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Appetite stimulants for people with cystic fibrosis.
Chinuck, R, Dewar, J, Baldwin, DR, Hendron, E
The Cochrane database of systematic reviews. 2014;(7):CD008190
Abstract
BACKGROUND Chronic loss of appetite in cystic fibrosis concerns both individuals and families. Appetite stimulants have been used to help cystic fibrosis patients with chronic anorexia attain optimal body mass index and nutritional status. However, these may have adverse effects on clinical status. OBJECTIVES The aim of this review is to systematically search for and evaluate evidence on the beneficial effects of appetite stimulants in the management of CF-related anorexia and synthesize reports of any side-effects. SEARCH METHODS Trials were identified by searching the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register, MEDLINE, Embase, CINAHL, handsearching reference lists and contacting local and international experts.Last search of online databases: 01 April 2014.Last search of the Cystic Fibrosis Trials Register: 08 April 2014. SELECTION CRITERIA Randomised and quasi-randomised controlled trials of appetite stimulants, compared to placebo or no treatment for at least one month in adults and children with cystic fibrosis. DATA COLLECTION AND ANALYSIS Authors independently extracted data and assessed the risk of bias within eligible trials. Meta-analyses were performed. MAIN RESULTS Three trials (total of 47 recruited patients) comparing appetite stimulants (cyproheptadine hydrochloride and megesterol acetate) to placebo were included; the numbers of adults or children within each trial were not always reported. The risk of bias of the included trials was graded as moderate.A meta-analysis of all three trials showed appetite stimulants produced a larger increase in weight z score at three months compared to placebo, mean difference 0.61 (95% confidence interval 0.29 to 0.93) (P < 0.001) (n = 40) with no evidence of a difference in effect between two different appetite stimulants. One of these trials also reported a significant weight increase with megesterol acetate compared to placebo at six months (n = 17). The three trials reported no significant differences in forced expiratory volume at one second (per cent predicted) between the appetite stimulant groups and placebo at follow up, with durations ranging from two to nine months. A meta-analysis of two trials showed a significantly higher proportion of patients reporting increased appetite, odds ratio 45.25 (95% confidence interval 3.57 to 573.33) (P = 0.003) (n = 23), but the frequency of reported side effects was undetermined. AUTHORS' CONCLUSIONS In the short term (six months) in adults and children, appetite stimulants improved only two of the outcomes in this review - weight (or weight z score) and appetite; and side effects were insufficiently reported to determine the full extent of their impact. Whilst the data may suggest the potential use of appetite stimulants in treating anorexia in adults and children with cystic fibrosis, this is based upon moderate quality data from a small number of trials and so this therapy cannot be conclusively recommended based upon the findings in the review. Clinicians need to be aware of the potential adverse effects of appetite stimulants and actively monitor any patients prescribed these medications accordingly.Research is needed to determine meaningful surrogate measures for appetite and define what constitutes quality weight gain. Future trials of appetite stimulants should use a validated measure of symptoms including a disease-specific instrument for measuring poor appetite. This review highlights the need for multicentred, adequately powered and well-designed trials to evaluate agents to safely increase appetite in people with cystic fibrosis and to establish the optimal mode of treatment.
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2.
Muscle wasting in hemodialysis patients: new therapeutic strategies for resolving an old problem.
Chen, CT, Lin, SH, Chen, JS, Hsu, YJ
TheScientificWorldJournal. 2013;:643954
Abstract
Muscle wasting has long been recognized as a major clinical problem in hemodialysis (HD) patients. In addition to its impact on quality of life, muscle wasting has been proven to be associated with increased mortality rates. Identification of the molecular mechanisms underlying muscle wasting in HD patients provides opportunities to resolve this clinical problem. Several signaling pathways and humeral factors have been reported to be involved in the pathogenic mechanisms of muscle wasting in HD patients, including ubiquitin-proteasome system, caspase-3, insulin/insulin-like growth factor-1 (IGF-1) signaling, endogenous glucocorticoids, metabolic acidosis, inflammation, and sex hormones. Targeting the aforementioned crucial signaling and molecules to suppress protein degradation and augment muscle strength has been extensively investigated in HD patients. In addition to exercise training, administration of megestrol acetate has been proven to be effective in improving anorexia and muscle wasting in HD patients. Correction of metabolic acidosis through sodium bicarbonate supplements can decrease muscle protein degradation and hormone therapy with nandrolone decanoate has been reported to increase muscle mass. Although thiazolidinedione has been shown to improve insulin sensitivity, its role in the treatment of muscle wasting remains unclear. This review paper focuses on the molecular pathways and potential new therapeutic approaches to muscle wasting in HD patients.
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3.
Effects of megestrol acetate in patients with cancer anorexia-cachexia syndrome--a systematic review and meta-analysis.
Leśniak, W, Bała, M, Jaeschke, R, Krzakowski, M
Polskie Archiwum Medycyny Wewnetrznej. 2008;(11):636-44
Abstract
INTRODUCTION Anorexia-cachexia syndrome (ACS) often occurs in patients with advanced cancer. OBJECTIVES To review the effect of megestrol acetate (MA) in patients with ACS. PATIENTS AND METHODS To identify eligible studies, systematic review by Lopez et al. (2004) was used, electronic databases (MEDLINE, EMBASE and CENTRAL) were searched and reference lists of included studies were reviewed. The studies were included in the review if they were randomized, enrolled patients with non-hormone-sensitive cancer and ACS and assessed the effects of MA compared with placebo, other drugs or different doses of MA. RESULTS The study population is characterized by high mortality and progressive weight loss irrespective of the treatment. Compared to placebo, the effect of MA on survival is similar, but MA increases appetite (number needed to treat [NNT]: 3) and leads to weight gain (NNT: 8) in more patients. The data on other aspects of the quality of life are limited. The comparison of MA and glucocorticosteroids showed no statistical difference in their effect on appetite and weight. CONCLUSIONS Compared to placebo, MA reduces the symptoms of ACS, with no effect on survival. The beneficial effect of MA on the overall quality of life has not been confirmed. In identified studies the effect of MA and glucocorticosteroids on anorexia and cachexia is similar. The estimation of the treatment utility in ACS depends on the weight attributed to discomfort caused by symptoms, adverse effects of the drugs and the treatment cost. Because of the low quality of the included studies a new randomized controlled trial is needed for valid assessment of the effects of MA.
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Treatment of the cancer anorexia-cachexia syndrome: a critical reappraisal.
Lelli, G, Montanari, M, Gilli, G, Scapoli, D, Antonietti, C, Scapoli, D
Journal of chemotherapy (Florence, Italy). 2003;(3):220-5
Abstract
Cancer anorexia-cachexia syndrome (CACS) is a combination of anorexia, tissue wasting, weight loss and poor performance status. Some CACS symptoms are due to a macrophage production of TNF and IL-1, while the metabolic effects are mainly explained by the release of IL-6 from tumor cells. Clinical treatment of CACS involves progestational agents (medroxyprogesterone acetate, MPA, megestrol acetate, MA) for long term treatment. The use of prokinetic agents (like metoclopramide) is recommended, especially if patients need concomitant opioid treatment for pain; if otherwise indicated, corticosteroids are useful for short periods. The administration of artificial nutrition should be individualized following the clinical condition of the patient and possibly taking into account the wishes of the patient. The practical evaluation criteria of the drugs employed for CACS are based on weight increase and appetite stimulation. Hence, a new approach to the mechanism of action of MPA, MA and of other agents is urgently needed.
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5.
Treating malnutrition with megestrol acetate: literature review and review of our experience.
Karcic, E, Philpot, C, Morley, JE
The journal of nutrition, health & aging. 2002;(3):191-200
Abstract
Megestrol acetate is a semi-synthetic progestational steroid that was originally used as a therapeutic modality for metastatic breast and endometrial cancers. What was originally considered to be it's most frequent side effect, an increase in appetite and in body weight, has gradually become an established treatment of malnutrition in patients with the acquired immuno-deficiency syndrome or with non-hormone responsive cancers. The use of megestrol acetate in treating malnutrition in older persons, in patients on dialysis and in a number of other situations is currently under investigation. The authors review the evidence available to support the use of megestrol acetate in treating malnutrition in these selected groups, and the problems associated with administering megestrol acetate; they also report on their own experience with megestrol acetate in the geriatric population.