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Sample records for blocker monotherapy failure

  1. β-Blocker pharmacogenetics in heart failure

    Science.gov (United States)

    Shin, Jaekyu

    2009-01-01

    β-Blockers (metoprolol, bisoprolol, and carvedilol) are a cornerstone of heart failure (HF) treatment. However, it is well recognized that responses to a β-blocker are variable among patients with HF. Numerous studies now suggest that genetic polymorphisms may contribute to variability in responses to a β-blocker, including left ventricular ejection fraction improvement, survival, and hospitalization due to HF exacerbation. This review summarizes the pharmacogenetic data for β-blockers in patients with HF and discusses the potential implications of β-blocker pharmacogenetics for HF patients. PMID:18437562

  2. Non-selective beta-blockers decrease thrombotic events in patients with heart failure

    NARCIS (Netherlands)

    De Peuter, Olav R.; Souverein, Patrick C.; Klungel, Olaf H.; Lip, Gregory Y.; Buller, Harry R.; De Boer, Anthonius; Kamphuisen, Pieter W.

    2010-01-01

    Background: Beta-blockers are often prescribed to patients with heart failure (HF) without distinctions between types of beta-blockers. The 2002 COMET study showed superiority of carvedilol (a non-selective beta-blocker) over metoprolol (selective beta-blocker) on mortality and cardiovascular events

  3. HEART FAILURE, DIABETES, BETA-BLOCKERS AND RISK OF HYPOGLYCEMIA

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    A. A. Aleksandrov

    2008-01-01

    Full Text Available Aim. To evaluate an influence of carvedilol on risk of hypoglycemia in patients with diabetes type 2 (D2 and chronic heart failure (CHF treated with angiotensin converting enzyme (ACE inhibitors.Material and methods. 13 patients (10 men, 3 women; aged 59,8±6,7 y.o. with D2 and CHF caused by ischemic heart disease were included in the study. Before inclusion all patients were treated with ACE inhibitors and various beta-blockers (atenolol, metoprolol, bisoprolol. These beta-blockers were changed for carvedilol. Heart ultrasonography, blood pressure control, glycemia monitoring, HbA1c level determination were performed before, during and after carvedilol therapy.Results. Carvedilol reduces frequency and duration of hypoglycaemia episodes. There were not episodes of severe hypoglycaemia during carvedilol therapy.Conclusion. Carvedilol reduces risk of hypoglycemia when it is used in combination with ACE inhiditors in diabetic patients with CHF.

  4. [Elderly heart failure patients and the role of beta-blocker therapy

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    Middeljans-Tijssen, C.W.; Jansen, R.W.M.M.

    2006-01-01

    In this article different aspects of chronic heart failure in old age are described. We mainly focus on the place of beta-blocker therapy in chronic heart failure. Beta-blockers are recommended for the treatment of stable chronic heart failure with left ventricular systolic dysfunction. There is

  5. Poor tolerance of beta-blockers by elderly patients with heart failure

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    Satoshi Yanagisawa

    2010-11-01

    Full Text Available Satoshi Yanagisawa, Noriyuki Suzuki, Toshikazu TanakaDepartment of Cardiology, Okazaki City Hospital, Aichi, JapanAbstract: Despite the well-understood importance of beta-blocker therapy in heart failure, it is sometimes not possible to use beta-blockers in elderly patients due to poor tolerance. In this report, we describe the case of an 83-year-old patient with severe systolic heart failure complicated by aortic valve stenosis and atrial fibrillation. A simple therapeutic approach involving discontinuation of beta-blockers remarkably alleviated the symptoms such as left ventricular ejection fraction, and improved the chest radiography and laboratory findings; further, atrial fibrillation converted to sinus rhythm. It is important to carefully administer beta-blocker therapy to elderly patients with heart failure, especially after considering cardiac output.Keywords: elderly, octogenarians, beta-blockers, heart failure

  6. EARLY-ESLI study: Long-term experience with eslicarbazepine acetate after first monotherapy failure.

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    Villanueva, V; Bermejo, P; Montoya, J; Toledo, M; Gómez-Ibáñez, A; Garcés, M; Vilella, L; López-González, F J; Rodriguez-Osorio, X; Campos, D; Martínez, P; Giner, P; Zurita, J; Rodríguez-Uranga, J; Ojeda, J; Mauri, J A; Camacho, J L; Ruiz-Giménez, J; Poza, J J; Massot-Tarrús, A; Galiano, M L; Bonet, M

    2017-09-01

    Evaluate real-life experience with eslicarbazepine acetate (ESL) after first monotherapy failure in a large series of patients with focal epilepsy. Multicentre, retrospective, 1-year, observational study in patients older than 18 years, with focal epilepsy, who had failed first antiepileptic drug monotherapy and who received ESL. Data from clinical records were analysed at baseline, 3, 6 and 12 months to assess effectiveness and tolerability. Eslicarbazepine acetate was initiated in 253 patients. The 1-year retention rate was 92.9%, and the final median dose of ESL was 800 mg. At 12 months, 62.3% of patients had been seizure free for 6 months; 37.3% had been seizure free for 1 year. During follow-up, 31.6% of the patients reported ESL-related adverse events (AEs), most commonly somnolence (8.7%) and dizziness (5.1%), and 3.6% discontinued due to AEs. Hyponatraemia was observed in seven patients (2.8%). After starting ESL, 137 patients (54.2%) withdrew the prior monotherapy and converted to ESL monotherapy; 75.9% were seizure free, 87.6% were responders, 4.4% worsened, and 23.4% reported ESL-related AEs. Use of ESL after first monotherapy failure was associated with an optimal seizure control and tolerability profile. Over half of patients were converted to ESL monotherapy during follow-up. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. COMPARATIVE EFFECTS OF MONOTHERAPY WITH MAGNESIUM AND COMBINED THERAPY WITH MAGNESIUM AND Β-BLOCKER ON PRIMARY MITRAL VALVE PROLAPSE WITH HEART RHYTHM DISORDERS

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    E. G. Nurtdinova

    2007-01-01

    Full Text Available Aim. To compare effects of monotherapy with magnesium and combined therapy with magnesium and β-blocker on primary mitral valve prolapse (MVP with heart rhythm disorders.Material and methods. 71 patients with primary MVP 1-2 degree and heart rhythm disorders were involved in the study. The patients were split into three groups. Group I (25 persons received monotherapy with magnesium orotate at a dose of 1-3 g per day; group II (28 persons received combined therapy with magnesium orotate and betaxolol. The control group (18 persons received no therapy. Initially and after 12 weeks of observation all the patients underwent electrocardiography (ECG, ECG-Holter monitoring, echocardiography and autonomic balance assessment by A.M. Vein’s questionnaire.Results. In 12 weeks of treatment groups I and II showed positive dynamics in the MVP manifestations, including significant reduction in severity of the autonomic dysfunction syndrome, ECG positive dynamics, antiarrhythmic effect, decrease in the degree of prolapse, diminution of mitral regurgitation and left auricle volumes. More substantial hemodynamic effects were found in the group of patients who received combination therapy.Conclusion. Combined therapy has proven advantages in comparison with magnesium monotherapy in terms of daily quantity of extrasystoles, reduction in heart rate, decrease in autonomic disfunction and normalization of intracardiac hemodynamics.

  8. COMPARATIVE EFFECTS OF MONOTHERAPY WITH MAGNESIUM AND COMBINED THERAPY WITH MAGNESIUM AND Β-BLOCKER ON PRIMARY MITRAL VALVE PROLAPSE WITH HEART RHYTHM DISORDERS

    Directory of Open Access Journals (Sweden)

    E. G. Nurtdinova

    2015-12-01

    Full Text Available Aim. To compare effects of monotherapy with magnesium and combined therapy with magnesium and β-blocker on primary mitral valve prolapse (MVP with heart rhythm disorders.Material and methods. 71 patients with primary MVP 1-2 degree and heart rhythm disorders were involved in the study. The patients were split into three groups. Group I (25 persons received monotherapy with magnesium orotate at a dose of 1-3 g per day; group II (28 persons received combined therapy with magnesium orotate and betaxolol. The control group (18 persons received no therapy. Initially and after 12 weeks of observation all the patients underwent electrocardiography (ECG, ECG-Holter monitoring, echocardiography and autonomic balance assessment by A.M. Vein’s questionnaire.Results. In 12 weeks of treatment groups I and II showed positive dynamics in the MVP manifestations, including significant reduction in severity of the autonomic dysfunction syndrome, ECG positive dynamics, antiarrhythmic effect, decrease in the degree of prolapse, diminution of mitral regurgitation and left auricle volumes. More substantial hemodynamic effects were found in the group of patients who received combination therapy.Conclusion. Combined therapy has proven advantages in comparison with magnesium monotherapy in terms of daily quantity of extrasystoles, reduction in heart rate, decrease in autonomic disfunction and normalization of intracardiac hemodynamics.

  9. A meta-analysis of the effects of β-adrenergic blockers in chronic heart failure.

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    Zhang, Xiaojian; Shen, Chengwu; Zhai, Shujun; Liu, Yukun; Yue, Wen-Wei; Han, Li

    2016-10-01

    Adrenergic β-blockers are drugs that bind to, but do not activate β-adrenergic receptors. Instead they block the actions of β-adrenergic agonists and are used for the treatment of various diseases such as cardiac arrhythmias, angina pectoris, myocardial infarction, hypertension, headache, migraines, stress, anxiety, prostate cancer, and heart failure. Several meta-analysis studies have shown that β-blockers improve the heart function and reduce the risks of cardiovascular events, rate of mortality, and sudden death through chronic heart failure (CHF) of patients. The present study identified results from recent meta-analyses of β-adrenergic blockers and their usefulness in CHF. Databases including Medline/Embase/Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed were searched for the periods May, 1985 to March, 2011 and June, 2013 to August, 2015, and a number of studies identified. Results of those studies showed that use of β-blockers was associated with decreased sudden cardiac death in patients with heart failure. However, contradictory results have also been reported. The present meta-analysis aimed to determine the efficacy of β-blockers on mortality and morbidity in patients with heart failure. The results showed that mortality was significantly reduced by β-blocker treatment prior to the surgery of heart failure patients. The results from the meta-analysis studies showed that β-blocker treatment in heart failure patients correlated with a significant decrease in long-term mortality, even in patients that meet one or more exclusion criteria of the MERIT-HF study. In summary, the findings of the current meta-analysis revealed beneficial effects different β-blockers have on patients with heart failure or related heart disease.

  10. Comparison of the clinical outcome of different beta-blockers in heart failure patients

    DEFF Research Database (Denmark)

    Bølling, Rasmus; Scheller, Nikolai Madrid; Køber, Lars

    2014-01-01

    AIM: To compare survival on different beta-blockers in heart failure. METHODS AND RESULTS: We identified all Danish patients ≥35 years of age who were hospitalized with a first admission for heart failure and who initiated treatment with a beta-blocker within 60 days of discharge. The study period....... In an unadjusted model carvedilol was associated with a lower mortality [hazard ratio (HR) 0.737, 0.714-0.761] compared with metoprolol (reference) while bisoprolol was not associated with an increased mortality (HR 1.020, 0.973-1.069). In a model adjusted for possible confounders and stratified according to beta-blocker...... receiving high-dose carvedilol (≥50 mg daily) showed significantly lower all-cause mortality risk and hospitalization risk, compared with other beta-blockers....

  11. Tolerability to beta-blocker therapy among heart failure patients in clinical practice.

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    Butler, Javed; Khadim, Ghazanfar; Belue, Rhonda; Chomsky, Don; Dittus, Robert S; Griffin, Marie; Wilson, John R

    2003-06-01

    Although beta-blockers were well-tolerated by heart failure (HF) patients in clinical trials, tolerability of these drugs in a general population of HF patients is not well-described. We studied a total of 308 encounters with beta-blockers therapy in 268 ambulatory HF patients. Side effects and frequency and predictors of discontinuation of therapy were studied. Independent predictors of discontinuation were assessed. Weight gain (59%), fatigue (56%), dizziness (41%), and dyspnea (29%) were the most common side effects. Fifty-one patients (19%) were discontinued on therapy with any 1 particular beta-blocker. Fatigue (30%) and hypotension (28%) were the most common reasons for discontinuation. Forty (78%) of these were given a trial with a different beta-blocker. Of these, 22 (55%) attempts with a different beta-blocker were tolerated. Thus the overall absolute discontinuation rate was only 7% for patients who were given a trial with different beta-blockers or 11% for the entire study population. Independent predictors of discontinuation of therapy included advanced symptoms, nonischemic etiology, history of pulmonary disease, and higher diuretic doses. Side effects with beta-blockers in a general population of HF patients are common; however, with changes in medical management, most patients can tolerate them eventually. In case of intolerance to one kind, a trial with a different beta-blocker is indicated.

  12. Relationship between heart failure, concurrent chronic obstructive pulmonary disease and beta-blocker use

    DEFF Research Database (Denmark)

    Sessa, Maurizio; Mascolo, Annamaria; Mortensen, Rikke Nørmark

    2018-01-01

    Aims: To compare the hazard of all-cause, chronic obstructive pulmonary disease (COPD) and heart failure (HF) hospitalization in carvedilol vs. metoprolol/bisoprolol/nebivolol users with COPD and concurrent HF from 2009 to 2012, and to evaluate the use and persistence in treatment of these β-blockers...... with COPD and concurrent HF. Additionally, we found a widespread phenomenon of carvedilol prescription at variance with the European Society of Cardiology guidelines and potential for improving the proportion of patients treated with β-blockers....

  13. 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.

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

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    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.

  15. Effect of beta-blocker therapy on functional status in patients with heart failure--a meta-analysis

    DEFF Research Database (Denmark)

    Abdulla, Jawdat; Køber, Lars; Christensen, Erik

    2005-01-01

    BACKGROUND: The results of randomised control trials (RCTs) evaluating the effect of beta-blockers on functional status in patients with chronic heart failure are conflicting. AIM: To perform a systematic review and meta-analysis of RCTs evaluating the effect of beta-blockers on New York Heart...... Association (NYHA) classification and exercise tolerance in chronic heart failure. METHODS AND RESULTS: We selected 28 RCTs evaluating beta-blocker versus placebo in addition to ACE inhibitor therapy. Combined results of 23 RCTs showed that beta-blockers improved NYHA class by at least one class with odds...... ratio (OR) 1.80 (1.33-2.43) pbeta-blockers had no significant effect...

  16. Clinical tolerability of generic versus brand beta blockers in heart failure with reduced left ventricular ejection fraction: a retrospective cohort from heart failure clinic.

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    Chanchai, Rattanachai; Kanjanavanit, Rungsrit; Leemasawat, Krit; Amarittakomol, Anong; Topaiboon, Paleerat; Phrommintikul, Arintaya

    2018-01-01

    Background: Beta-blockers have been shown to decrease mortality and morbidity in heart failure with reduced ejection fraction (HFrEF) patients. However, the side effects are also dose-related, leading to the underdosing. Cost constraint may be one of the limitations of appropriate beta-blocker use; this can be improved with generic drugs. However, the effects in real life practice have not been investigated. Methods and results: This study aimed to compare the efficacy and safety of generic and brand beta-blockers in HFrEF patients. We performed a retrospective cohort analysis in HFrEF patients who received either generic or brand beta-blocker in Chiang Mai Heart Failure Clinic. The primary endpoint was the proportion of patients who received at least 50% target dose of beta-blocker between generic and brand beta-blockers. Adverse events were secondary endpoints. 217 patients (119 and 98 patients received generic and brand beta-blocker, respectively) were enrolled. There were no differences between groups regarding age, gender, etiology of heart failure, New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF), rate of receiving angiotensin converting enzyme inhibitor (ACEI), angiotensin recepter blocker (ARB), or spironolactone. Patients receiving brand beta-blockers had lower resting heart rate at baseline (74.9 and 84.2 bpm, p  = .001). Rate of achieved 50% target dose and target daily dose did not differ between groups (40.4 versus 44.5% and 48.0 versus 55.0%, p  > .05, respectively). Rate of side effects was not different between groups (32.3 versus 29.5%, p  > .05) and the most common side effect was hypotension. Conclusion: This study demonstrated that beta-blocker tolerability was comparable between brand and generic formulations. Generic or brand beta-blockers should be prescribed to HFrEF patients who have no contraindications.

  17. Prevalence and prognostic significance of adrenergic escape during chronic beta-blocker therapy in chronic heart failure.

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    Frankenstein, Lutz; Zugck, Christian; Schellberg, Dieter; Nelles, Manfred; Froehlich, Hanna; Katus, Hugo; Remppis, Andrew

    2009-02-01

    Like aldosterone escape to ACE-inhibitors, adrenergic escape (AE) to beta-blockers appears conceivable in chronic heart failure (CHF), as generalized systemic neurohumoral activation has been described as the pathophysiological basis of this syndrome. The aim of this study was to examine the prevalence and prognostic value of AE with respect to different beta-blocker agents and doses. This was a prospective, observational study of 415 patients with systolic CHF receiving chronic stable beta-blocker therapy. AE was defined by norepinephrine levels above the upper limit of normal. Irrespective of the individual beta-blocker agents used and the dose equivalent taken, the prevalence of AE was 31-39%. Norepinephrine levels neither correlated with heart rate (r=0.02; 95% CI: -0.08-0.11; P=0.74) nor were they related to underlying rhythm (P=0.09) or the individual beta-blocker agent used (P=0.87). The presence of AE was a strong and independent indicator of mortality (adjusted HR: 1.915; 95% CI: 1.387-2.645; chi2: 15.60). We verified the presence of AE in CHF patients on chronic stable beta-blocker therapy, irrespective of the individual beta-blocker agent and the dose equivalent. As AE might indicate therapeutic failure, the determination of AE could help to identify those patients with CHF that might benefit from more aggressive treatment modalities. Heart rate, however, is not a surrogate for adrenergic escape.

  18. Has beta-blocker use increased in patients with heart failure in internal medicine settings? Prognostic implications: RICA registry.

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    González-García, Andrés; Montero Pérez-Barquero, Manuel; Formiga, Francesc; González-Juanatey, José R; Quesada, M Angustias; Epelde, Francisco; Oropesa, Roberto; Díez-Manglano, Jesús; Cerqueiro, José M; Manzano, Luis

    2014-03-01

    Underuse of beta-blockers has been reported in elderly patients with heart failure. The aim of this study was to evaluate the current prescription of beta-blockers in the internal medicine setting, and its association with morbidity and mortality in heart failure patients. The information analyzed was obtained from a prospective cohort of patients hospitalized for heart failure (RICA registry] database, patients included from March 2008 to September 2011) with at least one year of follow-up. We investigated the percentage of patients prescribed beta-blockers at hospital discharge, and at 3 and 12 months, and the relationship of beta-blocker use with mortality and readmissions for heart failure. Patients with significant valve disease were excluded. A total of 515 patients were analyzed (53.5% women), with a mean age of 77.1 (8.7) years. Beta-blockers were prescribed in 62.1% of patients at discharge. A similar percentage was found at 3 months (65.6%) and 12 months (67.9%) after discharge. All-cause mortality and the composite of all-cause mortality and readmission for heart failure were significantly lower in patients treated with beta-blockers (hazard ratio=0.59, 95% confidence interval, 0.41-0.84 vs hazard ratio=0.64, 95% confidence interval, 0.49-0.83). This decrease in mortality was maintained after adjusting by age, sex, ejection fraction, functional class, comorbidities, and concomitant treatment. The findings of this study indicate that beta-blocker use is increasing in heart failure patients (mainly elderly) treated in the internal medicine setting, and suggest that the use of these drugs is associated with a reduction in clinical events. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  19. Thyroid Storm with Heart Failure Treated with a Short-acting Beta-adrenoreceptor Blocker, Landiolol Hydrochloride.

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    Yamashita, Yugo; Iguchi, Moritake; Nakatani, Rieko; Usui, Takeshi; Takagi, Daisuke; Hamatani, Yasuhiro; Unoki, Takashi; Ishii, Mitsuru; Ogawa, Hisashi; Masunaga, Nobutoyo; Abe, Mitsuru; Akao, Masaharu

    2015-01-01

    Beta-adrenoreceptor blockers are essential in controlling the peripheral actions of thyroid hormones and a rapid heart rate in patients with thyroid storm, although they should be used with great caution when there is the potential for heart failure. A 67-year-old woman was diagnosed as having thyroid storm in addition to marked tachycardia with atrial fibrillation and heart failure associated with a reduced left ventricular function. The administration of an oral beta blocker, bisoprolol fumarate, induced hypotension and was not tolerable for the patient, whereas landiolol hydrochloride, a short-acting intravenous beta-adrenoreceptor blocker with high cardioselectivity and a short elimination half-life, was useful for controlling the patient's tachycardia and heart failure without causing hemodynamic deterioration.

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

    Science.gov (United States)

    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.

  1. 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....

  2. 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

  3. 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

  4. 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.

  5. Prevalence and prognostic significance of adrenergic escape during chronic β-blocker therapy in chronic heart failure

    Science.gov (United States)

    Frankenstein, Lutz; Zugck, Christian; Schellberg, Dieter; Nelles, Manfred; Froehlich, Hanna; Katus, Hugo; Remppis, Andrew

    2009-01-01

    Aims Like aldosterone escape to ACE-inhibitors, adrenergic escape (AE) to β-blockers appears conceivable in chronic heart failure (CHF), as generalized systemic neurohumoral activation has been described as the pathophysiological basis of this syndrome. The aim of this study was to examine the prevalence and prognostic value of AE with respect to different β-blocker agents and doses. Methods and results This was a prospective, observational study of 415 patients with systolic CHF receiving chronic stable β-blocker therapy. AE was defined by norepinephrine levels above the upper limit of normal. Irrespective of the individual β-blocker agents used and the dose equivalent taken, the prevalence of AE was 31–39%. Norepinephrine levels neither correlated with heart rate (r = 0.02; 95% CI: −0.08–0.11; P = 0.74) nor were they related to underlying rhythm (P = 0.09) or the individual β-blocker agent used (P = 0.87). The presence of AE was a strong and independent indicator of mortality (adjusted HR: 1.915; 95% CI: 1.387–2.645; χ2: 15.60). Conclusion We verified the presence of AE in CHF patients on chronic stable β-blocker therapy, irrespective of the individual β-blocker agent and the dose equivalent. As AE might indicate therapeutic failure, the determination of AE could help to identify those patients with CHF that might benefit from more aggressive treatment modalities. Heart rate, however, is not a surrogate for adrenergic escape. PMID:19168516

  6. 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...... of heart failure diagnosis have similar prognosis.Treatment options for patients developing heart failure while already treated with ACE inhibitors/ARBs and beta-blockers are very limited if current heart failure guidelines are followed. In this review possible strategies are outlined and important areas...

  7. 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...

  8. 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

  9. 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...

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  12. 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.

  13. 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.

  14. 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.

    Science.gov (United States)

    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.

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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.

  18. 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...

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

    Directory of Open Access Journals (Sweden)

    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

  20. 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.)

  1. 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.)

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

    Directory of Open Access Journals (Sweden)

    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

  3. Pharmacogenetics of β-Blockers

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

  6. Alpha Blockers

    Science.gov (United States)

    ... 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 ...

  7. 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.

  8. 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 ...

  9. H2 blockers

    Science.gov (United States)

    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 ...

  10. 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)

  11. 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.

  12. Calcium channel blocker poisoning

    Directory of Open Access Journals (Sweden)

    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.

  13. 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.

  14. 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...

  15. Efficacy and safety of telmisartan monotherapy in the black ...

    African Journals Online (AJOL)

    The use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in addition to control of blood pressure delays the development of end organ damage associated with hypertension. This study was undertaken to investigate the efficacy and safety of telmisartan as monotherapy in Nigerian black ...

  16. The Evolution of the Use of β-Blockers to Treat Heart Failure: A Conversation With Finn Waagstein, MD.

    Science.gov (United States)

    Waagstein, Finn; Rutherford, John D

    2017-09-05

    Finn Waagstein was born in Copenhagen in 1938. He graduated from Aarhus University Medical School in 1964. He received his cardiology training in the Sahlgrenska University Hospital at the University of Gothenburg, Sweden. He was appointed Associate Professor in 1980, and he assisted in establishing and directing the first Swedish heart transplant program. From 1990 he directed the heart failure and cardiomyopathy research programs. He is currently Professor of Cardiology and senior physician at Wallenberg Laboratory. In 2002, he was awarded the King Faisal International Prize for Medicine. © 2017 American Heart Association, Inc.

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

    Science.gov (United States)

    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.

  18. 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.

  19. EFFECTS OF BETA-BLOCKER METOPROLOL ON QUALITY OF LIFE IN ELDERLY PATIENTS WITH CHRONIC HEART FAILURE

    Directory of Open Access Journals (Sweden)

    I. V. Vologdina

    2007-01-01

    Full Text Available Aim. To study effect of cardioselective β-adrenoblocker metoprolol tartrate (in retarded formulation on quality of life in elderly patients with chronic heart failure (CHF of ischemic etiology.Material and methods. 78 patients with CHF class III (NYHA were involved in the study. Patients were 81,6±0,25 y.o. in average. All patients had clinical signs of mild-to-moderate depressive disorders. Patients were split on 2 groups comparable in sex and age. Patients of the 1st group (n=43 received metoprolol tartrate (Egilok Retard, 50-100 mg/d additionally to standard therapy. Patients of the 2nd group (n=35 received only standard therapy. The somatic status was assessed before and after 1 and 3 months of therapy by clinical condition evaluated scale (CCES, 6-minute walking test, left ventricular ejection fraction (Echocardiography as well as mental status by special tests (SMSP, BDI, Hamilton scale, C.D.Spilberger-Y.L.Hanin scale and qualities of life (MLHFQ, SF-36.Results. Reduction of CHF class from III to II was observed in 31 (76,7% patients of the 1st group and in 23 (65,7% patients of the 2nd group. Tolerability of Egilok Retard was good and there were not cessations because of side effects. In 3 months of therapy severity of the somatic status according to CCES reduced more significantly in the 1st group in comparison with the 2nd group (29,5 % vs 11,5 %, p <0,001. The exercise tolerance increased higher in the 1st group comparing with the 2nd one (34 % vs 17 %, respectively, p<0,001. The severity of depression reduced (according to SMSP, Hamilton scale more significantly in the 1st group in comparison with this in the 2nd one. Quality of life also improved more significantly in the 1st group according to MLHFQ and SF-36 (physical functions, role physical functions, social function scales at the end of therapy.Conclusion. Metoprolol tartrate (in retarded formulation improves somatic and mental status as well as quality of life in elderly

  20. 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...

  1. 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.

  2. 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...

  3. 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 ...

  4. 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.

  5. Perfil do tratamento da insuficiência cardíaca na era dos betabloqueadores Heart failure treatment profile at the beta blockers era

    Directory of Open Access Journals (Sweden)

    Christiano Pereira Silva

    2007-04-01

    perspective of survival in these patients, as well as allowing the improvement of the quality of life. The aim of this study was to evaluate the reality of the treatment employed and its impact on the disease in patients followed at a specialized heart failure (HF outpatient clinic. METHODS: A sample of 96 patients followed at the HF and Transplant Outpatient Clinic of Heart Institute of the University of São Paulo School of Medicine (InCor -HCFMUSP were evaluated. The data were collected during the ambulatory consultation from the medical files and through physical examination. Patients were randomly selected for the study. RESULTS: Most of the patients were Functional Class II (42.3% and evolution stage C (94.9%. The medical prescription given to the patients was quite similar to the one recommended by the directives. Approximately 95% of them received RAAS inhibitors (ACE inhibitor - enalapril and captopril - or angiotensin receptor antagonist - losartan, whereas 85% of the patients additionally received beta blockers (carvedilol. The mean dose prescribed was also similar to the one used in large studies and reached more than 60% of the maximum dose for each medication. The hemodynamic data show that patients were stable, despite the intensity of the dysfunction and ventricular remodeling observed in these patients. CONCLUSION: Patients with HF followed by a specialized medical team receive a medical prescription that is closer to the recommended one. These patients, despite the marked characteristics of disease severity, achieve hemodynamic and clinical stability with an adequate therapeutic optimization.

  6. 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...

  7. 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....

  8. Calcium Channel Blockers

    Science.gov (United States)

    ... 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 ...

  9. Treatment of febrile neutropenia with cefepime monotherapy.

    Science.gov (United States)

    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

  10. Multiple treatment comparisons in epilepsy monotherapy trials

    Directory of Open Access Journals (Sweden)

    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

  11. 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.

    Science.gov (United States)

    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.

  12. 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.

  13. 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

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

    Directory of Open Access Journals (Sweden)

    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

  15. 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....

  16. 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....

  17. Beta-blockers for preventing aortic dissection in Marfan syndrome.

    Science.gov (United States)

    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

  18. 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...

  19. A randomized and double-blind comparison of isradipine and spirapril as monotherapy and in combination on the decline in renal function in patients with chronic renal failure and hypertension

    DEFF Research Database (Denmark)

    Petersen, L J; Petersen, J R; Talleruphuus, U

    2001-01-01

    Treatment of hypertension in patients with chronic renal failure has been shown to postpone the decline in renal function. Treatment with an ACE inhibitor has been shown to be superior to conventional antihypertensive treatment, but it is not known how an ACE inhibitor compares to treatment with ...

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

    Directory of Open Access Journals (Sweden)

    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

  1. 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

    Directory of Open Access Journals (Sweden)

    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

  2. [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.

  3. Há evidências favorecendo o uso de betabloqueadores e dobutamina na insuficiência cardíaca aguda? Is there evidence favoring the use of beta-blockers and dobutamine in acute heart failure?

    Directory of Open Access Journals (Sweden)

    Luiz Carlos Santana Passos

    2013-02-01

    Full Text Available Diversos estudos relataram os benefícios dos betabloqueadores (BB para pacientes com insuficiência cardíaca sistólica. No entanto, muitos pacientes hospitalizados em decorrência de insuficiência cardíaca aguda já estão usando os BB e requerem dobutaminas para hipotensão arterial e baixo débito cardíaco. Portanto, deve-se tomar uma decisão a respeito de se o BB deve ser mantido ou até mesmo iniciado nesses casos. O objetivo deste estudo foi determinar se há provas que sustentem a segurança e a eficácia dos BB junto com a dobutamina para pacientes com insuficiência cardíaca aguda descompensada (ICAD. Foi realizada uma pesquisa na literatura de língua inglesa nas bases de dados MEDLINE, ISI Web of Science, Biblioteca Virtual em Saúde, Cochrane Library e o Portal de Revistas Científicas do Capes para identificar estudos relacionados. Literatura adicional foi obtida mediante a análise das respectivas referências encontradas nos artigos identificados. Os resultados esperados incluíram informações sobre o prognóstico (intra-hospitalar e na mortalidade no acompanhamento, número de dias de internação e reinternação, eficácia e segurança (agravamento dos sintomas, choque, intolerância do uso concomitante desses medicamentos em pacientes hospitalizados com ICAD e baixo débito cardíaco. Esta análise incluiu nove estudos. No entanto, não foram encontrados ensaios clínicos randomizados sobre o assunto. A maioria dos estudos inclui baixo número de pacientes, e não foram encontrados estudos que abordem a segurança do uso concomitante desses medicamentos. Os dados resultantes sugerem que uma cuidadosa revisão da literatura não forneceu evidências para o uso sistemático de BB em pacientes com síndrome de baixo débito cardíaco que necessitam de suporte inotrópico com dobutamina.Several studies have reported the benefits of beta-blockers (BB for patients presenting with systolic heart failure. however, many

  4. Use of β-Blockers in Pulmonary Hypertension.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  9. 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.

  10. 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.

  11. 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.

  12. 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...

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

    Science.gov (United States)

    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.

  14. 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

  15. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  17. [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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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

  20. 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.

  1. 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 ...

  2. 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...

  3. 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

  4. β-Blocker Therapy Prior to Admission for Acute Coronary Syndrome in Patients Without Heart Failure or Left Ventricular Dysfunction Improves In-Hospital and 12-Month Outcome: Results From the GULF-RACE 2 (Gulf Registry of Acute Coronary Events-2).

    Science.gov (United States)

    Abi Khalil, Charbel; AlHabib, Khalid F; Singh, Rajvir; Asaad, Nidal; Alfaleh, Hussam; Alsheikh-Ali, Alawi A; Sulaiman, Kadhim; Alshamiri, Mostafa; Alshaer, Fayez; AlMahmeed, Wael; Al Suwaidi, Jassim

    2017-12-20

    The prognostic impact of β-blockers (BB) in acute coronary syndrome (ACS) patients without heart failure (HF) or left ventricular dysfunction is controversial, especially in the postreperfusion era. We sought to determine whether a BB therapy before admission for ACS has a favorable in-hospital outcome in patients without HF, and whether they also reduce 12-month mortality if still prescribed on discharge. The GULF-RACE 2 (Gulf Registry of Acute Coronary Events-2) is a prospective multicenter study of ACS in 6 Middle Eastern countries. We studied in-hospital cardiovascular events in patients hospitalized for ACS without HF in relation to BB on admission, and 1-year mortality in relation to BB on discharge. Among the 7903 participants, 7407 did not have HF, of whom 5937 (80.15%) patients were on BB. Patients on BB tended to be older and have more comorbidities. However, they had a lower risk of in-hospital mortality, mitral regurgitation, HF, cardiogenic shock, and ventricular tachycardia/ventricular fibrillation. Furthermore, 4208 patients were discharged alive and had an ejection fraction ≥40%. Among those, 84.1% had a BB prescription. At 12 months, they also had a reduced risk of mortality as compared with the non-BB group. Even after correcting for confounding factors in 2 different models, in-hospital and 12-month mortality risk was still lower in the BB group. In this cohort of ACS, BB therapy before admission for ACS is associated with decreased in-hospital mortality and major cardiovascular events, and 1-year mortality in patients without HF or left ventricular dysfunction if still prescribed on discharge. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  5. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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 ...

  8. 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

  9. 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

  10. 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

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

    Science.gov (United States)

    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.

  12. Reassessing guidelines for heart failure

    Directory of Open Access Journals (Sweden)

    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.

  13. 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;.

  14. 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-.

  15. 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.

  16. Beta-blocker withdrawal among patients presenting for surgery from home

    Science.gov (United States)

    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

  17. 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

  18. Adição de Bloqueador do receptor de angiotensina II na insuficiência cardíaca descompensada Adición de bloqueante del receptor de angiotensina II en la insuficiencia cardiaca descompensada Angiotensin II receptor blocker add-on therapy for low cardiac output in decompensated heart failure

    Directory of Open Access Journals (Sweden)

    Marcelo E. Ochiai

    2010-02-01

    pacientes internados por descompensación de la insuficiencia cardiaca y con empleo por más de 15 días de dobutamina, o una o más intentos sin éxito de retirada; dosis optimizada de IECA; y FEVI BACKGROUND: During heart failure (HF decompensation, an intense activation of the renin-angiotensin-aldosterone system occurs; however, the use of angiotensin-converting enzyme inhibitor (ACEI cannot block it completely. Otherwise, the addition of angiotensin II receptor blocker (ARB can be useful when the inotropic dependence occurs. We evaluated the efficacy of the ARB-ACEI association on dobutamine withdrawal in advanced decompensated HF. OBJECTIVE: To assess the efficacy of association angiotensin receptor blocker - angiotensin converting enzyme inhibitor to withdraw the intravenous inotropic support in decompensated severe heart failure. METHODS: In a case-control study (N = 24, we selected patients admitted at the hospital due to HF that had been using dobutamine for more than 15 days, with one or more unsuccessful drug withdrawal attempts; optimized dose of ACEI and ejection fraction (EF < 0.45. Then, the patients additionally received ARB (n=12 or not (control, n=12. The outcome was the successful dobutamine withdrawal, evaluated by logistic regression, with a p < 0.05. RESULTS: The EF was 0.25 and the age was 53 years, with a dobutamine dose of 10.7 μg/kg.min. The successful drug withdrawal was observed in 8 patients from the ARB group (67.7% and in 2 patients from the control group (16.7%. The odds ratio (OR was 10.0 (95%CI: 1.4 to 69.3; p = 0.02. The worsening in renal function was similar (ARB group: 42% vs. control group: 67%; p=0.129. CONCLUSION: In this pilot study, the ARB-ACEI association was associated with successful dobutamine withdrawal in advanced decompensated heart failure. The worsening in renal function was similar in both groups. Further studies are necessary to clarify the issue.

  19. Monotherapy for partial epilepsy: focus on levetiracetam

    Directory of Open Access Journals (Sweden)

    Antonio Gambardella

    2008-03-01

    Full Text Available Antonio Gambardella1,2, Angelo Labate1,2, Eleonora Colosimo1, Roberta Ambrosio1, Aldo Quattrone1,21Institute of Neurology, University Magna Græcia, Catanzaro, Italy; 2Institute of Neurological Sciences, National Research Council, Piano Lago di Mangone, Cosenza, ItalyAbstract: Levetiracetam (LEV, the S-enantiomer of alpha-ethyl-2-oxo-1-pyrollidine acetamide, is a recently licensed antiepileptic drug (AED for adjunctive therapy of partial seizures. Its mechanism of action is uncertain but it exhibits a unique profile of anticonvulsant activity in models of chronic epilepsy. Five randomized, double-blind, placebo-controlled trials enrolling adult or pediatric patients with refractory partial epilepsy have demonstrated the efficacy of LEV as adjunctive therapy, with a responder rate (≥50% reduction in seizure frequency of 28%–45%. Long-term efficacy studies suggest retention rates of 60% after one year, with 13% of patients seizure-free for 6 months of the study and 8% seizure-free for 1 year. More recent studies illustrated successful conversion to monotherapy in patients with refractory epilepsy, and its effectiveness as a single agent in partial epilepsy. LEV has also efficacy in generalized epilepsies. Adverse effects of LEV, including somnolence, lethargy, and dizziness, are generally mild and their occurrence rate seems to be not significantly different from that observed in placebo groups. LEV also has no clinically significant pharmacokinetic interactions with other AEDs, or with commonly prescribed medications. The combination of effective antiepileptic properties with a relatively mild adverse effect profile makes LEV an attractive therapy for partial seizures.Keywords: levetiracetam, partial epilepsy, antiepileptic drugs

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  2. 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.

  3. 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

  4. 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.

  5. 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...

  6. 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

  7. Can Beta Blockers Cause Weight Gain?

    Science.gov (United States)

    ... 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 ...

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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...

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

    Science.gov (United States)

    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.

  11. 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

  12. 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.

  13. Redução da prevalência de apneia central em pacientes com insuficiência cardíaca sob uso de betabloqueador Reducción de la prevalencia de apnea central en pacientes con insuficiencia cardiaca bajo uso de betabloqueante Reduction of central sleep apnea in heart failure patients with beta-blockers therapy

    Directory of Open Access Journals (Sweden)

    Christiano Pereira Silva

    2010-02-01

    portadores de IC. MÉTODOS: 65 pacientes portadores de IC fueron sometidos a polisonografía diagnóstica. Los resultados de la polisonografía se evaluaron según el empleo o no de BB. El día del examen, los pacientes contestaron el cuestionario de Minnesota para la calidad de vida con IC. Tras 6 y 12 meses de la fecha de la polisonografía, hubo contacto telefónico con todos los pacientes, para la repetición del cuestionario de Minnesota. RESULTADOS: La prevalencia de apnea del sueño (IAH > 15/h fue de un 46,1% en la población total, además de la apnea central se identificó en solamente un 18,4% de los pacientes. El empleo de BB, en análisis multivariado, fue el único predictor de ocurrencia de menor índice de apnea e hipopnea (IAH central (p=0,002, mayor saturación (p=0,02 y menor desaturación promedio de oxígeno (p=0,03. Además de ello, el empleo de BB fue predictor de mejor calidad de vida tras 6 y 12 meses (p=0,002 y 0,001 respectivamente y de menor número de hospitalizaciones en estos períodos (p=0,001 y p=0,05 respectivamente. CONCLUSIÓN: El empleo de BB reduzco la incidencia de apnea central en la población total, si lo comparamos con los datos de la literatura. Además de esto, los BB mejoran parámetros de la calidad del sueño y de vida de portadores de IC.BACKGROUND: Sleep apneas are frequent in patients with heart failure (HF. Estimate of the pre-beta blocker age (BB point out to 45% of central apneas in these patients. OBJECTIVE: Assess the influence of BB in central apneas and their interference in the quality of sleep and life of patients with heart failure. METHODS: 65 patients with heart failure underwent diagnostic polysomnography. Polysomnography have been assessed according to the use or not of BB. On the day of examination, the patients answered the Minessota questionnaire for quality of life with HF. After 6 and 12 months from the polysomnography date, all patients were contacted by phone, in order to repeat the Minessota

  14. 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.

  15. Associação de betabloqueadores e treinamento físico na insuficiência cardíaca de camundongos Asociación de betabloqueantes y entrenamiento físico en la insuficiencia cardíaca de ratones Association of physical training with beta-blockers in heart failure in mice

    Directory of Open Access Journals (Sweden)

    Andréa Somolanji Vanzelli

    2010-09-01

    tolerancia al esfuerzo se evaluó por prueba progresivo máxima y la fracción de acortamiento se evaluó (FE por ecocardiografía. El diámetro de los cardiomiocitos y la fracción de colágeno fueron evaluados por medio de análisis histológico. Los dados fueron comparados por ANOVA de un camino con post hoc de Duncan. El nivel de significancia se consideró como p BACKGROUND: Currently there are several types of interventions for the treatment of heart failure (HF. Among these are beta-blocker therapy (BB and physical training (PT. However, the effects of the combination of these therapies are poorly studied. OBJECTIVE: To investigate the effects of BB treatment with metoprolol (M and carvedilol (C associated with PT in mice with HF. METHODS: We used a genetic model of sympathetic hyperactivity-induced heart failure in mice. Initially, we divided the HF animals into three groups: sedentary (S; trained (T; treated with M (138 mg/kg (M; or C (65 mg/kg (C. In the second part, we divided the groups into three subgroups: sedentary (S; trained and treated with M (TM; and trained and treated with C (CT. The PT consisted of aerobic training on a treadmill for 8 weeks. Exercise tolerance was assessed by maximal graded test, and fractional shortening (FS was assessed by echocardiography. Cardiomyocyte diameter and collagen volume fraction were evaluated by histological analysis. Data were compared by one way ANOVA and post hoc Duncan test. The significance level was set at p < 0.05. RESULTS: As to FS and cardiac remodeling, we found that, in isolation, T, M, and C showed an improvement of the variables analyzed. As to therapy combination, after the intervention period, we observed an increase in exercise tolerance in MT and CT (43.0% and 33.0% respectively. There was also a reduction in cardiomyocyte diameter (10.0% and 9.0% respectively and in collagen volume fraction (52.0% and 63.0% after the intervention. However, only CT significantly improved FS. CONCLUSION: The association

  16. 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.

  17. 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

  18. 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...

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Topical antibiotic monotherapy prescribing practices in acne vulgaris.

    Science.gov (United States)

    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.

  4. 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.

  5. 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)

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

    Science.gov (United States)

    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.

  7. 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.

  8. Use of calcium channel blockers in hypertension.

    Science.gov (United States)

    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

  9. 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

  10. 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 ...

  11. 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....

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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.

    Science.gov (United States)

    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.

  18. Extensive Darier Disease Successfully Treated with Doxycycline Monotherapy

    Directory of Open Access Journals (Sweden)

    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.

  19. 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...

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

    Science.gov (United States)

    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.

  1. 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.

  2. 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.

  3. Discovery and Development of Calcium Channel Blockers

    Directory of Open Access Journals (Sweden)

    Théophile Godfraind

    2017-05-01

    Full Text Available In the mid 1960s, experimental work on molecules under screening as coronary dilators allowed the discovery of the mechanism of calcium entry blockade by drugs later named calcium channel blockers. This paper summarizes scientific research on these small molecules interacting directly with L-type voltage-operated calcium channels. It also reports on experimental approaches translated into understanding of their therapeutic actions. The importance of calcium in muscle contraction was discovered by Sidney Ringer who reported this fact in 1883. Interest in the intracellular role of calcium arose 60 years later out of Kamada (Japan and Heibrunn (USA experiments in the early 1940s. Studies on pharmacology of calcium function were initiated in the mid 1960s and their therapeutic applications globally occurred in the the 1980s. The first part of this report deals with basic pharmacology in the cardiovascular system particularly in isolated arteries. In the section entitled from calcium antagonists to calcium channel blockers, it is recalled that drugs of a series of diphenylpiperazines screened in vivo on coronary bed precontracted by angiotensin were initially named calcium antagonists on the basis of their effect in depolarized arteries contracted by calcium. Studies on arteries contracted by catecholamines showed that the vasorelaxation resulted from blockade of calcium entry. Radiochemical and electrophysiological studies performed with dihydropyridines allowed their cellular targets to be identified with L-type voltage-operated calcium channels. The modulated receptor theory helped the understanding of their variation in affinity dependent on arterial cell membrane potential and promoted the terminology calcium channel blocker (CCB of which the various chemical families are introduced in the paper. In the section entitled tissue selectivity of CCBs, it is shown that characteristics of the drug, properties of the tissue, and of the stimuli are

  4. 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.

  5. 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.

  6. 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.

  7. 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...

  8. 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....

  9. 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 ...

  10. 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

  11. 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....

  12. Systematic review of use of β-blockers in sepsis.

    Science.gov (United States)

    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.

  13. [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.

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

    Directory of Open Access Journals (Sweden)

    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. 

  15. Sulfonylurea versus metformin monotherapy in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Hemmingsen, Bianca; Schroll, Jeppe B; Wetterslev, Jørn

    2014-01-01

    BACKGROUND: Guidelines recommend metformin as the first-line oral treatment for type 2 diabetes. We conducted a systematic review to assess whether the use of second- and third-generation sulfonylurea agents is associated with benefits and harms in terms of patient-important outcomes compared...... with metformin. METHODS: We searched several electronic databases and other sources for randomized clinical trials published to August 2011. We included trials that compared sulfonylurea versus metformin monotherapy among patients 18 years or older with type 2 diabetes and that had an intervention period...... of at least 24 weeks. We assessed risk of bias and extracted data related to interventions and outcomes. The risk of random errors was assessed by trial sequential analysis. RESULTS: We included 14 trials (4560 participants). All trials were judged to be at high risk of bias. Data on patient...

  16. Lymphocutaneous Sporotrichosis during Treatment with Anti-TNF-Alpha Monotherapy

    Directory of Open Access Journals (Sweden)

    Francesco Ursini

    2015-01-01

    Full Text Available Sporotrichosis is an infectious disease caused by Sporothrix schenckii, a dimorphic fungus isolated for the first time in 1896 by Benjamin Schenck from a 36-year-old male patient presenting lesions on the right hand and arm. The infection generally occurs by traumatic inoculation of soil, plants, and organic matter contaminated with the fungus. Different clinical syndromes are described as a direct consequence of S. schenckii infection, including lymphocutaneous and disseminated forms, although extracutaneous presentations are reported most frequently in AIDS patients. Here we describe the case of a 57-year-old Caucasian male diagnosed in 2004 with ankylosing spondylitis under stable treatment with adalimumab monotherapy (40 mg every other week. During a routine follow-up visit in March 2013, he presented with multiple nodular lesions arranged in a linear fashion along the left hand and forearm. After diagnostic aspiration of the lesions, lymphocutaneous sporotrichosis was diagnosed and appropriate therapy started.

  17. Improvement of Brain Reward Abnormalities by Antipsychotic Monotherapy in Schizophrenia

    DEFF Research Database (Denmark)

    Nielsen, Mette Ødegaard; Rostrup, Egill; Wulff, Sanne

    2012-01-01

    CONTEXT Schizophrenic symptoms are linked to a dysfunction of dopamine neurotransmission and the brain reward system. However, it remains unclear whether antipsychotic treatment, which blocks dopamine transmission, improves, alters, or even worsens the reward-related abnormalities. OBJECTIVE....... Antipsychotic treatment tends to normalize the response of the reward system; this was especially seen in the patients with the most pronounced treatment effect on the positive symptoms. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01154829....... To investigate changes in reward-related brain activations in schizophrenia before and after antipsychotic monotherapy with a dopamine D2/D3 antagonist. DESIGN Longitudinal cohort study. SETTING Psychiatric inpatients and outpatients in the Capital Region of Denmark. PARTICIPANTS Twenty-three antipsychotic...

  18. Severe pneumonia associated with ibrutinib monotherapy for CLL and lymphoma.

    Science.gov (United States)

    Kreiniz, Natalia; Bejar, Jacob; Polliack, Aaron; Tadmor, Tamar

    2018-02-01

    In recent years, there have been major advances in the treatment of chronic lymphocytic leukemia (CLL) particularly since the development of novel therapeutic agents, mostly "biological drugs." One of the obvious advantages of these agents is the decreased rate of infectious complications occurring during the course of therapy, compared to the use of standard immuno-chemotherapy regimens. Here, we describe 3 patients with CLL and 1 with mantle cell lymphoma who developed severe life-threatening pneumonias, during monotherapy with ibrutinib. The first case was a 70-year-old woman with relapsed CLL who developed bilateral pneumonia with hypoxia 1 week after starting ibrutinib. She did not respond to broad-spectrum antibiotics and was treated empirically with trimethoprim-sulphamethoxazole and improved. In the second case, we describe a 76-year-old woman with relapsed CLL who developed recurrent pneumonia after 3 years of treatment with ibrutinib. Presuming that ibrutinib was the cause of pneumonitis with secondary infection, it was stopped with subsequent improvement. The third patient a 67 year-old man died because of severe bilateral necrotizing pneumonia due to invasive aspergillosis and mucormycosis with pulmonary hemorrhage. The fourth patient with relapsed mantle cell lymphoma died because of severe bilateral pneumonia, caused by pseudomonas and candida, despite receiving appropriate antibiotics. From this experience, we hypothesize that the etiology of severe pneumonia associated with ibrutinib treatment is probably multifactorial, involving factors like preexisting immune-suppression, drug induced pneumonitis and infections. We suggest that patients with CLL or other lymphoproliferative disorders with suspected pneumonia during monotherapy with ibrutinib should be very carefully evaluated and need to undergo complete diagnostic workup to establish an exact diagnosis. Understanding which patients with CLL or lymphoma treated with kinase inhibitors are at a

  19. Methotrexate: an effective monotherapy for refractory generalized morphea

    Directory of Open Access Journals (Sweden)

    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

  20. 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.

  1. 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

  2. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

  4. 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.

  5. 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 ⁎ .

  6. 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)

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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.

  9. 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

  10. 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

  11. Oxcarbazepine versus carbamazepine monotherapy for partial onset seizures.

    Science.gov (United States)

    Koch, Marcus W; Polman, Susanne Kl

    2009-10-07

    Partial onset seizures are often treated with the standard antiepileptic drug carbamazepine. Oxcarbazepine is a newer antiepileptic drug related to carbamazepine that is claimed to be better tolerated. To compare efficacy and tolerability of carbamazepine and oxcarbazepine monotherapy for partial onset seizures. We searched the Cochrane Epilepsy Group Specialised Register (4 August 2009), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library issue 3, 2009), MEDLINE (January 1966 to May 2008), reference lists of relevant articles and conference proceedings. We also contacted manufacturers and researchers in the field for published or unpublished data. Blinded and unblinded randomised controlled trials of carbamazepine versus oxcarbazepine monotherapy for partial onset seizures. Both authors independently assessed trial quality, according to the guidelines in the Cochrane Reviewer's Handbook, and extracted information about study population, type of intervention, outcome measures and study design. All analyses in this review are by intention-to-treat. We tested for statistical heterogeneity among the identified studies using the chi-squared test. Three trials (723 participants) were included. Only one trial used adequate outcome measures of efficacy; therefore, the results pertaining to efficacy are based on a single trial, whereas the results pertaining to adverse events are based on all three included trials. There was no overall difference in time to treatment withdrawal between the two drugs (hazard ratio (HR) of oxcarbazepine (OXC) versus carbamazepine (CBZ): 1.04, 95% confidence interval (CI) 0.78 to 1.39). Further analyses showed no significant difference in treatment withdrawal for unacceptable side effects (HR of OXC versus CBZ: 0.85, 95% CI 0.59 to 1.24) and in treatment withdrawal for inadequate seizure control (HR of OXC versus CBZ: 1.33, 95% CI 0.82 to 2.15). Oxcarbazepine and carbamazepine appeared to be similarly effective

  12. 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...

  13. TNFα blockers and infectious risk in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    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.

  14. 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

  15. 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....

  16. 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

  17. 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

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

    Directory of Open Access Journals (Sweden)

    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

  19. 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

  20. 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.

  1. 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.

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

    Science.gov (United States)

    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.

  3. 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.

  4. 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?

  5. 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.

  6. 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

  7. 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 }.

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

    Directory of Open Access Journals (Sweden)

    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

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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....

  14. Comparison of the efficacy of colistin monotherapy and colistin ...

    African Journals Online (AJOL)

    of nosocomial pneumonia and ventilator-associated ... University Medical Faculty Hospital and diagnosed with nosocomial pneumonia/VAP caused by A. baumannii between January. 2009 and ... were to investigate clinical response, bacterial eradication and ... Organ Failure Assessment (SOFA) scores, and the severity of.

  15. 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

  16. 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

  17. Beta-blockers and statins in the context of asthma

    Directory of Open Access Journals (Sweden)

    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.

  18. Respiratory Failure

    Science.gov (United States)

    Respiratory failure happens when not enough oxygen passes from your lungs into your blood. Your body's organs, ... brain, need oxygen-rich blood to work well. Respiratory failure also can happen if your lungs can' ...

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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.

  1. Effects of gap junction blockers on human neocortical synchronization.

    Science.gov (United States)

    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.

  2. 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

  3. 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.

  4. 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.

  5. Heart Failure

    Science.gov (United States)

    Heart failure is a condition in which the heart can't pump enough blood to meet the body's needs. Heart failure does not mean that your heart has stopped ... and shortness of breath Common causes of heart failure are coronary artery disease, high blood pressure and ...

  6. 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...

  7. Are beta-blockers effective in heart failure with preserved ejection fraction?

    Directory of Open Access Journals (Sweden)

    Javier Alegría

    2016-12-01

    Full Text Available Resumen Los betabloqueadores tienen un beneficio demostrado en el tratamiento de la insuficiencia cardíaca con fracción de eyección disminuida. Sin embargo, su rol en pacientes con fracción de eyección preservada no está tan claro. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en múltiples bases de datos, identificamos cuatro revisiones sistemáticas que en conjunto incluyen 19 estudios primarios, entre ellos siete estudios aleatorizados que responden la pregunta de este resumen. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que el uso de betabloqueadores en pacientes con insuficiencia cardiaca con fracción de eyección preservada probablemente resulta en poca o nula diferencia en el riesgo de muerte u hospitalización por cualquier causa.

  8. 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.

    Directory of Open Access Journals (Sweden)

    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.

  9. 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....

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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...

  15. 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...

  16. 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

  17. Contraceptive failure

    DEFF Research Database (Denmark)

    Rasch, Vibeke

    2002-01-01

    Most studies focusing on contraceptive failure in relation to pregnancy have focused on contraceptive failure among women having induced abortions, thereby neglecting those women who, despite contraceptive failure, accept the pregnancy and intend to carry the fetus to term. To get a more complete...... picture of the problem of contraceptive failure, this study focuses on contraceptive failure among women with diverse pregnancy outcomes. In all, 3520 pregnant women attending Odense University Hospital were included: 373 had induced abortions, 435 had spontaneous abortions, 97 had ectopic pregnancies......, and 2614 received antenatal care. The variables studied comprise age, partner relationship, number of births, occupational and economical situation, and contraceptive use.Contraceptive failure, defined as contraceptive use (condom, diaphragm, IUD, oral contraception, or another modern method...

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

    Science.gov (United States)

    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

  19. Heart Failure

    OpenAIRE

    McMurray, John; Ponikowski, Piotr

    2011-01-01

    Heart failure occurs in 3% to 4% of adults aged over 65 years, usually as a consequence of coronary artery disease or hypertension, and causes breathlessness, effort intolerance, fluid retention, and increased mortality. The 5-year mortality in people with systolic heart failure ranges from 25% to 75%, often owing to sudden death following ventricular arrhythmia. Risks of cardiovascular events are increased in people with left ventricular systolic dysfunction (LVSD) or heart failure.

  20. 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

  1. 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.

  2. 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

  3. High-Dose-Rate Brachytherapy as a Monotherapy for Favorable-Risk Prostate Cancer: A Phase II Trial

    Energy Technology Data Exchange (ETDEWEB)

    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

  4. 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.

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

    Science.gov (United States)

    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.

  6. 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.

  7. Metaflumizone is a novel sodium channel blocker insecticide.

    Science.gov (United States)

    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.

  8. Angiotensin receptor blockers & endothelial dysfunction: Possible correlation & therapeutic implications

    Directory of Open Access Journals (Sweden)

    Miroslav Radenkovic

    2016-01-01

    Full Text Available The endothelium is one of the most important constituents of vascular homeostasis, which is achieved through continual and balanced production of different relaxing and contractile factors. When there is a pathological disturbance in release of these products, endothelial dysfunction (ED will probably occur. ED is considered to be the initial step in the development of atherosclerosis. This pathological activation and inadequate functioning of endothelial cells was shown to be to some extent a reversible process, which all together resulted in increased interest in investigation of different beneficial treatment options. To this point, the pharmacological approach, including for example, the use of angiotensin-converting enzyme inhibitors or statins, was clearly shown to be effective in the improvement of ED. One of many critical issues underlying ED represents instability in the balance between nitric oxide and angiotensin II (Ang II production. Considering that Ang II was confirmed to be important for the development of ED, the aim of this review article was to summarize the findings of up to date clinical studies associated with therapeutic application of angiotensin receptor blockers and improvement in ED. In addition, it was of interest to review the pleiotropic actions of angiotensin receptor blockers linked to the improvement of ED. The prospective, randomized, double-blind, placebo or active-controlled clinical trials were identified and selected for the final evaluation.

  9. Reappraisal of role of angiotensin receptor blockers in cardiovascular protection

    Directory of Open Access Journals (Sweden)

    Ram CV

    2011-05-01

    Full Text Available C Venkata S RamTexas Blood Pressure Institute, Clinical Research Institute of Dallas Nephrology Associates; and Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USAAbstract: Angiotensin-converting enzyme inhibitors (ACEIs and angiotensin receptor blockers (ARBs have shown cardioprotective and renoprotective properties. These agents are recommended as first-line therapy for the treatment of hypertension and the reduction of cardiovascular risk. Early studies pointed to the cardioprotective and renoprotective effects of ARBs in high-risk patients. The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET established the clinical equivalence of the cardioprotective and renoprotective effects of telmisartan and ramipril, but did not find an added benefit of the combination over ramipril alone. Similar findings were observed in the Telmisartan Randomized AssessmeNt Study in aCE INtolerant subjects with cardiovascular Disease (TRANSCEND trial conducted in ACEI-intolerant patients. In ONTARGET, telmisartan had a better tolerability profile with similar renoprotective properties compared with ramipril, suggesting a potential clinical benefit over ramipril. The recently completed Olmesartan Reducing Incidence of Endstage Renal Disease in Diabetic Nephropathy Trial (ORIENT and Olmesartan and Calcium Antagonists Randomized (OSCAR studies will further define the role of ARBs in cardioprotection and renoprotection for high-risk patients.Keywords: angiotensin receptor blockers, hypertension, outcomes, clinical trials

  10. 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

  11. 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.

  12. The Hriday Card: A checklist for heart failure

    Directory of Open Access Journals (Sweden)

    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.

  13. THE ROLE OF S-AMLODIPINE IN ARTERIAL HYPERTENSION THERAPY WITH COMBINATION OF CALCIUM CHANNEL BLOCKERS AND BETA-BLOCKERS

    Directory of Open Access Journals (Sweden)

    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.

  14. Beta-blocker under-use in COPD patients

    Directory of Open Access Journals (Sweden)

    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

  15. Heart Failure

    Science.gov (United States)

    ... Other diseases. Chronic diseases — such as diabetes, HIV, hyperthyroidism, hypothyroidism, or a buildup of iron (hemochromatosis) or ... transplantation or support with a ventricular assist device. Prevention The key to preventing heart failure is to ...

  16. 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

  17. 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 ...

  18. 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

  19. 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....

  20. 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

  1. 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

  2. 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....

  3. 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

  4. 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...

  5. 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...

  6. 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-

  7. 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

  8. 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.

  9. 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

  10. The Effects of Enzalutamide Monotherapy on Multiparametric 3T MR Imaging in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Rosanne CV. Van der Roest

    2016-07-01

    Full Text Available The effects of enzalutamide monotherapy on prostate tumor downsizing and multiparametric MRI are currently unknown. Here we present the first case in literature of a patient with high-grade prostate cancer who underwent 3 months of neoadjuvant enzalutamide, for which the effects on mpMRI and histology were determined. Tumor size reduction and downstaging were noted. Neoadjuvant enzalutamide resulted in an increase in ADC value on the DWI-MRI sequences. Histological changes were also observed.

  11. Success of electromagnetic shock wave lithotripter as monotherapy in large renal calculi—Our experience

    OpenAIRE

    K.S. Meitei; S Gupta; A.K. Singh

    2013-01-01

    Objectives: To evaluate the success of shock wave lithotripsy (SWL) as monotherapy for solitary renal stones larger than 2 cm without ureteral stenting. Hence, if our study result demonstrates acceptable success and safety, we can recommend ESWL as a treatment option for patients with large renal calculi. Subjects and methods: This is a prospective study conducted in the Department of Urology, Regional Institute of Medical Sciences, Imphal, India, from January 2011 to December 2012. A tota...

  12. Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis

    OpenAIRE

    Fleischmann, Roy M; Huizinga, Tom W J; Kavanaugh, Arthur F; Wilkinson, Bethanie; Kwok, Kenneth; DeMasi, Ryan; van Vollenhoven, Ronald F

    2016-01-01

    Introduction 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 patients with RA. In this post hoc analysis, we compared efficacy and safety of tofacitinib in patients with early (disease duration

  13. The renin-angiotensin system and its blockers

    Directory of Open Access Journals (Sweden)

    Igić Rajko

    2014-01-01

    Full Text Available Research on the renin-angiotensin system (RAS has contributed significantly to advances in understanding cardiovascular and renal homeostasis and to the treatment of cardiovascular diseases. This review offers a brief history of the RAS with an overview of its major components and their functions, as well as blockers of the RAS, their clinical usage and current research that targets various components of the RAS. Because angiotensin-converting enzyme (ACE metabolizes two biologically active peptides, one in the kallikrein-kinin system (KKS and one in the RAS, it is the essential connection between the two systems. ACE releases very powerful hypertensive agent, angiotensin II and also inactivates strong hypotensive peptide, bradykinin. Inhibition of ACE thus has a dual effect, resulting in decreased angiotensin II and increased bradykinin. We described the KKS as well.

  14. Effect of alpha1-blockers on stentless ureteroscopic lithotripsy

    Directory of Open Access Journals (Sweden)

    Jianguo Zhu

    2016-02-01

    Full Text Available ABSTRACT Objective To evaluate the clinical efficiency of alpha1-adrenergic antagonists on stentless ureteroscopic lithotripsy treating uncomplicated lower ureteral stones. Materials and Methods From January 2007 to January 2013, 84 patients who have uncomplicated lower ureteral stones treated by ureteroscopic intracorporeal lithotripsy with the holmium laser were analyzed. The patients were divided into two groups, group A (44 patients received indwelled double-J stents and group B (40 patients were treated by alpha1-adrenergic antagonists without stents. All cases of group B were treated with alpha1 blocker for 1 week. Results The mean operative time of group A was significantly longer than group B. The incidences of hematuria, flank/abdominal pain, frequency/urgency after surgery were statistically different between both groups. The stone-free rate of each group was 100%. Conclusions The effect of alpha1-adrenergic antagonists is more significant than indwelling stent after ureteroscopic lithotripsy in treating uncomplicated lower ureteral stones.

  15. 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,

  16. Alpha-adrenergic blocker mediated osteoblastic stem cell differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yoon Jung [Craniomaxillofacial Reconstructive Sciences Major, College of Dentistry, Seoul National University, Seoul 110-749 (Korea, Republic of); Lee, Jue Yeon [Craniomaxillofacial Reconstructive Sciences Major, College of Dentistry, Seoul National University, Seoul 110-749 (Korea, Republic of); Research Center, Nano Intelligent Biomedical Engineering Corporation (NIBEC), Seoul (Korea, Republic of); Lee, Seung Jin [Department of Industrial Pharmacy, College of Pharmacy, Ewha Womans University, Seoul (Korea, Republic of); Research Center, Nano Intelligent Biomedical Engineering Corporation (NIBEC), Seoul (Korea, Republic of); Chung, Chong-Pyoung [Department of Periodontology, School of Dentistry, Seoul National University, Seoul (Korea, Republic of); Research Center, Nano Intelligent Biomedical Engineering Corporation (NIBEC), Seoul (Korea, Republic of); Park, Yoon Jeong, E-mail: parkyj@snu.ac.kr [Craniomaxillofacial Reconstructive Sciences Major, College of Dentistry, Seoul National University, Seoul 110-749 (Korea, Republic of); Research Center, Nano Intelligent Biomedical Engineering Corporation (NIBEC), Seoul (Korea, Republic of)

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer Doxazocin directly up-regulated bone metabolism at a low dose. Black-Right-Pointing-Pointer Doxazocin induced osteoblastic stem cell differentiation without affecting cell proliferation. Black-Right-Pointing-Pointer This osteogenic stem cell differentiation is mediated by ERK-signal dependent pathway. -- Abstract: Recent researches have indicated a role for antihypertensive drugs including alpha- or beta-blockers in the prevention of bone loss. Some epidemiological studies reported the protective effects of those agents on fracture risk. However, there is limited information on the association with those agents especially at the mechanism of action. In the present study, we investigated the effects of doxazosin, an alpha-blocker that is clinically used for the treatment of benign prostatic hyperplasia (BPH) along with antihypertensive medication, on the osteogenic stem cell differentiation. We found that doxazosin increased osteogenic differentiation of human mesenchymal stem cells, detected by Alizarin red S staining and calcein. Doxazosin not only induced expression of alkaline phosphatase, type I collagen, osteopontin, and osteocalcin, it also resulted in increased phosphorylation of extracellular signal-regulated kinase (ERK1/2), a MAP kinase involved in osteoblastic differentiation. Treatment with U0126, a MAP kinase inhibitor, significantly blocked doxazosin-induced osteoblastic differentiation. Unrelated to activation of osteogenic differentiation by doxazosin, we found that there were no significant changes in adipogenic differentiation or in the expression of adipose-specific genes, including peroxisome proliferator-activated receptor {gamma}, aP2, or LPL. In this report, we suggest that doxazosin has the ability to increase osteogenic cell differentiation via ERK1/2 activation in osteogenic differentiation of adult stem cells, which supports the protective effects of antihypertensive drug on fracture risk and

  17. Alpha-adrenergic blocker mediated osteoblastic stem cell differentiation

    International Nuclear Information System (INIS)

    Choi, Yoon Jung; Lee, Jue Yeon; Lee, Seung Jin; Chung, Chong-Pyoung; Park, Yoon Jeong

    2011-01-01

    Highlights: ► Doxazocin directly up-regulated bone metabolism at a low dose. ► Doxazocin induced osteoblastic stem cell differentiation without affecting cell proliferation. ► This osteogenic stem cell differentiation is mediated by ERK-signal dependent pathway. -- Abstract: Recent researches have indicated a role for antihypertensive drugs including alpha- or beta-blockers in the prevention of bone loss. Some epidemiological studies reported the protective effects of those agents on fracture risk. However, there is limited information on the association with those agents especially at the mechanism of action. In the present study, we investigated the effects of doxazosin, an alpha-blocker that is clinically used for the treatment of benign prostatic hyperplasia (BPH) along with antihypertensive medication, on the osteogenic stem cell differentiation. We found that doxazosin increased osteogenic differentiation of human mesenchymal stem cells, detected by Alizarin red S staining and calcein. Doxazosin not only induced expression of alkaline phosphatase, type I collagen, osteopontin, and osteocalcin, it also resulted in increased phosphorylation of extracellular signal-regulated kinase (ERK1/2), a MAP kinase involved in osteoblastic differentiation. Treatment with U0126, a MAP kinase inhibitor, significantly blocked doxazosin-induced osteoblastic differentiation. Unrelated to activation of osteogenic differentiation by doxazosin, we found that there were no significant changes in adipogenic differentiation or in the expression of adipose-specific genes, including peroxisome proliferator-activated receptor γ, aP2, or LPL. In this report, we suggest that doxazosin has the ability to increase osteogenic cell differentiation via ERK1/2 activation in osteogenic differentiation of adult stem cells, which supports the protective effects of antihypertensive drug on fracture risk and according to our data doxazosin might be useful for application in the field of bone

  18. 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.

  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.

  20. 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.

  1. 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

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

    Science.gov (United States)

    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.

  3. 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...

  4. 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....

  5. 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

  6. 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...

  7. Impact of statins and beta-blocker therapy on mortality after coronary artery bypass graft surgery

    Science.gov (United States)

    Blackstone, Eugene; Kapadia, Samir R.

    2015-01-01

    Background We conducted a retrospective cohort study of patients after first-time isolated coronary artery bypass graft surgery (CABG) and assessed the impact of a discharge regimen including beta-blockers and statin therapy and their relationship to long-term all cause mortality and major adverse cardiovascular events (MACE). Methods We identified patients age >18 years, undergoing first time isolated CABG from 1993 to 2005. Patients were identified using the Cardiovascular Information Registry (CVIR). We collected follow-up information at 30, 60, 90 days and yearly follow-up. The registry is approved for use in research by the institutional review broad. Results We identified 5,205 patients who underwent single isolated CABG between January 1993 and December 2005. The mean age was 64.5±9.7 years and over 70% were male. There was a significant difference in the low density lipoproteins (LDL) concentration between those with or without statin medications (134±41.9 mg/dL) (no statin) vs. 126±44.8 mg/dL (with statin), P=0.001. A discharge regimen with statin therapy was associated with and overall reduction in 30 day, 1 year and long-term mortality. In addition, overall the triple ischemic endpoint of death, myocardial infarction (MI) and stroke was also significantly lower in the statin vs. no-statin group. In addition, statin and beta-blockers exerted synergistic effect on overall mortality outcomes short-term and in the long-term. We note that the predictors of overall death include no therapy with statin therapy and age [hazard ratios (HR) 1.1, 95% CI: 1.04-1.078, P<0.001] and presence of renal failure (HR 2.0, P=0.005). The estimated 11-year Kaplan Meier curves for mortality between the two groups starts to diverge immediately post discharge after single isolated CABG and continue to diverge through out the follow-up period. Conclusions A post-discharge regimen of statins independently reduces overall and 1 year mortality. These results confirm those of

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

    Science.gov (United States)

    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.

  9. 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.

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

    Science.gov (United States)

    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

  11. 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...

  12. 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...

  13. 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.

  14. 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

  15. 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.

  16. 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...

  17. Failure Modes

    DEFF Research Database (Denmark)

    Jakobsen, K. P.; Burcharth, H. F.; Ibsen, Lars Bo

    1999-01-01

    The present appendix contains the derivation of ten different limit state equations divided on three different failure modes. Five of the limit state equations can be used independently of the characteristics of the subsoil, whereas the remaining five can be used for either drained or undrained s...

  18. [Assessment of the utilization of angiotensin receptor blockers in hypertension].

    Science.gov (United States)

    Peña Cabia, S; Ricote Lobera, I; Santos Mena, B; Hidalgo Correas, F J; Climent Florez, B; García Díaz, B

    2013-01-01

    To assess the degree in which the utilization of angiotensin receptor blockers (ARBs) in our Healthcare Area fits the criteria proposed by the Autonomous Community of Madrid (CAM) before setting «Plan de Actuación de ARA-II» («Action Plan ARA-II»). To study the indications for which are prescribed and to identify those factors that can show influence in prescription. Drug utilization study of the type indication-prescription, descriptive and transversal, for which ARBs-treated and hypertensive patients admitted to a University General Hospital for a study period of 3 months were selected. Based on the clinical situations summarized in the CAM Document «Criterios para establecer el lugar en la terapéutica de los antagonistas de los receptores de la angiotensina II» («Criteria for the place of angiotensin receptor blockers in the therapeutic»), a percentage of patients with «appropriate prescription» and «inadequate prescription« of ARBs was calculated and analyzed in order to determine if the age and the sex were related to the type of prescription or the main indications for which they had been prescribed. Out of the 153 patients included in the study, 67.3% had a «inadequate prescription«, 47.6% of them due to an ARBs prescription as the first drug inhibitor of the reninangiotensin- aldosterone system and 34.0% owing to a poor control of blood pressure with angiotensin-converting enzyme inhibitors (ACEi). There were no statistically significant differences found either by age or sex in the type of prescription or in the main indications for which they were prescribed. The adequacy of the criteria for the utilisation of ARBs Document occurred in 32.7% of cases. In addition, factors such as age and sex did not seem to affect the type of prescription. Misconceptions of superiority of ARBs versus ACEi were evidenced as well. Copyright © 2013 SEFH. Published by AULA MEDICA. All rights reserved.

  19. Consensus statement on management of chronic heart failure in India

    Directory of Open Access Journals (Sweden)

    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

  20. 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.

  1. 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

  2. Types of Heart Failure

    Science.gov (United States)

    ... Introduction Types of Heart Failure Classes of Heart Failure Heart Failure in Children Advanced Heart Failure • Causes and ... and procedures related to heart disease and stroke. Heart Failure Questions to Ask Your Doctor Use these questions ...

  3. Classes of Heart Failure

    Science.gov (United States)

    ... Introduction Types of Heart Failure Classes of Heart Failure Heart Failure in Children Advanced Heart Failure • Causes and ... and Advanced HF • Tools and Resources • Personal Stories Heart Failure Questions to Ask Your Doctor Use these questions ...

  4. Beta blockers, norepinephrine, and cancer: an epidemiological viewpoint

    Directory of Open Access Journals (Sweden)

    Fitzgerald PJ

    2012-06-01

    Full Text Available Paul J FitzgeraldThe Zanvyl Krieger Mind/Brain Institute, Solomon H Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD, USAAbstract: There is growing evidence that the neurotransmitter norepinephrine (NE and its sister molecule epinephrine (EPI (adrenaline affect some types of cancer. Several recent epidemiological studies have shown that chronic use of beta blocking drugs (which antagonize NE/EPI receptors results in lower recurrence, progression, or mortality of breast cancer and malignant melanoma. Preclinical studies have shown that manipulation of the levels or receptors of NE and EPI with drugs affects experimentally induced cancers. Psychological stress may play an etiological role in some cases of cancer (which has been shown epidemiologically, and this could be partly mediated by NE and EPI released by the sympathetic nervous system as part of the body’s “fight or flight” response. A less well-appreciated phenomenon is that the genetic tone of NE/EPI may play a role in cancer. NE and EPI may affect cancer by interacting with molecular pathways already implicated in abnormal cellular replication, such as the P38/MAPK pathway, or via oxidative stress. NE/EPI-based drugs other than beta blockers also may prevent or treat various types of cancer, as may cholinesterase inhibitors that inhibit the sympathetic nervous system, which could be tested epidemiologically.Keywords: clonidine, guanfacine, aspirin, acetylcholine, epinephrine, adrenaline, sympathetic nervous system, parasympathetic nervous system, inflammation

  5. Angiotensin Receptor Blockers: Cardiovascular Protection in the Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Prakash C Deedwania

    2006-03-01

    Full Text Available It is well recognised that the metabolic syndrome, a constellation of risk factors including obesity, hypertension, insulin resistance and dyslipidaemia, is associated with an increased risk of cardiovascular complications and the development of Type 2 diabetes. Consequently, timely identification and management of all components of the metabolic syndrome is warranted. In particular, guidelines have emphasised the importance of targeting elevated blood pressure (BP and dyslipidaemia as a method of reducing global cardiovascular risk.Findings from the Valsartan Antihypertensive Long-term Use Evaluation (VALUE trial show that the angiotensin receptor blocker, valsartan, reduces cardiovascular events and the development of Type 2 diabetes in high-risk individuals. This profile is being further explored in the ongoing Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR trial.Given the potential advantages to patients and physicians of tackling more than one of the components of the metabolic syndrome, antihypertensive agents such as valsartan would appear to be an important addition to the management of vulnerable patients at high risk of cardiovascular events.

  6. 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.

  7. QT interval prolongation related to psychoactive drug treatment: a comparison of monotherapy versus polytherapy

    Directory of Open Access Journals (Sweden)

    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

  8. Failure Analysis

    International Nuclear Information System (INIS)

    Iorio, A.F.; Crespi, J.C.

    1987-01-01

    After ten years of operation at the Atucha I Nuclear Power Station a gear belonging to a pressurized heavy water reactor refuelling machine, failed. The gear box was used to operate the inlet-outlet heavy-water valve of the machine. Visual examination of the gear device showed an absence of lubricant and that several gear teeth were broken at the root. Motion was transmitted with a speed-reducing device with controlled adjustable times in order to produce a proper fitness of the valve closure. The aim of this paper is to discuss the results of the gear failure analysis in order to recommend the proper solution to prevent further failures. (Author)

  9. Intravenous Immunoglobulin Monotherapy for Granulomatous Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency.

    Science.gov (United States)

    Hasegawa, Mizue; Sakai, Fumikazu; Okabayashi, Asako; Sato, Akitoshi; Yokohori, Naoko; Katsura, Hideki; Asano, Chihiro; Kamata, Toshiko; Koh, Eitetsu; Sekine, Yasuo; Hiroshima, Kenzo; Ogura, Takashi; Takemura, Tamiko

    2017-11-01

    Common variable immunodeficiency (CVID) is a heterogeneous subset of immunodeficiency disorders. Recurrent bacterial infection is the main feature of CVID, but various non-infectious complications can occur. A 42-year-old woman presented with cough and abnormal chest X-ray shadows. Laboratory tests showed remarkable hypogammaglobulinemia. Computed tomography revealed multiple consolidation and nodules on the bilateral lung fields, systemic lymphadenopathy, and splenomegaly. A surgical lung biopsy specimen provided the final diagnosis of lymphoproliferative disease in CVID, which was grouped under the term granulomatous lymphocytic interstitial lung disease. Interestingly, the lung lesions of this case resolved immediately after the initiation of intravenous immunoglobulin monotherapy.

  10. 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

  11. 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.

    Science.gov (United States)

    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

  12. 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.

  13. Adherence to placebo and mortality in the Beta Blocker Evaluation of Survival Trial (BEST).

    Science.gov (United States)

    Pressman, Alice; Avins, Andrew L; Neuhaus, John; Ackerson, Lynn; Rudd, Peter

    2012-05-01

    Randomized controlled trials have reported lower mortality among patients who adhere to placebo compared with those who do not. We explored this phenomenon by reanalyzing data from the placebo arm of the Beta Blocker Evaluation of Survival Trial (BEST), a randomized, double-blind, placebo-controlled trial of bucindolol and mortality. Our primary aim was to measure and explain the association between adherence to placebo and total mortality among the placebo-allocated participants in the BEST trial. Secondary aims included assessment of the association between placebo adherence and cause-specific mortality. Participants with "higher placebo adherence" were defined as having taken at least 75% of their placebo study medication over the entire course of each individual's participation in the study, while those with "lower placebo adherence" took <75%. Primary outcome was in-study all-cause mortality. To account for confounding, we adjusted for all available modifiable, non-modifiable and psychosocial variables. Adherent participants had a significantly lower total mortality compared to less-adherent participants (HR=0.61, 95% Confidence Interval: 0.46-0.82). Adjusting for available confounders did not change the magnitude or significance of the estimates. When considering cause-specific mortality, CVD and pump failure showed similar associations. Analyses of the BEST trial data support a strong association between adherence to placebo study medication and total mortality. While probably not due to publication bias or simple confounding by healthy lifestyle factors, the underlying explanation for the association remains a mystery. Prospective examination of this association is necessary to better understand the underlying mechanism of this observation. Copyright © 2012 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    2017-01-01

    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 approa...

  15. Effect of glucose infusion on endurance performance after beta-adrenoceptor blocker administration

    NARCIS (Netherlands)

    van Baak, M.A.; Mooij, J.M.

    1994-01-01

    Effect of glucose infusion on endurance performance after beta-adrenoceptor blocker administration. Van Baak MA, Mooij JM. Department of Human Biology, University of Limburg, Maastricht, The Netherlands. To investigate the effect of glucose (Glc) infusion on endurance performance after

  16. 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.

  17. Dutch pediatricians' views on the use of neuromuscular blockers for dying neonates: a qualitative study

    NARCIS (Netherlands)

    ten Cate, K.; van de Vathorst, S.

    2015-01-01

    To assess Dutch pediatricians' views on neuromuscular blockers for dying neonates. Qualitative study involving in-depth interviews with 10 Dutch pediatricians working with severely ill neonates. Data were analyzed using appropriate qualitative research techniques. Participants explained their view

  18. 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...

  19. 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...

  20. 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....

  1. 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).

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. Double-blind, randomized, controlled trial of rasagiline as monotherapy in early Parkinson's disease patients.

    Science.gov (United States)

    Stern, Matthew B; Marek, Kenneth L; Friedman, Joseph; Hauser, Robert A; LeWitt, Peter A; Tarsy, Daniel; Olanow, C Warren

    2004-08-01

    Rasagiline (N-propargyl-1(R)-aminoindan) mesylate is a potent, selective, and irreversible monoamine oxidase-B inhibitor. This study was designed to evaluate the safety, tolerability, and preliminary efficacy of rasagiline monotherapy in early Parkinson's disease (PD) patients not receiving levodopa. The study was performed as a multicenter, parallel-group, double-blind, randomized, placebo-controlled, 10-week study. Fifty-six PD patients were randomly assigned to rasagiline mesylate 1, 2, or 4 mg once daily, or placebo. A 3-week dose-escalation period was followed by a 7-week maintenance phase. At week 10, the mean (+/-SE) changes from baseline in total Unified Parkinson's Disease Rating Scale (UPDRS) score were -1.8 (+/-1.3), -3.6 (+/-1.7), -3.6 (+/-1.2), and -0.5 (+/-0.8) in the rasagiline 1, 2, and 4 mg/day and placebo groups, respectively. Analysis of responders showed that 28% of patients (12 of 43) receiving rasagiline had an improvement in total UPDRS score of greater than 30%, compared with none of the patients receiving placebo (P rasagiline-treated and placebo-treated patients were similar. These results suggest that rasagiline monotherapy is well tolerated and efficacious in early PD. Copyright 2004 Movement Disorder Society

  8. Aspirin mono-therapy continuation does not result in more bleeding after knee arthroplasty.

    Science.gov (United States)

    Schwab, Pierre-Emmanuel; Lavand'homme, Patricia; Yombi, JeanCyr; Thienpont, Emmanuel

    2017-08-01

    Current clinical practice guidelines sometimes still recommend stopping aspirin five to seven days before knee arthroplasty surgery. Literature regarding multimodal blood management and continuation of anti-platelet therapy in this type of surgery is scant. The study hypothesis was that knee arthroplasty under low-dose aspirin mono-therapy continuation does not cause more total blood loss than knee arthroplasty performed without aspirin. Blood loss would be measured by haemoglobin (Hb) and haematocrit (HTC) levels drop at day 2 or day 4 for patients who benefit from multimodal bleeding control measures. A database of all patients undergoing knee arthroplasty between 2006 and 2014 was analysed. Demographic, surgical and complete blood workup data were collected. A retrospective comparison study analysed both groups in terms of blood loss, by mean calculated blood loss as haemoglobin or haematocrit drop between the preoperative Nadir value and the postoperative day 2 and 4 value. A group of 198 (44 UKA and 154 TKA) patients underwent surgery without interrupting their aspirin therapy for cardiovascular prevention. Mean (SD) age was 71 (8) and the mean (SD) BMI was 29 (5.5) kg/m 2 . The control group consisted of 403 (102 UKA and 301 TKA) patients who were not under aspirin, or any other anti-platelet agent. Mean (SD) age was 65 (10) (p aspirin mono-therapy for cardiovascular prevention. III.

  9. Impact of national guidelines on brachytherapy monotherapy practice patterns for prostate cancer.

    Science.gov (United States)

    Tseng, Yolanda D; Paciorek, Alan T; Martin, Neil E; D'Amico, Anthony V; Cooperberg, Matthew R; Nguyen, Paul L

    2014-03-15

    In 1999 and 2000, 2 national guidelines recommended brachytherapy monotherapy (BT) primarily for treatment of low-risk prostate cancer but not high-risk prostate cancer. This study examined rates of BT use before and after publication of these guidelines, as compared with 4 other treatment options. From 1990 to 2011, 8128 men with localized prostate cancer (≤ T3cN0M0) were treated definitively within the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry with 1 of 5 primary treatments: BT, external beam radiotherapy (EBRT), EBRT with androgen deprivation therapy, EBRT+BT, or radical prostatectomy. Men were categorized into low-, intermediate-, and high-risk groups based on the guidelines' risk-group definitions. Within each risk group, logistic regression was used to estimate odds ratios (OR) comparing BT with other treatment options between the 1990-1998 and 1999-2011 periods, adjusting for age, disease characteristics, and clinic type. In total, 1117 men received BT alone for low- (n = 658), intermediate- (n = 244), or high-risk disease (n = 215). BT comprised 6.1% of all treatments in 1990-1998 versus 16.6% in 1999-2011 (P guidelines did not appear to influence practice patterns, as BT monotherapy use increased relative to other treatments from the 1990-1998 to 1999-2011 periods in unfavorable risk groups including men with high-risk prostate cancer. © 2013 American Cancer Society.

  10. Extracorporeal shock wave lithotripsy (ESWL) monotherapy in children: Predictors of successful outcome.

    Science.gov (United States)

    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.

  11. Rapid and Complete Remission of Metastatic Adrenocortical Carcinoma Persisting 10 Years After Treatment With Mitotane Monotherapy

    Science.gov (United States)

    Ghorayeb, Nada El; Rondeau, Geneviève; Latour, Mathieu; Cohade, Christian; Olney, Harold; Lacroix, André; Perrotte, Paul; Sabourin, Alexis; Mazzuco, Tania L; Bourdeau, Isabelle

    2016-01-01

    Abstract Mitotane has been used for more than 5 decades as therapy for adrenocortical carcinoma (ACC). However its mechanism of action and the extent of tumor response remain incompletely understood. To date no cases of rapid and complete remission of metastatic ACC with mitotane monotherapy has been reported. A 52-year-old French Canadian man presented with metastatic disease 2 years following a right adrenalectomy for stage III nonsecreting ACC. He was started on mitotane which was well tolerated despite rapid escalation of the dose. The patient course was exceptional as he responded to mitotane monotherapy after only few months of treatment. Initiation of chemotherapy was not needed and he remained disease-free with good quality of life on low maintenance dose of mitotane during the following 10 years. A germline heterozygous TP53 exon 4 polymorphism c.215C>G (p. Pro72Arg) was found. Immunohistochemical stainings for IGF-2 and cytoplasmic β-catenin were positive. Advanced ACC is an aggressive disease with poor prognosis and the current therapeutic options remain limited. These findings suggest that mitotane is a good option for the treatment of metastatic ACC and might result in rapid complete remission in selected patients. PMID:27043680

  12. Identifying a predictive model for response to atypical antipsychotic monotherapy treatment in south Indian schizophrenia patients.

    Science.gov (United States)

    Gupta, Meenal; Moily, Nagaraj S; Kaur, Harpreet; Jajodia, Ajay; Jain, Sanjeev; Kukreti, Ritushree

    2013-08-01

    Atypical antipsychotic (AAP) drugs are the preferred choice of treatment for schizophrenia patients. Patients who do not show favorable response to AAP monotherapy are subjected to random prolonged therapeutic treatment with AAP multitherapy, typical antipsychotics or a combination of both. Therefore, prior identification of patients' response to drugs can be an important step in providing efficacious and safe therapeutic treatment. We thus attempted to elucidate a genetic signature which could predict patients' response to AAP monotherapy. Our logistic regression analyses indicated the probability that 76% patients carrying combination of four SNPs will not show favorable response to AAP therapy. The robustness of this prediction model was assessed using repeated 10-fold cross validation method, and the results across n-fold cross-validations (mean accuracy=71.91%; 95%CI=71.47-72.35) suggest high accuracy and reliability of the prediction model. Further validations of these results in large sample sets are likely to establish their clinical applicability. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. 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.

  14. 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...

  15. Heart failure - tests

    Science.gov (United States)

    CHF - tests; Congestive heart failure - tests; Cardiomyopathy - tests; HF - tests ... the best test to: Identify which type of heart failure (systolic, diastolic, valvular) Monitor your heart failure and ...

  16. 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

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  19. Heart failure - home monitoring

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000113.htm Heart failure - home monitoring To use the sharing features on ... your high blood pressure Fast food tips Heart failure - discharge Heart failure - fluids and diuretics Heart failure - what to ...

  20. 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.

  1. 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.

  2. 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

  3. 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)

  4. 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

  5. Nationwide, Multicenter, Retrospective Study on High-Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yoshioka, Yasuo, E-mail: yoshioka@radonc.med.osaka-u.ac.jp [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka (Japan); Kotsuma, Tadayuki [Department of Radiation Oncology, Osaka National Hospital, Osaka (Japan); Komiya, Akira [Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama (Japan); Department of Urology, Chiba University Hospital, Chiba (Japan); Kariya, Shinji [Department of Radiology, Kochi Medical School, Kochi (Japan); Konishi, Koji [Department of Radiation Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Nonomura, Norio [Department of Urology, Osaka University Graduate School of Medicine, Osaka (Japan); Ogawa, Kazuhiko [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka (Japan); Tanaka, Eiichi [Department of Radiation Oncology, Osaka National Hospital, Osaka (Japan); Nishimura, Kensaku [Department of Urology, Osaka National Hospital, Osaka (Japan); Fujiuchi, Yasuyoshi; Kitamura, Hiroshi [Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama (Japan); Yamagami, Takuji [Department of Radiology, Kochi Medical School, Kochi (Japan); Yamasaki, Ichiro [Department of Urology, Kochi Medical School, Kochi (Japan); Nishimura, Kazuo [Department of Urology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Teshima, Teruki [Department of Radiation Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Nakamura, Katsumasa [Department of Radiation Oncology, Hamamatsu University School of Medicine, Shizuoka (Japan); Itami, Jun [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan)

    2017-04-01

    Purpose: To present, analyze, and discuss results of a nationwide, multicenter, retrospective study on high-dose-rate brachytherapy (HDR-BT) as monotherapy for low-, intermediate-, and high-risk prostate cancer. Methods and Materials: From 1995 through 2013, 524 patients, 73 (14%) with low-risk, 207 (40%) with intermediate-risk, and 244 (47%) with high-risk prostate cancer, were treated with HDR-BT as monotherapy at 5 institutions in Japan. Dose fractionations were 27 Gy/2 fractions for 69 patients (13%), 45.5 Gy/7 fractions for 168 (32%), 49 Gy/7 fractions for 149 (28%), 54 Gy/9 fractions for 130 (25%), and others for 8 (2%). Of these patients, 156 (30%) did not receive androgen deprivation therapy, and 202 patients (39%) did receive androgen deprivation therapy <1 year, 112 (21%) for 1-3 years, and 54 (10%) for >3 years. Median follow-up time was 5.9 years (range, 0.4-18.1 years), with a minimum of 2 years for surviving patients. Results: After 5 years, respective actuarial rates of no biochemical evidence of disease, overall survival, cause-specific survival, and metastasis-free survival for all patients were 92%, 97%, 99%, and 94%. For low/intermediate/high-risk patients, the 5-year no biochemical evidence of disease rates were 95%/94%/89%, the 5-year overall survival rates were 98%/98%/94%, the 5-year cause-specific survival rates were 98%/100%/98%, and the 5-year metastasis-free survival rates were 98%/95%/90%, respectively. The cumulative incidence of late grade 2 to 3 genitourinary toxicity at 5 years was 19%, and that of late grade 3 was 1%. The corresponding incidences of gastrointestinal toxicity were 3% and 0% (0.2%). No grade 4 or 5 of either type of toxicity was detected. Conclusions: The findings of this nationwide, multicenter, retrospective study demonstrate that HDR-BT as monotherapy was safe and effective for all patients with low-, intermediate-, and high-risk prostate cancer.

  6. Nationwide, Multicenter, Retrospective Study on High-Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Yoshioka, Yasuo; Kotsuma, Tadayuki; Komiya, Akira; Kariya, Shinji; Konishi, Koji; Nonomura, Norio; Ogawa, Kazuhiko; Tanaka, Eiichi; Nishimura, Kensaku; Fujiuchi, Yasuyoshi; Kitamura, Hiroshi; Yamagami, Takuji; Yamasaki, Ichiro; Nishimura, Kazuo; Teshima, Teruki; Nakamura, Katsumasa; Itami, Jun

    2017-01-01

    Purpose: To present, analyze, and discuss results of a nationwide, multicenter, retrospective study on high-dose-rate brachytherapy (HDR-BT) as monotherapy for low-, intermediate-, and high-risk prostate cancer. Methods and Materials: From 1995 through 2013, 524 patients, 73 (14%) with low-risk, 207 (40%) with intermediate-risk, and 244 (47%) with high-risk prostate cancer, were treated with HDR-BT as monotherapy at 5 institutions in Japan. Dose fractionations were 27 Gy/2 fractions for 69 patients (13%), 45.5 Gy/7 fractions for 168 (32%), 49 Gy/7 fractions for 149 (28%), 54 Gy/9 fractions for 130 (25%), and others for 8 (2%). Of these patients, 156 (30%) did not receive androgen deprivation therapy, and 202 patients (39%) did receive androgen deprivation therapy 3 years. Median follow-up time was 5.9 years (range, 0.4-18.1 years), with a minimum of 2 years for surviving patients. Results: After 5 years, respective actuarial rates of no biochemical evidence of disease, overall survival, cause-specific survival, and metastasis-free survival for all patients were 92%, 97%, 99%, and 94%. For low/intermediate/high-risk patients, the 5-year no biochemical evidence of disease rates were 95%/94%/89%, the 5-year overall survival rates were 98%/98%/94%, the 5-year cause-specific survival rates were 98%/100%/98%, and the 5-year metastasis-free survival rates were 98%/95%/90%, respectively. The cumulative incidence of late grade 2 to 3 genitourinary toxicity at 5 years was 19%, and that of late grade 3 was 1%. The corresponding incidences of gastrointestinal toxicity were 3% and 0% (0.2%). No grade 4 or 5 of either type of toxicity was detected. Conclusions: The findings of this nationwide, multicenter, retrospective study demonstrate that HDR-BT as monotherapy was safe and effective for all patients with low-, intermediate-, and high-risk prostate cancer.

  7. A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis.

    Science.gov (United States)

    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.

  8. Resolution of non-alcoholic steatohepatitis by rosuvastatin monotherapy in patients with metabolic syndrome.

    Science.gov (United States)

    Kargiotis, Konstantinos; Athyros, Vasilios G; Giouleme, Olga; Katsiki, Niki; Katsiki, Evangelia; Anagnostis, Panagiotis; Boutari, Chrysoula; Doumas, Michael; Karagiannis, Asterios; Mikhailidis, Dimitri P

    2015-07-07

    To investigate the effect of rosuvastatin monotherapy on non-alcoholic steatohepatitis (NASH). At present there is no effective treatment for non-alcoholic fatty liver disease or its advanced form NASH. This prospective study included 20 biopsy proven patients with NASH, metabolic syndrome (MetS) and dyslipidaemia. Biochemical parameters of the blood of the patients and an ultrasonography of the liver were performed at baseline. Then patients received lifestyle advice and were treated for a 12 mo period with rosuvastatin (10 mg/d) monotherapy. Patients were re-evaluated during the study at 3 mo intervals, during which biochemical parameters of the blood were measured including liver enzymes. A repeat biopsy and ultrasonography of the liver were performed at the end of the study in all 20 patients. Changes in liver enzymes, fasting plasma glucose, serum creatinine, serum uric acid (SUA), high sensitivity C reactive protein (hsCRP) and lipid profile were assessed every 3 mo. The primary endpoint was the resolution of NASH and the secondary endpoints were the changes in liver enzyme and lipid values. The repeat liver biopsy and ultrasonography showed complete resolution of NASH in 19 patients, while the 20(th), which had no improvement but no deterioration either, developed arterial hypertension and substantial rise in triglyceride levels during the study, probably due to changes in lifestyle including alcohol abuse. Serum alanine transaminase, aspartate transaminase, and γ-glutamyl transpeptidase were normalised by the 3(rd) treatment month (ANOVA P < 0.001), while alkaline phosphatase activities by the 6(th) treatment month (ANOVA, P = 0.01). Fasting plasma glucose and glycated haemoglobin were significantly reduced (P < 0.001). Lipid values were normalised by the 3(rd) treatment month. No patient had MetS by the 9(th) treatment month. Body mass index and waist circumference remained unchanged during the study. Thus, changes in liver pathology and function should

  9. 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/.

  10. Dramatic Clinical Response of Relapsed Metastatic Extramammary Paget’s Disease to Trastuzumab Monotherapy

    Directory of Open Access Journals (Sweden)

    S. Wakabayashi

    2012-01-01

    Full Text Available We report the first case of 68-year-old Japanese woman with metastatic HER2-positive extramammary Paget’s disease that showed the validity of trastuzumab monotherapy. We administered trastuzumab at a loading dose of 8 mg/kg i.v., followed by a 6 mg/kg maintenance dose every three weeks according to a protocol for HER2-positive metastatic breast cancers and a near-complete response was achieved after the tenth infusion. The patient experienced a moderate headache and flushing during the first infusion, but had no advanced effects during subsequent infusions with ibuprofen and d-chlorpheniramine maleate. Given the dramatic response, the patient has had 17 infusions of trastuzumab with no disease progression. Thus, trastuzumab has few side effects and is well tolerated for elderly patients. It may become a new choice of the adjubant therapy of this disease.

  11. Combination With Low-dose Dextromethorphan Improves the Effect of Amlodipine Monotherapy in Clinical Hypertension

    Science.gov (United States)

    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

  12. 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

  13. Comparison of the Efficacy of Glimepiride, Metformin, and Rosiglitazone Monotherapy in Korean Drug-Naïve Type 2 Diabetic Patients: The Practical Evidence of Antidiabetic Monotherapy Study

    Directory of Open Access Journals (Sweden)

    Kun Ho Yoon

    2011-02-01

    Full Text Available BackgroundAlthough many anti-diabetic drugs have been used to control hyperglycemia for decades, the efficacy of commonly-used oral glucose-lowering agents in Korean type 2 diabetic patients has yet to be clearly demonstrated.MethodsWe evaluated the efficacy of glimepiride, metformin, and rosiglitazone as initial treatment for drug-naïve type 2 diabetes mellitus patients in a 48-week, double-blind, randomized controlled study that included 349 Korean patients. Our primary goal was to determine the change in HbA1c levels from baseline to end point. Our secondary goal was to evaluate changes in fasting plasma glucose (FPG levels, body weight, frequency of adverse events, and the proportion of participants achieving target HbA1c levels.ResultsHbA1c levels decreased from 7.8% to 6.9% in the glimepiride group (P<0.001, from 7.9% to 7.0% in the metformin group (P<0.001, and from 7.8% to 7.0% (P<0.001 in the rosiglitazone group. Glimepiride and rosiglitazone significantly increased body weight and metformin reduced body weight during the study period. Symptomatic hypoglycemia was more frequent in the glimepiride group and diarrhea was more frequent in the metformin group.ConclusionThe efficacy of glimepiride, metformin, and rosiglitazone as antidiabetic monotherapies in drug-naïve Korean type 2 diabetic patients was similar in the three groups, with no statistical difference. This study is the first randomized controlled trial to evaluate the efficacy of commonly-used oral hypoglycemic agents in Korean type 2 diabetic patients. An additional subgroup analysis is recommended to obtain more detailed information.

  14. 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.

  15. Malformation risks of antiepileptic drug monotherapies in pregnancy: updated results from the UK and Ireland Epilepsy and Pregnancy Registers.

    LENUS (Irish Health Repository)

    Campbell, E

    2014-09-01

    Antiepileptic drug (AED) exposure during pregnancy increases the risk of major congenital malformations (MCMs). The magnitude of this risk varies by AED exposure. Here we provide updated results from the UK Epilepsy and Pregnancy Register of the risk of MCMs after monotherapy exposure to valproate, carbamazepine and lamotrigine.

  16. Effectiveness of and obstacles to antibiotic streamlining to amoxicillin monotherapy in bacteremic pneumococcal pneumonia.

    Science.gov (United States)

    Blot, Mathieu; Pivot, Diane; Bourredjem, Abderrahmane; Salmon-Rousseau, Arnaud; de Curraize, Claire; Croisier, Delphine; Chavanet, Pascal; Binquet, Christine; Piroth, Lionel

    2017-09-01

    Antibiotic streamlining is pivotal to reduce the emergence of resistant bacteria. However, whether streamlining is frequently performed and safe in difficult situations, such as bacteremic pneumococcal pneumonia (BPP), has still to be assessed. All adult patients admitted to Dijon Hospital (France) from 2005 to 2013 who had BPP without complications, and were alive on the third day were enrolled. Clinical, biological, radiological, microbiological and therapeutic data were recorded. A first analysis was conducted to assess factors associated with being on amoxicillin on the third day. A second analysis, adjusting for a propensity score, was performed to determine whether 30-day mortality was associated with streamlining to amoxicillin monotherapy. Of the 196 patients hospitalized for BPP, 161 were still alive on the third day and were included in the study. Treatment was streamlined to amoxicillin in 60 patients (37%). Factors associated with not streamlining were severe pneumonia (OR 3.11, 95%CI [1.23-7.87]) and a first-line antibiotic combination (OR 3.08, 95%CI [1.34-7.09]). By contrast, starting with amoxicillin monotherapy correlated inversely with the risk of subsequent treatment with antibiotics other than amoxicillin (OR 0.06, 95%CI [0.01-0.30]). The Cox model adjusted for the propensity-score analysis showed that streamlining to amoxicillin during BPP was not significantly associated with a higher risk of 30-day mortality (HR 0.38, 95%CI [0.08-1.87]). Streamlining to amoxicillin is insufficiently implemented during BPP. This strategy is safe and potentially associated with ecological and economic benefits; therefore, it should be further encouraged, particularly when antibiotic combinations are started for severe pneumonia. Copyright © 2017. Published by Elsevier B.V.

  17. Combination therapy or monotherapy for the depressed type of schizoaffective disorder

    Directory of Open Access Journals (Sweden)

    Lubomira Izáková

    2009-02-01

    Full Text Available Lubomira Izáková1, Ivan Andre1, Angelos Halaris21Psychiatric Clinic, Faculty of Medicine Comenius University and Faculty Hospital, Bratislava, Slovakia; 2Department of Psychiatry and Behavioral Neurosciences, Loyola University Medical Center, Maywood, IL, USAAbstract: Several studies have demonstrated the effectiveness of adjunctive antidepressant drug therapy to improve the depressive or negative symptoms of schizoaffective disorder, however, monotherapy with atypical antipsychotics may be advantageous. We compared the efficacy and safety of risperidone monotherapy versus combination therapy of haloperidol with sertaline for the acute treatment of schizoaffective disorder, depressed type. This is an open label study of 52 female inpatients randomly assigned to risperidone alone (N = 26 or haloperidol in combination with sertraline (N = 26 for 12 weeks. The mean daily doses of medications were: risperidone: 3.75–3.29 mg/day, haloperidol: 5.35–4.15 mg/day, sertraline: 65.39–133.82 mg/day. Efficacy was measured using clinical rating scales of treatment, safety, and tolerability. Risperidone patients showed statistically significant greater improvement than haloperidol-sertraline patients on efficacy measures including Positive and Negative Syndrome Scale and Clinical Global Impressions rating. A higher number of risperidone patients dropped out of the study early. Fewer adverse events and lesser need for concomitant medications occurred in patients on risperidone. The risperidone group showed better psychological, social and occupational functioning (Global Assessment of Functioning and higher quality of life (Heinrich’s Quality of Life Scale. Risperidone has higher antipsychotic efficacy and tolerability compared with haloperidol-sertraline combination for the acute treatment of schizoaffective disorder, depressed type. Both treatments were comparable in terms of antidepressant efficacy.Keywords: schizoaffective disorder, depressed type

  18. 3-D conformal HDR brachytherapy as monotherapy for localized prostate cancer. A pilot study

    International Nuclear Information System (INIS)

    Martin, T.; Baltas, D.; Kurek, R.; Roeddiger, S.; Kontova, M.; Anagnostopoulos, G.; Skazikis, G.; Zamboglou, N.; Dannenberg, T.; Buhleier, T.; Tunn, U.

    2004-01-01

    Purpose: pilot study to evaluate feasibility, acute toxicity and conformal quality of three-dimensional (3-D) conformal high-dose-rate (HDR) brachytherapy as monotherapy for localized prostate cancer using intraoperative real-time planning. Patients and methods: between 05/2002 and 05/2003, 52 patients with prostate cancer, prostate-specific antigen (PSA) ≤ 10 ng/ml, Gleason score ≤ 7 and clinical stage ≤ T2a were treated. Median PSA was 6.4 ng/ml and median Gleason score 5. 24/52 patients had stage T1c and 28/52 stage T2a. For transrectal ultrasound-(TRUS-)guided transperineal implantation of flexible plastic needles into the prostate, the real-time HDR planning system SWIFT trademark was used. After implantation, CT-based 3-D postplanning was performed. All patients received one implant for four fractions of HDR brachytherapy in 48 h using a reference dose (D ref ) of 9.5 Gy to a total dose of 38.0 Gy. Dose-volume histograms (DVHs) were analyzed to evaluate the conformal quality of each implant using D 90 , D 10 urethra, and D 10 rectum. Acute toxicity was evaluated using the CTC (common toxicity criteria) scales. Results: median D 90 was 106% of D ref (range: 93-115%), median D 10 urethra 159% of D ref (range: 127-192%), and median D 10 rectum 55% of D ref (range: 35-68%). Median follow-up is currently 8 months. In 2/52 patients acute grade 3 genitourinary toxicity was observed. No gastrointestinal toxicity > grade 1 occurred. Conclusion: 3-D conformal HDR brachytherapy as monotherapy using intraoperative real-time planning is a feasible and highly conformal treatment for localized prostate cancer associated with minimal acute toxicity. Longer follow-up is needed to evaluate late toxicity and biochemical control. (orig.)

  19. Prevalence and correlates of cigarette smoking among Chinese schizophrenia inpatients receiving antipsychotic mono-therapy.

    Directory of Open Access Journals (Sweden)

    Yan-Min Xu

    Full Text Available OBJECTIVE: To investigate the prevalence rate of cigarette smoking and its socio-demographic and clinical correlates in Chinese schizophrenia inpatients receiving antipsychotic mono-therapy. METHODS: This study was a cross-sectional, two-site, hospital-based survey. Four hundred and twenty-nine schizophrenia patients (male/female: 66.9% vs. 33.1% were consecutively recruited from psychosis inpatient wards of two large specialty psychiatric hospitals in mainland China. Patients were assessed using a cigarette smoking questionnaire, the Positive and Negative Symptom Scale, the Simpson Angus Scale, the Barnes Akathisia Rating Scale, and the Abnormal Involuntary Movement Scale. Socio-demographic and other clinical data were also collected. We calculated the prevalence of current smoking in our sample as well as its indirectly standardized prevalence ratio (ISPR using data from the 2010 Global Adult Tobacco Survey in China. RESULTS: The prevalence rate of current smoking was 40.6% in our sample, and 57.5% in males and 6.3% in females. The ISPRs of all patients, men and women were 1.11(95%CI: 0.95 ∼ 1.29, 1.07(95%CI = 0.91 ∼ 1.24 and 4.64(95% CI = 2.12 ∼ 8.82, respectively. The overall and male-specific prevalence of current smoking did not differ significantly between patients and the general population. In multiple logistic regression analysis, male sex, older age, poor marital status, alcohol use, use of first-generation antipsychotics, longer duration of illness, more frequent hospitalizations, and more severe negative symptoms were independently associated with current smoking. CONCLUSION: Male Chinese inpatients with schizophrenia who received a mono-therapy of antipsychotics were not more likely to smoke than the general population. Cigarette smoking is more common in schizophrenia patients with more severe illness.

  20. Fractional CO 2 laser resurfacing as monotherapy in the treatment of atrophic facial acne scars

    Directory of Open Access Journals (Sweden)

    Imran Majid

    2014-01-01

    Full Text Available Background: While laser resurfacing remains the most effective treatment option for atrophic acne scars, the high incidence of post-treatment adverse effects limits its use. Fractional laser photothermolysis attempts to overcome these limitations of laser resurfacing by creating microscopic zones of injury to the dermis with skip areas in between. Aim: The aim of the present study is to assess the efficacy and safety of fractional CO 2 laser resurfacing in atrophic facial acne scars. Materials and Methods: Sixty patients with moderate to severe atrophic facial acne scars were treated with 3-4 sessions of fractional CO 2 laser resurfacing at 6-week intervals. The therapeutic response to treatment was assessed at each follow up visit and then finally 6 months after the last laser session using a quartile grading scale. Response to treatment was labelled as ′excellent′ if there was >50% improvement in scar appearance and texture of skin on the grading scale while 25-50% response and <25% improvement were labelled as ′good′ and ′poor′ response, respectively. The overall satisfaction of the patients and any adverse reactions to the treatment were also noted. Results: Most of the patients showed a combination of different morphological types of acne scars. At the time of final assessment 6 months after the last laser session, an excellent response was observed in 26 patients (43.3% while 15 (25% and 19 patients (31.7% demonstrated a good and poor response respectively. Rolling and superficial boxcar scars responded the best while pitted scars responded the least to fractional laser monotherapy. The commonest reported adverse effect was transient erythema and crusting lasting for an average of 3-4 and 4-6 days, respectively while three patients developed post-inflammatory pigmentation lasting for 8-12 weeks. Conclusions: Fractional laser resurfacing as monotherapy is effective in treating acne scars especially rolling and superficial boxcar

  1. Seasonal variations in TSH serum levels in athyreotic patients under L-thyroxine replacement monotherapy.

    Science.gov (United States)

    Gullo, Damiano; Latina, Adele; Frasca, Francesco; Squatrito, Sebastiano; Belfiore, Antonino; Vigneri, Riccardo

    2017-08-01

    Whether serum TSH undergoes seasonal fluctuations in euthyroid and hypothyroid residents of temperate climates is controversial. Monthly TSH and thyroid hormone levels were cross-sectionally analysed in a large cohort of euthyroid subjects (n=11 806) and L-thyroxine (L-T4)-treated athyreotic patients (n=3 934). Moreover, in a small group (n=119) of athyreotic patients treated with an unchanged dosage of L-T4 monotherapy, hormones were measured both in the coldest and in the hottest seasons of the same year (longitudinal study). No seasonal hormone change was observed in the euthyroid subjects except for a small FT3 increase in winter (+2.9%, P<.001). In contrast, the L-T4-treated athyreotic patients had significantly higher serum TSH values in the cold season when the FT4 values were significantly lower. The differences were more notable in the longitudinal series (TSH, 0.80 vs. 0.20 mU/L and FT4, 16.3 vs. 17.8 pmol/L in December-March vs. June-September, respectively). In these patients also serum FT3 values significantly decreased in winter (in the longitudinal series, 3.80 in winter vs 4.07 pmol/L in summer). Regression analysis showed that in athyreotic subjects, a greater FT4 change is required to obtain a TSH change similar to that of euthyroid controls and that this effect is more pronounced in the summer. Athyreotic patients undergoing L-T4 monotherapy have abnormal seasonal variations in TSH. These changes are secondary to the FT4 and FT3 serum decreases in winter, which occur in spite of the constant treatment. The underlying mechanisms are unclear, but in some cases, these changes may be clinically relevant. © 2017 John Wiley & Sons Ltd.

  2. 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....

  3. 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.

  4. 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

  5. Chronic heart failure

    African Journals Online (AJOL)

    enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs) and aldosterone ... It has a predictive power of 90% in this situation (c-statistic. 0.90). It is a useful rule-out ... Psychosocial support and the treatment of depression are becoming ...

  6. 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...

  7. USE OF BETA-BLOCKERS IN THE PERIOPERATIVE PERIOD: HOW STRONG ARE THE EVIDENCES?

    Directory of Open Access Journals (Sweden)

    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.

  8. Combination monoamine oxidase inhibitor and beta-blocker treatment of migraine, with anxiety and depression.

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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.

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

    Science.gov (United States)

    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.

  12. 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

  13. 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...

  14. The value of β-blockers administration during recovery phase of dobutamine stress echocardiography: a review.

    Science.gov (United States)

    Nguyen, James; Juneman, Elizabeth; Movahed, Mohammad Reza

    2013-07-01

    Dobutamine stress echocardiography (DSE) is a successful technique for detection of ischemia in patients with suspected coronary artery disease (CAD). There are some data that administration of β-blocker after peak infusion of dobutamine can improve sensitivity. The goal of this manuscript is to review the current literature in regard to the mechanism and accuracy of post-dobutamine β-blocker administration for ischemia detection. In this review, we present 2 case reports followed by detailed review of the literature. © 2013. This article is a U.S. Government work and is in the public domain in the USA.

  15. 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.

  16. 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

  17. Evaluation of risk of falls and orthostatic hypotension in older, long-term topical beta-blocker users

    NARCIS (Netherlands)

    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

  18. 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

  19. 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...

  20. 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.

  1. Dosage of angiotensin-II receptor blockers in heart failure patients following changes in Danish drug reimbursement policies

    DEFF Research Database (Denmark)

    Selmer, Christian; Lamberts, Morten; Kristensen, Søren Lund

    2014-01-01

    -titrated to optimal or suboptimal ARB dosage. METHODS: A historical cohort study was performed including HF patients with at least one prescription of ARB in the months of May-Jul 2010 (baseline). Patients were considered up-titrated at doses 100, 16 or 160 mg for losartan, valsartan and candesartan, respectively....... RESULTS: Of 6036 individuals included (mean age 73.5 [standard deviation 11.2] years; 51% males), 3346 (55.4%) used losartan, 541 (9.0%) valsartan and 2149 (35.6%) candesartan at inclusion, respectively. 2887 (47.8%) were up-titrated at baseline (May-Jul 2010), followed by 2878 (48.2%) in the three months...

  2. Influence of diabetes mellitus on heart failure risk and outcome

    Directory of Open Access Journals (Sweden)

    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.

  3. 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

  4. Comparative effect of clopidogrel plus aspirin and aspirin monotherapy on hematological parameters using propensity score matching

    Directory of Open Access Journals (Sweden)

    Hayasaka M

    2013-02-01

    Full Text Available Masatoshi Hayasaka,1 Yasuo Takahashi,2 Yayoi Nishida,2 Yoshikazu Yoshida,1 Shinji Hidaka,3 Satoshi Asai41Department of Pharmacy, Nihon University Itabashi Hospital, Tokyo, 2Division of Genomic Epidemiology and Clinical Trials, Clinical Trials Research Center, Nihon University School of Medicine, Tokyo, 3Laboratory of Pharmaceutical Regulatory Science, Department of Pharmacy, School of Pharmacy, Nihon University, Chiba, 4Division of Pharmacology, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo, JapanBackground: Clopidogrel and aspirin are antiplatelet agents that are recommended to reduce the risk of recurrent stroke and other cardiovascular events. Dual antiplatelet therapy with clopidogrel and aspirin has been shown to increase the risk of hemorrhage, but the effects of the drugs on laboratory parameters have not been well studied in real-world clinical settings. Therefore, we evaluated and compared the effects of combination therapy with clopidogrel plus aspirin and aspirin monotherapy on laboratory parameters.Methods: We used data from the Nihon University School of Medicine Clinical Data Warehouse obtained between November 2004 and May 2011 to identify cohorts of new users (n = 130 of clopidogrel (75 mg/day plus aspirin (100 mg/day and a propensity score matched sample of new users (n = 130 of aspirin alone (100 mg/day. We used a multivariate regression model to compare serum levels of creatinine, aspartate aminotransferase, and alanine aminotransferase, as well as hematological parameters including hemoglobin level, hematocrit, and white blood cell, red blood cell, and platelet counts up to 2 months after the start of administration of the study drugs.Results: There were no significant differences for any characteristics and baseline laboratory parameters between users of clopidogrel plus aspirin and users of aspirin alone. Reductions in white blood cell and red blood cell counts, hemoglobin levels, and

  5. Who continues to stock oral artemisinin monotherapy? Results of a provider survey in Myanmar.

    Science.gov (United States)

    Thein, Si Thu; Sudhinaraset, May; Khin, Hnin Su Su; McFarland, Willi; Aung, Tin

    2016-06-22

    Artemisinin-based combination therapy (ACT) is a key strategy for global malaria elimination efforts. However, the development of artemisinin-resistant malaria parasites threatens progress and continued usage of oral artemisinin monotherapies (AMT) predisposes the selection of drug resistant strains. This is particularly a problem along the Myanmar/Thailand border. The artemisinin monotherapy replacement programme (AMTR) was established in 2012 to remove oral AMT from stocks in Myanmar, specifically by replacing oral AMT with quality-assured ACT and conducting behavioural change communication activities to the outlets dispensing anti-malarial medications. This study attempts to quantify the characteristics of outlet providers who continue to stock oral AMT despite these concerted efforts. A cross-sectional survey of all types of private sector outlets that were stocking anti-malarial drugs in 13 townships of Eastern Myanmar was implemented from July to August 2014. A total of 573 outlets were included. Bivariate and multivariable logistic regressions were conducted to assess outlet and provider-level characteristics associated with stocking oral AMT. In total, 2939 outlets in Eastern Myanmar were screened for presence of any anti-malarial drugs in August 2014. The study found that 573 (19.5 %) had some kind of oral anti-malarial drug in stock at the time of survey and among them, 96 (16.8 %) stocked oral AMT. In bivariate analyses, compared to health care facilities, itinerant drug vendors, retailers and health workers were less likely to stock oral AMT (33.3 vs 12.9, 10.0, 8.1 %, OR = 0.30, 0.22, 0.18, respectively). Providers who cut blister pack or sell partial courses (40.6 vs 11.7 %, OR 5.18, CI 3.18-8.44) and those who based their stock decision on consumer demand (32.8 vs 12.1 %, OR 3.54, CI 2.21-5.63) were more likely to stock oAMT. Multivariate logistic regressions produced similar significant associations. Private healthcare facilities and drug

  6. Oral artemisinin monotherapy removal from the private sector in Eastern Myanmar between 2012 and 2014.

    Science.gov (United States)

    Khin, Hnin Su Su; Aung, Tin; Thi, Aung; White, Chris

    2016-05-23

    In 2012 the Artemisinin Monotherapy Therapy Replacement (AMTR) project was implemented in Eastern Myanmar to increase access to subsidized, quality-assured artemisinin combination therapy (ACT) and to remove oral artemisinin monotherapy (AMT) from the private sector. The aim of this paper is to examine changes over time in the private sector anti-malarial landscape and to illustrate the value of complementary interventions in the context of a national ACT subsidy. Three rounds of cross-sectional malaria medicine outlet surveys were conducted, in 2012, 2013 and 2014. Project intervention areas were selected from the Myanmar Artemisinin Resistance Containment (MARC) area. Provider detailing was implemented in these selected areas. Comparison areas were selected outside of this catchment area, from townships in close proximity to the MARC framework. Within each domain, multi-staged sampling was used to select areas for the survey. Outlets with the potential to sell or distribute anti-malarials in the private sector were screened for eligibility. The total number of outlets approached for an interview was as follows in the intervention and comparison areas, respectively: 2012, N = 2046 and 1612; 2013, N = 1636 and 1884; 2014, N = 2939 and 2941. The percentage of pharmacies, general retailers and mobile providers (classed as 'priority outlets') with oral AMT in stock on the day of the survey decreased over time in the intervention areas (2012 = 68 %; 2013 = 48 %; 2014 = 10 %). Conversely, quality-assured ACT availability increased among these outlets (2012 = 4 %; 2013 = 62 %; 2014 = 79 %). Relative oral AMT market share among priority outlets also decreased over time (2012 = 44 %; 2013 = 18 %; 2014 = 14 %), while market share of quality-assured ACT increased (2012 = 3 %; 2013 = 59 %; 2014 = 51 %). Among priority outlets in the comparison area, similar trends were observed, though changes over time were less substantial

  7. Pegylated interferon monotherapy for hepatitis C virus infection in patients on hemodialysis: A single center study

    Directory of Open Access Journals (Sweden)

    S K Agarwal

    2016-01-01

    Full Text Available There is no published study from India on hepatitis C virus (HCV treatment in dialysis patients. Patients on dialysis with HCV infection treated with pegylated interferon (Peg-INF monotherapy were studied. All patients were subjected to HCV-polymerase chain reaction, viral load, genotype, and liver biopsy. Quantitative HCV-RNA was performed monthly. Patients with genotype 1 and 4 were given 12 month therapy while those with genotypes 2 and 3 were given 6 months therapy. Response was classified as per standard criteria of rapid virological response (RVR, early virological response (EVR, end of treatment response (ETR, and sustained virological response (SVR. A total of 85 patients were treated. Mean age was 35.2 ± 10.5 (range 15–67 years, and 77.6% were males. HCV genotypes were 1 in 40.9%, 2 in 12%, 3 in 36.1%, 4 in 3.6%, and others in 7.2%. Mean viral load was 106 copies/mL. Mean liver biopsy grade was 4 ± 1.7 and stage 0.8 ± 0.8. Mean time from diagnosis of HCV infection and the treatment start was 10.7 ± 14.3 months. One patient died of unrelated illness, one was lost to follow-up, and three could not sustain treatment due to cost. Forty-three of the 80 (54% patients had RVR while 49 (61% patients had EVR and ETR. There was no difference in term of RVR related to genotype. Fifty -four percentage had SVR. Mild flu-like symptoms were seen in all patients. Sixty-four (80% patients required increase in erythropoietin doses. Twenty-eight (35% patients developed leukopenia (three treatment-limiting and 16 (20% developed thrombocytopenia (one treatment-limiting. Five patients developed tuberculosis, five bacterial pneumonia, and one bacterial knee monoarthritis. None of the patients developed depression. Our study concludes that Peg-INF monotherapy resulted in 54% RVR and SVR in dialysis patients with HCV infection. Therapy was well-tolerated with minimal side effects. There was no effect of viral genotype on response to therapy.

  8. Heart failure - medicines

    Science.gov (United States)

    CHF - medicines; Congestive heart failure - medicines; Cardiomyopathy - medicines; HF - medicines ... You will need to take most of your heart failure medicines every day. Some medicines are taken ...

  9. Preadmission use of renin-angiotensin blockers and rupture of abdominal aortic aneurysm

    DEFF Research Database (Denmark)

    Wemmelund, Holger; Høgh, Annette; Hundborg, Heidi H.

    2016-01-01

    PURPOSE: Rupture of abdominal aortic aneurysms (rAAA) is associated with high mortality. Use of angiotensin converting enzyme inhibitors (ACE-inhibitors) and angiotensin receptor blockers (ARBs) has been suggested to reduce the risk of rAAA. This nationwide, combined case-control and follow-up st...

  10. 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

  11. Conversion to Silodosin in Men on Conventional α1 -Blockers for Symptomatic Benign Prostatic Hyperplasia.

    Science.gov (United States)

    Tanaka, Masahiko; Niimi, Aya; Tomita, Kyoichi; Homma, Yukio

    2010-04-01

    α1 -blockers have commonly been used as first-line medical therapy for symptomatic benign prostatic hyperplasia (BPH). Recently, a highly selective α1A -adrenoceptor antagonist, silodosin, was developed in Japan. We examined the efficacy and safety of conversion from conventional α1 -blockers to silodosin in men with BPH. Conversion to silodosin was proposed to consecutive patients on conventional α1 -blockers for symptomatic BPH for at least 6 months. The effects of conversion were examined by the International Prostate Symptom Score, quality of life index, overactive bladder symptom score, peak flow rate, residual urine volume, and adverse events at 12 weeks. The efficacy of silodosin was also evaluated by patients' impression. Eighty-one men underwent conversion, for the most part because of dissatisfaction with the efficacy of their current treatment in improving nocturia or weak stream. The International Prostate Symptom Score total score significantly improved from 12.7 ± 5.9 at baseline to 10.6 ± 5.4 at 4 weeks (P silodosin. Efficacy as judged by patients' impression was 76% (37/49) at 12 weeks of treatment. None of the overactive bladder symptom score, peak flow rate, and residual urine volume exhibited significant change. No serious adverse events were observed during the study period. Conversion to silodosin may be beneficial in men who are dissatisfied with conventional α1 -blockers for BPH, and be particularly useful in improving voiding symptoms. © 2010 Blackwell Publishing Asia Pty Ltd.

  12. Moderation of dietary sodium potentiates the renal and cardiovascular protective effects of angiotensin receptor blockers

    DEFF Research Database (Denmark)

    Lambers Heerspink, Hiddo J; Holtkamp, Frank A; Parving, Hans-Henrik

    2012-01-01

    Dietary sodium restriction has been shown to enhance the short-term response of blood pressure and albuminuria to angiotensin receptor blockers (ARBs). Whether this also enhances the long-term renal and cardiovascular protective effects of ARBs is unknown. Here we conducted a post-hoc analysis of...

  13. 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.

  14. 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...

  15. Structural adaptation to ischemia in skeletal muscle: effects of blockers of the renin-angiotensin system

    NARCIS (Netherlands)

    Scheidegger, K. J.; Nelissen-Vrancken, M. H.; Leenders, P. J.; Daemen, M. J.; Smits, J. F.; Wood, J. M.

    1997-01-01

    To investigate the effects of long-term treatment with blockers of the renin-angiotensin system on capillarization and growth of fibers in ischemic hind-limb muscles and in muscles under normal growth conditions. Ischemia was induced by partial ligation of the left common iliac artery. Ischemia

  16. Trends in co-prescribing of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in Ireland.

    LENUS (Irish Health Repository)

    Wan Md Adnan, Wan A H

    2011-03-01

    (i) To examine the trends in co-prescribing of angiotensin converting enzyme inhibitor (ACEI) and angiotensin-II receptor blocker (ARB) therapy and (ii) to examine the influence of major clinical trials (CALM, COOPERATE, VALIANT and ONTARGET) on co-prescribing.

  17. Non-selective beta-blockers may reduce risk of hepatocellular carcinoma

    DEFF Research Database (Denmark)

    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...

  18. Remission of post-transplant focal segmental glomerulosclerosis with angiotensin receptor blockers

    Directory of Open Access Journals (Sweden)

    S B Bansal

    2017-01-01

    Full Text Available Recurrence of focal segmental glomerulosclerosis (FSGS is common after kidney transplantation. Plasmapheresis (PP is considered to be the most effective treatment; however, results are variable and relapse is common after stopping plasmapheresis. Here, we report an unusual case of recurrent FSGS, who achieved complete remission with angiotensin receptor blocker therapy.

  19. 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.

  20. Bed blockers: A study on the elderly patients in a teaching hospital in India

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  2. 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

  3. 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 ...

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

    DEFF Research Database (Denmark)

    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...

  5. Preoperative depression symptom severity and its impact on adherence to preoperative beta-blocker therapy.

    Science.gov (United States)

    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.

  6. Fractional CO2 Laser Resurfacing as Monotherapy in the Treatment of Atrophic Facial Acne Scars.

    Science.gov (United States)

    Majid, Imran; Imran, Saher

    2014-04-01

    While laser resurfacing remains the most effective treatment option for atrophic acne scars, the high incidence of post-treatment adverse effects limits its use. Fractional laser photothermolysis attempts to overcome these limitations of laser resurfacing by creating microscopic zones of injury to the dermis with skip areas in between. The aim of the present study is to assess the efficacy and safety of fractional CO2 laser resurfacing in atrophic facial acne scars. Sixty patients with moderate to severe atrophic facial acne scars were treated with 3-4 sessions of fractional CO2 laser resurfacing at 6-week intervals. The therapeutic response to treatment was assessed at each follow up visit and then finally 6 months after the last laser session using a quartile grading scale. Response to treatment was labelled as 'excellent' if there was >50% improvement in scar appearance and texture of skin on the grading scale while 25-50% response and resurfacing as monotherapy is effective in treating acne scars especially rolling and superficial boxcar scars with minimal adverse effects.

  7. Reduced dose of salvage-line regorafenib monotherapy for metastatic colorectal cancer in Japan.

    Science.gov (United States)

    Hirano, Gen; Makiyama, Akitaka; Makiyama, Chinatsu; Esaki, Taito; Oda, Hisanobu; Uchino, Keita; Komoda, Masato; Tanaka, Risa; Matsushita, Yuzo; Mitsugi, Kenji; Shibata, Yoshihiro; Kumagai, Hozumi; Arita, Shuji; Ariyama, Hiroshi; Kusaba, Hitoshi; Akashi, Koichi; Baba, Eishi

    2015-01-01

    Salvage-line regorafenib monotherapy exhibited a marked survival benefit for metastatic colorectal cancer (mCRC). However, the toxicity of this regimen has resulted in the clinical use of a reduced dose of regorafenib. Thirty-two Japanese mCRC patients (median age=61 years) who had been treated with regorafenib were retrospectively examined. Best objective response rate was 0% and stable disease (SD) was 31%. Median progression-free survival was 81 days and median overall survival was 233 days. Adverse events of any grade were observed in all patients: 17 (53%) patients suffered grade 3 or 4 adverse events including fatigue (13%), anorexia (13%), hand-foot skin reaction (22%) and elevations of alanine aminotransferase/aspartate aminotransferase (19%/16%). One patient with grade 5 liver dysfunction was identified (3%). Twenty-nine (91%) patients required treatment dose reduction or a delay in treatment. The relative dose intensity was 59%. Regorafenib treatments were terminated because of disease progression (59%) or adverse events (34%). Despite a decrease in the intensity of regorafenib treatment, because of severe adverse events, a fairly favorable efficacy was achieved in Japanese patients. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  8. Omega-3 carboxylic acids monotherapy and combination with statins in the management of dyslipidemia

    Directory of Open Access Journals (Sweden)

    Benes LB

    2016-12-01

    Full Text Available Lane B Benes1, Nikhil S Bassi2, Michael H Davidson1 1Department of Medicine, Section of Cardiology, 2Department of Medicine, University of Chicago, Chicago, IL, USA Abstract: The 2013 American College of Cardiology/American Heart Association guidelines on cholesterol management placed greater emphasis on statin therapy given the well-established benefits in primary and secondary prevention of cardiovascular disease. Residual risk may remain after statin initiation, in part because of triglyceride-rich lipoprotein cholesterol. Several large trials have failed to show benefit with non-statin cholesterol-lowering medications in the reduction of cardiovascular events. Yet, subgroup analyses showed a benefit in those with hypertriglyceridemia and lower high-density lipoprotein cholesterol level, a high-risk pattern of dyslipidemia. This review discusses the benefits of omega-3 carboxylic acids, a recently approved formulation of omega-3 fatty acid with enhanced bioavailability, in the treatment of dyslipidemia both as monotherapy and combination therapy with a statin. Keywords: omega-3 carboxylic acids, non-HDL-C, hypertriglyceridemia, residual risk, statin

  9. [Clinical study of influential factors on renal scarring after ESWL monotherapy for renal stone disease].

    Science.gov (United States)

    Ishito, Noritaka; Takamoto, Hitoshi; Kunitomi, Kimito; Satoh, Eiichi; Ishii, Ayano; Shiotuka, Youichi; Sako, Shinichi; Ohta, Naoki; Araki, Tohru

    2002-11-01

    ESWL is now widely used for the treatment of renal stone disease. Although ESWL has many advantages for patients' quality of life, few reports have demonstrated the long-term outcomes of the alterations of renal morphology after ESWL. We reported renal scarring after ESWL monotherapy in patients with renal calyceal stones. In this study, we evaluated a large series of patients' cohort treated at our institution, and assessed the causal effect of ESWL on the late occurrence of renal scar formation. ESWL was performed with EDAP (LT-01,02) that generates shock wave energy by piezoelectric discharge. We analyzed the records of 285 kidneys treated between Dec. 1986 and Nov. 1998. Renal scarring was noted in 44 kidneys and not in 241 kidneys with periodical ultrasonography. We compared the backgrounds of the two groups using chi-square or non-parametric analysis. The Kaplan-Meier method and Cox regression model determined the analysis of renal scar formation. Univariate and multiple regression analysis revealed that the total amount of ESWL emission and hyperuricemia independently affected the probability of renal scar formation. Over-emission of ESWL (over 10,000 shots) must be care for the prevention of renal scarring in patients with renal calyceal calculi, especially when associated with hyperuricemia. After ESWL, periodical checkups with ultrasonography will provide useful information for the clinical diagnosis of renal scarring.

  10. 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.

  11. 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....

  12. Zidovudine (AZT monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase.

    Directory of Open Access Journals (Sweden)

    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.

  13. 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)

  14. 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  17. 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...

  18. Use of low-level laser therapy as monotherapy or concomitant therapy for male and female androgenetic alopecia.

    Science.gov (United States)

    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.

  19. 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.

    Directory of Open Access Journals (Sweden)

    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.

  20. 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.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  2. 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

  3. 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.

  4. Advanced Heart Failure

    Science.gov (United States)

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More Advanced Heart Failure Updated:May 9,2017 When heart failure (HF) ... Making This content was last reviewed May 2017. Heart Failure • Home • About Heart Failure • Causes and Risks for ...

  5. 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....

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. Immune mediated liver failure

    OpenAIRE

    Wang, Xiaojing; Ning, Qin

    2014-01-01

    Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capac...

  11. Chronic heart failure

    OpenAIRE

    Hopper, Ingrid; Easton, Kellie

    2017-01-01

    1. The common symptoms and signs of chronic heart failure are dyspnoea, ankle swelling, raised jugular venous pressure and basal crepitations. Other conditions may be confused with chronic heart failure, including dependent oedema or oedema due to renal or hepatic disease. Shortness of breath may be due to respiratory disease or severe anaemia. Heart failure secondary to lung disease (cor pulmonale) should be distinguished from congestive cardiac failure. Heart failure may also present with l...

  12. 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

  13. Niacin extended-release/simvastatin combination therapy produces larger favorable changes in high-density lipoprotein particles than atorvastatin monotherapy

    Directory of Open Access Journals (Sweden)

    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

  14. Comparison the Efficacy of Four Different Alpha Blockers in the Treatment of Benign Prostatic Hyperplasia

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  17. Hypofractionated stereotactic body radiation therapy as monotherapy for intermediate-risk prostate cancer

    Directory of Open Access Journals (Sweden)

    Ju Andrew W

    2013-01-01

    Full Text Available Abstract Background Hypofractionated stereotactic body radiation therapy (SBRT has been advanced as monotherapy for low-risk prostate cancer. We examined the dose distributions and early clinical outcomes using this modality for the treatment of intermediate-risk prostate cancer. Methods Forty-one sequential hormone-naïve intermediate-risk prostate cancer patients received 35–36.25 Gy of CyberKnife-delivered SBRT in 5 fractions. Radiation dose distributions were analyzed for coverage of potential microscopic ECE by measuring the distance from the prostatic capsule to the 33 Gy isodose line. PSA levels, toxicities, and quality of life (QOL measures were assessed at baseline and follow-up. Results All patients completed treatment with a mean coverage by the 33 Gy isodose line extending >5 mm beyond the prostatic capsule in all directions except posteriorly. Clinical responses were documented by a mean PSA decrease from 7.67 ng/mL pretreatment to 0.64 ng/mL at the median follow-up of 21 months. Forty patients remain free from biochemical progression. No Grade 3 or 4 toxicities were observed. Mean EPIC urinary irritation/obstruction and bowel QOL scores exhibited a transient decline post-treatment with a subsequent return to baseline. No significant change in sexual QOL was observed. Conclusions In this intermediate-risk patient population, an adequate radiation dose was delivered to areas of expected microscopic ECE in the majority of patients. Although prospective studies are needed to confirm long-term tumor control and toxicity, the short-term PSA response, biochemical relapse-free survival rate, and QOL in this interim analysis are comparable to results reported for prostate brachytherapy or external beam radiotherapy. Trial registration The Georgetown Institutional Review Board has approved this retrospective study (IRB 2009–510.

  18. Comprehensive Safety Analysis of Venetoclax Monotherapy for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Davids, Matthew S; Hallek, Michael; Wierda, William; Roberts, Andrew W; Stilgenbauer, Stephan; Jones, Jeffrey A; Gerecitano, John F; Kim, Su Young; Potluri, Jalaja; Busman, Todd; Best, Andrea; Verdugo, Maria E; Cerri, Elisa; Desai, Monali; Hillmen, Peter; Seymour, John F

    2018-06-12

    The oral BCL-2 inhibitor venetoclax is an effective therapy for patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), including disease with high-risk genomic features such as chromosome 17p deletion (del[17p]) or progressive disease following B-cell receptor pathway inhibitors. We conducted a comprehensive analysis of the safety of 400mg daily venetoclax monotherapy in 350 patients with CLL using an integrated dataset from three phase-I/II studies. Median age was 66 years and 60% had del(17p). Patients had received a median of three prior therapies (range: 0-15); 42% previously received ibrutinib or idelalisib. Median duration of exposure to venetoclax was 16 months (0-56). In the pooled analysis, the most common adverse events (AEs) of any grade were diarrhea (41%), neutropenia (40%), nausea (39%), anemia (31%), fatigue (28%), and upper respiratory tract infection (25%). The most common grade 3/4 AEs were neutropenia (37%), anemia (17%), and thrombocytopenia (14%). With the current 5-week ramp-up dosing, the incidence of laboratory TLS was 1.4% (2/166), none had clinical sequelae, and all of these patients were able to ramp-up to a daily dose of 400mg. Grade 3/4 neutropenia was manageable with growth-factor support and dose adjustments; the incidence of serious infections in these patients was 15%. Ten percent of patients discontinued venetoclax due to AEs and 8% died while on study, with the majority of deaths in the setting of disease progression. Venetoclax as a long-term continuous therapy is generally well-tolerated in patients with R/R CLL when initiated with the current treatment algorithm. Copyright ©2018, American Association for Cancer Research.

  19. Relationship between mono-hydroxy-carbazepine serum concentrations and adverse effects in patients on oxcarbazepine monotherapy.

    Science.gov (United States)

    Sattler, Annika; Schaefer, Marion; May, Theodor W

    2015-09-01

    To evaluate the relationship between serum concentrations of mono-hydroxy-carbazepine (MHD), the main metabolite of oxcarbazepine (OXC), and the occurrence of adverse effects (AE) in a large group of patients on OXC monotherapy. An antiepileptic drug (AED) therapeutic drug monitoring (TDM) database was analyzed especially with regard to OXC dosage, MHD serum concentration, and the occurrence of AE. In total, 893 blood samples of 442 patients were included in this retrospective study. The statistical evaluation was performed by means of Kaplan-Meier estimates, log-rank tests and generalized estimating equations (GEE). At least one AE was reported in 78 (17.6%) of the 442 patients. At MHD serum concentrations of 30.0 μg/ml and 43.7 μg/ml and OXC dosages of 33.1 mg/kg and 62.3 mg/kg, 25% and 75% of patients, respectively, experienced at least one AE. Log-rank tests indicated that younger patients (<18 years) may be able to tolerate higher MHD serum levels (p = 0.006) and higher OXC dosages per body weight (p < 0.001) compared to adult patients (≥ 18 years). Furthermore, AEs occurred at higher body-weight adjusted OXC dosages of extended release formulations compared to immediate-release formulations (p = 0.010), whereas MHD serum levels at which AEs occurred did not differ significantly between formulations (p = 0.125). Multivariate GEE confirmed the results. The occurrence of AEs is significantly (and non-linearly) dependent on MHD serum level, whereas the dependence of OXC dosage is less distinctive. But, tolerability of OXC seems to depend on age of the patients as well as on pharmaceutical formulation of OXC. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  20. Should leptin replace insulin as a lifetime monotherapy for diabetes type 1 and 2?

    Science.gov (United States)

    Kalra, Satya P

    2013-10-01

    Evidence accumulated during the last decade has affirmed that adipocyte leptin insufficiency in the hypothalamus is the primary etiological factor in the pathogenesis of diabetes type 1 and 2 and related metabolic morbidities. Leptin insufficiency disrupts the relay of hypothalamic regulatory information along three descending pathways to the organs in the periphery that normally participate in maintenance of glucose homeostasis on a minute-to-minute basis throughout lifetime. Reinstatement of leptin sufficiency in the hypothalamus by either systemic or central injections, or its provision selectively in the hypothalamus with the aid of gene therapy extinguished hyperglycemia and normalized blood glucose stably during the entire course of treatment in a variety of animal models of diabetes type 1 and 2. In follow-up clinical trials, twice daily leptin treatment in leptinopenic and insulinopenic type 1 diabetics and leptinopenic and hyperinsulinemic type 2 diabetics with congenital lipodystrophy or acquired lipoatrophy normalized blood glucose without any discernible adverse effects during the extended course of treatment. Taken together, these findings have amply endorsed the efficacy of leptin therapy to restore glucose homeostasis in insulin-deficient as well as hyperinsulinemic diabetic patients. Consequently, restoration of optimal hypothalmic signaling to reinstate glucose homeostasis with leptin is a highly suitable new therapeutic strategy to ameliorate diabetes type 1 and 2 for the lifetime and to replace the currently in vogue insulin monotherapy. In view of the relentless challenges posed by the worldwide epidemic of diabetes and soaring treatment costs, taken together with the well-known shortcomings of therapies based on restoring insulin signaling, it is highly critical and timely to undertake new clinical trials that ascertain appropriate dosage and route of leptin delivery to the hypothalamus capable of safely sustaining stable glycemia for lifetime.

  1. Should leptin replace insulin as a lifetime monotherapy for diabetes type 1 and 2?

    Directory of Open Access Journals (Sweden)

    Satya P Kalra

    2013-01-01

    Full Text Available Evidence accumulated during the last decade has affirmed that adipocyte leptin insufficiency in the hypothalamus is the primary etiological factor in the pathogenesis of diabetes type 1 and 2 and related metabolic morbidities. Leptin insufficiency disrupts the relay of hypothalamic regulatory information along three descending pathways to the organs in the periphery that normally participate in maintenance of glucose homeostasis on a minute-to-minute basis throughout lifetime. Reinstatement of leptin sufficiency in the hypothalamus by either systemic or central injections, or its provision selectively in the hypothalamus with the aid of gene therapy extinguished hyperglycemia and normalized blood glucose stably during the entire course of treatment in a variety of animal models of diabetes type 1 and 2. In follow-up clinical trials, twice daily leptin treatment in leptinopenic and insulinopenic type 1 diabetics and leptinopenic and hyperinsulinemic type 2 diabetics with congenital lipodystrophy or acquired lipoatrophy normalized blood glucose without any discernible adverse effects during the extended course of treatment. Taken together, these findings have amply endorsed the efficacy of leptin therapy to restore glucose homeostasis in insulin-deficient as well as hyperinsulinemic diabetic patients. Consequently, restoration of optimal hypothalmic signaling to reinstate glucose homeostasis with leptin is a highly suitable new therapeutic strategy to ameliorate diabetes type 1 and 2 for the lifetime and to replace the currently in vogue insulin monotherapy. In view of the relentless challenges posed by the worldwide epidemic of diabetes and soaring treatment costs, taken together with the well-known shortcomings of therapies based on restoring insulin signaling, it is highly critical and timely to undertake new clinical trials that ascertain appropriate dosage and route of leptin delivery to the hypothalamus capable of safely sustaining stable

  2. First-Line Cetuximab Monotherapy in KRAS/NRAS/BRAF Mutation-Negative Colorectal Cancer Patients.

    Science.gov (United States)

    Moiseyenko, Vladimir M; Moiseyenko, Fedor V; Yanus, Grigoriy A; Kuligina, Ekatherina Sh; Sokolenko, Anna P; Bizin, Ilya V; Kudriavtsev, Alexey A; Aleksakhina, Svetlana N; Volkov, Nikita M; Chubenko, Vyacheslav A; Kozyreva, Kseniya S; Kramchaninov, Mikhail M; Zhuravlev, Alexandr S; Shelekhova, Kseniya V; Pashkov, Denis V; Ivantsov, Alexandr O; Venina, Aigul R; Sokolova, Tatyana N; Preobrazhenskaya, Elena V; Mitiushkina, Natalia V; Togo, Alexandr V; Iyevleva, Aglaya G; Imyanitov, Evgeny N

    2018-06-01

    Colorectal carcinomas (CRCs) are sensitive to treatment by anti-epidermal growth factor receptor (EGFR) antibodies only if they do not carry activating mutations in down-stream EGFR targets (KRAS/NRAS/BRAF). Most clinical trials for chemo-naive CRC patients involved combination of targeted agents and chemotherapy, while single-agent cetuximab or panitumumab studies included either heavily pretreated patients or subjects who were not selected on the basis of molecular tests. We hypothesized that anti-EGFR therapy would have significant efficacy in chemo-naive patients with KRAS/NRAS/BRAF mutation-negative CRC. Nineteen patients were prospectively included in the study. Two (11%) patients experienced partial response (PR) and 11 (58%) subjects showed stable disease (SD). Median time to progression approached 6.1 months (range 1.6-15.0 months). Cetuximab efficacy did not correlate with RNA expression of EGFR and insulin-like growth factor 2 (IGF2). Only one tumor carried PIK3CA mutation, and this CRC responded to cetuximab. Exome analysis of patients with progressive disease (PD) revealed 1 CRC with high-level microsatellite instability and 1 instance of HER2 oncogene amplification; 3 of 4 remaining patients with PD had allergic reactions to cetuximab, while none of the subjects with PR or SD had this complication. Comparison with 19 retrospective KRAS/NRAS/BRAF mutation-negative patients receiving first-line fluoropyrimidines revealed no advantages or disadvantages of cetuximab therapy. Cetuximab demonstrates only modest efficacy when given as a first-line monotherapy to KRAS/NRAS/BRAF mutation-negative CRC patients. It is of question, why meticulous patient selection, which was undertaken in the current study, did not result in the improvement of outcomes of single-agent cetuximab treatment.

  3. Long-Term Quality of Life Outcome After Proton Beam Monotherapy for Localized Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Coen, John J., E-mail: jcoen@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); Paly, Jonathan J.; Niemierko, Andrzej; Weyman, Elizabeth [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); Rodrigues, Anita [Department of Medical Oncology, Massachusetts General Hospital, Boston, MA (United States); Shipley, William U.; Zietman, Anthony L. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); Talcott, James A. [Department of Medical Oncology, Massachusetts General Hospital, Boston, MA (United States)

    2012-02-01

    Objectives: High-dose external radiation for localized prostate cancer results in favorable clinical outcomes and low toxicity rates. Here, we report long-term quality of life (QOL) outcome for men treated with conformal protons. Methods: QOL questionnaires were sent at specified intervals to 95 men who received proton radiation. Of these, 87 men reported 3- and/or 12-month outcomes, whereas 73 also reported long-term outcomes (minimum 2 years). Symptom scores were calculated at baseline, 3 months, 12 months, and long-term follow-up. Generalized estimating equation models were constructed to assess longitudinal outcomes while accounting for correlation among repeated measures in an individual patient. Men were stratified into functional groups from their baseline questionnaires (normal, intermediate, or poor function) for each symptom domain. Long-term QOL changes were assessed overall and within functional groups using the Wilcoxon signed-rank test. Results: Statistically significant changes in all four symptom scores were observed in the longitudinal analysis. For the 73 men reporting long-term outcomes, there were significant change scores for incontinence (ID), bowel (BD) and sexual dysfunction (SD), but not obstructive/irritative voiding dysfunction (OID). When stratified by baseline functional category, only men with normal function had increased scores for ID and BD. For SD, there were significant changes in men with both normal and intermediate function, but not poor function. Conclusions: Patient reported outcomes are sensitive indicators of treatment-related morbidity. These results quantitate the long-term consequences of proton monotherapy for prostate cancer. Analysis by baseline functional category provides an individualized prediction of long-term QOL scores. High dose proton radiation was associated with small increases in bowel dysfunction and incontinence, with more pronounced changes in sexual dysfunction.

  4. Hypofractionated stereotactic body radiation therapy as monotherapy for intermediate-risk prostate cancer

    International Nuclear Information System (INIS)

    Ju, Andrew W; Lei, Siyuan; Suy, Simeng; Lynch, John H; Dritschilo, Anatoly; Collins, Sean P; Wang, Hongkun; Oermann, Eric K; Sherer, Benjamin A; Uhm, Sunghae; Chen, Viola J; Pendharkar, Arjun V; Hanscom, Heather N; Kim, Joy S

    2013-01-01

    Hypofractionated stereotactic body radiation therapy (SBRT) has been advanced as monotherapy for low-risk prostate cancer. We examined the dose distributions and early clinical outcomes using this modality for the treatment of intermediate-risk prostate cancer. Forty-one sequential hormone-naïve intermediate-risk prostate cancer patients received 35–36.25 Gy of CyberKnife-delivered SBRT in 5 fractions. Radiation dose distributions were analyzed for coverage of potential microscopic ECE by measuring the distance from the prostatic capsule to the 33 Gy isodose line. PSA levels, toxicities, and quality of life (QOL) measures were assessed at baseline and follow-up. All patients completed treatment with a mean coverage by the 33 Gy isodose line extending >5 mm beyond the prostatic capsule in all directions except posteriorly. Clinical responses were documented by a mean PSA decrease from 7.67 ng/mL pretreatment to 0.64 ng/mL at the median follow-up of 21 months. Forty patients remain free from biochemical progression. No Grade 3 or 4 toxicities were observed. Mean EPIC urinary irritation/obstruction and bowel QOL scores exhibited a transient decline post-treatment with a subsequent return to baseline. No significant change in sexual QOL was observed. In this intermediate-risk patient population, an adequate radiation dose was delivered to areas of expected microscopic ECE in the majority of patients. Although prospective studies are needed to confirm long-term tumor control and toxicity, the short-term PSA response, biochemical relapse-free survival rate, and QOL in this interim analysis are comparable to results reported for prostate brachytherapy or external beam radiotherapy. The Georgetown Institutional Review Board has approved this retrospective study (IRB 2009–510)

  5. 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...

  6. Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data.

    Science.gov (United States)

    Nevitt, Sarah J; Sudell, Maria; Weston, Jennifer; Tudur Smith, Catrin; Marson, Anthony G

    2017-12-15

    Epilepsy is a common neurological condition with a worldwide prevalence of around 1%. Approximately 60% to 70% of people with epilepsy will achieve a longer-term remission from seizures, and most achieve that remission shortly after starting antiepileptic drug treatment. Most people with epilepsy are treated with a single antiepileptic drug (monotherapy) and current guidelines from the National Institute for Health and Care Excellence (NICE) in the United Kingdom for adults and children recommend carbamazepine or lamotrigine as first-line treatment for partial onset seizures and sodium valproate for generalised onset seizures; however a range of other antiepileptic drug (AED) treatments are available, and evidence is needed regarding their comparative effectiveness in order to inform treatment choices. To compare the time to withdrawal of allocated treatment, remission and first seizure of 10 AEDs (carbamazepine, phenytoin, sodium valproate, phenobarbitone, oxcarbazepine, lamotrigine, gabapentin, topiramate, levetiracetam, zonisamide) currently used as monotherapy in children and adults with partial onset seizures (simple partial, complex partial or secondary generalised) or generalised tonic-clonic seizures with or without other generalised seizure types (absence, myoclonus). We searched the following databases: Cochrane Epilepsy's Specialised Register, CENTRAL, MEDLINE and SCOPUS, and two clinical trials registers. We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators, and experts in the field. The date of the most recent search was 27 July 2016. We included randomised controlled trials of a monotherapy design in adults or children with partial onset seizures or generalised onset tonic-clonic seizures (with or without other generalised seizure types). This was an individual participant data (IPD) review and network meta-analysis. Our primary outcome was 'time to withdrawal of allocated treatment', and our secondary

  7. [Sacubitril / Valsartan in patients with diabetes and heart failure].

    Science.gov (United States)

    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.

  8. Heart failure - surgeries and devices

    Science.gov (United States)

    ... surgery; HF - surgery; Intra-aortic balloon pumps - heart failure; IABP - heart failure; Catheter based assist devices - heart failure ... problem may cause heart failure or make heart failure worse. Heart valve surgery may be needed to repair or ...

  9. ACTION OF CHEMICALLY DIFFERENT PROSTAGLANDIN BLOCKERS ON THE ADRENAL HORMONES IN PIGEONS DURING STRESS.

    Science.gov (United States)

    Sarkar, S; Ghosh, S; Sengupta, S; Dasadhikari, S; Ghosh, A

    1999-01-01

    The effect of prostaglandin (PG) inhibitors differing in their chemical nature, viz. Aspirin (acetylsalicylic acid), Mefenamic acid (fenamates), Diclofenac (phenylacetic acid derivative) and Piroxicam (oxicam derivative) on the adrenal hormones was studied in acutely stressed pigeons. None of these PG blockers exerted any significant effect on the catecholamine and corticosterone content of the control, i.e. unstressed pigeon adrenal gland excepting mefenamic acid which caused a release of epinephrine. Aspirin, diclofenac and piroxicam did not modulate the catecholamine or corticosterone secretion whereas mefenamic acid caused a released of both epinephrine and norepinephrine and increased the adrenal corticosterone content in the acutely stressed pigeons. These results were compared with those obtained from studies on the effects of other chemically different PG blockers, indomethacin (a methylated indole derivative) and ibuprofen (a propionic acid derivative). It is suggested that chemically and structurally different PG inhibitors show diverse action in the same species under similar stress conditions.

  10. 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

  11. The role of nitrates, beta blockers, and calcium antagonists in stable angina pectoris.

    Science.gov (United States)

    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.

  12. Alpha 1-blockers vs 5 alpha-reductase inhibitors in benign prostatic hyperplasia. A comparative review

    DEFF Research Database (Denmark)

    Andersen, J T

    1995-01-01

    During recent years, pharmacological treatment of symptomatic benign prostatic hyperplasia (BPH) has become the primary treatment choice for an increasing number of patients. The 2 principal drug classes employed are alpha 1-blockers and 5 alpha-reductase inhibitors. Current information from...... of patients who will respond well to alpha 1-blockers have yet to be identified, and data concerning the long term effects of these drugs are not yet available. 5 alpha-Reductase inhibitors have a slow onset of effect, but treatment leads to improvement in symptoms, reduction of the size of the prostate gland...... and improvement in objective parameters for bladder outflow obstruction. Approximately 30 to 50% of patients will respond to treatment with 5 alpha-reductase inhibitors. The definitive role of pharmacological treatment in symptomatic BPH remains to be established, although it seems that patients unfit...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  15. 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.

  16. 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.

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

    Science.gov (United States)

    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.

  18. The challenge of analyzing beta-blocker drugs in sludge and wastewater.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  20. L-Carnitine for the treatment of a calcium channel blocker and metformin poisoning.

    Science.gov (United States)

    St-Onge, Maude; Ajmo, Ian; Poirier, Diane; Laliberté, Martin

    2013-09-01

    The object of the current communication is to discuss the theory and the evidence for the use of L-carnitine in calcium channel blocker and metformin poisonings. A 68-year-old male known for hypertension and type II diabetes was admitted to the critical care unit of a community hospital following an overdose of amlodipine and metformin. The patient was intubated, ventilated, and hemodynamically supported with vasopressors. Despite calcium, glucagon, high-dose insulin (HDI), and lipid emulsion for calcium channel blocker and bicarbonate for metabolic acidosis, the patient remained hemodynamically unstable. The patient was considered too unstable to initiate continuous renal replacement therapy; and without access to extracorporeal life support, the administration of L-carnitine was administered as a last resort. One hour after L-carnitine, the norepinephrine requirements started to decrease, the patient began to improve and was subsequently extubated successfully without apparent sequelae in less than 4 days. L-Carnitine combined with HDI may have helped with the calcium channel blocker (CCB) poisoning by decreasing insulin resistance, promoting intracellular glucose transport, facilitating the metabolism of free fatty acids, and increasing calcium channel sensitivity. It may have also stimulated oxidative utilization of glucose instead of converting pyruvate into lactate and contributed to decrease lactate production with metformin poisoning.

  1. Effects of a K+ channel blocker on glomerular filtration rate and electrolyte excretion in conscious rats.

    Science.gov (United States)

    Ludens, J H; Clark, M A; Lawson, J A

    1995-06-01

    Effects of a K+ channel blocker on glomerular filtration rate and electrolyte excretion in conscious rats were observed. Effects of K+ channel modulation on glomerular filtration rate and electrolyte excretion were studied using the adenosine-triphosphate- (ATP)-sensitive K+ channel blocker 4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexylhydr ochloride (U-37883A) in conscious rats previously equipped with catheters for clearance studies. In saline-loaded rats, i.v. doses of U-37883A of 1.7, 5.0 and 15 mg/kg increased absolute and fractional Na+ excretion dose-dependently without changing K+ excretion. The glomerular filtration rate remained constant during diuresis. In water-loaded (hypotonic dextrose) rats, free-water clearance studies revealed that the ATP-sensitive K+ channel blocker significantly decreased an index of solute reabsorption (free-water clearance adjusted for chloride clearance) in the diluting segment during peak natriuretic activity. In addition, U-37883A significantly decreased the osmolality of renal papillary interstitial fluid, indicative of an effect in the medullary portion of the diluting segment. Together, these findings suggest that ATP-sensitive K+ channels, possibly those located at the apical boarder, play a pivotal role in Na+ reabsorption in the thick ascending limb of the loop of Henle.

  2. Prognostic impact of peakVO2-changes in stable CHF on chronic beta-blocker treatment.

    Science.gov (United States)

    Frankenstein, L; Nelles, M; Hallerbach, M; Dukic, D; Fluegel, A; Schellberg, D; Katus, H A; Remppis, A; Zugck, C

    2007-11-15

    Peak oxygen uptake (pVO2) is used for risk stratification in chronic heart failure (CHF), but little is known about the prognostic impact of pVO2-changes in patients on chronic beta-blocker (BBL) therapy. We therefore prospectively evaluated individual pVO2-changes at a 6-month interval in patients all receiving BBL. 194 patients with stable CHF on stable medication were included (V1) and underwent clinical evaluation and exercise testing. Testing was repeated (V2) at 5.7+/-1.5 months after V1 and patients were followed >12 months after V2. Death or hospitalisation due to cardiac reasons was the predefined EP (EPP, end-point positive; n=62; EPN, end-point negative; n=113). Initial characteristics did not differ between EPP and EPN. Multivariate cox regression analysis revealed that change of pVO2 (EPP: -0.6+/-2.6 ml/kg min; EPN: +2.5+/-3.3 ml/kg min; p<0.001) was independent to pVO2, LVEF, NTproBNP and NYHA at V2 for prediction of the combined end-point during follow-up. An increase of pVO2 by 10% was identified as an adequate cut-off value for risk stratification and ROC-analysis showed the significant incremental prognostic value of the determination of pVO2 changes in combination with pVO2. Serial measurements of pVO2 yield additional information for risk stratification in clinically homogenous CHF patients receiving BBL. This is the first study demonstrating this fact within a narrow predefined interval with all patients on BBL.

  3. [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.

  4. 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...

  5. 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.

  6. 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.

  7. 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.

  8. Effects of treatment with β-blocker and aldosterone antagonist on central and peripheral haemodynamics and oxygenation in cirrhosis

    DEFF Research Database (Denmark)

    Winkler, Christine; Hobolth, Lise; Krag, Aleksander

    2011-01-01

    Patients with cirrhosis often exhibit abnormalities in cardiovascular regulation and oxygenation. Many of these patients are treated with β-blockers and aldosterone antagonists that may influence the regulation of systemic haemodynamics, but the specific effects on systemic haemodynamics and oxyg......Patients with cirrhosis often exhibit abnormalities in cardiovascular regulation and oxygenation. Many of these patients are treated with β-blockers and aldosterone antagonists that may influence the regulation of systemic haemodynamics, but the specific effects on systemic haemodynamics...

  9. Acute liver failure

    DEFF Research Database (Denmark)

    Larsen, Fin Stolze; Bjerring, Peter Nissen

    2011-01-01

    Acute liver failure (ALF) results in a multitude of serious complications that often lead to multi-organ failure. This brief review focuses on the pathophysiological processes in ALF and how to manage these.......Acute liver failure (ALF) results in a multitude of serious complications that often lead to multi-organ failure. This brief review focuses on the pathophysiological processes in ALF and how to manage these....

  10. Long-term use of angiotensin receptor blockers and the risk of cancer.

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. In Support of Failure

    Science.gov (United States)

    Carr, Allison

    2013-01-01

    In this essay, I propose a concerted effort to begin devising a theory and pedagogy of failure. I review the discourse of failure in Western culture as well as in composition pedagogy, ultimately suggesting that failure is not simply a judgement or indication of rank but is a relational, affect-bearing concept with tremendous relevance to…

  13. Late toxicity and five year outcomes after high-dose-rate brachytherapy as a monotherapy for localized prostate cancer

    International Nuclear Information System (INIS)

    Ghadjar, Pirus; Oesch, Sebastian L; Rentsch, Cyrill A; Isaak, Bernhard; Cihoric, Nikola; Manser, Peter; Thalmann, George N; Aebersold, Daniel M

    2014-01-01

    To determine the 5-year outcome after high-dose-rate brachytherapy (HDR-BT) as a monotherapy. Between 10/2003 and 06/2006, 36 patients with low (28) and intermediate (8) risk prostate cancer were treated by HDR-BT monotherapy. All patients received one implant and 4 fractions of 9.5 Gy within 48 hours for a total prescribed dose (PD) of 38 Gy. Five patients received concomitant androgen deprivation therapy (ADT). Toxicity was scored according to the common terminology criteria for adverse events from the National Cancer Institute (CTCAE) version 3.0. Biochemical recurrence was defined according to the Phoenix criteria and analyzed using the Kaplan Meier method. Predictors for late grade 3 GU toxicity were analyzed using univariate and multivariate Cox regression analyses. The median follow-up was 6.9 years (range, 1.5-8.0 years). Late grade 2 and 3 genitourinary (GU) toxicity was observed in 10 (28%) and 7 (19%) patients, respectively. The actuarial proportion of patients with late grade 3 GU toxicity at 5 years was 17.7%. Late grade 2 and 3 gastrointestinal (GI) toxicities were not observed. The crude erectile function preservation rate in patients without ADT was 75%. The 5 year biochemical recurrence-free survival (bRFS) rate was 97%. Late grade 3 GU toxicity was associated with the urethral volume (p = 0.001) and the urethral V 120 (urethral volume receiving ≥120% of the PD; p = 0.0005) after multivariate Cox regression. After HDR-BT monotherapy late grade 3 GU was observed relatively frequently and was associated with the urethral V 120 . GI toxicity was negligible, the erectile function preservation rate and the bRFS rate was excellent

  14. Efficacy and safety of eslicarbazepine acetate monotherapy for partial-onset seizures: Experience from a multicenter, observational study.

    Science.gov (United States)

    Toledano, Rafael; Jovel, Camilo Espinosa; Jiménez-Huete, Adolfo; Bayarri, Pau Giner; Campos, Dulce; Gomariz, Elena López; Giráldez, Beatriz González; García-Morales, Irene; Falip, Mercé; Agredano, Paula Martínez; Palao, Susana; Prior, María José Aguilar Amat; Pascual, María Rosa Querol; Navacerrada, Francisco José; González, Francisco Javier López; Ojeda, Joaquín; Sáez, Aránzazu Alfaro; Bermejo, Pedro Emilio; Gil-Nagel, Antonio

    2017-08-01

    Eslicarbazepine acetate (ESL, Aptiom™) is a once-daily anticonvulsant, approved as adjunctive treatment of partial-onset seizures (POS). Historical-controlled trials investigating the use of ESL as monotherapy have demonstrated a favorable efficacy and tolerability profile in patients with POS. This prospective, non-interventional study recruited POS patients in 17 hospitals in Spain. After a 3-month baseline period, ESL therapy was initiated as 400mg QD and up-titrated to an optimal maintenance dose based on clinical response and tolerance. The incidence of seizures was assessed via seizure calendars and the nature and severity of adverse events (AEs) were also recorded. A total of 117 patients (aged 9-87years) enrolled in the study and were treated with ESL at either 400mg/day (3.4% patients), 800mg/day (61% patients), 1200mg/day (27.1% patients) or 1600mg/day (8.5% patients). At 3months, 82.0% (n=72) of patients achieved a ≥50% reduction in seizure frequency, compared to 79.7% (n=67) of patients at 6months and 83.0% (n=49) at 12months. Patients who suffered secondary generalized tonic-clonic (SGTC) seizures had seizure-free rates of 71% (n=27), 69.6% (n=29), and 72.7% (n=16) at 3, 6, and 12months, respectively. Overall, 18 patients (15.3%) reported AEs of instability and dizziness (n=9), somnolence (n=3), mild hyponatremia (n=3), headache (n=1), hypertriglyceridemia (n=1), and allergic reaction (n=1), which caused ESL discontinuation of ESL treatment. ESL is effective and well tolerated as monotherapy for patients with POS, which supports previous findings. Early use is supported by its frequent use as monotherapy in this study and lack of severe side effects. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Short-term Effect of Tamsulosin and Finasteride Monotherapy and their Combination on Nigerian Men with Benign Prostatic Hyperplasia.

    Science.gov (United States)

    Odusanya, Benjamin O; Tijani, Kehinde H; Jeje, Emmanuel A; Ogunjimi, Moses A; Ojewola, Rufus W

    2017-01-01

    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). This is a prospective single-blind randomized study of ninety men with BPH who were managed using drugs. The International Prostate Symptom Score (IPSS), peak urinary flow rate, and prostate volume were measured as parameters for assessment at the beginning, 3 months, and 6 months of the study. The mean age of patients was 61.65 with a range of 44-81 years. There was a progressive and sustained improvement in the IPSS score in all patient groups with mean decrease at 3 months of 7.24 (42.59%), 7.60 (41.85%), and 7.24 (40.61%) and at 6 months of 8.14 (47.88%), 10.33 (56.88%), and 11.1 (62.25%) in the tamsulosin, finasteride, and combination groups, respectively. There was an increase in peak urinary flow rate in all groups with mean increase at 3 months of 0.98, 0.05, and 3.55 (ml/s) and at 6 months of 4.11, 0.87, and 3.74 (ml/s) in the tamsulosin, finasteride, and combination groups, respectively. There was a reduction in the prostate volume in the finasteride and combination groups at 6 months of 6.8 and 6.32 cm 3 , respectively, while the tamsulosin group recorded an increase. At the end of 6 months, tamsulosin monotherapy and combination therapy appear to be equally effective in the treatment of lower urinary tract symptoms BPH while finasteride monotherapy appears to be the least effective. Bothersome, side effects were more in patients taking finasteride alone or as combination therapy.

  16. Lithium monotherapy associated clinical improvement effects on amygdala-ventromedial prefrontal cortex resting state connectivity in bipolar disorder.

    Science.gov (United States)

    Altinay, Murat; Karne, Harish; Anand, Amit

    2018-01-01

    This study, for the first time, investigated lithium monotherapy associated effects on amygdala- ventromedial prefrontal cortex (vMPFC) resting-state functional connectivity and correlation with clinical improvement in bipolar disorder (BP) METHODS: Thirty-six medication-free subjects - 24 BP (12 hypomanic BPM) and 12 depressed (BPD)) and 12 closely matched healthy controls (HC), were included. BP subjects were treated with lithium and scanned at baseline, after 2 weeks and 8 weeks. HC were scanned at same time points but were not treated. The effect of lithium was studied for the BP group as a whole using two way (group, time) ANOVA while regressing out effects of state. Next, correlation between changes in amygdala-vMPFC resting-state connectivity and clinical global impression (CGI) of severity and improvement scale scores for overall BP illness was calculated. An exploratory analysis was also conducted for the BPD and BPM subgroups separately. Group by time interaction revealed that lithium monotherapy in patients was associated with increase in amygdala-medial OFC connectivity after 8 weeks of treatment (p = 0.05 (cluster-wise corrected)) compared to repeat testing in healthy controls. Increased amygdala-vMPFC connectivity correlated with clinical improvement at week 2 and week 8 as measured with the CGI-I scale. The results pertain to open-label treatment and do not account for non-treatment related improvement effects. Only functional connectivity was measured which does not give information regarding one regions effect on the other. Lithium monotherapy in BP is associated with modulation of amygdala-vMPFC connectivity which correlates with state-independent global clinical improvement. Copyright © 2017. Published by Elsevier B.V.

  17. Effect of inhaled N-acetylcysteine monotherapy on lung function and redox balance in idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Muramatsu, Yoko; Sugino, Keishi; Ishida, Fumiaki; Tatebe, Junko; Morita, Toshisuke; Homma, Sakae

    2016-05-01

    An oxidant-antioxidant imbalance is considered to be involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Therefore, administration of antioxidants, such as N-acetylcysteine (NAC), may represent a potential treatment option for IPF patients. The aim of this study was to evaluate the effect of inhaled NAC monotherapy on lung function and redox balance in patients with IPF. A retrospective observational study was done, involving 22 patients with untreated early IPF (19 men; mean [±S.D.] age, 71.8 [±6.3]y). At baseline and at 6 and 12 months after initiating inhaled NAC monotherapy, we assessed forced vital capacity (FVC) and measured the levels of total glutathione, oxidized glutathione (GSSG), and the ratio of reduced to oxidized glutathione in whole blood (hereafter referred to as the ratio), and of 8-hydroxy-2'-deoxyguanosine in urine. To evaluate response to treatment, we defined disease progression as a decrease in FVC of ≥5% from baseline and stable disease as a decrease in FVC of <5%, over a period of 6 months. Change in FVC in the stable group at 6 and 12 months were 95±170mL and -70±120mL, while those in the progressive group at 6 and 12 months were -210±80mL, -320±350mL, respectively. The serial mean change in GSSG from baseline decreased as the ratio of reduced to oxidized glutathione increased in patients with stable disease, while it increased as this ratio decreased in patients with progressive disease. Receiver operating characteristic curve analysis revealed that a baseline GSSG level of ≥1.579μM was optimal for identifying treatment responders. Inhaled NAC monotherapy was associated with improved redox imbalance in patients with early IPF. Copyright © 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  18. Effect of rosuvastatin monotherapy and in combination with fenofibrate or omega-3 fatty acids on serum vitamin D levels.

    Science.gov (United States)

    Makariou, Stefania E; Liberopoulos, Evangelos N; Agouridis, Aris P; Challa, Anna; Elisaf, Moses

    2012-12-01

    Low levels of 25(OH) vitamin D [25(OH)VitD] have been recognized as a new cardiovascular disease (CVD) risk factor. Statins seem to increase 25(OH)VitD concentration. To investigate whether combined treatment with the usual dose of rosuvastatin plus fenofibrate or omega-3 fatty acids would increase 25(OH)VitD levels compared with the high-dose rosuvastatin monotherapy in participants with mixed dislipidemia. We randomly allocated 60 patients with mixed dyslipidemia (low-density lipoprotein cholesterol: >160 mg/dL plus triglycerides: >200 mg/dL) to receive rosuvastatin 40 mg (n = 22), rosuvastatin 10 mg plus fenofibrate 200 mg (n = 21), or rosuvastatin 10 mg plus omega-3 fatty acids 2 g (n = 17) daily for 3 months. Our primary end point was changes in the levels of serum 25(OH)VitD. Rosuvastatin monotherapy was associated with a 53% increase in 25(OH)VitD (from 14.6 [1.0-38.0] to 17.8 [5.3-49.6] ng/mL; P = .000). Rosuvastatin plus micronized fenofibrate and rosuvastatin plus omega-3 fatty acids were associated with increases of 64% (from 14.1 [1.0-48.0] to 18.4 [6.7-52.4] ng/mL, P = .001) and 61% (from 10.4 [6.6-38.4] to 14.0 [9.6-37.6] ng/mL, P = .04), respectively. The changes in 25(OH)VitD after treatment were comparable in the 3 groups. High-dose rosuvastatin monotherapy and the usual dose of rosuvastatin plus fenofibrate or omega-3 fatty acids are associated with significant and similar increases in the 25(OH)VitD levels. This increase may be relevant in terms of CVD risk prevention.

  19. 125I Monotherapy Using D90 Implant Doses of 180 Gy or Greater

    International Nuclear Information System (INIS)

    Kao, Johnny; Stone, Nelson N.; Lavaf, Amir; Dumane, Vishruta; Cesaretti, Jamie A.; Stock, Richard G.

    2008-01-01

    Purpose: The purpose of this study was to characterize the oncologic results and toxicity profile of patients treated with 125 I implants using the dose delivered to 90% of the gland from the dose-volume histogram (D90) of greater than 144 Gy. Methods and Materials: From June 1995 to Feb 2005, a total of 643 patients were treated with 125 I monotherapy for T1-T2 prostate cancer with a D90 of 180 Gy or greater (median, 197 Gy; range, 180-267 Gy). Implantations were performed using a real-time ultrasound-guided seed-placement method and intraoperative dosimetry to optimize target coverage and homogeneity by using modified peripheral loading. We analyzed biochemical disease-free survival (bDFS) of 435 patients who had a minimum 2-year prostate-specific antigen follow-up (median follow-up, 6.7 years; range, 2.0-11.1 years). Results: Five-year bDFS rates for the entire cohort using the American Society for Therapeutic Radiology and Oncology and Phoenix definitions were 96.9% and 96.5%, respectively. Using the Phoenix definition, 5-year bDFS rates were 97.3% for low-risk patients and 92.8% for intermediate/high-risk patients. The positive biopsy rate was 4.1%. The freedom rate from Grade 2 or higher rectal bleeding at 5 years was 88.5%. Acute urinary retention occurred in 10.7%, more commonly in patients with high pretreatment International Prostate Symptom Scores (p < 0.01). In patients who were potent before treatment, 73.4% remained potent at 5 years after implantation. Conclusions: Patients with a minimum D90 of 180 Gy had outstanding local control based on prostate-specific antigen control and biopsy data. Toxicity profiles, particularly for long-term urinary and sexual function, were excellent and showed that D90 doses of 180 Gy or greater performed using the technique described were feasible and tolerable

  20. High-Dose-Rate Monotherapy for Localized Prostate Cancer: 10-Year Results

    Energy Technology Data Exchange (ETDEWEB)

    Hauswald, Henrik; Kamrava, Mitchell R.; Fallon, Julia M.; Wang, Pin-Chieh; Park, Sang-June; Van, Thanh; Borja, Lalaine; Steinberg, Michael L.; Demanes, D. Jeffrey, E-mail: JDemanes@mednet.ucla.edu

    2016-03-15

    Purpose: High-dose-rate (HDR) brachytherapy was originally used with external beam radiation therapy (EBRT) to increase the dose to the prostate without injuring the bladder or rectum. Numerous studies have reported HDR brachytherapy is safe and effective. We adapted it for use without EBRT for cases not requiring lymph node treatment. Patients and Methods: We entered the patient demographics, disease characteristics, and treatment parameters into a prospective registry and serially added follow-up data for 448 men with low-risk (n=288) and intermediate-risk (n=160) prostate cancer treated from 1996 to 2009. Their median age was 64 years (range 42-90). The median prostate-specific antigen (PSA) level was 6.0 ng/mL (range 0.2-18.2). The Gleason score was ≤6 in 76% and 7 in 24%. The median dose was 43.5 Gy in 6 fractions. The clinical and biochemical disease control and survival rates were calculated. Adverse events were graded according to the Common Toxicity Criteria of Adverse Events. Results: The median follow-up period was 6.5 years (range 0.3-15.3). The actuarial 6- and 10-year PSA progression-free survival was 98.6% (95% confidence interval [CI] 96.9%-99.4%) and 97.8% (95% CI 95.5%-98.9%). Overall survival at 10 years was 76.7% (95% CI 69.9%-82.2%). The local control, distant metastasis-free survival, and cause-specific survival were 99.7% (95% CI 97.9%-99.9%), 98.9% (95% CI 96.3%-99.7%), and 99.1% (95% CI 95.8%-99.8%). T stage, initial PSA level, Gleason score, National Comprehensive Cancer Network risk group, patient age, and androgen deprivation therapy did not significantly correlate with disease control or survival. No late grade 3 to 4 rectal toxicities developed. Late grade 3 to 4 genitourinary toxicity occurred in 4.9% (grade 3 in 4.7%). Conclusions: HDR monotherapy is a safe and highly effective treatment of low- and intermediate-risk prostate cancer.

  1. Comparison of several alternative uses of targeted antirheumatic drugs in monotherapy for early rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    O. V. Shatalova

    2017-01-01

    Full Text Available Objective: to evaluate the efficacy of tocilizumab (TCZ versus tofacitinib (TOFA in patients with severe and moderate rheumatoid arthritis (RA who have not previously received methotrexate (MTX. Material and methods. A systematic search for studies dealing with the evaluation of the efficacy of TCZ and TOFA was made in accordance with the provisions of the instruction «Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA». Indirect comparison of two Function and ORAL Start randomized clinical trials was done, as described by Н.C. Buchera. The trials were comparable in their design and in the baseline characteristics of patients. The efficiency of pharmacotherapy for early RA was evaluated based on the ACR20/50/70 response rates in MTX-naive patients from three endpoints. Results. The indirect comparison of TOFA and TCZ (A MTX general control after 52 weeks of treatment in MT-naive patients with severe and moderate RA indicated that the use of TOFA 5 mg twice daily and TCZ 8 mg/kg showed no difference in ACR20, ACR50, and ACR70 response rates. Nevertheless, there was a tendency to the greater efficiency of TOFA (5 mg twice daily than that of TCZ (8 mg/kg. The indirect comparison of TOFA (10 mg twice daily and TCZ (8 mg/kg established that TCZ therapy was associated with the lower response rate for ACR50 (by 37%: the relative risk (RR was 0.63; 95% confidence interval (CI, 0.44–0.90 and for ACR70 (by 51%: RR, 0.49; 95% CI, 0.29–0.83 as compared with TOFA therapy. Conclusion. The indirect comparisons confirmed that monotherapy with TOFA (10 mg twice daily produced a more pronounced antiinflammatory effect than that with TCZ in MTX-naive patients with early severe and moderate RA of less than one year's duration. There were no statistically significant differences in ACR response rates between the TOFA (5 mg twice daily and TCZ (8 mg/kg groups. 

  2. High dosages of sermion (30-60 mg per day) neuropsychiatric efficacy for encephalopathy monotherapy in irradiated patients

    International Nuclear Information System (INIS)

    Nyagu, A.I.; Loganovskij, K.N.; Yur'ev, K.L.; Petrova, I.V.; Bomko, M.A.

    1999-01-01

    Open randomised with parallel groups clinical trial was carried out for an assessment of neuropsychiatric efficacy of monotherapy by high dosages of Sermion (30-60 mg per day) in 57 liquidators at the age of 33-65 years irradiated by 50-900 mGy with organic mental disorders (encephalopathy) occurred following cleaning up works in the Chernobyl exclusion zone in 1986-1987. According to the obtained results Sermion 30-60 mg per day may be recommended for the treatment of patients with organic mental disorders (encephalopathy) exposed to ionising radiation

  3. Prospective noninterventional study on the use of panitumumab monotherapy in patients with recurrent or progressive colorectal cancer: the VECTIS study

    International Nuclear Information System (INIS)

    Lakomy, Radek; Rogowski, Wojciech; Piko, Bela; Mihaylova, Zh; Pritzova, Eva; Kvocekova, Lucia

    2015-01-01

    Epidermal growth factor receptor-targeted monoclonal antibodies are active as monotherapy beyond second-line treatment. Skin toxicities (STs) are common during treatment, and a positive association between ST severity and patient outcome has been reported. This study collected information on panitumumab monotherapy use in patients with KRAS exon 2 wild-type metastatic colorectal cancer in clinical practice. This open-label, prospective, observational, noninterventional study included adult patients who had failed prior chemotherapy with 5-fluorouracil, oxaliplatin, and irinotecan. Patients received panitumumab monotherapy (6 mg/kg every 2 weeks) for ≤18 cycles. Effectiveness was assessed as disease control rate (DCR), tumor response, and freedom from progression. The incidence of ST and other adverse drug reactions (ADRs) was recorded, as were Eastern Cooperative Oncology Group performance status (ECOG PS) and quality of life. The KRAS analysis process was also evaluated. The full analysis set included 632 patients (64.6% male; mean age, 62.3 years), who completed a mean of 9.6 panitumumab cycles. ST, mainly grade 1/2, occurred in 84.3% of patients, 82.7% of whom required treatment. Nonskin ADRs occurred in 3.5% of patients. By the end of treatment, the DCR was 58.9% overall, and was 53.8% and 62.7%, respectively in patients with ST grade 0/1 and grade 2/3. Significant associations were observed between maximum ST grade and best response (P=0.0009), DCR (P=0.0046), tumor response (P=0.0002), and freedom from progression (P=0.0084). At the end of the study, 67.4% of the patients had an ECOG PS of 0/1. Quality of life was rated as “very good” or “good” in 70.3% of patients. Mean time to obtain KRAS results was 18.2 days; satisfaction with different aspects of KRAS testing was “very good” or “good” in 80%–97% of patients. Panitumumab monotherapy showed adequate effectiveness and safety in patients with heavily pretreated KRAS exon 2 wild

  4. 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...

  5. 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