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1.
Acta Trop ; 242: 106920, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37028584

ABSTRACT

Benznidazole and nifurtimox are the drugs currently used for the treatment of Chagas disease, however its side effects may affect patient adherence. In the search for new alternative therapies, we previously identified isotretinoin (ISO), an FDA-approved drug widely used for the treatment of severe acne through a drug repurposing strategy. ISO shows a strong activity against Trypanosoma cruzi parasites in the nanomolar range, and its mechanism of action is through the inhibition of T. cruzi polyamine and amino acid transporters from the Amino Acid/Auxin Permeases (AAAP) family. In this work, a murine model of chronic Chagas disease (C57BL/6 J mice), intraperitoneally infected with T. cruzi Nicaragua isolate (DTU TcI), were treated with different oral administrations of ISO: daily doses of 5 mg/kg/day for 30 days and weekly doses of 10 mg/kg during 13 weeks. The efficacy of the treatments was evaluated by monitoring blood parasitemia by qPCR, anti-T. cruzi antibodies by ELISA, and cardiac abnormalities by electrocardiography. No parasites were detected in blood after any of the ISO treatments. The electrocardiographic study of the untreated chronic mice showed a significant decrease in heart rate, while in the treated mice this negative chronotropic effect was not observed. Atrioventricular nodal conduction time in untreated mice was significantly longer than in treated animals. Mice treated even with ISO 10 mg/kg dose every 7 days, showed a significant reduction in anti-T. cruzi IgG levels. In conclusion, the intermittent administration of ISO 10 mg/kg would improve myocardial compromise during the chronic stage.


Subject(s)
Chagas Disease , Nitroimidazoles , Trypanocidal Agents , Trypanosoma cruzi , Animals , Mice , Isotretinoin/pharmacology , Isotretinoin/therapeutic use , Pharmaceutical Preparations , Disease Models, Animal , Trypanocidal Agents/therapeutic use , Mice, Inbred C57BL , Chagas Disease/parasitology , Nitroimidazoles/therapeutic use
2.
Trop Med Int Health ; 28(1): 2-16, 2023 01.
Article in English | MEDLINE | ID: mdl-36420767

ABSTRACT

OBJECTIVES: To determine the comparative efficacy and safety of a fixed dose of benznidazole (BZN) with an adjusted-dose for Trypanosoma cruzi-seropositive adults without cardiomyopathy. METHODS: We conducted a systematic review and individual participant data (IPD) meta-analysis following Cochrane methods, and the PRISMA-IPD statement for reporting. Randomised controlled trials (RCTs) allocating participants to fixed or adjusted doses of BZN for T. cruzi-seropositive adults without cardiomyopathy were included. We searched (December 2021) Cochrane, MEDLINE, EMBASE, LILACS and trial registries and contacted Chagas experts. Selection, data extraction, risk of bias assessment using the Cochrane tool, and a GRADE summary of finding tables were performed independently by pairs of reviewers. We conducted a random-effects IPD meta-analysis using the one-stage strategy, or, if that was impossible, the two-stage strategy. RESULTS: Five RCTs (1198 patients) were included, none directly comparing fixed with adjusted doses of BZN. Compared to placebo, BZN therapy was strongly associated with negative qPCR and sustainable parasitological clearance regardless of the type of dose and subgroup analysed. For negative qPCR, the fixed/adjusted rate of odds ratios (RORF/A ) was 8.83 (95% CI 1.02-76.48); for sustained parasitological clearance, it was 4.60 (95% CI 0.40-52.51), probably indicating at least non-inferior effect of fixed doses, with no statistically significant interactions by scheme for global and most subgroup estimations. The RORF/A for treatment interruption due to adverse events was 0.44 (95% CI 0.14-1.38), probably indicating no worse tolerance of fixed doses. CONCLUSIONS: We found no direct comparison between fixed and adjusted doses of BZN. However, fixed doses versus placebo are probably not inferior to weight-adjusted doses of BZN versus placebo in terms of parasitological efficacy and safety. Network IPD meta-analysis, through indirect comparisons, may well provide the best possible answers in the near future. REGISTRATION: The study protocol was registered in PROSPERO (CRD42019120905).


Subject(s)
Cardiomyopathies , Chagas Disease , Trypanosoma cruzi , Adult , Humans , Evidence Gaps , Chagas Disease/drug therapy
3.
Estima (Online) ; 20(1): e2022, Jan-Dec. 2022.
Article in English, Portuguese | LILACS, BDENF - Nursing | ID: biblio-1425088

ABSTRACT

Objetivo:Relatar a experiência da utilização de sala de escape como estratégia educacional e de sensibilização para prevenção de lesão por pressão no contexto hospitalar. Métodos: Trata-se de um relato de experiência decorrente de atividade desenvolvida em novembro de 2021, com profissionais da equipe multiprofissional de um hospital filantrópico de grande porte localizado na região metropolitana de São Paulo (SP), Brasil. Resultados: Realizou-se o jogo como estratégia educacional associado a outras iniciativas sobre a temática, durante a campanha anual de prevenção de lesão por pressão. Participaram da atividade 82 profissionais, entre eles, enfermeiros, técnicos em enfermagem, nutricionistas e fisioterapeutas. O total de 57 participantes (69,5%) conseguiram desvendar os enigmas propostos e sair da sala de escape no tempo determinado. A avaliação de reação demonstrou alto nível de satisfação com a atividade, além de inúmeros elogios sobre a metodologia escolhida, bem como a criatividade com que o tema foi abordado e desenvolvido. Conclusão: A utilização de uma metodologia baseada na interação dos participantes, como as salas de escape, associada a outras atividades educativas parece ser interessante para promover a aprendizagem e a sensibilização na temática prevenção de lesão por pressão.


Objective:To report the experience of using the escape room as an educational and awareness strategy for the prevention of pressure injuries in the hospital context. Methods: This is an experience report about an activity developed in November 2021, with professionals from the multidisciplinary team of a large philanthropic hospital located in the metropolitan region of São Paulo (SP), Brazil. Results: The game was played as an educational strategy associated with other initiatives on the issue, during the annual pressure injury prevention campaign. Eighty-two professionals participated in the activity, including nurses, nursing technicians, nutritionists, and physiotherapists. A total of 57 participants (69.5%) managed to unravel the proposed puzzles and leave the escape room in the proposed time. The reaction evaluation showed a high level of satisfaction with the activity, in addition to numerous compliments on the chosen methodology, as well as the creativity in which the topic was approached and developed. Conclusion: The use of a methodology based on the interaction of the participants, such as escape rooms, associated with other educational activities seems to be interesting to promote learning and awareness about pressure injury prevention.


Objetivo:Reportar la experiencia del uso del escape room como estrategia educativa y de concientización para la prevención de lesiones por presión en el contexto hospitalario. Métodos: Este es un relato de experiencia, resultado de una actividad desarrollada en noviembre de 2021, con profesionales del equipo multidisciplinario de un gran hospital filantrópico, ubicado en la región metropolitana de São Paulo, Brasil. Resultados: El juego se realizó como una estrategia educativa asociada a otras iniciativas en el tema, durante la campaña anual de prevención de lesiones por presión. Participaron de la actividad 82 profesionales, entre enfermeros, técnicos de enfermería, nutricionistas y fisioterapeutas. Un total de 57 participantes (69,5%) consiguieron desentrañar los puzzles propuestos y salir del escape room en el tiempo propuesto. La evaluación de la reacción mostró un alto nivel de satisfacción con la actividad, además de numerosos elogios sobre la metodología elegida, así como la creatividad con la que se abordó y desarrolló el tema. Conclusión: El uso de una metodología basada en la interacción de los participantes, como las salas de escape, asociada a otras actividades educativas, parece interesante para promover el aprendizaje y la sensibilización en el tema de prevención de lesiones por presión.


Subject(s)
Health Education , Pressure Ulcer , Interdisciplinary Placement , Enterostomal Therapy
4.
Front Cell Infect Microbiol ; 11: 785166, 2021.
Article in English | MEDLINE | ID: mdl-35360222

ABSTRACT

Chronic Chagas disease cardiomyopathy (CCC) is the most important clinical manifestation of infection with Trypanosma cruzi (T. cruzi) due to its frequency and effects on morbidity and mortality. Peripheral blood mononuclear cells (PBMC) infiltrate the tissue and differentiate into inflammatory macrophages. Advances in pathophysiology show that myeloid cell subpopulations contribute to cardiac homeostasis, emerging as possible therapeutic targets. We previously demonstrated that fenofibrate, PPARα agonist, controls inflammation, prevents fibrosis and improves cardiac function in a murine infection model. In this work we investigated the spontaneous release of inflammatory cytokines and chemokines, changes in the frequencies of monocyte subsets, and fenofibrate effects on PBMC of seropositive patients with different clinical stages of Chagas disease. The results show that PBMC from Chagas disease patients display higher levels of IL-12, TGF-ß, IL-6, MCP1, and CCR2 than cells from uninfected individuals (HI), irrespectively of the clinical stage, asymptomatic (Asy) or with Chagas heart disease (CHD). Fenofibrate reduces the levels of pro-inflammatory mediators and CCR2 in both Asy and CHD patients. We found that CHD patients display a significantly higher percentage of classical monocytes in comparison with Asy patients and HI. Besides, Asy patients have a significantly higher percentage of non-classical monocytes than CHD patients or HI. However, no difference in the intermediate monocyte subpopulation was found between groups. Moreover, monocytes from Asy or CHD patients exhibit different responses upon stimulation in vitro with T. cruzi lysates and fenofibrate treatment. Stimulation with T. cruzi significantly increases the percentage of classical monocytes in the Asy group whereas the percentage of intermediate monocytes decreases. Besides, there are no changes in their frequencies in CHD or HI. Notably, stimulation with T. cruzi did not modify the frequency of the non-classical monocytes subpopulation in any of the groups studied. Moreover, fenofibrate treatment of T. cruzi-stimulated cells, increased the frequency of the non-classical subpopulation in Asy patients. Interestingly, fenofibrate restores CCR2 levels but does not modify HLA-DR expression in any groups. In conclusion, our results emphasize a potential role for fenofibrate as a modulator of monocyte subpopulations towards an anti-inflammatory and healing profile in different stages of chronic Chagas disease.


Subject(s)
Chagas Disease , Fenofibrate , Animals , Cytokines/metabolism , Fenofibrate/metabolism , Fenofibrate/pharmacology , Fenofibrate/therapeutic use , Humans , Leukocytes, Mononuclear/metabolism , Mice , Monocytes/metabolism
5.
Echocardiography ; 38(1): 39-46, 2021 01.
Article in English | MEDLINE | ID: mdl-33140890

ABSTRACT

BACKGROUND: Chagas disease is one of the most common diseases in Latin-America, and cardiac involvement is a significant cause of death. Assessment of myocardial strain may detect early myocardial damage. OBJECTIVES: To determine differences in longitudinal strain using speckle tracking to assess regional and global left ventricular function in patients with the indeterminate form of Chagas disease, in comparison with a control group. METHODS: This is a retrospective matched case-control study, conducted in a single center. We evaluated 45 adult patients with Chagas disease, diagnosed with 2 serological methods, without evidence of cardiac involvement, who were compared with 45 healthy control subjects, who were sex- and age-matched. All patients underwent Doppler echocardiography and longitudinal strain with speckle tracking. RESULTS: Median age was 59 years, and 60% were female. Echocardiographic parameters were similar in patients with Chagas and control subjects. In patients with Chagas, global strain differed significantly from that of control subjects (-17 vs -20.3, P < .001). Segmental strain showed 7 abnormal segments in patients with Chagas (P < .05). CONCLUSIONS: In patients with the indeterminate form of Chagas disease, global and segmental longitudinal peak systolic strain is reduced compared with healthy subjects, thus suggesting that it could be a sensitive technique to detect early myocardial damage. These findings could provide useful information regarding the pathophysiology of cardiac involvement and understand whether they might have prognostic usefulness or help develop strategies to modify the course and prognosis of patients with Chagas disease. A longitudinal prospective study would be necessary to validate our findings.


Subject(s)
Chagas Cardiomyopathy , Chagas Disease , Ventricular Dysfunction, Left , Adult , Case-Control Studies , Chagas Cardiomyopathy/diagnostic imaging , Chagas Disease/complications , Chagas Disease/diagnostic imaging , Echocardiography , Female , Humans , Middle Aged , Prospective Studies , Retrospective Studies
6.
PLoS Negl Trop Dis ; 14(8): e0008529, 2020 08.
Article in English | MEDLINE | ID: mdl-32804966

ABSTRACT

Chagas disease is a neglected disease that remains a public health threat, particularly in Latin America. The most important treatment options are nitroimidazole derivatives, such as nifurtimox and benznidazole (BZN). Some studies suggest that for adults seropositive to T. cruzi but without clinically evident chronic Chagas cardiomyopathy (CCC), a simple fixed-dose scheme of BZN could be equivalent to a weight-adjusted dose. We compared the efficacy and safety of a fixed dose of BZN with an adjusted dose for T. cruzi seropositive adults without CCC. We used the Cochrane methods, and reported according to the PRISMA statement. We included randomized controlled trials (RCTs) allocating participants to fixed and/or adjusted doses of BZN for T. cruzi seropositive adults without CCC. We searched (December 2019) Cochrane, MEDLINE, EMBASE, LILACS, Clinicaltrials.gov, and International Clinical Trials Registry Platform (ICTRP), and contacted Chagas experts. Selection, data extraction, and risk of bias assessment, using the Cochrane tool, were performed independently by pairs of reviewers. Discrepancies were solved by consensus within the team. Primary outcomes were parasite-related outcomes and efficacy or patient-related safety outcomes. We conducted a meta-analysis using RevMan 5.3 software and used GRADE summary of finding tables to present the certainty of evidence by outcome. We identified 655 records through our search strategy and 10 studies (four of them ongoing) met our inclusion criteria. We did not find any study directly comparing fixed vs adjusted doses of BZN, however, some outcomes allowed subgroup comparisons between fixed and adjusted doses of BZN against placebo. Moderate-certainty evidence suggests no important subgroup differences for positive PCR at one year and for three safety outcomes (drug discontinuation, peripheral neuropathy, and mild rash). The same effect was observed for any serious adverse events (low-certainty evidence). All subgroups showed similar effects (I2 0% for all these subgroup comparisons but 32% for peripheral neuropathy), supporting the equivalence of BZN schemes. We conclude that there is no direct evidence comparing fixed and adjusted doses of BZN. Based on low to very low certainty of evidence for critical clinical outcomes and moderate certainty of evidence for important outcomes, fixed and adjusted doses may be equivalent in terms of safety and efficacy. An individual patient data network meta-analysis could better address this issue.


Subject(s)
Cardiomyopathies , Chagas Disease/drug therapy , Nitroimidazoles/administration & dosage , Nitroimidazoles/therapeutic use , Adult , Databases, Factual , Humans , Nifurtimox/therapeutic use , Patient Safety , Randomized Controlled Trials as Topic , Treatment Outcome , Triazoles/therapeutic use , Trypanosoma cruzi/drug effects
7.
Echocardiography ; 37(8): 1205-1212, 2020 08.
Article in English | MEDLINE | ID: mdl-32686870

ABSTRACT

INTRODUCTION: Chagas disease (ChD) is one of the main parasitic diseases in Latin-America. Its heart involvement is the most important cause of death. The aim of this study is to evaluate if Doppler Tissue Imaging (DTI) may have a predictive value for later events in subjects with chronic ChD. METHODS: we analyses DTI variables of 543 patients with chronic ChD for the evaluation of predicting factors of events. Major adverse cardiovascular events (MACE) were considered as stroke, heart failure resistant to treatment, sustained ventricular tachycardia, implantable cardioverter-defibrillator, sudden death, and cardiovascular death. The following findings were also included in total evens: heart failure, bradycardia, ventricular arrhythmia, new conduction system abnormalities, and new echocardiographic abnormalities. Multivariate analysis with logistic regression was used in order to assess the Doppler and DTI parameters predicting events. Variables with a P-value ≤ .5 in the univariate analysis were included in the multivariate analysis. RESULTS: In patients with chronic ChD, the analysis of DTI parameters showed that S' wave and E' wave of the lateral wall of the left ventricle were significant predictors of MACE (OR: 0.83; 95% CI: 0.71-0.96; P-value: .015 and OR: 0.80; 95% CI: 0.66-0.98; P-value: .031, respectively). CONCLUSIONS: This study found that patients with chronic ChD who had events showed significantly lower parameters in the DTI. What is more, this study showed that even lower DTI parameters are significant predictors of events.


Subject(s)
Chagas Disease , Heart Failure , Chagas Disease/complications , Chagas Disease/diagnostic imaging , Echocardiography , Heart Ventricles , Humans , Ultrasonography, Doppler
8.
Rev Soc Bras Med Trop ; 53: e20190457, 2020.
Article in English | MEDLINE | ID: mdl-32130325

ABSTRACT

INTRODUCTION: Chagas disease is one of the most common diseases in Latin America and heart involvement is the main cause of death. This study aimed to determine differences in tissue Doppler imaging (TDI) parameters in the assessment left and right ventricular function in patients with the indeterminate form of Chagas disease compared to those in healthy controls. METHODS: We compared 194 patients with the indeterminate form of Chagas disease to 72 age-matched healthy individuals. We considered p-values <0.05 to be statistically significant. RESULTS: TDI analysis of the right ventricular (RV) showed lengthened isovolumic relaxation time (IRT) and higher RV index of myocardial performance (RIMP) and left ventricle (LV) index of myocardial performance (LIMP) in the Chagas group than in the control group, indicating RV and LV systolic and diastolic myocardial damage. TDI analysis of the myocardial velocities of the interventricular septum and the lateral wall of the LV also showed a systolic and diastolic myocardial damage. CONCLUSIONS: The study results demonstrated early LV systolic and diastolic myocardial damage in the RV and LV in patients with the indeterminate form of Chagas disease by TDI. These early findings of RV and LV dysfunction may help identify patients who will progress to heart failure during the disease course. TDI should be included in initial patient evaluations because it allows adequate follow-up and treatment.


Subject(s)
Chagas Disease/physiopathology , Heart/physiopathology , Ventricular Dysfunction, Left/physiopathology , Adult , Case-Control Studies , Chagas Disease/diagnostic imaging , Early Diagnosis , Echocardiography , Echocardiography, Doppler , Female , Heart/diagnostic imaging , Humans , Male , Middle Aged , Observer Variation , Ventricular Dysfunction, Left/diagnostic imaging
9.
Rev. Soc. Bras. Med. Trop ; 53: e20190457, 2020. tab, graf
Article in English | LILACS | ID: biblio-1092227

ABSTRACT

Abstract INTRODUCTION: Chagas disease is one of the most common diseases in Latin America and heart involvement is the main cause of death. This study aimed to determine differences in tissue Doppler imaging (TDI) parameters in the assessment left and right ventricular function in patients with the indeterminate form of Chagas disease compared to those in healthy controls. METHODS: We compared 194 patients with the indeterminate form of Chagas disease to 72 age-matched healthy individuals. We considered p-values <0.05 to be statistically significant. RESULTS: TDI analysis of the right ventricular (RV) showed lengthened isovolumic relaxation time (IRT) and higher RV index of myocardial performance (RIMP) and left ventricle (LV) index of myocardial performance (LIMP) in the Chagas group than in the control group, indicating RV and LV systolic and diastolic myocardial damage. TDI analysis of the myocardial velocities of the interventricular septum and the lateral wall of the LV also showed a systolic and diastolic myocardial damage. CONCLUSIONS: The study results demonstrated early LV systolic and diastolic myocardial damage in the RV and LV in patients with the indeterminate form of Chagas disease by TDI. These early findings of RV and LV dysfunction may help identify patients who will progress to heart failure during the disease course. TDI should be included in initial patient evaluations because it allows adequate follow-up and treatment.


Subject(s)
Humans , Male , Female , Adult , Chagas Disease/physiopathology , Ventricular Dysfunction, Left/physiopathology , Heart/physiopathology , Echocardiography , Echocardiography, Doppler , Case-Control Studies , Observer Variation , Chagas Disease/diagnostic imaging , Ventricular Dysfunction, Left/diagnostic imaging , Early Diagnosis , Heart/diagnostic imaging , Middle Aged
10.
Trials ; 20(1): 516, 2019 Aug 20.
Article in English | MEDLINE | ID: mdl-31429793

ABSTRACT

Following publication of the original article [1], the authors notified us of a few requested editions that were not implemented adequately during proofing. The publisher apologizes for the inconvenience caused to our authors and readers.

11.
Trials ; 20(1): 431, 2019 Jul 15.
Article in English | MEDLINE | ID: mdl-31307503

ABSTRACT

BACKGROUND: Either benznidazole (BZN) or nifurtimox (NFX) is recommended as equivalent to treat Trypanosoma cruzi infection. Nonetheless, supportive data from randomised trials is limited to individuals treated with BZN in southern cone countries of Latin America. METHODS: The goal of this randomised, concealed, blind, parallel-group trial is to inform the trypanocidal efficacy and safety of NFX and its equivalence to BZN among individuals with T. cruzi positive serology (TC+). Eligible individuals are TC+, 20-65 years old, with no apparent symptoms/signs or uncontrolled risk factors for cardiomyopathy and at negligible risk of re-infection. Consenting individuals (adherent to a 10-day placebo run-in phase) receive a 120-day BID blinded treatment with NFX, BZN or matching placebo (2:2:1 ratio). The four active medication arms include (1) a randomly allocated sequence of 60-day, conventional-dose (60CD) regimes (BZN 300 mg/day or NFX 480 mg/day, ratio 1:1), followed or preceded by a 60-day placebo treatment, or (2) 120-day half-dose (120HD) regimes (BZN 150 mg/day or NFX 240 mg/day, ratio 1:1). The primary efficacy outcome is the proportion of participants testing positive at least once for up to three polymerase chain reaction (PCR) assays (1 + PCR) 12-18 months after randomisation. A composite safety outcome includes moderate to severe adverse reactions, consistent blood marker abnormalities or treatment abandons. The trial outside Colombia (expected to recruit at least 60% of participants) is pragmatic; it may be open-label and not include all treatment groups, but it must adhere to the randomisation and data administration system and guarantee a blinded efficacy outcome evaluation. Our main comparisons include NFX groups with placebo (for superiority), NFX versus BZN groups and 60CD versus 120HD groups (for non-inferiority) and testing for the agent-dose and group-region interactions. Assuming a 1 + PCR ≥ 75% in the placebo group, up to 25% among BZN-treated and an absolute difference of up to ≥ 25% with NFX to claim its trypanocidal effect, 60-80 participants per group (at least 300 from Colombia) are needed to test our hypotheses (80-90% power; one-sided alpha level 1%). DISCUSSION: The EQUITY trial will inform the trypanocidal effect and equivalence of nitroderivative agents NFX and BZN, particularly outside southern cone countries. Its results may challenge current recommendations and inform choices for these agents. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02369978 . Registered on 24 February 2015.


Subject(s)
Chagas Disease/drug therapy , Nifurtimox/therapeutic use , Nitroimidazoles/therapeutic use , Trypanocidal Agents/therapeutic use , Trypanosoma cruzi/drug effects , Adult , Aged , Asymptomatic Diseases , Chagas Disease/diagnosis , Chagas Disease/parasitology , Colombia , Female , Humans , Male , Middle Aged , Multicenter Studies as Topic , Nifurtimox/adverse effects , Nitroimidazoles/adverse effects , Randomized Controlled Trials as Topic , Therapeutic Equivalency , Time Factors , Treatment Outcome , Trypanocidal Agents/adverse effects , Trypanosoma cruzi/pathogenicity , Young Adult
12.
Parasitology ; 146(3): 305-313, 2019 03.
Article in English | MEDLINE | ID: mdl-30301480

ABSTRACT

This study evaluated the effectiveness of low doses of benznidazole (BNZ) on continuous administration (BNZc), combined with allopurinol (ALO), in C57BL/6J and C3H/HeN mice infected with Trypanosoma cruzi Nicaragua strain and T. cruzi Sylvio-X10/4 clone. TcN-C57BL/6J was also treated with intermittent doses of BNZ (BNZit). The drug therapy started 3 months post infection (pi) in the chronic phase of mice with heart disease progression, followed-up at 6 months pi. TcN-C57BL/6J treated with BNZc was also monitored up to 12 months pi by serology and electrocardiogram. These mice showed severe electrical abnormalities, which were not observed after BNZc or BNZit. ALO only showed positive interaction with the lowest dose of BNZ. A clear parasitic effect, with significant reductions in antibody titres and parasitic loads, was achieved in all models with low doses of BNZ, and a 25% reduction of the conventional dose showed more efficacy to inhibit the development of the pathology. However, BNZ 75 showed partial efficacy in the TcSylvio-X10/4-C3H/HeN model. In our experimental designs, C57BL/6J allowed to clearly define a chronic phase, and through reproducible efficacy indicators, it can be considered a good preclinical model.


Subject(s)
Allopurinol/therapeutic use , Chagas Disease/drug therapy , Nitroimidazoles/therapeutic use , Trypanocidal Agents/therapeutic use , Trypanosoma cruzi/drug effects , Allopurinol/administration & dosage , Animals , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Nitroimidazoles/administration & dosage , Random Allocation , Specific Pathogen-Free Organisms , Trypanocidal Agents/administration & dosage
13.
Rev Soc Bras Med Trop ; 51(4): 557-559, 2018.
Article in English | MEDLINE | ID: mdl-30133646

ABSTRACT

Chagas disease is a chronic parasitological disease, which could cause cardiac manifestations in approximately one-third of affected individuals. Benznidazole and nifurtimox are used to treat this parasitological infection caused by Trypanosoma cruzi. Conventionally, the criterion for cure is consistently negative serological tests after treatment. We report a case of a patient who was treated when she was 13 years old and achieved T. cruzi negative seroconversion but developed Chagas disease cardiomyopathy as an adult.


Subject(s)
Chagas Cardiomyopathy/diagnosis , Chagas Disease/drug therapy , Disease Progression , Female , Humans , Middle Aged , Nitroimidazoles/therapeutic use , Recurrence , Trypanocidal Agents/therapeutic use
14.
Rev. Soc. Bras. Med. Trop ; 51(4): 557-559, July-Aug. 2018.
Article in English | LILACS | ID: biblio-957448

ABSTRACT

Abstract Chagas disease is a chronic parasitological disease, which could cause cardiac manifestations in approximately one-third of affected individuals. Benznidazole and nifurtimox are used to treat this parasitological infection caused by Trypanosoma cruzi. Conventionally, the criterion for cure is consistently negative serological tests after treatment. We report a case of a patient who was treated when she was 13 years old and achieved T. cruzi negative seroconversion but developed Chagas disease cardiomyopathy as an adult.


Subject(s)
Humans , Female , Chagas Cardiomyopathy/diagnosis , Recurrence , Trypanocidal Agents/therapeutic use , Chagas Disease/drug therapy , Disease Progression , Middle Aged , Nitroimidazoles/therapeutic use
15.
Rev Gaucha Enferm ; 38(1): e64484, 2017 Apr 20.
Article in Portuguese, English | MEDLINE | ID: mdl-28443974

ABSTRACT

OBJECTIVE: To narrate the nurses' training experience in the implementation of a systematic delirium screening tool using the Confusion Assessment Method for Intensive Care Unit. METHOD: Experience report covering the steps of situation diagnosis, planning, staff training and evaluation of the tool's implementation between January and March 2013 with nurses in the ICU of a tertiary hospital in São Paulo. RESULTS: The implementation of the assessment, using the Confusion Assessment Method for Intensive Care Unit, obtained significant nurse adhesion and became a service indicator. FINAL CONSIDERATIONS: The experience has shown that this assessment allows the results of the work process to be analyzed and the consequent transformation of daily initiatives.


Subject(s)
Critical Care Nursing/education , Delirium/diagnosis , Education, Nursing, Continuing , Mental Status and Dementia Tests , Nursing Diagnosis/methods , Nursing Staff, Hospital/education , Critical Illness/psychology , Critical Illness/therapy , Delirium/nursing , Early Diagnosis , Humans , Inservice Training , Nurse's Role , Patient Safety , Program Evaluation , Respiration, Artificial , Tertiary Care Centers
16.
Rev. gaúch. enferm ; 38(1): e64484, 2017.
Article in Portuguese | LILACS, BDENF - Nursing | ID: biblio-845212

ABSTRACT

RESUMO Objetivo Narrar a experiência de capacitação de enfermeiros para implementação da avaliação sistematizada do delirium pelo método do Confusion Assessment Method for Intensive Care Unit. Método Relato de experiência que abrangeu as etapas de diagnóstico situacional, planejamento, capacitação da equipe e avaliação da implementação do instrumento entre janeiro e março de 2013 com enfermeiros de uma UTI de um hospital terciário do município de São Paulo. Resultados A implementação da avaliação, utilizando o Confusion Assessment Method for Intensive Care Unit, obteve uma adesão significativa dos enfermeiros e se tornou um indicador de assistência. Considerações finais A experiência demonstrou que essa avaliação possibilita analisar os resultados do processo de trabalho e a transformação consequente das iniciativas no cotidiano.


RESUMEN Objetivo Contar la experiencia de formación de enfermeras para la implementación de la evaluación sistemática de delirio por el método de la confusión Método de Evaluación de la Unidad de Cuidados Intensivos. Método Relato de experiencia que cubría las etapas de análisis de la situación, la planificación, la formación del personal y la evaluación de la aplicación de instrumentos, entre enero y marzo de 2013, con la enfermería en una unidad de cuidados intensivos de un hospital de tercer nivel en São Paulo. Resultados La aplicación de la evaluación utilizando el Método de Evaluación de la confusión de la Unidad de Cuidados Intensivos, obtuvieron una importante participación de las enfermeras y se convirtieron en un indicador de servicio. Consideraciones finales La experiencia ha demostrado que esta evaluación permite analizar los resultados del proceso de trabajo y las iniciativas de transformación consiguientes en la vida diaria.


ABSTRACT Objective To narrate the nurses’ training experience in the implementation of a systematic delirium screening tool using the Confusion Assessment Method for Intensive Care Unit. Method Experience report covering the steps of situation diagnosis, planning, staff training and evaluation of the tool’s implementation between January and March 2013 with nurses in the ICU of a tertiary hospital in São Paulo. Results The implementation of the assessment, using the Confusion Assessment Method for Intensive Care Unit, obtained significant nurse adhesion and became a service indicator. Final considerations The experience has shown that this assessment allows the results of the work process to be analyzed and the consequent transformation of daily initiatives.


Subject(s)
Humans , Nursing Diagnosis/methods , Delirium/diagnosis , Education, Nursing, Continuing , Critical Care Nursing/education , Mental Status and Dementia Tests , Nursing Staff, Hospital/education , Respiration, Artificial , Program Evaluation , Critical Illness/psychology , Critical Illness/therapy , Nurse's Role , Delirium/nursing , Early Diagnosis , Patient Safety , Tertiary Care Centers , Inservice Training
17.
PLoS Negl Trop Dis ; 10(5): e0004651, 2016 05.
Article in English | MEDLINE | ID: mdl-27158908

ABSTRACT

BACKGROUND: Chronic infection by Trypanosoma cruzi could cause heart conduction disturbances. We sought to analyze electrocardiographic abnormalities among children with chronic T. cruzi infection with and without trypanocidal treatment with benznidazole. METHODOLOGY/PRINCIPAL FINDINGS: We studied 111 children 6-16 years of age with asymptomatic chronic T. cruzi infection who were recruited in 1991-1992 in Salta, Argentina. Most children were randomly assigned to benznidazole 5 mg/Kg/day (n = 47) or matching placebo (n = 48) for 60 days. Remaining children (n = 16) received treatment with benznidazole 5 mg/Kg/day open-label. Electrocardiograms were obtained at baseline and in 1995-1996, 1998, 2000 and 2005, and were analyzed using the Buenos Aires method. Among the 94 children with an electrocardiogram at baseline, 8 (8.5%) had electrocardiographic abnormalities, including 4 (4.7%) children with right bundle branch block. Proportion of abnormal electrocardiograms in the full population (n = 111) remained constant over time (media follow-up 8.6 years). Multivariable adjusted prevalence ratios (95% confidence interval [95%CI]) for electrocardiographic abnormalities in 1995-1996, 1998, 2000 and 2005 comparing children treated with benznidazole versus those not treated were 2.76 (0.66, 11.60), 2.33 (0.44, 12.31), 3.06 (0.48, 19.56), and 1.94 (0.33, 11.25), respectively. Among the 86 children with a normal electrocardiogram at baseline, 16 (18.6%) developed electrocardiographic abnormalities during follow-up. The multivariable adjusted hazard ratio for incident electrocardiographic abnormalities comparing children treated with benznidazole versus those not treated was 0.68 (95%CI: 0.25, 1.88). CONCLUSIONS/SIGNIFICANCE: Electrocardiographic abnormalities are frequent among children with chronic T. cruzi infection. Treatment with benznidazole for 60 days may not be associated with less electrocardiographic abnormalities.


Subject(s)
Chagas Cardiomyopathy/drug therapy , Electrocardiography , Nitroimidazoles/therapeutic use , Trypanocidal Agents/therapeutic use , Trypanosoma cruzi , Adolescent , Argentina/epidemiology , Chagas Cardiomyopathy/epidemiology , Chagas Cardiomyopathy/parasitology , Child , Cohort Studies , Double-Blind Method , Female , Humans , Male , Retrospective Studies
18.
Rio de Janeiro; s.n; 2010. 70 p. tab, graf.
Thesis in Spanish | LILACS | ID: lil-596737

ABSTRACT

Introducción y objetivos: El compromiso más avanzado de la Enfermedad de Chagas (ECH) crónica se manifiesta por una miocardiopatía de evolución lenta, progresiva e irreversible, originando discapacidad precoz y muerte temprana.El objetivo principal de este estudio fue analizar predictores de mortalidad en una cohorte de pacientes con ECH y compromiso miocárdico avanzado. Material y método: Se utilizó un diseño de cohortes prospectivo que incluyó 96 pacientes con 2 o 3 técnicas reactivas para Enfermedad de Chagas con dilatación ventricular izquierda y asintomáticos (Estadio II de Kurchnir) o con signos de insuficiencia cardíaca ( Estadio III de Kurchnir). Se incluyeron variables demográficas, clínicas, electro y ecocardiográficas en un análisis tradicional de sobrevida y como punto final la muerte cardiovascular. En el análisis del tiempo de sobrevida se utilizaron las curvas de Kaplan Meier y luego se utilizó un análisis de riesgos proporcionales de Cox hasta encontrar el modelo que mejor ajuste tuvo con mortalidad...


INTRODUCTION AND OBJETIVES The most advanced state of the Cronical Chagas Desease is manifested by a prolonged and irreversible evolution of a myocardiopathy causing in the process early disability and mortality. The main objective of this study was to analyse mortality predictors considering a patient cohort affected by the Chagas Desease with advanced Myocardial Compromise. MATERIAL AND METHODFor the development of the study a prospective cohort design was employed.The analysis considered a total number of 96 patients being subject to an specific treatment based on 2 or 3 reactive techniques and employed for Asymptomatic Chagas Desease involing Left Ventricular Dilation Cardiopathy (Kurchnir´s II state) or Heart Failure signs ( Kurchnir´s III state).In accordance with traditional mortality rate analysis, demographic, clinical, electro and ecocardiographic variables were included. In the Mortality rate analysis were employed Kaplan-Meier curves first and the Cox approach to proportional risk analysis later on in order to adopt the most accurate model represeting Mortality rate results...


Subject(s)
Humans , Chronic Disease , Cardiomyopathy, Dilated/mortality , Chagas Disease/epidemiology , Chagas Disease/physiopathology , Prognosis , Cohort Studies , Survival Analysis
19.
Cardiovasc Ultrasound ; 4: 18, 2006 Mar 31.
Article in English | MEDLINE | ID: mdl-16573837

ABSTRACT

BACKGROUND: Chagas' disease may cause left ventricular diastolic dysfunction and its early detection in asymptomatic patients would allow to stratify the risk and to optimize medical treatment. The aim of this study is to investigate if transmitral Doppler flow can detect early abnormalities of the diastolic left ventricular function in patients during the indeterminate phase of Chagas' disease, in which the electrocardiogram (ECG), chest x-ray and 2-D echocardiogram (2D-echo) are normal. METHODS: a group of 54 patients with Chagas' disease was studied and compared to a control group of 27 subjects of similar age. All were assessed with an ECG, chest X-ray, 2-D echo, and transmitral Doppler flow. RESULTS: both groups had similar values in the 2D-echo. In patients with Chagas' disease, the transmitral Doppler showed a higher peak A velocity (control group: 0.44 m/sec, Chagas group: 0.55 m/sec, p = 0.001), a lower E/A ratio (control group: 1.45, Chagas group: 1.22, p < 0.05), and a lengthening of the deceleration time of early diastolic filling (control: 138.7 +/- 26.8 msec, Chagas group: 167.9 +/- 34.6 msec, p = 001), thus revealing an early disorder of the diastolic left ventricular function in patients with Chagas' disease. CONCLUSION: in patients with Chagas' disease who are in the indeterminate phase, transmitral Doppler flow allowed to identify early abnormalities of the left ventricular diastolic function, which provide useful clinical information for prognostic stratification and treatment.


Subject(s)
Chagas Disease/complications , Chagas Disease/diagnostic imaging , Echocardiography, Doppler/methods , Stroke Volume , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/etiology , Adult , Female , Humans , Male , Middle Aged , Observer Variation , Reproducibility of Results , Sensitivity and Specificity
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