Specificity in Generalization Effects of Transcranial Direct Current Stimulation Over the Left Inferior Frontal Gyrus in Primary Progressive Aphasia.

OBJECTIVES: Generalization (or near-transfer) effects of an intervention to tasks not explicitly trained are the most desirable intervention outcomes. However, they are rarely reported and even more rarely explained. One hypothesis for generalization effects is that the tasks improved share the same brain function/computation with the intervention task. We tested this hypothesis in this study of transcranial direct current stimulation (tDCS) over the left inferior frontal gyrus (IFG) that is claimed to be involved in selective semantic retrieval of information from the temporal lobes. MATERIALS AND METHODS: In this study, we examined whether tDCS over the left IFG in a group of patients with primary progressive aphasia (PPA), paired with a lexical/semantic retrieval intervention (oral and written naming), may specifically improve semantic fluency, a nontrained near-transfer task that relies on selective semantic retrieval, in patients with PPA. RESULTS: Semantic fluency improved significantly more in the active tDCS than in the sham tDCS condition immediately after and two weeks after treatment. This improvement was marginally significant two months after treatment. We also found that the active tDCS effect was specific to tasks that require this IFG computation (selective semantic retrieval) but not to other tasks that may require different computations of the frontal lobes. CONCLUSIONS: We provided interventional evidence that the left IFG is critical for selective semantic retrieval, and tDCS over the left IFG may have a near-transfer effect on tasks that depend on the same computation, even if they are not specifically trained. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02606422.

Development of the Functional Assessment of Cancer Therapy-Carcinoid Syndrome Symptom Index.

OBJECTIVE: To develop a symptom-focused index to evaluate representative symptoms, treatment side effects, and emotional and functional well-being of patients with carcinoid syndrome (CS). METHODS: The development of the Functional Assessment of Cancer Therapy-Carcinoid Syndrome Symptom Index (FACT-CSI) followed US Food and Drug Administration guidelines for the development of patient-reported outcome (PRO) measures and involved the following: (a) literature review; (b) interviews with 14 CS patients; (c) interviews with 9 clinicians; and (d) instrument development involving input from a range of PRO measure development and CS experts. The resulting draft instrument underwent cognitive interviews with 7 CS patients. RESULTS: Forty-six CS sources were reviewed. Analysis of patient interviews produced 23 patient-reported symptoms. The most frequently endorsed physical symptoms were flushing, diarrhea, abdominal pain, fatigue, and food sensitivity/triggers. Seven priority CS emotional and functional themes were also identified by patients. Expert interviews revealed 12 unique priority symptoms - the most common being diarrhea, flushing, wheezing, edema, abdominal pain/cramping, fatigue, and 8 emotional and functional concerns. Through an iterative process of team and clinical collaborator meetings, data review, item reduction and measure revision, 24 items were selected for the draft symptom index representing symptoms, emotional concerns, global assessment of treatment side effects, and functional well-being. Cognitive interview results demonstrated strong content validity, including positive endorsement of item clarity (>86% across items), symptom relevance (>70% for most items), and overall measure content (86%). CONCLUSIONS: The FACT-CSI is a content-relevant, symptom-focused index reflecting the highest priority and clinically relevant symptoms and concerns of people with CS.

Symptom and needs assessment screening in oncology patients: Alternate outreach methods during COVID-19.

Patients with cancer are ideally screened for symptoms, including distress, using patient-reported outcome measures (PROMs). This initiative was developed to ensure patients without access to an electronic portal were screened for distress and related symptoms during the COVID-19 pandemic. Prior to the pandemic, these patients could complete screening in clinic. However, many visits transitioned to telehealth. We implemented a standardized telephone outreach process targeting patients without active electronic portal accounts to improve remote symptom monitoring. Outreach resulted in 172 completed screens, identifying 110 needs for 63 individuals. Twenty-eight patients completed patient portal enrollment. Outreach calls captured a higher percentage of Black patients (34%) and a higher percentage of 61-80 year olds (69%) compared to portal users. Telephone outreach during the pandemic captured data that otherwise would have been missed in elderly and minority patients without electronic patient portal access. Patient engagement is vital to the distress screening process.

Development of the Functional Assessment of Cancer Therapy-Immune Checkpoint Modulator (FACT-ICM): A toxicity subscale to measure quality of life in patients with cancer who are treated with ICMs.

BACKGROUND: Patients with cancer who are treated with immune checkpoint modulators (ICMs) have their health-related quality of life (HRQOL) measured using general patient-reported outcome (PRO) tools. To the authors' knowledge, no instrument has been developed to date specifically for patients treated with ICMs. The objective of the current study was to develop a toxicity subscale PRO instrument for patients treated with ICMs to assess HRQOL. METHODS: Input was collected from a systematic review as well as patients and physicians experienced with ICM treatment. Descriptive thematic analysis was used to evaluate the qualitative data obtained from patient focus groups and interviews, which informed an initial list of items that described ICM side effects and their impact on HRQOL. These inputs informed item generation and/or reduction to develop a toxicity subscale. RESULTS: Focus groups and individual interviews with 37 ICM-treated patients generated an initial list of 176 items. After a first round of item reduction that produced a shortened list of 76 items, 16 physicians who care for patients who are treated with ICMs were surveyed with a list of 49 patient-reported side effects and 11 physicians participated in follow-up interviews. A second round of item reduction was informed by the physician responses to produce a list of 25 items. CONCLUSIONS: To the authors' knowledge, this 25-item list is the first HRQOL-focused toxicity subscale for patients treated with ICMs and was developed in accordance with US Food and Drug Administration guidelines, which prioritize patient input in developing PRO tools. The subscale will be combined with the Functional Assessment of Cancer Therapy-General (FACT-G) to form the FACT-ICM. Prior to recommending the formal use of this PRO instrument, the authors will evaluate its validity and reliability in longitudinal studies involving substantially more patients.

Impact of brain atrophy on tDCS and HD-tDCS current flow: a modeling study in three variants of primary progressive aphasia.

BACKGROUND: During transcranial direct current stimulation (tDCS), the amount and distribution of current that reaches the brain depends on individual anatomy. Many progressive neurodegenerative diseases are associated with cortical atrophy, but the importance of individual brain atrophy during tDCS in patients with progressive atrophy, including primary progressive aphasia (PPA), remains unclear. OBJECTIVE: In the present study, we addressed the question whether brain anatomy in patients with distinct cortical atrophy patterns would impact brain current intensity and distribution during tDCS over the left IFG. METHOD: We developed state-of-the-art, gyri-precise models of three subjects, each representing a variant of primary progressive aphasia: non-fluent variant PPA (nfvPPA), semantic variant PPA (svPPA), and logopenic variant PPA (lvPPA). We considered two exemplary montages over the left inferior frontal gyrus (IFG): a conventional pad montage (anode over F7, cathode over the right cheek) and a 4 × 1 high-definition tDCS montage. We further considered whether local anatomical features, specifically distance of the cortex to skull, can directly predict local electric field intensity. RESULTS: We found that the differences in brain current flow across the three PPA variants fall within the distribution of anatomically typical adults. While clustering of electric fields was often around individual gyri or sulci, the minimal distance from the gyri/sulci to skull was not correlated with electric field intensity. CONCLUSION: Limited to the conditions and assumptions considered here, this argues against a specific need to adjust the tDCS montage for these patients any more than might be considered useful in anatomically typical adults. Therefore, local atrophy does not, in isolation, reliably predict local electric field. Rather, our results are consistent with holistic head anatomy influencing brain current flow, with tDCS producing diffuse and individualized brain current flow patterns and HD-tDCS producing targeted brain current flow across individuals.

Further content validation of the 18-item NCCN/FACT Ovarian Symptom Index and its Disease Related Symptom-Physical (DRS-P) subscale for use in advanced ovarian cancer clinical trials.

BACKGROUND: This study evaluated pre-defined aspects of content validity of the 18-item NCCN FACT-Ovarian Symptom Index (NFOSI-18) and its Disease-Related Symptoms-Physical (DRS-P) subscale, as clinical trial outcome tools for patients with advanced ovarian cancer. METHODS: Twenty-one women (mean age 59.5 years) diagnosed with advanced ovarian cancer completed the NFOSI-18 and participated in a cognitive interview to explore: (1) whether 'pain' and 'cramps' are considered redundant; (2) whether 'fatigue' and 'lack of energy' are overlapping concepts; (3) whether patients consider severity when responding to the item "I am bothered by constipation;" and (4) factors considered when responding to the item "I am sleeping well." Interviews were audio-recorded, transcribed, and analyzed qualitatively. RESULTS: Pain was associated with discomfort, hurt, and life interference; 'cramps' was associated with pain, muscle tightening, and menstrual or digestive issues. Most (81%) considered the items "I have pain" and "I have cramps in my stomach area" to be more different than similar. Participants associated 'fatigue' with intense tiredness and 'lack of energy' with motivation and capability to complete daily activities. Item comparisons revealed a majority (65%) considered the items to be more different than similar. When responding to "I am bothered by constipation," patients indicated constipation severity was related to bother. Finally, patients considered disease, treatment, and other factors when responding to "I am sleeping well." CONCLUSIONS: Findings support content validity of the NFOSI-18 and its DRS-P as originally constructed. We propose an alternative scoring option that excludes the item "I am sleeping well" from the DRS-P when used as a symptom-focused index for clinical research in a regulatory context.

Feasibility of a Mobile Application to Enhance Swallowing Therapy for Patients Undergoing Radiation-Based Treatment for Head and Neck Cancer.

Dysphagia following treatment for head and neck cancer is one of the most significant morbidities impacting quality of life. Despite the value of prophylactic exercises to mitigate the impact of radiation on long-term swallowing function, adherence to treatment is limited. The purpose of this investigation was to explore the feasibility of a mobile health application to support patient adherence to swallowing therapy during radiation-based treatment. 36 patients undergoing radiation therapy were provided with the Vibrent™ mobile application as an adjunct to standard swallowing therapy. The application included exercise videos, written instructions, reminders, exercise logging, and educational content. 80% of participants used the app during treatment and logged an average of 102 exercise sessions over the course of treatment. 25% of participants logged at least two exercise sessions per day over the 7-week treatment period, and 53% recorded at least one session per day. Exit interviews regarding the patient experience with the Vibrent™ mobile application were largely positive, but also provided actionable strategies to improve future versions of the application. The Vibrent™ mobile application appears to be a tool that can be feasibly integrated into existing patient care practices and may assist patients in adhering to treatment recommendations and facilitate communication between patients and providers between encounters.

Content validation of the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Lymphoma Symptom Index-18 (NFLymSI-18) in indolent B-cell non-Hodgkin's lymphoma.

BACKGROUND: The NFLymSI-18 is a patient-reported outcome measure comprised of the highest priority symptoms, emotional concerns, treatment side effects, and other concerns identified by lymphoma patients and oncologists. This study assessed the content validity of the NFLymSI-18 for patients with indolent B-cell non-Hodgkin's lymphoma (iNHL), with a focus on the Disease-Related Symptoms Physical (DRS-P) subscale. METHODS: Patients with a confirmed iNHL diagnosis who had received one or more lines of treatment were recruited during clinic visits. Patients described their symptoms, treatment side effects, and emotional concerns related to iNHL in a semi-structured interview. Qualitative data were analyzed using NVivo10. RESULTS: Data saturation was obtained by the 18th interview. Most participants (67%) had follicular lymphoma. 28% of participants had marginal zone lymphoma, and one participant had lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia. Mean age of the 18 participants was 67 years. 56% of the sample was male. Most participants (67%) had a college or advanced degree. When asked to describe their iNHL symptoms, patients most often discussed swelling (n = 14), fatigue (n = 11), and pain (n = 8). The following symptoms were mentioned by three patients each: anxiety, appetite loss, rash, sleep disruption, trouble breathing, and malaise. Mapping of NFLymSI-18 content to these concerns showed the instrument includes all those most frequently mentioned symptoms. CONCLUSIONS: This study supports the content validity of the NFLymSI-18, including its DRS-P Subscale, for patients with iNHL. The instrument shows strong validity for the most referenced symptoms of swelling, fatigue, and pain. The diversity of additional symptoms reported by patients is consistent with the heterogeneous symptomology of iNHL.

A mixed methods evaluation of patient perspectives on the implementation of an electronic health record-integrated patient-reported symptom and needs monitoring program in cancer care.

BACKGROUND: As cancer centers have increased focus on patient-centered, evidenced-based care, implementing efficient programs that facilitate effective patient-clinician communication remains critical. We implemented an electronic health record-integrated patient-reported symptom and needs monitoring program ('cPRO' for cancer patient-reported outcomes). To aid evaluation of cPRO implementation, we asked patients receiving care in one of three geographical regions of an academic healthcare system about their experiences. METHODS: Using a sequential mixed-methods approach, we collected feedback in two waves. Wave 1 included virtual focus groups and interviews with patients who had completed cPRO. In Wave 2, we administered a structured survey to systematically examine Wave 1 themes. All participants had a diagnosed malignancy and received at least 2 invitations to complete cPRO. We used rapid and traditional qualitative methods to analyze Wave 1 data and focused on identifying facilitators and barriers to cPRO implementation. Wave 2 data were analyzed descriptively. RESULTS: Participants (n = 180) were on average 62.9 years old; were majority female, White, non-Hispanic, and married; and represented various cancer types and phases of treatment. Wave 1 participants (n = 37) identified facilitators, including cPRO's perceived value and favorable usability, and barriers, including confusion about cPRO's purpose and various considerations for responding. High levels of clinician engagement with, and patient education on, cPRO were described as facilitators while low levels were described as barriers. Wave 2 (n = 143) data demonstrated high endorsement rates of cPRO's usability on domains such as navigability (91.6%), comprehensibility (98.7%), and relevance (82.4%). Wave 2 data also indicated low rates of understanding cPRO's purpose (56.7%), education from care teams about cPRO (22.5%), and discussing results of cPRO with care teams (16.3%). CONCLUSIONS: While patients reported high value and ease of use when completing cPRO, they also reported areas of confusion, emphasizing the importance of patient education on the purpose and use of cPRO and clinician engagement to sustain participation. These results guided successful implementation changes and will inform future improvements.

General population norms for the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI).

BACKGROUND: Metastatic renal cell cancer is associated with poor long-term survival and has no cure. Traditional clinical endpoints are best supplemented by patient-reported outcomes designed to assess symptoms and function. Normative data was obtained on the National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy-Kidney Symptom Index (NFKSI) to aid in score interpretation and planning of future trials. METHODS: General population data were obtained from 2000 respondents, who completed the 19-item NFKSI-19, as well the SF-36 (Short Form 36-item instrument) and the PROMIS-29 (29-item Patient Reported Outcomes Measurement Information System), both general health status measures. Basic demographic and self-reported comorbidity data were also collected. RESULTS: The sample was 50% female, 85.7% caucasian, with an equal distribution across age bands from 18 years to 75 years and older. Most respondents (62.8%) had more than a high school education and reported an Eastern Cooperative Oncology Group performance status of normal activity without symptoms (63.4%). Score distributions on the NFKSI-19, its subscales, and individual items are summarized. CONCLUSIONS: The NFKSI-19 and its subscales now have scores for the general US population, allowing comparability to generic questionnaires such as the SF-36 and PROMIS-29. These data can be used to guide treatment expectations and plan future comparative effectiveness research using the scales.

The development of a Functional Assessment of Cancer Therapy (FACT) questionnaire to assess dermatologic symptoms associated with epidermal growth factor receptor inhibitors (FACT-EGFRI-18).

PURPOSE: Dermatologic toxicities from epidermal growth factor receptor inhibitors (EGFRIs) are common, disrupt health-related quality of life (HRQL), and lead to dose reduction or discontinuation of potentially life-saving cancer therapy. The Functional Assessment of Cancer Therapy (FACT)-EGFRI was developed to measure HRQL among patients receiving EGFRIs. METHODS: The FACT-EGFRI was developed through the triangulation approach using the established functional assessment of chronic illness therapy method of patient questionnaire construction. This included literature review, qualitative data collection and analysis, and quantitative survey data collection on candidate items to identify the most important items related to EGFRI-induced dermatologic toxicities according to patients receiving EGFRIs and expert clinicians. RESULTS: Twelve expert clinicians and 20 patients were interviewed for the initial questionnaire development. Dermatologic symptoms associated with epidermal growth factor receptor inhibitors endorsed as high priority by both patients and oncologist experts were selected. The final version includes 18 items which assess the physical, emotional, social, and functional impact that skin, nail, and hair toxicities have on patients' HRQL. CONCLUSIONS: The FACT-EGFRI-18 measures the severity of patient-reported EGFRI-induced dermatologic toxicities and effects on HRQL and was developed using qualitative data from patients and expert clinicians. Further validation is underway. The FACT-EGFRI-18 may be useful for clinicians and researchers to quantify dermatologic toxicities from the patient perspective in standard clinical care, evaluate the effectiveness of interventions to prevent or reduce dermatologic toxicities, and to guide treatment decision making.

Measuring health-related quality of life in leukemia: the Functional Assessment of Cancer Therapy--Leukemia (FACT-Leu) questionnaire.

OBJECTIVE: Develop and validate a health-related quality-of-life (measure for patients with acute and chronic leukemia. METHODS: The study consisted of two phases: scale construction and scale validation. For the item-generation phase, a summary of the literature combined with qualitative results from item-generation interviews with 29 acute or chronic leukemia patients and 16 health care providers yielded an initial item pool reflecting leukemia-specific concerns and symptoms. Items underwent iterations of review and reduction according to defined retention criteria to support content validity, as defined by priority concerns of patients. Seventeen final leukemia-specific items were combined with the Functional Assessment of Cancer Therapy-General to create the FACT-Leukemia (FACT-Leu) scale. For the validation phase, 79 individuals with acute or chronic leukemia completed questionnaires at three time points. RESULTS: All FACT-Leu subscale and aggregated scores showed high internal consistency (αs ranging from 0.75 to 0.96). Test-retest reliability was adequate for all subscales (intraclass correlation range 0.765-0.890). The FACT-Leu scale demonstrated good convergent validity, with significant correlations with quality-of-life criteria and performance status, in the expected direction. FACT-Leu subscale scores were significantly different among the three performance status change groups, suggesting good responsiveness to change. CONCLUSIONS: The FACT-Leu scale is a valid, reliable, and efficient measure of leukemia-specific health-related quality of life for acute and chronic disease.

Sleep as a predictor of tDCS and language therapy outcomes.

STUDY OBJECTIVES: To determine whether sleep at baseline (before therapy) predicted improvements in language following either language therapy alone or coupled with transcranial direct current stimulation (tDCS) in individuals with primary progressive aphasia (PPA). METHODS: Twenty-three participants with PPA (mean age 68.13 ± 6.21) received written naming/spelling therapy coupled with either anodal tDCS over the left inferior frontal gyrus (IFG) or sham condition in a crossover, sham-controlled, double-blind design (ClinicalTrials.gov identifier: NCT02606422). The outcome measure was percent of letters spelled correctly for trained and untrained words retrieved in a naming/spelling task. Given its particular importance as a sleep parameter in older adults, we calculated sleep efficiency (total sleep time/time in bed x100) based on subjective responses on the Pittsburgh Sleep Quality Index (PSQI). We grouped individuals based on a median split: high versus low sleep efficiency. RESULTS: Participants with high sleep efficiency benefited more from written naming/spelling therapy than participants with low sleep efficiency in learning therapy materials (trained words). There was no effect of sleep efficiency in generalization of therapy materials to untrained words. Among participants with high sleep efficiency, those who received tDCS benefitted more from therapy than those who received sham condition. There was no additional benefit from tDCS in participants with low sleep efficiency. CONCLUSION: Sleep efficiency modified the effects of language therapy and tDCS on language in participants with PPA. These results suggest sleep is a determinant of neuromodulation effects.Clinical Trial: tDCS Intervention in Primary Progressive Aphasia https://clinicaltrials.gov/ct2/show/NCT02606422.

Treating lexical retrieval using letter fluency and tDCS in primary progressive aphasia: a single-case study.

Background: In early stages, individuals with Primary Progressive Aphasia (PPA) report language symptoms while scoring within norm in formal language tests. Early intervention is important due to the progressive nature of the disease. Method: We report a single case study of an individual with logopenic variant PPA (lvPPA). We tested whether letter fluency, used as a therapy task, can improve lexical retrieval when combined with tDCS to either the left inferior-frontal gyrus (IFG) or the left inferior parietal lobe (IPL), administered in two separate therapy phases separated by a wash-out period of three months. Outcomes and results: We observed increases in number of words retrieved during a letter fluency task in trained and untrained letters, when letter fluency therapy (LeFT) was administered with anodal tDCS. When LeFT was combined with left IFG stimulation, words produced in a letter fluency task were lower frequency and higher age of acquisition after treatment, compared to before treatment and there was also an increase in accuracy and response times in an untrained picture-naming task. Conclusions: The results indicate that letter fluency therapy combined anodal tDCS is effective in improving lexical retrieval, particularly when left IFG stimulation was used. Effects generalize beyond the trained task, albeit slowing down of responses in picture naming. This task may provide a useful clinical intervention strategy for patients with mild anomia, who are not challenged enough by traditional naming therapies.

Protocol for a type 2 hybrid effectiveness-implementation study expanding, implementing and evaluating electronic health record-integrated patient-reported symptom monitoring in a multisite cancer centre.

INTRODUCTION: Cancer symptom monitoring and management interventions can address concerns that may otherwise go undertreated. However, such programmes and their evaluations remain largely limited to trials versus healthcare systemwide applications. We previously developed and piloted an electronic patient-reported symptom and need assessment ('cPRO' for cancer patient-reported outcomes) within the electronic health record (EHR). This study will expand cPRO implementation to medical oncology clinics across a large healthcare system. We will conduct a formal evaluation via a stepped wedge trial with a type 2 hybrid effectiveness-implementation design. METHODS AND ANALYSIS: Aim 1 comprises a mixed method evaluation of cPRO implementation. Adult outpatients will complete cPRO assessments (pain, fatigue, physical function, depression, anxiety and supportive care needs) before medical oncology visits. Results are available in the EHR; severe symptoms and endorsed needs trigger clinician notifications. We will track implementation strategies using the Longitudinal Implementation Strategy Tracking System. Aim 2 will evaluate cPRO's impact on patient and system outcomes over 12 months via (a) a quality improvement study (n=4000 cases) and (b) a human subjects substudy (n=1000 patients). Aim 2a will evaluate EHR-documented healthcare usage and patient satisfaction. In aim 2b, participating patients will complete patient-reported healthcare utilisation and quality, symptoms and health-related quality of life measures at baseline, 6 and 12 months. We will analyse data using generalised linear mixed models and estimate individual trajectories of patient-reported symptom scores at baseline, 6 and 12 months. Using growth mixture modelling, we will characterise the overall trajectories of each symptom. Aim 3 will identify cPRO implementation facilitators and barriers via mixed methods research gathering feedback from stakeholders. Patients (n=50) will participate in focus groups or interviews. Clinicians and administrators (n=40) will complete surveys to evaluate implementation. We will graphically depict longitudinal implementation survey results and code qualitative data using directed content analysis. ETHICS AND DISSEMINATION: This study was approved by the Northwestern University Institutional Review Board (STU00207807). Findings will be disseminated via local and conference presentations and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04014751; ClinicalTrials.gov.

Tracking dynamic changes in implementation strategies over time within a hybrid type 2 trial of an electronic patient-reported oncology symptom and needs monitoring program.

Background: Longitudinal tracking of implementation strategies is critical in accurately reporting when and why they are used, for promoting rigor and reproducibility in implementation research, and could facilitate generalizable knowledge if similar methods are used across research projects. This article focuses on tracking dynamic changes in the use of implementation strategies over time within a hybrid type 2 effectiveness-implementation trial of an evidence-based electronic patient-reported oncology symptom assessment for cancer patient-reported outcomes in a single large healthcare system. Methods: The Longitudinal Implementation Strategies Tracking System (LISTS), a timeline follow-back procedure for documenting strategy use and modifications, was applied to the multiyear study. The research team used observation, study records, and reports from implementers to complete LISTS in an electronic data entry system. Types of modifications and reasons were categorized. Determinants associated with each strategy were collected as a justification for strategy use and a potential explanation for strategy modifications. Results: Thirty-four discrete implementation strategies were used and at least one strategy was used from each of the nine strategy categories from the Expert Recommendations for Implementing Change (ERIC) taxonomy. Most of the strategies were introduced, used, and continued or discontinued according to a prospective implementation plan. Relatedly, a small number of strategies were introduced, the majority unplanned, because of the changing healthcare landscape, or to address an emergent barrier. Despite changing implementation context, there were relatively few modifications to the way strategies were enacted, such as a change in the actor, action, or dose. Few differences were noted between the trial's three regional units under investigation. Conclusion: This study occurred within the ambulatory oncology clinics of a large, academic medical center and was supported by the Quality team of the health system to ensure greater uptake, uniformity, and implementation within established practice change processes. The centralized nature of the implementation likely contributed to the relatively low proportion of modified strategies and the high degree of uniformity across regions. These results demonstrate the potential of LISTS in gathering the level of data needed to understand the impact of the many implementation strategies used to support adoption and delivery of a multilevel innovation. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04014751, identifier: NCT04014751.

Effects of tDCS on Sound Duration in Patients with Apraxia of Speech in Primary Progressive Aphasia.

Transcranial direct current stimulation (tDCS) over the left inferior frontal gyrus (IFG) was found to improve oral and written naming in post-stroke and primary progressive aphasia (PPA), speech fluency in stuttering, a developmental speech-motor disorder, and apraxia of speech (AOS) symptoms in post-stroke aphasia. This paper addressed the question of whether tDCS over the left IFG coupled with speech therapy may improve sound duration in patients with apraxia of speech (AOS) symptoms in non-fluent PPA (nfvPPA/AOS) more than sham. Eight patients with non-fluent PPA/AOS received either active or sham tDCS, along with speech therapy for 15 sessions. Speech therapy involved repeating words of increasing syllable-length. Evaluations took place before, immediately after, and two months post-intervention. Words were segmented into vowels and consonants and the duration of each vowel and consonant was measured. Segmental duration was significantly shorter after tDCS compared to sham and tDCS gains generalized to untrained words. The effects of tDCS sustained over two months post-treatment in trained and untrained sounds. Taken together, these results demonstrate that tDCS over the left IFG may facilitate speech production by reducing segmental duration. The results provide preliminary evidence that tDCS may maximize efficacy of speech therapy in patients with nfvPPA/AOS.

Part of Speech Production in Patients With Primary Progressive Aphasia: An Analysis Based on Natural Language Processing.

Background Primary progressive aphasia (PPA) is a neurodegenerative disorder characterized by a progressive decline of language functions. Its symptoms are grouped into three PPA variants: nonfluent PPA, logopenic PPA, and semantic PPA. Grammatical deficiencies differ depending on the PPA variant. Aims This study aims to determine the differences between PPA variants with respect to part of speech (POS) production and to identify morphological markers that classify PPA variants using machine learning. By fulfilling these aims, the overarching goal is to provide objective measures that can facilitate clinical diagnosis, evaluation, and prognosis. Method and Procedure Connected speech productions from PPA patients produced in a picture description task were transcribed, and the POS class of each word was estimated using natural language processing, namely, POS tagging. We then implemented a twofold analysis: (a) linear regression to determine how patients with nonfluent PPA, semantic PPA, and logopenic PPA variants differ in their POS productions and (b) a supervised classification analysis based on POS using machine learning models (i.e., random forests, decision trees, and support vector machines) to subtype PPA variants and generate feature importance (FI). Outcome and Results Using an automated analysis of a short picture description task, this study showed that content versus function words can distinguish patients with nonfluent PPA, semantic PPA, and logopenic PPA variants. Verbs were less important as distinguishing features of patients with different PPA variants than earlier thought. Finally, the study showed that among the most important distinguishing features of PPA variants were elaborative speech elements, such as adjectives and adverbs.

Automatic Subtyping of Individuals with Primary Progressive Aphasia.

BACKGROUND: The classification of patients with primary progressive aphasia (PPA) into variants is time-consuming, costly, and requires combined expertise by clinical neurologists, neuropsychologists, speech pathologists, and radiologists. OBJECTIVE: The aim of the present study is to determine whether acoustic and linguistic variables provide accurate classification of PPA patients into one of three variants: nonfluent PPA, semantic PPA, and logopenic PPA. METHODS: In this paper, we present a machine learning model based on deep neural networks (DNN) for the subtyping of patients with PPA into three main variants, using combined acoustic and linguistic information elicited automatically via acoustic and linguistic analysis. The performance of the DNN was compared to the classification accuracy of Random Forests, Support Vector Machines, and Decision Trees, as well as to expert clinicians' classifications. RESULTS: The DNN model outperformed the other machine learning models as well as expert clinicians' classifications with 80% classification accuracy. Importantly, 90% of patients with nfvPPA and 95% of patients with lvPPA was identified correctly, providing reliable subtyping of these patients into their corresponding PPA variants. CONCLUSION: We show that the combined speech and language markers from connected speech productions can inform variant subtyping in patients with PPA. The end-to-end automated machine learning approach we present can enable clinicians and researchers to provide an easy, quick, and inexpensive classification of patients with PPA.

White Matter Integrity Predicts Electrical Stimulation (tDCS) and Language Therapy Effects in Primary Progressive Aphasia.

BACKGROUND: Transcranial direct current stimulation (tDCS), in conjunction with language therapy, improves language therapy outcomes in primary progressive aphasia (PPA). However, no studies show whether white matter integrity predicts language therapy or tDCS effects in PPA. OBJECTIVE: We aimed to determine whether white matter integrity, measured by diffusion tensor imaging (DTI), predicts written naming/spelling language therapy effects (letter accuracy on trained and untrained words) with and without tDCS over the left inferior frontal gyrus (IFG) in PPA. METHODS: Thirty-nine participants with PPA were randomly assigned to tDCS or sham condition, coupled with language therapy for 15 daily sessions. White matter integrity was measured by mean diffusivity (MD) and fractional anisotropy (FA) in DTI scans before therapy. Written naming outcomes were evaluated before, immediately after, 2 weeks, and 2 months posttherapy. To assess tDCS treatment effect, we used a mixed-effects model with treatment evaluation and time interaction. We considered a forward model selection approach to identify brain regions/fasciculi of which white matter integrity can predict improvement in performance of word naming. RESULTS: Both sham and tDCS groups significantly improved in trained items immediately after and at 2 months posttherapy. Improvement in the tDCS group was greater and generalized to untrained words. White matter integrity of ventral language pathways predicted tDCS effects in trained items whereas white matter integrity of dorsal language pathways predicted tDCS effects in untrained items. CONCLUSIONS: White matter integrity influences both language therapy and tDCS effects. Thus, it holds promise as a biomarker for deciding which patients will benefit from language therapy and tDCS.