 3Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Kobe, 4Terauchi-Takahashi Psychiatric Clinic, Ashiya, JapanPurpose: Although expert guidelines for the treatment of schizophrenia recommend antipsychotic monotherapy, the use of antipsychotic polypharmacy is common. This study identified characteristics that differentiate patients with schizophrenia who are treated with olanzapine monotherapy versus polypharmacy in usual care in Japan.Patients and methods: In a large (N = 1850 prospective, observational study, Japanese patients with schizophrenia who initiated treatment with olanzapine were followed for 1 year. Consistent with past research, antipsychotic polypharmacy was defined as the concurrent use of olanzapine and another antipsychotic for at least 60 days. Switching was defined as discontinuing a prior antipsychotic therapy rather than augmenting the medication regimen. Predictors of antipsychotic monotherapy were based on information available at the time of olanzapine initiation. Baseline characteristics were compared using t-tests and Χ2 tests. Stepwise logistic regression was used to identify independent predictors of monotherapy.Results: Patients treated with olanzapine monotherapy (43.2% differed from those treated with antipsychotic polypharmacy (56.8% on demographics, treatment history, baseline symptom levels, functional levels, and treatment-emergent adverse events. Stepwise logistic regression identified multiple variables that significantly predicted monotherapy: older age, shorter duration of schizophrenia, outpatient status, comorbid medical conditions, lower body mass index, no prior anticholinergic use, no prior mood stabilizer use, and switching from a previous antipsychotic (typical or atypical

Echocardiography and risk prediction in advanced heart failure: incremental value over clinical markers.

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Agha, Syed A; Kalogeropoulos, Andreas P; Shih, Jeffrey; Georgiopoulou, Vasiliki V; Giamouzis, Grigorios; Anarado, Perry; Mangalat, Deepa; Hussain, Imad; Book, Wendy; Laskar, Sonjoy; Smith, Andrew L; Martin, Randolph; Butler, Javed

2009-09-01

Incremental value of echocardiography over clinical parameters for outcome prediction in advanced heart failure (HF) is not well established. We evaluated 223 patients with advanced HF receiving optimal therapy (91.9% angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, 92.8% beta-blockers, 71.8% biventricular pacemaker, and/or defibrillator use). The Seattle Heart Failure Model (SHFM) was used as the reference clinical risk prediction scheme. The incremental value of echocardiographic parameters for event prediction (death or urgent heart transplantation) was measured by the improvement in fit and discrimination achieved by addition of standard echocardiographic parameters to the SHFM. After a median follow-up of 2.4 years, there were 38 (17.0%) events (35 deaths; 3 urgent transplants). The SHFM had likelihood ratio (LR) chi(2) 32.0 and C statistic 0.756 for event prediction. Left ventricular end-systolic volume, stroke volume, and severe tricuspid regurgitation were independent echocardiographic predictors of events. The addition of these parameters to SHFM improved LR chi(2) to 72.0 and C statistic to 0.866 (P advanced HF.

Pathophysiology of cardiac hypertrophy and heart failure: signaling pathways and novel therapeutic targets.

Science.gov (United States)

Tham, Yow Keat; Bernardo, Bianca C; Ooi, Jenny Y Y; Weeks, Kate L; McMullen, Julie R

2015-09-01

The onset of heart failure is typically preceded by cardiac hypertrophy, a response of the heart to increased workload, a cardiac insult such as a heart attack or genetic mutation. Cardiac hypertrophy is usually characterized by an increase in cardiomyocyte size and thickening of ventricular walls. Initially, such growth is an adaptive response to maintain cardiac function; however, in settings of sustained stress and as time progresses, these changes become maladaptive and the heart ultimately fails. In this review, we discuss the key features of pathological cardiac hypertrophy and the numerous mediators that have been found to be involved in the pathogenesis of cardiac hypertrophy affecting gene transcription, calcium handling, protein synthesis, metabolism, autophagy, oxidative stress and inflammation. We also discuss new mediators including signaling proteins, microRNAs, long noncoding RNAs and new findings related to the role of calcineurin and calcium-/calmodulin-dependent protein kinases. We also highlight mediators and processes which contribute to the transition from adaptive cardiac remodeling to maladaptive remodeling and heart failure. Treatment strategies for heart failure commonly include diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers and β-blockers; however, mortality rates remain high. Here, we discuss new therapeutic approaches (e.g., RNA-based therapies, dietary supplementation, small molecules) either entering clinical trials or in preclinical development. Finally, we address the challenges that remain in translating these discoveries to new and approved therapies for heart failure.

Vitreous changes after intravitreal bevacizumab monotherapy for retinopathy of prematurity: a case series.

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Shoeibi, Nasser; Hosseini, Seyedeh Maryam; Banaee, Touka; Ansari-Astaneh, Mohammad-Reza; Abrishami, Majid; Ahmadieh, Hamid

2018-01-01

Reporting a special clinical finding after intravitreal bevacizumab monotherapy for retinopathy of prematurity. In a retrospective case series, the clinical courses of five premature infants with similar vitreous changes after a single dose of intravitreal bevacizumab (IVB) injection without additional laser therapy were reported. The mean post-conceptional age at IVB injection was 39.8 ± 2.2 (range 37-43) weeks. Localized vitreous syneresis and linear fibrotic vitreous condensation occurred 8.2 ± 2.3 weeks after IVB monotherapy in our patients (15.5% of injections). The mean last post injection visit was 61.6 ± 5.3 weeks (post-conceptional age). Further regression and complete retinal vascularization occurred in all patients. Thread-like vitreous condensation with localized vitreous liquefaction may be related to involutional ROP disease itself, combined to anti VEGF therapy and may be a predictor factor for further regression and retinal vascularization. The case series describes a successful response to anti-VEGF monotherapy with no further complications.

Role of analgesics, sedatives, neuromuscular blockers, and delirium.

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Hall, Jesse B; Schweickert, William; Kress, John P

2009-10-01

A major focus on critical care medicine concerns the institution of life-support therapies, such as mechanical ventilation, during periods of organ failure to permit a window of opportunity to diagnose and treat underlying disorders so that patients may be returned to their prior functional status upon recovery. With the growing success of these intensive care unit-based therapies and longer-term follow-up of patients, severe weakness involving the peripheral nervous system and muscles has been identified in many recovering patients, often confounding the time course or magnitude of recovery. Mechanical ventilation is often accompanied by pharmacologic treatments including analgesics, sedatives, and neuromuscular blockers. These drugs and the encephalopathies accompanying some forms of critical illness result in a high prevalence of delirium in mechanically ventilated patients. These drug effects likely contribute to an impaired ability to assess the magnitude of intensive care unit-acquired weakness, to additional time spent immobilized and mechanically ventilated, and to additional weakness from the patient's relative immobility and bedridden state. This review surveys recent literature documenting these relationships and identifying approaches to minimize pharmacologic contributions to intensive care unit-acquired weakness.

PRESCRIBING OF ANTIHYPERTENSIVE AGENTS IN PUBLIC PRIMARY CARE CLINICS – IS IT IN ACCORDANCE WITH CURRENT EVIDENCE?

Directory of Open Access Journals (Sweden)

SAJARI J

2010-01-01

Full Text Available Background: Large population surveys in Malaysia have consistently shown minimal improvement of blood pressure control rates over the last 10 years. Poor adherence to antihypertensive medication has been recognized as a major reason for poor control of hypertension. This study aimed to describe the prescribing pattern of antihypertensive agents in 2 public primary care clinics and assess its appropriateness in relation to current evidence and guidelines. Methods: A cross-sectional survey to describe the prescribing pattern of antihypertensive agents was carried out in 2 publicprimary care clinics in Selangor from May to June 2009. Hypertensive patients on pharmacological treatment for ≥1 year who attended the clinics within the study period of 7 weeks were selected. Appropriate use of antihypertensive agents was defined based on current evidence and the recommendations by the Malaysian Clinical Practice Guidelines (CPG on the Management of Hypertension, 2008. Data were obtained from patients’ medical records and were analysed using the SPSS software version 16.0. Results: A total of 400 hypertensive patients on treatment were included. Mean age was 59.5 years (SD ±10.9, range 28 to91 years, of which 52.8% were females and 47.2% were males. With regards to pharmacotherapy, 45.7% were on monotherapy,43.3% were on 2 agents and 11.0% were on ≥3 agents. Target blood pressure of <140/90mmHg was achieved in 51.4% of patients on monotherapy, and 33.2% of patients on combination of ≥2 agents. The commonest monotherapy agents being prescribed were β-blockers (atenolol or propranolol, followed by the short-acting calcium channel blocker (nifedipine. The commonest combination of 2-drug therapy prescribed was β-blockers and short-acting calcium channel blocker. Conclusion: This study shows that the prescribing pattern of antihypertensive agents in the 2 primary care clinics was not in accordance with current evidence and guidelines. β-blockers

Beta blocker therapy is associated with reduced depressive symptoms 12 months post percutaneous coronary intervention.

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Battes, Linda C; Pedersen, Susanne S; Oemrawsingh, Rohit M; van Geuns, Robert J; Al Amri, Ibtihal; Regar, Evelyn; de Jaegere, Peter P T; Serruys, Patrick; van Domburg, Ron T

2012-02-01

Beta blocker therapy may induce depressive symptoms, although current evidence is conflicting. We examined the association between beta blocker therapy and depressive symptoms in percutaneous coronary intervention (PCI) patients and the extent to which there is a dose-response relationship between beta blocker dose and depressive symptoms. Patients treated with PCI (N=685) completed the depression scale of the Hospital Anxiety and Depression Scale 1 and 12 months post PCI. Information about type and dose of beta blocker use was extracted from medical records. Of all patients, 68% (466/685) were on beta blocker therapy at baseline. In adjusted analysis, beta blocker use at 1 month post PCI (OR: 0.82; 95% CI: 0.53-1.26) was not significantly associated with depressive symptoms. At 12 months post PCI, there was a significant relationship between beta blocker use and depressive symptoms (OR: 0.51; 95% CI: 0.31-0.84), with beta blocker therapy associated with a 49% risk reduction in depressive symptoms. There was a dose-response relationship between beta blocker dose and depressive symptoms 12 months post PCI, with the risk reduction in depressive symptoms in relation to a low dose being 36% (OR: 0.64; 95% CI: 0.37-1.10) and 58% (OR: 0.42; 95% CI: 0.24-0.76) in relation to a high dose. Patients treated with beta blocker therapy were less likely to experience depressive symptoms 12 months post PCI, with there being a dose-response relationship with a higher dose providing a more pronounced protective effect. Copyright © 2011 Elsevier B.V. All rights reserved.

Impact of beta-blockers on cardiopulmonary exercise testing in patients with advanced liver disease.

Science.gov (United States)

Wallen, M P; Hall, A; Dias, K A; Ramos, J S; Keating, S E; Woodward, A J; Skinner, T L; Macdonald, G A; Arena, R; Coombes, J S

2017-10-01

Patients with advanced liver disease may develop portal hypertension that can result in variceal haemorrhage. Beta-blockers reduce portal pressure and minimise haemorrhage risk. These medications may attenuate measures of cardiopulmonary performance, such as the ventilatory threshold and peak oxygen uptake measured via cardiopulmonary exercise testing. To determine the effect of beta-blockers on cardiopulmonary exercise testing variables in patients with advanced liver disease. This was a cross-sectional analysis of 72 participants who completed a cardiopulmonary exercise test before liver transplantation. All participants remained on their usual beta-blocker dose and timing prior to the test. Variables measured during cardiopulmonary exercise testing included the ventilatory threshold, peak oxygen uptake, heart rate, oxygen pulse, the oxygen uptake efficiency slope and the ventilatory equivalents for carbon dioxide slope. Participants taking beta-blockers (n = 28) had a lower ventilatory threshold (P advanced liver disease taking beta-blockers compared to those not taking the medication. This may incorrectly risk stratify patients on beta-blockers and has implications for patient management before and after liver transplantation. The oxygen uptake efficiency slope was not influenced by beta-blockers and may therefore be a better measure of cardiopulmonary performance in this patient population. © 2017 John Wiley & Sons Ltd.

Characteristics and outcome of patients with heart failure due to anabolic-androgenic steroids

DEFF Research Database (Denmark)

Søndergaard, Eva Bjerre; Thune, Jens Jakob; Gustafsson, Finn

2014-01-01

OBJECTIVES: The objective of the study was to analyse the outcome of patients with advanced heart failure due to abuse of anabolic-androgenic steroids. DESIGN: A retrospective chart review of patients admitted or referred for advanced heart failure, due to anabolic-androgenic steroid abuse...... with angiotensin-converting enzyme inhibitors and beta-blockers. The remaining 3 patients required implantation of a LV assist device (LVAD) and were listed for heart transplantation. No recovery of LV function in the patients treated with assist device was seen. CONCLUSION: Anabolic-androgenic steroid...

An Analysis of Forensic Imaging in the Absence of Write-Blockers

Directory of Open Access Journals (Sweden)

Gary C Kessler

2014-09-01

Full Text Available Best practices in digital forensics demand use of write-blockers when creating forensic copies of digital media and this has been a core of computer forensics training for decades. The practice is so in-grained that images created without a write-blocker are immediate suspect for integrity. This paper describes a research framework to examine what occurs when a forensic image is acquired without benefit of a write-blocker in order to understand the true impact of such an eventuality. The initial tests document the changes made to a hard drive and flash drive when imaged and examined with a Windows-based forensics workstation.

Effect of multidisciplinary disease management for hospitalized heart failure under a national health insurance programme.

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Mao, Chun-Tai; Liu, Min-Hui; Hsu, Kuang-Hung; Fu, Tieh-Cheng; Wang, Jong-Shyan; Huang, Yu-Yen; Yang, Ning-I; Wang, Chao-Hung

2015-09-01

Multidisciplinary disease management programmes (MDPs) for heart failure have been shown to be effective in Western countries. However, it is not known whether they improve outcomes in a high population density country with a national health insurance programme. In total, 349 patients hospitalized because of heart failure were randomized into control and MDP groups. All-cause death and re-hospitalization related to heart failure were analyzed. The median follow-up period was approximately 2 years. Mean patient age was 60 years; 31% were women; and 50% of patients had coronary artery disease. MDP was associated with fewer all-cause deaths [hazard ratio (HR) = 0.49, 95% confidence interval (CI) = 0.27-0.91, P = 0.02] and heart failure-related re-hospitalizations (HR = 0.44, 95% CI = 0.25-0.77, P = 0.004). MDP was still associated with better outcomes for all-cause death (HR = 0.53, 95% CI = 0.29-0.98, P = 0.04) and heart failure-related re-hospitalization (HR = 0.46, 95% CI = 0.26-0.81, P = 0.007), after adjusting for age, diuretics, diabetes mellitus, chronic kidney disease, hypertension, sodium, and albumin. However, MDPs' effect on all-cause mortality and heart failure-related re-hospitalization was significantly attenuated after adjusting for angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers or β-blockers. A stratified analysis showed that MDP combined with guideline-based medication had synergistic effects. MDP is effective in lowering all-cause mortality and re-hospitalization rates related to heart failure under a national health insurance programme. MDP synergistically improves the effectiveness of guidelines-based medications for heart failure.

What Is New in Heart Failure Management in 2017? Update on ACC/AHA Heart Failure Guidelines.

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Bozkurt, Biykem

2018-04-17

The goal of this paper is to provide a summary of the new recommendations in the most recent 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. The intent is to provide the background and the supporting evidence for the recommendations and to provide practical guidance for management strategies in treatment of heart failure patients. In the 2017 ACC/AHA/HFSA Focused Update of HF guidelines, important additions include new information on biomarkers, specifically on the topics of the diagnostic, prognostic role of natriuretic peptides in heart failure, and the role of natriuretic peptides in screening in patients high risk for HF and prevention of HF. There are important recommendations for treatment of patients with HF with reduced EF (HFrEF), including the beneficial role of angiotensin receptor blocker and neprilysin inhibition (ARNI) treatment in reducing outcomes including mortality, ivabradine in reducing heart failure hospitalizations in stable HFrEF patients with sinus rhythm and heart rate ≥ 70 bpm despite β-blockers. In patients with HF with preserved EF (HFpEF), though there are no studies demonstrating survival benefit, potential benefit with aldosterone antagonism in reducing HF hospitalizations is noted. In treatment of comorbidities, optimization of blood pressure control to less than 130 mmHg is recommended in hypertensive patients to prevent HF or in patients with hypertension and HFrEF or HFpEF. In addition to recognition on the potential role of treatment of iron deficiency anemia to improve symptoms and functional capacity, caution against use of adaptive servo-ventilation in patients with HFrEF and central sleep apnea and against use of erythropoietin stimulating agents in patients with HFrEF is provided. There are new treatment

β-Blockers, Cocaine, and the Unopposed α-Stimulation Phenomenon.

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Richards, John R; Hollander, Judd E; Ramoska, Edward A; Fareed, Fareed N; Sand, I Charles; Izquierdo Gómez, María Manuela; Lange, Richard A

2017-05-01

Cocaine abuse remains a significant worldwide health problem. Patients with cardiovascular toxicity from cocaine abuse frequently present to the emergency department for treatment. These patients may be tachycardic, hypertensive, agitated, and have chest pain. Several pharmacological options exist for treatment of cocaine-induced cardiovascular toxicity. For the past 3 decades, the phenomenon of unopposed α-stimulation after β-blocker use in cocaine-positive patients has been cited as an absolute contraindication, despite limited and inconsistent clinical evidence. In this review, the authors of the original studies, case reports, and systematic review in which unopposed α-stimulation was believed to be a factor investigate the pathophysiology, pharmacology, and published evidence behind the unopposed α-stimulation phenomenon. We also investigate other potential explanations for unopposed α-stimulation, including the unique and deleterious pharmacologic properties of cocaine in the absence of β-blockers. The safety and efficacy of the mixed β-/α-blockers labetalol and carvedilol are also discussed in relation to unopposed α-stimulation.

COPD predicts mortality in HF: the Norwegian Heart Failure Registry.

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De Blois, Jonathan; Simard, Serge; Atar, Dan; Agewall, Stefan

2010-03-01

Chronic obstructive pulmonary disease (COPD) and chronic heart failure (HF) are common clinical conditions that share tobacco as a risk factor. Our aim was to evaluate the prognostic impact of COPD on HF patients. The Norwegian Heart Failure Registry was used. The study included 4132 HF patients (COPD, n = 699) from 22 hospitals (mean follow-up, 13.3 months). COPD patients were older, more often smokers and diabetics, less often on beta-blockers and had a higher heart rate. They were more often in New York Heart Association (NYHA) Class III or IV (COPD, 63%; no COPD, 51%), although left ventricular ejection fraction (LVEF) distribution was similar. COPD independently predicted death (adjusted hazard ratio [HR], 1.188; 95% CI: 1.015 to 1.391; P = 0.03) along with age, creatinine, NYHA Class III/IV (HR, 1.464; 95% CI: 1.286 to 1.667) and diabetes. beta-blockers at baseline were associated with improved survival in patients with LVEF < or =40% independently of COPD. COPD is associated with a poorer survival in HF patients. COPD patients are overrated in terms of NYHA class in comparison with patients with similar LVEF. Nonetheless, NYHA class remains the strongest predictor of death in these patients. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Longterm Safety and Efficacy of Subcutaneous Tocilizumab Monotherapy: Results from the 2-year Open-label Extension of the MUSASHI Study.

Science.gov (United States)

Ogata, Atsushi; Amano, Koichi; Dobashi, Hiroaki; Inoo, Masayuki; Ishii, Tomonori; Kasama, Tsuyoshi; Kawai, Shinichi; Kawakami, Atsushi; Koike, Tatsuya; Miyahara, Hisaaki; Miyamoto, Toshiaki; Munakata, Yasuhiko; Murasawa, Akira; Nishimoto, Norihiro; Ogawa, Noriyoshi; Ojima, Tomohiro; Sano, Hajime; Shi, Kenrin; Shono, Eisuke; Suematsu, Eiichi; Takahashi, Hiroki; Tanaka, Yoshiya; Tsukamoto, Hiroshi; Nomura, Akira

2015-05-01

To evaluate the longterm safety and efficacy of subcutaneous tocilizumab (TCZ-SC) as monotherapy in patients with rheumatoid arthritis (RA). Of 346 patients who received 24 weeks of double-blind treatment with either TCZ-SC monotherapy, 162 mg every 2 weeks (q2w); or intravenous TCZ (TCZ-IV) monotherapy, 8 mg/kg every 4 weeks; 319 patients continued to receive TCZ-SC q2w in the 84-week open-label extension (OLE) of the MUSASHI study (JAPICCTI-101117). Efficacy, safety, and immunogenicity were evaluated for all patients treated with TCZ during 108 weeks. The proportions of patients who achieved American College of Rheumatology 20/50/70 responses, low disease activity [28-joint Disease Activity Score (DAS28) ≤ 3.2], or remission (DAS28 < 2.6) at Week 24 were maintained until Week 108. The incidences of adverse events and serious adverse events were 498.3 and 16.9 per 100 patient-years (PY), respectively. The overall safety of TCZ-SC monotherapy was similar to that of TCZ-IV monotherapy. Rates of injection site reactions (ISR) through 108 weeks remained similar to rates through 24 weeks. ISR were mild and did not cause any patient withdrawals. No serious hypersensitivity events (including anaphylactic reactions) occurred. Anti-TCZ antibodies were present in 2.1% of patients treated with TCZ-SC monotherapy. TCZ-SC monotherapy maintained a favorable safety profile and consistent efficacy throughout the 108-week study. Like TCZ-IV, TCZ-SC could provide an additional treatment option for patients with RA.

New therapies for arterial hypertension.

Science.gov (United States)

Pagliaro, Beniamino; Santolamazza, Caterina; Rubattu, Speranza; Volpe, Massimo

2016-03-01

Arterial hypertension is the most common chronic disease in developed countries and it is the leading risk factor for stroke, ischemic heart disease, congestive heart failure, chronic renal failure and peripheral artery disease. Its prevalence appears to be about 30-45% of the general population. Recent European guidelines estimate that up to 15-20% of the hypertensive patients are not controlled on a dual antihypertensive combination and they require three or more different antihypertensive drug classes to achieve adequate blood pressure control. The guidelines confirmed that diuretics, beta-blockers, calcium-channel blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are suitable for the initiation and maintenance of antihypertensive treatment, either as monotherapy or in combination therapy. Very few antihypertensive agents have reached the market over the last few years, but no new therapeutic class has really emerged. The long-term adherence to cardiovascular drugs is still low in both primary and secondary prevention of cardiovascular diseases. In particular, the issue of compliance is persistently high in hypertension, despite the fixed-dose combination therapy. As a consequence, a cohort of high-risk hypertensive population, represented by patients affected by refractory and resistant hypertension, can be identified. Therefore, the need of controlling BP in high-risk patients may be addressed, in part, by the development of new drugs, devices and procedures that are designed to treat hypertension and comorbidities. In this review we will comprehensively discuss the current literature on recent therapeutic advances in hypertension, including both medical therapy and interventional procedures.

Class III antiarrhythmic agents in cardiac failure: lessons from clinical trials with a focus on the Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA).

Science.gov (United States)

Doval, H C

1999-11-04

The results of previous clinical trials, in a variety of clinical settings, showed that class I agents may consistently increase mortality in sharp contrast to the effects of beta blockers. Attention has therefore shifted to class III compounds for potential beneficial effects on long-term mortality among patients with underlying cardiac disease. Clinical trials with d-sotalol, the dextro isomer (devoid of beta blockade) of sotalol, showed increased mortality in patients with low ejection fraction after myocardial infarction and in those with heart failure; whereas in the case of dofetilide, the impact on mortality was neutral. Because of the complex effects of its actions as an alpha-adrenergic blocker and a class III agent, the impact on mortality of amiodarone in patients with heart failure is of particular interest. A meta-analysis of 13 clinical trials revealed significant reductions in all-cause and cardiac mortality among patients with heart failure or previous myocardial infarction. Among these were 5 controlled clinical trials that investigated the effects of amiodarone on mortality among patients with heart failure. None of these trials was large relative to the beta-blocker trials in the postinfarction patients. However, the larger 2 of the 5 amiodarone trials produced discordant effects on mortality, neutral in one and significantly positive in the other. Some of the differences may be accounted for by the differences in eligibility criteria and baseline characteristics. Future trials that may be undertaken to resolve the discrepancies may need to allow for the newer findings on the effects of concomitant beta blockers, implantable devices, and possibly, spironolactone. All these modalities of treatment have been shown in controlled clinical trials to augment survival in patients with impaired ventricular function or manifest heart failure. Additional trials, some of which are currently in progress, compare amiodarone with implantable devices and other

Can Beta Blockers Cause Weight Gain?

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... cause weight gain? Can beta blockers cause weight gain? Answers from Sheldon G. Sheps, M.D. Yes. Weight gain can occur as a side effect of some ... and metoprolol (Lopressor, Toprol-XL). The average weight gain is about 2.6 pounds (about 1.2 ...

Efficacy and Safety of Switching Prostaglandin Analog Monotherapy to Tafluprost/Timolol Fixed-Combination Therapy

Science.gov (United States)

Kitamura, Kazuyoshi; Chiba, Tatsuya; Mabuchi, Fumihiko; Ishijima, Kiyotaka; Omoto, Shu; Kashiwagi, Fumiko; Godo, Takashi; Kogure, Satoshi; Goto, Teruhiko; Shibuya, Takashi; Tanabe, Jhoji; Tsukahara, Shigeo; Tsuchiya, Tadaharu; Tokunaga, Takaharu; Hosaka, Osamu; Saito, Tetsunori

2018-01-01

Purpose To assess the efficacy and safety of switching from prostaglandin analog (PGA) monotherapy to tafluprost/timolol fixed-combination (Taf/Tim) therapy. Subjects and Methods Patients with primary open-angle glaucoma, normal-tension glaucoma, or ocular hypertension who had received PGA monotherapy for at least 3 months were enrolled. Patients were examined at 1, 2, and 3 months after changing therapies. Subsequently, the patients were returned to PGA monotherapy. The examined parameters included intraocular pressure (IOP) and adverse events. A questionnaire survey was conducted after the switch to Taf/Tim therapy. Results Forty patients with a mean age of 66.5 ± 10.3 years were enrolled; 39 of these patients completed the study protocol. Switching to Taf/Tim significantly reduced the IOP from 18.2 ± 2.6 mmHg at baseline to 14.8 ± 2.5 mmHg at 1 month, 15.2 ± 2.8 mmHg at 2 months, and 14.9 ± 2.5 mmHg at 3 months (P Taf/Tim reduced the pulse rate insignificantly. No significant differences were observed in blood pressure, conjunctival hyperemia, or corneal adverse events. A questionnaire showed that the introduction of Taf/Tim did not significantly influence symptoms. Conclusions Compared with PGA monotherapy, Taf/Tim fixed-combination therapy significantly reduced IOP without severe adverse events. PMID:29675274

Low dose rate brachytherapy (LDR-BT) as monotherapy for early stage prostate cancer in Italy: practice and outcome analysis in a series of 2237 patients from 11 institutions.

Science.gov (United States)

Fellin, Giovanni; Mirri, Maria A; Santoro, Luigi; Jereczek-Fossa, Barbara A; Divan, Claudio; Mussari, Salvatore; Ziglio, Francesco; La Face, Beniamino; Barbera, Fernando; Buglione, Michela; Bandera, Laura; Ghedi, Barbara; Di Muzio, Nadia G; Losa, Andrea; Mangili, Paola; Nava, Luciano; Chiarlone, Renato; Ciscognetti, Nunzia; Gastaldi, Emilio; Cattani, Federica; Spoto, Ruggero; Vavassori, Andrea; Giglioli, Francesca R; Guarneri, Alessia; Cerboneschi, Valentina; Mignogna, Marcello; Paoluzzi, Mauro; Ravaglia, Valentina; Chiumento, Costanza; Clemente, Stefania; Fusco, Vincenzo; Santini, Roberto; Stefanacci, Marco; Mangiacotti, Francesco P; Martini, Marco; Palloni, Tiziana; Schinaia, Giuseppe; Lazzari, Grazia; Silvano, Giovanni; Magrini, Stefano; Ricardi, Umberto; Santoni, Riccardo; Orecchia, Roberto

2016-09-01

Low-dose-rate brachytherapy (LDR-BT) in localized prostate cancer is available since 15 years in Italy. We realized the first national multicentre and multidisciplinary data collection to evaluate LDR-BT practice, given as monotherapy, and outcome in terms of biochemical failure. Between May 1998 and December 2011, 2237 patients with early-stage prostate cancer from 11 Italian community and academic hospitals were treated with iodine-125 ((125)I) or palladium-103 LDR-BT as monotherapy and followed up for at least 2 years. (125)I seeds were implanted in 97.7% of the patients: the mean dose received by 90% of target volume was 145 Gy; the mean target volume receiving 100% of prescribed dose (V100) was 91.1%. Biochemical failure-free survival (BFFS), disease-specific survival (DSS) and overall survival (OS) were estimated using Kaplan-Meier method. Log-rank test and multivariable Cox regression were used to evaluate the relationship of covariates with outcomes. Median follow-up time was 65 months. 5- and 7-year DSS, OS and BFFS were 99 and 98%, 94 and 89%, and 92 and 88%, respectively. At multivariate analysis, the National Comprehensive Cancer Network score (p LDR-BT. This first multicentre Italian report confirms LDR-BT as an excellent curative modality for low-/intermediate-risk prostate cancer. Multidisciplinary teams may help to select adequately patients to be treated with brachytherapy, with a direct impact on the implant quality and, possibly, on outcome.

Beta blocker therapy is associated with reduced depressive symptoms 12 months post percutaneous coronary intervention

DEFF Research Database (Denmark)

Battes, Linda C; Pedersen, Susanne S.; Oemrawsingh, Rohit M

2012-01-01

Beta blocker therapy may induce depressive symptoms, although current evidence is conflicting. We examined the association between beta blocker therapy and depressive symptoms in percutaneous coronary intervention (PCI) patients and the extent to which there is a dose-response relationship between...... beta blocker dose and depressive symptoms....

Beta-blocker subtype and risks of perioperative adverse events following non-cardiac surgery

DEFF Research Database (Denmark)

Jørgensen, Mads E.; Sanders, Robert D.; Køber, Lars

2017-01-01

Aims Beta-blockers vary in pharmacodynamics and pharmacokinetic properties. It is unknown whether specific types are associated with increased perioperative risks. We evaluated perioperative risks associated with beta-blocker subtypes, overall and in patient subgroups. Methods and results We...... performed a Danish Nationwide cohort study, 2005-2011, of patients treated chronically with beta blocker (atenolol, bisoprolol, carvedilol, metoprolol, propranolol, or other) prior to non-cardiac surgery. Risks of 30-day all-cause mortality (ACM) and 30-day major adverse cardiovascular events (MACE) were...... in analyses stratified by age, surgery priority, duration of anaesthesia or surgery risk (all P for interaction >0.05). Conclusion Risks of ACM and MACE did not systematically differ by beta-blocker subtype. Findings may guide clinical practice and future trials....

Understanding the economic burden of heart failure in China: impact on disease management and resource utilization.

Science.gov (United States)

Huang, Jun; Yin, Hongjun; Zhang, Milun; Ni, Qian; Xuan, Jianwei

2017-05-01

This study has two objectives: (1) to examine healthcare resource utilization in heart failure (HF) patients; and (2) to examine the treatment costs associated with HF in China. The data used in this study was from the 2014 national insurance database sponsored by the China Health Insurance Research Association (CHIRA), that covers national urban employees and residents. ICD-10 codes and keywords indicating heart failure diagnoses were used to identify patients with heart failure. Drug utilization, hospital visits, re-admission, and treatment costs in different service categories were examined. A total of 7,847 patients were included in this analysis, of which 1,157 patients had a 1-year complete follow-up period. In total, 48.16% of patients received the combination treatment of angiotensin-converting-enzyme inhibitor (ACEI)/angiotensin II receptor blockers (ARB) and beta-blockers (BB); and 22.87% of patients received the combination treatment of ACEI/ARB, beta-blockers and Mineralocorticoid receptor antagonists (MRAs). The annual treatment cost per patient with HF diagnosis was RMB 28,974, of which 66% was for inpatient care. The cost on HF medications accounted for 8.2% of annual cost. Treatment cost was much higher in provincial-level municipalities than that of prefecture-level and other cities. Hospitalization is a major driver of HF treatment cost. Compared to the requirements in international treatment guidelines, HF standard of care medication treatment was under-utilized among HF patients in China. The high re-admission rate among Chinese patients indicates that the management of HF needs to be improved. The percentage of GDP spent on treating HF patients was much lower than that in the developed countries.

Clinical characteristics and causes of heart failure adherence to treatment guidelines and mortality of patients with acute heart failure: Experience at Groote Schuur Hospital Cape Town South Africa

Directory of Open Access Journals (Sweden)

P Szymanski

2018-02-01

Full Text Available Background. There is limited information on acute heart failure (AHF and its treatment in sub-Saharan Africa.Objective. To describe the clinical characteristics and causes of heart failure (HF, adherence to HF treatment guidelines, and mortality of patients with AHF presenting to Groote Schuur Hospital (GSH, Cape Town, South Africa.Methods. This sub-study of The Sub-Saharan Africa Survey of Heart Failure (THESUS-HF was a prospective and observational survey that focused on the enrolment and follow-up of additional patients with AHF presenting to GSH and entered into the existing registry after publication of the primary THESUS-HF article in 2012. The patients were classified into prevalent (existing or incident (new cases of HF.Results. Of the 119 patients included, 69 (58.0% were female and the mean (standard deviation age was 49.9 (16.3 years. The majority of prevalent cases were patients of mixed ancestry (63.3%, and prevalent cases had more hypertension (70.0%, diabetes mellitus (36.7%, hyperlipidaemia (33.3% and ischaemic heart disease (IHD (36.7% than incident cases. The top five causes of HF were cardiomyopathy (20.2%, IHD (19.3%, rheumatic valvular heart disease (RHD (18.5%, cor pulmonale (11.8% and hypertension (10.1%, with the remaining 20.1% consisting of miscellaneous causes including pericarditis, toxins and congenital heart disease. Most patients received renin-angiotensin system blockers and loop diuretics on discharge. There was a low rate of beta-blocker, aldosterone antagonist and digoxin use. Rehospitalisation within 180 days occurred in 25.2% of cases. In-hospital mortality was 8.4% and the case fatality rate at 6 months was 26.1%.Conclusion. In Cape Town, the main causes of AHF are cardiomyopathy, IHD and RHD. AHF affects a young population and is associated with a high rate of rehospitalisation and mortality. There is serious under-use of beta-blockers, aldosterone antagonists and digoxin. Emphasis on the rigorous

Late Pregnancy β Blocker Exposure and Risks of Neonatal Hypoglycemia and Bradycardia.

Science.gov (United States)

Bateman, Brian T; Patorno, Elisabetta; Desai, Rishi J; Seely, Ellen W; Mogun, Helen; Maeda, Ayumi; Fischer, Michael A; Hernandez-Diaz, Sonia; Huybrechts, Krista F

2016-09-01

β blockers are widely used in the treatment of hypertensive disorders during pregnancy. These medications cross the placenta and may cause physiologic changes in neonates exposed in utero. We sought to define the risks of neonatal hypoglycemia and bradycardia associated with maternal exposure to β blockers at the time of delivery in a large, nationwide cohort of Medicaid beneficiaries. We used a cohort of 2 292 116 completed pregnancies linked to liveborn infants of Medicaid-enrolled women from 2003 to 2007. We examined the risks of neonatal hypoglycemia and neonatal bradycardia associated with maternal exposure to β blockers at the time of delivery. Propensity score matching was used to control for potential confounders including maternal demographics, obstetric and medical conditions, and exposure to other medications. There were 10 585 (0.5%) pregnancies exposed to β blockers at the time of delivery. The risk of neonatal hypoglycemia was 4.3% in the β blocker-exposed neonates versus 1.2% in the unexposed; the risk of neonatal bradycardia was 1.6% in the exposed versus 0.5% in the unexposed. After controlling for confounders, risk remained elevated for both neonatal hypoglycemia and bradycardia among exposed pregnancies versus unexposed (adjusted odds ratio, 1.68, 95% confidence interval, 1.50-1.89 and adjusted odds ratio, 1.29, 95% confidence interval, 1.07-1.55, respectively). Our findings suggest that neonates born to mothers exposed to β blockers in late pregnancy, including labetalol, are at elevated risk for neonatal hypoglycemia and bradycardia. Copyright © 2016 by the American Academy of Pediatrics.

Polymer membrane electrodes for sensitive potentiometric determination of beta-blockers.

Science.gov (United States)

Wassil, Anwar A; Farag, Abd El-Ftaah Bastawy; Moukdad, Fatma A

2007-01-01

The construction of PVC matrix-type beta-blockers (sotalol, carvedilol, and betaxolol) ion selective electrodes and their use for direct potentiometry of their respective species are described. The proposed sensors are based on the complex ion associates of beta-blockers with tungstophosphate (TP) and Ammonium Reineckate (Rein) ionophoris in poly vinyl chloride membrane (PVC) with Dioctylphthalate (DOP) plasticizer. The four electrodes (Beta-TP), (Sota-TP), (Carve-TP), and (Cave-Rein) show stable potential response with near Nernstian slope of 50.8, 33.7, 32.35, and 33 mv per decade, range of concentration 10-2-10-7 M beta-blockers. Selectivity coefficients data obtained for 11 different organic and inorganic ions are presented. The electrodes have fast response time (30 and 40 s) and were used over wide range of pH 4.5-8.5. Validation of the method according to the quality assurance standers shows suitability of proposed sensors for use in the quality control assessment of these drugs. The results obtained for the determination of beta-blockers with the proposed electrodes show average recoveries of 100.78% and a mean standard deviation of +/-1.2. The nominal are obtained. The data agree well with those obtained by standard methods.

Quetiapine monotherapy in adolescents with bipolar disorder comorbid with conduct disorder.

Science.gov (United States)

Masi, Gabriele; Pisano, Simone; Pfanner, Chiara; Milone, Annarita; Manfredi, Azzurra

2013-10-01

Bipolar Disorders (BD) are often comorbid with disruptive behaviour disorders (DBDs) (oppositional-defiant disorder or conduct disorder), with negative implications on treatment strategy and outcome. The aim of this study was to assess the efficacy of quetiapine monotherapy in adolescents with BD comorbid with conduct disorder (CD). A consecutive series of 40 adolescents (24 males and 16 females, age range 12-18 years, mean age 14.9 ± 2.0 years), diagnosed with a clinical interview (Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime Version [K-SADS-PL]) according to American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria were included. All the patients were treated with quetiapine monotherapy (mean final dose 258 ± 124 mg/day, range 100-600 mg/day). At the end-point (3 months), 22 patients (55.0%) were responders (Clinical Global Impressions-Improvement [CGI-I] score of 1 or 2 and CGI-Severity [CGI-S] ≤ 3 and improvement of at least 30% Children's Global Assessment Scale [C-GAS] during 3 consecutive months). Both CGI-S and C-GAS significantly improved (pdisorder (ADHD) comorbidity. Eight patients (20.0%) experienced moderate to severe sedation and eight (20.0%) experienced increased appetite and weight gain. In these severely impaired adolescents, quetiapine monotherapy was well tolerated and effective in>50% of the patients.

Efficacy of escitalopram monotherapy in the treatment of major depressive disorder

Science.gov (United States)

Li, Guanjun; Shen, Yifeng; Luo, Jianfeng; Li, Huafang

2017-01-01

Abstract This study aimed to evaluate the efficacy of escitalopram monotherapy in the treatment of major depressive disorder (MDD) on the basis of pooled data analysis of 4 Chinese clinical trials. A total of 649 outpatients with MDD score of ≥18 at the 17-item Hamilton Depression Rating Scale (HAMD17) were included across 4 eligible studies. Patients were treated with 10 mg/day escitalopram for 2 weeks, and then 20 mg/day escitalopram was administered if the clinical response was poor. The change in total HAMD17 score was significantly greater in moderate MDD group than in other subgroups (P Escitalopram monotherapy is effective and safe in the treatment of MDD in Chinese patients, and therapeutic efficacy is dependent on the severity of MDD. Further study is needed to identify better predictors of therapeutic responses. PMID:28953649

Beta-blocker use and fall risk in older individuals: Original results from two studies with meta-analysis.

Science.gov (United States)

Ham, Annelies C; van Dijk, Suzanne C; Swart, Karin M A; Enneman, Anke W; van der Zwaluw, Nikita L; Brouwer-Brolsma, Elske M; van Schoor, Natasja M; Zillikens, M Carola; Lips, Paul; de Groot, Lisette C P G M; Hofman, Albert; Witkamp, Renger F; Uitterlinden, André G; Stricker, Bruno H; van der Velde, Nathalie

2017-10-01

To investigate the association between use of β-blockers and β-blocker characteristics - selectivity, lipid solubility, intrinsic sympathetic activity (ISA) and CYP2D6 enzyme metabolism - and fall risk. Data from two prospective studies were used, including community-dwelling individuals, n = 7662 (the Rotterdam Study) and 2407 (B-PROOF), all aged ≥55 years. Fall incidents were recorded prospectively. Time-varying β-blocker use was determined using pharmacy dispensing records. Cox proportional hazard models adjusted for age and sex were applied to determine the association between β-blocker use, their characteristics - selectivity, lipid solubility, ISA and CYP2D6 enzyme metabolism - and fall risk. The results of the studies were combined using meta-analyses. In total 2917 participants encountered a fall during a total follow-up time of 89 529 years. Meta-analysis indicated no association between use of any β-blocker, compared to nonuse, and fall risk, hazard ratio (HR) = 0.97 [95% confidence interval (CI) 0.88-1.06]. Use of a selective β-blocker was also not associated with fall risk, HR = 0.92 (95%CI 0.83-1.01). Use of a nonselective β-blocker was associated with an increased fall risk, HR = 1.22 (95%CI 1.01-1.48). Other β-blocker characteristics including lipid solubility and CYP2D6 enzyme metabolism were not associated with fall risk. Our study suggests that use of a nonselective β-blocker, contrary to selective β-blockers, is associated with an increased fall risk in an older population. In clinical practice, β-blockers have been shown effective for a variety of cardiovascular indications. However, fall risk should be considered when prescribing a β-blocker in this age group, and the pros and cons for β-blocker classes should be taken into consideration. © 2017 The British Pharmacological Society.

Risk of insomnia attributable to β-blockers in elderly patients with newly diagnosed hypertension.

Science.gov (United States)

Chang, Chia-Hsien; Yang, Yea-Huei Kao; Lin, Swu-Jane; Su, Jyun-Jhong; Cheng, Ching-Lan; Lin, Li-Jen

2013-01-01

Use of β-blockers may cause insomnia and central nervous system and/or psychological side effects, but data are limited on the relative risks of insomnia among β-blockers. This retrospective cohort study used Taiwan's National Health Insurance claims database from 2003 to 2007, where 4,063 patients aged above 65 years with newly diagnosed hypertension and treated with β-blockers were followed for 1 year. The primary endpoint was a new insomnia event within 30 days of treatment initiation. Adjusted odds ratios of insomnia were obtained by logistic regressions, controlling for baseline risk factors of insomnia. Using propranolol therapy as the reference, the adjusted odds ratio (95% confidence interval) for the insomnia risk was 0.47 (0.35-0.63) for non-propranolol users, 0.31 (0.19-0.50) for bisoprolol, and 0.46 (0.33-0.66) for atenolol. Compared to the patients using non-selective β-blockers, the adjusted odds ratio was 0.48 (0.36-0.34) for those using selective β(1)-blockers. Additionally, the adjusted odds ratio was 0.72 (0.53-0.96) for β-blockers with low lipophilicity when compared to those with high lipophilicity. The use of bisoprolol and atenolol was associated with the lowest risk of insomnia in elderly patients, as compared to propranolol. β-Blockers with high selectivity in β(1)-receptors and/or low lipophilicity were associated with a lower risk of insomnia.

Calcium channel blockers as the treatment of choice for hypertension in renal transplant recipients: fact or fiction.

Science.gov (United States)

Baroletti, Steven A; Gabardi, Steven; Magee, Colm C; Milford, Edgar L

2003-06-01

Posttransplantation hypertension has been identified as an independent risk factor for chronic allograft dysfunction and loss. Based on available morbidity and mortality data, posttransplantation hypertension must be identified and managed appropriately. During the past decade, calcium channel blockers have been recommended by some as the antihypertensive agents of choice in this population, because it was theorized that their vasodilatory effects would counteract the vasoconstrictive effects of the calcineurin inhibitors. With increasing data becoming available, reexamining the use of traditional antihypertensive agents, including diuretics and beta-blockers, or the newer agents, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers, may be beneficial. Transplant clinicians must choose antihypertensive agents that will provide their patients with maximum benefit, from both a renal and a cardiovascular perspective. Beta-blockers, diuretics, and ACE inhibitors have all demonstrated significant benefit on morbidity and mortality in patients with cardiovascular disease. Calcium channel blockers have been shown to possess the ability to counteract cyclosporine-induced nephrotoxicity. When compared with beta-blockers, diuretics, and ACE inhibitors, however, the relative risk of cardiovascular events is increased with calcium channel blockers. With the long-term benefits of calcium channel blockers on the kidney unknown and a negative cardiovascular profile, these agents are best reserved as adjunctive therapy to beta-blockers, diuretics, and ACE inhibitors.

The effects of high-dose amlodipine/benazepril combination therapies on blood pressure reduction in patients not adequately controlled with amlodipine monotherapy.

Science.gov (United States)

Chrysant, Steven G; Sugimoto, Daniel H; Lefkowitz, Marty; Salko, Thomas; Khan, Mahmudul; Arora, Vipin; Shi, Victor

2007-03-01

This study compared the efficacy and safety of amlodipine/benazepril (10/40 mg/day and 10/20 mg/day) with amlodipine 10 mg/day in patients whose blood pressure (BP) was not adequately controlled with amlodipine monotherapy. After a lead-in period with amlodipine monotherapy, 812 non-responder patients (mean sitting diastolic BP > or =95 mmHg) were randomized to one of three treatment groups. Ambulatory BP monitoring was conducted in 276 patients. Treatment with amlodipine/benazepril 10/40 mg/day and 10/20 mg/day resulted in a decrease of mean sitting systolic and mean sitting diastolic BP by 13.3/12.7 mmHg and 12.1/11.6 mmHg, respectively, compared with monotherapy (6.6/8.5 mmHg) (p benazepril 10/40 mg/day and 10/20 mg/day decreased ambulatory systolic and diastolic BP by 9.9/6.7 mmHg and 7.4/5.2 mmHg compared with monotherapy (p benazepril combinations compared with monotherapy (4.5%, 5.5% vs. 9.2%, respectively, p=NS). No significant metabolic side-effects were noted among the combination groups. Amlodipine/benazepril combinations were well tolerated and resulted in significant BP reductions and better BP responder rates than amlodipine monotherapy.

Pilot-Reported Beta-Blockers Identified by Forensic Toxicology Analysis of Postmortem Specimens.

Science.gov (United States)

Canfield, Dennis V; Dubowski, Kurt M; Whinnery, James M; Forster, Estrella M

2018-01-01

This study compared beta-blockers reported by pilots with the medications found by postmortem toxicology analysis of specimens received from fatal aviation accidents between 1999 and 2015. Several studies have compared drugs using the standard approach: Compare the drug found by toxicology analysis with the drug reported by the pilot. This study uniquely examined first the pilot-reported medication and then compared it to that detected by toxicology analysis. This study will serve two purposes: (i) to determine the capability of a toxicology laboratory to detect reported medications, and (ii) to identify pilots with medications below detectable limits. All information required for this study was extracted from the Toxicology Data Base system and was searched using ToxFlo or SQL Server Management Studio. The following information was collected and analyzed: pilot-reported trade and/or generic drug, date specimens received, time of accident, type of aviation operations (CFR), state, pilot level, age, class of medical, specimen type, specimen concentration, dose reported, frequency reported associated with the accident, quantity reported, National Transportation Safety Board (NTSB) accident event number, and all NTSB reports. There were 319 pilots that either reported taking a beta-blocker or were found to be taking a beta-blocker by postmortem toxicology analysis. Time of death, therapeutic concentration and specimen type were found to be factors in the ability of the laboratory to detect beta-blockers. Beta-blockers taken by pilots will, in most cases, be found by a competent postmortem forensic toxicology laboratory at therapeutic concentrations. The dose taken by the pilot was not found to be a factor in the ability of the laboratory to identify beta-blockers. Time of dose, route of administration, specimen tested and therapeutic concentration of the drug were found to be factors in the ability of the laboratory to identify beta-blockers in postmortem specimens

Implementation of a pharmacist-managed heart failure medication titration clinic.

Science.gov (United States)

Martinez, Amanda S; Saef, Jerold; Paszczuk, Anna; Bhatt-Chugani, Hetal

2013-06-15

The development, implementation, and initial results of a pharmacist-managed heart failure (HF) medication titration clinic are described. In a quality-improvement initiative at a Veterans Affairs health care system, clinical pharmacists were incorporated into the hospital system's interprofessional outpatient HF clinic. In addition, a separate pharmacist-managed HF medication titration clinic was established, in which pharmacists were granted an advanced scope of practice and prescribing privileges, enabling them to initiate and adjust medication dosages under specific protocols jointly established by cardiology and pharmacy staff. Pharmacists involved in the titration clinic tracked patients' daily body weight, vital signs, and volume status using telephone-monitoring technology and via patient interviews. A retrospective chart review comparing achievement of target doses of angiotensin-converting enzyme inhibitor (ACEI), angiotensin-receptor blocker (ARB), and β-blocker therapies in a group of patients (n = 28) whose dosage titrations were carried out by nurses or physicians prior to implementation of the pharmacist-managed HF medication titration clinic and a group of patients (n = 27) enrolled in the medication titration clinic during its first six months of operation indicated that target ACEI and ARB doses were achieved in a significantly higher percentage of pharmacist-managed titration clinic enrollees (52.9% versus 31%, p = 0.007). Patients enrolled in the pharmacist-managed HF medication titration clinic also had a significantly higher rate of attainment of optimal β-blocker doses (49% versus 24.7%, p = 0.012). Implementation of a pharmacist-managed HF medication titration clinic increased the percentage of patients achieving optimal ACEI, ARB, and β-blocker dosages.

How Do Beta Blocker Drugs Affect Exercise?

Science.gov (United States)

... in lieu of exercise. Exercise has many other benefits and is important to maintain your health. Read how physical activity improves the quality of life . Concerns About Exercising While on Beta Blockers “It’s important to remember ...

Angiotensin receptor blockers: Focus on cardiac and renal injury.

Science.gov (United States)

Arumugam, Somasundaram; Sreedhar, Remya; Thandavarayan, Rajarajan A; Karuppagounder, Vengadeshprabhu; Krishnamurthy, Prasanna; Suzuki, Kenji; Nakamura, Masahiko; Watanabe, Kenichi

2016-04-01

Angiotensin II, an important component of renin angiotensin system, is a potent vasopressor and its actions are mostly mediated via angiotensin II type 1 receptor (AT1R) and role of AT2R in counterbalancing the actions of AT1R stimulation are under extensive research. In addition to its physiological actions, angiotensin II plays important roles in the pathogenesis of atherosclerosis, hypertension, left ventricular hypertrophy, and heart failure. The effects of angiotensin II can be blocked by either suppressing its production by blocking angiotensin converting enzyme or by antagonizing its actions on AT1R using angiotensin II receptor blockers (ARBs). Instead of the extensive use of ARBs in the treatment of various cardiovascular diseases, proper selection of a particular ARB is crucial as the clinical condition of individual patient is different and also their economic status would play an essential role in medication compliance. Thus a critical review of the proven and promising actions of ARBs against various pathological conditions will be of great importance for the clinicians as well as for the researchers. Copyright © 2016 Elsevier Inc. All rights reserved.

QTc and psychopharmacs: are there any differences between monotherapy and polytherapy

Directory of Open Access Journals (Sweden)

Sisek-Šprem Mirna

2007-05-01

Full Text Available Abstract Background Some psychotropic drugs are connected with prolongation of QT interval, increased risk of cardiac arrhythmias and greater incidence of sudden death, especially when used in combination. Concomitant use of antipsychotics and antidepressants is not rare in our clinical practice. The study compares the length of QT interval in patients on monotherapy with an antipsychotic or an antidepressant and patients taking polytherapy (an antipsychotic agent combined with an antidepressant. Methods Sixty-one hospitalized women who met the ICD-10 criteria for schizophrenia, schizoaffective psychosis, delusional disorder and mood disorder were included in the study. The monotherapy group was consisted of thirty-two women treated with an antipsychotic or an antidepressant while the polytherapy group was composed of twenty-nine women treated with an antipsychotic agent plus an antidepressant. Two electrocardiograms (ECGs were obtained for each patient: the first was carried out before the treatment and the second after two weeks of treatment. Statistical analysis was carried out by SPSS program and included unpaired and paired t test and Fisher's exact test. Results Mean baseline QTc values did not differ between the groups (439 ± 22 ms was the same value found in the both groups; unpaired t test, p > 0.5. Mean QTc intervals after two weeks of treatment were also similar (439 ± 24 ms in the monotherapy group and 440 ± 20 ms in the polytherapy group; unpaired t test, p > 0.5. Fisher's exact test did not reveal significant difference in the number of patients with borderline (451–470 ms or prolonged (> 470 ms QTc between groups, neither before treatment nor after two weeks of treatment. Twenty two women of the total of sixty one patients (36% had QTc > 450 ms before applying therapy. Conclusion We did not find significant QT prolongation in our patients after two weeks of treatment with antipsychotics and/or antidepressants. The QTc

Systemic delivery of β-blockers via transdermal route for hypertension

Science.gov (United States)

Ahad, Abdul; Al-Jenoobi, Fahad I.; Al-Mohizea, Abdullah M.; Akhtar, Naseem; Raish, Mohammad; Aqil, Mohd.

2014-01-01

Hypertension is the most common cardiovascular disease worldwide. Moreover, management of hypertension requires long-term treatment that may result in poor patient compliance with conventional dosage forms due to greater frequency of drug administration. Although there is availability of a plethora of therapeutically effective antihypertensive molecules, inadequate patient welfare is observed; this arguably presents an opportunity to deliver antihypertensive agents through a different route. Ever since the transdermal drug delivery came into existence, it has offered great advantages including non-invasiveness, prolonged therapeutic effect, reduced side effects, improved bioavailability, better patient compliance and easy termination of drug therapy. Attempts were made to develop the transdermal therapeutic system for various antihypertensive agents, including β-blockers, an important antihypertensive class. β-blockers are potent, highly effective in the management of hypertension and other heart ailments by blocking the effects of normal amounts of adrenaline in the heart and blood vessels. The shortcomings associated with β-blockers such as more frequent dose administration, extensive first pass metabolism and variable bioavailability, make them an ideal candidate for transdermal therapeutic systems. The present article gives a brief view of different β-blockers formulated as transdermal therapeutic system in detail to enhance the bioavailability as well as to improve patient compliance. Constant improvement in this field holds promise for the long-term success in technologically advanced transdermal dosage forms being commercialized sooner rather than later. PMID:26702253

Discontinuation of beta-blockers and the risk of myocardial infarction in the elderly.

NARCIS (Netherlands)

Teichert, M.; Smet, P.A.G.M. de; Hofman, A.; Witteman, J.C.; Stricker, B.H.C.

2007-01-01

BACKGROUND: It has been shown that the abrupt cessation of treatment with beta-adrenoceptor antagonists (beta-blockers) increases the risk of myocardial infarction in patients with hypertension. As beta-blockers differ in their pharmacokinetic and pharmacodynamic properties, this risk of

Discontinuation of β-blockers and the risk of myocardial infarction in the elderly

NARCIS (Netherlands)

M. Teichert (Martina); P.A. de Smet (Peter); A. Hofman (Albert); J.C.M. Witteman (Jacqueline); B.H.Ch. Stricker (Bruno)

2007-01-01

textabstractBackground: It has been shown that the abrupt cessation of treatment with β-adrenoceptor antagonists (β-blockers) increases the risk of myocardial infarction in patients with hypertension. As β-blockers differ in their pharmacokinetic and pharmacodynamic properties, this risk of

Characteristics of patients with atrial fibrillation prescribed antiplatelet monotherapy compared with those on anticoagulants: insights from the GARFIELD-AF registry

NARCIS (Netherlands)

Verheugt, F.W.A.; Gao, H.; Mahmeed, W. Al; Ambrosio, G.; Angchaisuksiri, P.; Atar, D.; Bassand, J.P.; Camm, A.J.; Cools, F.; Eikelboom, J.; Kayani, G.; Lim, T.W.; Misselwitz, F.; Pieper, K.S.; Eickels, M. van; Kakkar, A.K.

2018-01-01

Aims: Current atrial fibrillation (AF) guidelines discourage antiplatelet (AP) monotherapy as alternative to anticoagulants (ACs). Why AP only is still used is largely unknown. Methods and results: Factors associated with AP monotherapy prescription were analysed in GARFIELD-AF, a registry of

Long-term exposure and safety of lacosamide monotherapy for the treatment of partial-onset (focal) seizures: Results from a multicenter, open-label trial.

Science.gov (United States)

Vossler, David G; Wechsler, Robert T; Williams, Paulette; Byrnes, William; Therriault, Sheila

2016-10-01

To assess long-term use and safety of lacosamide (LCM) ≤800 mg/day monotherapy in patients with partial-onset seizures (POS) enrolled previously in a historical-controlled, conversion-to-monotherapy study (SP902; NCT00520741). Patients completing or exiting SP902 with LCM as monotherapy or as adjunctive therapy were eligible to enter this 2-year open-label extension (OLE) trial (SP904; NCT00530855) at a starting dose ±100 mg/day of their final SP902 dose. Investigators could adjust the LCM dose to 100-800 mg/day and add up to two antiepileptic drugs to optimize tolerability and seizure reduction. Three hundred twenty-two patients received LCM: 210 patients (65.2%) completed and 112 (34.8%) discontinued, most commonly owing to withdrawal of consent (9.3%). Two hundred fifty-eight patients (80.1%) had ≥1 year of and 216 (67.1%) had ≥2 years of LCM exposure, of whom 179/258 (69.4%) achieved LCM monotherapy lasting for any 12-month period, and 126/216 (58.3%) patients exposed for ≥24 months achieved LCM monotherapy for any 24-month period. Total exposure = 525.5 patient-years. The median modal dose was 500 mg/day. Two hundred ninety-two patients (90.7%) achieved LCM monotherapy at some point during the study. Sixty-five of 87 patients who exited and 193/235 who completed SP902 were exposed for ≥12 months, and 43.1% and 78.2%, respectively, achieved LCM monotherapy for ≥12 months. Median LCM monotherapy duration was 587.0 days (2-791 days); 91.0% of patients reported treatment-emergent adverse events, of which the most common were dizziness (27.3%), headache (17.1%), and nausea (14.3%). Compared with the SP902 study baseline, 74.2% of patients had a ≥50% seizure reduction and 5.6% were seizure-free at 24 months. The majority of patients were receiving LCM monotherapy at 0, 12, and 24 months in this OLE. Lacosamide monotherapy (median dose of 500 mg/day) had a safety profile similar to that of adjunctive therapy studies. These results support the use of

Safe browsing - is an ad-blocker enough?

CERN Multimedia

CERN. Geneva

2015-01-01

An ad-blocker plugin in your browser stops advertisements and maybe some malware. But is it enough? Are you feeling secure while surfing the Web? If your answer is yes, think twice! What else can you do to protect yourself?

DMPD: Lipopolysaccharide-binding molecules: transporters, blockers and sensors. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 15241548 Lipopolysaccharide-binding molecules: transporters, blockers and sensors. ...binding molecules: transporters, blockers and sensors. PubmedID 15241548 Title Lipopolysaccharide-binding molecules: transport...Chaby R. Cell Mol Life Sci. 2004 Jul;61(14):1697-713. (.png) (.svg) (.html) (.csml) Show Lipopolysaccharide-

Oral Hypoglycemic Agents Added to Insulin Monotherapy for Type 2 Diabetes

NARCIS (Netherlands)

Vos, Rimke C.; Rutten, Guy E.H.M.

2017-01-01

Clinical Question: Among patients with type 2 diabetes mellitus who do not achieve optimal glycemic control with insulin monotherapy, is the addition of oral hypoglycemic agents associated with benefits (measured by lowering of hemoglobin A1c) or adverse effects? Bottom Line: Adding a sulfonylurea

Cardiac I123-MIBG Correlates Better than Ejection Fraction with Symptoms Severity in Systolic Heart Failure

Energy Technology Data Exchange (ETDEWEB)

Miranda, Sandra M.; Moscavitch, Samuel D.; Carestiato, Larissa R. [Programa de Pós-Graduação em Ciências Cardiovasculares, Hospital Universitário Antonio Pedro, Universidade Federal Fluminense, Rio de Janeiro, RJ (Brazil); Felix, Renata M. [Departamento de Medicina Nuclear, Hospital Pró-Cardíaco, Rio de Janeiro, RJ (Brazil); Rodrigues, Ronaldo C.; Messias, Leandro R. [Programa de Pós-Graduação em Ciências Cardiovasculares, Hospital Universitário Antonio Pedro, Universidade Federal Fluminense, Rio de Janeiro, RJ (Brazil); Azevedo, Jader C. [Programa de Pós-Graduação em Ciências Cardiovasculares, Hospital Universitário Antonio Pedro, Universidade Federal Fluminense, Rio de Janeiro, RJ (Brazil); Departamento de Medicina Nuclear, Hospital Pró-Cardíaco, Rio de Janeiro, RJ (Brazil); Nóbrega, Antonio Cláudio L.; Mesquita, Evandro Tinoco [Programa de Pós-Graduação em Ciências Cardiovasculares, Hospital Universitário Antonio Pedro, Universidade Federal Fluminense, Rio de Janeiro, RJ (Brazil); Mesquita, Claudio Tinoco, E-mail: ctinocom@cardiol.br [Programa de Pós-Graduação em Ciências Cardiovasculares, Hospital Universitário Antonio Pedro, Universidade Federal Fluminense, Rio de Janeiro, RJ (Brazil); Departamento de Medicina Nuclear, Hospital Pró-Cardíaco, Rio de Janeiro, RJ (Brazil)

2013-07-15

The association of autonomic activation, left ventricular ejection fraction (LVEF) and heart failure functional class is poorly understood. Our aim was to correlate symptom severity with cardiac sympathetic activity, through iodine-123-metaiodobenzylguanidine ({sup 123}I-MIBG) scintigraphy and with LVEF in systolic heart failure (HF) patients without previous beta-blocker treatment. Thirty-one patients with systolic HF, class I to IV of the New York Heart Association (NYHA), without previous beta-blocker treatment, were enrolled and submitted to {sup 123}I-MIBG scintigraphy and to radionuclide ventriculography for LVEF determination. The early and delayed heart/mediastinum (H/M) ratio and the washout rate (WR) were performed. According with symptom severity, patients were divided into group A, 13 patients in NYHA class I/II, and group B, 18 patients in NYHA class III/IV. Compared with group B patients, group A had a significantly higher LVEF (25% ± 12% in group B vs. 32% ± 7% in group A, p = 0.04). Group B early and delayed H/M ratios were lower than group A ratios (early H/M 1.49 ± 0.15 vs. 1.64 ± 0.14, p = 0.02; delayed H/M 1.39 ± 0.13 vs. 1.58 ± 0.16, p = 0.001, respectively). WR was significantly higher in group B (36% ± 17% vs. 30% ± 12%, p= 0.04). The variable that showed the best correlation with NYHA class was the delayed H/M ratio (r= -0.585; p=0.001), adjusted for age and sex. This study showed that cardiac {sup 123}I-MIBG correlates better than ejection fraction with symptom severity in systolic heart failure patients without previous beta-blocker treatment.

Efficacy of Daptomycin Monotherapy and In Combination with β-lactams for Daptomycin-Susceptible Enterococcus faecium Harboring LiaSR Substitutions: Influence of The Inoculum Effect.

Science.gov (United States)

Kebriaei, Razieh; Rice, Seth A; Singh, Kavindra V; Stamper, Kyle C; Dinh, An Q; Rios, Rafael; Diaz, Lorena; Murray, Barbara E; Munita, Jose M; Tran, Truc T; Arias, Cesar A; Rybak, Michael J

2018-05-14

Enterococcus faecium that harbor LiaFSR substitutions but are phenotypically susceptible to daptomycin (DAP) by current breakpoints are problematic since predisposition to resistance may lead to therapeutic failure. Using a simulated endocardial vegetation (SEV) PK/PD model, we investigated DAP regimens (6, 8 and 10 mg/kg/day) as monotherapy and in combination with ampicillin (AMP), ceftaroline (CPT) or ertapenem (ERT) against E. faecium HOU503, a DAP-susceptible strain that harbors common LiaS and LiaR substitutions found in clinical isolates (T120S and W73C, respectively). Of interest, the efficacy of DAP monotherapy, at any dose regimen, was dependent on the size of the inoculum. At an inoculum of ∼10 9 CFU/g, DAP doses of 6-8 mg/kg/d were not effective and led to significant regrowth with emergence of resistant derivatives. In contrast, at an inoculum of ∼10 7 , marked reductions in bacterial counts were observed with DAP 6 mg/kg/d with no resistance. The inoculum effect was confirmed in a rat model using humanized DAP exposures. Combinations of DAP with AMP, CPT or ERT demonstrated enhanced eradication and reduced potential for resistance allowing for de-escalation of the DAP dose. Persistence of the LiaRS substitutions were identified in DAP-resistant isolates recovered from the SEV model and in DAP-resistant derivatives of an initially DAP-susceptible clinical isolate of E. faecium (HOU668) harboring LiaSR substitutions and recovered from a patient with a recurrent bloodstream infection. Our results provide novel data for the use of DAP monotherapy and combinations for recalcitrant E. faecium infections and paves the way for testing these approaches in humans. Copyright © 2018 American Society for Microbiology.

Beneficial effects of metoprolol on myocardial sympathetic function: Evidence from a randomized, placebo-controlled study in patients with congestive heart failure

NARCIS (Netherlands)

de Milliano, Paul A. R.; de Groot, Andre C.; Tijssen, Jan G. P.; van Eck-Smit, Berthe L. F.; van Zwieten, Pieter A.; Lie, Kong I.

2002-01-01

BACKGROUND: We sought to investigate whether beta-blockers exert a presynaptic effect in the myocardium as measured by 123I-metaiodobenzylguanidine. METHODS: The study comprised 59 patients with congestive heart failure, New York Heart Association class II or III, and left ventricular ejection

Banding ligation versus beta-blockers for primary prevention in oesophageal varices in adults

DEFF Research Database (Denmark)

Gluud, Lise Lotte; Krag, Aleksander

2012-01-01

Non-selective beta-blockers are used as a first-line treatment for primary prevention in patients with medium- to high-risk oesophageal varices. The effect of non-selective beta-blockers on mortality is debated and many patients experience adverse events. Trials on banding ligation versus non...

Cellular Responses to Beta Blocker Exposures in Marine ...

Science.gov (United States)

β blockers are prescription drugs used for medical treatment of hypertension and arrhythmias. They prevent activation of adenylate cyclase and increases in blood pressure by limiting cAMP production and protein kinase A activation. After being taken therapeutically, β blockers may make their way to coastal habitats via discharge from waste water treatment plants, posing a potential risk to aquatic organisms. The aim of our research is to evaluate cellular biomarkers of β blocker exposure using two drugs, propranolol and metoprolol, in three commercially important marine bivalves -Crassostrea virginica, Mytilus edulis and Mercenaria mercenaria. Bivalves were obtained from Narragansett Bay (Rhode Island, USA) and acclimated in the laboratory. Following acclimation, gills and hepatopancreas tissues were harvested and separately exposed to 0, 1, 10, 100 and 1000 ng/l of each drug for 24 hours. Samples were preserved for cellular biomarker assays. Elevated cellular damage and changes in enzymatic activities were noted at environmentally relevant concentrations, and M. mercenaria was found to be the most sensitive bivalve out of the three species tested. These studies enhance our understanding of the potential impacts of commonly used prescription medication on organisms in coastal ecosystems, and demonstrate that filter feeders such as marine bivalves may serve as good model organisms to examine the effects of water soluble drugs. Evaluating a suite of biomarkers

Marine Bivalve Cellular Responses to Beta Blocker Exposures ...

Science.gov (United States)

β blockers are prescription drugs used for medical treatment of hypertension and arrhythmias. They prevent binding of agonists such as catecholamines to β adrenoceptors. In the absence of agonist induced activation of the receptor, adenylate cyclase is not activated which in turn limits cAMP production and protein kinase A activation, preventing increases in blood pressure and arrhythmias. After being taken therapeutically, commonly prescribed β blockers may make their way to coastal habitats via discharge from waste water treatment plants (WWTP) posing a potential risk to aquatic organisms. The aim of our research is to evaluate cellular responses of three commercially important marine bivalves - Eastern oysters, blue mussels and hard clams - upon exposure to two β blocker drugs, propranolol and metoprolol, and to find molecular initiating events (MIEs) indicative of the exposure. Bivalves were obtained from Narragansett Bay (Rhode Island, USA) and acclimated in the laboratory. Following acclimation, gills and hepatopancreas (HP) tissues were harvested and separately exposed to 0, 1, 10, 100 and 1000 ng/l of each drug. Tissues were bathed in 30 parts per thousand (ppt) filtered seawater, antibiotic mix, Leibovitz nutrient media, and the test drug. Exposures were conducted for 24 hours and samples were saved for cellular biomarker assays. A lysosomal destabilization assay, which is a marker of membrane damage, was also performed at the end of each exposure.

Cerebrospinal fluid analysis for HIV replication and biomarkers of immune activation and neurodegeneration in long-term atazanavir/ritonavir monotherapy treated patients.

Science.gov (United States)

Ferretti, Francesca; Bigoloni, Alba; Passeri, Laura; Galli, Laura; Longo, Valeria; Gerevini, Simonetta; Spagnuolo, Vincenzo; Gisslen, Magnus; Zetterberg, Henrik; Fuchs, Dietmar; Cattaneo, Dario; Caramatti, Giada; Lazzarin, Adriano; Cinque, Paola; Castagna, Antonella

2016-07-01

Cerebrospinal fluid (CSF) viral escape is a concern in ritonavir-boosted protease inhibitors monotherapy. The aim was to assess HIV-RNA, biomarkers of immune activation and neurodegeneration, and atazanavir concentrations in CSF of patients on successful long-term atazanavir/ritonavir (ATV/r) monotherapy. This is a substudy of the multicentric, randomized, open-label, noninferiority trial monotherapy once a day with atazanavir/ritonavir (NCT01511809), comparing the ongoing ATV/r along with 2 nucleoside retrotranscriptase inhibitors (NRTIs) regimen to a simplified ATV/r monotherapy. Patients with plasma HIV-RNA < 50 copies/mL after at least 96 study weeks were eligible.We assessed HIV-RNA, soluble (s)CD14, sCD163, CCL2, CXCL10, interleukin-6, and YKL40 by enzyme-linked immunosorbent assay; neopterin, tryptophan, kynurenine, and neurofilament by immunoassays; and ATV concentrations by liquid chromatography-mass spectrometry in paired plasma and CSF samples. Variables were compared with Wilcoxon rank-sum or Fisher exact test, as appropriate. HIV-RNA was detected in the CSF of 1/11 patients on ATV/r monotherapy (114 copies/mL), without neurological symptoms, who was successfully reintensified with his previous 2NRTIs, and in none of the 12 patients on ATV/r + 2NRTIs. CSF biomarkers and ATV concentrations did not differ between the 2 arms. CSF escape was uncommon in patients on long-term ATV/r monotherapy and was controlled with reintensification.

A randomised comparison of 'Casodex' (bicalutamide) 150 mg monotherapy versus castration in the treatment of metastatic and locally advanced prostate cancer

DEFF Research Database (Denmark)

Tyrrell, C J; Kaisary, A V; Iversen, P

1998-01-01

To evaluate the efficacy and tolerability of 'Casodex' monotherapy (150 mg daily) for metastatic and locally advanced prostate cancer.......To evaluate the efficacy and tolerability of 'Casodex' monotherapy (150 mg daily) for metastatic and locally advanced prostate cancer....

Are lipophilic beta-blockers preferable for peri-operative ...

African Journals Online (AJOL)

Adele

management of hypertension and post myocardial infarction.4-6. Are lipophilic ... studies in hypertensive medical patients showed no difference in cardiovascular ... atenolol and bendroflumethiazide arm.7 In meta-analyses of beta-blocker ...

Is There a Role for Ivabradine in the Contemporary Management of Patients with Chronic Heart Failure in Academic and Community Heart Failure Clinics in Canada?

Science.gov (United States)

Roth, Sherryn; Fernando, Carlos; Azeem, Sadia; Moe, Gordon W

2017-06-01

In patients with heart failure (HF) and reduced ejection fraction, increased heart rate (HR) is an independent risk factor for adverse outcomes. In systolic HF treatment with the If inhibitor ivabradine trial (SHIFT), Ivabradine improved survival when added to conventional treatment including β-blockers. However, the extent of benefit in the real world is unclear. We examined the characteristics of patients on guideline-directed therapy and determined who had SHIFT-like characteristics. A total of 1096 patients with chronic HF were reviewed from June 2014 to April 2015 in two HF clinics in Toronto: an academic institution (AI), and a community hospital (CH) clinic. SHIFT-like characteristics [left ventricular ejection fraction (LVEF) ≤35%; sinus rhythm; and HR ≥ 70 bpm] were described. For all patients, mean age was 75 ± 13 years, overall LVEF was 44 ± 15%, AI less than CH (41.9 ± 14.0% vs. 45.7 ± 15.0%; p < 0.0001). More than two-thirds of patients in both groups were on β-blockers; with less than one-third at target dose. The proportion of patients with SHIFT-like characteristics was 8.4% AI and 11.7% CH, respectively (p = 0.0658). In HF clinics from both academic and community hospitals in Toronto, up-titration in the dose of β-blockers and other guideline therapy can be improved on. A small proportion of patients with HF and SHIFT-like characteristics may potentially benefit from the addition of Ivabradine, just approved in Canada; this number will be further reduced if target dosage for β-blockers is achieved. Servier Inc.

Sacubitril/valsartan: an Important Piece in the Therapeutic Puzzle of Heart Failure

OpenAIRE

Marques da Silva, P; Aguiar, C

2017-01-01

Sacubitril/valsartan (LCZ696), a supramolecular sodium salt complex of the neprilysin inhibitor prodrug sacubitril and the angiotensin receptor blocker (ARB) valsartan, was recently approved in the EU and the USA for the treatment of chronic heart failure (HF) with reduced ejection fraction (HFrEF) (NYHA class II-IV). Inhibition of chronically activated neurohormonal pathways (the renin-angiotensin-aldosterone system [RAAS] and sympathetic nervous system [SNS]) is central to the treatment of ...

Optimal use of β-blockers in high-risk hypertension: A guide to dosing equivalence

Directory of Open Access Journals (Sweden)

Janet B McGill

2010-05-01

Full Text Available Janet B McGillDepartment of Medicine, Washington University School of Medicine, St. Louis, Missouri, USAAbstract: Hypertension is the number one diagnosis made by primary care physicians, placing them in a unique position to prescribe the antihypertensive agent best suited to the individual patient. In individuals with diabetes mellitus, blood pressure (BP levels > 130/80 mmHg confer an even higher risk for cardiovascular and renal disease, and these patients will benefit from aggressive antihypertensive treatment using a combination of agents. β‑blockers are playing an increasingly important role in the management of hypertension in high-risk patients. β‑blockers are a heterogeneous class of agents, and this review presents the differences between β‑blockers and provides evidence-based protocols to assist in understanding dose equivalence in the selection of an optimal regimen in patients with complex needs. The clinical benefits provided by β‑blockers are only effective if patients adhere to medication treatment long term. β‑blockers with proven efficacy, once-daily dosing, and lower side effect profiles may become instrumental in the treatment of hypertensive diabetic and nondiabetic patients.Keywords: antihypertensive, blood pressure, atenolol, carvedilol, labetalol, metoprolol, nebivolol

Beta-blocker therapy and cardiac events among patients with newly diagnosed coronary heart disease

DEFF Research Database (Denmark)

Andersson, Charlotte; Shilane, David; Go, Alan S

2014-01-01

BACKGROUND: The effectiveness of beta-blockers for preventing cardiac events has been questioned for patients who have coronary heart disease (CHD) without a prior myocardial infarction (MI). OBJECTIVES: The purpose of this study was to assess the association of beta-blockers with outcomes among...... patients with new-onset CHD. METHODS: We studied consecutive patients discharged after the first CHD event (acute coronary syndrome or coronary revascularization) between 2000 and 2008 in an integrated healthcare delivery system who did not use beta-blockers in the year before entry. We used time......-varying Cox regression models to determine the hazard ratio (HR) associated with beta-blocker treatment and used treatment-by-covariate interaction tests (pint) to determine whether the association differed for patients with or without a recent MI. RESULTS: A total of 26,793 patients were included, 19...

Levetiracetam monotherapy for treatment of structural epilepsy in dogs: 19 cases (2010-2015).

Science.gov (United States)

Kelly, Darren; Raimondi, Francesca; Shihab, Nadia

2017-10-14

To evaluate the efficacy and tolerability of levetiracetam monotherapy in dogs with structural epilepsy. Retrospective case series. Nineteen client-owned dogs with structural epilepsy. Seizure frequencies after initiation of treatment were used to evaluate the efficacy of levetiracetam monotherapy. Seizure control was considered good if no seizures occurred within three months of starting treatment or poor if seizures returned within one month of starting treatment. Tolerability was evaluated by considering the occurrence and severity of any reported side effects. Ten of the 19 dogs were considered to have a good response to treatment with 7 achieving complete seizure freedom. Nine dogs were considered to have poor response to treatment. There was a statistically significant reduction in the percentage of patients experiencing cluster seizures from 68.4% to 15.8% (p=0.002). Side effects were noted in 8 of the 19 dogs but were considered mild in all cases. Follow-up times ranged from 12 days to 426 days. When used in conjunction with other appropriate therapies, levetiracetam may be an efficacious option for monotherapy in dogs with structural epilepsy. Its tolerability makes it a suitable option for use in a wide variety of patients. © British Veterinary Association (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

High-Dose-Rate Monotherapy: Safe and Effective Brachytherapy for Patients With Localized Prostate Cancer

International Nuclear Information System (INIS)

Demanes, D. Jeffrey; Martinez, Alvaro A.; Ghilezan, Michel; Hill, Dennis R.; Schour, Lionel; Brandt, David; Gustafson, Gary

2011-01-01

Purpose: High-dose-rate (HDR) brachytherapy used as the only treatment (monotherapy) for early prostate cancer is consistent with current concepts in prostate radiobiology, and the dose is reliably delivered in a prospectively defined anatomic distribution that meets all the requirements for safe and effective therapy. We report the disease control and toxicity of HDR monotherapy from California Endocurietherapy (CET) and William Beaumont Hospital (WBH) in low- and intermediate-risk prostate cancer patients. Methods and Materials: There were 298 patients with localized prostate cancer treated with HDR monotherapy between 1996 and 2005. Two biologically equivalent hypofractionation protocols were used. At CET the dose was 42 Gy in six fractions (two implantations 1 week apart) delivered to a computed tomography–defined planning treatment volume. At WBH the dose was 38 Gy in four fractions (one implantation) based on intraoperative transrectal ultrasound real-time treatment planning. The bladder, urethral, and rectal dose constraints were similar. Toxicity was scored with the National Cancer Institute Common Toxicity Criteria for Adverse Events version 3. Results: The median follow-up time was 5.2 years. The median age of the patients was 63 years, and the median value of the pretreatment prostate-specific antigen was 6.0 ng/mL. The 8-year results were 99% local control, 97% biochemical control (nadir +2), 99% distant metastasis–free survival, 99% cause-specific survival, and 95% overall survival. Toxicity was scored per event, meaning that an individual patient with more than one symptom was represented repeatedly in the morbidity data table. Genitourinary toxicity consisted of 10% transient Grade 2 urinary frequency or urgency and 3% Grade 3 episode of urinary retention. Gastrointestinal toxicity was <1%. Conclusions: High disease control rates and low morbidity demonstrate that HDR monotherapy is safe and effective for patients with localized prostate cancer.

Apatinib plus icotinib in treating advanced non-small cell lung cancer after icotinib treatment failure: a retrospective study.

Science.gov (United States)

Xu, Jianping; Liu, Xiaoyan; Yang, Sheng; Zhang, Xiangru; Shi, Yuankai

2017-01-01

Treatment failure frequently occurs in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) who respond to EGFR tyrosine kinase inhibitors initially. This retrospective study tried to investigate the efficacy and safety of apatinib plus icotinib in patients with advanced NSCLC after icotinib treatment failure. This study comprised 27 patients with advanced NSCLC who had progressed after icotinib monotherapy. Initially, patients received oral icotinib (125 mg, tid) alone. When the disease progressed, they received icotinib plus apatinib (500 mg, qd, orally). Treatment was continued until disease progression, unacceptable toxicity or consent withdrawal. Followed up to December 2016, the median time of combined therapy was 7.47 months, and eight of 27 patients were dead. The median overall survival was not reached, and median progression-free survival (PFS) was 5.33 months (95% CI, 3.63-7.03 months). Moreover, the objective response rate (ORR) was 11.1%, and the disease control rate (DCR) was 81.5%. A total of 14 patients received combined therapy as the second-line treatment, and the ORR and DCR were 7.1% and 78.6%, respectively; 13 patients received drugs as the third- or later-line treatment, with an ORR and a DCR of 15.4% and 84.6%, respectively. In addition, 11 patients experienced icotinib monotherapy failure within 6 months with median PFS of 7.37 months, and 16 patients had progression after 6 months with median PFS of 2.60 months. The common drug-related toxic effects were hypertension (44.4%) and fatigue (37.0%). Apatinib plus icotinib is efficacious in treating patients with advanced NSCLC after icotinib treatment failure, with acceptable toxic effects.

The Effect of Combined Treatment with the (ProRenin Receptor Blocker HRP and Quinapril in Type 1 Diabetic Rats

Directory of Open Access Journals (Sweden)

Gábor Kökény

2017-04-01

Full Text Available Background/Aims: Diabetic nephropathy remains a major clinical problem. The effects of prorenin might be adverse, but the literature data are controversial. We compared the renal effects of the (prorenin receptor ((PRR blockade and angiotensin converting enzyme (ACE inhibition on the progression of diabetic nephropathy in rats. Methods: Diabetes (DM was induced by ip. streptozotocin administration in adult male Sprague-Dawley rats, followed by eight weeks of treatment with the (PRR blocker „handle region” decoy peptide (HRP, 0,1 mg/kg/day or with the ACE inhibitor Quinapril (Q, 50 mg/kg/day and grouped as follows: 1. Control (n=10; 2. DM (n=8; 3. DM+HRP (n=6; 4. DM+Q (n=10; 5. DM+Q+HRP (n=10. Renal functional parameters, histology and gene expressions were evaluated. Results: HRP reduced glomerulosclerosis and podocyte desmin expression, but did not affect proteinuria and tubular ERK(1/2 phosphorylation. Both Q and Q+HRP treatment reduced proteinuria, glomerular and tubular damage, tubular TGF-ß1 expression and ERK(1/2 phosphorylation to the same extent. Conclusion: The effects of HRP were partially beneficial on diabetic kidney lesions as HRP reduced damage but did not improve tubular damage and failed to reduce ERK(1/2 phosphorylation in rats. The combination of HRP with Quinapril had no additive effects over Quinapril monotherapy on the progression of diabetic nephropathy.

MicroRNAs in Heart Failure, Cardiac Transplantation, and Myocardial Recovery: Biomarkers with Therapeutic Potential.

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Shah, Palak; Bristow, Michael R; Port, J David

2017-12-01

Heart failure is increasing in prevalence with a lack of recently developed therapies that produce major beneficial effects on its associated mortality. MicroRNAs are small non-coding RNA molecules that regulate gene expression, are differentially regulated in heart failure, and are found in the circulation serving as a biomarker of heart failure. Data suggests that microRNAs may be used to detect allograft rejection in cardiac transplantation and may predict the degree of myocardial recovery in patients with a left ventricular assist device or treated with beta-blocker therapy. Given their role in regulating cellular function, microRNAs are an intriguing target for oligonucleotide therapeutics, designed to mimic or antagonize (antagomir) their biological effects. We review the current state of microRNAs as biomarkers of heart failure and associated conditions, the mechanisms by which microRNAs control cellular function, and how specific microRNAs may be targeted with novel therapeutics designed to treat heart failure.

Clinical Outcomes with β-blockers for Myocardial Infarction A Meta-Analysis of Randomized Trials

DEFF Research Database (Denmark)

Bangalore, Sripal; Makani, Harikrishna; Radford, Martha

2014-01-01

BACKGROUND: Debate exists regarding the efficacy of â-blockers in myocardial infarction and their required duration of usage in contemporary practice. METHODS: We conducted a MEDLINE/EMBASE/CENTRAL search for randomized trials evaluating â-blockers in myocardial infarction enrolling at least 100 ...

Effects of gap junction blockers on human neocortical synchronization.

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Gigout, S; Louvel, J; Kawasaki, H; D'Antuono, M; Armand, V; Kurcewicz, I; Olivier, A; Laschet, J; Turak, B; Devaux, B; Pumain, R; Avoli, M

2006-06-01

Field potentials and intracellular recordings were obtained from human neocortical slices to study the role of gap junctions (GJ) in neuronal network synchronization. First, we examined the effects of GJ blockers (i.e., carbenoxolone, octanol, quinine, and quinidine) on the spontaneous synchronous events (duration = 0.2-1.1 s; intervals of occurrence = 3-27 s) generated by neocortical slices obtained from temporal lobe epileptic patients during application of 4-aminopyridine (4AP, 50 muM) and glutamatergic receptor antagonists. The synchronicity of these potentials (recorded at distances up to 5 mm) was decreased by GJ blockers within 20 min of application, while prolonged GJ blockers treatment at higher doses made them disappear with different time courses. Second, we found that slices from patients with focal cortical dysplasia (FCD) could generate in normal medium spontaneous synchronous discharges (duration = 0.4-8 s; intervals of occurrence = 0.5-90 s) that were (i) abolished by NMDA receptor antagonists and (ii) slowed down by carbenoxolone. Finally, octanol or carbenoxolone blocked 4AP-induced ictal-like discharges (duration = up to 35 s) in FCD slices. These data indicate that GJ play a role in synchronizing human neocortical networks and may implement epileptiform activity in FCD.

Why do hypertensive patients of African ancestry respond better to calcium blockers and diuretics than to ACE inhibitors and β-adrenergic blockers? A systematic review

Science.gov (United States)

2013-01-01

Background Clinicians are encouraged to take an individualized approach when treating hypertension in patients of African ancestry, but little is known about why the individual patient may respond well to calcium blockers and diuretics, but generally has an attenuated response to drugs inhibiting the renin-angiotensin system and to β-adrenergic blockers. Therefore, we systematically reviewed the factors associated with the differential drug response of patients of African ancestry to antihypertensive drug therapy. Methods Using the methodology of the systematic reviews narrative synthesis approach, we sought for published or unpublished studies that could explain the differential clinical efficacy of antihypertensive drugs in patients of African ancestry. PUBMED, EMBASE, LILACS, African Index Medicus and the Food and Drug Administration and European Medicines Agency databases were searched without language restriction from their inception through June 2012. Results We retrieved 3,763 papers, and included 72 reports that mainly considered the 4 major classes of antihypertensive drugs, calcium blockers, diuretics, drugs that interfere with the renin-angiotensin system and β-adrenergic blockers. Pharmacokinetics, plasma renin and genetic polymorphisms did not well predict the response of patients of African ancestry to antihypertensive drugs. An emerging view that low nitric oxide and high creatine kinase may explain individual responses to antihypertensive drugs unites previous observations, but currently clinical data are very limited. Conclusion Available data are inconclusive regarding why patients of African ancestry display the typical response to antihypertensive drugs. In lieu of biochemical or pharmacogenomic parameters, self-defined African ancestry seems the best available predictor of individual responses to antihypertensive drugs. PMID:23721258

Therapeutic Approach to Patients with Heart Failure with Reduced Ejection Fraction and End-stage Renal Disease.

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Inampudi, Chakradhari; Alvarez, Paulino; Asleh, Rabea; Briasoulis, Alexandros

2018-03-14

Several risk factors including Ischemic heart disease, uncontrolled hypertension, high output Heart Failure (HF) from shunting through vascular hemodialysis access, and anemia, contribute to development of HF in patients with End-Stage Renal Disease (ESRD). Guidelinedirected medical and device therapy for Heart Failure with Reduced Ejection Fraction (HFrEF) has not been extensively studied and may have limited safety and efficacy in patients with ESRD. Maintenance of interdialytic and intradialytic euvolemia is a key component of HF management in these patients but often difficult to achieve. Beta-blockers, especially carvedilol which is poorly dialyzed is associated with cardiovascular benefit in this population. Despite paucity of data, Angiotensin-converting Enzyme Inhibitors (ACEI) or Angiotensin II Receptor Blockers (ARBs) when appropriately adjusted by dose and with close monitoring of serum potassium can also be administered to these patients who tolerate beta-blockers. Mineralocorticoid receptors in patients with HFrEF and ESRD have been shown to reduce mortality in a large randomized controlled trial without any significantly increased risk of hyperkalemia. Implantable Cardiac-defibrillators (ICDs) should be considered for primary prevention of sudden cardiac death in patients with HFrEF and ESRD who meet the implant indications. Furthermore in anemic iron-deficient patients, intravenous iron infusion may improve functional status. Finally, mechanical circulatory support with leftventricular assist devices may be related to increased mortality risk and the presence of ESRD poses a relative contraindication to further evaluation of these devices. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Long-term Efficacy and Safety of Enzalutamide Monotherapy in Hormone-naïve Prostate Cancer

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Tombal, Bertrand; Borre, Michael; Rathenborg, Per

2015-01-01

BACKGROUND: Enzalutamide is an androgen receptor inhibitor with a demonstrated overall survival benefit in metastatic castration-resistant prostate cancer. A phase 2 study of enzalutamide monotherapy in patients with hormone-naïve prostate cancer (HNPC) showed a high response rate...... cancer, enzalutamide maintained long-term reductions in prostate-specific antigen, with a minimal impact on total-body bone mineral density. TRIAL REGISTRATION: NCT01302041....... for the prespecified primary endpoint (ie, prostate-specific antigen [PSA] response at week 25), regardless of metastases at baseline, and favorable tolerability. OBJECTIVE: To determine the long-term efficacy and safety of enzalutamide monotherapy at 1 and 2 yr. DESIGN, SETTING, AND PARTICIPANTS: Open-label, single...

Fenofibrate monotherapy-induced rhabdomyolysis in a patient with hypothyroidism: A rare case report and literature review.

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Wang, Dawei; Wang, Yanqiu

2018-04-01

Fenofibrate is a fibric acid derivative indicated for use in hypertriglyceridemia and mixed dyslipidemia treatment among adults. Rhabdomyolysis is a syndrome characterized by muscle necrosis and the release of intracellular muscle contents into the systemic circulation, which is the most serious and fatal side effect of fenofibrate. The objective of this paper is to discuss fatal side effect of fenofibrate and keep safe medication. A patient with hypothyroidism who presented with rhabdomyolysis during fenofibrate monotherapy for hypertriglyceridemia was reported. Fenofibrate Monotherapy Induced Rhabdomyolysis. Fenofibrate was stopped. Adequate fluid resuscitation, mannitol diuresis, myocardium protection, hepatoprotection and urine alkalinization with sodium bicarbonate were performed. Blood tests were normal and the patient was good and discharged 2 weeks later. 13 cases associated with fenofibrate monotherapy-induced rhabdomyolysis were reviewed, which had been published in the English literature. The severity of fenofibrate muscle toxicity may be the result of the combination of two rhabdomyolysis enhancers, such as hypothyroidism and female gender. To avoid it, strict clinical and laboratory monitoring should be maintained, particularly hypothyroidism. Patients should be informed of possible potentially irreversible effects after taking fibrates.

Tamsulosin combined with solifenacin versus tamsulosin monotherapy for male lower urinary tract symptoms: a meta-analysis.

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Gong, Mancheng; Dong, Wenjing; Huang, Guiying; Gong, Zhaoyang; Deng, Decheng; Qiu, Shaopeng; Yuan, Runqiang

2015-01-01

To evaluate the efficacy and safety of tamsulosin and solifenacin combination therapy compared with tamsulosin monotherapy for male lower urinary tract symptoms (LUTS). We identified all eligible studies that compared tamsulosin and solifenacin combination therapy with tamsulosin monotherapy for male LUTS (up to January 2015). The fixed- or random-effects model was selected depending on the proportion of heterogeneity. Seven articles were identified as eligible for this meta-analysis, with a total of 3063 participants. Synthetic data showed combination therapy had significant improvements in Storage International Prostate Symptom Score (WMD = -0.60; 95% CI: -0.81 to -0.38, P tamsulosin and solifenacin combined therapy group (30.82%) was similar to the tamsulosin monotherapy group (25.75%). Acute urinary retention was seldom reported in the studies and no clinically significant changes regarding Qmax were showed in our meta-analysis. Tamsulosin and solifenacin combination therapy may be a reasonable option for male LUTS patients, especially for those who have significant storage symptoms. However, PVR should be measured during treatment to assess the increase in PVR or the incidence of AUR.

Beta-blocker therapy is not associated with symptoms of depression and anxiety in patients receiving an implantable cardioverter-defibrillator

DEFF Research Database (Denmark)

Hoogwegt, Madelein T; Kupper, Nina; Theuns, Dominic A M J

2012-01-01

Beta-blockers are frequently prescribed to implantable cardioverter-defibrillator (ICD) patients. Beta-blocker therapy has been proposed to induce emotional distress such as depression and anxiety, but a paucity of studies has examined the relationship between beta-blockers and distress. We...... investigated the association between beta-blocker therapy, including type and dosage, and symptoms of anxiety and depression in a consecutive cohort of patients receiving an ICD....

The association between COPD and heart failure risk: a review

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de Miguel Díez J

2013-06-01

Full Text Available Javier de Miguel Díez,1 Jorge Chancafe Morgan,1 Rodrigo Jiménez García2 1Pulmonology Department, Gregorio Maranon University Hospital, Complutense University of Madrid, Madrid, Spain; 2Preventive Medicine and Public Health Teaching and Research Unit, Department of Health Sciences, Rey Juan Carlos University, Madrid, Spain Abstract: Chronic obstructive pulmonary disease (COPD is commonly associated with heart failure (HF in clinical practice since they share the same pathogenic mechanism. Both conditions incur significant morbidity and mortality. Therefore, the prognosis of COPD and HF combined is poorer than for either disease alone. Nevertheless, usually only one of them is diagnosed. An active search for each condition using clinical examination and additional tests including plasma natriuretic peptides, lung function testing, and echocardiography should be obtained. The combination of COPD and HF presents many therapeutic challenges. The beneficial effects of selective ß1-blockers should not be denied in stable patients who have HF and coexisting COPD. Additionally, statins, angiotensin-converting enzyme inhibitors, and angiotensin-receptor blockers may reduce the morbidity and mortality of COPD patients. Moreover, caution is advised with use of inhaled ß2-agonists for the treatment of COPD in patients with HF. Finally, noninvasive ventilation, added to conventional therapy, improves the outcome of patients with acute respiratory failure due to hypercapnic exacerbation of COPD or HF in situations of acute pulmonary edema. The establishment of a combined and integrated approach to managing these comorbidities would seem an appropriate strategy. Additional studies providing new data on the pathogenesis and management of patients with COPD and HF are needed, with the purpose of trying to improve quality of life as well as survival of these patients. Keywords: chronic obstructive pulmonary disease, heart failure

Influence of diabetes mellitus on heart failure risk and outcome

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Van Belle Eric

2003-01-01

Full Text Available Abstract Our aim is to summarize and discuss the recent literature linking diabetes mellitus with heart failure, and to address the issue of the optimal treatment for diabetic patients with heart failure. The studies linking diabetes mellitus (DM with heart failure (HF The prevalence of diabetes mellitus in heart failure populations is close to 20% compared with 4 to 6% in control populations. Epidemiological studies have demonstrated an increased risk of heart failure in diabetics; moreover, in diabetic populations, poor glycemic control has been associated with an increased risk of heart failure. Various mechanisms may link diabetes mellitus to heart failure: firstly, associated comorbidities such as hypertension may play a role; secondly, diabetes accelerates the development of coronary atherosclerosis; thirdly, experimental and clinical studies support the existence of a specific diabetic cardiomyopathy related to microangiopathy, metabolic factors or myocardial fibrosis. Subgroup analyses of randomized trials demonstrate that diabetes is also an important prognostic factor in heart failure. In addition, it has been suggested that the deleterious impact of diabetes may be especially marked in patients with ischemic cardiomyopathy. Treatment of heart failure in diabetic patients The knowledge of the diabetic status may help to define the optimal therapeutic strategy for heart failure patients. Cornerstone treatments such as ACE inhibitors or beta-blockers appear to be uniformly beneficial in diabetic and non diabetic populations. However, in ischemic cardiomyopathy, the choice of the revascularization technique may differ according to diabetic status. Finally, clinical studies are needed to determine whether improved metabolic control might favorably influence the outcome of diabetic heart failure patients.

Progressive nature of heart failure and systems biology

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George E. Louridas

2015-01-01

Full Text Available The progressive nature of heart failure (HF is the predominant cause for the clinical course that the HF syndrome is taking. Systems biology methodology is of the utmost importance to explain and comprehend the built-in mechanisms of adverse clinical progression. Various heart diseases produce myocardial damage with subsequent left ventricular remodeling which is the principal underlying pathophysiological mechanism for the clinical progression of HF. The self-organized positive feedback stabilization mechanisms of left ventricular remodeling, adrenergic stimulation and activation of the renin-angiotensin-aldosterone system and natriuretic peptide systems, are hierarchical adaptive processes. These adaptive processes are responsible for further left ventricular remodeling with subsequent clinical deterioration and for the emergence of clinical phenotypes. These mechanisms are counteracted with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and β-blockers in an attempt to improve the adverse clinical phenomena of HF progression in a new but clinically worse stabilization level. In this review our intention is to underline the progressive nature of the HF syndrome and to demonstrate the significance of ventricular remodeling and the role of self-organized positive feedback adaptive processes.

An international, randomized, double-blind, placebo-controlled, phase III trial of pregabalin monotherapy in treatment of patients with fibromyalgia

DEFF Research Database (Denmark)

Pauer, Lynne; Winkelmann, Andreas; Arsenault, Pierre

2011-01-01

To evaluate the efficacy and safety of pregabalin monotherapy versus placebo for symptomatic pain relief and improvement of patient global assessment in patients with fibromyalgia (FM) enrolled from countries outside the United States.......To evaluate the efficacy and safety of pregabalin monotherapy versus placebo for symptomatic pain relief and improvement of patient global assessment in patients with fibromyalgia (FM) enrolled from countries outside the United States....

Endogenous endophthalmitis in a rheumatoid patient on tumor necrosis factor alpha blocker

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Agarwal Pankaj

2007-01-01

Full Text Available The development of anti-tumor necrosis factor (TNF therapies is a milestone in the therapy of rheumatic diseases. It is of concern whether all potential undesired complications of therapy have been evaluated within clinical trials which have led to treatment approval. Specialists prescribing TNF blockers should be aware of the unusual and severe complications that can occur. We describe a case of endogenous endophthalmitis in a rheumatoid patient on TNF alpha blocker.

Calcium channel blockers inhibit endogenous pyrogen fever in rats and rabbits.

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Stitt, J T; Shimada, S G

1991-09-01

We have previously shown that febrile responses in both rats and rabbits are elicited by the intravenous injection of a semipurified endogenous pyrogen (EP) prepared from human monocytes. We are now presenting evidence that these febrile responses are mediated via activation of Ca2+ channels by EP. The febrile responses of male New Zealand White rabbits and Sprague-Dawley rats to a standard dose of EP were determined at their respective thermoneutral ambient temperatures. The animals were then treated with Ca2+ channel blocker verapamil (7.5 mg/kg iv) 30-60 min before the EP challenge. In every case the febrile response to EP was markedly attenuated after verapamil pretreatment, while administration of verapamil by itself had no detectable effect on body temperature. Another Ca2+ channel blocker, nifedipine (5 mg/kg iv), was shown to possess antipyretic activity in rats also. To localize where in the fever pathway these Ca2+ channel blockers were acting, we investigated the effect of verapamil at the same dose on fevers that were produced by microinjection of prostaglandin E (PGE) directly into the brain. These PGE fevers were unaffected by verapamil pretreatment, indicating that the antipyretic action of Ca2+ channel blockers occurs before the formation of PGE in response to EP stimulation. The most likely locus of action is the activation of the enzyme phospholipase A2, which regulates the production of arachidonic acid from cellular phospholipids in the prostanoid cascade.

Beta-blocker therapy is not associated with symptoms of depression and anxiety in patients receiving an implantable cardioverter-defibrillator.

Science.gov (United States)

Hoogwegt, Madelein T; Kupper, Nina; Theuns, Dominic A M J; Jordaens, Luc; Pedersen, Susanne S

2012-01-01

Beta-blockers are frequently prescribed to implantable cardioverter-defibrillator (ICD) patients. Beta-blocker therapy has been proposed to induce emotional distress such as depression and anxiety, but a paucity of studies has examined the relationship between beta-blockers and distress. We investigated the association between beta-blocker therapy, including type and dosage, and symptoms of anxiety and depression in a consecutive cohort of patients receiving an ICD. Between 2003 and 2010, 448 consecutively implanted ICD patients were enrolled in the prospective Mood and personality as precipitants of arrhythmia in patients with an Implantable cardioverter Defibrillator: A prospective Study (MIDAS), of which 429 completed the Hospital Anxiety and Depression Scale (HADS) and the ICD Patient Concerns questionnaire (ICDC) at baseline. Eighty per cent of all patients received beta-blocker therapy. In univariate analysis, beta-blocker therapy was not significantly associated with symptoms of anxiety, depression, and ICD concerns (β = -0.030, β = 0.007, and β = -0.045, respectively; all P's >0.36). Type of beta-blocker showed a trend towards significance for mean levels of ICD concerns (P = 0.09). No association was found between dosage and emotional distress (all P's >0.21). After adjustment for relevant clinical and demographic variables, the association of beta-blocker therapy and symptoms of anxiety, depression, and ICD concerns remained non-significant (β = 0.009, β = 0.037, and β = 0.019, respectively; all P's >0.47). In patients receiving an ICD, beta-blocker therapy was not associated with symptoms of anxiety, depression, and ICD concerns. Research is warranted that further elucidates the link between beta-blocker therapy and emotional distress in this vulnerable patient group.

[Combined treatment of BPS with tamsulosin and finasteride : Literature review and prescription data].

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Höfner, K; Ulrich, S; Berges, R

2017-05-01

Combined therapy of benign prostatic syndrome (BPS) with α 1 -blockers and 5α-reductase (5AR)-inhibitors is recommended according to two leading studies on doxazosin/finasteride and tamsulosin/dutasteride for all 10 in Germany possible combinations (five α 1 -blockers and two 5AR inhibitors). Because tamsulosin and finasteride predominate in the treatment of BPS in Germany, the role of the combination tamsulosin/finasteride and its scientific basis from clinical studies has been investigated. A pharmacoepidemiological extrapolation from receipts of pharmacy data centres showed a strong increase of the combination tamsulosin/finasteride since 2003. As a free combination, tamsulosin/finasteride beside the fixed combination tamsulosin/dutasteride accounts to about 50% of all α 1 -blocker/5AR-inhibitor combinations today. Clinical studies on tamsulosin/finasteride have been published including controlled studies of the combination and both monotherapies. The results of improvement of lower urinary tract symptoms (LUTS), maximum urinary flow rate (Q max ), prostate volume (PV) and prostate-specific antigen (PSA) as well as adverse events and drug safety are in agreement with the leading studies. However, results due to chance cannot be excluded because of deficiencies in study design. A reliable comparison of the risk of progression between tamsulosin/finasteride and both monotherapies is lacking completely. Because of the great coherence and continuous evaluation of available data of all combinations, and with the established strong class effect of monotherapies, a continuation of the therapeutic practice with the combination tamsulosin/finasteride is possible.

Methotrexate: an effective monotherapy for refractory generalized morphea

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Platsidaki E

2017-05-01

Full Text Available Eftychia Platsidaki, Vassiliki Tzanetakou, Anargyros Kouris, Panagiotis G Stavropoulos Department of Dermatology and Venereology, Andreas Syggros Hospital, University of Athens, Athens, Greece Introduction: Morphea is an inflammatory skin disorder characterized by excessive collagen deposition. Although treatment algorithms for morphea subtypes have been suggested, no consistent recommendations are available. This study attempts to evaluate the clinical efficacy of methotrexate (MTX as monotherapy in refractory generalized morphea. Methods: It is a retrospective study, including 20 patients who had already been treated with various topical and systemic therapies with minimal clinical improvement. Patients received orally MTX at a of dosage 15 mg once weekly. Duration of the use, dosage of MTX, and adverse events were recorded. Clinical assessment of skin lesions was performed and documented. Results: The mean disease duration was 27 months before the initiation of MTX treatment. After 12 months of therapy, very good response was achieved in 6 patients (30%, good response in 10 patients (50%, and fair response in 2 patients (10%, while 2 patients (10% had failed treatment. Patients were followed up for a mean time interval of 21 months. No serious adverse event was recorded. Conclusion: MTX has been already proved to be an effective and well-tolerated treatment in pediatric patients with morphea. The majority of the group of adult patients showed very good and good improvement when treated with MTX. Although this is an uncontrolled study, MTX monotherapy was considered a safe and effective treatment for the management of this specific clinical subset of morphea in adults. Keywords: methotrexate, adults, generalized morphea

Autoantibodies Specifically Against β1 Adrenergic Receptors and Adverse Clinical Outcome in Patients With Chronic Systolic Heart Failure in the β-Blocker Era: The Importance of Immunoglobulin G3 Subclass.

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Nagatomo, Yuji; Li, Daniel; Kirsop, Jennifer; Borowski, Alan; Thakur, Akanksha; Tang, W H Wilson

2016-06-01

To elucidate the prevalence and role of β1 adrenergic receptor autoantibodies (β1AR-AAb) belonging to the immunoglobulin (Ig)G3 subclass in patients with heart failure (HF) treated with β-adrenergic blockers. Several cardiac AAbs have been reported to be present in sera from patients with dilated cardiomyopathy and other etiologies. Among AAbs, those recognizing β1AR-AAbs show agonist-like effects, have detrimental effects on cardiomyocytes, and may induce persistent myocardial damage. We quantify total IgG and IgG3 subclass β1AR-AAb in subjects with chronic stable HF with long-term follow-up. In our study cohort of 121 subjects, non-IgG3-β1AR-AAb and IgG3-β1AR-AAb were found to be positive in 20 (17%) and 26 patients (21%), respectively. The positive rate of IgG3-β1AR-AAb was significantly higher for those with nonischemic compared with ischemic HF etiology (27% vs 8%, P = .01), but the positive rate for non-IgG3-β1AR-AAb was similar between the 2 groups (18% vs 16%, respectively, P = NS). There were no significant differences in clinical and echocardiographic measures among total β1AR-AAb negative, non-IgG3-β1AR-AAb positive, and IgG3-β1AR-AAb positive groups at baseline. During 2.2 ± 1.2 years of follow-up, we observed similar rates of the composite endpoint of all-cause mortality, cardiac transplantation, or hospitalization resulting from HF between total IgG-β1AR-AAb negative and positive patients. However, the composite endpoint events were significantly more common in the patients without than in those with IgG3-β1AR-AAb (P = .048, log-rank test). Presence of IgG3-β1AR-AAb, not total IgG, was associated with paradoxically more favorable outcomes in our cohort of patients with chronic systolic HF largely treated by β-blockers. Copyright © 2016 Elsevier Inc. All rights reserved.

Beta blocker therapy is associated with reduced depressive symptoms 12 months post percutaneous coronary intervention

NARCIS (Netherlands)

Battes, L.C.; Pedersen, S.S.; Oemrawsingh, R.M.; van Geuns, R.-J.M.; Al Amri, I.; Regar, E.; de Jaegere, P.T.; Serruys, P.W.; van Domburg, R.T.

2012-01-01

Background Beta blocker therapy may induce depressive symptoms, although current evidence is conflicting. We examined the association between beta blocker therapy and depressive symptoms in percutaneous coronary intervention (PCI) patients and the extent to which there is a dose–response

Beta-blocker therapy is not associated with symptoms of depression and anxiety in patients receiving an implantable cardioverter-defibrillator

NARCIS (Netherlands)

M.T. Hoogwegt (Madelein); N. Kupper (Nina); D.A.M.J. Theuns (Dominic); L.J.L.M. Jordaens (Luc); S.S. Pedersen (Susanne)

2012-01-01

textabstractBeta-blockers are frequently prescribed to implantable cardioverter-defibrillator (ICD) patients. Beta-blocker therapy has been proposed to induce emotional distress such as depression and anxiety, but a paucity of studies has examined the relationship between beta-blockers and distress.

Beta-blockers for prevention and treatment of retinopathy of prematurity in preterm infants.

Science.gov (United States)

Kaempfen, Siree; Neumann, Roland P; Jost, Kerstin; Schulzke, Sven M

2018-03-02

Retinopathy of prematurity (ROP) is a vision-threatening disease of preterm neonates. The use of beta-adrenergic blocking agents (beta-blockers), which modulate the vasoproliferative retinal process, may reduce the progression of ROP or even reverse established ROP. To determine the effect of beta-blockers on short-term structural outcomes, long-term functional outcomes, and the need for additional treatment, when used either as prophylaxis in preterm infants without ROP, stage 1 ROP (zone I), or stage 2 ROP (zone II) without plus disease or as treatment in preterm infants with at least prethreshold ROP. We searched the Cochrane Neonatal Review Group Specialized Register; CENTRAL (in the Cochrane Library Issue 7, 2017); Embase (January 1974 to 7 August 2017); PubMed (January 1966 to 7 August 2017); and CINAHL (January 1982 to 7 August 2017). We checked references and cross-references and handsearched abstracts from the proceedings of the Pediatric Academic Societies Meetings. We considered for inclusion randomised or quasi-randomised clinical trials that used beta-blockers for prevention or treatment of ROP in preterm neonates of less than 37 weeks' gestational age. We used the standard methods of Cochrane and the Cochrane Neonatal Review Group. We used the GRADE approach to assess the quality of evidence. We included three randomised trials (N = 366) in this review. Two of these studies were at high risk of bias. All studies reported on prevention of ROP and compared oral propranolol with placebo or no treatment. We found no trials assessing beta-blockers in infants with established stage 2 or higher ROP with plus disease.In one trial, study medication was started after one week of life, i.e. prior to the first ROP screening. The other two trials included preterm infants if they had stage 2 or lower ROP without plus disease. Based on the GRADE assessment, we considered evidence to be of low quality for the following outcomes: rescue treatment with anti-VEGF or

Extensive Darier Disease Successfully Treated with Doxycycline Monotherapy

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Alicia Sfecci

2015-10-01

Full Text Available Darier disease (DD is a rare dominantly inherited genodermatosis characterized by loss of intercellular adhesion (acantholysis and abnormal keratinization. DD is often difficult to manage. Numerous treatments have reportedly been used for the treatment of DD, with limited success. Systemic retinoids are considered the drug of choice for treating DD. However, their use is limited by potential deleterious side effects. Considering the recently reported efficacy of doxycycline for Hailey-Hailey disease, an inherited acantholytic skin disorder pathogenetically similar to DD, we report the case of a patient with extensive DD who showed a dramatic response to oral doxycycline monotherapy.

Management and Long-Term Outcome of Acute Coronary Syndrome Patients Presenting with Heart Failure in a Contemporary New Zealand Cohort (ANZACS-QI 4).

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Kueh, Shaw Hua Anthony; Devlin, Gerry; Lee, Mildred; Doughty, Rob N; Kerr, Andrew J

2016-08-01

Acute heart failure (HF) associated with an acute coronary syndrome (ACS) predicts adverse outcome. There have been important recent improvements in ACS management. Our aim was to describe the management and outcomes in those with and without HF in a contemporary ACS cohort. Consecutive patients presenting with ACS between 2007 and 2011 were enrolled in the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry. Outcomes and medication dispensing were obtained using anonymised linkage to national data sets. A summary pharmacotherapy measure of "quadruple therapy" was defined as dispensing of at least one agent from each of the four evidence-based classes - anti-platelet, statin, angiotensin converting enzyme inhibitor/angiotensin receptor blocker and beta blocker. Of 3743 ACS patients 14% had acute HF. Acute heart failure patients were older (69.2±12.6 vs 62.3±12.8 years, pcoronary angiography (66% vs 86%, pAcute heart failure complicating ACS is associated with heightened risk of short-term and long-term mortality. One in three ACS patients with HF did not have coronary angiography and less than half received quadruple therapy a year after presentation. Copyright © 2016. Published by Elsevier B.V.

A Single-Center, Open-Label, 3-Way Crossover Trial to Determine the Pharmacokinetic and Pharmacodynamic Interaction Between Nebivolol and Valsartan in Healthy Volunteers at Steady State.

Science.gov (United States)

Chen, Chun Lin; Desai-Krieger, Daksha; Ortiz, Stephan; Kerolous, Majid; Wright, Harold M; Ghahramani, Parviz

2015-01-01

Combining different classes of antihypertensives is more effective for reducing blood pressure (BP) than increasing the dose of monotherapies. The aims of this phase I study were to investigate pharmacokinetic and pharmacodynamic interactions between nebivolol, a vasodilatory β1-selective blocker, and valsartan, an angiotensin II receptor blocker, and to assess safety and tolerability of the combination. This was a single-center, randomized, open-label, multiple-dose, 3-way crossover trial in 30 healthy adults aged 18-45 years. Participants were randomized into 1 of 6 treatment sequences (1:1:1:1:1:1) consisting of three 7-day treatment periods followed by a 7-day washout. Once-daily oral treatments comprised nebivolol (20 mg), valsartan (320 mg), and nebivolol-valsartan combination (20/320 mg). Outcomes included AUC0-τ,ss, Cmax,ss, Tmax,ss, changes in BP, pulse rate, plasma angiotensin II, plasma renin activity, 24-hour urinary aldosterone, and adverse events. Steady-state pharmacokinetic interactions were observed but deemed not clinically significant. Systolic and diastolic BP reduction was significantly greater with nebivolol-valsartan combination than with either monotherapy. The mean pulse rate associated with nebivolol and nebivolol-valsartan treatments was consistently lower than that associated with valsartan monotherapy. A sharp increase in mean day 7 plasma renin activity and plasma angiotensin II that occurred in valsartan-treated participants was significantly attenuated with concomitant nebivolol administration. Mean 24-hour urine aldosterone at day 7 was substantially decreased after combined treatment, as compared with either monotherapy. All treatments were safe and well tolerated. In conclusion, nebivolol and valsartan coadministration led to greater reductions in BP compared with either monotherapy; nebivolol and valsartan lower BP through complementary mechanisms.

Bradykinin receptor blockade restores the baroreflex control of renal sympathetic nerve activity in cisplatin-induced renal failure rats.

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Abdulla, M H; Duff, M; Swanton, H; Johns, E J

2016-11-01

This study investigated the effect of renal bradykinin B1 and B2 receptor blockade on the high- and low-pressure baroreceptor reflex regulation of renal sympathetic nerve activity (RSNA) in rats with cisplatin-induced renal failure. Cisplatin (5 mg/kg) or saline was given intraperitoneally 4 days prior to study. Following chloralose/urethane anaesthesia, rats were prepared for measurement of mean arterial pressure (MAP), heart rate and RSNA and received intrarenal infusions of either Lys-[des-Arg 9 , Leu 8 ]-bradykinin (LBK), a bradykinin B1 receptor blocker, or bradyzide (BZ), a bradykinin B2 receptor blocker. RSNA baroreflex gain curves and renal sympatho-inhibitory responses to volume expansion (VE) were obtained. In the control and renal failure groups, basal MAP (89 ± 3 vs. 80 ± 8 mmHg) and RSNA (2.0 ± 0.3 vs. 1.7 ± 0.6 μV.s) were similar but HR was lower in the latter group (331 ± 8 vs. 396 ± 9 beats/min). The baroreflex gain for RSNA in the renal failure rats was 39% (P renal failure rats. Intrarenal LBK infusion in the renal failure rats normalized the VE induced renal sympatho-inhibition whereas BZ only partially restored the response. These findings suggest that pro-inflammatory bradykinin acting at different receptors within the kidney generates afferent neural signals which impact differentially within the central nervous system on high- and low-pressure regulation of RSNA. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Beta-blockers and statins in the context of asthma

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Joanna Pawlak

2009-12-01

Full Text Available Asthma is a disease with a complex pathogenesis and differentiated clinical picture with airway inflammation in its background. Many cells and cell-released substances are engaged in the course of the disease. The basic treatment strategy in asthma is based on chronic administration of inhaled glucocorticosteroids (with a strong anti-inflammatory effect and beta2-adrenoreceptor agonists (bronchodilatory effect. Much attention has been recently paid to the effects of other medicines on mechanisms important in the pathogenesis of asthma, including beta-blockers and statins. Many researchers have suggested a potentially useful role of some beta-blockers in chronic asthma therapy, particularly considering their effect on the pharmacodynamics of beta receptors in the bronchi. Moreover, statins, due to their anti-inflammatory and immunomodulatory effects, can also be useful in the management of asthma.

Adverse respiratory effect of acute β-blocker exposure in asthma: a systematic review and meta-analysis of randomized controlled trials.

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Morales, Daniel R; Jackson, Cathy; Lipworth, Brian J; Donnan, Peter T; Guthrie, Bruce

2014-04-01

β-Blockers are avoided in asthma over concerns regarding acute bronchoconstriction. Risk is greatest following acute exposure, including the potential for antagonism of β2-agonist rescue therapy. A systematic review of databases was performed to identify all randomized, blinded, placebo-controlled clinical trials evaluating acute β-blocker exposure in asthma. Effect estimates for changes in respiratory function, symptoms, and β2-agonist response were pooled using random effects meta-analysis with heterogeneity investigated. Acute selective β-blockers in the doses given caused a mean change in FEV1 of −6.9% (95% CI, −8.5 to −5.2), a fall in FEV1 of ≥20% in one in eight patients (P=.03), symptoms affecting one in 33 patients (P=.18), and attenuation of concomitant β2-agonist response of −10.2% (95% CI, −14.0 to −6.4). Corresponding values for acute nonselective β-blockers in the doses given were −10.2% (95% CI, −14.7 to −5.6), one in nine patients (P=.02), one in 13 patients (P=.14), and −20.0% (95% CI, −29.4 to −10.7). Following investigation of heterogeneity, clear differences were found for celiprolol and labetalol. A dose-response relationship was demonstrated for selective β-blockers. Selective β-blockers are better tolerated but not completely risk-free. Risk from acute exposure may be mitigated using the smallest dose possible and β-blockers with greater β1-selectivity. β-Blocker-induced bronchospasm responded partially to β2-agonists in the doses given with response blunted more by nonselective β-blockers than selective β-blockers. Use of β-blockers in asthma could possibly be based upon a risk assessment on an individual patient basis.

Heart rate and use of beta-blockers in stable outpatients with coronary artery disease.

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Ph Gabriel Steg

Full Text Available BACKGROUND: Heart rate (HR is an emerging risk factor in coronary artery disease (CAD. However, there is little contemporary data regarding HR and the use of HR-lowering medications, particularly beta-blockers, among patients with stable CAD in routine clinical practice. The goal of the present analysis was to describe HR in such patients, overall and in relation to beta-blocker use, and to describe the determinants of HR. METHODS AND FINDINGS: CLARIFY is an international, prospective, observational, longitudinal registry of outpatients with stable CAD, defined as prior myocardial infarction or revascularization procedure, evidence of coronary stenosis of >50%, or chest pain associated with proven myocardial ischemia. A total of 33,438 patients from 45 countries in Europe, the Americas, Africa, Middle East, and Asia/Pacific were enrolled between November 2009 and July 2010. Most of the 33,177 patients included in this analysis were men (77.5%. Mean (SD age was 64.2 (10.5 years, HR by pulse was 68.3 (10.6 bpm, and by electrocardiogram was 67.2 (11.4 bpm. Overall, 44.0% had HR ≥ 70 bpm. Beta-blockers were used in 75.1% of patients and another 14.4% had intolerance or contraindications to beta-blocker therapy. Among 24,910 patients on beta-blockers, 41.1% had HR ≥ 70 bpm. HR ≥ 70 bpm was independently associated with higher prevalence and severity of angina, more frequent evidence of myocardial ischemia, and lack of use of HR-lowering agents. CONCLUSIONS: Despite a high rate of use of beta-blockers, stable CAD patients often have resting HR ≥ 70 bpm, which was associated with an overall worse health status, more frequent angina and ischemia. Further HR lowering is possible in many patients with CAD. Whether it will improve symptoms and outcomes is being tested.

Norepinephrine transporter blocker atomoxetine increases salivary alpha amylase

NARCIS (Netherlands)

Warren, C.M.; van den Brink, R.L.; Nieuwenhuis, S.; Bosch, J.A.

It has been suggested that central norepinephrine (NE) activity may be inferred from increases in salivary alpha-amylase (SAA), but data in favor of this proposition are limited. We administered 40mg of atomoxetine, a selective NE transporter blocker that increases central NE levels, to 24 healthy

Managing therapeutic competition in patients with heart failure, lower urinary tract symptoms and incontinence.

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Tannenbaum, Cara; Johnell, Kristina

2014-02-01

Up to 50% of heart failure patients suffer from lower urinary tract symptoms. Urinary incontinence has been associated with worse functional status in patients with heart failure, occurring three times more frequently in patients with New York Heart Association Class III and IV symptoms compared with those with milder disease. The association between heart failure and urinary symptoms may be directly attributable to worsening heart failure pathophysiology; however, medications used to treat heart failure may also indirectly provoke or exacerbate urinary symptoms. This type of drug-disease interaction, in which the treatment for heart failure precipitates incontinence, and removal of medications to relieve incontinence worsens heart failure, can be termed therapeutic competition. The mechanisms by which heart failure medication such as diuretics, angiotensin-converting enzyme (ACE) inhibitors and β-blockers aggravate lower urinary tract symptoms are discussed. Initiation of a prescribing cascade, whereby antimuscarinic agents or β3-agonists are added to treat symptoms of urinary urgency and incontinence, is best avoided. Recommendations and practical tips are provided that outline more judicious management of heart failure patients with lower urinary tract symptoms. Compelling strategies to improve urinary outcomes include titrating diuretics, switching ACE inhibitors, treating lower urinary tract infections, appropriate fluid management, daily weighing, and uptake of pelvic floor muscle exercises.

Metaflumizone is a novel sodium channel blocker insecticide.

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Salgado, V L; Hayashi, J H

2007-12-15

Metaflumizone is a novel semicarbazone insecticide, derived chemically from the pyrazoline sodium channel blocker insecticides (SCBIs) discovered at Philips-Duphar in the early 1970s, but with greatly improved mammalian safety. This paper describes studies confirming that the insecticidal action of metaflumizone is due to the state-dependent blockage of sodium channels. Larvae of the moth Spodoptera eridania injected with metaflumizone became paralyzed, concomitant with blockage of all nerve activity. Furthermore, tonic firing of abdominal stretch receptor organs from Spodoptera frugiperda was blocked by metaflumizone applied in the bath, consistent with the block of voltage-dependent sodium channels. Studies on native sodium channels, in primary-cultured neurons isolated from the CNS of the larvae of the moth Manduca sexta and on Para/TipE sodium channels heterologously expressed in Xenopus (African clawed frog) oocytes, confirmed that metaflumizone blocks sodium channels by binding selectively to the slow-inactivated state, which is characteristic of the SCBIs. The results confirm that metaflumizone is a novel sodium channel blocker insecticide.

SELECTIVE AND NONSELECTIVE β-BLOCKERS IN PRIMARY OPEN ANGLE GLAUCOMA THERAPY – RESULTS OF COLOR DOPPLER SONOGRAPHY

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Vukoslava Maričić-Došen

2002-12-01

Full Text Available Background. Primary open angle glaucoma (POAG is a syndrome of progressive optic neuropathy characterized by optic nerve head excavation and visual field defects. Poor correlation between IOP and progression of glaucoma disease sets vascular mechanism in the centre of attention. By Color Doppler sonography, quantification of blood flow changes in vessels, which supply optic nerve head, is possible. We wanted to find out whether there are changes in the circulation of central retinal artery and posterior ciliary arteries in patients with primary open angle glaucoma treated with selective or nonselective β -blockers.Methods. 44 patients (88 eyes were divided into two groups: group 1: 22 patients (44 eyes treated with selective β -blockers (Betaxolol 0.5% and group 2: 22 patients (44 eyes treated with nonselective β -blockers (Timolol 0.5%. Vascular indices (RI, PI were measured in the central retinal artery and posterior ciliary arteries.Results. We found decreased blood flow and increased vascular indices in both groups of patients, statistically significant difference between group 1 and group 2: blood flow velocity was higher and vascular indices were lower in group 1 (Betaxolol 0.5% compared to group 2 (Timolol 0..5%.Conclusions. Selective β -blockers (calcium channel blockers act more vasoactively and neuroprotectively comparing to nonselective β -blockers.

Worsening heart failure in 'real-world' clinical practice: predictors and prognostic impact.

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AlFaleh, Hussam; Elasfar, Abdelfatah A; Ullah, Anhar; AlHabib, Khalid F; Hersi, Ahmad; Mimish, Layth; Almasood, Ali; Al Ghamdi, Saleh; Ghabashi, Abdullah; Malik, Asif; Hussein, Gamal A; Al-Murayeh, Mushabab; Abuosa, Ahmed; Al Habeeb, Waleed; Kashour, Tarek

2017-08-01

The aim of this study was to compare the clinical features, predictors, and clinical outcomes of patients hospitalized with acute heart failure (AHF), with and without worsening heart failure (WHF). We used data from a multicentre prospective registry of AHF patients created in Saudi Arabia. WHF was defined as recurrence of heart failure symptoms or signs-with or without cardiogenic shock. In-hospital short- and long-term outcomes, as well as predictors of WHF are described. Of the 2609 AHF patients enrolled, 33.8% developed WHF. WHF patients were more likely to have a history of heart failure and ischaemic heart disease. Use of intravenous vasodilators, inotropic agents, furosemide infusions, and discharge beta-blockers was significantly higher in WHF patients, while use of discharge ACE inhibitors was higher in patients without WHF. Length of hospital stay was significantly longer for WHF patients than for those without WHF [median (interquartile range) 13 (14) vs. 7 (7) days, P world clinical practice, WHF during hospitalization for AHF is a strong predictor for short- and intermediate-term mortality, and a cause for longer hospital stays. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

Improving documentation of a beta-blocker quality measure through an anesthesia information management system and real-time notification of documentation errors.

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Nair, Bala G; Peterson, Gene N; Newman, Shu-Fang; Wu, Wei-Ying; Kolios-Morris, Vickie; Schwid, Howard A

2012-06-01

Continuation of perioperative beta-blockers for surgical patients who are receiving beta-blockers prior to arrival for surgery is an important quality measure (SCIP-Card-2). For this measure to be considered successful, name, date, and time of the perioperative beta-blocker must be documented. Alternately, if the beta-blocker is not given, the medical reason for not administering must be documented. Before the study was conducted, the institution lacked a highly reliable process to document the date and time of self-administration of beta-blockers prior to hospital admission. Because of this, compliance with the beta-blocker quality measure was poor (-65%). To improve this measure, the anesthesia care team was made responsible for documenting perioperative beta-blockade. Clear documentation guidelines were outlined, and an electronic Anesthesia Information Management System (AIMS) was configured to facilitate complete documentation of the beta-blocker quality measure. In addition, real-time electronic alerts were generated using Smart Anesthesia Messenger (SAM), an internally developed decision-support system, to notify users concerning incomplete beta-blocker documentation. Weekly compliance for perioperative beta-blocker documentation before the study was 65.8 +/- 16.6%, which served as the baseline value. When the anesthesia care team started documenting perioperative beta-blocker in AIMS, compliance was 60.5 +/- 8.6% (p = .677 as compared with baseline). Electronic alerts with SAM improved documentation compliance to 94.6 +/- 3.5% (p documentation and (2) enhance features in the electronic medical systems to alert the user concerning incomplete documentation.

Combination therapy with solifenacin and tamsulosin oral controlled absorption system in a single tablet for lower urinary tract symptoms in men: efficacy and safety results from the randomised controlled NEPTUNE trial

NARCIS (Netherlands)

van Kerrebroeck, Philip; Chapple, Christopher; Drogendijk, Ted; Klaver, Monique; Sokol, Roman; Speakman, Mark; Traudtner, Klaudia; Drake, Marcus J.; Kiss, G.; Marberger, M.; Strotski, A. V.; Varaksa, A. N.; Vashchula, V.; Dewilde, T.; Braeckman, J.; Roumeguere, T.; Wyndaele, J. J.; Ameye, F.; Everaert, K.; van Cleynenbruegel, B.; de Leval, J.; Vanderkerken, J.; Ackaert, K.; Hiblbauer, J.; Zhanel, P.; Klecka, J.; Lukes, M.; Novak, J.; Lisec, M.; Vrtal, R.; Ondra, D.; Liehne, J.; Tuma, J.; Azzouzi, A.-R.; Wellerand, H.; Jung, J.-L.; Mourey, E.; Colombel, M.; Claude, R.; Ibrahim, H.; Desgrandchamps, F.; Haab, F.; Zerbib, M.; Ruffion, A.; Vincendeau, S.; Haillot, O.; Hentschel, M.; Gerhardt, U.; Hechelmann, W.; de la Rosette, J.

2013-01-01

Storage symptoms are particularly bothersome in men with lower urinary tract symptoms (LUTS) but may not be adequately treated by α-blocker monotherapy. To assess the efficacy and safety of a fixed-dose combination (FDC) of solifenacin and an oral controlled absorption system (OCAS) formulation of

Patient and Provider Factors Affecting Clinical Inertia in Patients With Type 2 Diabetes on Metformin Monotherapy.

Science.gov (United States)

Mahabaleshwarkar, Rohan; Gohs, Frank; Mulder, Holly; Wilkins, Nick; DeSantis, Andrea; Anderson, William E; Ejzykowicz, Flavia; Rajpathak, Swapnil; Norton, H James

2017-08-01

Our aim was to determine the extent of clinical inertia and the associated patient and provider factors in patients with type 2 diabetes on metformin monotherapy (MM) at a large integrated health care system in the United States. The study cohort included patients with type 2 diabetes aged 18 to 85 years, on MM between January 2009 and September 2013, who experienced MM failure (had an uncontrolled glycosylated hemoglobin [HbA 1c ] reading (≥8.0% [64 mmol/mol]) after at least 90 days of MM). Clinical inertia was defined as absence of treatment intensification with an add-on therapy within 180 days after the MM failure (index date). The impact of patient and provider factors on clinical inertia was determined using generalized estimating equations. The study cohort consisted of 996 patients; 58% were men and 59% were white, with a mean age of 53 (11.8) years. Of these, 49.8% experienced clinical inertia. Lower HbA 1c at index date, absence of liver diseases, absence of renal diseases, and greater provider age were associated with clinical inertia. The clinical inertia rate in a secondary analysis considering HbA 1c inertia. Considerable clinical inertia rates were observed in our real-world patient population, suggesting the need of interventions to reduce clinical inertia in clinical practice. Information about patient and provider factors affecting clinical inertia provided by this study could help healthcare policymakers plan and implement such interventions. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Enhanced astroglial GABA uptake attenuates tonic GABAA inhibition of the presympathetic hypothalamic paraventricular nucleus neurons in heart failure.

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Pandit, Sudip; Jo, Ji Yoon; Lee, Sang Ung; Lee, Young Jae; Lee, So Yeong; Ryu, Pan Dong; Lee, Jung Un; Kim, Hyun-Woo; Jeon, Byeong Hwa; Park, Jin Bong

2015-08-01

γ-Aminobutyric acid (GABA) generates persistent tonic inhibitory currents (Itonic) and conventional inhibitory postsynaptic currents in the hypothalamic paraventricular nucleus (PVN) via activation of GABAA receptors (GABAARs). We investigated the pathophysiological significance of astroglial GABA uptake in the regulation of Itonic in the PVN neurons projecting to the rostral ventrolateral medulla (PVN-RVLM). The Itonic of PVN-RVLM neurons were significantly reduced in heart failure (HF) compared with sham-operated (SHAM) rats. Reduced Itonic sensitivity to THIP argued for the decreased function of GABAAR δ subunits in HF, whereas similar Itonic sensitivity to benzodiazepines argued against the difference of γ2 subunit-containing GABAARs in SHAM and HF rats. HF Itonic attenuation was reversed by a nonselective GABA transporter (GAT) blocker (nipecotic acid, NPA) and a GAT-3 selective blocker, but not by a GAT-1 blocker, suggesting that astroglial GABA clearance increased in HF. Similar and minimal Itonic responses to bestrophin-1 blockade in SHAM and HF neurons further argued against a role for astroglial GABA release in HF Itonic attenuation. Finally, the NPA-induced inhibition of spontaneous firing was greater in HF than in SHAM PVN-RVLM neurons, whereas diazepam induced less inhibition of spontaneous firing in HF than in SHAM neurons. Overall, our results showed that combined with reduced GABAARs function, the enhanced astroglial GABA uptake-induced attenuation of Itonic in HF PVN-RVLM neurons explains the deficit in tonic GABAergic inhibition and increased sympathetic outflow from the PVN during heart failure. Copyright © 2015 the American Physiological Society.

Cardiovascular and Renal Outcomes of Renin-Angiotensin System Blockade in Adult Patients with Diabetes Mellitus: A Systematic Review with Network Meta-Analyses.

Science.gov (United States)

Catalá-López, Ferrán; Macías Saint-Gerons, Diego; González-Bermejo, Diana; Rosano, Giuseppe M; Davis, Barry R; Ridao, Manuel; Zaragoza, Abel; Montero-Corominas, Dolores; Tobías, Aurelio; de la Fuente-Honrubia, César; Tabarés-Seisdedos, Rafael; Hutton, Brian

2016-03-01

Medications aimed at inhibiting the renin-angiotensin system (RAS) have been used extensively for preventing cardiovascular and renal complications in patients with diabetes, but data that compare their clinical effectiveness are limited. We aimed to compare the effects of classes of RAS blockers on cardiovascular and renal outcomes in adults with diabetes. Eligible trials were identified by electronic searches in PubMed/MEDLINE and the Cochrane Database of Systematic Reviews (1 January 2004 to 17 July 2014). Interventions of interest were angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and direct renin (DR) inhibitors. The primary endpoints were cardiovascular mortality, myocardial infarction, and stroke-singly and as a composite endpoint, major cardiovascular outcome-and end-stage renal disease [ESRD], doubling of serum creatinine, and all-cause mortality-singly and as a composite endpoint, progression of renal disease. Secondary endpoints were angina pectoris and hospitalization for heart failure. In all, 71 trials (103,120 participants), with a total of 14 different regimens, were pooled using network meta-analyses. When compared with ACE inhibitor, no other RAS blocker used in monotherapy and/or combination was associated with a significant reduction in major cardiovascular outcomes: ARB (odds ratio [OR] 1.02; 95% credible interval [CrI] 0.90-1.18), ACE inhibitor plus ARB (0.97; 95% CrI 0.79-1.19), DR inhibitor plus ACE inhibitor (1.32; 95% CrI 0.96-1.81), and DR inhibitor plus ARB (1.00; 95% CrI 0.73-1.38). For the risk of progression of renal disease, no significant differences were detected between ACE inhibitor and each of the remaining therapies: ARB (OR 1.10; 95% CrI 0.90-1.40), ACE inhibitor plus ARB (0.97; 95% CrI 0.72-1.29), DR inhibitor plus ACE inhibitor (0.99; 95% CrI 0.65-1.57), and DR inhibitor plus ARB (1.18; 95% CrI 0.78-1.84). No significant differences were showed between ACE inhibitors and ARBs with

Cardiovascular and Renal Outcomes of Renin-Angiotensin System Blockade in Adult Patients with Diabetes Mellitus: A Systematic Review with Network Meta-Analyses.

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Ferrán Catalá-López

2016-03-01

Full Text Available Medications aimed at inhibiting the renin-angiotensin system (RAS have been used extensively for preventing cardiovascular and renal complications in patients with diabetes, but data that compare their clinical effectiveness are limited. We aimed to compare the effects of classes of RAS blockers on cardiovascular and renal outcomes in adults with diabetes.Eligible trials were identified by electronic searches in PubMed/MEDLINE and the Cochrane Database of Systematic Reviews (1 January 2004 to 17 July 2014. Interventions of interest were angiotensin-converting enzyme (ACE inhibitors, angiotensin receptor blockers (ARBs, and direct renin (DR inhibitors. The primary endpoints were cardiovascular mortality, myocardial infarction, and stroke-singly and as a composite endpoint, major cardiovascular outcome-and end-stage renal disease [ESRD], doubling of serum creatinine, and all-cause mortality-singly and as a composite endpoint, progression of renal disease. Secondary endpoints were angina pectoris and hospitalization for heart failure. In all, 71 trials (103,120 participants, with a total of 14 different regimens, were pooled using network meta-analyses. When compared with ACE inhibitor, no other RAS blocker used in monotherapy and/or combination was associated with a significant reduction in major cardiovascular outcomes: ARB (odds ratio [OR] 1.02; 95% credible interval [CrI] 0.90-1.18, ACE inhibitor plus ARB (0.97; 95% CrI 0.79-1.19, DR inhibitor plus ACE inhibitor (1.32; 95% CrI 0.96-1.81, and DR inhibitor plus ARB (1.00; 95% CrI 0.73-1.38. For the risk of progression of renal disease, no significant differences were detected between ACE inhibitor and each of the remaining therapies: ARB (OR 1.10; 95% CrI 0.90-1.40, ACE inhibitor plus ARB (0.97; 95% CrI 0.72-1.29, DR inhibitor plus ACE inhibitor (0.99; 95% CrI 0.65-1.57, and DR inhibitor plus ARB (1.18; 95% CrI 0.78-1.84. No significant differences were showed between ACE inhibitors and ARBs with

Beta-blockers do not impair the cardiovascular benefits of endurance training in hypertensives.

Science.gov (United States)

Westhoff, T H; Franke, N; Schmidt, S; Vallbracht-Israng, K; Zidek, W; Dimeo, F; van der Giet, M

2007-06-01

Aerobic physical exercise is broadly recommended as a helpful adjunct to obtain blood pressure control in hypertension. Beta-blockade interacts with heart rate, sympathetic tone, maximal workload and local lactate production. In the present randomized-controlled study, we compared the cardiovascular effects of an endurance training programme in elderly hypertensives with or without beta-blockers and developed a first approach to determine a lactate-based training heart rate in presence of beta-blockade. Fifty-two patients (23 with beta-blocker, 29 without beta-blocker) > or =60 years with systolic 24-h ambulatory blood pressure (ABP) > or =140 mm Hg and/or antihypertensive treatment were randomly assigned to sedentary activity or a heart-rate controlled 12-week treadmill exercise programme (lactate 2.0 mmol/l). In the exercise group, the training significantly decreased systolic and diastolic 24-h ABP, blood pressure on exertion (100 W) and increased endothelium-dependent vasodilation (flow-mediated vasodilation, FMD) and physical performance both in the presence and absence of beta-blockade (Pendurance training evokes comparable cardiovascular benefits in the presence and absence of beta-blockade including a marked improvement of endothelial function. In the present study, target training heart rate with beta-blockers is about 18% lower than without.

Transport of beta-blockers and calcium antagonists by diffusion in cat myocardium

DEFF Research Database (Denmark)

Haunsø, Stig; Sejrsen, Per; Svendsen, Jesper Hastrup

1991-01-01

Beta-blockers and calcium antagonists have been claimed to possess cardioprotective properties. This study addresses the question of whether a significant amount of these drugs will reach the cardiac myocytes during no-flow ischemia, where solute transport depends solely on diffusion. In anesthet......Beta-blockers and calcium antagonists have been claimed to possess cardioprotective properties. This study addresses the question of whether a significant amount of these drugs will reach the cardiac myocytes during no-flow ischemia, where solute transport depends solely on diffusion...

Mortality and Reinfarction among Patients Using Different Beta-Blockers for Secondary Prevention after a Myocardial Infarction

DEFF Research Database (Denmark)

Andersen, Søren Skøtt; Hansen, Morten Lock; Gislason, Gunnar H

2009-01-01

Objectives: To study differences in the clinical efficacy of various brands of beta-blocker in secondary prevention after a myocardial infarction (MI). Methods: All patients hospitalized with a first MI between 1995 and 2002 who were still alive 30 days after discharge and had had at least one...... prescription for a beta-blocker filled were identified by individual-level linkage of nationwide registries of hospitalizations and drugs dispensed from pharmacies. A total of 32,259 MI patients were included in the study. Multivariable Cox proportional hazard models were used to analyze the risks of death...... and recurrent MI related to treatment with different beta-blockers. Results: The risks for death and recurrent MI were similar in patients using different beta-blockers, except that mortality from all causes among patients with a prescription for sotalol was higher. Subgroup analyses of high-risk patients...

Beta Blockers Suppress Dextrose-Induced Endoplasmic Reticulum Stress, Oxidative Stress, and Apoptosis in Human Coronary Artery Endothelial Cells.

Science.gov (United States)

Haas, Michael J; Kurban, William; Shah, Harshit; Onstead-Haas, Luisa; Mooradian, Arshag D

Beta blockers are known to have favorable effects on endothelial function partly because of their capacity to reduce oxidative stress. To determine whether beta blockers can also prevent dextrose-induced endoplasmic reticulum (ER) stress in addition to their antioxidative effects, human coronary artery endothelial cells and hepatocyte-derived HepG2 cells were treated with 27.5 mM dextrose for 24 hours in the presence of carvedilol (a lipophilic beta blockers with alpha blocking activity), propranolol (a lipophilic nonselective beta blockers), and atenolol (a water-soluble selective beta blockers), and ER stress, oxidative, stress and cell death were measured. ER stress was measured using the placental alkaline phosphatase assay and Western blot analysis of glucose regulated protein 78, c-Jun-N-terminal kinase (JNK), phospho-JNK, eukaryotic initiating factor 2α (eIF2α), and phospho-eIF2α and measurement of X-box binding protein 1 (XBP1) mRNA splicing using reverse transcriptase-polymerase chain reaction. Superoxide (SO) generation was measured using the superoxide-reactive probe 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo[1,2-A]pyrazin-3-one hydrochloride (MCLA) chemiluminescence. Cell viability was measured by propidium iodide staining method. The ER stress, SO production, and cell death induced by 27.5 mM dextrose were inhibited by all 3 beta blockers tested. The antioxidative and ER stress reducing effects of beta blockers were also observed in HepG2 cells. The salutary effects of beta blockers on endothelial cells in reducing both ER stress and oxidative stress may contribute to the cardioprotective effects of these agents.

Bicalutamide monotherapy compared with castration in patients with nonmetastatic locally advanced prostate cancer

DEFF Research Database (Denmark)

Iversen, P; Tyrrell, C J; Kaisary, A V

2000-01-01

Nonsteroidal antiandrogen monotherapy may be a treatment option for some patients with advanced prostate cancer. We report a survival and safety update from an analysis of 2 studies in which patients with nonmetastatic (M0) locally advanced disease were treated with either 150 mg. bicalutamide mo...

Risk of severe hematologic toxicities in cancer patients treated with PARP inhibitors: results of monotherapy and combination therapy trials

Directory of Open Access Journals (Sweden)

Alecu I

2018-02-01

Full Text Available Iulian Alecu, Tsveta Milenkova, Simon R Turner Research and Development, AstraZeneca UK Limited, Cambridge, UKThe tolerability profile of PARP inhibitors often includes hematologic toxicities, and the characterization of these adverse events is important to allow effective management by clinicians. Zhou et al1 recently carried out a meta-analysis of the incidence and relative risks of severe neutropenia, thrombocytopenia, and anemia events in 12 randomized controlled trials of PARP inhibitors, either as monotherapy or in combination with chemotherapy or radiotherapy. The authors concluded that olaparib resulted in a higher incidence of severe (common terminology criteria for adverse events [CTCAE] grade $3 neutropenia when compared with niraparib and veliparib; however, these conclusions are based on inappropriate and incomplete comparisons of hematologic toxicity with olaparib or veliparib in combination with myelotoxic chemotherapy versus niraparib monotherapy. While both monotherapy and combination therapy olaparib studies are discussed in the paper, the neutropenia analysis is based on olaparib data solely from studies in combination with paclitaxel or paclitaxel plus carboplatin. In order to inform the practicing clinician of the relative risk of hematologic toxicity associated with different PARP inhibitors, direct comparison needs to be conducted based on monotherapy, where applicable, as per the approved drug indication, otherwise the reader is given misleading information.View the original paper by Zhou et al.

Efficacy and safety of endocrine monotherapy as first-line treatment for hormone-sensitive advanced breast cancer: A network meta-analysis.

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Zhang, Jingwen; Huang, Yanhong; Wang, Changyi; He, Yuanfang; Zheng, Shukai; Wu, Kusheng

2017-08-01

Endocrine therapy was recommended as the preferred first-line treatment for hormone receptor-positive (HR+, i.e., ER+ and/or PgR+), human epidermal growth factor receptor-2-negative (HER2-) postmenopausal advanced breast cancer (ABC), but which endocrine monotherapy is optimal lacks consensus. We aimed to identify the optimal endocrine monotherapy with a network meta-analysis. We performed a network meta-analysis for a comprehensive analysis of 6 first-line endocrine monotherapies (letrozole, anastrozole, exemestane, tamoxifen, fulvestrant 250 mg and 500 mg) for HR+ HER2- metastatic or locally advanced breast cancer in postmenopausal patients. The main outcomes were objective response rate (ORR), time to progression (TTP), and progression-free survival (PFS). Secondary outcomes were adverse events. We identified 27 articles of 8 randomized controlled trials including 3492 patients in the network meta-analysis. For ORR, the treatments ranked in descending order of effectiveness were letrozole > exemestane > anastrozole > fulvestrant 500 mg > tamoxifen > fulvestrant 250 mg. For TTP/PFS, the order was fulvestrant 500 mg > letrozole > anastrozole > exemestane > tamoxifen > fulvestrant 250 mg. We directly compared adverse events and found that tamoxifen produced more hot flash events than fulvestrant 250 mg. Fulvestrant 500 mg and letrozole might be optimal first-line endocrine monotherapy choices for HR+ HER2- ABC because of efficacious ORR and TTP/PFS, with a favorable tolerability profile. However, direct comparisons among endocrine monotherapies in the first-line therapy setting are still required to robustly demonstrate any differences among these endocrine agents. Clinical choices should also depend on the specific disease situation and duration of endocrine therapy.

Association of Beta-Blocker Use With Less Prevalent Joint Pain and Lower Opioid Requirement in People With Osteoarthritis.

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Valdes, Ana M; Abhishek, Abhishek; Muir, Kenneth; Zhang, Weiya; Maciewicz, Rose A; Doherty, Michael

2017-07-01

Recent findings suggest that β-adrenergic blockers have antinociceptive properties. The aim of this study was to compare levels of large-joint pain between those taking adrenergic blockers and those taking other antihypertensive medications. Data from the Genetics of Osteoarthritis and Lifestyle (GOAL) study, a secondary-care cohort of osteoarthritis (OA) patients, were used. Joint pain was assessed using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores in 873 individuals with symptomatic hip and/or knee OA and hypertension, who were taking ≥1 prescription antihypertensive medications. The association between adrenergic blocker prescription and at least moderate joint pain (WOMAC score anxiety, and depression. The use of β-adrenergic blockers was associated with lower WOMAC pain scores and with a lower prevalence of joint pain after adjustment for demographic variables and comorbidity (adjusted odds ratio [OR adj ] for pain 0.68 [95% confidence interval (95% CI) 0.51, 0.92]; P blockers (OR adj for pain 0.94 [95% CI 0.55, 1.58]) or with any other class of antihypertensive medications. Prescription of beta-blockers was also associated negatively with opioid use (OR adj for opioids 0.73 [95% CI 0.54, 0.98]; P beta-blockers is associated with less joint pain and a lower use of opioids and other analgesics in individuals with symptomatic large-joint OA. This observation needs to be confirmed by other studies. © 2016, American College of Rheumatology.

Recent developments in HPLC analysis of β-blockers in biological samples.

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Saleem, Kishwar; Ali, Imran; Kulsum, Umma; Aboul-Enein, Hassan Y

2013-09-01

β-Adrenergic blockers represent a very important class of drugs that are used worldwide for treating various cardiac diseases. The present article describes the state-of-the art of analyses of β-adrenergic blockers using high-performance liquid chromatography (HPLC). Sample preparation techniques such as liquid-liquid extraction, solid-phase extraction and solid-phase microextraction have been discussed, which are essential prior to HPLC analysis. Additionally, applications of liquid chromatography coupled with tandem mass spectrometry are included. HPLC methods have been reported to include 0.6-26 min as the run times and 0.01 ng/mL to 25 µg/mL as detection limits. The most commonly used columns were C18 with various buffers as the mobile phases, along with various organic modifiers. The optimization of HPLC conditions has been discussed. It has been observed that the reported methods are quite satisfactory for the analyses of β-adrenergic blockers in biological samples. Future perspectives in the hyphenation of solid-phase microextraction-nano-liquid chromatography-tandem mass spectrometry have also been highlighted to achieve detections at nanogram and picogram levels. The present article is very useful for academicians, scientists, drug and pharmaceutical personnel and government regulatory authorities.

Safety and efficacy of miltefosine monotherapy and pentoxifylline associated with pentavalent antimony in treating mucosal leishmaniasis.

Science.gov (United States)

Ventin, Fernanda; Cincurá, Carolina; Machado, Paulo Roberto Lima

2018-03-01

Mucosal Leishmaniasis (ML) is a difficult to treat and severe form of Leishmaniasis. In general, more than 40% of subjects with ML have therapeutic failure upon the use of pentavalent antimony (Sb v ) at 20mg/kg/day during 30 days. Additionally, Sb v is a toxic drug that requires parenteral administration, and many patients will need several courses to be cured. In cases that cannot be treated or cured by Sb v , the alternative is amphotericin B, another toxic and parenteral drug. As a consequence, many ML patients will be cured only after years of disease and may present several morbidities due to the aggressiveness of the disease or toxicity related to the treatment. Areas covered: We aimed to review clinical trials with Miltefosine or Sb v associated with pentoxifylline in the treatment of ML. Expert commentary: There are few studies to define more effective and safer therapy in mucosal disease caused by Leishmania, with an urgent need to supporting and funding well designed trials. Miltefosine monotherapy, as well as pentoxifylline combined with Sb v are promising therapeutic approaches to increase the cure rate of this neglected disease.

Beta-blocker under-use in COPD patients

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Lim KP

2017-10-01

Full Text Available Kuan Pin Lim,1,2 Sarah Loughrey,1 Michael Musk,1,2 Melanie Lavender,1,2 Jeremy P Wrobel1–3 1Advanced Lung Disease Unit, Royal Perth Hospital, Perth, WA, Australia; 2Respiratory Department, Fiona Stanley Hospital, Murdoch, WA, Australia; 3School of Medicine, University of Notre Dame, Fremantle, WA, Australia Background: Cardiovascular (CVS comorbidities are common in COPD and contribute significantly to morbidity and mortality, especially following acute exacerbations of COPD (AECOPD. Beta-blockers (BBs are safe and effective in COPD patients, with demonstrated survival benefit following myocardial infarction. We sought to determine if BBs are under-prescribed in patients hospitalized with AECOPD. We also sought to determine inpatient rates of CVS and cerebrovascular complications, and their impact on patient outcomes. Methods: Retrospective hospital data was collected over a 12-month period. The medical records of all patients >40 years of age coded with a diagnosis of AECOPD were analyzed. Prevalent use and incident initiation of BBs were assessed. Comorbidities including indications and contraindications for BB use were analyzed. Results: Of the 366 eligible patients, 156 patients (42.6% had at least one indication for BB use – of these patients, only 53 (34.0% were on BB therapy and 61 (39.1% were not on BB therapy but had no listed contraindication. Prevalent use of BBs at the time of admission in all 366 patients was 19.7%, compared with 45.6%, 39.6% and 45.9% use of anti-platelets, statins and angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers, respectively. CVS and cerebrovascular complications were common in this population (57 patients, 16% and were associated with longer length of stay (p<0.01 and greater inpatient mortality (p=0.02. Conclusions: BBs are under-prescribed in COPD patients despite clear indication(s for their use. Further work is required to explore barriers to BB prescribing in COPD patients

Evaluation of risk of falls and orthostatic hypotension in older, long-term topical beta-blocker users

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W.D. Ramdas (Wishal); N. van der Velde (Nathalie); T.J.M. van der Cammen (Tischa); R.C.W. Wolfs (Roger)

2009-01-01

textabstractBackground: Falls are a serious problem in the elderly, and have recently been described as cardiovascular-mediated side effects of beta-blocker eye drops. Therefore, we investigated the possible association between the long-term use of beta-blockers, prostaglandins and their

Long-term use of angiotensin receptor blockers and the risk of cancer.

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Laurent Azoulay

Full Text Available The association between angiotensin receptor blockers (ARBs and cancer is controversial with meta-analyses of randomized controlled trials and observational studies reporting conflicting results. Thus, the objective of this study was to determine whether ARBs are associated with an overall increased risk of the four most common cancers, namely, lung, colorectal, breast and prostate cancers, and to explore these effects separately for each cancer type. We conducted a retrospective cohort study using a nested case-control analysis within the United Kingdom (UK General Practice Research Database. We assembled a cohort of patients prescribed antihypertensive agents between 1995, the year the first ARB (losartan entered the UK market, and 2008, with follow-up until December 31, 2010. Cases were patients newly-diagnosed with lung, colorectal, breast and prostate cancer during follow-up. We used conditional logistic regression to estimate adjusted rate ratios (RRs and 95% confidence intervals (CIs of cancer incidence, comparing ever use of ARBs with ever use of diuretics and/or beta-blockers. The cohort included 1,165,781 patients, during which 41,059 patients were diagnosed with one of the cancers under study (rate 554/100,000 person-years. When compared to diuretics and/or beta-blockers, ever use of ARBs was not associated with an increased rate of cancer overall (RR: 1.00; 95% CI: 0.96-1.03 or with each cancer site separately. The use of angiotensin-converting enzyme inhibitors and calcium channel blockers was associated with an increased rate of lung cancer (RR: 1.13; 95% CI: 1.06-1.20 and RR: 1.19; 95% CI: 1.12-1.27, respectively. This study provides additional evidence that the use of ARBs does not increase the risk of cancer overall or any of the four major cancer sites. Additional research is needed to further investigate a potentially increased risk of lung cancer with angiotensin-converting enzyme inhibitors and calcium channel blockers.

Preoperative depression symptom severity and its impact on adherence to preoperative beta-blocker therapy.

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Schonberger, Robert B; Feinleib, Jessica; Holt, Natalie; Dai, Feng; Brandt, Cynthia; Burg, Matthew M

2014-12-01

To test the association among depression symptoms, distressed personality type, and preoperative beta-blocker nonadherence and to estimate the prevalence of untreated major depression in this population. Prospective observational study. A veterans hospital. One hundred twenty patients on outpatient beta-blocker therapy presenting for surgery. The Patient Health Questionnaire (PHQ)-9, the D-Scale-14 (DS14), and Modified Morisky Scale (MMS) questionnaires. Of 99 participants who presented for surgery, the incidence of preoperative nonadherence was 14.1% (95% confidence interval 7%-21%), consistent with prior research. Nonadherence was 9.5% among those with no depression, 27.8% among those with mild depression, and 28.6% among those with moderate-to-severe depression (Cochran-Armitage test for trend p = 0.03). Distressed personality type was found in 35% of the cohort (95% confidence interval 26-45%) and was not associated with beta-blocker nonadherence (Fisher's exact test, p = 0.24). Among participants with symptoms of major depressive disorder (n = 25, 25.3%), more than half (n = 14, 56%) had no indication of depression listed at their most recent primary care visit. Patients with symptoms of depression on chronic beta-blocker therapy are susceptible to medication nonadherence on the day of surgery. Most surgical patients with symptoms of major depression lack a diagnosis of depression. Preoperative depression screening may thus (1) identify a population at increased risk of beta-blocker withdrawal, and (2) identify patients who may benefit from anesthesiologist-initiated referral for this treatable condition. Copyright © 2014 Elsevier Inc. All rights reserved.

The Use of Fish Oil Lipid Emulsion in the Treatment of Intestinal Failure Associated Liver Disease (IFALD

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Melissa I. Chang

2012-11-01

Full Text Available Since 2004, fish oil based lipid emulsions have been used in the treatment of intestinal failure associated liver disease, with a noticeable impact on decreasing the incidence of morbidity and mortality of this often fatal condition. With this new therapy, however, different approaches have emerged as well as concerns about potential risks with using fish oil as a monotherapy. This review will discuss the experience to date with this lipid emulsion along with the rational for its use, controversies and concerns.

USE OF BETA-BLOCKERS IN THE PERIOPERATIVE PERIOD: HOW STRONG ARE THE EVIDENCES?

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V. V. Samoylenko

2015-09-01

Full Text Available Optimization of the pharmacotherapy in preoperative period is the cornerstone of the concept of risk modification of cardiovascular complications in the perioperative period. Therefore, special attention has recently been focused on the use of beta-blockers in the postoperative period. Nowadays convincing evidence base for the use of this class of drugs in the perioperative period that was the basis for the development of clinical guidelines is accumulated. Moreover, results of large randomized trials of beta-blockers are controversial. This has resulted in significant differences in the classes of recommendations and levels of evidence.Analysis of the results of basic researches and the provisions of recommendations of the international and national professional medical societies on the use of beta-blockers in patients with cardiovascular disease to reduce the risk of cardiac complications in the perioperative period for planned extracardiac surgical procedures is presented.

Randomized trial of preladenant, given as monotherapy, in patients with early Parkinson disease.

Science.gov (United States)

Stocchi, Fabrizio; Rascol, Olivier; Hauser, Robert A; Huyck, Susan; Tzontcheva, Anjela; Capece, Rachel; Ho, Tony W; Sklar, Peter; Lines, Christopher; Michelson, David; Hewitt, David J

2017-06-06

To evaluate the adenosine 2a receptor antagonist preladenant as a nondopaminergic drug for the treatment of Parkinson disease (PD) when given as monotherapy. This was a randomized, 26-week, placebo- and active-controlled, parallel-group, multicenter, double-blind trial conducted in adults diagnosed with PD for rasagiline 1 mg (active-control) once daily, or placebo. The primary endpoint was the change from baseline at week 26 in the sum of UPDRS parts 2 (activities of daily living) and 3 scores (UPDRS 2+3 ). The number of patients treated was 1,007. Neither preladenant nor rasagiline was superior to placebo after 26 weeks. The differences vs placebo (95% confidence interval) in UPDRS 2+3 scores (with a negative difference indicating improvement vs placebo) were preladenant 2 mg = 2.60 (0.86, 4.30), preladenant 5 mg = 1.30 (-0.41, 2.94), preladenant 10 mg = 0.40 (-1.29, 2.11), and rasagiline 1 mg = 0.30 (-1.35, 2.03). Post hoc analyses did not identify a single causal factor that could explain the finding of a failed trial. Preladenant was generally well-tolerated with few patients discontinuing due to adverse events (preladenant 7%, rasagiline 3%, placebo 4%). No evidence supporting the efficacy of preladenant as monotherapy was observed in this phase 3 trial. The lack of efficacy of the active control rasagiline makes it difficult to interpret the results. Clinicaltrials.gov: NCT01155479. This study provides Class I evidence that for patients with early PD, preladenant is not effective as monotherapy at the doses studied (2, 5, 10 mg). © 2017 American Academy of Neurology.

Impact of introducing subsidized combination treatment with artemether-lumefantrine on sales of anti-malarial monotherapies: a survey of private sector pharmacies in Huambo, Angola.

Science.gov (United States)

Lussiana, Cristina; Floridia, Marco; Martinho do Rosário, Joana; Fortes, Filomeno; Allan, Richard

2016-12-01

Artemisinin-based combination therapies (ACTs) against malaria are subsidized in many African countries, but the impact of subsidy programs in reducing the sales of concomitantly available antimalarial monotherapies is poorly defined. Data from The MENTOR initiative, that introduced subsidized artemether-lumefantrine (sAL) in the private sector of Huambo province, Angola, were used. The main response variable was represented by sales of sAL and of monotherapies, measured as number of treatment courses. Sales in private pharmacies of sAL and four antimalarial monotherapies between 2009 and 2013 were organized in four time-periods, and analyzed using generalized linear models for repeated measures. A secondary analysis evaluated changes in relative market share. We analyzed data from 34 pharmacies at four time points, taken from a larger survey that involved 165 pharmacies between June 2009 and March 2013. The sAL, following its introduction, became the dominant antimalarial treatment in the private sector, usually exceeding the total sales of all antimalarial monotherapies combined (1480/2800 total treatment courses, 52.8% of all sales in March 2013). Sales of monotherapies decreased significantly, but did not stop, representing 36.7% (1028/2800) of sales at the end of the survey. Subsidized ACTs can attain rapidly a high relative market share. Their introduction reduced, but did not eliminate the demand for less effective monotherapies, that might favor parasite resistance. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Evaluation of risk of falls and orthostatic hypotension in older, long-term topical beta-blocker users

NARCIS (Netherlands)

Ramdas, Wishal D.; van der Velde, Nathalie; van der Cammen, Tischa J. M.; Wolfs, Roger C. W.

2009-01-01

Falls are a serious problem in the elderly, and have recently been described as cardiovascular-mediated side effects of beta-blocker eye drops. Therefore, we investigated the possible association between the long-term use of beta-blockers, prostaglandins and their combinations in eye drops, and

Simultaneous Response in Several Domains in Patients with Psoriatic Disease Treated with Etanercept as Monotherapy or in Combination with Conventional Synthetic Disease-modifying Antirheumatic Drugs.

Science.gov (United States)

Behrens, Frank; Meier, Lothar; Prinz, Jörg C; Jobst, Jürgen; Lippe, Ralph; Löschmann, Peter-Andreas; Lorenz, Hanns-Martin

2018-04-01

To evaluate patients with psoriatic arthritis (PsA) receiving etanercept (ETN) monotherapy or ETN plus conventional synthetic disease-modifying antirheumatic drugs (csDMARD) to determine the proportion achieving a clinically meaningful response in arthritis, psoriasis, and quality of life simultaneously. A prospective, multicenter, 52-week observational study in patients with active PsA evaluated treatment with ETN in clinical practice (ClinicalTrials.gov: NCT00293722). This analysis assessed simultaneous achievement of 3 treatment targets: low disease activity (LDA) based on 28-joint count Disease Activity Score (DAS28); body surface area (BSA) involvement ≤ 3%; and a score > 45 on the Medical Outcomes Study Short Form-12 (SF-12) physical component summary. Of 579 patients, 380 received ETN monotherapy and 199 received combination ETN plus csDMARD. At 52 weeks, data for all 3 disease domains were available for 251 patients receiving monotherapy and 151 receiving combination therapy. In the monotherapy and combination therapy groups, 61 (24.3%) and 37 (24.5%) patients, respectively, achieved all 3 treatment targets simultaneously. A significantly greater proportion of patients receiving monotherapy versus combination therapy achieved SF-12 > 45 (43.0% vs 31.8%; p < 0.05) and DAS28 LDA (72.5% vs 62.3%; p < 0.05). Conversely, BSA ≤ 3% was reached by a significantly greater proportion receiving combination therapy (75.5% vs 56.6%; p < 0.001). However, baseline BSA involvement was higher for the monotherapy group. While nearly half the patients achieved arthritis and psoriasis treatment targets simultaneously and one-fourth reached all 3 treatment targets, combining ETN and csDMARD did not substantially improve clinical response compared with ETN monotherapy in this real-world PsA patient population.

[Sacubitril / Valsartan in patients with diabetes and heart failure].

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Brandenburg, Vincent Matthias; Rocca, Hans-Peter Brunner-La; Marx, Nikolaus

2016-10-01

Sacubitril / Valsartan proofed to be an effective treatment compared to enalapril in reducing heart failure hospitalisations and mortality in patients with severe "Heart failure with reduced ejection fraction" (HFREF). Recent European cardiology guidelines attributed a class IB recommendation for Sacubitril / Valsartan in HFREF patients who remain symptomatic despite optimal treatment with ACE-I, a beta-blocker, and a mineralocorticoid receptor antagonist. There is a significant overlap between diabetic and HFREF patients and thus, efficacy assessment of Sacubitril / Valsartan is a clinically meaningful issue in the large subgroup of HFREF patients with diabetes. We discuss the present evidence why local authorities speculated about a potential interaction between the two diseases decreasing the efficacy of sacubitril/valsartan in terms of reducing relevant end-points in this cohort. Overall, Sacubitril / Valsartan is obviously a treatment option in diabetics with HFREF. However, diabetic cardiomyopathy needs to be recognised as a specific disease condition. © Georg Thieme Verlag KG Stuttgart · New York.

Use of low-level laser therapy as monotherapy or concomitant therapy for male and female androgenetic alopecia.

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Munck, Andréia; Gavazzoni, Maria Fernanda; Trüeb, Ralph M

2014-04-01

Androgenetic alopecia (AGA) is the most common form of hair loss in men and in women. Currently, minoxidil and finasteride are the treatments with the highest levels of medical evidence, but patients who exhibit intolerance or poor response to these treatments are in need of additional treatment modalities. The aim was to evaluate the efficacy and safety of low-level laser therapy (LLLT) for AGA, either as monotherapy or as concomitant therapy with minoxidil or finasteride, in an office-based setting. Retrospective observational study of male and female patients with AGA, treated with the 655 nm-HairMax Laser Comb(®), in an office-based setting. Efficacy was assessed with global photographic imaging. Of 32 patients (21 female, 11 male), 8 showed significant, 20 moderate, and 4 no improvement. Improvement was seen both with monotherapy and with concomitant therapy. Improvement was observed as early as 3 months and was sustained up to a maximum observation time of 24 months. No adverse reactions were reported. LLLT represents a potentially effective treatment for both male and female AGA, either as monotherapy or concomitant therapy. Combination treatments with minoxidil, finasteride, and LLLT may act synergistic to enhance hair growth.

Casodex (bicalutamide) 150-mg monotherapy compared with castration in patients with previously untreated nonmetastatic prostate cancer

DEFF Research Database (Denmark)

Iversen, P; Tyrrell, C J; Kaisary, A V

1998-01-01

To compare the efficacy, tolerability, and quality of life benefits of bicalutamide (Casodex) 150-mg/day monotherapy and castration in previously untreated nonmetastatic (M0) advanced prostate cancer....

Bisoprolol compared with carvedilol and metoprolol succinate in the treatment of patients with chronic heart failure.

Science.gov (United States)

Fröhlich, Hanna; Torres, Lorella; Täger, Tobias; Schellberg, Dieter; Corletto, Anna; Kazmi, Syed; Goode, Kevin; Grundtvig, Morten; Hole, Torstein; Katus, Hugo A; Cleland, John G F; Atar, Dan; Clark, Andrew L; Agewall, Stefan; Frankenstein, Lutz

2017-09-01

Beta-blockers are recommended for the treatment of chronic heart failure (CHF). However, it is disputed whether beta-blockers exert a class effect or whether there are differences in efficacy between agents. 6010 out-patients with stable CHF and a reduced left ventricular ejection fraction prescribed either bisoprolol, carvedilol or metoprolol succinate were identified from three registries in Norway, England, and Germany. In three separate matching procedures, patients were individually matched with respect to both dose equivalents and the respective propensity scores for beta-blocker treatment. During a follow-up of 26,963 patient-years, 302 (29.5%), 637 (37.0%), and 1232 (37.7%) patients died amongst those prescribed bisoprolol, carvedilol, and metoprolol, respectively. In univariable analysis of the general sample, bisoprolol and carvedilol were both associated with lower mortality as compared with metoprolol succinate (HR 0.80, 95% CI 0.71-0.91, p < 0.01, and HR 0.86, 95% CI 0.78-0.94, p < 0.01, respectively). Patients prescribed bisoprolol or carvedilol had similar mortality (HR 0.94, 95% CI 0.82-1.08, p = 0.37). However, there was no significant association between beta-blocker choice and all-cause mortality in any of the matched samples (HR 0.90; 95% CI 0.76-1.06; p = 0.20; HR 1.10, 95% CI 0.93-1.31, p = 0.24; and HR 1.08, 95% CI 0.95-1.22, p = 0.26 for bisoprolol vs. carvedilol, bisoprolol vs. metoprolol succinate, and carvedilol vs. metoprolol succinate, respectively). Results were confirmed in a number of important subgroups. Our results suggest that the three beta-blockers investigated have similar effects on mortality amongst patients with CHF.

Enzalutamide monotherapy: Phase II study results in patients with hormone-naive prostate cancer

DEFF Research Database (Denmark)

Tombal, Bertrand; Borre, Michael; Rathenborg, Per

2013-01-01

1 or 2). Most frequent treatment-emergent AEs included gynaecomastia (36%), fatigue (34%), and hot flush (18%). 7% of men experienced SAEs; none were drug-related. Conclusions: ENZA monotherapy (160 mg) was associated with significant PSA response in nearly all men with hormone-naïve prostate cancer...

Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis

NARCIS (Netherlands)

Fleischmann, Roy M.; Huizinga, Tom W. J.; Kavanaugh, Arthur F.; Wilkinson, Bethanie; Kwok, Kenneth; DeMasi, Ryan; van Vollenhoven, Ronald F.

2016-01-01

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib monotherapy was previously shown to inhibit structural damage, reduce clinical signs and symptoms of RA, and improve physical functioning over 24 months in methotrexate (MTX)-naive adult

Prognostic relevance of metabolic approach in patients with heart failure.

Science.gov (United States)

Di Napoli, P; Barsotti, A

2009-01-01

Progressions in acute cardiac care have improved survival after acute myocardial infarction, but in contraposition with this, there has been an increase in mortality because of heart failure. For this reason congestive heart failure is an increasingly widespread, costly and deadly disease, frequently named as epidemic of the XXI century. Despite advancement in modern treatment, mortality rate in heart failure patients remains high. In these patients more importance was attributed in the management of the left ventricle dysfunction. In fact, the heart failure patients have still a poor prognosis due to the ineluctable progression of contractile dysfunction and ventricular remodeling. The classical management of left ventricle dysfunction includes the pharmacological treatment with beta-blockers, ACE-inhibitors and aldosterone antagonists, and various surgical or electrophysiological interventions. Emerging evidence suggests that myocardium dysfunction is also due to substrate metabolism alterations. In particular, there is evidence that, in the failing heart, shifting metabolism away from a preference for fatty acids towards more carbohydrate oxidation could recover contractile function. Trimetazidine has been shown to improve symptoms and ventricular function and to have a beneficial effect on the inflammatory profile and endothelial function in these patients. Recently, it has been suggested that trimetazidine could also reduce ventricular remodeling, slowing down the progression of pump failure, and improve prognosis. These results suggest that trimetazidine is a useful adjunct to our current armamentarium for the treatment of heart failure patients.

Efficacy of α-blocker in improving ureteral stent-related symptoms: a meta-analysis of both direct and indirect comparison

Directory of Open Access Journals (Sweden)

He F

2016-05-01

Full Text Available Feng He, Li-bo Man, Gui-zhong Li, Ning Liu Department of Urinary Surgery, Beijing Jishuitan Hospital, Beijing, People’s Republic of China Objective: To critically evaluate the efficacy of an α-blocker in improving ureteral-stent-related symptoms and preliminarily investigate the difference between different types of α-blockers. Methods: Relevant randomized controlled trials were identified through searching PubMed, the Cochrane Library, Embase, and other sources. After quality assessment and data abstraction, direct comparison based on the Ureteral Stent-related Symptom Questionnaire (USSQ between α-blockers and control was performed by RevMan 5.3. Indirect comparison between different types of α-blockers was performed by ITC 1.0. Sensitive and subgroup analyses were used to handle important clinical factors. Results: Sixteen randomized controlled trials containing 1,489 cases were included. Compared with control, α-blockers significantly reduced the overall urinary symptom, pain index, general health index, and scores related to sexual matters, while no significant difference was found in work performance and additional problem scores. Subgroup analysis showed that the duration of stent insertion, patient’s age, stent size, and the type of α-blocker had the potential to influence the outcomes. Through indirect comparison, we found alfuzosin and terazosin to be better than tamsulosin in pain relief and general health improvement. Conclusion: α-Blocker was effective in treating ureteral stent-related symptoms, as it improved the major indexes of USSQ post-insertion or post-removal. Alfuzosin and terazosin seemed to be better than tamsulosin, which needs further verification because of the lack of direct comparison currently. Keywords: α-blocker, tamsulosin, alfuzosin, terazosin, ureteral stent-related discomfort

Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma

DEFF Research Database (Denmark)

Lokhorst, Henk M; Plesner, Torben; Laubach, Jacob P

2015-01-01

BACKGROUND: Multiple myeloma cells uniformly overexpress CD38. We studied daratumumab, a CD38-targeting, human IgG1κ monoclonal antibody, in a phase 1-2 trial involving patients with relapsed myeloma or relapsed myeloma that was refractory to two or more prior lines of therapy. METHODS: In part 1...... interval [CI], 4.2 to 8.1), and 65% (95% CI, 28 to 86) of the patients who had a response did not have progression at 12 months. CONCLUSIONS: Daratumumab monotherapy had a favorable safety profile and encouraging efficacy in patients with heavily pretreated and refractory myeloma. (Funded by Janssen...

Association of β-Blockers With Functional Outcomes, Death, and Rehospitalization in Older Nursing Home Residents After Acute Myocardial Infarction.

Science.gov (United States)

Steinman, Michael A; Zullo, Andrew R; Lee, Yoojin; Daiello, Lori A; Boscardin, W John; Dore, David D; Gan, Siqi; Fung, Kathy; Lee, Sei J; Komaiko, Kiya D R; Mor, Vincent

2017-02-01

Although β-blockers are a mainstay of treatment after acute myocardial infarction (AMI), these medications are commonly not prescribed for older nursing home residents after AMI, in part owing to concerns about potential functional harms and uncertainty of benefit. To study the association of β-blockers after AMI with functional decline, mortality, and rehospitalization among long-stay nursing home residents 65 years or older. This cohort study of nursing home residents with AMI from May 1, 2007, to March 31, 2010, used national data from the Minimum Data Set, version 2.0, and Medicare Parts A and D. Individuals with β-blocker use before AMI were excluded. Propensity score-based methods were used to compare outcomes in people who did vs did not initiate β-blocker therapy after AMI hospitalization. Functional decline, death, and rehospitalization in the first 90 days after AMI. Functional status was measured using the Morris scale of independence in activities of daily living. The initial cohort of 15 720 patients (11 140 women [70.9%] and 4580 men [29.1%]; mean [SD] age, 83 [8] years) included 8953 new β-blocker users and 6767 nonusers. The propensity-matched cohort included 5496 new users of β-blockers and an equal number of nonusers for a total cohort of 10 992 participants (7788 women [70.9%]; 3204 men [29.1%]; mean [SD] age, 84 [8] years). Users of β-blockers were more likely than nonusers to experience functional decline (odds ratio [OR], 1.14; 95% CI, 1.02-1.28), with a number needed to harm of 52 (95% CI, 32-141). Conversely, β-blocker users were less likely than nonusers to die (hazard ratio [HR], 0.74; 95% CI, 0.67-0.83) and had similar rates of rehospitalization (HR, 1.06; 95% CI, 0.98-1.14). Nursing home residents with moderate or severe cognitive impairment or severe functional dependency were particularly likely to experience functional decline from β-blockers (OR, 1.34; 95% CI, 1.11-1.61 and OR, 1.32; 95% CI, 1.10-1.59, respectively

Bed blockers: A study on the elderly patients in a teaching hospital in India

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Praveen Kumar N

2010-07-01

Full Text Available A cross-sectional study of in-patients over the age of 60 years was conducted at district McGann Hospital, Shimoga on patients who were classified as bed blockers. Level of dependency and cognitive function of these patients were assessed using Barthel scale and Abbreviated mental test (AMT respectively. Median age of the study population was 67 years; majority of them were men. Most of them were admitted in the medical ward and the median time to be labeled as bed blocker was 32 days. These bed blockers were a weak group of patients with an average 3.1 pathology per case. Majority of them suffered from neurological disorders and cardiovascular disease. High level of dependence was noted with a mean Barthel score of 29.68 (Range 0 -100. Low levels of cognitive function was also noted among these patients with a mean AMT of 4.76 (Range 0 -10.These findings demonstrate that the bed blockers in McGann hospital suffer not only from genuine health problems but also have a high dependency level in activities of daily living which hamper their discharge to the community. Community based rehabilitation using an intersectoral approach may help at least the less dependent to return home.

The role of solifenacin, as monotherapy or combination with tamsulosin in ureteral stent-related symptoms: a systematic review and meta-analysis.

Science.gov (United States)

Wang, Jue; Zhang, Xiaobei; Zhang, Tiande; Mu, Jianjun; Bai, Bing; Lei, Yi

2017-11-01

Ureteral stenting is associated with various morbidity and reduced quality of life. We systematically evaluated the efficacy and safety of solifenacin as monotherapy, or combined therapy with tamsulosin versus control or tamsulosin monotherapy in stent-related symptoms (SRSs). Randomized controlled trials evaluating solifenacin or its combination with tamsulosin for the treatment of SRSs were identified via a comprehensive search of Pubmed, Embase, Ovid, The Cochrane Library and relevant sources up to February 2017. Ureteral stent symptom questionnaire (USSQ) and drug-related complications were pooled for meta-analysis. Mean difference and risk difference were calculated as appropriate for each outcome to determine the cumulative effect size. There were 10 studies involving 1786 participants finally eligible in the quantitative analysis. Solifenacin monotherapy significantly reduced the total score of USSQ [MD -14.90; 95% CI (-25.19, -4.60); P = 0.005], as well as indexes of urinary symptoms, body pain, general health, sexual performance, and hematuria (P = 0.02, P = 0.009, P = 0.004, P = 0.02, P = 0.02, respectively), but the differences were insignificant when compared with tamsulosin except improved sexual performance (P = 0.004). Combined therapy of solifenacin and tamsulosin showed no beneficial effects in all indexes of USSQ over solifenacin monotherapy. Only slightly higher incidence of dry mouth (P = 0.02) was found with solifenacin versus control. The result demonstrates the safety and efficacy of solifenacin in reducing SRSs, but no significant advantage was found over tamsulosin. In addition, combination of solifenacin and tamsulosin did not show beneficial effects over solifenacin monotherapy. More high quality trials are warranted to further address this issue, however.

Beta-blocker use and fall risk in older individuals: Original results from two studies with meta-analysis

NARCIS (Netherlands)

Ham, Annelies C.; van Dijk, Suzanne C.; Swart, Karin M. A.; Enneman, Anke W.; van der Zwaluw, Nikita L.; Brouwer-Brolsma, Elske M.; van Schoor, Natasja M.; Carola Zillikens, M.; Lips, Paul; de Groot, Lisette C. P. G. M.; Hofman, Albert; Witkamp, Renger F.; Uitterlinden, André G.; Stricker, Bruno H.; van der Velde, Nathalie

2017-01-01

Aims To investigate the association between use of -blockers and beta-blocker characteristics - selectivity, lipid solubility, intrinsic sympathetic activity (ISA) and CYP2D6 enzyme metabolism - and fall risk. Methods Data from two prospective studies were used, including community-dwelling

Development of an amorphous surge blocker for a high voltage acceleration power supply of the neutral beam injectors

International Nuclear Information System (INIS)

Mizuno, Makoto; Ohara, Yoshihiro; Watanabe, Kazuhiro; Ozaki, Akira.

1993-10-01

An amorphous surge blocker for a high voltage acceleration power supply for the neutral beam injectors has been developed. Since the saturation magnetic flux density of the amorphous core is higher than that of the ferrite core, the surge blocker made of amorphous cores can be reduced in size appreciably compared to the conventional ferrite surge blocker. A 350 kV, 0.05 volt-second amorphous surge blocker was designed, fabricated and tested. The amorphous core was made by winding an amorphous tape with a film for the layer insulation and was heat-treated to recover the magnetic characteristics. The core is molded by epoxy resin and installed in a FRP insulator tube filled with SF 6 gas for the insulation. The volt-second measured was higher than the designed value and the electrical breakdown along the cores and between layers was not observed. This test result shows that the amorphous surge blocker is applicable for a dc acceleration power supply for high energy neutral beam injectors. (author)

Analysis of solar blocker through portable X-ray fluorescence

International Nuclear Information System (INIS)

Ferreira, Diego de Dio; Melquiades, Fabio Luiz; Appoloni, Carlos Roberto; Lopes, Fabio; Lonni, Audrey Stinghen G.; Oliveira, Frederico Minardi de; Duarte, Jose C.

2009-01-01

This paper estimates the concentration of TiO 2 by Energy Dispersion X-ray fluorescence (EDXRF) viewing t obtain the FPS due to the physical barrier in the composition of solar blockers, and identifies possible present metals in the samples. A portable EDXRF equipment was used and 27 commercial of different brands and solar protection factors were analysed. Also, three formulations (A, B and C) were prepared and measured estimated in FPS-30 using 5% or TiO 2 . The quantification was performed through calibration curves with 1% to 30% standards of TiO 2 . As result, it was possible to determine the contribution to physical protection in the FPS, associated to the Ti concentration present in some solar blocker samples available in the market. Also, it was possible to detect the presence of various metals in solar protectors, such as Fe, Zn, Br and Sr, and identify chemical elements which were not mentioned and their formulation as well

Comparative analysis of monotherapy versus duotherapy antiseizure drug management for postoperative seizure control in patients undergoing an awake craniotomy.

Science.gov (United States)

Eseonu, Chikezie I; Eguia, Francisco; Garcia, Oscar; Kaplan, Peter W; Quiñones-Hinojosa, Alfredo

2018-06-01

OBJECTIVE Postoperative seizures are a common complication in patients undergoing an awake craniotomy, given the cortical manipulation during tumor resection and the electrical cortical stimulation for brain mapping. However, little evidence exists about the efficacy of postoperative seizure prophylaxis. This study aims to determine the most appropriate antiseizure drug (ASD) management regimen following an awake craniotomy. METHODS The authors performed a retrospective analysis of data pertaining to patients who underwent an awake craniotomy for brain tumor from 2007 to 2015 performed by a single surgeon. Patients were divided into 2 groups, those who received a single ASD (the monotherapy group) and those who received 2 types of ASDs (the duotherapy group). Patient demographics, symptoms, tumor characteristics, hospitalization details, and seizure outcome were evaluated. Multivariable logistic regression was used to evaluate numerous clinical variables associated with postoperative seizures. RESULTS A total of 81 patients underwent an awake craniotomy for tumor resection of an eloquent brain lesion. Preoperative baseline characteristics were comparable between the 2 groups. The postoperative seizure rate was 21.7% in the monotherapy group and 5.7% in the duotherapy group (p = 0.044). Seizure outcome at 6 months' follow-up was assessed with the Engel classification scale. The duotherapy group had a significantly higher proportion of seizure-free (Engel Class I) patients than the monotherapy group (90% vs 60%, p = 0.027). The length of stay was similar, 4.02 days in the monotherapy group and 4.51 days in the duotherapy group (p = 0.193). The 90-day readmission rate was higher for the monotherapy group (26.1% vs 8.5% in the duotherapy group, p = 0.044). Multivariate logistic regression showed that preoperative seizure history was a significant predictor for postoperative seizures following an awake craniotomy (OR 2.08, 95% CI 0.56-0.90, p awake craniotomy and may

Sacubitril and valsartan fixed combination to reduce heart failure events in post-acute myocardial infarction patients.

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Zaid Iskandar, M; Lang, C C

2017-10-01

Heart failure is a term used to define a constellation of symptoms and signs that are commonly attributed to the inability of the heart to produce a cardiac output that meets the demands of the body. It remains a deadly disease, affecting between 1-2% of the population, and is more common in the elderly, with around 6-10% of patients over 65 suffering from the condition. Sacubitril/valsartan (LCZ-696) is a combined neprilysin inhibitor and angiotensin AT1 receptor blocker approved in recent years for the treatment of chronic heart failure with reduced ejection fraction. In an area where there have been limited pharmacological advances in the last 10 years, this drug was a game changer and a much welcomed addition to contemporary heart failure therapy. It is currently being studied in patients with heart failure with preserved ejection fraction and for the reduction of heart failure events post-acute myocardial infarction. Results from the ongoing PARADISE-MI study are awaited by the global cardiology community with great interest. Copyright 2017 Clarivate Analytics.

Safety and efficacy of a Nav1.7 selective sodium channel blocker in patients with trigeminal neuralgia

DEFF Research Database (Denmark)

Zakrzewska, Joanna M; Palmer, Joanne; Morisset, Valerie

2017-01-01

BACKGROUND: Current standard of care for trigeminal neuralgia is treatment with the sodium channel blockers carbamazepine and oxcarbazepine, which although effective are associated with poor tolerability and the need for titration. BIIB074, a Nav1.7-selective, state-dependent sodium-channel blocker...

THE ROLE OF S-AMLODIPINE IN ARTERIAL HYPERTENSION THERAPY WITH COMBINATION OF CALCIUM CHANNEL BLOCKERS AND BETA-BLOCKERS

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M. A. Maksimova

2013-01-01

Full Text Available Aim. To study efficacy and safety of calcium channel blocker, S-amlodipine, in combination with β-blocker, atenolol, in patients with arterial hypertension (HT 1-2 degree com- pared to fixed combination of racemic amlodipine and atenolol.Material and methods. Patients (n=31, 7 men and 24 women with HT 1–2 degree were included into the study. The patients were randomized into two groups by the com- binations sequence. Treatment with each combination lasted 4 weeks. Office blood pressure (BP was assessed at baseline and at the end of the treatment periods, possible side effects were registered.Results. All patients completed the study. Both combination of S-amlodipine+atenolol and fixed combination of racemic amlodipine+atenolol reduced systolic (in average, -15.9 and -12.7 mm Hg, respectively and diastolic (in average, -7.3 and -5.3 mmHg, respectively BP significantly. Heart rate also decreased during therapy (in average, -3 and -4 bt/min, respectively. The differences between combinations BP and heart rate effects were not significant. 8 and 16 adverse events were registered during S-amlodipine+atenolol and racemic amlodipine+atenolol therapies, respectively Conclusion. Combination of S-amlodipine+atenolol, as well as combination of racemic amlodipine+atenolol are effective in the treatment of patients with HT 1-2 degree, however combination with S-amlodipine has less number of adverse events.

Effect of beta-blocker therapy on the risk of infections and death after acute stroke--a historical cohort study.

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Ilko L Maier

Full Text Available BACKGROUND: Infections are a frequent cause for prolonged hospitalization and increased mortality after stroke. Recent studies revealed a stroke-induced depression of the peripheral immune system associated with an increased susceptibility for infections. In a mice model for stroke, this immunosuppressive effect was reversible after beta-blocker administration. The aim of our study was to investigate the effect of beta-blocker therapy on the risk of infections and death after stroke in humans. METHODS: 625 consecutive patients with ischemic or hemorrhagic stroke, admitted to a university hospital stroke unit, were included in this historical cohort study. The effect of beta-blocker therapy on post-stroke pneumonia, urinary tract infections and death was investigated using multivariable Poisson and Cox regression models. RESULTS: 553 (88.3% patients were admitted with ischemic stroke, the remaining 72 (11.7% had a hemorrhagic stroke. Median baseline NIHSS was 8 (IQR 5-16 points. 301 (48.2% patients received beta-blocker therapy. There was no difference in the risk of post-stroke pneumonia between patients with and without beta-blocker therapy (Rate Ratio = 1.00, 95%CI 0.77-1.30, p = 0.995. Patients with beta-blocker therapy showed a decreased risk for urinary tract infections (RR = 0.65, 95%CI 0.43-0.98, p = 0.040. 7-days mortality did not differ between groups (Hazard Ratio = 1.36, 95%CI 0.65-2.77, p = 0.425, while patients with beta-blocker therapy showed a higher 30-days mortality (HR = 1.93, 95%CI 1.20-3.10, p = 0.006. CONCLUSIONS: Beta-blocker therapy did not reduce the risk for post-stroke pneumonia, but significantly reduced the risk for urinary tract infections. Different immune mechanisms underlying both diseases might explain these findings that need to be confirmed in future studies.

Multi drug resistance to cancer chemotherapy: Genes involved and blockers

International Nuclear Information System (INIS)

Sayed-Ahmed, Mohamed M.

2007-01-01

During the last three decades, important and considerable research efforts had been performed to investigate the mechanism through which cancer cells overcome the cytotoxic effects of a variety of chemotherapeutic drugs. Most of the previously published work has been focused on the resistance of tumor cells to those anticancer drugs of natural source. Multidrug resistance (MDR) is a cellular cross-resistance to a broad spectrum of natural products used in cancer chemotherapy and is believed to be the major cause of the therapeutic failures of the drugs belonging to different naturally obtained or semisynthetic groups including vinca alkaloids, taxans, epipodophyllotoxins and certain antibiotics. This phenomenon results from overexpression of four MDR genes and their corresponding proteins that act as membrane-bound ATP consuming pumps. These proteins mediate the efflux of many structurally and functionally unrelated anticancer drugs of natural source. MDR may be intrinsic or acquired following exposure to chemotherapy. The existence of intrinsically resistant tumor cell clone before and following chemotherapeutic treatment has been associated with a worse final outcome because of increased incidence of distant metasis. In view of irreplaceability of natural product anticancer drugs as effective chemotherapeutic agents, and in view of MDR as a major obstacle to successful chemotherapy, this review is aimed to highlight the genes involved in MDR, classical MDR blockers and gene therapy approaches to overcome MDR. (author)

The use of guideline recommended beta-blocker therapy in primary prevention implantable cardioverter defibrillator patients

DEFF Research Database (Denmark)

Ruwald, Anne Christine; Gislason, Gunnar Hilmar; Vinther, Michael

2017-01-01

Aims: We aimed to examine the use of guideline recommended beta-blocker therapy prior to and after primary prevention implantable cardioverter defibrillator (ICD) implantation in a 'real-life' setting. Methods and results: From the Danish Pacemaker and ICD Registry we identified all 1st-time prim......Aims: We aimed to examine the use of guideline recommended beta-blocker therapy prior to and after primary prevention implantable cardioverter defibrillator (ICD) implantation in a 'real-life' setting. Methods and results: From the Danish Pacemaker and ICD Registry we identified all 1st......-time primary prevention ICD and cardiac resynchronization therapy defibrillator (CRT-D) implantations in Denmark from 2007-12 (n = 2935). Use of beta-blocker, type and dose was acquired through the Danish Prescription Registry. According to guideline recommendations, we defined target daily doses as ≥50 mg...... carvedilol and ≥200 mg metoprolol. Prior to implantation 2427 of 2935 (83%) patients received beta-blocker therapy, with 2166 patients (89%) having initiated treatment 3 months or more prior to implantation. The majority of patients was prescribed carvedilol (52%) or metoprolol (41%). Patients on carvedilol...

Long-term effects of beta-blocker use on lung function in Japanese patients with chronic obstructive pulmonary disease

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Oda N

2017-04-01

Full Text Available Naohiro Oda,1 Nobuaki Miyahara,1,2 Hirohisa Ichikawa,3 Yasushi Tanimoto,4 Kazuhiro Kajimoto,5 Makoto Sakugawa,6 Haruyuki Kawai,7 Akihiko Taniguchi,1 Daisuke Morichika,1 Mitsune Tanimoto,1 Arihiko Kanehiro,1 Katsuyuki Kiura1 1Department of Allergy and Respiratory Medicine, Okayama University Hospital, 2Department of Medical Technology, Okayama University Graduate School of Health Sciences, Okayama, 3Department of Respiratory Medicine, KKR Takamatsu Hospital, Takamatsu, 4Department of Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center, Okayama, 5Department of Respiratory Medicine, Kobe Red Cross Hospital, Kobe, 6Department of Respiratory Medicine, Okayama Red Cross Hospital, 7Department of Respiratory Medicine, Okayama Saiseikai Hospital, Okayama, Japan Background: Some recent studies have suggested that beta-blocker use in patients with chronic obstructive pulmonary disease (COPD is associated with a reduction in the frequency of acute exacerbations. However, the long-term effects of beta-blocker use on lung function of COPD patients have hardly been evaluated. Patients and methods: We retrospectively reviewed 31 Japanese COPD patients taking beta-blockers for >1 year and 72 patients not taking them. The association between beta-blocker use and the annual change in forced expiratory volume in 1 second (FEV1 was assessed. Results: At baseline, patient demographic characteristics were as follows: 97 males (mean age 67.0±8.2 years; 32 current smokers; and Global Initiative for Chronic Obstructive Lung disease (GOLD stages I: n=26, II: n=52, III: n=19, and IV: n=6. Patients taking beta-blockers exhibited a significantly lower forced vital capacity (FVC, FEV1, and %FVC, and a more advanced GOLD stage. The mean duration of beta-blocker administration was 2.8±1.7 years. There were no differences in the annual change in FEV1 between patients who did and did not use beta-blockers (-7.6±93.5 mL/year vs -4.7±118.9 m

Carvedilol Compared With Metoprolol Succinate in the Treatment and Prognosis of Patients With Stable Chronic Heart Failure: Carvedilol or Metoprolol Evaluation Study.

Science.gov (United States)

Fröhlich, Hanna; Zhao, Jingting; Täger, Tobias; Cebola, Rita; Schellberg, Dieter; Katus, Hugo A; Grundtvig, Morten; Hole, Torstein; Atar, Dan; Agewall, Stefan; Frankenstein, Lutz

2015-09-01

β-Blockers exert a prognostic benefit in the treatment of chronic heart failure. Their pharmacological properties vary. The only substantial comparative trial to date-the Carvedilol or Metoprolol European Trial-has compared carvedilol with short-acting metoprolol tartrate at different dose equivalents. We therefore addressed the relative efficacy of equal doses of carvedilol and metoprolol succinate on survival in multicenter hospital outpatients with chronic heart failure. Four thousand sixteen patients with stable systolic chronic heart failure who were using either carvedilol or metoprolol succinate were identified in the Norwegian Heart Failure Registry and The Heart Failure Registry of the University of Heidelberg, Germany. Patients were individually matched on both the dose equivalents and the respective propensity scores for β-blocker treatment. During a follow-up for 17 672 patient-years, it was found that 304 (27.2%) patients died in the carvedilol group and 1066 (36.8%) in the metoprolol group. In a univariable analysis of the general sample, metoprolol therapy was associated with higher mortality compared with carvedilol therapy (hazard ratio, 1.49; 95% confidence interval, 1.31-1.69; P<0.001). This difference was not seen after multivariable adjustment (hazard ratio, 0.93; 95% confidence interval, 0.57-1.50; P=0.75) and adjustment for propensity score and dose equivalents (hazard ratio, 1.06; 95% confidence interval, 0.94-1.20; P=0.36) or in the propensity and dose equivalent-matched sample (hazard ratio, 1.00; 95% confidence interval, 0.82-1.23; P=0.99). These results were essentially unchanged for all prespecified subgroups. In outpatients with chronic heart failure, no conclusive association between all-cause mortality and treatment with carvedilol or metoprolol succinate was observed after either multivariable adjustment or multilevel propensity score matching. © 2015 American Heart Association, Inc.

Can non-selective beta-blockers prevent hepatocellular carcinoma in patients with cirrhosis?

Science.gov (United States)

Thiele, Maja; Wiest, Reiner; Gluud, Lise Lotte; Albillos, Agustín; Krag, Aleksander

2013-11-01

Hepatocellular carcinoma is the main liver-related cause of death in patients with compensated cirrhosis. The early phases are asymptomatic and the prognosis is poor, which makes prevention essential. We propose that non-selective beta-blockers decrease the incidence and growth of hepatocellular carcinoma via a reduction of the inflammatory load from the gut to the liver and inhibition of angiogenesis. Due to their effect on the portal pressure, non-selective beta-blockers are used for prevention of esophageal variceal bleeding. Recently, non-hemodynamic effects of beta-blockers have received increasing attention. Blockage of β-adrenoceptors in the intestinal mucosa and gut lymphatic tissue together with changes in type and virulence of the intestinal microbiota lead to reduced bacterial translocation and a subsequent decrease in the portal load of pathogen-associated molecular patterns. This may reduce hepatic inflammation. Blockage of β-adrenoceptors also decrease angiogenesis by inhibition of vascular endothelial growth factors. Because gut-derived inflammation and neo-angiogenesis are important in hepatic carcinogenesis, non-selective beta-blockers can potentially reduce the development and growth of hepatocellular carcinoma. Rodent and in vitro studies support the hypothesis, but clinical verification is needed. Different study designs may be considered. The feasibility of a randomized controlled trial is limited due to the necessary large number of patients and long follow-up. Observational studies carry a high risk of bias. The meta-analytic approach may be used if the incidence and mortality of hepatocellular carcinoma can be extracted from trials on variceal bleeding and if the combined sample size and follow up is sufficient. Copyright © 2013 Elsevier Ltd. All rights reserved.

Empiric penicillin monotherapy of CAP is not associated with increased mortality; experiences from the retrospective CAP-North cohort

DEFF Research Database (Denmark)

Baunbæk-Knudsen, Getrud; Vestergaard Jensen, Andreas; Andersen, Stine

2016-01-01

Background: Community-acquired pneumonia (CAP) is a severe infection, with high morbidity and mortality. The antibiotic strategies for CAP differ across Europe. Objective: To assess the usage of Penicillin monotherapy in a real-life cohort and to evaluate predictors of treatment duration and the ......Background: Community-acquired pneumonia (CAP) is a severe infection, with high morbidity and mortality. The antibiotic strategies for CAP differ across Europe. Objective: To assess the usage of Penicillin monotherapy in a real-life cohort and to evaluate predictors of treatment duration......, and evaluated predictors of treatment duration by linear regression. Mortality of patients receiving empiric penicillin-G/V was compared to others by logistic regression analysis. The CAPNETZ database technology was used for data-capture. Results: We included 1320 patients. The incidence of hospitalized CAP...... was 3.1 per 1000 inhabitants. The median age was 71 years (IQR; 58.81). In-hospital mortality was 8%. Patients treated with penicillin-G/V as empiric monotherapy (45%) did not have a higher mortality than those treated with broader spectrum antibiotics (OR 1.30, CI 95% 0.84-2-02). The median duration...

Inhibition of N-type Ca2+ channels ameliorates an imbalance in cardiac autonomic nerve activity and prevents lethal arrhythmias in mice with heart failure.

Science.gov (United States)

Yamada, Yuko; Kinoshita, Hideyuki; Kuwahara, Koichiro; Nakagawa, Yasuaki; Kuwabara, Yoshihiro; Minami, Takeya; Yamada, Chinatsu; Shibata, Junko; Nakao, Kazuhiro; Cho, Kosai; Arai, Yuji; Yasuno, Shinji; Nishikimi, Toshio; Ueshima, Kenji; Kamakura, Shiro; Nishida, Motohiro; Kiyonaka, Shigeki; Mori, Yasuo; Kimura, Takeshi; Kangawa, Kenji; Nakao, Kazuwa

2014-10-01

Dysregulation of autonomic nervous system activity can trigger ventricular arrhythmias and sudden death in patients with heart failure. N-type Ca(2+) channels (NCCs) play an important role in sympathetic nervous system activation by regulating the calcium entry that triggers release of neurotransmitters from peripheral sympathetic nerve terminals. We have investigated the ability of NCC blockade to prevent lethal arrhythmias associated with heart failure. We compared the effects of cilnidipine, a dual N- and L-type Ca(2+) channel blocker, with those of nitrendipine, a selective L-type Ca(2+) channel blocker, in transgenic mice expressing a cardiac-specific, dominant-negative form of neuron-restrictive silencer factor (dnNRSF-Tg). In this mouse model of dilated cardiomyopathy leading to sudden arrhythmic death, cardiac structure and function did not significantly differ among the control, cilnidipine, and nitrendipine groups. However, cilnidipine dramatically reduced arrhythmias in dnNRSF-Tg mice, significantly improving their survival rate and correcting the imbalance between cardiac sympathetic and parasympathetic nervous system activity. A β-blocker, bisoprolol, showed similar effects in these mice. Genetic titration of NCCs, achieved by crossing dnNRSF-Tg mice with mice lacking CACNA1B, which encodes the α1 subunit of NCCs, improved the survival rate. With restoration of cardiac autonomic balance, dnNRSF-Tg;CACNA1B(+/-) mice showed fewer malignant arrhythmias than dnNRSF-Tg;CACNA1B(+/+) mice. Both pharmacological blockade of NCCs and their genetic titration improved cardiac autonomic balance and prevented lethal arrhythmias in a mouse model of dilated cardiomyopathy and sudden arrhythmic death. Our findings suggest that NCC blockade is a potentially useful approach to preventing sudden death in patients with heart failure. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Evaluation of the Efficacy of Combined Therapy of Methotrexate and Etanercept versus Methotrexate as a Mono-Therapy.

Science.gov (United States)

Rexhepi, Sylejman; Rexhepi, Mjellma; Rexhepi, Blerta; Sahatçiu-Meka, Vjollca; Mahmutaj, Vigan

2018-05-20

This study aims to evaluate the efficacy of Methotrexate (MTX) alone and combined therapy with Etanercept (ETN) and Methotrexate in patients with active rheumatoid arthritis (RA). In the randomised control study, conducted in the period from March 2014 until March 2016, we evaluated the efficacy of the treatment of patients with RA with MTX as monotherapy and combination treatment with MTX and ETN. In the Clinic of Rheumatology in Prishtina, 90 adult patients with RA were treated in combination with ETN (doses of 50 mg subcutaneously/weekly), with oral MTX (doses up to 20 mg weekly), and MTX alone (doses up to 20 mg weekly) during this period of two years. Clinical response was assessed using European League against Rheumatism (EULAR)/American College of Rheumatology (ACR) Criteria and the Disease Activity Score (DAS28). Radiographic changes were measured in the beginning and at the end of the study using Larsen's method. Of the cohort groups of 90 patients, mean age of 55.63, 15 patients, (16.6 %) were treated with combined therapy (ETN plus MTX) and 75 patients (83.3%) with monotherapy (MTX). After two years of treatment the group with combined therapy resulted with improvement of acute phase reactants as erythrocyte sedimentation rate (ESR) for the first hour (41.1 vs. 10.3 mm/hour) and C - reactive protein (CRP) (40.8 vs. 6 mg/liter), and compared to the group treated with monotherapy, there were no significant changes (ESR: 45.7 vs 34.3 mm/hour; CRP: 48 vs 24 mg/liter). Before the treatment, the severity of the disease was high, wherein the group with combined therapy DAS28 was 5.32, compared to the monotherapy group whom DAS28 was 5.90. After 2 years of treatment, we had significant changes in the results of DAS28, wherein the group treated with ETN plus MTX DAS28 was 2.12 ± 0.15, while in the group of patients treated with MTX DAS28 were 3.75 ± 0.39 (t = 13.03; df = 58; p < 0.0001). The group with combined therapy showed no evidence of radiographic

Safety and maintenance of response for tofacitinib monotherapy and combination therapy in rheumatoid arthritis: an analysis of pooled data from open-label long-term extension studies

NARCIS (Netherlands)

Fleischmann, Roy; Wollenhaupt, Jürgen; Takiya, Liza; Maniccia, Anna; Kwok, Kenneth; Wang, Lisy; van Vollenhoven, Ronald F.

2017-01-01

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. This post hoc analysis evaluated patients receiving tofacitinib monotherapy or combination therapy, as well as those who switched from monotherapy to combination therapy (mono→combo) or vice versa (combo→mono)

High-Dose-Rate Brachytherapy as a Monotherapy for Favorable-Risk Prostate Cancer: A Phase II Trial

International Nuclear Information System (INIS)

Barkati, Maroie; Williams, Scott G.; Foroudi, Farshad; Tai, Keen Hun; Chander, Sarat; Dyk, Sylvia van; See, Andrew; Duchesne, Gillian M.

2012-01-01

Purpose: There are multiple treatment options for favorable-risk prostate cancer. High-dose-rate (HDR) brachytherapy as a monotherapy is appealing, but its use is still investigational. A Phase II trial was undertaken to explore the value of such treatment in low-to-intermediate risk prostate cancer. Methods and Materials: This was a single-institution, prospective study. Eligible patients had low-risk prostate cancer features but also Gleason scores of 7 (51% of patients) and stage T2b to T2c cancer. Treatment with HDR brachytherapy with a single implant was administered over 2 days. One of four fractionation schedules was used in a dose escalation study design: 3 fractions of 10, 10.5, 11, or 11.5 Gy. Patients were assessed with the Common Terminology Criteria for Adverse Events version 2.0 for urinary toxicity, the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring schema for rectal toxicity, and the Expanded Prostate Cancer Index Composite (EPIC) questionnaire to measure patient-reported health-related quality of life. Biochemical failure was defined as a prostate-specific antigen (PSA) nadir plus 2 ng/ml. Results: Between 2003 and 2008, 79 patients were enrolled. With a median follow-up of 39.5 months, biochemical relapse occurred in 7 patients. Three- and 5-year actuarial biochemical control rates were 88.4% (95% confidence interval [CI], 78.0-96.2%) and 85.1% (95% CI, 72.5-94.5%), respectively. Acute grade 3 urinary toxicity was seen in only 1 patient. There was no instance of acute grade 3 rectal toxicity. Rates of late grade 3 rectal toxicity, dysuria, hematuria, urinary retention, and urinary incontinence were 0%, 10.3%, 1.3%, 9.0%, and 0%, respectively. No grade 4 or greater toxicity was recorded. Among the four (urinary, bowel, sexual, and hormonal) domains assessed with the EPIC questionnaire, only the sexual domain did not recover with time. Conclusions: HDR brachytherapy as a monotherapy for favorable

High-Dose-Rate Brachytherapy as a Monotherapy for Favorable-Risk Prostate Cancer: A Phase II Trial

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Barkati, Maroie [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Williams, Scott G., E-mail: scott.williams@petermac.org [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Department of Pathology, University of Melbourne, Melbourne (Australia); Foroudi, Farshad; Tai, Keen Hun; Chander, Sarat [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Department of Pathology, University of Melbourne, Melbourne (Australia); Dyk, Sylvia van [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); See, Andrew [Ballarat Austin Radiation Oncology Centre, Ballarat (Australia); Duchesne, Gillian M. [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Department of Pathology, University of Melbourne, Melbourne (Australia)

2012-04-01

Purpose: There are multiple treatment options for favorable-risk prostate cancer. High-dose-rate (HDR) brachytherapy as a monotherapy is appealing, but its use is still investigational. A Phase II trial was undertaken to explore the value of such treatment in low-to-intermediate risk prostate cancer. Methods and Materials: This was a single-institution, prospective study. Eligible patients had low-risk prostate cancer features but also Gleason scores of 7 (51% of patients) and stage T2b to T2c cancer. Treatment with HDR brachytherapy with a single implant was administered over 2 days. One of four fractionation schedules was used in a dose escalation study design: 3 fractions of 10, 10.5, 11, or 11.5 Gy. Patients were assessed with the Common Terminology Criteria for Adverse Events version 2.0 for urinary toxicity, the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring schema for rectal toxicity, and the Expanded Prostate Cancer Index Composite (EPIC) questionnaire to measure patient-reported health-related quality of life. Biochemical failure was defined as a prostate-specific antigen (PSA) nadir plus 2 ng/ml. Results: Between 2003 and 2008, 79 patients were enrolled. With a median follow-up of 39.5 months, biochemical relapse occurred in 7 patients. Three- and 5-year actuarial biochemical control rates were 88.4% (95% confidence interval [CI], 78.0-96.2%) and 85.1% (95% CI, 72.5-94.5%), respectively. Acute grade 3 urinary toxicity was seen in only 1 patient. There was no instance of acute grade 3 rectal toxicity. Rates of late grade 3 rectal toxicity, dysuria, hematuria, urinary retention, and urinary incontinence were 0%, 10.3%, 1.3%, 9.0%, and 0%, respectively. No grade 4 or greater toxicity was recorded. Among the four (urinary, bowel, sexual, and hormonal) domains assessed with the EPIC questionnaire, only the sexual domain did not recover with time. Conclusions: HDR brachytherapy as a monotherapy for favorable

Non-selective beta-blockers may reduce risk of hepatocellular carcinoma

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Thiele, Maja; Albillos, Agustín; Abazi, Rozeta

2015-01-01

BACKGROUND & AIMS: Non-selective beta-blockers (NSBB) are used in patients with cirrhosis and oesophageal varices. Experimental data suggest that NSBB inhibit angiogenesis and reduce bacterial translocation, which may prevent hepatocellular carcinoma (HCC). We therefore assessed the effect of NSBB...

Prescribing patterns of antihypertensive drugs in geriatric population in tertiary care hospital

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Renoy Philip

2016-03-01

Full Text Available Hypertension is one of the major chronic diseases with high mortality and morbidity in the today’s world. Present study was to assess the prescribing pattern of antihypertensive medications in geriatric population suffering mainly from hypertension with or without co morbidities like Diabetes Mellitus (DM. A prospective observational study was carried out for a period of six months in an in-patient general medicine department. Elderly patients who have been diagnosed with pure hypertension as per JNC 7 guidelines and hypertension with co- morbid condition like diabetes mellitus and patients receiving or prescribed with antihypertensive drugs were included. A total of 150 prescriptions were analyzed. The present study revealed that there were 93 patients with pure Hypertension and 57 patients with co morbid conditions like Diabetes Mellitus (DM. Among antihypertensive drugs in pure hypertensive cases, 53.76% of cases were prescribed with monotherapy, followed by 46.23% by combination therapy. The commonly prescribed antihypertensive monotherapy is calcium channel blockers. The most commonly prescribed combination therapy in severe cases was angiotensin receptor blockers with diuretics. This prescribing pattern of antihypertensives was as per Joint National Committee-7report on hypertension. In case of geriatric patients suffering from hypertension with Type 2 diabetes mellitus, most commonly prescribed antihypertensive as monotherapy was found to be amlodipine and combination therapy was telmisartan + hydrochlorothiazide.

Management of high blood pressure in Blacks: an update of the International Society on Hypertension in Blacks consensus statement.

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Flack, John M; Sica, Domenic A; Bakris, George; Brown, Angela L; Ferdinand, Keith C; Grimm, Richard H; Hall, W Dallas; Jones, Wendell E; Kountz, David S; Lea, Janice P; Nasser, Samar; Nesbitt, Shawna D; Saunders, Elijah; Scisney-Matlock, Margaret; Jamerson, Kenneth A

2010-11-01

Since the first International Society on Hypertension in Blacks consensus statement on the "Management of High Blood Pressure in African American" in 2003, data from additional clinical trials have become available. We reviewed hypertension and cardiovascular disease prevention and treatment guidelines, pharmacological hypertension clinical end point trials, and blood pressure-lowering trials in blacks. Selected trials without significant black representation were considered. In this update, blacks with hypertension are divided into 2 risk strata, primary prevention, where elevated blood pressure without target organ damage, preclinical cardiovascular disease, or overt cardiovascular disease for whom blood pressure consistently secondary prevention, where elevated blood pressure with target organ damage, preclinical cardiovascular disease, and/or a history of cardiovascular disease, for whom blood pressure consistently blood pressure is ≤10 mm Hg above target levels, monotherapy with a diuretic or calcium channel blocker is preferred. When blood pressure is >15/10 mm Hg above target, 2-drug therapy is recommended, with either a calcium channel blocker plus a renin-angiotensin system blocker or, alternatively, in edematous and/or volume-overload states, with a thiazide diuretic plus a renin-angiotensin system blocker. Effective multidrug therapeutic combinations through 4 drugs are described. Comprehensive lifestyle modifications should be initiated in blacks when blood pressure is ≥115/75 mm Hg. The updated International Society on Hypertension in Blacks consensus statement on hypertension management in blacks lowers the minimum target blood pressure level for the lowest-risk blacks, emphasizes effective multidrug regimens, and de-emphasizes monotherapy.

Sacubitril/Valsartan: A Review in Chronic Heart Failure with Reduced Ejection Fraction.

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McCormack, Paul L

2016-03-01

Sacubitril/valsartan (Entresto™; LCZ696) is an orally administered supramolecular sodium salt complex of the neprilysin inhibitor prodrug sacubitril and the angiotensin receptor blocker (ARB) valsartan, which was recently approved in the US and the EU for the treatment of chronic heart failure (NYHA class II-IV) with reduced ejection fraction (HFrEF). In the large, randomized, double-blind, PARADIGM-HF trial, sacubitril/valsartan reduced the incidence of death from cardiovascular causes or first hospitalization for worsening heart failure (composite primary endpoint) significantly more than the angiotensin converting enzyme (ACE) inhibitor enalapril. Sacubitril/valsartan was also superior to enalapril in reducing death from any cause and in limiting the progression of heart failure. Sacubitril/valsartan was generally well tolerated, with no increase in life-threatening adverse events. Symptomatic hypotension was significantly more common with sacubitril/valsartan than with enalapril; the incidence of angio-oedema was low. Therefore, sacubitril/valsartan is a more effective replacement for an ACE inhibitor or an ARB in the treatment of HFrEF, and is likely to influence the basic approach to treatment.

Does Combination Therapy with Tamsulosin and Tolterodine Improve Ureteral Stent Discomfort Compared with Tamsulosin Alone? A Double-Blind, Randomized, Controlled Trial.

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Sivalingam, Sri; Streeper, Necole M; Sehgal, Priyanka D; Sninsky, Brian C; Best, Sara L; Nakada, Stephen Y

2016-02-01

Ureteral stent discomfort is a significant postoperative problem for many patients. Despite the use of narcotics and α-blockers patients often experience bothersome lower urinary tract symptoms and pain, which impair daily activities. We compared combination therapy with an α-blocker and an anticholinergic to monotherapy with an α-blocker. A double-blind, randomized, controlled trial was performed from December 2012 to April 2014. A total of 80 patients were randomized, including 44 to the combination group (tamsulosin 0.4 mg and tolterodine early release 4 mg) and 36 to the monotherapy group (tamsulosin 0.4 mg and placebo). Patients with preexisting ureteral stent placement or current anticholinergic therapy were excluded from study. Patients completed USSQ (Urinary Stent Symptom Questionnaire) before stent placement on the day of surgery, the day after stent placement, the morning of stent removal and the day after stent removal. The questionnaire included questions regarding urinary symptoms, general health, body pain, and work and sexual history. A total of 80 patients (40 males and 40 females) were studied. Mean age was 51.5 vs 51.3 years (p = 0.95) and mean body mass index was 33.6 vs 31.9 kg/m(2) (p = 0.44) in monotherapy group 1 vs combination therapy group 2. Between the 2 groups there was no significant difference in urinary symptoms, body pain and activities of daily living from baseline to just before stent removal (p = 0.95, 0.40 and 0.95, respectively). Although there was no difference between the groups, both showed improvement in urinary symptoms from the time of initial stent insertion to just prior to stent removal (difference -0.50 for combination therapy and -0.40 for monotherapy). The mean stent indwelling time of 9.6 and 8.7 days in the combination and monotherapy groups, respectively, did not differ (p = 0.67). On ANOVA it had no significant impact on results (p = 0.64). Combination therapy with tamsulosin and tolterodine does not

Analysis of Prescriptions of Alpha-Blockers and Phosphodiesterase 5 Inhibitors from the Urology Department and Other Departments

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Dong Hyuk Kang

2011-12-01

Full Text Available PurposeWe analyzed the prescriptions of alpha-blockers and phosphodiesterase 5 inhibitors (PDE5Is in the urology department as well as in other departments of the general hospital.MethodsWe investigated the frequency of prescription of alpha-blockers and PDE5Is from 3 general hospitals from January 1, 2007 to December 31, 2009. For alpha-blockers, data were collected from patients to whom alpha-blockers were prescribed from among patients recorded as having benign prostatic hyperplasia according to the 5th Korean Standard Classification of Diseases. For PDE5Is, data were collected from patients to whom PDE5Is were prescribed by the urology department and by other departments. Alpha-blockers were classified into tamsulosin, alfuzosin, doxazosin, and terazosin, whereas PDE5Is were classified into sildenafil, tadalafil, vardenafil, udenafil, and mirodenafil.ResultsAlpha-blockers were prescribed to 11,436 patients in total over 3 years, and the total frequency of prescriptions was 68,565. Among other departments, the nephrology department had the highest frequency of prescription of 3,225 (4.7%, followed by the cardiology (3,101, 4.5%, neurology (2,576, 3.8%, endocrinology (2,400, 3.5%, pulmonology (1,102, 1.6%, and family medicine (915, 1.3% departments in order. PDE5Is were prescribed to 2,854 patients in total over 3 years, and the total frequency of prescriptions was 10,558. The prescription frequency from the urology department was 4,900 (46.4%. Among other departments, the endocrinology department showed the highest prescription frequency of 3,488 (33.0%, followed by the neurology (542, 5.1%, cardiology (467, 4.4%, and family medicine (407, 3.9% departments in order.ConclusionsA high percentage of prescriptions of alpha-blockers and PDE5Is were from other departments. For more specialized medical care by urologists is required in the treatment of lower urinary tract symptoms and erectile dysfunction.

A comparative study of the prevalence of hyperkalemia with the use of angiotensin-converting enzyme inhibitors versus angiotensin receptor blockers

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Seyed Ali Sadjadi

2009-07-01

Full Text Available Seyed Ali Sadjadi1, James I McMillan1, Navin Jaipaul1, Patricia Blakely1, Su Su Hline21Section of Nephrology (111N, Jerry L Pettis Memorial Veterans Medical Center, Loma Linda, CA, USA; 2Divison of Nephrology, Loma Linda University Medical Center, Loma Linda, CA, USABackground and objectives: Angiotensin-converting enzyme inhibitors (ACEI and angiotensin receptor blockers (ARB are increasingly used in a variety of settings including heart failure, renal failure, arterial hypertension, and diabetic nephropathy. The objective of this study was to investigate the prevalence of hyperkalemia with ACEI and ARB use, in a population of the United States veterans.Design, settings, material, and measurements: Retrospective observational cohort study of 1163 patients on ACEIs and 1168 patients on ARBs in a single Veterans Affairs Medical Center. Electronic medical records were reviewed over a 12-month period with data collected on various demographic, laboratory, comorbidity, and medication related variables. Results: Hyperkalemia (>5 mEq/L was observed in 20.4% of patients on ACEIs and 31.0% on ARBs. Severe hyperkalemia (6 mEq/L or higher, was observed in 0.8% of ACEI and 2.8% of ARB users. In univariate logistic regression analyses, diabetes mellitus; serum glucose, total carbon dioxide content, creatinine, and estimated glomerular filtration rate (GFR were significantly associated with hyperkalemia. ARB use, when compared to ACEI, was associated with a 42% increase in odds of hyperkalemia (odds ratio [OR] = 1.42; p = 0.001 in a model including adjustment for GFR and a 56% increase in odds of hyperkalemia (OR = 1.56; p < 0.001 in a model including adjustment for serum creatinine.Conclusions: Hyperkalemia, associated with the use of ACEIs and ARBs, is usually mild and severe hyperkalemia is rare. Hyperkalemia is more common with ARBs than ACEIs. ARB use, when compared to ACEI use, may significantly and independently be associated with increased odds of

Quantifying the effects of diuretics and β-adrenoceptor blockers on glycaemic control in diabetes mellitus - a systematic review and meta-analysis.

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Hirst, Jennifer A; Farmer, Andrew J; Feakins, Benjamin G; Aronson, Jeffrey K; Stevens, Richard J

2015-05-01

Although there are reports that β-adrenoceptor antagonists (beta-blockers) and diuretics can affect glycaemic control in people with diabetes mellitus, there is no clear information on how blood glucose concentrations may change and by how much. We report results from a systematic review to quantify the effects of these antihypertensive drugs on glycaemic control in adults with established diabetes. We systematically reviewed the literature to identify randomized controlled trials in which glycaemic control was studied in adults with diabetes taking either beta-blockers or diuretics. We combined data on HbA1c and fasting blood glucose using fixed effects meta-analysis. From 3864 papers retrieved, we found 10 studies of beta-blockers and 12 studies of diuretics to include in the meta-analysis. One study included both comparisons, totalling 21 included reports. Beta-blockers increased fasting blood glucose concentrations by 0.64 mmol l(-1) (95% CI 0.24, 1.03) and diuretics by 0.77 mmol l(-1) (95% CI 0.14, 1.39) compared with placebo. Effect sizes were largest in trials of non-selective beta-blockers (1.33, 95% CI 0.72, 1.95) and thiazide diuretics (1.69, 95% CI 0.60, 2.69). Beta-blockers increased HbA1c concentrations by 0.75% (95% CI 0.30, 1.20) and diuretics by 0.24% (95% CI -0.17, 0.65) compared with placebo. There was no significant difference in the number of hypoglycaemic events between beta-blockers and placebo in three trials. Randomized trials suggest that thiazide diuretics and non-selective beta-blockers increase fasting blood glucose and HbA1c concentrations in patients with diabetes by moderate amounts. These data will inform prescribing and monitoring of beta-blockers and diuretics in patients with diabetes. © 2014 The British Pharmacological Society.

Olanzapine monotherapy and olanzapine combination therapy in the treatment of mania: 12-week results from the European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM) observational study.

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Vieta, Eduard; Panicali, Francesco; Goetz, Iris; Reed, Catherine; Comes, Merce; Tohen, Mauricio

2008-02-01

To evaluate the 12-week outcomes (effectiveness, tolerability, and patterns of medication use) of olanzapine (either in antimanic monotherapy or in combination with other antipsychotics, anticonvulsants, and/or lithium) in patients with bipolar mania or mixed mania. EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication) is a 24-month prospective observational study of in- and outpatients with acute mania/mixed mania conducted in 14 European countries. Primary outcome measures included Clinical Global Impressions-Bipolar Disorder scale (overall, mania, and depression); 5-item Hamilton Depression Rating Scale; and Young Mania Rating Scale. Tolerability measures included a questionnaire to assess patients' symptomatic complaints. Overall, 2004 patients received olanzapine (olanzapine monotherapy, n=673; olanzapine combination, n=1331). Concomitant therapy with antidepressants and/or anxiolytics was possible in both groups. The countries significantly differed in the use of olanzapine monotherapy versus olanzapine combination (pEMBLEM results suggest that in naturalistic settings, olanzapine (both as monotherapy and combination) may be effective in treating patients with bipolar mania. The use of olanzapine monotherapy or combination varies significantly across countries, but combination is generally the rule, rather than the exception.

The challenge of analyzing beta-blocker drugs in sludge and wastewater.

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Scheurer, Marco; Ramil, Maria; Metcalfe, Chris D; Groh, Stefanie; Ternes, Thomas A

2010-01-01

In this study, different approaches were used to assess and overcome the severe effects of interference from the sample matrix from different types of sludges and wastewater on the analysis of nine beta-blockers and the beta sympathomimetic clenbuterol. The partitioning of the target compounds into sludge was investigated in wastewater treatment plants (WWTPs) in both Canada and Germany to evaluate whether this is an important mechanism for removal from sewage. Due to ion suppression in the electro spray interface, absolute recoveries were for certain compounds even lower than 20%. By using surrogate standards, acceptable relative recoveries of >75% were achieved for WWTP influents and effluents and for sludges. These matrix effects underline the need to use appropriate surrogate standards to aid in analyte quantitation. Using the developed methods, beta-blockers were detected at concentrations up to 2 microg/L in WWTP effluents, with metoprolol, sotalol, and atenolol present as the dominant compounds. Removal rates within WWTPs were highly inconsistent and ranged from 1-69%. Propranolol showed the greatest degree of partitioning into sludge with solid/water partition coefficients of one order of magnitude higher than those for all other compounds. However, even for propranolol, sorption did not contribute significantly to the overall elimination in WWTPs. It is likely that the removal of beta-blockers during waste water treatment can be attributed primarily to microbial biodegradation.

T Cell Subset and Stimulation Strength-Dependent Modulation of T Cell Activation by Kv1.3 Blockers.

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Wai-Ping Fung-Leung

Full Text Available Kv1.3 is a voltage-gated potassium channel expressed on T cells that plays an important role in T cell activation. Previous studies have shown that blocking Kv1.3 channels in human T cells during activation results in reduced calcium entry, cytokine production, and proliferation. The aim of the present study was to further explore the effects of Kv1.3 blockers on the response of different human T cell subsets under various stimulation conditions. Our studies show that, unlike the immune suppressor cyclosporine A, the inhibitory effect of Kv1.3 blockers was partial and stimulation strength dependent, with reduced inhibitory efficacy on T cells under strengthened anti-CD3/CD28 stimulations. T cell responses to allergens including house dust mites and ragweed were partially reduced by Kv1.3 blockers. The effect of Kv1.3 inhibition was dependent on T cell subsets, with stronger effects on CCR7- effector memory compared to CCR7+ central memory CD4 T cells. Calcium entry studies also revealed a population of CD4 T cells resistant to Kv1.3 blockade. Activation of CD4 T cells was accompanied with an increase in Kv1.3 currents but Kv1.3 transcripts were found to be reduced, suggesting a posttranscriptional mechanism in the regulation of Kv1.3 activities. In summary, Kv1.3 blockers inhibit T cell activation in a manner that is highly dependent on the T cell identity and stimulation strength, These findings suggest that Kv1.3 blockers inhibit T cells in a unique, conditional manner, further refining our understanding of the therapeutic potential of Kv1.3 blockers.

Profile of sacubitril/valsartan in the treatment of heart failure: patient selection and perspectives.

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Yandrapalli, Srikanth; Andries, Gabriela; Biswas, Medha; Khera, Sahil

2017-01-01

With an estimated prevalence of 5.8 million in the USA and over 23 million people worldwide, heart failure (HF) is growing in epidemic proportions. Despite the use of guideline-directed medical therapies such as angiotensin-converting enzyme inhibitors, beta-adrenergic blockers, angiotensin receptor blockers, and mineralocorticoid receptor antagonists for chronic systolic HF for almost two decades, HF remains a leading cause of morbidity, mortality, and health care expenditures. The Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial provided compelling evidence for the cardiovascular and mortality benefit of sacubitril/valsartan when compared to enalapril in patients with heart failure and reduced ejection fraction (HFrEF). Sacubitril/valsartan performed better than enalapril across various HFrEF patient characteristics and showed substantial benefit in patients with other common comorbidities. Following the trial, the US Food and Drug Administration approved this drug for the treatment of HF. Various international HF consensus guidelines endorse sacubitril/valsartan as a class I recommendation for the management of symptomatic HFrEF. Although this high-quality clinical study is the largest and the most globally represented trial in HFrEF patients, concerns have been raised regarding the generalizability of the trial results in real-world HF population. The gaps in US Food and Drug Administration labeling and guideline recommendations might lead to this medication being used in a larger population than it was studied in. In this review, we will discuss the current role of sacubitril/valsartan in the management of HF, concerns related to PARADIGM-HF and answers, shortcomings of this novel drug, effects on patient characteristics, real-world eligibility, and the role of ongoing and further investigations to clarify

Combination monoamine oxidase inhibitor and beta-blocker treatment of migraine, with anxiety and depression.

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Merikangas, K R; Merikangas, J R

1995-11-01

This paper presents the results of a study comparing the effectiveness of a beta-adrenergic blocking agent, atenolol, a monoamine oxidase inhibitor (MAO-I), phenelzine, and the combination in treatment of 61 adults with migraine headache. The goals of the study are (1) to investigate the safety of concomitant treatment of migraine with beta-blockers and phenelzine, (2) to assess whether orthostatic hypertension and other side effects would be relieved, and (3) to compare the results of this open trial of phenelzine to those of a previous study using similar methods. Phenelzine was associated with a large decrease in the frequency and severity of migraine attacks. Anxiety and depression were also reduced by phenelzine both alone, and in combination with a beta-blocker. The results show that the combination of MAO-I's and beta-blockers can be administered safely, and can lead to the reduction in the side effects with either drug alone.

Incidence and predictors of 6 months mortality after an acute heart failure event in rural Uganda: The Mbarara Heart Failure Registry (MAHFER).

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Abeya, Fardous Charles; Lumori, Boniface Amanee Elias; Akello, Suzan Joan; Annex, Brian H; Buda, Andrew J; Okello, Samson

2018-03-29

We sought to estimate the incidence and predictors of all-cause mortality 6 months after heart failure hospitalization in Uganda. Mbarara Heart Failure Registry is a cohort of patients hospitalized with a clinical diagnosis of heart failure at Mbarara Regional Referral Hospital, Uganda. We measured serum electrolytes, cardiac markers, and echocardiograms. All participants were followed until death or end of 6 months. We used Fine and Gray models to estimate the incidence and predictors all-cause mortality. A total of 215 participants were enrolled, 141 (66%) were women, and mean age 53 (standard deviation 22) years. Nineteen (9%) had diabetes, 40 (19%) had HIV, and 119 (55%) had hypertension. The overall incidence of all-cause mortality was 3.58 (95% CI 2.92, 4.38) per 1000 person-days. Men had higher incidence of death compared to women (4.02 vs 3.37 per 1000 person-days). The incidence of all-cause mortality during hospitalization was almost twice that of in the community (27.5 vs 14.77 per 1000 person-days). In adjusted analysis, increasing age, NYHA class IV, decreasing renal function, smoking, each unit increase in serum levels of Potassium, BNP, and Creatine kinase-MB predicted increased incidence of 6 months all-cause death whereas taking beta-blockers and having an index admission on a weekend compared to a week day predicted survival. There is a high incidence of all-cause mortality occurring in-hospital among patients hospitalized with heart failure in rural Uganda. Heart failure directed therapies should be instituted to curb heart failure-related mortality. Copyright © 2017 Elsevier B.V. All rights reserved.

Use of statins and beta-blockers after acute myocardial infarction according to income and education

DEFF Research Database (Denmark)

Rasmussen, Jeppe Nørgaard; Gislason, Gunnar H; Rasmussen, Søren

2007-01-01

OBJECTIVE: To study the initiation of and long-term refill persistency with statins and beta-blockers after acute myocardial infarction (AMI) according to income and education. DESIGN AND SETTING: Linkage of individuals through national registers of hospitalisations, drug dispensation, income...... and education. PARTICIPANTS: 30 078 patients aged 30-74 years surviving first hospitalisation for AMI in Denmark between 1995 and 2001. MAIN OUTCOME MEASURES: Initiation of statin or beta-blocker treatment (out-patient claim of prescriptions within 6 months of discharge) and refill persistency (first break.......66-0.82) and medium (HR 0.82; 95% CI 0.74-0.92) income compared with low income, whereas there was a trend in the opposite direction concerning a break in beta-blocker treatment. There was no gradient in re-initiation of treatment. CONCLUSION: Patients with low compared with high income less frequently initiated...

How are patients with heart failure treated in primary care?
.

Science.gov (United States)

Vaillant-Roussel, Hélène; Pereira, Bruno; Gibot-Boeuf, Sylvaine; Eschalier, Romain; Dubray, Claude; Boussageon, Rémy; Vorilhon, Philippe

2018-05-24

The aim of this study was to assess the adherence of general practitioners (GPs) to guidelines in patients with heart failure with reduced ejection fraction (HFrEF) and to describe GPs' prescribing behavior regarding patients with heart failure with preserved ejection fraction (HFpEF). Cross-sectional study as part of the ETIC trial. Five classes of drugs were described: angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs); β-blockers (BBs); mineralocorticoid receptor antagonists (MRAs); diuretics (thiazide or loop diuretics); and digoxin. 178 patients were studied: their mean age was 73.5 years (± 10.6). Of the 128 patients with HFpEF, 81.3% received ACEIs or ARBs, 63.3% received BBs, 13.3% received MRAs, 75.8% received diuretics, and 12.5% received digoxin. Of the 50 patients with HFrEF, 84% received ACEIs or ARBs, 74% received BBs, 20% received MRAs, 76% received diuretics, and 2% received digoxin. 25% of the patients were given a drug in accordance with the recommendations for drug class but not a drug authorized for the HFrEF indication. Among the patients with HFrEF who were treated in accordance with the recommendations, target doses were achieved in 1/3 given ACEIs/ARBs, 1/4 given BBs, and 1/2 given MRAs. Only 6% of the patients had a perfect Global Adherence Indicator-3 (GAI-3) with all target doses achieved. Several drugs were prescribed even though they were not recommended, and few patients were treated optimally. It seems to be necessary to develop a pragmatic tool to help GPs and cardiologists in optimizing treatment.
.

Why do hypertensive patients of African ancestry respond better to calcium blockers and diuretics than to ACE inhibitors and β-adrenergic blockers? A systematic review

NARCIS (Netherlands)

Brewster, Lizzy M.; Seedat, Yackoob K.

2013-01-01

Clinicians are encouraged to take an individualized approach when treating hypertension in patients of African ancestry, but little is known about why the individual patient may respond well to calcium blockers and diuretics, but generally has an attenuated response to drugs inhibiting the

Extracorporeal shock wave lithotripsy (ESWL) monotherapy in children: Predictors of successful outcome.

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Alsagheer, G; Abdel-Kader, M S; Hasan, A M; Mahmoud, O; Mohamed, O; Fathi, A; Abass, M; Abolyosr, A

2017-10-01

Although extracorporeal shock wave lithotripsy (ESWL) is the first choice for pediatric renal calculi ESWL. A prospective study including 100 children with renal stone burden ESWL at the present institution. The success rate after the first session was analyzed, and the predictors of success were investigated. The success of ESWL monotherapy was defined by absence of any residual fragments after 3 months, on non-contrast spiral computerized tomography (NCCT) scan, without need of any additional intervention. Between January 2013 and October 2015, 100 children were treated with a Dornier Gemini lithotripter at the present institution. The mean patients age and stone size were 6 years (range: 1.8-14) and 13.1 mm (range: 6-20), respectively. After one session, 47% of patients showed complete clearance 3 months postoperative, those patients versus those who required an additional session or auxiliary procedures were younger in age, with smaller stone size and lower density. On multivariate analysis, only patient age was an independent predictor of success (odds ratio (OR) 0.9; P ESWL monotherapy: not only did children respond better than adults, but age was also an independent predictor within the pediatric group. Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

The neprilysin pathway in heart failure: a review and guide on the use of sacubitril/valsartan.

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Jhund, Pardeep S; McMurray, John J V

2016-09-01

Inhibition of neurohumoural pathways such as the renin angiotensin aldosterone and sympathetic nervous systems is central to the understanding and treatment of heart failure (HF). Conversely, until recently, potentially beneficial augmentation of neurohumoural systems such as the natriuretic peptides has had limited therapeutic success. Administration of synthetic natriuretic peptides has not improved outcomes in acute HF but modulation of the natriuretic system through inhibition of the enzyme that degrades natriuretic (and other vasoactive) peptides, neprilysin, has proven to be successful. After initial failures with neprilysin inhibition alone or dual neprilysin-angiotensin converting enzyme (ACE) inhibition, the Prospective comparison of angiotensin receptor neprilysin inhibitor (ARNI) with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF) trial demonstrated that morbidity and mortality can be improved with the angiotensin receptor blocker neprilysin inhibitor sacubitril/valsartan (formerly LCZ696). In comparison to the ACE inhibitor enalapril, sacubitril/valsartan reduced the occurrence of the primary end point (cardiovascular death or hospitalisation for HF) by 20% with a 16% reduction in all-cause mortality. These findings suggest that sacubitril/valsartan should replace an ACE inhibitor or angiotensin receptor blocker as the foundation of treatment of symptomatic patients (NYHA II-IV) with HF and a reduced ejection fraction. This review will explore the background to neprilysin inhibition in HF, the results of the PARADIGM-HF trial and offer guidance on how to use sacubitril/valsartan in clinical practice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Switching Therapy from Intravenous Landiolol to Transdermal Bisoprolol in a Patient with Thyroid Storm Complicated by Decompensated Heart Failure and Gastrointestinal Dysfunction.

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Godo, Shigeo; Kawazoe, Yu; Ozaki, Hiroshi; Fujita, Motoo; Kudo, Daisuke; Nomura, Ryosuke; Shimokawa, Hiroaki; Kushimoto, Shigeki

2017-10-01

Thyroid storm is a life-threatening disorder that remains a therapeutic challenge. Although β-blockers are the mainstay for treatment, their use can be challenging in cases complicated by rapid atrial fibrillation and decompensated heart failure. We present a case of thyroid storm-associated atrial fibrillation and decompensated heart failure complicated by gastrointestinal dysfunction secondary to diffuse peritonitis that was successfully managed by a switching therapy, in which the continuous intravenous administration of landiolol was changed to bisoprolol via transdermal patch, in the acute phase treatment. This switching therapy may offer a promising therapeutic option for this potentially lethal disorder.

The anti-proliferative effect of cation channel blockers in T lymphocytes depends on the strength of mitogenic stimulation.

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Petho, Zoltan; Balajthy, Andras; Bartok, Adam; Bene, Krisztian; Somodi, Sandor; Szilagyi, Orsolya; Rajnavolgyi, Eva; Panyi, Gyorgy; Varga, Zoltan

2016-03-01

Ion channels are crucially important for the activation and proliferation of T lymphocytes, and thus, for the function of the immune system. Previous studies on the effects of channel blockers on T cell proliferation reported variable effectiveness due to differing experimental systems. Therefore our aim was to investigate how the strength of the mitogenic stimulation influences the efficiency of cation channel blockers in inhibiting activation, cytokine secretion and proliferation of T cells under standardized conditions. Human peripheral blood lymphocytes were activated via monoclonal antibodies targeting the TCR-CD3 complex and the co-stimulator CD28. We applied the blockers of Kv1.3 (Anuroctoxin), KCa3.1 (TRAM-34) and CRAC (2-Apb) channels of T cells either alone or in combination with rapamycin, the inhibitor of the mammalian target of rapamycin (mTOR). Five days after the stimulation ELISA and flow cytometric measurements were performed to determine IL-10 and IFN-γ secretion, cellular viability and proliferation. Our results showed that ion channel blockers and rapamycin inhibit IL-10 and IFN-γ secretion and cell division in a dose-dependent manner. Simultaneous application of the blockers for each channel along with rapamycin was the most effective, indicating synergy among the various activation pathways. Upon increasing the extent of mitogenic stimulation the anti-proliferative effect of the ion channel blockers diminished. This phenomenon may be important in understanding the fine-tuning of T cell activation. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Brain renin angiotensin system in cardiac hypertrophy and failure

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Luciana eCampos

2012-01-01

Full Text Available Brain renin-angiotensin system (RAS is significantly involved in the roles of the endocrine RAS in cardiovascular regulation. Our studies indicate that the brain RAS participates in the development of cardiac hypertrophy and fibrosis through sympathetic activation. Inhibition of sympathetic hyperactivity after myocardial infarction through suppression of the brain RAS appears beneficial. The brain RAS is involved in the modulation of circadian rhythms of arterial pressure, contributing to nondipping hypertension. We conclude that the brain RAS in pathophysiological states interacts synergistically with the chronically overactive RAS through a positive biofeedback in order to maintain a state of alert diseased conditions, such as cardiac hypertrophy and failure. Therefore, targeting brain RAS with drugs such as angiotensin converting inhibitors or receptor blockers having increased brain penetrability could be of advantage. These RAS-targeting drugs are first-line therapy for all heart failure patients. Since the RAS has both endocrine and local tissue components, RAS drugs are being developed to attain increased tissue penetrability and volume of distribution and consequently an efficient inhibition of both RAS components.

QT interval prolongation related to psychoactive drug treatment: a comparison of monotherapy versus polytherapy

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Piccinelli Marco

2005-01-01

Full Text Available Abstract Background Several antipsychotic agents are known to prolong the QT interval in a dose dependent manner. Corrected QT interval (QTc exceeding a threshold value of 450 ms may be associated with an increased risk of life threatening arrhythmias. Antipsychotic agents are often given in combination with other psychotropic drugs, such as antidepressants, that may also contribute to QT prolongation. This observational study compares the effects observed on QT interval between antipsychotic monotherapy and psychoactive polytherapy, which included an additional antidepressant or lithium treatment. Method We examined two groups of hospitalized women with Schizophrenia, Bipolar Disorder and Schizoaffective Disorder in a naturalistic setting. Group 1 was composed of nineteen hospitalized women treated with antipsychotic monotherapy (either haloperidol, olanzapine, risperidone or clozapine and Group 2 was composed of nineteen hospitalized women treated with an antipsychotic (either haloperidol, olanzapine, risperidone or quetiapine with an additional antidepressant (citalopram, escitalopram, sertraline, paroxetine, fluvoxamine, mirtazapine, venlafaxine or clomipramine or lithium. An Electrocardiogram (ECG was carried out before the beginning of the treatment for both groups and at a second time after four days of therapy at full dosage, when blood was also drawn for determination of serum levels of the antipsychotic. Statistical analysis included repeated measures ANOVA, Fisher Exact Test and Indipendent T Test. Results Mean QTc intervals significantly increased in Group 2 (24 ± 21 ms however this was not the case in Group 1 (-1 ± 30 ms (Repeated measures ANOVA p Conclusions No significant prolongation of the QT interval was found following monotherapy with an antipsychotic agent, while combination of these drugs with antidepressants caused a significant QT prolongation. Careful monitoring of the QT interval is suggested in patients taking a

Comparison the Efficacy of Four Different Alpha Blockers in the Treatment of Benign Prostatic Hyperplasia

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Fatih Fırat

2011-05-01

Full Text Available Aim: Benign prostatic hyperplasia (BPH also known as nodular hyperplasia, benign enlargement of the prostate refers to the increase in size of the prostate in middle aged and elderly men. Although four different types of specific alpha blocker have been used in the treatment of BPH it remains controversial that which alpha adrenergic blocker is effective than others. The aim of this study is to compare the efficacy of 4 different alpha blockers agents on the treatment of BPH. Material and Methods: Between June 2005 and December 2008 a total of 135 consecutive patients with diagnosed of BPH were evaluated in our clinic. Patients were randomized into four groups according to alpha blocker types as fallows: group I, doxazosin 4 mg; group II, tamsulosin 0.4 mg; group III, terazosin 5 mg; and group IV, alfuzosin 10 mg. All patients were followed up with International Prostatic Symptom Score (IPSS, maximal urinary flow rates (Qmax and adverse effects were determined at baseline and again at least 3 months as efficacy parameters. Results: The mean age of the patients were 59.8±5.4 years, 58.9±6.4 years, 58.7±5.1 years, and 59.2±5.5 years in group I, group II, group III, and group IV, respectively (p>0.05. After 3 months treatment with alpha blockers the improvements in IPSS were found as 2.73, 3.73, 3.55 and 4.44 in group I, group II, group III, and group IV, respectively. Maximum urine flow rates increased as 2.81 ml/sec, 3.24 ml/sec, 3.88 ml/sec and 4.49 ml/sec in group I, group II, group III, and group IV, respectively. However, among 4 alpha blockers statistically significant difference was found only between doxazosin and alfuzosin groups according to uroflowmetry and IPSS results. According to these results, when compared adverse effect, the significant difference was observed only in tamsulosine group. Conclusions: As a result we can say that except retrograde ejaculation in tamsulosine group, adverse effects are not different between the

Insulin monotherapy compared with the addition of oral glucose-lowering agents to insulin for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control

NARCIS (Netherlands)

Vos, Rimke C; van Avendonk, Mariëlle JP; Jansen, Hanneke; Goudswaard, Alexander N; van den Donk, Maureen; Gorter, Kees; Kerssen, Anneloes; Rutten, Guy EHM

2016-01-01

BACKGROUND: It is unclear whether people with type 2 diabetes mellitus on insulin monotherapy who do not achieve adequate glycaemic control should continue insulin as monotherapy or can benefit from adding oral glucose-lowering agents to the insulin therapy. OBJECTIVES: To assess the effects of

Improving medication titration in heart failure by embedding a structured medication titration plan.

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Hickey, Annabel; Suna, Jessica; Marquart, Louise; Denaro, Charles; Javorsky, George; Munns, Andrew; Mudge, Alison; Atherton, John J

2016-12-01

To improve up-titration of medications to target dose in heart failure patients by improving communication from hospital to primary care. This quality improvement project was undertaken within three heart failure disease management (HFDM) services in Queensland, Australia. A structured medication plan was collaboratively designed and implemented in an iterative manner, using methods including awareness raising and education, audit and feedback, integration into existing work practice, and incentive payments. Evaluation was undertaken using sequential audits, and included process measures (use of the titration plan, assignment of responsibility) and outcome measures (proportion of patients achieving target dose) in HFDM service patients with reduced left ventricular ejection fraction. Comparison of the three patient cohorts (pre-intervention cohort A n=96, intervention cohort B n=95, intervention cohort C n=89) showed increase use of the titration plan, a shift to greater primary care responsibility for titration, and an increase in the proportion of patients achieving target doses of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) (A 37% vs B 48% vs C 55%, p=0.051) and beta-blockers (A 38% vs B 33% vs C 51%, p=0.045). Combining all three cohorts, patients not on target doses when discharged from hospital were more likely to achieve target doses of ACEI/ARB (pplan. A medication titration plan was successfully implemented in three HFDM services and improved transitional communication and achievement of target doses of evidence-based therapies within six months of hospital discharge. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Quantifying the effects of diuretics and β-adrenoceptor blockers on glycaemic control in diabetes mellitus – a systematic review and meta-analysis

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Hirst, Jennifer A; Farmer, Andrew J; Feakins, Benjamin G; Aronson, Jeffrey K; Stevens, Richard J

2015-01-01

Aims Although there are reports that β-adrenoceptor antagonists (beta-blockers) and diuretics can affect glycaemic control in people with diabetes mellitus, there is no clear information on how blood glucose concentrations may change and by how much. We report results from a systematic review to quantify the effects of these antihypertensive drugs on glycaemic control in adults with established diabetes. Methods We systematically reviewed the literature to identify randomized controlled trials in which glycaemic control was studied in adults with diabetes taking either beta-blockers or diuretics. We combined data on HbA1c and fasting blood glucose using fixed effects meta-analysis. Results From 3864 papers retrieved, we found 10 studies of beta-blockers and 12 studies of diuretics to include in the meta-analysis. One study included both comparisons, totalling 21 included reports. Beta-blockers increased fasting blood glucose concentrations by 0.64 mmol l−1 (95% CI 0.24, 1.03) and diuretics by 0.77 mmol l−1 (95% CI 0.14, 1.39) compared with placebo. Effect sizes were largest in trials of non-selective beta-blockers (1.33, 95% CI 0.72, 1.95) and thiazide diuretics (1.69, 95% CI 0.60, 2.69). Beta-blockers increased HbA1c concentrations by 0.75% (95% CI 0.30, 1.20) and diuretics by 0.24% (95% CI −0.17, 0.65) compared with placebo. There was no significant difference in the number of hypoglycaemic events between beta-blockers and placebo in three trials. Conclusions Randomized trials suggest that thiazide diuretics and non-selective beta-blockers increase fasting blood glucose and HbA1c concentrations in patients with diabetes by moderate amounts. These data will inform prescribing and monitoring of beta-blockers and diuretics in patients with diabetes. PMID:25377481

Niacin extended-release/simvastatin combination therapy produces larger favorable changes in high-density lipoprotein particles than atorvastatin monotherapy

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Toth PP

2012-01-01

Full Text Available Peter P Toth1, Kamlesh M Thakker2, Ping Jiang2, Robert J Padley21University of Illinois College of Medicine, Peoria, and CGH Medical Center, Sterling, 2Abbott, Abbott Park, IL, USABackground: The purpose of this research was to compare the effects of niacin extended-release in combination with simvastatin (NER/S versus atorvastatin monotherapy on high-density lipoprotein (HDL particle number and size in patients with hyperlipidemia or dyslipidemia from the SUPREME study.Methods: This was a post hoc analysis of patients (n = 137 who completed the SUPREME study and who had lipid particle number and size measurements at both baseline and at week 12 by nuclear magnetic resonance spectroscopy. Following ≥4 weeks without lipid-modifying therapy (washout period, the patients received NER/S 1000/40 mg/day for 4 weeks followed by NER/S 2000/40 mg/day for 8 weeks, or atorvastatin 40 mg/day for 12 weeks. Median percent changes in HDL particle number and size from baseline to week 12 were compared between the NER/S and atorvastatin treatment groups using the Wilcoxon rank-sum test. Distribution of HDL particle subclasses at week 12 was compared between the treatment groups using the Cochran–Mantel–Haenszel test.Results: Treatment with NER/S resulted in a significantly greater percent reduction in small HDL particle number at week 12 compared with atorvastatin monotherapy (-1.8% versus 4.2%, P = 0.014, and a numerically greater percent increase in large HDL particle number (102.4% versus 39.2%, P = 0.078 compared with atorvastatin monotherapy. A significantly greater percent increase in HDL particle size from baseline at week 12 was observed with NER/S compared with atorvastatin (6.0% versus 1.3%, P < 0.001. NER/S treatment also resulted in a significant shift in HDL particle size from small and medium at baseline to large at week 12 (P < 0.0001.Conclusion: Treatment with NER/S resulted in larger favorable changes in number and size of HDL particle

Adjunctive medical therapy with α-blocker after extracorporeal shock wave lithotripsy of renal and ureteral stones: a meta-analysis.

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Mingchao Li

Full Text Available Although some trials assessed the efficacy and safety of the α-blocker in facilitating renal and ureteral stones expulsion after extracorporeal shock wave lithotripsy (ESWL, the role of the α-blocker in facilitating upper urinary calculi expulsion after ESWL remain controversial.To determine the efficacy and safety of the α-blocker in facilitating renal and ureteral stones expulsion after ESWL.A literature search was carried out using the PubMed database, EMBASE and the Cochrane Library database to identify relevant studies. Two reviewers independently extracted data and assessed methodological quality. Pooled effect estimates were obtained using a fixed- and random-effects meta-analysis.The meta-analysis included 23 RCTs, α-blocker significantly enhanced expulsion rate of upper urinary tract calculi after ESWL (P<0.00001; RR 1.21; 95% CI 1.12-1.31, significantly promoted steinstrasse expulsion (P=0.03; RR 1.25; 95% CI 1.03-1.53, significantly shortened the discharge time of upper urinary tract calculi (P=0.0001; MD -2.12; 95% CI -3.20--1.04, significantly reduced the patient's pain VAS score (P=0.001; RR -1.0; 95% CI -1.61--0.39. Compared with the control group, dizziness (P=0.002; RR 5.48; 95% CI 1.91-15.77, anejaculation (P=0.02; RR 12.17; 95% CI 1.61-91.99 and headache (P=0.04; RR 4.03; 95% CI 1.04-15.72 in the α-blocker group was associated with a higher incidence.Treatment with α-blocker after ESWL appears to be effective in enhancing expulsion rate of upper urinary tract calculi, shortening the discharge time of upper urinary tract calculi, reducing the patient's pain. The side effects of α-blocker were light and few.

A low-dose β1-blocker in combination with milrinone improves intracellular Ca2+ handling in failing cardiomyocytes by inhibition of milrinone-induced diastolic Ca2+ leakage from the sarcoplasmic reticulum.

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Shigeki Kobayashi

Full Text Available OBJECTIVES: The purpose of this study was to investigate whether adding a low-dose β1-blocker to milrinone improves cardiac function in failing cardiomyocytes and the underlying cardioprotective mechanism. BACKGROUND: The molecular mechanism underlying how the combination of low-dose β1-blocker and milrinone affects intracellular Ca(2+ handling in heart failure remains unclear. METHODS: We investigated the effect of milrinone plus landiolol on intracellular Ca(2+ transient (CaT, cell shortening (CS, the frequency of diastolic Ca(2+ sparks (CaSF, and sarcoplasmic reticulum Ca(2+ concentration ({Ca(2+}SR in normal and failing canine cardiomyocytes and used immunoblotting to determine the phosphorylation level of ryanodine receptor (RyR2 and phospholamban (PLB. RESULTS: In failing cardiomyocytes, CaSF significantly increased, and peak CaT and CS markedly decreased compared with normal myocytes. Administration of milrinone alone slightly increased peak CaT and CS, while CaSF greatly increased with a slight increase in {Ca(2+}SR. Co-administration of β1-blocker landiolol to failing cardiomyocytes at a dose that does not inhibit cardiomyocyte function significantly decreased CaSF with a further increase in {Ca(2+}SR, and peak CaT and CS improved compared with milrinone alone. Landiolol suppressed the hyperphosphorylation of RyR2 (Ser2808 in failing cardiomyocytes but had no effect on levels of phosphorylated PLB (Ser16 and Thr17. Low-dose landiolol significantly inhibited the alternans of CaT and CS under a fixed pacing rate (0.5 Hz in failing cardiomyocytes. CONCLUSION: A low-dose β1-blocker in combination with milrinone improved cardiac function in failing cardiomyocytes, apparently by inhibiting the phosphorylation of RyR2, not PLB, and subsequent diastolic Ca(2+ leak.

A low-dose β1-blocker in combination with milrinone improves intracellular Ca2+ handling in failing cardiomyocytes by inhibition of milrinone-induced diastolic Ca2+ leakage from the sarcoplasmic reticulum.

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Kobayashi, Shigeki; Susa, Takehisa; Ishiguchi, Hironori; Myoren, Takeki; Murakami, Wakako; Kato, Takayoshi; Fukuda, Masakazu; Hino, Akihiro; Suetomi, Takeshi; Ono, Makoto; Uchinoumi, Hitoshi; Tateishi, Hiroki; Mochizuki, Mamoru; Oda, Tetsuro; Okuda, Shinichi; Doi, Masahiro; Yamamoto, Takeshi; Yano, Masafumi

2015-01-01

The purpose of this study was to investigate whether adding a low-dose β1-blocker to milrinone improves cardiac function in failing cardiomyocytes and the underlying cardioprotective mechanism. The molecular mechanism underlying how the combination of low-dose β1-blocker and milrinone affects intracellular Ca(2+) handling in heart failure remains unclear. We investigated the effect of milrinone plus landiolol on intracellular Ca(2+) transient (CaT), cell shortening (CS), the frequency of diastolic Ca(2+) sparks (CaSF), and sarcoplasmic reticulum Ca(2+) concentration ({Ca(2+)}SR) in normal and failing canine cardiomyocytes and used immunoblotting to determine the phosphorylation level of ryanodine receptor (RyR2) and phospholamban (PLB). In failing cardiomyocytes, CaSF significantly increased, and peak CaT and CS markedly decreased compared with normal myocytes. Administration of milrinone alone slightly increased peak CaT and CS, while CaSF greatly increased with a slight increase in {Ca(2+)}SR. Co-administration of β1-blocker landiolol to failing cardiomyocytes at a dose that does not inhibit cardiomyocyte function significantly decreased CaSF with a further increase in {Ca(2+)}SR, and peak CaT and CS improved compared with milrinone alone. Landiolol suppressed the hyperphosphorylation of RyR2 (Ser2808) in failing cardiomyocytes but had no effect on levels of phosphorylated PLB (Ser16 and Thr17). Low-dose landiolol significantly inhibited the alternans of CaT and CS under a fixed pacing rate (0.5 Hz) in failing cardiomyocytes. A low-dose β1-blocker in combination with milrinone improved cardiac function in failing cardiomyocytes, apparently by inhibiting the phosphorylation of RyR2, not PLB, and subsequent diastolic Ca(2+) leak.

Use of angiotensin II receptor blockers in children- a review of ...

African Journals Online (AJOL)

2015-05-19

May 19, 2015 ... sex and height, whereas hypertension is defined as SBP and/or DBP persistently ... strated the efficacy of angiotensin receptor blockers in ... An open-label, multicenter, single-dose study was ..... sure among school children of.

Renal sympathetic denervation for treatment of patients with heart failure: summary of the available evidence.

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Nammas, Wail; Koistinen, Juhani; Paana, Tuomas; Karjalainen, Pasi P

2017-08-01

Heart failure syndrome results from compensatory mechanisms that operate to restore - back to normal - the systemic perfusion pressure. Sympathetic overactivity plays a pivotal role in heart failure; norepinephrine contributes to maintenance of the systemic blood pressure and increasing preload. Cardiac norepinephrine spillover increases in patients with heart failure; norepinephrine exerts direct toxicity on cardiac myocytes resulting in a decrease of synthetic activity and/or viability. Importantly, cardiac norepinephrine spillover is a powerful predictor of mortality in patients with moderate to severe HF. This provided the rationale for trials that demonstrated survival benefit associated with the use of beta adrenergic blockers in heart failure with reduced ejection fraction. Nevertheless, the MOXCON trial demonstrated that rapid uptitration of moxonidine (inhibitor of central sympathetic outflow) in patients with heart failure was associated with excess mortality and morbidity, despite reduction of plasma norepinephrine. Interestingly, renal norepinephrine spillover was the only independent predictor of adverse outcome in patients with heart failure, in multivariable analysis. Recently, renal sympathetic denervation has emerged as a novel approach for control of blood pressure in patients with treatment-resistant hypertension. This article summarizes the available evidence for the effect of renal sympathetic denervation in the setting of heart failure. Key messages Experimental studies supported a beneficial effect of renal sympathetic denervation in heart failure with reduced ejection fraction. Clinical studies demonstrated improvement of symptoms, and left ventricular function. In heart failure and preserved ejection fraction, renal sympathetic denervation is associated with improvement of surrogate endpoints.

A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis.

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Kowdley, Kris V; Luketic, Velimir; Chapman, Roger; Hirschfield, Gideon M; Poupon, Raoul; Schramm, Christoph; Vincent, Catherine; Rust, Christian; Parés, Albert; Mason, Andrew; Marschall, Hanns-Ulrich; Shapiro, David; Adorini, Luciano; Sciacca, Cathi; Beecher-Jones, Tessa; Böhm, Olaf; Pencek, Richard; Jones, David

2018-05-01

Obeticholic acid (OCA), a potent farnesoid X receptor agonist, was studied as monotherapy in an international, randomized, double-blind, placebo-controlled phase 2 study in patients with primary biliary cholangitis who were then followed for up to 6 years. The goals of the study were to assess the benefit of OCA in the absence of ursodeoxycholic acid, which is relevant for patients who are intolerant of ursodeoxycholic acid and at higher risk of disease progression. Patients were randomized and dosed with placebo (n = 23), OCA 10 mg (n = 20), or OCA 50 mg (n = 16) given as monotherapy once daily for 3 months (1 randomized patient withdrew prior to dosing). The primary endpoint was the percent change in alkaline phosphatase from baseline to the end of the double-blind phase of the study. Secondary and exploratory endpoints included change from baseline to month 3/early termination in markers of cholestasis, hepatocellular injury, and farnesoid X receptor activation. Efficacy and safety continue to be monitored through an ongoing 6-year open-label extension (N = 28). Alkaline phosphatase was reduced in both OCA groups (median% [Q1, Q3], OCA 10 mg -53.9% [-62.5, -29.3], OCA 50 mg -37.2% [-54.8, -24.6]) compared to placebo (-0.8% [-6.4, 8.7]; P OCA improved many secondary and exploratory endpoints (including γ-glutamyl transpeptidase, alanine aminotransferase, conjugated bilirubin, and immunoglobulin M). Pruritus was the most common adverse event; 15% (OCA 10 mg) and 38% (OCA 50 mg) discontinued due to pruritus. OCA monotherapy significantly improved alkaline phosphatase and other biochemical markers predictive of improved long-term clinical outcomes. Pruritus increased dose-dependently with OCA treatment. Biochemical improvements were observed through 6 years of open-label extension treatment. (Hepatology 2018;67:1890-1902). © 2017 The Authors. Hepatology published by Wiley Periodicals, Inc. on behalf of American Association for the Study of Liver Diseases.

Use of calcium channel blockers in hypertension.

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Conlin, P R; Williams, G H

1998-01-01

During the past 20 years the number of subclasses of calcium channel blockers has increased from one to four. Three classes have only a single clinically approved compound: verapamil, diltiazem, and mibefradil. The fourth class, dihydropyridines, contains numerous compounds. All agents are effective in lowering blood pressure in short-term studies, and side effects that trouble the patient are infrequent. Long-term studies in hypertensive patients are limited. Short-acting agents such as nifedipine have been associated with an increased cardiovascular risk in some, but not all studies. These agents also probably create a compliance problem for hypertensive patients because of the need for multiple daily doses and their unpleasant side effects, e.g., ankle edema, palpitations, and flushing. Therefore, they are not useful or indicated for the treatment of hypertensive patients. No data have suggested that long-acting dihydropyridines or nondihydropyridine calcium channel blockers share the same fate. Indeed, several lines of evidence suggest the opposite: they have a cardioprotective effect. However, definitive information will require the completion of several long-term trials, including ALLHAT, CONVINCE, HOT, INSIGHT and NORDIL. Finally, it is important to reflect on the lessons learned from the controversy associated with the potential risks of calcium channel blockers. First, disagreements are common when one uses case-controlled studies and are reflective of the poor precision of the methods used. What is statistically relevant in one study may not hold true for another and may have no clinical relevance, particularly if the relative risk is less than 2. Investigators need to temper their enthusiasm to reflect this reality. Second, at the cutting edge of science there is probably relatively little agreement about what is correct among equally competent scientists. All have bias in their positions and should both recognize and admit so to themselves and their

Efficacy evaluation of a pollen blocker cream against dust-mite allergy: A multicenter, randomized, double-blind, placebo-controlled crossover trial.

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Li, Yanqing; Cheng, Lei; Chen, Xiaoning; Yang, Beibei; Wang, Dehui

2015-01-01

To further evaluate the efficacy and safety of a pollen blocker cream against dust-mite allergy. A multicenter, randomized, double-blind, placebo-controlled, crossover trial was conducted in a Chinese population. Patients diagnosed with perennial allergic rhinitis, sensitive to dust-mite allergy including Dermatophagoides farinae and Dermatophagoides pteronyssinus were randomly allocated to receive a pollen blocker cream or placebo, which was applied and spread evenly to the lower internal nose region three times daily for a total of 30 days. The primary outcome measurements for efficacy were total nasal symptom score (TNSS) and individual nasal symptom score (iNSS). Adverse events were also monitored. After application of a pollen blocker, the mean TNSS decreased from 23.1 to 13.8, the decrease of the pollen blocker group (9.3) was highly significant compared with the placebo group (5.2; p 0.05), and no severe systematic reactions were observed. Pollen Blocker is a safe and effective alternative to the drugs for treatment of AR, especially for Chinese people allergic to dust-mite allergy.

[Cross-sectional analysis of heart failure among patients in the Internal Medicine Service at a third-level hospital. Part I: epidemiologic analysis].

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Cinza Sanjurjo, S; Cabarcos Ortiz de Barrón, A; Enrique Nieto Pol, E; Torre Carballada, J A

2007-06-01

To observe the epidemiologic characteristics of the patients intake during five years in a internal medicine department, with heart failure. A cross-sectional study of the intake patients in the Internal Medicine Service in the Hospital Clínico Universitario de Santiago de Compostela between 1999 to 2003. The variables analized were: sex, age, days of hospital stay, number of intake by failure cardiac, reason for admission (guide symptom), hypertension, diabetes mellitus, cardiac disease, fibrillation atrium, previous treatment with beta-blockers, blood pressure in the admission moment, to make echocardiography, disfunction systolic, etiology, deceased, treatment at the end. The statistical analysis was performed with qualitative and quantitative measures, chi-cuadrado and t-student, and multivariant analyses. 248 patients were accepted for the study. We observed more women than men (55.2%) and bigger median age (79 years old vs. 73 years old in men, p < 0.001). The mean income was 13.61 days and a median of 11 days. The 41,8% of the patients had hypertension, 30.9% diabetes mellitus and 81,9% had someone heart disease. The aetiologies of heart failure most frequent were ischemic cardiopathy (27.2%) and hypertension (24.2%). The most frequent symptom was the dyspnea (68.9%). It made echocardiography in 20.9% of patients and 45.1% showed systolic disfunction. The only factor related with this small percentage of echocardiographies was the incoming time. The most frequent etiology was respiratory infections (39.5%). The 8.6% of patients was deceased. The pharmacologic treatment more prescribed were the diuretics (86.9%) and transcutaneous nitrates (49.5%). It was indicated ECAI or AAR-II in the 86.9% of patients and beta-blockers in 0.9%. The number of echocardiograms practiced to the patients is smaller that the number advised by international associations and smaller to the cardiologist registers. The beta-blockers and ECAI use is smaller too.

Beta-1-Selective Beta-Blockers and Cognitive Functions in Patients With Coronary Artery Disease: A Cross-Sectional Study.

Science.gov (United States)

Burkauskas, Julius; Noreikaite, Aurelija; Bunevicius, Adomas; Brozaitiene, Julija; Neverauskas, Julius; Mickuviene, Narseta; Bunevicius, Robertas

2016-01-01

The association between current beta-1-selective beta-blocker use and cognitive function was evaluated in 722 patients with coronary artery disease without dementia. Beta-1-selective beta-blocker use was associated with worse incidental learning independently of sociodemographic characteristics, clinical coronary artery disease severity, and depression/anxiety.

CHRONIC HEART FAILURE AND IRON-DEFICIENT ANEMIA

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M. V. Melnik

2015-12-01

Full Text Available 62 chronic heart failure (CHF patients with iron-deficient anemia (IDA were studied. Standard CHF therapy (angiotensin converting enzyme inhibitors, β-blockers, diuretics, cardiac glycosides was accompanied with the correction of iron deficiency by intravenous injection of Venofer and subsequent Ferro-Folgamma prescription (average daily dose of iron 137,75±5mg. After treatment serum iron level increased by 95,5% and hemoglobin level – by 9,8%. Left ventricular ejection fraction increased by 32,2% and physical activity tolerance – by 47,6%. Before treatment 32 CHF patients with IDA (51,6% had III functional class (FC of CHF according to NYHA and 16 patients (25,8% – IV FC. After treatment I FC was observed in 18 CHF patients (29%, II FC – in 26 patients and only 18 patients demonstrated III FC of CHF.

CHRONIC HEART FAILURE AND IRON-DEFICIENT ANEMIA

Directory of Open Access Journals (Sweden)

M. V. Melnik

2007-01-01

Full Text Available 62 chronic heart failure (CHF patients with iron-deficient anemia (IDA were studied. Standard CHF therapy (angiotensin converting enzyme inhibitors, β-blockers, diuretics, cardiac glycosides was accompanied with the correction of iron deficiency by intravenous injection of Venofer and subsequent Ferro-Folgamma prescription (average daily dose of iron 137,75±5mg. After treatment serum iron level increased by 95,5% and hemoglobin level – by 9,8%. Left ventricular ejection fraction increased by 32,2% and physical activity tolerance – by 47,6%. Before treatment 32 CHF patients with IDA (51,6% had III functional class (FC of CHF according to NYHA and 16 patients (25,8% – IV FC. After treatment I FC was observed in 18 CHF patients (29%, II FC – in 26 patients and only 18 patients demonstrated III FC of CHF.

Spotlight on valsartan-sacubitril fixed-dose combination for heart failure: the evidence to date.

Science.gov (United States)

Vilela-Martin, José Fernando

2016-01-01

Heart failure is a global problem with elevated prevalence, and it is associated with substantial cardiovascular morbidity and mortality. Treating heart-failure patients has been a very challenging task. This review highlights the main pharmacological developments in the field of heart failure with reduced ejection fraction, giving emphasis to a drug that has a dual-acting inhibition of the neprilysin and renin-angiotensin-aldosterone system. Neprilysin is an enzyme that participates in the breakdown of biologically active natriuretic peptides and several other vasoactive compounds. The inhibition of neprilysin has been a therapeutic target for several drugs tested in cardiovascular disease, mainly for heart failure and/or hypertension. However, side effects and a lack of efficacy led to discontinuation of their development. LCZ696 is a first-in-class neprilysin- and angiotensin-receptor inhibitor that has been developed for use in heart failure. This drug is composed of two molecular moieties in a single crystalline complex: a neprilysin-inhibitor prodrug (sacubitril) and the angiotensin-receptor blocker (valsartan). The PARADIGM-HF trial demonstrated that this drug was superior to an angiotensin-converting enzyme inhibitor (enalapril) in reducing mortality in patients with heart failure with reduced ejection fraction. The ability to block the angiotensin receptor and augment the endogenous natriuretic peptide system provides a distinctive mechanism of action in cardiovascular disease.

Spotlight on valsartan–sacubitril fixed-dose combination for heart failure: the evidence to date

Science.gov (United States)

Vilela-Martin, José Fernando

2016-01-01

Heart failure is a global problem with elevated prevalence, and it is associated with substantial cardiovascular morbidity and mortality. Treating heart-failure patients has been a very challenging task. This review highlights the main pharmacological developments in the field of heart failure with reduced ejection fraction, giving emphasis to a drug that has a dual-acting inhibition of the neprilysin and renin–angiotensin–aldosterone system. Neprilysin is an enzyme that participates in the breakdown of biologically active natriuretic peptides and several other vasoactive compounds. The inhibition of neprilysin has been a therapeutic target for several drugs tested in cardiovascular disease, mainly for heart failure and/or hypertension. However, side effects and a lack of efficacy led to discontinuation of their development. LCZ696 is a first-in-class neprilysin- and angiotensin-receptor inhibitor that has been developed for use in heart failure. This drug is composed of two molecular moieties in a single crystalline complex: a neprilysin-inhibitor prodrug (sacubitril) and the angiotensin-receptor blocker (valsartan). The PARADIGM-HF trial demonstrated that this drug was superior to an angiotensin-converting enzyme inhibitor (enalapril) in reducing mortality in patients with heart failure with reduced ejection fraction. The ability to block the angiotensin receptor and augment the endogenous natriuretic peptide system provides a distinctive mechanism of action in cardiovascular disease. PMID:27274196

Aldosterone and aldosterone receptor antagonists in patients with chronic heart failure

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Nappi J

2011-06-01

associated with systolic heart failure will benefit from the addition of an aldosterone receptor antagonist to the standard therapies of angiotensin-converting enzyme inhibitors and beta-blockers. This review will address the pharmacologic basis of aldosterone receptor antagonists in patients with heart failure and the clinical impact of this therapy.Keywords: aldosterone receptor antagonists, eplerenone, spironolactone, systolic heart failure

Combination With Low-dose Dextromethorphan Improves the Effect of Amlodipine Monotherapy in Clinical Hypertension

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Yin, Wei-Hsian; Chen, Pei; Yeh, Hung-I; Wang, Kuo-Yang; Hung, Yi-Jen; Tseng, Wei-Kung; Wen, Ming-Shien; Wu, Tao-Cheng; Wu, Chau-Chung; Cheng, Shu-Meng; Chen, Jaw-Wen

2016-01-01

Abstract The combination of low rather than high dose of dextromethorphan (DXM) with amlodipine (AM) could improve blood pressure (BP) reduction in hypertensive animals. The study aimed to evaluate the feasibility of different doses of DXM combined with standard AM treatment in clinical hypertension. This was a prospective, 14-week, dose-escalation, multicenter study. After 2-week run-in period with AM 5 mg/day, hypertensive patients who got the BP goal of 140/90 mmHg kept receiving AM monotherapy for another 12 weeks. The nonresponders, while kept on AM 5 mg/day, received additional DXM treatment for 3 sequential dose-titrated periods with initially 2.5 mg/day, followed by 7.5 mg/day, and finally 30 mg/day. Each period was for 4 weeks. The patients at BP goal after each treatment period were defined as the responders and kept on the same combination till the end of the study. The responder rate of each treatment period was recorded. The changes of BP and serum antioxidant/endothelial markers between week 14 and week 2 were evaluated. Of the 103 patients initially enrolled, 89 entered the treatment period. In the 78 patients completing the study, 31 (40%) at BP goal after 2-week AM run-in kept on AM monotherapy (DXM0). The addition of 2.5 (DXM2.5) and 7.5 mg/day (DXM7.5) of DXM enabled BP goal achievement in 22 (47%) nonresponders to AM monotherapy including 16 (29%) with DXM2.5 and 6 (18%) with DXM7.5. Only 4 patients (16%) reached BP goal with the combination of DXM 30 mg/day (DXM30). Overall, 73% of the 78 patients reached BP goal at the end of the 14-week study. Mean systolic BP was reduced by 7.9% ± 7.0% with DXM2.5 (P < 0.001) and by 5.4% ± 2.4% with DXM7.5 (P = 0.003) respectively at week 14 from that at week 2, which was unchanged in either DXM0 or DXM30 group. Besides, the effects of combination treatment were particularly significant in the patients with impaired endothelial function suggested by reduced serum NOx level

Long-term results of interventional treatment of large unresectable hepatocellular carcinoma (HCC): significant survival benefit from combined transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) compared to TACE monotherapy; Langzeitergebnisse der interventionellen Therapie von grossen, inoperablen hepatozellulaeren Karzinomen (HCC): signifikanter Ueberlebensvorteil von transarterieller Chemoembolisation (TACE) und perkutaner Ethanolinjektion (PEI) gegenueber der TACE-Monotherapie

Energy Technology Data Exchange (ETDEWEB)

Lubienski, A.; Bitsch, R.G.; Grenacher, L.; Kauffmann, G.W. [Radiologische Universitaetsklinik Heidelberg, Abt. Radiodiagnostik, Heidelberg (Germany); Schemmer, P. [Chirurgische Universitaetsklinik Heidelberg (Germany); Duex, M. [Radiologisches Zentralinstitut Krankenhaus Nordwest Frankfurt (Germany)

2004-12-01

Purpose: A retrospective analysis of long-term efficacy of combined transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) and TACE monotherapy was conducted in patients with large, non-resectable hepatocellular carcinoma (HCC). Methods and Materials: Fifty patients with large, unresectable HCC lesions underwent selective TACE. Liver cirrhosis was present in 42 patients, due to alcohol abuse (n = 22) and viral infection (n = 17). In three patients, the underlying cause for liver cirrhosis remained unclear. Child A cirrhosis was found in 22 and Child B cirrhosis in 20 patients. Repeated and combined TACE and PEI were performed in 22 patients and repeated TACE monotherapy was performed in 28 patients. Survival and complication rates were determined and compared. Results: The 6-, 12-, 24- and 36-month survival rates were 61%, 21%, 4%, and 4% for TACE monotherapy and 77%, 55%, 39% and 22% for combined TACE and PEI (Kaplan-Meier method). The kind of treatment significantly affected the survival rate (p=0.002 log-rank test). Severe side effects were present in two patients of the monotherapy group and in three patients of the combination therapy group. (orig.)

Effectiveness of olanzapine monotherapy and olanzapine combination treatment in the long term following acute mania--results of a two year observational study in bipolar disorder (EMBLEM).

Science.gov (United States)

Gonzalez-Pinto, Ana; Vieta, Eduard; Reed, Catherine; Novick, Diego; Barraco, Alessandra; Aguado, Jaume; Haro, Josep Maria

2011-06-01

This study compared the 2-year outcomes of patients with a manic/mixed episode of bipolar disorder taking olanzapine monotherapy or olanzapine in combination with other agents. EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication) is a 2-year, prospective, observational study of clinical and functional outcomes of bipolar patients with an index manic/mixed episode. The study consisted of two phases: acute (12 weeks) and maintenance (follow-up over 2 years). The longitudinal outcome measure was the Clinical Global Impression-Bipolar Disorder scale. Cox regression models compared outcomes of both therapy groups using intention-to-treat and switching medication analysis. Treatment-emergent adverse events were also assessed. 1076 patients were included in this analysis. 29% took olanzapine as monotherapy (n = 313) and 71% as combination (n = 763) at 12-weeks post-baseline (end of study acute phase). After adjusting for patient characteristics using switching medication analysis, only relapse rates differed (p = 0.01) in favour of monotherapy-treated patients. There was no significant difference in rates of improvement, remission, and recovery. Patients treated with combination therapy reported more tremor (OR 2.37, 95%CI 1.44-3.89) and polyuria (OR 3.08, 95%CI 1.45-6.54) treatment-emergent events than monotherapy, although weight change was greater in the monotherapy group. Unknown confounding and potential selection bias may differentially impact treatment outcomes. EMBLEM patients benefitted from the selected therapy to a similar extent. Differences in patient characteristics between those prescribed monotherapy and combination therapy appear to be clinically relevant in the treatment decision. Physicians must balance the benefits and risks when determining appropriate treatment for individual patients. Copyright © 2010 Elsevier B.V. All rights reserved.

Adoption of Sacubitril/Valsartan for the Management of Patients With Heart Failure.

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Sangaralingham, Lindsey R; Sangaralingham, S Jeson; Shah, Nilay D; Yao, Xiaoxi; Dunlay, Shannon M

2018-02-01

The US Food and Drug Administration approved the use of sacubitril/valsartan in patients with heart failure with reduced ejection fraction in July 2015. We aimed to assess the adoption and prescription drug costs of sacubitril/valsartan in its first 18 months after Food and Drug Administration approval. Using a large US insurance database, we identified privately insured and Medicare Advantage beneficiaries who filled a first prescription for sacubitril/valsartan between July 1, 2015, and December 31, 2016. We compared them to patients treated with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Outcomes included adoption, prescription drug costs, and 180-day adherence, defined as a proportion of days covered ≥80%. A total of 2244 patients initiated sacubitril/valsartan. Although the number of users increased over time, the proportion of heart failure with reduced ejection fraction patients taking sacubitril/valsartan remained low (sacubitril/valsartan were younger, more often male, with less comorbidity than those taking an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. Although a majority of prescription costs were covered by the health plan (mean, $328.37; median, $362.44 per 30-day prescription), out-of-pocket costs were still high (mean, $71.16; median, $40.27). By comparison, median out-of-pocket costs were $2 to $3 for lisinopril, losartan, carvedilol, and spironolactone. Overall, 59.1% of patients were adherent to sacubitril/valsartan. Refill patterns suggested that nearly half of nonadherent patients discontinued sacubitril/valsartan within 180 days of starting. Adoption of sacubitril/valsartan after Food and Drug Administration approval has been slow and may be associated with the high cost. © 2018 American Heart Association, Inc.

Capacity for diagnosis and treatment of heart failure in sub-Saharan Africa.

Science.gov (United States)

Carlson, Selma; Duber, Herbert C; Achan, Jane; Ikilezi, Gloria; Mokdad, Ali H; Stergachis, Andy; Wollum, Alexandra; Bukhman, Gene; Roth, Gregory A

2017-12-01

Heart failure is a major cause of disease burden in sub-Saharan Africa (SSA). There is an urgent need for better strategies for heart failure management in this region. However, there is little information on the capacity to diagnose and treat heart failure in SSA. We aim to provide a better understanding of the capacity to diagnose and treat heart failure in Kenya and Uganda to inform policy planning and interventions. We analysed data from a nationally representative survey of health facilities in Kenya and Uganda (197 health facilities in Uganda and 143 in Kenya). We report on the availability of cardiac diagnostic technologies and select medications for heart failure (β-blockers, ACE inhibitors and furosemide). Facility-level data were analysed by country and platform type (hospital vs ambulatory facilities). Functional and staffed radiography, ultrasound and ECG were available in less than half of hospitals in Kenya and Uganda combined. Of the hospitals surveyed, 49% of Kenyan and 77% of Ugandan hospitals reported availability of the heart failure medication package. ACE inhibitors were only available in 51% of Kenyan and 79% of Ugandan hospitals. Almost one-third of the hospitals in each country had a stock-out of at least one of the medication classes in the prior quarter. Few facilities in Kenya and Uganda were prepared to diagnose and manage heart failure. Medication shortages and stock-outs were common. Our findings call for increased investment in cardiac care to reduce the growing burden of heart failure. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Zidovudine (AZT monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase.

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Jessica H Brehm

Full Text Available We previously demonstrated in vitro that zidovudine (AZT selects for A371V in the connection domain and Q509L in ribonuclease H (RNase H domain of HIV-1 reverse transcriptase (RT which, together with the thymidine analog mutations D67N, K70R and T215F, confer greater than 100-fold AZT resistance. The goal of the current study was to determine whether AZT monotherapy in HIV-1 infected patients also selects the A371V, Q509L or other mutations in the C-terminal domains of HIV-1 RT.Full-length RT sequences in plasma obtained pre- and post-therapy were compared in 23 participants who received AZT monotherapy from the AIDS Clinical Trials Group study 175. Five of the 23 participants reached a primary study endpoint. Mutations significantly associated with AZT monotherapy included K70R (p = 0.003 and T215Y (p = 0.013 in the polymerase domain of HIV-1 RT, and A360V (p = 0.041 in the connection domain of HIV-1 RT. HIV-1 drug susceptibility assays demonstrated that A360V, either alone or in combination with thymidine analog mutations, decreased AZT susceptibility in recombinant viruses containing participant-derived full-length RT sequences or site-directed mutant RT. Biochemical studies revealed that A360V enhances the AZT-monophosphate excision activity of purified RT by significantly decreasing the frequency of secondary RNase H cleavage events that reduce the RNA/DNA duplex length and promote template/primer dissociation.The A360V mutation in the connection domain of RT was selected in HIV-infected individuals that received AZT monotherapy and contributed to AZT resistance.

Early initiation of beta blockers following primary endoscopic therapy for bleeding esophageal varices in cirrhotics

International Nuclear Information System (INIS)

Salim, A.; Malik, K.; Farooq, M.O.; Butt, U.; Butt, A.K.

2017-01-01

Beta-blockers provide secondary prophylaxis following endoscopic therapy for variceal bleeding. Guidelines recommend starting beta-blockers 6 days after endoscopy to prevent masking hemodynamic signs of rebleeding. We aimed to see safety of earlier initiation of beta-blockers. Methods: Cirrhotic patients with upper GI bleed were given I.V vasoactive agents until undergoing endoscopy. Patients with only esophageal varices as source of bleed were recruited. Vasoactive agents were discontinued following variceal banding. The patients were observed for 12-18 hours, discharged on oral carvedilol 6.25 mg BID and monitored for 6 weeks for rebleeding and mortality. Results: 50 patients were included, 27 (54%) male and 23 (46%) female. Average age was 43+3 years. Etiology of cirrhosis was HCV in 42 (84%), HBV in 6 (12%), HCV and HBV in 2 (4%) and indeterminate in 1 (2%) patient. 17 (34%) patients had Child A, 22 (44%) Child B and 11 (22%) had Child C disease. Hospital stay was under 24 hours in 24 (48%), 24-48 hours in 15 (30%) and 48-72 hours in 11 (22%) patients. 5 (10%) patients underwent EGD within 6 hours of admission, 28 (56%) within 12 hours, 14 (28%) within 24 hours and 3 (6%) within 36 hours. No rebleeding, mortality or drug related adverse effects were noted during 6 weeks after discharge. Conclusions:Our study proves possibility of shorter management of variceal bleeding by having a 12-18 hour monitoring after endoscopic banding, followed by beta-blocker initiation and discharge. This will safely reduce physical and financial burden on health services. Background: Beta-blockers provide secondary prophylaxis following endoscopic therapy for variceal bleeding. Guidelines recommend starting beta-blockers 6 days after endoscopy to prevent masking hemodynamic signs of re-bleeding. We aimed to see safety of earlier initiation of beta-blockers. Methods: Cirrhotic patients with upper GI bleed were given intravenous vasoactive agents until undergoing endoscopy. Patients

Treatments for acute bipolar depression: meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics

NARCIS (Netherlands)

Selle, V.; Schalkwijk, S.J.; Vazquez, G.H.; Baldessarini, R.J.

2014-01-01

BACKGROUND: Optimal treatments for bipolar depression, and the relative value of specific drugs for that purpose, remain uncertain, including agents other than antidepressants. METHODS: We searched for reports of placebo-controlled, monotherapy trials of mood-stabilizing anticonvulsants,

Long-term compliance with beta-blockers, angiotensin-converting enzyme inhibitors, and statins after acute myocardial infarction

DEFF Research Database (Denmark)

Gislason, Gunnar H; Rasmussen, Jeppe Nørgaard; Abildstrøm, Steen Z

2006-01-01

AIMS: To study initiation, dosages, and compliance with beta-blockers, angiotensin-converting enzyme (ACE)-inhibitors, and statins in patients after acute myocardial infarction (AMI) and to identify likely targets for improvement. METHODS AND RESULTS: Patients admitted with first AMI between 1995...... and 2002 were identified by linking nationwide administrative registers. A total of 55 315 patients survived 30 days after discharge and were included; 58.3% received beta-blockers, 29.1% ACE-inhibitors, and 33.5% statins. After 1, 3, and 5 years, 78, 64, and 58% of survivors who had started therapy were...... still receiving beta-blockers, 86, 78, and 74% were receiving ACE-inhibitors, and 85, 80, and 82% were receiving statins, respectively. Increased age and female sex were associated with improved compliance. The dosages prescribed were generally 50% or less of the dosages used in clinical trials...

SU-F-J-211: Scatter Correction for Clinical Cone-Beam CT System Using An Optimized Stationary Beam Blocker with a Single Scan

International Nuclear Information System (INIS)

Liang, X; Zhang, Z; Xie, Y; Gong, S; Niu, T; Zhou, Q

2016-01-01

Purpose: X-ray scatter photons result in significant image quality degradation of cone-beam CT (CBCT). Measurement based algorithms using beam blocker directly acquire the scatter samples and achieve significant improvement on the quality of CBCT image. Within existing algorithms, single-scan and stationary beam blocker proposed previously is promising due to its simplicity and practicability. Although demonstrated effectively on tabletop system, the blocker fails to estimate the scatter distribution on clinical CBCT system mainly due to the gantry wobble. In addition, the uniform distributed blocker strips in our previous design results in primary data loss in the CBCT system and leads to the image artifacts due to data insufficiency. Methods: We investigate the motion behavior of the beam blocker in each projection and design an optimized non-uniform blocker strip distribution which accounts for the data insufficiency issue. An accurate scatter estimation is then achieved from the wobble modeling. Blocker wobble curve is estimated using threshold-based segmentation algorithms in each projection. In the blocker design optimization, the quality of final image is quantified using the number of the primary data loss voxels and the mesh adaptive direct search algorithm is applied to minimize the objective function. Scatter-corrected CT images are obtained using the optimized blocker. Results: The proposed method is evaluated using Catphan@504 phantom and a head patient. On the Catphan©504, our approach reduces the average CT number error from 115 Hounsfield unit (HU) to 11 HU in the selected regions of interest, and improves the image contrast by a factor of 1.45 in the high-contrast regions. On the head patient, the CT number error is reduced from 97 HU to 6 HU in the soft tissue region and image spatial non-uniformity is decreased from 27% to 5% after correction. Conclusion: The proposed optimized blocker design is practical and attractive for CBCT guided radiation

SU-F-J-211: Scatter Correction for Clinical Cone-Beam CT System Using An Optimized Stationary Beam Blocker with a Single Scan

Energy Technology Data Exchange (ETDEWEB)

Liang, X; Zhang, Z; Xie, Y [Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, GuangDong (China); Gong, S; Niu, T [Department of Radiation Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang (China); Institute of Translational Medicine, Zhejiang University, Hangzhou, Zhejiang (China); Zhou, Q [Department of Radiation Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang (China)

2016-06-15

Purpose: X-ray scatter photons result in significant image quality degradation of cone-beam CT (CBCT). Measurement based algorithms using beam blocker directly acquire the scatter samples and achieve significant improvement on the quality of CBCT image. Within existing algorithms, single-scan and stationary beam blocker proposed previously is promising due to its simplicity and practicability. Although demonstrated effectively on tabletop system, the blocker fails to estimate the scatter distribution on clinical CBCT system mainly due to the gantry wobble. In addition, the uniform distributed blocker strips in our previous design results in primary data loss in the CBCT system and leads to the image artifacts due to data insufficiency. Methods: We investigate the motion behavior of the beam blocker in each projection and design an optimized non-uniform blocker strip distribution which accounts for the data insufficiency issue. An accurate scatter estimation is then achieved from the wobble modeling. Blocker wobble curve is estimated using threshold-based segmentation algorithms in each projection. In the blocker design optimization, the quality of final image is quantified using the number of the primary data loss voxels and the mesh adaptive direct search algorithm is applied to minimize the objective function. Scatter-corrected CT images are obtained using the optimized blocker. Results: The proposed method is evaluated using Catphan@504 phantom and a head patient. On the Catphan©504, our approach reduces the average CT number error from 115 Hounsfield unit (HU) to 11 HU in the selected regions of interest, and improves the image contrast by a factor of 1.45 in the high-contrast regions. On the head patient, the CT number error is reduced from 97 HU to 6 HU in the soft tissue region and image spatial non-uniformity is decreased from 27% to 5% after correction. Conclusion: The proposed optimized blocker design is practical and attractive for CBCT guided radiation

Efficacy and tolerability of antihypertensive drugs in diabetic and nondiabetic patients

Directory of Open Access Journals (Sweden)

Maria Aslam

2017-01-01

Full Text Available Objectives of the Study: The aim of the study was to compare the efficacy and tolerability of different classes of antihypertensive drugs in diabetic and nondiabetic patients (NDPs with essential hypertension. Material and Methods: The study was conducted in Mayo Hospital, Punjab Institute of Cardiology, and National Defence Hospital, Lahore, Pakistan, on 200 hypertensive patients with diabetes and 230 hypertensive patients without (Three hospitals diabetes. Both male and female patients of age between 30 and 80 years with systolic blood pressure (SBP above 130 mmHg and diastolic blood pressure (DBP above 80 mmHg were enrolled in the study. Angiotensin converting enzyme inhibitors (ACEI, beta-blocker (βB, calcium-channel blocker (CCB, diuretics (D, angiotensin receptor blocker (ARB as well as α-blocker classes of antihypertensive drugs were used. These drugs were used as monotherapy as well as combination therapy. The study was conducted for 4 months (July–October. After 4 months, patients were assessed for efficacy by monitoring blood pressure (BP and tolerability by assessing safety profile on renal function, liver function as well as lipid profile. Results: Significant control in mean BP by all drug groups was observed in “both groups that is patients with diabetes and without diabetes.” The efficacy and tolerability data revealed that in diabetic patients with hypertension, the highest decrease in SBP and DBP was observed using monotherapy with ACEI, two-drug combination therapy with ACEI plus diuretic, ARBs plus diuretic, ACEI plus CCBs, three-drug combination therapy with ACEI plus CCBs plus diuretic, and four drug combination therapy with ACEI plus CCBs plus diuretic plus βBs, ARB's plus CCBs plus diuretic plus βBs while in NDPs, monotherapy with diuretic, two-drug combination therapy with ACEI plus CCBs, ACEI plus βBs, three-drug combination therapy with βBs plus ACEI plus D was found more effective in controlling SBP as well

Influence of baseline variables on changes in International Prostate Symptom Score after combined therapy with dutasteride plus tamsulosin or either monotherapy in patients with benign prostatic hyperplasia and lower urinary tract symptoms: 4-year results of the CombAT study.

Science.gov (United States)

Roehrborn, Claus G; Barkin, Jack; Tubaro, Andrea; Emberton, Mark; Wilson, Timothy H; Brotherton, Betsy J; Castro, Ramiro

2014-04-01

To examine, using post hoc analysis, the influence of baseline variables on changes in international prostate symptom score (IPSS), maximum urinary flow rate (Qmax ) and IPSS quality of life (QoL) in patients with moderate-to-severe lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) treated with either the α-blocker tamsulosin or the dual 5-alpha reductase inhibitor dutasteride, alone or in combination, as part of the 4-year Combination of Avodart and Tamsulosin (CombAT) study. CombAT was a 4-year, multicentre, randomized, double-blind, parallel-group study in 4844 men ≥50 years of age with a clinical diagnosis of BPH by medical history and physical examination, an IPSS ≥12 points, prostate volume (PV) ≥30 mL, total serum PSA level ≥1.5 ng/mL, and Qmax >5 mL/s and ≤15 mL/s with a minimum voided volume ≥125 mL. Eligible subjects were randomized to receive oral daily tamsulosin, 0.4 mg; dutasteride, 0.5 mg; or a combination of both. Baseline variable subgroups analysed were as follows: PV (30 to tamsulosin were performed from the general linear model with statistical significance defined as P ≤ 0.01. Combination therapy resulted in a significantly greater improvement from baseline IPSS at 48 months vs tamsulosin monotherapy across all baseline subgroups. The benefit of combination therapy over dutasteride was confined to groups with lower baseline PV (tamsulosin but not dutasteride monotherapy. Qmax improvement appeared to increase with PV and PSA level in combination therapy subjects. The proportion of subjects with an IPSS QoL ≤2 (at least mostly satisfied) at 48 months was significantly higher with combination therapy than with dutasteride for subgroups with PV 40-60 mL and PSA level tamsulosin for all PSA subgroups and PV subgroups ≥40 mL. CombAT data support the use of long-term combination therapy with dutasteride and tamsulosin in patients considered at risk for progression of BPH, as determined

[Controversies and dilemmas on the use of beta-blockers in treatment of associated cardiovascular disease in patients with chronic obstructive pulmonary disease].

Science.gov (United States)

Pescaru, Camelia; Tudorache, Voicu; Oancea, Cristian

2010-01-01

In the last decade, chronic obstructive pulmonary disease (COPD) has been considered a syndrome with multiple phenotypical facets and systemic components. Chronic diseases are associated, in time, with several comorbidities. Cardiovascular disease represents the most common comorbidity in COPD, increases its handicap and mortality indices. Most entities associated with cardiovascular disease require treatment with beta-blockers. However, beta-blockers are a "two-edged sword" when administered in obstructive pulmonary disorder. The use of beta-blockers should be assessed by their action on three areas: their effect on FEV1, their effect on bronchial hyperreactivity, the result obtained when additionally administering beta-agonists. The result of beta-blocker administration is influenced by the involvement of several other factors: the cardioselectivity of the beta-blocker, the dosage, the concomitant administration of beta-agonists, the stage of the disease (stable or exacerbation of COPD), smoker status etc. Their administration under strict monitoring results in a decreased morbidity and mortality, including in patients who had undergone cardiovascular surgery. The overall conclusion is that beta-blockers may be administered in COPD associated with cardiac comorbidity, but this administration requires utmost care.

Use of an indicator to evaluate physician adherence to prescription guidelines for the treatment of heart failure

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Márcio Galvão Oliveira

2013-12-01

Full Text Available The aim of this study was to use indicators to evaluate physician adherence to prescription guidelines for heart failure treatment in a university hospital. This was a prospective cohort study conducted in a university hospital. The information collected at the time of patient admission, including therapeutic indication, absolute contra indications and intolerance, was utilised for the formulation of a guideline adherence indicator (GAI. This indicator was calculated as follows: (the number of patients who used the medication/the number of eligible patients x 100. The percentage of eligible patients was calculated using the following formula: (the number of eligible patients/the total number patients x 100. The GAI was applied to a population of 53 patients. Inhibitors of angiotensin-converting enzyme/angiotensin receptor blocker (ACE-I/ARB combination therapy were used in the greatest percentage of eligible patients (92.4% and demonstrated the largest GAI value (73.5%. The percentages of patients who were eligible for beta-blockers, spironolactone and digitalis treatments were 81.1%, 52.8% and 60.4%, respectively. The GAI values for the use of beta-blockers, spironolactone and digitalis were 60.4%, 57.1% and 56.2%, respectively. For the studied patient population, the GAI was consistent with the proportion of patients who were eligible to receive digitalis and spironolactone.

Device therapy in heart failure with reduced ejection fraction-cardiac resynchronization therapy and more.

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Duncker, D; Veltmann, C

2018-05-09

In patients with heart failure with reduced ejection fraction (HFrEF), optimal medical treatment includes beta-blockers, ACE inhibitors/angiotensinreceptor-neprilysin inhibitors (ARNI), mineralocorticoid receptor antagonists, and ivabradine when indicated. In device therapy of HFrEF, implantable cardioverter-defibrillators and cardiac resynchronization therapy (CRT) have been established for many years. CRT is the therapy of choice (class I indication) in symptomatic patients with HFrEF and a broad QRS complex with a left bundle branch block (LBBB) morphology. However, the vast majority of heart failure patients show a narrow QRS complex or a non-LBBB morphology. These patients are not candidates for CRT and alternative electrical therapies such as baroreflex activation therapy (BAT) and cardiac contractility modulation (CCM) may be considered. BAT modulates vegetative dysregulation in heart failure. CCM improves contractility, functional capacity, and symptoms. Although a broad data set is available for BAT and CCM, mortality data are still lacking for both methods. This article provides an overview of the device-based therapeutic options for patients with HFrEF.

[Comparison of benazepril monotherapy to amlodipine plus benazepril in the treatment of patients with mild and moderate hypertension: a multicentre, randomized, double-blind, parallel-controlled study].

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Fan, Chao-mei; Yan, Li-rong; Tao, Yong-kang; Wang, Li; Li, Yu-qing; Gao, Ming-ming; Wang, Yan-ni; Li, Cheng-xiang; Wang, Xiao-wan; Lu, Xiao-lei; Pang, Hui-min; Li, Yi-shi

2011-01-01

To evaluate the efficacy and tolerability of the fixed combination of amlodipine 5 mg/benazepril 10 mg once-daily therapy, compared with benazepril, 10 mg, monotherapy in patients with mild and moderate hypertension, and to evaluate the 24 h antihypertensive efficacy and the duration of action by ambulatory blood pressure monitoring. In a multicenter, randomized, double-blind, parallel controlled trial, 356 cases of hypertensive patients after 2 weeks wash-out, and then given 4 weeks of benazepril 10 mg monotherapy, 220 patients with mean seated diastolic blood pressure (SeDBP) remained ≥ 90 mm Hg (1 mm Hg = 0.133 kPa) were randomly divided into benazepril 10 mg/amlodipine 5 mg (BZ10/AML5) fixed-dose combination therapy group (once a day, n = 113), and benazepril monotherapy group (daily 20 mg, n = 107). In the two groups the patients with SeDBP ≥ 90 mm Hg were doubled the dosage of the initial regimen at the end of 4-week treatment for additional 4 weeks, and the patients with SeDBP benazepril/amlodipine (10 mg/5 mg) and benazepril (20 mg) alone were 83.1%/76.0% and 85.8%/79.5%, respectively. Adverse events rates were 16.8% in the combination therapy group and 35.5% in the monotherapy group (P benazepril/amlodipine was superior to benazepril monotherapy and was well tolerated in patients with essential hypertension and allowing a satisfactory BP control for 24 hours.

Sartans: differences, similitudes and costs

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Orietta Zaniolo

2008-06-01

Full Text Available The search for a more specific and complete blockade of the hypertensive effects of angiotensin and of better tolerability than ACE-inhibitors has led to the development of angiotensin II receptor blockers (ARBs, which were introduced about 10 years ago. During this period they have been evaluated in several large studies in terms of efficacy and safety in reducing blood pressure, as well as for cardiovascular and renal protection. In patients with heart failure, valsartan, candesartan and, partially, losartan have been shown to be associated with positive outcomes both as monotherapy, when ACE-inhibitors are contraindicated or not tolerated, and in combination with ACE-inhibitors standard therapy. Among ARBs, valsartan is the only that is also approved for treatment of patients with both heart failure and recent myocardial infarction. In light of the high costs related to cardiovascular disorders, agents that reduce cardiovascular risk, like ARBs, represent a potential long-term health cost saving strategy, if used according to guidelines in approved indications. Valsartan has a daily cost which is lower than the mean cost of the class. Furthermore, this drug shows one of the lowest costs for patient brought to blood pressure goals in its class. In this paper, economic evaluations conducted on the results of large trials were reviewed. Their results add economic rationale to the therapeutic algorithms recommended by clinical guidelines on heart failure management; using valsartan, or other evaluated ARBs, in heart failure patients who are intolerant or contraindicated to ACE-inhibitors therapy, is expected to be highly cost/effective. In combination with ACE-inhibitors in those patients not on beta-blocker therapy, its cost/effectiveness is somewhat worse, but still acceptable, with an estimated cost of 15,000 USDs for life year saved. In summary, when used for approved indications, valsartan offers attractive economic features for the

The role of nitrates, beta blockers, and calcium antagonists in stable angina pectoris.

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Chan, P K; Heo, J Y; Garibian, G; Askenase, A; Segal, B L; Iskandrian, A S

1988-09-01

Numerous controlled studies have shown that nitrates, beta blockers, and calcium antagonists are effective in the treatment of stable angina pectoris. The pharmacokinetics, pharmacodynamics, and hemodynamic effects of these agents are different, and thus combination therapy offers additive improvement and also counterbalancing of the undesirable side effects of each drug. The choice of therapy depends on the severity of symptoms, associated diseases, compliance, side effects, and status of left ventricular function. The main mechanism of improvement is a decrease in myocardial oxygen consumption, though an increase in coronary blood flow is another potential reason for the use of calcium blockers. This review considers the properties of these drugs, their mechanism of action, and the results of randomized studies.

Efficacy and safety of icotinib in Chinese patients with advanced non-small cell lung cancer after failure of chemotherapy.

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Shao, Lan; Zhang, Beibei; He, Chunxiao; Lin, Baochai; Song, Zhengbo; Lou, Guangyuan; Yu, Xinmin; Zhang, Yiping

2014-01-01

The preclinical experiments and several clinical studies showed icotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in Chinese patients with advanced non-small cell lung cancer (NSCLC) who failed previous chemotherapy. We performed a retrospective study of the efficacy and safety of icotinib monotherapy in a different and more recent sample of Chinese patients. The clinical data of 149 patients with advanced NSCLC who were admitted to Zhejiang Cancer Hospital from August 1, 2011 to July 31, 2012 were retrospectively analyzed. All patients were given icotinib treatment after the failure of previous chemotherapy. Univariate and multivariate analyses were conducted based on the Kaplan Meier method and Cox proportional hazards model. The objective response rate was 33/149 and disease control rate was 105/149. No complete response occurred. Median progression free survival (PFS) with icotinib treatment was 5.03 months (95% CI: 3.51 to 6.55). Median overall survival was 12.3 months (95% CI: 10.68 to 13.92). Multivariate analysis showed that the mutation of EGFR and one regimen of prior chemotherapy were significantly associated with longer PFS. At least one drug related adverse event was observed in 65.8% (98/149) of patients, but mostly grade 1 or 2 and reversible and none grade 4 toxicity. Icotinib monotherapy is an effective and well tolerated regimen for Chinese patients with NSCLC after the failure of chemotherapy. It is a promising agent and further study with icotinib in properly conducted trials with larger patient samples and other ethnic groups is warranted.

Effects of prostatic inflammation on LUTS and alpha blocker treatment outcomes