Clinical Trials of Potential Cognitive-Enhancing Drugs in Schizophrenia: What Have We Learned So Far?

In light of the number of studies conducted to examine the treatment of cognitive impairment associated with schizophrenia (CIAS), we critically reviewed recent CIAS trials. Trials were identified through searches of the website “www.clinicaltrials.gov” using the terms “schizophrenia AND cognition,” “schizophrenia AND neurocognition,” “schizophrenia AND neurocognitive tests,” “schizophrenia AND MATRICS,” “schizophrenia AND MCCB,” “schizophrenia AND BACS,” “schizophrenia AND COGSTATE,” and “schizophrenia AND CANTAB” and “first-episode schizophrenia AND cognition.” The cutoff date was 20 April 2011. Included trials were conducted in people with schizophrenia, the effects on cognition were either a primary or secondary outcome, and the effect of a pharmacologically active substance was examined. Drug challenge, pharmacokinetic, pharmacodynamic, or prodrome of psychosis studies were excluded. We identified 118 trials, with 62% using an add-on parallel group design. The large majority of completed trials were underpowered to detect moderate effect sizes, had ≤8 weeks duration, and were performed in samples of participants with chronic stable schizophrenia. The ongoing add-on trials are longer, have larger sample sizes (with a number of them being adequately powered to detect moderate effect sizes), and are more likely to use a widely accepted standardized cognitive battery (eg, the MATRICS Consensus Cognitive Battery) and MATRICS guidelines. Ongoing studies performed in subjects with recent onset schizophrenia may help elucidate which subjects are most likely to show an effect in cognition. New insights into the demands of CIAS trial design and methodology may help increase the probability of identifying treatments with beneficial effect on cognitive impairment in schizophrenia.     

Management of increased intracranial pressure in the critically ill child with an acute neurological injury

Increased intracranial pressure reflects the presence of mass effect in the brain and is associated with a poor outcome in children with acute neurological injury. If sustained, it has a negative effect on cerebral blood flow and cerebral perfusion pressure, can cause direct compression of vital cerebral structures, and can lead to herniation. The management of the patient with increased intracranial pressure involves the maintenance of an adequate cerebral perfusion pressure, prevention of intracranial hypertension, and optimization of oxygen delivery. This article reviews the neurological assessment, pathophysiology, and management of increased intracranial pressure in the critically ill child who has sustained an acute neurological injury.     

Right ventricular outflow tract obstruction caused by a right coronary cusp prolapse: An unusual finding

Patients with large sub-pulmonic ventricular septal defect (VSD) present early as a results of their complications. Some present late, due to the restriction of VSD by the right coronary cusp (RCC) due to its prolapse. In this report, we present a rare case of sub-pulmonic VSD in a 33-year-old man who developed a sub-pulmonic stenosis due to the prolapse of the RCC into the right ventricular outflow tract.     

Unexpected mechanism of mitral regurgitation in a patient post ALCAPA repair: Added value of three-dimensional echocardiography

Accurate assessment of etiology of mitral regurgitation (MR) is one of the key steps in the decision-making process and further clinical management of patients with severe MR. Our clinical case illustrates the added value of three-dimensional echocardiography (3DE) in assessment of mitral valve morphology and identification of an unexpected mechanism of MR which was not previously diagnosed using conventional echocardiography. 3DE helped to choose appropriate management strategy in this patient.