Anthracyclines play a critical role in the treatment of a variety of childhood cancers. However, the cumulative cardiotoxic effects of anthracyclines limit the use of these agents in many treatment regimens. Dexrazoxane is a cardioprotectant that significantly reduces the incidence of adverse cardiac events in women with advanced breast cancer treated with doxorubicin-containing regimens. Clinical evidence for the efficacy of dexrazoxane as a cardioprotectant in children, especially from randomized clinical trials, is limited, but the available data support a short-term cardioprotective effect. Long-term follow-up in children treated with dexrazoxane has not been reported. Dexrazoxane’s impact on the antitumor effect and toxicity profile of the anthracyclines and the role of dexrazoxane in the development of secondary malignant neoplasms in patients who received dexrazoxane are reviewed. Based on the available data, dexrazoxane appears to be a safe and effective cardioprotectant in children, and it does not appear to alter overall survival times in children with cancer. Continued follow-up from previous trials is needed to determine the long-term effect of dexrazoxane on cardiac outcomes and quality of life. 
Day: 11/30/2010
Opioid Rotation in the Management of Chronic Pain: Where Is the Evidence?
The management of chronic pain remains a challenge because of its complexity and unpredictable response to pharmacological treatment. In addition, accurate pain management may be hindered by the prejudice of physicians and patients that strong opioids, classified as step 3 medications in the World Health Organization ladder for cancer pain management, are reserved for the end stage of life. Recent information indicates the potential value of strong opioids in the treatment of chronic nonmalignant pain. There are, up until now, insufficient data to provide indications about which opioid to use to initiate treatment or the dose to be used for any specific pain syndrome. The strong inter-patient variability in opioid receptor response and in the pharmacokinetic and pharmacodynamic behavior of strong opioids justifies an individual selection of the appropriate opioid and stepwise dose titration. Clinical experience shows that switching from one opioid to another may optimize pain control while maintaining an acceptable side effect profile or even improving the side effects. This treatment strategy, described as opioid rotation or switch, requires a dose calculation for the newly started opioid. Currently, conversion tables and equianalgesic doses are available. However, those recommendations are often based on data derived from studies designed to evaluate acute pain relief, and sometimes on single dose studies, which reduces this information to the level of an indication. In daily practice, the clinician needs to titrate the optimal dose during the opioid rotation from a reduced calculated dose, based on the clinical response of the patient. Further research and studies are needed to optimize the equianalgesic dosing tables.
source: Wiley library
Vascular Pathophysiology in Response to Increased Heart Rate
This review summarizes the current literature and the open questions regarding the physiology and pathophysiology of the mechanical effects of heart rate on the vessel wall and the associated molecular signaling that may have implications for patient care. Epidemiological evidence shows that resting heart rate is associated with cardiovascular morbidity and mortality in the general population and in patients with cardiovascular disease. As a consequence, increased resting heart rate has emerged as an independent risk factor both in primary prevention and in patients with hypertension, coronary artery disease, and myocardial infarction. Experimental and clinical data suggest that sustained elevation of heart rate—independent of the underlying trigger—contributes to the pathogenesis of vascular disease. In animal studies, accelerated heart rate is associated with cellular signaling events leading to vascular oxidative stress, endothelial dysfunction, and acceleration of atherogenesis. The underlying mechanisms are only partially understood and appear to involve alterations of mechanic properties such as reduction of vascular compliance. Clinical studies reported a positive correlation between increased resting heart rate and circulating markers of inflammation. In patients with coronary heart disease, increased resting heart rate may influence the clinical course of atherosclerotic disease by facilitation of plaque disruption and progression of coronary atherosclerosis. While a benefit of pharmacological or interventional heart rate reduction on different vascular outcomes was observed in experimental studies, prospective clinical data are limited, and prospective evidence determining whether modulation of heart rate can reduce cardiovascular events in different patient populations is needed.
source: americal journal of cardiology
Percutaneous endoscopic gastrostomy versus nasogastric tube feeding for adults with swallowing disturbances.
A number of conditions compromise the passage of food along the digestive tract. Nasogastric tube (NGT) feeding is a classic, time-proven technique, although its prolonged use can lead to complications such as lesions to the nasal wing, chronic sinusitis, gastro-oesophageal reflux, and aspiration pneumonia. Another method of infusion, percutaneous endoscopy gastrostomy (PEG), is generally used when there is a need for enteral nutrition for a longer time period. There is a high demand for PEG in patients with swallowing disorders, although there is no consistent evidence about its effectiveness and safety as compared to NGT.
OBJECTIVES: To evaluate the effectiveness and safety of PEG as compared to NGT for adults with swallowing disturbances.
SEARCH STRATEGY: We searched The Cochrane Library, MEDLINE, EMBASE, and LILACS from inception to August 2009, as well as contacting main authors in the subject area. There was no language restriction in the search.
SELECTION CRITERIA: We planned to include randomised controlled trials comparing PEG versus NGT for adults with swallowing disturbances or dysphagia and indications for nutritional support, with any underlying diseases. The primary outcome was intervention failures (feeding interruption, blocking or leakage of the tube, no adherence to treatment).
DATA COLLECTION AND ANALYSIS: Review authors performed selection, data extraction and evaluation of methodological quality of studies. For dichotomous and continuous variables, we used risk ratio (RR) and mean difference (MD), respectively with the random-effects statistical model and 95% confidence interval (CI). We assumed statistical heterogeneity when I(2) > 50%.
MAIN RESULTS: We included nine randomised controlled studies. Intervention failure occurred in 19/156 patients in the PEG group and 63/158 patients in the NGT group (RR 0.24 (95%CI 0.08 to 0.76, P = 0.01)) in favour of PEG. There was no statistically significant difference between comparison groups in complications (RR 1.00, 95%CI 0.91 to 1.11, P = 0.93).
AUTHORS’ CONCLUSIONS: PEG was associated to a lower probability of intervention failure, suggesting the endoscopic procedure is more effective and safe as compared to NGT. There is no significant difference of mortality rates between comparison groups, and pneumonia irrespective of underlying disease (medical diagnosis). Future studies should include previously planned and executed follow-up periods, the gastrostomy technique, and the experience of the professionals to allow more detailed subgroup analysis.
source: cochrane library
ARBs plus ACE Inhibitors, Used in Combination, Seem to Heighten Cancer Risk
Researchers, investigating the reported association between antihypertensive drugs and cancer, examined data from 70 randomized trials encompassing over 300,000 participants with a mean follow-up of 3.5 years. Their analysis found no added risk for cancer from ARBs, beta-blockers, ACE inhibitors, calcium-channel blockers, or diuretics, when compared with placebo. However, the combination of ACE inhibitors and ARBs posed a 14% relative risk increase.
Commentators say the finding of no increased risk with most antihypertensives is “hardly surprising,” given the short follow-up period. They also point out that the ACE inhibitor/ARB combination is often used in patients with severe heart failure, who have lower life expectancies.
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