D. Farmon. City University of Los Angeles.

Endoscopic trimodal imaging detects colonic neoplasia as well as standard video enscopy purchase generic escitalopram. Likelihood of missed and recurrent adenomas in the proximal versus the distal colon order escitalopram 5mg overnight delivery. Race and colorectal cancer disparities: health-care utilization vs different cancer susceptibilities purchase escitalopram 5mg with mastercard. Interval fecal immunochemical testing in a colonoscopic surveillance program speeds detection of colorectal neoplasia 10 mg escitalopram mastercard. Bowel cleansing for colonoscopy: prospective randomized assessment of efficacy and of induced mucosal abnormality with three preparation agents. Randomised clinical trial: the effects of perioperative probiotic treatment on barrier function and post- operative infectious complications in colorectal cancer surgery a double-blind study. Polyp recurrence after endoscopic mucosal resection of sessile and flat colonic adenomas. Effective bowel cleansing before colonoscopy: a randomized study of split-dosage versus non-split dosage regimens of high-volume versus low-volume polyethylene glycol solutions. A pooled analysis of advanced colorectal neoplasia diagnoses after colonoscopic polypectomy. Lower albumin levels in African Americans at colon cancer diagnosis; a potential explanation for outcome disparities between groups? A randomized, double-blind trial of succinylated gelatin submucosal injection for endoscopic resection of large sessile polyp of the colon. Endoscopic mucosal resection outcomes and prediction of submucosal cancer from advanced colonic mucosal neoplasia. Colonic work-up after incomplete colonoscopy: significant new findings during follow-up. Long-term outcomes of endoscopic submucosal dissection for colorectal epithelial neoplasms. Adverse events associated with use of the three major types of osmotically acting cathartics. Racial/ethnic differences in colorectal cancer risk: the multiethnic cohort study. Molecular mechanisms for chemoprevention of colorectal cancer by natural dietary compounds. Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. Colorectal cancers detected after colonoscopy frequently result from missed lesions. Pancolonic chromoendoscopy with indigo carmine versus standard colonoscopy for detection of neoplastic lesions: a randomized two-centre trial. Warm water infusion versus air insufflation for unsedated colonoscopy: a randomized controlled trial. A back-to-back comparison of white light video endoscopy with autofluorescence endoscopy for adenoma detection in high-risk subjects. American College of Gastroenterology Action Plan for Colorectal Cancer Prevention. American College of Gastroenterology guidelines for colorectal cancer screening 2008. Guidelines for colonoscopy surveillance after cancer resection: A consensus update by the American Cancer Society and the U. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomized trials. Colonoscopy and optical biopsy: bridging technological advances to clinical practice. A prospective, multicenter study of 1111 colorectal endoscopic submucosal dissections (with video). In vivo diagnosis and classification of colorectal neoplasia by chromoendoscopy-guided confocal laser endomicroscopy. Proximal and Large Hyperplastic and Nondysplastic Serrated Polyps Detected by Colonoscopy Are Associated With Neoplasia. American Journal of Physiology Gastrointestinal and Liver Physiology 2010;299:G807-G820. Rate and Predictors of Early/Missed Colorectal Cancers After Colonoscopy in Manitoba: A Population-Based Study. The reduction in colorectal cancer mortality after colonoscopy varies by site of the cancer. Development and validation of a novel patient educational booklet to enhance colonoscopy preparation. Effect of evidence based risk information on informed choice in colorectal cancer screening: randomized controlled trial. Genetic Testing for Hereditary Colorectal Cancer: Challenges in Identifying, Counseling, and Managing High-Risk Patients. Meta-analysisL the diagnostic yield of chromoendoscopy for detecting dysplasia in patients with colonic inflammatory bowel disease. Prospective randomized controlled trial evaluating cap-assisted colonoscopy vs standard colonoscopy. Colon neoplasms develop early in the course of inflammatory bowel disease and primary sclerosing cholangitis. Faster recovery of gastrointestinal transit after laparoscopy and fast-track care in patients undergoing colonic surgery. One to 2-year surveillance intervals reduce risk of colorectal cancer in families with Lynch syndrome. Predictive and Protective factors associated with colorectal cancer in ulcerative colitis: A Case- control study. The safety of intravenous fluorescein for confocal laser endomicroscopy in the gastrointestinal tract. A retrograde-viewing device improves detection of adenomas in the colon: a prospective efficacy evaluation. Eicosapentaenoic acid reduces rectal polyp number and size in familial adenomatous polyposis. Analysis of deaths occurring within the Nottingham trial of faecal occult blood screening for colorectal cancer. A comparison of colonoscopy and double-contrast barium enema for surveillance after polypectomy. Eight year prognosis of postinfectious irritable bowel syndrome following waterborne bacterial dysentery. Prednisolone and Budesonide for Short- and Long-Term Treatment of Microscopic Colitis: Systematic Review and Meta-analysis. The changing picture of high-grade anal intraepithelial neoplasia in men who have sex with men: the effects of 10 years of experience performing high-resolution anoscopy. Irritable bowel syndrome-type symptoms in patients with inflammatory bowel disease: a real association of reflection of occult inflammation? Mindfulness Training Reduces the Severity of Irritable Bowel Syndrome in Women: Results of a Randomized Controlled Trial. Validation of symptom-based diagnostic criteria for irritable bowel syndrome: a critical review. Hepatitis B virus surface antigen levels:a guide to sustained response to peginterferon alfa-2a in HbeAg- negative chronic hepatitis B. Entecavir treatment for up to 5 years in patients with hepatitis B e antigen positive chronic hepatitis B. Long-term therapy with Tenofovir is effective for patients co-infected with human immunodeficiency virus and Hepatitis B virus. American Gastroenterological Association Medical Position Statement on the Management of Hepatitis C. Three year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B. Not interferon, but interleukin-6 controls early gene expression in hepatitis B virus infection.

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Radiographic screening can be used for peripheral cardiac arrhythmias (usually transient) discount escitalopram online american express, pneumothorax generic escitalopram 5mg online, lesions which cannot be directly visualised buy cheapest escitalopram and escitalopram. The potential space created by the removal is The virus enters via the airway by droplet inhalation lled with remaining lung order escitalopram 5mg free shipping, elevation of the diaphragm and causes local inammation, inducing secretions and and mediastinal shift. The hilar vessels are ligated and the bronchus is divided and Clinical features closed close to the carina. The the operation not occupied by shift of other struc- patient may feel short of breath, wheezy and complain tures lls with blood and serum which organises and of chest tightness and retrosternal discomfort. Thecoughthenbecomeswet Thoracoscopy is used for diagnosis of pleural disease, and productive of yellow or green sputum. Discoloured mediastinoscopy to sample upper mediastinal lymph sputum signies infection, which may be of bacterial or nodes and mediastinotomy to sample lower mediasti- viralorigin. Single lung ventilation is used to allow the collapse of the lung being operated on, e. The airway mucosa becomes red and oedematous, there Specic complications following thoracic surgery in- is often an overlying mucopurulent exudate. Respiratory infections Investigations Acute bronchitis These are usually not required, there may be a mild neu- trophil leucocytosis even in viral infections. Patients presenting with acute bronchitis during an inuenza epidemic may ben- Incidence et from treatment with a neuraminidase inhibitor if Very common. Only if secondary bacterial infection is suspected should a course of antibiotics be Age prescribed. Any Prognosis Sex The illness usually lasts up to a week in healthy adults, M = F prolonged symptoms may occur. Conditions impairing Defence mechanism defence mechanism Pneumonia Cough Coma/anaesthesia Respiratory depression Denition Neuromuscular weakness Pneumonia is an infective, inammatory disease of the Ciliary function Smoking, inuenza, colds lung parenchyma. Bronchiectasis (including cystic brosis and Kartageners syndrome) Aetiology Ciliary function can also be It is useful to classify pneumonia according to the impaired mechanically by causative organism or the clinical setting, e. This helps to determine the choice of carcinoma Phagocytosis Smoking antibiotics for treatment. Alcohol Pneumonia most often occurs in children and the el- Hypoxia derly, but may also affect young, t adults. Viralpneumonia is less common, but bacterial pneumo- r Atypical pneumonias cause predominantly interstitial nia may be a secondary complication. Causes include the atypi- Pathophysiology cal bacteria Chlamydia, Coxiella, Mycoplasma and Le- The infection may be as a result of impairment of one or gionella. It is predisposed to by immobility and dation (such as dullness to percussion, increased vocal viral infections which lead to retention of secretions resonance, bronchial breathing) but even if frank con- especially in the lower lobes. The infection is centred solidation is not present, most patients have tachypnoea on the bronchi and bronchioles and spreads to involve (>20 breaths/minute) and crackles. In atypical pneu- adjacent alveoli, which become consolidated with an monia the signs of consolidation in the lung are often acute inammatory exudate. Red hepatisation Organisation of the uid into a brin mesh containing red cells, neutrophils and bacteria. Grey hepatisation Clearance of the red blood cells and neutrophils and predomination of macrophages in an attempt to clear the remaining bacteria. Resolution The brin meshwork is broken down, neutrophil debris is ingested by macrophages which are cleared through the lymphatics. The air spaces are lled with an acute 6weeks to ensure resolution, and to exclude any un- inammatory exudate causing the lung to be rm and derlyinglesionsuchascarcinomacausingobstruction. Several identiable secretions,analgesiaforpleuriticpainwherenecessary stages are seen in a pneumococcal lobar pneumonia andoxygenifthereishypoxia(guidedbyarterialblood (see Table 3. Outcome depends greatly on the age of the patient and r The white cell count will normally demonstrate a neu- concurrent disease (including diabetes mellitus, chronic trophilia. If patients require admission, sputum and renal failure, congestive heart failure and underlying res- blood cultures should be taken and specic serologi- piratory disease such as chronic obstructive pulmonary cal tests are available for Legionella and other atypical disease). If severe sepsis or in a neutropenic patient combination Pseudomonas, Proteus) 60% piperacillin/ tazobactam and gentamicin may be used Strep. Intermediate coexisting chronic disease, hypoxia (PaO2 < 8kPaor ratesoftuberculosisoccurinCentralandSouthAmerica, oxygen saturation < 92%), bilateral or multilobe in- Eastern Europe and Northern Africa. Ascoreof2ormorecorefeaturessuggestaseverepneu- Aetiology monia with indication for initial combined antibiotic M. It is spread by coughing up of live bacilli after invasion of the disease into a main bronchus (open tu- berculosis), which are then inhaled. Approximately 7000 new cases a year in the United r Theemergenceofmultipledrugresistanceduetonon- Kingdom and rising throughout Europe and the United States. It may occur at any time from weeks just below the pleura in the apex of the upper lobe or up to years after the original infection. It matory process forms the Ghon focus usually just differs from primary infection in its immunopathol- beneath the pleura. The lymph nodes are rarely involved, and there is lymph nodes at the lung hilum, and excite an immune reactivation of the immune response in the tissues. This pattern forms the primary r Inthelung,thebacteriahaveapreferencefortheapices complex with infection at the periphery of the lung (higher pO2), and form an apical lung lesion known and enlarged peribronchial lymph nodes. It begins as a small caseating r The outcome of the primary infection depends on the tuberculous granuloma, histologically similar to the balance between the virulence of the organism and Ghon focus, with destruction of lung tissue and cavi- the strength of the host response (see Table 3. T cells are re-induced by the secondary infec- the host can mount an active cell mediated immune tion, with activation of macrophages, and exactly as response the infection may be completely cleared. Collagen is healing of the apical region with collagen de- is deposited around these, often becoming calcied. This is called a progres- tissue, thinning of the collagen wall and increasing sive primary infection. Coughing disperses these bacilli into the at- Poor immune system eg Good immune response, e. This disease is sometimes Use of appropriate antibiotics called galloping consumption. By that time there may be no evidence of tu- comesinfectedbymiliarydisseminationwithmultiple berculosis elsewhere. The hypersensitivity reaction may produce patient mounts a good immune response, organisms atransient pleural effusion or erythema nodosum. Microscopy Formal culture of material is the only way of accu- The characteristic lesion, the tubercle (granuloma) con- rately determining virulence and antibiotic sensitivity sists of a central area of caseous tissue necrosis within and should be attempted in every case, results may which are viable mycobacteria. It relies on the hypersensitivity reaction, usually heals spontaneously but occasionally may per- and is rarely helpful in the diagnosis of tuberculosis: sist giving rise to bronchiectasis particularly of the i The Tine test and Heaf test are for screening: 4/6 middle lobe (Brocks Syndrome). If the spots are conuent, logicalfractures,particularlyofthespinetogetherwith the test is positive, indicating exposure. The reaction is read at Investigations 4872 hours and is said to be positive if the indura- r An abnormal chest X-ray is often found incidentally tion is 10 mm or more in diameter, negative if less in the absence of symptoms, but it is very rare for a than 5 mm. The X-ray shows puried protein derivative this can indicate active patchy or nodular shadowing in the upper zone with infection requiring treatment. In an immunocom- brosis and loss of volume; calcication and cavita- promised host (such as chronic renal failure, lym- tion may also be present. Human immunity depends largely on the haemag- niazid, ethambutol and pyrazinamide, and a further glutinin (H) antigen and the neuraminidase (N) antigen 4months of rifampicin and isoniazid alone. Major shifts in these antigenic re- taken 30 minutes before breakfast to aid absorption. Thesecancauseapandemic,whereasantigenicdrift organism is sensitive for a full 6 months to avoid de- causes the milder annual epidemics. Other upper and lower respiratory symptoms to6weeks after birth (without prior skin testing) in ar- may develop. Individuals are infective for 1 day prior to eas with a high incidence of tuberculosis. Less commonly, secondary Five per cent of patients do not respond to therapy, only Staph. Inuenza A causes worldwide annual epidemics and is Retrospective diagnosis can be made by a rise in spe- infamous for the much rarer pandemics, the most seri- ciccomplement-xingantibodyorhaemagglutininan- ous of which occurred in 1918 when 40 million people tibody measured 2 weeks apart, but this is usually un- died worldwide. Spread is by respiratory r Bed rest, antipyretics such as paracetamol for symp- droplets. Clinical features They are particularly indicated in the elderly, those Patients present with worsening features of pneumonia, with underlying respiratory disease such as chronic usually with a swinging pyrexia, and can be severely ill. Some are manufactured in strates one or more round opacities often with a uid chickembryosandtheseshouldnotbegiventoanyone level. Echocardiogram should be considered to look for infec- These predications depend on global surveillance or- tive endocarditis.

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This means that 9781444335118 our books are always published with you order escitalopram 20 mg with amex, the student best 20mg escitalopram, in mind buy escitalopram with mastercard. The Hands-on Guide for Junior Doctors generic escitalopram 20 mg with mastercard, Fourth Edition Anna Donald, Mike Stein and Ciaran Hill 2011 If you would like to be one 9781444334661 of our student reviewers, go to www. Blackwells publishing programme has been merged with Wileys global Scientic, Technical and Medical business to form Wiley-Blackwell. Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold on the understanding that the publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional should be sought. The seventh edition follows the format of Mark Gurnell previous editions of this book with two sections: Diana Wood Clinical Examination and Clinical Medicine. Each section has been updated to reect the increased Acknowledgements evidence upon which clinical practice is based and the more objective methods of assessment that are We would like to thank Dr Ellie Gurnell, Dr Mark now used. Lillicrap and Dr Narayanan Kandasamy for their con- It is rewarding to discover how many readers have tributions, help and advice during the preparation of found the text useful for study, for revision and for the the manuscript. P reface to th e irst ditio This book is intended primarily for the junior hospital working knowledge in a clinical situation. It should doctor in the period between qualication and the not be forgotten that some rare diseases are of great examination for Membership of the Royal Colleges importance in practice because they are treatable or of Physicians. Some for higher specialist qualications in surgery and conditions are important to examination candidates anaesthetics. The experienced phy- We have not attempted to cover the whole of sician has acquired some clinical perspective through medicine, but by cross-referencing between the two practice: we hope that this book imparts some of this sections of the book and giving information in sum- to the relatively inexperienced. A short account of psychiatry is given in the section The book as a whole is not suitable as a rst reader on neurology since many patients with mental illness for the undergraduate because it assumes much basic attendgeneralclinicsanditishopedthatreadersmaybe knowledge and considerable detailed information has warned of gaps in their knowledge of this important had to be omitted. The section on dermatology is incomplete but textbook of medicine and the information it contains should serve for quick revision of common skin must be supplemented by further reading. In are most commonly seen and where possible have the rst part we have considered the situation which a listed them in order of importance. The frequency candidate meets in the clinical part of an examination with which a disease is encountered by any individual or a physician in the clinic. This part of the book thus physician will depend upon its prevalence in the resembles a manual on techniques of physical exam- district from which his cases are drawn and also on ination, though it is more specically intended to help his known special interests. Nevertheless, rare condi- the candidate carry out an examiners request to tions are rarely seen; at least in the clinic. Wehave We should like to thank all those who helped included most common diseases but not all, and we us with producing this book and, in particular, have tried to emphasise points which are under- Sir Edward Wayne and Sir Graham Bull who have stressed in many textbooks. Accounts are given of kindly allowed us to benet from their extensive many conditions which are relatively rare. It is neces- experience both in medicine and in examining for sary for the clinician to know about these and to be on the Colleges of Physicians. Supplementary reading is essential to un- derstandtheirbasicpathology,buttheinformationwe David Rubenstein give is probably all that need be remembered by David Wayne the non-specialist reader and will provide adequate November 1975 1 T h e m edical in terview Good communication between doctor and patient forms the basis for excellent patient care and the clinical consultation lies at the heart of medical prac- Effective consultation tice. Good communication skills encompass more Effective consultations are patient-centred and ef- than the personality traits of individual doctors they cient, taking place within the time and other practical forman essentialcorecompetencefor medicalpracti- constraints that exist in everyday medical practice. In essence, good communication skills pro- Theuseofspeciccommunicationskillstogetherwith duce more effective consultations and, together with a structured approach to the medical interview can medical knowledge and physical examination skills, enhance this process. Important communication lead to better diagnostic reasoning and therapeutic skills can be considered in three categories: content, intervention. These skills are evidence-base shows that health outcomes for pa- closely interrelated so that, for example, effective tients and both patient and doctor satisfaction within use of process skills can improve the accuracy of the therapeutic relationship are enhanced by good information gathered from the patient, thus enhan- communication skills. Providing structure to the consultation is one of the There are a number of different models for most important features of effective consultation. They are generally similar and all em- that is responsive to the patient and exible for dif- phasise the importance of patient-centred inter- ferent consultations. Like all clinical skills, com- examination) munication skills can only be acquired by experien-. Before meeting a patient, the doctor should prepare by focusing him- or herself, Theinitialpartofaconsultationisessentialtoformthe tryingtoavoiddistractionsandreviewinganyavailable basis for relationship building and to set objectives for information such as previous notes or referral letters. Gathering information An accurate clinical history provides about 80% of the Explanation and planning information required to make a diagnosis. Tradition- ally, history-taking focused on questions related to the Explanationandplanningiscrucially importantto the biomedical aspects of the patients problems. Establishment of a manage- evidencesuggeststhatbetteroutcomesareobtainedby ment plan jointly between the doctor and the patient including the patients perspective of their illness and has important positive effects on patient recall, un- by taking this into account in subsequent parts of the derstanding of their condition, adherence to treat- consultation. Patient expectations should therefore include exploring the history from have changed and many wish to be more involved in boththebiomedicalandpatientperspectives,checking decision-making about investigation and treatment thattheinformationgatherediscompleteandensuring options. The goals of this part of the consultation are thatthepatientfeelsthatthedoctorislisteningtothem. Explanation and planning Gathering information Avoid jargon: use clear concise language; explain Ask the patient to tell their own story. Listen attentively: do not interrupt; leave the pa- Find out what the patient knows: establish prior tient time and space to think about what they are knowledge; nd out how much they wish to know saying. Encourage the patient to express their feelings: Involvethe patient:share thoughts; reveal rationale actively seek their ideas, concerns and expectations. The way in which these two are understand and which takes their perspectives into used is shown in Table 1. It encourages patient participation and collaboration and facilitates accurate information Closing the session gathering. Building a relationship with the patient in- Closing the interview allows the doctor to summarise volves a number of communication skills that enable and clarify the plans that have been made and what the doctor to establish rapport and trust between thenextstepswillbe. Itmaximisesthechances contingency plans are in place in case of unexpected of accurate information gathering, explanation and events and that the patient is clear about follow-up planning and can form part of the development of a arrangements. Itisvitaltopatient ent relationship in this way has positive effects on and doctor satisfaction with the consultation adherence to treatment and health outcomes. Closing the session Summarise:reviewtheconsultationandclarifythe Special circumstances plan of action; make a contract with the patient Certain circumstances demand a special approach to about the next steps. Sequencing Maintain a logical sequence to the Involve the Share your thoughts to interview; use exible but ordered patient encourage patient interaction; organisation by signposting and explain your rationale for doing summarising. The medical interview 5 Breaking bad news Approach to communication skills assessment Prepare: ensure you have all the clinical details and know the facts; set aside enough time; Past papers: the format of the examination should encourage the patient to bring a relative or be available for review; look at the communication friend. In some examinations spective; do not overwhelm with information in the clinical scenario is available in advance of the rst instance; check repeatedly that the pa- the examination to allow preparation of content tient understands. Make a plan: explain what will happen next; give Make a plan: before you enter the station, have a hope but be realistic; conrm your role as a clear plan as to how you will approach the partner in care. Complexsituationsrequirethedoctor present and discuss the case, listen carefully to to use basic skills to a higher level. Preparation and the examiner and present the salient features in planning, listening to the patient, delivering informa- a clear and logical manner. Closureisalsoimport- ant, ensuring the patient knows what is happening and is clear about the next steps. Communication skills are usually ments should have been through appropriate 6 The medical interview Concrete experience Consultation with a patient Interview a simulated patient Role play Reflection Active experimentation Think about the consultation Try a different approach Observe a recorded consultation in a learning environment Give and receive feedback Abstract conceptualisation What will I do differently next time? Thecycleenablesthelearnertobuildonexistingknowledgeand skills, to take responsibility for their own progress and to use real life clinical and simulated encounters to promote further learning. Dyspnoea may be observed and outstretched abnormal movements, including tremor or paucity of T resting tremor of Parkinsons disease hands facial expression, should be noted. Many patients with ischaemic heart disease have few or no physical signs and a characteristic history of peripheral vascular disease may be elicited.

Such practices are not acceptable buy escitalopram 20 mg overnight delivery, particularly for molecules 60 which are used as last resort medicine for humans buy escitalopram us. If clinical freedom of veterinarians must be stressed buy escitalopram 20mg overnight delivery, as they are the best placed to determine the right option treatment discount 5mg escitalopram with visa, we believe such practices should be better controlled as it represents a risk of increasing selection pressure. Defining a reduction percentage is the only way to achieve a significant reduction in antibiotic use as experience in several countries proved. In 2011 the Dutch government set a clear proven quantitative policy objective to achieve a 20% reduction in reduction targets antibiotic use compared with 2009. In the end the slashed antibiotics total sales of antibiotics dropped by nearly 32% in use. In addition the 2013 policy objective to achieve a 50% reduction in antibiotic use compared with 2009 has already been exceeded as the total sales of antibiotics dropped by 62 51% during the period 2009-2012. It shows that quantitative objectives help to efficiently reduce the need to recourse to antibiotics. In addition if controls of drug residues at farm level are important the European Commission should also consider testing the final product for the presence of antibiotic resistant bacteria. The priority is now to refine the data collection at species level and have consumption data, preferably at farm level. Today, sales data While such information is of great value it still lacks some do not detail specificity. Sales data do not provide information on the which antibiotic kind of species which received antibiotics while most was given to veterinary medicines are administered to several animal which species, species. As such it is impossible to know which species specific species have been treated. It will also provide information as to the classes of antibiotics used per species and help determine whether some antibiotics should not be allowed for certain species anymore. To have reliable sales data which allows comparison by species and helps policy makers to develop new strategies it is important to have data by weight groups or production type. Indeed larger animals may require larger doses, as this is the case in human medicine, so sales data per species alone might not always reflect reality. If sales data indicate how many tons of antibiotics were sold, it does not provide any information on the real consumption of antibiotics by farm animals. In addition, overall sales data might show a steady decline only because more powerful antibiotics are used at lower doses, which inaccurately reflect the risk posed to both animal and human health. Consequently harmonised methodology to collect and compare consumption data should be developed urgently. Collecting antibiotics consumption volumes in livestock farming is critical as it allows us to determine whether differences in antibiotic resistance amongst animal species can be related to differences in consumption patterns of antibiotics. It will help describe and quantify the consumption of antibiotics in full detail at animal species level to eventually determine which changes to make. The data will create transparency and help define benchmark indicators for veterinary consumption of antibiotics. It enables an estimation of the amounts of antimicrobial agents sold per species (limitations: weight group and production type information lacking). This allows comparison between farms with similar activities to help identify persistently high consumers. This is the reason invoked by the Danish government who implemented the yellow- card system in 2010. In this system pig farms are given a yellow card when they consume more than twice the average consumption. This highlights that greater 67 efforts are still needed to limit the use of antibiotics at farm level. It allows government officials to review the antibiotic use of individual farmers and to consequently issue warnings and require farm inspections as needed. At the same time farms who achieve good results could be used as a model for farms which rely too much on antibiotics. For instance the Consumption data German government recently set up a new central reflects the databank that will record antibiotic use on situation on the individual farms. Refining identify where antibiotics are used in excess and data at farm or vet enable farmers to compare their level of antibiotic level helps identify use with the national average. Indeed it is urgent inadequate that farmers report every single treatment behaviours. Under the banner of One Health, whereby animal and human health are closely interconnected, immediate action should be undertaken as the threat is growing and it might take several years to reverse the trend. Indeed positive effects could only be seen many years after antibiotic use has diminished while antibiotic resistance is happening right now in every region of the world and has the potential to affect anyone, of any age, in 68 any country. In view of the upcoming review of both Veterinary Medicines and Medicated Feed legislations it is critical to implement rules which will help to curb the use of antibiotics in food-producing animals and to effectively fight antibiotic resistance. We also call on the Commission to publish a progress report on the implementation of the 5 year action plan on antimicrobial resistance indicating areas where legislative changes are required. Those antibiotics should be restricted for species where a high risk of resistance transmission has been identified, as well as for therapeutic group treatment and eventually for metaphylaxis. Piddock Abstract | Antibiotic-resistant bacteria that are difficult or impossible to treat are becoming increasingly common and are causing a global health crisis. Antibiotic resistance is encoded by several genes, many of which can transfer between bacteria. New resistance mechanisms are constantly being described, and new genes and vectors of transmission are identified on a regular basis. This article reviews recent advances in our understanding of the mechanisms by which bacteria are either intrinsically resistant or acquire resistance to antibiotics, including the prevention of access to drug targets, changes in the structure and protection of antibiotic targets and the direct modification or inactivation of antibiotics. Antibiotics underpin modern medicine; their use has the Gram-negative genus Pseudomonas. A second example relates fatty acid-linked peptide chain infections is becoming a reality. The most recent World to the lipopeptide daptomycin (first approved for clinical that targets the cell membrane Economic Forum Global Risks reports have listed anti- use in 2003), which is active against Gram-positive bac- (for example, daptomycin). It is estimated that in Europe 25,000 people This is due to an intrinsic difference in the composition Glycopeptide A natural or semi-synthetic die each year as a result of multidrug-resistant bacte- of the cytoplasmic membrane; Gram-negative bacteria amino sugar-linked peptide rial infections and that this costs the European Union have a lower proportion of anionic phospholipids in the chain that targets terminal economy 1. In the United States cytoplasmic membrane than do Gram-positive bacte- d-Ala-d-Ala dipeptides (for more than 2 million people are infected with antibiotic- ria, which reduces the efficiency of the Ca2+-mediated example, vancomycin). In addition to increased resistance to existing brane that is required for its antibacterial activity8. The intrinsic resistance of a bacterial species to membrane and access these peptides in the periplasm9. The simplest example of to antibiotics of different classes, including -lactams, Correspondence to L. This was achieved e-mail: the absence of a susceptible target of a specific antibi- using high-throughput screens of high-density genome l. Therefore, this Review provides an update of the latest research for each type of antibiotic resist- ance mechanism and puts it into global context in terms of prevalence, the biological impact on the bacterium and the potential impact on clinical treatment. Hydrophilic antibiotics cross the outer membrane by diffusing through outer- membrane porin proteins. In most Enterobacteriaceae, Inner membrane Eux pump the major porins, such as the outer-membrane proteins OmpF and OmpC of E. The figure shows an overview ofNature Reviews | Microbiology non-specific channels; previous evidence that suggested intrinsic resistance mechanisms. Antibiotic A can enter the cell via a membrane-spanning now seems to be incorrect1820,. Therefore, reducing the porin protein, reach its target and inhibit peptidoglycan synthesis. Antibiotic B can also permeability of the outer membrane and limiting antibi- enter the cell via a porin, but unlike Antibiotic A, it is efficiently removed by efflux. This well-established mecha- nism of intrinsic antibiotic resistance in Gram-negative aeruginosa1011,. However, recent data have shown that in Entero- nations in which one agent can inhibit an intrinsic resist- bacteriaceae, Pseudomonas spp.

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