Impact of the insertion of the clinical pharmacist in the Allogeneic Hematopoietic Stem Cells Transplantation team.

INTRODUCTION: Allogeneic Hematopoietic Stem Cells Transplantation (allo-HSCT) is capable of curing patients with neoplastic or non-neoplastic hematologic disorders or of prolonging their survival. This study assessed if the insertion of the clinical pharmacist in the allo-HSCT team modified the outcomes: transplantation-related mortality, grafting failure, incidence of Graft versus Host Disease, hospitalization time, time for grafting, number of readmissions, number of drug-related problems (DRPs), adherence and knowledge about pharmacotherapy. METHODS: Interventional study with historical control carried out in an allo-HSCT unit, in which the intervention group (IG) included 33 individuals who received pharmacotherapy follow-up. Control Group (CG) consisted of 28 individuals. RESULTS: A total of 250 DRPs were identified, 59 team's doubts were clarified, and 309 interventions were conducted in the IG. The DRPs mainly arose from safety (51.60%) and effectiveness (38.40%) problems. A mean of 9.36 (SD = 6.97) interventions per patient was obtained, mainly including dose reductions (19.09%), adjustments in administration time (18.12%), educational activities (15.21%) and drug removal (10.68%). Clinical significance of the interventions was considered high (75.7% extremely significant, very significant or significant), as well as their acceptability (89.7% accepted). Each patient attended a mean of 4.68 pharmaceutical consultations (SD = 1.91) after hospital discharge, presenting increase in knowledge (p = 0.0001) and in adherence (p = 0.0115). There was no evidence of differences between the groups in the other outcomes analyzed. CONCLUSIONS: The pharmacotherapy follow-up allowed detecting several DRPs and performing interventions of high clinical relevance and acceptability, in addition to improving adherence and individualizing the pharmacotherapy.

Can pharmacotherapeutic follow-up after allogeneic hematopoietic stem cell transplantation improve medication compliance?

BACKGROUND: Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) is currently one of the most effective therapies in onco-hematology. For the treatment of the disease and prevention of such complications, a complex pharmacotherapeutic regimen is employed. Non-compliance is prevalent among adolescents and young adults with chronic hematological diseases, being reported by up to 50% of the patients. OBJECTIVE: To evaluate the results of pharmacotherapeutic follow-up on medication compliance and on the knowledge about pharmacotherapy of patients who underwent allo-HSCT. METHODS: A single-arm, open-label and non-randomized intervention study developed in an allo-HSCT outpatient clinic. The participants attended pharmaceutical consultations and had their knowledge about pharmacotherapy and medication compliance measured by MedTake and Brief Medication Questionnaire (BMQ), respectively. RESULTS: A total of 27 patients attended pharmaceutical consultations (4.81 consultations/patient; SD = 1.80). There was an improvement in medication compliance and in knowledge between the first and last consultations (p < 0.05). In the final consultation, 70.37% of the patients showed compliance, with a knowledge rate of 98.35% (SD = 3.63). Non-compliant individuals presented a greater tendency to hospital readmissions. There was no relationship between medication compliance and sociodemographic variables, graft-versus-host disease, and knowledge about pharmacotherapy. CONCLUSIONS: Pharmacotherapeutic follow-up contributed to improving medication compliance. Knowledge about pharmacotherapy alone does not translate into behaviors, which corroborates the complexity of the biopsychosocial factors associated with medication compliance.

[Central nervous system adverse events potentially associated with drugs used for COVID-19: scoping reviewEventos adversos en el sistema nervioso central potencialmente relacionados con los medicamentos para tratar la COVID-19: revisión exploratoria]. / Eventos adversos no sistema nervoso central potencialmente relacionados aos medicamentos utilizados na COVID-19: revisão de escopo.

Objective: To identify central nervous system (CNS) adverse events potentially associated with prophylaxis or drug treatment for COVID-19, and to describe the characteristic of the individuals affected. Methods: A scoping review was performed using a search strategy to retrieve articles from PubMed, EMBASE, SciELO, Scopus, CINAHL and BVS databases. Studies reporting on individuals receiving prophylactic or curative drugs for COVID-19 with at least one CNS adverse event were included. Articles reporting on CNS adverse events associated with medication for other health conditions were excluded. Results: The search retrieved 1 547 articles, eight of which met the inclusion criteria. Seven studies had an observational design. A total of 3 035 individuals were assessed, of whom 1 701 were health care professionals and 1 978 were women. Curative treatment with hydroxychloroquine, chloroquine, lopinavir/ritonavir, and azithromycin was the most frequent (n = 5). The most common adverse events were headache, dizziness, mood disturbances, and drowsiness. Suicide was the most frequent severe event. Six adverse events were unexpected for hydroxychloroquine, chloroquine, and doxycycline. Conclusion: Potential CNS adverse events were unspecific and in general potentially associated with the use of hydroxychloroquine (monotherapy or associated with antibiotics). The data confirm the unfavorable risk/benefit profile of these drugs for the prevention and management of signs and symptoms of SARS-CoV-2 infection.

Objetivo: Identificar los eventos adversos en el sistema nervioso central (SNC) potencialmente relacionados con el uso de medicamentos empleados para profilaxis o tratamiento de la COVID-19, y caracterizar a las personas afectadas. Métodos: Se realizó una revisión exploratoria a partir de una estrategia de búsqueda en las bases de datos PubMed, EMBASE, SciELO, Scopus, Cummulative Index to Nursing and Allied Health Literature (CINAHL) y la Biblioteca Virtual de Salud (BVS). Se incluyeron estudios de personas que emplearon medicamentos con fines profilácticos o curativos para la COVID-19 y presentaron al menos un evento adverso en el SNC. Se excluyeron los artículos en los cuales se notificaron eventos adversos en el SNC potencialmente relacionados con medicamentos para tratar otros problemas de salud. Resultados: Se recuperaron 1 547 artículos, de los cuales ocho cumplieron con los criterios de admisibilidad. Siete estudios tuvieron un diseño observacional. Se analizaron 3 035 personas, de las cuales 1 701 eran profesionales de salud y 1 978, mujeres. El tratamiento más utilizado fue el curativo (n = 5), con hidroxicloroquina, cloroquina, lopinavir/ritonavir y azitromicina. Los eventos adversos comúnmente citados fueron dolor de cabeza, mareos, trastornos del estado de ánimo y somnolencia. El suicidio fue el evento grave más frecuente. Seis eventos inesperados (mioclonías, temblor, trastorno de la marcha, disgeusia, hiperhidrosis y desasosiego) guardaron relación con el empleo de hidroxicloroquina, cloroquina y doxiciclina. Conclusión: Los eventos adversos del SNC fueron inespecíficos y, en general, posiblemente estuvieron relacionados con el uso de hidroxicloroquina (sola o combinada) para el tratamiento curativo de la COVID-19. Los datos corroboran la relación desfavorable de riesgo/beneficio de esos medicamentos en la prevención y el manejo de los signos y síntomas de la infección por el SARS-CoV-2.

A novel substitution in NS5A enhances the resistance of hepatitis C virus genotype 3 to daclatasvir.

Hepatitis C virus (HCV) genotype 3 presents a high level of both baseline and acquired resistance to direct-acting antivirals (DAAs), particularly those targeting the NS5A protein. To understand this resistance we studied a cohort of Brazilian patients treated with the NS5A DAA, daclatasvir and the nucleoside analogue, sofosbuvir. We observed a novel substitution at NS5A amino acid residue 98 [serine to glycine (S98G)] in patients who relapsed post-treatment. The effect of this substitution on both replication fitness and resistance to DAAs was evaluated using two genotype 3 subgenomic replicons. S98G had a modest effect on replication, but in combination with the previously characterized resistance-associated substitution (RAS), Y93H, resulted in a significant increase in daclatasvir resistance. This result suggests that combinations of substitutions may drive a high level of DAA resistance and provide some clues to the mechanism of action of the NS5A-targeting DAAs.

Screening microchip sites to predict body temperature in young calves.

Thermal microchip sensors can automate body temperature measurements. The best site of implantation is still unknown, and the accuracy and precision of body temperature predictions based on microchip data need to be investigated. The aim of this study was to investigate the best site for microchip implant for monitoring body temperature in dairy calves. Seventeen calves were used (32.2 ± 5.2 kg of body weight) and the microchips were implanted four days after birth. The microchips were implanted at navel, ear and tail base (subcutaneous), neck (cleidocephalicus) and internal face of leg (gracilis) (intramuscular). Rectal temperature (RT, °C), obtained with a clinical thermometer, was considered as core temperature. Air temperature (AT), relative humidity (RH) and the temperature and humidity index (THI) were evaluated at the same time of rectal and microchip temperature measurements over 56 days. The range of AT, RH and THI was 7.6-34.4 °C, 17.5-99.0% and 50.6 to 91.5. The average for rectum, ear, neck, tail, leg, and navel were 38.7; 36.9; 38.0; 37.0, 37.8 and 37.0 °C. The intramuscular implantations had closest values to RT. The correlations between RT and ear, neck, tail, leg, and navel temperatures were 0.56, 0.60, 0.60, 0.53 e 0.48. The RT prediction based on microchip data had precision (rc) ranged between 0.49 and 0.60 and accuracy (Cb) between 0.79 and 0.88. The inclusion of AT, RH and THI as predictive variables in models decrease the mean absolute error (23%) and increase the precision (21.3%) and accuracy (10.2%). The Concordance Correlation Coefficient and root-mean-square error for equations using tail or neck microchips were 0.68 and 0.67, and 0.29 and 0.28 °C, respectively. The tail base is a promising site for microchip implantation to predict rectal temperature. The inclusion of air temperature as a predictive variable in the models is recommended.

Estimating purine derivatives and nitrogen compound excretion using total urine collection or spot urine samples in grazing heifers.

The study aimed to evaluate the excretion of purine derivatives (PDs) and nitrogen compounds (NCs) and their ratios with creatinine in supplemented Zebu heifers kept on pastures by comparing total urine collection and spot sampling. Five Nelore heifers (400 ± 15 kg) were used in a 5 × 5 Latin square design. The treatments were the amount of concentrate (220 g of crude protein/kg dry matter) offered (0, 3, 6, 9 and 12 g/kg BW). In each period, the total urine collection was performed continuously for 3 days (subsampled at intervals of 4 h, 00:00-04:00 h, 04:00-08:00 h, 08:00-12:00 h, 12:00-16:00 h, 16:00-20:00 h and 20:00-24:00 h). The spot urine samplings were performed (in each period) for 24 h (0, 4, 8, 12, 16 and 20 h). Creatinine, total urinary nitrogen (UN), urea nitrogen (UreaN), allantoin and uric acid were analysed. Creatinine excretion was 23.01 ± 0.19 mg/kg BW and was not affected by collection day, treatment or their interactions (p > 0.05). Treatments affected (p < 0.05) PD excretions, however did not affect the ratio PD:creatinine (p > 0.05). Treatments and collection time affected (p < 0.05) NC excretion, whereas the UN:creatinine and UreaN:creatinine ratios were not affected (p > 0.05). Creatinine excretion and the PD:creatinine ratios in the urine samples estimated by the total or spot sampling were not different (p > 0.05). However, sampling method affected (p < 0.05) the UN:creatinine and UreaN:creatinine (p < 0.05) ratios. Creatinine can adequately estimate urinary excretion in grazing heifers, and a single spot urine sample at any time of the day can be used to estimate PD excretion in grazing heifers. But two spot urine samples are needed for proper NC excretion estimations in grazing heifers' urine.

Host cell protein LAMP-2 is the receptor for Trypanosoma cruzi surface molecule gp82 that mediates invasion.

Host cell invasion by Trypanosoma cruzi metacyclic trypomastigote (MT) is mediated by MT-specific surface molecule gp82, which binds to a still unidentified receptor, inducing lysosome spreading and exocytosis required for the parasitophorous vacuole formation. We examined the involvement of the major lysosome membrane-associated LAMP proteins in MT invasion. First, human epithelial HeLa cells were incubated with MT in the presence of antibody to LAMP-1 or LAMP-2. Antibody to LAMP-2, but not to LAMP-1, significantly reduced MT invasion. Next, HeLa cells depleted in LAMP-1 or LAMP-2 were generated. Cells deficient in LAMP-2, but not in LAMP-1, were significantly more resistant to MT invasion than wild-type controls. The possibility that LAMP-2 might be the receptor for gp82 was examined by co-immunoprecipitation assays. Protein A/G magnetic beads cross-linked with antibody directed to LAMP-1 or LAMP-2 were incubated with HeLa cell and MT detergent extracts. Gp82 bound to LAMP-2 but not to LAMP-1. Binding of the recombinant gp82 protein to wild-type and LAMP-1-deficient cells, which was dose dependent and saturable, had a similar profile and was much higher as compared with LAMP-2-depleted cells. These data indicate that MT invasion is accomplished through recognition of gp82 by its receptor LAMP-2.

Use of statins for the secondary prevention of stroke: are we respecting the scientific evidences?

BACKGROUND: Stroke accounts for approximately as 5.0% of disability-adjusted years of life and 10.0% of all deaths worldwide. Secondary stroke prevention in surviving individuals, which includes the use of statins, reduces atherothrombotic stroke recurrence, complications and mortality. The present study aimed to characterize the Brazilian population with stroke history and estimate the prevalence of statin use as secondary prevention. METHODS: This is a population-based cross-sectional study conducted in Brazilian urban areas. A total of 41.433 individuals were interviewed, representing 171 million of Brazilians, based on post-stratification weights. We included only participants aged 20 years or older who answered "yes" to the following question: "Did any doctor ever tell you that you had a stroke?" The main outcome was the prevalence of statin use among individuals who answered affirmatively. To identify the factors associated with stroke occurrence, the participants were categorized according to clinical and sociodemographic characteristics. RESULTS: Only 24.2% (95% CI 19.9 - 29.1) of those who reported history of stroke regardless of other conditions also reported statin use. However, the results indicated that 52.9% (95% CI 43.6 - 62.0) of individuals who reported a previous diagnosis of dyslipidemia stated the use of statins. Regarding patients who reported stroke and did not report dyslipidemia history, only 9.1% (95% CI 5.9 - 13.8) referred to use statins. CONCLUSION: This study showed a low prevalence of statin use by individuals with a history of stroke in Brazil. Actions involving the organization of services and training of professionals may positively impact the rates of stroke recurrence.

Effects of exogenous amylase on the in vitro digestion kinetics of whole-crop maize silages made from flint or dent grain type at different phenological stages grown in tropical condition.

The effect of exogenous amylase on the in vitro rumen digestion kinetics of whole-crop maize silage made from dent (RB9004) or flint grain type (RB9308) was evaluated at different phenological stages: soft dough (SOD), early dent (EAD), ½ milkline (½M) and ¾ milkline (¾M). Forage was harvested from 70 to 110 days after sowing. Two rumen-cannulated cows receiving or not exogenous amylase (0.7 g/kg dry matter-DM, provided to achieve 396 kilo Novo units of amylase activity/kg of TMR DM) were used as donor of ruminal fluid. The in vitro gas production kinetics was evaluated according to a dual-pool logistic model. The chemical composition and gas production kinetics were affected by the hybrid and phenological stages. The flint hybrid had lower range for chemical analysis among physiological stages. Harvesting at ½M and ¾M improved DM content, bromatological composition and silage quality parameters compared to dent or flint types. Amylase (i) increased methane (CH4 ) production and in vitro dry matter digestibility (IVDMD) in ½M stage, (ii) improved digestion kinetics by reducing lag time and increasing total gas production and fermentation rates of non-fibrous carbohydrates (NFC) and fibrous carbohydrates (FC), and (iii) increased extent and fermentation rate of NFC and increased fermentation rate of FC fraction in whole-crop maize silages produced from dent or flint types in all phenological stages. Harvesting between ½M and ¾M is the best phenological stage to improve chemical composition and silage quality parameters. Exogenous amylase showed improvements on fibre digestion of silages at ½M and ¾M phenological stages in both grain types of corn.

Oral infection of mice and host cell invasion by Trypanosoma cruzi strains from Mexico.

Oral infection by Trypanosoma cruzi has been responsible for frequent outbreaks of acute Chagas disease in the north of South America and in the Amazon region, where T. cruzi genetic group TcI predominates. TcI strains from different geographical regions have been used in oral infection in mice, but there is no information about strains from Mexico where TcI is prevalent. Here, we analyzed four Mexican strains as concerns the course of oral infection, the ability to invade host cells in vitro, and the profile of metacyclic trypomastigote surface molecules gp82 and gp90 that are implicated in parasite internalization. Oral infection of mice with metacyclic forms of all strains resulted in reduced blood and tissue parasitism, and mild to moderate inflammatory process in the heart/skeletal muscle. They expressed pepsin-resistant gp82 and gp90 molecules at high levels and invaded host cells poorly in full nutrient medium and efficiently under nutrient-deprived condition. The properties exhibited by Mexican strains were similar to those displayed by TcI strains from other geographical regions, reinforcing the notion that these features are common to the genetic group TcI as a whole.