Intervening to eliminate the centre-effect variation in home dialysis use: protocol for Inter-CEPt - a sequential mixed-methods study designing an intervention bundle

Introduction: Use of home dialysis by centres in the UK varies considerably and is decreasing despite attempts to encourage greater use. Knowing what drives this unwarranted variation requires in-depth understanding of centre cultural and organisational factors and how these relate to quantifiable centre performance, accounting for competing treatment options. This knowledge will be used to identify components of a practical and feasible intervention bundle ensuring this is realistic and cost-effective. Methods and analysis: Underpinned by the non-adoption, abandonment, scale-up, spread and sustainability framework, our research will use an exploratory sequential mixed-methods approach. Insights from multisited focused team ethnographic and qualitative research at four case study sites will inform development of a national survey of 52 centres. Survey results, linked to patient-level data from the UK Renal Registry, will populate a causal graph describing patient and centre-level factors, leading to uptake of home dialysis and multistate models incorporating patient-level treatment modality history and mortality. This will inform a contemporary economic evaluation of modality cost-effectiveness that will quantify how modification of factors facilitating home dialysis, identified from the ethnography and survey, might yield the greatest improvements in costs, quality of life and numbers on home therapies. Selected from these factors, using the capability, opportunity and motivation for behaviour change framework (COM-B) for intervention design, the optimal intervention bundle will be developed through workshops with patients and healthcare professionals to ensure acceptability and feasibility. Patient and public engagement and involvement is embedded throughout the project. Ethics and dissemination: Ethics approval has been granted by the Health Research Authority reference 20-WA-0249. The intervention bundle will comprise components for all stake holder groups: commissioners, provider units, recipients of dialysis, their caregivers and families. To reache all these groups, a variety of knowledge exchange methods will be used: short guides, infographics, case studies, National Institute for Health and Care Excellence guidelines, patient conferences, ‘Getting it Right First Time’ initiative, Clinical Reference Group (dialysis)

Aromatherapy Use for Post-operative Nausea and Vomiting for Patients Undergoing Same-day Surgeries

Description: Nausea and vomiting are frequent complications of anesthesia post-operatively. There is an increased prevalence of postoperative nausea and vomiting (PONV) in patients undergoing intra-abdominal and gynecologic surgeries. Many injectable and enteral medications are available for the prevention and treatment of PONV, each with the potential for side effects. Utilization of medications requires a provider order, which has the potential to delay initiation of therapy. The use of aromatherapy via inhalation for the treatment of PONV has been shown to eliminate nausea in up to 85% of patients. Patients have reported perceived effectiveness and favorable improvement with the use of aromatherapy for post-operative nausea. Aromatherapy products have been shown to be well tolerated with no adverse effects, drug interactions, or contraindications. Aim: To study the effectiveness of QueaseEASE® aromatherapy pods in the treatment of PONV in patients undergoing same-day intra-abdominal surgeries or hysterectomies. Intervention: We distributed 100 QueaseEASE® pods to patients scheduled for same-day intra-abdominal surgeries or hysterectomies. Informed consent was obtained preoperatively. Up to 24 hours after recovery, patients were instructed to document their episodes of nausea, severity at onset and severity 30 minutes after pod use. The severity of nausea was recorded using the visual analogue scale (0-100) where zero indicates no nausea and 100 indicates unbearable nausea. Use of traditional antiemetic medications was not excluded pursuant to individual provider practice. Data for concomitant antiemetic medication use was also recorded, including medication type, dose and frequency. Summary of Results: Results pending

Mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury at first presentation to hospital

Acetaminophen overdose is a common reason for hospital admission and the most frequent cause of hepatotoxicity in the Western world. Early identification would facilitate patient-individualized treatment strategies. We investigated the potential of a panel of novel biomarkers (with enhanced liver expression or linked to the mechanisms of toxicity) to identify patients with acetaminophen-induced acute liver injury (ALI) at first presentation to the hospital when currently used markers are within the normal range. In the first hospital presentation plasma sample from patients (n = 129), we measured microRNA-122 (miR-122; high liver specificity), high mobility group box-1 (HMGB1; marker of necrosis), full-length and caspase-cleaved keratin-18 (K18; markers of necrosis and apoptosis), and glutamate dehydrogenase (GLDH; marker of mitochondrial dysfunction). Receiver operator characteristic curve analysis and positive/negative predictive values were used to compare sensitivity to report liver injury versus alanine transaminase (ALT) and International Normalized Ratio (INR). In all patients, biomarkers at first presentation significantly correlated with peak ALT or INR. In patients presenting with normal ALT or INR, miR-122, HMGB1, and necrosis K18 identified the development of liver injury (n = 15) or not (n = 84) with a high degree of accuracy and significantly outperformed ALT, INR, and plasma acetaminophen concentration for the prediction of subsequent ALI (n = 11) compared with no ALI (n = 52) in patients presenting within 8 hours of overdose. Conclusion: Elevations in plasma miR-122, HMGB1, and necrosis K18 identified subsequent ALI development in patients on admission to the hospital, soon after acetaminophen overdose, and in patients with ALTs in the normal range. The application of such a biomarker panel could improve the speed of clinical decision-making, both in the treatment of ALI and the design/execution of patient-individualized treatment strategies

Multifidi muscle characteristics and physical function among older adults with and without chronic low back pain

To determine whether multifidi size, intramuscular fat, or both, are associated with self-reported and performance-based physical function in older adults with and without chronic low back pain (LBP).Case-control study.Individuals participated in a standardized evaluation in a clinical laboratory and underwent magnetic resonance imaging (MRI) of the lumbar spine at a nearby facility.A volunteer sample of community-dwelling older adults (N=106), aged 60 to 85 years, with (n=57) and without (n=49) chronic LBP were included in this secondary data analysis.Average right-left L5 multifidi relative (ie, total) cross-sectional area (CSA), muscle-fat infiltration index (MFI) (ie, a measure of intramuscular fat), and relative muscle CSA (rmCSA) (ie, total CSA minus intramuscular fat CSA) were determined from MRIs. Linear regression modeling was performed with physical function measures as the dependent variables. Age, sex, and body mass index were entered as covariates. The main effects of L5 multifidi MFI and rmCSA, as well as their interaction with group assignment, were compared as independent variables.Medical Outcomes Study 36-Item Short-Form Health Survey physical functioning subscale, timed Up and Go, gait speed, and fast stair descent performance.Interaction terms between L5 multifidi MFI and group assignment were found to be significant contributors to the variance explained in all physical function measures (P≤.012). Neither the main effect nor the interaction with group assignment for L5 multifidi rmCSA significantly contributed to the variance explained in any of the physical function measures (P>.012).Among older adults with chronic LBP of at least moderate intensity, L5 multifidi muscle composition, but not size, may help to explain physical function

TeV Particle Astrophysics II: Summary comments

A unifying theme of this conference was the use of different approaches to understand astrophysical sources of energetic particles in the TeV range and above. In this summary I review how gamma-ray astronomy, neutrino astronomy and (to some extent) gravitational wave astronomy provide complementary avenues to understanding the origin and role of high-energy particles in energetic astrophysical sources.Comment: 6 pages, 4 figures; Conference summary talk for "TeV Particle Astrophysics II" at University of Wisconsin, Madison, 28-31 August 200

Dysregulated protocadherin-pathway activity as an intrinsic defect in induced pluripotent stem cell-derived cortical interneurons from subjects with schizophrenia.

We generated cortical interneurons (cINs) from induced pluripotent stem cells derived from 14 healthy controls and 14 subjects with schizophrenia. Both healthy control cINs and schizophrenia cINs were authentic, fired spontaneously, received functional excitatory inputs from host neurons, and induced GABA-mediated inhibition in host neurons in vivo. However, schizophrenia cINs had dysregulated expression of protocadherin genes, which lie within documented schizophrenia loci. Mice lacking protocadherin-α showed defective arborization and synaptic density of prefrontal cortex cINs and behavioral abnormalities. Schizophrenia cINs similarly showed defects in synaptic density and arborization that were reversed by inhibitors of protein kinase C, a downstream kinase in the protocadherin pathway. These findings reveal an intrinsic abnormality in schizophrenia cINs in the absence of any circuit-driven pathology. They also demonstrate the utility of homogenous and functional populations of a relevant neuronal subtype for probing pathogenesis mechanisms during development