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Objectives/Goals: We aimed to discover treatment candidates for uterine fibroids, a common benign tumor with adverse impacts on quality of life. Repurposing already approved medications for fibroids can expedite treatment option expansion. Using genetic proxies, we identified novel fibroid drug candidates and estimated their effect on risk of fibroid diagnosis. Methods/Study Population: We performed a genetically predicted gene expression (GPGE) analysis using S-PrediXcan and GTEx tissue models with multi-ancestry genome-wide association study (GWAS) summary statistics of fibroids (cases = 74,294, controls = 465). There were 81 genes significantly associated with fibroid risk. Querying drug–gene interaction databases identified 56 approved medications that target these genes, including two antihypertensives, hydralazine, and spironolactone. Using independent multi-ancestry GWAS summary statistics (N = 635,969) for systolic (SBP) and diastolic blood pressure (DBP), we conducted GPGE analyses. Blood pressure (exposure) and fibroids (outcome) GPGE summary statistics in the same tissues were used for two-sample Mendelian randomization (MR) analyses to proxy medication effects. Results/Anticipated Results: GPGE analyses identified hydralazine/tumor protein P53 (TP53) activity and spironolactone/thyroid hormone receptor beta (THRB) activity as drug-gene candidate pairs. Both drugs increase gene activity of their paired gene. Increased TP53 expression was associated with SBP in four tissues (exposure). The MR results indicated hydralazine use, proxied by increased TP53 expression, may reduce fibroid risk by 42% per standard deviation of gene expression (odds ratio [OR] = 0.58, p = 1.43E-12). Increased THRB expression was associated with DBP in eight tissues and were included in the MR (exposure). The MR results suggest spironolactone use, proxied by increased THRB expression, may reduce fibroid risk by 23% per standard deviation of gene expression (OR = 0.77, p = 5.94E-6). Discussion/Significance of Impact: We provide biologically plausible evidence for repurposing hydralazine and spironolactone for reducing risk of fibroid diagnosis. Repurposing these hypertension medications could provide novel preventative treatments for fibroids, particularly for individuals disproportionately affected by both conditions.
Brown dwarfs are failed stars with very low mass (13 to 75 Jupiter mass), and an effective temperature lower than 2500 K. Their mass range is between Jupiter and red dwarfs. Thus, they play a key role in understanding the gap in the mass function between stars and planets. However, due to their faint nature, previous searches are inevitably limited to the solar neighbourhood (20 pc). To improve our knowledge of the low mass part of the initial stellar mass function and the star formation history of the MilkyWay, it is crucial to find more distant brown dwarfs. Using JamesWebb Space Telescope (JWST) COSMOS-Web data, this study seeks to enhance our comprehension of the physical characteristics of brown dwarfs situated at a distance of kpc scale. The exceptional sensitivity of the JWST enables the detection of brown dwarfs that are up to 100 times more distant than those discovered in the earlier all-sky infrared surveys. The large area coverage of the JWST COSMOS-Web survey allows us to find more distant brown dwarfs than earlier JWST studies with smaller area coverages. To capture prominent water absorption features around 2.7 μm, we apply two colour criteria, F115W – F277W + 1 < F277W – F444W and F277W – F444W > 0.9. We then select point sources by CLASS_STAR, FLUX_RADIUS, and SPREAD_MODEL criteria. Faint sources are visually checked to exclude possibly extended sources. We conduct SED fitting and MCMC simulations to determine their physical properties and associated uncertainties. Our search reveals 25 T-dwarf candidates and 2 Y-dwarf candidates, more than any previous JWST brown dwarf searches. They are located from 0.3 kpc to 4 kpc away from the Earth. The spatial number density of 900-1050 K dwarf is (2.0 ± 0.9) × 10–6 pc–3, 1050–1200 K dwarf is (1.2 ± 0.7) × 10–6 pc–3, and 1200–1350 K dwarf is (4.4 ± 1.3) × 10–6 pc–3. The cumulative number count of our brown dwarf candidates is consistent with the prediction from a standard double exponential model. Three of our brown dwarf candidates were detected by HST, with transverse velocities 12 ± 5 km s–1, 12 ± 4 km s–1, and 17 ± 6 km s–1. Along with earlier studies, the JWST has opened a new window of brown dwarf research in the MilkyWay thick disk and halo.
To incorporate a longitudinal palliative care curriculum into obstetrics and gynecology (Ob-Gyn) residency that could become standardized to ensure competencies in providing end of life (EOL) care.
Methods
This was a prospective cohort study conducted among 23 Ob-Gyn residents at a tertiary training hospital from 2021 to 2022. A curriculum intervention was provided via lecture and simulation. An inpatient palliative care rotation was also created for the intern class. Scores for knowledge and confidence were compared pre- and post-curriculum. Performance on patient simulations was compared for interns who had the inpatient palliative rotation versus those that had not in a crossover fashion. Number of palliative care consults was also compared before and during the curriculum. A pooled, weighted rank-based test was used for analysis of the data with a p-value < 0.05 considered significant.
Results
One hundred percent of the 23 eligible participants participated in this study. A statistically significant increase in scores on all quizzes (p-values 0.047, <0.001, and <0.001) and confidence surveys (composite score p-value < 0.001) was seen after curriculum completion. No statistically significant difference was able to be identified in standardized patient simulation performance. Palliative care consultation increased by 55%.
Significance of results
EOL care is a critical component of any physician’s practice including obstetrician gynecologists. However, prior studies demonstrate a lack of standardized training. Our study demonstrates that a multimodal palliative care curriculum is an effective method to train Ob-Gyn residents and improve palliative care involvement in patient care.
This pilot 2-week, randomized controlled trial examined integrating digital storytelling (DST) with heart rate variability biofeedback (HRVB) to enhance psycho-emotional well-being of hematopoietic cell transplantation (HCT) patients. HCT patients (N = 25; Mage = 51.9 years) were randomly assigned: (1) DST + HRVB intervention, or (2) DST-only control. Both groups viewed four emotionally-rich digital stories. The DST + HRVB group practiced HRVB at home for ten minutes/day. DST + HRVB participants decreased anger, depression, fatigue (d = 0.53) and increased emotional processing (d = 0.20), and HRV-assessed autonomic nervous system balance (3.5 vs. 0.9). This study supports feasibility of integrating DST with HRVB, and effect sizes indicate superiority of combining DST with HRVB.
Transcranial direct current stimulation (tDCS) is a promising treatment for major depressive disorder (MDD). This study evaluated its antidepressant and cognitive effects as a safe, effective, home-based therapy for MDD.
Methods
This double-blind, sham-controlled, randomized trial divided participants into low-intensity (1 mA, n = 47), high-intensity (2 mA, n = 49), and sham (n = 45) groups, receiving 42 daily tDCS sessions, including weekends and holidays, targeting the dorsolateral prefrontal cortex for 30 minutes. Assessments were conducted at baseline and weeks 2, 4, and 6. The primary outcome was cognitive improvement assessed by changes in total accuracy on the 2-back test from baseline to week 6. Secondary outcomes included changes in depressive symptoms (HAM-D), anxiety (HAM-A), and quality of life (QLES). Adverse events were monitored. This trial was registered with ClinicalTrials.gov (NCT04709952).
Results
In the tDCS study, of 141 participants (102 [72.3%] women; mean age 35.7 years, standard deviation 12.7), 95 completed the trial. Mean changes in the total accuracy scores from baseline to week 6 were compared across the three groups using an F-test. Linear mixed-effects models examined the interaction of group and time. Results showed no significant differences among groups in cognitive or depressive outcomes at week 6. Active groups experienced more mild adverse events compared to sham but had similar rates of severe adverse events and dropout.
Conclusions
Home-based tDCS for MDD demonstrated no evidence of effectiveness but was safe and well-tolerated. Further research is needed to address the technical limitations, evaluate broader cognitive functions, and extend durations to evaluate its therapeutic potential.
While early intervention in psychosis (EIP) programs have been increasingly implemented across the globe, many initiatives from Africa, Asia and Latin America are not widely known. The aims of the current review are (a) to describe population-based and small-scale, single-site EIP programs in Africa, Asia and Latin America, (b) to examine the variability between programs located in low-and-middle income (LMIC) and high-income countries in similar regions and (c) to outline some of the challenges and provide recommendations to overcome existing obstacles.
Methods
EIP programs in Africa, Asia and Latin America were identified through experts from the different target regions. We performed a systematic search in Medline, Embase, APA PsycInfo, Web of Science and Scopus up to February 6, 2024.
Results
Most EIP programs in these continents are small-scale, single-site programs that serve a limited section of the population. Population-based programs with widespread coverage and programs integrated into primary health care are rare. In Africa, EIP programs are virtually absent. Mainland China is one of the only LMICs that has begun to take steps toward developing a population-based EIP program. High-income Asian countries (e.g. Hong Kong and Singapore) have well-developed, comprehensive programs for individuals with early psychosis, while others with similar economies (e.g. South Korea and Japan) do not. In Latin America, Chile is the only country in the process of providing population-based EIP care.
Conclusions
Financial resources and integration in mental health care, as well as the availability of epidemiological data on psychosis, impact the implementation of EIP programs. Given the major treatment gap of early psychosis in Africa, Latin America and large parts of Asia, publicly funded, locally-led and accessible community-based EIP care provision is urgently needed.
This manuscript introduces a new Bayesian finite mixture methodology for the joint clustering of row and column stimuli/objects associated with two-mode asymmetric proximity, dominance, or profile data. That is, common clusters are derived which partition both the row and column stimuli/objects simultaneously into the same derived set of clusters. In this manner, interrelationships between both sets of entities (rows and columns) are easily ascertained. We describe the technical details of the proposed two-mode clustering methodology including its Bayesian mixture formulation and a Bayes factor heuristic for model selection. We present a modest Monte Carlo analysis to investigate the performance of the proposed Bayesian two-mode clustering procedure with respect to synthetically created data whose structure and parameters are known. Next, a consumer psychology application is provided examining physician pharmaceutical prescription behavior for various brands of prescription drugs in the neuroscience health market. We conclude by discussing several fertile areas for future research.
Five different ability estimators—maximum likelihood [MLE (θ)], weighted likelihood [WLE (θ)], Bayesian modal [BME (θ)], expected a posteriori [EAP (θ)] and the standardized number-right score [Z (θ)]—were used as scores for conventional, multiple-choice tests. The bias, standard error and reliability of the five ability estimators were evaluated using Monte Carlo estimates of the unknown conditional means and variances of the estimators. The results indicated that ability estimates based on BME (θ), EAP (θ) or WLE (θ) were reasonably unbiased for the range of abilities corresponding to the difficulty of a test, and that their standard errors were relatively small. Also, they were as reliable as the old standby—the number-right score.
A new Bayesian multinomial probit model is proposed for the analysis of panel choice data. Using a parameter expansion technique, we are able to devise a Markov Chain Monte Carlo algorithm to compute our Bayesian estimates efficiently. We also show that the proposed procedure enables the estimation of individual level coefficients for the single-period multinomial probit model even when the available prior information is vague. We apply our new procedure to consumer purchase data and reanalyze a well-known scanner panel dataset that reveals new substantive insights. In addition, we delineate a number of advantageous features of our proposed procedure over several benchmark models. Finally, through a simulation analysis employing a fractional factorial design, we demonstrate that the results from our proposed model are quite robust with respect to differing factors across various conditions.
From early on, infants show a preference for infant-directed speech (IDS) over adult-directed speech (ADS), and exposure to IDS has been correlated with language outcome measures such as vocabulary. The present multi-laboratory study explores this issue by investigating whether there is a link between early preference for IDS and later vocabulary size. Infants’ preference for IDS was tested as part of the ManyBabies 1 project, and follow-up CDI data were collected from a subsample of this dataset at 18 and 24 months. A total of 341 (18 months) and 327 (24 months) infants were tested across 21 laboratories. In neither preregistered analyses with North American and UK English, nor exploratory analyses with a larger sample did we find evidence for a relation between IDS preference and later vocabulary. We discuss implications of this finding in light of recent work suggesting that IDS preference measured in the laboratory has low test-retest reliability.
The United States Government (USG) public-private partnership “Accelerating COVID-19 Treatment Interventions and Vaccines” (ACTIV) was launched to identify safe, effective therapeutics to treat patients with Coronavirus Disease 2019 (COVID-19) and prevent hospitalization, progression of disease, and death. Eleven original master protocols were developed by ACTIV, and thirty-seven therapeutic agents entered evaluation for treatment benefit. Challenges encountered during trial implementation led to innovations enabling initiation and enrollment of over 26,000 participants in the trials. While only two ACTIV trials continue to enroll, the recommendations here reflect information from all the trials as of May 2023. We review clinical trial implementation challenges and corresponding lessons learned to inform future therapeutic clinical trials implemented in response to a public health emergency and the conduct of complex clinical trials during “peacetime,” as well.
The Korean Basketball League(KBL) holds an annual draft to allow teams to select new players, mostly graduates from the elite college basketball teams even though some are from high school teams. In sports games, many factors might influence the success of an athlete. In addition to possessing excellent physical and technical factors, success in a sports game is also influenced by remarkable psychological factors. Several studies reported that elite sports players can control their anxiety during competition, which may lead to better performance. In particular, the temperament and characteristics of players have been regarded as crucial determinants of the player’s performance and goal. In this regard, numerous studies suggest that personality is considered to be an important predictor of long-term success in professional sports
Objectives
Based on previous reports and studies, we hypothesized that physical status, temperament and characteristics, and neurocognitive functions of basketball players could predict the result of KBL draft selection. Especially, temperament and characteristics were associated with the result of KBL selection. The basketball performances including average scores and average rebound were associated with emotional perception and mental rotation.
Methods
We recruited the number of 44 college elite basketball players(KBL selection, n=17; Non-KBL selection, n=27), and the number of 35 age-matched healthy comparison subjects who major in sports education in college. All participants were assessed with the Temperament and Character Inventory(TCI), Sports Anxiety Scales(SAS), Beck Depression Inventory(BDI), Perceived Stress Scale (PSS-10), Trail Making Test(TMT), and Computerized Neuro-cognitive Test(CNT) for Emotional Perception and Mental Rotation.
Results
Current results showed that physical status, temperament and characteristics, and Neurocognitive functions of college basketball players could predict the KBL draft selection. Among temperament and characteristics, novelty seeking and reward dependence were associated with KBL draft selection. The basketball performances including average scores and average rebound were associated with emotional perception and mental rotation.
Conclusions
In order to be a good basketball player for a long time, it was confirmed that temperamental factors and Neurocognitive factors were very closely related. Furthermore, it is also judged that these results can be used as basic data to predict potential professional basketball players.
The bidirectional relationship between the effects of sleep and exercise is often underappreciated. We aim to explore the bidirectional relationship of sleep and exercise. We further discuss the prominence of poor sleep in both the athletic and general population and understand the underlying mechanisms of interdependencies between the two. The goal is to illuminate practical implications to improve both areas and optimize physical and mental health.
Objectives
- To explore the bidirectional relationship between sleep and exercise
- To understand how exercise can counterbalance the adverse metabolic consequences of sleep deprivation.
Methods
We conducted a systemic literature review from Pubmed, Scopus, and PsychINFO using the search terms: “(exercise) and (sleep),” “(exercise performance) and (sleep),” “(sleep quality) and (exercise).” We included original studies in English conducted on age groups 18 years and older.
Results
Data from 31 studies shows that a significant number of athletes experience poor sleep quality and daytime sleepiness. 68.5% of Qatar Stars League soccer players and 61% of collegiate athletes in NCAA institutions report daytime fatigue several times a week. Most common causes include overtraining, hectic travel schedules, and sleeping in unfamiliar settings. Studies confirm athletes often sleep less before intense training or competitions. Sleep deficiency may lead to reduced muscular strength and endurance, mood changes, increased perceived effort, impaired cognitive processing, and diminished motor skills. Athletes averaging less than 8 hours of sleep nightly were 1.7 times more prone to injuries. Physiologically, sleep loss alters ventilation, plasma lactate concentration, hormone secretion, and inflammatory responses, hinders muscle glycogen restoration. Extended sleep restriction decreases testosterone levels, which influence muscle mass, energy, bone strength, and more. On the contrary, exercise may counter adverse metabolic impacts of sleep deprivation. High-intensity interval exercise (HIIE) has shown to nullify negative metabolic effects of sleep deprivation, suggesting exercise’s protective potential.
Conclusions
Sleep and exercise are fundamental to maintaining physical, mental, emotional, and spiritual health. The bidirectional, interdependent relationship can be best utilized by the providers to optimize overall well being. The critical impact of adequate sleep, particularly among athletes, is frequently underestimated. Poor sleep can detrimentally affect performance, amplify injury risks, and disrupt physiological functions, yet contemporary lifestyles often downplay its significance. It is important for healthcare professionals to emphasize a balanced approach to optimize these vital aspects. Continued research can offer strategies that benefit athletes and the broader populace, aiming to uplift daily life functionality.
Despite the unclear nature of catatonia, the treatment response of catatonia to benzodiazepines is widely known for its typical, dramatic recovery. The neurobiological correlates of this phenomenon regarding specific receptors and neurotransmitters are unclear, as are the potential treatment options. This is important to consider when the most commonly recommended treatments of catatonia with Lorazepam or Electroconvulsive Therapy (ECT) are unavailable or unsuccessful. In this report, we describe a case of severe, malignant catatonia and psychosis mostly unresponsive to Lorazepam during two different hospitalizations, but with eventual return to baseline after successful treatment with Valproate.
Objectives
- To describe a unique case of malignant catatonia that was unresponsive to Lorazepam
- To illustrate the potential utility of Valproate as an alternative treatment strategy for catatonia
Methods
This is a case report.
Results
A 19-year-old Hispanic male presented to our hospital initially with family reports of severe and sudden depression with bizarre behavior. Prior to this admission, the patient had been discharged recently from another tertiary hospital following a 2-week admission for severe catatonia. Chart review from that admission scored the patient’s Bush-Francis Catatonia Rating Scale (BFCRS) at 16, which remained mostly unchanged after numerous additional intramuscular doses and standing oral doses of Lorazepam, with a reduction of BFCRS the next day of only 2. During the patient’s admission at our hospital, the patient endorsed bizarre, guilt-related delusions, and his catatonia was more severe and malignant with a BFCRS of 19, with tachycardia and diaphoresis. The patient was initially given a total of seven doses of a mix of intramuscular and oral Lorazepam (total 18mg), with a minimal 2-point reduction in BFCRS. As ECT was unavailable, Lorazepam was discontinued in favor of a trial of oral Valproate 500mg twice daily, and after his catatonia subsided (with a serum level of 60.8), he was started on oral Risperidone 0.5mg once at night, titrated up to 3mg twice daily, and eventually returned to baseline as confirmed by his family members.
Conclusions
The treatment of catatonia with Lorazepam is usually reliable and has been found to be up to 80% effective, but when the recommended use of benzodiazepines and ECT fail or are unavailable, there are few studies exploring the viability of alternative treatment options. With the use of Valproate, previous studies have shown it can treat even severe catatonia (KrÜger, J Neuropsychiatry 2001; 13:303-304), or can actually be its cause (Lauterbach, Neuropsychiatry, Neuropsychology, and Behavioral Neurology. 1998 Jul;11(3):157-163). As such, this case report highlights the importance of exploring alternative treatments for catatonia, including Valproate, in order to better tailor the management of this unique syndrome.
In Ontario, Canada, patients may be admitted to the hospital involuntarily if they are deemed to be suffering from symptoms of a mental disorder that may result in imminent serious bodily harm to themselves or others, or that may cause serious physical impairment to themselves (e.g., inability to keep themselves safe and warm in the winter). This measure can be life-saving. However, in addition to ethical and human rights considerations, resorting to coercive admissions may be an indication that those who are suffering from mental illness are not able to access or receive timely and appropriate intervention. While recent studies have suggested that the rate of involuntary hospital admission may be increasing, data on social determinants of involuntary hospital admissions are limited.
Objectives
We examined social factors associated with involuntary admissions using a Canadian provincial database.
Methods
Binary logistic regression models were conducted to examine the associations between social factors (low income, indigeneity, rurality, housing type) and involuntary admissions, controlling for age, sex, and psychiatric diagnoses. Data from March 2019 to March 2021 was extracted from the Ontario Mental Health Reporting System admission dataset, comprising of a sample of 9,848 patients admitted to eight psychiatric hospitals in Ontario. Odds ratios and 95% confidence intervals are reported.
Results
In 2021, the proportion of involuntary patients increased significantly by 6.8 percentage points to 55.7% compared to the previous year (48.9%). Indigenous status (First Nations, Metis, Inuit) [1.75 (1.38-2.21) **], living in rural areas [2.78 (2.48-3.12)], living in assisted residence [1.41 (1.21-1.64) **], homelessness [1.63 (1.38-1.91) **], male sex [1.21 (1.10-1.33) **] and younger age [0.99 (0.98-0.99) **] were associated with involuntary admissions, while income was not a significant factor. Compared to a diagnosis of a psychotic disorder, substance use disorders [0.11 (0.10-0.13) **] and mood and anxiety disorders [0.32 (0.29-0.36) **] showed decreased odds of involuntary admission, while neurocognitive disorders increased the odds of involuntary admission [3.86 (2.91-5.11) **].
Conclusions
Consistent with other findings, involuntary psychiatric hospital admissions in ON, Canada, have increased recently, which may in part be related to the pandemic. Rurality, indigenous status, and unstable housing have been found to be associated with involuntary admissions. The study findings support the need for better preventive and intervention strategies to serve vulnerable psychiatric patients, including addressing the social determinants of health such as housing, and increasing access to culturally competent and safe community-based mental health supports and services.
Mental healthcare services that address a variety of primary complaints which are highly related to maladaptive personality traits among the general population are important to prevent developing psychiatric disorders.
Objectives
This study aimed to examine the effectiveness of a digital mental health service (named “Mindling”) that focuses on maladaptive personality traits in the general population.
Methods
Participants were recruited through a South Korean community website and screened for adults between the ages of 18 and 60 in terms of personality traits such as perfectionism, low self-esteem, social isolation, or anxiety. Participants were allocated to four intervention programs (Riggy, Pleaser, Shelly, and Jumpy) based on their screening results and were randomly assigned to digital treatment and waitlist groups. Each intervention program was conducted online for 10 weeks. The primary outcomes were all measured by self-report questionnaires; in addition to stress levels, each program included measures of perfectionism (Riggy), low self-esteem (Pleaser), loneliness (Shelly), and anxiety (Jumpy). The secondary outcomes included self-efficacy, depression, and other psychological states. All participants completed pre-treatment (baseline), intervention (week 5), and post-treatment (week 10) assessments, and the treatment group completed a separate follow-up assessment (week 14).
Results
In the treatment group, 70.05% of the participants completed the full course of the digital intervention. The mean scores for each primary outcome measure and some secondary outcome measures were significantly different between baseline and post-treatment in the treatment group for the Total, Riggy, Pleaser, Shelly, and Jumpy programs, but these differences were not observed in the waitlist group. In addition, mean differences between the treatment and waitlist groups at post-treatment assessment were significant for all primary outcome measures and some secondary outcome measures. Specifically, the levels of stress (Total program), perfectionism (Riggy), loneliness (Shelly), and anxiety (Jumpy) were significantly lower in the treatment group, while self-esteem (Pleaser) was higher. In addition, the mean differences between post-treatment and follow-up assessment data were not statistically significant for all primary outcome measures and nearly all secondary outcome measures.
Conclusions
This study validated the effectiveness of the digital intervention program targeting maladaptive personality traits and suggested its sustainable effects.
Background: Long-term efficacy of inebilizumab (INEB), an anti-CD19+ B cell-depleting antibody approved for the treatment of seropositive-aquaporin-4-antibody (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) was evaluated over N-MOmentum (NCT02200770) open-label period (OLP) vs azathioprine and other immunosuppressants (AZA/IST) and vs PBO. Methods: Two historical comparator groups (HCGs), AZA/IST (N=132) and PBO (N=106), derived from published NMOSD studies, were used to compare efficacy of INEB (N=208) over the OLP. Hazard ratios (HR) for INEB vs HCGs were estimated using Cox proportional hazards (PH) regression. Time to NMOSD attack was analysed using parametric and flexible survival (spline) models. Results: Time to NMOSD attack for N-MOmentum PBO compared to PBO was HR 1.15;(95% CI:0.67–1.91; P=0.58). The HRs for time to NMOSD attack for INEB vs AZA/IST and PBO groups were 0.29(95% CI:0.17, 0.42; P<0.001) and 0.15 (95% CI:0.10, 0.21; P<0.001). At 4 years, estimated attack-free survival was 77% (95% CI:71, 83) for INEB, 36% (95% CI:27, 46) for AZA/IST, and 12% (95% CI:7, 20) for PBO. Conclusions: INEB was associated with a statistically significant reduction in risk of an NMOSD attack and provided a long-term attack-free probability over the OLP compared to the relative short-term benefit observed with AZA/IST.
Background: CHAMPION-NMOSD (NCT04201262) is an ongoing global, open-label, phase 3 study evaluating ravulizumab in AQP4+ NMOSD. Methods: Adult patients received an intravenous, weight-based loading dose of ravulizumab on day 1 and a maintenance dose on day 15 and every 8 weeks thereafter. Following a primary treatment period (PTP; up to 2.5 years), patients could enter a long-term extension (LTE). Results: 58 patients completed the PTP; 56/2 entered/completed the LTE. As of June 16, 2023, median (range) follow-up was 138.4 (11.0-183.1) weeks for ravulizumab (n=58), with 153.9 patient-years. Across the PTP and LTE, no patients had an adjudicated on-trial relapse during ravulizumab treatment. 91.4% (53/58 patients) had stable or improved Hauser Ambulation Index score. 91.4% (53/58 patients) had no clinically important worsening in Expanded Disability Status Scale score. The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events was 94.8% and 25.9%, respectively. Most TEAEs were mild to moderate in severity and unrelated to ravulizumab. TEAEs leading to withdrawal from ravulizumab occurred in 1 patient. Conclusions: Ravulizumab demonstrated long-term clinical benefit in the prevention of relapses in AQP4+ NMOSD with a safety profile consistent with prior analyses.
Background: The long-term outcomes of inebilizumab in participants from the N-MOmentum trial with a history of immunosuppressant therapy as compared to those without was evaluated. Methods: N-MOmentum (NCT02200770) was a 28-week randomized phase 2/3 trial of inebilizumab vs placebo, with an optional Open-Label Period (OLP) (>2 years). In this post hoc analysis, AQP4+ participants who received inebilizumab (through the OLP) were grouped by no history of immunosuppression therapy beyond treatment of acute NMOSD attacks (naïve), or prior azathioprine (AZA) and/or mycophenolate mofetil (MMF) therapy. Results: Among participants who received inebilizumab during the study, 94 received prior AZA/MMF and 103 were immunosuppressant naïve. Annualized relapse rate (95%CI) for participants with prior AZA/MMF was 0.11 (0.07, 0.17), compared to 0.08 (0.05, 0.14) for naïve. The hospitalization rate (annualized rate [95% CI]) for prior AZA/MMF was 0.15 (0.08, 0.27), and 0.12 (0.06, 0.22) for naïve. Participants with ≥1 study drug-related-treatment-emergent-adverse-event (TEAE) was 30.9% (29/94) in prior AZA/MMF and 46.6% (48/103) of naïve. Most adverse events were infection-related for both groups; 72.3% (68/94) for prior AZA/MMF and 77.7% (80/94) for naïve. Conclusions: This post hoc analysis evaluating long-term outcomes of inebilizumab in AQP4+ NMOSD participants treated with prior AZA/MMF therapy demonstrated a similar efficacy and safety profile as participants without prior immunosuppressant therapy.