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PRISMA 2009 Flow Diagram BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ Open Gastro Appendix Table 1. Electronic Database Searching Strategy........................................ 4 Table 2. Pooled Prevalence of Antibiotic Resistance Rates of H. pylori by Country ........................................................................................................ 5 Table 3. Narration of Enrolled Trials ............................................................ 6-9 Table 4A, 4B Characteristics of Enrolled Trials ............................................ 10-14 Table 5. Risk of Bias for Randomised Trials of Second-line H. pylori Eradication Therapies .................................................................................................... 15 Table 6. Design Inconsistency of Second-line H. pylori Eradication Therapies ..................................................................................................................... 16 Table 7. Loop Inconsistency of Second-line H. pylori Eradication Therapies ..................................................................................................................... 17 Table 8. Side-splitting Inconsistency of Second-line H. pylori Eradication Therapies ..................................................................................................... 18-20 Figure 1A. Network Comparisons Geometry of Second-line H. pylori Eradication Therapies (Clarithromycin Resistance ≥ 15%) ............................................. 21 Figure 1B. Network Comparisons Geometry of Second-line H. pylori Eradication Therapies (Levofloxacin Resistance ≥ 15%) ................................................ 22 Figure 1C. Network Comparisons Geometry of Second-line H. pylori Eradication Therapies (Failure of First-line Triple Therapy) ........................................... 23 Figure 1D. Network Comparisons Geometry of Second-line H. pylori Eradication Therapies (Dropout Rate) ........................................................................... 24 Figure 2A. Forest Plot of Direct Comparisons (ORs) of Second-line H. pylori Eradication Therapies (Overall) .................................................................. 25 Figure 2B. Forest Plot of Direct Comparisons (ORs) of Second-line H. pylori Eradication Therapies (Clarithromycin Resistance ≥ 15%) .......................... 26 Figure 2C. Forest Plot of Direct Comparisons (ORs) of Second-line H. pylori Eradication Therapies (Levofloxacin Resistance ≥ 15%) ............................. 27 Figure 2D. Forest Plot of Direct Comparisons (ORs) of Second-line H. pylori Eradication Therapies (Failure of First-line Triple Therapy) ........................ 28 1 Chang Y-L, et al. BMJ Open Gastro 2020; 7:e000472. doi: 10.1136/bmjgast-2020-000472 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ Open Gastro Figure 2E. Forest Plot of Direct Comparisons (ORs) of Second-line H. pylori Eradication Therapies (Dropout Rate) ........................................................ 29 Figure 3A. Cumulative SUCRA Ranking Curves for Overall Efficacy of Second- line H. pylori Eradication Therapies (Overall) .............................................. 30 Figure 3B. Cumulative SUCRA Ranking Curves for Overall Efficacy of Second- line H. pylori Eradication Therapies (Clarithromycin Resistance ≥ 15%) .... 31 Figure 3C. Cumulative SUCRA Ranking Curves for Overall Efficacy of Second- line H. pylori Eradication Therapies (Levofloxacin Resistance ≥ 15%) ....... 32 Figure 3D. Cumulative SUCRA Ranking Curves for Overall Efficacy of Second- line H. pylori Eradication Therapies (Failure of First-line Triple Therapy) ... 33 Figure 3E. Cumulative SUCRA Ranking Curves for Overall Efficacy of Second- line H. pylori Eradication Therapies (Dropout Rate) .................................... 34 Figure 4A. Comparison-adjusted Network Funnel Plot of Second-line H. pylori Eradication Therapies (Overall) .................................................................. 35 Figure 4B. Comparison-adjusted Network Funnel Plot of Second-line H. pylori Eradication Therapies (Clarithromycin Resistance ≥ 15%) ......................... 36 Figure 4C. Comparison-adjusted Network Funnel Plot of Second-line H. pylori Eradication Therapies (Levofloxacin Resistance ≥ 15%) ............................ 38 Figure 4D. Comparison-adjusted Network Funnel Plot of Second-line H. pylori Eradication Therapies (Failure of First-line Triple Therapy) ........................ 38 Figure 4E. Comparison-adjusted Network Funnel Plot of Second-line H. pylori Eradication Therapies (Dropout Rate) ........................................................ 39 Figure 5A. Egger's Test for Publication Bias of Second-line H. pylori Eradication Therapies (Overall) ..................................................................................... 40 Figure 5B. Egger's Test for Publication Bias of Second-line H. pylori Eradication Therapies (Clarithromycin Resistance ≥ 15%) ............................................ 41 Figure 5C. Egger's Test for Publication Bias of Second-line H. pylori Eradication Therapies (Levofloxacin Resistance ≥ 15%) ............................................... 42 Figure 5D. Egger's Test for Publication Bias of Second-line H. pylori Eradication Therapies (Failure of First-line Triple Therapy) ........................................... 43 2 Chang Y-L, et al. BMJ Open Gastro 2020; 7:e000472. doi: 10.1136/bmjgast-2020-000472 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ Open Gastro Figure 5E. Egger's Test for Publication Bias of Second-line H. pylori Eradication Therapies (Dropout Rate) ........................................................................... 44 Figure 6A. Network Forest Plot of Indirect Comparisons (ORs) of Second-line H. pylori Eradication Therapies (Clarithromycin Resistance ≥ 15%)................. 45 Figure 6B. Network Forest Plot of Indirect Comparisons (ORs) of Second-line H. pylori Eradication Therapies (Levofloxacin Resistance ≥ 15%).................... 46 Figure 6C. Network Forest Plot of Indirect Comparisons (ORs) of Second-line H. pylori Eradication Therapies (Failure of First-line Triple Therapy) ............... 47 Figure 6D. Network Forest Plot of Indirect Comparisons (ORs) of Second-line H. pylori Eradication Therapies (Dropout Rate) ............................................... 48 Reference ................................................................................................... 49-53 3 Chang Y-L, et al. BMJ Open Gastro 2020; 7:e000472. doi: 10.1136/bmjgast-2020-000472 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ Open Gastro Supplementary Table 1. Electronic Database Searching Strategy Electronic search strategy PubMed search Population / #1 ("Helicobacter"[Mesh] OR Helicobacter) Helicobacter infection Intervention/ #2 (Retreatment [Mesh] OR "Salvage Therapy"[Mesh] Second-line OR "second line" OR "second-line" OR rescue OR therapy salvage OR retreat* OR re-treat* OR fail*) Filters #3 Publication date from 2000/01/01 to 2018/12/31 Search algorithm #4 #1 AND #2 AND #3 Embase search Population / #1 ('helicobacter pylori'/exp OR 'campylobacter pylori' Helicobacter OR 'campylobacter pyloridis' OR 'campylobacter infection pyloris' OR 'helicobacter nemestrinae' OR 'helicobacter pylori') OR ('helicobacter'/exp OR helicobacter OR 'gastrospirillum' OR 'helicobacter') OR ('helicobacter infection'/exp OR 'helicobacter gastritis' OR 'helicobacter infection' OR 'helicobacter infections' OR 'helicobacter pylori gastritis' OR 'helicobacter pylori infection') Intervention/ #2 ('salvage therapy'/exp OR 'salvage procedure' OR Second-line 'salvage therapy') OR ('retreatment'/exp OR therapy retreatment OR 'retreatment') OR ('second line therapy'/exp OR 'second line therapy') OR ('second line':ti,ab,kw) OR (rescue:ti,ab,kw) OR (failure:ti,ab,kw) OR (failed:ti,ab,kw) OR (failing:ti,ab,kw) OR (retreated:ti,ab,kw OR 're treated':ti,ab,kw OR retreating:ti,ab,kw OR 're treating':ti,ab,kw OR retreatments:ti,ab,kw OR 're treatments':ti,ab,kw)) Filters #3 [2000-2018]/py Search algorithm #4 #1 AND #2 AND #3 Cochrane clinical trial search Population/ #1 MeSH descriptor Helicobacter explode all trees OR Helicobacter Helicobacter infection Intervention/ #2 MeSH descriptor Retreatment explode all trees OR Second-line MeSH descriptor Salvage Therapy explode all trees therapy OR "second line" OR "second-line" OR rescue OR salvage OR retreat* OR re-treat* OR fail* Search algorithm #3 #1 AND #2 4 Chang Y-L, et al. BMJ Open Gastro 2020; 7:e000472. doi: 10.1136/bmjgast-2020-000472 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ Open Gastro Supplementary Table 2. Pooled Prevalence of Antibiotic Resistance Rates of H. pylori by Country a Clarithromycin Levofloxacin Country Resistance rate
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