Epidemiological indicators and predictors of lethality associated with fungal infections in a NICU: a historical series

Abstract Objectives: Fungal infections (FI) pose a public health concern and significantly increase mortality rates, especially within Neonatal Intensive Care Units (NICU). Thus, this study aimed to investigate epidemiological indicators, risk factors, and lethality predictors associated with FI in a NICU. Methods: This study included 1,510 neonates admitted to the NICU of a reference hospital in Brazil between 2015 and 2022. Demographic data, such as sex, birth weight, gestational age, and use of invasive devices were analyzed. Results: Thirty neonates developed invasive FI, totaling 33 episodes and an incidence of 1.2 per 1,000 patient days. Candida albicans was the most frequent species (52.9 %), the bloodstream was the most affected site (78.9 %), and 72.7 % of infections occurred between 2015 and 2018. The lethality rate associated with FI was 33.3 %, and 90 % of deaths occurred within 30 days of diagnosis of infection. Weight < 750 g, prolonged hospital stay, use of parenteral nutrition, and broad-spectrum antimicrobials were independent risk factors for infection occurrence, especially glycopeptides and 4th generation cephalosporins, having a considerable role in the increase in fungal infections. Weight < 750 g was considered a significant predictor of lethality, and C. albicans had the highest lethality rate (40 %). Conclusion: These findings highlight the elevated lethality rate associated with these infections, reinforcing the importance of developing strategies to control FI within NICU.

The efficacy and safety of GLP-1 receptor agonists in youth with type 2 diabetes: a meta-analysis.

BACKGROUND: Glucagon-like peptide 1 receptor agonists have been proven to be effective in adults with diabetes and children with obesity. However, children with type 2 diabetes constitute an underrepresented subpopulation with limited treatment options. This meta-analysis aimed to determine more precise estimates of the efficacy and safety of glucagon-like peptide-1 agonists in pediatric type 2 diabetes mellitus. METHODS: Three databases were searched (PubMed, Embase, and Cochrane Central Register of Controlled Trials) for trials published until the end of March 2024. The search indexing terms included 3 categories: [1] type 2 diabetes mellitus [2], youth, and [3] glucagon-like peptide-1 receptor agonist (GLP-1 RA). Randomized controlled trials in youth with type 2 diabetes (age ≤ 18 years) that assessed anthropometric and metabolic parameters were included. A total of 1119 nonduplicate studies were retrieved, and 137 full-text articles were screened. The data were analyzed using mean differences (MDs) with 95% CIs and odds ratios (ORs) with 95% CIs. For outcomes with low heterogeneity, a fixed-effects model was used. Otherwise, we applied a random effects model. Our outcomes were Hb1Ac, fasting blood glucose (FBG), blood pressure, weight, and side effects. RESULTS: Five studies comprehending 415 children and adolescents were included. On average, GLP-1 RA reduced HbA1c levels (-1.01%; 95% CI, -1.26 to -0.76), fasting blood glucose levels (-1.88 mmol/L; 95% CI, -2.51 to -1.26), and body weight (-1.6 kg; 95% CI, -2.83 to -0.36). No significant reductions in systolic blood pressure (MD -0.19 mmHg; 95% CI, -3.9 to 3.52 mmHg) or diastolic blood pressure (MD 0.3 mmHg; 95% CI, -2.33 to 2.93 mmHg) were observed. Despite a higher incidence of side effects, withdrawal rates from the studies remained low. CONCLUSIONS: Within this specific population, GLP-1 RAs exhibit a notable association with substantial reductions in HbA1c, FBG, and body weight. The administration of these medications is concurrent with an elevated incidence of side effects, which are predominantly gastrointestinal and tolerable. TRIAL REGISTRATION: PROSPERO identifier: CRD42023393020.

Unraveling the epidemiology of urinary tract infections in neonates: Perspective from a Brazilian NICU.

BACKGROUND: Urinary tract infections (UTIs) can lead to neonatal complications like sepsis, worsened by empirical treatment, contributing to antimicrobial resistance (AMR). This study examined the incidence, etiology, risk factors, and antimicrobial susceptibility of uropathogens in a Neonatal Intensive Care Unit (NICU) in Brazil. METHODS: Medical records of neonates hospitalized in the NICU from January 2015 to June 2022 were retrospectively analyzed through the National Healthcare Safety Network system. RESULTS: Among 1,474 neonates, 3.9% developed UTI, with an alarming 24-fold increase in incidence from 2015 to 2021. Genitourinary complications (odds ratio = 4.8) were a major risk factor. Of the 71 uropathogens, 74.6% were Gram-negative bacteria (GNB), 21.2% Gram-positive bacteria (GPB), and 4.2% Candida albicans. AMR was notable, with 13.3% of GPB and 20.7% of GNB exhibiting multidrug-resistant (MDR), while 6.6% of GPB and 1.9% of GNB showed extensive drug-resistant (XDR). UTI was associated with prolonged hospitalization (16-59 days). In 57 neonates with UTI, 40.3% had bloodstream infections, elevating the risk of death (odds ratio = 1.8). CONCLUSIONS: The study underscores the urgency of implementing infection prevention and control measures in the NICU to curb rising UTI incidences, combat AMR, and mitigate severe complications in critically ill neonates.

Epidemiological indicators and predictors of lethality associated with fungal infections in a NICU: a historical series.

OBJECTIVES: Fungal infections (FI) pose a public health concern and significantly increase mortality rates, especially within Neonatal Intensive Care Units (NICU). Thus, this study aimed to investigate epidemiological indicators, risk factors, and lethality predictors associated with FI in a NICU. METHODS: This study included 1,510 neonates admitted to the NICU of a reference hospital in Brazil between 2015 and 2022. Demographic data, such as sex, birth weight, gestational age, and use of invasive devices were analyzed. RESULTS: Thirty neonates developed invasive FI, totaling 33 episodes and an incidence of 1.2 per 1,000 patient days. Candida albicans was the most frequent species (52.9 %), the bloodstream was the most affected site (78.9 %), and 72.7 % of infections occurred between 2015 and 2018. The lethality rate associated with FI was 33.3 %, and 90 % of deaths occurred within 30 days of diagnosis of infection. Weight < 750 g, prolonged hospital stay, use of parenteral nutrition, and broad-spectrum antimicrobials were independent risk factors for infection occurrence, especially glycopeptides and 4th generation cephalosporins, having a considerable role in the increase in fungal infections. Weight < 750 g was considered a significant predictor of lethality, and C. albicans had the highest lethality rate (40 %). CONCLUSION: These findings highlight the elevated lethality rate associated with these infections, reinforcing the importance of developing strategies to control FI within NICU.

Impact of intestinal colonization by Gram-negative bacteria on the incidence of bloodstream infections and lethality in critically ill neonates.

BACKGROUND: Early detection of antimicrobial-resistant microorganisms is crucial to prevent subsequent invasive infections and contain their spread in the Neonatal Intensive Care Unit (NICU). This study aims to investigate the association between intestinal colonization (IC) by Gram-negative bacteria and the risk of bloodstream infection (BSI) in critically ill neonates. METHODS: Data from the electronic medical records of 678 newborns admitted to a NICU Brazilian between 2018 and 2022 were retrospectively analyzed. Participants were monitored by the National Health Security Network. RESULTS: Among neonates, 6.9 % had IC (56.9 % attributed to Acinetobacter baumannii); of these, 19.1 % developed BSI (66.7 % by Staphylococcus spp.). Within the A. baumannii colonization, 34.5 % occurred during an outbreak in September 2021. Colonized individuals had a longer mean length of stay (49.3 ± 26.4 days) and higher mortality rate (12.8 %) compared to non-colonized individuals (22.2 ± 16.9 days; 6.7 %, respectively). Previous use of antimicrobials and invasive devices significantly increased the risk of colonization. Colonization by drug-resistant microorganisms, along with the occurrence of BSI, was associated with increased mortality and reduced survival time. CONCLUSIONS: IC contributed to the incidence of BSI, leading to more extended hospital stays and higher mortality rates. Its early detection proved to be essential to identify an outbreak and control the spread of resistant microorganisms within the NICU.

Influence of polymorphisms in CYP2C9, VKORC1, MDR1 and APOE genes on the warfarin maintenance dose in Brazilian patients.

Background: Polymorphisms in the CYP2C9, VKORC1, MDR1 and APOE genes may impact warfarin dose. Aim: To investigate the influence of sociodemographic, clinical factors and polymorphisms *1, *2 and *3 for CYP2C9, -1639G>A for VKORC1, 3435C>T for MDR1, and ϵ2, ϵ3 and ϵ4 for APOE genes on the mean weekly warfarin maintenance dose in adults. Methods: This cross-sectional study recruited a calculated sample of 315 patients in three anticoagulation clinics in Brazil. A model containing the variables significantly associated with warfarin dose was estimated. Results: The mean age of patients was 64.1 ± 13.1 years, with 173 (54.9%) women. Age, use of amiodarone, genotype VKORC1 GA, genotype VKORC1 AA, genotypes CYP2C9*1/*2 or *1/*3 and genotypes CYP2C9*2/*2 or *2/*3 or *3/*3 were associated with a reduced warfarin dose. Conclusion: This study pointed out factors that could impact the management of oral anticoagulation.

Perfil epidemiológico dos acidentes causados por animais peçonhentos no município de Patrocínio, Minas Gerais: retrato de uma década / Epidemiological profile of accidents caused by venomous animals in the municipality of Patrocínio, Minas Gerais: portrait of a decade / Perfil epidemiológico de accidentes causados por animales venenosos en el municipio de Patrocínio, Minas Gerais: retrato de una década

Justificativa e objetivos: apesar dos avanços na área assistencial, os acidentes por animais peçonhentos ainda são um importante problema de saúde pública no Brasil. Entre os anos de 2015 e 2016, a região Sudeste apresentou o maior número de notificações, e Minas Gerais foi o estado com mais ocorrências. O objetivo deste estudo foi descrever as características epidemiológicas dos acidentes por animais peçonhentos notificados entre 2008 e 2017 no município de Patrocínio, Minas Gerais. Métodos: estudo descritivo retrospectivo realizado por meio da análise das informações das fichas de notificação do Sistema de Informação de Agravos de Notificação (SINAN) de vítimas de acidentes por animais peçonhentos ocorridos durante os anos de 2008 a 2017 em Patrocínio. Resultados: foram registrados 1.084 casos, a maioria ocasionada por escorpiões (47,23%), seguida por serpentes (17,07%), aranhas (15,31%) e abelhas (11,07%). Sobre as vítimas, constatou-se o predomínio de homens (63,10%) na faixa etária entre 20 a 39 anos (32,56%). A maior parte dos acidentes foi classificada como leve (89,11%) e a cura ocorreu em 98,80% dos casos; um evoluiu para óbito. Conclusão: embora os acidentes por animais peçonhentos não apresentem altas taxas de letalidade no município estudado, a incidência desse agravo de saúde tem aumentado nos últimos anos. Além disso, informações epidemiológicas atualizadas podem contribuir com ações de políticas públicas e informar a população local sobre os riscos iminentes.(AU)

Background and objectives: despite advances in health care, accidents involving venomous animals are still a major public health problem in Brazil. Between 2015 and 2016, the Southeast region had the highest number of notifications, and Minas Gerais was the state with more occurrences. The objective of this study was to describe the epidemiological characteristics of accidents by venomous animal notified between 2008 and 2017 in the municipality of Patrocínio, Minas Gerais. Methods: this is a retrospective descriptive study conducted by analyzing the information from reporting forms of the Notifiable Diseases Information System for victims of accidents with venomous animals occurred during the years 2008 to 2017 in Patrocínio. Results: in total, 1084 cases were recorded, mostly caused by scorpions (47.23%), followed by snakes (17.07%), spiders (15.31%) and bees (11.07%). There was a predominance of male victims (63.10%), aged between 20-39 years (32.56%). Most accidents were classified as mild (89.11%) and the cure occurred in 98.80% of cases; one evolved to death. Conclusion: although accidents with venomous animals do not have high mortality rates in the municipality studied, the incidence of this health problem has increased in recent years. In addition, this updated epidemiological information may contribute to public policy actions and inform the local population about imminent risks.(AU)

Justificación y objetivos: a pesar de los avances en salud, los accidentes de animales venenosos siguen siendo un importante problema de salud pública en Brasil. Entre 2015 y 2016, la región sudeste tuvo el mayor número de notificaciones y Minas Gerais fue el estado con más casos. El objetivo de este estudio fue describir las características epidemiológicas de los accidentes por animales venenosos notificados entre 2008 y 2017 en el municipio de Patrocínio, Minas Gerais. Métodos: estudio descriptivo retrospectivo llevado a cabo mediante el análisis de la información de los formularios de notificación del Sistema de Información de Enfermedades Notificables de víctimas de accidentes con animales venenosos que ocurrieron durante los años 2008 a 2017 en Patrocínio. Resultados: se registraron 1084 casos, en su mayoría causados por escorpiones (47.23%), seguidos de serpientes (17.07%), arañas (15.31%) y abejas (11.07%). Predominaron las víctimas del sexo masculino (63,10%), con edades entre 20 y 39 años (32,56%). La mayoría de los accidentes se clasificaron como leves (89,11%) y la curación se produjo en el 98,80% de los casos; uno evolucionó hasta la muerte. Conclusiones: aunque los accidentes con animales venenosos no tienen altas tasas de mortalidad en el municipio estudiado, la incidencia de este problema de salud ha aumentado en los últimos años. Además, esta información epidemiológica actualizada puede contribuir a las acciones de política pública e informar a la población local sobre los riesgos inminentes.(AU)

Methods and strategies of tDCS for the treatment of pain: current status and future directions.

INTRODUCTION: Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique that has been widely studied for the treatment of chronic pain. It is considered a promising and safe alternative pain therapy. Different targets have been tested, each having their own particular mechanisms for modulating pain perception. AREAS COVERED: We discuss the current state of the art of tDCS to manage pain and future strategies to optimize tDCS' effects. Current strategies include primary motor cortex tDCS, prefrontal tDCS and tDCS combined with behavioral interventions while future strategies, on the other hand, include high-intensity tDCS, transcutaneous spinal direct current stimulation, cerebellar tDCS, home-based tDCS, and tDCS with extended number of sessions. EXPERT COMMENTARY: It has been shown that the stimulation of the prefrontal and primary motor cortex is efficient for pain reduction while a few other new strategies, such as high-intensity tDCS and network-based tDCS, are believed to induce strong neuroplastic effects, although the underlying neural mechanisms still need to be fully uncovered. Hence, conventional tDCS approaches demonstrated promising effects to manage pain and new strategies are under development to enhance tDCS effects and make this approach more easily available by using, for instance, home-based devices.

BthTX-I from Bothrops jararacussu induces apoptosis in human breast cancer cell lines and decreases cancer stem cell subpopulation.

BACKGROUND: Breast cancer is the neoplasm with both the highest incidence and mortality rate among women worldwide. Given the known snake venom cytotoxicity towards several tumor types, we evaluated the effects of BthTX-I from Bothrops jararacussu on MCF7, SKBR3, and MDAMB231 breast cancer cell lines. METHODS: BthTX-I cytotoxicity was determined via MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide assay. Cell death was measured by a hypotonic fluorescent solution method, annexin-V-FITC/propidium iodide staining and by apoptotic/autophagic protein expression. Cancer stem cells (CSCs) were quantified by flow cytometry using anti-CD24-FITC and anti-CD44-APC antibodies and propidium iodide. RESULTS: BthTX-I at 102 µg/mL induced cell death in all cell lines. The toxin induced apoptosis in MCF7, SKBR3, and MDAMB231 in a dose-dependent manner, as confirmed by the increasing number of hypodiploid nuclei. Expression of pro-caspase 3, pro-caspase 8 and Beclin-1 proteins were increased, while the level of the antiapoptotic protein Bcl-2 was diminished in MCF7 cells. BthTX-I changed the staining pattern of CSCs in MDAMB231 cells by increasing expression of CD24 receptors, which mediated cell death. CONCLUSIONS: BthTX-I induces apoptosis and autophagy in all breast cancer cell lines tested and also reduces CSCs subpopulation, which makes it a promising therapeutic alternative for breast cancer.

Recruitment challenges in stroke neurorecovery clinical trials.

There are multiple available treatments to enhance stroke rehabilitation, although few interventions have confirmed significant clinical improvements on motor function in pivotal Randomized Clinical Trials. Development of large Randomized Clinical Trials is limited by several barriers and low enrollment rate is considered an important factor. Consequently, most of the evidence comes from small sample size studies, often leading to limited conclusions. According to the National Institute of Health (NIH), about 80% of clinical trials in the United States do not achieve their timelines, increasing research costs and postponing regulatory approval of new therapies. Given that the success of a Randomized Clinical Trial is dependent on enrolling an adequate number of subjects, effective strategies to enhance recruitment rates are highly desirable. In addition, given the resources and time limitations, it is important to understand which strategies are most cost-effective. In this manuscript, we summarize and discuss nine recruitment strategies used in an NIH R21 sponsored clinical trial, including medical records review and online advertising, among others. In addition, we developed an index to compare the time spent benefit of each approach and guide the allocation of the recruitment efforts. For this trial, online advertising and referral from health care professionals other than physicians were the strategies with greater time-benefit, leading to the largest number of stroke subjects enrolled.

Combining Fluoxetine and rTMS in Poststroke Motor Recovery: A Placebo-Controlled Double-Blind Randomized Phase 2 Clinical Trial.

Background. Although recent evidence has shown a new role of fluoxetine in motor rehabilitation, results are mixed. We conducted a randomized clinical trial to evaluate whether combining repetitive transcranial magnetic stimulation (rTMS) with fluoxetine increases upper limb motor function in stroke. Methods. Twenty-seven hemiparetic patients within 2 years of ischemic stroke were randomized into 3 groups: Combined (active rTMS + fluoxetine), Fluoxetine (sham rTMS + fluoxetine), or Placebo (sham rTMS + placebo fluoxetine). Participants received 18 sessions of 1-Hz rTMS in the unaffected primary motor cortex and 90 days of fluoxetine (20 mg/d). Motor function was assessed using Jebsen-Taylor Hand Function (JTHF) and Fugl-Meyer Assessment (FMA) scales. Corticospinal excitability was assessed with TMS. Results. After adjusting for time since stroke, there was significantly greater improvement in JTHF in the combined rTMS + fluoxetine group (mean improvement: -214.33 seconds) than in the placebo (-177.98 seconds, P = 0.005) and fluoxetine (-50.16 seconds, P < 0.001) groups. The fluoxetine group had less improvement than placebo on both scales (respectively, JTHF: -50.16 vs -117.98 seconds, P = 0.038; and FMA: 6.72 vs 15.55 points, P = 0.039), suggesting that fluoxetine possibly had detrimental effects. The unaffected hemisphere showed decreased intracortical inhibition in the combined and fluoxetine groups, and increased intracortical facilitation in the fluoxetine group. This facilitation was negatively correlated with motor function improvement (FMA, r2 = -0.398, P = 0.0395). Conclusion. Combined fluoxetine and rTMS treatment leads to better motor function in stroke than fluoxetine alone and placebo. Moreover, fluoxetine leads to smaller improvements than placebo, and fluoxetine's effects on intracortical facilitation suggest a potential diffuse mechanism that may hinder beneficial plasticity on motor recovery.

Searching for the optimal tDCS target for motor rehabilitation.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been investigated over the years due to its short and also long-term effects on cortical excitability and neuroplasticity. Although its mechanisms to improve motor function are not fully understood, this technique has been suggested as an alternative therapeutic method for motor rehabilitation, especially those with motor function deficits. When applied to the primary motor cortex, tDCS has shown to improve motor function in healthy individuals, as well as in patients with neurological disorders. Based on its potential effects on motor recovery, identifying optimal targets for tDCS stimulation is essential to improve knowledge regarding neuromodulation as well as to advance the use of tDCS in clinical motor rehabilitation. METHODS AND RESULTS: Therefore, this review discusses the existing evidence on the application of four different tDCS montages to promote and enhance motor rehabilitation: (1) anodal ipsilesional and cathodal contralesional primary motor cortex tDCS, (2) combination of central tDCS and peripheral electrical stimulation, (3) prefrontal tDCS montage and (4) cerebellar tDCS stimulation. Although there is a significant amount of data testing primary motor cortex tDCS for motor recovery, other targets and strategies have not been sufficiently tested. This review then presents the potential mechanisms and available evidence of these other tDCS strategies to promote motor recovery. CONCLUSIONS: In spite of the large amount of data showing that tDCS is a promising adjuvant tool for motor rehabilitation, the diversity of parameters, associated with different characteristics of the clinical populations, has generated studies with heterogeneous methodologies and controversial results. The ideal montage for motor rehabilitation should be based on a patient-tailored approach that takes into account aspects related to the safety of the technique and the quality of the available evidence.

Magnesium and malic acid supplement for fibromyalgia. / Suplemento de magnesio y ácido málico para fibromialgia.

INTRODUCTION: Fibromyalgia is characterized by myalgia and a combination of different symptoms including pain, fatigue, insomnia, morning rigidity, depression and a reduction in every-day functioning. Its aetiology is not clear, but it has been suggested that deficiency in certain minerals such as magnesium may play a role both in the physiopathology and in contributing to the symptoms. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified seven systematic reviews which included 11 primary studies of which one was a randomized trial. Our conclusion is that the use of magnesium and malic acid in patients with fibromyalgia makes little or no difference on pain and on depressive symptoms.

INTRODUCCIÓN: La fibromialgia es una condición reumática no articular caracterizada por distintos síntomas, donde destacan principalmente el dolor, sensibilidad muscular, fatiga, insomnio, rigidez matinal, depresión y disminución de la funcionalidad cotidiana. Aún no existe claridad respecto de su etiología, pero se ha planteado que la deficiencia de elementos tales como el magnesio podría tener un rol tanto en la fisiopatología de la fibromialgia como también contribuir a sus síntomas clínicos. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos siete revisiones sistemáticas que en conjunto incluyeron 11 estudios primarios, de los cuales solo uno corresponde a un ensayo aleatorizado. Concluimos que el uso de magnesio y ácido málico en pacientes con fibromialgia tiene poco o nulo impacto en dolor y en los síntomas depresivos.

Emerging targets and uses of neuromodulation for pain.

INTRODUCTION: There has been great development in the testing of invasive and non-invasive neuromodulation for chronic pain. To date, it is known that central and peripheral stimulation targets, combined or not, may influence chronic pain sensation. Although most of the significant results of chronic pain studies come from motor cortex stimulation, novel targets are being explored to increase effect sizes and to induce pain relief in non-responders. Areas covered: In this article, we discuss three emerging targets of non-invasive neuromodulation for chronic pain: (i) a central target: prefrontal cortex stimulation; (ii) a peripheral target: vagal nerve stimulation (VNS); and (iii) a combined peripheral-central target: combination of central and peripheral neural stimulation. Expert commentary: Clinical trials' results on novel targets for chronic pain are at an earlier stage and the mechanisms involved with their combination remain unclear. An important challenge to validate new targets is to determine whether they may be equivalent or even more effective than traditional ones. In spite of the significant advance in this field, especially in refractory chronic pain, mechanistic elements are yet to be comprehended. Thus, exploring multifactorial aspects of novel brain stimulation approaches is fundamental to achieve meaningful results and further augment clinical practice.

BthTX-I from Bothrops jararacussu induces apoptosis in human breast cancer cell lines and decreases cancer stem cell subpopulation

Breast cancer is the neoplasm with both the highest incidence and mortality rate among women worldwide. Given the known snake venom cytotoxicity towards several tumor types, we evaluated the effects of BthTX-I from Bothrops jararacussu on MCF7, SKBR3, and MDAMB231 breast cancer cell lines. Methods: BthTX-I cytotoxicity was determined via MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide assay. Cell death was measured by a hypotonic fluorescent solution method, annexin-V-FITC/propidium iodide staining and by apoptotic/autophagic protein expression. Cancer stem cells (CSCs) were quantified by flow cytometry using anti-CD24-FITC and anti-CD44-APC antibodies and propidium iodide. Results: BthTX-I at 102 µg/mL induced cell death in all cell lines. The toxin induced apoptosis in MCF7, SKBR3, and MDAMB231 in a dose-dependent manner, as confirmed by the increasing number of hypodiploid nuclei. Expression of pro-caspase 3, pro-caspase 8 and Beclin-1 proteins were increased, while the level of the antiapoptotic protein Bcl-2 was diminished in MCF7 cells. BthTX-I changed the staining pattern of CSCs in MDAMB231 cells by increasing expression of CD24 receptors, which mediated cell death. Conclusions: BthTX-I induces apoptosis and autophagy in all breast cancer cell lines tested and also reduces CSCs subpopulation, which makes it a promising therapeutic alternative for breast cancer.(AU)

Assessment of oral anticoagulation control at two pharmacist-managed clinics in Brazil.

Background Warfarin remains widely used by patients with cardiovascular diseases. When using warfarin, the quality of oral anticoagulation control is a critical determinant to minimize the risk of bleeding and thromboembolic events. Pharmacist engagement in patient care is relevant towards improving the quality of warfarin therapy. Objective To assess the quality of oral anticoagulation control measured by time in therapeutic range (TTR) at two pharmacist-managed anticoagulation clinics (AC). Method This study included adults with indication of continuous warfarin use. Patients were recruited at two AC of public hospitals in Brazil (2014-2015). Anticoagulation control was assessed by TTR using the Rosendaal method. Laboratory INR values were collected for the maximum period of follow-up (2009-2015). Results A total of 554 patients were studied. The median age was 63.7 [Quartile 1 (Q1) 54.3; Quartile 3 (Q3) 73.6] years, 57.4% female. The median TTR was 64.3% [Q1 54.0%; Q3 74.0%], and 344 (61.6%) patients had TTR ≥ 60%. Conclusion Pharmacist-managed AC have achieved an adequate TTR in Brazilian patients with low socioeconomic status. Interventions include face-to-face appointments for individual patient education, warfarin-dosing adjustments and monitoring of drug interactions. Pharmacists are important to improve adherence and the quality of warfarin therapy in low- and middle income countries.

Complex chronic conditions in children and adolescents: hospitalizations in Brazil, 2013.

This article aims to estimate the extent of hospitalizations for complex chronic conditions in Brazil. Data from the Hospital Information System for 2013 were compiled according to the International Classification of Diseases 10th Revision. Hospitalization rates were estimated according to region, sex, age and disease chapter, taking into account the 2012 population as a reference, as well the percentage of highly complex procedures and mortality rates. Public hospitals treated 190,000 inpatients in 2013. The rate was highest among the population in the South of Brazil, those who were male and children under the age of one. The rate was lowest among the population in the North, females and children aged between 10 and 14years. The mean duration of hospitalization was six days, the percentage of highly complex procedures was 13.5% and the mortality rate was 1.3%. The three most common causes for hospitalizations were diseases of the respiratory system, neoplasms and diseases of the nervous system. The incidence of complex chronic conditions is 331 inwards per 100,000 children and adolescents in Brazil, with an estimate of 240,000 children and adolescents hospitalized. This panorama points to the problem as an emergent public health issue in Brazil.

Complex chronic conditions in children and adolescents: hospitalizations in Brazil, 2013 / Condições crônicas complexas em crianças e adolescents: internações no Brasil, 2013

Abstract This article aims to estimate the extent of hospitalizations for complex chronic conditions in Brazil. Data from the Hospital Information System for 2013 were compiled according to the International Classification of Diseases 10th Revision. Hospitalization rates were estimated according to region, sex, age and disease chapter, taking into account the 2012 population as a reference, as well the percentage of highly complex procedures and mortality rates. Public hospitals treated 190,000 inpatients in 2013. The rate was highest among the population in the South of Brazil, those who were male and children under the age of one. The rate was lowest among the population in the North, females and children aged between 10 and 14years. The mean duration of hospitalization was six days, the percentage of highly complex procedures was 13.5% and the mortality rate was 1.3%. The three most common causes for hospitalizations were diseases of the respiratory system, neoplasms and diseases of the nervous system. The incidence of complex chronic conditions is 331 inwards per 100,000 children and adolescents in Brazil, with an estimate of 240,000 children and adolescents hospitalized. This panorama points to the problem as an emergent public health issue in Brazil.

Resumo O objetivo deste artigo é estimar a magnitude das internações por doenças crônicas complexas no Brasil. Dados do Sistema de Informações Hospitalares referentes a 2013 foram compilados de acordo com a Classificação Internacional de Doenças 10ª revisão. Taxas de internação foram estimadas de acordo com a região, sexo, idade e doença, tendo como referência a população de 2012, bem como o percentual de procedimentos de alta complexidade e as taxas de mortalidade. Hospitais públicos tiveram 190.000 pacientes internados em 2013. A taxa foi maior entre a população do Sul do Brasil, entre homens e crianças menores de um ano de idade. A taxa foi menor entre a população do Norte, entre mulheres e crianças de 10 a 14 anos de idade. A duração média de internação foi de seis dias, a porcentagem de procedimentos de alta complexidade foi de 13,5% e a taxa de mortalidade foi de 1,3%. As três causas mais comuns para internações foram as doenças do sistema respiratório, neoplasias e doenças do sistema nervoso. A incidência de hospitalização por doenças crônicas complexas foi 331 para 100.000 crianças e adolescentes no Brasil, com uma estimativa de 240.000 crianças e adolescentes hospitalizados. Esse panorama aponta para as doenças crônicas complexas como problema emergente em saúde pública no Brasil.

Depression, anxiety, hopelessness and quality of life in users of cocaine/crack in outpatient treatment.

OBJECTIVE:: To identify symptoms of anxiety, depression, and feelings of hopelessness in patients in outpatient treatment for substance dependency and to test for correlations with various aspects of their quality of life. METHODS:: A cross-sectional study of a sample of 25 men in recuperation from substance dependency, selected by convenience. We assessed symptoms of depression (Beck Depression Inventory-II), anxiety (Beck Anxiety Inventory), hopelessness (Beck Hopelessness Scale), and quality of life (World Health Organization Quality of Life instrument-Abbreviated version [WHOQOL-Bref]), and also analyzed sociodemographic profile, substance abuse, and family history. Categorical variables were expressed as frequencies and percentages and quantitative variables as means and standard deviations or as medians and interquartile ranges. We also analyzed Spearman correlations to a 5% significance level. RESULTS:: The study revealed prevalence rates of 32% for depression, 24% for anxiety, and 12% for hopelessness, at a moderate/severe level. Correlations between Beck scales and WHOQOL-Bref were significant; but impacts differed in the four areas evaluated. CONCLUSIONS:: Overall, we observe global negative impacts on subjects' lives, affecting their psychiatric symptoms and quality of life and their relationships and occupational factors to a similar degree. The results show that the lower the scores on these scales, the better the quality of life in some areas, indicating that there is a negative correlation between psychiatric symptoms and quality of life.