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Surgery_Schwartz. Urol Int. 2014;92:41-49. 257. Mukhtar S, Ayres BE, Issa R, et al. Challenging boundaries: an enhanced recovery programme for radical cystectomy. Ann R Coll Surg Engl. 2013;95:200-206. 258. Campos PAC, Martinez JG, Fernandez PJG, et al. Periop-erative fast track program in intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreduc-tive surgery in advanced ovarian cancer. Eur J Surg Oncol. 2011;37:543-548.Brunicardi_Ch50_p2113-p2136.indd 213401/03/19 9:39 AM 2135OPTIMIZING PERIOPERATIVE CARE: ENHANCED RECOVERY AND CHINESE MEDICINECHAPTER 50 259. Chapman JS, Roddy E, Ueda S, et al. enhanced recovery path-ways for improving outcomes after minimally invasive gyne-cologic oncology surgery. Obstet Gynecol. 2016;128:138-144. 260. de Groot JJ, van Es LE, Maessen JM, et al. Diffusion of Enhanced Recovery principles in gynecologic oncology sur-gery: is active implementation still necessary? Gynecol Oncol. 2014;134:570-575. 261. Lindemann K, Kok PS, Stockler M, et al.


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Surgery_Schwartz. al. Diffusion of Enhanced Recovery principles in gynecologic oncology sur-gery: is active implementation still necessary? Gynecol Oncol. 2014;134:570-575. 261. Lindemann K, Kok PS, Stockler M, et al. enhanced recov-ery after surgery for advanced ovarian cancer: a system-atic review of interventions trialed. Int J Gynecol Cancer. 2017;27:1274-1282. 262. Marx C, Rasmussen T, Jakobsen DH, et al. The effect of accel-erated rehabilitation on recovery after surgery for ovarian malignancy. Acta Obstet Gynecol Scand. 2006;85:488-492. 263. Wijk L, Franzen K, Ljungqvist O, et al. Implementing a structured enhanced recovery after surgery (ERAS) protocol reduces length of stay after abdominal hysterectomy. Acta Obstet Gynecol Scand. 2014;93:749-756. 264. Khan SK, Malviya A, Muller SD, et al. Reduced short-term complications and mortality following enhanced recovery pri-mary hip and knee arthroplasty: results from 6,000 consecu-tive procedures. Acta Orthop. 2014;85:26-31. 265. Scott NB, McDonald


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Surgery_Schwartz. short-term complications and mortality following enhanced recovery pri-mary hip and knee arthroplasty: results from 6,000 consecu-tive procedures. Acta Orthop. 2014;85:26-31. 265. Scott NB, McDonald D, Campbell J, et al. The use of enhanced recovery after surgery (ERAS) principles in Scot-tish orthopaedic units—an implementation and follow-up at 1 year, 2010-2011: a report from the Musculoskeletal Audit, Scotland. Arch Orthop Trauma Surg. 2013;133:117-124. 266. Zhou B, Sun R. About the cultural support of the develop-ment of traditional chinese medicine. The 12th National Symposium on Chinese Medicine Culture. 74-79. 267. Yang M, Li J. Analysis on the development of tradi-tional chinese medicine. Contemporary Medicine Forum. 2014;12:277-278. 268. Yu M. Chinese medicine and Western medicine: two kinds of philosophies and two different cultures of medicine. Journal of Zhengzhou University of Light Industry (Social Science). 2012;13:7-12. 269. Yue X. The Historical stages of the


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Surgery_Schwartz. medicine: two kinds of philosophies and two different cultures of medicine. Journal of Zhengzhou University of Light Industry (Social Science). 2012;13:7-12. 269. Yue X. The Historical stages of the formation and develop-ment of traditional Chinese medicine. Guangming Journal of Chinese Medicine(CJGMCM). 2012;27:207-210. 270. Tong X, Zhang Z, Li A. The confusion of chinese medicine development and its countermeasures. Chinese Journal of Basic Medicine in Traditional Chinese Medicine. 2003;9:52-55. 271. Geng D. Research progress of shiquan dabu decoction. Chinese Traditional Patient Medicine. 2003;25:837-840. 272. Han D, Chen Z, Xing B. Therapeutic rules of analogous pre-scriptions for tonify and replenish the middle qi. Chinese Archives of Traditional Chinese Medicine. 2010;28:595-598. 273. Liu K, Wang B. Influences of Buzhong Yiqi Decoction on gastrointestinal feunction and nutrition status of gastric carcinoma after operation. Chinese Journal of Experimental Traditional Medical


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Surgery_Schwartz. K, Wang B. Influences of Buzhong Yiqi Decoction on gastrointestinal feunction and nutrition status of gastric carcinoma after operation. Chinese Journal of Experimental Traditional Medical Formulae. 2015;21:152-156. 274. Su P, Li W. The effect of Shiquan Dabu Decoction tegether with enteral nutrition for patients with lung cancer after sur-gery. Journal of Nanjing University of Traditional Chinese Medicine. 2015;31:17-20. 275. Yang A, Xiang F, Yang L. Effect of Shiquan Dabu Tang com-bined with Wuwei Xiaodu Yin on immune functions in post-operative Qi and blood deficiency patients with esophagus cancer. Chinese Journal of Experimental Traditional Medical Formulae. 2016;22:174-178. 276. Cui J. The effects of Shenmai injection on cellular immuno-logic function in the perioperative patients with gastroentero-logical tumors. Pract Clin Med. 2007;8:39-41. 277. Liang C. Clinical observation on the protective effect of huangqi injection on the myocardium of coronary heart dis-ease in the


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Surgery_Schwartz. with gastroentero-logical tumors. Pract Clin Med. 2007;8:39-41. 277. Liang C. Clinical observation on the protective effect of huangqi injection on the myocardium of coronary heart dis-ease in the perioperative period. Shan Xi Journal of Tradi-tional Chinese Medicine. 2011;17:17-18. 278. Ruan L, Deng Y. Study of effect of xiaoaiping in enhanc-ing efficacy of neoadjuvant chemotherapy for breast cancer and its mechanism. Journal of Chinese Materia Medica. 2005;40:749-752. 279. Tan M, Guo Z, Bin X. The effect of elemene local intra-arte-rial infusion to apoptosis and proliferation in breast cancer. Chinese J Clin Oncol. 2001;28:267-269. 280. Wu X. Research on Acute Abdomen. 1st ed. China; 1988. 281. Xie J, Wu X. Research on three cheng qi decoction used in the bowel preparation. Chinese Journal of Surgery of Integrated Traditional and Western Medicine. 1996;2:355-357. 282. Li X. Flavored pure ginseng decoction treating 75 cases of traumatic shock. Journal of Emergency in Traditional


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Surgery_Schwartz. Journal of Surgery of Integrated Traditional and Western Medicine. 1996;2:355-357. 282. Li X. Flavored pure ginseng decoction treating 75 cases of traumatic shock. Journal of Emergency in Traditional Chinese Medicine. 2003;12:413. 283. Ji C, Liu J, Chen H. Effect of Qingdan Decoction combined with biliary decompression on the liver function and inflam-matory factors in acute cholangitis severe type rats. Journal of Traditional Chinese Medicine. 2013;54:512-515. 284. Wang X, Zhang X. The effect of Qingyi decoction on bacte-rial and endotoxin translocation from intestine in acute hem-orrhagic necrotizing pancreatitis in rat. Chinese Journal of General Surgery. 2010;19:255-258. 285. Yao G, Wu X. Clinical study of treatment of severe acute pancreatitis with Qingyi decoction. Chinese Journal of Surgery of Integrated Traditional and Western Medicine. 1997;3:244-246. 286. Han J. Research on acupuncture anesthesia-analgesia. Acupunct Res. 2016;41:377-387. 287. Arranz L, Guayerbas N, Siboni L.


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Surgery_Schwartz. Surgery of Integrated Traditional and Western Medicine. 1997;3:244-246. 286. Han J. Research on acupuncture anesthesia-analgesia. Acupunct Res. 2016;41:377-387. 287. Arranz L, Guayerbas N, Siboni L. Effect of acupuncture treat-ment on the immune function impairment found in anxious women. Am J Chinese Med. 2007;35:35-51. 288. Liu Y. The effect of transcutaneous electroacupuncture on serum level of glucocose and cortisol in patient underwent thyroidectomy. Chinese Journal of Traditional Medical Science and Technology. 2013;20:180-181. 289. Sun Y, Gan TJ, Dubose JW, et al. Acupuncture and related techniques for postoperative pain: a systematic review of randomized controlled trials. Br J Anaesth. 2008;101:151-160. 290. Zhang Q, Gao Z, Wang H, et al. The effect of pre-treatment with transcutaneous electrical acupoint stimulation on the quality of recovery after ambulatory breast surgery: a pro-spective, randomised controlled trial. Anaesthesia. 2014;69: 832-839. 291. Zou D, Chen WH,


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Surgery_Schwartz. electrical acupoint stimulation on the quality of recovery after ambulatory breast surgery: a pro-spective, randomised controlled trial. Anaesthesia. 2014;69: 832-839. 291. Zou D, Chen WH, Iwakiri K, et al. Inhibition of transient lower esophageal sphincter relaxations by electrical acu-point stimulation. Am J Physiol Gastrointest Liver Physiol. 2005;289:G197-G201. 292. Shiotani A, Tatewaki M, Hoshino E, et al. Effects of elec-troacupuncture on gastric myoelectrical activity in healthy humans. Neurogastroenterol Motil. 2004;16:293-298. 293. Tatewaki M, Strickland C, Fukuda H, et al. Effects of acupuncture on vasopressin-induced emesis in con-scious dogs. Am J Physiol Regul Integr Comp Physiol. 2005;288:R401-R408. 294. Arnberger M, Stadelmann K, Alischer P, et al. Monitoring of neuromuscular blockade at the P6 acupuncture point reduces the incidence of postoperative nausea and vomiting. Anesthe-siology. 2007;107:903-908. 295. El-Deeb AM, Ahmady MS. Effect of acupuncture on nausea


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Surgery_Schwartz. blockade at the P6 acupuncture point reduces the incidence of postoperative nausea and vomiting. Anesthe-siology. 2007;107:903-908. 295. El-Deeb AM, Ahmady MS. Effect of acupuncture on nausea and/or vomiting during and after cesarean section in compari-son with ondansetron. J Anesth. 2011;25:698-703. 296. Feng C, Popovic J, Kline R, et al. auricular acupressure in the prevention of postoperative nausea and emesis a randomized controlled trial. Bull Hosp Jt Dis (2013). 2017;75:114-118. 297. Okuno S, Hirayama K, Inoue J. Effects of rikkunshito on the postoperative nausea and vomiting (PONV) after laparoscopic gynecological surgery. Masui. 2008;57:1502-1509.Brunicardi_Ch50_p2113-p2136.indd 213501/03/19 9:39 AM 2136SPECIFIC CONSIDERATIONSPART II 298. Zhang X, Zhang D, Yang Y. Effects of Houpupaiqi Heji on the gastrintestinal function of patients after gastric cancer surgery. Mod Oncol. 2015;23:1268-1270. 299. Zhang X, Yuan H, Qin W. Study on early enteral nutrition combined with


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Surgery_Schwartz. of Houpupaiqi Heji on the gastrintestinal function of patients after gastric cancer surgery. Mod Oncol. 2015;23:1268-1270. 299. Zhang X, Yuan H, Qin W. Study on early enteral nutrition combined with acupuncture to promote the recovery of gastro-intestinal function in patients after surgery. Chinese Journal of Surgery of Integrated Traditional and Western Medicine. 2016;22:542-545. 300. Jian W, Heng L, Hui QQ. Effect of Da-Cheng-Qi-Tang on gastrointestinal motility in patients undergoing laparotomy. Hepatogastroenterology. 2011;58:1887-1892. 301. You S, Wu X, Liu M. Effects of dachengqi decoction on gut hormones and intestinal movement after cholecystectomy. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1994;14:522-524. 302. Yang Y, Zuo HQ, Li Z, et al. Comparison of efficacy of simo decoction and acupuncture or chewing gum alone on postop-erative ileus in colorectal cancer resection: a randomized trial. Sci Rep. 2017;7:37826. 303. Chen Z, Cao L, Wen Z, et al. Study of Evodia hot compress plus


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Surgery_Schwartz. acupuncture or chewing gum alone on postop-erative ileus in colorectal cancer resection: a randomized trial. Sci Rep. 2017;7:37826. 303. Chen Z, Cao L, Wen Z, et al. Study of Evodia hot compress plus electro-acupuncture in patients who have undergone abdominal surgery. Int J Clin Exp Med. 2015;8:16167-16174. 304. Wu X. Practice of Abdominal Surgery. 3rd ed. Tianjin Science and Technology Press; 2004. 305. Cui Z, Kong D. 74 cases of biiliary liver abscess treated with integrated traditional and western medicine. Chinese Journal of Surgery of Integrated Traditional and Western Medicine. 2014;20:167-169. 306. Sun S, Xu W. Effects of TPN and immune regulator radix astragali on postoperative patients of obstructive jaundice. J Parenter Enteral Nutr. 2002;9:151-157. 307. Ma X, Yang W, Zhang X. The study of effect of shiquan dabu decoction in surgeical nutrition therapy. Beijing Journal of Traditional Chinese Medicine. 1991;4:31-32. 308. Dong Y, Cui Z. Acupuncture research on adhesive


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Surgery_Schwartz. X. The study of effect of shiquan dabu decoction in surgeical nutrition therapy. Beijing Journal of Traditional Chinese Medicine. 1991;4:31-32. 308. Dong Y, Cui Z. Acupuncture research on adhesive intestinal obstruction. Clin J Chinese Med. 2001;3:86-88. 309. Li G, Ma J, Shang H, et al. Application of Dechengqi decoc-tion in abdominal surgery. World Chinese Journal of Diges-tion. 2008;16:1672-1676. 310. Li H, Hong Y, Huang M. Clinical effect observation of Chinese herbal enema, external application and acupuncture in adhe-sive ileus. Journal of Guangzhou University of Traditional Chinese Medicine. 2007;24:282-285.Brunicardi_Ch50_p2113-p2136.indd 213601/03/19 9:39 AM


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Surgery_Schwartz. Understanding, Evaluating, and Using Evidence for Surgical PracticeAndrew J. Benjamin, Andrew B. Schneider, Jeffrey B. Matthews, and Gary An 51chapterINTRODUCTIONThe singular importance of this chapter rests on the following chain of reasoning:1. The state of surgical science and knowledge is constantly changing.2. The education of a surgeon is a continuous process.3. Surgeons need to know how to evaluate new surgical knowl-edge to maintain their education in order to best serve their patients.4. This chapter provides guidance as to how surgeons might navigate, interpret and apply this new knowledge.Notably, this reasoning also applies to the process of acquisition of new knowledge itself, which explains why this inaugural chapter on evidence-based medicine is occurring in the 11th edition of this book. Recognizing the impermanence and fluidity of knowledge is a critical insight for the responsible surgeon, but so too is realizing that “good practice” cannot occur without reference


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Surgery_Schwartz. of this book. Recognizing the impermanence and fluidity of knowledge is a critical insight for the responsible surgeon, but so too is realizing that “good practice” cannot occur without reference points as to what should be done given the current imperfect state of knowledge. These dual recognitions inform the organization of this chapter, which introduces and describes the currently accepted approach to evidence-based medicine, and then follows by noting a series of current issues that anticipate the likelihood that what is meant by “evidence-based medicine” will evolve over the coming years. Also note that this chapter is not intended to be a primer on statistics and clinical trial design; there are entire textbooks devoted to those subjects. Rather, this chapter will focus on how those tools are aggregated and presented in order to inform a surgeon how to keep abreast with current developments in practice.WHAT IS EVIDENCE-BASED MEDICINE?For centuries, the practice of medicine was


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Surgery_Schwartz. tools are aggregated and presented in order to inform a surgeon how to keep abreast with current developments in practice.WHAT IS EVIDENCE-BASED MEDICINE?For centuries, the practice of medicine was guided primarily by anecdotal experience, often based on rationales that did not arise from a rigorous scientific process and sustained by the fundamental barriers associated with being able to learn from one’s experience (e.g., cognitive bias). For example, treatments such as bloodletting and purging were based on ostensible prin-ciples of bodily humors originating from the Ancient Greeks, and persisted well into the 18th century despite repeated disas-trous outcomes. To a great degree, the goal of the Scientific Method, through its emphasis on skepticism and falsifiability, is predicated upon overriding observational/experiential bias by the application of rigorous methodology statistical analysis. The dangers of bias were recognized at the dawn of the Scien-tific Era, and continue to


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Surgery_Schwartz. overriding observational/experiential bias by the application of rigorous methodology statistical analysis. The dangers of bias were recognized at the dawn of the Scien-tific Era, and continue to manifest today (Box: The History and Sources of Bias in Biomedical Literature).Introduction2137What is Evidence-Based Medicine?2137Searching for Information: Patient/Population, Intervention, Comparison, and Outcome / 2139Types of Studies / 2139Hierarchies of Evidence / 2140Tools to Evaluate a Body of Evidence / 2140Synthesis of Evidence—Clinical Guidelines / 2142The Challenges of Applying EBM to Surgery2144Analysis of a Surgical Randomized Control Trial / 2144Internal Validity / 2144External Validity / 2146Additional Challenges to Conducting a Surgical RCT / 2146Use and Misuse of Statistical Significance2147Type I and Type II Errors / 2147P Values / 2147Alternative to P Values / 2148How do the Tools of EBM Perform?2148External Consistency / 2148Internal Consistency / 2148System


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Surgery_Schwartz. Significance2147Type I and Type II Errors / 2147P Values / 2147Alternative to P Values / 2148How do the Tools of EBM Perform?2148External Consistency / 2148Internal Consistency / 2148System Issues / 2148Validity / 2149Implications of EBM / 2149The Alternatives to EBM2149What can Researchers do to Improve the Validity of Research Findings?2149The History and Sources of Bias in Biomedical LiteratureIn Sir Francis Bacon’s initial description of the scientific method in his Novum Organum1 he notes what he terms the “idols of the mind,” in essence recognizing and classifying the sources of cognitive bias that limit the reliability of sub-jective observation and interpretation. These “idols” are:• Idols of the tribe (Idola tribus): A humans’ tendency to per-ceive more order and regularity in systems than truly exists, and arises from their preconceived ideas about things• Idols of the cave (Idola specus): Arising from an individ-ual’s personal limitations in reasoning due to particular


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Surgery_Schwartz. systems than truly exists, and arises from their preconceived ideas about things• Idols of the cave (Idola specus): Arising from an individ-ual’s personal limitations in reasoning due to particular personalities, subjective likes and dislikesBrunicardi_Ch51_p2137-p2152.indd 213728/02/19 4:19 PM 2138• Idols of the marketplace (Idola fori): Arising from the con-fusion in the use of language and taking some words in sci-ence to have a different meaning than their common usage• Idols of the theatre (Idola theatri): Arising from the following of academic dogma and not asking questions about the worldThese descriptions still resonate today, illustrating just how long the dangers of cognitive bias have been recognized, and just how embedded those tendencies may be. For instance, the following are sources of bias in biomedical literature:• Publication bias: publishers incentivized to accept posi-tive results• Prevailing field bias: supporting entrenched opinions• Citation bias: tendency


Surgery_Schwartz

Surgery_Schwartz. are sources of bias in biomedical literature:• Publication bias: publishers incentivized to accept posi-tive results• Prevailing field bias: supporting entrenched opinions• Citation bias: tendency to cite positive studies• Time-lag bias: delay the reporting of negative results• Reporting bias: emphasizing positive over negative resultsKey Points1 Cognitive bias is inescapable, and limits the ability of both individual practitioners and the surgical field in general, to advance and improve in a scientific fashion. Evidence Based Medicine is an attempt to codify the process of interpret-ing experience, assessing the literature and translating it into practice.2 Dealing with and interpreting the vast amount of surgical literature available on the Internet can be daunting, and this task can be aided by the application of identified formats for executing online search. The PICO (Patient/Population, Intervention, Comparison and Outcome) format is a com-monly used method for codifying online


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Surgery_Schwartz. aided by the application of identified formats for executing online search. The PICO (Patient/Population, Intervention, Comparison and Outcome) format is a com-monly used method for codifying online search.3 Not all literature or evidence is created equal. There exist various approaches, such as the Oxford Center for Evidence Based Medicine (CEBM) Levels of Evidence or the GRADE (Grading and Recommendations, Assessment, Development and Evaluation) system, that have been developed to provide guidance in assessing and reifying scientific literature.4 The conversion of evidence into clinical practice often mani-fests in the creation of clinical guidelines. As with all things related to evidence based medicine, not all guidelines are created equal, and therefore there are certain characteristics that can be used to evaluate the quality of a particular clini-cal guideline.5 There are specific challenges in the application of evidence based medicine to surgery, not least of which is the


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Surgery_Schwartz. that can be used to evaluate the quality of a particular clini-cal guideline.5 There are specific challenges in the application of evidence based medicine to surgery, not least of which is the difficulty in performing a truly randomized clinical trial. The CONSORT (Consolidated Standard of Reporting Clinical Trials) guidelines were developed to serve as minimal rec-ommendations for reporting randomized clinical trials.6 The well-known saying “There are lies, damn lies and then statistics” points to the recognition that statistical tools can be prone to misuse, and emphasizes the need to understand the appropriate application, limits of and interpretation of reported statistics.7 Evidence based medicine has not thus far been held to its own standards of evidence. Recognizing that available “evidence” is a constantly shifting landscape should warn one against the dangers of epistemic certainty, and further emphasizes the fact that surgical education is an ongoing and perpetual


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Surgery_Schwartz. available “evidence” is a constantly shifting landscape should warn one against the dangers of epistemic certainty, and further emphasizes the fact that surgical education is an ongoing and perpetual process.In the medical field, the transition from accumulated anec-dote to true statistical analysis can be seen in the emergence of clinical epidemiology as a field in 1938, which began to shift the focus from descriptions of individual patients to trends affect-ing entire populations. This shift, however, was accompanied by new challenges, as different means of turning anecdotal experience into statistics (e.g., case series, observational stud-ies, retrospective studies, prospective studies) meant that now practitioners needed to be able to compare these “scientific” presentations against each other in order to best establish their practices. The processes and methods of aggregating, compar-ing, and translating these different types of data from the medi-cal literature into clinical


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Surgery_Schwartz. each other in order to best establish their practices. The processes and methods of aggregating, compar-ing, and translating these different types of data from the medi-cal literature into clinical practice were explicitly established in the latter part of the 20th century, particularly arising from efforts at McMaster University, which eventually led to a fun-damental framework for literature-informed medical decision-making known as evidence-based medicine (EBM).EBM is defined as the “conscientious, explicit and judi-cious use of current best evidence in making decisions about treating individual patients.”2,3 This term was coined by Gordon Guyatt in 1991, focusing on assessing the credibility of the medical literature, understanding the presented results, and applying the information to individual practice. EBM is defined by three epistemological principles4:• Principle 1: Not all evidence is created equal, and the practice of medicine should be based on the best available


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Surgery_Schwartz. to individual practice. EBM is defined by three epistemological principles4:• Principle 1: Not all evidence is created equal, and the practice of medicine should be based on the best available evidence• Principle 2: The pursuit of truth is best accomplished by evaluation of the totality of the evidence, and not selecting evidence that favors a particular claim• Principle 3: Clinical decision-making requires consideration of patients’ values and preferenceThe adoption of EBM in the discipline of surgery has lagged compared to nonsurgical specialties. To a great extent, this is due to the challenges of achieving the highest level of evidence noted in principle 1: definitive conclusions from a randomized controlled trial (RCT). A literature analysis of MEDLINE from 1966 to 2000 demonstrated that only 15.1% of the 134,689 RCTs evaluated a surgical topic.5 In the early days of EBM during the 1990s, surgical RCTs accounted for only 7% of published articles in surgical journals; most of the


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Surgery_Schwartz. that only 15.1% of the 134,689 RCTs evaluated a surgical topic.5 In the early days of EBM during the 1990s, surgical RCTs accounted for only 7% of published articles in surgical journals; most of the articles were retrospective studies and case series,6 which are essentially aggregated anecdotes. Over the next decade, the rela-tive frequency of RCTs in surgery further decreased, account-ing for 3.4% of all publications in 2003.5 As a result, most of the available evidence to guide surgical practice today remains based on retrospective reviews, nonrandomized trials, and expert opinion. The barriers to performing prospective RCTs in surgery remain substantial: standardization of clinical pre-sentation and, of course, accounting for variations in operative technique and the ability to blind studies to reduce experimental bias. The relative paucity in RCTs in surgery make it even more 1Brunicardi_Ch51_p2137-p2152.indd 213828/02/19 4:19 PM 2139UNDERSTANDING, EVALUATING, AND USING


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Surgery_Schwartz. studies to reduce experimental bias. The relative paucity in RCTs in surgery make it even more 1Brunicardi_Ch51_p2137-p2152.indd 213828/02/19 4:19 PM 2139UNDERSTANDING, EVALUATING, AND USING EVIDENCE FOR SURGICAL PRACTICECHAPTER 51important that surgeons understand the best-practice methods to critically appraise available evidence, while recognizing the limitations and potential pitfalls of those methods, in order to optimize their practice and decision-making regarding patient care when high quality evidence may not be available. Herein we present the steps of such a workflow, starting with an initial search for information, identification of the classes of informa-tion that such a search can return, and then guidelines by which that information is evaluated, compared, and aggregated.Searching for Information: Patient/Population, Intervention, Comparison, and OutcomeTechnology has substantively changed how information can be sought and retrieved. Online search engines such as


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Surgery_Schwartz. for Information: Patient/Population, Intervention, Comparison, and OutcomeTechnology has substantively changed how information can be sought and retrieved. Online search engines such as MEDLINE via PubMed, which contains over 26 million citations, have dramatically enhanced the ability to access bio-medical literature.7 However, there is a very real potential for such access to become overwhelming. Effective and efficient use of search engines can be enhanced by framing the clinical question in a format designed to improve the relevancy of search results. PICO is one such format, where the acronym stands for Patient/Population, Intervention, Comparison, and Outcome.8• Patient or population is the specific group of individuals for which the questions is being asked.• Intervention is the treatment or technique of interest for the defined patient or population. Intervention might be a proce-dure, such as “laparoscopic appendectomy” or be defined as an exposure of interest, such as


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Surgery_Schwartz. the treatment or technique of interest for the defined patient or population. Intervention might be a proce-dure, such as “laparoscopic appendectomy” or be defined as an exposure of interest, such as “smoking.”• Comparison is the alternative treatment or technique to which you are comparing the intervention. Terms might include, for example, “open appendectomy” or “observation.”• Outcome of interest is the final step of the PICO format. Examples include “mortality,” “operative time,” and “wound infection.”As with all online search strategies, there is a trade-off between the specificity of the search and the breadth of the returned items. When using PICO to inform clinical decision-making, it is generally advantageous to be as precise and specific as possible when initiating a search: this increases the likelihood the search will return information most germane to the particular clinical scenario. This is accomplished by the use of “AND” in the framing of the search to encompass the


Surgery_Schwartz

Surgery_Schwartz. increases the likelihood the search will return information most germane to the particular clinical scenario. This is accomplished by the use of “AND” in the framing of the search to encompass the set of questions of interest. For example, one could construct a query consisting of a particular procedure, with a particular method, with a particular outcome metric, such as “(distal pancreatectomy) AND splenectomy AND (splenic preservation) AND morbidity” to frame a PICO question.Types of StudiesPrinciple 1 of EBM states that not all evidence is created equal; therefore, evaluating the evidentiary quality of the results of an online search requires classifying the returned search items by type of study. As noted earlier, acknowledging that the “gold standard” level of evidence, RCTs, are rare in the surgical literature, the application of EBM to surgery requires increased familiarity with the types of alternative studies available, with their relative strengths and weaknesses. These


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Surgery_Schwartz. rare in the surgical literature, the application of EBM to surgery requires increased familiarity with the types of alternative studies available, with their relative strengths and weaknesses. These types are listed below:• Meta-analysis: A meta-analysis is a technique to combine similarly published data in order to increase the overall 2statistical power compared to each study individually. The amount of interstudy heterogeneity (methods, study popula-tion, endpoints, etc.) should be limited to allow for the gen-eration of informative conclusions. The pooling of similar studies enables researchers to generate a new statistical con-clusion based on a substantially larger sample size. These approaches, though useful, have their limitations: the inclu-sion of inappropriate studies and the mislabeling of a meta-analysis leading to inaccurate conclusions. Attention should be directed toward this type of evidence when clinical guide-lines do not exist.• Systematic Review: Like


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Surgery_Schwartz. and the mislabeling of a meta-analysis leading to inaccurate conclusions. Attention should be directed toward this type of evidence when clinical guide-lines do not exist.• Systematic Review: Like meta-analyses, systematic reviews use standardized methods to search for and appraise studies in order to attempt to reduce bias. However, systematic reviews do not utilize quantitative methods to summarize the results. For this reason, systematic reviews are often not considered to provide the same strength of evidence as a meta-analysis.• Cross-Sectional Studies: In a cross-sectional study, expo-sures and outcomes are measured at a single point in time. The prevalence of the outcome is then compared in patients who did and did not have the exposure. Multiple exposures and outcomes can be measured at the same time, which is an advantage; however, there are important limitations. One significant limitation is that a temporal relationship cannot be determined between exposure and outcome


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Surgery_Schwartz. at the same time, which is an advantage; however, there are important limitations. One significant limitation is that a temporal relationship cannot be determined between exposure and outcome because they are measured simultaneously. These studies will often form the foundation for more definitive studies.• Case Control Study: In a case-control study, cohorts are determined by the presence or absence of a particular out-come of interest. This is in contrast to a cross-sectional study where samples are determined by the presence or absence of an exposure. Once the samples have been identi-fied based upon outcome, then possible prior exposures are identified, and the odds of those exposures are compared between cohorts.• Case Series: A Case Series involves a report of a small group of patients that share specified clinical features; this gener-ally does not include description of a control group. Case series are prevalent in the field of surgery, and some of the most famous eponymous


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Surgery_Schwartz. that share specified clinical features; this gener-ally does not include description of a control group. Case series are prevalent in the field of surgery, and some of the most famous eponymous procedures originated from case series, including the Whipple procedure9 and Nissen fundo-plication.10 This type of study provides weak evidence due to issues with patient selection, biases, and confounding factors. However, the findings from a case series can be used to gen-erate hypotheses for a randomized control trial.• Expert Opinion: Expert opinions represent the lowest level of evidence and is representative of a clinician’s individual experience and anecdotes. Prior to evidence-based medicine, expert opinion was the primary means of teaching medicine and shaping the field. However, the opinions of clinicians can vary substantially leading to a wide range of potential unproven treatments for a medical issue. Thus, expert opinion should only be solicited in the complete absence of


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Surgery_Schwartz. opinions of clinicians can vary substantially leading to a wide range of potential unproven treatments for a medical issue. Thus, expert opinion should only be solicited in the complete absence of evidence in the literature.It should also be noted that irrespective of the type of study or recommendation, there are additional factors that can contribute to bias in publication. To a great degree these are extrapolations of the sources of individual cognitive bias, but writ large across an entire community (see Box: The History and Sources of Bias in Biomedical Literature).Brunicardi_Ch51_p2137-p2152.indd 213928/02/19 4:19 PM 2140SPECIFIC CONSIDERATIONSPART IIHierarchies of EvidenceThe original architects of EBM codified the notion that certain types of evidence are superior to others based on charac-teristics of study design, depicting this concept as a “pyra-mid,” with expert opinion comprising the base of the pyramid and randomized controlled trials at the peak (Fig. 51-1).


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Surgery_Schwartz. based on charac-teristics of study design, depicting this concept as a “pyra-mid,” with expert opinion comprising the base of the pyramid and randomized controlled trials at the peak (Fig. 51-1). Although conceptually appealing, this initial attempt to “rank” the evidence was relatively simplistic and rested on unproven assumptions that RCT were inherently superior to observational studies. While RCTs theoretically provide higher quality evi-dence compared to observational studies, RCTs can also have significant limitations and biases (see later section, “The Chal-lenges of Applying EBM to Surgery”). Furthermore, translating the results from well-crafted RCTs can be challenging, where the specific restrictive criteria for executing a high-quality RCT can inherently limit its applicability to clinical scenarios not specifically noted or tested in the RCT. Therefore, one could find oneself in the situation of trying to compare an RCT on a related but clearly distinct use case with a


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Surgery_Schwartz. to clinical scenarios not specifically noted or tested in the RCT. Therefore, one could find oneself in the situation of trying to compare an RCT on a related but clearly distinct use case with a well performed obser-vational study that more closely approximated the clinical sce-nario in question. This led to the subsequent development of more refined frameworks to assess the quality of evidence in order to try and address these issues, although there is currently no consensus on a single framework. The current situation is that while many newer systems have devised ways in which studies can move up and down the pyramid, for well-designed studies, the pyramid largely remains intact.The initial hierarchies of evidence were limited because they entangled the method of evidence collection with underly-ing study design. They failed to recognize principle 2 of EBM: “the pursuit of truth is best accomplished by evaluation of the totality of evidence” and the principle that “health claims be


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Surgery_Schwartz. underly-ing study design. They failed to recognize principle 2 of EBM: “the pursuit of truth is best accomplished by evaluation of the totality of evidence” and the principle that “health claims be based upon systematic reviews which summarize the best avail-able evidence.”4 The earliest hierarchies positioned systematic reviews at the top of the pyramid followed by RCTs; how-ever, this classification failed to acknowledge that systematic reviews can summarize any type of evidence. Cohort studies, case-control studies, and even case reports can be the subject of systematic review. The importance of systematic review in EBM cannot be understated: systematic reviews are the most 3cited type of study, and these studies are essential for the devel-opment of clinical guidelines and influencing the direction of future studies.2,11 When applied in a timely manner, systematic reviews have resulted in major practice changes, for example, encouraging early postoperative enteral feeding compared


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Surgery_Schwartz. the direction of future studies.2,11 When applied in a timely manner, systematic reviews have resulted in major practice changes, for example, encouraging early postoperative enteral feeding compared to parenteral nutrition to prevent sepsis.12Tools to Evaluate a Body of EvidenceBy 2002, over 100 unique evidence rating systems existed,2 and the differences among them may be nontrivial. Depending upon the specific criteria used, the “strength” of evidence might dif-fer widely from system to system. For example, the American Association of Orthopedic Surgeons (AAOS) published guide-lines in 2009 for prevention of venous thromboembolism (VTE) in patients undergoing hip or knee surgery that conflicted with the widely used American College of Chest Physician (ACCP) guidelines, despite having access to the same data. While the ACCP considered VTE prophylaxis to be a grade 1 recommen-dation with level A evidence, the AAOS recommendation var-ied based upon risk of pulmonary embolism and


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Surgery_Schwartz. access to the same data. While the ACCP considered VTE prophylaxis to be a grade 1 recommen-dation with level A evidence, the AAOS recommendation var-ied based upon risk of pulmonary embolism and bleeding, with no recommendation being greater than B and all recommenda-tions being based upon level III evidence.13 In the following section we present a few of the most widely accepted tools for assessing the quality of evidence.CEBM Levels of Evidence. One of the most widely adopted systems for grading evidence is the Oxford Center for Evi-dence Based Medicine (CEBM) Levels of Evidence. The origi-nal CEBM system was released in 2000 and was subsequently updated in 2011. Earlier systems of evidence ranking were criti-cized because they categorically placed randomized trials above observational studies, although observational studies and even anecdotes can occasionally give the “best” evidence in certain clinical situations. CEBM was therefore developed to not only improve the ranking of


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Surgery_Schwartz. studies, although observational studies and even anecdotes can occasionally give the “best” evidence in certain clinical situations. CEBM was therefore developed to not only improve the ranking of evidence but also to aid clinicians in quickly searching for the best evidence available for a given clinical question (Table 51-1). It is designed as both a tool for traditional critical appraisal as well as a pragmatic system that clinicians can use to answer clinical questions in real time. It can be used as a heuristic that clinicians and patients can utilize to answer clinical questions quickly and without resorting to preap-praised sources.14 The CEBM Levels of Evidence system begins with choosing a clinical question from the first column of the table provided by the creators (see Table 51-1) (for example, “How common is the problem?”, “Does this intervention help?”, or “Is this test worthwhile?”). Therefore, each row of the CEBM Levels of Evidence represents a series of steps one


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Surgery_Schwartz. 51-1) (for example, “How common is the problem?”, “Does this intervention help?”, or “Is this test worthwhile?”). Therefore, each row of the CEBM Levels of Evidence represents a series of steps one should fol-low to find the best evidence for the question chosen. Strong evidence is likely to be found in columns to the left of the table, while weak evidence will be found in columns to the right. After completing a clinical query using the table, a final “level” of evidence is assigned on a scale from 1 to 5 based upon the types of studies found to answer the initial question (1 = highest rated evidence; 5 = lowest rated evidence). However, the levels are not intended to provide one with a definitive judgment regarding the quality of evidence. There may be cases where “lower level” evi-dence—for example, an observational study with a large treat-ment effect—provides stronger evidence than a “higher level” study, such as a systematic review with an inconclusive result.CEBM should be


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Surgery_Schwartz. example, an observational study with a large treat-ment effect—provides stronger evidence than a “higher level” study, such as a systematic review with an inconclusive result.CEBM should be thought of as a hierarchy of the likely best evidence. An advantage of CEBM is that it allows the potential of resorting to individual studies for the best evidence, while other systems generally assume that there is a systematic RCTCohort studyCase control studyCase seriesCase reportsAnimal researchIn-vitro researchExpert experience/opinionFigure 51-1. Evidence-based hierarchy.Brunicardi_Ch51_p2137-p2152.indd 214028/02/19 4:19 PM 2141UNDERSTANDING, EVALUATING, AND USING EVIDENCE FOR SURGICAL PRACTICECHAPTER 51Table 51-1Oxford center for evidence-based medicine 2011 levels of evidenceQUESTIONSTEP 1 (LEVEL 1*)STEP 2 (LEVEL 2*)STEP 3 (LEVEL 3*)STEP 4 (LEVEL 4*)STEP 5 (LEVEL 5)How common is the problem?Local and current random sample surveys (or censuses)Systematic review of surveys that allow


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Surgery_Schwartz. 1 (LEVEL 1*)STEP 2 (LEVEL 2*)STEP 3 (LEVEL 3*)STEP 4 (LEVEL 4*)STEP 5 (LEVEL 5)How common is the problem?Local and current random sample surveys (or censuses)Systematic review of surveys that allow matching to local circumstances**Local non-random sample**Case-series**n/aIs this diagnostic or monitoring test accurate? (Diagnosis)Systematic review of cross-sectional studies with consistently applied reference standard and blindingIndividual cross-sectional studies with consistently applied reference standard and blindingNon-consecutive studies, or studies without consistently applied reference standards**Case-control studies, or “poor or non-independent reference standard**Mechanism-based reasoningWhat will happen if we do not add a therapy? (Prognosis)Systematic review of inception cohort studiesInception cohort studiesCohort study or control arm of randomized trial*Case-series or case-control studies, or poor quality prognostic cohort study**n/aDoes this intervention help? (Treatment


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Surgery_Schwartz. studiesInception cohort studiesCohort study or control arm of randomized trial*Case-series or case-control studies, or poor quality prognostic cohort study**n/aDoes this intervention help? (Treatment Benefits)Systematic review of randomized trials or n-of-1 trialsRandomized trial or observational study with dramatic effectNon-randomized controlled cohort/follow-up study**Case-series, case-control studies, or historically controlled studies**Mechanism-based reasoningWhat are the COMMON harms? (Treatment Harms)Systematic review of randomized trials, systematic review of nested case-control studies n-of-1 trial with the patient you are raising the question about, or observational study with dramatic effectIndividual randomized trial or (exceptionally) observational study with dramatic effectNon-randomized controlled cohort/follow-up study (post-marketing surveillance) provided there are sufficient numbers to rule out a common harm. (For long-term harms the duration of follow-up must be


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Surgery_Schwartz. controlled cohort/follow-up study (post-marketing surveillance) provided there are sufficient numbers to rule out a common harm. (For long-term harms the duration of follow-up must be sufficient.)**Case-series, case-control, or historically controlled studies**Mechanism-based reasoningWhat are the RARE harms? (Treatment Harms)Systematic review of randomized trials or n-of-1 trialRandomized trial or (exceptionally) observational study with dramatic effect Is this (early detection) test worthwhile? (Screening)Systematic review of randomized trialsRandomized trialNon-randomized controlled cohort/follow-up study**Case-series, case-control, or historically controlled studies**Mechanism-based reasoning*Level may be graded down on the basis of study quality, Imprecision, Indirectness (study PICO does not match questions PICO), because of inconsistency between studies, or because the absolute effect size is very small; Level may be graded up if there is a large or very large effect


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Surgery_Schwartz. PICO does not match questions PICO), because of inconsistency between studies, or because the absolute effect size is very small; Level may be graded up if there is a large or very large effect size.**As always, a systematic review is generally better than an individual study.How to cite the Levels of Evidence TableOCEBM Levels of Evidence Working Group*. “The Oxford 2011 Levels of Evidence”.Oxford Centre for Evidence-Based Medicine. http://www.cebm.net/index.aspx?o=5653*OCEBM Table of Evidence Working Group = Jeremy Howick, Iain Chalmers (James Lind Library), Paul Glasziou, Trish Greenhaigh, Carl Heneghan, Alessandro Liberati, Ivan Moschetti, Bob Phillips, Hazel Thornton, Olive Goddard, and Mary HodgkinsanBrunicardi_Ch51_p2137-p2152.indd 214128/02/19 4:19 PM 2142SPECIFIC CONSIDERATIONSPART IIDefinitions of GRADE Evidence QualityHigh quality – Further research is very unlikely to change confidence in the estimate of effect.Moderate quality – Further research is likely to have an


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Surgery_Schwartz. of GRADE Evidence QualityHigh quality – Further research is very unlikely to change confidence in the estimate of effect.Moderate quality – Further research is likely to have an important impact confidence in the estimate of effect and may change the estimate.Low quality – Further research is very likely to have an important impact on confidence in the estimate of effect and is likely to change the estimate.Very low quality – Any estimate of effect is very uncertain.review available. Additionally, other systems are built around considering the strength of evidence for therapeutic effects and harms, while CEBM allows appraisal of evidence for prevalence of disease, accuracy of diagnostic tests, prognosis, therapeutic effects, rare harms, common harms, and usefulness of screening.Grading and Recommendations, Assessment, Development, and Evaluation. Alternatively, the Grading and Recommendations, Assessment, Development and Evaluation (GRADE) system classifies the quality of evidence


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Surgery_Schwartz. and Recommendations, Assessment, Development, and Evaluation. Alternatively, the Grading and Recommendations, Assessment, Development and Evaluation (GRADE) system classifies the quality of evidence into one of four levels: high, moderate, low, and very low15 (Box: Definitions of GRADE Evidence Quality). Evidence quality in the GRADE system is not assigned solely on study design. For example, a randomized controlled trial begins at “high quality,” but may be demoted due to one or more of the following: study limitations, inconsistent results, indirectness of evidence, imprecision, or reporting bias. Alternatively, observational studies (cohort or case-control studies) start as “low quality” but may be upgraded if there is a large magnitude of the treatment effect, evidence of a dose-response relationship, or if all plausible biases would decrease the magnitude of a treatment effect. Thus, the GRADE system of evaluating the quality of evidence provides more granularity than the


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Surgery_Schwartz. relationship, or if all plausible biases would decrease the magnitude of a treatment effect. Thus, the GRADE system of evaluating the quality of evidence provides more granularity than the traditional hierarchy system, which assigns quality based upon study design alone. Although the GRADE system has significant advantages, it is more complex and has a steeper learning curve than traditional systems. Finally, GRADE is intended for appraising a body of evidence, such as in a systematic review.In addition to providing a transparent approach to grading evidence quality, the GRADE system outlines an approach to the development and assignment of strength to clinical recommendations. GRADE’s sophisticated hierarchy of evidence allows the system to protect against both superficial assessment and unwarranted confidence in all classes of study design. Since its development, the increasing use of GRADE has resulted in higher quality and rigor of systematic reviews due to standards outlined by


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Surgery_Schwartz. unwarranted confidence in all classes of study design. Since its development, the increasing use of GRADE has resulted in higher quality and rigor of systematic reviews due to standards outlined by the system.15 In creating a recommendation regarding a body of evidence, GRADE allows experts to account for limitations in bodies of evidence comprising of RCTs, while also allowing for the rating of observational studies as high quality in cases where RCTs are not feasible (i.e., an RCT cannot ethically be performed). GRADE therefore potentially allows for observational studies to provide definitive evidence of causal association (e.g., alcohol causing cirrhosis or asbestos causing mesothelioma) where RCTs may not be ethical or necessary.One of the major advantages of GRADE is that it specifi-cally addresses the process of moving from evidence to recom-mendations. The process begins with the creation of a summary of findings table. A summary of findings table consists of a presentation


Surgery_Schwartz

Surgery_Schwartz. addresses the process of moving from evidence to recom-mendations. The process begins with the creation of a summary of findings table. A summary of findings table consists of a presentation not only of evidence quality but also estimates of the relative and absolute effects of patient-centered outcomes (Fig. 51-2). The summary of findings format was created to min-imize framing effects, where different raters may come to varied conclusions based upon identical information due to the infor-mation having a contrasting presentation in terms of gain versus loss.16 GRADE and similar EBM systems specifically takes into consideration judgement of risk versus benefit, resource use, feasibility, and equity to attempt to make decision-making as consistent as possible across a range of reviewers.2 Despite all of the aforementioned considerations when constructing a guide-line, it is important to realize that patient values or preferences may immediately invalidate any recommendation. Evidence


Surgery_Schwartz

Surgery_Schwartz. Despite all of the aforementioned considerations when constructing a guide-line, it is important to realize that patient values or preferences may immediately invalidate any recommendation. Evidence is often constructed based upon measurement of outcomes such as morbidity, mortality, or survival; however, patients may be more concerned with quality of life or avoiding invasive inter-ventions. GRADE attempts to acknowledges this intrinsic vari-ability within its system of grading.In terms of the overall strength of a recommendation that GRADE can assign, two grades are possible: “strong” and “weak.” A strong recommendation is one where positive effects of an intervention clearly outweigh the negative effects or vice versa. A weak recommendation is one where the asso-ciation is less clear, either because of low quality evidence or because the evidence clearly suggests that the positive and negative effects are similar. However, quality of evidence is not the only factor that affects the


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Surgery_Schwartz. because of low quality evidence or because the evidence clearly suggests that the positive and negative effects are similar. However, quality of evidence is not the only factor that affects the strength of a recommenda-tion (Table 51-2). Factors such as uncertainty of patient values or whether an intervention is an appropriate use of resources can play a role in the strength of a recommendation as well. Therefore, it is important to note that a “strong” or “weak” rec-ommendation may be given regardless of the classification of the evidence. For example, there is a strong recommendation that patients with Zollinger-Ellison syndrome be treated with PPI. This recommendation is made despite weak evidence to support this practice because the potential benefits far out-weigh the potential risks.17Although the systems for grading evidence are well devel-oped, it is important to remember that the studies used for evi-dence are judged based on their internal validity, or the extent to which a


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Surgery_Schwartz. the systems for grading evidence are well devel-oped, it is important to remember that the studies used for evi-dence are judged based on their internal validity, or the extent to which a causal conclusion is warranted based upon applica-tion of the results to the study population. This means that care must be exercised when applying a recommendation to a given patient, as the external validity of a recommendation, or gener-alizability of a causal conclusion to populations outside of the scope of the original studies, may not be appropriate. Therefore, all evidence must be applied within the context of the patient in front of you.Synthesis of Evidence—Clinical GuidelinesThe Institute of Medicine defines a clinical guideline as “state-ments that include recommendations, intended to optimize patient care, that are informed by a systematic review of evidence and an assessment of the benefits and harms of alterna-tive care options.”18 Clinical guidelines may reflect previous published


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Surgery_Schwartz. patient care, that are informed by a systematic review of evidence and an assessment of the benefits and harms of alterna-tive care options.”18 Clinical guidelines may reflect previous published studies of varying design and quality, as well as expert opinion, and often represent the highest level of applied clinical evidence. Numerous guidelines have been published; however, like individual studies, even guidelines can vary in quality. The highest quality and most clinically useful guide-lines tend to have the following qualities:4Brunicardi_Ch51_p2137-p2152.indd 214228/02/19 4:19 PM 2143UNDERSTANDING, EVALUATING, AND USING EVIDENCE FOR SURGICAL PRACTICECHAPTER 51Summary of findings:Compression stockings compared with no compression stockings for people taking long flightsPatients or population: Anyone taking a long flight (lasting more than 6 hours)Settings: International air travelIntervention: Compression stockings1Comparison: Without stockingsOutcomesIllustrative comparative


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Surgery_Schwartz. population: Anyone taking a long flight (lasting more than 6 hours)Settings: International air travelIntervention: Compression stockings1Comparison: Without stockingsOutcomesIllustrative comparative risks* (95% CI)Relativeeffect(95% CI)Number ofparticipants(studies)Qualityof theevidence(GRADE)Comments Assumed riskCorresponding riskWithout stockingsWith stockingsSymptomaticdeep vein thrombosis (DVT)See comment See comment Not estimable2821(9 studies)See comment0 participants developed symptomatic DVT in these studies.Symptom-lessdeep vein thrombosis Low risk population2RR 0.10(0.04 to 0.26) 2637(9 studies) ++++High10 per 10001 per 1000 (0 to 3)High risk population230 per 10003 per 1000(1 to 8)Superficial vein thrombosis13 per 10006 per 1000(2 to 15)RR 0.45(0.18 to 1.13)1804(8 studies)+++OModerate3 OedemaPost-flight values measured on a scale from 0, no oedema, to 10, maximum oedema.The mean oedema score ranged across control groups from6 to 9.The mean oedema score in the


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Surgery_Schwartz. studies)+++OModerate3 OedemaPost-flight values measured on a scale from 0, no oedema, to 10, maximum oedema.The mean oedema score ranged across control groups from6 to 9.The mean oedema score in the intervention groups was on average4.7 lower(95% CI –4.9 to –4.5). 1246(6 studies)++OOLow4 Pulmonary embolusSee commentSee commentNot estimable2821(9 studies)See comment0 participants developed pulmonary embolus in these studies.5DeathSee commentSee commentNot estimable2821(9 studies)See comment0 participants died in these studies.Adverse effectsSee commentSee commentNot estimable1182(4 studies)See commentThe tolerability of the stockings was described as very good with no complaints of side effects in 4 studies.6*The basis for the assumed risk is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the intervention group and the relative effect of the intervention (and its 95% CI).CI: Confidence interval; RR: Risk ratio GRADE:


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Surgery_Schwartz. (and its 95% confidence interval) is based on the assumed risk in the intervention group and the relative effect of the intervention (and its 95% CI).CI: Confidence interval; RR: Risk ratio GRADE: GRADE Working Group grades of evidence (see explanations)11 All the stockings in the 9 trials included in this review were below-knee compression stockings. In four trials the compression strength was 20–30 mmHg at the ankle. It was 10–20 mmHg in the other four trials. Stockings come in different sizes. If a stocking is too tight around the knee it can prevent essential venous return causing the blood to pool around the knee. Compression stockings should be fitted properly. A stocking that is too tight could cut into the skin on a long flight and potentially cause ulceration and increased risk of DVT. Some stockings can be slightly thicker than normal leg covering and can be potentially restrictive with tight foot wear. It is a good idea to wear stockings around the house prior to travel to


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Surgery_Schwartz. DVT. Some stockings can be slightly thicker than normal leg covering and can be potentially restrictive with tight foot wear. It is a good idea to wear stockings around the house prior to travel to ensure a good, comfortable fitting. Stockings were put on 2 to 3 hours before the flight in most of the trials. The availability and cost of stockings can vary.2Two trials recruited high risk participants defined as those with previous episodes of DVT, coagulation disorders, severe obesity, limited mobility due to bone or joint problems, neoplastic disease within the previous two years, large varicose veins or, in one of the studies, participants taller than 190 cm and heavier than 90 kg. The incidence for 7 trials that excluded high risk participants was 1.45% and the incidence for the 2 trials that recruited high-risk participants (with at least one risk factor) was 2.43%. We have rounded these off to 10 and 30 per 1000 respectively.3The confidence interval crosses no difference and does


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Surgery_Schwartz. that recruited high-risk participants (with at least one risk factor) was 2.43%. We have rounded these off to 10 and 30 per 1000 respectively.3The confidence interval crosses no difference and does not rule out a small increase.4The measurement of oedema was not validated or blinded to the intervention. All of these studies were conducted by the same investigators.5If there are very few or no events and the number of participants is large, judgement about the quality of evidence (particularly judgements about precision) may be based on the absolute effect. Here the quality rating may be considered “high” if the outcome was appropriately assessed and the event, in fact, did not occur in 2821 studied participants.6None of the other trials reported adverse effects, apart from 4 cases of superficial vein thrombosis in varicose veins in the knee region that were compressed by the upper edge of the stocking in one trial.Figure 51-2. Example of a “summary of findings”


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Surgery_Schwartz. from 4 cases of superficial vein thrombosis in varicose veins in the knee region that were compressed by the upper edge of the stocking in one trial.Figure 51-2. Example of a “summary of findings” table.Brunicardi_Ch51_p2137-p2152.indd 214328/02/19 4:19 PM 2144SPECIFIC CONSIDERATIONSPART IITable 51-2Factors that affect the strength of a recommendationFACTOREXAMPLES OF STRONG RECOMMENDATIONSEXAMPLES OF WEAK RECOMMENDATIONSQuality of evidenceMany high quality randomized trials have shown the benefit of inhaled steroids in asthmaOnly case series have examined the utility of pleurodesis in pneumothoraxUncertainty about the balance between desirable and undesirable effectsAspirin in myocardial infarction reduces mortality with minimal toxicity, inconvenience, and costWarfarin in low risk patients with atrial fibrillation results in small stroke reduction but increased bleeding risk and substantial inconvenienceUncertainty or variability in values and preferencesYoung patients with


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Surgery_Schwartz. patients with atrial fibrillation results in small stroke reduction but increased bleeding risk and substantial inconvenienceUncertainty or variability in values and preferencesYoung patients with lymphoma will invariably place a highervalue on the life prolonging effects of chemotherapy than on treatment toxicityOlder patients with lymphoma may not place a higher value on the life prolonging effects of chemotherapy than on treatment toxicityUncertainty about whether the intervention represents a wise use of resourcesThe low cost of aspirin as prophylaxis against stroke in patients with transient ischemic attacksThe high cost of clopidogrel and of combination dipyridamole and aspirin as prophylaxis against stroke in patients with transient ischaemic attacks1. An explicit description of development and funding pro-cesses that is publicly available.2. A transparent process that minimizes bias, distortion, and conflicts of interest.3. Developed by a multidisciplinary panel composed of:


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Surgery_Schwartz. and funding pro-cesses that is publicly available.2. A transparent process that minimizes bias, distortion, and conflicts of interest.3. Developed by a multidisciplinary panel composed of: clini-cians, methodological experts, and representatives, includ-ing a patient or consumer, of populations expected to be affected by the guideline.4. Utilizes rigorous systematic evidence review and considers quality, quantity, and consistency of the aggregate of avail-able evidence.5. Summarizes evidence about potential benefits and harms relevant to each recommendation.6. Explains the parts that values, opinion, theory, and clinical experience play in deriving recommendations.7. Provides a rating of the level of confidence in the evidence underpinning each recommendation and a rating of the strength of each recommendation.8. Undergoes extensive external review that includes an open period for public comment.9. Has a mechanism for revision when new evidence becomes available.Depending upon the


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Surgery_Schwartz. of each recommendation.8. Undergoes extensive external review that includes an open period for public comment.9. Has a mechanism for revision when new evidence becomes available.Depending upon the clinical question, such guidelines are often interpreted as the standard of care. However, multiple clinical guidelines may be applicable with respect to various aspects of a given clinical situation and must not be followed blindly without considering specific situational issues through the lens of an experienced clinician. Moreover, guidelines do not (and probably cannot) exist for all clinical situations. Clini-cians often must resort to other resources to enrich the context in which decisions are made, and, as with all evidence, care must be taken not to extrapolate the application of a clinical guideline beyond its specific conditions.THE CHALLENGES OF APPLYING EBM TO SURGERYAs noted earlier, the application of EBM to surgery has lagged behind other fields of medicine, and this has been


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Surgery_Schwartz. guideline beyond its specific conditions.THE CHALLENGES OF APPLYING EBM TO SURGERYAs noted earlier, the application of EBM to surgery has lagged behind other fields of medicine, and this has been attributed to the difficulty in establishing a sufficient mass of evidence with the “gold standard” RCT. Here we describe the process of evaluating the quality of a RCT and note the challenges related to the execution of a high-quality RCT in a surgical context.Analysis of a Surgical Randomized Control TrialSufficient knowledge of the trial’s methodological accuracy and results are essential for critical appraisal. However, less than half of journal articles adequately report the study design.19 This deficiency led to the development of the Consoli-dated Standards of Reporting Trials (CONSORT) guidelines in 1992, which was subsequently revised in 2010.20 These guide-lines are a minimal set of recommendations for reporting RCTs (blinding, randomization, etc) to facilitate critical appraisal.


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Surgery_Schwartz. in 1992, which was subsequently revised in 2010.20 These guide-lines are a minimal set of recommendations for reporting RCTs (blinding, randomization, etc) to facilitate critical appraisal. Many of the surgical journals now require completion of a CONSORT checklist prior to submission of the RCT manu-script (Fig. 51-3). Establishing this requirement has standard-ized the way articles are presented and analyzed. The two key aspects to focus on when assessing a RCT are internal and external validity.Internal ValidityDetermining the degree that the results of the RCT are accurate and consistent for the sample patients is called internal validity. Without internal validity, a study cannot be properly appraised, as the study was not constructed properly to answer the hypoth-esis without avoiding bias or confounding factors.21 The internal validity of a RCT requires the evaluation of several properties: randomization, blinding, equivalence among groups, complete-ness of follow-up, and


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Surgery_Schwartz. bias or confounding factors.21 The internal validity of a RCT requires the evaluation of several properties: randomization, blinding, equivalence among groups, complete-ness of follow-up, and accuracy of analysis. These properties are discussed in the following section.Randomization. Randomization is the creation of participant groups with similar known and unknown prognostic factors to achieve the goal of eliminating selection bias. For example, if the investigator can decide which treatment the patient receives, he or she may assign a participant to a study arm that is more favorable for that specific patient. On outcomes analysis, certain groups may have an overestimated treatment effect due to patient selec-tion and not necessarily the intervention itself. The methodology 5Brunicardi_Ch51_p2137-p2152.indd 214428/02/19 4:19 PM 2145UNDERSTANDING, EVALUATING, AND USING EVIDENCE FOR SURGICAL PRACTICECHAPTER 51SectionItem NoChecklist itemTitle and Abstract1aIdentification as a


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Surgery_Schwartz. 214428/02/19 4:19 PM 2145UNDERSTANDING, EVALUATING, AND USING EVIDENCE FOR SURGICAL PRACTICECHAPTER 51SectionItem NoChecklist itemTitle and Abstract1aIdentification as a randomized trial in the title1bStructured summary of trial design, methods, results, and conclusionsBackground and Objectives2aScientific background and explanation of rationale2bSpecific objectives or hypothesesTrial Design3aDescription of trial design (such as parallel, factorial) including allocation ratio3bImportant changes to methods after trial commencement with reasonsParticipants4aEligibility criteria for participants4bSettings and locations where the data were collectedInterventions5The interventions for each group with sufficient details to allow replication, including how and when they were administeredOutcomes6aCompletely defined pre-specified primary and secondary outcome measures, including how and when they were assessed6bAny changes to trial outcomes after the trial commenced, with reasonsSample


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Surgery_Schwartz. defined pre-specified primary and secondary outcome measures, including how and when they were assessed6bAny changes to trial outcomes after the trial commenced, with reasonsSample size7aHow sample size was determined7bWhen applicable, explanation of any interim analyses and stopping guidelinesRandomization: Sequence Generation8aMethod used to generate the random allocation sequence8bType of randomization; details of any restriction (such as blocking and block size)Allocation concealment mechanism9Mechanism used to implement the random allocation sequenceImplementation10Who generated the random allocation sequence, who enrolled participants, and who assigned interventionsBlinding11aIf done, who was blinded after assignment to interventions and how11bIf relevant, description of the similarity of interventionsResults Participant flow13aFor each group, the numbers of participants who were randomly assigned, received intended treatment, and were analyzed for the primary outcome13bFor each