Sex differences in residual somatic symptoms in patients with first-episode depression after acute-phase treatment.

BACKGROUND: Residual somatic symptoms (RSS) are common in depressed patients, predicting treatment effectiveness. However, sex differences in RSS have received little systematic study. This study was conducted to compare sex differences of RSS in patients with first-episode depression (FED). METHODS: Nine hundred eighty-two patients with FED were selected and treated for 8 to 12 weeks. We evaluated the subjects' socio-demographic characteristics and residual depressive symptoms. Using the Patient Health Questionnaire-15 (PHQ-15) scale to assess residual somatic symptoms, the Sheehan Disability Scale (SDS) for the assessment of patients' function, the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) for quality of life. RESULTS: The incidence of RSS with FED was 46.4%. For patients with residual symptoms, the age and age of onset in females were higher than males, but males had more years of education than females. The degree of "stomach pain" in females was more severe than in males, while "trouble sleeping" in males was more severe than that in females. Multiple regression analysis showed that the total Q-LES-Q-SF score was an independent influencing factor of RSS in both males and females, while the total SDS score only affected female RSS. CONCLUSIONS: The prevalence of RSS in FED after acute-phase treatment is high. The symptom of "stomachache" is more pronounced in females, while "trouble sleeping" is more severe in males. Quality of life plays an essential role in RSS in both genders. Thus, sex needs to be considered when assessing the relationship between RSS and therapeutic effect in depression.

Design and in vivo evaluation of solid lipid nanoparticulate systems of Olanzapine for acute phase schizophrenia treatment: Investigations on antipsychotic potential and adverse effects.

The present paper discusses the design, characterization and in vivo evaluation of glyceryl monostearate nanoparticles of Olanzapine, an atypical antipsychotic drug for acute schizophrenia treatment, during which hospitalization is mandatory and adverse effects are at its peak. The solid lipid nanoparticulate system was obtained by emulsification-ultra sonication technique wherein three factors such as solid lipid content, concentration of surfactant and drug: solid lipid ratio were selected at three different levels in order to study their influence on significant characteristic responses such as particle size, encapsulation efficiency and drug content. A Box Behnken design with 17 runs involving whole factors at three levels was employed for the study. The optimized formulation was further coated with Polysorbate 80 in order to enhance its brain targeting potential through endocytosis transport process via blood brain barrier. The designed formulations were pre-clinically tested successfully in Wistar rat model for in vivo antipsychotic efficacy (apomorphine induced psychosis) and adverse effects (weight gain study for 28days). The results obtained indicated that solid lipid nanoparticles had very narrow size distribution (151.29±3.36nm) with very high encapsulation efficiency (74.51±1.75%). Morphological studies by SEM have shown that solid lipid nanoparticles were spherical in shape with smooth surface. Olanzapine-loaded nanoparticles prepared from solid lipid, extended the release of drug for 48h, as found by the in vitro release studies. The formulations also exhibited high redispersibility after freeze-drying and stability study results demonstrated good stability, with no significant change for a period of 6months. In vivo evaluation and adverse effects studies of Olanzapine-loaded nanoparticulate systems in animal model have demonstrated an improved therapeutic efficacy than pure Olanzapine. The antipsychotic effect of drug loaded nanoparticulate systems was maintained for 48h as compared to 8h antipsychotic action of pure Olanzapine solution. The weight gain studies for 28days demonstrated a significant inhibition in weight gain for Olanzapine-loaded nanoparticulate systems as compared to the pure Olanzapine. The present research findings indicate that OLN-loaded nanoparticulate systems may be highly promising for effective delivery of Olanzapine with better efficacy and minimum adverse effects.

A closer look at acute heart failure: Putting Portuguese and European data into perspective.

INTRODUCTION AND OBJECTIVES: Acute heart failure (AHF) is a heterogeneous clinical syndrome requiring urgent therapy. The prognosis is poor after the index hospitalization, with a high risk for rehospitalization and early death. The costs of managing AHF are thus increasing rapidly. A literature review was performed to gather and compare data on prevalence and treatment and to identify gaps in AHF management, based on European and Portuguese studies. METHODS: A literature search from 1995 to 2014 was conducted in selected databases (BIOSIS Previews, EMBASE and Ovid MEDLINE). RESULTS AND DISCUSSION: Seven Portuguese and nine European studies were analyzed. The mean age of AHF patients was ≥65 years and 30-50% were women. Coronary artery disease (42.3% vs. 61.9%) and hypertension (53.3% vs. 76.7%) were identified as primary etiologies in Europe and in Portugal. Similar proportions of heart failure with preserved ejection fraction were found in the Portuguese (19.9-44.7%) and European (32.8-39.1%) studies. Overall, all-cause mortality rates were comparable (six months: 9.3-25.5% vs. 13.5-27.4%; one year: 15.9-31% vs. 17.4-46.5%), as was in-hospital mortality (5.5-14% vs. 3.8-12%) in Portuguese and European studies, respectively. Length of stay was comparable. The studies were performed in very different hospital settings and data on treatment were scarce. CONCLUSIONS: Gaps were identified in treatment and clinical pathways of patients with AHF. Based on the results of this review, collection and investigation of data on the disease and treatment solutions, training in disease management, and improved organization of healthcare should be the subject of further investment.

Tratamiento con antipsicóticos en la fase aguda del paciente adulto con diagnóstico de esquizofrenia / Antipsychotic Treatment of the Adult Patient in the Acute Phase of Schizophrenia

Objetivos: Determinar la efectividad y seguridad de los diferentes antipsicóticos para el manejo de los pacientes adultos con diagnóstico de esquizofrenia en fase aguda. Formular las recomendaciones sobre las estrategias del manejo farmacológico con antipsicóticos (AP) basadas en la evidencia para el tratamiento del adulto con diagnóstico de esquizofrenia en fase aguda. Método: Se elaboró una guía de práctica clínica bajo los lineamientos de la Guía Metodológica del Ministerio de Salud y Protección Social para identificar, sintetizar, evaluar la evidencia y formular recomendaciones respecto al manejo y seguimiento de los pacientes adultos con diagnóstico de esquizofrenia. Se adoptó y actualizó la evidencia de la guía NICE 82, que contestaba la pregunta sobre manejo de fase aguda de los adultos con diagnóstico de esquizofrenia. Se presentó la evidencia y su graduación al grupo desarrollador de la guía (GDG) para la formulación de las recomendaciones siguiendo la metodología propuesta por el abordaje GRADE. Resultados: La clozapina, olanzapina, risperidona, ziprasidona, amisulprida, paliperidona, haloperidol, quetiapina y aripiprazol fueron más eficaces que el placebo para la mejoría de síntomas psicóticos y el abandono del tratamiento, pero no lo fue la asenapina. La paliperidona, risperidona, quetiapina, clozapina y olanzapina presentaron incrementos significativos de peso al compararlos con placebo. El haloperidol, risperidona, ziprasidona y paliperidona tuvieron mayor riesgo de síntomas extrapiramidales que el placebo. Tuvieron un riesgo significativo de sedación o somnolencia: risperidona, haloperidol, ziprasidona, quetiapina, olanzapina y clozapina en las comparaciones con placebo. De los resultados de las comparaciones entre AP se evidenció que la clozapina y la paliperidona mostraron una efectividad clínicamente significativa frente al haloperidol y la quetiapina, respectivamente. La olanzapina y la risperidona tuvieron menor riesgo de abandono del tratamiento en general y por efectos adversos en dos comparaciones cada uno, el haloperidol fue el medicamento con más riesgo de abandono por efectos adversos, seguido por la clozapina. La amisulprida, el haloperidol y la ziprasidona tuvieron resultados favorables en varias comparaciones respecto al aumento de peso. El aripiprazol y la paliperidona obtuvieron un mayor número de resultados favorables en cuanto a sedación, y todos los atípicos (salvo la paliperidona) tuvieron menos riesgo de uso de antiparkinsonianos. De la evidencia de los estudios observacionales se encontró que en sujetos con factores de riesgo para diabetes, como son la edad, la hipertensión y la dislipidemia, el tratamiento inicial y actual con olanzapina, así como el tratamiento actual con clozapina, pueden promover el desarrollo de esta enfermedad. Conclusión: Es imperativo prescribir un antipsicótico para el tratamiento de la fase aguda; sin embargo, la selección del medicamento está supeditada a la condición clínica particular de cada paciente y al perfil de efectos colaterales de estos.

Objectives: To determine the efficacy and safety of different antipsychotic drugs in the management of patients diagnosed with schizophrenia in the acute phase. To formulate evidence-based recommendations on the antipsychotic (AP) drug management strategies for the treatment of the adult diagnosed with schizophrenia in the acute phase. Method: Clinical practice guidelines were prepared, using the guidelines of the Methodology Guide of the Ministry of Health and Social Protection, in order to identify, synthesise, and evaluate the evidence and formulate recommendations as regards the management and follow-up of adult patients diagnosed with schizophrenia. The evidence of the NICE 82 guideline was adopted and updated, which answered the question on the management of the acute phase of adults with a diagnosis of schizophrenia. The evidence and its level were presented to the Guideline Development Group (GDG) in order to formulate recommendations following the methodology proposed by the GRADE approach. Results: Clozapine, olanzapine, risperidone, ziprasidone, amisulpride, paliperidone, haloperidol, quetiapine, and aripiprazole were more effective than placebo for the majority of psychotic symptoms and the abandonment of treatment, but asenapine was not. Paliperidone, risperidone, quetiapine, clozapine, and olanzapine showed significant increases in weight compared to placebo. Haloperidol, risperidone, ziprasidone, and paliperidone had a higher risk of extrapyramidal symptoms than placebo. There was a significant risk of sedation or drowsiness with, risperidone, haloperidol, ziprasidone, quetiapine, olanzapine, and clozapine in the comparisons with placebo. Of the results of the comparisons between AP, it was shown that clozapine and paliperidone had a clinically significant effect compared to haloperidol and quetiapine, respectively. Olanzapine and risperidone had a lower risk of abandoning the treatment in general, and due to adverse reactions in two comparisons of each one, haloperidol was the drug with more risk of abandoning due to adverse effects, followed by clozapine. Amisulpride, haloperidol and ziprasidone had favourable results as regards weight increase in several comparisons. Aripiprazole and paliperidone obtained a higher number of favourable results as regards sedation, and all the atypical drugs (except paliperidone) had a lower risk than the use of anti-parkinsonian drugs. Of the evidence from observational studies, it was found that, in subjects with risk factors for diabetes, such as age, hypertension, and dyslipidaemia, the initial treatment and current treatment with olanzapine, as well as current treatment with clozapine, may promote the development of this disease. Conclusion: Although it is imperative to prescribe an antipsychotic for treatment of the acute phase, the selection of the drug depends on the particular clinical condition of each patient and their collateral effects profile.

Brain proteomics identifies potential simvastatin targets in acute phase of stroke in a rat embolic model.

Finding an efficient neuroprotectant is of urgent need in the field of stroke research. The goal of this study was to test the effect of acute simvastatin administration after stroke in a rat embolic model and to explore its mechanism of action through brain proteomics. To that end, male Wistar rats were subjected to a Middle Cerebral Arteria Occlusion and simvastatin (20 mg/kg s.c) (n = 11) or vehicle (n = 9) were administered 15 min after. To evaluate the neuroprotective mechanisms of simvastatin, brain homogenates after 48 h were analyzed by two-dimensional fluorescence Difference in Gel Electrophoresis (DIGE) technology. We confirmed that simvastatin reduced the infarct volume and improved neurological impairment at 48 h after the stroke in this model. Considering our proteomics analysis, 66 spots, which revealed significant differences between groups, were analyzed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry allowing the identification of 27 proteins. From these results, we suggest that simvastatin protective effect can be partly explained by the attenuation of the oxidative and stress response at blood-brain barrier level after cerebral ischemia. Interestingly, analyzing one of the proteins (HSP75) in plasma from stroke patients who had received simvastatin during the acute phase, we confirmed the results found in the pre-clinical model. Our aim was to study statins benefits when administered during the acute phase of stroke and to explore its mechanisms of action through brain proteomics assay. Using an embolic model, simvastatin-treated rats showed significant infarct volume reduction and neurological improvement compared to vehicle-treated group. Analyzing their homogenated brains by two-dimensional fluorescence Difference in Gel Electrophoresis (DIGE) technology, we concluded that the protective effect of simvastatin can be attributable to oxidative stress response attenuation and blood-brain barrier protection after cerebral ischemia.

[Antipsychotic Treatment of the Adult Patient in the Acute Phase of Schizophrenia]. / Tratamiento con antipsicóticos en la fase aguda del paciente adulto con diagnóstico de esquizofrenia.

OBJECTIVES: To determine the efficacy and safety of different antipsychotic drugs in the management of patients diagnosed with schizophrenia in the acute phase. To formulate evidence-based recommendations on the antipsychotic (AP) drug management strategies for the treatment of the adult diagnosed with schizophrenia in the acute phase. METHOD: Clinical practice guidelines were prepared, using the guidelines of the Methodology Guide of the Ministry of Health and Social Protection, in order to identify, synthesise, and evaluate the evidence and formulate recommendations as regards the management and follow-up of adult patients diagnosed with schizophrenia. The evidence of the NICE 82 guideline was adopted and updated, which answered the question on the management of the acute phase of adults with a diagnosis of schizophrenia. The evidence and its level were presented to the Guideline Development Group (GDG) in order to formulate recommendations following the methodology proposed by the GRADE approach. RESULTS: Clozapine, olanzapine, risperidone, ziprasidone, amisulpride, paliperidone, haloperidol, quetiapine, and aripiprazole were more effective than placebo for the majority of psychotic symptoms and the abandonment of treatment, but asenapine was not. Paliperidone, risperidone, quetiapine, clozapine, and olanzapine showed significant increases in weight compared to placebo. Haloperidol, risperidone, ziprasidone, and paliperidone had a higher risk of extrapyramidal symptoms than placebo. There was a significant risk of sedation or drowsiness with, risperidone, haloperidol, ziprasidone, quetiapine, olanzapine, and clozapine in the comparisons with placebo. Of the results of the comparisons between AP, it was shown that clozapine and paliperidone had a clinically significant effect compared to haloperidol and quetiapine, respectively. Olanzapine and risperidone had a lower risk of abandoning the treatment in general, and due to adverse reactions in two comparisons of each one, haloperidol was the drug with more risk of abandoning due to adverse effects, followed by clozapine. Amisulpride, haloperidol and ziprasidone had favourable results as regards weight increase in several comparisons. Aripiprazole and paliperidone obtained a higher number of favourable results as regards sedation, and all the atypical drugs (except paliperidone) had a lower risk than the use of anti-parkinsonian drugs. Of the evidence from observational studies, it was found that, in subjects with risk factors for diabetes, such as age, hypertension, and dyslipidaemia, the initial treatment and current treatment with olanzapine, as well as current treatment with clozapine, may promote the development of this disease. CONCLUSION: Although it is imperative to prescribe an antipsychotic for treatment of the acute phase, the selection of the drug depends on the particular clinical condition of each patient and their collateral effects profile.