Ventral Pallidal GABAergic Neuron Calcium Activity Encodes Cue-Driven Reward Seeking and Persists in the Absence of Reward Delivery.

Reward-seeking behavior is often initiated by environmental cues that signal reward availability. This is a necessary behavioral response; however, cue reactivity and reward-seeking behavior can become maladaptive. To better understand how cue-elicited reward seeking becomes maladaptive, it is important to understand the neural circuits involved in assigning appetitive value to rewarding cues and actions. Ventral pallidum (VP) neurons are known to contribute to cue-elicited reward-seeking behavior and have heterogeneous responses in a discriminative stimulus (DS) task. The VP neuronal subtypes and output pathways that encode distinct aspects of the DS task remain unknown. Here, we used an intersectional viral approach with fiber photometry to record bulk calcium activity in VP GABAergic (VP GABA) neurons in male and female rats as they learned and performed the DS task. We found that VP GABA neurons are excited by reward-predictive cues but not neutral cues and that this response develops over time. We also found that this cue-evoked response predicts reward-seeking behavior and that inhibiting this VP GABA activity during cue presentation decreases reward-seeking behavior. Additionally, we found increased VP GABA calcium activity at the time of expected reward delivery, which occurred even on trials when reward was omitted. Together, these findings suggest that VP GABA neurons encode reward expectation, and calcium activity in these neurons encodes the vigor of cue-elicited reward seeking.SIGNIFICANCE STATEMENT VP circuitry is a major driver of cue-evoked behaviors. Previous work has found that VP neurons have heterogenous responses and contributions to reward-seeking behavior. This functional heterogeneity is because of differences of neurochemical subtypes and projections of VP neurons. Understanding the heterogenous responses among and within VP neuronal cell types is a necessary step in further understanding how cue-evoked behavior becomes maladaptive. Our work explores the canonical GABAergic VP neuron and how the calcium activity of these cells encodes components of cue-evoked reward seeking, including the vigor and persistence of reward seeking.

Healthcare resource utilization of patients with warm autoimmune hemolytic anemia initiating first line therapy of oral corticosteroids with or without rituximab.

This retrospective cohort study described real-world treatment patterns and healthcare resource utilization (HCRU) of patients with warm autoimmune hemolytic anemia (wAIHA) initiating treatment with first-line (1L) oral corticosteroids (OCS) + rituximab (R) compared to 1L OCS. Patients with a wAIHA diagnosis code (D59.11) between 8/2020-3/2022 were identified using US pharmacy and medical claims databases. Patients initiating 1L OCS ± R were identified (date of initiation = 'index date') with a 1-year pre-index period and a variable (minimum 1-year) follow-up period. The final sample comprised 77 1L OCS + R patients and 400 1L OCS patients (~ 60% female, mean age > 64 years). Over the 1-year follow-up, HCRU was higher in the OCS + R cohort with higher mean number of physician office visits (22.9 and 14.4; p < 0.01), including hematology/oncology office visits, and higher utilization of rescue therapy (59.7% and 33.3%; p < 0.01), driven by higher use of injectable corticosteroids. Patients in OCS + R and OCS groups completed 1L therapy after a similar mean duration of 103.5 and 134.6 days, respectively (p = 0.24). In the majority of patients, second-line (2L) therapy was initiated at a similar timepoint: 66.2% OCS + R and 72.0% OCS cohorts (p = 0.31) initiated 2L in a mean of 218.3 and 203.2 days (p = 0.76) after the end of 1L treatment, respectively. The addition of rituximab in 1L did not extend the remission period, with most patients in both cohorts initiating 2L therapy within less than 1 year of completing 1L treatment. 1L OCS + R patients also had substantial HCRU burden. More effective novel therapies are needed to address the high unmet need in wAIHA.

A qualitative analysis of male eating disorder symptoms.

Insights into how males experience eating disorder symptoms early in the course of illness are important to improve detection efforts and may also provide valuable information for treatment. In this qualitative study, 10 adolescent males and 10 matched female patients completed standardized questionnaires and were interviewed. Results indicated that although there were many similarities between the genders, females were more likely to describe the involvement of family systems and males were more likely to describe involvement in sports as being catalysts for their disorders. Males in this study were more positive about being in treatment.

Potential job facilitation benefits of "water cooler" conversations: the importance of social interactions in the workplace.

This study looked at the extent to which personality and cultural factors predicted participants' perceptions of the importance private interactions played in the workplace. The 134 participants read a vignette (where a new employee socially interacted at low or high levels with co-workers) and completed the Big Five Inventory, Social Axioms Survey, and questions concerning expected workplace experiences. Results indicated employees who engaged in high levels of private interaction with co-workers were expected to be better liked, to receive better performance evaluations, were more likely to receive co-worker assistance, and were thought to be more likely chosen for future projects. However, the personality and social axiom variables studied did not significantly interact with social interaction to influence expectations of workplace outcomes.

Breaking constraint: axial patterning in Trichechus (Mammalia: Sirenia).

Meristic variation is often limited in serially homologous systems with high internal differentiation and high developmental modularity. The mammalian neck, an extreme example, has a fixed (at seven) count of diversely specialized segments. Imposition of the mammalian cervical constraint has been tentatively linked to the origin of the diaphragm, which is muscularized by cells that migrate from cervical somites during development. With six cervical vertebrae, the genus Trichechus (manatee) has apparently broken this constraint, although the mechanism of constraint escape is unknown. Hypotheses for the developmental origin of Trichechus cervical morphology include cervical rib 7 repatterning, a primaxial/abaxial patterning shift, and local homeosis at the cervical/thoracic boundary. We tested predictions of these hypotheses by documenting vertebral morphology, axial ossification patterns, regionalization of the postcranial skeleton, and the relationship of thoracic ribs to sternal subunits in a large data set of fetal and adult Trichechus and Dugong specimens. These observations forced rejection of all three hypotheses. We propose alternatively that a global slowing of the rate of somitogenesis reduced somite count and disrupted alignment of Hox-generated anatomical markers relative to somite (and vertebral) boundaries throughout the Trichechus column. This hypothesis is consistent with observations of the full range of traditional cervical morphologies in the six cervical vertebrae, conserved postcranial proportions, and column-wide reduction in count relative to its sister taxon, Dugong. It also suggests that the origin of the mammalian cervical constraint lies in patterning, not in count, and that Trichechus and the tree sloths have broken the constraint using different developmental mechanisms.

Ventral pallidum neurons projecting to the ventral tegmental area reinforce but do not invigorate reward-seeking behavior.

Reward-predictive cues acquire motivating and reinforcing properties that contribute to the escalation and relapse of drug use in addiction. The ventral pallidum (VP) and ventral tegmental area (VTA) are two key nodes in brain reward circuitry implicated in addiction and cue-driven behavior. In the current study, we use in vivo fiber photometry and optogenetics to record from and manipulate VP→VTA in rats performing a discriminative stimulus task to determine the role these neurons play in invigoration and reinforcement by reward cues. We find that VP→VTA neurons are active during reward consumption and that optogenetic stimulation of these neurons biases choice behavior and is reinforcing. Critically, we find no encoding of reward-seeking vigor, and optogenetic stimulation does not enhance the probability or vigor of reward seeking in response to cues. Our results suggest that VP→VTA activity is more important for reinforcement than for invigoration of reward seeking by cues.

Racial and Ethnic Disparities in Treatment Initiation Among Patients with Newly Diagnosed Psoriatic Arthritis: A Retrospective Medicaid Claims Database Study.

INTRODUCTION: In patients with psoriatic arthritis (PsA), potential differences in care by race/ethnicity have not been well studied. METHODS: This retrospective, observational cohort analysis utilized the IBM MarketScan® Multi-State Medicaid database. Patients aged ≥ 18 years with two or more PsA-related claims between January 1, 2010 and December 31, 2019, and ≥ 12 months of continuous enrollment before the first diagnosis of PsA (index date) were included. Outcomes evaluated were the use of disease-modifying antirheumatic drugs (DMARDs) overall and by type (conventional synthetic, biologic, targeted synthetic) within 12 months following initial PsA diagnosis, as well as the time to DMARD initiation after initial PsA diagnosis, stratified by race/ethnicity. Multivariate Cox proportional hazards models were used to assess potential associations between patient baseline characteristics and time to DMARD initiation. RESULTS: Among patients with newly diagnosed PsA (N = 3432), the mean age was 44.4 years, 69.9% were female, 77.4% were White, and 10.1% were Black. Of the 2993 patients with at least 12 months of follow-up, fewer Black patients received any DMARD therapy compared with White patients (68.4 vs. 76.4%, respectively, p = 0.002), and, specifically, a lower percentage of Black patients received biologic DMARDs compared with White patients (33.6 vs. 42.6%, respectively, p = 0.003). After adjusting for baseline characteristics, Black patients had significantly longer time to initiation of any DMARD (HR [95% CI] 0.82 [0.71-0.94]) and biologic DMARD (0.84 [0.71-0.99]) compared with White patients. Other baseline variables such as older age, anxiety, and hepatitis C were also significantly associated with longer time to any DMARD initiation after initial PsA diagnosis. CONCLUSIONS: Time to treatment initiation was significantly longer in Black patients compared with White patients with newly diagnosed PsA. These findings suggest care delivery disparities in patients with PsA and highlight the need for future studies to understand factors that drive the observed differences in drug therapy by race/ethnicity.

Amantadine-Induced Craniofacial Myoclonus: Distinctive Iatrogenic Dysarthria in Parkinson's Disease.

Background: Amantadine is a widely prescribed medication in Parkinson's disease (PD). A distinctive craniofacial distribution of myoclonus with speech impairment is an underrecognized iatrogenic complication in amantadine-treated patients with PD. Cases: We report 7 patients with idiopathic PD (disease duration, 6-21 years) who developed speech-induced craniofacial-predominant myoclonus with "stuttering-like" dysarthria and speech arrests days to months after amantadine initiation or dose increase. Renal insufficiency was identified as a risk factor in 4 cases. In all cases, reduction or discontinuation of amantadine markedly attenuated the myoclonus and restored speech intelligibility. Literature Review: Amantadine can induce subcortical segmental or generalized myoclonus. A report in 1996 of "vocal myoclonus" in an amantadine-treated patient with PD was the first observation of a focal distribution of myoclonus, particularly affecting speech. Since then, few cases of craniofacial myoclonus with speech impairment have been reported, none with accompanying video. With 1 exception, the craniofacial distribution was part of a generalized pattern of amantadine-induced myoclonus. Comorbid renal insufficiency is a recognized risk factor. Conclusions: Speech-induced craniofacial myoclonus, with marked "stuttering-like" dysarthria and speech arrests, is a disabling iatrogenic complication in PD that resolves upon amantadine discontinuation.

Six-Month Persistence and Multi-domain Effectiveness of Guselkumab in Adults with Psoriatic Arthritis: Real-World Data from the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.

INTRODUCTION: The aim of this work is to evaluate treatment persistence and clinical outcomes after 6 months of on-label guselkumab use in patients with rheumatologist-diagnosed active psoriatic arthritis (PsA) enrolled in the CorEvitas PsA/Spondyloarthritis Registry. METHODS: Participants with PsA who initiated and persisted with on-label guselkumab use post-Food and Drug Administration (FDA) approval for active PsA (7/13/2020; subcutaneous 100 mg at weeks 0, 4, and every 8 weeks) at their 6-month follow-up visit (occurring through 3/31/2023) comprised the primary analysis population (On-Label Persisters). Hierarchical, multiplicity-controlled primary and secondary outcomes were mean (95% confidence interval) changes from baseline at 6 months in clinical Disease Activity Index for PsA (cDAPSA; primary), Physician Global Assessment (PGA) of arthritis and psoriasis (visual analog scale [VAS] 0-100), patient-reported pain (VAS 0-100), and percent body surface area with psoriasis (%BSA). Paired t tests determined changes that were statistically significantly different from 0 (α = 0.05). RESULTS: Among 114 patients who initiated on-label guselkumab and had eligible baseline and 6-month visits, 90 (78.9%) had persistent use. Among these On-Label Persisters at baseline, mean duration of PsA symptoms = 13.6 years; mean cDAPSA, PGA, and patient-reported pain = 22.0, 42.3, and 57.0, respectively; 94.4% had a history of psoriasis (mean BSA 7.6%); and 18.9% and 73.3%, respectively, previously received 1 or ≥ 2 biologic/targeted synthetic disease-modifying antirheumatic drugs. The mean change (improvement) in cDAPSA was - 5.4 (- 8.5, - 2.3; p < 0.001) at 6 months. Significant mean improvements in PGA (- 19.0 [- 24.2, - 13.8]), patient-reported pain (- 9.1 [- 14.4, - 3.8]), and %BSA (- 5.1 [- 7.6, - 2.7]) were also observed (all p < 0.001). CONCLUSIONS: In this real-world PsA population, generally characterized by longstanding, treatment-resistant, active disease at baseline, persistent guselkumab use in nearly 80% of patients with on-label use was accompanied by significant improvements in joint and skin symptoms and patient-reported pain at 6 months. These registry data support results from randomized clinical trials demonstrating the efficacy of guselkumab in improving PsA signs and symptoms. TRIAL REGISTRATION: clinicaltrials.gov: NCT02530268.

Course of Impulse Control Disorder Symptoms in Parkinson's Disease: Deep Brain Stimulation Versus Medications.

Background: The effect of surgery on impulse control disorders (ICDs) remains unclear in Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS). Objective: To examine changes in ICD symptoms in PD patients undergoing DBS compared to a medication-only control group. Methods: The study was a 2-center, 12-month, prospective, observational investigation of PD patients undergoing DBS and a control group matched on age, sex, dopamine agonist use, and baseline presence of ICDs. Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) and total levodopa equivalent daily dose (LEDD) were collected at baseline, 3, 6, and 12 months. Linear mixed-effects models assessed changes in mean QUIP-RS score (sum of buying, eating, gambling, and hypersexuality items). Results: The cohort included 54 participants (DBS = 26, controls = 28), mean (SD) age 64.3 (8.1) and PD duration 8.0 (5.2) years. Mean baseline QUIP-RS was higher in the DBS group at baseline (8.6 (10.7) vs. 5.3 (6.9), P = 0.18). However, scores at 12 months follow-up were nearly identical (6.6 (7.3) vs. 6.0 (6.9) P = 0.79). Predictors of change in QUIP-RS score were baseline QUIP-RS score (ß = 0.483, P < 0.001) and time-varying LEDD (ß = 0.003, P = 0.02). Eight patients (four in each group) developed de novo ICD symptoms during follow-up, although none met diagnostic criteria for an impulse control disorder. Conclusions: ICD symptoms (including de novo symptoms) at 12 months follow-up were similar between PD patients undergoing DBS and patients treated with pharmacological therapy only. Monitoring for emergence of ICD symptoms is important in both surgically- and medication-only-treated PD patients.

Are we asking the right questions? A review of assessment of males with eating disorders.

Most of the commonly used eating disorders (ED) assessments were normed and developed for females, and their status among male populations is rarely addressed in the literature. Recently, some male-specific instruments have been developed that may have some utility with this population. This article aims to: (a) briefly outline some special considerations and challenges when assessing ED in male populations; (b) review the utility of some of the most commonly used ED assessments with males; and (c) review some of the measures that have recently been developed to assess male-specific ED-related symptoms, with the hope that a greater understanding of male-specific presentation may be elucidated.

Improvement in disease activity among patients with rheumatoid arthritis who switched from intravenous infliximab to intravenous golimumab in the ACR RISE registry.

Infliximab and golimumab are intravenously (IV) administered tumor necrosis factor inhibitors approved to treat moderate-to-severe rheumatoid arthritis (RA) with concomitant methotrexate. Owing to differences in biologic construct, patients with IV-infliximab treatment failure may benefit from switching to IV-golimumab. Utilizing the ACR's Rheumatology Informatics System for Effectiveness (RISE), a large electronic health records registry based in the USA, we assessed RA disease activity in patients switching from IV-infliximab to IV-golimumab. This retrospective, longitudinal, single-arm study included adults (≥ 18 years) with ≥ 1 RA diagnosis code between 2014 and 2018 and ≥ 1 IV-infliximab prescription within 6 months of a new IV-golimumab order (index date). Longitudinal assessments of disease activity using the Clinical Disease Activity Index (CDAI) were calculated in patients continuing IV-golimumab for 6-9- and 9-12-months post-switch. Paired t-tests evaluated significance of mean improvements during the follow-up periods. Most RA patients with disease activity assessments during the 6-month follow-up (N = 100; mean age: 65.3 years; 81% female; 74% white) demonstrated moderate-to-high disease activity (CDAI: 73% [38/52]) at enrollment. On average, patients showed significant improvement in disease activity within 6-9 months of switching; mean CDAI scores improved from 21.3 to 14.1 (p < 0.0001) and were durable through 9-12 months of treatment. Real-world patients with moderate-to-high disease activity who switched from IV-infliximab to IV-golimumab demonstrated significant and sustained improvements post-switch as measured by the CDAI. Key Points • This study used real-world data from the Rheumatology Informatics System for Effectiveness (RISE) registry to evaluate the efficacy of directly switching from intravenous (IV)-infliximab to IV-golimumab to control rheumatoid arthritis (RA) disease activity. • Most IV-infliximab patients had moderate-to-high disease activity at the time of the switch. • On average, IV-golimumab was effective in improving RA disease activity after switching from IV-infliximab as measured by the Clinical Disease Activity Index. • These data suggest that real-world RA patients with persistent symptoms despite treatment with IV-infliximab may realize improved disease control with a switch to IV-golimumab.

Impact of switching to infliximab biosimilars on treatment patterns among US veterans receiving innovator infliximab.

OBJECTIVE: To compare treatment patterns of United States (US) veterans stable on innovator infliximab (IFX) who switched to an IFX biosimilar (switchers) or remained on innovator IFX (continuers). METHODS: US Veterans Healthcare Administration data (01/2012-12/2019) were used to identify adults with rheumatoid arthritis (RA), psoriatic arthritis (PsA), plaque psoriasis (PsO), ankylosing spondylitis (AS), or Crohn's disease and ulcerative colitis (i.e. inflammatory bowel disease [IBD]), treated with innovator or biosimilar IFX. Index date was the first IFX biosimilar administration for switchers or a random innovator IFX administration for continuers. Patients were required to have ≥5 innovator IFX administrations during the 12 months pre-index (prevalent population). Patients with ≥12 months of observation prior to the first innovator IFX administration were analyzed as the primary population (incident population), and data were assessed from start of innovator IFX. Inverse probability of treatment weighting was used to balance baseline characteristics between cohorts. Treatment patterns were evaluated post-index; continuers were censored before switching to IFX biosimilar. Discontinuation was defined as switching to another biologic (including innovator IFX) or having ≥120 days between 2 consecutive index treatment records. RESULTS: In the incident population, mean [median] duration of follow-up was 737 [796] days among switchers (N = 838) and 479 [337] days among continuers (N = 849). Compared to continuers, switchers were 2.88-times more likely to discontinue index therapy (hazard ratio [HR] = 2.88, p < .001) and 4.99-times more likely to switch to another innovator biologic (HR = 4.99, p < .001). Of 653 switchers switching to another innovator biologic, 594 (91.0%) switched back to innovator IFX. Results were similar among the prevalent population and RA and IBD subgroups. CONCLUSION: Patients switching from innovator to biosimilar IFX were more likely to discontinue treatment and switch to another innovator biologic (notably back to innovator IFX) than those remaining on innovator IFX; however, reasons for discontinuation and switching are unknown.

Treatment Responses in Patients With Psoriatic Arthritis Axial Disease According to Human Leukocyte Antigen-B27 Status: An Analysis From the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.

OBJECTIVE: Axial disease is common and burdensome in patients with psoriatic arthritis (PsA). Human leukocyte antigen-B27 (HLA-B27) is a risk factor for axial PsA; treatment response by HLA-B27 status is inadequately characterized. This study evaluated responses to biologic disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) overall and by HLA-B27 status in patients with PsA axial disease. METHODS: This observational study included participants in the CorEvitas (formerly Corrona) PsA/Spondyloarthritis Registry who initiated bDMARD or tsDMARD treatment at baseline, had a 6-month follow-up visit, fulfilled Classification Criteria for Psoriatic Arthritis, had a baseline Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of ≥4, and had known HLA-B27 status. Disease characteristics at baseline and 6 months were evaluated overall and by HLA-B27 status. Association between HLA-B27 status and treatment response was evaluated using an analysis of covariance model. RESULTS: The analysis included 173 bDMARD or tsDMARD treatment initiations (54 [31.2%] among patients with HLA-B27+ status and 119 [68.8%] among patients with HLA-B27- status). BASDAI total and component scores decreased by ≤0.84 across groups after 6 months of bDMARD or tsDMARD therapy; these changes are not considered clinically meaningful. HLA-B27 status was not statistically significantly associated with changes in axial-related outcomes. CONCLUSION: In patients with PsA axial disease, 6 months of bDMARD or tsDMARD therapy provided only mild improvements in axial-related outcomes, irrespective of HLA-B27 status. This continued high disease activity reflects a critical unmet need for focus on the axial domain of PsA and for additional safe and effective therapies for psoriatic axial disease.

Association of the built environment and neighborhood resources with obesity-related health behaviors in older veterans with hypertension.

OBJECTIVE: To evaluate the association of the built environment and neighborhood resources with exercise, diet, and body mass index (BMI). METHOD: Person-level data were collected from 533 veterans with uncontrolled hypertension. Neighborhood measures were: (a) census-tract level walkability; and (b) healthy food proximity (HFP). Robust or logistic regression (adjusting for age, race, education, comorbidity, and clustered by provider) was used to evaluate associations between neighborhood and exercise duration (hours/week), exercise adherence (% adherent), saturated fat index (0-10), Healthy Eating Index (HEI; 0-100), HEI adherence (≥ 74 score), stage of change (SOC) for exercise and diet (% in action/maintenance), BMI (kg/m²), and obesity (BMI ≥ 30 kg/m²). RESULTS: The adjusted difference in HEI score (standard error [SE]) between the highest and lowest walkability tertiles was 3.67 (1.35), p = .006; the corresponding comparison for the saturated fat index was 1.03 (.50), p = .041 and BMI was -1.12 (.45), p = .013. The adjusted odds ratio (OR; 95% confidence intervals [CI]) between the highest and lowest walkability tertiles for HEI adherence was 2.16 [1.22, 3.82], p = .009 and for action/maintenance for exercise SOC was 1.78 [1.15, 2.76], p = .011. The adjusted difference (SE) between the highest and lowest HFP tertiles for exercise duration was .65 (.31), p = .03. The adjusted OR [95% CI] between the highest and lowest HFP tertiles for exercise adherence was 1.74 [1.08, 2.79], p = .023 and for action/maintenance for exercise SOC was 1.75 [1.10, 2.79], p = .034. CONCLUSIONS: Geographical location is associated with exercise and diet. Environment-tailored health recommendations could promote healthier lifestyles and decrease obesity-related cardiovascular disease. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Clinical Characteristics of Registry Participants with Psoriatic Arthritis Initiating Guselkumab: An Analysis from the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.

BACKGROUND: The monoclonal antibody guselkumab is the first selective inhibitor of the interleukin-23 p19 subunit approved to treat adults with moderate-to-severe plaque psoriasis and active psoriatic arthritis (PsA). Given its recent approval for active PsA, data describing patients with PsA initiating guselkumab outside of clinical trials are limited. OBJECTIVE: This analysis describes characteristics of patients with rheumatologist-diagnosed PsA initiating guselkumab in the US-based, prospective, observational CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry. METHODS: Demographics, lifestyle/disease characteristics, comorbidities, prior treatment, and disease activity were summarized for patients with PsA initiating guselkumab from registry inception through 30 September, 2021. RESULTS: Of 113 patients initiating guselkumab, the majority were female (63%), obese (67%), had psoriasis (89%), and initiated guselkumab as monotherapy (81%). Common comorbidities were hypertension (32%), depression (30%), and diabetes mellitus (26%). Mean tender (6.8) and swollen (2.0) joint counts, clinical Disease Activity Index for PsA score (19.1), and 57% of participants with ≥ 3% body surface area affected by psoriasis indicated moderate disease activity. Axial involvement was identified in 49% of patients. Median patient-reported pain and fatigue visual analog scale scores (0-100) were 60 and 59, respectively. Prior to guselkumab, 76% of patients had received two or more biologic disease-modifying antirheumatic drugs; the last therapy prior to guselkumab was a biologic disease-modifying antirheumatic drug in 81% of patients. CONCLUSIONS: Registry participants with PsA initiating guselkumab had active peripheral joint and skin disease, with substantial pain and fatigue; a considerable proportion had axial involvement. Future studies will evaluate the effectiveness of guselkumab in this population.

Human vs. Machine Learning Based Detection of Facial Weakness Using Video Analysis.

Background: Current EMS stroke screening tools facilitate early detection and triage, but the tools' accuracy and reliability are limited and highly variable. An automated stroke screening tool could improve stroke outcomes by facilitating more accurate prehospital diagnosis and delivery. We hypothesize that a machine learning algorithm using video analysis can detect common signs of stroke. As a proof-of-concept study, we trained a computer algorithm to detect presence and laterality of facial weakness in publically available videos with comparable accuracy, sensitivity, and specificity to paramedics. Methods and Results: We curated videos of people with unilateral facial weakness (n = 93) and with a normal smile (n = 96) from publicly available web-based sources. Three board certified vascular neurologists categorized the videos according to the presence or absence of weakness and laterality. Three paramedics independently analyzed each video with a mean accuracy, sensitivity and specificity of 92.6% [95% CI 90.1-94.7%], 87.8% [95% CI 83.9-91.7%] and 99.3% [95% CI 98.2-100%]. Using a 5-fold cross validation scheme, we trained a computer vision algorithm to analyze the same videos producing an accuracy, sensitivity and specificity of 88.9% [95% CI 83.5-93%], 90.3% [95% CI 82.4-95.5%] and 87.5 [95% CI 79.2-93.4%]. Conclusions: These preliminary results suggest that a machine learning algorithm using computer vision analysis can detect unilateral facial weakness in pre-recorded videos with an accuracy and sensitivity comparable to trained paramedics. Further research is warranted to pursue the concept of augmented facial weakness detection and external validation of this algorithm in independent data sets and prospective patient encounters.

Treatment Persistence and Adherence Among Patients With Psoriatic Arthritis Who Initiated Targeted Immune Modulators in the US: A Retrospective Cohort Study.

INTRODUCTION: This study compared treatment persistence and adherence among psoriatic arthritis (PsA) patients in the US who initiated an interleukin-12/23 inhibitor (IL-12/23i) versus those who initiated tumor necrosis factor inhibitors (TNFis), targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), or interleukin-17 inhibitors (IL-17is). METHODS: Adults diagnosed with PsA with ≥ 1 claim for a targeted immune modulator were selected from the IBM MarketScan® Commercial and Medicare Supplemental databases (October 1, 2013-October 31, 2018). The date of the first claim was the index date. Patients had continuous health plan enrollment for ≥ 12 months pre-index and ≥ 12-month post-index period. Pairwise propensity score matching with nearest-neighbor technique was performed. Persistence duration, discontinuation rate, and the proportion of days covered (PDC) were evaluated in biologic/tsDMARD naïve patients who initiated TNFis, IL-17is, tsDMARDs, or IL-12/23i (reference group). RESULTS: There were 238 matched patient pairs for TNFi versus IL-12/23i, 238 pairs for tsDMARD versus IL-12/23i, and 189 pairs for IL-17is versus IL-12/23i. Duration of persistence was longer for the IL-12/23i cohort than for the TNFi (269 vs. 215 days, p < 0.001) or tsDMARD (269 vs. 213 days, p < 0.001) cohorts, but comparable between the IL-12/23i and IL-17i cohorts (267 vs. 246 days, p = 0.199). Fewer patients in the IL-12/23i cohort discontinued their index medication than in the TNFi (53.4% vs. 73.9%, p < 0.001) or tsDMARD (53.4% vs. 71.8%, p < 0.001) cohorts, but no significant difference was observed between the IL-12/23i and IL-17i cohorts (52.9% vs. 58.2%, p = 0.288). During the 12-month follow-up, adherence (i.e., PDC) was higher among those who initiated an IL-12/23i than among those who initiated TNFis (0.64 vs. 0.56, p = 0.004) or tsDMARDs (0.64 vs. 0.58, p = 0.027), but similar to those who initiated IL-17is (0.64 vs. 0.65, p = 0.589). CONCLUSION: In this real-world study of PsA therapies with differing mechanisms of action, the IL-12/23i demonstrated longer persistence and higher adherence than either TNFis or tsDMARDs, and comparability to IL-17is.

Basement membrane degeneration is common in lichenoid mucositis with dysplasia.

Background: Two subtypes of lichenoid mucositis (LM) with oral epithelial dysplasia have been proposed, with differing risks of malignant transformation. However, no research has been done to authenticate this hypothesis. The study objective was to determine whether there are 2 subcategories within this entity, one with primary lichenoid and secondary dysplastic features (L1D2), and the other with primary dysplastic and secondary lichenoid features (D1L2), and to compare the proportion of malignant progression in these groups. Methods: Patients with a diagnosis of lichenoid mucositis with low-grade (mild/moderate) oral epithelial dysplasia, no history of head and neck cancer, and who had at least 5 years of follow-up were eligible to participate in this nested case-control study. Cases (n = 10) were defined as lesions that progressed to severe dysplasia, carcinoma in situ or squamous cell carcinoma; controls (n = 32) were defined as those that did not progress. Immunohistochemistry was performed to assess for basement membrane (BM) degeneration using collagen IV-an integral BM protein. Results: Lesions that progressed to cancer exhibited a similar proportion of BM degeneration at baseline (70%) compared to non-progressors (78%), with no statistically significant difference between groups (p = 0.69). Conclusion: BM degeneration is frequently seen in LM with dysplasia and alone does not appear to be a predictor of malignant progression in lesions with both lichenoid and low-grade dysplastic features. Dysplasia should not be discounted in the presence of LM. Lesions that display any degree of dysplasia warrant clinical follow-up and continued monitoring.

Contexte: Deux sous-types de mucosites lichénoïdes (ML) avec dysplasie épithéliale buccale ont été proposés, avec des risques différents de transformation maligne. Cependant, aucune recherche n'a été faite pour valider cette hypothèse. L'objectif de l'étude était de déterminer s'il y a 2 sous-catégories au sein de cette entité, la première avec des caractéristiques lichénoïdes primaires et dysplasiques secondaires (L1D2), et l'autre avec des caractéristiques dysplasiques primaires et lichénoïdes secondaires (D1L2), et de comparer la proportion de progression maligne dans ces groupes. Méthodologie: Les patients ayant reçu un diagnostic de mucosite lichénoïde avec une dysplasie épithéliale buccale de faible intensité (faible/modérée), qui n'avaient aucun antécédent de cancer de la tête et du cou, et qui avaient eu au moins 5 ans de suivi, étaient admissible à participer à cette étude de cas-témoins emboîtés. Les cas (n = 10) étaient définis comme des lésions qui ont progressé à la dysplasie sévère, un carcinome in situ ou un carcinome squameux; les contrôles (n = 32) étaient définis comme ceux qui n'ont pas progressé. L'immunohistochimie a été effectuée pour évaluer s'il y avait eu une dégénérescence de la membrane basale (MB) en utilisant du collagène IV, une protéine MB intrinsèque. Résultats: Les lésions qui ont évolué en cancer ont présenté une proportion semblable de dégénérescence de MB au début (70 %) par rapport aux non-progresseurs (78 %), et aucune différence statistiquement significative entre les groupes (p = 0,69). Conclusion: La dégénérescence des MB est fréquemment constatée dans les ML avec dysplasie et seule, ne paraît pas être une variable explicative de l'évolution maligne dans les lésions à caractéristiques à la fois lichénoïdes et dysplasiques de faible intensité. Il ne faut pas sous-estimer la dysplasie en présence de ML. Les lésions qui présentent de la dysplasie, peu importe son étendue, exigent un suivi clinique et une surveillance continue.

Intraoral Photography Recommendations for Remote Risk Assessment and Monitoring of Oral Mucosal Lesions.

Oral cancer is a global health issue with substantial morbidity and a high mortality rate mainly because of late-stage diagnosis. Cancerous lesions are often preceded by potentially malignant lesions that may be detected during routine dental examinations. Not only is the oral cavity easily accessible for screening, but the clinical risk factors of the disease are also known. However, patients may not always be able to access screening services or receive follow-up for diagnosed lesions. In these circumstances, intraoral photos are crucial for timely triage, risk assessment, and monitoring of oral lesions. Further, photos form an integral part of a patient's records, facilitate patient education and communication between health care providers, and provide important information during the referral process. To ensure that intraoral photos are of good quality and standardised there is a need to establish recommendations regarding intraoral photography in oral mucosal screening. This article recommends methods to help health professionals and patients obtain interpretable intraoral photographs. Suggestions to achieve ideal lighting, mirror placement, camera angle, and retraction have been discussed. These recommendations are adaptable to easily available smartphone or point-and-shoot cameras and may be further used to develop future teledentistry platforms.