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The paths from research to improved health outcomes
Evidence-based medicine aims to provide clinicians and patients Getting the evidence used
with choices about the most effective care based on the best Clinicians frequently have questions about the medical care of available research evidence. To patients, this is a natural expec- their patients, but most go unanswered (15). Even if an “answer” tation. To clinicians, it’s a nearly impossible dream. The U.S.
is provided, it usually comes from an out-of-date textbook within Institute of Medicine report “Crossing the Quality Chasm” has the immediate clinical setting. The main predictors of the attempt documented and drawn attention to the gap between what we to answer a question are the belief that an answer exists and the know and what we do (1). The report identified 3 types of quality urgency of the patient’s problem (16).
problems—overuse, underuse, and misuse. It suggested that “The This lack of bedside use of evidence inspired the 4-step model burden of harm conveyed by the collective impact of all of our of bedside evidence-based medicine (8, 17): Ask an answerable health care quality problems is staggering.” While attention has question; track down the best evidence; critically appraise the evi- focused on misuse (or error), a larger portion of the preventable dence for validity, impact, and applicability; and integrate the burden is likely to be the evidence-practice gaps of underuse and results with the patient’s unique biology, circumstances, and values.
In teaching evidence-based medicine, integration of the steps into Research that should change practice is often ignored for years.
the clinical setting and for real patient problems is crucial for For example, crystalloid (rather than colloid) for shock (2), supine changing attitudes and behavior (18). Following these steps in position after lumbar puncture (3), bed rest for any medical con- clinical practice is challenging, especially given the time constraints dition (3), and appropriate use of anticoagulants and aspirin among patients with atrial fibrillation (4). Antman and colleagues(5) documented the substantial delays between cardiovascular trial results and textbook recommendations. However, even when best What underlies substantial gaps between the best evidence and practices are well-known they are often poorly implemented: the management patients receive? Pathman and colleagues (19) National surveys show that most cases of hypertension are unde- described 4 stages from evidence to action: The clinician needs to tected, untreated, or inadequately controlled (6). This has led to be aware, then agree, then adopt, and then adhere. Their survey of the current interest in knowledge translation (7).
physicians’ use of vaccine guidelines showed a steady decline ateach stage. For example, the rates with respect to vaccination foracellular pertussis were 90% aware, 67% agree, 46% adopt, and P r a c t i c e f a m i n e a m i d s t t h e e v i d e n c e g l u t What role does evidence-based medicine (8) have in bridging the 35% adhere. This is consistent with findings from research on the research-practice gap? Surveys of clinicians suggest that a major diffusion of innovations (20), which generally suggests a 5-stage barrier to using current research evidence is the time, effort, and model of knowing, accepting, deciding, implementing, and con- skills needed to access the right information among the massive tinuing. A subsequent systematic review of barriers to the use of volumes of research (9). Even for a (mythical) up-to-date clinician, evidence (9) suggested that several further stages might be added.
the problem of maintaining currency is immense. Each year, The Figure extends the awareness-to-adherence model to include MEDLINE indexes over 560 000 new articles and Cochrane these newer elements—in particular, patient involvement.
Central adds about 20 000 new randomized trials. This is about1500 new articles and 55 new trials per day! Clinicians need clearand efficient strategies to sift, digest, and act on new research like-ly to benefit their patients. 2 stages can be considered: getting the evidence straight, and getting the straight evidence used (10, 11).
G e t t i n g t h e e v i d e n c e s t r a i g h t While individual new research articles are peer-reviewed and pub- lished, there is little effort to set their results systematically in thecontext of other, similar studies (12). Ideally, clinicians could accessan updated, well-conducted systematic review for all questions, orat least for all clinical research. However, only about 10% of ran- domized trials have currently been incorporated into Cochrane systematic reviews (13). For nontherapy questions, the situation is worse. Guidelines are not a panacea here, as they usually rely on existing reviews or, more often, ignore evidence (14) and are rarely presented in clinician-friendly formats. Hence, the Institute of Medicine report recommended that we “establish and maintain a comprehensive program aimed at making scientific evidence more (primary research studies: sound & unsound) useful and accessible to clinicians and patients” (1).
March/April 2005 | Volume 142 • Number 2 The model illustrates that even with high rates of transfer between stages, there may be little effect on patient outcomes.
To carry out an intervention requires both access and know-how.
Thus, even 80% transfer at each of 7 stages would result in only a For medications, this is challenging enough—becoming familiar with dosing, contraindications, initiation, adverse effects, and Using this model, we shall look, first, at the initial problem of monitoring. For more complex interventions, such as brief coun- getting the valid and relevant evidence into the clinical “pipelines” seling or spinal manipulation, the learning curve is even steeper and how this can be improved and, second, at methods for reduc- and hence is a greater barrier to changing practice. For many such complex interventions as smoking cessation, external cephalic ver-sion, or problem-solving therapy for depression, clinicians mayrequire additional training before carrying these out as compe- 1 . A w a r eGiven the information glut, it is not surprising that individual cli- tently as in the trials that documented their benefits.
nicians find it difficult to be aware of all relevant, valid evidence.
Profitable new interventions are likely to have a substantial mar- 5 . A c t e d o nEven when we know and accept what to do, we often forget or keting campaign. However, for many important practice changes, neglect to do it. Habits do not change easily, despite our best such as low-cost pharmaceuticals or nonpharmaceuticals, aware- intentions. Omissions are particularly easy for preventive proce- ness is more problematic. To ease the burden, several scanning dures, as they are often not the pressing focus of a consultation.
and alert services have arisen that help clinicians become aware of Not surprisingly, rates of appropriate preventive procedures are important changes. For example, each issue of the ACP Journal frequently low. A simple reminder is often sufficient for such sim- Club and the Evidence-Based journals results from the scanning of ple omissions of interventions that we believe in and can do. A more than 100 journals to identify new evidence that is valid and review of 16 randomized trials of reminders for preventive proce- important. This process has been augmented to build a new serv- dures showed substantial increase in adherence for most but not all ice, bmjupdates+ (http://bmjupdates.mcmaster.ca), which allows areas (27). Similar but less dramatic results have been shown for practitioners to tap into just those articles that their peers rate as reminders in some areas of medication management (28).
highly relevant and interesting for clinical practice.
When we have remembered to suggest an applicable treatment, the While practitioners may have heard of the benefits of a new inter- above steps may begin all over again for the patient. For the patient vention or the harms of an old one, they may not be persuaded to to agree, they must be aware of the options, accept that the man- change management based on this evidence. A central problem is agement recommended is appropriate, and be able to undertake it.
that clinicians may be persuaded by many means other than unbi- This may involve a complex mixture of the patient’s values and ased evidence, such as marketing techniques, reciprocity (the obli- beliefs, which thus need to be explored. To assist communication gation arising from “gifts”), authority, social validation (acceptance and understanding, patient decision aids have been developed.
by peers), and friendship/personal relationships (21, 22).
While such aids can reduce patients’ decisional conflict with their Pharmaceutical companies and others invest considerable resources final choice, it is less clear whether aided decisions result in better in such methods. Hence, more work is needed to identify methods that can best “vaccinate” clinicians against poor evidence.
Patients must also contend with competing claims and advice, adverse Even if evidence is accepted, clinicians and guidelines may not target effects or fear thereof, and sometimes lack of ability to pay for tests the correct groups. For example, a review of 20 guidelines for atrial and treatments. If resources to inform prescribers of current best evi- fibrillation (most of which were not evidence-based) showed that the dence are inadequate, they are woefully more so for patients, despite proportion of patients recommended for warfarin varied between such pioneering efforts as DipEx (www.dipex.org). Even when 13% and 100% (23). Whether there are net benefits of anticoagula- patients accept the benefits of therapy and wish to comply, they may tion depends on balancing the risk for stroke against the risk for not. We may all agree to exercise more, eat less, or stop smoking, but hemorrhage. A survey of physicians in Australia suggested good too few do. Even for medications, dosing frequency, pill size, and knowledge of factors that increased the hemorrhage risk, but only half simple forgetfulness can all cause problems. Typical adherence rates correctly identified a patient with a previous stroke as being at high for medications are < 50%. Improving adherence to short courses of risk for stroke recurrence (24). Similarly, a Dutch study showed that treatment is relatively easy, but enhancing adherence with long-term risk factors that should predict a higher prescription rate of warfarin regimens is more difficult. Helpful elements include information did not (25). Unfortunately, the relation between diagnosis and treat- about the regimen, counseling about the importance of adherence ment is rarely 1 to 1. Clinicians must usually learn about and under- and how to organize medication taking, reminders, rewards and stand the multiple factors that go into making a good decision that recognition for the patient’s efforts in following the regimen, and enlisting social support from family and friends (30).
March/April 2005 | Volume 142 • Number 2 13. Mallett S, Clarke M. How many Cochrane reviews are needed to cover exist-
Even when most clinicians are aware of evidence, there may be little ing evidence on the effects of health care interventions? ACP J Club. 2003 effect on quality of care without further attention to the other stages.
14. Shaneyfelt TM, Mayo-Smith MF, Rothwangl J. Are guidelines following
However, we would see the initial awareness (and discrimination) of guidelines? The methodological quality of clinical practice guidelines in the high-quality research as the first large hurdle. While bedside evi- peer-reviewed medical literature. JAMA. 1999;281:1900-5. dence-based medicine has focused on clinicians becoming aware of 15. Dawes M, Sampson U. Knowledge management in clinical practice: a sys-
and accepting the best-quality research, it is clearly important but tematic review of information seeking behavior in physicians. Int J MedInform. 2003;71:9-15. insufficient. Not all clinicians will have or use the skills of bedside 16. Gorman PN, Helfand M. Information seeking in primary care: how physi-
evidence-based medicine (31), and even the well skilled will not cians choose which clinical questions to pursue and which to leave unan- implement intended changes fully. Hence, evidence-based medi- swered. Med Decis Making. 1995;15:113-9. cine should not just be concerned with clinical content but also 17. Sackett DL, Straus SE. Finding and applying evidence during clinical rounds:
the “evidence cart”. JAMA. 1998;280:1336-8. with the processes of changing care and systems of care.
18. Coomarasamy A, Khan KS. What is the evidence that postgraduate teaching
in evidence based medicine changes anything? A systematic review. BMJ.
2004;329:1017. 19. Pathman DE, Konrad TR, Freed GL, Freeman VA, Koch GG. The aware-
ness-to-adherence model of the steps to clinical guideline compliance. The case of pediatric vaccine recommendations. Med Care. 1996;34:873-89. 20. Rogers EM. Diffusion of Innovations, 5th ed. New York: Free Press; 2003.
21. Cialdini RB. Influence: The Psychology of Persuasion. New York: Quill; 1998.
22. Roughead EE, Harvey KJ, Gilbert AL. Commercial detailing techniques
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Acknowledgments: The authors thank Iain Chalmers and Sharon
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controlled trials published in general medical journals. JAMA. 2002;287:2799-801. March/April 2005 | Volume 142 • Number 2

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241umb_shinitzky.qxd

Eur Arch Psychiatry Clin Neurosci (1999) 249 : 238–246 I. Leykin · B. Spivak · A. Weizman · I. R. Cohen · M. Shinitzky Elevated Cellular Immune Response to Human Heat-Shock Protein-60 in Schizophrenic PatientsReceived: 26 November 1998 / Accepted: 10 July 1999 Abstract Heat shock protein-60 (HSP60) is implicated patients and in controls. Titers of IgA against HSP60 werein several aut

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Nagoya University Graduate School of Medicine Education: Bachelor of Engineering, Dept. of Transportation Engineering, Tokyo Univ. of Sci., Master of Engineering, Dept. of Civil Engineering, Tokyo Univ. of Sci., 1993 Degree: Doctor of Engineering, Tokyo Univ. of Sci., 1999, Title of the Thesis: Design and analysis of randomized clinical trials with recurrent events. Employment: 1993.4-1995.

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