Risk of neutropenia among clozapine users and non-users: results from 5,847 patients

Objective: Clozapine is underprescribed due to neutropenia risk. Blood tests every 3 months in those on continuous treatment for > 1 year who have never had an absolute neutrophil count (ANC) < 2,000/µL has been proposed as a monitoring strategy; however, there are no South American data to support this recommendation. This study sought to investigate whether clozapine use and other variables could explain the occurrence of ANC < 1,000/µL in patients with severe mental disorders. Methods: A total of 5,847 subjects were included, 1,038 on clozapine. We performed a Cox regression considering the outcome as ANC < 1,000/µL at any time point. Predictors were sex, age, ethnicity, clozapine use, ANC > 2,000/µL during the first year of blood monitoring, and presence of a severe medical condition. Results: In the Cox regression model, ethnicity (white) (hazard ratio [HR] 0.53; 95%CI 0.29-0.99, p < 0.05) and ANC > 2,000/µL (HR 0.04; 95%CI 0.01-0.10, p < 0.001) were protective factors, while presence of a severe medical condition (HR 69.35; 95%CI 37.45-128.44, p < 0.001) was a risk factor for ANC < 1,000/µL. Other variables were not significant, including clozapine use (HR 1.33; 95%CI 0.74-2.39, p > 0.05). Conclusions: These findings suggest that clozapine does not increase the risk of neutropenia in subjects with ANC > 2,000/µL during the first year of use and in the absence of a severe medical condition. These results could help guide clinical and public-health decisions regarding clozapine blood monitoring guidelines.

Management of the pseudobulbar affect (PBA) in Kabuki syndrome combined dextromethorphan-fluoxetine treatment as an alternative to dextromethorphan/quinidine

A case report of a patient with pseudo bulbar affect previous treatments included haloperidol (10mg), Inosina pranobex (600mg), clozapine (600mg), olanzapine (20mg), carbamazepine (200mg), paroxetine (20mg), phenobarbital (100mg) and topiramate (50mg), all suspended at August 2016, with current use of quetiapine (700mg) Chlorpromazine (600mg) (+ 200mg on demand of aggression), clonazepam (4 mg), valproate 2500 mg, propranolol (40mg). that was successful treated with off label treatment (dextromethorphan plus quinidine). Previous Brief Psychiatric Rating Scale and Clinical Global Impression-Improvement was applied after and before treatment with dextromethorphan (20mg) plus fluoxetine (20 mg, further increased to 40 mg). Previous Brief Psychiatric Rating Scale BPRS score 56 points and Clinical Global Impression-Severity (CGI-S) Score was 6 (severely ill). The addition of dextromethorphan (20mg) and fluoxetine (20 mg, further increased to 40 mg), allowed clear improvement of pathological crying and outbursts, with BPRS decrease of 8 points and Clinical Global Impression-Improvement (CGI-I) 2 (much improved) ­ especially pertaining to PBA related symptoms and aggressive behavior. There were no noticeable side-effects. This case report shown an interesting clinical response. It's could be a great alternative in treatment of pseudobulbar affect symptoms. Even though an only case and a great clinical study be necessary. (AU)

Neurobiological underpinnings of bipolar disorder focusing on findings of diffusion tensor imaging: a systematic review

Objective: To review the available data on diffusion tensor imaging (DTI) of subjects with bipolar disorder (BD), with a particular focus on fractional anisotropy (FA) in white matter (WM) tracts. Methods: The PubMed/MEDLINE database was searched for relevant articles, which were included in a systematic review of the literature. FA reductions and WM abnormalities were divided anatomically into three groups: commissural tracts, association tracts, and projection tracts. Results: Eighteen studies met the inclusion criteria. The corpus callosum was the main impaired commissural tract as demonstrated by FA reductions. Five studies reported FA reductions in the cingulum. Two studies reported decreased FA in the anterior thalamic radiation, and one in the corticospinal tract. Conversely, three studies found increased FA values in WM tracts involved in BD pathophysiology. Conclusion: Despite considerable heterogeneity, these results indicate a direct link between executive cognitive functioning and abnormal WM microstructural integrity of fronto-limbic tracts in patients with remitted BD, providing further evidence of the neuronal disruption that underlies BD symptomatology.

Grau de escolaridade materna e baixo peso ao nascer: uma meta-análise / Maternal education level and low birth weight: a meta-analysis

OBJETIVO: Analisar a associação entre grau de escolaridade materna e peso de nascimento, considerando-se a hipótese de que a utilização em excesso das tecnologias na área da saúde, assim como a escassez de recursos, pode produzir desfechos similares. MÉTODOS: Realizou-se uma meta-análise com estudos transversais e de coorte, selecionados por revisão sistemática na base de dados bibliográficos MEDLINE com os descritores: socioeconomic factors; infant, low birth weight; cohort studies; cross-sectional studies. As medidas de sumário de efeito foram obtidas pelo modelo de efeito aleatório, e os seus resultados apresentados por intermédio dos gráficos Forest Plot. O viés de publicação foi analisado pelo Teste de Egger, e a avaliação da qualidade dos estudos utilizou a Escala de Newcastle-Ottawa. RESULTADOS: A busca inicial encontrou 729 artigos. Destes, foram excluídos 594, após a leitura do título e do resumo; 21, após reuniões de consenso entre os três revisores; 102, após leitura do texto completo; e três, por não possuírem o desfecho adequado. Dos nove artigos finais, 88,8% apresentavam uma qualidade igual ou superior a seis estrelas (Escala de Newcastle-Ottawa), configurando boa qualidade aos estudos. A heterogeneidade dos artigos foi considerada moderada. A escolaridade materna elevada mostrou um efeito protetor de 33% sobre o baixo peso ao nascer, enquanto que o grau médio não apresentou proteção significativa, quando comparados à escolaridade materna baixa. CONCLUSÕES: A hipótese de similaridade entre os graus extremos da distribuição social, traduzidas pelo nível de escolaridade materna, em relação à proporção de baixo peso ao nascer, não foi confirmada.

OBJECTIVE: To assess the association between maternal education level and birth weight, considering the circumstances in which the excess use of technology in healthcare, as well as the scarcity of these resources, may result in similar outcomes. METHODS: A meta-analysis of cohort and cross-sectional studies was performed; the studies were selected by systematic review in the MEDLINE database using the following key words: socioeconomic factors, infant, low birth weight, cohort studies, cross-sectional studies. The summary measures of effect were obtained by random effect model, and its results were obtained through forest plot graphs. The publication bias was assessed by Egger’s test, and the Newcastle-Ottawa scale was used to assess study quality. RESULTS: The initial search found 729 articles. Of these, 594 were excluded after reading the title and abstract; 21, after consensus meetings among the three reviewers; 102, after reading the full text; and three for not having the proper outcome. Of the nine final articles, 88.8% had quality > six stars (Newcastle-Ottawa Scale), showing good quality studies. The heterogeneity of the articles was considered moderate. High maternal education showed a 33% protective effect against low birth weight, whereas medium degree of education showed no significant protection when compared to low maternal education. CONCLUSIONS: The hypothesis of similarity between the extreme degrees of social distribution, translated by maternal education level in relation to the proportion of low birth weight, was not confirmed.