Cited by 367Medication Adherence and CompliancePharmacy and Medical PracticesPatient Safety and Medication Errors

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Medication adherence outcomes of 771 intervention trials: Systematic review and meta-analysis

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Conn, Vicki S., Ruppar, Todd M.·2017·Preventive Medicine

DOI 10.1016/j.ypmed.2017.03.008PMC PMC5467216

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Abstract

Excellent medication adherence contributes to decreases in morbidity, mortality, and health care costs. Although researchers have tested many interventions to increase adherence, results are sometimes conflicting and often unclear. This systematic review applied meta-analytic procedures to integrate primary research that tested medication adherence interventions. Comprehensive searching completed in 2015 located 771 published and unpublished intervention studies with adherence behavior outcomes. Random-effects model analysis calculated standardized mean difference effect sizes. Meta-analytic moderator analyses examined the association between adherence effect sizes and sample, design, and intervention characteristics. Analyses were conducted in 2016. A standardized mean difference effect size of 0.290 comparing treatment and control groups was calculated. Moderator analyses revealed larger effect sizes for habit-based and behavioral-targeted (vs. cognitive-focused) interventions. The most effective interventions were delivered face-to-face, by pharmacists, and administered directly to patients. Effect sizes were smaller in studies with older and homeless participants. Risks of bias were common; effect sizes were significantly lower among studies with masked data collectors and intention-to-treat analyses. The largest effect sizes were reported by studies using medication electronic event monitoring and pill count medication adherence measures. Publication bias was present. This most comprehensive review to date documented that, although interventions can increase adherence, much room remains for improvement. Findings suggest health care providers should focus intervention content on behavioral strategies, especially habit-based interventions, more so than cognitive strategies designed to change knowledge and beliefs.

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Bias in meta-analysis detected by a simple, graphical test
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“[29] Although there is extensive research on interventions to increase adherence of one or possibly two medication classes, [30] less is known about the association of better medication adherence for multiple chronic conditions with Alzheimer’s disease/dementia status.”
Background
Clinical trials of pharmacological interventions for SARS‐CoV‐2 published in leading medical journals report adherence but not how it was assessed
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“10 13 – 16 Prior to this streamlined process, compliance with TIDieR guidelines has been shown to be suboptimal, including Items 11 and 12.”
Method
Nonadherence to antiseizure medications: what have we learned and what can be done next?
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Background
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“One major advantage to BE interventions is that they can address biases and improve behavior with minimal cognitive effort [69].”
Background
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“Previous intervention studies to improve medication adherence only have weak or modest effect sizes, partially because the complexity of adherence is not fully taken into account.(2,37) Our results again highlight the need to identify the underlying reasons for nonadherence, as different aspects of nonadherence may di…”
Background
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“As stronger medication-taking habit has been shown to be associated with better medication adherence [4,10-13], in particular its implementation component, some successful interventions have focused on improving habit [5,14].”
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Method
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“Interventions delivered by pharmacists are significantly more effective at improving adherence than those from other health care professionals, especially when delivered in person with patients at pharmacy counters.(10) A proactive approach to address nonadherence in pharmacies should be undertaken by the following:”
Background
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“Findings can inform design of interventions to improve MA (Conn and Ruppar 2017; Ruppar et al. 2016; Readdean, Heuer, and Scott Parrott 2018) and reduce healthcare cost burdens (Zivin et al. 2010; Holt et al. 2014).”
Background
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“B, in adherence interventions, 11,34 although it takes more than one week to fully form a habit.”
Background
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Kokenge, M. C., & Ruppar, T. M. (2024) · The Journal of Cardiovascular Nursing · doi:10.1097/jcn.0000000000001077 · Cited by 3
Self-citation
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Sun, S., Zhang, B., Zhang, N., Zhang, Y., Zhu, M., & Zhang, M. (2024) · Supportive Care in Cancer · doi:10.1007/s00520-024-08339-z · Cited by 5
“Notably, in most studies conducted thus far, treatment was mainly delivered in a face-to-face manner [12].”
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Yu, Y., Huang, Q., & Qin, K. (2025) · Psychology Health & Medicine · doi:10.1080/13548506.2025.2478659 · Cited by 3
“Poor medication adherence directly influences care efficacy, with substantial adverse effects on treatment outcomes exceeding the implications of healthcare reforms (Conn & Ruppar, 2017).”
Health psychology interventions to improve adherence to maintenance therapies in asthma
Normansell, R., Chan, A. H. Y., Katzer, C. B., Kew, K. M., Mes, M. A., Newby, C., Chauhan, A., Taylor, S. J., Pinnock, H., Sheikh, A., et al. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd013147 · Cited by 3
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Background
Patients’ Educational Program Could Improve Azathioprine Adherence in Crohn’s Disease Maintenance Therapy
Wang, L., Fan, R., Zhang, C., Hong, L., Zhang, T., Wang, Z., & Zhong, J. (2020) · Gastroenterology Research and Practice · doi:10.1155/2020/6848293 · Cited by 3
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Costa, A. T., Lima, H. R. D. S., de Lyra, D. P., Filho, A. D. O., & Walker, C. I. B. (2025) · International Journal of Pharmacy Practice · doi:10.1093/ijpp/riaf029 · Cited by 2
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Taher, S. G., Schutte, A. E., Hurst, J. R., Gale, C. P., & Ansari, S. (2025) · Journal of Multimorbidity and Comorbidity · doi:10.1177/26335565251341389 · Cited by 2
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Reggiani, L. C., Londero, I., & da Rocha, N. S. (2025) · Scientific Reports · doi:10.1038/s41598-025-12176-3 · Cited by 2
“Ways to improve therapeutic adherence were reviewed in a meta-analysis carried out by Conn & Ruppar (2017) 56 in which the best interventions found were those focused on behavior (e.g. goal setting, rewards) and habits (e.g. attachment of adherence to pre-existing habits), carried out face-to-face…”
Adherence, Persistence, and Blood Pressure Control in Hypertensive Patients: A Cross-Sectional Study in Mureș County, Romania
Tătar, R., Mărușteri, M., Iancu, D.-G., Mareş, R. G., Moldovan, D.-A., Varga, A., & Ţilea, I. (2025) · Medical Sciences · doi:10.3390/medsci13030119 · Cited by 5
“This finding, typical in behavioral research, underscores why multifaceted interventions addressing multiple barriers simultaneously consistently outperform single-component approaches [67].”
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“Practice-based pharmacists have the appropriate expertise to not only assist with adherence but also to rationalise medication regimes to improve MA, with previous intervention trials showing that pharmacists are the most effective interventionists when looking to improve MA [27].”
Influential
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“Moreover, among behavioral strategies, those aimed at developing habits benefit adherence to medication the most [11].”
Background
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“…realiza-das en todo el mundo y entre sus resultados destaca que aquellas intervenciones realizadas por los farmacéuticos comunitarios (FC) aumentaban de manera significati-va la adherencia al tratamiento de los pacientes frente a aquellas realizadas por otros profesionales sanitarios (15).”
Background
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“12 Habits are associations between contexts and actions that develop through repeated rewards and learning.”
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“A meta-analysis of 771 intervention trials showed that the most effective interventions to improve patients’ medication adherence in chronic diseases like asthma were face-to-face, direct-to-patient services provided by pharmacists [11, 12].”
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Retracted
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Background
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Symposium Summaries
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“Adherence interventions designed to build habits are amongst those with the largest effect sizes (Conn & Ruppar, 2017), and previous work has indicated that habit strength is a potentially important intervention target for supporting self-management behaviors (Phillips et al., 2016).”
Background
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Efficacy of a Health Belief Model-Based Intervention for Anticoagulant Adherence in Patients With Atrial Fibrillation: A Randomized Controlled Trial
Chen, P.-T., HSIEH, M., Shih-Chang, K., & Wang, T.-J. T. (2022) · Research and theory for nursing practice · doi:10.1891/rtnp-2021-0068 · Cited by 1
Addressing Contamination Bias in Child Maltreatment Research: Innovative Methods for Enhancing the Accuracy of Causal Estimates
Shenk, C. E., Olson, A. E., Dunning, E. D., Shores, K., Ram, N., Fisher, Z. F., Felt, J. M., & Chimed‐Ochir, U. (2023) · Child maltreatment solutions network · doi:10.1007/978-3-031-33739-0_2 · Cited by 1
Construction of Personalized Predictive Models for Missed Medication Doses Using Wearable Device Data: Prospective Observational Study
Iino, H., Kizaki, H., Imai, S., & Hori, S. (2025) · JMIR Formative Research · doi:10.2196/72113 · Cited by 1
“Various factors influence medication adherence and are closely related to the patient’s lifestyle [9-12].”
The educational level impact on treatment adherence in PDE5i‐naïve men with erectile dysfunction: A real‐life cross‐sectional study
Birolini, G., Bertini, A., Pozzi, E., Raffo, M., Negri, F., Corsini, C., Belladelli, F., d’Arma, A., Boeri, L., Montorsi, F., et al. (2025) · Andrology · doi:10.1111/andr.70092 · Cited by 1
“25,26 Our study examined the association between educational status and PDE5i adherence patterns in men with new onset ED and totally naïve to PDE5i therapy, revealing differences in treatment continuation across education levels.”
Ambient Computing to Support in-home Seniors Medication Habits
Valenzuela-Beltrán, M., & Rodríguez, M. D. (2018) · Mexican Conference on Human-Computer Interaction (MexIHC) · doi:10.1145/3293578.3298779 · Cited by 1
“And among behavioral strategies, those aimed at forming habits are those that best benefit adherence to medication [4].”
Background
Patients' Perceptions of Compliance with Tuberculosis Medication in Lamongan
Octavia, D., & Utami, P. (2020) · JURNAL MIDPRO · doi:10.30736/md.v12i2.238
Diseño, implantación y evaluación de un servicio de Sistemas Personalizados de Dosificación en una farmacia institucional de la ciudad de Córdoba
Martin, Y., Cabral, G., Zaffaroni, M. F. S., & Armando, P. D. (2022) · Revista de la Facultad de Ciencias Médicas de Córdoba · doi:10.31053/1853.0605.v79.n4.35951 · Cited by 1
“Aquel SPFA ligado directamente a mejorar la adherencia terapéutica, significativamente valioso y efectivo según los estudios clínicos((7-8)), es el servicio de provisión de Sistemas Personalizados de Dosificación (SPD).”
Background
Medication discharge teaching in pediatric hematopoietic stem cell transplantation: teaching characteristics, caregiver perceptions, and postdischarge adherence
Szulczewski, L., Carmody, J. K., Tillery, R., Nelson, A. S., & Pai, A. L. H. (2022) · Journal of Psychosocial Oncology Research and Practice · doi:10.1097/or9.0000000000000088 · Cited by 1
“It is well established that both knowledge and behavior must be targeted for optimal adherence([13]) with behavioral interventions demonstrating a more robust change in outcomes.([14]) Therefore, specific behavioral training for pharmacists might be beneficial to optimize adherence promotion.”
Is it possible to diagnose therapeutic adherence in mild cognitive impairment and dementia patients in clinical practice?
Barnestein‐Fonseca, P., Guerrero-Pertiñez, G., Parra, J. G., Valera-Moreno, E., & Mayoral, F. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1362168 · Cited by 2
“After half a century of adherence research and increased knowledge about the more than 200 factors known to in ﬂ uence adherence, adherence rates remain relatively unchanged (Vrijens et al., 2012; Conn and Ruppar, 2017; Ellis et al., 2023).”
Background
The phenomenon of complete treatment refusal in patients with acute cerebrovascular accident (according to the LIS-2 registry)
Lukina, Y. V., Кутишенко, Н. П., Zagrebelny, A. V., Ginzburg, М. L., Martsevich, S. Y., & Drapkina, O. M. (2024) · Rational Pharmacotherapy in Cardiology · doi:10.20996/1819-6446-2024-3040 · Cited by 1
Optimizing the Use of Personal Values to Promote Medication Adherence: A Randomized Controlled Trial Comparing Affective and Behavioral Responses to Theory-Driven Domain Congruent Versus Incongruent Values Approaches
Finkelstein, L. B., Bright, E. E., Gu, H. C. J., & Arch, J. J. (2024) · Annals of Behavioral Medicine · doi:10.1093/abm/kaae064 · Cited by 1
Nurse-led medication self-management intervention in the improvement of medication adherence in adult patients with multi-morbidity: A Protocol for a Feasibility Randomized controlled trial
Singh, K., Joy, G. V., Bulushi, A. A., Alomari, A. M. A., Mannethodi, K., Kunjavara, J., Hassan, N. P., Idris, Z., Yassin, M. A., & Lenjawi, B. A. (2025) · Global Epidemiology · doi:10.1016/j.gloepi.2025.100184 · Cited by 1
Analysis of factors affecting treatment adherence in patients with keloid disease
Ge, Q., Huang, Y., Wu, J., Ma, J., He, T., Zhang, Q., Wang, Q. K., & Quan, G. (2025) · Archives of Dermatological Research · doi:10.1007/s00403-025-03849-0 · Cited by 1
“Treatment adherence refers to the degree to which patients follow medical advice [14].”
A simple experiment to improve adherence for taking the oral contraceptive pill: An exploratory study of behavioural mechanisms
Liddelow, C., Mullan, B. A., & Boyes, M. E. (2025) · British Journal of Health Psychology · doi:10.1111/bjhp.12788 · Cited by 1
“…et al., 2007) to see the minimum number of participants needed to detect a small-medium effect size ( f = 0.25; based on meta-analysis findings from Conn and Ruppar (2017)) using a repeated measures within-between ANOVA, with α = .05, power = 0.80, four groups and two-time points, a minimum sample…”
Influential
Turkish translation and cultural adaptation of the Ascertaining Barriers to Compliance taxonomy for medication adherence
Göncüoğlu, C., Kara, E., Ceylan, C., Ay, P., Sancar, M., & Okuyan, B. (2025) · British Journal of Clinical Pharmacology · doi:10.1002/bcp.70077 · Cited by 1
Psycho-Social Determinants and Strategies for Facilitating Adherence to a Complex Medication Regimen in Cancer Treatment
Song, Y. (2019) · doi:10.7916/d8-qxym-5233 · Cited by 1
Novel Phototherapy Kiosk Shows Promise as a Treatment Option for Low Vitamin D
McCarthy, M. S., Elshaw, E. B., Szekely, B. M., & Beltran, T. (2021) · Military Medicine · doi:10.1093/milmed/usaa411 · Cited by 1
The Relationship Between Medication Adherence and Health-Related Quality of Life among Type 2 Diabetes Mellitus (T2DM) Patients
Zakaria, N., Mohamed, N. F., Tajuddin, N. A. A., & Sari, N. A. M. (2021) · International Journal of Academic Research in Business and Social Sciences · doi:10.6007/ijarbss/v11-i7/10525 · Cited by 1
“By taking into considerations 20% of data being incomplete or missing in patient medical records, the sample size was 240 (Conn & Ruppar, 2017).”
Background
Training Future Health Professionals in Communication Skills
Rodrigues, S., Baptista, A. C., Nascimento, T., & Galinha, V. (2022) · Advances in medical education, research, and ethics (AMERE) book series · doi:10.4018/978-1-7998-9578-7.ch003 · Cited by 1
Studies of Medication Adherence
Lauffenburger, J. C., Acri, T., & Gross, R. (2021) · doi:10.1002/9781119701101.ch21 · Cited by 1
Medication Adherence Reminder System for Virtual Home Assistants: Mixed Methods Evaluative Study (Preprint)Preprint
Corbett, C. F., Combs, E. M., Chandarana, P. S., Stringfellow, I., Worthy, K., Nguyen, T., Wright, P. J., & O’Kane, J. M. (2021) · doi:10.2196/preprints.27327 · Cited by 1
Ninety days to predict a year: a Bayesian journey into medication adherence post-myocardial infarction
Magné, J., & Jost, J. (2025) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwaf023 · Cited by 1
Which Interventions Are Useful?
Ruppar, T. M. (2018) · Updates in hypertension and cardiovascular protection · doi:10.1007/978-3-319-76593-8_16
Self-citation
Medication Adherence: does Patient Participation in Randomized Clinical Trials Affect on it?
Vasyukova, N. O., Lukina, Y. V., Кутишенко, Н. П., Martsevich, S. Y., & Zvonareva, O. (2019) · Rational Pharmacotherapy in Cardiology · doi:10.20996/1819-6446-2019-15-3-386-392
Identifying strategies to inform interventions for the secondary prevention of stroke in UK primary care
Jamison, J. (2017) · Apollo (University of Cambridge) · doi:10.17863/cam.32310
“Total participants identified in posts 84 Number of posts in the forum/ participant Number of posts about secondary prevention medications/ participant 16 (1-4932) 1 (1-37)”
Background
Health and habits
Arden, M. A. (2019) · SHURA (Sheffield Hallam University Research Archive) (Sheffield Hallam University)
Assessing the effect of clinical trial evidence and anecdote on caregivers’ willingness to use corticosteroids: a randomized controlled trial: a critical appraisal
Brown, A. C., Tsianou, Z., & Williams, H. C. (2020) · British Journal of Dermatology · doi:10.1111/bjd.18956
Capsule Commentary on Muench et. al., Scope-of-practice for Nurse Practitioners and Adherence to Medications for Chronic Illness in Primary Care
Lauffenburger, J. C. (2020) · Journal of General Internal Medicine · doi:10.1007/s11606-020-06016-5
Compliance in canine epilepsy: can the owner be the cause of treatment failure?
Jokinen, T. S. (2021) · Veterinary Record · doi:10.1002/vetr.224
Adherence to somatostatin analog therapy for acromegaly
Ilovayskaya, I. (2021) · Meditsinskiy sovet = Medical Council · doi:10.21518/2079-701x-2021-7-142-149
Unravelling adherence and flourishing acceptance in people with haemophilia
Hoefnagels, J. W. (2021) · Utrecht University Repository (Utrecht University) · doi:10.33540/271
Pharmacology for cardiovascular nurses
Keenan, J., Khatib, R., McKee, G., Ruppar, T. M., & Wilson, F. (2021) · doi:10.1093/med/9780198849315.003.0012
Self-citation
Aderência e características da utilização dos inibidores do receptor plaquetário P2Y12 após intervenção coronária percutânea com implante de stent farmacológico
Morita, F. (2019) · doi:10.31744/pg2019.106813
Telemonitoring and mobile follow-up strategy supported by self-assessment of blood pressure with wrist sphygmomanometer in primary health care establishments to control patients with cardiovascular diseases in COVID 19 pandemic context (Preprint)Preprint
Stegmeier, R. E. P., Millar, D. A., Rivera, S. A., & Navia, V. H. (2020) · doi:10.2196/preprints.22144
Educational Interventions to Improve Heart Failure Self-Care
Hernandez, M., Barker, C., & Rosa, D. C. D. L. (2022) · The Journal for Nurse Practitioners · doi:10.1016/j.nurpra.2022.04.018
Reporting of medication adherence in randomized controlled trials of pharmacological interventions for SARS-CoV-2: a cross-sectional analysisPreprint
Lee, C., Otunla, A. A., Brennan, Aronson, J. K., & Nunan, D. (2022) · medRxiv · doi:10.1101/2022.10.30.22281709
We Are No Better Than the Weakest Link: Nurses’ Experiences With Medication Management in Primary Healthcare
Knutsen, I. R., Johnsrud, U. S., Slorafoss, S. J., Haugen, A. G., & Joranger, P. (2022) · doi:10.23865/noasp.172.ch17
Introduction: Medication Safety in Municipal Health and Care Services
Olsen, R. M., & Sletvold, H. (2022) · doi:10.23865/noasp.172.ch1
The Role of Medication Management in Hospital Readmissions in Norwegian Primary Healthcare Services: A Secondary Analysis
Glette, M. K., & Wiig, S. (2022) · doi:10.23865/noasp.172.ch16

Authors: Conn, V. S., & Ruppar, T. M.
Affiliations: University of Missouri (US)
Corresponding author: Conn, Vicki S.
ORCID: Conn, Vicki S.
Ruppar, Todd M.
Venue: Preventive Medicine
Publisher: Elsevier BV
Published: 2017-06
Volume: 99
Pages: 269-276
ISSN: 0091-7435 (ISSN-L)
DOI: 10.1016/j.ypmed.2017.03.008
PMC: PMC5467216
OpenAlex: W2597284704
Cited by: 367
References: 36
Citations by year: 2026: 20 · 2025: 39 · 2024: 41 · 2023: 47 · 2022: 57 · 2021: 55 · 2020: 52 · 2019: 37 · 2018: 11 · 2017: 6
FWCI: 4.87
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Preventive Medicine (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (R01NR011990)
Topics: Health Sciences › Medicine › Family Practice › Medication Adherence and Compliance
Health Sciences › Health Professions › Pharmacy › Pharmacy and Medical Practices
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Patient Safety and Medication Errors
Keywords: medication adherence, adherence interventions, behavioral interventions, cognitive intervention, pill count, publication bias, risk of bias, older adults, homeless patients
MeSH terms: Assessment of Medication Adherence, Humans, Research Design, Bias, Drug Monitoring, Medication Adherence

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Medication adherence outcomes of 771 intervention trials: Systematic review and meta-analysis

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