ABSTRACT
BACKGROUND: Progressive disseminated histoplasmosis is a significant issue in Latin America, particularly in Brazil, contributing to high mortality rates. OBJECTIVES: Our objectives were to comprehensively describe histoplasmosis treatment with various amphotericin B (AmB) formulations, including mortality rates, adverse effects and risk factors for mortality. METHODS: This multicentre retrospective cohort study (January 2014-December 2019) evaluated medical records of patients with proven or probable histoplasmosis treated with at least two doses of AmB in seven tertiary medical centres in Brazil. We assessed risk factors associated with death during hospitalization using univariate and multivariate analyses. RESULTS: The study included 215 patients, mostly male (nâ=â158, 73%) with HIV infection (nâ=â187, 87%), and a median age of 40 years. Only 11 (5%) patients initiated treatment with liposomal amphotericin B (L-AmB). Amphotericin B deoxycholate (D-AmB) was administered to 159 (74%) patients without changes in the treatment. The overall mortality during hospitalization was 23% (50/215). Variables independently associated with mortality were use of D-AmB (OR 4.93) and hospitalization in ICU (OR 9.46). There was a high incidence of anaemia (nâ=â19, 90%), acute kidney injury (nâ=â96, 59%), hypokalaemia (nâ=â73, 55%) and infusion reactions (nâ=â44, 20%) during treatment. CONCLUSIONS: We found that D-AmB was the main formulation, which was also associated with a higher mortality rate. Lipid formulations of AmB have become more readily available in the public health system in Brazil. Further studies to evaluate the effectiveness of L-AmB will likely show improvements in the treatment outcomes for patients with disseminated histoplasmosis.
ABSTRACT
Cryptococcosis is traditionally associated with immunocompromised patients but is increasingly being identified in those without the human immunodeficiency virus (HIV) or other immunocompetent individuals. We aim to describe the characteristics, mortality, and associated variables with death among hospitalized patients with cryptococcosis in Brazil. This is the first multicenter retrospective cohort study conducted in seven public tertiary Brazilian hospitals. A total of 384 patients were included; the median age was 39 years and 283 (73.7%) were men. In all, 304 HIV-positive were hosts (79.2%), 16 (4.2%) solid organ transplant (SOT), and 64 (16.7%) non-HIV-positive/non-transplant (NHNT). Central nervous system (CNS) cryptococcosis had a significantly higher number across disease categories, with 313 cases (81.5%). A total of 271 (70.6%) patients were discharged and 113 (29.4%) died during hospitalization. In-hospital mortality among HIV-positive, SOT, and NHNT was 30.3% (92/304), 12.5% (2/16), and 29.7% (19/64), respectively. Induction therapy with conventional amphotericin B (AMB) mainly in combination with fluconazole (234; 84.2%) was the most used. Only 80 (22.3%) patients received an AMB lipid formulation: liposomal (n = 35) and lipid complex (n = 45). Most patients who died belong to the CNS cryptococcosis category (83/113; 73.4%) when compared with the others (P = .017). Multivariate analysis showed that age and disseminated cryptococcosis had a higher risk of death (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.05; P = .008 and OR, 1.84; 95% CI, 1.01-3.53; P = .048, respectively). Understanding the epidemiology of cryptococcosis in our settings will help to recognize the burden and causes of mortality and identify strategies to improve this scenario.
This multicenter cohort study included 384 hospitalized individuals with cryptococcosis in Brazil. Most individuals were men (74%), HIV-positive (79%), had central nervous system involvement (82%), and received conventional amphotericin plus fluconazole (84%). In-hospital mortality was high (29%).
Subject(s)
Cryptococcosis , Organ Transplantation , Male , Animals , Humans , Female , Brazil/epidemiology , Retrospective Studies , Cryptococcosis/drug therapy , Cryptococcosis/epidemiology , Cryptococcosis/complications , Cryptococcosis/veterinary , Organ Transplantation/adverse effects , Organ Transplantation/veterinary , Amphotericin B/therapeutic use , Lipids/therapeutic use , Antifungal Agents/therapeutic useABSTRACT
BACKGROUND AND OBJECTIVE: Amphotericin B deoxycholate (AMB-D) remains an antifungal agent with great therapeutic value in pediatric patients. The currrent consensus is that its use in neonates is safer than in older children. However, childhood presents different periods of development that deserve to be evaluated more precisely. Our goal was to assess the usage profile of AMB-D in stratified pediatric age groups, adapted according to the National Institute of Child Health and Human Development classification. METHODS: This retrospective cross-sectional observational study was conducted at a Brazilian tertiary children's hospital between January 2014 and December 2019. Data of patients who received at least two doses of intravenous AMB-D while hospitalized were extracted from electronic health files. Information on patient demographics, underlying diseases and comorbidities, laboratory examinations, fungal infection diagnosis, and AMB-D use were gathered following specific criteria. Nonparametric tests were applied, such as the chi-square test to compare proportions and Fisher's exact test to assess the association between categorical variables or contingency tables. RESULTS: One hundred and twenty-seven (127) medical records were stratified as preterm neonatal (birth <37 weeks postmenstrual age), term neonatal (birth-27 days), infants (28 days-12 months), toddlers (13 months-2 years), early childhood (3-5 years), middle childhood (6-11 years), and early adolescence (12-18 years). The criteria for the indication of AMB-D followed empirical use as the main indication (n = 74; 58.26%), proven and probable fungal infection (n = 39; 30.71%), and medical suspicion (n = 14; 11.02%). Candida spp. was the main etiologic agent isolated in cultures, with the highest frequency of C. albicans (n = 18; 40%), followed by Candida parapsilosis (n = 14; 31.11%), and Candida tropicalis (n = 6; 13.33%). Very few acute infusion-related adverse effects were observed during the administration of AMB-D in pediatric patients. We found an unfavorable impact of AMB-D use in patients from 13 months of age onwards suggesting this group as a turning point for a greater chance of adverse events, and not soon after the neonatal period. CONCLUSIONS: Clinical or observational studies based on age stratification are essential to accurately elucidate whether potentially toxic drugs can be used safely in the pediatric population. Our search for a turning point was shown to contribute to the accuracy of the study, as it provided data on the impact of D-AMB in specific pediatric age groups.
Subject(s)
Amphotericin B , Mycoses , Adolescent , Amphotericin B/adverse effects , Antifungal Agents/adverse effects , Child , Child, Preschool , Cross-Sectional Studies , Humans , Infant , Infant, Newborn , Mycoses/chemically induced , Mycoses/drug therapy , Retrospective StudiesABSTRACT
Sertraline hydrochloride is a first-line antidepressant with potential antineoplastic properties because of its structural similarity with other drugs capable to inhibit the translation-controlled tumor protein (TCTP), a biomolecule involved in cell proliferation. Recent studies suggest it could be repositioned for cancer treatment. In this review, we systematically map the findings that repurpose sertraline as an antitumoral agent, including the mechanisms of action that support this hypotesis. From experimental in vivo and in vitro tumor models of thirteen different types of neoplasms, three mechanisms of action are proposed: apoptosis, autophagy, and drug synergism. The antidepressant is able to inhibit TCTP, modulate chemotherapeutical resistance and exhibit proper cytotoxicity, resulting in reduced cell counting (in vitro) and shrunken tumor masses (in vivo). A mathematical equation determined possible doses to be used in human beings, supporting that sertraline could be explored in clinical trials as a TCTP-inhibitor.
ABSTRACT
Introduced in the late 1950s, polyenes represent the oldest family of antifungal drugs. The discovery of amphotericin B and its therapeutic uses is considered one of the most important scientific milestones of the twentieth century . Despite its toxic potential, it remains useful in the treatment of invasive fungal diseases owing to its broad spectrum of activity, low resistance rate, and excellent clinical and pharmacological action. The well-reported and defined toxicity of the conventional drug has meant that much attention has been paid to the development of new products that could minimize this effect. As a result, lipid-based formulations of amphotericin B have emerged and, even keeping the active principle in common, present distinct characteristics that may influence therapeutic results. This study presents an overview of the pharmacological properties of the different formulations for systemic use of amphotericin B available for the treatment of invasive fungal infections, highlighting the characteristics related to their chemical, pharmacokinetic structures, drug-target interactions, stability, and others, and points out the most relevant aspects for clinical practice.
ABSTRACT
A insuficiência renal crônica compromete as funções fisiológicas dos rins, e leva o paciente à diálise como terapia; contudo, essa condição gera suscetibilidade à desnutrição. O objetivo deste estudo foi descrever o perfil epidemiológico e nutricional dos pacientes em hemodiálise e compará-los em relação à doença renal de base. É estudo retrospectivo, descritivo e transversal. Foram coletados dados demográficos, clínicos, antropométricos e laboratoriais de pacientes que estiveram em diálise. Foram incluídos pacientes com insuficiência renal crônica e excluídos menores de 18 anos, com dados insuficientes ou com comorbidades que alterassem processo nutricional. Em conclusão, observaram-se 4 principais causas para doença renal crônica: hipertensão arterial crônica, doença renal policística, doença renal terminal e nefropatia diabética, que foi a mais prevalente, com pouca evidência de desnutrição
Chronic renal failure compromises the physiological functions of the kidneys and leads the patient to dialysis as a therapy; however, this condition generates susceptibility to malnutrition. The aim of this study was to describe the epidemiological and nutritional profile of patients on hemodialysis and to compare them in relation to the underlying renal disease. It is a retrospective, descriptive and cross-sectional study. Demographic, clinical, anthropometric and laboratory data were collected from patients who were on dialysis. Patients with chronic renal failure were included and those under 18 years of age, with insufficient data or with comorbidities that altered the nutritional process, were excluded. In conclusion, 4 main causes of chronic kidney disease were observed: chronic arterial hypertension, polycystic kidney disease, end-stage renal disease and diabetic nephropathy, which was the most prevalent, with little evidence of malnutrition
Subject(s)
Humans , Health Profile , Cross-Sectional Studies , Dialysis , Renal Insufficiency, Chronic , Kidney , Deficiency Diseases , MalnutritionABSTRACT
A insuficiência renal crônica compromete as funções fisiológicas dos rins, e leva o paciente à diálise como terapia; contudo, essa condição gera suscetibilidade àdesnutrição. O objetivo deste estudo foi descrever o perfil epidemiológico e nutricional dos pacientes em hemodiálise e compará-los em relação à doença renal de base. Éestudo retrospectivo, descritivo e transversal. Foram coletados dados demográficos, clínicos, antropométricos e laboratoriais de pacientes que estiveram em diálise. Foram incluídos pacientes com insuficiência renal crônica e excluídos menores de 18 anos, com dados insuficientes ou com comorbidades que alterassem processo nutricional. Em conclusão, observaram-se 4 principais causas para doença renal crônica: hipertensão arterial crônica, doença renal policística, doença renal terminal e nefropatia diabética, que foi a mais prevalente, com pouca evidência de desnutrição
Chronic renal failure compromises the physiological functions of the kidneys and leads the patient to dialysis as a therapy; however, this condition generates susceptibility to malnutrition. The aim of this study was to describe the epidemiological and nutritional profile of patients on hemodialysis and to compare them in relation to the underlying renal disease. It is a retrospective, descriptive and cross-sectional study. Demographic, clinical, anthropometric and laboratory data were collected from patients who were on dialysis. Patients with chronic renal failure were included and those under 18 years of age, with insufficient data or with comorbidities that altered the nutritional process, were excluded. In conclusion, 4 main causes of chronic kidney disease were observed: chronic arterial hypertension, polycystic kidney disease, end-stage renal disease and diabetic nephropathy, which was the most prevalent, with little evidence of malnutrition.
Subject(s)
Humans , Adult , Renal Dialysis , Malnutrition , Renal Insufficiency, Chronic , EpidemiologyABSTRACT
Racional: A insuficiência renal crônica compromete as funções fisiológicas dos rins, e leva o paciente a diálise como terapia; contudo, essa condição gera suscetibilidade à desnutrição. Objetivo: Descrever o perfil epidemiológico e nutricional dos pacientes em hemodiálise e compará-los em relação à doença renal de base. Métodos: Trata-se de estudo retrospectivo, descritivo e transversal, realizado em hospital terciário. Foram coletados dados demográficos, clínicos, antropométricos e laboratoriais de pacientes que estiveram em diálise. Foram incluídos pacientes com insuficiência renal crônica e excluídos menores de 18 anos, com dados insuficientes ou com comorbidades que alterassem processo nutricional. Resultados: Observaram-se 4 principais causas para doença renal crônica: hipertensão arterial crônica, doença renal policística, doença renal terminal e nefropatia diabética, que foi a mais prevalente. Conclusão: O perfil foi: feminino, com 60 anos de idade e que fazia tratamento dialítico há 2,6 anos, com sobrepeso, anêmica e sem depleção. Entre os grupos houve diferenças estatisticamente significativas quanto aos fatores demográficos, mas como tinham quadro dialítico recente, havia poucas evidências de desnutrição.
Background: Chronic renal failure compromises the physiological functions of the kidneys, and leads the patient to dialysis as a therapy, however, this condition generates a susceptibility to malnutrition. Objective: To describe the epidemiological and nutritional profile of hemodialysis patients and compare them in relation to the underlying renal disease. Methods: This is a retrospective, descriptive and cross-sectional study carried out in a tertiary hospital. Demographic, clinical, anthropometric and laboratory data were collected from patients who were on dialysis. Patients with chronic renal failure were included and those under 18 years of age, with insufficient data or with comorbidities that altered the nutritional process, were excluded. Results: Four main causes of chronic kidney disease were observed: chronic arterial hypertension, polycystic kidney disease, end-stage renal disease and diabetic nephropathy, which was the most prevalent. Conclusion: The profile was: female, 60 years old and undergoing dialysis for 2.6 years, overweight, anemic and without depletion. There were statistically significant differences between the groups regarding demographic factors, but as they had recent dialysis, there was little evidence of malnutrition.
ABSTRACT
OBJECTIVE: This study aimed at assessing the adequacy of thromboprophylaxis in a high complexity hospital in Vitória-ES, analysing the possible predictors of inadequate prescriptions and/or procedures. METHODS: A cross-sectional study was carried out through prompt-book analysis. The included patients were hospitalized in 2007 and had their Venous thromboembolism (VTE) risk stratified using the 8th Edition of the American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines. The thromboprophylaxis adequacy was determined through a comparison between the adopted prescriptions and/or procedures and the guideline recommendations. EpiInfo 3.4.3 and SPSS 13.0 were the software applications used. RESULTS: In 47% of the patients the thromboprophylaxis was inadequate, being the non-prescription of the indicated medication the major reason (33%). There was no statistically significant difference in inadequate tromboprophylaxis rate between clinical and surgical patients, or ward and Intensive care unit (ICU) ones. An inverse relationship was observed between the inadequate tromboprophylaxis rate and the number of VTE risk factors presented by the patients, as well as their age, and the length of hospital stay (p < 0.05). CONCLUSION: The results show alarming levels of thromboprophylaxis inadequacy, inacceptable in these times of well-established published guidelines. Therefore, a continuing education program should be implanted for all the assistance team.
Subject(s)
Venous Thromboembolism/prevention & control , Chemoprevention/standards , Cross-Sectional Studies , Female , Hospitals , Humans , Male , Middle AgedABSTRACT
OBJETIVO: Avaliar a adequação da tromboprofilaxia em um hospital de grande porte em Vitória-ES, analisando possíveis preditores de aplicação de conduta inadequada. MÉTODOS: Trata-se de um estudo de corte transversal realizado através de análise de prontuários. Os pacientes analisados estiveram internados no hospital durante o ano de 2007, e tiveram seu risco de tromboembolismo venoso estratificado segundo a 8ª Diretriz para Profilaxia do TEV do American College of Chest Physicians (8º ACCP). A adequação da tromboprofilaxia foi determinada de acordo com a concordância entre a conduta instituída e a conduta preconizada nas diretrizes. Foram utilizados os softwares EpiInfo 3.4.3 e SPSS 13.0. RESULTADOS: Em 47 por cento dos pacientes a tromboprofilaxia foi inadequada, sendo a não prescrição da medicação indicada o principal motivo (33 por cento). Não houve diferença estatisticamente significante quando comparadas as taxas de inadequação da tromboprofilaxia entre pacientes clínicos e cirúrgicos, ou, entre pacientes internados em enfermaria e UTI. O número de fatores de risco para TEV foi inversamente proporcional à taxa de inadequação (p<0,05), assim como a faixa etária do paciente e a duração da internação (p<0,05). CONCLUSÃO: Os resultados obtidos apontam para níveis alarmantes de inadequação da tromboprofilaxia, o que evidencia a necessidade de programas de educação continuada no assunto para toda a equipe assistente.
OBJECTIVE: This study aimed at assessing the adequacy of thromboprophylaxis in a high complexity hospital in Vitória - ES, analysing the possible predictors of inadequate prescriptions and/or procedures. METHODS: A cross-sectional study was carried out through prompt-book analysis. The included patients were hospitalized in 2007 and had their Venous thromboembolism (VTE) risk stratified using the 8th Edition of the American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines. The thromboprophylaxis adequacy was determined through a comparison between the adopted prescriptions and/or procedures and the guideline recommendations. EpiInfo 3.4.3 and SPSS 13.0 were the software applications used. RESULTS: In 47 percent of the patients the thromboprophylaxis was inadequate, being the non-prescription of the indicated medication the major reason (33 percent). There was no statistically significant difference in inadequate tromboprophylaxis rate between clinical and surgical patients, or ward and Intensive care unit (ICU) ones. An inverse relationship was observed between the inadequate tromboprophylaxis rate and the number of VTE risk factors presented by the patients, as well as their age, and the length of hospital stay (p < 0,05). CONCLUSION: The results show alarming levels of thromboprophylaxis inadequacy, inacceptable in these times of well-established published guidelines. Therefore, a continuing education program should be implanted for all the assistance team.
Subject(s)
Female , Humans , Male , Middle Aged , Venous Thromboembolism/prevention & control , Cross-Sectional Studies , Chemoprevention/standards , HospitalsABSTRACT
Os autores relatam a experiência com a colecistectomia laparoscópica em 26 animais de laboratório, utilizando o porco como modelo experimental para treinamento da técnica. Nenhum dos profissionais tinha qualquer experiência prática em cirurgia laparoscópica e não se contava com um orientador experimentado na atividade. A intubação orotraqueal foi possível realizar em todos os animais e as condutas anestésicas iniciais foram modificadas por causa da hipertermia, maior consumo de anestésico e retardo na recuperação. Inicialmente dois animais morreram na operação em função dessas dificuldades. A anestesia era orientada pelo próprio grupo. Houve extravasamento biliar em quatro animais, em dois, decorrente de perfuração da vesícula e, em outros dois devido a desprendimento dos clips do cístico. As intercorrências de técnica deram-se mais por inexperiência do grupo e foram contornadas no decorrer do trabalho. Achou-se que os objetivos propostos para o adestramento foram atingidos individual e coletivamente. As cirurgias foram concluídas em todos os animais e não houve óbitos no pós-operatório. Observou-se um custo mínimo do treinamento para cada operação (colecistectomia laparoscópica), em torno de US$ 118,00 (cento e dezoito dólares americanos), relativos aos gastos por operação, não se incluindo os equipamentos permanentes