Efficacy and safety of deuruxolitinib, an oral selective Janus kinase inhibitor, in adults with alopecia areata: Results from the Phase 3 randomized, controlled trial (THRIVE-AA1).

BACKGROUND: Alopecia areata (AA) is a hair loss disorder that can seriously impact quality of life. Janus kinase (JAK) inhibitors, including deuruxolitinib, have previously demonstrated significant hair regrowth in AA. OBJECTIVE: The Phase 3 THRIVE-AA1 randomized, double-blinded, placebo-controlled trial (NCT04518995) evaluated the safety and efficacy of the oral JAK1/JAK2 inhibitor deuruxolitinib in adult patients with AA. METHODS: Patients aged 18-65 years with ≥50% hair loss were randomized to deuruxolitinib 8 mg twice daily, deuruxolitinib 12 mg twice daily, or placebo for 24 weeks. The primary end point was the percentage of patients achieving a Severity of Alopecia Tool score ≤20. A key secondary end point was the percentage of satisfaction of hair patient-reported outcome responders. RESULTS: Significantly higher proportions of patients taking deuruxolitinib met the primary end point (8 mg 29.6%; 12 mg 41.5% versus placebo 0.8%). Both deuruxolitinib doses achieved significant improvements in all secondary end points versus placebo, including satisfaction of hair patient-reported outcome (8 mg 42.1%; 12 mg 53.0% versus placebo 4.7%). Most treatment-emergent adverse events were mild or moderate, consistent with other oral JAK inhibitors. LIMITATIONS: Further studies are required to understand longer-term safety, efficacy, and impact of treatment cessation. CONCLUSION: Both doses of deuruxolitinib were effective for hair regrowth. Patient satisfaction aligned with hair growth.

Phase 2 randomized, dose-ranging trial of CTP-543, a selective Janus Kinase inhibitor, in moderate-to-severe alopecia areata.

BACKGROUND: Janus kinase (JAK) activation is suggested to have a pathological role in alopecia areata (AA). CTP-543, a deuterated compound that selectively inhibits JAK1 and JAK2, is being developed as an oral treatment for AA. OBJECTIVE: To assess the safety and efficacy of a 24-week regimen of CTP-543 in patients with chronic, moderate-to-severe AA. METHODS: In this phase 2, randomized, double-blind, placebo-controlled, sequential-design trial, patients were randomized to receive CTP-543 (4 mg, 8 mg, or 12 mg) or placebo every 12 hours for 24 weeks. RESULTS: A dose-related increase was observed in the percentage of patients with ≥50% relative reduction in Severity of Alopecia Tool scores from baseline at week 24 (9% placebo, 21% 4 mg twice daily, 47% 8 mg twice daily, and 58% 12 mg twice daily), with statistical significance versus placebo (P < .001) observed for the 8-mg twice daily and 12-mg twice daily groups, with differences from placebo noted as early as 12 weeks after the initiation of treatment. Safety results were consistent with the known safety profiles of JAK inhibitors. LIMITATIONS: These initial findings are from a relatively small controlled trial, and additional studies are needed to fully characterize the safety and efficacy of CTP-543 in adult patients with AA. CONCLUSIONS: Patients treated with CTP-543 (8 or 12 mg, twice daily) had a significant reduction in the severity of AA.

Personal Protective Equipment Adherence of Pediatric Resuscitation Team Members During the COVID-19 Pandemic.

STUDY OBJECTIVE: During the COVID-19 pandemic, health care workers have had the highest risk of infection among essential workers. Although personal protective equipment (PPE) use is associated with lower infection rates, appropriate use of PPE has been variable among health care workers, even in settings with COVID-19 patients. We aimed to evaluate the patterns of PPE adherence during emergency department resuscitations that included aerosol-generating procedures. METHODS: We conducted a retrospective, video-based review of pediatric resuscitations involving one or more aerosol-generating procedures during the first 3 months of the COVID-19 pandemic in the United States (March to June 2020). Recommended adherence (complete, inadequate, absent) with 5 PPE items (headwear, eyewear, masks, gowns, gloves) and the duration of potential exposure were evaluated for individuals in the room after aerosol-generating procedure initiation. RESULTS: Among the 345 health care workers observed during 19 resuscitations, 306 (88.7%) were nonadherent (inadequate or absent adherence) with the recommended use of at least 1 PPE type at some time during the resuscitation, 23 (6.7%) of whom had no PPE. One hundred and forty health care workers (40.6%) altered or removed at least 1 type of PPE during the event. The aggregate time in the resuscitation room for health care workers across all events was 118.7 hours. During this time, providers had either absent or inadequate eyewear for 46.4 hours (39.1%) and absent or inadequate masks for 35.2 hours (29.7%). CONCLUSION: Full adherence with recommended PPE use was limited in a setting at increased risk for SARS-CoV-2 virus aerosolization. In addition to ensuring appropriate donning, approaches are needed for ensuring ongoing adherence with PPE recommendations during exposure.

Regulation of spine structural plasticity by Arc/Arg3.1.

Dendritic spines are actin-rich, postsynaptic protrusions that contact presynaptic terminals to form excitatory chemical synapses. These synaptic contacts are widely believed to be the sites of memory formation and information storage, and changes in spine shape are thought to underlie several forms of learning-related plasticity. Both membrane trafficking pathways and the actin cytoskeleton drive activity-dependent structural and functional changes in dendritic spines. A key molecular player in regulating these processes is the activity-regulated cytoskeleton-associated protein (Arc), a protein that has diverse roles in expression of synaptic plasticity. In this review, we highlight important findings that have shaped our understanding of Arc's functions in structural and functional plasticity, as well as Arc's contributions to memory consolidation and disease.

Disparities in Acute Lymphocytic Leukemia Outcomes Among Young Adults.

Background: Age is a strong prognostic factor in acute lymphocytic leukemia (ALL), with children doing better than adults with the same disease. One hypothesis for this age-based disparity is differences in treatment regimens. Optimizing care for adolescents and young adults (AYA) with ALL has not been well defined and disparities in care exist. We conducted a retrospective study of all veterans with ALL diagnosed between the ages of 18 and 45 since the year 2000 to evaluate disparities among prognostication methods, treatment regimens, and accrual to clinical trials with regard to age and race/ethnicity and how these factors influence overall survival. Methods: Electronic medical record data from the VA Informatics and Computing Infrastructure (VINCI) were used to identify 6,724 patients with an ICD-9 or 10 code for ALL. All patients were chart checked to confirm an ALL diagnosis between the ages of 18 and 45 and excluded if they were diagnosed before 2000, had childhood ALL, or if induction protocol was not recorded. A total of 252 patients were included in the final analysis. Multivariate analysis was performed with controls for age, ALL subtype (B, T, mixed phenotype), Ph status, cytogenetic risk (based on modified Medical Research Council-Eastern Cooperative Oncology Group (MRC-ECOG) study), obesity (body mass index (BMI) > 30), and race. Results: Patients treated with pediatric regimens, including pediatric-inspired regimens, have statistically significant (P = 0.009) survival gains, with a hazard ratio (HR) of 0.52 after controlling for age, obesity, ALL subtype, cytogenetic risk and race. White patients had significantly improved OS compared to people of color (HR 0.57, P = 0.02) after controlling for the aforementioned covariates. Black patients were far less likely (23%) to receive a transplant than non-Black patients (46%). Only 7% of patients were treated on a clinical trial. Conclusions: These data demonstrate that treatment with a pediatric regimen significantly improves overall survival in patients up to the age of 45 and suggests ongoing shortcomings in treatment for young adults with ALL, especially 30 to 45 years old, including persistently high use of adult induction regimens, low rates of referral to clinical trials, and significant racial disparities in bone marrow transplants for Black patients.

Opportunities to Foster Efficient Communication in Labor and Delivery Using Simulation.

Introduction Communication errors are an important contributing factor in adverse outcomes in labor and delivery (L&D) units. The objective of this study was to identify common lapses in verbal communication using simulated obstetrical scenarios and propose alternative formats for communication. Methods Health care professionals in L&D participated in three simulated clinical scenarios. Scenarios were recorded and reviewed to identify questions repeated within and across scenarios. Questions that were repeated more than once due to ineffective communication were identified. The frequency with which the questions were asked across simulations was identified. Results Questions were commonly repeated both within and across 27 simulated scenarios. The median number of questions asked was 27 per simulated scenario. Commonly repeated questions focused on three general topics: (1) historical data/information (i.e., estimated gestational age), (2) maternal clinical status (i.e., estimated blood loss), and (3) personnel (i.e., "Has anesthesiologist been called?"). Conclusion Inefficient verbal communication exists in the process of transferring information during obstetric emergencies. These findings can inform improved training and development of information displays to improve teamwork and communication. A visual display that can report static historical information and specific dynamic clinical data may facilitate optimal human performance.