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Long-term macrolide antibiotics in asthma therapy  [cached]
Daisuke Takekoshi,Patrick Belvitch,Israel Rubinstein
Reviews in Health Care , 2011, DOI: 10.7175/rhc.6124243-258
Abstract: Macrolide antibiotics drew worldwide attention when their use was dramatically successful in the treatment of diffuse panbronchiolitis in 1980s. The success was attributed to their immunomodulatory effects, rather than their antimicrobial properties. Since then, studies have shown that macrolides exert their immunomodulatory effects through several mechanisms, including suppression of proinflammatory cytokines, promoting apoptosis of inflammatory cells, improving phagocytic function, ameliorating airway hypersecretion, and inhibiting production of reactive oxygen species. Macrolides have also been studied in the treatment of asthma. This review highlights the role of macrolides in the treatment of asthma, presenting an overview of the main clinical trials. Despite favourable preclinical data and reports of anecdotal successes, the results of clinical trials are conflicting. This may be due to the heterogeneous nature of asthma. Further studies are needed to identify particular subgroup of asthma that will respond to macrolides.
Low-dose, long-term macrolide therapy in asthma: An overview
Umur Hatipo?lu, Israel Rubinstein
Clinical and Molecular Allergy , 2004, DOI: 10.1186/1476-7961-2-4
Abstract: The purpose of this overview is to outline the immunomodulatory effects of macrolide antibiotics in patients with asthma.Asthma is a chronic inflammatory disease characterized by airway narrowing. There are three distinct components of reduction in airway caliber: secretions, smooth muscle contraction and airway wall thickening. While pathogenetic changes that bring about airway narrowing may be heterogeneous, it is generally accepted that inflammatory cell infiltration with secretion of pro-inflammatory cytokines plays a major role in pathogenesis of asthma. The major inflammatory cells that are involved in this process are type 2 helper T (Th2) cells, eosinophils and mast cells.Upon stimulation, Th2 cells elaborate various cytokines (IL-4, IL-5, IL-13 and GM-CSF in particular) that stimulate the plasma cells to switch to specific IgE production and induce myeloid differentiation. IgE bind to mast cells that result in secretion of preformed mediators of bronchoconstriction and glandular secretion (histamine, leukotrienes and kallikrein) as well as secretion of cytokines (IL-4 and IL-5), which increase eosinophil chemotaxis and Th2 and mast cell proliferation (positive feedback). When stimulated by IgE, eosinophils release a number of compounds cytotoxic to airway epithelium such as eosinophil cationic protein (ECP) as well as IL-8, a chemotactic factor for eosinophils and neutrophils. Neutrophilic inflammation becomes more pronounced and is related to airflow obstruction particularly in the airways of chronic asthmatics.The airway epithelium may also play an important role in initiation and maintenance of the inflammatory response through secretion of chemokines such as Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES) that attracts eosinophils, basophils and lymphocytes to the airway. Airway epithelium also elaborates nitric oxide (NO), which is thought to suppress Th1 cells thereby augmenting Th2 cell induced inflammation. Through a process t
Clinical utility of adjunctive retigabine in partial onset seizures in adults
Rejdak K, Luszczki JJ, B aszczyk B, Chwedorowicz R, Czuczwar SJ
Therapeutics and Clinical Risk Management , 2012, DOI: http://dx.doi.org/10.2147/TCRM.S22605
Abstract: ical utility of adjunctive retigabine in partial onset seizures in adults Review (3013) Total Article Views Authors: Rejdak K, Luszczki JJ, B aszczyk B, Chwedorowicz R, Czuczwar SJ Published Date January 2012 Volume 2012:8 Pages 7 - 14 DOI: http://dx.doi.org/10.2147/TCRM.S22605 Received: 25 November 2011 Accepted: 15 December 2011 Published: 20 January 2012 Konrad Rejdak1, Jarogniew J Luszczki2,3, Barbara Blaszczyk4, Roman Chwedorowicz5, Stanislaw J Czuczwar2,5 1Department of Neurology, Medical University of Lublin, Lublin, 2Department of Pathophysiology, Medical University of Lublin, Lublin, 3Isobolography Analysis Laboratory, Institute of Agricultural Medicine, Lublin, 4Faculty of Health Sciences, High School of Economics and Law, Kielce, 5Department of Physiopathology, Institute of Agricultural Medicine, Lublin, Poland Abstract: In ~30% of epileptic patients, full seizure control is not possible, which is why the search for novel antiepileptic drugs continues. Retigabine exhibits a mechanism of action that is not shared by the available antiepileptic drugs. This antiepileptic enhances potassium currents via Kv7.2–7.3 channels, which very likely results from destabilization of a closed conformation or stabilization of the open conformation of the channels. Generally, the pharmacokinetics of retigabine are linear and the drug undergoes glucuronidation and acetylation. Results from clinical trials indicate that, in the form of an add-on therapy, retigabine proves an effective drug in refractory epileptic patients. The major adverse effects of the add-on treatment are dizziness, somnolence, and fatigue. This epileptic drug is also considered for other conditions – neuropathic pain, affective disorders, stroke, or even Alzheimer’s disease.
Adjunctive Aripiprazole Versus Placebo for Antipsychotic-Induced Hyperprolactinemia: Meta-Analysis of Randomized Controlled Trials  [PDF]
Xianbin Li, Yilang Tang, Chuanyue Wang
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0070179
Abstract: Objective To compare the safety and efficacy of adjunctive aripiprazole versus placebo for antipsychotic-induced hyperprolactinemia. Methods Population: adult patients presenting with antipsychotic-induced hyperprolactinemia diagnosed by prolactin level with or without prolactin-related symptoms. Interventions: adjunctive aripiprazole vs. adjunctive placebo. Outcome measures: adverse events and efficacy of treatment. Studies: randomized controlled trials. Results Five randomized controlled trials with a total of 639 patients (326 adjunctive aripiprazole, 313 adjunctive placebo) met the inclusion criteria. Adjunctive aripiprazole was associated with a 79.11% (125/158) prolactin level normalization rate. Meta-analysis of insomnia, headache, sedation, psychiatric disorder, extrapyramidal symptom, dry mouth, and fatigue showed no significant differences in the adjunctive aripiprazole treatment group compared with the placebo group (risk difference (Mantel-Haenszel, random or fixed) ?0.05 to 0.04 (95% confidence interval ?0.13 to 0.16); I2 = 0% to 68%, P = 0.20 to 0.70). However, sedation, insomnia, and headache were more frequent when the adjunctive aripiprazole dose was higher than 15 mg/day. Meta-analysis of the prolactin level normalization indicated adjunctive aripiprazole was superior to placebo (risk difference (Mantel-Haenszel, random) 0.76 (95% confidence interval 0.67 to 0.85); I2 = 43%, P<0.00001). The subgroup analysis confirmed that the subjects who received adjunctive aripiprazole 5 mg/day showed a degree of prolactin normalization similar to that of all participants. No significant differences between groups in discontinuation and improvements of psychiatric symptoms. Conclusion Adjunctive aripiprazole is both safe and effective as a reasonable choice treatment for patients with antipsychotic-induced hyperprolactinemia. The appropriate dose of adjunctive aripiprazole may be 5 mg/day.
Macrolide Therapy in Adults and Children with Non-Cystic Fibrosis Bronchiectasis: A Systematic Review and Meta-Analysis  [PDF]
Yong-hua Gao, Wei-jie Guan, Gang Xu, Yan Tang, Yang Gao, Zhi-ya Lin, Zhi-min Lin, Nan-shan Zhong, Rong-chang Chen
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0090047
Abstract: Background A systematic review and meta-analysis was conducted to evaluate the efficacy and safety of macrolide therapy in adults and children with bronchiectasis. Methods We searched the PUBMED, EMBASE, CENTRAL databases to identify relevant studies. Two reviewers evaluated the studies and extracted data independently. The primary outcome was the number of bronchiectasis exacerbations. Secondary outcomes included exacerbation-related admissions, quality of life (QoL), spirometry, 6-minute walk test (6MWT) and adverse events. Results Nine eligible trials with 559 participants were included. Six were conducted on adults, and the remaining on children. Macrolide therapy significantly reduced the number of patients experiencing one or more exacerbation in adults [risk ratio (RR) = 0.59; 95% CI, 0.40 to 0.86; P = 0.006; I2 = 65%] and children [RR = 0.86; 95% CI, 0.75–0.99; P = 0.04; I2 = 0%], but not the number of patients with admissions for exacerbation. Macrolide therapy was also associated with reduced frequency of exacerbations in adults (RR = 0.42; 95% CI, 0.29 to 0.61; P<0.001; I2 = 64%) and children (RR = 0.50; 95% CI, 0.35 to 0.71; P<0.001). Pooled analyses suggested that spirometry, including FEV1 and FVC, were significantly improved in adults but not in children. Macrolide therapy improved the QoL (WMD, ?6.56; 95% CI, ?11.99 to ?1.12; P = 0.02; I2 = 86%) but no significant difference in 6MWT (WMD, 4.15; 95% CI, ?11.83 to 20.13; P = 0.61; I2 = 31%) and the overall adverse events (RR, 0.96; 95% CI, 0.82 to 1.13; P = 0.66; I2 = 0%) in adults. However, reports of diarrhea and abdominal discomforts were higher with macrolide therapy. Conclusions Macrolide maintenance therapy, both in adults and children, was effective and safe in reducing bronchiectasis exacerbations, but not the admissions for exacerbations. In addition, macrolide administration in adults was associated with improvement in QoL and spirometry, but not 6WMT. Future studies are warranted to verify the optimal populations and clarify its potential effects on antimicrobial resistance.
Mapping oligogenes for atopy and asthma by meta-analysis
Collins, A.;Ennis, S.;Tapper, W.;Morton, N.E.;
Genetics and Molecular Biology , 2000, DOI: 10.1590/S1415-47572000000100001
Abstract: meta-analysis is presented for published studies on linkage or allelic association that have in common only reported significance levels. reporting is biassed, and nonsignificance is seldom quantified. therefore meta-analysis cannot identify oligogenes within a candidate region nor establish their significance, but it defines candidate regions well. applied to a database on atopy and asthma, candidate regions are identified on chromosomes 6, 5, 16, 11, 12, 13, 14, 7, 20, and 10, in rank order from strongest to weakest evidence. on the other hand, there is little support for chromosomes 9, 8, 18, 1, and 15 in the same rank order. the evidence from 156 publications is reviewed for each region. with reasonable type i and ii errors several thousand affected sib pairs would be required to detect a locus accounting for 1/10 of the genetic effect on asthma. identification of regions by a genome scan for linkage and allelic association requires international collaborative studies to reach the necessary sample size, using lod-based methods that specify a weakly parametric alternative hypothesis and can be combined over studies that differ in ascertainment, phenotypes, and markers. this has become the central problem in complex inheritance.
Mapping oligogenes for atopy and asthma by meta-analysis
Collins A.,Ennis S.,Tapper W.,Morton N.E.
Genetics and Molecular Biology , 2000,
Abstract: Meta-analysis is presented for published studies on linkage or allelic association that have in common only reported significance levels. Reporting is biassed, and nonsignificance is seldom quantified. Therefore meta-analysis cannot identify oligogenes within a candidate region nor establish their significance, but it defines candidate regions well. Applied to a database on atopy and asthma, candidate regions are identified on chromosomes 6, 5, 16, 11, 12, 13, 14, 7, 20, and 10, in rank order from strongest to weakest evidence. On the other hand, there is little support for chromosomes 9, 8, 18, 1, and 15 in the same rank order. The evidence from 156 publications is reviewed for each region. With reasonable type I and II errors several thousand affected sib pairs would be required to detect a locus accounting for 1/10 of the genetic effect on asthma. Identification of regions by a genome scan for linkage and allelic association requires international collaborative studies to reach the necessary sample size, using lod-based methods that specify a weakly parametric alternative hypothesis and can be combined over studies that differ in ascertainment, phenotypes, and markers. This has become the central problem in complex inheritance.
Evaluating preference weights for the Asthma Symptom Utility Index (ASUI) across countries
Emuella M Flood, Erwin De Cock, Ann-Christin M?rk, Dennis A Revicki
Health and Quality of Life Outcomes , 2006, DOI: 10.1186/1477-7525-4-51
Abstract: Data were collected from ninety asthma patients from Italy, France, and the United Kingdom using the Asthma Control Questionnaire, the Asthma Quality of Life Questionnaire, and the ASUI. Subjects rated their preferences for 10 asthma health states using a visual analogue scale (VAS) and a standard gamble (SG) interview.All multi-symptom states showed statistically significant differences (p < 0.001) between countries in mean VAS scores. Mean SG utility scores between the US and France and the US and Italy demonstrated statistically significant differences (p < 0.001) for three states: severe wheeze; moderate cough and wheeze; and moderate cough and dyspnea. Because of these differences, the multi-attribute utility functions derived within countries were somewhat different. Despite these differences, country-specific algorithms captured a similar rank ordering of patients by disease severity, were strongly correlated (r = 0.971 to 0.995), and demonstrated similar relationships with symptom and AQLQ scores.Results of this study suggest that the ASUI may be a complementary patient-reported outcome for clinical studies and may be useful for applications in cost-effectiveness studies comparing different asthma treatments.Patient-reported outcomes, such as patient perceptions of symptom frequency and severity and their health-related quality of life (HRQL) are important for clinical management and for evaluating new treatments for asthma [1]. These patient based outcomes have been used to evaluate pharmacologic and behavioral interventions in asthma [2-5]. Evaluation of the cost-effectiveness of new treatments requires careful collection of medical costs and assessment of relevant and clinically meaningful outcomes from the patient's perspective. While symptom-free days [6] and quality-adjusted life years can capture overall effectiveness, these measures may not be sensitive enough to differentiate among different active treatments for asthma [7].The Asthma Symptom Utilit
Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV infection: a meta-analysis of randomised controlled trials
Matthias Briel, Remy Boscacci, Hansjakob Furrer, Heiner C Bucher
BMC Infectious Diseases , 2005, DOI: 10.1186/1471-2334-5-101
Abstract: We conducted a systematic search of the literature for randomised trials published up to December 2004. Selected trials compared adjunctive corticosteroids with placebo or usual care in HIV-infected patients with PCP and reported mortality data. Two teams of reviewers independently evaluated the methodology and extracted data from each primary study.Six studies were included in the meta-analysis. Risk ratios for overall mortality for adjunctive corticosteroids were 0.54 (95% confidence interval [CI], 0.38–0.79) at 1 month and 0.67 (95% CI, 0.49–0.93) at 3–4 months of follow-up. Numbers needed to treat, to prevent 1 death, are 9 patients in a setting without highly active antiretroviral therapy (HAART) available and 22 patients with HAART available. Only the 3 largest trials provided data on the need for mechanical ventilation with a risk ratio of 0.37 (95% CI, 0.20–0.70) in favour of adjunctive corticosteroids.The number and size of trials investigating adjunctive corticosteroids for HIV-infected patients with PCP is small, but our results suggest a beneficial effect for patients with substantial hypoxemia.With the introduction of highly active antiretroviral therapy (HAART) more than a decade ago, the incidence of Pneumocystis jiroveci pneumonia (PCP) [1] has decreased significantly in the Western hemisphere. However, PCP still remains the most common opportunistic infection in patients infected with the human immunodeficiency virus (HIV) [2]. Among patients with HIV infection and PCP the mortality rate is 10 to 20% during the initial infection and increases substantially with the need for mechanical ventilation [3]. In 1990 an expert panel recommended the use of corticosteroids for HIV-infected patients with PCP and substantial hypoxemia (initial arterial oxygen partial pressure of <70 mmHg or alveolar-arterial gradient >35 mmHg on room air) based on the evidence from five randomised controlled trials [4]. This consensus statement still represents the basis of cur
Utility of Meta-Heuristics for Solving Scheduling Problems
E.O. Oyetunji,A.E. Oluleye
Journal of Engineering and Applied Sciences , 2012,
Abstract: Meta-heuristics, are increasingly being applied by many researchers to solve scheduling problems. In this study, we discuss 5 unique characteristics of meta-heuristics that have endeared them to researchers. These are: ability to escape local optima, obtain better solution quality, solve larger instances of problems, suitable for multi-objective scheduling problems and have wide applicability.
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