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Adolescence is a critical time period for the onset of depression, and many patients do not respond to treatment. Transcutaneous auricular vagus nerve stimulation may be a promising alternative. Here, we present the case of an adolescent girl with treatment-resistant depression who received transcutaneous auricular vagus nerve stimulation over the course of 7.5 months.
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Transtorno Depressivo Resistente a Tratamento , Estimulação Elétrica Nervosa Transcutânea , Estimulação do Nervo Vago , Humanos , Feminino , Estimulação do Nervo Vago/métodos , Adolescente , Estimulação Elétrica Nervosa Transcutânea/métodos , Transtorno Depressivo Resistente a Tratamento/terapiaRESUMO
Purpose: The therapeutic decision for the management of breast cancer (BC) patients is based on the evaluation of prognostic factors alongside clinical and pathological parameters. Despite the use of standard biomarkers, response and resistance to therapy represent a challenge for clinicians. Among the new potential biomarkers for BC the ZNF217 gene have gained importance in recent years. However, while associations between ZNF217 gene copy number and clinicopathological characteristics have been established, its correlation with treatment response remains unclear. Patients and Methods: This study aimed to evaluate the ZNF217 gene copy number and establish its associations with treatment response in estrogen receptor positive (ERα+) and ERα negative (ERα-) BC cell lines. In addition, a validation of the relationship between ZNF217 gene copy number and its prognostic value was performed using datasets of BC patients retrieved from the cBioPortal public database. Results: Our data show that in ERα+ cells, ZNF217 gene copy number increase (amplification), while cell proliferation decreases in response to standard drug treatments. In contrast, both ZNF217 gene copy number (gain) and cell proliferation increases in response to standard drug treatments in ERα- cells. The results obtained align with findings from the cBioPortal database analysis, demonstrating that ERα+/HER2- low proliferation patients, exhibiting ZNF217 gene amplification or gain, have a significantly higher survival probability after treatment, compared to ERα-/HER2- and HER2+ patients. Conclusion: Our results suggest that in ERα+ BC cells, ZNF217 gene amplification could be indicative of a favorable response, while in ERα- BC cells, ZNF217 gene gain could be postulated as a potential predictor of treatment resistance. A broader understanding of the role of ZNF217 gene in treatment response, together with prospective studies in BC patients, could contribute to confirming our data, as well as optimizing existing treatments and exploring novel approaches to improve overall cancer treatment outcomes.
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There is no established treatment for patients with clozapine-resistant schizophrenia (CRS). Clozapine augmentation strategies with antipsychotics or others substances are effective in comparison with placebo while and Electroconvulsive therapy (ECT) showed to be effective in comparison with treatment as usual (TAU) but not with placebo (sham-ECT). In the present double- blind randomized controlled trial, we compared 40 outpatients who received 20 sessions of ECT (n = 21) or sham-ECT (n = 19) (age = 37.40 ± 9.62, males = 77.5 %, illness duration = 14.95 ± 8.32 years, mean total Positive and Negative Syndrome Scale (PANSS) = 101.10 ± 24.91) who fulfilled well-defined CRS criteria including baseline clozapine plasma levels ≥350 ng/mL. The primary outcome was the ≥50 % PANSS Total Score reduction; secondary outcomes were the scores of the PANSS subscales, PANSS five-factor dimensions, PANSS-6 and the Calgary Depression Rating Scale (CDRS). Treatment response was analyzed by percentage reduction, Linear Mixed Models and effect sizes. At baseline both groups showed no differences except for years of school education (included as a covariate). At endpoint, only 1/19 of the completers (5.26 %) in the ECT group and 0/17 in the sham-ECT group showed a ≥50 % total PANSS score reduction. Both groups showed no significant differences of the total PANSS score (F = 0.12; p = 0.73), Positive (F = 0.27, p = 0.61), Negative (F = 0.25, p = 0.62), and General Psychopathology scores (F = 0.01, p = 0.94) as well for all PANSS five factors, the PANSS-6 and CDRS. Thus, the present study found no evidence that ECT is better than Sham-ECT in patients with CRS. Future sham-ECT controlled studies with larger sample sizes are warranted to test the efficacy of ECT for patients with CRS.
Assuntos
Antipsicóticos , Clozapina , Eletroconvulsoterapia , Esquizofrenia Resistente ao Tratamento , Humanos , Masculino , Feminino , Eletroconvulsoterapia/efeitos adversos , Adulto , Clozapina/uso terapêutico , Clozapina/efeitos adversos , Método Duplo-Cego , Antipsicóticos/uso terapêutico , Pessoa de Meia-Idade , Esquizofrenia Resistente ao Tratamento/terapia , Esquizofrenia Resistente ao Tratamento/tratamento farmacológico , Escalas de Graduação Psiquiátrica , Resultado do Tratamento , Esquizofrenia/terapia , Esquizofrenia/tratamento farmacológico , Avaliação de Resultados em Cuidados de SaúdeRESUMO
Brain-derived neurotrophic factor (BDNF) has been studied as a biomarker of major depressive disorder (MDD). Besides diagnostic biomarkers, clinically useful biomarkers can inform response to treatment. We aimed to review all studies that sought to relate BDNF baseline levels, or BDNF polymorphisms, with response to treatment in MDD. In order to achieve this, we performed a systematic review of studies that explored the relation of BDNF with both pharmacological and non-pharmacological treatment. Finally, we reviewed the evidence that relates peripheral levels of BDNF and BDNF polymorphisms with the development and management of treatment-resistant depression.
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Transtorno Depressivo Maior , Transtorno Depressivo Resistente a Tratamento , Humanos , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/uso terapêutico , Biomarcadores , Polimorfismo GenéticoRESUMO
L-Asparaginase (ASNase) is a biopharmaceutical used as an essential drug in the treatment of acute lymphoblastic leukemia (ALL). Yet, some cases of ALL are naturally resistant to ASNase treatment, which results in poor prognosis. The REH ALL cell line, used as a model for studying the most common subtype of ALL, is considered resistant to treatment with ASNase. Cathepsin B (CTSB) is one of the proteases involved in the regulation of in vivo ASNase serum half-life and it has also been associated with the progression and resistance to treatment of several solid tumors. Previous works have shown that, in vitro, ASNase is degraded when incubated with REH cell lysate, which is prevented by a specific CTSB inhibitor, suggesting a function of this protease in the ASNase resistance of REH cells. In this work, we utilized a combination of CRISPR/Cas9 gene targeting and enzymatic measurements to investigate the relevance of CTSB on ASNase treatment resistance in the ALL model cell line. We found that deletion of CTSB in REH ALL cells did not confer ASNase treatment sensitivity, thus suggesting that intrinsic expression of CTSB is not a mechanism that drives the resistant nature of these ALL cells to enzymes used as the first-line treatment against leukemia.
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Antineoplásicos , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Asparaginase/farmacologia , Asparaginase/metabolismo , Fator Intrínseco/uso terapêutico , Catepsina B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Linhagem Celular , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêuticoRESUMO
BACKGROUND: Approximately 30% of individuals with schizophrenia (SZ) are resistant to conventional antipsychotic drug therapy (AP). Of these, one-third are also resistant to the second-line treatment, clozapine. Treatment resistance and refractoriness are associated with increased morbidity and disability, making timely detection of these issues critical. Variability in treatment responsiveness is partly genetic, but research has yet to identify variants suitable for personalizing antipsychotic prescriptions. METHODS: We evaluated potential associations between response to AP and candidate gene variants previously linked to SZ or treatment response. Two groups of patients with SZ were evaluated: one receiving clozapine (n = 135) and the other receiving another second-generation AP (n = 61). Single-nucleotide polymorphisms (SNPs) in the genes OXT, OXTR, CNR1, DDC, and DRD2 were analyzed. RESULTS: Several SNPs were associated with response vs. resistance to AP or clozapine. CONCLUSIONS: This is the first study of its kind, to our knowledge, in our admixed Chilean population to address the complete treatment response spectrum. We identified SNPs predictive of treatment-resistant SZ in the genes OXT, CNR1, DDC, and DRD2.
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Antipsicóticos , Clozapina , Esquizofrenia , Humanos , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Polimorfismo de Nucleotídeo Único/genética , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genéticaRESUMO
This is a case description of a patient with clozapine and ECT resistance schizophrenia with several suicide attempts. We discussed evidence-based clinical decisions to deal with such conditions.
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Antipsicóticos , Clozapina , Eletroconvulsoterapia , Esquizofrenia , Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Terapia Combinada , Humanos , Esquizofrenia/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: Moderate to severe asthma could be induced by diverse proinflammatory cytokines, as IL-17 and IFN-γ, which are also related to treatment resistance and airway hyperresponsiveness. Oxazolidines emerged as a novel approach for asthma treatment, since some chemical peculiarities were suggested by previous studies. OBJECTIVE: The present study aimed to evaluate the IL-17A and IFN-γ modulatory effect of two new oxazolidine derivatives (LPSF/NB-12 and -13) on mononucleated cells of patients with moderate and severe asthma. METHODS: The study first looked at potential targets for oxazolidine derivatives using SWISS-ADME. After the synthesis of the compounds, cytotoxicity and cytokine levels were analyzed. RESULTS: We demonstrated that LPSF/NB-12 and -13 reduced IFN-γ and IL-17 production in peripheral blood mononucleated cells from asthmatic patients in a concentrated manner. Our in silico analysis showed the neurokinin-1 receptor as a common target for both compounds, which is responsible for diverse proinflammatory effects of moderate and severe asthma. CONCLUSION: The work demonstrated a novel approach against asthma, which deserves further studies of its mechanisms of action.
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Asma/metabolismo , Interferon gama/metabolismo , Interleucina-17/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Oxazóis/química , Oxazóis/farmacologia , Asma/tratamento farmacológico , Relação Dose-Resposta a Droga , Desenho de Fármacos , Humanos , Simulação de Acoplamento Molecular , Oxazóis/metabolismo , Oxazóis/uso terapêutico , Conformação Proteica , Receptores da Neurocinina-1/química , Receptores da Neurocinina-1/metabolismoRESUMO
Acyl-CoA synthetase 4 (ACSL4) is an isoenzyme of the fatty acid ligase-coenzyme-A family taking part in arachidonic acid metabolism and steroidogenesis. ACSL4 is involved in the development of tumor aggressiveness in breast and prostate tumors through the regulation of various signal transduction pathways. Here, a bioinformatics analysis shows that the ACSL4 gene expression and proteomic signatures obtained using a cell model was also observed in tumor samples from breast and cancer patients. A well-validated ACSL4 inhibitor, however, has not been reported hindering the full exploration of this promising target and its therapeutic application on cancer and steroidogenesis inhibition. In this study, ACSL4 inhibitor PRGL493 was identified using a homology model for ACSL4 and docking based virtual screening. PRGL493 was then chemically characterized through nuclear magnetic resonance and mass spectroscopy. The inhibitory activity was demonstrated through the inhibition of arachidonic acid transformation into arachidonoyl-CoA using the recombinant enzyme and cellular models. The compound blocked cell proliferation and tumor growth in both breast and prostate cellular and animal models and sensitized tumor cells to chemotherapeutic and hormonal treatment. Moreover, PGRL493 inhibited de novo steroid synthesis in testis and adrenal cells, in a mouse model and in prostate tumor cells. This work provides proof of concept for the potential application of PGRL493 in clinical practice. Also, these findings may prove key to therapies aiming at the control of tumor growth and drug resistance in tumors which express ACSL4 and depend on steroid synthesis.
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Proliferação de Células/efeitos dos fármacos , Coenzima A Ligases/metabolismo , Resistencia a Medicamentos Antineoplásicos , Inibidores Enzimáticos/farmacologia , Animais , Sítios de Ligação , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Coenzima A Ligases/antagonistas & inibidores , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Simulação de Acoplamento Molecular , Próstata/citologia , Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Esteroides/sangue , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
INTRODUCTION: Schizophrenia is a complex psychiatric disorder that affects approximately twenty million people worldwide. Various factors have been associated with the physiopathology of this disease such as oxidative stress, which is an imbalance between pro-oxidant and antioxidant molecules. OBJECTIVE: This study evaluated the association between biomarkers of oxidative stress and response to pharmacological treatment among patients with schizophrenia in the context of their clinical information, demographic data, and lifestyle. METHODS: A total of 89 subjects were included, 26 of whom were treatment-responsive schizophrenia patients (Group 1), 27 treatment-resistant schizophrenia patients (Group 2), and 36 healthy controls (Group 3). All of the subjects completed a questionnaire to provide clinical and demographic data, and all provided peripheral blood samples. The oxidative stress markers analyzed using spectrophotometry were catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), total glutathione (GSH-t), malondialdehyde (MDA), and Trolox-equivalent antioxidant capacity (TEAC; p < 0.05). RESULTS: When all schizophrenia patients (G1 + G2) were compared to the control group, SOD levels were found to be lower among schizophrenia patients (p < 0.0001), while MDA and CAT levels were higher (p < 0.0001 and p = 0.0191, respectively). GPx, GSH-t, and TEAC levels were similar in all three groups (p > 0.05). CONCLUSION: Lower SOD levels and higher MDA and CAT levels indicate oxidative damage in schizophrenia patients, regardless of their response to pharmacological treatment. Smoking is associated with oxidative stress, in addition, a family history of the disease was also found to be correlated with cases of schizophrenia, which reflects the relevance of genetics in disease development.
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Esquizofrenia , Biomarcadores , Glutationa Peroxidase/metabolismo , Humanos , Estresse Oxidativo , Esquizofrenia/tratamento farmacológico , Esquizofrenia Resistente ao TratamentoRESUMO
Breast cancer (BC) is one of the most important cancers worldwide, and usually, chemotherapy can be used in an integrative approach. Usually, chemotherapy treatment is performed in association with surgery, radiation or hormone therapy, providing an increased outcome to patients. However, tumors can develop resistance to different drugs, progressing for a more aggressive phenotype. In this scenario, the use of nanocarriers could help to defeat tumor cell resistance, providing a new therapeutic perspective for patients. Thus, this systematic review aims to bring the molecular mechanisms involved in BC chemoresistance and extract from the previous literature information regarding the use of nanoparticles as potential treatment for chemoresistant breast cancer.
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Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the BCR-ABL oncoprotein, known to drive leukemogenesis by orchestrating multiple signaling pathways ultimately involved in cell survival. Despite successful response rates of CML patients to tyrosine kinase inhibitors (TKIs), resistance eventually arises due to BCR-ABL-dependent and independent mechanisms. Survivin is an inhibitor of apoptosis protein acting in the interface between apoptosis deregulation and cell cycle progression. In CML, high levels of survivin have been associated with late stages of disease and therapy resistance. In this review, we provide an overview of important aspects concerning survivin subcellular localization and expression pattern in CML patients and cell lines. Moreover, we highlight the relevance of molecular networks involving survivin for disease progression and treatment resistance. Finally, we discuss the mechanisms accounting for survivin overexpression, as well as novel therapeutic interventions that have been designed to counteract survivin-associated malignancy in CML.
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Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Survivina/genética , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Terapia de Alvo Molecular , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Survivina/análise , Regulação para Cima/efeitos dos fármacosRESUMO
OBJECTIVE: The aim of this study is to analyze the immune-endocrine profile in neurocysticercosis (NC) patients resistant to cysticidal treatment. METHODS: The inflammatory and regulatory responses of 8 resistant NC patients with extraparenchymal parasites and 5 healthy controls were evaluated through flow cytometry. Serum interleukin levels were measured by ELISA and catecholamines levels by high performance liquid chromatography. RESULTS: Higher percentages of Tr1, CD4+CD25+FOXP3+CD127- and CD4+CD45RO+FOXP3HI were found in NC patients compared with healthy controls, but no difference was found in catecholamine levels. Antigen-specific proliferative immune response was observed in NC patients. Neither anti-inflammatory nor pro-inflammatory cytokines showed differences between patients and controls, but IL-6 levels were lower in treatment-resistant NC patients. In addition, TGFß showed a significant negative correlation with dopamine. CONCLUSIONS: Altogether, these results may point to a modulation of the neuroinflammation in these patients that could indirectly favor cysticercal survival in CNS microenvironment.
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Antiparasitários/uso terapêutico , Imunidade Celular/imunologia , Mediadores da Inflamação/sangue , Mediadores da Inflamação/imunologia , Neurocisticercose/sangue , Neurocisticercose/imunologia , Adulto , Idoso , Antiparasitários/farmacologia , Biomarcadores/sangue , Catecolaminas/sangue , Catecolaminas/imunologia , Feminino , Humanos , Imunidade Celular/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Neurocisticercose/tratamento farmacológico , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Resultado do TratamentoRESUMO
En este artículo describiremos brevemente ciertos pacientes que consultan por cuadros psiquiátricos agudos y que además sufren de difusión de identidad. Estos pacientes ofrecen dificultades importantes a su propio tratamiento porque tienden a no persistir en una tarea, no cuidar de sí mismos, no confiar en las personas y a no recuperarse de las fallas de mentalización que puedan tener en sus relaciones interpersonales, produciendo graves complicaciones en el proceso terapéutico. Describiremos el Programa de Intervención Psicoeducativa y Control Farmacológico en Grupo que hemos implementado en el Instituto Psiquiátrico José Horwitz Barak para manejar de mejor forma las dificultades terapéuticas que estos pacientes ofrecen.
In this article we will briefly describe certain patients who consult for acute psychiatric symptoms and who also suffer from identity diffusion. These patients offer significant difficulties to their own treatment because they tend not to persist in a task, do not take care of themselves, do not trust people and do not recover from the mentalization failures they may have in their interpersonal relationships, producing serious complications in the therapeutic process. We will describe the Program of Psychoeducative Intervention and Pharmacological Control in Group that we have implemented in the José Horwitz Barak Psychiatric Institute to better manage the therapeutic difficulties that these patients offer.
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Humanos , Transtornos da Personalidade/psicologia , Transtornos da Personalidade/terapia , Transtornos da Personalidade/tratamento farmacológico , Psicoterapia de Grupo , Educação de Pacientes como Assunto , Recusa do Paciente ao Tratamento , Cooperação do PacienteRESUMO
Introducción. El asma grave representa 5-7% del total de asmáticos. La OMS propuso un protocolo de seguimiento para categorizarlos como asma grave resistente al tratamiento (AGRT) o asma grave de difícil control (AGDC). Objetivo. Analizar las características clínicas, funcionales y terapéuticas de pacientes con AGRT o AGDC. Métodos. Estudio transversal, observacional y analítico para evaluar el diagnóstico, grado de control (clínico y funcional), comorbilidades, adherencia al tratamiento, técnica inhalatoria y factores ambientales en pacientes con asma grave. Resultados. Se incluyeron 69 pacientes: AGRT (n= 33) y AGDC (n= 36). El 100% del grupo con AGRT fue hospitalizado previamente por asma vs. 87,8% del grupo con AGDC (p= 0,03). El 63% del grupo AGRT requirió cuidados intensivos (UCI)), 82%, asistencia ventilatoria y uno fue traqueostomizado. En el AGDC, 54% requirió internación en la UCI , y 33%, asistencia ventilatoria (p= 0,03). La espirometría basal fue normal en el AGDC; se observó incapacidad ventilatoria obstructiva leve en el AGRT (p= 0,009). En el AGDC, hubo menor cumplimiento del tratamiento (p= 0,01). Se requirieron dosis mayores de corticoides inhalados en AGRT (p= 0,0001). Omalizumab fue indicado en AGRT (p= 0,0001). A los 6 meses de seguimiento, más del 75% de los niños en ambos grupos presentó asma controlada. Conclusiones. Se observó significativa falta de adherencia al tratamiento en el grupo AGDC. Se redujeron las dosis de tratamiento en este grupo. Se logró controlar la enfermedad en un alto porcentaje de niños con AGRT y AGDC.
Introduction. Severe asthma accounts for 5-7% of all asthma cases. The World Health Organization proposed a follow-up protocol to classify cases into severe, treatment-resistant asthma (STRA) or severe, difficult-to-control asthma (SDCA). Objective. To analyze the clinical, functional, and therapeutic characteristics of patients with STRA or SDCA. Methods. Cross-sectional, observational, and analytical study to assess the diagnosis, the extent of control (clinical and functional), comorbidities, treatment adherence, inhalation technique, and environmental factors in patients with severe asthma. Results. A total of 69 patients were included: STRA (n= 33) and SDCA (n= 36). In the group with STRA, 100% of patients had been previously hospitalized due to asthma compared to 87.8% in the group with SDCA (p= 0.03). In the group with STRA, 63% required admission to the intensive care unit (ICU); 82%, ventilatory support; and 1 patient, tracheostomy. In the group with SDCA, 54% required admission to the ICU; and 33%, ventilatory support (p= 0.03). The baseline spirometry was normal in the SDCA group; a mild obstructive ventilatory defect was observed in the STRA group (p= 0.009). In the SDCA group, treatment adherence was lower (p= 0.01). Higher inhaled corticosteroid doses were required in the STRA group (p= 0.0001). Omalizumab was indicated in the case of STRA (p= 0.0001). After 6 months of follow-up, more than 75% of children in both groups achieved asthma control. Conclusions. A significant lack of treatment adherence was observed in the SDCA group. In this group, treatment doses were reduced. Asthma was controlled in a high percentage of children with STRA and SDCA.
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Humanos , Masculino , Feminino , Criança , Adolescente , Asma/diagnóstico , Asma/etiologia , Asma/terapia , Índice de Gravidade de Doença , Asma/complicações , Protocolos Clínicos , Estudos Transversais , Seguimentos , Cooperação do Paciente , Resultado do Tratamento , Terapia Combinada , HospitalizaçãoRESUMO
BACKGROUND: Failure to respond to antipsychotic medication in schizophrenia is a common clinical scenario with significant morbidity. Recent studies have highlighted that many patients present treatment-resistance from disease onset. We here present an analysis of clozapine prescription patterns, used as a real-world proxy marker for treatment-resistance, in a cohort of 1195 patients with schizophrenia from a Latin-American cohort, to explore the timing of emergence of treatment resistance and possible subgroup differences. METHODS: Survival analysis from national databases of clozapine monitoring system, national disease notification registers, and discharges from an early intervention ward. RESULTS: Echoing previous studies, we found that around 1 in 5 patients diagnosed with schizophrenia were eventually prescribed clozapine, with an over-representation of males and those with a younger onset of psychosis. The annual probability of being prescribed clozapine was highest within the first year (probability of 0.11, 95% confidence interval of 0.093-0.13), compared to 0.018 (0.012-0.024) between years 1 and 5, and 0.006 (0-0.019) after 5years. Age at psychosis onset, gender, dose of clozapine used, and compliance with hematological monitoring at 12months, was not related to the onset of treatment resistance. A similar pattern was observed in a subgroup of 230 patients discharged from an early intervention ward with a diagnosis of non-affective first episode of psychosis. CONCLUSIONS: Our results highlight that treatment resistance is frequently present from the onset of psychosis. Future studies will shed light on the possible different clinical and neurobiological characteristics of this subtype of psychosis.
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Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Resistência a Medicamentos , Esquizofrenia/tratamento farmacológico , Adolescente , Adulto , Antipsicóticos/efeitos adversos , Chile , Clozapina/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Masculino , Esquizofrenia/epidemiologia , Fatores de Tempo , Falha de Tratamento , Adulto JovemRESUMO
INTRODUCTION: Severe asthma accounts for 5-7% of all asthma cases. The World Health Organization proposed a follow-up protocol to classify cases into severe, treatment-resistant asthma (STRA) or severe, difficult-to-control asthma (SDCA). OBJECTIVE: To analyze the clinical, functional, and therapeutic characteristics of patients with STRA or SDCA. METHODS: Cross-sectional, observational, and analytical study to assess the diagnosis, the extent of control (clinical and functional), comorbidities, treatment adherence, inhalation technique, and environmental factors in patients with severe asthma. RESULTS: A total of 69 patients were included: STRA (n= 33) and SDCA (n= 36). In the group with STRA, 100% of patients had been previously hospitalized due to asthma compared to 87.8% in the group with SDCA (p= 0.03). In the group with STRA, 63% required admission to the intensive care unit (ICU); 82%, ventilatory support; and 1 patient, tracheostomy. In the group with SDCA, 54% required admission to the ICU; and 33%, ventilatory support (p= 0.03).The baseline spirometry was normal in the SDCA group; a mild obstructive ventilatory defect was observed in the STRA group (p= 0.009).In the SDCA group, treatment adherence was lower (p= 0.01). Higher inhaled corticosteroid doses were required in the STRA group (p= 0.0001). Omalizumab was indicated in the case of STRA (p= 0.0001). After 6 months of follow-up, more than 75% of children in both groups achieved asthma control. CONCLUSIONS: A significant lack of treatment adherence was observed in the SDCA group. In this group, treatment doses were reduced. Asthma was controlled in a high percentage of children with STRA and SDCA.
INTRODUCCIÓN: El asma grave representa 5-7% del total de asmáticos. La OMS propuso un protocolo de seguimiento para categorizarlos como asma grave resistente al tratamiento (AGRT) o asma grave de difícil control (AGDC). OBJETIVO: Analizar las características clínicas, funcionales y terapéuticas de pacientes con AGRT o AGDC. MÉTODOS: Estudio transversal, observacional y analítico para evaluar el diagnóstico, grado de control (clínico y funcional), comorbilidades, adherencia al tratamiento, técnica inhalatoria y factores ambientales en pacientes con asma grave. RESULTADOS: Se incluyeron 69 pacientes: AGRT (n= 33) y AGDC (n= 36). El 100% del grupo con AGRT fue hospitalizado previamente por asma vs. 87,8% del grupo con AGDC (p= 0,03). El 63% del grupo AGRT requirió cuidados intensivos (UCI)), 82%, asistencia ventilatoria y uno fue traqueostomizado. En el AGDC, 54% requirió internación en la UCI , y 33%, asistencia ventilatoria (p= 0,03). La espirometría basal fue normal en el AGDC; se observó incapacidad ventilatoria obstructiva leve en el AGRT (p= 0,009).En el AGDC, hubo menor cumplimiento del tratamiento (p= 0,01). Se requirieron dosis mayores de corticoides inhalados en AGRT (p= 0,0001). Omalizumab fue indicado en AGRT (p= 0,0001). A los 6 meses de seguimiento, más del 75% de los niños en ambos grupos presentó asma controlada. CONCLUSIONES: Se observó significativa falta de adherencia al tratamiento en el grupo AGDC. Se redujeron las dosis de tratamiento en este grupo. Se logró controlar la enfermedad en un alto porcentaje de niños con AGRT y AGDC.
Assuntos
Asma/diagnóstico , Asma/terapia , Índice de Gravidade de Doença , Adolescente , Asma/complicações , Asma/etiologia , Criança , Protocolos Clínicos , Terapia Combinada , Estudos Transversais , Feminino , Seguimentos , Hospitalização , Humanos , Masculino , Cooperação do Paciente , Resultado do TratamentoRESUMO
OBJECTIVES: Recent schizophrenia (SCZ) research aims to establish biomarkers with high predictive value for the diagnosis, severity of illness or treatment resistance. SCZ is accompanied by activated immune-inflammatory pathways, including increased levels of cytokines and chemokines, but few studies tried to identify predictive properties of such measures. METHODS: We included 54 medicated SCZ patients and 118 healthy controls and examined 15 cytokines and chemokines. Possible associations between these immune-inflammatory biomarkers and the diagnosis of SCZ, severity of illness and treatment resistance were investigated. RESULTS: SCZ is associated with a specific cytokine - chemokine profile, i.e., increased CCL11, MIP-1α, sTNF-R1 and sTNF-R2 levels, and decreased levels of IP-10, TNF-α, IL-2 and IL-4. The combination of five biomarkers (sTNF-R1, sTNF-R2, CCL11, IP-10, IL-4) may predict the diagnosis of SCZ with a sensitivity of 70.0% and a specificity of 89.4%. There was a weak association between the negative symptoms and biomarkers, i.e., IL-2 (inversely) and CCL11 (positively). Patients with treatment resistance showed increased levels of sTNF-R1, sTNF-R2 and MCP-1. CONCLUSIONS: The findings of this study reinforce that SCZ is associated with a pro-inflammatory profile and suggest that some immune mediators may be used as reliable biomarkers for the diagnosis of SCZ and treatment resistance.
RESUMO
OBJECTIVE: Major Depressive Disorder (MDD) is a debilitating condition with a marked social impact. The impact of MDD and Treatment-Resistant Depression (TRD+) within the Brazilian health system is largely unknown. The goal of this study was to compare resource utilization and costs of care for treatment-resistant MDD relative to non-treatment-resistant depression (TRD-). METHODS: We retrospectively analyzed the records of 212 patients who had been diagnosed with MDD according to the ICD-10 criteria. Specific criteria were used to identify patients with TRD+. Resource utilization was estimated, and the consumption of medication was annualized. We obtained information on medical visits, procedures, hospitalizations, emergency department visits and medication use related or not to MDD. RESULTS: The sample consisted of 90 TRD+ and 122 TRD- patients. TRD+ patients used significantly more resources from the psychiatric service, but not from non-psychiatric clinics, compared to TRD- patients. Furthermore, TRD+ patients were significantly more likely to require hospitalizations. Overall, TRD+ patients imposed significantly higher (81.5%) annual costs compared to TRD- patients (R$ 5,520.85; US$ 3,075.34 vs. R$ 3,042.14; US$ 1,694.60). These findings demonstrate the burden of MDD, and especially of TRD+ patients, to the tertiary public health system. Our study should raise awareness of the impact of TRD+ and should be considered by policy makers when implementing public mental health initiatives.
OBJETIVO: O Transtorno Depressivo Maior (TDM) é uma condição debilitante com um forte impacto social. O impacto do TDM e Depressão Resistente ao Tratamento (DRT+) no sistema de saúde brasileiro é praticamente desconhecido. Nosso objetivo é comparar a utilização de recursos e custos dos cuidados para o tratamento de DRT+ em relação ao TDM não resistente (DRT-). MÉTODOS: Foram analisados retrospectivamente os prontuários de 212 pacientes diagnosticados com TDM segundo a CID-10. Critérios específicos foram utilizados para identificar pacientes com DRT+. A utilização dos recursos foi estimada e consumo de medicamentos foram anualizados. Foram obtidas informações sobre consultas, procedimentos, internações, atendimentos no serviço de emergência e uso de medicação relacionada ou não ao TDM. RESULTADOS: A amostra foi composta de 90 pacientes DRT+ e 122 DRT-. Pacientes DRT+ utilizaram significativamente mais recursos do serviço de psiquiatria, mas não em clínicas não psiquiátricas, em relação a DRT-. Eles eram significativamente mais propensos a exigir internações. Pacientes DRT+ apresentaram um custo direto anual significativamente maior (81,5%) do que pacientes com depressão não resistente (R$ 5.520,85; US$ 3.075,34 contra R$ 3.042,14, US$ 1.694,60). Estes resultados demonstram o impacto do TDM, principalmente da DRT+ ao sistema de saúde público terciário. Nosso estudo deve aumentar a sensibilização para o impacto da DRT + e deve ser considerado pelos formuladores de políticas públicas na implementação de iniciativas de saúde mental.
Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno Depressivo Maior/economia , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Resistente a Tratamento/economia , Custos de Cuidados de Saúde , Recursos em Saúde/economia , Brasil , Custos e Análise de Custo , Recursos em Saúde , Hospitalização/economia , Tempo de Internação/economia , Estudos RetrospectivosRESUMO
INTRODUCCION: El síndrome de la epilepsia mesial temporal con esclerosis del hipocampo (EMTEH) se comporta frecuentemente como fármaco-resistente. La variabilidad interindividual en el grado de respuesta al tratamiento farmacológico podría depender de la compleja interrelación entre factores ambientales y genéticos. Aunque los últimos años han mostrado avances de la farmacogenética en la epilepsia, todavía no se ha identificado ningún factor genético capaz de predecir la respuesta terapéutica. Entre los posibles genes implicados se cuentan el transportador de la serotonina (SLC6A4) y el de la subunidad alfa del canal de sodio voltaje-dependiente tipo 1 (SCN1A).OBJETIVO: Tipificar estos genes en la atención de los pacientes con esta forma frecuente de epilepsia, ya que ello permitiría establecer el pronóstico y seleccionar la mejor alternativa terapéutica desde el inicio del diagnóstico.METODOS: A través de un estudio de cohorte prospectivo, se evaluó la genotipificación de 2 polimorfismos en SLC6A4 y SCN1A y su efecto predictivo sobre la respuesta al tratamiento farmacológico. Se verificó el efecto experimentado tras un año del inicio del tratamiento en una población de pacientes con diagnóstico de EMTEH.RESULTADOS: Se encontró una frecuencia mayor a la esperada para el genotipo CC en el gen SCN4B en los pacientes con baja frecuencia de crisis luego de instaurado/cambiado el tratamiento, pero esto no fue estadísticamente significativo. Los pacientes con el genotipo de mayor eficiencia transcripcional del VNTR-2 no tuvieron mayor frecuencia de crisis que los otros genotipos.CONCLUSIONES: No se encontró asociación alguna entre los distintos alelos del VNTR-2 y SNA4B y la respuesta farmacológica exhibida por los pacientes con esclerosis de hipocampo. El estudio no logró replicar resultados de trabajos anteriores.
INTRODUCTION: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLEHS) often has a drug-resistant behavior. The variability in the degree of response to drug treatment may depend on the complex interplay between environmental and genetic factors. Although recent years have shown progress in epilepsy pharmacogenetics, it was still not possible to consistently identify any genetic factor capable of predicting therapeutic response. Among genes that might be involved, it is possible to mention the serotonin transporter (SLC6A4) and the alpha subunit of voltage-gated sodium channel type 1 (SCN1A).OBJECTIVE: To genotype these genes in the care of patients with this common form of epilepsy, in order to establish a prognosis and select the best therapeutic alternative from the beginning of diagnosis.METHODS: A prospective cohort study was conducted to evaluate the predictive effect of genotyping two polymorphisms in SLC6A4 and SCN1A on the response to drug therapy, experienced during the first year after starting treatment in a population of patients with MTLHS.RESULTS: The frequency was higher than expected for the CC genotype in the gene SCN4B in patients with low seizure frequency after establishing/changing the treatment, but this was not statistically significant. Patients with the genotype of highest transcriptional efficiency of VNTR-2 did not have more frequent crises than those with other genotypes.CONCLUSIONS: No association was found between the different alleles of VNTR-2 and SNA4B and drug response in patients with hippocampal sclerosis. The study failed to replicate results of previous works.