- Email: [email protected]
Medical synopsis: Can acupuncture be an alternative treatment option for patients with refractory functional dyspepsia?
Accepted Manuscript Title: Medical synopsis: Can acupuncture be an alternative treatment option for patients with refractory functional dyspepsia? Author: Robin S.T. Ho Charlene H.L. Wong Vincent C.H. Chung PII: DOI: Reference:
S2212-9588(16)30005-2 http://dx.doi.org/doi:10.1016/j.aimed.2016.02.004 AIMED 78
To appear in: Received date: Accepted date:
5-2-2016 5-2-2016
Please cite this article as: Ho RST, Wong CHL, Chung VCH, Medical synopsis: Can acupuncture be an alternative treatment option for patients with refractory functional dyspepsia?, Adv. Integr. Med. (2016), http://dx.doi.org/10.1016/j.aimed.2016.02.004 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Medical synopsis: Can acupuncture be an alternative treatment option for patients with refractory functional dyspepsia? Robin ST Ho a, Charlene HL Wonga, Vincent CH Chung a,b.c *
a. Jockey Club School of Public Health and Primary Care, The Chinese University of Hong
ip t
Kong, Hong Kong b. Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, Hong
cr
Kong
c. Australian Research Centre in Complementary and Integrative Medicine, University of
us
Technology Sydney
an
*Corresponding author
Tel.: +852 2252 8453; Fax: +852 2606 3500.
M
Dr. Vincent CH Chung, 4/F, School of Public Health Building, Prince of Wales Hospital, Shatin, New Territories, Hong Kong
Ac ce pt e
d
E-mail address: [email protected] (Vincent CH Chung)
Medical synopsis: Can acupuncture be an alternative treatment option for patients with refractory functional dyspepsia?
The synopsis is based on the following article: Lan L, Zeng F, Liu GJ, Ying L, Wu X, Liu M, Liang FR. Acupuncture for functional dyspepsia. Cochrane Database of Systematic Reviews 2014, Issue 10. Art. No.: CD008487. DOI: 10.1002/14651858.CD008487.pub2.
Keywords: acupuncture; functional dyspepsia; meta-analysis; systematic review.
1 Page 1 of 6
Design
ip t
Systematic review of seven randomized control trials (RCTs).
Participants
us
cr
542 patients (mean age range: 18-70 years, male % range: 21-49%) satisfying Rome II or III diagnostic criteria for functional dyspepsia (FD).
Intervention
Comparator
M
an
Among included RCTs, patients received acupuncture at a frequency of 3-7 sessions per week for 3-4 weeks. Total number of acupuncture sessions varied from 6 to 28 sessions.
d
Comparison 1: Acupuncture versus sham acupuncture.
Ac ce pt e
Comparison 2: Acupuncture versus prokinetic drugs.
Major outcomes
Outcome 1: Generic patient reported quality of life measured by the Short Form 36 Health Survey (SF-36). Outcome 2: Disease specific patient reported quality of life measured by the Nepean Dyspepsia Life Quality Index (NDLQI). Outcome 3: Patient reported global FD symptom change rated on a continuous scale. Outcome 4: Patient reported global FD symptom change rated on a 4 point Likert scale (“cure”, “clear improvement”, “slight improvement”, and “no improvement”). Outcome data was then transformed to a dichotomous format, with “cure”, “clear improvement”, and “slight improvement” being categorized as “favourable” effect from treatment, while “no improvement” was categorized as “unfavorable” effect from treatment.
Settings Included studies were conducted in outpatient settings. 2 Page 2 of 6
Comparison 1: Acupuncture versus sham acupuncture Main results
ip t
Compared to sham acupuncture, patients in manual acupuncture group experienced significant improvement in quality of life measured by SF-36 (pooled mean difference (MD): 12.18, 95% confidence interval (CI): 8.45, 15.91), with low heterogeneity (I2 = 1%) among included trials (Table 1).
cr
Significant improvement in disease specific quality of life measured by NDLQI (pooled MD: 9.23, 95%CI: 4.85, 13.61) were also observed among patients in the manual acupuncture group, but there were moderate heterogeneity (I2 = 49%) among included trials (Table 1).
an
us
It was also observed that acupuncture also decrease patient rated global FD symptom severity in two included trials (MD: -2.24, 95%CI: -2.94, -1.54 and MD: -16.43, 95%CI: -20.39, -12.47) [1,2]. However, due to substantial heterogeneity (I2 = 98%), pooling of these trials was considered inappropriate (Table 1).
Main results
M
Comparison 2: Acupuncture versus prokinetic drugs
Ac ce pt e
d
Due to heterogeneous interventions and controls among included trials, pooling was not performed by the systematic review authors. Descriptive analyses of trials results on lowering global FD symptom severity were reported. In one trial, no significant difference between manual acupuncture and domperidone was observed (Risk Ratio (RR): 1.24, 95% CI: 0.97, 1.58) [3]. Similar results were observed in other trials comparing electroacupuncture with domperidone (Risk Ratio (RR): 1.14, 95% CI: 1.00, 1.30) [4], and in comparison between electroacupuncture and itopride (Risk Ratio (RR): 1.11, 95% CI: 0.98, 1.27) [5] (Table 2).
Conclusion Benefits
Compared to sham acupuncture, acupuncture provided stronger effect on improving quality of life among FD patients. The effectiveness of acupuncture in reducing patient reported symptom severity is also on par with commonly used prokinetics including domperidone and itopride. Harms No serious adverse events were reported among included trials.
Commentary
3 Page 3 of 6
FD is one of the most common types of functional gastrointestinal disorder. A range of symptoms originating in upper gastrointestinal tract may include postprandial fullness, early satiation, epigastric pain or burning, with unidentified causes [6]. Although current clinical guideline [7] recommends the use of pharmacological treatments, including proton pump inhibitors (PPI) and prokinetic drugs as first line treatment, effectiveness of proton pump inhibitors and prokinetic drugs is limited; with their number needed to treat (NNT) being 14.6 and 16
ip t
respectively [8,9]. Those who do not respond to these drugs are considered to suffer from refractory FD. As the NNT of both drugs are high, incidence of refractory FD is very common. Potential side
cr
effects of proton pump inhibitors and prokinetic drugs have also raised concern on their longer term use. For instance, in recently published 14-year population-based cohort study has shown the
us
association between proton pump inhibitors use and increased risk of chronic kidney disease [10]. Another meta-analysis has also demonstrated the association between domperidone use and cardiac arrhythmia and sudden cardiac death [11]. There is a need for addressing health needs of those who
an
are experiencing refractory FD, or those who are contraindicated with proton pump inhibitors or prokinetics. Favorable results from the current systematic review indicate that acupuncture can be
M
considered as an alternative to pharmacological treatment among these patients. Appropriate choice of outcome measure is the key for improving quality for future trials. Current consensus recommends the following outcomes should be used in future trials [12]. For primary
d
endpoint, weekly binary assessment of adequate relief of FD symptoms over time should be used, and
Ac ce pt e
achievement of adequate relief for a substantial proportion of time can be regarded as treatment success. For secondary endpoints, assessment of individual symptoms, including changes in postprandial fullness, early satiety, epigastric pain, epigastric burning and postprandial nausea should be performed. The comprehensive use of Nepean Dyspepsia Index and objective nutrient drink test can also be used to evaluate treatment impact [13].
Table 1
Acupuncture versus sham acupuncture among patients with functional dyspepsia. Outcome
No. of studies (total number of participants)
Heterogeneity (I2 value)
1
2 (116)
1%
Outcome
No. of studies (total number of participants)
Heterogeneity (I2 value)
2
2 (128)
49%
Outcome
No. of studies (total number of participants)
Heterogeneity (I2 value)
pooled MD (95%CI) 12.18 (8.45 to 15.91) pooled MD (95%CI) 9.23 (4.85 to 13.61) MD (95%CI)
4 Page 4 of 6
3
1 (60)
NA
-2.24 (-2.94 to -1.54)
Outcome
No. of studies (total number of participants)
Heterogeneity (I2 value)
3
1 (56)
NA
MD (95%CI) -16.43 (-20.39 to -12.47)
ip t
Keys: MD: mean difference; CI = confidence interval
Acupuncture versus prokinetic drugs among patients with functional dyspepsia. No. of studies (total number of participants)
4
1 (62)
Outcomes
No. of studies (total number of participants)
4
1 (126)
Outcomes
No. of studies (total number of participants)
4
1 (80)
Heterogeneity (I2 value) NA
us
Outcomes
cr
Table 2
an
Heterogeneity (I2 value) NA
M
Heterogeneity (I2 value)
1.24 (0.97 to 1.58) RR (95%CI) 1.14 (1.00 to 1.30) RR (95%CI) 1.11 (0.98 to 1.27)
d
NA
RR (95%CI)
Ac ce pt e
Keys: RR = risk ratio; CI = confidence interval
Acknowledgements
This synopsis is not funded by any parties.
References [1]
[2] [3]
X.R. Chang, L. Lan, J. Yan, X.J. Wang, H.M. Chen. Efficacy of acupuncture at FootYangming Meridian in the treatment of patients with functional dyspepsia: an analysis of 30 cases. World Chinese Journal of Digestology 2010;18(8):839-44. Y. Jin. Efficacy of acupuncture in the treatment of patients with functional dyspepsia. Unpublished medicine master dissertation. Beijing University of Chinese Medicine. 2011. S. Tang, Z. Xu, P. Tang, L. Liang. Acupuncture for functional dyspepsia: a randomised controlled trial. Journal of Sichuan Traditional Chinese Medicine 2006;24(4):101-2. 5 Page 5 of 6
[10] [11]
[12]
[13]
ip t
cr
[9]
us
[8]
an
[7]
M
[6]
d
[5]
Y. Zhou, J.G. Zheng. Clinical observation on acupuncture treatment of functional dyspepsia. Journal of Acupuncture and Tuina Science. 2005;3(2):20-2. M. Yang. EIectroacupuncture treatment of functionaI dyspepsia from a cIinical research. Unpublished medicine master dissertation. Hubei University of TCM. 2009. J. Tack, N.J. Talley. Functional dyspepsia—symptoms, definitions and validity of the Rome III criteria. Nature Reviews Gastroenterology and Hepatology. 2013;10(3):134-41. N.J. Talley, N. Vakil. Guidelines for the management of dyspepsia. The American journal of gastroenterology. 2005;100(10):2324-37. W.H. Wang, J.Q. Huang, G.F. Zheng, H.H. Xia, W.M. Wong, X.G. Liu, J. Karlberg, B.C. Wong. Effects of proton-pump inhibitors on functional dyspepsia: a meta-analysis of randomized placebo-controlled trials. Clinical Gastroenterology and Hepatology. 2007;5(2):178-85. M. Hojo, A. Nagahara, D. Asaoka, S. Watanabe. Emerging pharmacological therapy for functional dyspepsia. Clinical journal of gastroenterology. 2013;6(5):352-6. B. Lazarus, Y. Chen, F. Wilson, Y. Sang, A. Chang, J. Coresh, M.E. Grams. Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease. JAMA internal medicine. 2016:238-46. N. Leelakanok, A. Holcombe, M.L. Schweizer. Domperidone and Risk of Ventricular Arrhythmia and Cardiac Death: A Systematic Review and Meta-analysis. Clinical drug investigation. 2015:1-11. D. Ang, N.J. Talley, M. Simrén, P. Janssen, G. Boeckxstaens, J. Tack. Review article: endpoints used in functional dyspepsia drug therapy trials. Alimentary pharmacology & therapeutics. 2011;33(6):634-49. B.E. Lacy, N.J. Talley, M. Camilleri. Functional Dyspepsia: Time to Change Clinical Trial Design&quest. The American journal of gastroenterology. 2010;105(12):2525-9.
Ac ce pt e
[4]
6 Page 6 of 6
S2212-9588(16)30005-2 http://dx.doi.org/doi:10.1016/j.aimed.2016.02.004 AIMED 78
To appear in: Received date: Accepted date:
5-2-2016 5-2-2016
Please cite this article as: Ho RST, Wong CHL, Chung VCH, Medical synopsis: Can acupuncture be an alternative treatment option for patients with refractory functional dyspepsia?, Adv. Integr. Med. (2016), http://dx.doi.org/10.1016/j.aimed.2016.02.004 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Medical synopsis: Can acupuncture be an alternative treatment option for patients with refractory functional dyspepsia? Robin ST Ho a, Charlene HL Wonga, Vincent CH Chung a,b.c *
a. Jockey Club School of Public Health and Primary Care, The Chinese University of Hong
ip t
Kong, Hong Kong b. Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, Hong
cr
Kong
c. Australian Research Centre in Complementary and Integrative Medicine, University of
us
Technology Sydney
an
*Corresponding author
Tel.: +852 2252 8453; Fax: +852 2606 3500.
M
Dr. Vincent CH Chung, 4/F, School of Public Health Building, Prince of Wales Hospital, Shatin, New Territories, Hong Kong
Ac ce pt e
d
E-mail address: [email protected] (Vincent CH Chung)
Medical synopsis: Can acupuncture be an alternative treatment option for patients with refractory functional dyspepsia?
The synopsis is based on the following article: Lan L, Zeng F, Liu GJ, Ying L, Wu X, Liu M, Liang FR. Acupuncture for functional dyspepsia. Cochrane Database of Systematic Reviews 2014, Issue 10. Art. No.: CD008487. DOI: 10.1002/14651858.CD008487.pub2.
Keywords: acupuncture; functional dyspepsia; meta-analysis; systematic review.
1 Page 1 of 6
Design
ip t
Systematic review of seven randomized control trials (RCTs).
Participants
us
cr
542 patients (mean age range: 18-70 years, male % range: 21-49%) satisfying Rome II or III diagnostic criteria for functional dyspepsia (FD).
Intervention
Comparator
M
an
Among included RCTs, patients received acupuncture at a frequency of 3-7 sessions per week for 3-4 weeks. Total number of acupuncture sessions varied from 6 to 28 sessions.
d
Comparison 1: Acupuncture versus sham acupuncture.
Ac ce pt e
Comparison 2: Acupuncture versus prokinetic drugs.
Major outcomes
Outcome 1: Generic patient reported quality of life measured by the Short Form 36 Health Survey (SF-36). Outcome 2: Disease specific patient reported quality of life measured by the Nepean Dyspepsia Life Quality Index (NDLQI). Outcome 3: Patient reported global FD symptom change rated on a continuous scale. Outcome 4: Patient reported global FD symptom change rated on a 4 point Likert scale (“cure”, “clear improvement”, “slight improvement”, and “no improvement”). Outcome data was then transformed to a dichotomous format, with “cure”, “clear improvement”, and “slight improvement” being categorized as “favourable” effect from treatment, while “no improvement” was categorized as “unfavorable” effect from treatment.
Settings Included studies were conducted in outpatient settings. 2 Page 2 of 6
Comparison 1: Acupuncture versus sham acupuncture Main results
ip t
Compared to sham acupuncture, patients in manual acupuncture group experienced significant improvement in quality of life measured by SF-36 (pooled mean difference (MD): 12.18, 95% confidence interval (CI): 8.45, 15.91), with low heterogeneity (I2 = 1%) among included trials (Table 1).
cr
Significant improvement in disease specific quality of life measured by NDLQI (pooled MD: 9.23, 95%CI: 4.85, 13.61) were also observed among patients in the manual acupuncture group, but there were moderate heterogeneity (I2 = 49%) among included trials (Table 1).
an
us
It was also observed that acupuncture also decrease patient rated global FD symptom severity in two included trials (MD: -2.24, 95%CI: -2.94, -1.54 and MD: -16.43, 95%CI: -20.39, -12.47) [1,2]. However, due to substantial heterogeneity (I2 = 98%), pooling of these trials was considered inappropriate (Table 1).
Main results
M
Comparison 2: Acupuncture versus prokinetic drugs
Ac ce pt e
d
Due to heterogeneous interventions and controls among included trials, pooling was not performed by the systematic review authors. Descriptive analyses of trials results on lowering global FD symptom severity were reported. In one trial, no significant difference between manual acupuncture and domperidone was observed (Risk Ratio (RR): 1.24, 95% CI: 0.97, 1.58) [3]. Similar results were observed in other trials comparing electroacupuncture with domperidone (Risk Ratio (RR): 1.14, 95% CI: 1.00, 1.30) [4], and in comparison between electroacupuncture and itopride (Risk Ratio (RR): 1.11, 95% CI: 0.98, 1.27) [5] (Table 2).
Conclusion Benefits
Compared to sham acupuncture, acupuncture provided stronger effect on improving quality of life among FD patients. The effectiveness of acupuncture in reducing patient reported symptom severity is also on par with commonly used prokinetics including domperidone and itopride. Harms No serious adverse events were reported among included trials.
Commentary
3 Page 3 of 6
FD is one of the most common types of functional gastrointestinal disorder. A range of symptoms originating in upper gastrointestinal tract may include postprandial fullness, early satiation, epigastric pain or burning, with unidentified causes [6]. Although current clinical guideline [7] recommends the use of pharmacological treatments, including proton pump inhibitors (PPI) and prokinetic drugs as first line treatment, effectiveness of proton pump inhibitors and prokinetic drugs is limited; with their number needed to treat (NNT) being 14.6 and 16
ip t
respectively [8,9]. Those who do not respond to these drugs are considered to suffer from refractory FD. As the NNT of both drugs are high, incidence of refractory FD is very common. Potential side
cr
effects of proton pump inhibitors and prokinetic drugs have also raised concern on their longer term use. For instance, in recently published 14-year population-based cohort study has shown the
us
association between proton pump inhibitors use and increased risk of chronic kidney disease [10]. Another meta-analysis has also demonstrated the association between domperidone use and cardiac arrhythmia and sudden cardiac death [11]. There is a need for addressing health needs of those who
an
are experiencing refractory FD, or those who are contraindicated with proton pump inhibitors or prokinetics. Favorable results from the current systematic review indicate that acupuncture can be
M
considered as an alternative to pharmacological treatment among these patients. Appropriate choice of outcome measure is the key for improving quality for future trials. Current consensus recommends the following outcomes should be used in future trials [12]. For primary
d
endpoint, weekly binary assessment of adequate relief of FD symptoms over time should be used, and
Ac ce pt e
achievement of adequate relief for a substantial proportion of time can be regarded as treatment success. For secondary endpoints, assessment of individual symptoms, including changes in postprandial fullness, early satiety, epigastric pain, epigastric burning and postprandial nausea should be performed. The comprehensive use of Nepean Dyspepsia Index and objective nutrient drink test can also be used to evaluate treatment impact [13].
Table 1
Acupuncture versus sham acupuncture among patients with functional dyspepsia. Outcome
No. of studies (total number of participants)
Heterogeneity (I2 value)
1
2 (116)
1%
Outcome
No. of studies (total number of participants)
Heterogeneity (I2 value)
2
2 (128)
49%
Outcome
No. of studies (total number of participants)
Heterogeneity (I2 value)
pooled MD (95%CI) 12.18 (8.45 to 15.91) pooled MD (95%CI) 9.23 (4.85 to 13.61) MD (95%CI)
4 Page 4 of 6
3
1 (60)
NA
-2.24 (-2.94 to -1.54)
Outcome
No. of studies (total number of participants)
Heterogeneity (I2 value)
3
1 (56)
NA
MD (95%CI) -16.43 (-20.39 to -12.47)
ip t
Keys: MD: mean difference; CI = confidence interval
Acupuncture versus prokinetic drugs among patients with functional dyspepsia. No. of studies (total number of participants)
4
1 (62)
Outcomes
No. of studies (total number of participants)
4
1 (126)
Outcomes
No. of studies (total number of participants)
4
1 (80)
Heterogeneity (I2 value) NA
us
Outcomes
cr
Table 2
an
Heterogeneity (I2 value) NA
M
Heterogeneity (I2 value)
1.24 (0.97 to 1.58) RR (95%CI) 1.14 (1.00 to 1.30) RR (95%CI) 1.11 (0.98 to 1.27)
d
NA
RR (95%CI)
Ac ce pt e
Keys: RR = risk ratio; CI = confidence interval
Acknowledgements
This synopsis is not funded by any parties.
References [1]
[2] [3]
X.R. Chang, L. Lan, J. Yan, X.J. Wang, H.M. Chen. Efficacy of acupuncture at FootYangming Meridian in the treatment of patients with functional dyspepsia: an analysis of 30 cases. World Chinese Journal of Digestology 2010;18(8):839-44. Y. Jin. Efficacy of acupuncture in the treatment of patients with functional dyspepsia. Unpublished medicine master dissertation. Beijing University of Chinese Medicine. 2011. S. Tang, Z. Xu, P. Tang, L. Liang. Acupuncture for functional dyspepsia: a randomised controlled trial. Journal of Sichuan Traditional Chinese Medicine 2006;24(4):101-2. 5 Page 5 of 6
[10] [11]
[12]
[13]
ip t
cr
[9]
us
[8]
an
[7]
M
[6]
d
[5]
Y. Zhou, J.G. Zheng. Clinical observation on acupuncture treatment of functional dyspepsia. Journal of Acupuncture and Tuina Science. 2005;3(2):20-2. M. Yang. EIectroacupuncture treatment of functionaI dyspepsia from a cIinical research. Unpublished medicine master dissertation. Hubei University of TCM. 2009. J. Tack, N.J. Talley. Functional dyspepsia—symptoms, definitions and validity of the Rome III criteria. Nature Reviews Gastroenterology and Hepatology. 2013;10(3):134-41. N.J. Talley, N. Vakil. Guidelines for the management of dyspepsia. The American journal of gastroenterology. 2005;100(10):2324-37. W.H. Wang, J.Q. Huang, G.F. Zheng, H.H. Xia, W.M. Wong, X.G. Liu, J. Karlberg, B.C. Wong. Effects of proton-pump inhibitors on functional dyspepsia: a meta-analysis of randomized placebo-controlled trials. Clinical Gastroenterology and Hepatology. 2007;5(2):178-85. M. Hojo, A. Nagahara, D. Asaoka, S. Watanabe. Emerging pharmacological therapy for functional dyspepsia. Clinical journal of gastroenterology. 2013;6(5):352-6. B. Lazarus, Y. Chen, F. Wilson, Y. Sang, A. Chang, J. Coresh, M.E. Grams. Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease. JAMA internal medicine. 2016:238-46. N. Leelakanok, A. Holcombe, M.L. Schweizer. Domperidone and Risk of Ventricular Arrhythmia and Cardiac Death: A Systematic Review and Meta-analysis. Clinical drug investigation. 2015:1-11. D. Ang, N.J. Talley, M. Simrén, P. Janssen, G. Boeckxstaens, J. Tack. Review article: endpoints used in functional dyspepsia drug therapy trials. Alimentary pharmacology & therapeutics. 2011;33(6):634-49. B.E. Lacy, N.J. Talley, M. Camilleri. Functional Dyspepsia: Time to Change Clinical Trial Design&quest. The American journal of gastroenterology. 2010;105(12):2525-9.
Ac ce pt e
[4]
6 Page 6 of 6