1. Opioid-Induced Constipation Relief From Fixed-Ratio Combination Prolonged-Release Oxycodone/Naloxone Compared With Oxycodone and Morphine for Chronic Nonmalignant Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials 
Lang Huang, MD, Jian-Guo Zhou, MD, Yu Zhang, MM, Fei Wang, MM, Yi Wang, MM, Da-Hai Liu, MM, Xin-Juan Li, MM, Shui-Ping Lv, MM, Su-Han Jin, MM, Yu-Ju Bai, MD, Hu Ma, MD, PhD 
Journal of Pain and Symptom Management 
Volume 54, Issue 5, Pages e3 (November 2017)
DOI: /j.jpainsymman
Copyright © 2017 American Academy of Hospice and Palliative Medicine Terms and Conditions

2. Fig. 1 Flow chart of the systematic review process.
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3. Fig. 2
Appraisal of risk of bias of the included trials using the Cochrane risk-of-bias tool. Low risk = bias, if present, is unlikely to alter the results seriously, unclear risk = bias raises some doubt about the results, and high risk = bias may alter the results seriously.
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4. Fig. 3
Meta-analysis result of the RR of constipation at the end of double-blind trial phase. A lower incidence of constipation was found in the OXN PR treatment group compared with OXY PR or MOR PR. OXY = oxycodone; OXN = OXY:naloxone PR = 2:1; PR = prolonged release; RR = relative risk.
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5. Fig. 4
Meta-analysis result of the MD of BFI change from baseline to the end of double-blind trial. a) The BFI of included patients had lower BFI in baseline and at the end of the treatment (12 weeks) of the BFI became higher; b) The BFI of involved patients had higher BFI in baseline, and BFI was decreased after 12 weeks double-blind trial. The BFI change of (b) was significantly lower in treatment group, and clinical meaningful was found. A change in BFI score of ≥12 points is considered to be clinically meaningful difference. BFI = bowel function index; MD = mean difference.
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Copyright © 2017 American Academy of Hospice and Palliative Medicine Terms and Conditions

6. Fig. 5
The BFI of included studies at the end of double-blind trial phase. A lower BFI was found in treatment group. BFI score of 0–28.8 is the reference range for nonconstipated patients with chronic pain, and VAS from 0 = freedom from the symptom to 100 = maximum difficulty or most severe symptom. BFI = bowel function index; VAS = Visual Analog Scale.
Journal of Pain and Symptom Management  , e3DOI: ( /j.jpainsymman )
Copyright © 2017 American Academy of Hospice and Palliative Medicine Terms and Conditions

7. Fig. 6
Meta-analysis result of the MD of BFI at end of double-blind trial phase. The BFI of was significantly lower in treatment group, and clinically meaningful difference was found. A change in BFI score of ≥12 points is considered to be clinically meaningful. BFI = bowel function index; MD = mean difference.
Journal of Pain and Symptom Management  , e3DOI: ( /j.jpainsymman )
Copyright © 2017 American Academy of Hospice and Palliative Medicine Terms and Conditions

8. Fig. 7
Meta-analysis result of the MD of pain intensity at end of double-blind trial phase. The pain intensity was significant lower in treatment group, whereas the pain relief was not of clinically meaningful difference. We reported a 10-point difference on this 0- to 100-point scale as a “minimal” difference and a 20-point difference as a “clinically important” difference. MD = mean difference.
Journal of Pain and Symptom Management  , e3DOI: ( /j.jpainsymman )
Copyright © 2017 American Academy of Hospice and Palliative Medicine Terms and Conditions

9. Fig. 8
Percentage of trial participants receiving an opioid analgesic who left the trial and the percentage who completed the double-blind trial. Loss to follow-up includes patients withdrawn from trial owing to loss of follow-up, lack of efficacy, insufficient efficacy, and for other reasons. AE = adverse event; PR = prolonged release; OXY = oxycodone; OXN = OXY:naloxone PR = 2:1.
Journal of Pain and Symptom Management  , e3DOI: ( /j.jpainsymman )
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10. Fig. 9
Meta-analysis result of the RR of total AEs at end of double-blind trial phase. The incidence of adverse effects was lower in treatment group. AE = adverse effect; RR = relative risk.
Journal of Pain and Symptom Management  , e3DOI: ( /j.jpainsymman )
Copyright © 2017 American Academy of Hospice and Palliative Medicine Terms and Conditions

11. Supplementary Data 3
Meta-analysis result of the mean difference (MD) of pain intensity between OXY PR vs. MOR PR. RR = relative risk; PR = prolonged-release; OXY = oxycodone; OXN = OXY:naloxone; PR = 2:1.
Journal of Pain and Symptom Management  , e3DOI: ( /j.jpainsymman )
Copyright © 2017 American Academy of Hospice and Palliative Medicine Terms and Conditions