Efficacy and safety of antifibrinolytics in oncological surgery: a systematic review and meta-analysis / Eficácia e segurança de antifibrinolíticos em cirurgia oncológica: uma revisão sistemática e metanálise

Abstract Background and objectives: The administration of antifibrinolytics has been shown to be effective in reducing blood loss and the need for transfusions in surgeries. However, few studies have evaluated these drugs in cancer surgery. The objective was to review the efficacy and safety of the treatment with antifibrinolytics in patients who underwent oncologic surgeries. Contents: An electronic bibliographic research was conducted in PubMed, OVID, MEDLINE, EMBASE, EBSCO and in the Cochrane Library data basis in order to identify randomized clinical trials performed in any type of oncologic surgery. The data evaluated were blood loss, need for transfusion and incidence of arteriovenous thromboembolism. Five randomized controlled trials evaluating 838 patients met the inclusion requirements. In the analysis of the incidence of thromboembolic events in the five RCTs, there was no statistically significant difference between the administration of tranexamic acid when compared with the placebo (OR = 0.36, 95% IC: 0.11‒1.19, p= 0.09, I2 = 0%). However, when total estimated blood loss and need for blood transfusion are analyzed, the use of tranexamic acid was associated with a significant reduction over placebo (MD = −135.79, 95% CI: −179.50 to −92.08, p< 0.00001, I2= 68%) and (OR = 0.45, 95% CI: 0.32‒0.65, p< 0.00001, I2= 60%), respectively. Conclusions: This meta-analysis found no evidence that the administration of antifibrinolytics increases the risk of thromboembolic complications in patients submitted to oncologic surgery, and has shown evidence that it is effective in reducing total perioperative blood loss and the need for blood transfusion.

Resumo Justificativa e objetivos: A administração de agentes antifibrinolíticos mostrou ser eficaz para reduzir a perda sanguínea e a necessidade de transfusões em cirurgias. No entanto, poucos estudos avaliaram esses agentes em cirurgias oncológicas. O objetivo foi revisar a eficácia e segurança do tratamento com antifibrinolíticos em pacientes submetidos a cirurgias oncológicas. Conteúdo: Uma pesquisa bibliográfica foi conduzida nos bancos de dados eletrônicos PubMed, OVID, MEDLINE, EMBASE, EBSCO e na Biblioteca Cochrane para identificar ensaios clínicos randomizados feitos em qualquer tipo de cirurgia oncológica. Os dados analisados foram perda sanguínea, necessidade de transfusão e incidência de tromboembolismo arteriovenoso. Cinco ensaios clínicos randomizados que avaliaram 838 pacientes atenderam aos critérios de inclusão. Na análise da incidência de eventos tromboembólicos em cinco ECR, não houve diferença estatisticamente significativa entre a administração do ácido tranexâmico, comparado ao placebo (OR = 0,36, IC 95%: 0,11-1,19, p = 0,09; I2 = 0%). No entanto, quando a perda sanguínea total estimada e a necessidade de transfusão de sangue foram analisadas, o uso do ácido tranexâmico foi associado a uma redução significativa, comparado ao placebo. (DM: -135,79, IC 95%: -179,50 a -92,08, p < 0,00001, I2 = 68%) e (OR = 0,45, IC 95%: 0,32-0,65, p < 0,00001, I2 = 60%), respectivamente. Conclusões: Esta metanálise não encontrou evidências de que a administração de antifibrinolíticos aumente o risco de complicações tromboembólicas em pacientes submetidos à cirurgia oncológica e apresentou evidências de que é eficaz para reduzir a perda sanguínea total no perioperatório e a necessidade de transfusão de sangue.

Prevalence of oral anticoagulation in atrial fibrillation

OBJECTIVES: Atrial fibrillation is the most common sustained arrhythmia and is associated with poor outcomes, including stroke. The ability of anticoagulation therapy to reduce the risk of stroke has been well established; however, the prevalence of anticoagulation therapy use in the Public Health System is unknown. The aim of this study is to evaluate both the prevalence of anticoagulation therapy among patients with atrial fibrillation and the indications for the treatment. METHODS: In this cross-sectional study, we included consecutive patients who had atrial fibrillation documented by an electrocardiogram performed between September 2011 and March 2012 at a university hospital of the Public Health System. The variables analyzed included the risk of a thromboembolic event and/or bleeding, the use of antiplatelet or anticoagulation therapy, the location where the electrocardiogram report was initially reviewed and the specialty of the physician who initially reviewed it. RESULTS: We included 162 patients (mean age 68.9 years, 56% men). Hypertension (90.1%), heart failure (53.4%) and stroke (38.9%) were the most prevalent diseases found. Only 50.6% of the patients knew that they had atrial fibrillation. Regarding the use of therapy, only 37.6% of patients classified as high risk according to the CHADS2 scores and 35.5% according to the CHA2DS2VASc used oral anticoagulation. A presumptive diagnosis of heart failure and the fact that the electrocardiogram was evaluated by a cardiologist were the only independent predictors of the use of anticoagulants. CONCLUSIONS: Our study found a low prevalence of oral anticoagulation therapy among patients with atrial fibrillation and an indication for stroke prophylaxis for the use of this therapy, including among those with high CHADS2 and CHA2DS2VASc scores. .

Tumor necrosis factor-α antagonists: Side effects and their management.

As elevated levels of tumor necrosis factor-alpha (TNF-α) are associated with disease severity in psoriasis and psoriatic arthritis, TNF-α antagonists are being used to treat moderate to severe disease in patients who have contraindications, fail to respond or develop side effects to conventional systemic therapies. It is of utmost importance to be well versed with the possible adverse effects and contraindications of TNF-α antagonists so that they can be used effectively and safely. Many of their adverse effects have been well studied in patients of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) and may not be completely applicable in psoriasis. This is because patients with RA and IBD are on multiple immunosuppressants while those with psoriasis are mostly receiving single systemic therapy and often have comorbidities that distinguish them from those with RA or IBD. Also, some of the side effects are still controversial and debated. Long-term prospective randomized controlled studies are needed to better understand the associated risk in patients of psoriasis. Baseline screening and periodic monitoring during treatment can reduce and help in early identification and appropriate management of the adverse outcomes. This article reviews the side effects known to be associated with TNF-α antagonists, their pathomechanisms and management guidelines. Some of the common side effects include infusion and injection site reactions, infections particularly reactivation of tuberculosis, autoantibody formation and drug induced lupus erythematosus, liver function abnormalities, hematological, and solid organ malignancies.

Tumor necrosis factor-α antagonists: Side effects and their management.

As elevated levels of tumor necrosis factor-alpha (TNF-α) are associated with disease severity in psoriasis and psoriatic arthritis, TNF-α antagonists are being used to treat moderate to severe disease in patients who have contraindications, fail to respond or develop side effects to conventional systemic therapies. It is of utmost importance to be well versed with the possible adverse effects and contraindications of TNF-α antagonists so that they can be used effectively and safely. Many of their adverse effects have been well studied in patients of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) and may not be completely applicable in psoriasis. This is because patients with RA and IBD are on multiple immunosuppressants while those with psoriasis are mostly receiving single systemic therapy and often have comorbidities that distinguish them from those with RA or IBD. Also, some of the side effects are still controversial and debated. Long-term prospective randomized controlled studies are needed to better understand the associated risk in patients of psoriasis. Baseline screening and periodic monitoring during treatment can reduce and help in early identification and appropriate management of the adverse outcomes. This article reviews the side effects known to be associated with TNF-α antagonists, their pathomechanisms and management guidelines. Some of the common side effects include infusion and injection site reactions, infections particularly reactivation of tuberculosis, autoantibody formation and drug induced lupus erythematosus, liver function abnormalities, hematological, and solid organ malignancies.

Progestógenos: farmacologia e uso clínico / Progestagens: pharmacology and clinical use

Os progestógenos são esteroides que podem ser sintéticos ou naturais. A progesterona é o único progestágeno natural. Os progestógenos sintéticos tentam mimetizar o efeito da progesterona, e são chamados de progestinas. Cada progestina apresenta diferentes propriedades farmacológicas, dependendo da molécula da qual foi originada, usualmente testosterona e progesterona. Pequenas mudanças estruturais nas moléculas originais levam a diferenças consideráveis na atividade de cada uma das progestinas. O objetivo deste trabalho é revisar a origem dos progestógenos, as peculiaridades de cada grupo e seu uso clínico mais comum. As informações já levantadas sobre o efeito das progestinas em patologias importantes e prevalentes, como o câncer de mama e eventos tromboembólicos, também será abordado.

Progestagens are natural or synthetic steroids, and progesterone is the only natural one. Synthetic progestagens, called progestins, were created to mimic the effects of natural progesterone. The progestins have different pharmacological properties depending on the parent molecule, usually testosterone or progesterone, from which they are derived. Very small structural changes in the original molecule may induce considerable differences in the activity of the derivative. The aim of this paper is to review the origin of each progestin, the peculiarities of each group and its most common clinical use. The current knowledge about the effect of progestins on important and prevalent diseases, such as breast cancer and thromboembolic events, will also be addressed.

Terapia hormonal na menopausa: quando não usar: [revisão] / Hormone therapy in menopause: when not to use: [review]

A menopausa corresponde à cessação permanente da menstruação, conseqüente à perda da função folicular ovariana ou à remoção cirúrgica dos ovários. A idade média para ocorrência da menopausa natural gira em torno de 50 anos. A deficiência estrogênica decorrente da menopausa está associada com sintomas vasomotores, atrofia urogenital, declínio cognitivo, assim como a um aumento no risco de doenças crônico-degenerativas, aterosclerose e doença cardiovascular, osteoporose e doença de Alzheimer. A estrogenioterapia permanece sendo o tratamento mais efetivo para o manejo dos sintomas vasomotores e atrofia urogenital. Em mulheres com útero presente, a progesterona natural ou os progestogênios devem ser associados ao tratamento com estradiol para antagonizar os efeitos proliferativos deste hormônio sobre o endométrio e anular o risco de hiperplasia/carcinoma endometrial. Por outro lado, em determinadas condições clínicas, a terapia hormonal não é recomendada ou é mesmo contra-indicada. Neste artigo, focalizamos criticamente essas situações clínicas em que não se deve indicar a terapia hormonal na menopausa.

Menopause is defined as the permanent cessation of menses, as a result of the loss of ovarian follicular function or of surgical removal of ovaries. The mean age for occurrence of natural menopause is around 50 years. Estrogen deficiency has been associated with vasomotor symptoms, urogenital atrophy, and cognitive impairment, as well as increased risk of chronic degenerative diseases such as osteoporosis and Alzheimer’s disease. Estrogen therapy remains the most effective treatment for the management of vasomotor symptoms and urogenital atrophy. Progesterone or progestins should be added to estrogen treatment in women with uterus, in order to antagonize the estrogen-induced endometrial proliferation. In turn, in specific clinical conditions hormone therapy is not recommended. In the present article, the authors critically focus these clinical conditions in which hormone therapy should not be used.

Risk of cardiovascular diseases with oral contraceptives.

Oral contraceptive pills (OCs) are widely used method of contraception for its effectiveness and easier compliance. However, adverse effects associated with OCs use notably the increased risk of cardiovascular diseases (CVD), manifesting as ischaemic and haemorrhagic stroke, myocardial infarction (MI) and venous thromboembolic diseases were reported soon after their introduction to the market in the early 1960s. Various modifications were made in an attempt to lower these risks including a reduction in the estrogen dose and changes in the progestogen compound. Currently used OCs containing the new progestin (Levonorgestrel, Desogestrel, gestodene or norgestimate) classified as low dose because all contain less than 35 microg of ethinyl estradiol. Despite their low steroid content, all have proved to be highly effective. The rationale of this reviewed study based upon cardiovascular risks in relation to these monophasic low-dose oral contraceptives. To review all relevant articles it is concluded that the risk for cardiovascular disease is lower with current preparations of oral contraceptives. Cardiovascular diseases occur mainly among oral contraceptive users who smoke or have predisposing factors--such as age more than 35 years, overweight, diabetes & hypertension.

Cefaléia e anticoncepcionais orais / Headache and oral contraceptives

O autor estuda a incidência, os possíveis fatores causais e as modalidades de cefaléias induzidas ou agravadas pelo uso dos anticoncepcionais orais

Contracepçäo oral e coagulaçäo / Oral contraception and coagulation

Os autores fazem uma revisäo sobre os anticoncepcionais orais e seus efeitos sobre a coagulaçäo sanguínea. Abordam aspectos fisiológicos da hemostasia, coagulaçäo e trombose. Analisam pormenorizadamente os fatores de risco para trombose em usuárias dos anticonceptivos orais e relatam as principais conclusöes de interesse prático para o dia a dia do ginecologista