• Will Plan S put learned societies in jeopardy?

      Purton, Mary; Michelangeli, Francesco; Fésüs, László (Wiley, 2019-02-25)
    • Tuberculosis notification in a private tertiary care teaching hospital in South India: a mixed-methods study

      Siddaiah, Archana; Ahmed, Mohammad Naseer; Kumar, Ajay M. V.; D’Souza, George; Wilkinson, Ewan; Maung, Thae Maung; Rodrigues, Rashmi (BMJ Publishing Group, 2019-02-05)
      Objectives India contributes approximately 25% of the ‘missing’ cases of tuberculosis (TB) globally. Even though ~50% of patients with TB are diagnosed and treated within India’s private sector, few are notified to the public healthcare system. India’s TB notification policy mandates that all patients with TB are notified through Nikshay (TB notification portal). We undertook this study in a private hospital to assess the proportion notified and factors affecting TB notifications. We explored barriers and probable solutions to TB notification qualitatively from health provider’s perspective. Study setting Private, tertiary care, teaching hospital in Bengaluru, South India. Methodology This was a mixed-methods study. Quantitative component comprised a retrospective review of hospital records between 1 January 2015 and 31 December 2017 to determine TB notifications. The qualitative component comprised key informant interviews and focus groups to elicit the barriers and facilitators of TB notification. Results Of 3820 patients diagnosed and treated, 885 (23.2%) were notified. Notifications of sputum smear-positive patients were significantly more likely, while notifications of children were less likely. Qualitative analysis yielded themes reflecting the barriers to TB notification and their solutions. Themes related to barriers were: (1) basic diagnostic procedures and treatment promote notification; (2) misconceptions regarding notification and its process are common among healthcare providers; (3) despite a national notification system other factors have prevented notification of all patients; and (4) establishing hospital systems for notification will go a long way in improving notifications. Conclusions The proportion of patients with TB notified by the hospital was low. A comprehensive approach both by the hospital management and the national TB programme is necessary for improving notification. This includes improving awareness among healthcare providers about the requirement for TB notifications, establishing a single notification portal in hospital, digitally linking hospital records to Nikshay and designating one person to be responsible for notification.
    • Standards and core components for cardiovascular disease prevention and rehabilitation; BACPR

      Cowie, Aynsley; Buckley, John P.; Doherty, Patrick; Furze, Gill; Hayward, Jo; Jones, Jennifer; Speck, Linda; Dalal, Hayes; Mills, Joseph; University Centre Shrewsbury (BMJ, 2019-01-30)
      In 2017, the British Association for Cardiovascular Prevention and Rehabilitation published its official document detailing standards and core components for cardiovascular prevention and rehabilitation. Building on the success of previous editions of this document (published in 2007 and 2012), the 2017 update aims to further emphasise to commissioners, clinicians, politicians and the public the importance of robust, quality indicators of cardiac rehabilitation (CR) service delivery. Otherwise, its overall aim remains consistent with the previous publications—to provide a precedent on which all effective cardiovascular prevention and rehabilitation programmes are based and a framework for use in assessment of variation in service delivery quality. In this 2017 edition, the previously described seven standards and core components have both been revised to six, with a greater focus on measurable clinical outcomes, audit and certification. The principles within the updated document underpin the six-stage pathway of care for CR, and reflect the extensive evidence base now available within the field. To help improve current services, close collaboration between commissioners and CR providers is advocated, with use of the CR costing tool in financial planning of programmes. The document specifies how quality assurance can be facilitated through local audit, and advocates routine upload of individual-level data to the annual British Heart Foundation National Audit of Cardiac Rehabilitation, and application for national certification ensuring attainment of a minimum quality standard. Although developed for the UK, these standards and core components may be applicable to other countries.
    • Stent Frame Movement Following Endovascular Aneurysm Sealing in the Abdominal Aorta

      Yafawi, Asma; McWilliams, Richard G.; Fisher, Robert K.; England, Andrew; Karouki, Maria; Torella, Francesco (SAGE Publications, 2018-11-28)
    • Conscientious objection and physician-assisted suicide: a viable option in the UK?

      Willis, Derek; George, Rob (2018-11-15)
      Conscience objection is a proposed way of ensuring that medical practitioners who object to physician-assisted suicide may avoid having to be involved in such a procedure if this is legalised. This right on the part of healthcare professionals already exists in certain circumstances. This paper examines the ethical and legal grounds for conscientious objection for medical professionals and shows how it is heavily criticised in circumstances where it is already used. The paper comes to the conclusion that as the grounds and application of conscience objection are no longer as widely accepted, its future application in any legislation can be called into question. [Abstract copyright: © Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.]
    • Embedding recovery based approaches into mental health nurse training- a reflective account

      Jones, Steven; Bifarin, Oladayo O.; University of Chester (Mark Allen Healthcare, 2018-11-02)
      Background: Mental health nursing has undoubtedly progressed as a profession but is at a hiatus that is not assisted by government policy and decreased resources. Aims: This reflective account explores some of the considerable expectations placed upon qualified nurses and the real tensions that influence care delivery standards. Methods: Reflecting on experiences gained in clinical settings, underpinned by literature on recovery, some of the expectations placed on qualified nurses in contemporary mental health service delivery are examined. Conclusion: In order to adequately inform the practices and skill set of contemporary mental health nurses, recovery models and clinical staff input should play a central role in nurse education. Education and clinical practice areas should continue to move towards each other and seize every initiative to ensure both are on the same page.
    • Human adipose tissue-derived mesenchymal stem/stromal cells adhere to and inhibit the growth of Staphylococcus aureus and Pseudomonas aeruginosa.

      Wood, Chelsea R.; Al Dhahri, Douaa; Pickles, Neil; Sammons, Rachel L.; Worthington, Tony; Wright, Karina T.; Johnson, William Eustace Basil; Al-Delfi, Ibtesam R. T. (2018-10-23)
      We have cultured and phenotyped human adipose tissue-derived mesenchymal stem/stromal cells (AT MSCs) and inoculated these cultures with bacteria common to infected skin wounds, i.e. Staphylococcus aureus and Pseudomonas aeruginosa. Cell interactions were examined by scanning electron microscopy (SEM), whilst bacterial growth was measured by colony forming unit (c.f.u.) and biofilm assays. AT MSCs appeared to attach to the bacteria and to engulf S. aureus. Significantly fewer bacterial c.f.u. were present in AT MSC : bacterial co-cultures compared with bacteria cultured alone. Antibacterial activity, including an inhibition of P. aeruginosa biofilm formation, was observed when bacteria were treated with conditioned medium harvested from the AT MSC :  bacterial co-cultures, irrespective of the bacterial species to which the AT MSCs had been exposed to previously. Hence, we have demonstrated that AT MSCs inhibit the growth of two common bacterial species. This was associated with bacterial adhesion, potential engulfment or phagocytosis, and the secretion of antibacterial factors.
    • What is the effect of aerobic exercise intensity on cardiorespiratory fitness in those undergoing cardiac rehabilitation? A systematic review with meta-analysis

      Mitchell, Braden L.; Lock, Merilyn J.; Parfitt, Gaynor; Buckley, John P.; Davison, Kade; Eston, Roger; University of South Australia, University Centre Shrewsbury/University of Chester (BMJ, 2018-08-18)
      18 Objective: Assess the role of exercise intensity on changes in cardiorespiratory fitness (CRF) in 19 patients with cardiac conditions attending exercise-based cardiac rehabilitation. 20 Design: Systematic review with meta-analysis. 21 Data sources: MEDLINE, Embase, CINAHL, SPORTDiscus, PsycINFO and Web of Science. 22 Eligibility criteria for selection: Studies assessing change in CRF (reported as peak oxygen uptake; 23 V̇O2peak) in patients post-myocardial infarction and revascularisation, following exercise-based 24 cardiac rehabilitation. Studies establishing V̇O2peak via symptom-limited exercise test with ventilatory 25 gas analysis and reported intensity of exercise during rehabilitation were included. Studies with 26 mean ejection fraction <40% were excluded. 27 Results: 128 studies including 13,220 patients were included. Interventions were classified as 28 moderate, moderate-to-vigorous or vigorous intensity based on published recommendations. 29 Moderate and moderate-to-vigorous intensity interventions were associated with a moderate 30 increase in relative V̇O2peak (standardised mean difference ± 95% CI = 0.94 ± 0.30 and 0.93 ± 0.17, 31 respectively), and vigorous-intensity exercise with a large increase (1.10 ± 0.25). Moderate and 32 vigorous intensity interventions were associated with moderate improvements in absolute V̇O2peak 33 (0.63 ± 0.34 and 0.93 ± 0.20, respectively), whereas moderate-to-vigorous intensity interventions 34 elicited a large effect (1.27 ± 0.75). Large heterogeneity among studies was observed for all analyses. 35 Subgroup analyses yielded statistically significant, but inconsistent, improvements in CRF. 36 Conclusion: Engagement in exercise-based cardiac rehabilitation was associated with significant 37 improvements in both absolute and relative V̇O2peak. Although exercise of vigorous intensity 38 produced the greatest pooled effect for change in relative V̇O2peak, differences in pooled effects 39 between intensities could not be considered clinically meaningful.
    • Patients’ Perspectives of Oral and Injectable Type 2 Diabetes Medicines, Their Body Weight and Medicine-Taking Behavior in the UK: A Systematic Review and Meta-Ethnography

      Psarou, Aikaterini; Cooper, Helen; Wilding, John P. H. (Springer Healthcare, 2018-08-17)
      AbstractThe aim of this review is to identify peoples’ perspectives of their glucose-lowering and anti-obesity drugs in relation to diabetes and weight control and to explore how these views affect medication adherence. Theoretical perspectives associated with medicine-taking behavior are also explored. The systematic review was based on a meta-ethnography of qualitative studies identified through a search of 12 medical and social science databases and subsequent citation searches. The quality of all studies was assessed. Sixteen studies were included with data from 360 UK individuals. No relevant studies were identified which focused on anti-obesity and non-insulin injectable drugs. The review revealed that the patients’ perspectives and emotional state were influenced by starting and/or changing to a new glucose-lowering medicine. These were also influenced by prior medication experience, disease perceptions and interactions with clinicians. Despite reports of positive experiences with and positive perceptions of medicines, and of participation in strategies to regain life control, medication non-adherence was common. Accepting glucose-lowering medicines impacted on the individual’s perception of lifestyle changes, and it was notable that weight loss was not perceived as a strategy to support diabetes management. Synthesis revealed that more than one theory is required to explain medicine-taking behavior. New insights into the underlying factors of poor adherence and the specific practical issues identified in this review can help in the development of patient-centered interventions.Funding: Diabetes UK.
    • High drug related mortality rates following prison release: Assessing the acceptance likelihood of a naltrexone injection and related concerns

      Murphy, Philip N.; Mohammed, Faizal; Wareing, Michelle; Cotton, Angela; McNeil, John; Irving, Paula; Jones, Steven; Sharples, Louisa; Monk, Rebecca; Elton, Peter; et al. (Elsevier, 2018-07-04)
      Background and aims. High drug related mortality amongst former prisoners in the 4 weeks following release is an internationally recognised problem. Naltrexone injections at release could diminish this by blockading opioid receptors, but naltrexone is not licenced for injection for treating opiate misuse in the United Kingdom and some other countries. This study examined the likelihood of accepting a naltrexone injection at release, and the relationship of this likelihood to other relevant variables. Method. Sixty-one male prisoners with a history of heroin use, who were approaching release from two prisons in the north-west of England, provided likelihood ratings for accepting a naltrexone injection if it were to have been available. Additional data was gathered regarding demographic and drug use histories, and also from psychometric instruments relevant to drug misuse and treatment preparedness. Results. Maximum likelihood ratings for accepting a naltrexone injection were recorded by 55.7% of the sample with only 9.8% indicating no likelihood of accepting an injection. Likelihood ratings were positively related to serving a current sentence for an acquisitive offence compared to drug related or violence offences, and negatively related to peak methadone dosages during the current sentence. Conclusions. Although naltrexone injections were not available to participants in this study, the findings suggest that the potential uptake for this intervention is sufficient to warrant a clinical trial with this population of British prisoners, with a view to potential changes to its current licencing status
    • Oesophageal stenting: Status quo and future challenges.

      Kaltsidis, Harry; Mansoor, Wasat; Park, Jung-Hoon; Song, Ho-Young; Edwards, Derek W.; Laasch, Hans-Ulrich (2018-06-11)
      Oesophageal stents are widely used for palliating dysphagia from malignant obstruction. They are also used with increasing frequency in the treatment of oesophageal perforation, as well as benign strictures from a variety of causes. Improved oncological treatments have led to prolonged survival of patients treated with palliative intent; as a consequence, stents need to function and last longer in order to avoid repeat procedures. There is also increasing need for meticulous procedure planning, careful selection of the device most appropriate for the individual patient and planned follow-up. Furthermore, as more patients are cured, there will be more issues with resultant long-term side-effects, such as recalcitrant strictures due to radiotherapy or anastomotic scarring, which will have to be addressed. Stent design needs to keep up with the progress of cancer treatment, in order to offer patients the best possible long-term result. This review article attempts to illustrate the changing realities in oesophageal stenting, differences in current stent designs and behaviour, as well as the pressing need to refine and modify devices in order to meet the new challenges.
    • Comparison of Mesenchymal Stromal Cells Isolated From Murine Adipose Tissue and Bone Marrow in the Treatment of Spinal Cord Injury

      Takahashi, Ai; Johnson, William Eustace Basil; Uchida, Kenzo; Matsumine, Akihiko; University of Chester, University of Fukui (SAGE, 2018-05-10)
      The use of mesenchymal stromal cell (MSC) transplantation to repair the injured spinal cord has shown consistent benefits in preclinical models. However, the low survival rate of grafted MSC is one of the most important problems. In the injured spinal cord, transplanted cells are exposed to hypoxic conditions and exposed to nutritional deficiency caused by poor vascular supply. Also, the transplanted MSCs face cytotoxic stressors that cause cell death. The aim of this study was to compare adipose-derived MSCs (AD-MSCs) and bone marrow-derived MSCs (BM-MSCs) isolated from individual C57BL6/J mice in relation to: (i) cellular characteristics, (ii) tolerance to hypoxia, oxidative stress and serum-free conditions, and (iii) cellular survival rates after transplantation. AD-MSCs and BM-MSCs exhibited a similar cell surface marker profile, but expressed different levels of growth factors and cytokines. To research their relative stress tolerance, both types of stromal cells were incubated at 20.5% O2 or 1.0% O2 for 7 days. Results showed that AD-MSCs were more proliferative with greater culture viability under these hypoxic conditions than BM-MSCs. The MSCs were also incubated under H2O2-induced oxidative stress and in serum-free culture medium to induce stress. AD-MSCs were better able to tolerate these stress conditions than BMMSCs; similarly when transplanted into the spinal cord injury region in vivo, AD-MSCs demonstrated a higher survival rate post transplantation Furthermore, this increased AD-MSC survival post transplantation was associated with preservation of axons and enhanced vascularization, as delineated by increases in anti-gamma isotype of protein kinase C and CD31 immunoreactivity, compared with the BM-MSC transplanted group. Hence, our results indicate that AD-MSCs are an attractive alternative to BM-MSCs for the treatment of severe spinal cord injury. However, it should be noted that the motor function was equally improved following moderate spinal cord injury in both groups, but with no significant improvement seen unfortunately following severe spinal cord injury in either group
    • Two independent proteomic approaches provide a comprehensive analysis of the synovial fluid proteome response to Autologous Chondrocyte Implantation

      Hulme, Charlotte H.; Wilson, Emma L.; Fuller, Heidi R.; Roberts, Sally; Richardson, James B.; Gallacher, Pete; Peffers, Mandy J.; Shirran, Sally L.; Botting, Catherine H.; Wright, Karina T.; et al. (BioMed Central, 2018-05-02)
      Background: Autologous chondrocyte implantation (ACI) has a failure rate of approximately 20%, but it is yet to be fully understood why. Biomarkers are needed that can pre-operatively predict in which patients it is likely to fail, so that alternative or individualised therapies can be offered. We previously used label-free quantitation (LF) with a dynamic range compression proteomic approach to assess the synovial fluid (SF) of ACI responders and non-responders. However, we were able to identify only a few differentially abundant proteins at baseline. In the present study, we built upon these previous findings by assessing higher-abundance proteins within this SF, providing a more global proteomic analysis on the basis of which more of the biology underlying ACI success or failure can be understood. Methods: Isobaric tagging for relative and absolute quantitation (iTRAQ) proteomic analysis was used to assess SF from ACI responders (mean Lysholm improvement of 33; n = 14) and non-responders (mean Lysholm decrease of 14; n = 13) at the two stages of surgery (cartilage harvest and chondrocyte implantation). Differentially abundant proteins in iTRAQ and combined iTRAQ and LF datasets were investigated using pathway and network analyses. Results: iTRAQ proteomic analysis confirmed our previous finding that there is a marked proteomic shift in response to cartilage harvest (70 and 54 proteins demonstrating ≥ 2.0-fold change and p < 0.05 between stages I and II in responders and non-responders, respectively). Further, it highlighted 28 proteins that were differentially abundant between responders and non-responders to ACI, which were not found in the LF study, 16 of which were altered at baseline. The differential expression of two proteins (complement C1s subcomponent and matrix metalloproteinase 3) was confirmed biochemically. Combination of the iTRAQ and LF proteomic datasets generated in-depth SF proteome information that was used to generate interactome networks representing ACI success or failure. Functional pathways that are dysregulated in ACI non-responders were identified, including acute-phase response signalling. Conclusions: Several candidate biomarkers for baseline prediction of ACI outcome were identified. A holistic overview of the SF proteome in responders and non-responders to ACI  has been profiled, providing a better understanding of the biological pathways underlying clinical outcome, particularly the differential response to cartilage harvest in non-responders.
    • CIP2A- and SETBP1-mediated PP2A inhibition reveals AKT S473 phosphorylation to be a new biomarker in AML

      Hills, Robert; Burnett, Alan; Lucas, Claire; Scott, Laura; Carmell, Natasha; Holcroft, Alison; Clark, Richard; University of Liverpool, Royal Liverpool University hospital, University of Cardiff (American Society for Hematology, 2018-04-27)
      Key Points PP2A inhibition occurs in AML by 2 different pathways: CIP2A in normal karyotype patients and SETBP1 in adverse karyotype patients. AKTS473 phosphorylation is a predictor of survival, and diagnostic levels of AKTS473 could be a novel biomarker in AML.
    • Commentary: Endovascular Sealing of Abdominal Aortic Aneurysms: Do Current Data Justify Wider Use?

      Torella, Francesco; McWilliams, Richard G.; Fisher, Robert K. (SAGE Publications, 2018-04-12)
    • Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)

      Huang, Hongyun; Young, Wise; Chen, Lin; Feng, Shiqing; Zoubi, Ziad M. Al.; Sharma, Hari Shanker; Saberi, Hooshang; Moviglia, Gustavo A.; He, Xijing; Muresanu, Dafin F.; et al. (SAGE Publications, 2018-04-11)
    • Human placental oxygenation in late gestation: experimental and theoretical approaches

      Nye, Gareth; Ingram, Emma; Jenson, Oliver; Johnstone, Edward; Schneider, Henning; Lewis, Rohan; Chernyavsky, Igor; Brownbill, Paul; University of Manchester, University of Southampton, University of Bern (Wiley, 2018-01-26)
      The placenta is crucial for life. It is an ephemeral but complex organ acting as the barrier interface between maternal and fetal circulations, providing exchange of gases, nutrients, hormones, waste products and immunoglobulins. Many gaps exist in our understanding of the detailed placental structure and function, particularly in relation to oxygen handling and transfer in healthy and pathological states in utero. Measurements to understand oxygen transfer in vivo in the human are limited, with no general agreement on the most appropriate methods. An invasive method for measuring partial pressure of oxygen in the intervillous space through needle electrode insertion at the time of Caesarean sections has been reported. This allows for direct measurements in vivo whilst maintaining near normal placental conditions; however, there are practical and ethical implications in using this method for determination of placental oxygenation. Furthermore, oxygen levels are likely to be highly heterogeneous within the placenta. Emerging non-invasive techniques, such as MRI, and ex vivo research are capable of enhancing and improving current imaging methodology for placental villous structure and increase the precision of oxygen measurement within placental compartments. These techniques, in combination with mathematical modelling, have stimulated novel cross-disciplinary approaches that could advance our understanding of placental oxygenation and its metabolism in normal and pathological pregnancies, improving clinical treatment options and ultimately outcomes for the patient.
    • Electro Convulsive Therapy: Milestones in its history

      Jones, Colin; Jones, Steven; University of Chester (Mental Health Nurses Association, 2018)
      ECT is a treatment where an electrical current is passed briefly through electrodes applied to the scalp to induce generalised seizure activity. This article explores the origins and developmental milestones of ECT, examines the literature on the history of ECT and concludes with the author’s work experiences.
    • Comparison of whole body SOD1 knockout with muscle specific SOD1 knockout mice reveals a role for nerve redox signaling in regulation of degenerative pathways in skeletal muscle.

      Nye, Gareth; Sakellariou, Giorgos; McDonagh, Brian; Porter, Helen; Giakoumaki, Ifigeneia; Earl, Kate; Vasilaki, Aphrodite; Brooks, Susan; Richardson, Arlan; Van Remmen, Holly; et al. (Mary Ann Liebert, 2017-12-12)
      Aims: Lack of Cu,Zn-superoxide dismutase (CuZnSOD) in homozygous knockout mice (Sod1−/−) leads to accelerated age-related muscle loss and weakness, but specific deletion of CuZnSOD in skeletal muscle (mSod1KO mice) or neurons (nSod1KO mice) resulted in only mild muscle functional deficits and failed to recapitulate the loss of mass and function observed in Sod1−/− mice. To dissect any underlying cross-talk between motor neurons and skeletal muscle in the degeneration in Sod1−/− mice, we characterized neuromuscular changes in the Sod1−/− model compared with mSod1KO mice and examined degenerative molecular mechanisms and pathways in peripheral nerve and skeletal muscle. Results: In contrast to mSod1KO mice, myofiber atrophy in Sod1−/− mice was associated with increased muscle oxidative damage, neuromuscular junction degeneration, denervation, nerve demyelination, and upregulation of proteins involved in maintenance of myelin sheaths. Proteomic analyses confirmed increased proteasomal activity and adaptive stress responses in muscle of Sod1−/− mice that were absent in mSod1KO mice. Peripheral nerve from neither Sod1−/− nor mSod1KO mice showed increased oxidative damage or molecular responses to increased oxidation compared with wild type mice. Differential cysteine (Cys) labeling revealed a specific redox shift in the catalytic Cys residue of peroxiredoxin 6 (Cys47) in the peripheral nerve from Sod1−/− mice. Innovation and Conclusion: These findings demonstrate that neuromuscular integrity, redox mechanisms, and pathways are differentially altered in nerve and muscle of Sod1−/− and mSod1KO mice. Results support the concept that impaired redox signaling, rather than oxidative damage, in peripheral nerve plays a key role in muscle loss in Sod1−/− mice and potentially sarcopenia during aging. Antioxid. Redox Signal. 28, 275–295. Innovation This is the first study to compare the molecular mechanisms and pathways that occur in both skeletal muscle and peripheral nerve of Sod1−/− and mSod1KO mice in an effort to examine the relative cross-talk and role of pre- and postsynaptic changes in redox homeostasis in loss of neuromuscular integrity and function that occurs with aging. This study highlights that impaired redox signaling in peripheral nerve rather than oxidative damage appears to play a key role in altering the integrity of peripheral nerves and motor neurons and potentially age-associated muscle atrophy and functional deficits. These results are potentially clinically significant and have widespread implications for the understanding of sarcopenia during aging.