RESUMO
BACKGROUND: The equilibrium radionuclide angiocardiography (ERNA) scan is an established imaging modality for assessing left ventricular ejection fraction (LVEF) in oncology patients. This study aimed to explore the interchangeability of two commercially available software packages (MIM and JS) for LVEF measurement for a cancer-therapy-related cardiac dysfunction (CTRCD) diagnosis. METHODS: This is a single-center retrospective study among 322 patients who underwent ERNA scans. A total of 582 scans were re-processed using MIM and JS for cross-sectional and longitudinal LVEF measurements. RESULTS: The median LVEF for MIM and JS were 56% and 66%, respectively (P < 0.001). LVEF processed by JS was 9.91% higher than by MIM. In 87 patients with longitudinal ERNA scans, serial studies processed by MIM were classified as having CTRCD in a higher proportion than serial studies processed by JS (26.4% vs 11.4%, P = 0.020). There were no significant differences in intra- or inter-observer LVEF measurement variability (R = 0.99, P < 0.001). CONCLUSIONS: Software packages for processing ERNA studies are not interchangeable; thus, reports of ERNA studies should include details on the post-processing software. Serial ERNA studies should be processed on the same software when feasible to avoid discrepancies in the diagnosis and management of CTRCD.
Assuntos
Neoplasias , Disfunção Ventricular Esquerda , Humanos , Função Ventricular Esquerda , Volume Sistólico , Imagem do Acúmulo Cardíaco de Comporta/métodos , Cardiotoxicidade , Estudos Retrospectivos , Estudos Transversais , Neoplasias/complicações , Neoplasias/diagnóstico por imagem , SoftwareRESUMO
AIMS: Chimeric antigen receptor T-cell therapy (CAR-T) harnesses a patient's immune system to target cancer. There are sparse existing data characterizing death outcomes after CAR-T-related cardiotoxicity. This study examines the association between CAR-T-related severe cardiovascular events (SCE) and mortality. METHODS AND RESULTS: From a multi-centre registry of 202 patients receiving anti-CD19 CAR-T, covariates including standard baseline cardiovascular and cancer parameters and biomarkers were collected. Severe cardiovascular events were defined as a composite of heart failure, cardiogenic shock, or myocardial infarction. Thirty-three patients experienced SCE, and 108 patients died during a median follow-up of 297 (interquartile range 104-647) days. Those that did and did not die after CAR-T were similar in age, sex, and prior anthracycline use. Those who died had higher peak interleukin (IL)-6 and ferritin levels after CAR-T infusion, and those who experienced SCE had higher peak IL-6, C-reactive protein (CRP), ferritin, and troponin levels. The day-100 and 1-year Kaplan-Meier overall mortality estimates were 18% and 43%, respectively, while the non-relapse mortality (NRM) cumulative incidence rates were 3.5% and 6.7%, respectively. In a Cox model, SCE occurrence following CAR-T was independently associated with increased overall mortality risk [hazard ratio (HR) 2.8, 95% confidence interval (CI) 1.6-4.7] after adjusting for age, cancer type and burden, anthracycline use, cytokine release syndrome grade ≥ 2, pre-existing heart failure, hypertension, and African American ancestry; SCEs were independently associated with increased NRM (HR 3.5, 95% CI 1.4-8.8) after adjusting for cancer burden. CONCLUSION: Chimeric antigen receptor T-cell therapy recipients who experience SCE have higher overall mortality and NRM and higher peak levels of IL-6, CRP, ferritin, and troponin.
Assuntos
Insuficiência Cardíaca , Neoplasias , Receptores de Antígenos Quiméricos , Humanos , Receptores de Antígenos Quiméricos/uso terapêutico , Interleucina-6 , Biomarcadores , Proteína C-Reativa , Troponina , Terapia Baseada em Transplante de Células e TecidosRESUMO
PURPOSE OF REVIEW: Modern therapeutics have led to improved survival for many types of cancer but have also been associated with adverse effects including potentially life-threatening cardiotoxicities. We sought to review the uses of multimodality cardiac imaging for risk stratification, prevention, and identification of cardiotoxicities in patients undergoing cancer treatment. RECENT FINDINGS: Advancements in both echocardiography and emerging modalities, like cardiac magnetic resonance imaging and cardiac computed tomography, continue to improve the pre- and during therapy cardiac evaluation of cancer patients. Echocardiography and cardiac magnetic resonance imaging, with the incorporation of global longitudinal strain, can identify overt and subclinical cancer therapy-related cardiac dysfunction and myocarditis, and stress echocardiography and cardiac computed tomography can noninvasively screen and monitor for coronary artery disease. Multimodality cardiac imaging is an evolving and critical tool for the pre-therapy screening and risk stratification, as well as during therapy surveillance of cancer treatment-related cardiotoxicity.
Assuntos
Antineoplásicos , Neoplasias , Humanos , Cardiotoxicidade/diagnóstico por imagem , Cardiotoxicidade/etiologia , Antineoplásicos/efeitos adversos , Coração/diagnóstico por imagem , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Neoplasias/induzido quimicamente , Ecocardiografia/métodosRESUMO
OBJECTIVE: To evaluate the relation of coronary artery calcifications (CAC) on non-ECG-gated CT pulmonary angiography (CTPA) with short-term mortality in patients with acute pulmonary embolism (PE). METHODS: We retrospectively included all in-patients between May 2007 and December 2014 with an ICD-9 code for acute PE and CTPA and transthoracic echocardiography available. CAC was qualitatively graded as absent, mild, moderate, or severe. Relations of CAC with overall and PE-related 30-day mortality were assessed using logistic regression analyses. The independence of those relations was assessed using a nested approach, first adjusting for age and gender, then for RV strain, peak troponin T, and cardiovascular risk factors for an overall model. RESULTS: Four hundred seventy-nine patients were included (63 ± 16 years, 52.8% women, 47.2% men). In total, 253 (52.8%) had CAC-mild: 143 (29.9%); moderate: 89 (18.6%); severe: 21 (4.4%). Overall mortality was 8.8% (n = 42) with higher mortality with any CAC (12.6% vs. 4.4% without; odds ratio [OR] 3.1 [95%CI 2.1-14.5]; p = 0.002). Mortality with severe (19.0%; OR 5.1 [95%CI 1.4-17.9]; p = 0.011), moderate (11.2%; OR 2.7 [95%CI 1.1-6.8]; p = 0.031), and mild CAC (12.6%; OR 3.1 [95%CI 1.4-6.9]; p = 0.006) was higher than without. OR adjusted for age and gender was 2.7 (95%CI 1.0-7.1; p = 0.050) and 2.6 (95%CI 0.9-7.1; p = 0.069) for the overall model. PE-related mortality was 4.0% (n = 19) with higher mortality with any CAC (5.9% vs. 1.8% without; OR 3.5 [95%CI 1.1-10.7]; p = 0.028). PE-related mortality with severe CAC was 9.5% (OR 5.8 [95%CI 1.0-34.0]; p = 0.049), with moderate CAC 6.7% (OR 4.0 [95%CI 1.1-14.6]; p = 0.033), and with mild 4.9% (OR 2.9 [95%CI 0.8-9.9]; p = 0.099). OR adjusted for age and gender was 4.2 (95%CI 0.9-20.7; p = 0.074) and 3.4 (95%CI 0.7-17.4; p = 0.141) for the overall model. Patients with sub-massive PE showed similar results. CONCLUSION: CAC is frequent in acute PE patients and associated with short-term mortality. Visual assessment of CAC may serve as an easy, readily available tool for early risk stratification in those patients. KEY POINTS: ⢠Coronary artery calcification assessed on computed tomography pulmonary angiography is frequent in patients with acute pulmonary embolism. ⢠Coronary artery calcification assessed on computed tomography pulmonary angiography is associated with 30-day overall and PE-related mortality in patients with acute pulmonary embolism. ⢠Coronary artery calcification assessed on computed tomography pulmonary angiography may serve as an additional, easy readily available tool for early risk stratification in those patients.
Assuntos
Vasos Coronários , Embolia Pulmonar , Angiografia , Angiografia por Tomografia Computadorizada , Ecocardiografia , Feminino , Humanos , Masculino , Artéria Pulmonar/diagnóstico por imagem , Embolia Pulmonar/diagnóstico por imagem , Estudos Retrospectivos , Medição de Risco , Tomografia Computadorizada por Raios XRESUMO
OPINION STATEMENT: Cardio-oncology is a field dedicated to the prevention, diagnosis, and management of cardiovascular disease in cancer patients before, during, and after cancer therapy. It is an emerging field with limited opportunities for structured education and training. In the year 2021, we cannot define the requirements of cardio-oncology training without acknowledging the impact of the global coronavirus disease 19 (COVID-19) pandemic. While this pandemic poses significant health risks to patients with cancer and cardiovascular disease as well as the providers who care for them, it also allows novel opportunities for the nascent field of cardio-oncology to readily adapt. In this article, we detail how the COVID-19 pandemic has impacted all aspects of cardio-oncology training, how programs and trainees can adapt to these challenges, and how lessons learned from the COVID-19 era can continue to positively impact cardio-oncology training for the foreseeable future.
Assuntos
COVID-19/complicações , Doenças Cardiovasculares/prevenção & controle , Neoplasias/tratamento farmacológico , COVID-19/virologia , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/virologia , Humanos , Oncologia/tendências , Neoplasias/complicações , Neoplasias/patologia , Neoplasias/virologia , SARS-CoV-2/patogenicidadeRESUMO
Patients with acute pulmonary embolism (PE) can present with various clinical manifestations including syncope. The mechanism of syncope in PE is not fully elucidated and data of right ventricular (RV) function in patients has been limited. We retrospectively identified 477 consecutive patients hospitalized with acute PE diagnosed with a computed tomogram (CT) who also had a transthoracic echocardiogram (TTE) 24 h prior to or 48 h after diagnosis. Parameters of RV strain on CT, TTE, electrocardiogram (ECG), and clinical characteristics and adverse outcomes were collected. Patients with all three studies available for assessment were included (n = 369) and those with syncope (n = 34) were compared to patients without syncope (n = 335). Patients with syncope were more likely to demonstrate RV strain on all three modes of assessment compared to those without syncope [17 (50%) vs. 67 (20%); p = 0.001], and those patients were more likely to receive advanced therapies [9 (53%) vs. 15 (22%); p = 0.02]. PE-related mortality was highest among those presenting with high-risk PE and syncope (36%, OR 20.1, 95% CI 5.3-81.1; p < 0.001) and was low in patients with syncope without criteria for high-risk PE (3%, OR 1.2, 95% CI 0.2-10.0; p < 0.001). In conclusion, acute PE patients with syncope are more likely to demonstrate multimodality evidence of RV strain and to receive advanced therapies. Syncope was only associated with increased PE-related mortality in patients presenting with a high-risk PE. Syncope alone without evidence of RV strain is associated with low short-term adverse events and is similar to those without syncope.
Assuntos
Ecocardiografia/métodos , Ventrículos do Coração , Embolia Pulmonar , Síncope , Disfunção Ventricular Direita , Correlação de Dados , Feminino , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/mortalidade , Embolia Pulmonar/fisiopatologia , Medição de Risco/métodos , Fatores de Risco , Síncope/diagnóstico , Síncope/etiologia , Tomografia Computadorizada por Raios X/métodos , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Disfunção Ventricular Direita/diagnóstico , Disfunção Ventricular Direita/fisiopatologiaRESUMO
INTRODUCTION: Risk stratification for acute pulmonary embolism (PE) incorporates metrics of right ventricle (RV) function. Significant RV dysfunction influences left ventricular (LV) function, though LV function metrics are not utilized for stratifying outcomes in patients with PE. Mitral annular plane systolic excursion (MAPSE) is a linear echocardiographic (TTE) measure that evaluates longitudinal LV function and may aid in risk stratification for acute PE. METHODS: Using a single-center database of patients with PE from 2007 to 2014, MAPSE was calculated for all TTE's available with sufficient quality (n = 362). A MAPSE of ≥11 mm was used as a normal reference. Thirty-day adverse outcomes were defined as administration of vasopressor, fibrinolytic therapy, open embolectomy, or 30-day PE-related mortality. Odds ratios (OR) and adjusted OR (AOR) were calculated using logistic regression analysis. Tricuspid annular plane systolic excursion (TAPSE) measurements were incorporated to determine the additive benefit of MAPSE. RESULTS: Compared with the reference MAPSE ≥ 11 mm and LVEF > 50%, patients with MAPSE < 11 mm and an LVEF > 50% had worse outcomes (AOR 2.94 [95% CI: 1.08-7.98], P = 0.035). Among patients with LVEF > 50%, the presence of both a MAPSE < 11 mm and TAPSE < 16 mm was associated with greater odds of adverse outcomes compared with isolated depressed TAPSE (AOR 10.75 [95% CI: 3.06-37.8], P < 0.01 vs AOR 1.68 [95% CI: 0.18-15.6], P = 0.65). CONCLUSION: A depressed MAPSE, in patients with preserved LVEF, is associated with worse outcomes in patients with acute PE. The addition of MAPSE to TAPSE appears to have a greater prognostic value than either alone and may further aid in risk stratification, but for confirmation further prospective data are needed.
Assuntos
Embolia Pulmonar , Valva Tricúspide , Ecocardiografia , Humanos , Embolia Pulmonar/complicações , Embolia Pulmonar/diagnóstico por imagem , Medição de Risco , Valva Tricúspide/diagnóstico por imagem , Função Ventricular DireitaRESUMO
Background: Approximately one-third of people with schizophrenia have elevated levels of anti-gliadin antibodies of the immunoglobulin G type (AGA IgG) a higher rate than seen in healthy controls. We performed the first double-blind clinical trial of gluten-free versus gluten-containing diets in a subset of patients with schizophrenia who were positive for AGA IgG. Methods: In this pilot feasibility study, 16 participants with schizophrenia or schizoaffective disorder who had elevated AGA IgG (≥ 20 U) but were negative for celiac disease were admitted to an inpatient unit for a 5-week trial. All participants received standardized gluten-free meals and were randomized in a double-blind fashion to receive a shake containing 10 g of gluten flour or 10 g of rice flour each day. Participants were rated for psychiatric, cognitive and gastrointestinal symptoms at baseline and endpoint. Results: Of the 16 participants, 14 completed the 5-week trial (2 discontinued early for administrative reasons). Compared with participants on the gluten-containing diet, participants on the gluten-free diet showed improvement on the Clinical Global Impressions scale (Cohen d = 0.75) and in negative symptoms (Cohen d = 0.53). We noted no improvement in positive or global cognitive symptoms, but did observe an improvement in attention favouring the gluten-free diet (Cohen d = 0.60). Robust improvements in gastrointestinal adverse effects occurred in the gluten-free group relative to the glutencontaining group. Adverse effects were similar between groups. Limitations: This study was limited by its small sample size; larger studies are needed. Conclusion: This feasibility study suggests that removal of gluten from the diet is associated with improvement in psychiatric and gastrointestinal symptoms in people with schizophrenia or schizoaffective disorder.
Assuntos
Gliadina/imunologia , Transtornos Psicóticos/dietoterapia , Transtornos Psicóticos/imunologia , Esquizofrenia/dietoterapia , Esquizofrenia/imunologia , Adulto , Anticorpos/imunologia , Dieta Livre de Glúten , Método Duplo-Cego , Estudos de Viabilidade , Feminino , Humanos , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Projetos PilotoRESUMO
PURPOSE/BACKGROUND: Prolactin-related adverse effects contribute to nonadherence and adverse health consequences, particularly in women with severe mental illness. Treating these adverse effects may improve treatment acceptability, adherence, and long-term outcomes. METHODS/PROCEDURES: Premenopausal women with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder were recruited for a randomized, double-blind, placebo-controlled 16-week trial of adjunct aripiprazole (5-15 mg/d). Participants had elevated prolactin (>24 ng/mL) and were experiencing galactorrhea, amenorrhea, oligomenorrhea, or sexual dysfunction on a prolactin-elevating antipsychotic. Participants were evaluated biweekly for prolactin elevation and galactorrhea and completed a menstrual diary review. Psychiatric symptoms and adverse effects were closely monitored. FINDINGS/RESULTS: Forty-six women were randomized (n = 25 aripiprazole, n = 21 placebo). Thirty-seven completed at least 8 weeks of the study (n = 20 [80%] aripiprazole and n = 17 [81%] placebo). Aripiprazole (mean dose, 11.7 ± 2.4 mg/d) was effective for lowering prolactin relative to placebo (P = 0.04). In addition, 45% (9/20) of the aripiprazole group had a normalized prolactin (<24 mg/mL) compared with 12% (2/17) of the placebo group (P = 0.028). Galactorrhea resolved in 77% (10/13) of the aripiprazole-treated participants compared with 33% (4/12) in the placebo group (P = 0.028). Normalization of sexual function (<16 on the Arizona Sexual Experience Scale) occurred in 50% on aripiprazole (7/14) versus 9% (1/11) on placebo (P = 0.030). No differences between groups in symptoms or adverse effects were noted. Overall, women rated a mean score of 4.6 ± 0.6 on a 5-point Likert scale for sexual function improvement, suggesting their particular satisfaction with improvement in this domain. IMPLICATIONS/CONCLUSIONS: Building upon prior studies, this rigorous evaluation confirms the utility of adjunctive aripiprazole as a strategy for improving prolactin and managing prolactin-related adverse effects in premenopausal women with psychosis.
Assuntos
Antipsicóticos/uso terapêutico , Aripiprazol/uso terapêutico , Quimioterapia Combinada/métodos , Pré-Menopausa/efeitos dos fármacos , Prolactina/sangue , Transtornos Psicóticos/tratamento farmacológico , Adulto , Amenorreia/induzido quimicamente , Amenorreia/prevenção & controle , Antipsicóticos/efeitos adversos , Aripiprazol/administração & dosagem , Método Duplo-Cego , Feminino , Galactorreia/induzido quimicamente , Galactorreia/prevenção & controle , Humanos , Adesão à Medicação , Oligomenorreia/induzido quimicamente , Oligomenorreia/prevenção & controle , Qualidade de VidaRESUMO
Popular media often portray people with a mental illness as being aggressive, violent, and incarcerated as a result of their behavior. Despite exaggeration in the media, risks for some aggressive behaviors are in fact higher in individuals with schizophrenia. This is often the case with influence of comorbid substance use disorders. It is essential that mental health professionals are aware of treatments that may help with attenuating and treating behaviors that contribute to violence, aggression and incarceration. This paper reviews violence and incarceration in individuals with schizophrenia as well as recommendations, guidelines and benefits for the use of clozapine in this population. Clozapine remains one of the most underutilized evidence-based medications available in the psychiatric arena in the United States. It is a viable and recommended option in the forensic population and it may be helpful on the path to recovery as well as bring substantial savings to the criminal justice system.
Assuntos
Agressão/efeitos dos fármacos , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Direito Penal , Criminosos , Esquizofrenia/tratamento farmacológico , Violência/prevenção & controle , HumanosRESUMO
Clozapine is the sole antipsychotic agent effective for the treatment of refractory schizophrenia. Sixty percent of clozapine-treated patients, however, fail to adequately respond. Minocycline, a tetracycline antibiotic, possesses antiinflammatory and neuroprotective properties that may play a role in schizophrenia. Clozapine is mainly metabolized by CYP1A2 enzymes, and minocycline may potentially inhibit CYP1A2 as hypothesized by case report data. To date, no pharmacokinetic interaction has been reported between minocycline and clozapine. This is a secondary analysis of a 10-week controlled study of adjunctive minocycline to clozapine in treatment refractory schizophrenia. Clozapine plasma levels were collected every two weeks during the study. 28 participants assigned to receive minocycline and 22 assigned to placebo were included. No differences existed in baseline demographics, clozapine dose or plasma levels. Average changes from baseline in clozapine plasma level (p = 0.033) were significantly higher in the minocycline group despite maintenance of stable doses. No statistically significant treatment differences were found in the norclozapine (p = 0.754) or total clozapine (p = 0.053) changes in plasma levels, although possible changes in total clozapine levels require further investigation. This analysis suggests that minocycline administration may lead to increased clozapine plasma levels. Further study is needed to examine possible explanations.
Assuntos
Antipsicóticos/sangue , Clozapina/sangue , Minociclina/farmacologia , Fármacos Neuroprotetores/farmacologia , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/administração & dosagem , Clozapina/administração & dosagem , Clozapina/análogos & derivados , Interações Medicamentosas , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Minociclina/administração & dosagem , Fármacos Neuroprotetores/administração & dosagemRESUMO
OBJECTIVE: This study sought to examine the predictors of health risk perception in smokers with or without schizophrenia. METHODS: The health risk subscale from the Smoking Consequences Questionnaire was dichotomized and used to measure health risk perception in smokers with (n = 67) and without schizophrenia (n = 100). A backward stepwise logistic regression was conducted using variables associated at the bivariate level to determine multivariate predictors. RESULTS: Overall, 62.5% of smokers without schizophrenia and 40.3% of smokers with schizophrenia completely recognize the health risks of smoking (p ≤ .01). Multivariate predictors for smokers without schizophrenia included: sex (Exp (B) = .3; p < .05), Smoking Consequences Questionnaire state enhancement (Exp (B) = .69; p < .01), and craving relief (Exp (B) = 1.8; p < .01). Among smokers with schizophrenia, predictors were education (Exp (B) = .7; p < .05), nicotine dependence (Exp (B) = .5; p < .01), motivation to quit (Exp (B) = 1.8; p < .01), and Smoking Consequences Questionnaire craving relief (Exp (B) = 1.8; p < .01). CONCLUSIONS: There was overlap and differences between predictors in smokers with and without schizophrenia. Commonly used techniques for education on the health consequences of cigarettes may work in smokers with schizophrenia, but intervention efforts specifically tailored to smokers with schizophrenia might be more efficacious.
Assuntos
Atitude Frente a Saúde , Esquizofrenia/complicações , Psicologia do Esquizofrênico , Fumar/psicologia , Tabagismo/psicologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Tabagismo/complicaçõesRESUMO
OBJECTIVE: Nicotine dependence is high in schizophrenia, and craving is known to impact relapse during quit attempts. METHODS: We compared tobacco craving in smokers with schizophrenia treated with different antipsychotics. RESULTS: Mean craving scores were lowest in participants receiving first-generation antipsychotics, although these differences were not statistically significant. Craving with clozapine was not lower than with other antipsychotics. CONCLUSIONS: Further research is needed to determine whether differences in craving exist between antipsychotic classes.
Assuntos
Antipsicóticos/uso terapêutico , Fissura/efeitos dos fármacos , Esquizofrenia/complicações , Psicologia do Esquizofrênico , Fumar/psicologia , Tabagismo/psicologia , Adulto , Benzodiazepinas/uso terapêutico , Clozapina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Olanzapina , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Tabagismo/complicaçõesRESUMO
People with schizophrenia are 3-4 times more likely to die from cardiovascular disease than the general population. Clozapine (CLZ) is the gold standard of treatment for refractory schizophrenia. It has been associated with tachycardia and recent evidence shows individuals prescribed CLZ may develop blood pressure (BP) elevation and hypertension. The purpose of this study was to examine the effects of CLZ on BP and heart rate (HR). This was a retrospective chart review of patients 18-75 years old with a DSM IV diagnosis of Schizophrenia or Schizoaffective disorder. Primary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR measured 12 weeks before and 24 weeks during CLZ treatment. Eighteen patient records were included in this study. The mean stabilized CLZ dose was 441.7 ± 171.8 mg/day. DBP (t = 1.02, df = 79.5, = 2.00, 0.049) and HR (t = 1.32, df = 355 = -4.61, < 0.0001) were significantly higher after CLZ initiation. A trend was noted for increase in SBP (p = 0.071). 22 % of patients met criteria for hypertension before CLZ and 67 % during CLZ treatment (Chi Square = 6.25, df = 1, p = 0.0124). No significant changes in weight or renal function occured during CLZ treatment. No patients had evidence of cardiomyopathy. The data suggest CLZ may be associated with a rise in BP and HR. The results of this study support previous literature that found an increase in SBP/DBP regardless of CLZ dose, occurring early in treatment. Due to high risk of cardiovascular morbidity and mortality, more work is needed to determine risk factors and understand the mechanism of action that may cause this side effect.
Assuntos
Antipsicóticos/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Clozapina/efeitos adversos , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/induzido quimicamente , Esquizofrenia/tratamento farmacológico , Adolescente , Adulto , Idoso , Antipsicóticos/administração & dosagem , Clozapina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taquicardia/induzido quimicamente , Adulto JovemRESUMO
OBJECTIVE: Clozapine is the most effective antipsychotic for treatment refractory people with schizophrenia, yet many patients only partially respond. Accumulating preclinical and clinical data suggest benefits with minocycline. We tested adjunct minocycline to clozapine in a 10-week, double-blind, placebo-controlled trial. Primary outcomes tested were positive, and cognitive symptoms, while avolition, anxiety/depression, and negative symptoms were secondary outcomes. METHODS: Schizophrenia and schizoaffective participants (n = 52) with persistent positive symptoms were randomized to receive adjunct minocycline (100 mg oral capsule twice daily; n = 29) or placebo (n = 23). RESULTS: Brief Psychiatric Rating Scale (BPRS) psychosis factor (P = 0.098; effect size [ES], 0.39) and BPRS total score (P = 0.075; ES, 0.55) were not significant. A change in total BPRS symptoms of more than or equal to 30% was observed in 7 (25%) of 28 among minocycline and 1 (4%) of 23 among placebo participants, respectively (P = 0.044). Global cognitive function (MATRICS Consensus Cognitive Battery) did not differ, although there was a significant variation in size of treatment effects among cognitive domains (P = 0.03), with significant improvement in working memory favoring minocycline (P = 0.023; ES, 0.41). The Scale for the Assessment of Negative Symptoms total score did not differ, but significant improvement in avolition with minocycline was noted (P = 0.012; ES, 0.34). Significant improvement in the BPRS anxiety/depression factor was observed with minocycline (P = 0.028; ES, 0.49). Minocycline was well tolerated with significantly fewer headaches and constipation compared with placebo. CONCLUSIONS: Minocycline's effect on the MATRICS Consensus Cognitive Battery composite score and positive symptoms were not statistically significant. Significant improvements with minocycline were seen in working memory, avolition, and anxiety/depressive symptoms in a chronic population with persistent symptoms. Larger studies are needed to validate these findings.
Assuntos
Antipsicóticos/administração & dosagem , Clozapina/administração & dosagem , Minociclina/administração & dosagem , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Adulto , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoAssuntos
Autoanticorpos/sangue , Citocinas/sangue , Dieta Livre de Glúten , Ácido Cinurênico/sangue , Esquizofrenia/sangue , Triptofano/sangue , Adolescente , Adulto , Biomarcadores/sangue , Dieta Livre de Glúten/efeitos adversos , Método Duplo-Cego , Feminino , Gliadina/imunologia , Humanos , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Transdução de Sinais , Adulto JovemRESUMO
OBJECTIVE: The goal of the present study was to demonstrate that the analytical assay of interest can detect antipsychotics in human urine specimens. METHOD: Forty inpatients treated with haloperidol, quetiapine, risperidone, or olanzapine were recruited to participate in a one visit study. During the study visit, demographic and clinical information was collected as well as one urine sample that was forwarded to the Ameritox Laboratory and assayed for the presence of antipsychotic medications and/or metabolites. Urine samples were analyzed to determine detection sensitivity for four antipsychotic medications and their metabolites (risperidone, quetiapine, olanzapine, and/or haloperidol) using Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry. RESULTS: All urine samples produced positive results for the antipsychotic(s) the participants were known to be taking. Urine concentrations (level of quantification) for parent drugs ranged from <25-417 ng/mL for haloperidol, <25-4017 ng/mL for quetiapine, 0-997 ng/mL for risperidone, and 57-700 ng/mL for olanzapine. CONCLUSION: The analytical assay produced by Ameritox, Ltd using Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry can qualitatively detect antipsychotics in human urine specimens. The present study highlights the potential utility of the urine assay to help monitor adherence to antipsychotic medications.
Assuntos
Antipsicóticos/urina , Benzodiazepinas/urina , Bioensaio/métodos , Haloperidol/urina , Fumarato de Quetiapina/urina , Risperidona/urina , Adulto , Cromatografia Líquida , Humanos , Masculino , Espectrometria de Massas , Adesão à Medicação , Pessoa de Meia-Idade , Olanzapina , Projetos PilotoRESUMO
BACKGROUND: Bispecific T-cell engagers (BTEs) are novel agents used to treat hematological malignancies. Early trials were underpowered to define cardiovascular adverse events (CVAE) and no large-scale studies systematically examined the CVAEs associated with BTEs. METHODS: Leveraging the US Food and Drug Administration's Adverse Event Reporting System-(FAERS), we identified the relative frequency of CVAEs after initiation of five BTE products approved by the Food and Drug Administration between 2014 and 2023 for the treatment of hematological malignancies. Adjusted reporting ORs (aROR) were used to identify disproportionate reporting of CVAEs with BTEs compared with background rates in the database. Fatality rates and risk ratios (RRs) for each adverse event (AE) were calculated. RESULTS: From 3668 BTE-related cases reported to FAERS, 747 (20.4%) involved CVAEs. BTEs as a class were associated with fatal CVAEs (aROR 1.29 (95% CI 1.12 to 1.50)), an association mainly driven by teclistamab (aROR 2.44 (95% CI 1.65 to 3.60)). Teclistamab was also associated with a disproportionate risk of myocarditis (aROR 25.70 (95% CI 9.54 to 69.23)) and shock (aROR 3.63 (95% CI 2.30 to 5.74)), whereas blinatumomab was associated with a disproportionate risk of disseminated intravascular coagulation (aROR 3.02 (95% CI 1.98 to 4.60)) and hypotension (aROR 1.59 (95% CI 1.25 to 2.03)). CVAEs were more fatal compared with non-CVAEs (31.1% vs 17.4%; RR 1.76 (95% CI 1.54 to 2.03)). Most CVAEs (83.3%) did not overlap with cytokine release syndrome. CONCLUSION: In the first postmarketing surveillance study of BTEs, CVAEs were involved in approximately one in five AE reports and carried a significant mortality risk.
Assuntos
Antineoplásicos , Neoplasias Hematológicas , HumanosRESUMO
Prolactin elevations occur in people treated with antipsychotic medications and are often much higher in women than in men. Hyperprolactinemia is known to cause amenorrhea, oligomenorrhea, galactorrhea and gynecomastia in females and is also associated with sexual dysfunction and bone loss. These side effects increase risk of antipsychotic nonadherence and suicide and pose significant problems in the long term management of women with schizophrenia. In this manuscript, we review the literature on prolactin; its physiology, plasma levels, side effects and strategies for treatment. We also present the rationale and protocol for an ongoing clinical trial to treat symptomatic hyperprolactinemia in premenopausal women with schizophrenia. More attention and focus are needed to address these significant side effects and help the field better personalize the treatment of women with schizophrenia.