• The Differences in Acute Management of Asthma in Adults and Children

      Chavasse, Richard; Scott, Stephen; email: stephenscott2@nhs.net (Frontiers Media S.A., 2019-03-11)
      Acute asthma or wheeze is a common presentation to emergency services for both adults and children. Although there are phenotypic differences between asthma syndromes, the management of acute symptoms follow similar lines. This article looks at the similarities and differences in approaches for children and adults. Some of these may be age dependent, such as the physiological parameters used to define the severity of the attack or the use of age appropriate inhaler devices. Other differences may reflect the availability of evidence. In other areas there is conflicting evidence between adult and pediatric studies such as a temporary increase in dose of inhaled corticosteroids during an acute attack. Overall there are more similarities than differences.
    • In vitro cyto-toxic assessment of heavy metals and their binary mixtures on mast cell-like, rat basophilic leukemia (RBL-2H3) cells.

      ThankGod Eze, Chukwuebuka; email: thankgod.eze@fuoye.edu.ng; Michelangeli, Francesco; email: f.michelangeli@chester.ac.uk; Otitoloju, Adebayo Akeem; email: aotitoloju@unilag.edu.ng (2019-02-11)
      We investigated the cytotoxicity and mechanisms of cell death induced by salts of Cadmium (Cd ), Lead (Pb ), Arsenic (AsO ) and Chromium (Cr ) on RBL-2H3 cells (a model mast cell line). In addition, cyto-toxic effect on cell viability was assessed to reveal their nature of interaction in binary mixture. The individual cytotoxic characteristics of these metals on RBL-2H3 cell viability showed a concentration-dependent reduction of cell viability. We observed that concentration-dependent cytotoxic potency on RBL-2H3 cells of these metals range in the following order Cd >Cr >As O > Pb with LC values of 0.11 μM, 93.58 μM, 397.9 μM and 485.3 μM respectively. Additive effects were observed with Pb  + Cd , Pb  + AsO , Pb  + Cr and AsO  + Cr . The study revealed that Pb , Cd , AsO and Cr could induce significant (P < 0.01) cell death by apoptosis in RBL-2H3. Highly significant necrotic cell death was observed with Pb and Cr (P < 0.01) than Cd and AsO (P < 0.05). Overall, it can be deduced that several cell death executing pathways may be concomitantly activated on exposure to heavy metals and the predominance of one over others might depend on the type of heavy metal, concentration and the metabolic state of the cell. Eventually, binary mixtures of some of these metals showed less cytotoxicity than would be expected from their individual actions and may depend on the co-exposure of the metal ions and their modes of action. [Abstract copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.]
    • 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; orcid: 0000-0002-1265-3813; 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.
    • Stent Frame Movement Following Endovascular Aneurysm Sealing in the Abdominal Aorta

      Yafawi, Asma; orcid: 0000-0002-8390-9951; 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; email: derekwillis35@hotmail.com; 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.]
    • 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; orcid: 0000-0002-0447-4452; email: kpsarou@yahoo.co.uk; 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.
    • John Holden: an appreciation: Born 9 May 1953; died 15 July 2018.

      Cox, Steve; email: Steve.Cox@sthelensccg.nhs.uk (2018-09)
    • 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; orcid: 0000-0002-8091-2549; Lock, Merilyn J; Davison, Kade; Parfitt, Gaynor; Buckley, John P; Eston, Roger G (2018-08-18)
      Assess the role of exercise intensity on changes in cardiorespiratory fitness (CRF) in patients with cardiac conditions attending exercise-based cardiac rehabilitation. Systematic review with meta-analysis. MEDLINE, Embase, CINAHL, SPORTDiscus, PsycINFO and Web of Science. Studies assessing change in CRF (reported as peak oxygen uptake; V̇O ) in patients post myocardial infarction and revascularisation, following exercise-based cardiac rehabilitation. Studies establishing V̇O via symptom-limited exercise test with ventilatory gas analysis and reported intensity of exercise during rehabilitation were included. Studies with mean ejection fraction <40% were excluded. 128 studies including 13 220 patients were included. Interventions were classified as moderate, moderate-to-vigorous or vigorous intensity based on published recommendations. Moderate and moderate-to-vigorous-intensity interventions were associated with a moderate increase in V̇O (standardised mean difference±95% CI=0.94±0.30 and 0.93±0.17, respectively), and vigorous-intensity exercise with a large increase (1.10±0.25). Moderate and vigorous-intensity interventions were associated with moderate improvements in V̇O (0.63±0.34 and 0.93±0.20, respectively), whereas moderate-to-vigorous-intensity interventions elicited a large effect (1.27±0.75). Large heterogeneity among studies was observed for all analyses. Subgroup analyses yielded statistically significant, but inconsistent, improvements in CRF. Engagement in exercise-based cardiac rehabilitation was associated with significant improvements in both absolute and relative V̇O . Although exercise of vigorous intensity produced the greatest pooled effect for change in relative V̇O , differences in pooled effects between intensities could not be considered clinically meaningful. Prospero CRD42016035638. [Abstract copyright: © Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.]
    • 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.; Sharma, Alok; Otom, Ali; Andrews, Russell J.; Al-Zoubi, Adeeb; Bryukhovetskiy, Andrey S.; Chernykh, Elena R.; Domańska-Janik, Krystyna; Jafar, Emad; Johnson, W. Eustace; Li, Ying; Li, Daqing; Luan, Zuo; Mao, Gengsheng; Shetty, Ashok K.; Siniscalco, Dario; Skaper, Stephen; Sun, Tiansheng; Wang, Yunliang; Wiklund, Lars; Xue, Qun; You, Si-Wei; Zheng, Zuncheng; Dimitrijevic, Milan R.; Masri, W. S. El; Sanberg, Paul R.; Xu, Qunyuan; Luan, Guoming; Chopp, Michael; Cho, Kyoung-Suok; Zhou, Xin-Fu; Wu, Ping; Liu, Kai; Mobasheri, Hamid; Ohtori, Seiji; Tanaka, Hiroyuki; Han, Fabin; Feng, Yaping; Zhang, Shaocheng; Lu, Yingjie; Zhang, Zhicheng; Rao, Yaojian; Tang, Zhouping; Xi, Haitao; Wu, Liang; Shen, Shunji; Xue, Mengzhou; Xiang, Guanghong; Guo, Xiaoling; Yang, Xiaofeng; Hao, Yujun; Hu, Yong; Li, Jinfeng; AO, Qiang; Wang, Bin; Zhang, Zhiwen; Lu, Ming; Li, Tong (SAGE Publications, 2018-04-11)
    • Oesophageal stenting: Status quo and future challenges.

      Kaltsidis, Harry; Mansoor, Wasat; Park, Jung-Hoon; Song, Ho-Young; Edwards, Derek William; Laasch, Hans-Ulrich; orcid: 0000-0003-3109-6933 (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.
    • 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)
    • 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.; Keele University; Robert Jones and Agnes Hunt Orthopaedic Hospital; University of Chester; University of Liverpool; University of St Andrews (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.
    • The experience of stigma in inflammatory bowel disease: an interpretive (hermeneutic) phenomenological study

      Dibley, Lesley; Norton, Christine; Whitehead, Elizabeth; University of Chester (John Wiley & Sons Ltd, 2017-12-05)
      Aim to explore experiences of stigma in people with inflammatory bowel disease. Background Diarrhoea, urgency and incontinence are common symptoms in inflammatory bowel disease. Social rules stipulate full control of bodily functions in adulthood: poor control may lead to stigmatisation, affecting patients’ adjustment to disease. Disease-related stigma is associated with poorer clinical outcomes but qualitative evidence is minimal. Design An interpretive (hermeneutic) phenomenological study of the lived experience of stigma in inflammatory bowel disease. Methods Forty community-dwelling adults with a self-reported diagnosis of inflammatory bowel disease were recruited purposively. Participants reported feeling stigmatised or not and experiencing faecal incontinence or not. Unstructured interviews took place in participants’ homes in the United Kingdom (September 2012 – May 2013). Data were analysed using Diekelmann's interpretive method. Findings Three constitutive patterns - Being in and out of control, Relationships and social Support and Mastery and mediation - reveal the experience of disease-related stigma, occurring regardless of continence status and because of name and type of disease. Stigma recedes when mastery over disease is achieved through development of resilience - influenced by humour, perspective, mental wellbeing and upbringing (childhood socialisation about bodily functions). People travel in and out of stigma, dependent on social relationships with others including clinicians and tend to feel less stigmatised over time. Conclusion Emotional control, social support and mastery over disease are key to stigma reduction. By identifying less resilient patients, clinicians can offer appropriate support, accelerating the patient's path towards disease acceptance and stigma reduction.
    • Nicotinamide alone accelerates the conversion of mouse embryonic stem cells into mature neuronal populations.

      Griffin, Sile M.; Pickard, Mark R.; Orme, Rowan P.; Hawkins, Clive P.; Williams, Adrian C.; Fricker, Rosemary A.; Keele University; University of Chester; University Hospital of North Staffordshire; University of Birmingham (Public Library of Science, 2017-08-17)
      Vitamin B3 has been shown to play an important role during embryogenesis. Specifically, there is growing evidence that nicotinamide, the biologically active form of vitamin B3, plays a critical role as a morphogen in the differentiation of stem cells to mature cell phenotypes, including those of the central nervous system (CNS). Detailed knowledge of the action of small molecules during neuronal differentiation is not only critical for uncovering mechanisms underlying lineage-specification, but also to establish more effective differentiation protocols to obtain clinically relevant cells for regenerative therapies for neurodegenerative conditions such as Huntington's disease (HD). Thus, this study aimed to investigate the potential of nicotinamide to promote the conversion of stem cells to mature CNS neurons. METHODS: Nicotinamide was applied to differentiating mouse embryonic stem cells (mESC; Sox1GFP knock-in 46C cell line) during their conversion towards a neural fate. Cells were assessed for changes in their proliferation, differentiation and maturation; using immunocytochemistry and morphometric analysis methods. RESULTS: Results presented indicate that 10 mM nicotinamide, when added at the initial stages of differentiation, promoted accelerated progression of ESCs to a neural lineage in adherent monolayer cultures. By 14 days in vitro (DIV), early exposure to nicotinamide was shown to increase the numbers of differentiated βIII-tubulin-positive neurons. Nicotinamide decreased the proportion of pluripotent stem cells, concomitantly increasing numbers of neural progenitors at 4 DIV. These progenitors then underwent rapid conversion to neurons, observed by a reduction in Sox 1 expression and decreased numbers of neural progenitors in the cultures at 14 DIV. Furthermore, GABAergic neurons generated in the presence of nicotinamide showed increased maturity and complexity of neurites at 14 DIV. Therefore, addition of nicotinamide alone caused an accelerated passage of pluripotent cells through lineage specification and further to non-dividing mature neurons. CONCLUSIONS: Our results show that, within an optimal dose range, nicotinamide is able to singly and selectively direct the conversion of embryonic stem cells to mature neurons, and therefore may be a critical factor for normal brain development, thus supporting previous evidence of the fundamental role of vitamins and their metabolites during early CNS development. In addition, nicotinamide may offer a simple effective supplement to enhance the conversion of stem cells to clinically relevant neurons.
    • Retroviral insertional mutagenesis implicates E3 ubiquitin ligase RNF168 in the control of cell proliferation and survival

      Kizilors, Aytug; Pickard, Mark R.; Schulte, Cathleen E.; Yacqub-Usman, Kiren; McCarthy, Nicola J.; Gan, Shu-Uin; Darling, David; Gäken, Joop; Williams, Gwyn T.; Farzaneh, Farzin; Kings College London; Keele University; University of Chester; University of Nottingham; National University of Singapore (Portland Press, 2017-08-14)
      The E3 ubiquitin ligase RNF168 is a ring finger protein that has previously been identified to play an important regulatory role in the repair of double-strand DNA breaks. In the present study, an unbiased forward genetics functional screen in mouse granulocyte/ macrophage progenitor cell line FDCP1 has identified E3 ubiquitin ligase RNF168 as a key regulator of cell survival and proliferation. Our data indicate that RNF168 is an important component of the mechanisms controlling cell fate, not only in human and mouse haematopoietic growth factor-dependent cells, but also in the human breast epithelial cell line MCF-7. These observations therefore suggest that RNF168 provides a connection to key pathways controlling cell fate, potentially through interaction with PML nuclear bodies and/or epigenetic control of gene expression. Our study is the first to demonstrate a critical role for RNF168 in the in the mechanisms regulating cell proliferation and survival, in addition to its well-established role in DNA repair.
    • PWE-055 Stigma in inflammatory bowel disease: building resilience

      Dibley, L.; Norton, C.; Mason-Whitehead, Elizabeth; Kings College; University of Chester (BMJ Publishing Group, 2015-06-01)
      qualitative study aimed to: a) understand the experience of stigma in people with IBD and whether stigma derives from the bowel disorder diagnosis or from related FI; b) understand how stigma affects social, personal and emotional wellbeing, and how people with IBD manage these issues. Using purposive stratified sampling, 40 members of a UK IBD charity were recruited. Participants self-identified as having FI or not, and feeling stigmatised or not.
    • Autologous chondrocyte implantation-derived synovial fluids display distinct responder and non-responder proteomic profiles

      Hulme, Charlotte H.; Wilson, Emma L.; Peffers, Mandy J.; Roberts, Sally; Simpson, Deborah M.; Richardson, James B.; Gallacher, Pete; Wright, Karina T.; Keele University; Robert Jones and Agnes Hunt Orthopaedic Hospital; University of Chester; University of Liverpool (BioMed Central, 2017-06-30)
      Background Autologous chondrocyte implantation (ACI) can be used in the treatment of focal cartilage injuries to prevent the onset of osteoarthritis (OA). However, we are yet to understand fully why some individuals do not respond well to this intervention. Identification of a reliable and accurate biomarker panel that can predict which patients are likely to respond well to ACI is needed in order to assign the patient to the most appropriate therapy. This study aimed to compare the baseline and mid-treatment proteomic profiles of synovial fluids (SFs) obtained from responders and non-responders to ACI. Methods SFs were derived from 14 ACI responders (mean Lysholm improvement of 33 (17–54)) and 13 non-responders (mean Lysholm decrease of 14 (4–46)) at the two stages of surgery (cartilage harvest and chondrocyte implantation). Label-free proteome profiling of dynamically compressed SFs was used to identify predictive markers of ACI success or failure and to investigate the biological pathways involved in the clinical response to ACI. Results Only 1 protein displayed a ≥2.0-fold differential abundance in the preclinical SF of ACI responders versus non-responders. However, there is a marked difference between these two groups with regard to their proteome shift in response to cartilage harvest, with 24 and 92 proteins showing ≥2.0-fold differential abundance between Stages I and II in responders and non-responders, respectively. Proteomic data has been uploaded to ProteomeXchange (identifier: PXD005220). We have validated two biologically relevant protein changes associated with this response, demonstrating that matrix metalloproteinase 1 was prominently elevated and S100 calcium binding protein A13 was reduced in response to cartilage harvest in non-responders. Conclusions The differential proteomic response to cartilage harvest noted in responders versus non-responders is completely novel. Our analyses suggest several pathways which appear to be altered in non-responders that are worthy of further investigation to elucidate the mechanisms of ACI failure. These protein changes highlight many putative biomarkers that may have potential for prediction of ACI treatment success.
    • Magnetic nanoparticle-mediated gene delivery to two- and three-dimensional neural stem cell cultures: magnet-assisted transfection and multifection approaches to enhance outcomes

      Pickard, Mark R.; Adams, Christopher F.; Chari, Divya M.; University of Chester; Keele University (Wiley, 2017-02-02)
      Neural stem cells (NSCs) have high translational potential in transplantation therapies for neural repair. Enhancement of their therapeutic capacity by genetic engineering is an important goal for regenerative neurology. Magnetic nanoparticles (MNPs) are major non-viral vectors for safe bioengineering of NSCs, offering critical translational benefits over viral vectors, including safety, scalability, and ease of use. This unit describes protocols for the production of suspension (neurosphere) and adherent (monolayer) murine NSC cultures. Genetic engineering of NSCs with MNPs and the application of 'magnetofection' (magnetic fields) or 'multifection' (repeat transfection) approaches to enhance gene delivery are described. Magnetofection of monolayer cultures achieves optimal transfection, but neurospheres offer key advantages for neural graft survival post-transplantation. A protocol is presented which allows the advantageous features of each approach to be combined into a single procedure for transplantation. The adaptation of these protocols for other MNP preparations is considered, with emphasis on the evaluation of procedural safety.
    • Neuropsychiatric symptoms following metal-on-metal implant failure with cobalt and chromium toxicity

      Green, Ben; Griffiths, Emily; Almond, Solomon; University of Chester; Public Health England (BioMed Central, 2016-01-24)
      Background: There were at least 31,171 metal-on-metal (MoM) hip implants in the UK between 2003 and 2011. Some of these were subject to failure and widescale recalls and revisions followed. Method This is a presentation of ten cases (mean age 60 years) where we evaluated neuropsychiatric morbidity following metal-on-metal hip implant failure and revision. Implants were ASR total hip replacement (acetabular implant, taper sleeve adaptor and unipolar femoral implants) performed between 2005 and 2009. This case series describes, for the first time, neuropsychiatric complications after revision where there has been cobalt and chromium toxicity. Results Pre-revision surgery, nine patients had toxic levels of chromium and cobalt (mean level chromium 338 nmol/l, mean cobalt 669.4 nmol/l). Depression assessment showed 9 of 9 respondents fulfilled the BDI criteria for depression and 3 of these were being treated. 7 of 9 patients showing short term memory deficit with mean mini mental state examination score of 24.2. The normal population mean MMSE for this group would be expected to be 28 with <25 indicating possible dementia. Conclusions We found neurocognitive and depressive deficits after cobalt and chromium metallosis following MoM implant failure. Larger studies of neurocognitive effects are indicated in this group. There may be implications for public health.