The use of eculizumab as a bridge to retransplantation for chronic antibody-mediated rejection in a heart transplant recipient: a case report.

BackgroundAntibody-mediated rejection (AMR) remains a major management challenge in heart transplantation given the complexity of pathological diagnosis and dearth of evidence for effective management. Eculizumab, an anti-C5 monoclonal antibody which inhibits terminal complement activation, has been reported to decrease early AMR in sensitized renal transplant recipients.Case summaryWe report a case of a 29-year-old gentleman with chronic AMR 8 years after heart transplantation, manifesting as significant graft dysfunction. Donor-specific antibodies to DQ7 were found to be causative. Antibody-mediated rejection was managed with quadruple oral immunosuppressive therapy (mycophenolate, prednisolone, everolimus, and tacrolimus) as well as a sequence of broad-spectrum immunological therapies; intravenous (IV) methylprednisolone, plasmapheresis, IV immunoglobulin, rituximab, bortezomib, tocilizumab, and splenic irradiation. No treatment had a sustained impact on donor-specific anti-HLA antibodies (DSAs) or graft function. After testing showed the DQ7 antibodies were complement-binding, a trial of eculizumab was started. This improved DSAs somewhat, and improved graft function and New York Heart Association functional class substantially. The patient was relisted for heart transplantation and successfully retransplanted in March 2018. Specifically, the new organ and recipient were matched at DQ7. After discontinuation of eculizumab, the patient has remained healthy and well, with normal graft function 28 months after retransplantation.DiscussionTo the best of our knowledge, this is the first case of chronic AMR in a heart transplant patient, successfully stabilized with eculizumab and bridged to retransplantation

‘Around the edges’: using behaviour change techniques to characterise a multilevel implementation strategy for a fall prevention programme

Abstract Background Implementation strategies are needed to ensure that evidence-based healthcare interventions are adopted successfully. However, strategies are generally poorly described and those used in everyday practice are seldom reported formally or fully understood. Characterising the active ingredients of existing strategies is necessary to test and refine implementation. We examined whether an implementation strategy, delivered across multiple settings targeting different stakeholders to support a fall prevention programme, could be characterised using the Behaviour Change Technique (BCT) Taxonomy. Methods Data sources included project plans, promotional material, interviews with a purposive sample of stakeholders involved in the strategy’s design and delivery and observations of staff training and information meetings. Data were analysed using TIDieR to describe the strategy and determine the levels at which it operated (organisational, professional, patient). The BCT Taxonomy identified BCTs which were mapped to intervention functions. Data were coded by three researchers and finalised through consensus. Results We analysed 22 documents, 6 interviews and 4 observation sessions. Overall, 21 out a possible 93 BCTs were identified across the three levels. At an organisational level, identifiable techniques tended to be broadly defined; the most common BCT was restructuring the social environment. While some activities were intended to encourage implementation, they did not have an immediate behavioural target and could not be coded using BCTs. The largest number and variety of BCTs were used at the professional level to target the multidisciplinary teams delivering the programme and professionals referring to the programme. The main BCTs targeting the multidisciplinary team were instruction on how to perform the (assessment) behaviour and demonstration of (assessment) behaviour; the main BCT targeting referrers was adding objects to the environment. At the patient level, few BCTs were used to target attendance. Conclusion In this study, several behaviour change techniques were evident at the individual professional level; however, fewer techniques were identifiable at an organisational level. The BCT Taxonomy was useful for describing components of a multilevel implementation strategy that specifically target behaviour change. To fully and completely describe an implementation strategy, including components that involve organisational or systems level change, other frameworks may be needed

Increased gravitational force reveals the mechanical, resonant nature of physiological tremor

Human physiological hand tremor has a resonant component. Proof of this is that its frequency can be modified by adding mass. However, adding mass also increases the load which must be supported. The necessary force requires muscular contraction which will change motor output and is likely to increase limb stiffness. The increased stiffness will partly offset the effect of the increased mass and this can lead to the erroneous conclusion that factors other than resonance are involved in determining tremor frequency. Using a human centrifuge to increase head-to-foot gravitational field strength, we were able to control for the increased effort by increasing force without changing mass. This revealed that the peak frequency of human hand tremor is 99% predictable on the basis of a resonant mechanism. We ask what, if anything, the peak frequency of physiological tremor can reveal about the operation of the nervous system.This work was funded by a BBSRC Industry Interchange Award to J.P.R.S. and R.F.R. C.J.O. was funded by BBSRC grant BB/I00579X/1. C.A.V. was funded by A∗Midex (Aix-Marseille Initiative of Excellence

Effectiveness of physical activity interventions for overweight and obesity during pregnancy: a systematic review of the content of behaviour change interventions

Background Behaviour change techniques (BCTs) employed within PA intervention for pregnant women with a healthy body mass index (BMI) have been previously identified, however, these BCTS may differ for other weight profiles during pregnancy. The aim of this current review was to identify and summarise the evidence for effectiveness of PA interventions on PA levels for pregnant women with overweight and obesity, with an emphasis on the BCTs employed. Methods A systematic review and meta-analysis of PA intervention studies using the PRISMA statement was conducted. Searches were conducted of eight databases in January 2019. Strict inclusion/exclusion criteria were employed. The validity of each included study was assessed using the Cochrane Collaboration’s tool for assessing risk of bias. The primary outcome measure was change in PA levels, subjectively or objectively measured, with physical fitness as a secondary outcome. All intervention descriptions were double coded by two authors using Michie’s et al’s BCT taxonomy V1. Meta-analyses using random effect models assessed the intervention effects on PA. Other PA outcomes were summarised in a narrative synthesis. Results From 8389 studies, 19 met the inclusion criteria 13 of which were suitable for inclusion in a meta-analysis. The remaining 6 studies were described narratively due to insufficient data and different outcome measures reported. In the meta-analysis, comparing interventions to a control group, significant increases were found in the intervention group for metabolic equivalent (SMD 0.39 [0.14, 0.64], Z = 3.08 P = 0.002) and physical fitness (VO2 max) (SMD 0.55 [0.34, 0.75], Z = 5.20 P = < 0.001). Of the other six, five studies reported an increase in PA for the intervention group versus the control with the other study reporting a significant decrease for women in their 3rd trimester (p = 0.002). ‘Self-monitoring of behaviour’ was the most frequently used BCTs (76.5%), with ‘social support’ being newly identified for this pregnant population with overweight or obesity. Conclusions This review identified a slight increase in PA for pregnant women with overweight and obesity participating in interventions. However, due to the high risk of bias of the included studies, the results should be interpreted with caution. PA measures should be carefully selected so that studies can be meaningfully compared and standardised taxonomies should be used so that BCTs can be accurately assessed

Direct evidence for a piezoelectriclike effect in coherently strained SiGe/Si heterostructures

A hybrid acoustic spectroscopy technique has been used to demonstrate the (reversible) conversion of high frequency electric fields into longitudinal acoustic waves within a modulation-doped pseudomorphic Si/Si0.88Ge0.12/Si heterostructure. This provides compelling evidence for the existence of a piezoelectriclike coupling within such structures

Prospective reporting of statistical analysis plans for randomised controlled trials

In 2017, JAMA published a statistical analysis plan (SAP) guidance document for randomised clinical trials (RCTs). This guidance is part of the EQUATOR Network of reporting resources and includes a checklist of minimum items for reporting details of statistical analysis of RCTs [1]. While the clinical trial protocol should describe the principal features of the statistical analysis, a separate detailed SAP containing sufficient information to support replication by an independent statistician may be needed [2,3,4]

A Study of Hormonal Effects in Cervical Smear Samples Using Raman Spectroscopy

Raman spectroscopy is a powerful tool that has the potential to be used as a screening method for cervical cancer. It is a label-free, low-cost method providing a biochemical fingerprint of a given sample. The objective of this study was to address patient-to-patient variability contributed by hormonal effects due to the menstrual cycle, the use of hormone-based contraceptives (HC) and the onset of menopause, and to determine if these changes would affect the ability to successfully identify dyskaryotic cells. Raman spectra were recorded from unstained ThinPrep cervical samples (45 cytology negative and 15 high-grade dyskaryosis (high-grade squamous intraepithelial lesion, HSIL) samples using a HORIBA Jobin Yvon XploRA system. HPV DNA testing was also performed. Clinical data collected included date of the last menstrual period, the use of HC and/or menopausal status. Spectral changes were observed depending on the day of the menstrual cycle and on the use of HC. Despite this, HSIL could be discriminated from normal cells regardless of the day on which the sample was taken or the use of HC