Developing consensus-based clinical competencies to guide stroke clinicians in the implementation of psychological care in aphasia rehabilitation.

Background People with aphasia experience depression and anxiety associated with negative outcomes across a range of time post-stroke. Stroke clinicians are well-positioned to facilitate low-intensity psychotherapeutic interventions after aphasia (e.g. mood screening, behavioural activation, problem-solving therapy, relaxation therapy); however, they self-report a lack of knowledge, skills and confidence to do so. The Theoretical Domains Framework (TDF) provides a lens through which to view and target clinician behaviours and training needs in this area of practice. The aim of this study was to develop and gain consensus on items for a rating scale of clinical competencies in facilitating individual-based, low-intensity psychotherapeutic interventions for people with aphasia. Methods An e-Delphi methodology using focus groups and survey rounds was used to gain consensus on clinical competencies considered important. Results Eight stroke clinicians (speech pathologists and psychologists), two people with aphasia and three family members participated in one of four focus groups. Four themes were derived from the data: (1) Communication support, (2) Assessment and therapy structure, (3) Interpersonal skills, and (4) Needs of the significant other (family or friend). Themes informed an initial list of 23 self-rated and observer-rated competency items. Following two rounds of e-Delphi surveys, 11 stroke clinicians (six speech pathologists and five psychologists) reached consensus (80-100%) for 19 competencies. Conclusions The Psychological Care in Aphasia Rehabilitation Competency scale offers a preliminary list of items to guide and train clinicians to implement low-intensity psychotherapeutic interventions for people with aphasia.

Aphasia Depression and Psychological Therapy (ADaPT): Perspectives of People with Post-Stroke Aphasia on Participating in a Modified Cognitive Behavioral Therapy.

Aphasia, a communication disability commonly caused by stroke, can profoundly affect a person's mood and identity. We explored the experiences of stroke survivors with aphasia and depression who received a modified cognitive behavioral therapy (CBT)-based psychological intervention. The therapy is manualized with a flexible treatment protocol, including 10 individually based therapy sessions (+2 booster sessions) either via telehealth or in person. Six participants with chronic aphasia (60% of the total sample) participated in in-depth interviews that were analyzed using reflexive thematic analysis. Two core themes were derived from the data: the first theme, helpful elements of therapy-doing enjoyable activities, new ways of thinking, problem solving, working with the experienced therapist, and using telehealth; and the second theme, making progress-mood, communication, acceptance of the 'new me', and improving relationships. All participants found the therapy to be helpful in managing mood problems with various elements being beneficial depending on the individual, highlighting the importance of tailoring the intervention. Therefore, delivering modified CBT to individuals with aphasia is likely to be acceptable both in person and through telehealth. Further evaluation of the intervention and its impact on mood would be beneficial.

Comprehensive quality assessment for aphasia rehabilitation after stroke: protocol for a multicentre, mixed-methods study.

INTRODUCTION: People with aphasia following stroke experience disproportionally poor outcomes, yet there is no comprehensive approach to measuring the quality of aphasia services. The Meaningful Evaluation of Aphasia SeRvicES (MEASuRES) minimum dataset was developed in partnership with people with lived experience of aphasia, clinicians and researchers to address this gap. It comprises sociodemographic characteristics, quality indicators, treatment descriptors and outcome measurement instruments. We present a protocol to pilot the MEASuRES minimum dataset in clinical practice, describe the factors that hinder or support implementation and determine meaningful thresholds of clinical change for core outcome measurement instruments. METHODS AND ANALYSIS: This research aims to deliver a comprehensive quality assessment toolkit for poststroke aphasia services in four studies. A multicentre pilot study (study 1) will test the administration of the MEASuRES minimum dataset within five Australian health services. An embedded mixed-methods process evaluation (study 2) will evaluate the performance of the minimum dataset and explore its clinical applicability. A consensus study (study 3) will establish consumer-informed thresholds of meaningful change on core aphasia outcome constructs, which will then be used to establish minimal important change values for corresponding core outcome measurement instruments (study 4). ETHICS AND DISSEMINATION: Studies 1 and 2 have been registered with the Australian and New Zealand Clinical Trial Registry (ACTRN12623001313628). Ethics approval has been obtained from the Royal Brisbane and Women's Hospital (HREC/2023/MNHB/95293) and The University of Queensland (2022/HE001946 and 2023/HE001175). Study findings will be disseminated through peer-reviewed publications, conference presentations and engagement with relevant stakeholders including healthcare providers, policy-makers, stroke and rehabilitation audit and clinical quality registry custodians, consumer support organisations, and individuals with aphasia and their families.

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.

Mental health support after stroke: A qualitative exploration of lived experience.

PURPOSE: Unmanaged mental health problems following a stroke can be detrimental to recovery. We aimed to explore the lived experience of (a) poststroke mental health difficulties, (b) help-seeking for mental health, including factors that influenced treatment access and utilization, and (c) receiving treatment and support. RESEARCH METHOD: Individual semistructured interviews were conducted in 2022 with 13 participants (62% female, age at stroke 35-76 years) who had experienced mental health difficulties following their stroke. Data were analyzed using reflexive thematic analysis with a critical realist approach. RESULTS: Six themes were identified. Mental health challenges poststroke were diverse in nature. Attitudes and previous experiences relating to mental health influenced the inclination to seek help. Participants valued an individualized approach to the provision and timing of psychoeducation. Accessibility of services was impacted by financial and transportation barriers, as well as availability of services and appropriately trained clinicians. Participation in support groups was a positive experience for most participants. Lived experience of mental health treatment ranged from positive to negative, and participants conveyed helpful and unhelpful aspects. CONCLUSIONS: Findings highlight the importance of early screening and psychoeducation provision for poststroke mental health difficulties, alongside accessible community-based mental health support services throughout the stroke recovery journey. Having varied options for mental health support and treatment may aid stroke survivors in finding an approach that personally works for them. Additionally, it may be helpful to train clinicians to tailor mental health treatment to accommodate stroke-related impairments (e.g., cognitive, sensorimotor). (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The Excess Costs of Hospitalization for Acute Stroke in People With Communication Impairment: A Stroke123 Data Linkage Substudy.

OBJECTIVE: To describe the costs of hospital care for acute stroke for patients with aphasia or dysarthria. DESIGN: Observational study from the Stroke123 project. SETTING: Data from patients admitted with stroke (2009-2013) from 22 hospitals in Queensland participating in the Australian Stroke Clinical Registry (AuSCR) were linked to administrative datasets. PARTICIPANTS: Communication impairments were identified using International Classification of Diseases, 10th Revision, Australian Modification codes. Overall, 1043 of 4195 (25%) patients were identified with aphasia (49% were women; median age 78 years; 83% with ischemic stroke), and 1005 (24%) with dysarthria (42% were women; median age 76 years; 85% with ischemic stroke). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Linked patient-level, hospital clinical costing related to the stroke, were adjusted to 2013/2014 Australian dollars (AU$, US$ conversion x 0.691) using recommended national price indices and multivariable regression analysis with clustering by hospital performed. RESULTS: Compared with patients without aphasia, the median hospital costs/patient were greater for those with aphasia for medical (aphasia AU$2273 vs AU$1727, P<.001), nursing (aphasia AU$3829 vs AU$2748, P<.001) and allied health services (aphasia AU$1138 vs AU$720, P<.001). Similarly, costs were greater for patients with dysarthria compared with those without dysarthria. Adjusted median total costs were AU$2882 greater for patients with aphasia compared with patients without aphasia (95% confidence interval, AU$1880-3884), and AU$843 greater for patients with dysarthria compared with those without dysarthria (95% confidence interval, AU$-301 to 1987). CONCLUSIONS: People with communication impairment after stroke incur greater hospital costs, in particular for medical, allied health, and nursing resources.

Pathologic Complete Response and Oncologic Outcomes in Locally Advanced Breast Cancers Treated With Neoadjuvant Radiation Therapy: An Australian Perspective.

PURPOSE: To assess the degree of pathologic complete response (pCR), postoperative surgical complication rates, and oncological outcomes in women with locally advanced breast cancer or high-risk breast cancers treated with neoadjuvant radiation therapy (NART). METHODS AND MATERIALS: This retrospective, multi-institutional review involved 138 clinically staged patients with 140 breast cancers treated with NART between January 2014 and February 2021. Treatments involved sequential neoadjuvant chemotherapy and NART, followed by mastectomy with or without axillary surgery and immediate autologous breast reconstruction. Descriptive statistics were used to assess patient and disease features, treatment regimens, pathologic response, and factors affecting postoperative complications. Kaplan-Meier curves were performed to assess locoregional recurrence-free, distant metastasis-free, and overall survival outcomes. RESULTS: Median age was 47 years (interquartile range, 42-52). The median follow-up was 35.2 months (interquartile range, 17.1-46.5). pCR was achieved in 36.4% (as defined by Chevallier classification) or 42.1% (as defined by Miller-Payne scores) of patients. Greater pCR rates were achieved for HER2+ (73.8%-85.7%) and triple-negative phenotypes (47.6%-57.1%). There were 21 grade 3 surgical complications including 10 grade 3B breast events and 8 grade 3B donor-site events, where surgical reintervention was required. At 3-years' follow-up, the locoregional recurrence-free survival was 98.1%, distant metastasis-free survival was 83.6%, and overall survival was 95.3%%. CONCLUSIONS: NART is feasible to facilitate a single-stage mastectomy and immediate autologous breast reconstruction. This study demonstrated comparable rates of postoperative complication to standard of care, and high rates of pCR, which translates to high rates of locoregional control, distant metastasis-free survival, and overall survival.

Internal mammary node involvement in patients with axilla-negative early breast cancer: a narrative review.

Early breast cancer staging involves radiological and pathological evaluation of the tumour and regional lymph nodes. The internal mammary nodes (IMN) are an important site of possible metastasis and influence disease stage and prognosis. However, the recommendation for routine IMN assessment remains unclear. Internal mammary sentinel lymph node biopsy (SLNB) is associated with increased morbidity and an unknown survival benefit. Furthermore, the IMN are traditionally thought to be involved only synchronous with, or following, axillary node (AXN) metastasis. The aim of this review is to determine the prevalence of IMN metastasis in patients with axilla-negative early breast cancer. A narrative review of studies assessing IMN metastasis was performed. The literature search was completed using the database Medline (Ovid). Twenty-two retrospective studies were identified. The studies included data from SLNB, US, MRI, PET/CT and opportunistic biopsy during free-flap reconstruction (FFR). The prevalence of isolated IMN metastasis ranged from 1.2% to 17.9%.

Coupled myovascular expansion directs cardiac growth and regeneration.

Heart regeneration requires multiple cell types to enable cardiomyocyte (CM) proliferation. How these cells interact to create growth niches is unclear. Here, we profile proliferation kinetics of cardiac endothelial cells (CECs) and CMs in the neonatal mouse heart and find that they are spatiotemporally coupled. We show that coupled myovascular expansion during cardiac growth or regeneration is dependent upon VEGF-VEGFR2 signaling, as genetic deletion of Vegfr2 from CECs or inhibition of VEGFA abrogates both CEC and CM proliferation. Repair of cryoinjury displays poor spatial coupling of CEC and CM proliferation. Boosting CEC density after cryoinjury with virus encoding Vegfa enhances regeneration. Using Mendelian randomization, we demonstrate that circulating VEGFA levels are positively linked with human myocardial mass, suggesting that Vegfa can stimulate human cardiac growth. Our work demonstrates the importance of coupled CEC and CM expansion and reveals a myovascular niche that may be therapeutically targeted for heart regeneration.

Outcomes of Convalescent Plasma with Defined High versus Lower Neutralizing Antibody Titers against SARS-CoV-2 among Hospitalized Patients: CoronaVirus Inactivating Plasma (CoVIP) Study.

COVID-19 convalescent plasma (CCP) was an early and widely adopted putative therapy for severe COVID-19. Results from randomized control trials and observational studies have failed to demonstrate a clear therapeutic role for CCP for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Underlying these inconclusive findings is a broad heterogeneity in the concentrations of neutralizing antibodies (nAbs) between different CCP donors. We conducted this study to evaluate the effectiveness and safety of nAb titer-defined CCP in adults admitted to an academic referral hospital. Patients positive by a SARS-CoV-2 nucleic acid amplification test and with symptoms for <10 days were eligible. Participants received either CCP with nAb titers of >1:640 (high-titer group) or ≥1:160 to 1:640 (standard-titer group) in addition to standard of care treatments. The primary clinical outcome was time to hospital discharge, with mortality and respiratory support evaluated as secondary outcomes. Adverse events were contrasted by CCP titer. Between 28 August and 4 December 2020, 316 participants were screened, and 55 received CCP, with 14 and 41 receiving high- versus standard-titer CCP, respectively. Time to hospital discharge was shorter among participants receiving high- versus standard-titer CCP, accounting for death as a competing event (hazard ratio, 1.94; 95% confidence interval [CI], 1.05 to 3.58; Gray's P = 0.02). Severe adverse events (SAEs) (≥grade 3) occurred in 4 (29%) and 23 (56%) of participants receiving the high versus standard titer, respectively, by day 28 (risk ratio, 0.51; 95% CI, 0.21 to 1.22; Fisher's P = 0.12). There were no observed treatment-related AEs. (This study has been registered at ClinicalTrials.gov under registration no. NCT04524507). IMPORTANCE In this study, in a high-risk population of patients admitted for COVID-19, we found an earlier time to hospital discharge among participants receiving CCP with nAb titers of >1:640 compared with participants receiving CCP with a lower nAb titer and no CCP-related AEs. The significance of our research is in identifying a dose response of CCP and clinical outcomes based on nAb titer. Although limited by a small study size, these findings support further study of high-nAb-titer CCP defined as >1:640 in the treatment of COVID-19.

Combined noncanonical NF-κB agonism and targeted BET bromodomain inhibition reverse HIV latency ex vivo.

Latency reversal strategies for HIV cure using inhibitor of apoptosis protein (IAP) antagonists (IAPi) induce unprecedented levels of latent reservoir expression without immunotoxicity during suppressive antiretroviral therapy (ART). However, full targeting of the reservoir may require combinatorial approaches. A Jurkat latency model screen for IAPi combination partners demonstrated synergistic latency reversal with bromodomain (BD) and extraterminal domain protein inhibitors (BETi). Mechanistic investigations using CRISPR-CAS9 and single-cell RNA-Seq informed comprehensive ex vivo evaluations of IAPi plus pan-BET, bD-selective BET, or selective BET isoform targeting in CD4+ T cells from ART-suppressed donors. IAPi+BETi treatment resulted in striking induction of cell-associated HIV gag RNA, but lesser induction of fully elongated and tat-rev RNA compared with T cell activation-positive controls. IAPi+BETi resulted in HIV protein induction in bulk cultures of CD4+ T cells using an ultrasensitive p24 assay, but did not result in enhanced viral outgrowth frequency using a standard quantitative viral outgrowth assay. This study defines HIV transcriptional elongation and splicing as important barriers to latent HIV protein expression following latency reversal, delineates the roles of BET proteins and their BDs in HIV latency, and provides a rationale for exploration of IAPi+BETi in animal models of HIV latency.

A systematic review of non-drug interventions to prevent and treat anxiety in people with aphasia after stroke.

PURPOSE: To investigate the effectiveness of non-drug interventions for people with aphasia in the prevention and/or treatment of anxiety post-stroke as either a primary or secondary outcome. MATERIALS AND METHODS: A systematic search of Medline, CINAHL, PsycINFO and Cochrane Library up to March 2021 was carried out. Studies of stroke populations were included if people with aphasia represented 25% or more of the enrolled participants. Quality of the evidence was assessed. A narrative synthesis of results is presented. The PROSPERO record ID for this study is 106451. RESULTS: Ten studies were included: five randomised controlled trials (RCTs), a single case experimental design, and four pre-post studies. The quality of the RCT trials was at least adequate but none demonstrated a benefit to anxiety outcomes. Those studies that reported benefit were of lower-level evidence with respect to National Health and Medical Research Classifications. No studies were found that evaluated the prevention of anxiety after stroke for people with aphasia. CONCLUSION: Definitive conclusions about the effectiveness of non-drug interventions for the prevention and/or treatment of anxiety in people with aphasia post-stroke cannot be made. Interventions that may show promise for those with aphasia and symptoms of anxiety include mindfulness meditation, modified cognitive behaviour therapy, unilateral nostril breathing, and the "Enhance Psychological Coping after Stroke" programme. Further high-quality research with better reporting of the inclusion of participants with aphasia and their specific sub-group results are required.Implications for RehabilitationIt is important for rehabilitation professionals to consider prevention of anxiety post-stroke as well as treatment.Mindfulness meditation, modified cognitive behavioural therapy, unilateral nostril breathing, and the and the "Enhance Psychological Coping after Stroke" programme may be of benefit to people with aphasia post-stroke.Adapting intervention protocols to be more communicatively accessible and training health professionals in supported communication may help people with aphasia engage in psychological therapies.

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).

Multicentre evaluation of magnetic technology for localisation of non-palpable breast lesions and targeted axillary nodes.

BACKGROUND: Magseed technology is a recently introduced localisation technique for impalpable breast lesions with possible advantages over traditional techniques. These include improved theatre logistics, flexibility in incision placement and improved patient experience. This multicentre study evaluates the experience of introducing Magseed technology into routine surgical practice. METHODS: A prospective multicentre study of Magseed localised procedures was performed. Insertion data were recorded by the radiologist including lesion characteristics and Magseed insertion accuracy. The surgical team recorded time from insertion to operation, operating time and surgical satisfaction. Pathology results were reviewed for specimen weight and margins. RESULTS: Between February 2019 and June 2020, 100 patients were enrolled. Magseed localised procedures included 18 excisional biopsies, 23 wide local excisions (WLE), 50 WLE with axillary surgery and four cases of Magseed localised breast WLE with Magseed localised axillary surgery. There were three therapeutic mammoplasties and two cases of Magseed localised targeted axillary node dissection alone. A total of 90% of Magseeds were radiologically placed within 5 mm of the target lesion/node. Time between incision and specimen removal was 17 min (range 6-40 min). All breast and axillary Magseeds were successfully identified and retrieved during surgery. The target lesion was identified in the specimen in all cases. A total of 10% of cases required further surgery for pathologically positive margins. Overall, surgeons reported that Magseed localisation was "easy" or "very easy" in 77% of cases. CONCLUSION: Magseed is a reliable, safe and accurate surgical technique that provides logistical advantages and flexibility of surgical approach. The method was well-accepted by all users.

Neoadjuvant radiotherapy for locally advanced and high-risk breast cancer.

INTRODUCTION: Neoadjuvant radiotherapy (NART) as part of a multi-modality approach for locally advanced breast cancer (LABC) requires further investigation. Importantly, this approach may allow for a single-staged surgical procedure, with mastectomy and immediate autologous reconstruction. Multiple other potential benefits of NART include improved pathological downstaging of breast disease, reduced overall treatment time, elimination of time period with breast tissue deficit and improved patient satisfaction. METHODS: This is a retrospective multi-institutional review of patients with LABC and high-risk breast disease undergoing NART. Eligible patients sequentially underwent neoadjuvant chemotherapy (NACT) with or without HER2-targeted therapy, NART, followed by mastectomy with immediate autologous breast reconstruction (BR) 4- to 6 weeks post-completion of radiotherapy. Patient and tumour characteristics were analysed using descriptive statistics. Surgical complications were assessed using the Clavien-Dindo Classification (Ann Surg 2004; 240: 205). RESULTS: From 3/2013 to 9/2019, 153 patients were treated with NART. The median age was 47 years (IQR 42-52), with median body mass index of 27. Eighteen patients experienced Grade 3 acute surgical complications. This included 13 Grade 3B breast-site events and 9 Grade 3B donor-site events, where further surgical intervention was required for management of wound infection, wound dehiscence, flap or mastectomy skin necrosis, haematoma and internal mammary venous anastomotic thrombosis. No autologous flap loss was observed. CONCLUSION: Neoadjuvant radiotherapy facilitates a single-stage surgical procedure with mastectomy and immediate autologous BR, eliminating the delay to reconstructive surgery and thus shortening a woman's breast cancer journey. The findings of this review support the use of NART, with comparable rates of surgical complications to standard sequencing.

Progressive silicone lymphadenopathy post mastectomy and implant reconstruction for breast cancer.

A 56-year-old woman with a 12-year history of recurrent triple-negative invasive carcinoma of the breast presented with progressive enlargement of lymph nodes in the setting of established rupture of the ipsilateral silicone breast implant. Although this was proven to be benign on cytology, its progressive nature led to repeated core biopsies for histology, which were necessary given the high-risk nature of triple-negative breast cancer and the multiple proven previous recurrences. The histology demonstrated features of silicone deposits without evidence of malignancy. This case demonstrates the dilemma in surveillance of high-risk patients with breast cancer who have had previous silicone lymphadenopathy.

Stroke health professionals' management of depression after post-stroke aphasia: a qualitative study.

Background: People with post-stroke aphasia commonly experience mental health conditions, with depression having a high prevalence. An understanding of current practice may inform ways to improve psychological care for people with aphasia.Aim: To explore current practice for managing depression after post-stroke aphasia from the perspective of stroke health professionals.Method: Five semi-structured focus groups were conducted with 39 stroke health professionals across the care continuum. Focus groups were transcribed verbatim and analyzed using the method of Interpretive Description.Results: Analysis of verbatim transcripts revealed four core themes: (1) concomitant aphasia and depression after stroke is a challenging area of rehabilitation, (2) mood difficulties and depression are not always a high stroke rehabilitation priority, (3) approaches to identification and management are ad hoc, and (4) stroke health professionals are trying to bridge the gap between clients' psychological care needs and limited services. Sub-themes were also identified.Conclusion: This study demonstrates that health professionals are challenged by and limited in managing depression after post-stroke aphasia. Health professionals have the opportunity to improve services through the translation of evidence-based interventions. The integration of mental health care into stroke rehabilitation may be achieved through policy development, leadership and specialist training.Implications for rehabilitationPeople with aphasia need routine mood screening using aphasia-specific clinical tools and communication support.Stroke health professionals report a need for communication partner training to facilitate mental healthcare for people with aphasia.Family members need to be involved in aphasia rehabilitation to gain psychological care for themselves and the person with aphasia.

Longitudinal Dynamics of Intact HIV Proviral DNA and Outgrowth Virus Frequencies in a Cohort of Individuals Receiving Antiretroviral Therapy.

BACKGROUND: The replication-competent human immunodeficiency virus (HIV) reservoir is the major barrier to cure. The quantitative viral outgrowth assay (QVOA), the gold-standard method to quantify replication-competent HIV, is resource intensive, which limits its application in large clinical trials. The intact proviral DNA assay (IPDA) requires minimal cell input relative to QVOA and quantifies both defective and intact proviral HIV DNA, the latter potentially serving as a surrogate marker for replication-competent provirus. However, there are limited cross-sectional and longitudinal data on the relationship between IPDA and QVOA measurements. METHODS: QVOA and IPDA measurements were performed on 156 resting CD4 T-cell (rCD4) samples from 83 antiretroviral therapy-suppressed HIV-positive participants. Longitudinal QVOA and IPDA measurements were performed on rCD4 from 29 of these participants. RESULTS: Frequencies of intact, defective, and total proviruses were positively associated with frequencies of replication-competent HIV. Longitudinally, decreases in intact proviral frequencies were strikingly similar to that of replication-competent virus in most participants. In contrast, defective proviral DNA frequencies appeared relatively stable over time in most individuals. CONCLUSIONS: Changes in frequencies of IPDA-derived intact proviral DNA and replication-competent HIV measured by QVOA are similar. IPDA is a promising high-throughput approach to estimate changes in the frequency of the replication-competent reservoir.

Sequence Evaluation and Comparative Analysis of Novel Assays for Intact Proviral HIV-1 DNA.

The HIV proviral reservoir is the major barrier to cure. The predominantly replication-defective proviral landscape makes the measurement of virus that is likely to cause rebound upon antiretroviral therapy (ART)-cessation challenging. To address this issue, novel assays to measure intact HIV proviruses have been developed. The intact proviral DNA assay (IPDA) is a high-throughput assay that uses two probes to exclude the majority of defective proviruses and determine the frequency of intact proviruses, albeit without sequence confirmation. Quadruplex PCR with four probes (Q4PCR) is a lower-throughput assay that uses limiting dilution long-distance PCR amplification followed by quantitative PCR (qPCR) and near-full-length genome sequencing (nFGS) to estimate the frequency of sequence-confirmed intact proviruses and provide insight into their clonal composition. To explore the advantages and limitations of these assays, we compared IPDA and Q4PCR measurements from 39 ART-suppressed people living with HIV. We found that IPDA and Q4PCR measurements correlated with one another, but frequencies of intact proviral DNA differed by approximately 19-fold. This difference may be in part due to inefficiencies in long-distance PCR amplification of proviruses in Q4PCR, leading to underestimates of intact proviral frequencies. In addition, nFGS analysis within Q4PCR explained that some of this difference is explained by proviruses that are classified as intact by IPDA but carry defects elsewhere in the genome. Taken together, this head-to-head comparison of novel intact proviral DNA assays provides important context for their interpretation in studies to deplete the HIV reservoir and shows that together the assays bracket true reservoir size.IMPORTANCE The intact proviral DNA assay (IPDA) and quadruplex PCR (Q4PCR) represent major advances in accurately quantifying and characterizing the replication-competent HIV reservoir. This study compares the two novel approaches for measuring intact HIV proviral DNA in samples from 39 antiretroviral therapy (ART)-suppressed people living with HIV, thereby informing ongoing efforts to deplete the HIV reservoir in cure-related trials.