Showing papers by "Achille P. Caputi published in 2011"
TL;DR: The authors' systematic review of MAs included information on the incidence of CV and GI events and identified important knowledge gaps regarding, in particular, the CV safety of traditional NSAIDs.
Abstract: As part of the Safety of Non-Steroidal Anti-Inflammatory Drugs (SOS) Project, we reviewed the incidence of cardiovascular (CV) and gastrointestinal (GI) events associated with the use of this category of drugs. We collected data from published meta-analyses (MAs) of clinical trials of nonsteroidal anti-inflammatory drugs (NSAIDs). The Medline, Cochrane, ISI, and SCOPUS databases were systematically searched for MAs of NSAID clinical trials that could potentially contain data on adverse incidents such as myocardial infarction (MI), cerebrovascular events (CeVs), stroke, thromboembolic events (ThEs), heart failure (HF), gastrointestinal bleeding (GIB), and perforation, ulcer, and bleeding (PUB). From 1,733 identified references, 29 MAs were selected for the review. This allowed 109 estimations of incidence rates of CV adverse events and 26 estimations of incidence rates for GI adverse events. No data were found on hemorrhagic stroke or LGIB. Coxibs were studied in more MAs than traditional NSAIDs were (21 MAs for coxibs vs. 7 for traditional NSAIDs; one meta-analysis studied both). Many NSAIDs were not considered in any of the MAs. Our systematic review of MAs included information on the incidence of CV and GI events and identified important knowledge gaps regarding, in particular, the CV safety of traditional NSAIDs.
110 citations
TL;DR: Data indicate the existence of a link between serotonergic and endocannabinoid systems in the mechanisms underlying mood disorders caused by nicotine abstinence and suggest that these interactions are potential targets for pharmacological aid in smoking cessation.
Abstract: Introduction Endocannabinoid and serotonin systems are implicated in mechanisms underlying depression-like symptoms. Involvement of serotonin in mood disorders occurring after smoking cessation has been observed. We studied the interactions between endocannabinoid and serotonergic systems in mood and behavioral disorders caused by nicotine cessation. The effects of the endocannabinoid transport inhibitor AM404 and the cannabinoid receptor 1 antagonist AM251 in a nicotine-dependent rodent model were investigated. Methods Dependence was induced by subcutaneous injections of nicotine (2 mg/kg, 4 injections daily) for 15 consecutive days in mice. Animals treated with AM404 or AM251 were tested for locomotor activity and abstinence signs 24 hr after nicotine withdrawal and in forced swimming test (FST) at different times: immediately after last nicotine injection (t = 0) and 15 and 30 days after nicotine withdrawal. In nicotine-dependent mice treated with AM404 or AM251, expression of diencephalic serotonin receptor 1(A) (5-HT1(A)) was also measured. Effects of AM404, AM251, and WAY 100635 (5-HT(1A) receptor antagonist) in mice subjected to FST were evaluated. Results A decrease in diencephalic 5-HT(1A) levels was observed in mice previously injected with nicotine. In the same animals, AM251 caused (0.5-2 mg/kg) a significant decrease of abstinence signs and AM404 (0.5-2 mg/kg) provoked a significant dose-dependent reduction in immobility time in the FST. Either AM251 or WAY 100635 antagonized anti-immobility effects of AM404. Conclusions Data indicate the existence of a link between serotonergic and endocannabinoid systems in the mechanisms underlying mood disorders caused by nicotine abstinence and suggest that these interactions are potential targets for pharmacological aid in smoking cessation.
21 citations
TL;DR: Eminent geriatricians have voiced that the current practice produces an evidence-biased rather and evidencebased medicine and have called for the conduction of appropriately designed trials involving real geriatric patients.
Abstract: 66 Discussions about the most appropriate methods for testing the effectiveness and safety of pharmacological intervention for older patients crowded the literature of the past decade, but little action has followed from such a wide discussion. The number of patients aged 65 years and older included in randomized controlled trials raised. However, epidemiological studies have generally demonstrated that the phenotypic emergence of the negative consequences of aging occur much later in life, in the eighth and ninth decade. Interestingly, this is the section of the population that is experiencing a steep demographic expansion, is often affected by severe comorbidity and disability, is the most eager consumer of drugs, and also the most likely to suffer from the iatrogenic consequences of chronic treatment and polypharmacy (1). In the United States, nearly 90% of patients over 75 years of age receive one or more medications, and the probability of having multiple prescription increases geometrically with age, severity of illness, and poor physical and cognitive function (2). There are many reasons why frail older persons that assume multiple drugs are prone to develop iatrogenesis, including drug–drug interactions, reduced physiological reserve, changes in pharmacokinetics, and poor compliance (3). The management of comorbid conditions with multiple medications is indeed one of the greatest challenges in geriatrics. The Hippocratic oath “primum non nocere” is translated into the “unchallenged principle” in geriatric medicine: The number of medications should be kept as low as possible. However, when facing the “brown bag full of pills” brought by your patient, deciding which treatment can stay and which one should go is challenging. Of course, only drugs with proven efficacy should stay, but this is also not an easy decision. Elderly patients with comorbidity, disability, and polypharmacy are systematically excluded from clinical trials, even those trials that test drugs mostly used in those same elderly patients with comorbidity, disability, and polypharmacy. Due to those exclusion criteria, the findings of these trials cannot be extended to our typical patients: Therefore, we are left with an “unchallenged principle” and impossible decisions (4,5). We are certainly not the first to denounce this difficult situation. Eminent geriatricians have voiced that the current practice produces an evidence-biased rather and evidencebased medicine and have called for the conduction of appropriately designed trials involving real geriatric patients (6,7). Letter to the Editor
14 citations