Incidence of thromboembolism and associated factors in multiple myeloma patients treated with immunomodulatory drugs: a retrospective analysis in Belo Horizonte, Brazil.

PURPOSE: The use of immunomodulators in the treatment of multiple myeloma (MM) patients has been associated with venous thromboembolism (VTE). Due to the increase in mortality of cancer patients, venous thromboembolism is an important concern for newly diagnosed multiple myeloma (NDMM) patients. The aim of this study was to determine the incidence of thromboembolic events and evaluate associated risk factors among Brazilian NDMM patients using immunomodulators. METHODS: Real-life retrospective cohort study in two Brazilian institutions with newly diagnosed multiple myeloma (NDMM) patients treated with immunomodulators from January 2009 to December 2019. Data was collected from patients' medical records for the period of 1 year, and Cox regression was performed to identify risk factors on the development of VTE. RESULTS: We included 131 patients of which there was a mean age of 61.5 years (SD 11.3), 51.9% female, and predominantly using thalidomide (97.7%) as immunomodulator. We found 9 VTE episodes among our patients, with a 12-month cumulative incidence of 6.97% (95% CI 3.41-12.24). Associated factors after multivariate analysis were recent sepsis, recent traumatic injury, previous VTE, and thromboprophylaxis. CONCLUSION: Our real-life retrospective cohort presented a low incidence of VTE among Brazilian NDMM patients treated with immunomodulators.

Comparison of three risk assessment models for thromboembolism in multiple myeloma patients receiving immunomodulators: a Brazilian historical cohort.

Venous thromboembolism (VTE) is among the complications of Multiple Myeloma (MM) and may occur in up to 10% of this patient population. However, medications used in MM therapy such as immunomodulators (IMID) may raise these rates. Thus, risk prediction models have been developed to quantify the risk of VTE in MM patients. The aim of this study is to compare the performance of three risk assessment models for VTE in newly diagnosed MM (NDMM) patients using immunomodulatory agents. A historical cohort study during a 10-year period in a Brazilian metropolis with NDMM treated with IMID. Data were collected from patient's medical charts for the period of one year to calculate the scores using IMPEDE VTE, SAVED, and International Myeloma Working Group (IMWG) guidelines. The area under the curve (AUC) of the Receiver Operating Characteristic curve analysis was calculated to assess the discriminative power of three risk assessment models. We included 131 patients (9 in the VTE group versus 122 in the non VTE group). According to IMPEDE, 19.1, 62.6, and 18.3% of patients were considered low, intermediate, and high risk, respectively. SAVED classified 32.1% as high risk and 64.9% had ≥2 risk factors based on IMWG guidelines. The AUC of the IMPEDE VTE score was 0.80 (95% CI 0.66-0.95, p = 0.002), of the SAVED score was 0.69 (95% CI 0.49-0.89, p = 0.057), and of the IMWG risk score was 0.68 (95% CI 0.48-0.88, p = 0.075). IMPEDE VTE was the most accurate in predicting the development of VTE in Brazilian patients on IMID therapy. The SAVED score and the IMWG guidelines did not show discriminative ability in predicting VTE based on the population involved in this study.

Potentially inappropriate medications in older kidney transplant recipients: a Brazilian prevalence study.

Background Older kidney transplant recipients take a larger number of medications than younger patients, but there is currently no evidence that this affects health outcomes or that is it associated with potentia medicine-related problems. Objective To evaluate the prevalence and number of potentially inappropriate medications in older kidney transplant recipients and also the possible associated factors (sex, age, comorbidities, number of medications, etc.). Setting A renal post-transplant ambulatory outpatient clinic of a university hospital in Fortaleza, Brazil. Method PIMs were defined according to the Beers criteria, version 2015. Medications were classified following the Anatomical Therapeutic Chemical Classification System. Chi squared tests and analysis of variance were used for the analyses. Main outcome measure Prevalence of potentially inappropriate medications and medication groups with higher prevalence rates of PIMs, including associated factors. Results Among 143 kidney transplant recipients, 77.6% had at least one potentially inappropriate medication as part of their prescription regime. Medication groups that were most implicated in PIM are medicines that act on the alimentary tract and metabolism (55.9%), cardiovascular system (32.2%) and nervous system (21.7%). We detected a high prevalence (63.6%) of self-medication (use of OTC medicines without indication of a healthcare professional) among the population studied. There was a statistically significant association between the number of prescribed medications and the presence of potentially inappropriate medication in the prescription regime (P < 0.01). Conclusion Our data draw attention to the need of medicine therapy management by clinical pharmacists and clinicians in this group of patients and also assessing the real clinical impacts of these medications in the prescription regimes of elderly renal transplant patients.

Behavioral effects induced by antitumor cleronade diterpenes from Casearia sylvestris and in silico interactions with neuron receptors.

ETHNOPHARMACOLOGICAL RELEVANCE: Casearia sylvestris is a medicinal plant traditionally used to treat snakebites, wounds, inflammation and gastric ulcers and scientific supports for have demonstrated its antitumor, antihyperlipidemic and antiparasitic properties. AIM OF THE STUDY: To assess the effects of a fraction with casearins (FC) on adult mice using classical experimental models of animal behavior and theoretical calculations to verify the interaction of Casearin X (Cas X) with neuron receptors. MATERIALS AND METHODS: Animals divided in 6 groups (n=9/group) were intraperitoneally treated with vehicle (DMSO 4%), FC (2.5, 5, 10 and 25mg/kg/day) and diazepam (2mg/kg) for 7 days. Thirty minutes after the last dose of treatment, acute toxicity and behavioral experiments were performed. RESULTS: The highest dose of FC (25mg/kg/day) caused diarrhea, weight loss and death of one animal. Elevated plus maze test showed that lower doses [2.5mg/kg/day (36.4±5.1s) and 5mg/kg/day (43.9±6.2s)] increased the time spent in open arms (TSOA). Open field test revealed reduction in the number of crossings (54.9%, 51.1%, 48% and 67.7% for 2.5, 5, 10 and 25mg/kg/day, respectively) in all doses of FC studied and decrease of rearings at 25mg/kg/day (p<0.05). Computational calculations showed that the inhibition constant (Ki) for the Cas X-D1 complex is up to 1000-fold more favourable than the Cas X-GABAA complex. All ∆G° values obtained for Cas X-D1 complexes were more negative than those seen with Cas X-GABAA complexes. CONCLUSIONS: Findings indicate a probable anxiolytic action of the FC since it reduces the number of crossings and rearings and prolonged the time spent in open arms, without sedative and myorelaxant effects, probably due to the interaction of Cas X with dopaminergic system.

Evaluation of p-cymene, a natural antioxidant.

CONTEXT: Several studies have demonstrated that essential oils and their major components have antioxidant activity. p-Cymene is a monoterpene and a major constituent of essential oils of various species of plants. OBJECTIVE: This paper evaluated the antioxidant potential of p-cymene in the hippocampus of mice by determining the levels of thiobarbituric acid reactive substances (TBARS), nitrite content, and activity of catalase (CAT) and superoxide dismutase (SOD). MATERIALS AND METHODS: Swiss mice were intraperitoneally treated with 0.05% Tween 80 dissolved in 0.9% saline solution, ascorbic acid 250 mg/kg, and p-cymene at doses of 50, 100, and 150 mg/kg, respectively. After treatment, all groups were observed for 24 h, afterwards, the groups were euthanized for removal of the brain and dissection of the hippocampus. RESULTS: The results of treatment with p-cymene were a significant decrease in lipid peroxidation and nitrite content at a dose of CYM 50: 65.54%, CYM 100: 73.29%, CYM 150: 89.83%, and CYM 50: 71.21%; CYM 100: 68.61% and CYM 150:67%, respectively, when compared with the control group. The results showed that at all tested doses, p-cymene produces an increase in SOD and catalase activity significantly at a dose of CYM 50: 22.7%, CYM 100: 33.9%, CYM 150: 63.1%, and CYM 50: 119.25%, CYM 100: 151.83% and CYM 150: 182.70%, respectively, when compared with the vehicle-treated group. DISCUSSION AND CONCLUSION: The result of this study shows that p-cymene has an antioxidant potential in vivo and may act as a neuroprotective agent in the brain. This compound may present a new strategy in the development of treatment for many diseases in which oxidative stress plays an important pathophysiological role.