Evidence-based medicine

1. Evidence-based medicine 指導醫師 董淳武 醫師 98.11.26 R2王鼎堯

2. Situation • 60歲的陳媽媽在十年前因為糖尿病腎病變併發尿毒症開始接受長期血液透析治療。雙臂的人工廔管因為狹窄阻塞，已不能使用，所以在今年初接受了右側股動靜脈人工廔管手術。 • 但是在一個月前開始產生反覆發燒現象，經檢查發現原來是才剛做沒多久的股動靜脈人工廔管發生感染化膿的現象。在把人工廔管移除和2周的抗生素治療之後，現在發燒和感染的現象都已經緩解。由於其左下肢有嚴重的膕動脈粥狀動脈硬化現象併發壞疽，半年前已接受過膝下截肢手術，所以主治醫師與外科醫師討論後，為避免加重其末端缺血情形，並不建議在陳媽媽的左側股動靜脈做吻合或是置放人工廔管。 • 目前陳媽媽是經由右側內頸靜脈的「永久性」導管(permanent catheter) 做透析治療。其實陳媽媽的血糖控制情形還可以，飯前血糖約略在130～140 mg/dl，A1c:7.1%. 聽一起坐計程車來洗腎的王先生說，利用中心靜脈導管來透析更容易會有感染的問題，陳媽媽聽了更煩惱了，因為她很害怕再住院。她問查房的主治醫師它應該要如何去照顧她的中心靜脈導管，或是洗腎室有甚麼特殊的措施可以避免讓她的中心靜脈導管發生感染的問題？

3. Ask

4. Evidence-Based Practice Tools Summary Cochrane Library Cochrane Database of Systematic Reviews (Cochrane Reviews) Database of Abstracts of Reviews of Effects (Other Reviews - DARE)     PubMed MEDLINE - Systematic Reviews BMJ Clinical Evidence DynaMed USPSTF Guidelines |AHRQ Evidence Reports |FPIN Clinical Inquiries included in Journal of Family Practice and American Family Physician Indexed in PrimeAnswers      PubMed Clinical Queries Cochrane Library Cochrane Central Register of Controlled Trials (Clinical Trials)    ACP Journal Club POEMS (Patient Oriented Evidence that Matters) Bandolier | BestBETs   Natural Medicines Comprehensive Database   PubMed National Guideline Clearinghouse   PrimeAnswers | Care Provider Toolkit

5. Acquire • The Cochrane Library (www.thecochranelibrary.com) • Main search keywords: • H*emodialysis • Catheter* • Infection* • Advanced Search: (Cochrane or meta-analysis or Systematic review)

6. Acquire Cochrane Database of Systematic Reviews (Cochrane Reviews) No related topics was found !

7. Acquire Database of Abstracts of Reviews of Effects (Other Reviews - DARE) 3 related topics was found !

8. Acquired Journal (1) • Meta-analysis: Antibiotics for Prophylaxis against Hemodialysis Catheter–Related Infections • Ann Intern Med. 2008;148:596-605.

9. Appraisal 選擇的文獻是否適當 選擇的文獻能有效回答問題 各研究的結果是否相似

11. Appraisal Check List • 1. PICO • P: Adults receiving long-term hemodialysis using a central venous catheter • I: Use of an antibiotic applied topically to the catheter exit site or instilled intraluminally into the catheter • C: With another or no antimicrobial agent • O: Catheter-related bloodstream infection rate or secondary outcomes of interest

12. 2．Is any study missed？ • ①Database？　 • MEDLINE (1966 through October 2007) • EMBASE (1980 through October 2007) • Cochrane Central Register of Controlled Trials (1996 through October 2007) • ②Keywords? • Catheter-related bloodstream infection (searching for catheter-related bloodstream infection, bacteremia, or septicemia) • Dialysis (searching for renal dialysis) • Catheter (searching for indwelling catheter, catheterization, central venous catheter, or hemodialysis catheter)

13. Appraisal Check List • ③Reference list review: YES • ④Contact to Authors: YES • ⑤Unpublished studies: Eligible • ⑥Duplicate publications: Excluded • ⑦Language: regardless

14. Appraisal Check List • 3.Publication Bias: • Using funnel plots, the Begg test(P=0.001) for asymmetry, and an Egger test (P=0.085) for trials of intraluminal antibiotics • No test for trials of topical antimicrobial agents (∵ small number of these studies) • Funnel plot suggested an absence of publication of small studies that showed lesser benefits for intraluminal antibiotics than seen in the identified trials.

15. 4. Reviewer numbers: • 2 reviewers independently evaluated articles for eligibility in a 2-stage procedure.

16. 5. Quality Assesssment of Included Trials

21. 無異質性 無異質性 減少78%的感染率 減少68%的感染率

22. 無異質性

25. Apply • Both topical and intraluminal antibiotics reducedthe rate of bacteremia as well as the need for catheter removal secondary to complications. • Whether these strategies will lead to anti-microbial resistance and loss of efficacy over longer periods remains unclear.

26. Limitation • The evidence base included only 16 trials • Most had less than 6 months of follow-up • Only one third of studies were blinded. • Publication bias was evident.

28. Acquire (2) • A meta-analysis of hemodialysis catheter locking solutions in the prevention of catheter-related infection • American Journal of Kidney Diseases, Vol 51, No 2 (February), 2008: pp 233-241

29. Appraisal Check List • 1. PICO • P: Adults receiving long-term hemodialysis using a central venous catheter • I: Useantimicrobial lock solutions (ALSs) • C: Heparin only • O: CRI per 1,000 catheter-days

30. 2．Is any study missed？ • ①Database？　 • Cochrane Central Register of Controlled Trials • MEDLINE 1966 to 2005, • EMBASE (up to 2005 • CINAHL • ②Keywords? • end stage renal disease • h(a)emodialysis, • catheter related bacter(a)emia • antibiotic lock(ing) solution

31. Appraisal Check List • ③Reference list review: YES • ④Contact to Authors: not mention • ⑤Unpublished studies: Eligible • ⑥Duplicate publications: Nil • ⑦Language: English only

32. Appraisal Check List • 3.Publication Bias: Not mentioned • 4. Reviewer numbers: • 2 reviewers independently evaluated articles for eligibility in a 2-stage procedure. Differences were resolved by discussion

33. 所收錄文章其中六篇被收錄於第一篇Systematic review

34. 星星數代表Jadad Score

35. 並非使用抗生素

36. Using absolute risk reduction for each study, this translates to a number needed to treat (NNT) of 3 to prevent 1 CRI/100 catheter-days

37. 高異質性

38. Apply • This meta-analysis of randomized controlled trials supports the effectiveness of ALSs as a successful strategy to decrease the incidence of CRI in HD patients. All ALSs studied were effective in this way, and the overall number needed to treat to prevent 1 CRI was small.

40. Acquire (3) • Preventing haemodialysis catheter-related bacteraemia with an antimicrobial lock solution: a meta-analysis of prospective randomized trials • Nephrol Dial Transplant (2008) 23: 1666–1672

41. Appraisal Check List • 1. PICO • P: Adults receiving long-term hemodialysis using a central venous catheter • I: Useantimicrobial lock solutions (ALSs) • C: Heparin only • O: CRI per 1,000 catheter-days

42. 2．Is any study missed？ • ①Database？　 • Pubmed, from 1990 until March 2007. (same in below) • Medline • Web of Science • The Cochrane Library database • Major nephrology journals • ②Keywords? • Dialysis, Catheter lock, Bacteraemia, Sepsis, Septicaemia, Infection and prophylaxis

43. Appraisal Check List • ③Reference list review: YES • ④Contact to Authors: YES • ⑤Unpublished studies: Exclude • ⑥Duplicate publications: Exclude • ⑦Language: Regardless

44. Appraisal Check List • 3.Publication Bias: Funnel plot showed under-representation of small studies with a low or no effect. • 4. Reviewer numbers: • Not mentioned, perhaps only one (group of) reviewer

45. Bleyer Saxena

47. 除了Bleyer et al.的study外其餘都與第二篇的搜尋結果相同

48. 無顯著差異

50. Apply • Catheter interdialytic locking with an ALS reduces the incidence of CRB. • Achieved incidence of CRB in the ALS groups is similar to published reports from units with low CRB incidence • Limit: follow-up of studies included in this meta-analysis does not exclude the onset of adverse events or bacterial resistance with longer use of ALS.