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Introduction: The impact of upadacitinib on rheumatoid arthritis (RA) symptoms was evaluated during the first 12 weeks of treatment via patient-reported outcomes (PROs) using a mobile health application (app)., Methods: Participating rheumatologists from the CorEvitas RA Registry (prospective, observational cohort) recruited patients with RA initiating upadacitinib treatment. A modified version of the ArthritisPower® app was used to collect PROs, including the Routine Assessment of Patient Index Data 3 (RAPID3), duration of morning joint stiffness, and the Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue 7a Short Form at baseline and weeks 1-4, 8, and 12. RAPID3 responses over time were assessed using Kaplan-Meier estimation to determine the proportion of patients achieving disease activity improvement and minimal clinically important difference (MCID). Results were analyzed for all patients initiating upadacitinib and a subsample of TNF inhibitor (TNFi)-experienced patients with moderate to severe disease at baseline., Results: A total of 103 patients with RA initiating upadacitinib (62.1% TNFi-experienced) were included. At week 12, 53 patients (51.4%) completed the study and provided PRO data via the app. Among all patients, improvements in RAPID3, pain, morning stiffness, and fatigue were observed at week 1 and were maintained or further improved through week 12. At week 12, 37.5% of patients achieved RAPID3 low disease activity. Starting at week 1, improvements in RAPID3 disease activity category (19.4% of patients) and achievement of MCID (16.3%) were reported, with nearly 50% of patients achieving these outcomes by week 4 (RAPID3 category: 48.8%; MCID: 49.2%) and 60% by week 12 (RAPID3 category: 59.6%; MCID: 59.8%). TNFi-experienced patients generally reported similar outcomes. Patient-reported medication convenience and compliance were generally high., Conclusions: In this real-world cohort of patients with RA, treatment with upadacitinib was associated with early and significant improvement in RAPID3, pain, morning stiffness, and fatigue regardless of prior TNFi experience. Clinically meaningful improvement in RAPID3 patient-reported disease activity was observed as early as week 1, with continued improvement reported through week 12., (© 2023. The Author(s).)

Objective: To determine the presence of axial symptoms in patients with psoriatic arthritis (PsA) and examine differences between those with or without a diagnosis of axial PsA (axPsA)., Methods: Patients with PsA at their Corevitas' (formerly Corrona) Psoriatic Arthritis/Spondyloarthritis Registry enrollment visit were stratified into 4 mutually exclusive groups based on axial manifestations: physician-diagnosed axPsA only (Dx + Sx - ), patient-reported elevated spine symptoms only (Dx - Sx + ; defined as Bath Ankylosing Spondylitis Disease Activity Index ≥ 4 and spine pain visual analog scale ≥ 40), physician-diagnosed and patient-reported manifestations (Dx + Sx + ), and no axial manifestations (Dx - Sx - ). Patient characteristics, disease activity, and patient-reported outcomes (PROs) at enrollment in each axial manifestation group were compared with the Dx - Sx - group. Associations of patient characteristics with the odds of having axial manifestations were estimated using multinomial logistic regression (reference: Dx - Sx - )., Results: Of 3393 patients included, 226 (6.7%) had Dx + Sx - , 698 (20.6%) had Dx - Sx + , 165 (4.9%) had Dx + Sx + , and 2304 (67.9%) had Dx - Sx - . Patients with Dx - Sx + or Dx + Sx + were more frequently women and had a history of depression and fibromyalgia (FM) vs patients who had Dx - Sx - . Patients with Dx + Sx - or Dx + Sx + were more frequently HLA-B27 positive than those with Dx - Sx - . FM was significantly associated with increased odds of Dx + Sx - or Dx + Sx + . Disease activity and PROs were worse in patients with Dx - Sx + or Dx + Sx + than in those with Dx - Sx - ., Conclusion: Patients who had self-reported elevated spine symptoms, with or without physician-diagnosed axPsA, had worse quality of life and higher disease activity overall than patients without axial manifestations, suggesting an unmet need in this patient population., (Copyright © 2022 by the Journal of Rheumatology.)

Background: Longer-term feeding studies suggest that a low-carbohydrate diet increases energy expenditure, consistent with the carbohydrate-insulin model of obesity. However, the validity of methodology utilized in these studies, involving doubly labeled water (DLW), has been questioned., Objective: The aim of this study was to determine whether dietary energy requirement for weight-loss maintenance is higher on a low- compared with high-carbohydrate diet., Methods: The study reports secondary outcomes from a feeding study in which the primary outcome was total energy expenditure (TEE). After attaining a mean Run-in weight loss of 10.5%, 164 adults (BMI ≥25 kg/m2; 70.1% women) were randomly assigned to Low-Carbohydrate (percentage of total energy from carbohydrate, fat, protein: 20/60/20), Moderate-Carbohydrate (40/40/20), or High-Carbohydrate (60/20/20) Test diets for 20 wk. Calorie content was adjusted to maintain individual body weight within ± 2 kg of the postweight-loss value. In analyses by intention-to-treat (ITT, completers, n = 148) and per protocol (PP, completers also achieving weight-loss maintenance, n = 110), we compared the estimated energy requirement (EER) from 10 to 20 wk of the Test diets using ANCOVA., Results: Mean EER was higher in the Low- versus High-Carbohydrate group in models of varying covariate structure involving ITT [ranging from 181 (95% CI: 8-353) to 246 (64-427) kcal/d; P ≤0.04] and PP [ranging from 245 (43-446) to 323 (122-525) kcal/d; P ≤0.02]. This difference remained significant in sensitivity analyses accounting for change in adiposity and possible nonadherence., Conclusions: Energy requirement was higher on a low- versus high-carbohydrate diet during weight-loss maintenance in adults, commensurate with TEE. These data are consistent with the carbohydrate-insulin model and lend qualified support for the validity of the DLW method with diets varying in macronutrient composition. This trial was registered at clinicaltrials.gov as NCT02068885., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Ptpn6 is a cytoplasmic phosphatase that functions to prevent autoimmune and interleukin-1 (IL-1) receptor-dependent, caspase-1-independent inflammatory disease. Conditional deletion of Ptpn6 in neutrophils (Ptpn6 ∆PMN ) is sufficient to initiate IL-1 receptor-dependent cutaneous inflammatory disease, but the source of IL-1 and the mechanisms behind IL-1 release remain unclear. Here, we investigate the mechanisms controlling IL-1α/β release from neutrophils by inhibiting caspase-8-dependent apoptosis and Ripk1-Ripk3-Mlkl-regulated necroptosis. Loss of Ripk1 accelerated disease onset, whereas combined deletion of caspase-8 and either Ripk3 or Mlkl strongly protected Ptpn6 ∆PMN mice. Ptpn6 ∆PMN neutrophils displayed increased p38 mitogen-activated protein kinase-dependent Ripk1-independent IL-1 and tumor necrosis factor production, and were prone to cell death. Together, these data emphasize dual functions for Ptpn6 in the negative regulation of p38 mitogen-activated protein kinase activation to control tumor necrosis factor and IL-1α/β expression, and in maintaining Ripk1 function to prevent caspase-8- and Ripk3-Mlkl-dependent cell death and concomitant IL-1α/β release.

Navigating health care systems can be a challenge for families. A retrospective descriptive cohort analysis was conducted assessing referrals to patient navigators (PNs) in one urban academic pediatric primary care practice. PNs tracked referral processes and a subset of PN referrals was assessed for markers of successful referrals. The most common reasons for referral were assistance overcoming barriers to care (46%), developmental concerns (38%), and adherence/care coordination concerns (14%). Significant predictors of referral were younger age, medical complexity, public insurance, male sex, and higher rates of no-show to visits in primary or subspecialist care. The majority of referrals were resolved. The referrals for process-oriented needs were significantly more successful than those for other concerns. PNs were more effective for discrete process tasks than for those that required behavior change by patients or families. Future directions include analysis of cost effectiveness of the PN program and analysis of parent and primary care provider experience.

A research team from Boston Children's Hospital and Harvard Medical School conducted a community-based feeding study in collaboration with Framingham State University (FSU) and Sodexo, the food service contractor at FSU. The study was a randomized controlled trial, implemented on the FSU campus. For the final year of the study, a satellite feeding site was established at Assabet Valley Regional Technical High School. The purpose of the study was to assess the biological effects of different macronutrient diets. An academia-industry partnership was developed to overcome common challenges associated with hospital-based feeding studies. Benefits included the following: a study site outside of Boston (reducing inconvenience for participants), access to a large commercial kitchen and study-specific kiosk (promoting efficiency), collaboration with Sodexo chefs (ensuring palatability of meals), and opportunity to procure food from contracted vendors. The research (academia) and food service (industry) teams worked together to design, plan, and execute intervention protocols using an integrated approach. During execution, the research team was primarily responsible for overseeing treatment fidelity, whereas the food service team provided culinary expertise, with a strong focus on hospitality and food quality. The study was conducted in 3 cohorts between August 2014 and May 2017. Participants received all of their food for ∼30 wk, totaling >160,000 meals. For all 3 cohorts combined, 234 participants provided informed consent, 229 started a standard run-in weight-loss diet, 164 lost a mean ± SD 12% ± 2% of baseline body weight and were randomly assigned to different macronutrient diets for weight-loss maintenance, and 148 completed the study. During the final and largest cohort, as many as 114 participants received daily meals concurrently. The daily cost per participant for preparation and service of weighed meals and snacks was ∼$65. This academia-industry partnership provides a model for controlled feeding protocols in nutrition research, potentially with enhanced cost-effectiveness, practicality, and generalizability. This trial was registered at http://www.clinicaltrials.gov as NCT02068885.

Objective: Transition readiness assessment has focused attention on adolescent knowledge and skills, but data-driven benchmarks have not been established., Methods: Patients with inflammatory bowel disease (IBD), ages 25 to 50 years, attending an outpatient gastroenterology clinic, were recruited to complete a voluntary, confidential survey asking patients to recall medications and potential side effects, and to rate their degree of independence performing health maintenance tasks., Results: The 141 respondents (48% response rate) had mean age of 36 years with median disease duration of 11 years. They were 60% female, 54% had Crohn disease, and 23% were diagnosed before age 18. Nearly all patients were fully independent answering doctor's questions during the visit (93%) and scheduling office visits (92%). Excluding pharmacy pick up, full independence seen in only 57%, whereas 16% significantly delegated tasks. No differences by sex, disease type, medication class, age at disease onset, or disease duration were found across levels of self-management. Almost all (97%) respondents could recall medication name, whereas fewer were able to recall dose (63%) or frequency (65%). Side effect knowledge was poor; among 81 patients on a biologic or immunomodulator, only 17 (21%) cited cancer and 22 (27%) cited infection., Conclusions: Adolescent IBD transition programs now have empirical data from the present study about adult benchmarks for independence in self-management skills. Further research can establish which skills correlate with medication adherence and active collaboration with the medical team. The present study also exposes important gaps in medication risk knowledge and may allow improved patient education for subgroups of adult patients with IBD.