贝那普利联合美托洛尔治疗慢性心力衰竭的180例疗效观察

目的探讨贝那普利联合美托洛尔治疗慢性心力衰竭的有效性和安全性。方法选取2010年12月—2012年12月期间就诊于该院的慢性心力衰竭患者180例进行回顾性分析并随机分为2组,每组90例。其中,对照组在常规方法（如强心、利尿、扩血管等）治疗的基础上,给予贝那普利治疗,而观察组则在对照组的基础上联合美托洛尔进行治疗。观察用药前后两组患者心功能的改善情况,比较2种治疗方法的临床疗效和不良反应的发生情况。结果治疗后,观察组患者的心功能明显改善,总有效率为95.56%,不良反应率为12.22%,而对照组总有效率则为83.33%,不良反应率为11.11%,可见观察组的有效性明显优于对照组,经分析,差异有统计学意义（P〈0.05）,而不良反应的发生差异无统计学意义（P〉0.05）。结论贝那普利联合美托洛尔治疗能够显著改善慢性心力衰竭患者的临床症状,其疗效确切,安全性高,值得在临床上推广使用。     

Efficacy and Safety of Rivastigmine in Patients with Alzheimer's Disease who Failed to Benefit from Treatment with Donepezil

Summary

Background: Selective acetylcholinesterase (AChE) and dual acetyl- and butyrylcholinesterase inhibitors constitute the only approved agents for the symptomatic treatment of Alzheimer's disease (AD). Donepezil is a specific, reversible inhibitor of AChE, while rivastigmine is a slowly reversible (pseudoirreversible) dual cholinesterase (ChE) inhibitor, with brain-regional specificity for the cerebral cortex and hippocampus. According to the European Marketing Authorisations, the clinical benefit of ChE inhibitors should be reassessed on a regular basis and discontinuation should be considered when evidence of a therapeutic effect is no longer present. However, substantial differences in the pharmacological and pharmacokinetic profiles of the available ChE inhibitors suggest that it may be desirable to switch between ChE inhibitors if patients fail to show efficacy, deteriorate or are unable to tolerate their initially prescribed medication.

Design: This open-label, six-month study evaluated the efficacy and safety of rivastigmine in 382 AD patients who had previously failed to benefit from treatment with donepezil (80% due to lack of efficacy, 11% due to tolerability problems, 9% both reasons).

Results: At the end of the study, 56.2% of patients were responders to rivastigmine, as assessed using a global function scale (the Clinicians’ Global Impression of Change). Cognitive performance (measured by the Mini-Mental State Examination) and the ability to perform activities of daily living (measured by the Instrumental Activities of Daily Living scale) were improved/stabilised in 48.9% and 57.0% of patients, respectively. Rivastigmine was generally well tolerated, the most common adverse events being nausea and vomiting, consistent with reports from previous clinical studies. The occurrence of side-effects or lack of efficacy with donepezil treatment was not a predictor of similar problems when treated with rivastigmine.

Conclusion: Rivastigmine treatment appears to be beneficial in AD patients who have previously failed to benefit from, or were unable to tolerate treatment with, donepezil.     

Comparison of safety outcomes among Caucasian,Hispanic, Black,and Asian patients in duloxetine studies of chronic painful conditions

Abstract

Objective:

This post-hoc analysis was conducted to investigate if safety outcomes differed among race/ethnic subgroups of patients treated with duloxetine for chronic painful conditions.     

Long-term effectiveness and tolerability of sublingual fentanyl orally disintegrating tablet for the treatment of breakthrough cancer pain

Abstract

Background and objectives:

Breakthrough cancer pain (BTcP) is a transient exacerbation of cancer pain in patients with otherwise stable, persistent background pain. This study evaluated the long-term effectiveness and tolerability of sublingual fentanyl orally disintegrating tablet (sublingual fentanyl ODT), for the treatment of BTcP in opioid-tolerant patients with cancer.     

Randomized,double-blind trial of carisoprodol 250 mg compared with placebo and carisoprodol 350 mg for the treatment of low back spasm

Abstract

Background:

Carisoprodol, a centrally active skeletal muscle relaxant, is widely used for the treatment of acute, painful musculoskeletal disorders. When administered at a dose of 350?mg four times daily, carisoprodol demonstrated significant clinical benefit in its early clinical development trials; however, some unfavorable side effects, such as drowsiness and dizziness, were reported. Recently, research was conducted to determine if a lower dose of carisoprodol would retain efficacy but improve tolerability compared to the higher 350-mg dose.     

Key barriers to optimal manage­ment of adult asthma in Australia: physician and patient perspectives

ABSTRACT

Objective: Despite recent advances in asthma treatment, its management in many patients remains sub-optimal. The aim of the Global Asthma Physicians and Patient (GAPP) survey was to identify barriers to optimal asthma management and to explore the content and dynamics of physician–patient communications. Here we present the key findings for adults with asthma in Australia.

Research design and methods: Patients with asthma aged ≥ 18 years and physicians who treat adults (generalists; specialists) participated in telephone interviews conducted in May–June 2005, using close-end questionnaires. The survey examined physicians’ beliefs and prescribing habits; patients’ experiences with asthma; doctor–patient communication; satisfaction with asthma medications and interest in new asthma treatment.

Results: A total of 101 adults with asthma and 100 physicians treating asthma patients in Australia completed the survey. Overall, key barriers to optimal asthma management included medication side effects, treatment compliance and patient education. These barriers may be exacerbated by poor patient–physician communication that fails to address patients concerns regarding side effects and may lead to poor treatment compliance. Both physicians and patients expressed safety concerns regarding the long-term use of inhaled corticosteroid and both groups would welcome new treatment options with improved safety profiles, efficacy and once-daily dosing.

Conclusion: From both a physician and patient perspective, the safety profile of asthma medication constitutes a key factor in promoting treatment compliance and, ultimately, treatment outcomes. The results highlight discrepancies in perceived patient–physician communication and a need for improved patient education in asthma management.     

Efficacy and safety of single therapeutic and supratherapeutic doses of indacaterol versus salmeterol and salbutamol in patients with asthma

ABSTRACT

Objective: This study compared the bronchodilator efficacy and safety of indacaterol with placebo, salbutamol and salmeterol, in patients with persistent asthma, at single therapeutic and supratherapeutic doses.

Research design and methods: This was a randomised, open-label crossover study in adult subjects with asthma (forced expiratory volume in 1 second [FEV₁] ≥?60% predicted). In part A, patients (n = 20) received single doses of indacaterol 200?µg, salbutamol 200?µg, salmeterol 50?µg and placebo. In part B, patients (n = 19) received single doses of indacaterol 1000?µg, salbutamol 1000?µg, salmeterol 250?µg and placebo.

Main outcomes measures; Results: For the primary endpoint, FEV₁ area under the effect curve during 0–24?h, indacaterol 200?µg was statistically superior to placebo and salbutamol. Indacaterol 200?µg FEV₁ was higher than placebo (5?min to 24?h), salbutamol 200?µg (4–24?h), and salmeterol 50?µg (5 and 15?min and 22 and 24?h). Few adverse events were reported; all were mild or moderate in severity. Initial changes were observed in glucose, potassium, heart rate and QTc interval, but all values remained within normal ranges. Values matched placebo levels after a shorter time for indacaterol 1000?µg than for salmeterol 250?µg.

Conclusions: In this single-dose, open-label study, indacaterol 200?µg provided effective 24‐h bronchodilation, with a longer duration than salmeterol 50?µg and a good overall safety profile. The sustained bronchodilation of indacaterol 1000?µg was not associated with sustained systemic adverse effects.     

Therapeutic effects of epoetin zeta in the treatment of chemotherapy-induced anaemia

ABSTRACT

Objective: To perform an open, non-controlled, multiple-dose, international, multicentre, phase III study to evaluate epoetin zeta, a biosimilar epoetin referenced to epoetin alfa, for the treatment of chemotherapy-induced anaemia in patients with cancer.

Methods: Safety, tolerability and efficacy of subcutaneously administered epoetin zeta were assessed in 216 patients with solid tumours or non-myeloid haematological malignancies receiving chemotherapy and at risk of transfusion.

Results: A significant (p?<?0.0001) increase in mean haemoglobin (Hb) level (1.8?g/dL) was observed between baseline and week 12 (intent-to-treat population); 176/216 (81.5%) patients achieved a response (increase in Hb?≥?1?g/dL or reticulocyte count ≥40?000 cells/μL) by week 8. Over the treatment period, 231 treatment-emergent adverse events were experienced by 91 patients; 9/216 (4.2%) experienced a clinically significant thrombotic event within the first 12 weeks of epoetin zeta treatment, significantly lower than the assumed 18% baseline incidence (p?<?0.0001) based on historical data from epoetin trials. No transfusion was necessary for 175/216 patients (81.0%) and quality of life improved over the study. No patients developed anti-erythropoietin antibodies. Sponsor trial no: CT-830-05-0009.

Conclusion: This study demonstrates that subcutaneously administered epoetin zeta is well-tolerated and has efficacy in the treatment of anaemia in patients with cancer receiving chemotherapy and at risk of transfusion.     

Long-term safety and tolerability of ezetimibe coadministered with simvastatin in hypercholesterolemic patients: a randomized, 12-month double-blind extension study

ABSTRACT

Objectives: To assess the long-term safety and tolerability and to further evaluate the effect of ezetimibe plus simvastatin on LDL-C, HDL-C, and triglyceride levels in subjects with primary hypercholesterolemia.

Methods: This was a 12-month, double-blind, placebo-controlled extension study that enrolled patients with primary hypercholesterolemia who had successfully completed the 12-week, double-blind, placebo-controlled trial of ezetimibe coadministered with simvastatin. The initial dose administered to patients in the extension was ezetimibe 10 mg coadministered with simvastatin 10 mg with the option to up-titrate statin dosage if LDL-C goals were not met. Safety and tolerability were assessed through clinical and laboratory adverse experiences (AEs). Changes from baseline in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglyceride levels were measured.

Results: Overall, 87 patients were randomized to receive ezetimibe + simvastatin and 22 were randomized to receive simvastatin and placebo. Treatment-emergent AEs were reported for 72/87 (83%) ezetimibe + simvastatin-treated patients and for 17/22 (77%) simvastatin-treated patients. The most commonly reported AEs in the simvastatin treatment group were hypertension, gastro-esophageal reflux, and musculoskeletal pain (each reported by 3/22 [14%] patients); and in the ezetimibe + simvastatin group were upper respiratory tract infection (16/87 [18%]), arthralgia and musculoskeletal pain (both reported by 10/87 [11%] patients). Drug-related AEs were reported for 3/22 (14%) simvastatin-treated patients and 21/87 (24%) patients in the coadministration group. AEs considered serious by the investigator were reported by 2/22 (9%) patients taking simvastatin monotherapy and by 20/87 (23%) patients taking ezetimibe + simvastatin. Discontinuations due to AEs occurred in no patients taking simvastatin monotherapy and in 7/87 (8%) patients taking ezetimibe + simvastatin. Percent change ± standard deviation from baseline in LDL-C was ?29% ± 15.4 and ?44% ± 14.2 in subjects taking simvastatin monotherapy and ezetimibe + simvastatin, respectively.

Conclusions: Ezetimibe coadministered with simvastatin was generally well-tolerated and no new safety concerns were raised. Both treatments effectively maintained improvements in lipid parameters throughout the course of the studies. Interpretation of these results was limited by the small convenience sample included in the trial.     

Safety profile of carmustine wafers in malignant glioma: a review of controlled trials and a decade of clinical experience

ABSTRACT

Background: Carmustine (1,3-bis [2-chloroethyl]-1-nitrosourea, or BCNU) wafers are approved for recurrent glioblastoma and newly diagnosed malignant glioma (MG). Based on considerable clinical experience and use in multimodal regimens, the safety of BCNU wafers needs a re-evaluation.

Scope: A review of literature from 1996 to February 2008 was conducted on the safety of BCNU wafer in MG patients using search criteria in Medline, EMBASE, and BIOSIS. Abstracts from relevant US and European meetings were also evaluated. Three Phase III (two were pivotal) and 26 non-Phase III studies met inclusion criteria. Overall incidence was estimated for each adverse event (AE), and data from individual studies were summarised as median (range) rates. Comparisons were based on consistent similarities or differences across overall incidence, median rate and range.

Findings: BCNU wafer group AE rates from the two pivotal Phase III trials ranged from 4–23% for cerebral oedema, 4–9% for intracranial hypertension, 14–16% for healing abnormalities, 5% for CSF leaks, 4–5% for intracranial infection, 19–33% for seizures, 10% for deep vein thrombosis, and 8% for pulmonary embolus. There were no notable differences in AE rates between the two pivotal Phase III and 26 non-Phase III studies. For the non-pivotal studies, the overall incidence of AEs was low, ranging from 0.2% for intracranial hypertension to 9.6% for healing abnormalities. Healing abnormalities, intracranial infection, and seizures were the most consistently reported AEs, having been observed in 16, 12, and 11 studies, respectively. Rates of healing abnormalities appeared higher in recurrent than in newly diagnosed disease. There were no notable differences between BCNU wafer plus adjuvant treatment (e.g., temozolomide) and BCNU wafer alone, with the exception of haematologic toxicity.

Conclusion: This review of safety data for BCNU wafers provides reassurance that the AE rates reported in current treatment strategies including multimodal treatment approaches are comparable to those observed in the initial registration studies. The broad range of AE rates may reflect differences in the perioperative and postoperative management. Clinical experience suggests that strategies may exist to reduce the risk of complications.