Multi-disciplinary and pharmacological interventions to reduce post-operative delirium in elderly patients: A systematic review and meta-analysis

Study objective: An estimated 80% of older people undergoing surgery develop postoperative delirium (POD) making them a high-risk group. Research in this area is growing fast but there is no established consensus on strategies for POD prevention or management. A systematic review and meta-analysis were conducted to synthesise data on clinical interventions used to reduce POD among older people undergoing elective and emergency surgery. Methods: A range of database searches generated 336 papers. A total of 25 studies met the inclusion criteria and were assessed using the Joanna Briggs Institute Critical Appraisal Checklist. The studies were undertaken across the world. Results: This review identified a range of intervention approaches: comparisons between anaesthetic and sedatives agents, medication-specific interventions and multidisciplinary models of care. Results found more consistencies across multidisciplinary interventions than the pharmacological interventions. In pooled analyses, haloperidol (OR 0.74; 95% CI (confidence interval) 0.44, 1.26) was not statistically significantly associated with reduced POD incidence any more than a placebo. Conclusion: There is a need to implement multidisciplinary interventions, as well as collaboration between clinicians on pre- and postoperative care practices regarding pharmacological interventions to more effectively reduce and manage POD in older people

The Democratic Biopolitics of PrEP

PrEP (Pre-Exposure Prophylaxis) is a relatively new drug-based HIV prevention technique and an important means to lower the HIV risk of gay men who are especially vulnerable to HIV. From the perspective of biopolitics, PrEP inscribes itself in a larger trend of medicalization and the rise of pharmapower. This article reconstructs and evaluates contemporary literature on biopolitical theory as it applies to PrEP, by bringing it in a dialogue with a mapping of the political debate on PrEP. As PrEP changes sexual norms and subjectification, for example condom use and its meaning for gay subjectivity, it is highly contested. The article shows that the debate on PrEP can be best described with the concepts ‘sexual-somatic ethics’ and ‘democratic biopolitics’, which I develop based on the biopolitical approach of Nikolas Rose and Paul Rabinow. In contrast, interpretations of PrEP which are following governmentality studies or Italian Theory amount to either farfetched or trivial positions on PrEP, when seen in light of the political debate. Furthermore, the article is a contribution to the scholarship on gay subjectivity, highlighting how homophobia and homonormativity haunts gay sex even in liberal environments, and how PrEP can serve as an entry point for the destigmatization of gay sexuality and transformation of gay subjectivity. ‘Biopolitical democratization’ entails making explicit how medical technology and health care relates to sexual subjectification and ethics, to strengthen the voice of (potential) PrEP users in health politics, and to renegotiate the profit and power of Big Pharma

Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD.

Objective: To develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment. Methods: To illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks. Results: As of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous relatives of patients with NMOSD represented 43.6% of the control cohort. Of the 599 active cases with complete data, 84% were female, and 76% were anti-AQP4 seropositive. The majority were white/Caucasian (52.6%), whereas blacks/African Americans accounted for 23.5%, Hispanics/Latinos 12.4%, and Asians accounted for 9.0%. The median age at disease onset was 38.4 years, with a median ARR of 0.5. Seropositive cases were older at disease onset, more likely to be black/African American or Hispanic/Latino, and more likely to be female. Conclusions: Collectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD

Factors influencing early withdrawal from a drug and alcohol treatment program and client perceptions of successful recovery and employment: A qualitative study

Background: Substance use disorders are a major contributor to the economic and healthcare burden in Australia. Therapeutic communities (TCs) are utilised treatment methods globally, though low program completion rates continue to represent a major obstacle in effective and sustainable drug and alcohol treatment. The aim of this study was to explore reasons for early withdrawal from TC programs and perceptions of successful recovery. This study also aimed to explore how employment and volunteering related to early exit and perceptions of successful recovery. Methods: Semi-structured qualitative interviews were conducted with 13 ex-residents from a long-term TC program at a community-based rehab organisation in regional Australia. Results: Thematic analysis revealed a complex interplay of factors contributing to early TC withdrawal, and perceptions of successful recovery from a lived experience perspective and how this was shaped by employment and volunteering. Eleven themes were identified. Three relating to reasons for joining the program, which connected with ultimate withdrawal from the program: Pre-program existing relationships, pre-program employment situation and needing a \u27circuit breaker\u27 in their life. Three relating to reasons for early withdrawal: TC program characteristics, relationships during the program and planning future employment. Five relating to perceptions of successful recovery: Improved understanding of their addiction, reduced substance use, improved physical and psychological health, relationship success and employment success. Conclusions: Reasons for leaving treatment early are multi-faceted and revolve around relationships, planning future employment and program characteristics. The influence that each plays on their decision to leave early is varied and determined by the value they assign it. Perceived success extends far beyond achieving and maintaining abstinence to encompass improved relationships, psychological and physical wellbeing, understanding of addiction and employment, studying or volunteering. Self-worth and feeling able to contribute to society through employment, study and volunteering were perceived to be essential elements of successful recovery. Clinicians, policy makers and program developers should use the extended definition of successful recovery from the ex-clients perspective when determining the clinical and economic effectiveness of TC programs

Distribution of Glycerophospholipids in the Adult Human Lens

In humans, the age of fibre cells differs across the ocular lens, ranging from those formed before birth in the core of the lens to those formed just prior to death in the outer cortex. The distribution of glycerophospholipids in the adult human lens should reflect this range; however, limited data currently exists to confirm this hypothesis. Accordingly, this study aimed to determine the distribution of glycerophospholipids in adult human lens using mass spectrometry imaging. To achieve this, 20-µm thick slices of two human lenses, aged 51 and 67 were analysed by matrix-assisted laser desorption ionisation imaging mass spectrometry. The data clearly indicate that intact glycerophospholipids such as phosphatidylethanolamine, phosphatidylserine, and phosphatidic acid are mainly present in the outer cortex region, corresponding to the youngest fibre cells, while lyso-phosphatidylethanolamine, likely produced by the degradation of phosphatidylethanolamine, is present in the nucleus (older fibre cells). This study adds further evidence to the relationship between fibre cell age and glycerophospholipid composition

Systematic differences in membrane acyl composition associated with varying body mass in mammals occur in all phospholipid classes: an analysis of kidney and brain

The acyl composition of membrane phospholipids in kidney and brain of mammals of different body mass was examined. It was hypothesized that reduction in unsaturation index (number of double bonds per 100 acyl chains) of membrane phospholipids with increasing body mass in mammals would be made-up of similar changes in acyl composition across all phospholipid classes and that phospholipid class distribution would be regulated and similar in the same tissues of the different-sized mammals. Theresults of this study supported both hypotheses. Differences in membrane phospholipid acyl composition (i.e. decreased omega- 3 fats, increased monounsaturated fats and decreased unsaturation index with increasing body size) were not restricted to any specific phospholipid molecule or to any specific phospholipid class but were observed in all phospholipid classes. With increase in body mass of mammals both monounsaturates and use of less unsaturated polyunsaturates increases at the expense of the long-chain highly unsaturated omega-3 and omega-6 polyunsaturates, producing decreases in membrane unsaturation. The distribution of membrane phospholipid classes was essentially the same in the different-sized mammals with phosphatidylcholine (PC) and phosphatidylethanolamine (PE) together constituting ~91% and ~88% of all phospholipids in kidney and brain, respectively. The lack of sphingomyelin in the mouse tissues and higher levels in larger mammals suggests an increasedpresence of membrane lipid rafts in larger mammals. The results of this study support the proposal that the physical properties of membranes are likely to be involved in changing metabolic rate

Distribution of Glycerophospholipids in the Adult Human Lens

In humans, the age of fibre cells differs across the ocular lens, ranging from those formed before birth in the core of the lens to those formed just prior to death in the outer cortex. The distribution of glycerophospholipids in the adult human lens should reflect this range; however, limited data currently exists to confirm this hypothesis. Accordingly, this study aimed to determine the distribution of glycerophospholipids in adult human lens using mass spectrometry imaging. To achieve this, 20-µm thick slices of two human lenses, aged 51 and 67 were analysed by matrix-assisted laser desorption ionisation imaging mass spectrometry. The data clearly indicate that intact glycerophospholipids such as phosphatidylethanolamine, phosphatidylserine, and phosphatidic acid are mainly present in the outer cortex region, corresponding to the youngest fibre cells, while lyso-phosphatidylethanolamine, likely produced by the degradation of phosphatidylethanolamine, is present in the nucleus (older fibre cells). This study adds further evidence to the relationship between fibre cell age and glycerophospholipid composition

Liraglutide prevents metabolic side-effects and improves recognition and working memory during antipsychotic treatment in rats

BACKGROUND: Antipsychotic drugs (APDs), olanzapine and clozapine, do not effectively address the cognitive symptoms of schizophrenia and can cause serious metabolic side-effects. Liraglutide is a synthetic glucagon-like peptide-1 (GLP-1) receptor agonist with anti-obesity and neuroprotective properties. The aim of this study was to examine whether liraglutide prevents weight gain/hyperglycaemia side-effects and cognitive deficits when co-administered from the commencement of olanzapine and clozapine treatment. METHODS: Rats were administered olanzapine (2 mg/kg, three times daily (t.i.d.)), clozapine (12 mg/kg, t.i.d.), liraglutide (0.2 mg/kg, twice daily (b.i.d.)), olanzapine + liraglutide co-treatment, clozapine + liraglutide co-treatment or vehicle (Control) ( n = 12/group, 6 weeks). Recognition and working memory were examined using Novel Object Recognition (NOR) and T-Maze tests. Body weight, food intake, adiposity, locomotor activity and glucose tolerance were examined. RESULTS: Liraglutide co-treatment prevented olanzapine- and clozapine-induced reductions in the NOR test discrimination ratio ( p \u3c 0.001). Olanzapine, but not clozapine, reduced correct entries in the T-Maze test ( p \u3c 0.05 versus Control) while liraglutide prevented this deficit. Liraglutide reduced olanzapine-induced weight gain and adiposity. Olanzapine significantly decreased voluntary locomotor activity and liraglutide co-treatment partially reversed this effect. Liraglutide improved clozapine-induced glucose intolerance. CONCLUSION: Liraglutide co-treatment improved aspects of cognition, prevented obesity side-effects of olanzapine, and the hyperglycaemia caused by clozapine, when administered from the start of APD treatment. The results demonstrate a potential treatment for individuals at a high risk of experiencing adverse effects of APD

Fatty Acid Uptake and Incorporation into Phospholipids in the Rat Lens

This study provides evidence that, after 16 hours, diffusion of fatty acids from the aqueous humor is limited to the outer 25% to 30% of the rat lens radius. It also demonstrates that incorporation of these fatty acids into molecular phospholipids is limited, supporting the hypothesis that there is no active remodeling of fiber cell phospholipids

Lipid pathway alterations in Parkinson\u27s Disease primary visual cortex

Background: We present a lipidomics analysis of human Parkinson’s disease tissues. We have focused on the primary visual cortex, a region that is devoid of pathological changes and Lewy bodies; and two additional regions, the amygdala and anterior cingulate cortex which contain Lewy bodies at different disease stages but do not have as severe degeneration as the substantia nigra. Methodology/Principal Findings: Using liquid chromatography mass spectrometry lipidomics techniques for an initial screen of 200 lipid species, significant changes in 79 sphingolipid, glycerophospholipid and cholesterol species were detected in the visual cortex of Parkinson’s disease patients (n = 10) compared to controls (n = 10) as assessed by two-sided unpaired t-test (p-value ,0.05). False discovery rate analysis confirmed that 73 of these 79 lipid species were significantly changed in the visual cortex (q-value ,0.05). By contrast, changes in 17 and 12 lipid species were identified in the Parkinson’s disease amygdala and anterior cingulate cortex, respectively, compared to controls; none of which remained significant after false discovery rate analysis. Using gas chromatography mass spectrometry techniques, 6 out of 7 oxysterols analysed from both non-enzymatic and enzymatic pathways were also selectively increased in the Parkinson’s disease visual cortex. Many of these changes in visual cortex lipids were correlated with relevant changes in the expression of genes involved in lipid metabolism and an oxidative stress response as determined by quantitative polymerase chain reaction techniques. Conclusions/Significance: The data indicate that changes in lipid metabolism occur in the Parkinson’s disease visual cortex in the absence of obvious pathology. This suggests that normalization of lipid metabolism and/or oxidative stress status in the visual cortex may represent a novel route for treatment of non-motor symptoms, such as visual hallucinations, that are experienced by a majority of Parkinson’s disease patients