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Open Access 01-12-2022 | Opioids | Study protocol

An adaptive design to screen, treat, and retain people with opioid use disorders who use methamphetamine in methadone clinics (STAR-OM): study protocol of a clinical trial

Authors: Le Minh Giang, Nguyen Thu Trang, Nguyen Bich Diep, Dao Thi Dieu Thuy, Dinh Thanh Thuy, Han Dinh Hoe, Hoang Thi Hai Van, Thai Thanh Truc, Hoa H. Nguyen, Nguyen Ly Lai, Pham Thi Dan Linh, Vu Thi Tuong Vi, Cathy J. Reback, Arleen Leibowitz, Li Li, Chunqing Lin, Michael Li, Do Van Dung, Steve Shoptaw

Published in: Trials | Issue 1/2022

Abstract

Background

Methamphetamine use could jeopardize the current efforts to address opioid use disorder and HIV infection. Evidence-based behavioral interventions (EBI) are effective in reducing methamphetamine use. However, evidence on optimal combinations of EBI is limited. This protocol presents a type-1 effectiveness-implementation hybrid design to evaluate the effectiveness, cost-effectiveness of adaptive methamphetamine use interventions, and their implementation barriers in Vietnam.

Method

Design: Participants will be first randomized into two frontline interventions for 12 weeks. They will then be placed or randomized to three adaptive strategies for another 12 weeks. An economic evaluation and an ethnographic evaluation will be conducted alongside the interventions.

Participants: We will recruit 600 participants in 20 methadone clinics. Eligibility criteria: (1) age 16+; (2) Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) scores ≥ 10 for methamphetamine use or confirmed methamphetamine use with urine drug screening; (3) willing to provide three pieces of contact information; and (4) having a cell phone.

Outcomes: Outcomes are measured at 13, 26, and 49 weeks and throughout the interventions. Primary outcomes include the (1) increase in HIV viral suppression, (2) reduction in HIV risk behaviors, and (3) reduction in methamphetamine use.

COVID-19 response: We developed a response plan for interruptions caused by COVID-19 lockdowns to ensure data quality and intervention fidelity.

Discussion

This study will provide important evidence for scale-up of EBIs for methamphetamine use among methadone patients in limited-resource settings. As the EBIs will be delivered by methadone providers, they can be readily implemented if the trial demonstrates effectiveness and cost-effectiveness.

Trial registration

ClinicalTrials.gov NCT04706624. Registered on 13 January 2021. https://clinicaltrials.gov/ct2/show/NCT04706624

Ellis MS, Kasper ZA, Cicero TJ. Twin epidemics: the surging rise of methamphetamine use in chronic opioid users. Drug Alcohol Depend. 2018;193:14–20. https://doi.org/10.1016/j.drugalcdep.2018.08.029.CrossRefPubMed

Giang L, Thuy D, Trang N, Okafor C, Li M, Shoptaw S. Severity of methamphetamine use among methadone patients in Vietnam: prevalence and correlates. San Antonio; 2019.

Michel L, Des Jarlais DC, Duong Thi H, Khuat Thi Hai O, Pham Minh K, Peries M, et al. Intravenous heroin use in Haiphong, Vietnam: need for comprehensive care including methamphetamine use-related interventions. Drug Alcohol Depend. 2017;179:198–204. https://doi.org/10.1016/j.drugalcdep.2017.07.004.CrossRefPubMedPubMedCentral

UNODC GS programme. Synthetic drugs in East and Southeast Asia - latest developments and challenges; 2020. p. 116.

Bao Y-P, Liu Z-M, Li J-H, Zhang R-M, Hao W, Zhao M, et al. Club drug use and associated high-risk sexual behaviour in six provinces in China. Addiction. 2015;110(Suppl 1):11–9. https://doi.org/10.1111/add.12770.CrossRefPubMed

Carrico AW, Nil E, Sophal C, Stein E, Sokunny M, Yuthea N, et al. Behavioral interventions for Cambodian female entertainment and sex workers who use amphetamine-type stimulants. J Behav Med. 2016;39(3):502–10. https://doi.org/10.1007/s10865-016-9713-2.CrossRefPubMedPubMedCentral

Colfax G, Santos G-M, Chu P, Vittinghoff E, Pluddemann A, Kumar S, et al. Amphetamine-group substances and HIV. Lancet Lond Engl. 2010;376(9739):458–74. https://doi.org/10.1016/S0140-6736(10)60753-2.CrossRef

Zhang C, Liu Y, Sun X, Wang J, Lu H-Y, He X, et al. Substance use and HIV-risk behaviors among HIV-positive men who have sex with men in China: repeated measures in a cohort study design. AIDS Care. 2017;29(5):644–53. https://doi.org/10.1080/09540121.2016.1255709.CrossRefPubMed

Liu D, Gu J, Xu H, Hao C, Jiao M, Zhang X, et al. Club drugs and alcohol abuse predicted dropout and poor adherence among methadone maintenance treatment patients in Guangzhou, China. AIDS Care. 2017;29(4):458–63. https://doi.org/10.1080/09540121.2016.1259452.CrossRefPubMed

10.

Wang R, Ding Y, Bai H, Duan S, Ye R, Yang Y, et al. Illicit heroin and methamphetamine use among methadone maintenance treatment patients in Dehong Prefecture of Yunnan Province, China. PLoS One. 2015;10(7):e0133431. https://doi.org/10.1371/journal.pone.0133431.CrossRefPubMedPubMedCentral

11.

Carrico AW, Cherenack EM, Roach ME, Riley ED, Oni O, Dilworth SE, et al. Substance-associated elevations in monocyte activation among methamphetamine users with treated HIV infection. AIDS Lond Engl. 2018;32(6):767–71. https://doi.org/10.1097/QAD.0000000000001751.CrossRef

12.

Carrico AW, Hunt PW, Neilands TB, Dilworth SE, Martin JN, Deeks SG, et al. Stimulant use and viral suppression in the era of universal antiretroviral therapy. J Acquir Immune Defic Syndr. 2019;80(1):89–93. https://doi.org/10.1097/QAI.0000000000001867.CrossRefPubMedPubMedCentral

13.

Carrico AW, Flentje A, Kober K, Lee S, Hunt P, Riley ED, et al. Recent stimulant use and leukocyte gene expression in methamphetamine users with treated HIV infection. Brain Behav Immun. 2018;71:108–15. https://doi.org/10.1016/j.bbi.2018.04.004.CrossRefPubMedPubMedCentral

14.

Horvath KJ, Carrico AW, Simoni J, Boyer EW, Amico KR, Petroll AE. Engagement in HIV medical care and technology use among stimulant-using and nonstimulant-using men who have sex with men. AIDS Res Treat. 2013;2013:121352–11. https://doi.org/10.1155/2013/121352.CrossRefPubMedPubMedCentral

15.

Korthuis P, Todd B, Gavin KL, Diep NB, Brinkerhoff C, Giang LM. Buprenorphine versus Methadone impact on the HIV care continuum in Vietnam: BRAVO study 6-month outcomes. San Diego; 2018.

16.

Alam-mehrjerdi Z, Mokri A, Dolan K. Methamphetamine use and treatment in Iran: a systematic review from the most populated Persian Gulf country. Asian J Psychiatr. 2015;16:17–25. https://doi.org/10.1016/j.ajp.2015.05.036.CrossRefPubMed

17.

Shariatirad S, Maarefvand M, Ekhtiari H. Methamphetamine use and methadone maintenance treatment: an emerging problem in the drug addiction treatment network in Iran. Int J Drug Policy. 2013;24(6):e115–6. https://doi.org/10.1016/j.drugpo.2013.05.003.CrossRefPubMed

18.

Watt MH, Meade CS, Kimani S, MacFarlane JC, Choi KW, Skinner D, et al. The impact of methamphetamine (“tik”) on a peri-urban community in Cape Town, South Africa. Int J Drug Policy. 2014;25(2):219–25. https://doi.org/10.1016/j.drugpo.2013.10.007.CrossRefPubMed

19.

Baingana F. al’Absi M, Becker AE, Pringle B. Global research challenges and opportunities for mental health and substance-use disorders. Nature. 2015;527(7578):S172–7. https://doi.org/10.1038/nature16032.CrossRefPubMedPubMedCentral

20.

Petersen I, Evans-Lacko S, Semrau M, Barry MM, Chisholm D, Gronholm P, et al. Promotion, prevention and protection: interventions at the population- and community-levels for mental, neurological and substance use disorders in low- and middle-income countries. Int J Ment Heal Syst. 2016;10(1):30. https://doi.org/10.1186/s13033-016-0060-z.CrossRef

21.

AshaRani P, Hombali A, Seow E, Ong WJ, Tan JH, Subramaniam M. Non-pharmacological interventions for methamphetamine use disorder: a systematic review. Drug Alcohol Depend. 2020;212:108060. https://doi.org/10.1016/j.drugalcdep.2020.108060.CrossRefPubMed

22.

Knight R, Karamouzian M, Carson A, Edward J, Carrieri P, Shoveller J, et al. Interventions to address substance use and sexual risk among gay, bisexual and other men who have sex with men who use methamphetamine: a systematic review. Drug Alcohol Depend. 2019;194:410–29. https://doi.org/10.1016/j.drugalcdep.2018.09.023.CrossRefPubMed

23.

Radfar SR, Rawson RA. Current research on methamphetamine: epidemiology, medical and psychiatric effects, treatment, and harm reduction efforts. Addict Health. 2014;6(3–4):146–54.PubMedPubMedCentral

24.

Polcin DL, Bond J, Korcha R, Nayak MB, Galloway GP, Evans K. Randomized trial of intensive motivational interviewing for methamphetamine dependence. J Addict Dis. 2014;33(3):253–65. https://doi.org/10.1080/10550887.2014.950029.CrossRefPubMedPubMedCentral

25.

Galloway GP, Polcin D, Kielstein A, Brown M, Mendelson J. A nine session manual of motivational enhancement therapy for methamphetamine dependence: adherence and efficacy. J Psychoactive Drugs. 2007;39(sup4):393–400.CrossRef

26.

Benishek LA, Dugosh KL, Kirby KC, Matejkowski J, Clements NT, Seymour BL, et al. Prize-based contingency management for the treatment of substance abusers: a meta-analysis. Addiction. 2014;109(9):1426–36. https://doi.org/10.1111/add.12589.CrossRefPubMedPubMedCentral

27.

Brown HD, DeFulio A. Contingency management for the treatment of methamphetamine use disorder: a systematic review. Drug Alcohol Depend. 2020;216:108307. https://doi.org/10.1016/j.drugalcdep.2020.108307.CrossRefPubMed

28.

Dutra L, Stathopoulou G, Basden SL, Leyro TM, Powers MB, Otto MW. A meta-analytic review of psychosocial interventions for substance use disorders. Am J Psychiatry. 2008;165(2):179–87. https://doi.org/10.1176/appi.ajp.2007.06111851.CrossRefPubMed

29.

Griffith JD, Rowan-Szal GA, Roark RR, Simpson DD. Contingency management in outpatient methadone treatment: a meta-analysis. Drug Alcohol Depend. 2000;58(1–2):55–66. https://doi.org/10.1016/S0376-8716(99)00068-X.CrossRefPubMed

30.

Prendergast M, Podus D, Finney J, Greenwell L, Roll J. Contingency management for treatment of substance use disorders: a meta-analysis: Centre for Reviews and Dissemination (UK); 2006. [cited 2020 Feb 25]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK72392/

31.

Lussier JP, Heil SH, Mongeon JA, Badger GJ, Higgins ST. A meta-analysis of voucher-based reinforcement therapy for substance use disorders. Addiction. 2006;101(2):192–203. https://doi.org/10.1111/j.1360-0443.2006.01311.x.CrossRefPubMed

32.

Ginley MK, Pfund RA, Rash CJ, Zajac K. Long-term efficacy of contingency management treatment based on objective indicators of abstinence from illicit substance use up to 1 year following treatment: a meta-analysis. J Consult Clin Psychol. 2021;89(1):58–71. https://doi.org/10.1037/ccp0000552.CrossRefPubMedPubMedCentral

33.

Rawson RA, Marinelli-Casey P, Anglin MD, Dickow A, Frazier Y, Gallagher C, et al. A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence. Addiction. 2004;99(6):708–17. https://doi.org/10.1111/j.1360-0443.2004.00707.x.CrossRefPubMed

34.

Reback CJ, Fletcher JB, Shoptaw S, Mansergh G. Exposure to theory-driven text messages is associated with HIV risk reduction among methamphetamine-using men who have sex with men. AIDS Behav. 2015;19(Suppl 2):130–41. https://doi.org/10.1007/s10461-014-0985-7.CrossRefPubMed

35.

Reback CJ, Fletcher JB, Swendeman DA, Metzner M. Theory-based text-messaging to reduce methamphetamine use and HIV sexual risk behaviors among men who have sex with men: automated unidirectional delivery outperforms bidirectional peer interactive delivery. AIDS Behav. 2019;23(1):37–47. https://doi.org/10.1007/s10461-018-2225-z.CrossRefPubMedPubMedCentral

36.

Reback CJ, Fletcher JB, Kisler KA. Text messaging improves HIV care continuum outcomes among young adult trans women living with HIV: Text Me, Girl! AIDS Behav. 2021;25(9):3011–23. https://doi.org/10.1007/s10461-021-03352-3.CrossRefPubMed

37.

Reback CJ, Fletcher JB, Leibowitz AA. Cost effectiveness of text messages to reduce methamphetamine use and HIV sexual risk behaviors among men who have sex with men. J Subst Abus Treat. 2019;100:59–63. https://doi.org/10.1016/j.jsat.2019.02.006.CrossRef

38.

Gómez W, Olem D, Andrews R, Discepola MV, Ambrose P, Dilworth SE, et al. Optimizing contingency management with methamphetamine-using men who have sex with men. Cogn Behav Pract. 2018;25(2):286–95. https://doi.org/10.1016/j.cbpra.2017.08.003.CrossRef

39.

Parsons JT, John SA, Millar BM, Starks TJ. Testing the efficacy of combined motivational interviewing and cognitive behavioral skills training to reduce methamphetamine use and improve HIV medication adherence among HIV-positive gay and bisexual men. AIDS Behav. 2018;22(8):2674–86. https://doi.org/10.1007/s10461-018-2086-5.CrossRefPubMedPubMedCentral

40.

Dugosh K, Abraham A, Seymour B, McLoyd K, Chalk M, Festinger D. A systematic review on the use of psychosocial interventions in conjunction with medications for the treatment of opioid addiction. J Addict Med. 2016;10(2):91–101. https://doi.org/10.1097/ADM.0000000000000193.CrossRefPubMedCentral

41.

Assanangkornchai S, Balthip Q, Edwards JG. assistance of the ASSIST-SBI Development Co-investigators. Implementing the Alcohol, Smoking, Substance Involvement Screening Test and linked brief intervention service in primary care in Thailand. J Public Health Oxf Engl. 2014;36(3):443–9. https://doi.org/10.1093/pubmed/fdu011.CrossRef

42.

Sorsdahl K, Myers B, Ward C, Matzopoulos R, Mtukushe B, Nicol A, et al. Screening and brief interventions for substance use in emergency departments in the Western Cape province of South Africa: views of health care professionals. Int J Inj Control Saf Promot. 2014;21(3):236–43. https://doi.org/10.1080/17457300.2013.811267.CrossRef

43.

Wechsberg WM, Luseno WK, Karg RS, Young S, Rodman N, Myers B, et al. Alcohol, cannabis, and methamphetamine use and other risk behaviours among Black and Coloured South African women: a small randomized trial in the Western Cape. Int J Drug Policy. 2008;19(2):130–9. https://doi.org/10.1016/j.drugpo.2007.11.018.CrossRefPubMedPubMedCentral

44.

Chen W, Hong Y, Zou X, McLaughlin MM, Xia Y, Ling L. Effectiveness of prize-based contingency management in a methadone maintenance program in China. Drug Alcohol Depend. 2013;133(1):270–4. https://doi.org/10.1016/j.drugalcdep.2013.05.028.CrossRefPubMed

45.

Hser Y-I, Li J, Jiang H, Zhang R, Du J, Zhang C, et al. Effects of a randomized contingency management intervention on opiate abstinence and retention in methadone maintenance treatment in China. Addiction. 2011;106(10):1801–9. https://doi.org/10.1111/j.1360-0443.2011.03490.x.CrossRefPubMedPubMedCentral

46.

Cohen A, McGregor C. The emergence of methamphetamine in Thailand: interventions and treatment. In: Pates R, Riley D, editors. Interventions for Amphetamine Misuse. Oxford: Wiley-Blackwell Publishing; 2010. p. 159–71.

47.

Magidson JF, Gouse H, Burnhams W, Wu CYY, Myers B, Joska JA, et al. Beyond methamphetamine: Documenting the implementation of the Matrix model of substance use treatment for opioid users in a South African setting. Addict Behav. 2017;66:132–7. https://doi.org/10.1016/j.addbeh.2016.11.014.CrossRefPubMed

48.

Nguyen Huu C, Thuy KC. Application of Matrix model in support of trreatment and recovery for ATS dependents (Nghiên cứu sử dụng liệu pháp tâm lý Matrix trong hỗ trợ điều trị nghiện và phục hồi chức năng cho người nghiện ma túy tổng hợp dạng amphetamine). Hanoi; 2016.

49.

Curran GM, Bauer M, Mittman B, Pyne JM, Stetler C. Effectiveness-implementation hybrid designs. Med Care. 2012;50(3):217–26. https://doi.org/10.1097/MLR.0b013e3182408812.CrossRefPubMedPubMedCentral

50.

Damschroder LJ, Aron DC, Keith RE, Kirsh SR, Alexander JA, Lowery JC. Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science. Implement Sci. 2009;4(1):50. https://doi.org/10.1186/1748-5908-4-50.CrossRefPubMedPubMedCentral

51.

Damschroder LJ, Hagedorn HJ. A guiding framework and approach for implementation research in substance use disorders treatment. Psychol Addict Behav. 2011;25(2):194–205. https://doi.org/10.1037/a0022284.CrossRefPubMed

52.

Hanoi Centre for Disease Control. MMT program data. 2021.

53.

HCMC Centre for Disease Control. MMT program data. 2021.

54.

Roll JM, Shoptaw S. Contingency management: Schedule effects. Psychiatry Res. 2006;144(1):91–3. https://doi.org/10.1016/j.psychres.2005.12.003.CrossRefPubMed

55.

Giang LM, Li MJ, Okafor CN, Diep NB, Shoptaw SJ. Correlates of methamphetamine use severity among patients receiving methadone maintenance treatment for opioid use disorder in Vietnam. J Subst Abus Treat. 2022;132:108461. https://doi.org/10.1016/j.jsat.2021.108461.CrossRef

56.

McGregor C, Srisurapanont M, Mitchell A, Longo MC, Cahill S, White JM. Psychometric evaluation of the Amphetamine Cessation Symptom Assessment. J Subst Abus Treat. 2008;34(4):443–9. https://doi.org/10.1016/j.jsat.2007.05.007.CrossRef

57.

Bush K, Kivlahan DR, McDonell MB, Fihn SD, Bradley KA. The AUDIT alcohol consumption questions (AUDIT-C): an effective brief screening test for problem drinking. Ambulatory Care Quality Improvement Project (ACQUIP). Alcohol Use Disorders Identification Test. Arch Intern Med. 1998;158(16):1789–95. https://doi.org/10.1001/archinte.158.16.1789.CrossRefPubMed

58.

Clement S, Brohan E, Jeffery D, Henderson C, Hatch SL, Thornicroft G. Development and psychometric properties the Barriers to Access to Care Evaluation scale (BACE) related to people with mental ill health. BMC Psychiatry. 2012;12(1):36. https://doi.org/10.1186/1471-244X-12-36.CrossRefPubMedPubMedCentral

59.

Lovibond PF, Lovibond SH. The structure of negative emotional states: comparison of the Depression Anxiety Stress Scales (DASS) with the Beck Depression and Anxiety Inventories. Behav Res Ther. 1995;33(3):335–43. https://doi.org/10.1016/0005-7967(94)00075-U.CrossRefPubMed

60.

Tran TD, Tran T, Fisher J. Validation of the depression anxiety stress scales (DASS) 21 as a screening instrument for depression and anxiety in a rural community-based cohort of northern Vietnamese women. BMC Psychiatry. 2013;13(1):24. https://doi.org/10.1186/1471-244X-13-24.CrossRefPubMedPubMedCentral

61.

Sherbourne CD, Stewart AL. The MOS social support survey. Soc Sci Med. 1991;32(6):705–14. https://doi.org/10.1016/0277-9536(91)90150-B.CrossRefPubMed

62.

Khuong LQ, Vu T-VT, Huynh V-AN, Thai TT. Psychometric properties of the medical outcomes study: social support survey among methadone maintenance patients in Ho Chi Minh City, Vietnam: a validation study. Subst Abuse Treat Prev Policy. 2018;13(1):8. https://doi.org/10.1186/s13011-018-0147-4.CrossRefPubMedPubMedCentral

63.

Mai VQ, Sun S, Minh HV, Luo N, Giang KB, Lindholm L, et al. An EQ-5D-5L value set for Vietnam. Qual Life Res Int J Qual Life Asp Treat Care Rehab. 2020;29(7):1923–33. https://doi.org/10.1007/s11136-020-02469-7.CrossRef

64.

UNAIDS. Costing guidelines for HIV prevention strategies. 2000.

65.

Hintz J. PASS 12. 2013 [cited 2021 Apr 23]. Available from: https://www.ncss.com/

66.

Dai T, Shete S. Time-varying SMART design and data analysis methods for evaluating adaptive intervention effects. BMC Med Res Methodol. 2016;16(1):112. https://doi.org/10.1186/s12874-016-0202-7.CrossRefPubMedPubMedCentral

67.

Neumann PJ, Sanders GD, Russell LB, Ganiats TG, Siegel JE. Cost-effectiveness in health and medicine: Oxford University Press; 2017. p. 537. https://doi.org/10.1093/acprof:oso/9780190492939.001.0001.CrossRef

68.

Kenward M. The handling of missing data in clinical trials. Clin Investig. 2013;3(3):241–50. https://doi.org/10.4155/cli.13.7.CrossRef

69.

Li P, Stuart EA. Best (but oft-forgotten) practices: missing data methods in randomized controlled nutrition trials. Am J Clin Nutr. 2019;109(3):504–8. https://doi.org/10.1093/ajcn/nqy271.CrossRefPubMedPubMedCentral

70.

Dawson R, Lavori PW. Design and inference for the intent-to-treat principle using adaptive treatment. Stat Med. 2015;34(9):1441–53. https://doi.org/10.1002/sim.6421.CrossRefPubMedPubMedCentral

71.

De Crescenzo F, Ciabattini M, D’Alò GL, De Giorgi R, Del Giovane C, Cassar C, et al. Comparative efficacy and acceptability of psychosocial interventions for individuals with cocaine and amphetamine addiction: A systematic review and network meta-analysis. PLoS Med. 2018;15(12):e1002715. https://doi.org/10.1371/journal.pmed.1002715.CrossRefPubMedPubMedCentral

Title: An adaptive design to screen, treat, and retain people with opioid use disorders who use methamphetamine in methadone clinics (STAR-OM): study protocol of a clinical trial
Authors: Le Minh Giang
Nguyen Thu Trang
Nguyen Bich Diep
Dao Thi Dieu Thuy
Dinh Thanh Thuy
Han Dinh Hoe
Hoang Thi Hai Van
Thai Thanh Truc
Hoa H. Nguyen
Nguyen Ly Lai
Pham Thi Dan Linh
Vu Thi Tuong Vi
Cathy J. Reback
Arleen Leibowitz
Li Li
Chunqing Lin
Michael Li
Do Van Dung
Steve Shoptaw
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Opioids
Opioids
Human Immunodeficiency Virus
Methadone
Published in: Trials / Issue 1/2022
Electronic ISSN: 1745-6215
DOI: https://doi.org/10.1186/s13063-022-06278-w

Keynote webinar | Spotlight on medication adherence

Springer Medicine

An adaptive design to screen, treat, and retain people with opioid use disorders who use methamphetamine in methadone clinics (STAR-OM): study protocol of a clinical trial

Abstract

Background

Method

Discussion

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Method

Discussion

Trial registration

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