Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).

The principle of the similitude, the basis of homeopathy, has correspondences in the clinical studies of secondary effects of many modern pharmaceutical agents through the observation of the rebound effects of these drugs. Through clinical pharmacology, I proposed a model on which to base the scientificism of the homeopathic model. We have studied the effects of the drugs in the human body using pharmacological compendia and recent scientific works, confirming the mechanism of the homeopathic medicines' action through the verification of the primary action of the drugs and the consequent secondary reaction of the organism in hundreds of pharmaceutical agents. Treatment exploiting the "rebound" effect (curative vital reaction) may also be observed. This work suggests a research methodology to scientifically base the therapeutic principle of similitude.

<p>A demanda da população pela medicina alternativa e complementar (CAM) vem aumentando substancialmente nas últimas décadas, exigindo dos médicos noções básicas dessas diversas terapias, a fim de que possam orientar os pacientes em tratamentos diferentes dos que estão habituados a prescrever. Assim sendo, compete às escolas de medicina propiciar aos estudantes o conhecimento das evidências científicas, dos pressupostos teóricos e das abordagens práticas empregadas por estas distintas formas de tratamento. A presente revisão tem o propósito de fomentar a discussão sobre o ensino de terapêuticas não convencionais nas escolas de medicina, enfocando o interesse da população e da classe médica, a importância das iniciativas na graduação e na pós-graduação (residência), e as perspectivas da educação médica em terapêuticas não convencionais.</p>

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Introduction In addition to the four pillars of homeopathy, vitalism and the miasmatic theory are often used to explain the health–disease process. According to Hahnemann's concepts, homeopathic miasms are the main obstacle to the cure of chronic diseases, with psora being the fundamental cause of all forms of diseases. According to modern genetics, the disease-promoting epigenetic alterations are the fundamental cause of the manifestation of chronic diseases. Objective This article develops a philosophical–scientific correlation between chronic miasms and disease-promoting epigenetic modifications, aiming to justify the isopathic use of auto-sarcode of an individual's DNA as homeopathic medicine. Results Based on the study of homeopathic doctrine and epigenetics, a conceptual and functional correlation is observed between homeopathic chronic miasms and disease-promoting epigenetic modifications. Additionally, several experimental studies suggest that homeopathy's mechanism of action may be by modulating gene expression. Conclusions By the philosophical–scientific correlations described, it is inferred that disease-promoting epigenetic alterations are the biological representation of the chronic miasms, suggesting the isopathic use of auto-sarcode of DNA as homeopathic therapeutic modulator of gene expression for the management of chronic diseases.

Samuel Hahnemann attributed fundamental importance to the principle of similitude, promoting it to a 'natural law'. Observing that enantiopathic or allopathic treatment produced enduring aggravation of the disease symptoms after a brief and transitory initial relief, he systematised homeopathic treatment, prescribing substances that provoke similar symptoms in healthy individual. Based on clinical and experimental observations, he anticipated the concept of homeostasis, dividing the effects of substances into: primary action of the medicine followed by secondary action or reaction of the organism. This reaction, known as the rebound effect or paradoxical action by modern pharmacology, used to awake the curative response of the body when the principle of similitude is applied, is responsible for several iatrogenic diseases when used on the basis of the principle of contraries. This study discusses the role of this paradoxical reaction of the organism in the fatal side effects of four important drugs, used according to the model of enantiopathic treatment of the symptoms. I present evidence relating to acetylsalicylic acid, rofecoxib, antidepressants and long-acting bronchodilators. The consequences of the allopathic treatment could be decreased if health professionals valued homeostasis, minimising the rebound effect of the organism by gradual suspension of palliative drugs.

Rebound and withdrawal effects, including suicidality occur with antidepressant drugs. They are relatively rare but more intense than the primary action of the drug. The probability of such effects is influenced by patient factors including age and diagnosis, and drug factors including half-life.

Bronchodilators, fatal asthma, rebound effect and similitudeSir, After the publication of my article 'Evidence of the principle of similitude in modern fatal iatrogenic events', 1 new evidence was published which I brought to the attention of your readers through a Letter to the Editor. 2 In a similar way to the non-steroidal antiinflammatory drugs (NSAIDs), 3 important new studies were recently published reinforcing the hypothesis that long-acting bronchodilators (b-agonists) may increase the risk for severe or fatal asthma exacerbations, as a consequence of the irreversible paradoxical bronchospasm (rebound effect of modern pharmacology or vital reaction of the homeopathic model).After numerous scientific protests, since GlaxoSmithKline presented the partial data of the 'Salmeterol Multicenter Asthma Research Trial (SMART)' at the Annual International Scientific Assembly of The American College of Chest Physicians in 2003, claiming that 'the interim analysis was inconclusive', the full results of the 26,355 randomized subjects were published in 2006. Exploratory analyses of each outcome event within subpopulations were conducted, finding a significant increase in respiratory-related deaths (RR 2.16, 95% CI 1.06-4.41) and asthmarelated deaths (RR 4.37, 95% CI 1.25-15.34), and in combined asthma-related deaths or life-threatening experiences (RR 1.71, 95% CI 1.01-2.89) in subjects receiving salmeterol vs placebo. African-American subpopulation was particularly affected (compared with Caucasian subjects): respiratory-related deaths or life-threatening experiences (RR 4.10, 95% CI 1.54-10.90) and combined asthma-related deaths or lifethreatening experiences (RR 4.92, in subjects receiving salmeterol vs placebo. 4 In 2006, Salpeter et al published a meta-analysis of 19 randomized, placebo-controlled trials involving 33,826 participants with asthma followed for 16,848 patient-year (mean trial duration 6.0 months). Approximately 15% of the participants were African-American. The long-acting b-agonists used in the studies were salmeterol, formoterol, and eformoterol. During the trials, concomitant inhaled corticosteroids were used in approximately 53% of participants in both groups. The objective of the study was to assess the effects of long-acting b-agonists on severe asthma exacerbations requiring hospitalization, life-threatening asthma attacks, and asthmarelated deaths. Subgroup analyses compared results for salmeterol and formoterol and for children and adults. 5