Real-life evidence about the use of intravenous brivaracetam in urgent seizures: The BRIV-IV study.

PURPOSE: Urgent seizures are a medical emergency for which new therapies are still needed. This study evaluated the use of intravenous brivaracetam (IV-BRV) in an emergency setting in clinical practice. METHODS: BRIV-IV was a retrospective, multicenter, observational study. It included patients ≥18 years old who were diagnosed with urgent seizures (including status epilepticus (SE), acute repetitive seizures, and high-risk seizures) and who were treated with IV-BRV according to clinical practice in 14 hospital centers. Information was extracted from clinical charts and included in an electronic database. Primary effectiveness endpoints included the rate of IV-BRV responder patients, the rate of patients with a sustained response without seizure relapse in 12 h, and the time between IV-BRV administration and clinical response. Primary safety endpoints were comprised the percentage of patients with adverse events and those with adverse events leading to discontinuation. RESULTS: A total of 156 patients were included in this study. The mean age was 57.7 ± 21.5 years old with a prior diagnosis of epilepsy for 57.1% of patients. The most frequent etiologies were brain tumor-related (18.1%) and vascular (11.2%) epilepsy. SE was diagnosed in 55.3% of patients. The median time from urgent seizure onset to IV treatment administration was 60.0 min (range: 15.0-360.0), and the median time from IV treatment to IV-BRV was 90.0 min (range: 30.0-2400.0). Regarding dosage, the mean bolus infusion was 163.0 ± 73.0 mg and the mean daily dosage was 195.0 ± 87.0 mg. A total of 77.6% of patients responded to IV-BRV (66.3% with SE vs. 91% other urgent seizures) with a median response time of 30.0 min (range: 10.0-60.0). A sustained response was achieved in 62.8% of patients. However, adverse events were reported in 14.7%, which were predominantly somnolence and fatigue, with 4.5% leading to discontinuation. Eighty-six percent of patients were discharged with oral brivaracetam. CONCLUSION: IV-BRV in emergency settings was effective, and tolerability was good for most patients. However, a larger series is needed to confirm the outcomes.

Short-term improvements in the body schema can modulate pain perception in fibromyalgia syndrome.

OBJECTIVES: This study aimed to evaluate the pain perception and several aspects of disrupted body schema, in a sample of patients suffering from fibromyalgia (FM) syndrome. METHODS: Twenty-six patients were organised into two groups: the tactile discrimination group and control group (exposed to tactile stimulation alone). Outcome measures were the pain intensity in body regions commonly described as painful (visual analogue scale) and clinical status, body esteem scale (BES), interoceptive awareness. Tactile acuity was measured by the two-point discrimination test (TPD), hits in the location of the stimulus, the probe size discrimination and the graphesthesia task. RESULTS: The group exposed to tactile discrimination experienced a significant improvement in all tactile acuity outcome measures. The decrease of the Fibromyalgia Impact Questionnaire variable was relevant (81.58, SEM 3.29 vs. 72.91, SEM 6.43; p=0.07). Likewise, pain perception was lower in all of the body regions evaluated (reduction of 12.2% in the stimulated body region (cervical VAS) with a large effect size, a pain reduction of 11.3% in the wrists and 9.2% in the knees. The correlation index showed association between the cervical VAS and TPD (ρ=0.53; p<0.05). CONCLUSIONS: There was no improvement in pain scores in the control group but the TPD was decreased also. The BES scores did not show differences between groups. However, interoceptive awareness showed a slight reduction in the group exposed to tactile discrimination (3.68, SEM 0.15 vs. 3.35, SEM 0.19; p=0.01). After short-term tactile discrimination protocol, the group exposed to tactile discrimination experienced a significant improvement in all tactile acuity outcome measures: pain perception, tactile acuity and body perception, compatible with adjustments in the body schema. The tactile stimulation alone group did not show the same improvement.

Apomorphine for the Treatment of Erectile Dysfunction: Systematic Review and Meta-Analysis.

Sublingual apomorphine could be an option in patients with erectile dysfunction who cannot take phosphodiesterase type 5 inhibitors (e.g., using nitrates). We have completed a systematic review to evaluate the effects of sublingual apomorphine comparing with placebo for treating erectile dysfunction. The evidence searching process finished on 9 January 2019. We included nine randomized controlled trials (RCTs). Treatment length varied from 4 to 8 weeks and doses ranged from 2 to 6 mg. The percent of successful sexual intercourse attempts per ingested dose of apomorphine was evaluated in eight studies. All the studies found that apomorphine was better than placebo (6-27% more successful intercourse attempts than with placebo), but differences were not statistically significant in one study done in patients previously treated with radical prostatectomy. Regarding erectile function scores, three studies reported higher improvement on the erectile function scores for apomorphine. Differences with placebo were not clinically relevant in another two studies, one in which only diabetic patients were included and one in which only patients with radical prostatectomy were involved. Discontinuation of treatment due to adverse events was higher for apomorphine, particularly for higher doses. Available evidence suggests that sublingual apomorphine is more effective than placebo, except for patients previously treated with radical prostatectomy, and is generally well tolerated at doses of 2 or 3 mg. Nowadays, sublingual apomorphine is the only licensed oral drug for erectile dysfunction not absolutely contraindicated with nitrates use, and more RCTs should be performed to evaluate its effects and safety for treating ED.

L-acetylcarnitine for treating fragile X syndrome.

BACKGROUND: People with fragile X syndrome (FXS) have an intellectual dysfunction that can range from very mild to severe. Symptoms can include speech and language delays and behavioural difficulties such as aggression or self injurious behaviours, emotional lability, and anxiety-related problems (for example obsessive-compulsive symptoms and perseverative behaviours). In some cases, affected people may have an additional diagnosis of attention deficit hyperactivity disorder or an autism spectrum disorder. OBJECTIVES: To review the efficacy and safety of L-acetylcarnitine in improving the psychological, intellectual, and social performance of people with FXS. SEARCH METHODS: In May 2015 we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, Web of Science, and two other databases. We also searched three trials registers, four theses databases, and the reference lists of relevant studies and reviews. SELECTION CRITERIA: Randomised controlled trials (RCTs) that assessed the efficacy of L-acetylcarnitine, at any dose, in people of any age diagnosed with FXS compared with placebo. DATA COLLECTION AND ANALYSIS: For each trial, two review authors independently extracted data on the children included and interventions compared, and assessed the risk of bias of the studies across the following domains: randomisation sequence generation, allocation concealment, blinding (of participants, personnel, and outcome assessors), incomplete outcome data, selective outcome reporting, and other potential sources of bias. MAIN RESULTS: We found only two RCTs that compared oral L-acetylcarnitine (LAC) with oral placebo in children with FXS. The studies included a total of 83 participants, all of them male, who were treated and followed for one year. The age of participants at the start of treatment ranged from 6 to 13 years, with a mean age of 9 years. Neither study provided information on randomisation, allocation concealment procedures, or blinding of outcome assessment, and we received no responses from the authors we emailed for clarification. We therefore rated studies as being at unclear risk of bias on these domains. We judged both studies to be at low risk of bias for blinding of participants and personnel, incomplete outcome data, and selective reporting, but to be at high risk of other bias, as at least one study was funded by a drug company, and in both studies people working for the company were part of the research team.We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the quality of the available evidence. Overall, the quality of the evidence was low due to the imprecision of results and high risk of other bias.Regarding the primary outcome of psychological and learning capabilities, both studies assessed the effect of interventions on children's verbal and non-verbal intellectual functioning using the Wechsler Intelligence Scale for Children - Revised. The authors did not provide detailed data on those results but said that they found no important differences between treatment and placebo.Both studies evaluated the impact of the treatment on hyperactive behaviour using the Conners' Abbreviated Parent-Teacher Questionnaire. In one study, teachers' assessments of the children found no clear evidence of a difference (mean difference (MD) 0.50, 95% confidence interval (CI) -5.08 to 6.08, n = 51; low-quality evidence). The other study stated that there were no differences between treated and untreated participants, but did not provide detailed data for inclusion in the meta-analysis.Parents' assessments favoured LAC in one study (MD -0.57, 95% CI -0.94 to -0.19, n = 17; low-quality evidence), but not in the other (MD -2.80, 95% CI -7.61 to 2.01, n = 51; low-quality evidence), though changes were not large enough to be considered clinically relevant.Regarding social skills, one study reported no clear evidence of a difference in Vineland Adaptive Behavior composite scores (MD 8.20, 95% CI -0.02 to 16.42, n = 51; low-quality evidence), yet results in the socialisation domain favoured LAC (MD 11.30, 95% CI 2.52 to 20.08, n = 51; low-quality evidence).Both studies assessed the safety of the active treatment and recorded no side effects. Neither of the included studies assessed the secondary outcome of caregiver burden. AUTHORS' CONCLUSIONS: Low-quality evidence from two small trials showed that when compared to placebo, LAC may not improve intellectual functioning or hyperactive behaviour in children with FXS.

Toronto alexithymia scale for patients with eating disorder: [corrected] performance using the non-parametric item response theory.

BACKGROUND: The aim of this study was to investigate the performance of the Toronto Alexithymia Scale (TAS-20) in patients with eating disorders. As a secondary objective, we analyzed a subset of items in order to determine whether the total score is a good tool for classifying these patients and whether the items are ordered according to the difficulty of choosing a particular answer depending on the severity of the patient's condition. SUBJECTS AND METHODS: We administered the TAS-20 to 103 consecutive patients who met DSM-IV-R criteria for anorexia nervosa, bulimia nervosa, or eating disorders not otherwise specified. Mokken scale analysis, nonparametric item response theory (NIRT), and confirmatory factor analysis (CFA) were used to test the psychometric properties of the scale. To improve our understanding of the structure underlying the TAS-20, we used an automated item selection procedure based on the Mokken scale. RESULTS: We identified a subset of 13 independent and clinically interpretable items that are potentially sufficient to rate patients with alexithymia. This subset was considered a unidimensional reduction of the TAS-20. However, the scale composed of this subset needs to be validated. Thirteen of the 20 items were maximally related to alexithymia because they have a one-dimensional structure. The NIRT and CFA enabled us to identify a maximal subset of items that conform to the requirements for good measurement of alexithymia in patients with eating disorders.

Depressive dimensions and item response analysis of the Hamilton Depression Rating Scale-17 in eating disorders.

BACKGROUND: Most patients having eating disorders (EDs) experience depressive symptoms. To date, there have been few reports about the different depressive dimensions in EDs. OBJECTIVE: The aim of this study was to investigate the dimensions of depressive symptoms and highlight the distribution of the symptoms. The psychometric properties of these measures were tested using item response theory methods. METHODS: A total of 103 consecutively admitted inpatients and outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, Revised Fourth Edition, criteria for anorexia nervosa, bulimia nervosa, and EDs not otherwise specified were rated with the Hamilton Depression Rating Scale (HDRS-17). A factor analysis of the HDRS-17 was carried out with the Cf-varimax rotation. RESULTS: Factor analysis showed 2 independent and clinically interpretable factors corresponding to "anxious depression" and "somatic complaints" that constituted the core of depression. For the HDRS-17, item response theory analyses revealed that most of the items were maximally related to the core concept of depression and provided a good functioning. The 17 items were distributed in almost the same way as in the factor analyses found by other authors with different clinical groups. We conclude therefore that for the sample of EDs, 2 factors constitute the core symptoms of depression and most of the items provided a good functioning.

Folic acid for fragile X syndrome.

BACKGROUND: It has been argued that individuals with fragile X syndrome could have low folate levels in their bodies and that supplementing their dietary intake might remediate the adverse developmental and behavioural effects of the condition. OBJECTIVES: To review the efficacy and safety of folic acid in the treatment of people with fragile X syndrome. SEARCH STRATEGY: We searched four databases in November 2010: CENTRAL, PubMed, EMBASE and PsycINFO. SELECTION CRITERIA: Randomised controlled trials. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias using the Cochrane 'Risk of bias' tool. MAIN RESULTS: We included five trials, which were published between 1986 and 1992. Overall, they included 67 patients, all male, with ages ranging from one to 54 years. Intellectual disability in participants varied from borderline to severe and some studies included patients with an additional diagnosis of autism or autistic behaviour. Four of the studies were placebo-controlled cross-over trials and one study was a parallel design. The duration of follow-up ranged from two months to 12 months and the period on folic acid or placebo ranged from two to eight months. Doses of folic acid ranged from 10 mg to 250 mg per day, 10 mg per day being the most common. Most of the younger patients involved were also taking part in special education programmes (usually involving language and occupational therapy).We were not able to perform meta-analysis to combine results but none of the individual studies found evidence of clinical benefit with the use of folic acid medication in fragile X syndrome patients on any of the areas of interest, either psychological and learning capabilities or behaviour and social performance, as measured with standardised tools. Separate analysis of evidence for patients of different age groups, i.e. prepubertal children and postpubertal young people, found some statistically significant results, but did not show clear evidence of benefit for either group. Adverse effects of folic acid treatment were rare, not serious and transient.Studies were generally poorly reported and we classified only one study as being at low risk of bias. AUTHORS' CONCLUSIONS: The quality of available evidence is low and not suitable for drawing conclusions about the effect of folic acid on fragile X syndrome patients. It consists of few studies with small samples of patients, all of them male, with little statistical power to detect anything other than huge effects.

A Distorted Body Schema and Susceptibility to Experiencing Anomalous Somatosensory Sensations in Fibromyalgia Syndrome.

OBJECTIVE: Evidence suggests that there is an association between chronic pain and disruption of the body schema. We tested the hypothesis in fibromyalgia syndrome (FMS). MATERIALS AND METHODS: We investigated distinct perceptual aspects of the body schema both in a sample of patients with FMS and in pain-free controls. Performances on the left/right judgment task were measured; tactile acuity was assessed by using the 2-point discrimination test. Furthermore, we evaluated sensations evoked by tactile stimulation with von Frey filaments to body parts that were experiencing pain. Anomalous sensations elicited by sensory-motor conflict (SMC) were also investigated. RESULTS: Patients with FMS showed inferior performance on the right/left judgment task, both in terms of correct matches (75.38% vs. 89.67%, respectively; P<0.05) and response time (2.58 s vs. 1.89 s, respectively; P<0.05). Effect sizes were large and very large, respectively. Two-point discrimination thresholds were significantly higher (P<0.05) in participants from the FMS sample (mean of 49.71 mm, SD: 12.09 mm) relative to controls (mean of 37.36 mm, SD: 7.81 mm). Nine of 14 participants with FMS, but no control participants, reported referred sensations upon tactile stimulation, including tingling, pins and needles, weight, and cramps. Referral sites included regions both adjacent and remote to stimulated sites. Patients with FMS scored across all items within the administered questionnaire addressing anomalous sensations on the mirror setup (Cohen d=1.04 to 2.42 across all items), and FMS patients perceived pain during the SMC (the required statistical power for it to be statistically significant was 96% and for it to be recognized as a difference of means in pain item). CONCLUSION: Our present findings suggest a disrupted body schema and propensity to experiencing anomalous somatosensory sensations during SMC in people with FMS.

Cognitive improvement of acetylcholinesterase inhibitors in schizophrenia.

BACKGROUND: Schizophrenia is a severe, persistent mental disorder, and a leading cause of disability worldwide. Cognitive impairments presented in schizophrenia lead to a worse prognostic, thus treatments targeted to enhance cognition in schizophrenia may be clinically relevant. AIMS: The purpose of this study was to assess the efficacy of acetylcholinesterase inhibitors as add-on medication to antipsychotics on cognition in patients with schizophrenia. METHODS: Search strategies were developed for Medline, Embase and Cochrane Central Register of Controlled Trials, and are current to March 2018. We included randomised controlled trials that compared antipsychotics plus acetylcholinesterase inhibitors versus antipsychotics plus placebo on prespecified cognitive domains (speed of processing, attention and working memory). Two review authors independently evaluated study eligibility, extracted data and assessed the risk of bias of included studies. We used random-effects model for meta-analyses and assessed the quality of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: We included nine randomised controlled trials. Six randomised controlled trials ( n=219) presented evidence that acetylcholinesterase inhibitors improve speed of processing (standardised mean difference -0.52, 95% confidence interval (-0.79 to -0.25); p value=0.0002). However, eight randomised controlled trials ( n=252) did find placebo was better than acetylcholinesterase inhibitors in the attention domain (-0.43, (-0.72 to -0.13); p value=0.005) and eight randomised controlled trials ( n=273) did not find differences in the working memory (-0.14, (-0.51 to 0.24), p value=0.47). CONCLUSIONS: The current evidence is too weak to base recommendations on the use of acetylcholinesterase inhibitors as adjunctive treatments to antipsychotics to improve basic cognitive functions. We have limited confidence in the effect estimates.

Cerebral magnetic resonance changes associated with fibromyalgia syndrome. / Cambios en la resonancia magnética cerebral asociados al síndrome de fibromialgia.

Fibromyalgia syndrome is a chronic disease, of unknown origin, whose diagnostic criteria were established in 1990 by the American College of Rheumatology. New criteria were proposed in 2010 that have not yet been validated. It is characterized by a generalized chronic musculoskeletal pain, accompanied by hyperalgesia and allodynia, as well as other motor, vegetative, cognitive and affective symptoms and signs. We have reviewed a set of studies with cerebral magnetic resonance (morphometry, connectivity and spectroscopy) that refer to changes in areas involved in pain processing. Modifications in gray and white matter volume, as well as in levels of N-acetylaspartate, choline or glutamate, among other metabolites, have been observed in the hippocampus, insula, prefrontal and cingular cortex. Neuroradiological findings are nonspecific and similar to those found in other examples of chronic pain. An increase in the sample size and a standardized methodology would facilitate comparison, allowing the drawing of general conclusions.

Cambios en la resonancia magnética cerebral asociados al síndrome de fibromialgia / Cerebral magnetic resonance changes associated with fibromyalgia syndrome

El síndrome de fibromialgia es un trastorno crónico, de origen desconocido, cuyos criterios diagnósticos estableció en 1990 el Colegio Americano de Reumatología; en 2010 propuso unos criterios nuevos que aún no están validados. Se caracteriza por dolor musculoesquelético generalizado, crónico, acompañado de fenómenos de hiperalgesia y alodinia, así como otros síntomas y signos, motores, vegetativos, cognitivos y afectivos. Revisamos un conjunto de estudios con resonancia magnética cerebral (morfometría, conectividad y espectroscopia) que refieren alteraciones en áreas de procesamiento del dolor. Se observan cambios en el volumen de la sustancia gris y blanca, así como de los niveles de N-acetilaspartato, colina o glutamato, entre otros metabolitos, en hipocampo, ínsula, corteza prefrontal y cingular, principalmente. Los hallazgos neurorradiológicos son inespecíficos y superponibles a los de otros cuadros de dolor crónico, pero un aumento del tamaño muestral y una metodología estandarizada facilitaría la comparación entre series, permitiendo extraer conclusiones generalizables (AU)

Fibromyalgia syndrome is a chronic disease, of unknown origin, whose diagnostic criteria were established in 1990 by the American College of Rheumatology. New criteria were proposed in 2010 that have not yet been validated. It is characterized by a generalized chronic musculoskeletal pain, accompanied by hyperalgesia and allodynia, as well as other motor, vegetative, cognitive and affective symptoms and signs. We have reviewed a set of studies with cerebral magnetic resonance (morphometry, connectivity and spectroscopy) that refer to changes in areas involved in pain processing. Modifications in gray and white matter volume, as well as in levels of N-acetylaspartate, choline or glutamate, among other metabolites, have been observed in the hippocampus, insula, prefrontal and cingular cortex. Neuroradiological findings are nonspecific and similar to those found in other examples of chronic pain. An increase in the sample size and a standardized methodology would facilitate comparison, allowing the drawing of general conclusions (AU)

Shame, sensitivity to punishment and psychiatric disorders

No disponible

Background and objectives: Various studies have found significant correlations between feelings of shame and psychopathologies, as depression or eating disorders. Since some authors have shown an association between inhibition, neuroticism and shame, we hypothesize that Sensibility to Punishment (SP) would relate positively to shame. We also propose that patients diagnosed with depression should score higher in shame domain than the rest of the diagnostic groups. Finally we predict that psychotic patients, since they have poor self-consciousness, should score the lowest in shame proneness. Methods: The Spanish version of the TOSCA, the Sensitivity to Punishment and Reward Questionnaire (SPSRQ) and The Clinical Global Impressions (CGI) were applied to a sample of 172 individuals, from which 93 were university students and 79 were patients receiving psychiatric treatment. Results: In the Sensitivity to Punishment domain we found statistically significant mean differences between patients with Major Depression and the comparative group. We have found a positive correlation between Sensitivity to Punishment and Shame in the general population and also for the Major depressive subgroup. The relation between depression and shame proneness was statistically significant. Shame and Guilt correlated in the TOSCA and the Major Depressive patients scores higher on both domains. Bipolar and schizophrenics patients showed lower scores in Shame than depressives. Conclusions: Among other conclusions we recommend that future studies in the field should use dimensional diagnoses besides the categorical ones (AU)