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By S. Nemrok. Rhodes College. 2018.

Not all investigations will fnd that ideas for improving health services are successful 4mg doxazosin fast delivery, or that the provision of new services actually improves health safe 1 mg doxazosin. In mapping the route to universal coverage order doxazosin 1 mg without prescription, the negative results of research studies are just as valuable as the positive ones 4mg doxazosin mastercard. Which research methods are used to answer questions about universal health coverage? Te examples described in Chapter 3 expose the diversity of questions about uni- versal health coverage, and also the variety of research methods used to investigate them. Methods include quantitative and qualitative evaluations, observational and case-control studies, intervention studies, randomized controlled trials, and sys- tematic reviews and meta-analyses. Te report shows the benefts of having evidence from multiple sources, explores the link between experimental design and strength of inference, and highlights the compromises in study design (better evidence is ofen more costly, but not always) that must be made by all investigators. Te survey xiv Executive summary of research methods reveals the nature of the research cycle, where questions lead to answers that lead to yet more questions. Te chapter illustrates some of the ways in which research is linked with health policy and practice. What can be done to strengthen national health research systems? Research is likely to be most productive when it is conducted within a supportive national research system. Chapter 4 is an introduction to the essential functions of national health research systems, namely: to set research priorities, to develop research capacity, to defne norms and standards for research, and to translate evidence into practice. Standard methods have been developed to set research priorities. Tese meth- ods should be used more widely by governments to set national priorities across all aspects of health and to determine how best to spend limited funds on research. With regard to strengthening capacity, efective research needs transparent and accountable methods for allocating funds, in addition to well-equipped research institutions and networks. However, it is the people who do research – with their curiosity, imagination, motivation, technical skills, experience and connections – that are most critical to the success of the research enterprise. Codes of practice, which are the cornerstone of any research system, are already in use in many countries. Te task ahead is to ensure that such codes of practice are comprehensive and apply in all countries, and to encourage adherence everywhere. Achieving universal health coverage depends on research ranging from studies of causation to studies of how health systems function. However, because many existing cost-efective interventions are not widely used, there is a particular need to close the gap between existing knowledge and action. Areas of research that need special attention concern the implementation of new and existing technologies, health service operations, and the design of efective health systems. To help bridge the gap between science and practice, research should be strengthened not only in academic centres but also in public health programmes, close to the supply of and demand for health services. How can research for universal health coverage be supported nationally and internationally? In the wake of many previous reports, Chapter 4 presents three mechanisms to stimulate and facilitate research for universal health coverage – monitoring, coor- dination and fnancing. Provided there is a commitment to share data, national and global observatories could be established to monitor research activities. Observatories could serve a variety of functions, acting as repositories of data on xv Research for universal health coverage the process of doing research and presenting and sharing the fndings of research studies. Such data would help in tracking progress towards universal health cover- age, country by country. Monitoring supports the second function, coordination, on various levels – by sharing information, by jointly setting research priorities, or by facilitating col- laboration on research projects. Regarding the third function, fnancing, health research is more efective and productive if there is a guaranteed, regular income. Sustained fnancing guarantees that research projects are not interrupted or otherwise compromised by a sudden lack of resources. Various mechanisms for raising and disbursing additional research funds have been proposed and are under discussion. Whatever mecha- nism is adopted, international donors and national governments should measure progress against their own commitments to investing in health research. How will WHO support research for universal health coverage? Chapter 5 draws out the dominant themes of the report, and proposes a set of actions by which the research community, national governments, donors, civil society and international organizations, including WHO, can support the research that is needed if we are to reach universal health coverage. Tis report is closely aligned with the aims of the WHO strategy, which encourages the highest-quality research in order to deliver the greatest health ben- efts to the maximum number of people. Key points ■ The goal of universal health coverage is to ensure that all people obtain the health services they need – prevention, promotion, treatment, rehabilitation and palliation – without risk of financial ruin or impoverishment, now and in the future. This is illustrated by progress towards the health- related Millennium Development Goals (MDGs), and in the widespread fall in cash payments made for using health services. Thus nearly half of all HIV-infected people eligible for antiretroviral therapy were still not receiving it in 2011; and an estimated 150 million people suffer financial catastrophe each year because they have to pay out-of-pocket for health services. Consequently, given limited resources, each nation must determine its own priorities for improving health, the services that are needed, and the appropriate mechanisms for financial risk protection. First, and most important, are questions about improving health and well-being – questions that help us to define the interventions and services that are needed, including financial risk protection, discover how to expand the coverage of these services, including the reduction of inequities in coverage, and investigate the effects of improved coverage on health. The second set of questions is about measurement – of the indicators and data needed to monitor service coverage, financial risk protection, and health impact. One task for research is to help define a set of common indicators for comparing progress towards universal coverage across all countries. Through the cycle of research – questions yield answers which provoke yet more questions – there will always be new opportunities to improve health. As a descendant of the “Health for All” movement (Box 1. Tese services range from clinical care for individual patients to the public services that protect the health of whole populations. Tey include services that come from both within and beyond the health sector. Financial risk protection is one element in the package of measures that provides overall social protection (7). And protection against severe fnancial difculties in the event of illness gives the peace of mind that is an integral part of well-being. Tese are personal and moral choices regarding the kind of society that people wish to live in, taking universal cov- erage beyond the technicalities of health fnancing, public health and clinical care. With a greater understanding of the scope of universal health coverage, many national governments now view progress towards that goal as a guiding principle for the development of health systems, and for human development generally. It is clear that healthier environments mean healthier people (9). Preventive and curative services protect health and protect incomes (10, 11).

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O wen W F trusted doxazosin 4 mg, Lew N L generic 1mg doxazosin with amex, Liu Y discount doxazosin 2 mg, Lowrie EG: The urea reduction ratio and 7 1mg doxazosin mastercard. H akim RM , Breyer J, Ism ail N , Schulm an G: Effects of dose of dialysis 8. Gutierrez A, Alvestrand A, Bergstrom J: M em brane selection and on m orbidity and m ortality. H ornberger JC, Chernew M , Petersen J, Garber AM : A m ultivariate patient m ortality. H em odialysis Adequacy W ork Group: Dialysis O utcom es Q uality patients in the United States is im proved with a greater quantity of Initiative (DO Q I). H akim RM , W ingard RL, Parker RA: Effect of the dialysis m em brane 5. H em odialysis Adequacy W ork Group: Dialysis O utcom es Q uality in the treatm ent of patients with acute renal failure. H akim , RM : Clinical im plications of hem odialysis m em brane biocom - 12. Hamilton omplications observed in end-stage renal disease may be due to the side effects of treatment or to the alterations of pathophys- Ciology that go with kidney failure. This patient was switched from a cellulose acetate dialysis membrane to a cuprammonium cellulose one. W ithin FIGURE 7-1 8 m inutes of starting hem odialysis he developed apprehension, diaphoresis, pruritus, palpitations, and wheezing. This eruption Com plications associated with hem odialysis. Throm bosis can be a com - Dilation of a stricture of the left innom inate vein using balloon plication of reliance on subclavian catheters for vascular access for angioplasty in the patient shown in Figure 7-3. This was discovered during investigation of edem a of the left arm. O ccasionally the arteriovenous fistula results in radial-to- brachiocephalic steal, leaving inadequate blood supply to the fingers. This risk is especially com m on in diabetic patients. M ultiple carpal bone cysts without joint space narrowing in a patient treated with dialysis for 11 years. This phenom enon has been attributed to inadequate clearance of b-2microglobulin using low-permeability, cellulose dialysis membranes. Bladder perforation can be a com plication of blind insertion of a peritoneal catheter. It is recognized by the sudden appearance of glucose-positive “urine” on instillation of the first bag of dialysate. Instillation of radiographic contrast m edium confirm s the diagnosis. In continuous am bulatory peritoneal dialysis (CAPD) peritonitis can easily be recognized by the fact that drained peritoneal FIGURE 7-9 (see Color Plate) fluid becom es opacified. The inability to read the writing on the opposite side of the drained bag (or a newspaper through the bag) Tunnel abscess in patient undergoing continuous ambulatory peritoneal correlates with a peritoneal leukocyte count of m ore than 100 cells dialysis. Pericatheter infections are a com m on source of peritonitis. Som etim es, the findings are m ore subtle than in this case. If the infection fails to respond, rem oval of the catheter is indicated. This patient had several bouts of peritonitis during the course of her treatment on peritoneal dialysis. Abdominal computed tom ography revealed a hom ogeneous m ass filling the anterior peri- toneum. At laparotom y the m esentery was encased in a “m arble- like” fibrotic m ass. The patient required long-term hom e parenteral hyperalim entation for recovery. Pericardial tam ponade m ay present as dialysis-induced pericardial friction rub suggest pericarditis (a frequent hypotension. Pappas, M D, M edical College com plication of urem ia) especially in patients with chest of O hio. The skin of urem ic patients can be intensely Acquired cystic disease of the kidney. Earlier, it was attributed to deposition of calcium and raphy dem onstrates cystic disease in this patient, who had focal phosphorus in the skin. Today, we know that is the result of segm ental glom erulosclerosis com plicated by protein C deficiency repeated traum a to the skin associated with scratching. Eleven years after the initial diagnosis, he developed renal failure requiring hem odialysis. Two years after starting dialysis, he developed hem aturia, and these cysts were found. The appearance and clinical course are consistent with acquired cystic disease of the kidney. These cysts carry som e risk of m alignant transform ation. M alnutrition is an important risk factor for dialysis patients, as reflected in this graph depicting the relation of death to serum albumin values. Low concentrations of serum album in m ay favor oxidation of lipids, which renders them m ore atherogenic. The shoulder Diffuse bone dem ineralization as dem onstrated in skull radiograph. There is distal resorption This radiograph dem onstrates the generalized granular appear- of the clavicle. A sm all am ount of calcification can be seen on the ance that is characteristic of the diffuse dem ineralization seen in clavicular side of the coracoclavicular ligam ent. The hands demonstrate diffuse bilateral osteoporosis. The resorption FIGURE 7-18 of the distal phalanges is best seen in the first and second digits of Parathyroid scan. The radial side of the middle phalanges of the second Tc Cardiolite. This technique is often useful to determ ine the location and num ber Soft tissue calcification is present on the radial side of the proxim al of parathyroid glands before performing subtotal parathyroidectomy.

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The DOP author recently diagnosed a patient with conversion disorder who was later found to have a large mediastinal tumour on X-ray discount doxazosin 1 mg visa. In the general hospital setting discount doxazosin 2mg visa, 20-25% of patients have individual symptoms of conversion cheap 4 mg doxazosin with mastercard. Some 5% of patients in general hospital meet the criteria for the full syndrome generic 1 mg doxazosin with amex. The greatest prevalence of full conversion syndrome (up to 20%) is found in neurology clinics. Personality disorder and conversion disorder frequently co-occur. Hassa et al (2017) have recentenly described dysregulation of the emotion processing and motor control circuits. Functional MRI has been used to examine people with loss of sensation. When vibration was applied to the sensate limb there was the expected contralateral somatosensory activation, however, no such activation when the stimulus was applied to the anaesthetic side (Ghaffar et al, 2006). Vibration on the anaesthetic side produced activation in the orbitofrontal and cingulate regions. The emerging theory is that in conversion disorder certain brain areas are able to override the activation of the motor and sensory cortices. Attention has focused on the cingulate: possibly, the caudal segment, which is responsible for willed action, can be deactivated by the pregenual anterior cingulated cortex as it processes information. Thus, discrete neural networks involved in processing emotion and executive control may be able to suppress regions associated with a range of other functions [motor, sensory, vision]. It is important for any hospitalization to be active and brief. Such patients may become more dependent if placed in a passive role. There is support for cognitive behaviour therapy in Somatic Symptom and Related Disorders in general (Krocnke, 2007), but less for conversion than the others. There is some support for the use of antidepressants and TMS (Schonfeldt-Lecuona et al, 2006). Psychiatric assessment should continue, and problems should be discussed. Solutions to problems should be developed with the participation of the patient. It is useful to send the patient to be mobilized in the physiotherapy department. While there is no significant physical lesion, such assistance allows the patient to recover and offers a “face-saving” explanation for the recovery. Conversion disorder received close attention from psychoanalysts. The classical view is that unconscious conflicts between id drives and the superego are resolved by the unconscious production of physical symptoms. The relief of the intolerable conflict was designated the “primary gain”. The subsequent support from others and the release from responsibilities of daily life was designated “secondary gain”. The term secondary gain has leached out into broader use, but from the purist perspective, it should only be used when we are applying psychoanalytic explanations. Acute onset which is actively treated usually gives a good outcome, especially if concurrent psychiatric disorder is present, and responds to treatment. Chronic disorder may involve a wheel-chair existence and be difficult to assist (Mace & Trimble, 1996). Individuals have enduring attributional styles (Garcia-Campayo et al, 1997), such that when a symptom is experienced, it is likely to be attributed to a physical, psychological or environmental explanation (Robins and Kirmayer, 1991). Not surprisingly, general practice attendees with hypochondriacal tendencies have more physical attributions than those with anxiety disorders (MacLeod et al, 1998). Educational programs designed to modify attribution style are useful in the management of chronic pain conditions and somatization (Neng & Weck, 2013). In chronic pain conditions, the patient often attributes the pain to progressive damage and is therefore reluctant to be active. This leads to disuse atrophy and unnecessary disability. When the patient attributes the pain to an abnormal process (inappropriate pain) rather than progressive anatomical destruction, the scene is set for improved function. Medical Anthropology Illness may be defined, anthropologically, as “the human experience of sickness”. The process begins with personal awareness of a change in body feeling and continues with the labelling of the sufferer by the sufferer and his/her family as “ill” (Kleinman et al, 1978). Illness is greatly dependent on cultural beliefs about disease and discomfort and has been viewed as a “cultural construction” (Wexler, 1974). Some claim that medical doctors treat illness poorly, while traditional and alternative therapists, who listen and give culturally relevant explanations, treat illness well (Stimson, 1994). Disease has been defined as “abnormalities in the structure and function of body organs and systems”. This may be construed as the medical view of clinical reality (medical view). One criticism of modern medicine is that it focuses on the treatment of disease and ignores the treatment of illness (Engel, 1977). Common sense suggests a better outcome will be achieved if both illness and disease are treated. Abnormal Illness Behaviour Abnormal illness behaviour (AIB) provides an intellectual framework for a range of human behaviours (Pilowsky, 1969). It depends on two sociological concepts, 1) illness behaviour, and 2) the sick role. The sick role is conceptualized as bringing obligations and privileges (Parsons, 1964). The obligations include that the person seeking the role, 1) accepts that the role is undesirable, 2) co-operates with others to achieve health, and 3) utilizes the services of those regarded by society as competent in healing. If these obligations are fulfilled, the individual is granted the following privileges, a) regarded as not being responsible for his/her condition, b) accepted as someone requiring care, and c) exempted from normal obligations (such as work). It highlights the connection between social influences and health and provides a unifying conceptual basis for illness related behaviour, including but extending beyond the above disorders, to factitious disorder and malingering. It also extends in another direction, to the denial of illness. It casts the individual who denies illness and stays at work under the same umbrella as the individual who pretends illness and goes to the football - with the majority of illness behaviours lying somewhere between these two extremes. In addition, AIB gives context for the responsibility of the doctor as the socially designated controller of sick role privileges; a frequently onerous and unwelcome duty.

Ubiquitin ligase a PDZ-containing phosphoprotein that associates with members activity and tyrosine phosphorylation underlie suppression of of the ezrin–radixin–moesin family generic 2 mg doxazosin fast delivery. J Cell Biol 1997;139: growth factor signaling by c-Cbl/Sli-1 generic doxazosin 1 mg mastercard. Membrane transport in the endocytic G protein-coupled receptor kinase phosphorylation sites in the pathway discount doxazosin 1 mg otc. Muscarinic super- treatment: a multiple step process purchase doxazosin 2 mg with mastercard. Mutational coupled receptor kinase 5-deficient mice. Neuron 1999;24: analysis of adrenergic receptor sequestration. Two distinct pathways reveal in vivo specificity of G protein-coupled receptor kinases for cAMP-mediated down-regulation of the beta 2-adrenergic in the heart. Phosphorylation of the receptor and regulation of its 85. Rapid endocytosis of 70 Neuropsychopharmacology: The Fifth Generation of Progress a G protein-coupled receptor: substance P evoked internalization 90. Beta-arrestin-depen- of its receptor in the rat striatum in vivo. Proc Natl Acad Sci dent formation of beta2 adrenergic receptor-Src protein kinase USA1995;92:2622–2626. Beta-arrestin-dependent of the m2 muscarinic acetylcholine receptor. Arrestin-indepen- endocytosis of proteinase-activated receptor 2 is required for in- dent and -dependent pathways. J Biol Chem 1997;272: tracellular targeting of activated ERK1/2. Beta-arrestin1 interacts nalization of the m1, m3, and m4 subtypes of muscarinic cholin- with the catalytic domain of the tyrosine kinase c-SRC. Heptahelical receptor sig- mine receptors to different endocytic membranes. We provide physicians in the United Kingdom and overseas with education, training and support throughout their careers. As an independent body representing over 20,000 Fellows and Members worldwide, we advise and work with government, the public, patients and other professions to improve health and healthcare. National Collaborating Centre for Chronic Conditions The National Collaborating Centre for Chronic Conditions (NCC-CC) is a collaborative, multiprofessional centre undertaking commissions to develop clinical guidance for the National Health Service (NHS) in England and Wales. It is an independent body, housed within the Clinical Standards Department at the Royal College of Physicians of London. The NCC-CC is funded by the National Institute for Health and Clinical Excellence (NICE) to undertake commissions for national clinical guidelines on an annual rolling programme. Citation for this document National Collaborating Centre for Chronic Conditions. Chronic kidney disease: national clinical guideline for early identification and management in adults in primary and secondary care. London: Royal College of Physicians, September 2008. ISBN 978-1-86016-340-1 ROYAL COLLEGE OF PHYSICIANS 11 St Andrews Place, London NW1 4LE www. No part of this publication may be reproduced in any form (including photocopying or storing it in any medium by electronic means and whether or not transiently or incidentally to some other use of this publication) without the written permission of the copyright owner. Typeset by Dan-Set Graphics, Telford, Shropshire Printed in Great Britain by The Lavenham Press Ltd, Sudbury, Suffolk Contents Guideline Development Group members v Preface ix Acronyms, abbreviations and glossary x DEVELOPMENT OF THE GUIDELINE 1 Introduction 1. Dr Indranil Dasgupta, Consultant Nephrologist, invited to contribute at a specific meeting as an expert representing the Type 2 Diabetes Guideline but was not a full member of the GDG. Dr Patrick Fitzgerald acted as a deputy for Dr Ivan Benett at a GDG meeting. Dr Neil Iggo, Consultant Nephrologist, acted as a deputy for Dr Lawrence Goldberg at a GDG meeting. Dr Kanchana Imrapur acted as a deputy for Dr David Stephens at a GDG meeting. Dr Marta Lapsley acted as a deputy for Dr Edmund Lamb at a GDG meeting. Ms Nicola Thomas acted as a deputy for Ms Natasha McIntyre at a GDG meeting. The NHS is increasingly focussing on prevention and on the early detection and treatment of potentially progressive disease, whilst the prevalence of risk factors for CKD, such as diabetes, obesity and hypertension is rising. It is therefore a great pleasure to introduce this timely new guideline on CKD from the National Collaborating Centre for Chronic Conditions (NCC-CC) and the National Institute for Health and Clinical Excellence (NICE). The recommendations you will read here are the result of a thorough review of the published research. The field of renal medicine has a complex evidence base, and enormous thanks are due to the Guideline Development Group for their hard work and attention to detail, and to the NCC-CC Technical Team who worked enthusiastically alongside them. Readers involved in research in this field, and those who want to find the full rationale behind a particular recommendation, will find this an invaluable resource. The Department of Health, in commissioning this guideline, was clear that the focus was to be on early detection and management. This is the area in which the guideline can deliver its greatest potential benefit, through delaying progression of disease and thus reducing the need for dialysis or transplantation. The key priority recommendations singled out in the guideline reflect this emphasis. They present clear criteria for testing for CKD, suspecting progressive CKD, and referring people for specialist assessment, all of which should be useful in primary care. Recommendations are also provided on starting treatment once proteinuria has been assessed. In common with other guideline topics in chronic conditions, there are some areas in CKD which remain in need of good quality research to inform difficult clinical decisions. The GDG have not shirked from addressing these questions and their expertise informed debates which led to some forward-thinking recommendations, for example those dealing with testing for proteinuria. For many practitioners a change in practice will be required as a result, but great effort has been taken to explain the rationale for this change within the guideline, and to demonstrate that the necessary effort is worthwhile. As healthcare professionals in primary care take on an increasing role in the management of CKD, it is hoped that this guideline will be a single useful and accessible reference promoting a consistent high quality of care and hence improved quality of life for longer for people with CKD. Dr Bernard Higgins MD FRCP Director, National Collaborating Centre for Chronic Conditions ix Acronyms, abbreviations and glossary Acronyms and abbreviations AASK African American Study of Kidney Diseases and Hypertension ABLE A Better Life through Education and Empowerment ACEI Angiotensin-converting enzyme inhibitor ACR Albumin:creatinine ratio ACS Acute coronary syndrome ADPKD Autosomal dominant polycystic kidney disease ALP Alkaline phosphatase ARB Angiotensin receptor blocker ARIC Atherosclerosis Risk in Communities BMD Bone mineral density BMI Body mass index BNF British National Formulary BP Blood pressure CABG Coronary artery bypass grafting CAD Coronary artery disease CARI Caring for Australasians with Renal Impairment CHS Cardiovascular Health Studies CRF Chronic renal failure CRI Chronic renal insufficiency CURE Clopidogrel in Unstable Angina to Prevent Recurrent Events CI Confidence interval CKD Chronic kidney disease CrCl Creatinine clearance CV Coefficient of variation CVD Cardiovascular disease DBP Diastolic blood pressure DMP Disease management programme DNCSG Diabetic Nephropathy Collaborative Study Group eGFR Estimated glomerular filtration rate ESRD End stage renal disease GDG Guideline Development Group GFR Glomerular filtration rate HDL High-density lipoprotein ICER Incremental cost-effectiveness ratio KEEP Kidney Early Evaluation Program x Acronyms, abbreviations and glossary HF Heart failure HR Hazard ratio HYP Hypertension IDMS Isotope dilution mass spectrometry IDNT Irbesartan in Diabetic Nephropathy Trial IgA-GN Immunoglobulin-A glomerulonephritis iPTH Intact parathyroid hormone KDIGO Kidney Disease Improving Global Outcomes KDOQI Kidney Disease Outcomes Quality Initiative LDL Low density lipoprotein LDL-C Low density lipoprotein cholesterol LPD Low protein diet LVEF Left ventricular ejection fraction MAP Mean arterial pressure MDRD Modification of Diet in Renal Disease MI Myocardial infarction NCC-CC National Collaborating Centre for Chronic Conditions NEOERICA New Opportunities for Early Renal Intervention by Computerised Assessment NHANES National Health and Nutrition Examination Surveys NHS National Health Service NICE National Institute for Health and Clinical Excellence NKF-KDOQI National Kidney Foundation Kidney Disease Outcomes Quality Initiative NNS Number needed to screen NNT Number needed to treat NS Non-significant NSAIDs Non-steroidal anti-inflammatory drugs NSF National service framework NSTEACS Non-ST-segment elevation acute coronary syndrome OR Odds ratio PCR Protein:creatinine ratio PREVEND Prevention of Renal and Vascular Endstage Disease PTH Parathyroid hormone pmp Per million population QOF Quality and Outcomes Framework QALY Quality-adjusted life year RBC Red blood cells RCT Randomised controlled trial REIN RCT Ramipril Efficacy in Nephropathy RCT RENAAL Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan study xi Chronic kidney disease ROC Receiver-operator curve RR Relative risk RRT Renal replacement therapy SBP Systolic blood pressure SCr Serum creatinine SHARP Study of Heart and Renal Protection SIGN Scottish Intercollegiate Guidelines Network SLT Systemic lupus erythematosus STEACS ST-segment elevation acute coronary syndrome UKPDS UK Prospective Diabetes Study UPD Usual protein diet WMD Weighted mean difference Glossary ACEI A drug that inhibits ACE (angiotensin-converting enzyme) which is important to the formation of angiotensin II. ACE inhibitors are used for blood pressure control and congestive heart failure. Adverse events A harmful, and usually relatively rare, event arising from treatment.

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