Glucose degradation products in peritoneal dialysis fluids may have both local and systemic effects: a study of residual fluid and mesothelial cells.

OBJECTIVE: When peritoneal dialysis (PD) fluids are heat sterilized, glucose is degraded to carbonyl compounds. These compounds are known to interfere with many cellular functions and to promote the formation of advanced glycation end-products. However, little is known about what actually happens with glucose degradation products (GDPs) after infusion into the peritoneal cavity. The aim of the present study was to investigate possible targets for GDPs in the peritoneal cavity. DESIGN: In vitro reactions between residual fluid and GDPs were studied by incubating unused PD fluid with overnight dialysate. Confluent monolayer cultures of human mesothelial cells were used as a model to study the reactions of GDPs with the cells lining the peritoneal cavity. METHODS: Samples were analyzed, using high pressure liquid chromatography, for the presence of formaldehyde, acetaldehyde, 5-hydroxymethyl-2-furaldehyde (5-HMF), methylglyoxal, and 3-deoxyglucosone (3-DG). Cytotoxicity was determined as inhibition of proliferation of cultured fibroblasts. RESULTS: None of the analyzed GDPs reacted with overnight dialysate. Formaldehyde and methylglyoxal, in contrast to 3-DG and 5-HMF, reacted with the cultured mesothelial cells. CONCLUSIONS: Low molecular weight carbonyls such as formaldehyde and methylglyoxal most probably react with the mesothelial cells lining the peritoneal cavity, and could be responsible for the disappearance of these cells during long-term treatment. 3-Deoxyglucosone showed remarkably low reactivity and was most probably transported within the patient.     

Evaluating health management programmes over time: application of propensity score-based weighting to longitudinal data

Health management programmes are generally evaluated as point treatment studies in which only a baseline and outcome measurement are used in the analysis, even when multiple observations for each individual are available. By summarizing observations into two distinct measurements the evaluator loses any ability to discern patterns of change in the outcome variable over time in relation to the intervention. There are several statistical models available to evaluate longitudinal data that are typically regression-like in form and designed to adjust for clustering at the individual level. Most evaluators of longitudinal studies tend to adjust for the effect of time-dependent confounding by including these covariates as independent variables in the model. However, this standard adjustment approach is likely to provide biased estimates. In this paper we describe the application of the propensity score-based weighting technique to longitudinal data to estimate the effect of treatment on an outcome. This method reweights each treatment pattern to represent the entire population at each time point and provides an unbiased treatment effect. We illustrate the technique using data from a disease management programme and demonstrate its superiority over standard analytical adjustments in correcting for time-dependent confounding for each time period under study.     

Fractures in the maxillofacial region: A four year retrospective study

Introduction: The incidence of maxillofacial injuries is on the rise due to motor vehicle accidents and increased incidence of violence in recent times. The aim of this retrospective study was to determine the incidence, aetiology, the pattern of fractures, their management with open reduction and internal fixation (ORIF) and complications, if any.     

Preliminary structure and predictive value of attenuated negative symptoms in 22q11.2 deletion syndrome

Current research in schizophrenia suggests that negative symptoms cannot be considered a unitary construct and should be divided in two dimensions: lack of motivation and impoverishment of expression. In addition, negative symptoms are particularly related to decreased daily-life functioning. In the present study, we aimed to replicate these results in a sample of participants with 22q11.2 deletion syndrome (22q11DS), a neurogenetic condition associated with high risk of developing schizophrenia. We also expected to observe an association between the COMT Val/Met polymorphism and negative symptoms. We examined the factorial structure of negative symptoms in a sample of 47 individuals with 22q11DS using the Structured Interview for Prodromal Symptoms (SIPS) and the Positive and Negative Syndrome Scale (PANSS). We also performed stepwise regression analyses to investigate the associations between negative symptoms, adaptive skills and the COMT Val/Met polymorphism. Negative symptoms were explained by a two-factor solution, namely the "amotivation and social withdrawal" and the "emotional withdrawal and expression" dimensions. The motivational dimension was significantly associated with daily-life functioning. Met carriers were rated as experiencing significantly more symptoms of amotivation. The results are interpreted in the light of existing cognitive models in the field of motivation and schizophrenia.     

Brain imaging and psychotherapy: methodological considerations and practical implications

The development of psychotherapy has been based on psychological theories and clinical effects. However, an investigation of the neurobiological mechanisms of psychological interventions is also needed in order to improve indication and prognosis, inform the choice of parallel pharmacotherapy, provide outcome measures and potentially even aid the development of new treatment protocols. This neurobiological investigation can be informed by animal models, for example of learning and conditioning, but will essentially need the non-invasive techniques of functional neuroimaging in order to assess psychotherapy effects on patients’ brains, which will be reviewed here. Most research so far has been conducted in obsessive compulsive disorder (OCD), anxiety disorders and depression. Effects in OCD were particularly exciting in that both cognitive behavioural therapy and medication with a selective serotonin inhibitor led to a reduction in blood flow in the caudate nucleus. In phobia, brief courses of behavioural therapy produced marked reductions of paralimbic responses to offensive stimuli in line with the clinical improvement. Findings in depression are less consistent, with both increases and decreases in prefrontal metabolism being reported. However, they are important in pointing to different mechanisms for the clinical effects of pharmacotherapy (more “bottom up”) and psychotherapy (more “top down”). For the future it would be desirable if the findings of psychotherapy changes to brain activation patterns were confirmed in larger groups with homogenous imaging protocols. Functional imaging has already made great contributions to the understanding of the neural correlates of psychopathology. For example, evidence converges to suggest that the subgenual cingulate is crucial for mood regulation. One current clinical application of these findings is deep brain stimulation in areas highlighted by such imaging studies. I will discuss their initial application in depression and OCD, and suggest potential alternative options based on recent developments in neurofeedback technology.

     

Using balance statistics to determine the optimal number of controls in matching studies

When a randomized controlled trial is not feasible, investigators typically turn to matching techniques as an alternative approach to evaluate the effectiveness of health care interventions. Matching studies are designed to minimize imbalances on measured pre‐intervention characteristics, thereby reducing bias in estimates of treatment effects. Generally, a matching ratio up to 4:1 (control to treatment) elicits the lowest bias. However, when matching techniques are used in prospective studies, investigators try to maximize the number of controls matched to each treated individual to increase the likelihood that a sufficient sample size will remain after attrition. In this paper, we describe a systematic approach to managing the trade‐off between minimizing bias and maximizing matched sample size. Our approach includes the following three steps: (1) run the desired matching algorithm, starting with 1:1 (one control to one treated individual) matching and iterating until the maximum desired number of potential controls per treated subject is reached; (2) for each iteration, test for covariate balance; and (3) generate numeric summaries and graphical plots of the balance statistics across all iterations in order to determine the optimal solution. We demonstrate the implementation of this approach with data from a medical home pilot programme and with a simulation study of populations of 100 000 in which 1000 individuals receive the intervention. We advocate undertaking this methodical approach in matching studies to ensure that the optimal matching solution is identified. Doing so will raise the overall quality of the literature and increase the likelihood of identifying effective interventions.     

Supporting parents in the NICU: A new app from the US, ‘MyPreemie’: A tool to provide parents of premature babies with support,empowerment, education and participation in their infant's care

This article describes the new MyPreemie app for iPhone and iPad, designed to inform, assist, empower, and support parents of premature babies in the NICU and afterwards. Created by the same team who wrote the book Preemies: The Essential Guide for Parents of Premature Babies, the app contains information on medical and developmental issues; suggested questions for parents to ask doctors and nurses to understand their baby's care; a combined baby journal and adult diary with focused prompts to record events and emotions; tools to track growth; and organizing lists for questions to ask, tasks to do, and mementos to collect. The app's pages can be shared by email or Facebook to facilitate communication with family and friends, and printed in PDF and saved. Overall, the app aims to ease parents' distress by providing meaningful parenting activities during a baby's NICU stay and an increased sense of normality, control, and connection. Nurses are encouraged to advise their patients' families about the MyPreemie app as a way to help meet their practical and emotional needs and support them through the stressful experience of prematurity.     

Treatment with quercetin and 3′,4′-dihydroxyflavonol inhibits platelet function and reduces thrombus formation in vivo

Flavonols are polyphenolic compounds with reported cardiovascular benefits and have been shown to exhibit antiplatelet properties in vitro. While some studies have shown inhibition of platelet aggregation following dietary supplementation with flavonol rich foods, few studies have assessed the ability of flavonols to inhibit platelet mediated thrombus generation in vivo. Furthermore, the duration of benefit and the influence of different dosing regimens remain unclear. In this study we investigate the ability of two structurally related flavonols; quercetin (Que) and 3′,4′-dihydroxyflavonol (DiOHF) to inhibit platelet aggregation, platelet granule exocytosis and vessel occlusion in a well characterized mouse model of platelet mediated arterial thrombosis. We investigated the effect of a single 6 mg/kg intravenous bolus and daily 6 mg/kg intraperitoneal doses over seven consecutive days. Carotid artery blood flow after injury was better maintained in mice treated with both Que and DiOHF when compared to the vehicle for both dosage regimens. This improved blood flow corresponded to inhibition of platelet aggregation and platelet dense granule exocytosis following chemical stimulation of PAR4. We therefore provide evidence of inhibition of platelet-mediated arterial thrombosis by flavonols in vivo, and demonstrate that this effect persists for at least 24 h after the last intraperitoneal dose. These data suggest a potential clinical role for flavonols as anti-platelet therapy.