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BACKGROUND: Among ambulatory people with incomplete spinal cord injury (iSCI), balance deficits are a primary factor limiting participation in walking activities. There is broad recognition that effective interventions are needed to enhance walking balance following iSCI. Interventions that amplify self-generated movements (e.g., error augmentation) can accelerate motor learning by intensifying sensorimotor feedback and facilitating exploration of motor control strategies. These features may be beneficial for retraining walking balance after iSCI. We have developed a cable-driven robot that creates a movement amplification environment during treadmill walking. The robot applies a continuous, laterally-directed, force to the pelvis that is proportional in magnitude to real-time lateral velocity. Our purpose is to investigate the effects of locomotor training in this movement amplification environment on walking balance. We hypothesize that for ambulatory people with iSCI, locomotor training in a movement amplification environment will be more effective for improving walking balance and participation in walking activities than locomotor training in a natural environment (no applied external forces). METHODS: We are conducting a two-arm parallel-assignment intervention. We will enroll 36 ambulatory participants with chronic iSCI. Participants will be randomized into either a control or experimental group. Each group will receive 20 locomotor training sessions. Training will be performed in either a traditional treadmill environment (control) or in a movement amplification environment (experimental). We will assess changes using measures that span the International Classification of Functioning, Disability and Health (ICF) framework including 1) clinical outcome measures of gait, balance, and quality of life, 2) biomechanical assessments of walking balance, and 3) participation in walking activities quantified by number of steps taken per day. DISCUSSION: Training walking balance in people with iSCI by amplifying the individual's own movement during walking is a radical departure from current practice and may result in new strategies for addressing balance impairments. Knowledge gained from this study will expand our understanding of how people with iSCI improve walking balance and how an intervention targeting walking balance affects participation in walking activities. Successful outcomes could motivate development of clinically feasible tools to replicate the movement amplification environment within clinical settings. TRIAL REGISTRATION: NCT04340063.
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Marcha , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/reabilitação , Traumatismos da Medula Espinal/fisiopatologia , Humanos , Marcha/fisiologia , Adulto , Terapia por Exercício/métodos , Equilíbrio Postural/fisiologia , Caminhada/fisiologia , Masculino , Feminino , Robótica/métodos , Método Simples-Cego , Pessoa de Meia-Idade , Locomoção/fisiologiaRESUMO
Infections are increasingly recognized as a common complication of chimeric antigen receptor (CAR) T-cell therapy. The incidence of clinically-defined infection after CD19.CAR T-cell therapy for relapsed/refractory lymphoma ranges from 60-90% in the first year after CAR T-cell therapy and is the most common cause for non-relapse mortality. However, infectious risk after CAR T-cell therapy targeting other malignancies is not well understood. Herein, we report for the first time, infectious complications after CD30.CAR T-cell treatment for patients with Hodgkin's lymphoma and peripheral T-cell lymphoma. Since CD30 is only expressed on a subset of activated T and B-cells, we hypothesized that CD30.CAR T-cell patients would have reduced incidence and severity of infections after infusion compared to CD19.CAR T-cell patients. We retrospectively evaluated all 64 patients who received CD30.CAR T-cells at a single institution between 2016-2021, and assessed infections within one year after cell infusion, comparing these data to a contemporary cohort of 50 patients who received CD19.CAR T-cells at the same institution between 2018-2021. 23 CD30.CAR T-cell patients (36%) and 18 CD19.CAR T-cell patients (36%) developed a microbiologically confirmed infection. Infection severity and bacterial infections were higher in the CD19.CAR T-cell group compared to CD30.CAR T-cell recipients who more commonly had grade 1 respiratory viral infections. Our data reflect expected outcomes for severity and infection type in CD19.CAR T-cell patients and provide a benchmark for comparison with the novel CD30.CAR T-cell product. Although our findings require replication in a larger cohort, they have implications for antimicrobial prophylaxis guidelines after CD30.CAR T-cell therapy. KEY POINTS: 1) The incidence of infections within the first year after CD30.CAR T-cell therapy was equivalent to that following CD19.CAR T-cell therapy2) Viral infections were more common after CD30.CAR T-cell therapy but bacterial infections predominated after CD19.CAR T-cell therapy.
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Children with a history of behaviorally inhibited (BI) temperament face a heightened risk for anxiety disorders and often use control strategies that are less planful. Although these relations have been observed concurrently in early childhood, middle childhood, and adolescence, few studies leverage longitudinal data to examine long-term prospective relations between cognitive control and anxiety. Using longitudinal data from 149 adolescents (55% female; from predominantly White middle-class families), we assessed temperament in toddlerhood and cognitive control and anxiety at 4, 12, 15, and 18 years of age. At age 4, separate measures of task switching and inhibitory control were obtained via the Dimensional Change Card Sort and Stroop tasks, respectively. At 12, 15, and 18 years of age, planful control was assessed with the AX-Continuous Performance Test, and anxiety symptoms were assessed via self-report. Growth curve models revealed that children with greater inhibitory control at age 4, regardless of BI status, experienced a sharper increase in anxiety symptoms across adolescence. Children with heightened BI during early childhood displayed lower levels of planful control at age 12, but experienced a more rapid improvement in these skills across adolescence. Children with greater task switching ability at age 4 displayed higher levels of planful control at age 12, but experienced a smaller increase in these skills across adolescence. Finally, children's growth rate for anxiety was unrelated to their growth rate for planful control. These findings reveal that early-life temperament, cognitive control, and anxiety remain interconnected across development, from toddlerhood to at least late adolescence. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Ansiedade , Função Executiva , Inibição Psicológica , Temperamento , Humanos , Temperamento/fisiologia , Feminino , Masculino , Pré-Escolar , Criança , Estudos Longitudinais , Adolescente , Função Executiva/fisiologia , Desenvolvimento Infantil/fisiologia , Cognição/fisiologiaRESUMO
In 2016, we implemented a non-targeted Emergency Department (ED)-based HIV screening program at our academic medical center following revised CDC guidelines utilizing the Abbott Alinity 4th generation HIV-1/2 antigen (Ag)/antibody (Ab) immunoassay (Abbott Laboratories, Abbott Park, IL). Following the CDC algorithm, after reactive fourth-generation testing, HIV-1/2 Ab testing is conducted. Patients undergoing acute seroconversion (acutes) may express p24 Ag but have a negative confirmatory Ab test. Acutes have the same laboratory signature during the ED encounter as those that are false positive (False +), and the two patient groups are denoted as "equivocals" until viral load testing specifies a definitive HIV status. Among False + patients (Ab/Ag positive, Ab negative, viral load undetectable), there have been limited studies on those also demonstrating a reduction in CD4+ count, an uncommon phenomenon known as "idiopathic CD4 lymphocytopenia." We review a patient with a reactive fourth-generation HIV Ab/p24 Ag test on two separate occasions. Despite lymphopenia with a reduced CD4 count, his symptoms resolved, and an RNA PCR test did not detect any presence of HIV (False +). This patient was unique as False + patient with p24 Ag reactive, as well as a coincidental low CD4 count in the absence of HIV infection. A low CD4 count is often a sign of significant HIV infection.
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BACKGROUND: In the USA, nirmatrelvir/ritonavir is authorized for the treatment of mild-to-moderate COVID-19 in patients at least 12â years of age, at high risk for progression to severe COVID-19. OBJECTIVES: To estimate the impact of outpatient nirmatrelvir/ritonavir on COVID-19 hospitalization risk in a US healthcare system. METHODS: We conducted a cohort study using electronic health records among outpatients with a positive SARS-CoV-2 PCR test between January and August 2022. We evaluated the association of nirmatrelvir/ritonavir therapy with time to hospitalization by estimating adjusted HRs and assessed the impact of nirmatrelvir/ritonavir on predicted COVID-19 hospitalizations using machine-learning methods. RESULTS: Among 44â671 patients, 4948 (11%) received nirmatrelvir/ritonavir, and 201 (0.4%) were hospitalized within 28â days of COVID-19 diagnosis. Nirmatrelvir/ritonavir recipients were more likely to be older, white, vaccinated, have comorbidities and reside in areas with higher average socioeconomic status. The 28â day cumulative incidence of hospitalization was 0.06% (95% CI: 0.02%-0.17%) among nirmatrelvir/ritonavir recipients and 0.52% (95% CI: 0.46%-0.60%) among non-recipients. For nirmatrelvir/ritonavir versus no therapy, the age-adjusted HR was 0.08 (95% CI: 0.03-0.26); the fully adjusted HR was 0.16 (95% CI: 0.05-0.50). In the machine-learning model, the primary features reducing predicted hospitalization risk were nirmatrelvir/ritonavir, younger age, vaccination, female gender and residence in a higher socioeconomic status area. CONCLUSIONS: COVID-19 hospitalization risk was reduced by 84% among nirmatrelvir/ritonavir recipients in a large, diverse healthcare system during the Omicron wave. These results suggest that nirmatrelvir/ritonavir remained highly effective in a setting substantially different than the original clinical trials.
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COVID-19 , Lactamas , Leucina , Nitrilas , Pacientes Ambulatoriais , Prolina , Humanos , Feminino , COVID-19/epidemiologia , North Carolina , Teste para COVID-19 , Estudos de Coortes , Ritonavir/uso terapêutico , SARS-CoV-2 , Tratamento Farmacológico da COVID-19 , Hospitalização , Antivirais/uso terapêuticoRESUMO
Behavioral inhibition (BI) is a temperamental style characterized by cautious and fearful behaviors in novel situations. The present multi-method, longitudinal study examined whether young children's observed and parent-reported BI in social versus non-social contexts predicts different long-term psychosocial outcomes. Participants (N = 279) were drawn from a longitudinal study of socioemotional development. BI in social contexts ("social BI") was measured via children's observed wariness toward unfamiliar adults and peers at 24 and 36 months and parents' reports of children's social fear/shyness at 24, 36, and 48 months. BI in non-social contexts ("non-social BI") was measured via children's observed fearful responses to masks and novel toys, and parents' reports of children's distress to non-social novelty at 9 months and non-social fear at 48 months. At 15 years, anxiety was assessed via adolescent- and parent-reports, and global internalizing and externalizing problems were assessed via parent-reports. Confirmatory factor analysis showed that a two-factor model fit the BI data significantly better than a single-factor model, providing evidence for the dissociation of BI in social versus non-social contexts. Social BI was uniquely associated with adolescent social anxiety, whereas non-social BI was specifically associated with adolescent separation anxiety. Neither social BI nor non-social BI predicted global internalizing and externalizing problems, providing evidence for the specific relations between BI and anxiety problems. Together, these results suggest that young children's inhibited responses in social versus non-social situations predict different subtypes of anxiety problems in adolescence, highlighting the multifaceted nature of BI and the divergent trajectories of different anxiety problems.