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
The RELEASE Collaborators, Marian Brady, Myzoon Ali, Kathryn VandenBerg, Linda Williams, Louise R. Williams, Masahiro Abo, Frank Becker, Audrey Bowen, Caitlin Brandenburg, Caterina Breitenstein, Stefanie Bruehl, David A. Copland, Tamara Cranfill, Marie di Pietro-Bachmann, Pam Enderby, Joanne Fillingham, Federica Galli, Marialuisa Gandolfi, Bertrand Glize, Erin Godecke, Neil Hawkins, Katerina Hilari, Jacqueline Hinckley, Simon Horton, David Howard, Petra Jaecks, Elizabeth Jefferies, Luís M. T. Jesus, Maria Kambanaros, Eun Kyoung Kang, Eman M. Khedr, Anthony Pak‐Hin Kong, Tarja Kukkonen, Marina Laganaro, Matthew A. Lambon Ralph, Ann Charlotte Laska, Béatrice Leemann, Alexander Leff, Roxele Ribeiro Lima, Antje Lorenz, Brian MacWhinney, Rebecca Shisler Marshall, Flavia Mattioli, İlknur Maviş, Marcus Meinzer, Reza Nilipour, Enrique Noé, Nam‐Jong Paik, Rebecca Palmer, Ilias Papathanasiou, Brígida Patrício, Isabel Pavão Martins, Cathy J. Price, Tatjana Prizl Jakovac, Elizabeth Rochon, Miranda L. Rose, Charlotte Rosso, Ilona Rubi‐Fessen, Marina B. Ruiter, Claerwen Snell, Benjamin Stahl, Jerzy P. Szaflarski, Shirley Thomas, Mieke van de Sandt‐Koenderman, Ineke van der Meulen, Evy Visch‐Brink, Linda Worrall, Heather Harris Wright
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: . 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.