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Impact of routine surgical ward and intensive care unit admission surveillance cultures on hospital-wide nosocomial methicillin-resistant Staphylococcus aureus infections in a university hospital: an interrupted time-series analysis discount dutasteride 0.5 mg mastercard. Rapid detection of methicillin-resistant Staphylococcus aureus directly from sterile or nonsterile clinical samples by a new molecular assay cheap dutasteride 0.5 mg on line. Detection of methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci on the gowns and gloves of healthcare workers. An outbreak of the methicillin-resistant Staphylococcus aureus on a burn unit: potential role of contaminated hydrotherapy equipment. Evidence that hospital hygiene is important in the control of methicillin resistant Staphylococcus aureus. The best hospital practices for controlling methicillin- resistant Staphylococcus aureus: on the cutting edge. Mupirocin ointment with and without chlorhexidine baths in the eradication of Staphylococcus aureus nasal carriage in nursing home residents. Mupirocin for controlling methicillin-resistant Staphylococcus aureus: lessons from a decade of use at a university hospital. Enteral vancomycin to control methicillin-resistant Staphylococcus aureus outbreak in mechanically ventilated patients. Use of surveillance cultures and enteral vancomycin to control methicillin-resistant Staphylococcus aureus in a paediatric intensive care unit. Topical antimicrobials in combination with admission screening and barrier precautions to control endemic methicillin-resistant Staphylococcus aureus in an intensive care unit. Eradication of methicillin-resistant Staphylococcus aureus from a neonatal intensive care unit by active surveillance and aggressive infection control measures. Elimination of Staphylococcus aureus nasal carriage in healthcare workers: analysis of six clinical trials with calcium mupirocin ointment. Elimination of coincident Staphylococcus aureus nasal and hand carriage with intranasal application of mupirocin calcium ointment. Identification of vancomycin resistance protein VanA as a D-Alanine: D-Alanine ligase of altered substrate specificity. Variant esp gene as a marker of a distinct genetic lineage of vancomycin-resistant Enterococcus faecium spreading in hospitals. A potential virulence gene, hylEfm, predominates in Enterococcus faecium of clinical origin. Epidemiology and mortality risk of vancomycin- resistant enterococcal bloodstream infections. Vancomycin-resistant enterococcal bacteremia: natural history and attributable mortality. Risk factors for development of vancomycin-resistant enterococcal bloodstream infection in patients with cancer who are colonized with vancomycin-resistant enterococci. Catheter-related vancomycin-resistant Enterococcus faecium bacteremia: clinical and molecular epidemiology. Successful treatment of vancomycin-resistant Enterococcus faecium meningitis with linezolid: case report and literature review. Successful treatment of vancomycin-resistant Enterococcus meningitis with linezolid: case report and review of the literature. Epidemiology of bacteriuria caused by vancomycin-resistant enterococci: a retrospective study. Epidemiology and control of vancomycin-resistant enterococci in a regional neonatal intensive care unit. Epidemiology of colonization of patients and environment with vancomycin-resistant enterococci. A semiquantitative analysis of the fecal flora of patients with vancomycin-resistant enterococci: colonized patients pose an infection control risk. Vancomycin-resistant enterococci in intensive care units: high frequency of stool carriage during a non-outbreak period. Effectiveness of gloves in the prevention of hand carriage of vancomycin-resistant Enterococcus species by health care workers after patient care. Risk of hand or glove contamination after contact with patients colonized with vancomycin-resistant Enterococcus or the colonized patients’ environment. Recovery of vancomycin-resistant enterococci on fingertips and environmental surfaces. Long-term survival of vancomycin-resistant Enterococcus faecium on a contaminated surface.

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Proove Narcotic Risk is a genetic test to identify patients at increased risk for chem- ical imbalances in the brain that lead to tolerance order dutasteride 0.5 mg fast delivery, dependence dutasteride 0.5mg on line, or abuse of prescrip- tion pain medications. These tests help select the appropriate analgesic for a patient and reduce the risk of adverse effects and addiction thus facilitating personalized management of pain. Pharmacogenetics of Opioids Although morphine is the analgesic of choice for moderate to severe cancer pain, 10–30 % of patients do not tolerate morphine. Variations in genes involved in mu- opioid receptor signaling influence clinical response to morphine. Clinically relevant genetic as well as nongenetic factors influencing analgesic responses and side effects of opioids. Although available evidence on individual genotype associations with pain, anal- gesia and opioid adverse outcome are promising, conflicting data in the literature indicates that there is a need for larger and more robust studies with appropriate popu- lation stratification and consideration of nongenetic and other genetic risk factors. This study sug- gests that application of genotyping can improve surgical pain management in children. Therefore, small changes, be they splice variants or mutations, may produce dramatic effects. No definite studies have been done on this topic but the phenomenon appears to be widespread as products from approximately one-third of human genes undergo alternative splicing. Also, polymorphisms Universal Free E-Book Store Personalized Management of Pain 451 that alter splice variant expression could predispose patients to differences in disease progression. Genetically defined variations might account for differences of the intensity of inflammatory disease progression. Mechanism-Specific Management of Pain The is a need for the development of diagnostic tools that will allow us to identify the mechanisms of pain in an individual patient and pharmacologic tools that act specifically on these mechanisms. This strategy will enable a rational rather than an empirical trial-and-error approach to controlling pain. Treatment with antiinflam- matory drugs would be helpful in pain associated with inflammatory conditions but these drugs may not benefit patients whose pain is due mainly due to excitability caused by abnormal sodium channel activity after nerve injury as in painful diabetic peripheral neuropathy. Preoperative Testing to Tailor Postoperative Analgesic Requirements Patients vary a great deal in requirement for analgesics after surgery. Determining the best dose for each patient can be difficult because of individual differences in pain tolerance. If patients are undertreated and have severe pain, it can lead to ongo- ing, chronic pain. On the other hand, over treatment with pain medicine is associ- ated with bothersome side effects. About 2 weeks before surgery, the women answered questionnaires to measure anxiety, their expectations about pain and the levels of pain they were hav- ing during pregnancy. In addition, a small heat element was applied to their arms and backs and the women were asked to rate the intensity and unpleasantness. The heat was not applied long enough to cause skin damage and could be stopped by the patient at any time. After surgery, the women reported on their pain severity levels and researchers measured their requirements for pain medication. The researchers found that six groups of predictive factors accounted for 90 % of the total variances in patients’ postsurgical pain severity and medication requirements. The best pre- dictor of the total amount of pain medication required was a validated questionnaire that measured anxiety. The best predictors of overall postsurgical pain were blood pressure readings shortly before surgery and patients’ responses to the heat element that was performed before surgery. The model was also useful in identifying patients in the top 20 % of pain severity and amount of pain medication required after sur- gery. This study shows that it is possible to identify patients at risk for high pain levels after surgery to allow tailored treatments to improve their quality of care. Universal Free E-Book Store 452 12 Personalized Management of Neurological Disorders Personalized Analgesics Pharmacogenetics has been used in drug development and clinical pharmacology of various diseases but not for pain because the genetic aspects of pain are just begin- ning to be unraveled. Moreover, the effect of a drug on acute pain and any adverse reaction are apparent immediately, enabling the switching over to another drug. Pharmacogenetics may be applicable in the treatment of some chronic pain syn- dromes, particularly those with neuropathic pain.

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Early evidence suggests that m ycophenolate m ofetil (an antim etabolite drug) m ay be a useful alternative to azathioprine as m aintenance postoperative im m unosuppression generic 0.5 mg dutasteride visa. Although it is som etim es used for induction follow ing transplantation it is now m ore frequently em ployed in the m anagem ent of severe episodes of acute cardiac rejection generic 0.5 mg dutasteride amex. Com m on com plications follow ing transplantation include allograft rejection and infection. It is of param ount im portance to im m unosuppress the patient to m inim ise the risk of allograft rejection, w ithout over-im m unosuppressing and thereby increasing susceptibility to opportunistic infection. For this reason, cyclosporin-A blood levels are regularly m onitored post- operatively. Side effects include renal failure, hypertension, hyperkalaem ia, hirsutism , gum hypertrophy and increased susceptibility to opportunistic infection and to lym pho- proliferative disorders. Tacrolim us acts in a sim ilar w ay to cyclosporin-A although it m ay be a m ore potent im m unosup- pressive agent. Although its side effect profile is sim ilar, diabetes m ellitus can be a com plication. Azathioprine is an antim etabolite w hose m ajor side effects include bone m arrow suppression and hepatic cholestasis. Som e patients w ho are intolerant of azathioprine are prescribed m ycophenolate m ofetil (w hich is less likely to cause bone m arrow suppression) or cyclophospham ide. At the present tim e the precise role of tacrolim us and m ycophenolate in post-cardiac 130 100 Questions in Cardiology and pulm onary transplant im m unosuppression is unclear and requires further study. In addition to regular m onitoring of drug levels and haem ato- logical (full blood count) and biochem ical (renal and hepatic function, blood glucose) indices, one should be aw are of drug interactions w hich m ay reduce or increase the levels or effectiveness of im m unosuppressive agents. Non-steroidal anti- inflam m atory agents can potentiate nephrotoxicity w hen given w ith cyclosporin-A or tacrolim us. The dose of azathioprine has to be reduced by 70% if patients are also prescribed allopurinol. The m edical m anagem ent of patients w ith cystic fibrosis follow ing heart-lung transplantation. Brendan Madden Post-transplant cardiac denervation theoretically abolishes the perception of cardiac chest pain. How ever, som e patients m ay develop postoperative typical anginal chest pain precipitated by exercise or by increasing heart rate. Such sym ptom s, how ever, are usually described by patients w ho are m ore than five years follow ing transplantation. Chest pain associated w ith coronary artery disease is uncom m on in patients w ho are less than five years post-cardiac transplantation. Interestingly, recent evidence show s an absence of bradycardic response to apnoea and hypoxia in cardiac transplant recipients w ith obstructive sleep apnoea. It m ay be that prospective overnight polysom nography studies w ill identify parasym pa- thetic re-innervation in this group. The m ajority of patients w ith transplant associated coronary artery disease do not get chest pain. Presenting features include progressive dyspnoea w ith exertion or the signs and sym ptom s of cardiac failure. Cardiac auscultation m ay reveal a third or fourth heart sound or features of heart failure. Transthoracic 2D echocardiography m ay reveal evidence of poor biventricular function. M ost units do not advocate routine annual coronary angiography for asym ptom atic patients, since the angio- graphic findings do not usually alter clinical m anagm ent. Furtherm ore, conventional coronary angiography does not alw ays confirm the diagnosis; intravascular ultrasound m ay be m ore sensitive. The condition is frequently diffuse and distal and not usually am enable to intervention, e. In those patients w ho have a localised lesion, the disease m ay progress despite successful intervention. The m ajority of centres do not usually offer cardiac re-transplan- tation on account of shortage of donor organs and poor results attendant on cardiac re-transplantation. Absence of bradycardic response to apnoea and hypoxia in cardiac transplant recipients w ith obstructive sleep apnoea. Suzanna Hardman and Martin Cowie The natural history of patients w ith paroxysm al atrial fibrillation is that over a period of tim e (and often m any years) there is a gradual tendency to an increased frequency and duration of attacks.

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It involves the study of mechanism of action of the drugs on the cells as revealed by gene expression patterns 0.5mg dutasteride mastercard. Pharmacogenetics is a term recognized in pharmacology in the pre-genomic era and concerns the study of influence of genetic factors on response to drugs buy 0.5mg dutasteride with mastercard. With advances in genomics, role of gene polymorphisms on action of drugs has been added to this. Pharmacoproteomics is the application of proteomics to drug discovery and development. Discovery of protein biomarkers may serve as a common basis of diagnostics and therapeutics. Subtyping patients on the basis of protein analysis may help to match a particular target-based therapy to a particular marker in a subgroup of patients. Pharmacometabolomics is the application of metabolomics for study of diseases, discovery of biomarkers, for development of diagnostics and therapeutics. However, the definition of pharmacogenetics will com- plicate the situation as it is erroneous. The main reasons for this are: • Pharmacogenetics existed long before pharmacogenomics and cannot be a sub- set of genomics any more than genetics can be a subset of genomics. Conventional Medicine Versus Personalized Medicine Conventional medicines had a start as empirical therapies. Even as mechanism- based therapies started to develop, lack of efficacy and adverse effects were noted and accepted to a certain extent. Most of conventional medicines were developed as universal drugs for a certain disease. For diseases with multiple pharmacotherapies, the choice was usually left to the prescribing physician’s experience and prefer- ences. With the advances in pharmacogenetics, it became obvious that something could be done for the following problems with conventional medicines. Personalized Medicine and Evidence-Based Medicine Guidelines for evidence-based medicine are generated from the highest level of evidence from multiple randomized controlled clinical trials to address a particular clinical problem. Randomized clinical trials have specific inclusion and exclusion criteria designed to represent a population broad enough and sufficiently enriched to attain a requisite number of end points and demonstrate a statistically and clinically significant dif- ference in outcome. Development of evidence-based guidelines based on relatively broad enrolment criteria inhibits the subsequent development of personalized medi- cine within the enrolment criteria (Goldberger and Buxton 2013). Although claimed are made that evidence-based medicine has the care of individual patients as its top priority that these two approaches can be compatible, it is difficult to reconcile these concepts. Role of Genetics in Future Approaches to Healthcare Genetic Medicine Genetics plays an important role in almost every disease. Our risk of contracting common diseases is generally thought to be determined largely by environment and lifestyle but there is strong epidemiological evidence that genes contribute to overall risk. In multiple sclerosis, for example, the siblings of an affected person have a 25-fold increase in risk of developing the disease compared with the general popu- lation. One may consider trauma to be unrelated to genetic factors but there are genetic factors leading to risk-prone behavior in some individuals and genetic fac- tors may explain the variations in the body’s response to an equivalent amount of trauma in various individuals. Genetics is the study of single genes and their effects whereas genomics is the study not only of single genes, but also of the functions and interactions of all the genes in the genome. Genetic medicine is already beginning to enter the realms of pri- mary care through the availability of testing for predisposition to certain cancers and carrier screening and diagnostic tests for common recessive disorders such as cystic fibrosis and hereditary hemochromatosis. This involvement will broaden as personalized medicine develops and pharmacogenetics will become increasingly Universal Free E-Book Store 22 1 Basic Aspects relevant in decisions about prescribing. Ultimately, pharmacogenetics may be a much greater driving force for the application of genetic medicine in primary care than specific genetic screening programs. Genetics will not remain the exclusive prerogative of specialist centers but every physician will need to use genetic knowl- edge to aid prescribing and clinical management. In the absence of demonstrated function, a gene may be characterized by sequence, transcription or homology. For practical pur- poses, a gene is a physical and functional unit of heredity, which carries information from one generation to the next. The sequencing of the human genome has revealed considerable information to study the genetic basis of disease.

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