The effect of associative strength on semantic priming in schizophrenia.

The present research was designed to investigate the pattern of semantic priming in schizophrenia as a function of strength of association (or semantic distance between concepts in the semantic network). Thirty schizophrenia patients, without formal thought disorder, and twenty-nine healthy controls participated in a lexical decision task in which prime-target associative strength (strong, weak and not related) and stimulus-onset asynchrony (SOA: 250ms and 750ms) were manipulated. Patients and controls showed the same associative strength effect on RTs. In the short SOA condition priming effects were obtained for both strong and weak prime-target associative conditions. However in the long SOA priming was only significant for strongly associated pairs. This pattern of priming effects was similar in both groups, with higher priming on the short SOA and strong association conditions. Altogether results suggest that automatic semantic spreading activation is unimpaired in schizophrenia patients without formal thought disorder. These results are in line with the general evidence of impaired implicit priming observed only in patients with formal thought disorder. At the same time patients use context as controls to facilitate word processing. Finally, these findings evidence that, prime-target associative strength could moderate results in studies of semantic memory deficits in schizophrenia.

Impact of ornithine phenylacetate (OCR-002) in lowering plasma ammonia after upper gastrointestinal bleeding in cirrhotic patients.

BACKGROUND: Ornithine phenylacetate (OP) has been proven effective in lowering ammonia plasma levels in animals, and to be well tolerated in cirrhotic patients. A trial to assess OP efficacy in lowering plasma ammonia levels versus placebo in cirrhotic patients after an upper gastrointestinal bleeding was performed. The primary outcome was a decrease in venous plasma ammonia at 24 hours. METHODS: A total of 38 consecutive cirrhotic patients were enrolled within 24 hours of an upper gastrointestinal bleed. Patients were randomized (1:1) to receive OP (10 g/day) or glucosaline for 5 days. RESULTS: The primary outcome was not achieved. A progressive decrease in ammonia was observed in both groups, being slightly greater in the OP group, with significant differences only at 120 hours. The subanalysis according to Child-Pugh score showed a statistically significant ammonia decrease in Child-Pugh C-treated patients at 36 hours, as well as in the time-normalized area under the curve (TN-AUC) 0-120 hours in the OP group [40.16 µmol/l (37.7-42.6); median (interquartile range) (IQR)] versus placebo group [65.5 µmol/l (54-126);p = 0.036]. A decrease in plasma glutamine levels was observed in the treated group compared with the placebo group, and was associated with the appearance of phenylacetylglutamine in urine. Adverse-event frequency was similar in both groups. No differences in hepatic encephalopathy incidence were observed. CONCLUSIONS: OP failed to significantly decrease plasma ammonia at the given doses (10 g/day). Higher doses of OP might be required in Child-Pugh A and B patients. OP appeared well tolerated.

Effects of intravenous albumin in patients with cirrhosis and episodic hepatic encephalopathy: a randomized double-blind study.

BACKGROUND & AIMS: Episodic hepatic encephalopathy is frequently precipitated by factors that induce circulatory dysfunction, cause oxidative stress-mediated damage or enhance astrocyte swelling. The administration of albumin could modify these factors and improve the outcome of hepatic encephalopathy. The aim of this study is to assess the efficacy of albumin in a multicenter, prospective, double-blind, controlled trial (ClinicalTrials.gov number, NCT00886925). METHODS: Cirrhotic patients with an acute episode of hepatic encephalopathy (grade II-IV) were randomized to receive albumin (1.5g/kg on day 1 and 1.0g/kg on day 3) or isotonic saline, in addition to the usual treatment (laxatives, rifaximin 1200mg per day). The primary end point was the proportion of patients in which encephalopathy was resolved on day 4. The secondary end points included survival, length of hospital stay, and biochemical parameters. RESULTS: Fifty-six patients were randomly assigned to albumin (n=26) or saline (n=30) stratified by the severity of HE. Both groups were comparable regarding to demographic data, liver function, and precipitating factors. The percentage of patients without hepatic encephalopathy at day 4 did not differ between both groups (albumin: 57.7% vs. saline: 53.3%; p>0.05). However, significant differences in survival were found at day 90 (albumin: 69.2% vs. saline: 40.0%; p=0.02). CONCLUSIONS: Albumin does not improve the resolution of hepatic encephalopathy during hospitalization. However, differences in survival after hospitalization suggest that the development of encephalopathy may identify a subgroup of patients with advanced cirrhosis that may benefit from the administration of albumin.

Safety of ornithine phenylacetate in cirrhotic decompensated patients: an open-label, dose-escalating, single-cohort study.

AIMS: Confirm in patients with cirrhosis and gastrointestinal bleeding the safety of ornithine phenylacetate (OP) and assess the pharmacokinetic profile of OP and its effects on plasma ammonia. BACKGROUND: OP is a drug that has shown experimentally to decrease hyperammonemia and improve hepatic encephalopathy. OP is safe in healthy subjects and in stable patients with cirrhosis, but there are no data in decompensated cirrhosis. METHODS: We performed a study to assess safety and tolerance of OP in cirrhotic patients after an episode of upper gastrointestinal bleeding.Ten patients were included within 24 hours of an upper gastrointestinal bleeding. OP was administered as a continuous infusion up to a maximum of 10 g/24 h (0.42 g/h) for 5 days. The infusion was started at 33% of the target dose and increased at 12-hour intervals achieving target dose at 24 hours. Ammonia was also assessed in control group of 10 patients. RESULTS: No severe adverse events were observed. Mild adverse events were reported in 4 patients. Plasma ammonia (baseline: 80±43 µmol/L) showed a progressive drop between baseline and 36 hours (42±15 µmol/L), 72 hours (44±15 µmol/L), 96 hours (40±24 µmol/L), and 120 hours (33±14 µmol/L). Plasma ammonia at 24 hours was significantly higher in the control group. Plasma glutamine showed a significant decrease (-37% at day 5) and its excretion in urine as phenylacetylglutamine, a progressive rise (52±35 mmol at day 5). CONCLUSIONS: OP is a safe and well-tolerated drug in decompensated cirrhotics that may decrease plasma ammonia by inducing its appearance as phenylacetylglutamine in urine.

Effectiveness of the cognitive differentiation program of the integrated psychological therapy: group versus individual treatment.

The aim of the current pilot study was to compare two strategies in the application of the cognitive differentiation program of Integrated Psychological Therapy for people with schizophrenia. Twenty-six outpatients were randomly assigned to the application of the program in group sessions (CDg), or to its application in individualized sessions (CDi). The program provides cognitive exercises to promote better performance in cognition, and both groups of participants completed the same number of exercises following the same number of sessions per week. Outcomes were assessed on neuropsychological measures of attention, executive functioning and everyday memory, and everyday functioning. Effect sizes showed the absence of effects in everyday memory and social functioning, higher improvements in the CDi group in attention, and a higher improvement in the CDg condition in executive functioning. The results suggest that the program application model could be individualized, depending on patient-specific cognitive deficits.

Perceptual priming in schizophrenia evaluated by word fragment and word stem completion.

Implicit memory seems to be preserved in schizophrenia as a whole, but dissociations between conceptual and perceptual tasks and between accuracy and reaction time measures have appeared. The present research has revealed some methodological limitations in many studies to date that are focused on the study of perceptual implicit memory in schizophrenic patients using accuracy measures. The review of these studies revealed that limitations are related to an inadequate definition of performance and priming measures, a lack of control over the characteristics of the stimuli, and the absence of information on the experimental procedures used in data collection. Moreover, the task used in these studies is word stem completion, a task that makes use of perceptual and conceptual processes. In the experiment reported here we use a pure perceptual implicit task and stimuli selected from a normative database to measure perceptual implicit memory in schizophrenic patients. Their performance was compared with that of normal participants. Thirty-two schizophrenic patients and 30 healthy control participants were administered a word fragment completion task. Direct comparison between the two groups yielded similar results in priming, suggesting that perceptual implicit memory is preserved in schizophrenia.

Cognitive Rehabilitation Programs in Schizophrenia: Current Status and Perspectives

This study reviews the main rehabilitation programs that have been developed to improve cognitive functioning in patients diagnosed with schizophrenia: it describes their main components and procedures and highlights the most relevant outcomes of each one. Additionally, it highlights which lead to subsequent improvement in social functioning. Cognitive rehabilitation is now being commonly included in treatment of schizophrenic patients with cognitive impairment or cognitive deficit. Hence, it is very important to have empirical data on the efficacy of these programs, data which is not always readily available in current literature (AU)

Este artículo presenta una revisión de los principales programas que se han desarrollado para la mejora del funcionamiento cognitivo en los pacientes con diagnóstico de esquizofrenia. Se describen sus principales componentes, la manera de proceder de cada uno de ellos y sobre que aspectos muestran efectos positivos. Se indica además cuales presentan una mayor relación con la mejora posterior en el funcionamiento social. El entrenamiento cognitivo está pasando a formar parte, de manera habitual, de las de intervenciones que se llevan a cabo con pacientes que presentan déficit o deterioro cognitivo, que son la mayor parte de ellos. Por ello son muy importante los datos empíricos sobre la eficacia de los programas, y no siempre podemos encontrar en la literatura esta información (AU)

Consent in clinical trials: what do patients know?

OBJECTIVE: To assess participants' knowledge of key aspects about the clinical trials in which they are enrolled, describe the consent process, and assess the importance that investigators give to various aspects of trial information when verbally informing candidates. DESIGN: Prospective study based on a structured questionnaire interview of participants within 3 months after trial enrollment and an anonymous questionnaire sent to clinical trial investigators. SUBJECTS: A total of 140 participants included in 40 clinical trials were interviewed, and 51 investigators answered the questionnaire. RESULTS: The formal steps to obtain informed consent were usually carried out. Participants were aware of the purpose of the trial and the right to discontinue participation, but only 23% knew that treatment was randomly allocated, 57% knew they might receive a placebo, and 42% was aware that adverse effects could occur. Patients who had read the information sheet had better knowledge of most aspects, except for the risk of adverse effects. The investigators considered that compensation, insurance coverage, possibility of receiving a placebo, and treatment allocation were the least important aspects of the trial when informing candidates for participation. CONCLUSIONS: Although the formal steps for obtaining informed consent were usually carried out, a relevant percentage of patients included in clinical trials were unaware of important aspects of their participation. Patients showed more limited knowledge about the same points that investigators considered less important when informing potential participants. Deferring signature on the consent form and encouraging reading of the information sheet may improve participants' knowledge about clinical trials.

The DEC-net European register of paediatric drug therapy trials: contents and context.

OBJECTIVE: To describe the results and conclusions of DEC-net, an international, publicly available register of paediatric drug therapy clinical trials, and to assess which paediatric health areas are covered by research and by which trial types. METHODS: The contents of the register, which was set up by four groups (Italy, UK, France, Spain) who searched for paediatric trials and collected data between 2004-2006, were analysed. The disease areas reflected were compared with those covered by published trials and Burden of Disease (BD) data. RESULTS: In all, 257 trial records were analysed, 86 of which were entered by the Italian partner, 84 by the UK partner, 56 by the French partner and 31 by the Spanish partner. Spain entered the majority of multinational trials, while the UK had the majority of single-centre national trials. Most trials were experimental (79%), and the most commonly represented diseases were neoplasms (14% trials). In all, 28% were double-blind randomised controlled trials (RCTs). The most common disease areas addressed in the 257 trials were similar to the published trials' areas. In contrast, the primary research area was low on the BD list. CONCLUSIONS: DEC-net has demonstrated that international research efforts exist, even for paediatrics, although there may be an imbalance between national and multinational studies and a limited approach to double-blind RCTs. Recent initiatives will increase the number of children participating in research, and European legislation will require prospective registration. Paediatric research priorities must be better defined, however, and this can be done by registering research and making the information available to all relevant actors.

Intellectual functioning and memory deficits in schizophrenia.

BACKGROUND: There is converging evidence about the existence of different subgroups of patients with schizophrenia in relation to intellectual ability (intelligence quotient [IQ]). Studying cognitive deficits in such patients in relation to IQ, and more specifically to memory, could help determine the patterns of preserved and impaired functioning in cognitive abilities in association with patterns of preserved and compromised intellect. This information could serve to delimit the possibilities of treatment and rehabilitation in those patients. METHODS: A total of 44 patients with schizophrenia completed a cognitive battery that included executive functioning, attention, speed of information processing, working memory, explicit memory, implicit memory, and everyday memory. Their IQ was also measured to identify 2 subgroups with an IQ of 85 as the cutoff point. Then, differences between the groups in the neurocognitive measures were studied. RESULTS: Performance in executive functioning, attention, working memory, and everyday memory, but not that in speed of information processing, explicit memory, and implicit memory, was associated with intellectual functioning. Patients performed at the same level in perceptual implicit memory but at a lower level in conceptual implicit memory as did healthy control subjects. DISCUSSION: Cognitive deficits in schizophrenia are associated with intellectual functioning. Implicit memory should not be considered as a unique entity. It is suggested that conceptual implicit memory deficit may be a core feature of schizophrenia.