Lurasidone for the treatment of bipolar depression: an evidence-based review

Bipolar disorder (BD) is a debilitating and difficult-to-treat psychiatric disease that presents a serious burden to patients’ lives as well as health care systems around the world. The essential diagnostic criterion for BD is episodes of mania or hypomania; however, the patients report that the majority of their time is spent in a depressive phase. Current treatment options for this component of BD have yet to achieve satisfactory remission rates. Lurasidone is a drug in the benzisothiazole class approved by the US Food and Drug Administration in June 2013 for the acute treatment of bipolar depression. Its pharmacological profile features high-affinity antagonism at D[subscript 2], 5-HT[subscript 2A], and 5-HT[subscript 7] receptors; moderate-affinity antagonism at α[subscript 2C]-adrenergic receptors; low- to very low-affinity antagonism at α[subscript 1A]-adrenergic, α[subscript 2A]-adrenergic, H[subscript 1], M[subscript 1], and 5-HT[subscript 2C] receptors; and high-affinity partial agonism at 5-HT1A. Preliminary findings from two recent double-blinded clinical trials suggest that lurasidone is efficacious in treating bipolar I depression, with clinical effects manifesting as early as the first 2–3 weeks of treatment (as measured by the Montgomery–Åsberg Depression Rating Scale and Clinical Global Impressions Scale for use in bipolar illness). Its therapeutic benefit appears to be comparable to the current US Food and Drug Administration-indicated treatments: quetiapine and olanzapine–fluoxetine, according to a measure of effect size known as number needed to treat. These studies reported relatively limited extrapyramidal and metabolic side effects as a result of treatment with lurasidone, with the most common side effect being nausea. Safety data drawn from these studies, as well as a more extensive body of schizophrenia research, indicate that in comparison with other atypical antipsychotics, treatment with lurasidone is less likely to result in metabolic side effects such as weight gain or disturbances of serum glucose or lipid levels. Lurasidone holds clinical potential as a novel, efficacious pharmacological treatment for bipolar depression. However, current data on its use for the treatment of BD are limited, and more extensive research, both longer in duration as well as independently conducted, is needed

The Disappearance of Moral Choice in Serially Reproduced Narratives

How do narratives influence moral decision-making? Our ongoing studies use serial reproduction of narratives, that is multiple retellings as in the telephone game, of morally ambiguous situations. In particular, we tested stories that include a minor misdemeanor, but leave open whether the wrongdoer will be punished by a bystander. It turns out that serial reproduction (retelling) of stories tends to eliminate the possibility of intervention by the bystander under certain conditions. We reason that this effect can be explained either by preferences of the readers or by the reader\u27s discomfort to get involved. A second finding is that retellings of third-person narratives of moral situations lead to a higher degree of change and invention of the outcome than first-person narratives

PRISM II: an open-label study to assess effectiveness of dextromethorphan/quinidine for pseudobulbar affect in patients with dementia, stroke or traumatic brain injury

BACKGROUND: Phase 3 trials supporting dextromethorphan/quinidine (DM/Q) use as a treatment for pseudobulbar affect (PBA) were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). The PRISM II study provides additional DM/Q experience with PBA secondary to dementia, stroke, or traumatic brain injury (TBI). METHODS: Participants in this open-label, multicenter, 90-day trial received DM/Q 20/10 mg twice daily. The primary outcome was the Center for Neurologic Study-Lability Scale (CNS-LS), assessing change in PBA episode frequency and severity. The CNS-LS final visit score was compared to baseline (primary analysis) and to the response in a previously conducted placebo-controlled trial with DM/Q in patients with ALS or MS. Secondary outcomes included change in PBA episode count and Clinical Global Impression of Change with respect to PBA as rated by a clinician (CGI-C) and by the patient or caregiver (PGI-C). RESULTS: The study enrolled 367 participants with PBA secondary to dementia, stroke, or TBI. Mean (standard deviation [SD]) CNS-LS score improved significantly from 20.4 (4.4) at baseline to 12.8 (5.0) at Day 90/Final Visit (change, -7.7 [6.1]; P < .001, 95 % CI: -8.4, -7.0). This magnitude of improvement was consistent with DM/Q improvement in the earlier phase-3, placebo-controlled trial (mean [95 % CI] change from baseline, -8.2 [-9.4, -7.0]) and numerically exceeds the improvement seen with placebo in that study (-5.7 [-6.8, -4.7]). Reduction in PBA episode count was 72.3 % at Day 90/Final Visit compared with baseline (P < .001). Scores on CGI-C and PGI-C showed that 76.6 and 72.4 % of participants, respectively, were "much" or "very much" improved with respect to PBA. The most frequently occurring adverse events (AEs) were diarrhea (5.4 %), headache (4.1 %), urinary tract infection (2.7 %), and dizziness (2.5 %); 9.8 % had AEs that led to discontinuation. Serious AEs were reported in 6.3 %; however, none were considered treatment related. CONCLUSIONS: DM/Q was shown to be an effective and well-tolerated treatment for PBA secondary to dementia, stroke, or TBI. The magnitude of PBA improvement was similar to that reported in patients with PBA secondary to ALS or MS, and the adverse event profile was consistent with the known safety profile of DM/Q. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01799941, registered on 25 February 2013

Computational models and motor learning paradigms: Could they provide insights for neuroplasticity after stroke? An overview

Computational approaches for modelling the central nervous system (CNS) aim to develop theories on processes occurring in the brain that allow the transformation of all information needed for the execution of motor acts. Computational models have been proposed in several fields, to interpret not only the CNS functioning, but also its efferent behaviour. Computational model theories can provide insights into neuromuscular and brain function allowing us to reach a deeper understanding of neuroplasticity. Neuroplasticity is the process occurring in the CNS that is able to permanently change both structure and function due to interaction with the external environment. To understand such a complex process several paradigms related to motor learning and computational modeling have been put forward. These paradigms have been explained through several internal model concepts, and supported by neurophysiological and neuroimaging studies. Therefore, it has been possible to make theories about the basis of different learning paradigms according to known computational models. Here we review the computational models and motor learning paradigms used to describe the CNS and neuromuscular functions, as well as their role in the recovery process. These theories have the potential to provide a way to rigorously explain all the potential of CNS learning, providing a basis for future clinical studies

Chronic pain following COVID-19: Implications for rehabilitation

National Institute for Health Researc

Extracorporeal Membrane Oxygenation for Acute Pediatric Respiratory Failure

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.The use of extracorporeal membrane oxygenation (ECMO) to support children with acute respiratory failure has steadily increased over the past several decades, with major advancements having been made in the care of these children. There are, however, many controversies regarding indications for initiating ECMO in this setting and the appropriate management strategies thereafter. Broad indications for ECMO include hypoxia, hypercarbia, and severe air leak syndrome, with hypoxia being the most common. There are many disease-specific considerations when evaluating children for ECMO, but there are currently very few, if any, absolute contraindications. Venovenous rather than veno-arterial ECMO cannulation is the preferred configuration for ECMO support of acute respiratory failure due to its superior side-effect profile. The approach to lung management on ECMO is variable and should be individualized to the patient, with the main goal of reducing the risk of VILI. ECMO is a relatively rare intervention, and there are likely a minimum number of cases per year at a given center to maintain competency. Patients who have prolonged ECMO runs (i.e., greater than 21 days) are less likely to survive, though no absolute duration of ECMO that would mandate withdrawal of ECMO support can be currently recommended