老年患者多重用药处方精简干预临床效果的Meta分析
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摘要
目的系统评价处方精简干预对老年多重用药患者临床结局的影响。方法检索数据库公开发表有关老年多重用药患者处方精简干预及相关结局的文献。根据纳入排除标准进行筛选,采用Review Manager 5.3软件,利用I~2衡量文献研究内容的异质性,运用固定效应模型或随机效应模型合并分析处方精简干预对老年多重用药患者临床结局的影响。结果本研究最终纳入18篇随机对照研究(RCT),文献总体质量较好。Meta分析显示,处方精简干预不能降低老年多重用药患者全因死亡率[OR=0.86, 95%CI(0.67～1.09)]。不同干预方式比较:特异性处方精简干预在一定程度上降低全因死亡率[OR=0.68, 95%CI(0.51～0.92);P<0.05]。随访时间长短比较:随访时间较长(>6个月)相较于随访时间较短(≤6个月)的处方精简干预在降低全因死亡率方面具有一定优势[OR=0.58, 95%CI(0.39～0.86)vsOR=1.02, 95%CI(0.76～1.36);P<0.05]。不同年龄段比较:对不同年龄段患者进行精简干预,全因死亡率没有变化[OR=0.63, 95%CI(0.40～1.02)vsOR=0.95, 95%CI(0.72～1.25);P>0.05]。认知状态比较:对不同认知状态患者进行精简干预,全因死亡率不发生改变[OR=0.63, 95%CI(0.37～1.07)vsOR=0.93, 95%CI(0.71～1.22);P>0.05]。处方精简干预不能减少跌倒患者的数量[OR=0.98, 95%CI(0.74～1.27)],但可以显著降低年人均跌倒次数[MD=-0.11, 95%CI(-0.21～-0.02)],缩短患者住院时长[MD=-0.49, 95%CI(-0.76～-0.22)]。结论现有数据分析表明,处方精简干预不能降低老年多重用药患者的全因死亡率,特异性或长时间随访的处方精简干预在降低患者全因死亡率方面有一定优势;处方精简干预不能减少跌倒患者人数但可以减少患者跌倒次数;处方精简干预有缩短住院时长的趋势。特异性处方精简干预在减少不适当的多重用药方面是安全可行的。
Objective To perform a systematic review to evaluate the impact of deprescribing interventions on the clinical outcomes in the elderly patients with polypharmacy.Methods A thorough search was made in the databases of the literature related to deprescribing interventions in the elderly patients with polypharmacy.The studies were screened according to the inclusion and the exclusion criteria.I~2 test for heterogeneity among studies was performed using Review Manager 5.3.Fixed effect model or random effect model was employed to analyze the impact of deprescribing interventions in the elderly patients with polypharmacy.Results A total of 18 studies were selected for the final randomized controlled trials(RCT),with overall quality of the literature being good.Meta-analysis showed that deprescribing interventions were not able to decrease all-cause mortality among elderly patients with polypharmacy [OR=0.86,95%CI(0.67-1.09)].The comparison between different intervention methods showed that patient-specific interventions decreased all-cause mortality [OR=0.68,95%CI(0.51-0.92)].The comparison of the follow-up length showed that long follow-up(>6 months) outperformed shorter follow-up(≤6 months) in decreasing all-cause mortality [OR=0.58,95%CI(0.39-0.86) vs OR=1.02,95%CI(0.76-1.36);P<0.05].The comparison between different age groups showed no change in all-cause mortality [OR=0.63,95% CI(0.40-1.02) vs OR=0.95,95%CI(0.72-1.25);P>0.05].The comparison of cognitive status showed that deprescribing interventions in the groups of different cognitive statuses did not alter all-cause mortality [OR=0.63,95%CI(0.37-1.07) vs OR=0.93,95%CI(0.71-1.22);P>0.05].Deprescribing interventions did not decrease the number of patients with falls [OR=0.98,95%CI(0.74-1.27)] but were able to significantly decrease the average falls they experienced [MD=-0.11 95%CI(-0.21--0.02) ] and the length of hospital stay [MD =-0.49,95% CI(-0.76--0.22) ].Conclusion The analysis of data available suggested that deprescribing interventions did not decrease all-cause mortality in elderly patients with polypharmacy,but patient-specific or long-term follow-up seemed to have an advantage in decreasing it;that deprescribing interventions did not decrease the number of patients with falls but reduced the number of falls they experienced and the length of hospital stay.Patient-specific deprescribing interventions seem to be safe and feasible in decreasing inappropriate polypharmacy.
Objective To perform a systematic review to evaluate the impact of deprescribing interventions on the clinical outcomes in the elderly patients with polypharmacy.Methods A thorough search was made in the databases of the literature related to deprescribing interventions in the elderly patients with polypharmacy.The studies were screened according to the inclusion and the exclusion criteria.I~2 test for heterogeneity among studies was performed using Review Manager 5.3.Fixed effect model or random effect model was employed to analyze the impact of deprescribing interventions in the elderly patients with polypharmacy.Results A total of 18 studies were selected for the final randomized controlled trials(RCT),with overall quality of the literature being good.Meta-analysis showed that deprescribing interventions were not able to decrease all-cause mortality among elderly patients with polypharmacy [OR=0.86,95%CI(0.67-1.09)].The comparison between different intervention methods showed that patient-specific interventions decreased all-cause mortality [OR=0.68,95%CI(0.51-0.92)].The comparison of the follow-up length showed that long follow-up(>6 months) outperformed shorter follow-up(≤6 months) in decreasing all-cause mortality [OR=0.58,95%CI(0.39-0.86) vs OR=1.02,95%CI(0.76-1.36);P<0.05].The comparison between different age groups showed no change in all-cause mortality [OR=0.63,95% CI(0.40-1.02) vs OR=0.95,95%CI(0.72-1.25);P>0.05].The comparison of cognitive status showed that deprescribing interventions in the groups of different cognitive statuses did not alter all-cause mortality [OR=0.63,95%CI(0.37-1.07) vs OR=0.93,95%CI(0.71-1.22);P>0.05].Deprescribing interventions did not decrease the number of patients with falls [OR=0.98,95%CI(0.74-1.27)] but were able to significantly decrease the average falls they experienced [MD=-0.11 95%CI(-0.21--0.02) ] and the length of hospital stay [MD =-0.49,95% CI(-0.76--0.22) ].Conclusion The analysis of data available suggested that deprescribing interventions did not decrease all-cause mortality in elderly patients with polypharmacy,but patient-specific or long-term follow-up seemed to have an advantage in decreasing it;that deprescribing interventions did not decrease the number of patients with falls but reduced the number of falls they experienced and the length of hospital stay.Patient-specific deprescribing interventions seem to be safe and feasible in decreasing inappropriate polypharmacy.
引文
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[6] Rodríguez-Pérez A, Alfaro-Lara ER, Albiňana-Perez S, et al. Novel tool for deprescribing in chronic patients with multimorbidity: List of Evidence-Based Deprescribing for Chronic Patients criteria[J]. Geriatr Gerontol Int, 2017,17 (11): 2200-2207. DOI: 10.1111/ggi.13062.
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[8] Thillainadesan J, Gnjidic D, Green S, et al. Impact of deprescribing interventions in older hospitalised patients on prescribing and clinical outcomes: a systematic review of randomised trials[J]. Drugs Aging, 2018, 35(4): 303-319. DOI: 10.1007/s40266-018-0536-4.
[9] Hanlon JT, Weinberger M, Samsa GP, et al. A randomized, controlled trial of a clinical pharmacist intervention to improve inappropriate prescribing in elderly outpatients with polypharmacy[J]. Am J Med, 1996, 100(4): 429-437. DOI: 10.1016/S0002-9343(97)89519-8.
[10] Tabloski PA, Cooke KM, Thoman EB, et al. A procedure for withdrawal of sleep medication in elderly women who have been long-term users[J]. J Gerontol Nurs,1998, 24(9): 20-28.
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[12] Allard J, Hébert R, Rioux M, et al. Efficacy of a clinical medication review on the number of potentially inappropriate prescriptions prescribed for community-dwelling elderly people[J]. CMAJ, 2001, 164(9): 1291-1296.
[13] Weber V, White A, McIlvried R, et al. An electronic medical record (EMR)-based intervention to reduce polypharmacy and falls in an ambulatory rural elderly population[J]. J Gen Intern Med, 2008, 23(4): 399-404.DOI: 10.1007/s11 606-007-0482-z.
[14] Gnjidic D, Le Couteur DG, Abernethy DR, et al. A pilot rando-mized clinical trial utilizing the drug burden index to reduce exposure to anticholinergic and sedative medications in older people[J]. Ann Pharmacother, 2010, 44(11): 1725-1732.DOI: 10.1345/aph.1P310.
[15] Beer C, Loh PK, Peng YG, et al. A pilot randomized controlled trial of deprescribing[J]. Ther Adv Drug Saf, 2011, 2(2): 37-43. DOI: 10.1177/2042098611400332.
[16] Gallagher PF, O′Connor MN, O′Mahony D, et al. Prevention of potentially inappropriate prescribing for elderly patients: a randomized controlled trial using STOPP/START criteria[J]. Clin Pharmacol Ther, 2011, 89(6): 845-854. DOI: 10.1038/clpt.2011.44.
[17] Dalleur O, Boland B, Losseau C, et al. Reduction of potentially inappropriate medications using the STOPP criteria in frail older inpatients: a randomised controlled study[J]. Drugs Aging, 2014, 31(4): 291-298. DOI: 10.1007/s40266-014-0157-5.
[18] Gollarte FG, Júlvez JB, López IF, et al. An educational intervention on drug use in nursing homes improves health outcomes resource utilization and reduces inappropriate drug prescription[J]. J Am Med Dir Assoc, 2014, 15(12): 885-891. DOI: 10.1016/j.jamda.2014.04.010.
[19] Pitkala KH, Juola AL, Kautiainen H, et al. Education to reduce potentially harmful medication use among residents of assisted living facilities: a randomized controlled trial[J]. J Am Med Dir Assoc, 2014, 15(12): 892-898. DOI: 10.1016/j.jamda.2014.04.002.
[20] Tannenbaum C, Martin P, Tamblyn R, et al. Reduction of inappropriate benzodiazepine prescriptions among older adults through direct patient education: the EMPOWER cluster randomized trial[J]. JAMA Int Med, 2014, 174(6): 890-898. DOI:10.1001/jamainternmed.2014.949.
[21] Potter K, Flicker L, Page A, et al. Deprescribing in frail older people: a randomised controlled trial[J]. PLoS One, 2016, 11(3): e0149984. DOI:10.1371/journal.pone.0149984.
[22] Wehling M, Burkhardt H, Kuhn-Thiel A, et al. VALFORTA: a randomised trial to validate the FORTA (Fit fOR The Aged) classification[J]. Age Ageing, 2016, 45(2): 262-267. DOI: 10.109 3/ageing/afv200.
[23] Boyé ND, van der Velde N, de Vries OJ, et al. Effectiveness of medication withdrawal in older fallers: results from the Improving Medication Prescribing to reduce Risk Of FALLs (IMPROveFALL) trial[J]. Age Ageing, 2017, 46(1): 142-146. DOI: 10.1093/ageing/afw161.
[24] Polinder S, BoyéNicole D, Mattace-Raso FU, et al. Cost-utility of medication withdrawal in older fallers: results from the improving medication prescribing to reduce risk of FALLs (IMPROveFALL) trial[J]. BMC Geriatr, 2016, 16(1): 179-189. DOI: 10.1186/s12877-016-0354-7.
[25] Wouters H, Scheper J, Koning H, et al. Discontinuing inappropriate medication use in nursing home residents: a cluster rando-mized controlled trial[J]. Ann Intern Med, 2017, 167(9): 609-617. DOI: 10.7326/M16-2729.
[26] Pazan F, Burkhardt H, Frohnhofen H, et al. Changes in prescription patterns in older hospitalized patients: the impact of FORTA on disease-related over- and under-treatments[J]. Eur J Clin Pharmacol, 2018, 74(3): 339-347. DOI: 10.1007/s00228-017-2383-3.
[27] 曾英彤, 杨敏, 伍俊妍, 等. 药学服务新模式——处方精简(Deprescribing)[J]. 今日药学, 2017, 27(6): 390-393. DOI: 10.12048/j.issn.1674-229X.2017.06.008. Zeng YT, Yang M, Wu JY, et al. A new model of pharmaceutical services — Deprescribing[J]. Pharmacy Today, 2017, 27(6): 339-347. DOI:10.1007/s00228-017-2383-3.
[28] Turner JP, Jamsen KM, Shakib S, et al. Polypharmacy cut-points in older people with cancer: how many medications are too many[J]. Support Care Cancer, 2016, 24(4): 1831-1840. DOI: 10.1007/s00520-015-2970-8.
[29] Huizer-Pajkos A, Kane AE, Howlett SE, et al. Adverse geriatric outcomes secondary to polypharmacy in a mouse model: the influence of aging[J]. J Gerontol A Biol Sci Med Sci, 2016, 71(5): 5771-5777. DOI: 10.1093/gerona/glv046.
[30] Iyer S, Naganathan V, McLachlan AJ, et al. Medication withdrawal trials in people aged 65 years and older[J]. Drugs Aging, 2008, 25(12): 1021-1031. DOI: 10.2165/0002512-200825120-00004.
[2] Tangiisuran B, Wright J, Van der Cammen T, et al. Adverse drug reactions in elderly: challenges in identification and improving preventative strategies[J]. Age Ageing, 2009,38(4): 358-359. DOI: 10.1093/ageing/afp050.
[3] Woodward M. Deprescribing: achieving better health outcomes for older people through reducing medications[J]. J Pharm Pract Res, 2003, 33(4): 323-328.DOI:10.1002/jppr2003334323.
[4] The PrescQIPP Polypharmacy and Deprescribing webkit. 2016, PrescQIPP. https://www.prescqipp.info/projects/polypharmacy-and-deprescribing.
[5] Farrell B. Deprescribing Guidelines and Algorithms[EB].[2016-10-23], http://deprescribing.org/resource/deprescribing-guidelines and algorithms.
[6] Rodríguez-Pérez A, Alfaro-Lara ER, Albiňana-Perez S, et al. Novel tool for deprescribing in chronic patients with multimorbidity: List of Evidence-Based Deprescribing for Chronic Patients criteria[J]. Geriatr Gerontol Int, 2017,17 (11): 2200-2207. DOI: 10.1111/ggi.13062.
[7] Cooper JA, Cadogan CA, Patterson SM, et al. Interventions to improve the appropriate use of polypharmacy for older people: a cochrane systematic review[J]. Br Med J, 2015, 5(12): e009235. DOI: 10.1136/bmjopen-2015-009235.
[8] Thillainadesan J, Gnjidic D, Green S, et al. Impact of deprescribing interventions in older hospitalised patients on prescribing and clinical outcomes: a systematic review of randomised trials[J]. Drugs Aging, 2018, 35(4): 303-319. DOI: 10.1007/s40266-018-0536-4.
[9] Hanlon JT, Weinberger M, Samsa GP, et al. A randomized, controlled trial of a clinical pharmacist intervention to improve inappropriate prescribing in elderly outpatients with polypharmacy[J]. Am J Med, 1996, 100(4): 429-437. DOI: 10.1016/S0002-9343(97)89519-8.
[10] Tabloski PA, Cooke KM, Thoman EB, et al. A procedure for withdrawal of sleep medication in elderly women who have been long-term users[J]. J Gerontol Nurs,1998, 24(9): 20-28.
[11] Campbell AJ, Robertson MC, Gardner MM, et al. Psychotropic medication withdrawal and a home-based exercise program to prevent falls: a randomized controlled trial[J]. J Am Geriatr Soc, 1999, 47(7): 850-853. DOI:10.1111/j.1532-5415.1999.tb03843.x.
[12] Allard J, Hébert R, Rioux M, et al. Efficacy of a clinical medication review on the number of potentially inappropriate prescriptions prescribed for community-dwelling elderly people[J]. CMAJ, 2001, 164(9): 1291-1296.
[13] Weber V, White A, McIlvried R, et al. An electronic medical record (EMR)-based intervention to reduce polypharmacy and falls in an ambulatory rural elderly population[J]. J Gen Intern Med, 2008, 23(4): 399-404.DOI: 10.1007/s11 606-007-0482-z.
[14] Gnjidic D, Le Couteur DG, Abernethy DR, et al. A pilot rando-mized clinical trial utilizing the drug burden index to reduce exposure to anticholinergic and sedative medications in older people[J]. Ann Pharmacother, 2010, 44(11): 1725-1732.DOI: 10.1345/aph.1P310.
[15] Beer C, Loh PK, Peng YG, et al. A pilot randomized controlled trial of deprescribing[J]. Ther Adv Drug Saf, 2011, 2(2): 37-43. DOI: 10.1177/2042098611400332.
[16] Gallagher PF, O′Connor MN, O′Mahony D, et al. Prevention of potentially inappropriate prescribing for elderly patients: a randomized controlled trial using STOPP/START criteria[J]. Clin Pharmacol Ther, 2011, 89(6): 845-854. DOI: 10.1038/clpt.2011.44.
[17] Dalleur O, Boland B, Losseau C, et al. Reduction of potentially inappropriate medications using the STOPP criteria in frail older inpatients: a randomised controlled study[J]. Drugs Aging, 2014, 31(4): 291-298. DOI: 10.1007/s40266-014-0157-5.
[18] Gollarte FG, Júlvez JB, López IF, et al. An educational intervention on drug use in nursing homes improves health outcomes resource utilization and reduces inappropriate drug prescription[J]. J Am Med Dir Assoc, 2014, 15(12): 885-891. DOI: 10.1016/j.jamda.2014.04.010.
[19] Pitkala KH, Juola AL, Kautiainen H, et al. Education to reduce potentially harmful medication use among residents of assisted living facilities: a randomized controlled trial[J]. J Am Med Dir Assoc, 2014, 15(12): 892-898. DOI: 10.1016/j.jamda.2014.04.002.
[20] Tannenbaum C, Martin P, Tamblyn R, et al. Reduction of inappropriate benzodiazepine prescriptions among older adults through direct patient education: the EMPOWER cluster randomized trial[J]. JAMA Int Med, 2014, 174(6): 890-898. DOI:10.1001/jamainternmed.2014.949.
[21] Potter K, Flicker L, Page A, et al. Deprescribing in frail older people: a randomised controlled trial[J]. PLoS One, 2016, 11(3): e0149984. DOI:10.1371/journal.pone.0149984.
[22] Wehling M, Burkhardt H, Kuhn-Thiel A, et al. VALFORTA: a randomised trial to validate the FORTA (Fit fOR The Aged) classification[J]. Age Ageing, 2016, 45(2): 262-267. DOI: 10.109 3/ageing/afv200.
[23] Boyé ND, van der Velde N, de Vries OJ, et al. Effectiveness of medication withdrawal in older fallers: results from the Improving Medication Prescribing to reduce Risk Of FALLs (IMPROveFALL) trial[J]. Age Ageing, 2017, 46(1): 142-146. DOI: 10.1093/ageing/afw161.
[24] Polinder S, BoyéNicole D, Mattace-Raso FU, et al. Cost-utility of medication withdrawal in older fallers: results from the improving medication prescribing to reduce risk of FALLs (IMPROveFALL) trial[J]. BMC Geriatr, 2016, 16(1): 179-189. DOI: 10.1186/s12877-016-0354-7.
[25] Wouters H, Scheper J, Koning H, et al. Discontinuing inappropriate medication use in nursing home residents: a cluster rando-mized controlled trial[J]. Ann Intern Med, 2017, 167(9): 609-617. DOI: 10.7326/M16-2729.
[26] Pazan F, Burkhardt H, Frohnhofen H, et al. Changes in prescription patterns in older hospitalized patients: the impact of FORTA on disease-related over- and under-treatments[J]. Eur J Clin Pharmacol, 2018, 74(3): 339-347. DOI: 10.1007/s00228-017-2383-3.
[27] 曾英彤, 杨敏, 伍俊妍, 等. 药学服务新模式——处方精简(Deprescribing)[J]. 今日药学, 2017, 27(6): 390-393. DOI: 10.12048/j.issn.1674-229X.2017.06.008. Zeng YT, Yang M, Wu JY, et al. A new model of pharmaceutical services — Deprescribing[J]. Pharmacy Today, 2017, 27(6): 339-347. DOI:10.1007/s00228-017-2383-3.
[28] Turner JP, Jamsen KM, Shakib S, et al. Polypharmacy cut-points in older people with cancer: how many medications are too many[J]. Support Care Cancer, 2016, 24(4): 1831-1840. DOI: 10.1007/s00520-015-2970-8.
[29] Huizer-Pajkos A, Kane AE, Howlett SE, et al. Adverse geriatric outcomes secondary to polypharmacy in a mouse model: the influence of aging[J]. J Gerontol A Biol Sci Med Sci, 2016, 71(5): 5771-5777. DOI: 10.1093/gerona/glv046.
[30] Iyer S, Naganathan V, McLachlan AJ, et al. Medication withdrawal trials in people aged 65 years and older[J]. Drugs Aging, 2008, 25(12): 1021-1031. DOI: 10.2165/0002512-200825120-00004.