Cognitive function following a major depressive episode: a systematic review and meta-analysis.

BACKGROUND: Substantial evidence suggests that cognitive deficits might persist after remission of a major depressive episode. However, results are inconsistent relative to the importance, pattern, severity, and moderating factors of this impairment. We aimed to determine how cognitive function following a major depressive episode compares with normal function, to specify the pattern and severity of persistent cognitive dysfunctions, and to examine the potential moderator effect of ten prespecified clinical and demographic variables. METHODS: We did a systematic review and meta-analysis of the published research. We searched systematically MEDLINE, Embase, PsycARTICLES, PsycINFO, the Cochrane Library, and relevant reviews identified by our database search, for research published from Jan 1, 1972, up to Jan 31, 2018, for studies of patients with past depression. We included all independent studies of patients who were assessed while in remission from a major depressive episode with at least one cognitive test, with inclusion of a healthy control group assessed with either the same test(s) as the major depressive episode group or with a standardised test with published age-stratified normative data. The main outcome was the difference in cognitive performance between major depressive episode remitters and healthy controls. Effect sizes were calculated using random-effects models for cognitive outcomes classified into 18 standard domains. Moderators of between-study variability were assessed using mixed-effects subgroup analyses and meta-regressions. FINDINGS: Of 10 126 citations identified by our search, 75 cognitive variables from 252 eligible studies (11 882 major depressive episode remitters and 8533 healthy controls) were included in our meta-analysis. Significant deficits following major depressive episode remission were observed in 55 (73%) of the 75 cognitive variables. These deficits (in the domains of processing speed, visual selective attention, working memory, verbal learning, and executive functioning), were generally small (30 [40%] of the 75 variables) or medium (22 [29%]) in size, although three long-term memory variables showed large deficits: g=-0·81 [95% CI -1·01 to -0·61] for logical memory immediate recall, g=-0·88 [-1·19 to -0·57] for logical memory delayed recall, and g=-0·84 [-1·18 to -0·50] for Cambridge Neuropsychological Test Automated Battery pattern recognition latency. Auditory attention, general autobiographical memory, inhibition ability unconstrained by speed, and intellectual functioning unconstrained by speed were equivalent between major depressive episode remitters and matched controls. The number of previous depressive episodes explained heterogeneity in the majority of variables (z=-2·06 [p=0·039] to z=-4·26 [p<0·0001]). INTERPRETATION: Deficits in selective attention, working memory, and long-term memory persist in remission from a major depressive episode and worsen with repeated episodes. Depression treatments, including relapse prevention, need to target these cognitive functions to optimise prognosis. FUNDING: None.

Liposomal bupivacaine for regional anesthesia.

PURPOSE OF REVIEW: Using a regional block in a multimodal approach to postoperative analgesia management involves addressing, which local anesthetic and how much should be used to ensure adequate pain relief to reduce related morbidity and mortality. This article will review literature surrounding the recently approved formulation of slow release liposomal bupivacaine, define its proven benefits, and identify ongoing studies to further examine the utility of this novel formulation by various routes. RECENT FINDINGS: Recent Phase II and III clinical trials have demonstrated the ability of liposomal bupivacaine to provide prolonged analgesia, maintain a high safety profile in therapeutic doses, and decrease opioid requirements when compared with placebo in local infiltration applications for up to 24 h. Between 24 and 72 h after study drug administration, there was minimal to no difference between EXPAREL and placebo treatments on mean pain intensity. Conventional bupivacaine or ropivacaine groups (current standard practice in many hospitals in the USA) were not compared. In addition, the analgesic efficacy, cost-effectiveness, and safety profile of liposomal bupivacaine has not thoroughly been studied in various standard clinical settings such as perineural, intrathecal, and epidural administration. SUMMARY: Current published data do not provide superior clinical results for EXPAREL over conventional bupivacaine based upon the lack of adequately powered multicentered clinical trials with comparison groups. Further investigation is necessary to identify the analgesic efficacy and safety profile of liposomal bupivacaine versus standard local anesthetics and to define the optimal clinical indication for liposomal bupivacaine administration in regional anesthesia.

Decoy calcium channel beta subunits modulate contractile function in myocytes.

To test the hypothesis that mutated beta2-subunits of the L-type calcium channel could serve as a decoy and interdict calcium channel trafficking and function, we engineered a beta2 subunit that contained the beta interaction domain for alpha1c subunit interaction, but lacked N- and C-terminal domains that might be essential for sarcolemmal localization. An adenoviral vector was constructed containing the gene for the beta-interaction domain (BID) fused to green fluorescence protein (GFP), using a vector containing only GFP as control. Freshly plated, dissociated adult rat myocytes were infected and expression and function were assessed at 60 h. Fluorescence microscopy confirmed GFP expression; immunoblot analysis confirmed dose-dependent GFP-BID expression. Mechanical properties of adult rat ventricular myocytes were evaluated using a video edge-detection system. Contractility analysis (optical/video, field stimulation) demonstrated that contracting cells decreased from 60 to 2%. Contractile amplitude (percent shortening) decreases significantly from 5.6 vs. 2.4% with no change in time to peak twitch. Recombinant adenovirus overexpressing mutated beta2 subunits in adult mammalian myocytes can markedly alter excitation-contraction coupling. This paradigm may offer new approaches to understanding and modulating EC coupling.