Top-Down Priors Disambiguate Target and Distractor Features in Simulated Covert Visual Search.

Several models of visual search consider visual attention as part of a perceptual inference process, in which top-down priors disambiguate bottom-up sensory information. Many of these models have focused on gaze behavior, but there are relatively fewer models of covert spatial attention, in which attention is directed to a peripheral location in visual space without a shift in gaze direction. Here, we propose a biologically plausible model of covert attention during visual search that helps to bridge the gap between Bayesian modeling and neurophysiological modeling by using top-down priors over target features that are acquired through Hebbian learning and spatial resampling of modeled cortical receptive fields to enhance local spatial resolution of image representations for downstream target classification. By training a simple generative model using a Hebbian update rule, top-down priors for target features naturally emerge without the need for hand-tuned or predetermined priors. Furthermore, the implementation of covert spatial attention in our model is based on a known neurobiological mechanism, providing a plausible process through which Bayesian priors could locally enhance the spatial resolution of image representations. We validate this model during simulated visual search for handwritten digits among nondigit distractors, demonstrating that top-down priors improve accuracy for estimation of target location and classification, relative to bottom-up signals alone. Our results support previous reports in the literature that demonstrated beneficial effects of top-down priors on visual search performance while extending this literature to incorporate known neural mechanisms of covert spatial attention.

Personality Traits and eHealth Study Enrollment Among Racial and Sexual Minoritized Men Living with HIV.

Inequities in eHealth research enrollment persist among Black and Latinx sexual minoritized men (SMM) partly due to socio-ecological barriers. Less is known about how personality traits are associated with their study enrollment. We examined the role of personality traits among 1,285 U.S. Black and Latinx SMM living with HIV recruited from sexual networking websites/apps for an eHealth intervention. Lower neuroticism and higher openness were associated with greater odds of study enrollment among Latinx SMM. Given these exploratory findings, future research should examine this phenomenon, along with well-established socio-ecological factors such as medical mistrust to better understand eHealth study enrollment gaps among Black and Latinx SMM.

Comparison of Nebulized Ketamine to Intravenous Subdissociative Dose Ketamine for Treating Acute Painful Conditions in the Emergency Department: A Prospective, Randomized, Double-Blind, Double-Dummy Controlled Trial.

STUDY OBJECTIVE: We aimed to assess and compare the analgesic efficacy and adverse effects of intravenous subdissociative-dose ketamine to nebulized ketamine in emergency department (ED) patients with acute painful conditions. METHODS: We conducted a prospective, randomized, double-blind, double-dummy clinical trial in adult patients (ages 18 and older) with a numerical rating scale pain score of ≥5. We randomized subjects to receive either a single dose of 0.3 mg/kg of intravenous (IV) ketamine or 0.75 mg/kg of nebulized ketamine through a breath-actuated nebulizer. Primary outcome was the difference in pain scores on the numerical rating scale between groups at 30 minutes postmedication administration. The secondary outcomes included the need for rescue analgesia, occurrences of adverse events in each group, and the difference in pain scores at 15, 30, 60, 90, and 120 minutes. We calculated a 95% confidence interval (CI) for a mean difference at 30 minutes, with a minimum clinically important difference set at 1.3 points. RESULTS: We enrolled 150 subjects (75 per group). Mean pain scores through numerical rating scale were 8.2 for both groups at baseline, which decreased to 3.6 and 3.8 at 30 minutes, yielding a mean difference of 0.23 (95% CI -1.32 to 0.857). We observed no clinically concerning changes in vital signs. No serious adverse events occurred in any of the groups throughout the study period. CONCLUSION: We found no difference between the administration of IV and nebulized ketamine for the short-term treatment of moderate to severe acute pain in the ED, with both treatments providing a clinically meaningful reduction in pain scores at 30 minutes.

Initial Feeding Method, WIC-Provided Lactation Support, and Breastfeeding Duration at an Urban Pediatric Primary Care Practice.

Breastfeeding (BF) is associated with improved maternal and infant health outcomes. However, underserved populations have limited access to lactation support. Our urban pediatric primary care practice partnered with WIC to integrate a BF peer counselor (BFPC) into newborn visits. To study the association of BF duration with (1) BFPC integration, (2) initial infant feeding methods (IFM). This is a retrospective cohort study of patients receiving BFPC support matched with those that did not based on race, ethnicity, and insurance. IFM were compared using chi-square. BF duration was compared using a t-test. These variables were compared across IFM using ANOVA. A cohort of 111 infant-mother dyads received BFPC support and 222 dyads did not (7/09/2019-4/25/2022). There was no significant difference in feeding methods between these groups. Compared to infants whose IFM was exclusive BF, fewer infants who initially used formula or both formula and breastmilk were exclusively BF at 2-month (55.8%, 8.2%, 10.9%), 4-month (54.8%, 6.3%, 14.5%), and 6-month visits (54.8%, 4.3%, 14.1%) (p < 0.001). There was a significant association between IFM and duration of any and exclusive BF (Formula only: 1 week; BF and Formula: 3 weeks; Exclusive BF: 14 weeks; p < 0.001). A significant association was found between IFM and duration of BF. Early formula introduction was negatively associated with BF duration. The prenatal period may therefore be optimal for initiating BF support. Although there was no association between BFPC and BF duration, additional benefits of this intervention should be explored.

The Use of Telemedicine for Screening and Addressing Social Needs in a Primary Care Pediatric Population in Brooklyn, New York.

The objective of this study was to analyze temporal changes in social needs (SN), comparing those who received routine annual in-person care to those receiving SN screenings through a combination of tele-social care and in-person care biannually. Our prospective cohort study used a convenience sample of patients from primary care practices. Baseline data were collected from April 2019 to March 2020. The intervention group (n = 336) received SN screening and referral telephone outreach from June 2020 to August 2021. The control group (n = 2890) was screened, in person, during routine visits at baseline and summer 2021. We used a repeated-measures logistic regression with general estimating equations to assess incremental change in individual SN for the intervention group. Food, housing, legal and benefit needs increased and peaked at the beginning of the pandemic and decreased after interventions (P < 0.001). There was a 32% decrease in the odds of food insecurity for those in the intervention group compared to the control group (adjusted OR 0.668, 95% confidence interval 0.444-1.004, P = 0.052), and a 75% decrease in the odds of housing insecurity (adjusted OR 0.247, 95% confidence interval 0.150-0.505, P < 0.001). During COVID-19, there was an increase in SN followed by a decrease after interventions were offered. Those who completed tele-social care showed greater improvements in social needs than those in routine care, with the greatest improvements in food and housing needs.

Comparative Outcomes of Candida auris Bloodstream Infections: A Multicenter Retrospective Case-Control Study.

BACKGROUND: This study was performed to compare clinical characteristics and outcomes between patients with bloodstream infections (BSIs) caused by Candida auris and those with BSIs caused by other Candida spp. METHODS: A multicenter retrospective case-control study was performed at 3 hospitals in Brooklyn, New York, between 2016 and 2020. The analysis included patients ≥18 years of age who had a positive blood culture for any Candida spp. and were treated empirically with an echinocandin. The primary outcome was the 30-day mortality rate. Secondary outcomes were 14-day clinical failure, 90-day mortality rate, 60-day microbiologic recurrence, and in-hospital mortality rate. RESULTS: A total of 196 patients were included in the final analysis, including 83 patients with candidemia caused by C. auris. After inverse propensity adjustment, C. auris BSI was not associated with increased 30-day (adjusted odds ratio, 1.014 [95% confidence interval, .563-1.828]); P = .96) or 90-day (0.863 [.478-1.558]; P = .62) mortality rates. A higher risk for microbiologic recurrence within 60 days of completion of antifungal therapy was observed in patients with C. auris candidemia (adjusted odds ratio, 4.461 [95% confidence interval, 1.033-19.263]; P = .045). CONCLUSIONS: C. auris BSIs are not associated with a higher mortality risk than BSIs caused by other Candida spp. The rate of microbiologic recurrence was higher in the C. auris group.

Lack of Racial Diversity in Surgery and Pathology Textbooks Depicting Diseases of the Breast.

INTRODUCTION: The lack of racial diversity depicted in medical education texts may contribute to an implicit racial bias among clinicians. This bias influences outcomes, as familiarity with the various cutaneous manifestations of disease is essential to making an accurate diagnosis. To better understand the racial disparities in breast surgery, we sought to determine the extent of skin tone representation depicted in images of breast surgery and pathology textbooks. METHODS: Textbooks were screened for color images of conditions with sufficient skin tissue present to assign the Fitzpatrick skin phototype (FSP). Figures were independently assigned an FP score (range: 1-6), and subdivided into "light skin" (FP 1-3) and "dark skin" (FP 4-6). Number of figures in each category and percentage of patients with each skin tone were calculated. RESULTS: 557 figures were included. Among 12 textbooks reviewed, seven textbooks were from the discipline of surgery, while five were pathology-related. Textbook year of publication spanned from 1996 to 2018. Overall, 533 (95.7%) figures depicted patients with light skin color versus 24 (4.3%) with dark skin color. There was no association between FP score and year of textbook publication (P = 0.69). CONCLUSIONS: Patient images in breast textbooks are overwhelmingly of light skin tones, excluding patients with darker skin tones. The dearth of images depicting dark skinned individuals did not improve over time. Inclusion of patients of color in future textbooks may help reduce racial disparities within breast cancer care.

The aftermath of the COVID-19 pandemic on pediatric mental health: A pediatric emergency department's perspective.

BACKGROUND: Pediatric mental health visits in the United States has become a public health crisis. Pediatric emergency departments (PED) encounter these patients during mental health emergencies. The COVID-19 pandemic disrupted the social environment of pediatric patients which potentially lead to new and worsening mental health issues. This study examined the proportion of mental health visits to PED around the first wave of the COVID-19 pandemic. METHODS: This retrospective cohort study assessed the proportion of mental health visits at a urban, PED between September 2019 to February 2022. Inclusion criteria were subjects aged 6 to 18 years with a holding order assigned, and one of identified mental health International Classification of Disease, Tenth Division (ICD-10) codes: F01-F99, T14.19, R45, R46.89. Proportion of mental health visits were compared in 6-month periods with the first 6-months representing the pre-COVID-19 period. Secondary analysis compared demographic information and ICD-10 codes. RESULTS: A total of 1036 charts were studied: 126 charts from 2019 to 2020, 512 from 2020 to 2021, and 398 from 2021 to 2022. The proportion of mental health visits from September 2019 to February 2020 was 1.4%, and for the following 6-month periods, the proportion of mental health visits was 1.2%, 7.5%, 4.9%, and 5.7%. There was a statistically significant difference (p < 0.001) demonstrating a higher proportion of mental health visits after the start of the COVID-19 pandemic. Secondary analysis demonstrated statistically significant difference in both median age (p < 0.001) and median length of hospitalization (p < 0.001). CONCLUSION: This study demonstrated a significant increase in pediatric mental health visits following the start of the COVID-19 pandemic. We believe further investigation into the needs and management during acute surges will improve the care we provide to this vulnerable population.

The evolving relationship between COVID-19 and serious bacterial infection evaluation in febrile neonates.

AIM: The COVID-19 omicron variant surge highlighted the evolving impact of COVID-19. Febrile infants <60 days old are high risk for serious bacterial infections (SBI). This study evaluated the rate of SBI based on COVID-19 infection. METHODS: We conducted a retrospective chart review at an urban, academic paediatric emergency department. The study enrolled infants 60 days old or less with documented fever. The primary outcome was SBI diagnosed by blood, urine, and/or cerebrospinal fluid cultures. We compared the rate of SBI between COVID-19 groups with an omicron variant and 29- to 60-day-old subgroup analyses. RESULTS: Two hundred and thirty-three (233) infants meet the criteria. The incidence of SBI was 18.7% in the COVID-19 negative and 1.7% in the COVID-19-positive group which is statistically significant (p < 0.001). Omicron subgroup analysis did not achieve statistical significance (p = 0.62) while COVID-19-positive infants 29-60 days old had a statistically significant lower rate of SBI (p = 0.006). CONCLUSION: The omicron variant surge provided an additional understanding of the impact of COVID-19 on these high-risk infants. These results can lead to decreased invasive testing and exposure to antibiotics as well as examine the utility of viral testing for risk stratification.

COVID-19 Vaccine Hesitancy in an Underrepresented Minority Community.

To assess factors influencing acceptability of COVID-19 vaccine in a population of predominantly indigent, minority, pregnant and non-pregnant people of reproductive age. Cross-sectional survey using a modified Health Belief model administered between January 2021 and January 2022 at four hospitals in Brooklyn. Participants included English-speaking reproductive aged persons attending clinics at the participating sites. Descriptive and univariate data analyses were used for analysis. 283 eligible reproductive persons were approached of whom 272 completed the survey (96%). Three quarters said they would take the vaccine under certain circumstances ("as soon as it is ready" [28.6%], "when my doctor recommends it" [21.3%] or "when enough people have received it to know if it works" [25%]), while 25% said they would never take the vaccine. When comparing persons that would take it under certain circumstances to those that never would, the "never" group was significantly more likely to note that, "they would not trust any COVID vaccine" (71.4% vs. 28.5%; p ≤ 0.0001). This greater level of distrust extended to greater distrust of doctors, government, family, newspapers, and media. However, 36% said they would be influenced by their doctor's recommendation. Pregnant participants were significantly more likely to wait until their doctor recommended it (17.6% of pregnant persons compared to 3.7% of non-pregnant p < 0.0001). Despite mistrust and other discouraging factors, many persons, under appropriate circumstances (e.g., reassurance about vaccine safety) may be motivated to take the vaccine. Even those who claimed that they wouldn't take the vaccine under any circumstance may be influenced by their health care providers.

Cesarean Birth Morbidity among Women with SARS-CoV-2.

OBJECTIVE: The objective of this study was to compare maternal outcomes of women with and without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections who underwent cesarean births. STUDY DESIGN: This was a matched cohort study of pregnant women who had a cesarean birth between March 15, 2020, and May 20, 2020. Cases included women who tested positive for SARS-CoV-2. For every case, two patients who tested negative for SARS-CoV-2 were matched by maternal age, gestational age, body mass index, primary or repeat cesarean birth, and whether the procedure was scheduled or unscheduled. We compared rates of adverse postcesarean complications (intraoperative bladder or bowel injury, estimated blood loss more than or equal to 1,000 mL, hemoglobin drop more than 3 g/dL, hematocrit drop more than 10%, need for blood transfusion, need for hysterectomy, maternal intensive care unit admission, postoperative fever, and development of surgical site infection), with the primary outcome being a composite of those outcomes. We also assessed duration of postoperative stay. Fisher's exact tests were performed to compare the primary outcome between both groups. RESULTS: Between March and May 2020, 202 women who subsequently underwent cesarean birth were tested for SARS-CoV-2. Of those 202, 43 (21.3%) patients were positive. They were matched to 86 patients who tested negative. There was no significant difference in the rate of composite adverse surgical outcomes between the groups (SARS-CoV-2 infected 27.9%, SARS-CoV-2 uninfected 25.6%; p = 0.833). There was a higher rate of postoperative fevers (20.9 vs. 5.8%; p = 0.015), but that did not result in a longer length of stay (p = 0.302). CONCLUSION: Pregnant women with SARS-CoV-2 who underwent a cesarean birth did not have an increased risk of adverse surgical outcomes, other than fever, compared with pregnant women without SARS-CoV-2. KEY POINTS: · Women with SARS-CoV-2 had more postoperative fevers.. · Length of stay did not differ based on SARS-CoV-2 status.. · Composite postoperative outcome did not differ based on SARS-CoV-2 status..

Temporal Trend in SARS-CoV-2 Symptoms in Pregnant Women.

OBJECTIVE: The objective of this study was to examine temporal trends in the clinical presentation of patients diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in pregnancy. STUDY DESIGN: This is a retrospective cohort study of pregnant women who were universally screened for SARS-CoV-2 and tested positive. This multi-center study of admissions to labor and delivery units in New York City and Long Island included all SARS-CoV-2-infected pregnant women admitted to labor and delivery units between April 10th and June 4th 2020. Six Northwell Health hospitals and Maimonides Medical Center were included in the study. The main measures of the study included patient reports of COVID-19 symptoms: fever, cough, chest pain, shortness of breath, nausea, vomiting, and intensive care unit (ICU) admissions. The main outcome measure was the percentage of all infected women who reported any of the above symptoms. RESULTS: In total, 427 infected pregnant women were included in the study. There was a statistically significant decline in the percentage of patients presenting with any symptoms over the course of the study. In addition, disease severity, symptoms of fever, cough, and chest pain/shortness of breath also significantly declined over time, and no ICU admissions were noted after the third week of April. CONCLUSION: There was a temporal shift away from symptomatic presentation in pregnant women diagnosed with SARS-CoV-2 over the course of the first months of the epidemic in New York. Further studies are necessary to elucidate the cause of this change in presentation among pregnant women, to determine whether this trend is also observed in other patient populations. KEY POINTS: · Retrospective cohort review of 427 SARS-CoV-2-infected pregnant women admitted to labor and delivery units.. · A significant decline in the percentage of patients presenting with symptoms over time was noted.. · Further studies are necessary to elucidate the cause of this change in presentation.. · Theories for the noted trend: viral evolution, decreased viral inoculums, and prolonged polymerase chain reaction positivity..

Enhanced perceptual selection of predicted stimulus orientations following statistical learning.

Perception is influenced by predictions about the sensory environment. These predictions are informed by past experience and can be shaped by exposure to recurring patterns of sensory stimulation. Predictions can enhance perception of a predicted stimulus, but they can also suppress it by favoring novel and unexpected sensory information that is inconsistent with the predictions. Here we employed statistical learning to assess the effects of exposure to consistent sequences of oriented gratings on subsequent visual perceptual selection, as measured with binocular rivalry. Following statistical learning, the first portion of a learned sequence of stimulus orientations was presented to both eyes, followed by simultaneous presentation of the next grating in the sequence to one eye and an orthogonal unexpected orientation to the other eye. We found that subjects were more likely to perceive the grating that matched the orientation that was consistent with the predictive context. That is, observers were more likely to see what they expected to see, compared to the likelihood of perceiving the unexpected stimulus. Some other studies in the literature have reported the opposite effect of prediction on visual perceptual selection, and we suggest that these inconsistencies may be due to differences across studies in the level of the visual processing hierarchy at which competing perceptual interpretations are resolved.

Effects of involuntary and voluntary attention on critical spacing of visual crowding.

Visual spatial attention can be allocated in two distinct ways: one that is voluntarily directed to behaviorally relevant locations in the world, and one that is involuntarily captured by salient external stimuli. Precueing spatial attention has been shown to improve perceptual performance on a number of visual tasks. However, the effects of spatial attention on visual crowding, defined as the reduction in the ability to identify target objects in clutter, are far less clear. In this study, we used an anticueing paradigm to separately measure the effects of involuntary and voluntary spatial attention on a crowding task. Each trial began with a brief peripheral cue that predicted that the crowded target would appear on the opposite side of the screen 80% of the time and on the same side of the screen 20% of the time. Subjects performed an orientation discrimination task on a target Gabor patch that was flanked by other similar Gabor patches with independent random orientations. For trials with a short stimulus onset asynchrony between cue and target, involuntary capture of attention led to faster response times and smaller critical spacing when the target appeared on the cue side. For trials with a long stimulus onset asynchrony, voluntary allocation of attention led to faster reaction times but no significant effect on critical spacing when the target appeared on the opposite side to the cue. We additionally found that the magnitudes of these cueing effects of involuntary and voluntary attention were not strongly correlated across subjects for either reaction time or critical spacing.

Open conversion after failed endovascular aneurysm repair is increasing and its 30-day mortality is higher than that after primary open repair.

BACKGROUND: Endovascular aneurysm repair (EVAR) has become the preferred treatment of abdominal aortic aneurysms (AAAs). Recent studies have demonstrated that cases of EVAR failure repair and subsequent open conversion have increased. The aim of the present study was to evaluate the national trend of annual cases and assess the 30-day outcomes of conversion to open repair after failed EVAR compared with primary open repair. METHODS: The National Surgical Quality Improvement Program database was queried for relevant Current Procedural Terminology and International Classification of Diseases, Ninth and Tenth Revision, codes to identify patients who had undergone conversion to open repair or primary open repair of nonruptured AAAs from 2009 to 2018. The annual trend of cases was assessed, and the perioperative outcomes of both procedures were compared. Multivariable logistic regression analyses were conducted to identify independent perioperative factors associated with mortality. RESULTS: Of the 9635 patients with nonruptured AAAs included in the present analysis, 9250 had undergone primary repair and 385 had required open conversion. During the 10-year period, the annual number of cases of open conversion had steadily increased and that of primary repair had decreased. The incidence of postoperative complications was similar between both groups, except for cardiac arrest, which had occurred more frequently in the open conversion group. The 30-day mortality was higher in the open conversion group than in the primary group (9.6% vs 3.9%; P < .0001). Open conversion was also independently associated with higher odds of death (adjusted odds ratio [OR], 2.1; 95% confidence interval [CI], 1.8-2.4; P < .0001). When the average mortality in both groups was compared between the first and last 5 years, no difference was found (open conversion: 9.8% vs 9.5% [P = 1.00]; primary repair: 3.6% vs 4.2% [P = .19]). Other perioperative factors independently associated with mortality included increased age (OR, 1.8; 95% CI, 1.5-2.1; P < .0001), American Society of Anesthesiologists class ≥III (OR, 2.7; 95% CI, 1.1-6.6; P = .029), insulin-dependent diabetes (OR, 2.0; 95% CI, 1.2-3.3; P = .005), chronic obstructive pulmonary disease (OR, 1.4; 95% CI, 1.1-1.8; P = .006), the presence of dyspnea at rest (OR, 3.3; 95% CI, 1.8-6.1; P < .0001), and a high preoperative hematocrit (OR, 0.94; 95% CI, 0.93-0.97; P < .0001). CONCLUSIONS: Open conversion to treat nonruptured AAAs after failed EVAR was independently associated with higher mortality. Also, the annual cases of open conversion have continued to increase without any significant changes in postoperative mortality. This highlights the danger of open conversion and stresses the need for better solutions to prevent and manage EVAR failure.

Interpersonal Stigma, Mental Health, and Sexual Compulsivity Among an Online U.S. Sample of Men Who Have Sex with Men Living with HIV.

This cross-sectional study sought to determine whether HIV-related interpersonal stigma was associated with the presence of sexual compulsivity (SC) in a national online sample of 936 men who have sex with men (MSM) living with HIV who reported recent suboptimal adherence to their antiretroviral therapy (ART) or virologic non-suppression. A modest association was found between perceptions of HIV-related interpersonal stigma and SC that was partially mediated by current mental health symptoms. White MSM were significantly more likely than Black MSM to report SC or HIV-related interpersonal stigma. Findings signal the need for therapeutic interventions that include behavioral and/or pharmacologic therapy to address overlapping intervention targets, including mental health, substance use, and sexual health. Future research should assess temporality of HIV-related interpersonal stigma and SC, as well as racial differences in relation to these constructs.

Oral Aspirin/ketamine versus oral ketamine for emergency department patients with acute musculoskeletal pain.

OBJECTIVE: The purpose of this study is to investigate if an orally administered combination of aspirin and ketamine will provide better analgesia than a ketamine alone in adult patients presenting to the Emergency Department (ED) with acute musculoskeletal pain. METHODS: We conducted a prospective, randomized, open-label trial of ED patients aged 18 and older presenting with moderate to severe acute musculoskeletal pain as defined by an 11-point numeric rating scale (NRS) with an initial score of ≥5. Patients were randomized to receive either 324 mg of VTS-Aspirin™ and 0.5 mg/kg of oral ketamine (AOK) that is directly swallowed or 0.5 mg/kg of oral ketamine (OK) alone that is swished first and then swallowed. Patients were assessed at baseline, 30, 60, 90, and 120 min. The primary outcome was a difference in pain scores between the two groups at 60 min post-administration. Secondary outcomes included adverse events and the need for rescue analgesia. RESULTS: We enrolled 60 patients in the study (30 per group). The difference in mean pain scores at 60 min between the AOK and OK groups was 2.6 [95% CI: 1.38-3.77] showing a lower mean pain score in the OK group. At 60 min, the AOK group had a change in mean pain score from 8.4 to 6.3 (difference 2.1; 95% CI: 1.35-3.00). The OK group had a change in mean pain score from 7.8 to 3.7 (difference 4.1, 95% CI: 3.25-4.90). No clinically concerning changes in vital signs were observed. No serious adverse events occurred in either group. The most commonly reported adverse effects were dizziness and fatigue. None of the participants required rescue analgesia at 60 min post-medications administration. CONCLUSION: The administration of an oral combination of VTS-Aspirin ™ and ketamine resulted in less analgesia compared to oral ketamine alone, for the short-term treatment of moderate to severe acute musculoskeletal pain in the ED. CLINICALTRIALS: govRegistration: NCT04860804.

P031 Impact of Prior Biologic Exposure on Response to Ozanimod for Moderate-to-Severe Ulcerative Colitis in the Phase 3 True North Study.

BACKGROUND: Ozanimod, an oral sphingosine 1-phosphate (S1P) receptor modulator selectively targeting S1P1 and S1P5, demonstrated superior efficacy and safety vs placebo for up to 52 weeks in adults with moderately to severely active ulcerative colitis (UC) in a phase 3 study (True North). In this post-hoc analysis, we evaluated the impact of prior biologic exposure on response to ozanimod. METHODS: True North consisted of two cohorts. In cohort 1, patients with UC received double-blind treatment with once-daily ozanimod 0.92 mg (equivalent to ozanimod HCl 1 mg) or placebo. In cohort 2, patients received open-label once daily ozanimod 0.92 mg. Ozanimod responders after a 10-week induction were re-randomized to double-blind maintenance with ozanimod 0.92 mg or placebo through week 52. Outcomes based on prior biologic exposure (biologic-naïve, 1 biologic, and 2+ biologics) and prior biologic type (anti-tumor necrosis factor [TNF] agents, vedolizumab, or both) were analyzed for clinical remission, clinical response, endoscopic improvement, and mucosal healing. Patients exposed to only a JAK inhibitor were excluded from the analysis. RESULTS: A total of 992 patients (n = 213 placebo and n = 426 ozanimod in cohort 1, n = 353 ozanimod in cohort 2) were included in the analysis for induction; 616 were biologic-naïve, 162 had exposure to 1 biologic, and 214 were exposed to 2 or more biologics. At baseline, biologic-exposed patients had more prior corticosteroid use, longer disease duration, and more extensive disease than biologic-naïve patients. During induction, greater therapeutic effects of ozanimod were generally seen in biologic-naïve vs biologic-exposed patients, and ozanimod-treated patients had greater responses on nearly all reported endpoints at week 10 (cohort 1). Clinical remission was achieved in 23% vs 6.6% of patients on ozanimod vs placebo who were biologic naïve, 17.2% vs 8.3% on 1 prior biologic, and 3.7% vs 2.5% on 2 or more biologics. Clinical response was reached in 53% vs 28% of patients on ozanimod vs placebo who were biologic naïve, 50% vs 33% on 1 biologic, and 27% vs 15% on 2 or more biologics. During maintenance, ozanimod-treated patients had greater responses on all endpoints versus placebo, with similar proportions of patients achieving clinical response to ozanimod regardless of prior biologic exposure (61% for biologic naïve, 60% for 1 biologic, and 55% for 2 or more biologics). At week 52, the proportion of patients on ozanimod with clinical remission was similar in the 1-biologic and 2+-biologic exposure groups (28% and 26%, respectively), and proportions of patients on ozanimod with endoscopic improvement and mucosal healing were similar for the 1-biologic and biologic-naïve groups (47% and 50%, 30%, and 33%, respectively). Among patients with inadequate response to prior anti-TNF agents, vedolizumab, or both at baseline, treatment effects favored ozanimod vs placebo on these endpoints in all three groups during both induction and maintenance. CONCLUSION: Ozanimod improved clinical, endoscopic, and histologic outcomes in both biologic-exposed and -naïve patients. Patients with prior biologic use may require additional time to respond to treatment. Outcomes were improved with ozanimod regardless of prior use of anti-TNF agents and vedolizumab.

P035 Ozanimod for Moderate-to-Severe Ulcerative Colitis: North American Population Results During Induction and Maintenance in the Phase 3 True North Study.

BACKGROUND: True North is a phase 3, randomized, double-blind, placebo-controlled trial conducted at 285 sites in 30 countries (NCT02435992). Treatment with once-daily ozanimod (an oral sphingosine 1-phosphate [S1P] receptor modulator selectively targeting S1P1 and S1P5) in patients with moderately-to-severely active ulcerative colitis (UC) showed significant improvements in primary and all key secondary endpoints. Here we report findings on the consistency of clinical and endoscopic endpoints in the global and North American population. METHODS: In True North, patients received either double-blind treatment with ozanimod 0.92 mg (equivalent to ozanimod HCl 1 mg) or matching placebo, or open-label ozanimod 0.92 mg over a 10-week induction period. Patients with clinical response to ozanimod at Week 10 were re-randomized 1:1 to receive double-blind maintenance treatment with ozanimod 0.92 mg or placebo through Week 52. The primary endpoint was proportion of patients in clinical remission at Weeks 10 and 52; key secondary endpoints included clinical response and endoscopic improvement. The global population included 1012 patients who received at least 1 dose of study medication during induction, and 457 who received at least 1 dose of study medication during maintenance. Here, we examine the results from the patients in the North American sites. RESULTS: A total of 247 patients were enrolled in North America, of which 167 received double-blind ozanimod (n=107) or placebo (n=60) during induction. At baseline, 41.1% and 48.3% of patients in the ozanimod and placebo groups, respectively, had previously received a biologic treatment for UC. At Week 10, 15.9% and 3.3% of patients in the ozanimod and placebo groups, respectively, achieved clinical remission. In addition, 46.7% and 15.0% achieved clinical response and 26.2% and 10.0% achieved endoscopic improvement in the ozanimod and placebo groups, respectively. In patients with prior exposure to tumor necrosis factor inhibitor (TNFi), the proportion with clinical response favored ozanimod (35.7%) vs placebo (11.5%), while the proportion with clinical remission and endoscopic improvement did not favor ozanimod. In patients with no prior TNFi exposure, greater responses were seen with ozanimod vs placebo for all 3 endpoints. During maintenance, 105 patients from North America were re-randomized to treatment with ozanimod (n=56) or placebo (n=49). At Week 52, 39.3% and 12.2% of patients in the ozanimod and placebo groups, respectively, achieved clinical remission. In addition, 58.9% and 26.5% achieved clinical response and 50.0% and 16.3% achieved endoscopic improvement in the ozanimod and placebo groups, respectively. The proportion of patients with clinical remission, clinical response, and endoscopic improvement favored ozanimod vs placebo regardless of prior TNFi use. These outcomes from the North American population are generally consistent with those previously reported from the global population. CONCLUSION: In this post-hoc analysis, consistent with the global population, ozanimod treatment for up to 52 weeks in North American patients with moderately-to-severely active UC showed benefits on clinical and endoscopic endpoints.

Spatial Attention Enhances Crowded Stimulus Encoding Across Modeled Receptive Fields by Increasing Redundancy of Feature Representations.

Any visual system, biological or artificial, must make a trade-off between the number of units used to represent the visual environment and the spatial resolution of the sampling array. Humans and some other animals are able to allocate attention to spatial locations to reconfigure the sampling array of receptive fields (RFs), thereby enhancing the spatial resolution of representations without changing the overall number of sampling units. Here, we examine how representations of visual features in a fully convolutional neural network interact and interfere with each other in an eccentricity-dependent RF pooling array and how these interactions are influenced by dynamic changes in spatial resolution across the array. We study these feature interactions within the framework of visual crowding, a well-characterized perceptual phenomenon in which target objects in the visual periphery that are easily identified in isolation are much more difficult to identify when flanked by similar nearby objects. By separately simulating effects of spatial attention on RF size and on the density of the pooling array, we demonstrate that the increase in RF density due to attention is more beneficial than changes in RF size for enhancing target classification for crowded stimuli. Furthermore, by varying target/flanker spacing, as well as the spatial extent of attention, we find that feature redundancy across RFs has more influence on target classification than the fidelity of the feature representations themselves. Based on these findings, we propose a candidate mechanism by which spatial attention relieves visual crowding through enhanced feature redundancy that is mostly due to increased RF density.