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Precision rehabilitation for aphasia by patient age, sex, aphasia severity, and time since stroke? A prespecified, systematic review-based, individual participant data, network, subgroup meta-analysis

Brady, M. C., Ali, M., VandenBerg, K. , Williams, L. J., Williams, L. R. ORCID: 0000-0003-2430-1142, Abo, M., Becker, F., Bowen, A., Brandenburg, C., Breitenstein, C., Bruehl, S., Copland, D. A., Cranfill, T. B., di Pietro-Bachmann, M., Enderby, P., Fillingham, J., Galli, F. L., Gandolfi, M., Glize, B., Godecke, E., Hawkins, N., Hilari, K. ORCID: 0000-0003-2091-4849, Hinckley, J., Horton, S., Howard, D., Jaecks, P., Jefferies, E., Jesus, L.M.T., Kambanaros, M., Kang, E. K., Khedr, E. M., Kong, A. P., Kukkonen, T., Laganaro, M., Ralph, M. L., Laska, A., Leemann, B., Leff, A. P., Lima, R. R., Lorenz, A., MacWhinney, B., Marshall, R. S., Mattioli, F., Mavis, I., Meinzer, M., Nilipour, R., Noe, E., Paik, N-J., Palmer, R., Papathanasiou, I., Patrício, B., Martins, I., Price, C., Jakovac, T. P., Rochon, E., Rose, M. L., Rosso, C., Rubi-Fessen, I., Ruiter, M. B., Snell, C., Stahl, B., Szaflarski, J. P., Thomas, S. A, van de Sandt-Koenderman, M., van der Meulen, I., Visch-Brink, E., Worrall, L. & Wright, H. H. (2022). Precision rehabilitation for aphasia by patient age, sex, aphasia severity, and time since stroke? A prespecified, systematic review-based, individual participant data, network, subgroup meta-analysis. International Journal of Stroke, doi: 10.1177/17474930221097477

Abstract

Background:
Stroke rehabilitation interventions are routinely personalized to address individuals’ needs, goals, and challenges based on evidence from aggregated randomized controlled trials (RCT) data and meta-syntheses. Individual participant data (IPD) meta-analyses may better inform the development of precision rehabilitation approaches, quantifying treatment responses while adjusting for confounders and reducing ecological bias.

Aim:
We explored associations between speech and language therapy (SLT) interventions frequency (days/week), intensity (h/week), and dosage (total SLT-hours) and language outcomes for different age, sex, aphasia severity, and chronicity subgroups by undertaking prespecified subgroup network meta-analyses of the RELEASE database.

Methods:
MEDLINE, EMBASE, and trial registrations were systematically searched (inception-Sept2015) for RCTs, including ⩾ 10 IPD on stroke-related aphasia. We extracted demographic, stroke, aphasia, SLT, and risk of bias data. Overall-language ability, auditory comprehension, and functional communication outcomes were standardized. A one-stage, random effects, network meta-analysis approach filtered IPD into a single optimal model, examining SLT regimen and language recovery from baseline to first post-intervention follow-up, adjusting for covariates identified a-priori. Data were dichotomized by age (⩽/> 65 years), aphasia severity (mild–moderate/ moderate–severe based on language outcomes’ median value), chronicity (⩽/> 3 months), and sex subgroups. We reported estimates of means and 95% confidence intervals. Where relative variance was high (> 50%), results were reported for completeness.

Results:
959 IPD (25 RCTs) were analyzed. For working-age participants, greatest language gains from baseline occurred alongside moderate to high-intensity SLT (functional communication 3-to-4 h/week; overall-language and comprehension > 9 h/week); older participants’ greatest gains occurred alongside low-intensity SLT (⩽ 2 h/week) except for auditory comprehension (> 9 h/week). For both age-groups, SLT-frequency and dosage associated with best language gains were similar. Participants ⩽ 3 months post-onset demonstrated greatest overall-language gains for SLT at low intensity/moderate dosage (⩽ 2 SLT-h/week; 20-to-50 h); for those > 3 months, post-stroke greatest gains were associated with moderate-intensity/high-dosage SLT (3–4 SLT-h/week; ⩾ 50 hours). For moderate–severe participants, 4 SLT-days/week conferred the greatest language gains across outcomes, with auditory comprehension gains only observed for ⩾ 4 SLT-days/week; mild–moderate participants’ greatest functional communication gains were associated with similar frequency (⩾ 4 SLT-days/week) and greatest overall-language gains with higher frequency SLT (⩾ 6 days/weekly). Males’ greatest gains were associated with SLT of moderate (functional communication; 3-to-4 h/weekly) or high intensity (overall-language and auditory comprehension; (> 9 h/weekly) compared to females for whom the greatest gains were associated with lower-intensity SLT (< 2 SLT-h/weekly). Consistencies across subgroups were also evident; greatest overall-language gains were associated with 20-to-50 SLT-h in total; auditory comprehension gains were generally observed when SLT > 9 h over ⩾ 4 days/week.

Conclusions:
We observed a treatment response in most subgroups’ overall-language, auditory comprehension, and functional communication language gains. For some, the maximum treatment response varied in association with different SLT-frequency, intensity, and dosage. Where differences were observed, working-aged, chronic, mild–moderate, and male subgroups experienced their greatest language gains alongside high-frequency/intensity SLT. In contrast, older, moderate–severely impaired, and female subgroups within 3 months of aphasia onset made their greatest gains for lower-intensity SLT. The acceptability, clinical, and cost effectiveness of precision aphasia rehabilitation approaches based on age, sex, aphasia severity, and chronicity should be evaluated in future clinical RCTs.

Publication Type: Article
Additional Information: Copyright ©2022, the authors.
Publisher Keywords: Stroke, aphasia, rehabilitation, speech and language therapy, individual participant data, network meta-analysis
Subjects: P Language and Literature > P Philology. Linguistics
R Medicine > RC Internal medicine
Departments: School of Health & Psychological Sciences > Language & Communication Science
School of Health & Psychological Sciences > Midwifery & Radiography
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