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1.
Med Care ; 59(6): 550-556, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-33797509

RESUMEN

BACKGROUND: The Veterans Health Administration (VHA) does not routinely collect and document sexual orientation and gender identity (SOGI) data despite research on health disparities among sexual and gender minority (SGM) veterans. Due to the legacy of previous Department of Defense policies that prohibited disclosure of sexual or gender minority identities among active-duty personnel, minority veterans may be reluctant to respond to SOGI questions on confidential VHA surveys and in discussions with their VHA providers. Veterans may generally find SOGI questions uncomfortable and may not appreciate their relevance to health care. OBJECTIVE: The purpose of this research was to examine veterans' comfort in reporting identity characteristics on confidential VHA surveys and in discussion with their VHA providers and whether comfort differed by sociodemographic characteristics. RESEARCH DESIGN: The project involves the secondary analysis of quantitative data from a quality improvement survey project. SUBJECTS: A total of 806 veterans were surveyed. RESULTS: Overall, 7.15% endorsed sexual or gender minority identity which is a higher rate than the 4.5% noted in the general US population. Cisgender and heterosexual veterans were more comfortable reporting identity characteristics both on VHA confidential surveys and in discussion with VHA providers compared with SGM veterans. CONCLUSIONS: These data suggest that the majority of veterans feel comfortable reporting their identities both on surveys and in the context of health care. Understanding these perceptions can assist VHA programs in implementing SOGI data collection and disclosure in clinical care, creating a welcoming environment of care for SGM veterans that does not make veterans from other backgrounds feel uncomfortable.


Asunto(s)
Revelación , Identidad de Género , Conducta Sexual , Veteranos/psicología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Estados Unidos , United States Department of Veterans Affairs
2.
Phys Occup Ther Pediatr ; 37(4): 444-455, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28121255

RESUMEN

AIMS: To explore parents' perceptions of their youth's transition from rehabilitation to school following an Acquired Brain Injury (ABI) and how physiotherapy influenced the youth's participation and physical function during the transition. METHODS: The study utilized phenomenological qualitative methodology using semi-structured interviews with 11 parents of youth 10 to 18 years of age recruited from one pediatric rehabilitation hospital in Ontario. Each interview was audiotaped, transcribed verbatim, and thematically analyzed. RESULTS: Parents valued physiotherapy and highlighted potential areas of improved service delivery to promote participation in an active lifestyle during this transition. In addition to being parents, they had to assume new roles and responsibilities in order to motivate their youth to continue with therapy and physical activity and had to facilitate their participation in school, recreational and social activities. CONCLUSION: For youth following an ABI, the transition back to school is complex and strategies should be supportive and responsive. Implications for physiotherapists include improved collaboration with community partners to motivate youth and promote physical activity; engage youth with their peers early in the rehabilitation process; and ongoing support for parents.


Asunto(s)
Lesiones Encefálicas/rehabilitación , Niños con Discapacidad/psicología , Modalidades de Fisioterapia/estadística & datos numéricos , Adolescente , Niño , Niños con Discapacidad/rehabilitación , Femenino , Humanos , Masculino , Motivación , Ontario , Padres/psicología , Investigación Cualitativa , Servicios de Salud Escolar , Instituciones Académicas
3.
Sci Rep ; 14(1): 17741, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39085467

RESUMEN

Cities generate large amounts of plastic waste and thus are often major sources of plastic pollution. Microplastics (particles < 5 mm) are a growing ecological concern as they are readily transported through the environment by wind, flowing water, and other transport processes. Here, we report the findings of an intensive field study that tested associations between prevailing winds and the distribution of plastic pollution around urban lakes (n = 20 lakes) in offshore sediments, shoreline sediments, and surface waters. We tested and found support for the hypothesis that prevailing winds influence the distribution of plastics around lakes. Overall, lakes had greater proportions of macroplastics (i.e., large plastic trash) and microplastics in sediments collected along northern lake shorelines. Notably, we found that macroplastic trash and total microplastics were, respectively, 1.7 and 3 times more abundant in sediments sampled along northern shorelines. Contrary to our expectation, we also found that microplastics in offshore sediments were in greater proportions along western lake shorelines, indicating that wind-driven processes might not explain the distribution of plastics in all lake zones. Furthermore, we observed no discernable patterns within lake surface waters and only captured a handful of suspended microplastic fragments and films from the water column. Overall, our findings revealed that the heterogeneous accumulation of plastic pollution at a lake is influenced, in part, by wind-driven processes. Moreover, these patterns extend across a network of lakes that were distributed across an urbanized landscape.

4.
CHEST Crit Care ; 2(2)2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38957855

RESUMEN

BACKGROUND: Nearly one-quarter of all Americans die in the ICU. Many of their deaths are anticipated and occur following the withdrawal of mechanical ventilation (WMV). However, there are few data on which to base best practices for interdisciplinary ICU teams to conduct WMV. RESEARCH QUESTION: What are the perceptions of current WMV practices among ICU clinicians, and what are their opinions of processes that might improve the practice of WMV at end of life in the ICU? STUDY DESIGN AND METHODS: This prospective two-center observational study conducted in Boston, Massachusetts, the Observational Study of the Withdrawal of Mechanical Ventilation (OBSERVE-WMV) was designed to better understand the perspectives of clinicians and experience of patients undergoing WMV. This report focuses on analyses of qualitative data obtained from in-person surveys administered to the ICU clinicians (nurses, respiratory therapists, and physicians) caring for these patients. Surveys assessed a broad range of clinician perspectives on planning, as well as the key processes required for WMV. This analysis used independent open, inductive coding of responses to open-ended questions. Initial codes were reconciled iteratively and then organized and interpreted using a thematic analysis approach. Opinions were assessed on how WMV could be improved for individual patients and the ICU as a whole. RESULTS: Among 456 eligible clinicians, 312 in-person surveys were completed by clinicians caring for 152 patients who underwent WMV. Qualitative analyses identified two main themes characterizing high-quality WMV processes: (1) good communication (eg, mutual understanding of family preferences) between the ICU team and family; and (2) medical management (eg, planning, availability of ICU team) that minimizes patient distress. Team member support was identified as an essential process component in both themes. INTERPRETATION: Clinician perceptions of the appropriateness or success of WMV prioritize the quality of team and family communication and patient symptom management. Both are modifiable targets of interventions aimed at optimizing overall WMV.

5.
Neuroimage ; 75: 97-107, 2013 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-23470982

RESUMEN

Practicing a musical instrument has a profound impact on the structure and function of the human brain. The present fMRI study explored how relative hemispheric asymmetries in task-related activity during music processing (same/different discrimination) are shaped by musical training (quantified as cumulative hours of instrument practice), using both a large (N=84) cross-sectional data set of children and adults, and a smaller (N=20) two time-point longitudinal data set of children tracked over 3 to 5 years. The cross-sectional analysis revealed a significant leftward asymmetry in task-related activation, with peaks in Heschl's gyrus and supramarginal gyrus (SMG). The SMG peak was further characterized by a leftward asymmetry in the partial correlation strength with subjects' cumulative hours of practice, controlling for subjects' age and task performance. This SMG peak was found to exhibit a similar pattern of response in the longitudinal data set (in this case, with subjects' cumulative hours of practice over the course of the study), controlling for age, scan interval, and amount of instrument practice prior to the first scan. This study presents novel insights into the ways musical instrument training shapes task-related asymmetries in neural activity during music processing.


Asunto(s)
Percepción Auditiva/fisiología , Encéfalo/fisiología , Lateralidad Funcional/fisiología , Memoria a Corto Plazo/fisiología , Música , Adulto , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Adulto Joven
6.
Ann N Y Acad Sci ; 1519(1): 173-185, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36349876

RESUMEN

Patients with large left-hemisphere lesions and post-stroke aphasia often remain nonfluent. Melodic intonation therapy (MIT) may be an effective alternative to traditional speech therapy for facilitating recovery of fluency in those patients. In an open-label, proof-of-concept study, 14 subjects with nonfluent aphasia with large left-hemisphere lesions (171 ± 76 cc) underwent two speech/language assessments before, one at the midpoint, and two after the end of 75 sessions (1.5 h/session) of MIT. Functional MR imaging was done before and after therapy asking subjects to vocalize the same set of 10 bi-syllabic words. We found significant improvements in speech output after a period of intensive MIT (75 sessions for a total of 112.5 h) compared to two pre-therapy assessments. Therapy-induced gains were maintained 4 weeks post-treatment. Imaging changes were seen in a right-hemisphere network that included the posterior superior temporal and inferior frontal gyri, inferior pre- and postcentral gyri, pre-supplementary motor area, and supramarginal gyrus. Functional changes in the posterior right inferior frontal gyri significantly correlated with changes in a measure of fluency. Intense training of intonation-supported auditory-motor coupling and engaging feedforward/feedback control regions in the unaffected hemisphere improves speech-motor functions in subjects with nonfluent aphasia and large left-hemisphere lesions.


Asunto(s)
Afasia de Broca , Logopedia , Humanos , Afasia de Broca/terapia , Afasia de Broca/patología , Logopedia/métodos , Imagen por Resonancia Magnética , Habla , Corteza Prefrontal
7.
Neuroimage ; 60(3): 1902-12, 2012 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-22348885

RESUMEN

Two major influences on how the brain processes music are maturational development and active musical training. Previous functional neuroimaging studies investigating music processing have typically focused on either categorical differences between "musicians versus nonmusicians" or "children versus adults." In the present study, we explored a cross-sectional data set (n=84) using multiple linear regression to isolate the performance-independent effects of age (5 to 33 years) and cumulative duration of musical training (0 to 21,000 practice hours) on fMRI activation similarities and differences between melodic discrimination (MD) and rhythmic discrimination (RD). Age-related effects common to MD and RD were present in three left hemisphere regions: temporofrontal junction, ventral premotor cortex, and the inferior part of the intraparietal sulcus, regions involved in active attending to auditory rhythms, sensorimotor integration, and working memory transformations of pitch and rhythmic patterns. By contrast, training-related effects common to MD and RD were localized to the posterior portion of the left superior temporal gyrus/planum temporale, an area implicated in spectrotemporal pattern matching and auditory-motor coordinate transformations. A single cluster in right superior temporal gyrus showed significantly greater activation during MD than RD. This is the first fMRI which has distinguished maturational from training effects during music processing.


Asunto(s)
Envejecimiento/fisiología , Percepción Auditiva/fisiología , Corteza Cerebral/fisiología , Neuroimagen Funcional/métodos , Imagen por Resonancia Magnética/métodos , Música , Análisis y Desempeño de Tareas , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Adulto Joven
8.
Ann N Y Acad Sci ; 1515(1): 266-275, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35754007

RESUMEN

We tested an intonation-based speech treatment for minimally verbal children with autism (auditory-motor mapping training, AMMT) against a nonintonation-based control treatment (speech repetition therapy, SRT). AMMT involves singing, rather than speaking, two-syllable words or phrases. In time with each sung syllable, therapist and child tap together on electronic drums tuned to the same pitches, thus coactivating shared auditory and motor neural representations of manual and vocal actions, and mimicking the "babbling and banging" stage of typical development. Fourteen children (three females), aged 5.0-10.8, with a mean Autism Diagnostic Observation Schedule-2 score of 22.9 (SD = 2.5) and a mean Kaufman Speech Praxis Test raw score of 12.9 (SD = 13.0) participated in this trial. The main outcome measure was percent syllables approximately correct. Four weeks post-treatment, AMMT resulted in a mean improvement of +12.1 (SE = 3.8) percentage points, compared to +2.8 (SE = 5.7) percentage points for SRT. This between-group difference was associated with a large effect size (Cohen's d = 0.82). Results suggest that simultaneous intonation and bimanual movements presented in a socially engaging milieu are effective factors in AMMT and can create an individualized, interactive music-making environment for spoken-language learning in minimally verbal children with autism.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Música , Trastorno del Espectro Autista/terapia , Trastorno Autístico/complicaciones , Trastorno Autístico/terapia , Niño , Preescolar , Femenino , Humanos , Lenguaje , Masculino , Habla
9.
Stroke ; 42(8): 2251-6, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21719773

RESUMEN

BACKGROUND AND PURPOSE: Previous studies have suggested that patients' potential for poststroke language recovery is related to lesion size; however, lesion location may also be of importance, particularly when fiber tracts that are critical to the sensorimotor mapping of sounds for articulation (eg, the arcuate fasciculus) have been damaged. In this study, we tested the hypothesis that lesion loads of the arcuate fasciculus (ie, volume of arcuate fasciculus that is affected by a patient's lesion) and of 2 other tracts involved in language processing (the extreme capsule and the uncinate fasciculus) are inversely related to the severity of speech production impairments in patients with stroke with aphasia. METHODS: Thirty patients with chronic stroke with residual impairments in speech production underwent high-resolution anatomic MRI and a battery of cognitive and language tests. Impairment was assessed using 3 functional measures of spontaneous speech (eg, rate, informativeness, and overall efficiency) as well as naming ability. To quantitatively analyze the relationship between impairment scores and lesion load along the 3 fiber tracts, we calculated tract-lesion overlap volumes for each patient using probabilistic maps of the tracts derived from diffusion tensor images of 10 age-matched healthy subjects. RESULTS: Regression analyses showed that arcuate fasciculus lesion load, but not extreme capsule or uncinate fasciculus lesion load or overall lesion size, significantly predicted rate, informativeness, and overall efficiency of speech as well as naming ability. CONCLUSIONS: A new variable, arcuate fasciculus lesion load, complements established voxel-based lesion mapping techniques and, in the future, may potentially be used to estimate impairment and recovery potential after stroke and refine inclusion criteria for experimental rehabilitation programs.


Asunto(s)
Afasia/fisiopatología , Encéfalo/fisiopatología , Recuperación de la Función/fisiología , Accidente Cerebrovascular/fisiopatología , Anciano , Afasia/etiología , Afasia/patología , Encéfalo/patología , Mapeo Encefálico , Femenino , Humanos , Pruebas del Lenguaje , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vías Nerviosas/patología , Vías Nerviosas/fisiopatología , Medición de la Producción del Habla , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/patología
10.
Am J Speech Lang Pathol ; 30(3S): 1542-1557, 2021 06 18.
Artículo en Inglés | MEDLINE | ID: mdl-33852328

RESUMEN

Purpose Understanding what limits speech development in minimally verbal (MV) children with autism spectrum disorder (ASD) is important for providing highly effective targeted therapies. This preliminary investigation explores the extent to which developmental speech deficits predicted by Directions Into Velocities of Articulators (DIVA), a computational model of speech production, exemplify real phenotypes. Method Implementing a motor speech disorder in DIVA predicted that speech would become highly variable within and between tokens, while implementing a motor speech plus an auditory processing disorder predicted that DIVA's speech would become highly centralized (schwa-like). Acoustic analyses of DIVA's output predicted that acoustically measured phoneme distortion would be similar between the two cases, but that in the former case, speech would show more within- and between-token variability than in the latter case. We tested these predictions quantitatively on the speech of children with MV ASD. In Study 1, we tested the qualitative predictions using perceptual analysis methods. Speech pathologists blinded to the purpose of the study tallied the signs of childhood apraxia of speech that appeared in the speech of 38 MV children with ASD. K-means clustering was used to create two clusters from the group of 38, and analysis of variance was used to determine whether the clusters differed according to perceptual features corresponding to within- and between-token variability. In Study 2, we employed acoustic analyses on the speech of the child from each cluster who produced the largest number of analyzable tokens to test the predictions of differences in within-token variability, between-token variability, and vowel space area. Results Clusters produced by k-means analysis differed by perceptual features that corresponded to within-token variability. Nonsignificant differences between clusters were found for features corresponding to between-token variability. Subsequent acoustic analyses of the selected cases revealed that the speech of the child from the high-variability cluster showed significantly more quantitative within- and between-token variability than the speech of the child from the low-variability cluster. The vowel space of the child from the low-variability cluster was more centralized than that of typical children and that of the child from the high-variability cluster. Conclusions Results provide preliminary evidence that subphenotypes of children with MV ASD may exist, characterized by (a) comorbid motor speech disorder and (b) comorbid motor speech plus auditory processing disorder. The results motivate testable predictions about how these comorbidities affect speech. Supplemental Material https://doi.org/10.23641/asha.14384432.


Asunto(s)
Apraxias , Trastorno del Espectro Autista , Trastornos del Desarrollo del Lenguaje , Trastorno del Espectro Autista/complicaciones , Trastorno del Espectro Autista/diagnóstico , Niño , Humanos , Trastornos del Desarrollo del Lenguaje/diagnóstico , Trastornos del Desarrollo del Lenguaje/terapia , Habla , Trastornos del Habla/diagnóstico , Trastornos del Habla/terapia
11.
J Neurosci ; 29(10): 3019-25, 2009 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-19279238

RESUMEN

The human brain has the remarkable capacity to alter in response to environmental demands. Training-induced structural brain changes have been demonstrated in the healthy adult human brain. However, no study has yet directly related structural brain changes to behavioral changes in the developing brain, addressing the question of whether structural brain differences seen in adults (comparing experts with matched controls) are a product of "nature" (via biological brain predispositions) or "nurture" (via early training). Long-term instrumental music training is an intense, multisensory, and motor experience and offers an ideal opportunity to study structural brain plasticity in the developing brain in correlation with behavioral changes induced by training. Here we demonstrate structural brain changes after only 15 months of musical training in early childhood, which were correlated with improvements in musically relevant motor and auditory skills. These findings shed light on brain plasticity and suggest that structural brain differences in adult experts (whether musicians or experts in other areas) are likely due to training-induced brain plasticity.


Asunto(s)
Encéfalo/crecimiento & desarrollo , Aprendizaje/fisiología , Música , Neurogénesis/fisiología , Factores de Edad , Niño , Preescolar , Femenino , Humanos , Estudios Longitudinales , Masculino , Plasticidad Neuronal/fisiología , Factores de Tiempo
12.
Neurol Clin Pract ; 10(2): 162-169, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32309035

RESUMEN

OBJECTIVE: To determine the contributions of apraxia of speech (AOS) and anomia to conversational dysfluency. METHODS: In this observational study of 52 patients with chronic aphasia, 47 with concomitant AOS, fluency was quantified using correct information units per minute (CIUs/min) from propositional speech tasks. Videos of patients performing conversational, how-to and picture-description tasks, word and sentence repetition, and diadochokinetic tasks were used to diagnose AOS using the Apraxia of Speech Rating Scale (ASRS). Anomia was quantified by patients' scores on the 30 even-numbered items from the Boston Naming Test (BNT). RESULTS: Together, ASRS and BNT scores accounted for 51.4% of the total variance in CIUs/min; the ASRS score accounted for the majority of that variance. The BNT score was associated with lesions in the left superior temporal gyrus, left inferior frontal gyrus, and large parts of the insula. The global ASRS score was associated with lesions in the left dorsal arcuate fasciculus (AF), pre- and post-central gyri, and both banks of the central sulcus of the insula. The ASRS score for the primary distinguishing features of AOS (no overlap with features of aphasia) was associated with less AF and more insular involvement. Only ∼27% of this apraxia-specific lesion overlapped with lesions associated with the BNT score. Lesions associated with AOS had minimal overlap with the frontal aslant tract (FAT) (<1%) or the extreme capsule fiber tract (1.4%). Finally, ASRS scores correlated significantly with damage to the insula but not to the AF, extreme capsule, or FAT. CONCLUSIONS: Results are consistent with previous findings identifying lesions of the insula and AF in patients with AOS, damage to both of which may create dysfluency in patients with aphasia.

13.
J Commun Disord ; 87: 106033, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32877838

RESUMEN

PURPOSE: To investigate the latent factors underlying signs of childhood apraxia of speech (CAS) in a group of 57 children with CAS. METHOD: The speech of 57 children with CAS (aged 3;5-17;0) was coded for signs of CAS. All participants showed at least five signs of CAS and were judged to have CAS by speech pathologists experienced in pediatric speech disorders. Participants were selected to represent a range of severity of CAS: 30 children were verbal and 27 were minimally verbal with comorbid autism. Participants' scores for each sign (the number of times that sign appeared during a child's speech sample) were converted to z-scores, then entered as variables into an exploratory factor analysis. Models were compared using the Akaike Information Criterion (AIC). RESULTS: The three-factor model had the lowest AIC and best fit the data. After oblique rotation, syllable segmentation, slow rate, and stress errors loaded most highly on Factor 1. Groping, addition of phonemes other than schwa, and difficulty with coarticulation loaded most highly on Factor 2. Variable errors loaded most highly on Factor 3. Thus, factors were interpreted as being associated with (1) prosody, (2) coarticulation, and (3) inconsistency. CONCLUSIONS: Results are consistent with the three consensus criteria for CAS from the American Speech-Language-Hearing Association: Inappropriate prosody, disrupted coarticulatory transitions, and inconsistent errors on repeated tokens. High loading of the syllable segmentation sign on the inappropriate prosody factor also supports the use of a pause-related biomarker for CAS.


Asunto(s)
Apraxias , Trastornos del Habla , Patología del Habla y Lenguaje , Adolescente , Apraxias/diagnóstico , Niño , Preescolar , Análisis Factorial , Humanos , Habla , Trastornos del Habla/diagnóstico
14.
Trials ; 21(1): 544, 2020 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-32560744

RESUMEN

OBJECTIVES: Phase I - To determine the optimal dose of each candidate (or combination of candidates) entered into the platform. Phase II - To determine the efficacy and safety of each candidate entered into the platform, compared to the current Standard of Care (SoC), and recommend whether it should be evaluated further in a later phase II & III platforms. TRIAL DESIGN: AGILE-ACCORD is a Bayesian multicentre, multi-arm, multi-dose, multi-stage open-label, adaptive, seamless phase I/II randomised platform trial to determine the optimal dose, activity and safety of multiple candidate agents for the treatment of COVID-19. Designed as a master protocol with each candidate being evaluated within its own sub-protocol (Candidate Specific Trial (CST) protocol), randomising between candidate and SoC with 2:1 allocation in favour of the candidate (N.B the first candidate has gone through regulatory approval and is expected to open to recruitment early summer 2020). Each dose will be assessed for safety sequentially in cohorts of 6 patients. Once a phase II dose has been identified we will assess efficacy by seamlessly expanding into a larger cohort. PARTICIPANTS: Patient populations can vary between CSTs, but the main eligibility criteria include adult patients (≥18 years) who have laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We will include both severe and mild-moderate patients defined as follows: Group A (severe disease) - patients with WHO Working Group on the Clinical Characteristics of COVID-19 infection 9-point ordinal scale of Grades 4 (hospitalised, oxygen by mask or nasal prongs), 5 (hospitalised, non-invasive ventilation or high flow oxygen), 6 (hospitalised, intubation and mechanical ventilation) or 7 (hospitalised, ventilation and additional organ support); Group B (mild-moderate disease) - ambulant or hospitalised patients with peripheral capillary oxygen saturation (SpO2) >94% RA. If any CSTs are included in the community setting, the CST protocol will clarify whether patients with suspected SARS-CoV-2 infection are also eligible. Participants will be recruited from England, North Ireland, Wales and Scotland. INTERVENTION AND COMPARATOR: Comparator is the current standard of care (SoC), in some CSTs plus placebo. Candidates that prevent uncontrolled cytokine release, prevention of viral replication, and other anti-viral treatment strategies are at various stages of development for inclusion into AGILE-ACCORD. Other CSTs will be added over time. There is not a set limit on the number of CSTs we can include within the AGILE-ACCORD Master protocol and we will upload each CST into this publication as each opens to recruitment. MAIN OUTCOMES: Phase I: Dose limiting toxicities using Common Terminology Criteria for Adverse Events v5 Grade ≥3 adverse events. Phase II: Agreed on a CST basis depending on mechanism of action of the candidate and patient population. But may include; time to clinical improvement of at least 2 points on the WHO 9-point category ordinal scale [measured up to 29 days from randomisation], progression of disease (oxygen saturation (SaO2) <92%) or hospitalization or death, or change in time-weighted viral load [measured up to 29 days from randomisation]. RANDOMISATION: Varies with CST, but default is 2:1 allocation in favour of the candidate to maximise early safety data. BLINDING (MASKING): For the safety phase open-label although for some CSTs may include placebo or SoC for the efficacy phase. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Varies between CSTs. However simulations have shown that around 16 participants are necessary to determine futility or promise of a candidate at a given dose (in efficacy evaluation alone) and between 32 and 40 participants are required across the dose-finding and efficacy evaluation when capping the maximum number of participants contributing to the evaluation of a treatment at 40. TRIAL STATUS: Master protocol version number v5 07 May 2020, trial is in setup with full regulatory approval and utilises several digital technology solutions, including Medidata's Rave EDC [electronic data capture], RTSM for randomisation and patient eConsent on iPads via Rave Patient Cloud. The recruitment dates will vary between CSTs but at the time of writing no CSTs are yet open for recruitment. TRIAL REGISTRATION: EudraCT 2020-001860-27 14th March 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Asunto(s)
Antivirales/uso terapéutico , Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Antivirales/efectos adversos , COVID-19 , Humanos , Pandemias , SARS-CoV-2 , Tratamiento Farmacológico de COVID-19
15.
Music Percept ; 25(4): 315-323, 2008 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-21197418

RESUMEN

It has been reported that patients with severely nonfluent aphasia are better at singing lyrics than speaking the same words. This observation inspired the development of Melodic Intonation Therapy (MIT), a treatment whose effects have been shown, but whose efficacy is unproven and neural correlates remain unidentified. Because of its potential to engage/unmask language-capable regions in the unaffected right hemisphere, MIT is particularly well suited for patients with large left-hemisphere lesions. Using two patients with similar impairments and stroke size/location, we show the effects of MIT and a control intervention. Both interventions' post-treatment outcomes revealed significant improvement in propositional speech that generalized to unpracticed words and phrases; however, the MIT-treated patient's gains surpassed those of the control-treated patient. Treatment-associated imaging changes indicate that MIT's unique engagement of the right hemisphere, both through singing and tapping with the left hand to prime the sensorimotor and premotor cortices for articulation, accounts for its effect over nonintoned speech therapy.

16.
Front Hum Neurosci ; 12: 69, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29535619

RESUMEN

Functional imaging studies have provided insight into the effect of rate on production of syllables, pseudowords, and naturalistic speech, but the influence of rate on repetition of commonly-used words/phrases suitable for therapeutic use merits closer examination. Aim: To identify speech-motor regions responsive to rate and test the hypothesis that those regions would provide greater support as rates increase, we used an overt speech repetition task and functional magnetic resonance imaging (fMRI) to capture rate-modulated activation within speech-motor regions and determine whether modulations occur linearly and/or show hemispheric preference. Methods: Twelve healthy, right-handed adults participated in an fMRI task requiring overt repetition of commonly-used words/phrases at rates of 1, 2, and 3 syllables/second (syll./sec.). Results: Across all rates, bilateral activation was found both in ventral portions of primary sensorimotor cortex and middle and superior temporal regions. A repeated measures analysis of variance with pairwise comparisons revealed an overall difference between rates in temporal lobe regions of interest (ROIs) bilaterally (p < 0.001); all six comparisons reached significance (p < 0.05). Five of the six were highly significant (p < 0.008), while the left-hemisphere 2- vs. 3-syll./sec. comparison, though still significant, was less robust (p = 0.037). Temporal ROI mean beta-values increased linearly across the three rates bilaterally. Significant rate effects observed in the temporal lobes were slightly more pronounced in the right-hemisphere. No significant overall rate differences were seen in sensorimotor ROIs, nor was there a clear hemispheric effect. Conclusion: Linear effects in superior temporal ROIs suggest that sensory feedback corresponds directly to task demands. The lesser degree of significance in left-hemisphere activation at the faster, closer-to-normal rate may represent an increase in neural efficiency (and therefore, decreased demand) when the task so closely approximates a highly-practiced function. The presence of significant bilateral activation during overt repetition of words/phrases at all three rates suggests that repetition-based speech production may draw support from either or both hemispheres. This bihemispheric redundancy in regions associated with speech-motor control and their sensitivity to changes in rate may play an important role in interventions for nonfluent aphasia and other fluency disorders, particularly when right-hemisphere structures are the sole remaining pathway for production of meaningful speech.

17.
Autism Res ; 11(10): 1356-1365, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30230700

RESUMEN

We investigated the relationship between eight theoretically motivated behavioral variables and a spoken-language-related outcome measure, after 25 sessions of treatment for speech production in 38 minimally verbal children with autism. After removing potential predictors that were uncorrelated with the outcome variable, two remained. We used both complete-case and multiple-imputation analyses to address missing predictor data and performed linear regressions to identify significant predictors of change in percent syllables approximately correct after treatment. Baseline phonetic inventory (the number of English phonemes repeated correctly) was the most robust predictor of improvement. In the group of 17 participants with complete data, ADOS score also significantly predicted the outcome. In contrast to some earlier studies, nonverbal IQ, baseline levels of expressive language, and younger age did not significantly predict improvement. The present results are not only consistent with previous studies showing that verbal imitation and autism severity significantly predict spoken language outcomes in preschool-aged minimally verbal children with autism, but also extend these findings to older minimally verbal children with autism. Autism Res 2018, 11: 1356-1365. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We wished to understand what baseline factors predicted whether minimally verbal children with autism would improve after treatment for spoken language. The outcome measure was change in percentage (%) syllables approximately correct on a set of 30 two-syllable words or phrases. Fifteen were both practiced in treatment and tested; the remainder were not practiced in treatment, but only tested, to assess how well children were able to generalize their new skills to an untrained set of words. Potential predictors tested were sex, age, expressive language, phonetic inventory (the number of English speech sounds repeated correctly), autism severity, and nonverbal IQ. Phonetic inventory and (for some children) autism severity predicted children's posttreatment improvement. Nonverbal IQ and expressive language ability did not predict improvement, nor did younger age, suggesting that some older children with autism may be candidates for speech therapy.


Asunto(s)
Trastorno del Espectro Autista/complicaciones , Trastorno del Espectro Autista/fisiopatología , Conducta Infantil/fisiología , Trastornos del Desarrollo del Lenguaje/complicaciones , Trastornos del Desarrollo del Lenguaje/fisiopatología , Habla/fisiología , Trastorno Autístico , Niño , Preescolar , Femenino , Humanos , Trastornos del Desarrollo del Lenguaje/terapia , Masculino , Evaluación de Resultado en la Atención de Salud
18.
Front Hum Neurosci ; 11: 175, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28424605

RESUMEN

We investigated the relationship between imaging variables for two language/speech-motor tracts and speech fluency variables in 10 minimally verbal (MV) children with autism. Specifically, we tested whether measures of white matter integrity-fractional anisotropy (FA) of the arcuate fasciculus (AF) and frontal aslant tract (FAT)-were related to change in percent syllable-initial consonants correct, percent items responded to, and percent syllable insertion errors (from best baseline to post 25 treatment sessions). Twenty-three MV children with autism spectrum disorder (ASD) received Auditory-Motor Mapping Training (AMMT), an intonation-based treatment to improve fluency in spoken output, and we report on seven who received a matched control treatment. Ten of the AMMT participants were able to undergo a magnetic resonance imaging study at baseline; their performance on baseline speech production measures is compared to that of the other two groups. No baseline differences were found between groups. A canonical correlation analysis (CCA) relating FA values for left- and right-hemisphere AF and FAT to speech production measures showed that FA of the left AF and right FAT were the largest contributors to the synthetic independent imaging-related variable. Change in percent syllable-initial consonants correct and percent syllable-insertion errors were the largest contributors to the synthetic dependent fluency-related variable. Regression analyses showed that FA values in left AF significantly predicted change in percent syllable-initial consonants correct, no FA variables significantly predicted change in percent items responded to, and FA of right FAT significantly predicted change in percent syllable-insertion errors. Results are consistent with previously identified roles for the AF in mediating bidirectional mapping between articulation and acoustics, and the FAT in its relationship to speech initiation and fluency. They further suggest a division of labor between the hemispheres, implicating the left hemisphere in accuracy of speech production and the right hemisphere in fluency in this population. Changes in response rate are interpreted as stemming from factors other than the integrity of these two fiber tracts. This study is the first to document the existence of a subgroup of MV children who experience increases in syllable- insertion errors as their speech develops in response to therapy.

19.
Front Hum Neurosci ; 11: 426, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28928645

RESUMEN

We tested the effect of Auditory-Motor Mapping Training (AMMT), a novel, intonation-based treatment for spoken language originally developed for minimally verbal (MV) children with autism, on a more-verbal child with autism. We compared this child's performance after 25 therapy sessions with that of: (1) a child matched on age, autism severity, and expressive language level who received 25 sessions of a non-intonation-based control treatment Speech Repetition Therapy (SRT); and (2) a matched pair of MV children (one of whom received AMMT; the other, SRT). We found a significant Time × Treatment effect in favor of AMMT for number of Syllables Correct and Consonants Correct per stimulus for both pairs of children, as well as a significant Time × Treatment effect in favor of AMMT for number of Vowels Correct per stimulus for the more-verbal pair. Magnitudes of the difference in post-treatment performance between AMMT and SRT, adjusted for Baseline differences, were: (a) larger for the more-verbal pair than for the MV pair; and (b) associated with very large effect sizes (Cohen's d > 1.3) in the more-verbal pair. Results hold promise for the efficacy of AMMT for improving spoken language production in more-verbal children with autism as well as their MV peers and suggest hypotheses about brain function that are testable in both correlational and causal behavioral-imaging studies.

20.
PLoS One ; 11(11): e0164930, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27829034

RESUMEN

This study compared Auditory-Motor Mapping Training (AMMT), an intonation-based treatment for facilitating spoken language in minimally verbal children with autism spectrum disorder (ASD), to a matched control treatment, Speech Repetition Therapy (SRT). 23 minimally verbal children with ASD (20 male, mean age 6;5) received at least 25 sessions of AMMT. Seven (all male) were matched on age and verbal ability to seven participants (five male) who received SRT. Outcome measures were Percent Syllables Approximated, Percent Consonants Correct (of 86), and Percent Vowels Correct (of 61) produced on two sets of 15 bisyllabic stimuli. All subjects were assessed on these measures several times at baseline and after 10, 15, 20, and 25 sessions. The post-25 session assessment timepoint, common to all participants, was compared to Best Baseline performance. Overall, after 25 sessions, AMMT participants increased by 19.4% Syllables Approximated, 13.8% Consonants Correct, and19.1% Vowels Correct, compared to Best Baseline. In the matched AMMT-SRT group, after 25 sessions, AMMT participants produced 29.0% more Syllables Approximated (SRT 3.6%);17.9% more Consonants Correct (SRT 0.5); and 17.6% more Vowels Correct (SRT 0.8%). Chi-square tests showed that significantly more AMMT than SRT participants in both the overall and matched groups improved significantly in number of Syllables Approximated per stimulus and number of Consonants Correct per stimulus. Pre-treatment ability to imitate phonemes, but not chronological age or baseline performance on outcome measures, was significantly correlated with amount of improvement after 25 sessions. Intonation-based therapy may offer a promising new interventional approach for teaching spoken language to minimally verbal children with ASD.


Asunto(s)
Trastorno Autístico/fisiopatología , Trastornos del Desarrollo del Lenguaje/terapia , Terapia del Lenguaje/métodos , Trastornos del Habla/terapia , Logopedia/métodos , Análisis de Varianza , Corteza Auditiva/fisiopatología , Trastorno Autístico/complicaciones , Niño , Preescolar , Femenino , Humanos , Trastornos del Desarrollo del Lenguaje/complicaciones , Trastornos del Desarrollo del Lenguaje/fisiopatología , Masculino , Corteza Motora/fisiopatología , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Habla/fisiología , Trastornos del Habla/complicaciones , Trastornos del Habla/fisiopatología , Percepción del Habla/fisiología , Conducta Verbal/fisiología
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