High-Intensity Aphasia Therapy Is Cost-Effective in People With Poststroke Aphasia: Evidence From the COMPARE Trial.

BACKGROUND: Evidence from systematic reviews confirms that speech and language interventions for people with aphasia during the chronic phase after stroke (>6 months) improve word retrieval, functional communication, and communication-related quality of life. However, there is limited evidence of their cost-effectiveness. We aimed to estimate the cost per quality-adjusted life year gained from 2 speech and language therapies compared with usual care in people with aphasia during the chronic phase (median, 2.9 years) after stroke. METHODS: A 3-arm, randomized controlled trial compared constraint-induced aphasia therapy plus (CIAT-Plus) and multimodality aphasia therapy (M-MAT) with usual care in 216 people with chronic aphasia. Participants were administered a standardized questionnaire before intervention and at 12 weeks after the 2-week intervention/control period to ascertain health service utilization, employment changes, and informal caregiver burden. Unit prices from Australian sources were used to estimate costs in 2020. Quality-adjusted life years were estimated using responses to the EuroQol-5 Dimension-3 Level questionnaire. To test uncertainty around the differences in costs and outcomes between groups, bootstrapping was used with the cohorts resampled 1000 times. RESULTS: Overall 201/216 participants were included (mean age, 63 years, 29% moderate or severe aphasia, 61 usual care, 70 CIAT-Plus, 70 M-MAT). There were no statistically significant differences in mean total costs ($13 797 usual care, $17 478 CIAT-Plus, $11 113 M-MAT) and quality-adjusted life years (0.19 usual care, 0.20 CIAT-Plus, 0.20 M-MAT) between groups. In bootstrapped analysis of CIAT-Plus, 21.5% of iterations were likely to result in better outcomes and be cost saving (dominant) compared with usual care. In contrast, 72.4% of iterations were more favorable for M-MAT than usual care. CONCLUSIONS: We observed that both treatments, but especially M-MAT, may result in better outcomes at an acceptable additional cost, or potentially with cost savings. These findings are relevant in advocating for the use of these therapies for chronic aphasia after stroke.

High-Intensity Aphasia Intervention Is Minimally Fatiguing in Chronic Aphasia: An Analysis of Participant Self-Ratings From a Large Randomized Controlled Trial.

BACKGROUND: High-intensity therapy is recommended in current treatment guidelines for chronic poststroke aphasia. Yet, little is known about fatigue levels induced by treatment, which could interfere with rehabilitation outcomes. We analyzed fatigue experienced by people with chronic aphasia (>6 months) during high-dose interventions at 2 intensities. METHODS: A retrospective observational analysis was conducted on self-rated fatigue levels of people with chronic aphasia (N=173) collected during a previously published large randomized controlled trial of 2 treatments: constraint-induced aphasia therapy plus and multi-modality aphasia therapy. Interventions were administered at a higher intensity (30 hours over 2 weeks) or lower intensity (30 hours over 5 weeks). Participants rated their fatigue on an 11-point scale before and after each day of therapy. Data were analyzed using Bayesian ordinal multilevel models. Specifically, we considered changes in self-rated participant fatigue across a therapy day and over the intervention period. RESULTS: Data from 144 participants was analyzed. Participants were English speakers from Australia or New Zealand (mean age, 62 [range, 18-88] years) with 102 men and 42 women. Most had mild (n=115) or moderate (n=52) poststroke aphasia. Median ratings of the level of fatigue by people with aphasia were low (1 on a 0-10-point scale) at the beginning of the day. Ratings increased slightly (+1.0) each day after intervention, with marginally lower increases in the lower intensity schedule. There was no evidence of accumulating fatigue over the 2- or 5-week interventions. CONCLUSIONS: Findings suggest that intensive intervention was not associated with large increases in fatigue for people with chronic aphasia enrolled in the COMPARE trial (Constraint-Induced or Multimodality Personalised Aphasia Rehabilitation). Fatigue did not change across the course of the intervention. This study provides evidence that intensive treatment was minimally fatiguing for stroke survivors with chronic aphasia, suggesting that fatigue is not a barrier to high-intensity treatment.

Results of the COMPARE trial of Constraint-induced or Multimodality Aphasia Therapy compared with usual care in chronic post-stroke aphasia.

BACKGROUND: While meta-analyses confirm treatment for chronic post-stroke aphasia is effective, a lack of comparative evidence for different interventions limits prescription accuracy. We investigated whether Constraint-Induced Aphasia Therapy Plus (CIAT-plus) and/or Multimodality Aphasia Therapy (M-MAT) provided greater therapeutic benefit compared with usual community care and were differentially effective according to baseline aphasia severity. METHODS: We conducted a three-arm, multicentre, parallel group, open-label, blinded endpoint, phase III, randomised-controlled trial. We stratified eligible participants by baseline aphasia on the Western Aphasia Battery-Revised Aphasia Quotient (WAB-R-AQ). Groups of three participants were randomly assigned (1:1:1) to 30 hours of CIAT-Plus or M-MAT or to usual care (UC). Primary outcome was change in aphasia severity (WAB-R-AQ) from baseline to therapy completion analysed in the intention-to-treat population. Secondary outcomes included word retrieval, connected speech, functional communication, multimodal communication, quality of life and costs. RESULTS: We analysed 201 participants (70 in CIAT-Plus, 70 in M-MAT and 61 in UC). Aphasia severity was not significantly different between groups at postintervention: 1.05 points (95% CI -0.78 to 2.88; p=0.36) UC group vs CIAT-Plus; 1.06 points (95% CI -0.78 to 2.89; p=0.36) UC group vs M-MAT; 0.004 points (95% CI -1.76 to 1.77; p=1.00) CIAT-Plus vs M-MAT. Word retrieval, functional communication and communication-related quality of life were significantly improved following CIAT-Plus and M-MAT. Word retrieval benefits were maintained at 12-week follow-up. CONCLUSIONS: CIAT-Plus and M-MAT were effective for word retrieval, functional communication, and quality of life, while UC was not. Future studies should explore predictive characteristics of responders and impacts of maintenance doses. TRIAL REGISTRATION NUMBER: ACTRN 2615000618550.

Stroke communication partner training: a national survey of 122 clinicians on current practice patterns and perceived implementation barriers and facilitators.

BACKGROUND: Communication partners (CPs) find it challenging to communicate with people with communication disorders post-stroke. Stroke communication partner training (CPT) can enhance CPs' ability to support the communication and participation of people post-stroke. While evidence for the efficacy of aphasia-based CPT is strong, implementation in healthcare settings is unclear. AIMS: To investigate Australian speech pathologists' current stroke CPT practices, factors influencing the implementation of CPT and how reported practice compares with the research evidence. METHODS & PROCEDURES: Speech pathologists in Australia who had worked with people post-stroke were invited to complete a 99-item online survey. The survey was informed by a comprehensive review of the literature review, the Template for Intervention Description and Replication (TIDieR) intervention taxonomy, and the theoretical domains framework. data were analyzed using descriptive statistics and content analysis. OUTCOMES & RESULTS: A total of 122 clinicians were surveyed. Most participants reported providing CPT to treat a range of post-stroke communication disorders. While 98.3% reported training familiar CPs, only 66.1% reported training unfamiliar CPs. Current stroke CPT practice is characterized by one to two < 1 h sessions of informal face-to-face education and skills training. Only 13.3% and 10.0% of participants used evidence-based published programmes with unfamiliar and familiar CPs respectively. The main barriers included the perceived lack of behavioural regulation, skills, reinforcement, beliefs about consequences, positive social influences and resources. The main facilitators included clinicians' intentions to provide CPT, perception of CPT as part of their role and perceived compatibility of CPT with clinical practice. CONCLUSION & IMPLICATIONS: A significant evidence-practice gap exists. Research exploring the implementation of stroke CPT in healthcare settings, expanding evidence to support CPT for the range of post-stroke communication disorders, developing freely accessible step-by-step CPT programmes that consider restrictions in current practice and providing explicit instructions of CPT best practice are warranted. A supportive workplace culture and freely accessible formal training opportunities are also needed.

'That doesn't translate': the role of evidence-based practice in disempowering speech pathologists in acute aphasia management.

BACKGROUND: An evidence-practice gap has been identified in current acute aphasia management practice, with the provision of services to people with aphasia in the acute hospital widely considered in the literature to be inconsistent with best-practice recommendations. The reasons for this evidence-practice gap are unclear; however, speech pathologists practising in this setting have articulated a sense of dissonance regarding their limited service provision to this population. A clearer understanding of why this evidence-practice gap exists is essential in order to support and promote evidence-based approaches to the care of people with aphasia in acute care settings. AIMS: To provide an understanding of speech pathologists' conceptualization of evidence-based practice for acute post-stroke aphasia, and its implementation. METHODS & PROCEDURES: This study adopted a phenomenological approach, underpinned by a social constructivist paradigm. In-depth interviews were conducted with 14 Australian speech pathologists, recruited using a purposive sampling technique. An inductive thematic analysis of the data was undertaken. OUTCOMES & RESULTS: A single, overarching theme emerged from the data. Speech pathologists demonstrated a sense of disempowerment as a result of their relationship with evidence-based practice for acute aphasia management. Three subthemes contributed to this theme. The first described a restricted conceptualization of evidence-based practice. The second revealed speech pathologists' strained relationships with the research literature. The third elucidated a sense of professional unease over their perceived inability to enact evidence-based clinical recommendations, despite their desire to do so. CONCLUSIONS & IMPLICATIONS: Speech pathologists identified a current knowledge-practice gap in their management of aphasia in acute hospital settings. Speech pathologists place significant emphasis on the research evidence; however, their engagement with the research is limited, in part because it is perceived to lack clinical utility. A sense of professional dissonance arises from the conflict between a desire to provide best practice and the perceived barriers to implementing evidence-based recommendations clinically, resulting in evidence-based practice becoming a disempowering concept for some.

Identifying communication difficulty and context-specific communication supports for patient-provider communication in a sub-acute setting: A prospective mixed methods study.

PURPOSE: To identify the sub-acute rehabilitation inpatients who have communication difficulty and the range of communication supports that can facilitate communicative success. METHOD: A prospective cohort mixed methods study was conducted on two inpatient sub-acute rehabilitation wards. Nurses screened all new admissions for communication difficulty using the Inpatient Functional Communication Interview, Screening Questionnaire (IFCI-SQ). Patients identified as having communication difficulty were interviewed by a speech-language pathologist (SLP) using the Inpatient Functional Communication Interview (IFCI). During the interview, the SLP trialled different communication supports. The number of patients who had communication difficulty on the IFCI-SQ was calculated. The number and type of communication supports that improved communication within the patient-SLP interview were calculated. Deductive-dominant qualitative content analysis was conducted on the communication supports used during the IFCI. RESULT: Seventy patients were screened. Nurses reported communication difficulty in 45/70 (64%) of patients. A total of 15/45 patients were interviewed by an SLP using the IFCI. The provision of communication supports improved communication for all patients within the context of the patient-SLP interview. CONCLUSION: Many sub-acute rehabilitation inpatients have communication difficulty in the hospital setting. A range of communication supports facilitated communication. These insights could inform future communication partner training (CPT) programs.

The health care experiences of people with head and neck cancer: A scoping review.

BACKGROUND: Understanding health care experience in head and neck cancer (HNC) is becoming increasingly important due to changes in the disease profile, survivorship, and a greater appreciation of patient health care experience as an important outcome measure. People with HNC encounter many different types of health care professionals and health care touchpoints. METHOD: Through systematic database searching, this scoping review of qualitative English-language studies describes the self-reported care experiences of those with HNC across the health care continuum, and describes the current state of the literature. RESULTS: Overall, the 95 studies identified were heterogeneous and investigated a broad range of topics. Trends across studies showed research centered on hospital-based care, conducted in developed countries, with more studies on feeding than other aspects of care. Generic qualitative research frameworks, with individual interviews, were the preferred method of data collection. CONCLUSION: Despite identifying many studies, there are significant gaps in our understanding of the HNC patient experience.

Acceptability, feasibility and preliminary efficacy of low-moderate intensity Constraint Induced Aphasia Therapy and Multi-Modality Aphasia Therapy in chronic aphasia after stroke.

BACKGROUND: High-intensity Constraint-Induced Aphasia Therapy Plus (CIAT-Plus) and Multi-Modality Aphasia Therapy (M-MAT) are effective interventions for chronic post-stroke aphasia but challenging to provide in clinical practice. Providing these interventions may be more feasible at lower intensities, but comparative evidence is lacking. We therefore explored feasibility, acceptability, and preliminary efficacy of the treatments at a lower intensity. METHODS: A multisite, single-blinded, randomized Phase II trial was conducted within the Phase III COMPARE trial. Groups of participants with chronic aphasia from the usual care arm of the COMPARE trial were randomized to M-MAT or CIAT-Plus, delivered at the same dose as the COMPARE trial but at lower intensity (6 hours/week × 5 weeks rather than 15 hours/week × 2 weeks). Blinded assessors measured aphasia severity (Western Aphasia Battery-Revised Aphasia Quotient), word retrieval, connected speech, multimodal communication, functional communication, and quality of life immediately post interventions and after 12 weeks. Feasibility and acceptability were explored. RESULTS: Of 70 eligible participants, 77% consented to the trial; 78% of randomized participants completed intervention and 98% of assessment visits were conducted. Fatigue and distress ratings were low with no related withdrawals. Adverse events related to the trial (n = 4) were mild in severity. Statistically significant treatment effects were demonstrated on word retrieval and functional communication and both interventions were equally effective. CONCLUSIONS: Low-moderateintensity CIAT-Plus and M-MAT were feasible and acceptable. Both interventions show preliminary efficacy at a low-moderate intensity. These results support a powered trial investigating these interventions at a low-moderate intensity.

Glutamine deamidation does not increase the immunogenicity of C-peptide in people with type 1 diabetes.

Type 1 diabetes (T1D) is a T-cell mediated autoimmune disease in which the insulin-producing beta cells are destroyed. While it is clear that full-length C-peptide, derived from proinsulin, is a major antigen in human T1D it is not clear how and why C-peptide becomes a target of the autoimmune CD4+ T-cell responses in T1D. Neoepitopes formed by the conversion of glutamine (Q) residues to glutamic acid (E) by deamidation are central to the immune pathogenesis of coeliac disease and have been implicated in autoimmune responses in T1D. Here, we asked if the immunogenicity of full-length C-peptide, which comprises four glutamine residues, was enhanced by deamidation, which we mimicked by substituting glutamic acid for glutamine residue. First, we used a panel of 18 well characterized CD4+ T-cell lines specific for epitopes derived from human C-peptide. In all cases, when the substitution fell within the cognate epitope the response was diminished, or in a few cases unchanged. In contrast, when the substitution fell outside the epitope recognized by the TCR responses were unchanged or slightly augmented. Second, we compared CD4+ T-cell proliferation responses, against deamidated and unmodified C-peptide, in the peripheral blood of people with or without T1D using the CFSE-based proliferation assay. While, as reported previously, responses were detected to unmodified C-peptide, no deamidated C-peptide was consistently more stimulatory than native C-peptide. Overall responses were weaker to deamidated C-peptide compared to unmodified C-peptide. Hence, we conclude that deamidated C-peptide does not play a role in beta-cell autoimmunity in people with T1D.

Management of communication disability in the first 90 days after stroke: a scoping review.

INTRODUCTION: People with communication disability after stroke need interventions to optimise healthcare communication and rehabilitation outcomes. Current evidence syntheses do not adequately inform the management of communication disability during the first 90 days post-stroke. PURPOSE: To explore the scope of literature for the management of communication disability in the first 90 days after stroke. MATERIALS AND METHODS: A scoping review was conducted using a systematic keyword search of six databases. A descriptive synthesis was generated using communication-related domains related to the biopsychosocial framework of the International Classification of Functioning, Disability, and Health (ICF). RESULTS: A total of 129 studies met eligibility criteria. Aphasia was the most frequently addressed communication disability after stroke (76/129 studies) with a paucity of evidence investigating other acquired neurogenic communication impairments. Management predominantly focused on communication-related: body functions and structures (62 studies) (e.g., linguistic-behavioural therapies), followed by environmental factors (39 studies) (e.g., communication partner training/support); activities and participation (15 studies) (e.g., augmentative and alternative communication); and personal factors (13 studies) (e.g., assessment of depression after aphasia). CONCLUSION: A coordinated, integrated approach to developing and testing acute and subacute interventions for all communication disabilities across all communication-related domains is required.IMPLICATIONS FOR REHABILITATIONInterdisciplinary stroke clinicians need to manage communication disabilities in the first 90 days after stroke to optimise healthcare communication and rehabilitation outcomes.There is some evidence to guide clinicians in aphasia management but less in other disabilities of speech and cognitive functioning.Most interventions to inform clinical practice address communication-related body functions and structures (e.g., linguistic and speech therapies). Clinicians need to address all domains and more evidence is needed to address environmental factors (e.g., communication support); activities and participation (e.g., person-centred goal setting); and personal factors (e.g., psychological care).

Constraint-induced or multi-modal personalized aphasia rehabilitation (COMPARE): A randomized controlled trial for stroke-related chronic aphasia.

RATIONALE: The comparative efficacy and cost-effectiveness of constraint-induced and multi-modality aphasia therapy in chronic stroke are unknown. AIMS AND HYPOTHESES: In the COMPARE trial, we aim to determine whether Multi-Modal Aphasia Treatment (M-MAT) and Constraint-Induced Aphasia Therapy Plus (CIAT-Plus) are superior to usual care (UC) for chronic post-stroke aphasia. Primary hypothesis: CIAT-Plus and M-MAT will reduce aphasia severity (Western Aphasia Battery-Revised Aphasia Quotient (WAB-R-AQ)) compared with UC: CIAT-Plus superior for moderate aphasia; M-MAT superior for mild and severe aphasia. SAMPLE SIZE ESTIMATES: A total of 216 participants (72 per arm) will provide 90% power to detect a 5-point difference on the WAB-R-AQ between CIAT-Plus or M-MAT and UC at α = 0.05. METHODS AND DESIGN: Prospective, randomized, parallel group, open-label, assessor blinded trial. Participants: Stroke >6 months; aphasia severity categorized using WAB-R-AQ. Computer-generated blocked and stratified randomization by aphasia severity (mild, moderate, and severe), to 3 arms: CIAT-Plus, M-MAT (both 30 h therapy over two weeks); UC (self-reported usual community care). STUDY OUTCOMES: WAB-R-AQ immediately post-intervention. Secondary outcomes: WAB-R-AQ at 12-week follow-up; naming scores, discourse measures, Communicative Effectiveness Index, Scenario Test, and Stroke and Aphasia Quality of Life Scale-39 g immediately and at 12 weeks post-intervention; incremental cost-effectiveness ratios compared with UC at 12 weeks. DISCUSSION: This trial will determine whether CIAT-Plus and M-MAT are superior and more cost-effective than UC in chronic aphasia. Participant subgroups with the greatest response to CIAT-Plus and M-MAT will be described.

The Consequences of the Consequences: The Impact of the Environment on People With Aphasia Over Time.

Understanding the impact of the environment on the participation of people with aphasia depends on one's perspective. A long-term perspective provides a unique insight into the myriad of ways in which the environment can influence the participation of people living with aphasia over decades. In this article, the authors present the real-life story of "Hank," who has lived with aphasia for more than 15 years. The authors consider how 2 different conceptual frameworks-the International Classification of Functioning, Disability and Health and the Social Determinants of Health-account for Hank's experience. The International Classification of Functioning, Disability and Health is useful to conceptualize the range of factors that influence living with aphasia at a particular point in time. In contrast, the Social Determinants of Health is useful to conceptualize the cumulative impact of living with aphasia on long-term health and well-being. Viewing aphasia as a social condition that impacts social determinants of health has potentially wide ranging implications for service design and delivery and the role of speech-language pathologists.

'I do the best I can': an in-depth exploration of the aphasia management pathway in the acute hospital setting.

PURPOSE: While research has begun to explore the management of aphasia across the continuum of care, to date there is little in-depth, context specific knowledge relating to the speech pathology aphasia management pathway. This research aimed to provide an in-depth understanding of the current aphasia management pathway in the acute hospital setting, from the perspective of speech pathologists. METHOD: Underpinned by a social constructivist paradigm, the researchers implemented an interpretive phenomenological method when conducting in-depth interviews with 14 Australian speech pathologists working in the acute hospital setting. Interview transcripts and interviewer field notes were subjected to a qualitative content analysis. RESULTS: Analysis identified a single guiding construct and five main categories to describe the management of aphasia in the acute hospital setting. The guiding construct, First contact with the profession, informed the entire management pathway. Five additional main categories were identified: Referral processes; Screening and assessment; Therapeutic intervention; Educational and affective counselling; and Advocacy. CONCLUSIONS: Findings suggest significant diversity in the pathways of care for people with aphasia and their families in the acute hospital setting. Additional support mechanisms are required in order to support speech pathologists to minimise the evidence-practice gap. Implications for Rehabilitation Significant diversity exists in the current aphasia management pathway for people with acute post-stroke aphasia and their families in the acute hospital setting. Mechanisms that support speech pathologists to minimise the evidence-practice gap, and consequently reduce their sense of professional dissonance, are required.

1,4-dibenzylpiperazines possess anticocaine activity.

N,N-dibenzylpiperazines have high affinity for sigma receptors, and we aimed to increase their anticocaine activity by introducing substituents known to enhance such activity in other sigma ligands. Ligands with high affinity for sigma-1 receptors resulted, but their activity in attenuating cocaine-induced convulsions did not correlate with sigma-1 binding affinity, and may be more closely related to their sigma-2 binding affinities.