Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders guidelines for the treatment of adult obsessive-compulsive disorder. Part II: cognitive-behavioral therapy

Objectives: To summarize evidence-based cognitive-behavioral therapy (CBT) treatment and propose clinical interventions for adult patients with obsessive-compulsive disorder (OCD). Methods: The literature on CBT interventions for adult OCD, including BT and exposure and response prevention, was systematically reviewed to develop updated clinical guidelines for clinicians, providing comprehensive details about the necessary procedures for the CBT protocol. We searched the literature from 2013-2020 in five databases (PubMed, Cochrane, Embase, PsycINFO, and Lilacs) regarding study design, primary outcome measures, publication type, and language. Selected articles were assessed for quality with validated tools. Treatment recommendations were classified according to levels of evidence developed by the American College of Cardiology and the American Heart Association. Results: We examined 44 new studies used to update the 2013 American Psychiatric Association guidelines. High-quality evidence supports CBT with exposure and response prevention techniques as a first-line treatment for OCD. Protocols for Internet-delivered CBT have also proven efficacious for adults with OCD. Conclusion: High-quality scientific evidence supports the use of CBT with exposure and response prevention to treat adults with OCD.

Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders guidelines for the treatment of adult obsessive-compulsive disorder. Part I: pharmacological treatment

Objectives: To summarize evidence-based pharmacological treatments and provide guidance on clinical interventions for adult patients with obsessive-compulsive disorder (OCD). Methods: The American Psychiatric Association (APA) guidelines for the treatment of OCD (2013) were updated with a systematic review assessing the efficacy of pharmacological treatments for adult OCD, comprising monotherapy with selective serotonin reuptake inhibitors (SSRIs), clomipramine, serotonin and norepinephrine reuptake inhibitors (SNRIs), and augmentation strategies with clomipramine, antipsychotics, and glutamate-modulating agents. We searched for the literature published from 2013-2020 in five databases, considering the design of the study, primary outcome measures, types of publication, and language. Selected articles had their quality assessed with validated tools. Treatment recommendations were classified according to levels of evidence developed by the American College of Cardiology and the American Heart Association (ACC/AHA). Results: We examined 57 new studies to update the 2013 APA guidelines. High-quality evidence supports SSRIs for first-line pharmacological treatment of OCD. Moreover, augmentation of SSRIs with antipsychotics (risperidone, aripiprazole) is the most evidence-based pharmacological intervention for SSRI-resistant OCD. Conclusion: SSRIs, in the highest recommended or tolerable doses for 8-12 weeks, remain the first-line treatment for adult OCD. Optimal augmentation strategies for SSRI-resistant OCD include low doses of risperidone or aripiprazole. Pharmacological treatments considered ineffective or potentially harmful, such as monotherapy with antipsychotics or augmentation with ketamine, lamotrigine, or N-acetylcysteine, have also been detailed.

Cognitive profile of patients with and without speech impairment in Parkinson's disease / Perfil cognitivo de pacientes com e sem alteração de fala na doença de Parkinson

ABSTRACT. Cognitive functions have been the subject of studies evaluating the pathophysiological mechanism of speech control. Objective: To compare the groups of patients with and without speech disorders with cognitive assessment, demographic, and clinical data (disease duration, functionality, and motor symptoms). Methods: Retrospective, cross-sectional study. Patients were evaluated using the Addenbrooke's Cognitive Examination III and neuropsychological tests. The following speech subsystems were analyzed: articulation, phonation, resonance, and prosody, through auditory-perceptual evaluation (based on the Protocol for the Evaluation of Acquired Speech Disorders in Individuals with Parkinson's Disease — PADAF Protocol tests), observing aspects of speech programming and execution. The patients were distributed into three subgroups (normal cognition, mild cognitive impairment, and dementia). After speech evaluation, they were divided into two subgroups (with and without speech disorders). Results: A total of 150 patients participated in this study, 104 men and 46 women, 63.58 (8.81) years of age, 11.03 (4.00) years of schooling, 6.61 (4.69) years of disease progression, and with the highest proportion of individuals in stage I-II of the Hoehn & Yarh (H&Y) scale (86, or 57.33%). Statistically significant differences were observed between subgroups with and without speech alteration. Worse performance was verified in the Trail Making Test (TMT) TMT-Δ and a tendency of difference in the TMT-B of the subgroup with speech disorders, in addition to worse severity of motor symptoms (H&Y) and cognitive complaints. Conclusion: Individuals with speech disorders brought more frequent cognitive complaints and impairment below expected in tests assessing executive functions. Future studies, with stratification by type of speech disorder, are necessary to contribute to and validate these results.

RESUMO. As funções cognitivas têm sido alvo de estudos que avaliam o mecanismo patofisiológico do controle da fala. Objetivo: Comparar subgrupos de pacientes com e sem alterações de fala quanto à avaliação cognitiva, dados demográficos e clínicos (tempo de evolução da doença, funcionalidade e gravidade dos sintomas motores). Métodos: Estudo retrospectivo, de corte transversal. Os pacientes foram avaliados pelo Exame Cognitivo de Addenbrooke III e testes neuropsicológicos. Foram analisados os seguintes subsistemas da fala: articulação, fonação, ressonância e prosódia, por meio de avaliação perceptivo-auditiva (baseada em testes do Protocolo de Avaliação dos Distúrbios Adquiridos de Fala em Indivíduos com Doença de Parkinson — PADAF), sendo observados aspectos da programação e execução da fala. Os pacientes foram distribuídos em três subgrupos (cognição normal, comprometimento cognitivo leve e demência). Após a avaliação da fala, foram divididos em dois subgrupos (com desordens da fala e sem desordens da fala). Resultados: Participaram deste estudo 150 pacientes, 104 homens e 46 mulheres, com 63,58 (8,81) anos de idade, 11,03 (4,00) anos de escolaridade e 6,61 (4,69) anos de evolução da doença, e maior proporção de indivíduos no estágio I-II da Escala de Hoehn & Yarh — H&Y (86, ou 57,33%). Foram observadas diferenças estatisticamente significantes entre os subgrupos com e sem alteração da fala. Houve pior desempenho no Trail Making Test (TMT) TMT-Δ e tendência de diferença no TMT-B no subgrupo com desordens da fala, além de pior gravidade dos sintomas motores (H&Y) e queixa cognitiva. Conclusão: Os indivíduos com desordens da fala trouxeram queixas cognitivas com maior frequência e prejuízo abaixo do esperado nos testes que avaliam as funções executivas. Estudos futuros, com estratificação por tipo de distúrbio da fala, são necessários para a contribuição e validação destes resultados.

Sinais de Injúria Cardíaca em Pacientes Pediátricos com COVID-19 Gravemente Enfermos: Uma Experiência de Centro Único no Brasil / Signs of Cardiac Injury in Critically Ill Paediatric Patients with COVID-19: a Single-Center Experience in Brazil

Resumo Fundamento Alguns pacientes com COVID-19 apresentam injúria miocárdica. Objetivo Detectar a injúria miocárdica em pacientes criticamente doentes, e comparar o envolvimento cardíaco entre crianças com síndrome respiratória aguda grave (SARS) e crianças com síndrome inflamatória multissistêmica (MIS-C). Métodos Todas as crianças acometidas da COVID-19 admitidas em uma unidade de terapia intensiva de referência foram cadastradas de forma prospectiva e fizeram uma ecografia transtorácica bidimensional (ETT-2D) e um teste de troponina I cardíaca (cTnI) nas primeiras 72 horas. Para a análise estatística, um p <0,05 bilateral foi considerado significativo. Resultados 33 pacientes foram incluídos, dos quais 51,5% apresentaram cTnI elevada e/ou ETT-2D anormal e 36,4% precisaram de suporte cardiovascular, que foi mais frequente em pacientes com cTnI elevada e anormalidades em ETT-2D do que em pacientes com exames normais (83,3% e 33,3%, respectivamente; p 0,006, 95% IC = 0,15-0,73). Os achados de ETT-2D mais comuns foram efusão pericárdica (15,2%) e regurgitação tricúspide/mitral (15,2%). Sinais de envolvimento cardíaco foram mais comuns na MIS-C que na SARS. Pacientes com MIS-C também apresentaram um índice mais alto de necessidade de suporte cardiovascular (66,7% X 25%, p 0,03, 95% IC = -0,7 a -0,04) e um índice mais frequente de cTnI elevada (77,8% X 20,8%; p 0,002, 95% IC = 0,19 a 0,79). Os valores preditivos negativos de cTnI para detecção de anormalidades de ETT-2D foram 100% para pacientes com MIS-C, e 73,7% para pacientes com SARS. Conclusão Sinais de injúria cardíaca foram comuns, especialmente em pacientes com MIS-C. As anormalidades na ETT-2D foram sutis. A realização de um teste de cTnI na admissão pode ajudar os prestadores de assistência de saúde a discriminar os pacientes com uma necessidade mais urgente de uma ETT-2D.

Abstract Background Some patients with COVID-19 present myocardial injury. Objective To detect myocardial injury in critically ill paediatric patients, and to compare cardiac involvement between children with severe acute respiratory syndrome (SARS) and children with multisystemic inflammatory syndrome (MIS-C). Methods All COVID-19 children admitted to a referral intensive care unit were prospectively enrolled and had a two-dimensional echocardiogram (2D-TTE) and a cardiac troponin I (cTnI) assay within the first 72 hours. For statistical analysis, two-sided p < 0.05 was considered significant. Results Thirty-three patients were included, of which 51.5% presented elevated cTnI and/or abnormal 2D-TTE and 36.4% needed cardiovascular support, which was more frequent in patients with both raised cTnI and 2D-TTE abnormalities than in patients with normal exams (83.3% and 33.3%, respectively; p 0.006, 95% CI = 0.15-0.73). The most common 2D-TTE findings were pericardial effusion (15.2%) and mitral/tricuspid regurgitation (15.2%). Signs of cardiac involvement were more common in MIS-C than in SARS. MIS-C patients also presented a higher rate of the need for cardiovascular support (66.7% vs 25%, p 0.03, 95% CI = -0.7 to -0.04) and a more frequent rate of raised cTnI (77.8% vs 20.8%; p 0.002, 95% CI = 0.19 to 0.79). The negative predictive values of cTnI for the detection of 2D-TTE abnormalities were 100% for MIS-C patients and 73.7% for SARS patients. Conclusion signs of cardiac injury were common, mainly in MIS-C patients. 2D-TTE abnormalities were subtle. To perform a cTnI assay upon admission might help providers to discriminate those patients with a more urgent need for a 2D-TTE.

Gestational diabetes mellitus and obesity are related to persistent hyperglycemia in the postpartum period / Diabetes mellitus gestacional e obesidade estão relacionados à hiperglicemia persistente no período pós-parto

Abstract Objective To evaluate the obstetric and sociodemographic characteristics of gestational diabetic women who maintained hyperglycemia in the postpartum period (6-12 weeks postpartum). Methods This is a longitudinal cohort study with women who have had gestational diabetes and/or macrosomic children between March 1st, 2016 and March 1st, 2017. Between 6 and 12 weeks after birth, women who had gestational diabetes collected fasting glycemia, glucose tolerance test, and glycated hemoglobin results. The data were collected from medical records and during an interview in the first postpartum consultation. A statistical analysis was performed using frequency, percentage, Chi- Squared test, Fisher exact test, Mann-Whitney test, and multivariate Poisson regression. The significance level adopted for the statistical tests was 5%. Results One hundred and twenty-two women were included. Most of the women were younger than 35 years old (70.5%), white, multiparous, and with no history of gestational diabetes. Thirteen percent of the participants developed persistent hyperglycemia. A univariate analysis showed that maternal age above 35 years, being overweight, having grade 1 obesity and weight gain under 5 kg was related to the persistence of hyperglycemia in the postpartum period. Conclusion Maternal age above 35 years, obesity and overweight, and the diagnosis of gestational diabetes in the first trimester of pregnancy are associated with hyperglycemia during the postpartum period.

Resumo Objetivo Avaliar características sociodemográficas e obstétricas de mulheres com diabetes gestacional que mantêm hiperglicemia no período pós-parto (6-12 semanas pós-parto). Métodos Este é um estudo longitudinal de coorte com mulheres com diagnóstico de diabetes gestacional e/ou macrossomia fetal entre 1° de março de 2016 a 1° de março de 2017. As mulheres coletaram glicemia de jejum, teste de tolerância a glicose e hemoglobina glicada entre 6 a 12 semanas pós-parto. Os dados foram coletados de prontuários médicos e durante entrevista na primeira consulta de revisão pós-parto. Uma análise estatística foi realizada através do cálculo de frequências, porcentagens, teste do qui-quadrado, teste exato de Fisher, teste de Mann-Whitney e regressão multivariada de Poisson. A significância estatística adotada foi de 5%. Resultados Cento e vinte e duas mulheres foram incluídas. A maioria delas tinha menos de 35 anos de idade (70,5%), eram brancas, multíparas, e não tinham história de diabetes gestacional. Treze por cento das participantes desenvolveu hiperglicemia persistente. A análise univariada mostrou que os fatores relacionados com a persistência de hiperglicemia no período pós-natal foram: idade materna acima de 35 anos, sobrepeso, obesidade grau 1 e ganho de peso abaixo de 5 quilos. A análisemultivariada incluiu o diagnóstico no primeiro trimestre como fator de risco para hiperglicemia persistente. Conclusão Mulheres acima de 35 anos, obesidade, sobrepeso e diagnóstico de diabetes gestacional no primeiro trimestre estão relacionados com hiperglicemia persistente no período pós-parto.

Sacrospinous ligament suspension with transobturator mesh versus sacral colpopexy for genital prolapse

OBJECTIVE: To compare the safety and efficacy of abdominal sacral colpopexy and sacrospinous ligament suspension with the use of vaginal mesh for apical prolapse. METHOD: This retrospective study was conducted from 2005 to 2012 and included 89 women with apical prolapse who underwent surgery. Assessments included pre- and postoperative Pelvic Organ Prolapse Quantification (POP-Q) stage. Rates of objective cure and immediate/late complications were compared. RESULTS: In total, 41 of the 89 women underwent sacrospinous ligament suspension, and 48 of the women underwent abdominal sacral colpopexy. A total of 40.4% of the women had vault prolapse (p=0.9361). Most of them had no complications (93.2%) (p=0.9418). Approximately 30% of the women had late complications; local pain was the main symptom and was found only in women who underwent the abdominal procedure (25.6%) (p=0.001). Only the women who were submitted to the vaginal procedure had mesh exposure (18.4%). The objective success rate and the rate of anterior vaginal prolapse (p=0.2970) were similar for both techniques. CONCLUSION: Sacrospinous ligament suspension was as effective and had a similar objective success rate as abdominal sacral colpopexy for the treatment of apical prolapse. Sacrospinous ligament suspension performed with the use of vaginal mesh in the anterior compartment was effective in preventing anterior vaginal prolapse after surgery.

Brain derived neurotrophic factor mediated learning, fear acquisition and extinction as targets for developing novel treatments for anxiety / Aprendizado, aquisição e extinção de medo mediados pelo fator neurotrófico derivado do cérebro, como alvos para o desenvolvimento de novos tratamentos para ansiedade

ABSTRACT Anxiety and obsessive-compulsive related disorders are highly prevalent and disabling disorders for which there are still treatment gaps to be explored. Fear is a core symptom of these disorders and its learning is highly dependent on the activity of the neurotrophin brain-derived neurotrophic factor (BDNF). Should BDNF-mediated fear learning be considered a target for the development of novel treatments for anxiety and obsessive-compulsive related disorders? We review the evidence that suggests that BDNF expression is necessary for the acquisition of conditioned fear, as well as for the recall of its extinction. We describe the findings related to fear learning and genetic/epigenetic manipulation of Bdnf expression in animals and BDNF allelic variants in humans. Later, we discuss how manipulation of BDNF levels represents a promising potential treatment target that may increase the benefits of therapies that extinguish previously conditioned fear.

RESUMO Os transtornos da ansiedade e o transtorno obsessivo-compulsivo (TOC) e transtornos relacionados são altamente prevalentes e incapacitantes. Apesar disso, ainda existem lacunas a serem exploradas em relação ao tratamento desses transtornos. O medo é um sintoma central desses transtornos e sua aprendizagem é altamente dependente da atividade do fator neurotrófico derivado do cérebro (BDNF). Porém, será que a aprendizagem de medo mediada pelo BDNF deve ser considerada um alvo para o desenvolvimento de novos tratamentos para transtornos da ansiedade, TOC e transtornos relacionados? Revisamos as evidências que sugerem que a expressão de BDNF é necessária para a aquisição do medo condicionado, bem como para a evocação de sua extinção. Descrevemos os resultados relacionados a aprendizagem de medo, manipulação genética e epigenética da expressão de Bdnf em animais e variantes alélicas de BDNF em seres humanos. Posteriormente, discutimos como a manipulação dos níveis de BDNF representa um alvo em potencial para o tratamento, o que pode aumentar os benefícios das terapias que extinguem o medo previamente condicionado.

Possible solutions to the shortcomings of the Yale-Brown Obsessive-Compulsive Scale / Possíveis soluções para as deficiências da escala de Yale-Brown para avaliação do transtorno obsessivo-compulsivo

OBJECTIVE: The Yale-Brown Obsessive-Compulsive Scale is the most frequently used instrument to measure obsessive-compulsive symptom severity. We describe its shortcomings and propose new methods of evaluating current severity and treatment response. METHOD: The Yale-Brown Obsessive-Compulsive Scale total and subscale scores were pooled from one cross-sectional study database containing information on 1,000 obsessive-compulsive disorder patients from seven specialized mental health care centers. Additional longitudinal data were pooled for 155 patients who participated in a 12-week trial that evaluated the effectiveness of fluoxetine vs. cognitive-behavior therapy as first-line treatment options. All patients were followed by a clinician who provided a clinical opinion of improvement. Neither patients nor clinicians were aware of the classifications proposed in this study. New methods for using the severity scores were compared with the clinical opinion of improvement. RESULTS: In the Yale-Brown Obsessive-compulsive scale, the summing-up of subscale scores to compose a total score does not accurately reflect clinical severity. In addition, the reduction of scores with treatment does not usually reach score zero in either subscale. To overcome such problems, we suggest (a) use of the maximum score of any of the subscales; (b) use of a minimum score of 4 in each subscale or 5 for the maximum in any subscale as the goal after treatment. This method performed better than traditional ones regarding sensitivity and specificity against the gold standard represented by the clinical opinion of improvement. CONCLUSION: The new proposed response criteria are coherent with the clinical opinion of improvement and perform better than the traditional methodology.

RESUMO OBJETIVO: A escala de Yale-Brown para avaliação do transtorno obsessivo-compulsivo é o instrumento mais utilizado para medir a gravidade desse transtorno. Descrevemos as deficiências dessa escala e propomos novos métodos de cálculo dos escores para avaliação de gravidade e resposta ao tratamento. MÉTODO: Os escores totais e subtotais da escala de Yale-Brown foram recuperados de um banco de dados de um estudo transversal com informações sobre 1.000 pacientes com transtorno obsessivo-compulsivos atendidos em sete centros especializados em saúde mental. Foram acrescentados os dados longitudinais de 155 pacientes participantes de um ensaio clínico de 12 semanas que avaliou a eficácia da fluoxetina ou da terapia cognitivo-comportamental como opções de tratamento de primeira linha. Todos os pacientes foram acompanhados por um médico que forneceu um parecer clínico de melhora. Nem os pacientes nem os médicos estavam conscientes das classificações propostas neste estudo. Novos métodos para avaliar os escores de gravidade foram comparados com o parecer clínico de melhora. RESULTADOS: Na escala obsessivo-compulsiva Yale-Brown, a soma de sub-escalas para compor a pontuação total não reflete com precisão a gravidade clínica. Além disso, a redução da pontuação com o tratamento, normalmente, não atinge o valor zero em qualquer das sub-escalas. Para superar esses problemas, sugerimos (a) o uso da pontuação máxima de qualquer das sub-escalas antes do tratamento; (b) o uso de um score mínimo de 4 em cada sub-escala ou um escore mínimo de 5 como o máximo de qualquer das sub-escalas como a meta para o pós-tratamento. Os novos métodos propostos tiveram melhor desempenho do que os tradicionais quanto a sensibilidade e especificidade contra o padrão ouro representado pelo parecer clínico de melhora. CONCLUSÃO: Os novos critérios propostos são coerentes com o parecer clínico de melhora e desempenham melhor do que a metodologia tradicional.

Impacto de um bundle nas taxas de pneumonia associada à ventilação mecânica (PAV) em uma unidade de terapia intensiva pediátrica em Londrina-PR / Impact of the ventilator bundle on ventilator-associated pneumonia (VAP) rates in a pediatric intensive care unit in Londrina-PR

Infecções associadas aos cuidados de saúde (IRAS) constituem importante preocupação à segurança do paciente ao redor do mundo. Pneumonia associada à ventilação mecânica (VAP) é a principal causa de morte entre IRAS, com mortalidade de 15 a 70%, dependendo da população de pacientes. O Centro de Controle e Prevenção de Doenças (CDC) recomendou que todas as UTIs implementassem um bundle depara reduzir a taxa de PAV. Os objetivos do presente estudo foram analisar o efeito do pacote de intervenções de controle da infecção, a educação, as taxas de PAV na Unidade Pediátrica de Terapia Intensiva (UTIP)do Hospital Universitário de Londrina-PR. Este estudo foi realizado entre janeiro e dezembro de 2013 e consistiu em três períodos: pré-intervenção, intervenção e pós-intervenção. A intervenção educativa foi dada a 86 trabalhadores da saúde (PS), e um questionário também foi realizado no pré e pós-intervenção. No geral,foram avaliadas 135 oportunidades de atendimento ao paciente. A higiene das mãos diminuiu do período pré para o pós-intervenção, entretanto a intubação gástrica por via oral, a manutenção da cabeceira da cama entre 30-45º, a pressão do cuff endotraqueal e remoção de condensação do circuito respirador aumentaram significativamente do período pré para o pós-intervenção. A taxa de PAV foi 49,6% durante o período de pré-intervenção e 17,5% durante o período pós-intervenção demonstrando uma redução de 64,8%. Nossos resultados mostram que a implementação do pacote de intervenções de controlo da infecção foi associada com uma redução significativa na taxa de VAP.

Healthcare-associated infections (HAI) are an important patient safety concern around the globe. Ventilator associated pneumonia (VAP) is the leading cause of death among HAI, with attributable mortality ranging from 15 to 70% depending on the patient population. The Center for Disease Control and Prevention (CDC) has recommended that all ICUs implement a ventilator bundle to reduce the VAP rate. The purposes of the present study were to examine the effect of the bundle of infection control interventions, education, VAP rates in the Pediatric Intensive Care Unit (PICU) of the Hospital Universitário of Londrina-PR. This study was conducted between January and December 2013 and consisted of three periods: pre-intervention, intervention and post-intervention. An educational intervention was given to 86 health care workers (HCWs) about bundles to prevent VAP, and a questionnaire was also performed pre and post-intervention. Overall, 135 opportunities of patient care were evaluated. The compliance with hand hygiene and the use of gloves and gowns did not improve, but orotracheal intubation, maintenance of the patients in a 30-45º head of bed elevation, endotracheal cuff pressure and removal of condensate from ventilator circuts increased significantly when comparing pre-and post-intervention. The VAP rate was 49.6% during the pre-intervention period and 17.5% during the post-intervention period demonstrating a 64.8% reduction in VAP rate. Our results show that implementation of the bundle of infection control interventions was associated with a significant reduction in VAP rate.

Outlining new frontiers for the comprehension of obsessive-compulsive disorder: a review of its relationship with fear and anxiety / Desenhando as novas fronteiras para a compreensão do transtorno obsessivo-compulsivo: uma revisão de sua relação com o medo e a ansiedade

Anxiety is an important component of the psychopathology of the obsessive-compulsive disorder (OCD). So far, most interventions that have proven to be effective for treating OCD are similar to those developed for other anxiety disorders. However, neurobiological studies of OCD came to conclusions that are not always compatible with those previously associated with other anxiety disorders. OBJECTIVES: The aim of this study is to review the degree of overlap between OCD and other anxiety disorders phenomenology and pathophysiology to support the rationale that guides research in this field. RESULTS: Clues about the neurocircuits involved in the manifestation of anxiety disorders have been obtained through the study of animal anxiety models, and structural and functional neuroimaging in humans. These investigations suggest that in OCD, in addition to dysfunction in cortico-striatal pathways, the functioning of an alternative neurocircuitry, which involves amygdalo-cortical interactions and participates in fear conditioning and extinction processes, may be impaired. CONCLUSION: It is likely that anxiety is a relevant dimension of OCD that impacts on other features of this disorder. Therefore, future studies may benefit from the investigation of the expression of fear and anxiety by OCD patients according to their type of obsessions and compulsions, age of OCD onset, comorbidities, and patterns of treatment response.

A ansiedade é um componente importante da psicopatologia do transtorno obsessivo-compulsivo (TOC). Até o momento, a maioria das intervenções que provaram ser eficazes para o tratamento de TOC é semelhante àquelas desenvolvidas para outros transtornos de ansiedade. No entanto, estudos que investigaram a neurobiologia do TOC chegaram a conclusões que nem sempre são compatíveis com aquelas anteriormente associadas aos demais transtornos de ansiedade. OBJETIVOS: Neste artigo, revisamos o grau de sobreposição entre as características do TOC e a fenomenologia e fisiopatologia dos demais transtornos de ansiedade com o intuito de dar suporte ao racional que orienta a pesquisa nesse campo. RESULTADOS: Alguns dados sobre os neurocircuitos envolvidos na manifestação dos transtornos de ansiedade foram obtidos a partir do estudo de modelos animais de ansiedade, e da neuroimagem estrutural e funcional em humanos. Esses trabalhos sugerem que no TOC, além da disfunção das vias corticoestriatais, o funcionamento do circuito amigdalocortical, essencial para a apresentação da resposta de medo e processos de extinção dessa resposta, também pode estar prejudicado. CONCLUSÃO: É provável que a ansiedade seja uma dimensão relevante do TOC, com impacto em outras características desse transtorno. Consequentemente, estudos futuros podem se beneficiar da investigação dos fenômenos de medo e ansiedade e de suas relações com os tipos de obsessões e compulsões, idade de início do TOC, comorbidades e padrões de resposta ao tratamento.

Risk factors for early treatment discontinuation in patients with obsessive-compulsive disorder

INTRODUCTION: In obsessive-compulsive disorder, early treatment discontinuation can hamper the effectiveness of first-line treatments. OBJECTIVE: This study aimed to investigate the clinical correlates of early treatment discontinuation among obsessive-compulsive disorder patients. METHODS: A group of patients who stopped taking selective serotonin reuptake inhibitors (SSRIs) or stopped participating in cognitive behavioral therapy before completion of the first twelve weeks (total n = 41; n = 16 for cognitive behavioral therapy and n = 25 for SSRIs) were compared with a paired sample of compliant patients (n = 41). Demographic and clinical characteristics were obtained at baseline using structured clinical interviews. Chisquare and Mann-Whitney tests were used when indicated. Variables presenting a p value <0.15 for the difference between groups were selected for inclusion in a logistic regression analysis that used an interaction model with treatment dropout as the response variable. RESULTS: Agoraphobia was only present in one (2.4 percent) patient who completed the twelve-week therapy, whereas it was present in six (15.0 percent) patients who dropped out (p = 0.044). Social phobia was present in eight (19.5 percent) patients who completed the twelve-week therapy and eighteen (45 percent) patients who dropped out (p = 0.014). Generalized anxiety disorder was present in eight (19.5 percent) patients who completed the twelve-week therapy and twenty (50 percent) dropouts (p = 0.004), and somatization disorder was not present in any of the patients who completed the twelveweek therapy; however, it was present in six (15 percent) dropouts (p = 0.010). According to the logistic regression model, treatment modality (p = 0.05), agoraphobia, the Brown Assessment of Beliefs Scale scores (p = 0.03) and the Beck Anxiety Inventory (p = 0.02) scores were significantly associated with the probability of treatment discontinuation irrespective of interactions with other variables. DISCUSSION AND CONCLUSION: Early treatment discontinuation is a common phenomenon in obsessive-compulsive disorder patients from our therapeutic setting. Psychiatric comorbidities were associated with discontinuation rates of specific treatments. Future studies might use this information to improve management for increased compliance and treatment effectiveness.

Percepção da doença arterial obstrutiva periférica por pacientes classe I ou II de Fontaine de um programa de saúde da família / Perception of the peripheral arterial occlusive disease in Fontaine class I or II patients included in a family health program

CONTEXTO: A doença arterial obstrutiva periférica (DAOP) se destaca por deteriorar a qualidade de vida dos pacientes, quando associada a elevado risco de eventos cardiovasculares e cerebrovasculares. O diagnóstico clínico é sensível e específico, por meio do índice tornozelo-braquial (ITB), que, se precocemente detectado, otimiza o controle dos fatores de risco. OBJETIVO: Avaliar a percepção da DAOP em pacientes classe I ou II de Fontaine assistidos pela Estratégia de Saúde da Família em Pará de Minas (MG), analisando características socioeconômicas e determinantes da qualidade de vida. MÉTODOS: Após cálculo amostral estratificado por gênero e idade, um questionário elaborado para o estudo foi respondido por 123 indivíduos com diagnóstico de DAOP classe I ou II de Fontaine. Para as associações, utilizaram-se testes do c² e exato de Fisher (p<0,05). RESULTADOS: Dos indivíduos que responderam o questionário, 96 (78 por cento) eram do gênero feminino e tinham baixa escolaridade. Observou-se associação entre claudicação intermitente, o sintoma mais frequente da doença, e aperto nas pernas, câimbras, adormecimento dos pés, cansaço, inchaço e agulhadas. Não houve associação com tabagismo, hipertensão arterial sistêmica, diabetes e alteração do colesterol. Dos participantes, 76 (61,8 por cento) nunca ouviram falar da doença, apesar de serem portadores. Dor durante execução de tarefas dentro e fora de casa foi relatada por 48 (39 por cento) indivíduos. A prática de atividade física foi mais recomendada por médico clínico geral - mencionada por 18 (14,6 por cento) indivíduos - sendo que a caminhada, única atividade praticada em níveis recomendados, foi relatada por 102 (27,7 por cento). CONCLUSÃO: É necessário esclarecimento para essa população quanto ao tratamento clínico não-farmacológico para controle das manifestações crônicas irreversíveis. Ressalta-se a relevância da veiculação de informações sobre a evolução silenciosa e sintomatologia da doença.

BACKGROUND: The peripheral arterial occlusive disease (PAOD) is characterized by the deterioration in the quality of life of patients when associated with high risk of cardiovascular or cerebrovascular events. The clinical diagnosis is sensitive and specific, by means of the Ankle Brachial Pressure Index (ABPI), and, when there is early detection, the control of risk factors is optimized. OBJECTIVE: To assess the perception of PAOD in Fontaine class I or II patients by means of the Family Health Strategy in Pará de Minas (MG), Brazil, through an analysis of the socioeconomic characteristics and life quality determinants. METHODS: After the sample calculation, stratified by genre and age, a questionnaire elaborated for the purposes of this study was applied to 123 individuals who were diagnosed with Fontaine class I or II PAOD. Aiming at the associations, the c² and Fisher's exact tests were used (p<0.05). RESULTS: Among the participants who answered to the questionnaire, 96 (78 percent) were women and had low schooling. An association between intermittent claudication, the most common symptom, and the sensation of pressure on the legs, cramps, foot paresthesia, fatigue, swelling, and tingling was observed. There was no association with smoking, systemic arterial hypertension, diabetes and cholesterol alterations. Among the participants, 76 (61.8 percent) had never heard about the disease despite the fact that they had it. Pain during activities at home or elsewhere was reported by 48 individuals (39 percent). The practice of physical activities was more recommended by clinicians - mentioned by 18 (14.6 percent) individuals - and walking, the only activity that was practiced according to the recommended levels, was reported by 102 participants (27.7 percent)...

Estratégia de potencialização medicamentosa no transtorno obsessivo-compulsivo resistente: um estudo duplo-cego controlado / Pharmacological augmentation strategies in treatment resistant obsessive-compulsive disorder: a double-blind placebo-controlled trial

O transtorno obsessivo-compulsivo (TOC) é um transtorno psiquiátrico freqüentemente crônico caracterizado pela presença de obsessões e/ou compulsões. Tratamentos de primeira linha, que incluem os inibidores seletivos da recaptura de serotonina (ISRS) e a terapia cognitivocomportamental com técnicas de exposição e prevenção de respostas não conseguem melhora satisfatória em até 40% dos pacientes. Para estes casos, existem evidências que apóiam o uso de antipsicóticos como a quetiapina, na potencialização dos ISRS. No entanto, os antipsicóticos são eficazes para apenas um terço dos pacientes e estão associados a eventos adversos preocupantes no longo prazo. Este estudo tem como objetivo comparar a eficácia da potencialização do ISRS fluoxetina com a clomipramina, um inibidor de recaptura da serotonina não-seletivo, ou quetiapina, versus placebo. Para inclusão neste estudo, os pacientes precisavam: relatar os sintomas de TOC como sendo seu problema principal; estar em uso da dose máxima tolerada ou recomendada de fluoxetina por pelo menos oito semanas; ter um escore total na escala Yale Brown Obsessive-Compulsive Disorder Scale (YBOCS) de pelo menos 16; e ter tido uma redução do escore inicial da YBOCS menor do que 35% após tratamento com fluoxetina. Os pacientes (N=54) foram alocados por meio de um método de minimização em três grupos: quetiapina (até 200mg/dia) com fluoxetina (até 40mg/dia) (QTP/FLX) (N=18); clomipramina (até 75mg/dia) com fluoxetina (até 40mg/dia) (CMI/FLX) (N=18); e placebo com dose máxima de fluoxetina (até 80mg/dia) (PLC/FLX) (N=18). Avaliadores cegos obtiveram os escores da YBOCS nas semanas 0 e 12. As análises foram realizadas por intenção de tratar, com imputação do tipo hot-deck para os dados faltantes. Teste de Wald por ANCOVA não paramétrico para medidas ordinais repetidas foi utilizado para avaliar efeitos de grupo, tempo e interação para os resultados da YBOCS e desfechos secundários, tendo as medidas iniciais como co-variáveis...

Obsessive-compulsive disorder (OCD) manifests often as a chronic illness and is characterized by the presence of obsessions and compulsions. Firstline treatment options, which include selective serotonin reuptake inhibitors (SSRI) and cognitive-behavior therapy with exposure and response prevention techniques, fail to achieve a satisfactory response in up to 40% of patients. Current evidence supports the augmentation of SSRI with antipsychotics, such as quetiapine. However, anti-psychotics are effective for only one-third of the patients and have been associated with severe long term side effects. This study aimed to compare clomipramine and quetiapine augmentation of the SSRI fluoxetine. Previously to the beginning of this trial all patients had to: report OCD as they primary diagnosis, be taking the highest tolerated or recommended dose of fluoxetine for at least eight weeks, have a current Yale Brown Obsessive-Compulsive Scale (YBOCS) total of at least 16, and have had a reduction of less than 35% of the initial total YBOCS score with fluoxetine treatment. Fifty-four patients were allocated trough a minimization procedure in one of three arms: quetiapine (up to 200 mg/day) plus fluoxetine (up to 40 mg/day) (QTP/FLX) (N=18), clomipramine (up to 75 mg/day) plus fluoxetine (up to 40 mg/day) (CMI/FLX) (N=18) and 18 placebo plus sustained maximum dose fluoxetine (up to 80 mg/day) (PLC/FLX) (N=18). Blinded raters collected YBOCS scores at weeks 0 and 12. Analyses were made with intention-to-treat and hot-deck imputation of missing data. Wald statistics from non-parametric ANCOVA for ordinal categorical repeated measures were used to evaluate group, time and interaction effects for YBOCS scores and secondary outcome measures considering initial measures as covariates. Clinical Global Impression scores of improvement (CGI-I) were used to classify individuals in responders or non-responders. Chi-square was used to evaluate frequency of responders in each group...

The drug-naïve OCD patients imaging genetics, cognitive and treatment response study: methods and sample description / Estudo de genética, imagem, cognição e resposta a tratamento em pacientes com TOC virgens de tratamento: métodos e descrição da amostra

OBJECTIVE: To describe a protocol that was based on an integrative neurobiological model of scientific investigation to better understand the pathophysiology of obsessive-compulsive disorder and to present the clinical and demographic characteristics of the sample. METHOD: A standardized research protocol that combines different methods of investigation (genetics, neuropsychology, morphometric magnetic resonance imaging and molecular neuroimaging of the dopamine transporter) obtained before and after treatment of drug-naïve adult obsessive-compulsive disorder patients submitted to a sequentially allocated 12-week clinical trial with a selective serotonin reuptake inhibitor (fluoxetine) and group cognitive-behavioral therapy. RESULTS: Fifty-two treatment-naïve obsessive-compulsive disorder patients entered the clinical trial (27 received fluoxetine and 25 received group cognitive-behavioral therapy). At baseline, 47 blood samples for genetic studies, 50 neuropsychological evaluations, 50 morphometrical magnetic resonance images and 48 TRODAT-1 single-photon emission computed tomography (SPECT) exams were obtained. After 12 weeks, 38 patients completed the protocol (fluoxetine = 20 and GCBT = 18). Thirty-eight neuropsychological evaluations, 31 morphometrical magnetic resonance images and 34 TRODAT-1 SPECT exams were obtained post-treatment. Forty-one healthy controls matched for age, gender, socioeconomic status, level of education and laterality were submitted to the same research procedures at baseline. CONCLUSION: The comprehensive treatment response protocol applied in this project allowing integration on genetic, neuropsychological, morphometrical and molecular imaging of the dopamine transporter data in drug-naïve patients has the potential to generate important original information on the neurobiology of obsessive-compulsive disorder, and at the same time be clinically meaningful.

OBJETIVO: Descrever um protocolo integrativo de investigação neurobiológica para melhor compreender as bases patofisiológicas do transtorno obsessivo-compulsivo e apresentar as características clínicas e demográficas da amostra. MÉTODO: Protocolo padronizado que combina diferentes modalidades de investigação (genética, neuropsicologia, ressonância magnética cerebral e imagem molecular do transportador de dopamina) obtidas antes e depois do tratamento em pacientes com transtorno obsessivo-compulsivo nunca expostos à medicação submetidos a um ensaio clínico comparando um inibidor seletivo da recaptação de serotonina (fluoxetina) e terapia cognitivo-comportamental em grupo. RESULTADOS: Cinquenta e dois pacientes com transtorno obsessivo-compulsivo entraram no ensaio clínico (27 no grupo fluoxetina e 25 no grupo de terapia). No início, foram realizadas 47 coletas de sangue para genética, 50 avaliações neuropsicológicas, 50 ressonâncias magnéticas cerebrais e 48 exames de tomografia computadorizada por emissão de fóton único (SPECT) com TRODAT-1. Depois de 12 semanas, 38 pacientes terminaram o protocolo (20 no grupo de fluoxetina e 18 no grupo de terapia). Trinta e oito reavaliações neuropsicológicas, 31 ressonâncias magnéticas de crânio e 34 exames de SPECT foram obtidos após o tratamento. Quarenta e um controles pareados foram submetidos ao mesmo protocolo inicial. CONCLUSÃO: Os dados genéticos, neuropsicológicos, volumétricos e moleculares do transportador de dopamina aliados à resposta a tratamento podem tanto gerar informações importantes a respeito da neurobiologia do transtorno obsessivo-compulsivo quanto ter uma aplicação clínica.

Experiência inicial de um novo centro no Brasil na abordagem híbrida para a síndrome de hipoplasia do coração esquerdo / Hybrid approach for treatment of the hypoplastic left heart syndrome: initial experience of a new center in Brazil

Objetivo: Apresentar os resultados iniciais com o emprego do procedimento híbrido na síndrome de hipoplasia do coração esquerdo (SHCE). Método: Oito pacientes com SHCE foram submetidos ao primeiro estágio do procedimento. As indicações foram: preferência do grupo em quatro (50%) pacientes, infecção sistêmica em evolução em dois (25%), disfunção ventricular grave em um (12,5%) e lesão encefálica grave com hipertensão pulmonar em um (12,5%). Resultados: Três (37,5%) pacientes morreram no primeiro estágio, dois (25%) foram submetidos ao segundo estágio, e nenhum foi submetido ao terceiro estágio. Três (37,5%) crianças aguardam o segundo estágio, e duas delas estão internadas, uma por insuficiência respiratória grave e infecção sistêmica e outra pós-atriosseptostomia com colocação de stent, evoluindo com infecção pulmonar. Reintervenções foram necessárias em 50% dos casos, em dois deles mais de uma vez (atriosseptostomias por balão em três e colocação de stent na comunicação interatrial em um). O tempo médio de ventilação no primeiro estágio foi de 585 horas e de internação na unidade de terapia intensiva, de 32 dias. Duas crianças já oram submetidas ao segundo estágio e ambas morreram: morte súbita em uma e durante dilatação da artéria pulmonar esquerda por estenose residual em outra...

Objective: Our objective was to review the early results of hybrid procedures in hypoplastic left heart syndrome (HLHS) at our institution. Methods: Eight HLHS patients were submitted to the first stage of the procedure and the indications were the surgeon's preference in 4 (50%), sepsis in 2 (25%), severe ventricular dysfunction in 1 (12.5%) and severe brain damage with pulmonary hypertension in the latter (12.5%). Results: Three (37.5%) patients died after the intervention, 2 (25%) underwent the second stage and none underwent the third stage. Three (37.5%) patients are currently waiting for the second stage and 2 of these are currently hospitalized: one with pneumonia-related sepsis and the other with pneumonia post atrial septal defect stenting. Reinterventions were necessary in 50% of the cases, more than once in 2 patients (balloon atrioseptostomy in 3 and atrial septal defect stenting in 1). Mean mechanical ventilation duration in the first stage was 585 hours and mean hospitalization time in the intensive care unit was 32 days. Both patients undergoing the second stage died: sudden death in one and residual left pulmonary artery stenosis after percutaneous dilatation in the other...

Sequential allocation to balance prognostic factors in a psychiatric clinical trial

OBJECTIVE: This paper aims to describe and discuss a minimization procedure specifically designed for a clinical trial that evaluates treatment efficacy for OCD patients. METHOD: Aitchison's compositional distance was used to calculate vectors for each possibility of allocation in a covariate adaptive method. Two different procedures were designed to allocate patients in small blocks or sequentially one-by-one. RESULTS: We present partial results of this allocation procedure as well as simulated data. In the clinical trial for which this procedure was developed, successful balancing between treatment arms was achieved. Separately, in an exploratory analysis, we found that if the arrival order of patients was altered, most patients were allocated to a different treatment arm than their original assignment. CONCLUSION: Our results show that the random arrival order of patients determine different assignments and therefore maintains the unpredictability of the allocation method. We conclude that our proposed procedure allows for the use of a large number of prognostic factors in a given allocation decision. Our method seems adequate for the design of the psychiatric trials used as models. Trial registrations are available at clinicaltrials.gov NCT00466609 and NCT00680602.