LC-QToF-MS method for quantification of ethambutol, isoniazid, pyrazinamide and rifampicin in human plasma and its application.

In this research, we developed and validated a liquid chromatography coupled to mass spectrometry (LC-QToF-MS) method for simultaneous quantification of the anti-tuberculosis drugs ethambutol, isoniazid, pyrazinamide and rifampicin in human plasma. Plasma samples spiked with cimetidine (internal standard) were extracted using protein precipitation with acetonitrile containing 1% formic acid. Separation was performed using a C18 column under flow gradient conditions with water and acetonitrile, both containing 5 mm ammonium formate and 0.1% formic acid. The method was validated according to the ANVISA and US Food and Drug Administration guidelines for bioanalytical method validation. The calibration curve was linear over a concentration range of 0.2-5 µg ml-1 for ethambutol, 0.2-7.5 µg ml-1 for isoniazid, 1-40 µg ml-1 for pyrazinamide and 0.25-2 µg ml-1 for rifampicin, all with adequate precision and accuracy. The method was reproducible, selective and free of carryover and matrix effects. The validated LC-QToF-MS method was successfully applied to real samples and shown to be applicable to future therapeutic and pharmacokinetic monitoring studies.

A multivariate analysis of risk factors associated with death by Covid-19 in the USA, Italy, Spain, and Germany.

Aim: Our aim was to investigate the risk factors associated with death from COVID-19 in four countries: The USA, Italy, Spain, and Germany. Subject and methods: We used data from the Institute for Health Metrics and Evaluation with projection information from January-August 2020. A multivariate analysis of logistic regression was performed. The following factors were analyzed (per day): number of beds needed for the hospital services, number of intensive care units (ICU) beds required, number of ventilation devices, number of both hospital and ICU admissions due to COVID-19. Nagelkerke's R2 coefficient of determination was used to evaluate the model's predictive ability. The quality of the model's fit was assessed by the Hosmer-Lemeshow and the chi-square tests. Results: Among the evaluated countries, Italy presented greater need for ICU beds/day (≤ 98; OR = 2315.122; CI 95% [334.767-16,503.502]; p < 0.001) and daily ventilation devices (≤ 118; OR = 1784.168; CI 95% [250.217-12,721.995]; p < 0.001). It is expected that both Italy and Spain have a higher ICU admission rate due to COVID-19 (n = 14/day). Spain will need more beds/day (≤ 357; OR = 146.838; CI 95% [113.242-190.402]; p  < 0.001) and probably will have a higher number of daily hospital admissions (n = 48/day). All the above-mentioned factors have an important impact on patients' mortality due to COVID-19 in all four countries. Conclusions: Further investments in hospitals' infrastructure, as well as the development of innovative devices for patient's ventilation, are paramount to fight the pandemic in the USA, Italy, Spain, and Germany.

Vitamin D in patients with Hashimoto's disease: a systematic review and meta-analysis

One of the most common thyroid dysfunctions is Hashimoto's disease (HD), characterized by the production of specific antibodies against thyroid gland antigens (Anti-Tg and Anti-TPO). Recent studies have suggested that vitamin D supplementation, associated with levothyroxine, may contribute to the control of this autoimmune disease. However, secondary studies on this topic, such as systematic reviews and meta-analyses, are still scarce. Thus, the present study aimed to evaluate the efficacy and safety of vitamin D in patients with HD through a systematic review with meta-analysis. Randomized clinical trials were selected on the Pubmed, Scopus, and Web of Science databases. Studies comparing groups of HD patients supplemented with vitamin D and non-supplemented HD patients were included. The following outcomes were considered: TSH, T3, T4, Anti-Tg, Anti-TPO, and adverse drug reactions. The risk of bias was performed according to the Cochrane recommendations (RoB v. 2.0), and the quality of evidence was evaluated by the GRADE system. A total of 766 studies were identified in the databases, of which 7 met the eligibility criteria. None of the studies indicated the occurrence of adverse reactions with vitamin D supplementation in any administered dosage. Supplemented patients had a significant reduction in serum TSH levels compared to the control group (mean difference = -0.180 (95% CI [-0.316 to -0.045]), p = 0.009), suggesting that thyroid function was more controlled in the intervention group. However, for the other outcomes, no statistically significant differences were observed between the groups. Additionally, most of included articles (n=5/7) had some concerns or high risk of bias, and the quality of evidence revealed a moderate confidence for almost all outcomes; so the results must be interpreted with caution. Thus, more consistent, and robust clinical trials need to be carried out to confirm the efficacy of vitamin D supplementation in patients with HD.