Phase 3 randomized trial of mavorixafor, CXCR4 antagonist, in WHIM syndrome.

We investigated efficacy and safety of mavorixafor, an oral CXCR4 antagonist for participants with Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) syndrome, a rare immunodeficiency caused by CXCR4 gain-of-function variants. This randomized (1:1), double-blind, placebo-controlled, phase 3 trial enrolled participants aged ≥12 years with WHIM syndrome and absolute neutrophil count (ANC) ≤400/µL. Participants received once-daily mavorixafor or placebo for 52 weeks. Primary endpoint was time (hours) above ANC threshold ≥500/µL (TATANC; over 24 hours). Secondary endpoints included TAT absolute lymphocyte count ≥1000/µL (TATALC; defined similar to TATANC); absolute changes in white blood cell (WBC), ANC, and ALC from baseline; annualized infection rate; infection duration and total infection score (combined infection number/severity). In 31 participants (mavorixafor, n=14; placebo, n=17), mavorixafor least squares (LS) mean TATANC was 15.0 hours, placebo 2.8 hours (P<0.001). Mavorixafor LS mean TATALC was 15.8 hours, placebo 4.6 hours (P<0.001). Higher absolute WBC, ANC, and ALC levels were seen with mavorixafor than placebo at each timepoint assessed. Annualized infection rates were 60% lower with mavorixafor versus placebo (LS mean 1.7 versus 4.2; nominal P=0.007) and total infection scores were 40% lower (7.4 [95% CI, 1.6-13.2] versus 12.3 [95% CI, 7.2-17.3]). Treatment with mavorixafor reduced infection frequency, severity, duration, and antibiotic use. No discontinuations occurred due to treatment-emergent adverse events (TEAEs); no related serious TEAEs were observed. Overall, mavorixafor-treated participants showed significant increases in LS mean TATANC and TATALC, reduced infection frequency, severity/duration. Mavorixafor was well tolerated in participants with WHIM syndrome. Trial was registered at ClinicalTrials.gov NCT03995108.

Cross-Modal Somatosensory Repetition Priming and Speech Processing.

BACKGROUND: Motor speech treatment approaches have been applied in both adults with aphasia and apraxia of speech and children with speech-sound disorders. Identifying links between motor speech intervention techniques and the modes of action (MoA) targeted would improve our understanding of how and why motor speech interventions achieve their effects, along with identifying its effective components. The current study focuses on identifying potential MoAs for a specific motor speech intervention technique. OBJECTIVES: We aim to demonstrate that somatosensory inputs can influence lexical processing, thus providing further evidence that linguistic information stored in the brain and accessed as part of speech perception processes encodes information related to speech production. METHODS: In a cross-modal repetition priming paradigm, we examined whether the processing of external somatosensory priming cues was modulated by both word-level (lexical frequency, low- or high-frequency) and speech sound articulatory features. The study participants were divided into two groups. The first group consisted of twenty-three native English speakers who received somatosensory priming stimulation to their oro-facial structures (either to labial corners or under the jaw). The second group consisted of ten native English speakers who participated in a control study where somatosensory priming stimulation was applied to their right or left forehead as a control condition. RESULTS: The results showed significant somatosensory priming effects for the low-frequency words, where the congruent somatosensory condition yielded significantly shorter reaction times and numerically higher phoneme accuracy scores when compared to the incongruent somatosensory condition. Data from the control study did not reveal any systematic priming effects from forehead stimulation (non-speech related site), other than a general (and expected) tendency for longer reaction times with low-frequency words. CONCLUSIONS: These findings provide further support for the notion that speech production information is represented in the mental lexicon and can be accessed through exogenous Speech-Language Pathologist driven somatosensory inputs related to place of articulation.

Measuring and Training Speech-Language Pathologists' Orofacial Cueing: A Pilot Demonstration.

Tactile-kinesthetic-proprioceptive (TKP) input used to facilitate speech motor control is considered an active ingredient within speech motor interventions. Objective metrics identifying skill level differences across speech-language pathologists (S-LP) providing TKP cues are crucial for monitoring treatment delivery fidelity. The study examined three kinematic measures indicating accuracy and consistency of TKP inputs by 3 S-LPs with varying experience levels (S-LP 1: novice; S-LP 2 and S-LP 3: advanced). Confidence interval measures were used to compare the accuracy of jaw movement amplitudes of the vowel /a/ made by a model participant versus S-LPs giving the TKP input. Generalised Orthogonal Procrustes Analysis (GPA) and cyclic Spatial Temporal Index (cSTI) were used to determine movement consistency. Results revealed passive jaw excursions induced by S-LP 2 and 3 to be not statistically significant from the model participant's active jaw movements. cSTI values decreased with advanced level of experience (19.28, 12.14, and 9.33 for S-LP 1, S-LP 2, and S-LP 3, respectively). GPA analyses revealed a similar pattern for S-LPs with more experience demonstrating lower mean RMS values (0.22, 0.03, and 0.11 for S-LP 1, S-LP 2, and S-LP 3, respectively). Findings suggest kinematic measures adapted from the motor control literature can be applied to assess S-LP skill differences in providing TKP cues.

Laparoscopic and Robotic-Assisted Hysterectomy for Uterine Leiomyomas: A Comparison of Complications and Costs.

OBJECTIVE: Robotic surgery is increasingly being used for treatment of malignant and benign gynaecologic diseases. The purpose of our study is to compare patient perioperative complications and costs of laparoscopic versus robotic-assisted hysterectomy for uterine leiomyomas. METHODS: A retrospective cohort study using the Nationwide Inpatient Sample database from the United States was conducted, comparing patients who underwent robotic-assisted hysterectomy and laparoscopic hysterectomy (total laparoscopic hysterectomy and laparoscopic-assisted vaginal hysterectomy) for uterine fibroids between 2008 and 2012. Baseline characteristics were compared between the two groups, and logistic regression was used to compare postoperative outcomes between laparoscopic and robotic approaches. Direct costs were compared between the two groups using linear regression models. RESULTS: Over a five-year period, the total number of hysterectomies performed increased. Patients undergoing robotic hysterectomy were older and had more comorbidities. In adjusted analyses, women who underwent robotic surgery were more likely to have respiratory failure (0.71% vs. 0.39%; P < 0.0108), postoperative fever (1.05% vs. 0.67%, P < 0.0002), and ileus (1.76% vs. 1.3%; P < 0.0060), and less likely to require transfusions (3.4% vs. 3.96%; P < 0.0037). Robotic surgery was consistently more expensive, with a median cost of $33 928.00 compared with $23 753.00 for laparoscopic hysterectomy. CONCLUSION: While there are only slight differences in postoperative complications between laparoscopic-assisted hysterectomy and robotic-assisted hysterectomy, robotic-assisted hysterectomy is associated with considerably greater direct costs. Unless specific indications for robotic-assisted hysterectomy exist, laparoscopic-assisted hysterectomy should be the preferred approach for minimally invasive surgical treatment of leiomyomas.

Quality of statistical reporting in developmental disability journals.

Null hypothesis significance testing (NHST) dominates quantitative data analysis, but its use is controversial and has been heavily criticized. The American Psychological Association has advocated the reporting of effect sizes (ES), confidence intervals (CIs), and statistical power analysis to complement NHST results to provide a more comprehensive understanding of research findings. The aim of this paper is to carry out a sample survey of statistical reporting practices in two journals with the highest h5-index scores in the areas of developmental disability and rehabilitation. Using a checklist that includes critical recommendations by American Psychological Association, we examined 100 randomly selected articles out of 456 articles reporting inferential statistics in the year 2013 in the Journal of Autism and Developmental Disorders (JADD) and Research in Developmental Disabilities (RDD). The results showed that for both journals, ES were reported only half the time (JADD 59.3%; RDD 55.87%). These findings are similar to psychology journals, but are in stark contrast to ES reporting in educational journals (73%). Furthermore, a priori power and sample size determination (JADD 10%; RDD 6%), along with reporting and interpreting precision measures (CI: JADD 13.33%; RDD 16.67%), were the least reported metrics in these journals, but not dissimilar to journals in other disciplines. To advance the science in developmental disability and rehabilitation and to bridge the research-to-practice divide, reforms in statistical reporting, such as providing supplemental measures to NHST, are clearly needed.