Balance Therapeutics (United States)

BACKGROUNDCisplatin is often the cytotoxic drug of choice for chemoradiation therapy (CRT) for head and neck squamous cell carcinoma (HNSCC), but it can lead to irreversible hearing loss. There may be similar oncologic outcomes but different toxicity profiles depending on whether cisplatin is given at 75–100 mg/m2 every 3 weeks or 30–40 mg/mg2 weekly. This study compares cisplatin-induced hearing loss in patients with HNSCC receiving similar cumulative doses of cisplatin administered either on higher-dose or lower-dose treatment schedules.METHODSUsing the Enhancing Cancer Hearing Outcomes (ECHO) dataset from 5 academic centers, we conducted a multicenter retrospective cohort study of adults (≥18 years) with HNSCC receiving cisplatin-based CRT. Participants were grouped by cisplatin dose schedule: every 3 weeks (≥75 mg/m²) or weekly (<75 mg/m²). Hearing loss was assessed using American Speech-Language-Hearing Association (ASHA) and Common Terminology Criteria for Adverse Events (CTCAE) v5.0 threshold shift criteria based on audiograms obtained ≤120 days before and after treatment. Risk differences and predictors of hearing loss were evaluated using χ2 analyses and multivariate regression. Kaplan-Meier curves assessed overall and disease-free survival.RESULTSAmong 564 participants (1,127 ears), lower-dose weekly cisplatin was associated with significantly lower incidence of hearing loss (ASHA criteria: 57% vs. 82%; CTCAE criteria: 39% vs. 69%). CTCAE grade ≥2 hearing loss occurred in 18% of the weekly group versus 50% of the 3-week group. Multivariate analysis confirmed treatment schedule as an independent predictor of ototoxicity. Two-year survival outcomes did not differ between groups.CONCLUSIONSWeekly low-dose cisplatin significantly reduced the incidence and severity of hearing loss without compromising survival, supporting its broader use in CRT for HNSCC.

Accessibility to developmental interventions for children and adolescents could be increased through virtual, at-home delivery of training programs. Virtual childhood training programs and their effects on cognitive outcomes have not been well studied. To that end, this study examined the effects of the at-home Brain Balance® (BB) program on the cognitive task performance of children and adolescents with baseline developmental and attentional difficulties. The study included students with reported diagnosis of ADHD, autism, anxiety, sensory processing disorder, or dyslexia, and students with no reported diagnosis (aged 4-17 years). The at-home BB program is delivered through (1) a computer-based format utilizing multimodal program activities previously studied in-center (multisensory stimulation, gross motor, coordination, balance, and nutritional recommendations); and (2) the BB app (visual motor, auditory and visual processing, and rhythm and timing training) - creating a comprehensive program experience delivered remotely. Cognitive performance was measured by six cognitive tasks from Creyos Health before and after 3 months of participation in the at-home BB program (N = 316) or in-center BB program (N = 4,232), compared to controls. Results showed that overall cognitive assessment scores (including attention, response inhibition, and working memory) improved after participation in either the at-home or the in-center program, compared to controls. Importantly, significant improvements over the controls were observed for two tasks involving attention and inhibitory control, in both programs. Further, two analyses support that the effects on cognitive performance from either delivery format, in-center or at home, are comparable in magnitude. This research: (1) presents new findings demonstrating improved cognitive performance after completing the at-home BB program; (2) replicates previous findings of cognitive improvements after completing the BB program; and (3) suggests that the cognitive effects of virtual at-home BB training are similar to those observed for in-center BB training. Overall, the results demonstrate the effectiveness of the at-home BB program in improving cognitive functioning in pediatric populations with preexisting developmental and attentional difficulties. Virtual delivery and ease of use, provide at-home programs the potential to reduce barriers of access to much-needed developmental and cognitive support, for individuals who may otherwise lack access to high-quality, evidence-based developmental programs.

In this article, we enjoin the United Nations (UN) to forge a path out of our plight of multiple environmental and social crises. With other analysts, we identify ‘overshoot’ – the state in which humanity has substantially outpaced Earth’s capacity to regenerate its natural systems and to absorb our waste output – as the root cause of the existential threats we face. This dangerous condition demands rethinking our relationship with Earth and embarking on scaling down the human enterprise within policy frameworks of equity and rights. We argue that when the UN first articulated its international unity and prosperity mission, it did so within a ‘growth’ paradigm that treats Earth and its nonhuman inhabitants as mere resources at humanity’s disposal. The 1994 Cairo Conference on Population and Development reinforced this agenda, with its sharp turn away from the earlier emphasis on population concerns and their link to environmental protection. Today, it is clear that the UN’s foundational goals of peace, human rights and sustainability flounder within a growth-driven framework of human exceptionalism and nature domination. To correct course and reverse our advanced state of ecological overshoot we urge the UN to lead in contracting the large-scale variables of the human enterprise – population, economy, technosphere – and to resist co-optation by political, ideological and special interest pressures that would derail this mandate.

The Head Shake Sensory Organization Test (HS-SOT) assesses postural stability while the head is moving and may also identify deficits in attention associated with the dual task conditions of moving the head at a specified speed while maintaining balance. Normative values for the HS-SOT have not been established in a healthy military population or other highly trained populations such as athletes. Establishing normative values in a military population will enable clinicians to compare the scores of patients with medical conditions that affect postural stability and sensory integration such as concussion or traumatic brain injury, vestibular dysfunction, or migraine to those of a healthy population to determine a need for intervention and for return to duty considerations. The purposes of this cross-sectional study were to establish normative values for the HS-SOT within the military population, to determine whether HS-SOT scores differed between men and women or among age groups, and to determine whether HS-SOT scores differed from scores on similar conditions of the Sensory Organization Test (SOT). Active duty service members (n = 237, 54 female) at Joint Base Lewis-McChord, Washington, Fort Campbell, Kentucky, and the National Capitol Region (Washington, D.C, Maryland, and Virginia) completed the SOT and HS-SOT on the NeuroCom® Balance Master™. Parametric and non-parametric comparisons were analyzed for the equilibrium scores for the SOT and HS-SOT conditions 2 (SOT-2, HS-SOT-2, respectively) and 5 (SOT-5, HS-SOT-5, respectively) and the equilibrium score ratios (ESRs) for HS-SOT-2 and HS-SOT-5 for the total sample, men and women, and age group categories (18-26 years, 27-35 years, and 36-45 years). There were no differences in HS-SOT-2 or HS-SOT-5 equilibrium ratio scores between men (0.99 ±.029 and 0.83 ±0.25, respectively) and women (1.00 ±0.03 and 0.81 ±0.21, respectively). There were no differences in the SOT-2 equilibrium scores (F = 2.29, P = 0.10) or SOT-5 equilibrium scores (Kruskal-Wallis H = 3.26, P = 0.20) among the different age groups. SOT-2 equilibrium scores were higher than the HS-SOT-2 equilibrium scores (Z = -4.10, P < 0.001). SOT-5 equilibrium scores were also higher than HS-SOT-5 equilibrium scores (Z = -12.22, P < 0.001), and the HS-SOT-2 and HS-SOT-5 equilibrium scores differed from each other (Z = -13.26, P < 0.001). This study established normative values for the HS-SOT in a military population. Equilibrium scores did not differ between men and women or among age groups, suggesting that these values can be used as reference points for most service members. Postural stability was found to be significantly challenged during head motion, indicating the HS-SOT is a valuable tool for identifying subtle impairments in postural stability. These findings have important implications for early detection and intervention in individuals with medical conditions affecting balance, particularly concussions or vestibular disorders.

ObjectiveCurrent treatments for Friedreich's ataxia, a neurodegenerative disorder characterized by decreased intramitochondrial frataxin, do not address low frataxin concentrations. Nomlabofusp (previously CTI‐1601) is a frataxin replacement therapy with a unique mechanism of action that directly addresses this underlying frataxin deficiency. Phase 1 studies assessed the safety, pharmacokinetic, and pharmacodynamic profiles of subcutaneously administered nomlabofusp in adults with Friedreich's ataxia.MethodsPatients were enrolled in two Phase 1, double‐blind, placebo‐controlled studies. The single ascending‐dose (SAD) study (NCT04176991) evaluated single doses of nomlabofusp (25, 50, 75, or 100 mg) or placebo. The multiple ascending‐dose (MAD) study (NCT04519567) evaluated nomlabofusp (25 mg daily for 4 days then every third day, 50 mg daily for 7 days then every 2 days, or 100 mg daily) or placebo for 13 days.ResultsPatients aged 19–69 years were enrolled (SAD, N = 28; MAD, N = 27). Nomlabofusp was generally well tolerated through 13 days. Most adverse events were mild and resolved quickly. No serious adverse events or deaths were reported. Peak nomlabofusp plasma concentrations occurred 15 min after subcutaneous administration. Nomlabofusp plasma exposures increased with increasing doses and daily administration and decreased with reduced dosing frequency. Increased frataxin concentrations were observed in buccal cells, skin, and platelets with higher and more frequent nomlabofusp administration.InterpretationResults from this study support a favorable safety profile for nomlabofusp. Subcutaneous nomlabofusp injections were quickly absorbed; higher doses and daily administration resulted in increased tissue frataxin concentrations. Future studies will evaluate longer‐term safety and possible efficacy of nomlabofusp.

La psicoterapia constituye una columna importante en donde descansa el tratamiento terapéutico. La Psicoterapia Grupal no es la excepción, aunque el Teatro Espontáneo no está catalogada como una técnica propia del Psicodrama, esta constituye un eficaz recurso que se viene utilizando desde hace muchos años, y que se comprueba su eficacia en la aplicación a grupos, en donde el individuo sin previo entrenamiento logra aflorar sus diferentes expresiones, sentimientos, emociones, permitiendo mejorar su estilo y calidad de vida. El presente artículo, hace referencia a la aplicación del teatro espontáneo, como parte de la Psicoterapia. Se toma en especial atención la etapa de la niñez y adolescencia, porque presentan una serie de problemas conductuales que se refleja en las relaciones sociales, dentro de los planteles educativos, en el aula escolar, en su grupo familiar y en actividades extracurriculares en las que participan los adolescentes. Por tal razón, con el Teatro Espontáneo lo que se pretende es, desarrollar Habilidades Sociales; para este proceso las actividades terapéuticas se realizo una revisión bibliográfica de fuentes con la finalidad de contrastar datos acerca de la presencia de una posible efectividad entre el teatro espontáneo y el mejoramiento de las habilidades sociales.

This study aimed to refine and validate a multidomain developmental survey (MDS) used by the Brain Balance® (BB) program. Data were analyzed on 47,571 participants (68.5% male; 4–18 years) whose parents completed the survey before/after 3 months of in-center BB participation. Exploratory Factor Analysis was applied to a training sample (n = 28,254), reducing the original item pool from 98 to 31 items and suggesting a six-factor solution. The six factors were labeled as negative emotionality, reading/writing difficulties, hyperactive-disruptive, academic disengagement, motor/coordination problems, and social communication problems. Exploratory Structural Equation Modeling was applied to two validation samples (n = 9394 and 9923), and the factor structure demonstrated strong goodness-of-fit. Test–retest reliability coefficients (per Pearson correlations) were high for each of the subscales. Finally, the survey’s factor structure appeared equivalent across four groups stratified by reported gender and adolescent status. Overall, the BB-MDS demonstrated strong measurement properties, including validated factor structure, internal reliability, test–retest reliability, and measurement invariance.

The development of attention can be influenced through various nonpharmacologic approaches such as training and practice. More research is needed on these approaches in children and adolescents with attentional difficulties. To this end, we investigated the effect of 3 months of participation in the Brain Balance® (BB) program (a multimodal childhood training program) on attentional issues in children and adolescents, using the Brown Attention-Deficit Disorder Scales® (BADDS) administered as a parental questionnaire before and after program participation. At baseline, participants (N = 71; aged 4–18 years; 69% male) had BADDS scores that were approximately 1.5 standard deviations above the normative BADDS sample. A Wilcoxon test indicated that scores differed significantly from pre- to post-program, with an average decline of 7 T-score points. The probability of a BB participant improving from pre- to post-program was 81%. The Reliable Change Index (RCI) indicated that 36 participants (49.3%) observed a large enough change to meet the criteria for reliable change, 34 participants (46.6%) did not meet the criteria for reliable change, and three participants (4.1%) observed reliable deterioration. Finally, logistic regression showed that baseline BADDS scores significantly predicted reliable change, such that a one-unit increase in baseline BADDS T-score was associated with a 15% odds increase in reliable change. This suggests that children with more severe ADHD symptoms at baseline are more likely to observe a decrease in symptoms over the course of the BB program than are children with less severe symptoms. Age (but not gender) was also a significant predictor, such that younger participants were more likely to observe reliable change. These data provide evidence of statistically significant reliable change in attentional functioning in BB participants from pre- to post-program, especially for participants who are younger in age or have more pronounced attentional issues at baseline.

Abnormal knee frontal plane projection angles (FPPA) during movement have been associated with patellofemoral pain. As such, clinicians are interested in valid and reliable instruments suitable for broad-based clinical use that allow them to objectively measure such variables. Therefore, the purpose of the current study was to examine the criterion validity and reliability of knee FPPA measures obtained by clinicians using a free tablet application called Technique. Validity/reliability study. To examine validity, the same raters measured 10, two-dimensional criterion reference angles at the first testing session. To examine reliability, the knee FPPA of 16 subjects was measured by 6 raters (3 physical therapists and 3 student physical therapists) on 2 separate occasions while performing a single-limb step-down task. Validity was investigated by calculating the 95% limits of agreement, mean absolute differences, and Bland-Altman plots. Reliability was examined by calculating intraclass correlation coefficients and the SE of measure. For validity, the mean absolute difference between rater and criterion reference angle measures ranged from 0.20° to 0.90°. Ninety-five percent of expected errors between rater and criterion reference angle measures were 2.04° or less. For reliability, the intraclass correlation coefficient values for interrater and intrarater reliability were excellent ranging from .994 to .998 with SE of measure ranging from 0.44° to 0.84°. These findings indicate that knee FPPA measures obtained during a single-limb step-down task using the Technique tablet application are valid and reliable, and suitable for clinical use.