Team approach to polypharmacy evaluation and reduction: study protocol for a randomized controlled trial

Dee Mangin, Larkin Lamarche, Gina Agarwal, Hoan Linh Banh, Naomi Dore Brown, Alan Cassels, Kiska Colwill, Lisa Dolovich, Barbara Farrell, Scott Garrison, James Gillett, Lauren E Griffith, Anne Holbrook, Jane Jurcic-Vrataric, James McCormack, Daria O'Reilly, Parminder Raina, Julie Richardson, Cathy Risdon, Mat Savelli, Diana Sherifali, Henry Siu, Jean-Éric Tarride, Johanna Trimble, Abbas Ali, Karla Freeman, Jessica Langevin, Jenna Parascandalo, Jeffrey A Templeton, Steven Dragos, Sayem Borhan, Lehana Thabane, Dee Mangin, Larkin Lamarche, Gina Agarwal, Hoan Linh Banh, Naomi Dore Brown, Alan Cassels, Kiska Colwill, Lisa Dolovich, Barbara Farrell, Scott Garrison, James Gillett, Lauren E Griffith, Anne Holbrook, Jane Jurcic-Vrataric, James McCormack, Daria O'Reilly, Parminder Raina, Julie Richardson, Cathy Risdon, Mat Savelli, Diana Sherifali, Henry Siu, Jean-Éric Tarride, Johanna Trimble, Abbas Ali, Karla Freeman, Jessica Langevin, Jenna Parascandalo, Jeffrey A Templeton, Steven Dragos, Sayem Borhan, Lehana Thabane

Abstract

Background: Polypharmacy in older adults can be associated with negative outcomes including falls, impaired cognition, reduced quality of life, and general and functional decline. It is not clear to what extent these are reversible if the number of medications is reduced. Primary care does not have a systematic approach for reducing inappropriate polypharmacy, and there are few, if any, approaches that account for the patient's priorities and preferences. The primary objective of this study is to test the effect of TAPER (Team Approach to Polypharmacy Evaluation and Reduction), a structured operationalized clinical pathway focused on reducing inappropriate polypharmacy. TAPER integrates evidence tools for identifying potentially inappropriate medications, tapering, and monitoring guidance and explicit elicitation of patient priorities and preferences. We aim to determine the effect of TAPER on the number of medications (primary outcome) and health-related outcomes associated with polypharmacy in older adults.

Methods: We designed a multi-center randomized controlled trial, with the lead implementation site in Hamilton, Ontario. Older adults aged 70 years or older who are on five or more medications will be eligible to participate. A total of 360 participants will be recruited. Participants will be assigned to either the control or intervention arm. The intervention involves a comprehensive multidisciplinary medication review by pharmacists and physicians in partnership with patients. This review will be focused on reducing medication burden, with the assumption that this will reduce the risks and harms of polypharmacy. The control group is a wait list, and control patients will be given appointments for the TAPER intervention at a date after the final outcome assessment. All patients will be followed up and outcomes measured in both groups at baseline and 6 months.

Discussion: Our trial is unique in its design in that it aims to introduce an operationalized structured clinical pathway aimed to reduce polypharmacy in a primary care setting while at the same time recording patient's goals and priorities for treatment.

Trial registration: Clinical Trials.gov NCT02942927. First registered on October 24, 2016.

Keywords: Deprescribing; Health outcomes; Medication reduction; Multimorbidity; Older adults; Operationalized clinical model; Overmedication; Physician pharmacist collaboration; Polypharmacy.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Operational steps of TaperMD
Fig. 2
Fig. 2
SPIRIT figure with study timeline and data collection time points

References

    1. Farrell B, Mangin D. Deprescribing is an essential part of good prescribing. Am Fam Physician. 2019;99(1):7–9.
    1. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA. 1998;279(15):1200–1205. doi: 10.1001/jama.279.15.1200.
    1. Lipska KJ, Ross JS, Wang Y, Inzucchi SE, Minges K, Karter AJ, Huang ES, Desai MM, Gill TM, Krumholz HM. National trends in US hospital admissions for hyperglycemia and hypoglycemia among Medicare beneficiaries, 1999 to 2011. JAMA Intern Med. 2014;174(7):1116–1124. doi: 10.1001/jamainternmed.2014.1824.
    1. Malvezzi M, Bertuccio P, Levi F, La Vecchia C, Negri E. European cancer mortality predictions for the year 2013. Ann Oncol. 2013;24(3):792–800. doi: 10.1093/annonc/mdt010.
    1. Tinetti ME, Han L, Lee DS, McAvay GJ, Peduzzi P, Gross CP, et al. Antihypertensive medications and serious fall injuries in a nationally representative sample of older adults. JAMA Intern Med. 2014;174(4):588–595. doi: 10.1001/jamainternmed.2013.14764.
    1. Commission of the European Communities. Regulation of the European Parliament and of the council amending, as regards pharmacovigilance of medicinal products for human use. 2008. . Accessed 23 March 2021.
    1. Masnoon N, Shakib S, Kalisch-Ellett L, Caughey GE. What is polypharmacy? A systematic review of definitions. BMC Geriatr. 2017;17(1):230. doi: 10.1186/s12877-017-0621-2.
    1. Jyrkka J, Enlund H, Lavikainen P, Sulkava R, Hartikainen S. Association of polypharmacy with nutritional status, functional ability and cognitive capacity over a three-year period in an elderly population. Pharmacoepidemiol Drug Saf. 2011;20(5):514–522. doi: 10.1002/pds.2116.
    1. Leipzig RM, Cumming RG, Tinetti ME. Drugs and falls in older people: a systematic review and meta-analysis: I. Psychotropic drugs. J Am Geriatr Soc. 1999;47(1):30–39. doi: 10.1111/j.1532-5415.1999.tb01898.x.
    1. Mangin D, Bahat G, Golomb BA, Mallery LH, Moorhouse P, Onder G, et al. International Group for Reducing Inappropriate Medication Use & Polypharmacy (IGRIMUP): Position Statement and 10 Recommendations for Action. Drugs Aging. 2018;35(7):575–587. doi: 10.1007/s40266-018-0554-2.
    1. Moore AR, O'Keeffe ST. Drug-induced cognitive impairment in the elderly. Drugs Aging. 1999;15(1):15–28. doi: 10.2165/00002512-199915010-00002.
    1. Hilmer SN, Gnjidic D. The effects of polypharmacy in older adults. Clin Pharmacol Ther. 2009;85(1):86–88. doi: 10.1038/clpt.2008.224.
    1. Maher RL, Hanlon J, Hajjar ER. Clinical consequences of polypharmacy in elderly. Expert Opin Drug Saf. 2014;13(1):57–65. doi: 10.1517/14740338.2013.827660.
    1. May C, Montori VM, Mair FS. We need minimally disruptive medicine. BMJ. 2009;339(aug11 2):b2803. doi: 10.1136/bmj.b2803.
    1. Cooper JA, Cadogan CA, Patterson SM, Kerse N, Bradley MC, Ryan C, Hughes CM. Interventions to improve the appropriate use of polypharmacy in older people: a Cochrane systematic review. BMJ Open. 2015;5(12):e009235. doi: 10.1136/bmjopen-2015-009235.
    1. Dills H, Shah K, Messinger-Rapport B, Bradford K, Syed Q. Deprescribing medications for chronic diseases management in primary care settings: a systematic review of randomized controlled trials. J Am Med Dir Assoc. 2018;19(11):923–935. doi: 10.1016/j.jamda.2018.06.021.
    1. Gnjidic D, Le Couteur DG, Kouladjian L, Hilmer SN. Deprescribing trials: methods to reduce polypharmacy and the impact on prescribing and clinical outcomes. Clin Geriatr Med. 2012;28(2):237–253. doi: 10.1016/j.cger.2012.01.006.
    1. Johansson T, Abuzahra ME, Keller S, Mann E, Faller B, Sommerauer C, Höck J, Löffler C, Köchling A, Schuler J, Flamm M, Sönnichsen A. Impact of strategies to reduce polypharmacy on clinically relevant endpoints: a systematic review and meta-analysis. Br J Clin Pharmacol. 2016;82(2):532–548. doi: 10.1111/bcp.12959.
    1. Lee JQ, Ying K, Lun P, Tan KT, Ang W, Munro Y, Ding YY. Intervention elements to reduce inappropriate prescribing for older adults with multimorbidity receiving outpatient care: a scoping review. BMJ Open. 2020;10(8):e039543. doi: 10.1136/bmjopen-2020-039543.
    1. Rankin A, Cadogan CA, Patterson SM, Kerse N, Cardwell CR, Bradley MC, Ryan C, Hughes C, Cochrane Effective Practice and Organisation of Care Group Interventions to improve the appropriate use of polypharmacy for older people. Cochrane Database Syst Rev. 2018;9(9):CD008165. doi: 10.1002/14651858.CD008165.pub4.
    1. Garfinkel D, Mangin D. Feasibility study of a systematic approach for discontinuation of multiple medications in older adults: addressing polypharmacy. Arch Intern Med. 2010;170(18):1648–1654. doi: 10.1001/archinternmed.2010.355.
    1. Ailabouni N, Mangin D, Nishtala PS. DEFEAT-polypharmacy: deprescribing anticholinergic and sedative medicines feasibility trial in residential aged care facilities. Int J Clin Pharm. 2019;41(1):167–178. doi: 10.1007/s11096-019-00784-9.
    1. Curtin D, Gallagher PF, O'Mahony D. Explicit criteria as clinical tools to minimize inappropriate medication use and its consequences. Ther Adv Drug Saf. 2019;10:2042098619829431. doi: 10.1177/2042098619829431.
    1. Dunn RL, Harrison D, Ripley TL. The beers criteria as an outpatient screening tool for potentially inappropriate medications. Consult Pharm. 2011;26(10):754–763. doi: 10.4140/TCP.n.2011.754.
    1. Gallagher PF, O'Connor MN, O'Mahony D. Prevention of potentially inappropriate prescribing for elderly patients: a randomized controlled trial using STOPP/START criteria. Clin Pharmacol Ther. 2011;89(6):845–854. doi: 10.1038/clpt.2011.44.
    1. Buck MD, Atreja A, Brunker CP, Jain A, Suh TT, Palmer RM, Dorr DA, Harris CM, Wilcox AB. Potentially inappropriate medication prescribing in outpatient practices: prevalence and patient characteristics based on electronic health records. Am J Geriatr Pharmacother. 2009;7(2):84–92. doi: 10.1016/j.amjopharm.2009.03.001.
    1. Hamilton H, Gallagher P, Ryan C, Byrne S, O'Mahony D. Potentially inappropriate medications defined by STOPP criteria and the risk of adverse drug events in older hospitalized patients. Arch Intern Med. 2011;171(11):1013–1019. doi: 10.1001/archinternmed.2011.215.
    1. Hill-Taylor B, Sketris I, Hayden J, Byrne S, O'Sullivan D, Christie R. Application of the STOPP/START criteria: a systematic review of the prevalence of potentially inappropriate prescribing in older adults, and evidence of clinical, humanistic and economic impact. J Clin Pharm Ther. 2013;38(5):360–372. doi: 10.1111/jcpt.12059.
    1. Hill-Taylor B, Walsh KA, Stewart S, Hayden J, Byrne S, Sketris IS. Effectiveness of the STOPP/START (Screening Tool of Older Persons’ potentially inappropriate Prescriptions/Screening Tool to Alert doctors to the Right Treatment) criteria: systematic review and meta-analysis of randomized controlled studies. J Clin Pharm Ther. 2016;41(2):158–169. doi: 10.1111/jcpt.12372.
    1. O'Connor MN, O'Sullivan D, Gallagher PF, Eustace J, Byrne S, O'Mahony D. Prevention of hospital-acquired adverse drug reactions in older people using screening tool of older persons’ prescriptions and screening tool to alert to right treatment criteria: a cluster randomized controlled trial. J Am Geriatr Soc. 2016;64(8):1558–1566. doi: 10.1111/jgs.14312.
    1. Gokula M, Holmes HM. Tools to reduce polypharmacy. Clin Geriatr Med. 2012;28(2):323–341. doi: 10.1016/j.cger.2012.01.011.
    1. Hilmer SN, Mager DE, Simonsick EM, Cao Y, Ling SM, Windham BG, Harris TB, Hanlon JT, Rubin SM, Shorr RI, Bauer DC, Abernethy DR. A drug burden index to define the functional burden of medications in older people. Arch Intern Med. 2007;167(8):781–787. doi: 10.1001/archinte.167.8.781.
    1. Lu WH, Wen YW, Chen LK, Hsiao FY. Effect of polypharmacy, potentially inappropriate medications and anticholinergic burden on clinical outcomes: a retrospective cohort study. CMAJ. 2015;187(4):E130–E1E7. doi: 10.1503/cmaj.141219.
    1. Bjerre LM, Farrell B, Hogel M, Graham L, Lemay G, McCarthy L, Raman-Wilms L, Rojas-Fernandez C, Sinha S, Thompson W, Welch V, Wiens A. Deprescribing antipsychotics for behavioural and psychological symptoms of dementia and insomnia: Evidence-based clinical practice guideline. Can Fam Physician. 2018;64(1):17–27.
    1. Farrell B, Black C, Thompson W, McCarthy L, Rojas-Fernandez C, Lochnan H, Shamji S, Upshur R, Bouchard M, Welch V. Deprescribing antihyperglycemic agents in older persons: evidence-based clinical practice guideline. Can Fam Physician. 2017;63(11):832–843.
    1. Farrell B, Pottie K, Thompson W, Boghossian T, Pizzola L, Rashid FJ, Rojas-Fernandez C, Walsh K, Welch V, Moayyedi P. Deprescribing proton pump inhibitors: evidence-based clinical practice guideline. Can Fam Physician. 2017;63(5):354–364.
    1. Pottie K, Thompson W, Davies S, Grenier J, Sadowski CA, Welch V, Holbrook A, Boyd C, Swenson R, Ma A, Farrell B. Deprescribing benzodiazepine receptor agonists: evidence-based clinical practice guideline. Can Fam Physician. 2018;64(5):339–351.
    1. Reeve E, Farrell B, Thompson W, Herrmann N, Sketris I, Magin PJ, Chenoweth L, Gorman M, Quirke L, Bethune G, Hilmer SN. Deprescribing cholinesterase inhibitors and memantine in dementia: guideline summary. Med J Aust. 2019;210(4):174–179. doi: 10.5694/mja2.50015.
    1. Steinman MA, Fick DM. Using Wisely: a reminder on the proper use of the American Geriatrics Society Beers Criteria(R) J Am Geriatr Soc. 2019;67(4):644–646. doi: 10.1111/jgs.15766.
    1. Mangin D, Stephen G, Bismah V, Risdon C. Making patient values visible in healthcare: a systematic review of tools to assess patient treatment priorities and preferences in the context of multimorbidity. BMJ Open. 2016;6(6):e010903. doi: 10.1136/bmjopen-2015-010903.
    1. Fried TR, Tinetti M, Agostini J, Iannone L, Towle V. Health outcome prioritization to elicit preferences of older persons with multiple health conditions. Patient Educ Couns. 2011;83(2):278–282. doi: 10.1016/j.pec.2010.04.032.
    1. Mangin D. Team approach to polypharmacy evaluation and reduction: feasibility study of usual care versus a structured clinical pathway to reduce polypharmacy. In Preparation. 2021.
    1. Mangin D, Heath I, Jamoulle M. Beyond diagnosis: rising to the multimorbidity challenge. BMJ. 2012;344(jun13 2):e3526. doi: 10.1136/bmj.e3526.
    1. Anderson K, Stowasser D, Freeman C, Scott I. Prescriber barriers and enablers to minimising potentially inappropriate medications in adults: a systematic review and thematic synthesis. BMJ Open. 2014;4(12):e006544. doi: 10.1136/bmjopen-2014-006544.
    1. Mangin D. Theoretical underpinnings of a model to reduce polypharmacy and its negative health effects: Introducing the Team Approach to Polypharmacy Evaluation and Reduction (TAPER). In Preparation. 2021.
    1. Reeve E, To J. Hendrix I, Shakib S, Roberts MS, Wiese MD. Patient barriers to and enablers of deprescribing: a systematic review. Drugs Aging. 2013;30(10):793–807. doi: 10.1007/s40266-013-0106-8.
    1. Wallis KA, Andrews A, Henderson M. Swimming against the tide: primary care physicians’ views on deprescribing in everyday practice. Ann Fam Med. 2017;15(4):341–346. doi: 10.1370/afm.2094.
    1. Pottegard A, Haastrup MB, Stage TB, Hansen MR, Larsen KS, Meegaard PM, Meegaard LHV, Horneberg H, Gils C, Dideriksen D, Aagaard L, Almarsdottir AB, Hallas J, Damkier P. SearCh for humourIstic and Extravagant acroNyms and Thoroughly Inappropriate names For Important Clinical trials (SCIENTIFIC): qualitative and quantitative systematic study. BMJ. 2014;349(dec16 13):g7092. doi: 10.1136/bmj.g7092.
    1. Mangin D. TaperMD: About. 2021.
    1. Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gotzsche PC, Krleza-Jeric K, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013;158(3):200–207. doi: 10.7326/0003-4819-158-3-201302050-00583.
    1. Hoffmann TC, Glasziou PP, Boutron I, Milne R, Perera R, Moher D, Altman DG, Barbour V, Macdonald H, Johnston M, Lamb SE, Dixon-Woods M, McCulloch P, Wyatt JC, Chan AW, Michie S. Better reporting of interventions: template for intervention description and replication (TIDieR) checklist and guide. BMJ. 2014;348(mar07 3):g1687. doi: 10.1136/bmj.g1687.
    1. Mangin D, Lawson J, Cuppage J, Shaw E, Ivanyi K, Davis A, Risdon C. Legacy drug-prescribing patterns in primary care. Ann Fam Med. 2018;16(6):515–520. doi: 10.1370/afm.2315.
    1. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–381. doi: 10.1016/j.jbi.2008.08.010.
    1. Dowden A. Deprescribing: reducing inappropriate polypharmacy. Prescriber. 2017;28(2):45–49. doi: 10.1002/psb.1541.
    1. Kesselheim AS, Avorn J, Sarpatwari A. The high cost of prescription drugs in the United States: origins and prospects for reform. JAMA. 2016;316(8):858–871. doi: 10.1001/jama.2016.11237.
    1. Mangin D, Risdon C, Lamarche L, Langevin J, Ali A, Parascandalo J, Stephen G, Trimble J. ‘I think this medicine actually killed my wife’: patient and family perspectives on shared decision-making to optimize medications and safety. Ther Adv Drug Saf. 2019;10:2042098619838796. doi: 10.1177/2042098619838796.
    1. Reeve E, Wiese MD. Benefits of deprescribing on patients’ adherence to medications. Int J Clin Pharm. 2014;36(1):26–29. doi: 10.1007/s11096-013-9871-z.
    1. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–383. doi: 10.1016/0021-9681(87)90171-8.
    1. Barenholtz LH. Self-administered medication-risk questionnaire in an elderly population. Ann Pharmacother. 2003;37(7-8):982–987. doi: 10.1345/aph.1C305.
    1. Rolfson DB, Majumdar SR, Tsuyuki RT, Tahir A, Rockwood K. Validity and reliability of the Edmonton Frail Scale. Age Ageing. 2006;35(5):526–529. doi: 10.1093/ageing/afl041.
    1. Horne R, Weinman J, Hankins M. The beliefs about medicines questionnaire: the development and evaluation of a new method for assessing the cognitive representation of medication. Psychology & Health. 1999;14(1):1–24. doi: 10.1080/08870449908407311.
    1. Smith SM, Wallace E, Salisbury C, Sasseville M, Bayliss E, Fortin M. A Core Outcome Set for Multimorbidity Research (COSmm) Ann Fam Med. 2018;16(2):132–138. doi: 10.1370/afm.2178.
    1. Canada H. Reporting adverse reactions to marketed health products - guidance document for industry. 2018.
    1. Stone AA, Shiffman S, Schwartz JE, Broderick JE, Hufford MR. Patient compliance with paper and electronic diaries. Control Clin Trials. 2003;24(2):182–199. doi: 10.1016/S0197-2456(02)00320-3.
    1. May C, Rapley T, Mair FS, Treweek S, Murray E, Ballini L, et al. Normalization Process Theory On-line Users’ Manual, Toolkit and NoMAD instrument. 2015. . .
    1. May C, Finch T, Mair F, Ballini L, Dowrick C, Eccles M, Gask L, MacFarlane A, Murray E, Rapley T, Rogers A, Treweek S, Wallace P, Anderson G, Burns J, Heaven B. Understanding the implementation of complex interventions in health care: the normalization process model. BMC Health Serv Res. 2007;7(1):148. doi: 10.1186/1472-6963-7-148.
    1. Xie F, Pullenayegum E, Gaebel K, Bansback N, Bryan S, Ohinmaa A, Poissant L, Johnson JA, Canadian EQ-5D-5L Valuation Study Group A Time Trade-off-derived Value Set of the EQ-5D-5L for Canada. Med Care. 2016;54(1):98–105. doi: 10.1097/MLR.0000000000000447.
    1. Ramsey SD, Willke RJ, Glick H, Reed SD, Augustovski F, Jonsson B, Briggs A, Sullivan SD. Cost-effectiveness analysis alongside clinical trials II-An ISPOR Good Research Practices Task Force report. Value Health. 2015;18(2):161–172. doi: 10.1016/j.jval.2015.02.001.
    1. Guidelines for the economic evaluation of health technologies: Canada. 4th ed. Ottawa: CADTH; 2017 Mar.
    1. Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O'Neal L, et al. The REDCap consortium: building an international community of software platform partners. J Biomed Inform. 2019;95:103208. doi: 10.1016/j.jbi.2019.103208.
    1. Blom JW, Muth C, Glasziou P, McCormack JP, Perera R, Poortvliet RKE, et al. Describing deprescribing trials better: an elaboration of the CONSORT statement. J Clin Epidemiol. 2020;127:87–95. doi: 10.1016/j.jclinepi.2020.07.011.
    1. Thabane L, Akhtar-Danesh N. Guidelines for reporting descriptive statistics in health research. Nurse Res. 2008;15(2):72–81. doi: 10.7748/nr2008.01.15.2.72.c6331.
    1. Little RJA, Rubin DB. Statistical analysis with missing data. John Wiley & Sons, Inc: Hoboken, New Jersey; 2002.
    1. Ali M, Sherafali D, Fitzpatrick-Lewis D, Kenny M, Lamarche L, Mangin D, et al. Interventions to address polypharmacy in older adults living with multimorbidity: A review of reviews. Can Fam Physician. 2021. Accepted. .
    1. Page AT, Clifford RM, Potter K, Schwartz D, Etherton-Beer CD. The feasibility and effect of deprescribing in older adults on mortality and health: a systematic review and meta-analysis. Br J Clin Pharmacol. 2016;82(3):583–623. doi: 10.1111/bcp.12975.
    1. Braun V, Clarke V. Using thematic analysis in psychology. Qualitative Research in Psychology. 2006;3(2):77–101. doi: 10.1191/1478088706qp063oa.
    1. Dedoose. 8.0.35 ed. Los Angeles: SocioCultural Research Consultants; 2018. p. Web application for managing, analyzing, and presenting qualitative and mixed method research data.
    1. Lincoln YS, Guba EG. But is it rigorous? Trustworthiness and authenticity in naturalistic evaluation. New Directions for Program Evaluation. 1986;1986(30):73–84. doi: 10.1002/ev.1427.
    1. Schwandt TA, Lincoln YS, Guba EG. Judging interpretations: But is it rigorous? trustworthiness and authenticity in naturalistic evaluation. New Directions for Evaluation. 2007;2007(114):11–25. doi: 10.1002/ev.223.
    1. Mangin D, Dowson C, Mulder R, Wells E, Toop L, Dowel T, et al. The effectiveness of maintenance SSRI treatment in primary care depression to prevent recurrence: multicentre double blinded placebo controlled RCT. North American Primary Care Research Group Annual Meeting; Cancun, Mexico. 2015.

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