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the happier abroad guide to global dating for menLearn More. Wrote the first draft of the paper: BPK. Copyright Brian P. Kavanagh. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. This article has been cited by other articles in PMC. Introduction Professional medical groups commonly issue clinical practice guidelines. Such guidelines are traditionally the result of consensus conferences or expert panels and represent attempts to synthesize—from the best available evidence and expertise—practical guidance on the best possible care. Beyond issuing a guideline, many organizations have felt the need to provide a grading of each guideline's quality, thereby conveying to the reader a sense of the confidence that might be placed in it. This article addresses only the grading of guidelines, not their use or development. Yet there is a central paradox: while GRADE has evolved through the evidence-based medicine movement, there is no evidence that GRADE itself is reliable. Are Different Guidelines Externally Consistent. GRADE is one of several different systems for grading clinical evidence and creating clinical practice guidelines based on this underlying evidence. How do these systems compare with each other. Twelve assessors independently evaluated each system on the basis of 12 criteria to assess the “sensibility” (overall usefulness) of the different approaches. There was poor agreement between them. Nonetheless, the SSC illustrates some of the important difficulties with grading in general and with the GRADE system in particular. There are three reasons why I focus here on the SSC. Third, the SSC is the best known source of advice on managing sepsis and all of its recommendations carry a grading.http://www.yumeguri.jp/userfiles/bowtech-captain-owners-manual.xml
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Although all the studies indicated that antibiotic delay has an adverse effect, they told the clinician nothing that was new: once the need for an antibiotic is confirmed, the sooner it is administered the better. Thus it is unclear why the grading went from grade E in 2004 to grade 1B or 1D in 2004. Was the different grading simply due to the use of a different grading system in these two different years. It seems improbable that two systems describing the validity of a recommendation could arrive at such discordant conclusions. Although most clinicians use PEEP, almost none would be able to quantify lung collapse at the end of expiration, given that atelectasis is seldom quantified. Thus, there is no rationale as to how either grading was arrived at, and no basis for the difference in grading from 2004 to 2008. Is GRADE Internally Consistent. Is GRADE Inherently Logical. Strength of recommendation and quality of evidence GRADE provides an expression of the strength of the recommendation and also provides a rating on the quality of the evidence upon which the recommendation is based. This component makes sense, but less so when the strength of the recommendation is dissociated from its foundation (i.e., the quality of the evidence that underpins the recommendation). One can envision having “high-quality” knowledge that points to a small effect (high quality, low strength). The converse, low quality knowledge that yields a high-strength recommendation seems implausible, other than perhaps the avoidance of substances such as potent toxins. Combining incommensurate elements Another problem is the “leveling” process proposed to determine the quality of the evidence. GRADE ranks the quality of evidence on the basis of the type of study, “quality” issues (e.g., blinding, follow-up, sparseness of data), consistency, directness (generalizability), and effect size.http://designbeginnings.com/upload/bowtech-manual.xml At first glance, this may seem reasonable but there could be unanticipated consequences, such as stifling debate about many important topics, with the result that there is less thought and less research on that topic. A major concern about any grading system is that if enshrined, potentially life-saving prospective studies might not be permitted by research ethics boards on the basis that because a guideline has been assigned a “confident” grading, equipoise does not exist. Popularity and Uptake The GRADE system has been adopted as is, or with minor modifications, by a large number of professional, statutory, and medically related governance organizations ( Box 1 ). But it is not clear to me why the GRADE group needed to be involved at all in the grading decisions given that all the SSC members are experts. While grading experts might be helpful to explain technical elements of grading, the above scenario raises the possibility of the grading process shaping the medical message. It is not clear that the opinion of a conscientious, judicious, well-educated, and experienced clinician would necessarily be inferior to a systemized opinion, such as GRADE, especially if GRADE is not valid. What Should Replace GRADE. A key question that arises when a system is questioned is: what is the alternative. There is a very good alternative to using the GRADE system to rate clinical guidelines: clinicians and organizations should use published guidelines while considering the clinical context, the credentials, and any conflicts of interest among the authors, as well as the expertise, experience, and education of the practitioner. If in the future a guideline grading system is shown to improve outcome and is without harm, it could usefully be incorporated into clinical practice. Footnotes The author has declared that no competing interests exist. This perspective was written without funding contributions from any source. References 1.https://www.thebiketube.com/acros-3m-airmate-papr-manual Canadian Task Force on the Periodic Health Examination. The periodic health examination. Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists clinical practice guideline. A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. An official ATS statement: grading the quality of evidence and strength of recommendations in ATS guidelines and recommendations. Systems for grading the quality of evidence and the strength of recommendations I: critical appraisal of existing approaches The GRADE Working Group. Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Wang HE, Shapiro NI, Angus DC, Yealy DM. National estimates of severe sepsis in United States emergency departments. Clermont G, Angus DC, Kalassian KG, Linde-Zwirble WT, Ramakrishnan N, et al. Reassessing the value of short-term mortality in sepsis: comparing conventional approaches to modeling. Available:. Accessed 15 April 200. 15. Eichacker PQ, Natanson C, Danner RL. Atkins D, Briss PA, Eccles M, Flottorp S, Guyatt GH, et al. Systems for grading the quality of evidence and the strength of recommendations II: pilot study of a new system. Fowler RA, Annane D. The highs and lows of intensive insulin therapy. Brunkhorst FM, Engel C, Bloos F, Meier-Hellmann A, Ragaller M, et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. Egi M, Bellomo R, Stachowski E, French CJ, Hart G, et al. Intensive insulin therapy in postoperative intensive care unit patients: a decision analysis. Gandhi GY, Nuttall GA, Abel MD, Mullany CJ, Schaff HV, et al.http://emadjoe.com/images/boston-micro-90x-manual.pdf Intensive intraoperative insulin therapy versus conventional glucose management during cardiac surgery: a randomized trial. Van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, et al. Intensive insulin therapy in the medical ICU.Intensive insulin therapy in the critically ill patients. Preiser JC, Devos P, Ruiz-Santana S, Melot C, Annane D, et al. A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study. Finfer S, Chittock DR, Su SY, Blair D, Foster D, et al. Intensive versus conventional glucose control in critically ill patients. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. SSC Maintain adequate central venous oxygen saturation. Available:. Accessed 15 April 2009. 27. Australian and New Zealand Intensive Care Society. The Australasian Resuscitation in Sepsis Evaluation (ARISE) Observational Study. 2008. Available:. Accessed 15 April 2009. 28. National Institute of General Medical Sciences. New study aims to stop sepsis in its tracks. 2006. Available:. Accessed 15 April 2009. 29. Guyatt G, Gutterman D, Baumann MH, Addrizzo-Harris D, Hylek EM, et al. Guyatt G, Vist G, Falck-Ytter Y, Kunz R, Magrini N, et al. Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, et al. Guyatt GH, Sackett DL, Sinclair JC, Hayward R, Cook DJ, et al. Users' guides to the medical literature. IX. A method for grading health care recommendations. Eagle KA, Berger PB, Calkins H, Chaitman BR, Ewy GA, et al. Fleisher LA, Beckman JA, Brown KA, Calkins H, Chaikof E, et al. Devereaux PJ, Yang H, Yusuf S, Guyatt G, Leslie K, et al. Schunemann HJ, Best D, Vist G, Oxman AD. Swiglo BA, Murad MH, Schunemann HJ, Kunz R, Vigersky RA, et al.https://wakingbeauty.com/wp-content/plugins/formcraft/file-upload/server/content/files/16274341f60538---brookstone-cube-clock-radio-manual.pdf A case for clarity, consistency, and helpfulness: state-of-the-art clinical practice guidelines in endocrinology using the grading of recommendations, assessment, development, and evaluation system. National Guideline Clearinghouse. Available:. Accessed 15 April 2009. 40. National institute for Health and Clinical Excellence. Fein IA, Corrato RR. Clinical practice guidelines: culture eats strategy for breakfast, lunch, and dinner. Houck PM, Bratzler DW, Nsa W, Ma A, Bartlett JG. Timing of antibiotic administration and outcomes for Medicare patients hospitalized with community-acquired pneumonia. Kumar A, Haery C, Paladugu B, Kumar A, Symeoneides S, et al. The duration of hypotension before the initiation of antibiotic treatment is a critical determinant of survival in a murine model of Escherichia coli septic shock: association with serum lactate and inflammatory cytokine levels. Gacouin A, Le Tulzo Y, Lavoue S, Camus C, Hoff J, et al. Severe pneumonia due to Legionella pneumophila: prognostic factors, impact of delayed appropriate antimicrobial therapy. Kang CI, Kim SH, Kim HB, Park SW, Choe YJ, et al. Pseudomonas aeruginosa bacteremia: risk factors for mortality and influence of delayed receipt of effective antimicrobial therapy on clinical outcome. Larche J, Azoulay E, Fieux F, Mesnard L, Moreau D, et al. Improved survival of critically ill cancer patients with septic shock. Lodise TP, McKinnon PS, Swiderski L, Rybak MJ. Outcomes analysis of delayed antibiotic treatment for hospital-acquired Staphylococcus aureus bacteremia. Meehan TP, Fine MJ, Krumholz HM, Scinto JD, Galusha DH, et al. Miner JR, Heegaard W, Mapes A, Biros M. Presentation, time to antibiotics, and mortality of patients with bacterial meningitis at an urban county medical center. Brower RG, Lanken PN, MacIntyre N, Matthay MA, Morris A, et al. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome.cuacuonbinhduong.com/upload/files/cardiostyle-et150-manual.pdf Meade MO, Cook DJ, Guyatt GH, Slutsky AS, Arabi YM, et al. Mercat A, Richard JC, Vielle B, Jaber S, Osman D, et al. Evidence from randomised controlled trials starts at high quality and, because of residual confounding, evidence that includes observational data starts at low quality. The certainty in the evidence is increased or decreased for several reasons, described in more detail below. Two persons evaluating the same body of evidence might reasonably come to different conclusions about its certainty.Authors must, therefore, make a judgement about whether the risk of bias in the individual studies is sufficiently large that their confidence in the estimated treatment effect is lower.Certainty can be rated down if the patients studied are different from those for whom the recommendation applies. Indirectness can also occur when the interventions studied are different than the real outcomes (for example, a study of a new surgical procedure in a highly specialized centre only indirectly applies to centres with less experience).Several statistical and visual methods are helpful in detecting publication bias, despite having serious limitations. Publication bias is more common with observational data and when most of the published studies are funded by industry.First, when there is a very large magnitude of effect, we might be more certain that there is at least a small effect. Second, when there is a clear dose-response gradient. Third, when residual confounding is likely to decrease rather than increase the magnitude of effect (in situations with an effect).Strong recommendations suggest that all or almost all persons would choose that intervention. Weak recommendations imply that there is likely to be an important variation in the decision that informed persons are likely to make.https://www.uppld.org/wp-content/plugins/formcraft/file-upload/server/content/files/16274342f58727---brookstone-digital-photo-frame-manual.pdf The strength of recommendations are actionable: a weak recommendation indicates that engaging in a shared decision making process is essential, while a strong recommendation suggests that it is not usually necessary to present both options. What is “quality of evidence” and why is it important to clinicians. BMJ (Clinical research ed). 2008;336(7651):995-8. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ (Clinical research ed). 2008;336(7650):924-6. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. Journal of clinical epidemiology. 2011;64(4):383-94. GRADE guidelines: 2. Framing the question and deciding on important outcomes. Journal of clinical epidemiology. 2011;64(4):395-400. GRADE guidelines: 3. Rating the quality of evidence. Journal of clinical epidemiology. 2011;64(4):401-6. GRADE guidelines: 11. Making an overall rating of confidence in effect estimates for a single outcome and for all outcomes. Journal of clinical epidemiology. 2013;66(2):151-7. The GRADE approach is reproducible in assessing the quality of evidence of quantitative evidence syntheses. Journal of clinical epidemiology. 2013;66(7):736-42; quiz 42.e1-5. Journal of clinical epidemiology. 2011;64(4):407-15. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ (Clinical research ed). 2011;343:d5928. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa: Ottawa Hospital Research Institute; 2011. oxford. asp; 2011. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ (Clinical research ed). 2016;355:i4919. Journal of clinical epidemiology. 2011;64(12):1283-93. The statistical significance of randomized controlled trial results is frequently fragile: a case for a Fragility Index. Journal of clinical epidemiology. 2014;67(6):622-8. Journal of clinical epidemiology. 2011;64(12):1294-302.https://doubletroubels.com/wp-content/plugins/formcraft/file-upload/server/content/files/16274343d842b4---brookstone-digital-photo-keychain-manual.pdf Journal of clinical epidemiology. 2011;64(12):1303-10. Journal of clinical epidemiology. 2011;64(12):1277-82. GRADE guidelines: 9. Rating up the quality of evidence. Journal of clinical epidemiology. 2011;64(12):1311-6. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 1: Introduction. BMJ (Clinical research ed). 2016;353:i2016. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 2: Clinical practice guidelines. BMJ (Clinical research ed). 2016;353:i2089. Going from evidence to recommendations. BMJ (Clinical research ed). 2008;336(7652):1049-51. Understanding statistics: other resources How to calculate risk. The working group has developed a common, sensible and transparentMany international organizationsBecause resources are always limited and money thatReviewers and people who use reviews draw conclusions about the quality of the evidence,Such judgments guide subsequent decisions. For example, clinical actions are likelyUsing the same example, a guideline that recommends that patients with atrialTo avoid adding to this confusion by having multipleAlso, while users may believeAs most scientific approaches toIdeally, evidence profiles should be used to assess the certainty in the evidence and these should be based on systematic reviews. At a minimum, the evidence that was assessed and the methods that were used to identify and appraise that evidence should be clearly described. Ideally, GRADE evidence to decision frameworks should be used to document the considered research evidence, additional considerations and judgments transparently. We'll get you started in no time. It also includes the GRADE handbook.We suggest reading our BMJ series.You can also learn more about howGRADE centers and networks. All content is available on the global site. Specialized in clinical effectiveness, learning, research and safety.www.easyhairstyler.com/tmp/phpNr4TSN' to '/home/www/happyhair/easyhairstyler.com/htdocs/www/img/files/cardiostyle-et150-elliptical-trainer-manual.pdf Time to rethink patient education With workflows optimized by technology and guided by deep domain expertise, we help organizations grow, manage, and protect their businesses and their client’s businesses. We specialize in unifying and optimizing processes to deliver a real-time and accurate view of your financial position. We streamline legal and regulatory research, analysis, and workflows to drive value to organizations, ensuring more transparent, just and safe societies. We also offer everyday resources to help optimize your usage of UpToDate and connect you to the latest healthcare news and best practices.The international GRADE group has suggested an approach that may be useful for many groups developing guidelines; UpToDate has adopted the GRADE approach. The grading scheme classifies recommendations as strong (Grade 1) or weak (Grade 2), according to the balance between benefits, risks, burden, and cost, and the degree of confidence in estimates of benefits, risks, and burden. The system classifies quality of evidence (as reflected in confidence in estimates of effects) as high (Grade A), moderate (Grade B), or low (Grade C) according to factors that include the risk of bias, precision of estimates, the consistency of the results, and the directness of the evidence. UpToDate provides recommendations for management of typical patients. To integrate these recommendations with their own clinical judgement, and with individual patient's values and preferences, clinicians need to understand the basis for the recommendations that expert guidelines offer. A systematic approach to grading the strength of management recommendations can minimize bias and aid interpretation. Indeed, most guideline groups have accepted the necessity for some sort of grading scheme. Methodologists and guideline developers have given much thought and effort to considering criteria and approaches to an optimal grading system.If desirable consequences outweigh undesirable consequences, experts will recommend that clinicians offer a treatment to appropriately chosen patients. The uncertainty associated with the trade-off between desirable and undesirable consequences will determine the strength of recommendations. A two-level grading system has the merit of simplicity. We offer three ways editors and clinicians can interpret strong and weak recommendations. Less frequently, a strong recommendation may follow when high quality evidence suggests that two therapies share equivalent benefits, and low quality evidence points to appreciably more harm in one than the other (recommendation for acetaminophen over aspirin in children with chickenpox). If they believe that benefits and risks and burdens are finely balanced, or appreciable uncertainty exists about the magnitude of both benefits and risks, they offer a weak (Grade 2) recommendation. A second way to interpret strong and weak recommendations is in relation to patient values and preferences. For decisions in which it is clear that benefits far outweigh risks, or risks far outweigh benefits, virtually all patients will make the same choice (see Box 1). In such instances, editors can offer a strong (Grade 1) recommendation. In contrast, there are other choices in which patient values and preferences will play a crucial role and in which patients will, as a result, make different choices (see Box 2). When, across the range of patient values, fully informed patients are liable to make different choices, editors should offer weak (Grade 2) recommendations. Aspirin hasThe small, imprecise, and possibly transient benefit leaves us less confident about any recommendation to use heparin in this situation. Hence, the recommendation is likely to be weak. On the other hand, when clinicians face weak recommendations, or when they face patients with very atypical circumstances or values, they should carefully consider the benefits, risks, and burden in the context of the individual patient before them. For strong recommendations, using a decision aid is likely, for most patients, to constitute a poor use of time and energy.One issue is their confidence in the best estimates of benefit and harm. In low risk patients who have suffered a myocardial infarction one might need to treat 100 patients with agents such as aspirin, beta blockers, ACE inhibitors, or statins to extend one life. Despite the much higher number needed to treat (NNT), since we value prolongation of life more highly than relieving dyspnea, the latter intervention may warrant a stronger recommendation. A systematic review and meta-analysis found a relative risk reduction (RRR) of 46 percent in all strokes with warfarin versus aspirin. This large effect supports a strong recommendation for warfarin. Furthermore, the relatively narrow 95 percent confidence interval (RRR 29 to 57 percent) suggests that warfarin provides a RRR of at least 29 percent, and further supports a strong recommendation. At the same time, warfarin is associated with an inevitable burden of keeping dietary intake of vitamin K constant, monitoring the intensity of anticoagulation with blood tests, and living with the increased risk of both minor and major bleeding. Most patients, however, are much more stroke averse than they are bleeding averse. As a result, almost all patients with high risk of stroke would choose warfarin, suggesting the appropriateness of a strong recommendation. Consider a 65 year-old patient with atrial fibrillation and no other risk factors for stroke. This individual's risk for stroke in the next year is approximately 2 percent. Considering the relative risk reduction and this baseline risk, one can derive the absolute magnitude of an effect (see table 2). Some patients who are very stroke averse may consider the down sides of taking warfarin well worth it. Given the relative narrow range that follows from the confidence interval around the relative risk reduction one could make a strong recommendation to use warfarin if all patients were equally stroke adverse. When, across the range of patient values, fully informed patients are liable to make different choices, editors should offer weak (Grade 2) recommendations. When value or preference judgements are particularly salient, editors should describe the key values attached to these outcomes and that influenced the direction of a recommendation or its grade. The limited literature regarding what average patient values and preferences actually are, and the range of preferences, emphasizes the importance of making explicit the key values and preference judgements that drive their recommendations. UpToDate editors,The fundamental study design remains critically important in determining our confidence in estimates of beneficial and detrimental treatment effects. Because of prognostic differences between groups, and lack of safeguards such as blinding that can avoid biased ascertainment of outcomes, evidence based on observational studies will, in general, be appreciably weaker than evidence from RCTs. Recent years have seen, however, an increased awareness of a number of other factors that influence our confidence in our estimates of risk and benefit (see table 3). RCTs suffer from major deficiencies that are likely to result in a. These methodologicalHow lack ofThe randomized trial evidence for danaproid useAs a result, an ACCP guideline panel rated the quality of the evidence asFor instance, drugs may have larger relative effects in sicker, or in less sick, populations. For example, RCTs of pentoxifylline in patients with intermittent claudication have shown conflicting results that so far defy explanation.For instance, while graduated compression stockings have proved of benefit in a variety of populations at risk of venous thrombosis, they have never been tested directly in trauma patients.Consider sigmoidoscopic screening for colon cancer. The relevant evidence includes not only direct but weak evidence from observational studies, but also stronger but indirect evidence from randomized trials of fecal occult blood screening. For instance, a well-designed and rigorously conducted RCT addressed the use of nadroparin, a low molecular weight heparin, in patients with cerebral venous sinus thrombosis. Of 30 treated patients, 3 had a poor outcome, as did 6 of 29 patients in the control group.For example, oralWhile the observational studies are likely to overestimate the trueThe magnitude of the association in these trials constitutes moderate or even high quality evidence. In other words, the actual treatment effect is very likely to be larger than what the data suggests. For instance, a rigorous systematic review of observational studies including a total of 38 million patients compared private for-profit versus private not-for-profit hospital care.It is likely that,Thus, to the extent that residualSince for-profit hospitals areBecause the plausible biases would allRecommendations, however, depend on evidence regarding a variety of outcomes. Thus, it may occasionally be necessary to report a single evidence grade when the quality of evidence differs across important outcomes. Consider, for instance, administration of clopidogrel versus aspirin for threatened stroke. A very large well-conducted RCT has shown a small incremental benefit of clopidogrel over aspirin in reducing vascular events. In deciding on whether to recommend clopidogrel over aspirin, however, one must also consider toxicity. The quality of this evidence is low. Should the overall quality of evidence for clopidogrel versus aspirin, therefore, be considered moderate, or low? If they are, one must rate the overall quality of the evidence according to the studies that address toxicity. If not, the overall rating of the evidence is based on the evidence regarding benefit. For example, if one considers thrombotic thrombocytopenic purpura to be a critical outcome, then one would rate the overall quality of the evidence regarding clopidogrel versus aspirin as low. If, on the other hand, one considered that the outcome was so rare that it should not be considered critical, the overall evidence rating would remain moderate. The followingObservational studies suggestObservational studies suggest steroidQuality of Evidence The critical outcome is mortality. While studies are observational,Best estimates Large mortality reduction, toxicity, and burden variable depending onJudgement of benefits versus risks, burden, and cost Benefit in mortality reduction greater than all down sides, recommendObservational studies of 202 patients suggest high rates of remissionRandomized trials or 143Quality of Evidence Randomized trials without serious limitations provide direct andB). Best estimates Greater remission and lower infection with pulse therapy, increaseJudgement of benefits versus risks, burden, and cost Information available suggests benefits of pulse therapy outweigh downWe grade the tradeoff between benefits and risks and burden in two categories; 1, in which the tradeoff is clear enough that most patients, despite differences in values, would make the same choice, leading to a strong recommendation; and 2, in which the tradeoff is less clear, and individual patients values will likely lead to different choices, leading to a weak recommendation.