Search

Bipolar disorder is a relatively common mental illness, characterised by recurrent episodes of mania (or hypomania) and major depression, and associated with a significant burden of morbidity and premature mortality. Physicians across all specialities are likely to encounter individuals with the condition within their clinical practice. This short review provides an up-to-date overview of the clinical features, epidemiology, pathophysiology, evidence-based management, prognosis and future directions for treatment and research in bipolar disorder. Aspects of cross-specialty relevance are highlighted, including the physical health burden associated with the condition, and the side effects and safety considerations of medication regimes used in bipolar disorder.

Objectives: To identify and analyse ethical considerations raised when individuals with body dysmorphic disorder (BDD) consult for non-surgical cosmetic procedures., Methods: Ethical analysis was conducted addressing the issues of best interests and capacity to consent for non-surgical cosmetic procedures in individuals with BDD. Analysis was informed by the findings of semistructured interviews with non-surgical cosmetic practitioners and mental health professionals., Findings: Non-surgical cosmetic interventions were viewed not to be in the best interests of individuals with BDD, as they fail to address core psychological issues, result in dissatisfaction post-procedure, and risk harm. Referral to mental health services was advocated, however numerous obstacles to this were perceived. The issue of capacity to consent to non-surgical cosmetic procedures raised questions regarding whether standard capacity assessment is sensitive to the manner in which BDD may influence decision-making processes. In addition, concerns were voiced that decisions made by individuals with BDD in this context may be judged foolish, and thus wrongly equated with lack of capacity., Discussion/conclusions: Ethical analysis, informed by the available evidence base, suggests that it is generally not in the best interests of individuals with BDD to undergo non-surgical cosmetic intervention, and referral to mental health services is indicated. Analysis of capacity draws parallels between BDD and anorexia nervosa, as decision-making capacity in both conditions can be impaired by pathological values derived from the disorder. Means of differentiating clinical assessment of pathological values from inappropriate value judgements are advocated, in order to safeguard against the latter encroaching into capacity assessment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Risk prediction for psychosis has advanced to the stage at which it could feasibly become a clinical reality. Neuroimaging biomarkers play a central role in many risk prediction models. Using such models to predict the likelihood of transition to psychosis in individuals known to be at high risk has the potential to meaningfully improve outcomes, principally through facilitating early intervention. However, this compelling benefit must be evaluated in light of the broader ethical ramifications of this prospective development in clinical practice. This paper advances ethical discussion in the field in two ways: firstly, through in-depth consideration of the distinctive implications of the clinical application of predictive tools; and, secondly, by evaluating the manner in which newer predictive models incorporating neuroimaging alter the ethical landscape. We outline the current state of the science of predictive testing for psychosis, with a particular focus on emerging neuroimaging biomarkers. We then proceed to ethical analysis employing the four principles of biomedical ethics as a conceptual framework. We conclude with a call for scientific advancement to proceed in tandem with ethical consideration, informed by empirical study of the views of high risk individuals and their families. This collaborative approach will help ensure that predictive testing progresses in an ethically acceptable manner that minimizes potential adverse effects and maximizes meaningful benefits for those at high risk of psychosis., Competing Interests: Declaration of Competing Interests The authors have no relevant conflicts of interest to declare., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The heart is characterized by a remarkable degree of heterogeneity, the basis of which is a subject of active investigation. Myofilament protein post-translational modifications (PTMs) represent a critical mechanism regulating cardiac contractility, and emerging evidence shows that pathological cardiac conditions induce contractile heterogeneity that correlates with transmural variations in the modification status of myofilament proteins. Nevertheless, whether there exists basal heterogeneity in myofilament protein PTMs in the heart remains unclear. Here we have systematically assessed chamber-specific and transmural variations in myofilament protein PTMs, specifically, the phosphorylation of cardiac troponin I (cTnI), cardiac troponin T (cTnT), tropomyosin (Tpm), and myosin light chain 2 (MLC2). We show that the phosphorylation of cTnI and αTm vary in the different chambers of the heart, whereas the phosphorylation of MLC2 and cTnT does not. In contrast, no significant transmural differences were observed in the phosphorylation of any of the myofilament proteins analyzed. These results highlight the importance of appropriate tissue sampling-particularly for studies aimed at elucidating disease mechanisms and biomarker discovery-in order to minimize potential variations arising from basal heterogeneity in myofilament PTMs in the heart., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Actin is the major component of the cytoskeleton, playing an essential role in the structure and motility of both muscle and nonmuscle cells. It is highly conserved and encoded by a multigene family. α-Cardiac actin (αCAA) and α-skeletal actin (αSKA), encoded by two different genes, are the primary actin isoforms expressed in striated muscles. The relative expression levels of αSKA and αCAA have been shown to vary between species and under pathological conditions. In particular, an increased αSKA expression is believed to be a programmed response of a diseased heart. Therefore, it is essential to quantify the relative expression of αSKA and αCAA, which remains challenging due to the high degree of sequence similarity between these isoforms (98.9%). Herein, we developed a top-down liquid chromatography/mass spectrometry-based ("LC/MS+") method for the rapid purification and comprehensive analysis of α-actin extracted from muscle tissues. We thoroughly investigated all of the actin isoforms in healthy human cardiac and skeletal muscles. We found that αSKA is the only isoform expressed in skeletal muscle, whereas αCAA and αSKA are coexpressed in cardiac muscle. We then applied our method to quantify the α-actin isoforms in human healthy hearts and failing hearts with dilated cardiomyopathy (DCM). We found that αSKA is augmented in DCM compared with healthy controls, 43.1 ± 0.9% versus 23.7 ± 1.7%, respectively. As demonstrated, top-down LC/MS+ provides an effective and comprehensive method for the purification, quantification, and characterization of α-actin isoforms, enabling assessment of their clinical potential as cardiac disease markers.

Objective: To assess the potential effect of a computer-based system on accrual to clinical trials, we have developed methodology to identify retrospectively and prospectively patients who are eligible or potentially eligible for protocols., Design: Retrospective chart abstraction with computer screening of data for potential protocol eligibility., Setting: A county-operated clinic serving human immunodeficiency virus (HIV) positive patients with or without acquired immune deficiency syndrome (AIDS)., Patients: A randomly selected group of 60 patients who were HIV-infected, 30 of whom had an AIDS-defining diagnosis., Design: Using a computer-based eligibility screening system, for each clinic visit and hospitalization, patients were categorized as eligible, potentially eligible, or ineligible for each of the 17 protocols active during the 7-month study period. Reasons for ineligibility were categorized., Results: None of the patients was enrolled on a clinical trial during the 7-month period. Thirteen patients were identified as eligible for protocol; three patients were eligible for two different protocols; and one patient was eligible for the same protocol during two different time intervals. Fifty-four patients were identified as potentially eligible for a total of 165 accrual opportunities, but important information, such as the result of a required laboratory test, was missing, so that eligibility could not be determined unequivocally. Ineligibility for protocol was determined in 414 (35%) potential opportunities based only on conditions that were amenable to modification, such as the use of concurrent medications; 194 (17%) failed only laboratory tests or subjective determinations not routinely performed; and 346 (29%) failed only routine laboratory tests., Conclusions: There are substantial numbers of eligible and potentially eligible patients who are not enrolled or evaluated for enrollment in prospective clinical trials. Computer-based eligibility screening when coupled with a computer-based medical record offers the potential to identify patients eligible or potentially eligible for clinical trial, to assist in the selection of protocol eligibility criteria, and to make accrual estimates.

The task of determining patients' eligibility for clinical trials is knowledge and data intensive. In this paper, we present a model for the task of eligibility determination, and describe how a computer system can assist clinical researchers in performing that task. Qualitative and probabilistic approaches to computing and summarizing the eligibility status of potentially eligible patients are described. The two approaches are compared, and a synthesis that draws on the strengths of each approach is proposed. The result of applying these techniques to a database of HIV-positive patient cases suggests that computer programs such as the one described can increase the accrual rate of eligible patients into clinical trials. These methods may also be applied to the task of determining from electronic patient records whether practice guidelines apply in particular clinical situations.

The purpose of this study was to determine whether waterbeds enhance preterm infants' sleep and reduce irritability, and whether plain, continuously, or intermittently oscillating waterbeds are differentially effective in producing these effects. The baseline states and motility of 52 stable preterm infants were assessed on two consecutive days for 100 minutes each. The infants then were randomly assigned to four groups: a control group who remained on the incubator mattress, or to one of the three experimental groups, each using a different waterbed. On days 3 and 4 in the assigned test condition, the infants' states and motility were again assessed for 100 minutes each day. The results indicate that, compared with infants in the control group, infants assigned to any of the waterbed groups slept significantly more and better, had significantly fewer unsmooth movements, state changes, and transitional states, and were significantly less irritable. Differential treatment effects were found, with infants on continuously oscillating waterbeds showing the most marked reductions in irritability, restlessness, state changes, and unsmooth movements. Thus, to enhance restful sleep and to reduce irritability and/or restlessness, it would be clinically advantageous to use waterbeds in the care of preterm infants. Since even the simple, nonoscillating waterbed improved sleep and reduced restlessness, the use of these beds would be the least costly to achieve these effects.

In a longitudinal study with the Neurobehavioral Maturity Assessment (NB-MAP), developmental changes and stability of individual differences were assessed in 2 independent samples of preterm infants ranging from 32 weeks conceptional age to term. Individual stability of response was assessed using regression analysis with repeated measures on subjects. The large majority of the functions tested showed highly significant developmental gains with age and highly significant individual stability of performance across age. These findings replicated well across the 2 cohorts. The results are discussed in the light of the neurobiological stage of development of preterm infants during the last 8 weeks prior to term.