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Objectives: Perampanel is an antiepileptic drug (AED) approved for add‐on treatment of focal seizures (with or without generalization) and primary generalized tonic‐clonic (GTC) seizures. Our objective was to explore the effectiveness and tolerability of adjunctive perampanel in patients with drug‐resistant myoclonic seizures, after failure of other AEDs. Materials and methods: Retrospective, multicenter, observational study. Data were collected from individual patient clinical files and analysed using appropriate descriptive statistics and inferential analyses. Results: Data are reported for 31 patients with mean age 36.4 years, who had an average epilepsy duration of 18 years, previously taken an average of 5.03 AEDs, and were taking an average of 2.4 AEDs on perampanel initiation. Patients exhibited myoclonic, GTC, absence, tonic and focal seizures, and most had associated cognitive decline and/or ataxia. Median time on perampanel was 6 months, most common dose was 6 mg, and overall retention rate was 84%. The responder rate for myoclonic seizures was defined via reduction of days with myoclonic seizures per month. At 6 months, 15 (48.4%) of the 31 patients were classed as myoclonic seizure responders, 10 (32.3%) were myoclonic seizure free, and 39% saw improvements in functional ability. Of 17 patients with GTC seizures at baseline, 9 (53%) were responders at 6 months, and 8 (47.1%) were seizure free. The most frequent side effects were psychiatric disorders, instability, dizziness and irritability, and mostly resolved with dose reduction. Five patients discontinued perampanel due to side effects. Conclusions: Perampanel caused clinically meaningful improvements in patients with drug‐resistant myoclonic seizures. It was generally well tolerated, but psychiatric and neurological side effects sometimes required follow‐up and dose reduction. [ABSTRACT FROM AUTHOR]

The aim of this systematic review is to assess the available evidence concerning the effectiveness of semi-permeable dressings, on the full range of skin reactions, related to radiation therapy in cancer patients, from local erythema to moist desquamation, including subjective symptoms such as pain, discomfort, itchiness, burning and the effect on daily life activities. The bibliographic search was carried out looking for Randomised Clinical Trials ( RCTs) indexed in PubMed, Cinhal, Cochrane plus and Biblioteca Nacional de Salud, published in the English and Spanish language, between 2010 and 2015. Data extraction and evaluation of study quality was undertaken by peer reviewers using the Critical Appraisal Skills Programme ( CASP). Of 181 studies, nine full texts were assessed. Finally, six RCT were included in the final synthesis: three analysed the application of Mepilex® Lite in breast cancer and head & neck cancer; one evaluated the application of Mepitel® Film in breast cancer; and two assessed the use of silver nylon dressings in breast cancer and in patients with lower gastrointestinal cancer. The results show that semi-permeable dressings are beneficial in the management of skin toxicity related to radiation therapy. However, rigorous trials showing stronger evidence are needed. [ABSTRACT FROM AUTHOR]

Objectives: To describe a case diagnosed with intracranial teratoma in week 32 of gestation, as well as review of the literature in order to discern the appropriate treatment method and general prognosis of this anomaly.Methods: A literature search was performed on the prenatal diagnosis of congenital intracranial teratomas in MEDLINE, EMBASE, Cochrane library data bases. Evaluated in this review are parameters such as time of prenatal diagnosis, associated pathology, size of tumors, method of terminating pregnancy, perinatal outcome and histological study of the tumor.Results: A total of 49 cases were found, of which 12 were finished gestation, 28 cesarean section was performed and only nine had vaginal delivery. All died in the neonatal period except in three cases with intrauterine death after diagnosis.Conclusion: As the incidence of intracranial immature teratomas is very low and the prognosis is poor, their prenatal diagnosis and obstetric management present a great challenge for the planning of a follow-up and treatment of the disease in accordance with the preferences of the parents. [ABSTRACT FROM AUTHOR]

Background:We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose.Methods:Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using 99Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry.Results:Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1±8.9 vs 31.3±12.9 mg (P=0.01). Both, AUC24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P<0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P=0.03) in tumour specimens.Conclusion:Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies. [ABSTRACT FROM AUTHOR]

BACKGROUND: Stereotactic thermocoagulative lesions of the subthalamic nucleus (STN) have been shown to induce significant motor improvement in patients with Parkinson’s disease (PD). PATIENTS AND METHODS: 89 patients with PD were treated with unilateral subthalamotomy. 68 patients were available for evaluations after 12 months, 36 at 24 months and 25 at 36 months. RESULTS: The Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores improved significantly contralaterally to the lesion in the "off" and "on" states throughout the follow-up, except for the "on" state at the last evaluation. Axial features and signs ipsilateral to the lesion progressed steadily throughout the study. Levodopa daily doses were significantly reduced by 45%, 36% and 28% at 12, 24 and 36 months post-surgery. 14 patients (15%) developed postoperative hemichorea-ballism which required pallidotomy in eight. These 14 patients had significantly higher dyskinesia scores (levodopa induced) preoperatively than the entire cohort. CONCLUSION: Unilateral subthalamotomy was associated with significant and sustained motor benefit contralateral to the lesion. Further work is needed to ascertain what factors led to severe, persistent chorea-ballism in a subset of patients. Subthalamotomy may be considered an option in circumstances when deep brain stimulation is not viable. [ABSTRACT FROM AUTHOR]

Objectives. To determine and compare effectiveness, tolerability and safety of venlafaxine extended release (VXR) and other conventional antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs), for the treatment of elderly patients diagnosed of depressive disorder in an out-patient psychiatry setting. Methods. Multicenter, naturalistic, randomized, open-label study performed in elderly patients with depressive disorder (according to DSM-IV). Patients were randomized to 6 months of treatment with VXR or another conventional antidepressant (CA). Effectiveness was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Scale (HAM-A). Response was considered as a ≥ 50 % decrease and remission as a < 9 score in the MADRS. Results. Sample of 120 patients older than 60 years; 68 received VXR and 52 CA (SSRI: 94.1 %). Most frequently used SSRI were citalopram (40.8 %), paroxetine (24.5 %) and sertraline (20.4 %). After 6 months of treatment, VXR achieved a higher response (75 %, VXR; 50 %, CA; p = 0.048) and remission (50 %, VXR; 28.9 %, CA; p = 0.048) and a higher decrease in the HAM-A score (-14.77, VXR; -10.84, CA). There were no significant differences in compliance rates (67.6, VXR; 71.1 %, CA) and adverse reactions (14.7 %, VXR; 13.46 %, CA) between both treatment groups. Blood pressure and heart rate remained within normal, limits in both treatment groups. Conclusions. In this study, venlafaxine extended release shows higher effectiveness than other conventional antidepressants, mainly SSRIs, in the treatment of depressive elderly patients in the out-patient psychiatry setting. [ABSTRACT FROM AUTHOR]

There is little evidence assessing compliance with clinical practice guidelines for antiretroviral treatment and its impact on clinical outcomes. The Spanish national guidelines for antiretroviral treatment are published by the Spanish AIDS Study Group (GeSIDA). The aim of this study was to assess compliance with national guidelines for the treatment of naïve patients from a multicentre Spanish cohort (CoRIS). The specific aims were to evaluate the proportion of patients treated according to the guidelines' recommendations, to investigate factors associated with the prescription of a non-recommended treatment, and to assess the impact of non-recommended treatments on mortality and on virological and immunological response (defined as undetectable viral load and increase of 100 CD4/ml, respectively, after 1 year). Drug combinations were classified as recommended, alternative, or not recommended, according to the guidelines' 'what to start with' recommendations. 6225 naïve patients were included between the years 2004 and 2010. Among 4516 patients who started treatment, 3592 (79.5%), 540 (12%), and 384 (8.5%) started with a recommended, alternative and not-recommended treatment, respectively. The use of a not-recommended treatment was significantly associated with CD4 count >500/ml (OR: 2.03, 95% CI: 1.14-3.59), hepatitis B infection (OR: 2.23, 95% CI: 1.50-3.33), treatment in a hospital with <500 beds, and starting treatment in the years 2004 to 2006. There was no significant association of having a not-recommended treatment with gender, route of transmission, hepatitis C infection, country of origin, education, or viral load. The use of a not-recommended regimen was significantly associated with mortality (HR: 1.61, 95% CI: 1.03-2.52, p=0.035) and lack of virological response (OR: 0.65, 95% CI: 0.45-0.93, p=0.019), but it was not associated with immunological response (OR: 0.90, 95% CI: 0.75-1.08, p=0.273). In conclusion, compliance with 'what to start with' recommendations of Spanish national guidelines was high. The use of not-recommended regimens was more likely in patients with >500 CD4/ml, hepatitis B infection, and starting treatment in the years 2004-2006 and in small hospitals. Not-recommended regimens were associated with higher mortality and lack of virological response. [ABSTRACT FROM AUTHOR]

Huntington’s disease (HD) is a hereditary neurodegenerative disease, with peripheral consequences that negatively contribute to quality of life. Circulating microRNAs (cmiRNAs) are being explored for their roles in intercellular communication and gene expression regulation, which allows gaining insight into the regulation of crosstalk between neuronal and peripheral tissues. Here, we explore the cmiRNA profile of plasma samples from fifteen symptomatic patients, with 40–45 CAG repeats in the HTT gene, and seven healthy matched controls. Isolated miRNAs from plasma samples were run against human miRNome panels, which have sequences for 752 human mature miRNAs. We found that 168 cmiRNAs are altered in symptomatic patients. Considering Bonferroni’s correction, miR-877-5p, miR-223-3p, miR-223-5p, miR-30d-5p, miR-128, miR-22-5p, miR-222-3p, miR-338-3p, miR-130b-3p, miR-425-5p, miR-628-3p, miR-361-5p, miR-942 are significantly increased in HD patients as compared with controls. Moreover, after patient’s organization according to approved HD scales, miR-122-5p is significantly decreased in HD patients with Unified Huntington’s Disease Rating Scale >24, whereas an increase in miR-100-5p levels and a decrease in miR-641 and miR-330-3p levels were recorded when patients were rearranged by Total Functional Capacity. These results suggest that cmiRNA profile could be further modified by disease progression, making cmiRNAs useful as monitoring biomarkers. Analysis of target genes indicated a general overexpression of cmiRNAs implicated in metabolism regulation. Profiling cmiRNA of HD subjects opens the possibility of personalized therapies for different groups of HD patients, based on disease modifiers: regulation of altered pathways might contribute to not only alleviate disease symptoms, but also influence HD progression. [ABSTRACT FROM AUTHOR]

Treatment with second-generation antipsychotic agents such as olanzapine frequently results in metabolic adverse effects, e.g. hyperphagia, weight gain and dyslipidaemia in patients of both genders. The molecular mechanisms underlying metabolic adverse effects are still largely unknown, and studies in rodents represent an important approach in their exploration. However, the validity of the rodent model is hampered by the fact that antipsychotics induce weight gain in female, but not male, rats. When administered orally, the short half-life of olanzapine in rats prevents stable plasma concentrations of the drug. We recently showed that a single intramuscular injection of long-acting olanzapine formulation yields clinically relevant plasma concentrations accompanied by several dysmetabolic features in the female rat. In the current study, we show that depot injections of 100–250 mg/kg olanzapine yielded clinically relevant plasma olanzapine concentrations also in male rats. In spite of transient hyperphagia, however, olanzapine resulted in weight loss rather than weight gain. The resultant negative feed efficiency was accompanied by a slight elevation of thermogenesis markers in brown adipose tissue for the highest olanzapine dose, but the olanzapine-related reduction in weight gain remains to be explained. In spite of the absence of weight gain, an olanzapine dose of 200 mg/kg or above induced significantly elevated plasma cholesterol levels and pronounced activation of lipogenic gene expression in the liver. These results confirm that olanzapine stimulates lipogenic effects, independent of weight gain, and raise the possibility that endocrine factors may influence gender specificity of metabolic effects of antipsychotics in the rat. [ABSTRACT FROM AUTHOR]

Highlights: [•] Evaluation of surface and soluble TREM-1 levels in DENV-infected patients was made. [•] A significant reduction of TREM-1 expression was observed in neutrophils. [•] Sera from DENV-infected patients exhibited significantly higher of soluble TREM-1 levels during the first 5 days after the symptoms onset. [•] The increment of sTREM-1 could be a compensatory mechanism to counteract the inflammatory process elicited by DENV infection. [•] These data are the first to show the involvement of TREM-1 during DENV infection. [Copyright &y& Elsevier]