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Howman A.,University of Birmingham | Chapman T.L.,University of Bristol | Langdon M.M.,University of Bristol | Ferguson C.,Royal Infirmary | And 7 more authors.
The Lancet | Year: 2013

Background Membranous nephropathy leads to end-stage renal disease in more than 20% of patients. Although immunosuppressive therapy benefits some patients, trial evidence for the subset of patients with declining renal function is not available. We aimed to assess whether immunosuppression preserves renal function in patients with idiopathic membranous nephropathy with declining renal function. Methods This randomised controlled trial was undertaken in 37 renal units across the UK. We recruited patients (18-75 years) with biopsy-proven idiopathic membranous nephropathy, a plasma creatinine concentration of less than 300 μmol/L, and at least a 20% decline in excretory renal function measured in the 2 years before study entry, based on at least three measurements over a period of 3 months or longer. Patients were randomly assigned (1:1:1) by a random number table to receive supportive treatment only, supportive treatment plus 6 months of alternating cycles of prednisolone and chlorambucil, or supportive treatment plus 12 months of ciclosporin. The primary outcome was a further 20% decline in renal function from baseline, analysed by intention to treat. The trial is registered as an International Standard Randomised Controlled Trial, number 99959692. Findings We randomly assigned 108 patients, 33 of whom received prednisolone and chlorambucil, 37 ciclosporin, and 38 supportive therapy alone. Two patients (one who received ciclosporin and one who received supportive therapy) were ineligible, so were not included in the intention-to-treat analysis, and 45 patients deviated from protocol before study end, mostly as a result of minor dose adjustments. Follow up was until primary endpoint or for minimum of 3 years if primary endpoint was not reached. Risk of further 20% decline in renal function was significantly lower in the prednisolone and chlorambucil group than in the supportive care group (19 [58%] of 33 patients reached endpoint vs 31 [84%] of 37, hazard ratio [HR] 0•44 [95% CI 0•24-0•78]; p=0•0042); risk did not differ between the ciclosporin (29 [81%] of 36) and supportive treatment only groups (HR 1•17 [0•70-1•95]; p=0•54), but did differ significantly across all three groups (p=0•003). Serious adverse events were frequent in all three groups but were higher in the prednisolone and chlorambucil group than in the supportive care only group (56 events vs 24 events; p=0•048). Interpretation For the subset of patients with idiopathic membranous nephropathy and deteriorating excretory renal function, 6 months' therapy with prednisolone and chlorambucil is the treatment approach best supported by our evidence. Ciclosporin should be avoided in this subset. Funding Medical Research Council, Novartis, Renal Association, Kidney Research UK.


Roberts I.S.D.,John Radcliffe Hospital | Benamore R.E.,Churchill Hospital | Benbow E.W.,Royal Infirmary | Lee S.H.,Royal Infirmary | And 7 more authors.
The Lancet | Year: 2012

Background: Public objection to autopsy has led to a search for minimally invasive alternatives. Imaging has potential, but its accuracy is unknown. We aimed to identify the accuracy of post-mortem CT and MRI compared with full autopsy in a large series of adult deaths. Methods: This study was undertaken at two UK centres in Manchester and Oxford between April, 2006, and November, 2008. We used whole-body CT and MRI followed by full autopsy to investigate a series of adult deaths that were reported to the coroner. CT and MRI scans were reported independently, each by two radiologists who were masked to the autopsy findings. All four radiologists then produced a consensus report based on both techniques, recorded their confidence in cause of death, and identified whether autopsy was needed. Findings: We assessed 182 unselected cases. The major discrepancy rate between cause of death identified by radiology and autopsy was 32 (95 CI 26-40) for CT, 43 (36-50) for MRI, and 30 (24-37) for the consensus radiology report; 10 (3-17) lower for CT than for MRI. Radiologists indicated that autopsy was not needed in 62 (34; 95 CI 28-41) of 182 cases for CT reports, 76 (42; 35-49) of 182 cases for MRI reports, and 88 (48; 41-56) of 182 cases for consensus reports. Of these cases, the major discrepancy rate compared with autopsy was 16 (95 CI 9-27), 21 (13-32), and 16 (10-25), respectively, which is significantly lower (p<0·0001) than for cases with no definite cause of death. The most common imaging errors in identification of cause of death were ischaemic heart disease (n=27), pulmonary embolism (11), pneumonia (13), and intra-abdominal lesions (16). Interpretation: We found that, compared with traditional autopsy, CT was a more accurate imaging technique than MRI for providing a cause of death. The error rate when radiologists provided a confident cause of death was similar to that for clinical death certificates, and could therefore be acceptable for medicolegal purposes. However, common causes of sudden death are frequently missed on CT and MRI, and, unless these weaknesses are addressed, systematic errors in mortality statistics would result if imaging were to replace conventional autopsy. Funding: Policy Research Programme, Department of Health, UK. © 2012 Elsevier Ltd.


Flook E.P.,Hope Hospital | Kumar B.N.,Royal Infirmary
Rhinology | Year: 2011

Background: Acid reflux into the oesophagus, larynx, pharynx or nasopharynx has been suggested as a causal factor in chronic rhino-sinusitis (CRS), which can then be refractory to nasal treatments. The aim of this review was to conclude on the strength of the link between GORD, LPR, nasopharyngeal reflux, nasal symptoms and CRS. Method: Medline and Embase search. Results: Nineteen papers describing varying studies on CRS, GORD, LPR and PPI therapy were found. Four adult case-controlled studies showed more acid reflux events/symptoms in refractory CRS patients. Paediatric cohort studies showed more reflux events in rhinosinusitis patients than the general paediatric population, but they are not conclusive. Many papers do not use robust CRS diagnostic criteria for inclusion into studies and take no confounding factors into consideration. Conclusion: The evidence of a link is poor with no good randomised controlled trials available. The few adult studies that show any link between acid reflux and nasal symptoms are small case-controlled studies with moderate levels of potential bias. There is not enough evidence to consider anti-reflux therapy for adult refractory CRS and there is no evidence that acid reflux is a significant causal factor in CRS.


Guly H.R.,Derriford Hospital | Bouamra O.,University of Manchester | Spiers M.,Hope Hospital | Dark P.,University of Manchester | And 2 more authors.
Resuscitation | Year: 2011

Aim: The Advanced Trauma Life Support (ATLS) system classifies the severity of shock. The aim of this study is to test the validity of this classification. Methods: Admission physiology, injury and outcome variables from adult injured patients presenting to hospitals in England and Wales between 1989 and 2007 and stored on the Trauma Audit and Research Network (TARN) database, were studied. For each patient, the blood loss was estimated and patients were divided into four groups based on the estimated blood loss corresponding to the ATLS classes of shock. The median and interquartile ranges (IQR) of the heart rate (HR) systolic blood pressure (SBP), respiratory rate (RR) and Glasgow Coma Score (GCS) were calculated for each group. Results: The median HR rose from 82 beats per minute (BPM) in estimated class 1 shock to 95. BPM in estimated class 4 shock. The median SBP fell from 135. mm Hg to 120. mm Hg. There was no significant change in RR or GCS. Conclusion: With increasing estimated blood loss there is a trend to increasing heart rate and a reduction in SBP but not to the degree suggested by the ATLS classification of shock. © 2011 Elsevier Ireland Ltd.


McGrath B.A.,University of Manchester | Thomas A.N.,Hope Hospital
Postgraduate Medical Journal | Year: 2010

Background: Tracheostomies are increasingly common in hospital wards due to the rising use of percutaneous and surgical tracheostomies in critical care and bed pressures in these units. Hospital wards may lack appropriate infrastructure to care for this vulnerable group and significant patient harm may result. Objectives: To identify and analyse tracheostomy related incident reports from hospital wards between 1 October 2005 and 30 September 2007, and to make recommendations to improve patient safety based on the recurrent themes identified. The study was performed between August 2008 and August 2009. Methods: 968 tracheostomy related critical incidents reported to the National Patient Safety Agency over the 2 year period, identified by key letter searches, were analysed. Incidents were categorised to identify common themes, and root cause analysis attempted where possible. Results: In the 453 incidents where patients were directly affected, 338 (75%) were associated with some identifiable patient harm, of which 83 (18%) were associated with more than temporary harm. In 29 incidents (6%) some intervention was required to maintain life, and in 15 cases the incident may have contributed to the patient's death. Equipment was involved in 176 incidents and 276 incidents involved tracheostomies becoming blocked or displaced. Conclusions: By identifying and analysing themes in incident reports associated with tracheostomies, recommendations can be made to improve safety for this group of patients. These recommendations include improvements in infrastructure, competency and training, equipment provision, and in communication.


Galpin A.,University of Salford | Tipper S.P.,Bangor University | Dick J.P.R.,Hope Hospital | Poliakoff E.,University of Manchester
Cortex | Year: 2011

Movement in Parkinson's disease (PD) is strongly influenced by sensory stimuli. Here, we investigated two features of visual stimuli known to affect response times in healthy individuals; the spatial location of an object (the spatial effect) and its action-relevance (the 'affordance' effect). Poliakoff et al. (2007) found that while PD patients show normal spatial effects, they do not show an additional affordance effect. Here we investigated whether these effects are driven by facilitation or inhibition, and whether the affordance effect emerges over a longer time-course in PD. Participants (24 PD and 24 controls) viewed either a lateralised door handle (affordance condition), a lateralised abstract stimulus (spatial condition), or a centrally presented baseline stimulus (baseline condition), and responded to a colour change in the stimulus occurring after 0. msec, 500. msec or 1000. msec. The colour change indicated whether to respond with the left or right hand, which were either spatially compatible or incompatible with the lateralised stimulus orientation in the affordance and spatial conditions. The baseline condition allowed us to assess whether compatibility effects were driven by facilitation of the compatible response or inhibition of the incompatible response. The results indicate that stimulus orientation elicited faster responses from the nearest hand. For controls, the affordance effect was stronger and driven by facilitation, whilst the spatial condition was driven by inhibition. In contrast, the affordance and spatial-compatibility effects did not differ between conditions in the PD group and both were driven by facilitation. This suggests that the PD group responded as if all stimuli were action-relevant, and may have implications for understanding the cueing of movement in PD. © 2010 Elsevier Srl.


Morris G.E.,Robert Jones and Agnes Hunt Orthopaedic Hospital | Randles K.N.,Keele University | Randles K.N.,Hope Hospital
Biochemical Society Transactions | Year: 2010

The giant isoforms of nesprins 1 and 2 are emerging as important players in cellular organization, particularly in the positioning of nuclei, and possibly other organelles, within the cytoplasm. The experimental evidence suggests that nesprins also occur at the inner nuclear membrane, where they interact with the nuclear lamina. In this paper, we consider whether this is consistent with current ideas about nesprin anchorage and about mechanisms for nuclear import of membrane proteins. © The Authors Journal compilation.


Jackson C.A.,University of London | Clatworthy J.,University of London | Robinson A.,Hope Hospital | Horne R.,University of London
American Journal of Gastroenterology | Year: 2010

Objectives: Adherence is generally associated with improved treatment outcomes. Risk factors for non-adherence must be understood to improve adherence. A systematic review was undertaken to determine which variables were consistently associated with non-adherence to oral medication in inflammatory bowel disease (IBD).Methods: The databases EMBASE, Medline, and PsycINFO were searched for titles relating to adherence, medication, and IBD (1980-2008). Primary, quantitative studies were included if they concerned adult patients with IBD, measured adherence to oral medication, and measured characteristics associated with adherence. The resulting 17 papers were independently reviewed by two researchers who also assessed their quality according to pre-defined criteria. The main outcome was the frequency with which demographic, clinical, treatment, and psychosocial variables were found to be statistically significantly associated with non-adherence.Results: Non-adherence rates ranged from 7 to 72%, with most studies reporting that 30-45% of patients were non-adherent. No demographic, clinical, or treatment variables were consistently associated with non-adherence. Psychological distress and patients beliefs about medications were both related to non-adherence in four out of five studies, and doctor-patient discordance was associated with non-adherence in two out of three studies.Conclustions: This is the largest review of factors associated with non-adherence in IBD. Demographic, clinical, and treatment variables were not consistently associated with non-adherence. Psychological distress, patients beliefs about medications, and doctor-patient discordance were associated with non-adherence. These findings call into question some of the conclusions of earlier reviews that did not take into account nonsignificant findings. Practical suggestions for gastroenterologists and future research are discussed. © 2010 by the American College of Gastroenterology.


News Article | December 13, 2016
Site: www.prweb.com

Dr. Jason Fader, a son of medical missionaries and now on a team of American physicians in Burundi--the world’s hungriest nation--today was awarded $500,000 in the first-ever Gerson L’Chaim Prize for Outstanding Christian Medical Missionary Service. “Because of the L’Chaim Prize, hundreds of people will walk, thousands will receive care, and tens of thousands will be helped by the doctors we train,” Dr. Fader said. The L’Chaim Prize, the largest ever in clinical care, is awarded by the African Mission Healthcare Foundation (AMHF), founded by New York entrepreneur Mark Gerson and his friend Dr. Jon Fielder, a medical missionary serving in Kenya. “Missionary doctors are this era’s untold humanitarian story,” said Gerson, who underwrites the prize with his wife, Rabbi Erica Gerson. "Forsaking every comfort and convenience to bring skilled compassion to the continent’s poor, Dr. Fader and his team are links in a string of unsung heroes across Africa.” With the L’Chaim prize, Fader and his colleagues—serving with the agency SERGE—will: ■    add critically needed hospital beds at rural Kibuye Hope Hospital ■    create Burundi’s first postgraduate medical training ■    expand lower-limb fracture care in a nation that travels by foot “It’s hard to overstate the value,” Fader said. “In one of the world’s poorest countries, a prize of this magnitude, for one hospital, is far reaching.” Burundi--called the world’s hungriest nation by the World Bank--has but 13 surgeons for 10 million people. For their part, Fader and his on-the-ground team are training doctors, performing surgical procedures, and upgrading and expanding medical facilities. Every team member raises individual financial support and arrives having studied both French and Kirundi. Since 2013, the team has served at the Kibuye Hope Hospital, the teaching hospital for Hope Africa University Medical School. “To move forward, to provide higher volume and better quality care, and to train more national healthcare workers, this hospital must expand,” Fader said. He plans to serve in Burundi “for many years to come.” Medical care is Africa’s most endangered species. Since missions and agencies peaked in the last century, the docs still there, and their African colleagues, receive shrinking support amid rising and complex medical challenges—from AIDS to surgical problems to cancer. Fielder and Gerson, with friends and supporters, formed AMHF to bolster Africa’s white-lab-coat heroes and their institutions. The 2016 Gerson L'Chaim Prize drew 26 applications from long-term medical missionaries, Catholic and Protestant, in 12 countries. Candidate projects span women’s health centers, African doctor training, cancer diagnosis and treatment, pediatric surgery training and care, heart surgery, mobile HIV care, malaria prevention, and ER centers. For interviews, contact: Michael Conrad michael(at)lovell-fairchild(dot)com 214-616-0320: ●     Learn more at http://www.amhf.us ●     Read the Gerson’s essay on Medium ●     Watch the Prize and Finalist videos ●     Read official prize policies ●     Follow #LChaimPrize via AMHF’s profile on Twitter or Facebook ●     Donate About African Mission Healthcare Foundation A registered U.S. 501(c)3 charity, AMHF enhances access to health services for the tens of millions of Africans who fail to receive quality, life-saving care. It advances financial, logistical, personnel and management support to African mission health facilities, which, through thousands of centers, provide roughly one-third of medical services on the continent. AMHF directly supports care for 70,000 patients annually and finances formal training of 100 African healthcare professionals—a credit to its partners’ efficiency. In Kenya, a clubfoot may be corrected for $100. In Malawi, a child’s malaria treatment costs less than $10. In eight countries—including Malawi, Uganda, South Sudan and Tanzania—AMHF has built clinics, procured x-ray machines, educated surgeons and doctors, and sponsored life-changing operations, particularly pediatric rehabilitative treatments. AMHF oversees Kenya’s largest HIV and tuberculosis clinical mentorship program.


Schiffmann R.,Baylor Research Institute | Waldek S.,Hope Hospital | Benigni A.,Mario Negri Institute for Pharmacological Research | Auray-Blais C.,Université de Sherbrooke
Clinical Journal of the American Society of Nephrology | Year: 2010

It is suggested that biomarkers of renal complications of Fabry disease are likely to be useful for diagnosis and to follow the natural disease progression or the effect of specific therapeutic interventions. Traditionally, globotriaosylceramide (Gb3) in urine has been used to evaluate the effect of specific therapy, such as enzyme replacement therapy (ERT). Although urinary Gb3 decreases significantly with ERT, it has not yet been shown to be a valid surrogate marker in treatment trials. We propose a detailed study of the nature and origin of Gb3 combined with a prospective collaborative trial that combines Gb3 changes with the effect of ERT on clinical nephrological outcome measures. Existing biomarkers such as general proteinuria/albuminuria or specific proteins such as N-acetyl-β-D- glucosaminidase should be evaluated along with novel proteomic or metabolomic studies for biomarker discovery using mass spectrometry or nuclear magnetic resonance. Standard scoring of all pathologic aspects of kidney biopsies may also be a promising way to assess the effect of therapy. Copyright © 2010 by the American Society of Nephrology.

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