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The target trial framework has emerged as a powerful tool for addressing causal questions in clinical practice and in public health. In the healthcare sector, where decision-making is increasingly data-driven, transactional databases, such as electronic health records (EHR) and insurance claims, present an untapped potential for answering complex causal questions. This narrative review explores the potential of the integration of the target trial framework with real-world data to enhance healthcare decision-making processes. We outline essential elements of the target trial framework, and identify pertinent challenges in data quality, privacy concerns, and methodological limitations, proposing solutions to overcome these obstacles and optimize the framework's application.
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Registros Electrónicos de Salud , Humanos , Bases de Datos FactualesRESUMEN
BACKGROUND: Although a large variety of antidepressants agents (AD) with different mechanisms of action are available, no significant differences in efficacy and safety have been shown. However, there have been few attempts to incorporate data on subjective experiences under different AD. METHOD: We conducted a qualitative and quantitative analysis of the posts from the website www.askapatient.com from different AD. We reviewed a random sample of 1000 posts. RESULT: After applying the inclusion and exclusion criteria, we included a final sample of 450 posts, 50 on each of the most used AD: sertraline, citalopram, paroxetine, escitalopram, fluoxetine, venlafaxine, duloxetine, mirtazapine, and bupropion. Bupropion, citalopram, and venlafaxine had the higher overall satisfaction ratings. Sertraline, paroxetine, and fluoxetine had high reports of emotional blunting, while bupropion very few. Overall satisfaction with AD treatment was inversely associated with the presence of the following side-effects: suicidality, irritability, emotional blunting, cognitive disturbances, and withdrawal symptoms. After adjusting for confounders, only emotional blunting was shown to be more frequently reported by users of serotonergic agents, as compared to non-serotoninergic agents. CONCLUSION: This research points out that the subjective experience of patients under treatment should be taken into consideration when selecting an AD as differences between agents were evident. In contrast to the more frequent treatment decisions, users might prefer receiving a non-serotoninergic agent over a serotonergic one due to their lower propensity to produce emotional blunting.
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Citalopram , Paroxetina , Humanos , Clorhidrato de Venlafaxina/efectos adversos , Fluoxetina/efectos adversos , Bupropión/efectos adversos , Sertralina , Antidepresivos/efectos adversosRESUMEN
OBJECTIVE: Mounting evidence suggests that antipsychotics may have immunomodulatory effects, but their impact on disseminated infections remains unknown. This study thus sought to estimate the effect of antipsychotic treatment on the occurrence of bloodstream infection during long-term follow-up in adult patients with chronic obstructive pulmonary disease. METHODS: This retrospective cohort study, with new user and active comparator design, included adult patients seen from January 2008 to June 2018 in a tertiary teaching hospital in Buenos Aires, Argentina. New users of antipsychotic drugs were compared to new users of any benzodiazepine. The primary outcome of interest was incident bloodstream infection at 1 year of follow-up. Propensity score methods and a Cox proportional hazards model were used to adjust for baseline confounding. RESULTS: A total of 923 patients were included in the present analysis. Mean (SD) age was 75.0 (9.8) years, and 51.9% of patients were female. The cumulative incidence of bloodstream infections at 1 year was 6.0% and 2.3% in the antipsychotic and benzodiazepine groups, respectively. Antipsychotic use was associated with a higher risk of bloodstream infections during the first year of follow-up (hazard ratio [HR] = 2.41; 95% CI, 1.13 to 5.14) compared to benzodiazepine use. Antipsychotics with high dopamine receptor affinity presented greater risk than less selective agents (HR = 5.20; 95% CI, 1.53 to 17.67). CONCLUSIONS: Antipsychotic use is associated with bloodstream infections during the first year of follow-up in adult patients with chronic obstructive pulmonary disease. Further studies are warranted to confirm our findings and evaluate this effect in a broader population of patients.
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Antipsicóticos/uso terapéutico , Benzodiazepinas/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Sepsis/epidemiología , Anciano , Anciano de 80 o más Años , Antipsicóticos/efectos adversos , Argentina/epidemiología , Benzodiazepinas/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
OBJECTIVE: In this study, we aimed to evaluate the role of cognitive performance and measures of clinical course-including both syndromal and subsyndromal symptomatology-as determinants of the functional outcome of patients with Bipolar Disorder (BD) during a mean follow-up period of more than 4 years. METHODS: Seventy patients with euthymic BD completed a neurocognitive battery at study entry. Clinical course was assessed prospectively for a period longer than 48 months by two measures: time spent ill (documented using a modified life charting technique) and density of affective episodes (defined as the number of depressive and hypo/manic episodes per year of follow-up). Psychosocial functioning was assessed during euthymia using the Functioning Assessment Short Test (FAST) total score at the end of follow-up period. RESULTS: Baseline deficits in phonological fluency, a measure of executive functions (ß = -2.49; 95% CI = -3.98, -0.99), and density of hypo/manic episodes during follow-up (ß = 6.54; 95% CI = 0.43, 12.65) were independently associated with FAST total score at the end of study. CONCLUSIONS: Although interrelated, manic morbidity and executive function impairments independently contribute to long-term psychosocial dysfunction in BD and could be potential targets of intervention.
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Trastorno Bipolar , Trastornos del Conocimiento , Trastorno Bipolar/complicaciones , Trastorno Bipolar/epidemiología , Función Ejecutiva , Humanos , Morbilidad , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: Venous thromboembolism (VTE) represents a major cause of morbidity and mortality worldwide. Antipsychotic treatment is associated with an increased risk of thromboembolic disease, an effect that seems to be constant across the spectrum of distinct agents. This study sought to delineate the effect of new antipsychotic use on the risk of recurrent thromboembolic events after a first episode of either deep venous thrombosis or pulmonary embolism. METHODS: This cohort study, conducted between January 2010 and June 2017, was based on a prospectively collected database of adult patients with VTE. The main exposure was the new onset of antipsychotic treatment after having a first episode of venous thromboembolic disease. The primary outcome was defined as recurrent VTE, either deep venous thrombosis or pulmonary embolism, during long-term follow-up. The composite of all-cause mortality and recurrent VTE served as the secondary outcome. An inverse probability weighted multivariable Cox proportional hazards model was fitted to adjust for measured confounding and competing risks. RESULTS: One thousand one hundred three patients were included in the present analysis, of whom 136 were identified as new users of antipsychotic agents. A total of 67% of patients were currently treated with full-dose anticoagulation at baseline. No association was found between the new use of antipsychotic agents and recurrent VTE during follow-up (adjusted hazard ratio (HR) = 1.08; 95% CI, 0.38-3.08). However, the use of these agents was associated with a 63% increased risk of recurrent VTE or all-cause mortality (adjusted HR = 1.63; 95% CI, 1.26-2.10). CONCLUSIONS: The use of antipsychotic agents among patients with a first episode of VTE and full-dose anticoagulation was not associated with an increased risk of recurrent thromboembolic events. However, antipsychotic treatment was associated with a higher risk of both VTE and all-cause mortality. Further studies are warranted to confirm these findings.
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Antipsicóticos/efectos adversos , Embolia Pulmonar/epidemiología , Sistema de Registros/estadística & datos numéricos , Tromboembolia Venosa/epidemiología , Trombosis de la Vena/epidemiología , Anciano , Argentina/epidemiología , Comorbilidad , Femenino , Humanos , Masculino , Recurrencia , Estudios Retrospectivos , Tromboembolia Venosa/mortalidadRESUMEN
OBJECTIVES: Characterization of clinical course in old age bipolar disorder (OABD) is scarce and based solely on episode density (ED). The aim of this study was to explore mood instability (MI) and subsyndromal symptomatology (SS) in a prospective cohort of OABD. Further, we contrasted these measures with a cohort of young age bipolar disorder (YABD). METHODS: Life charts from weekly mood ratings were used to compute the number of weeks spent with subsyndromal symptoms (SD), the ED, and the MI during follow-up for a cohort of OABD (N = 38) that excluded late onset BD. Linear and logistic regression models were fitted to compare the clinical course of OABD with a cohort of YABD (N = 52) and to explore the relationship between these measures and functional outcomes. RESULTS: Median follow-up was 5 years (IQR: 3.6-7.9). OABD (61.6 years, SD: 8.3) spent 15%, 6%, and 3% of their follow-up with depressive, manic, and mixed symptoms, respectively, and suffered 4.2 mood changes per year (SD: 2.6). No significant differences between OABD and YABD regarding ED or MI emerged in multivariate analysis, while a higher subsyndromal manic symptom burden was observed in OABD (ß coefficient: 3.79, 95%CI: 0.4-7.2). Both SS and MI were associated with functional outcomes in OABD. CONCLUSIONS: The course of illness throughout OABD was similar to the one observed in YABD except for a higher subsyndromal manic burden. This study extended the association of MI and SD with global functioning to the late-life BD.
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Trastorno Bipolar/psicología , Memoria Episódica , Trastornos del Humor/psicología , Adolescente , Adulto , Anciano , Trastorno Bipolar/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Análisis de Regresión , Adulto JovenRESUMEN
The aim of this study was to explore outcome to antidepressants profile in melancholic unipolar depression. We conducted a systematic review of electronic databases and meta-analysis of randomized and nonrandomized trials comparing: 1) outcome to antidepressants and placebo between melancholic and non-melancholic depression; 2) outcome to different antidepressant classes in melancholic depression. Two outcomes were considered: clinical remission and response. Significant lower odds of remission to antidepressants in melancholic than in non-melancholic depressions were found. Although no significant differences were observed in the response to antidepressants between both subtypes of depression, those with melancholic features had lower odds of response to placebo. Finally, treatment of melancholic depression with serotonin reuptake inhibitors was associated with lower odds of remission compared with tricyclic antidepressants, and similar outcome compared with venlafaxine. Melancholia seems to show a differential pattern of outcome to antidepressants, which could be clinically valuable for a better implementation of personalized medicine of depression. Due to several limitations, further research is needed to support these preliminary findings.
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Antidepresivos Tricíclicos/uso terapéutico , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Antidepresivos/uso terapéutico , Trastorno Depresivo/psicología , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/psicología , Humanos , Resultado del Tratamiento , Clorhidrato de Venlafaxina/uso terapéuticoRESUMEN
We aimed to compare the mortality risk between patients with affective disorders and dementia under treatment with antipsychotics. To do this, a matched-cohort study based on an electronic database of a tertiary teaching hospital in Argentina was performed. Antipsychotic exposure was defined as any antipsychotic drug initiated by the patient. Primary outcome was defined as all-cause mortality during the 5-year follow-up period. To estimate the association between baseline diagnosis (affective disorders vs. dementia) and all-cause mortality, we used a multivariate generalized linear model with robust standard errors. Of 1008 eligible patients, 114 age-matched pairs were included in the present study. The primary event occurred in 23 patients (20%) and 17 patients (15%) in the dementia and affective disorder group respectively. In the adjusted model, the risk of all cause mortality for the affective disorders group was 0.92 times the risk for the dementia group (95%CI, 0.54-1.59, pâ¯=â¯0.77). In conclusion, older patients with affective disorders starting antipsychotic treatment presented with a similar risk of all-cause mortality during the 5-year follow-up when compared to older patients with dementia who were also initiating either typical or atypical antipsychotic medications. Closer medical attention to older patients with mental conditions under antipsychotic treatment remains warranted.
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Antipsicóticos/efectos adversos , Demencia/tratamiento farmacológico , Demencia/mortalidad , Trastornos del Humor/tratamiento farmacológico , Trastornos del Humor/mortalidad , Anciano , Anciano de 80 o más Años , Antipsicóticos/uso terapéutico , Argentina/epidemiología , Causas de Muerte/tendencias , Estudios de Cohortes , Bases de Datos Factuales/tendencias , Demencia/psicología , Femenino , Humanos , Masculino , Trastornos del Humor/psicología , Mortalidad/tendencias , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Introducción: comprender los factores que condicionan el uso off-label de los agentes monoclonales es crucial para su utilización racional. El objetivo de nuestro estudio fue describir la prevalencia de uso off-label de rituximab y los factores médicos, clínicos y socioeconómicos que se vinculan con dicha práctica. Métodos: estudio de corte transversal retrospectivo. Incluimos pacientes adultos con una primera indicación de rituximab entre 2010 y 2016. La exposición primaria fue definida como el momento de la pérdida de patente de rituximab. Otros factores considerados fueron el diagnóstico de base y las comorbilidades, así como también datos referentes a los médicos tratantes. El evento primario fue la prevalencia de prescripción off-label de rituximab. Utilizamos un modelo de regresión logística para estimar la asociación entre el tiempo y el evento primario. Resultados: de 160 pacientes adultos que iniciaron tratamiento con rituximab y fueron potencialmente elegibles se tomó una muestra aleatoria; 22 de ellos fueron incluidos en el análisis final. La prevalencia de uso off-label fue del 30,4% (IC 95%, 13,9 a 54,9%). No evidenciamos un cambio en el patrón de prescripción de rituximab asociado al tiempo de caída de la patente. El único factor predictor de dicho uso fueron las internaciones previas (7 vs. 1, p = 0,04). Conclusión: el uso off-label de rituximab es frecuente en nuestra población. Futuros estudios deberían estar dirigidos a determinar los factores asociados a esta práctica, así como a estimar el impacto en términos de eficacia y potencial toxicidad en esta población. (AU)
Background: the description of those characteristics that are associated with the off-label use of monoclonal antibodies remains paramount if we are to maximize the rational use of available resources. Our main objective was to describe the prevalence of off-label use of Rituximab, in addition to its associated factors (for example, prescribing physician and patient´s clinical and socioeconomic characteristics). Methods: we designed a retrospective cross-sectional study which included patients starting treatment with Rituximab between 2010 and 2016. Our main exposure was the time when Rituximab´s patent expired. Other potential factors associated with the off-label prescription pattern were baseline diagnosis and comorbidities in addition to the main characteristics of the prescribing physician. The main outcome was the prevalence of off-label use of Rituximab. We used a multivariate logistic regression model in order to estimate the association between time and our main endpoint. Results: out of 160 eligible patients that started treatment with Rituximab we included 22 adult patients in our main analysis by conducting a random sampling procedure. The prevalence of off-label use was 30.4% (95% CI, 13.9 to 54.9%). We did not find a change in the prescription pattern of Rituximab with regards to time and patent expiration. The only factor associated with off-label use were previous hospitalizations (7 vs. 1, p = 0.04). Conclusions: the off-label use of Rituximab is common in our population. Future studies evaluating distinct factors associated with such use as well as its impact in both potential efficacy and toxicity are warranted. (AU)
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Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Adulto Joven , Uso Fuera de lo Indicado/estadística & datos numéricos , Rituximab/administración & dosificación , Prescripciones de Medicamentos/estadística & datos numéricos , Factores Socioeconómicos , Factores Epidemiológicos , Estudios Transversales , Factores de Riesgo , Razón de Prevalencias , Propiedad Intelectual de Productos y Procesos Farmacéuticos , Rituximab/efectos adversos , Rituximab/toxicidad , Rituximab/uso terapéutico , Anticuerpos Monoclonales/administración & dosificaciónRESUMEN
OBJECTIVE: Chronic treatment with antipsychotics may result in both metabolic side effects and cardiovascular disease. Our aim was to evaluate the effect of antipsychotic medications categorized by their metabolic side effect profiles as low, intermediate, or high risk on major cardiovascular events. METHODS: A retrospective cohort study was conducted in adult outpatients aged 30 years or older initiating antipsychotic treatment from 2002 to 2007. Antipsychotic medications were divided into 3 groups (low-, intermediate-, and high-risk) according to the severity of their side-effect profiles in developing metabolic abnormalities associated with cardiovascular disease. The primary outcome measure was the time to the composite of acute myocardial infarction, acute coronary syndrome, ischemic stroke, peripheral artery disease, or a new revascularization procedure. Inverse probability weighting of a marginal structural Cox model was used to adjust for confounding. RESULTS: A total of 1,008 patients were included (mean age = 72.4 years, median follow-up = 36.5 months), and 19.6% of patients experienced the primary outcome. The adjusted hazard ratios of a major cardiovascular event for patients in the high- or intermediate-risk medication groups compared to the low-risk group were 2.82 (95% CI, 1.57-5.05) and 2.57 (95% CI, 1.43-4.63), respectively. CONCLUSIONS: Older adult patients under antipsychotic regimens with high or intermediate risk of metabolic side effects may face a higher incidence of major cardiovascular events than those under a low-risk regimen during long-term follow-up.
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Antipsicóticos , Enfermedades Cardiovasculares , Efectos Adversos a Largo Plazo , Trastornos Mentales/tratamiento farmacológico , Adulto , Anciano , Antipsicóticos/administración & dosificación , Antipsicóticos/efectos adversos , Antipsicóticos/farmacocinética , Argentina/epidemiología , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/metabolismo , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/efectos adversos , Preparaciones de Acción Retardada/farmacocinética , Femenino , Humanos , Incidencia , Efectos Adversos a Largo Plazo/inducido químicamente , Efectos Adversos a Largo Plazo/diagnóstico , Efectos Adversos a Largo Plazo/epidemiología , Efectos Adversos a Largo Plazo/metabolismo , Masculino , Trastornos Mentales/epidemiología , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
BACKGROUND: Behavioral and emotional adverse events induced by drugs commonly prescribed to patients with bipolar disorders are of paramount importance to clinical practice and research. However, no reviews on the topic have been published so far. METHODS: An extensive search was performed. Reports were reviewed if they described behavioral side effects related to pharmacological treatments for bipolar disorders in healthy subjects or patients with different neuropsychiatric disorders. For this review, lithium, antipsychotics, anticonvulsants and selective serotonin reuptake inhibitors were included. RESULTS: Apathy or emotional blunting, diminished sexual desire, and inability to cry were reported to be associated with exposure to selective serotonin reuptake inhibitors. Neuroleptic-induced deficit syndrome/emotional detachment and obsessive-compulsive symptomatology and decision-making modifications. A lithium-related amotivational syndrome was also reported in the literature. Furthermore, hypersexuality and obsessive-compulsive symptoms have been noted in subjects treated with lamotrigine. LIMITATIONS: Primary studies on drug-related adverse events are scant so far and most of the data currently available derive from case reports. Moreover, most of the evidence reviewed is based on studies performed on healthy subjects and patients with neuropsychiatric conditions other than bipolar disorders. DISCUSSION: There is a remarkable dearth of data on behavioral adverse events of pharmacological treatment for bipolar disorders. However, the pieces of evidence available at present, though scant and scattered, suggest that different behavioral adverse events may be related to pharmacological treatment for these disorders. The implications of these findings for research and management of patients with mood disorders are discussed.
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Despite recent findings on the treatment of schizophrenia, it is an illness still associated with high morbidity and incapacity in social and work domains. There is a growing interest in examining the phases prior to the development of the illness so as to make early interventions that would potentially change its devastating course. The attenuated psychosis syndrome was included in the section III of the last version of the Diagnostic and Statistical Manual of Mental Disorders as a condition in which a patient exhibits mild psychotic symptoms, an intact reality testing and certain degree of social or occupational impairment. The present work is a review of the available literature on this subject. The main findings were: the risk of conversion to a psychotic disorder is relatively low and there are some variables (social withdrawal, negative symptoms, neurocognitive impairment, poor global functioning and certain neuroimaging findings) that increase this risk. Those people diagnosed with attenuated psychosis syndrome had one or more other current psychiatric comorbid conditions and these are the main reason to warrant medical attention. Regarding to the treatment of this condition, there are available evidence on atypical antipsychotics, cognitive-behavioral therapy and omega 3 fatty acid.
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Trastornos Psicóticos , Humanos , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/terapia , SíndromeRESUMEN
Abstract Background In recent years, growing interest in the neuropsychology of bipolar disorder has emerged, giving rise to the accumulation of a robust body of evidence on this topic and to several related questions. Objective To provide a state-of-the-art overview of the neuropsychological profile of bipolar disorder. Method A thorough literature search was performed. Published research evidence was summarized and organized along three key pathways: findings from cross-sectional studies of cognition in bipolar patients, cognitive heterogeneity among affected subjects, and trajectory of neuropsychological deficits. Results At least two thirds of bipolar patients display neuropsychological deficits, even in euthymia. Although bipolar disorder was found to be associated with an increased risk of dementia, data from elderly subjects and longitudinal research do not support a worsening of cognitive performance over time. Discussion Cognitive dysfunctions are part of the clinical conceptualization of bipolar illness. However, they may not be present in all affected subjects and their course appears to be stable in most cases. Available evidence may be highlighting the fact that bipolar disorder is characterized by remarkable heterogeneity regarding cognitive outcomes. Different variables may be related to such heterogeneity and should be the focus of therapeutic approaches and further research.
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BACKGROUND: There is an increasing use of ayahuasca for recreational purposes. Furthermore, there is a growing evidence for the antidepressant properties of its components. However, there are no reports on the effects of this substance in the psychiatric setting. Harmaline, one of the main components of ayahuasca, is a selective and reversible MAO-A inhibitor and a serotonin reuptake inhibitor. CASE REPORT: We present the case of a man with bipolar disorder who had a manic episode after an ayahuasca consumption ritual. This patient had had at least one hypomanic episode in the past and is currently depressed. We discuss the diagnostic repercussion of this manic episode. CONCLUSION: There is lack of specificity in the diagnosis of substance-induced mental disorder. The knowledge of the pharmacodynamic properties of ayahuasca consumption allows a more physiopathological approach to the diagnosis of the patient.