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Published in: Trials 1/2013

Open Access 01-12-2013 | Study protocol

Efficacy of individualized homeopathic treatment and fluoxetine for moderate to severe depression in peri- and postmenopausal women (HOMDEP-MENOP): study protocol for a randomized, double-dummy, double-blind, placebo-controlled trial

Authors: Emma del Carmen Macías-Cortés, Leopoldo Aguilar-Faisal, Juan Asbun-Bojalil

Published in: Trials | Issue 1/2013

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Abstract

Background

The perimenopausal period refers to the interval when women’s menstrual cycles become irregular and is characterized by an increased risk of depressive symptoms. Use of homeopathy to treat depression is widespread but there is a lack of clinical trials about its efficacy in depression in peri- and postmenopausal women. Previous trials suggest that individualized homeopathic treatments improve depression. In classical homeopathy, an individually selected homeopathic remedy is prescribed after a complete case history of the patient. The aim of this study is to assess the efficacy and safety of the homeopathic individualized treatment versus placebo or fluoxetine in peri- and postmenopausal women with moderate to severe depression.

Methods/design

A randomized, placebo-controlled, double-blind, double-dummy, three-arm trial with a six-week follow-up study was designed. The study will be conducted in a public research hospital in Mexico City (Juárez de México Hospital) in the outpatient service of homeopathy. One hundred eighty nine peri- and postmenopausal women diagnosed with major depression according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (moderate to severe intensity) will be included. The primary outcome is change in the mean total score among groups on the 17-item Hamilton Rating Scale for Depression after the fourth and sixth week of treatment. Secondary outcomes are: Beck Depression Inventory change in mean score, Greene’s Scale change in mean score, response and remission rates and safety. Efficacy data will be analyzed in the intention-to-treat population. To determine differences in the primary and secondary outcomes among groups at baseline and weeks four and six, data will be analyzed by analysis of variance for independent measures with the Bonferroni post-hoc test.

Discussion

This study is the first trial of classical homeopathy that will evaluate the efficacy of homeopathic individualized treatment using C-potencies versus placebo or fluoxetine in peri- and postmenopausal women with moderate to severe depression. It is an attempt to deal with the obstacles of homeopathic research due to the need for individual prescriptions in one of the most common psychiatric diseases.

Trial registration

ClinicalTrials.gov Identifier: NCT01635218.
Appendix
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Literature
1.
go back to reference Greenberg PE, Stiglin LE, Finkelstein SN, Berndt ER: The economic burden of depression in 1990. J Clin Psychiatry. 1993, 54: 405-418.PubMed Greenberg PE, Stiglin LE, Finkelstein SN, Berndt ER: The economic burden of depression in 1990. J Clin Psychiatry. 1993, 54: 405-418.PubMed
2.
go back to reference Murray CJ, Lopez AD: Evidence-based health policy-lessons from the Global Burden of Disease Study. Science. 1996, 274: 740-743. 10.1126/science.274.5288.740.CrossRefPubMed Murray CJ, Lopez AD: Evidence-based health policy-lessons from the Global Burden of Disease Study. Science. 1996, 274: 740-743. 10.1126/science.274.5288.740.CrossRefPubMed
3.
go back to reference Kesler RC, Berglund P, Dernler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS, National Comorbidity Survey Replication: The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003, 289: 3095-3105. 10.1001/jama.289.23.3095.CrossRef Kesler RC, Berglund P, Dernler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS, National Comorbidity Survey Replication: The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003, 289: 3095-3105. 10.1001/jama.289.23.3095.CrossRef
4.
go back to reference Williams LM, Rush AJ, Koslow SH, Wisniewski SR, Cooper NJ, Nemeroff CB, Schatzberg AF, Gordon E: International study to predict optimized treatment for depression (ISPOT-D), a randomized clinical trial: rationale and protocol. Trials. 2011, 12: 4-10.1186/1745-6215-12-4.CrossRefPubMedPubMedCentral Williams LM, Rush AJ, Koslow SH, Wisniewski SR, Cooper NJ, Nemeroff CB, Schatzberg AF, Gordon E: International study to predict optimized treatment for depression (ISPOT-D), a randomized clinical trial: rationale and protocol. Trials. 2011, 12: 4-10.1186/1745-6215-12-4.CrossRefPubMedPubMedCentral
5.
go back to reference Simon GE, Von Korff M, Barlow W: Health care costs of primary care patients with recognized depression. Arch Gen Psychiatry. 1995, 52: 850-10.1001/archpsyc.1995.03950220060012.CrossRefPubMed Simon GE, Von Korff M, Barlow W: Health care costs of primary care patients with recognized depression. Arch Gen Psychiatry. 1995, 52: 850-10.1001/archpsyc.1995.03950220060012.CrossRefPubMed
6.
go back to reference Cohen LS, Soares CN, Vitonis AF, Otto MW, Harlow BL: Risk for new onset of depression during menopausal transition. Arch Gen Psychiatry. 2006, 63: 385-390. 10.1001/archpsyc.63.4.385.CrossRefPubMed Cohen LS, Soares CN, Vitonis AF, Otto MW, Harlow BL: Risk for new onset of depression during menopausal transition. Arch Gen Psychiatry. 2006, 63: 385-390. 10.1001/archpsyc.63.4.385.CrossRefPubMed
7.
go back to reference Hale GE, Zhao X, Hughes CL, Burger HG, Robertson DM, Fraser IS: Endocrine features of menstrual cycle in middle and late reproductive age and the menopausal transition classified according to the Staging of Reproductive Aging Workshop (STRAW) Staging System. J Clin Endocrinol Metab. 2007, 92: 3060-3067. 10.1210/jc.2007-0066.CrossRefPubMed Hale GE, Zhao X, Hughes CL, Burger HG, Robertson DM, Fraser IS: Endocrine features of menstrual cycle in middle and late reproductive age and the menopausal transition classified according to the Staging of Reproductive Aging Workshop (STRAW) Staging System. J Clin Endocrinol Metab. 2007, 92: 3060-3067. 10.1210/jc.2007-0066.CrossRefPubMed
8.
go back to reference Freeman EW, Sammel MD, Hui L, Nelson DB: Associations of hormones and menopausal status with depressed mood in women with no history of depression. Arch Gen Psychiatry. 2006, 63: 375-382. 10.1001/archpsyc.63.4.375.CrossRefPubMed Freeman EW, Sammel MD, Hui L, Nelson DB: Associations of hormones and menopausal status with depressed mood in women with no history of depression. Arch Gen Psychiatry. 2006, 63: 375-382. 10.1001/archpsyc.63.4.375.CrossRefPubMed
9.
go back to reference Freeman EW, Sammel MD, Liu L, Garcia CR, Nelson DB, Hollander L: Hormones and menopausal status as predictors of depression in women in transition to menopause. Arch Gen Psychiatry. 2004, 61: 62-70. 10.1001/archpsyc.61.1.62.CrossRefPubMed Freeman EW, Sammel MD, Liu L, Garcia CR, Nelson DB, Hollander L: Hormones and menopausal status as predictors of depression in women in transition to menopause. Arch Gen Psychiatry. 2004, 61: 62-70. 10.1001/archpsyc.61.1.62.CrossRefPubMed
10.
go back to reference Rapkin AJ: Vasomotor symptoms in menopause: physiologic condition and central nervous system approaches to treatment. Am J Obstet Gynecol. 2007, 196: 97-106. 10.1016/j.ajog.2006.05.056.CrossRefPubMed Rapkin AJ: Vasomotor symptoms in menopause: physiologic condition and central nervous system approaches to treatment. Am J Obstet Gynecol. 2007, 196: 97-106. 10.1016/j.ajog.2006.05.056.CrossRefPubMed
11.
go back to reference Greene JG: Constructing a standard climacteric scale. Maturitas. 1998, 29: 25-31. 10.1016/S0378-5122(98)00025-5.CrossRefPubMed Greene JG: Constructing a standard climacteric scale. Maturitas. 1998, 29: 25-31. 10.1016/S0378-5122(98)00025-5.CrossRefPubMed
12.
go back to reference Hernández-Valencia M, Córdova-Pérez N, Basurto L, Saucedo R, Vargas C, Vargas A, Ruiz M, Manuel L, Zárate A: Frequency of symptoms of the climacteric syndrome. Ginecol Obstet Mex. 2010, 78: 232-237. SpanishPubMed Hernández-Valencia M, Córdova-Pérez N, Basurto L, Saucedo R, Vargas C, Vargas A, Ruiz M, Manuel L, Zárate A: Frequency of symptoms of the climacteric syndrome. Ginecol Obstet Mex. 2010, 78: 232-237. SpanishPubMed
13.
go back to reference Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT: Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med. 2008, 5: e45-10.1371/journal.pmed.0050045.CrossRefPubMedPubMedCentral Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT: Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med. 2008, 5: e45-10.1371/journal.pmed.0050045.CrossRefPubMedPubMedCentral
14.
go back to reference National Institute for Clinical Excellence: Depression: Management of Depression in Primary and Secondary Care. Clinical Practice Guideline. 2004, London, No. 23. 670 National Institute for Clinical Excellence: Depression: Management of Depression in Primary and Secondary Care. Clinical Practice Guideline. 2004, London, No. 23. 670
15.
go back to reference Kirsch I, Moore TJ, Scoboria A, Nicholls SS: The emperor’s new drugs: an analysis of antidepressant medication data submitted to the US Food and Drug Administration. Prev Treat. 2002, 5: art 23- Kirsch I, Moore TJ, Scoboria A, Nicholls SS: The emperor’s new drugs: an analysis of antidepressant medication data submitted to the US Food and Drug Administration. Prev Treat. 2002, 5: art 23-
16.
go back to reference Fava M, Davidson KG: Definition and epidemiology of treatment-resistant depression. Psychiatr Clin North Am. 1996, 19: 179-200. 10.1016/S0193-953X(05)70283-5.CrossRefPubMed Fava M, Davidson KG: Definition and epidemiology of treatment-resistant depression. Psychiatr Clin North Am. 1996, 19: 179-200. 10.1016/S0193-953X(05)70283-5.CrossRefPubMed
17.
go back to reference Frank E, Prien R, Jarrett RB, Keller MB, Kupfer DJ, Lavon PW, Rush AJ, Weissman MM: Conceptualization and rationale for consensus definitions of terms in major depressive disorder. Remission, recovery, relapse and recurrence. Arch Gen Psychiatry. 1991, 48: 851-855. 10.1001/archpsyc.1991.01810330075011.CrossRefPubMed Frank E, Prien R, Jarrett RB, Keller MB, Kupfer DJ, Lavon PW, Rush AJ, Weissman MM: Conceptualization and rationale for consensus definitions of terms in major depressive disorder. Remission, recovery, relapse and recurrence. Arch Gen Psychiatry. 1991, 48: 851-855. 10.1001/archpsyc.1991.01810330075011.CrossRefPubMed
18.
go back to reference Trivedi MH, Rush AJ, Wisneiwski SR, Nierenberg AA, Warden D, Ritz I, Norquist G, Howland RH, Lebowitz B, McGrath PJ, Shores-Wilson K, Biggs MM, Balasubramani GK, Fava M, STAR*D Study Team: Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006, 163: 28-40. 10.1176/appi.ajp.163.1.28.CrossRefPubMed Trivedi MH, Rush AJ, Wisneiwski SR, Nierenberg AA, Warden D, Ritz I, Norquist G, Howland RH, Lebowitz B, McGrath PJ, Shores-Wilson K, Biggs MM, Balasubramani GK, Fava M, STAR*D Study Team: Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006, 163: 28-40. 10.1176/appi.ajp.163.1.28.CrossRefPubMed
19.
go back to reference Jonas W, Jacobs J: Healing with Homeopathy. 1996, New York: Warner Jonas W, Jacobs J: Healing with Homeopathy. 1996, New York: Warner
20.
go back to reference Linde K, Clausius N, Ramirez G, Melchart D, Eitel F, Hedges LV, Jonas WB: Are the clinical effects of homeopathy placebo effects? A meta-analysis of placebo-controlled trials. Lancet. 1997, 350: 834-843. 10.1016/S0140-6736(97)02293-9.CrossRefPubMed Linde K, Clausius N, Ramirez G, Melchart D, Eitel F, Hedges LV, Jonas WB: Are the clinical effects of homeopathy placebo effects? A meta-analysis of placebo-controlled trials. Lancet. 1997, 350: 834-843. 10.1016/S0140-6736(97)02293-9.CrossRefPubMed
21.
go back to reference Adler UC, Krüger S, Teut M, Lüdtke R, Bartsch I, Schützler L, Melcher F, Willich SN, Linde K, Witt CM: Homeopathy for depression –DEP-HOM: study protocol for randomized, partially double-blind, placebo controlled, four armed study. Trials. 2011, 12: 43-10.1186/1745-6215-12-43.CrossRefPubMedPubMedCentral Adler UC, Krüger S, Teut M, Lüdtke R, Bartsch I, Schützler L, Melcher F, Willich SN, Linde K, Witt CM: Homeopathy for depression –DEP-HOM: study protocol for randomized, partially double-blind, placebo controlled, four armed study. Trials. 2011, 12: 43-10.1186/1745-6215-12-43.CrossRefPubMedPubMedCentral
22.
go back to reference Davidson JR, Crawford C, Ives JA, Jonas WB: Homeopathic treatments in psychiatry: a systematic review of randomized placebo-controlled studies. J Clin Psychiatry. 2011, 72: 795-805. 10.4088/JCP.10r06580.CrossRefPubMed Davidson JR, Crawford C, Ives JA, Jonas WB: Homeopathic treatments in psychiatry: a systematic review of randomized placebo-controlled studies. J Clin Psychiatry. 2011, 72: 795-805. 10.4088/JCP.10r06580.CrossRefPubMed
23.
go back to reference Freeman MP, Mischoulon D, Tedeschini E, Goodness T, Cohen LS, Fava M, Papakostas GI: Complementary and alternative medicine for major depressive disorder: a meta-analysis of patient characteristics, placebo-response rates, and treatment outcomes relative to standard antidepressants. J Clin Psychiatry. 2010, 71: 682-688. 10.4088/JCP.10r05976blu.CrossRefPubMed Freeman MP, Mischoulon D, Tedeschini E, Goodness T, Cohen LS, Fava M, Papakostas GI: Complementary and alternative medicine for major depressive disorder: a meta-analysis of patient characteristics, placebo-response rates, and treatment outcomes relative to standard antidepressants. J Clin Psychiatry. 2010, 71: 682-688. 10.4088/JCP.10r05976blu.CrossRefPubMed
24.
go back to reference Jonas WB, Kaptchuk YJ, Linde K: A critical overview of homeopathy. Ann Intern Med. 2003, 138: 393-399. 10.7326/0003-4819-138-5-200303040-00009.CrossRefPubMed Jonas WB, Kaptchuk YJ, Linde K: A critical overview of homeopathy. Ann Intern Med. 2003, 138: 393-399. 10.7326/0003-4819-138-5-200303040-00009.CrossRefPubMed
25.
go back to reference Linde K, Melchart D: Randomized controlled trials of individualized homeopathy: a state-of-the-art review. J Altern Complement Med. 1998, 4: 371-388. 10.1089/acm.1998.4.371.CrossRefPubMed Linde K, Melchart D: Randomized controlled trials of individualized homeopathy: a state-of-the-art review. J Altern Complement Med. 1998, 4: 371-388. 10.1089/acm.1998.4.371.CrossRefPubMed
26.
go back to reference Ernst E: Homeopathy: what does the “best” evidence tell us?. Med J Aust. 2010, 192: 458-460.PubMed Ernst E: Homeopathy: what does the “best” evidence tell us?. Med J Aust. 2010, 192: 458-460.PubMed
27.
go back to reference Shang A, Huwler-Müntener K, Nartey I, Jüni P, Dörig S, Sterne JA, Pewsner D, Egger M: Are the clinical effects of homeopathy placebo effects? Comparative study of placebo-controlled trials of homeopathy and allopathy. Lancet. 2005, 366: 726-732. 10.1016/S0140-6736(05)67177-2.CrossRefPubMed Shang A, Huwler-Müntener K, Nartey I, Jüni P, Dörig S, Sterne JA, Pewsner D, Egger M: Are the clinical effects of homeopathy placebo effects? Comparative study of placebo-controlled trials of homeopathy and allopathy. Lancet. 2005, 366: 726-732. 10.1016/S0140-6736(05)67177-2.CrossRefPubMed
28.
go back to reference Lüdke R, Rutten AL: The conclusions on the effectiveness of homeopathy highly depend on the set of analyzed trials. J Clin Epidemiol. 2008, 61: 1197-1204. 10.1016/j.jclinepi.2008.06.015.CrossRef Lüdke R, Rutten AL: The conclusions on the effectiveness of homeopathy highly depend on the set of analyzed trials. J Clin Epidemiol. 2008, 61: 1197-1204. 10.1016/j.jclinepi.2008.06.015.CrossRef
29.
go back to reference Bordet MF, Colas A, Marijnen P, Masson JL, Trichard M: Treating hot flushes in menopausal women with homeopathic treatment –results of an observational study. Homeopathy. 2008, 97: 10-15. 10.1016/j.homp.2007.11.005.CrossRefPubMed Bordet MF, Colas A, Marijnen P, Masson JL, Trichard M: Treating hot flushes in menopausal women with homeopathic treatment –results of an observational study. Homeopathy. 2008, 97: 10-15. 10.1016/j.homp.2007.11.005.CrossRefPubMed
30.
go back to reference Jacobs J, Hermann P, Heron K, Olsen S, Vaughters L: Homeopathy for menopausal symptoms in breast cancer survivors: a preliminary randomized controlled study. J Altern Complement Med. 2005, 11: 21-27. 10.1089/acm.2005.11.21.CrossRefPubMed Jacobs J, Hermann P, Heron K, Olsen S, Vaughters L: Homeopathy for menopausal symptoms in breast cancer survivors: a preliminary randomized controlled study. J Altern Complement Med. 2005, 11: 21-27. 10.1089/acm.2005.11.21.CrossRefPubMed
31.
go back to reference Adler UC, Paiva NM, Cesar AT, Adler MS, Molina A, Padula AE, Calil HM: Homeopathic individualized Q-potencies versus fluoxetine for moderate to severe depression: double-blind, randomized non-inferiority trial. Evid Based Complement Altern Med. 2011, 2011: 520182-10.1093/ecam/nep114.CrossRef Adler UC, Paiva NM, Cesar AT, Adler MS, Molina A, Padula AE, Calil HM: Homeopathic individualized Q-potencies versus fluoxetine for moderate to severe depression: double-blind, randomized non-inferiority trial. Evid Based Complement Altern Med. 2011, 2011: 520182-10.1093/ecam/nep114.CrossRef
32.
go back to reference Schulz KF, Altman DG, Moher D, CONSORT Group: CONSORT 2010 statement updated guidelines for reporting parallel group randomized trials. PLoS Med. 2010, 7: e1000251-10.1371/journal.pmed.1000251.CrossRefPubMedPubMedCentral Schulz KF, Altman DG, Moher D, CONSORT Group: CONSORT 2010 statement updated guidelines for reporting parallel group randomized trials. PLoS Med. 2010, 7: e1000251-10.1371/journal.pmed.1000251.CrossRefPubMedPubMedCentral
33.
go back to reference Dean ME, Coulter MK, Fisher P, Jobst KA, Walach H: Reporting data on homeopathic treatments (RedHot): a supplement to CONSORT. J Altern Complement Med. 2007, 13: 19-23. 10.1089/acm.2006.6352.CrossRefPubMed Dean ME, Coulter MK, Fisher P, Jobst KA, Walach H: Reporting data on homeopathic treatments (RedHot): a supplement to CONSORT. J Altern Complement Med. 2007, 13: 19-23. 10.1089/acm.2006.6352.CrossRefPubMed
34.
go back to reference Chan AW, Tetzlaff JM, Gфtzsche PC, Altman DG, Mann H, Berlin JA, Dickersin K, Hróbjartsson A, Schulz KF, Parulekar WR, Krleza-Jeric K, Laupacis A, Moher D: SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013, 346: e7586-10.1136/bmj.e7586.CrossRefPubMedPubMedCentral Chan AW, Tetzlaff JM, Gфtzsche PC, Altman DG, Mann H, Berlin JA, Dickersin K, Hróbjartsson A, Schulz KF, Parulekar WR, Krleza-Jeric K, Laupacis A, Moher D: SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013, 346: e7586-10.1136/bmj.e7586.CrossRefPubMedPubMedCentral
35.
go back to reference Thompson TD, Weiss M: Homeopathy –what are the active ingredients? An exploratory study using the UK Medical Research Council’s framework for the evaluation of complex interventions. BMC Complement Altern Med. 2006, 6: 37-10.1186/1472-6882-6-37.CrossRefPubMedPubMedCentral Thompson TD, Weiss M: Homeopathy –what are the active ingredients? An exploratory study using the UK Medical Research Council’s framework for the evaluation of complex interventions. BMC Complement Altern Med. 2006, 6: 37-10.1186/1472-6882-6-37.CrossRefPubMedPubMedCentral
36.
go back to reference Mulrow CD, Williams JW, Chiquette E, Aguilar C, Hitchcock-Noel P, Lee S, Cornell J, Stamm K: Efficacy of newer medications for treating depression in primary care patients. Am J Med. 2000, 108: 54-64. 10.1016/S0002-9343(99)00316-2.CrossRefPubMed Mulrow CD, Williams JW, Chiquette E, Aguilar C, Hitchcock-Noel P, Lee S, Cornell J, Stamm K: Efficacy of newer medications for treating depression in primary care patients. Am J Med. 2000, 108: 54-64. 10.1016/S0002-9343(99)00316-2.CrossRefPubMed
37.
go back to reference Dawson MY, Michalak EE, Anderson JE, Lam RW: Is remission of depressive symptoms in primary care a realistic goal? A meta-analysis. BMC Fam Pract. 2004, 5: 19-10.1186/1471-2296-5-19.CrossRefPubMedPubMedCentral Dawson MY, Michalak EE, Anderson JE, Lam RW: Is remission of depressive symptoms in primary care a realistic goal? A meta-analysis. BMC Fam Pract. 2004, 5: 19-10.1186/1471-2296-5-19.CrossRefPubMedPubMedCentral
38.
go back to reference Gibbons RD, Hur K, Brown CH, Davis JM, Mann JJ: Who benefits from antidepressants? Synthesis of 6-week patient-level outcomes from double-blind placebo controlled randomized trials of fluoxetine and venlafaxine. Arch Gen Psychiatry. 2012, 69: 572-579. 10.1001/archgenpsychiatry.2011.2044.PubMedPubMedCentral Gibbons RD, Hur K, Brown CH, Davis JM, Mann JJ: Who benefits from antidepressants? Synthesis of 6-week patient-level outcomes from double-blind placebo controlled randomized trials of fluoxetine and venlafaxine. Arch Gen Psychiatry. 2012, 69: 572-579. 10.1001/archgenpsychiatry.2011.2044.PubMedPubMedCentral
Metadata
Title
Efficacy of individualized homeopathic treatment and fluoxetine for moderate to severe depression in peri- and postmenopausal women (HOMDEP-MENOP): study protocol for a randomized, double-dummy, double-blind, placebo-controlled trial
Authors
Emma del Carmen Macías-Cortés
Leopoldo Aguilar-Faisal
Juan Asbun-Bojalil
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Trials / Issue 1/2013
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/1745-6215-14-105

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