Improvement in Patient-Reported Outcomes in Patients with Psoriatic Arthritis Treated with Upadacitinib Versus Placebo or Adalimumab: Results from SELECT-PsA 1

Introduction: The aim of this work is to assess the effect of upadacitinib versus adalimumab and placebo on patient-reported outcomes (PROs) in psoriatic arthritis (PsA) patients with inadequate responses to ≥ 1 non-biologic disease-modifying anti-rheumatic drugs (non-bDMARD-IR) in SELECT PsA-1. Methods: In this placebo- and active comparator, phase 3 randomized, controlled trial, patients received daily upadacitinib 15 or 30 mg, placebo, or adalimumab 40 mg every other week through 56 weeks. At week 24, placebo-assigned patients were rerandomized to upadacitinib 15 or 30 mg. PROs included Patient Global Assessment of Disease Activity (PtGA), pain, Health Assessment Questionnaire Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Short Form 36 Health Survey (SF-36), EQ-5D-5L index score, Bath Ankylosing Spondylitis Disease Activity Index, morning stiffness, Self-Assessment of Psoriasis Symptoms, and Work Productivity and Activity Impairment. Mean changes from baseline in PROs, improvements ≥ minimum clinically important differences (MCID), scores ≥ normative values, and sustained clinically meaningful responses were compared between treatment groups. Results: At weeks 12 and 24, upadacitinib treatment resulted in improvements from baseline versus placebo across all PROs as well as improvements versus adalimumab in HAQ-DI and SF-36 Physical Component Summary score (nominal p < 0.05). Improvements in PtGA, pain, and HAQ-DI were reported as early as week 2. At week 12, significantly (nominal p < 0.05) more upadacitinib- versus placebo-treated patients reported improvements ≥ MCID across all PROs including seven SF-36 domains. The proportions of upadacitinib-treated patients reporting clinically meaningful improvements at week 12 were similar to or greater than with adalimumab and sustained through week 56. Significantly (nominal p < 0.05) more upadacitinib-treated (both doses) patients reported scores ≥ normative values at week 12 versus placebo, and scores were generally similar to or greater than adalimumab. Conclusions: Upadacitinib treatment provides rapid, sustained, and clinically meaningful improvements in PROs in non-bDMARD-IR patients with PsA. SELECT-PsA 1 ClinicalTrials.gov number, NCT03104400

Upadacitinib for psoriatic arthritis refractory to biologics : SELECT-PsA 2

Background: Upadacitinib is a Janus kinase inhibitor under evaluation for the treatment of psoriatic arthritis (PsA). We evaluated upadacitinib in patients with PsA and prior inadequate response or intolerance to at least one biologic disease-modifying antirheumatic drug (DMARD). Methods: In this 24-week randomised, placebo-controlled, double-blind, phase 3 trial, 642 patients were randomised (2:2:1:1) to once per day upadacitinib 15 mg or 30 mg, placebo followed by upadacitinib 15 mg or placebo followed by upadacitinib 30 mg at week 24. The primary endpoint was the proportion of patients achieving American College of Rheumatology (ACR) 20 response at week 12. Achievement of minimal disease activity (MDA) was assessed at week 24. Treatment-emergent adverse events are reported for all patients who received at least one dose of trial drug. Results: At week 12, significantly more patients receiving upadacitinib 15 mg and 30 mg versus placebo achieved ACR20 (56.9% and 63.8% vs 24.1%; p<0.001 for both comparisons). At week 24, MDA was achieved by more upadacitinib 15 mg-treated (25.1%) and 30 mg-treated patients (28.9%) versus placebo (2.8%; p<0.001 for both comparisons). Generally, the rates of treatment-emergent adverse events were similar with placebo and upadacitinib 15 mg and higher with upadacitinib 30 mg at week 24. Rates of serious infections were 0.5%, 0.5% and 2.8% with placebo, upadacitinib 15 mg and upadacitinib 30 mg, respectively. Conclusion: In this trial of patients with active PsA who had inadequate response or intolerance to at least one biologic DMARD, upadacitinib 15 mg and 30 mg was more effective than placebo over 24 weeks in improving signs and symptoms of PsA

Differences in Physiological Responses to Cardiopulmonary Exercise Testing in Adults With and Without Type 1 Diabetes: A Pooled Analysis

OBJECTIVE To investigate physiological responses to cardiopulmonary exercise (CPX) testing in adults with type 1 diabetes compared with age-, sex-, and BMI-matched control participants without type 1 diabetes.RESEARCH DESIGN AND METHODS We compared results from CPX tests on a cycle ergometer in individuals with type 1 diabetes and control participants without type 1 diabetes. Parameters were peak and threshold variables of VO2, heart rate, and power output. Differences between groups were investigated through restricted maximum likelihood modeling and post hoc tests. Differences between groups were explained by stepwise linear regressions (P < 0.05).RESULTS Among 303 individuals with type 1 diabetes (age 33 [interquartile range 22; 43] years, 93 females, BMI 23.6 [22; 26] kg/m2, HbA1c 6.9% [6.2; 7.7%] [52 (44; 61) mmol/mol]), VO2peak (32.55 [26.49; 38.72] vs. 42.67 ± 10.44 mL/kg/min), peak heart rate (179 [170; 187] vs. 184 [175; 191] beats/min), and peak power (216 [171; 253] vs. 245 [200; 300] W) were lower compared with 308 control participants without type 1 diabetes (all P < 0.001). Individuals with type 1 diabetes displayed an impaired degree and direction of the heart rate-to-performance curve compared with control participants without type 1 diabetes (0.07 [−0.75; 1.09] vs. 0.66 [−0.28; 1.45]; P < 0.001). None of the exercise physiological responses were associated with HbA1c in individuals with type 1 diabetes.CONCLUSIONS Individuals with type 1 diabetes show altered responses to CPX testing, which cannot be explained by HbA1c. Intriguingly, the participants in our cohort were people with recent-onset type 1 diabetes; heart rate dynamics were altered during CPX testing

Study of Trends and Outcomes of Prescription Medications Continued During Hospice Care (STOP Med)

Hospice was founded with the primary goal of eliminating aggressive treatment measures and providing holistic, end of life palliative care aimed at relieving pain and symptoms and maximizing quality of life. This includes the discontinuation of limited benefit medications (LBMs) which may no longer provide a patient benefit in the context of limited life expectancy. The continued use of LBMs in the hospice population was poorly characterized in the literature, and evidence was needed to inform providers and policy makers regarding the scope of suboptimal medication use in this vulnerable patient group. This dissertation aimed to broadly characterize LBM use and continuation and identify factors associated with LBM continuation after admission among patients admitted to hospice for cancer and non-cancer causes. Our research aims were accomplished via a series of retrospective cross-sectional and cohort studies in the Medicare hospice population using patient-level administrative claims data from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database between 2007 and 2013. LBMs for the purposes of this research consisted of anti-hyperlipidemics, antihypertensives, oral antidiabetics, antiplatelets, anti-dementia and anti-osteoporotic medications, and proton pump inhibitors, with medication use measured via Medicare Part D dispensing claims. We found that the prevalence of LBM use after hospice admission was high, differed by primary hospice admission diagnosis and LBM class, and was relatively stable among patient cohorts defined by hospice admission year. After hospice enrollment, approximately 30% of patients continued at least one LBM that had been used prior to hospice admission. Anti-dementia medications were the most frequently continued LBM class while anti-osteoporotic medications were continued least often. In adjusted analysis, the likelihood of continuing at least one LBM after hospice admission was significantly greater in older patients, patients admitted to hospice in a nursing or assisted-living facility (compared to home hospice), and patients with longer hospice stays. Patients experiencing a care transition from a hospice to a non-hospice setting after hospice admission, particularly those experiencing hospitalizations, were also at an increased risk of continuing LBMs. Despite hospice care principles, use and continuation of LBMs in the hospice population is common. This work provides critical evidence on the scope of problematic medication use at the end of life and will ideally be used to promote the development of tailored medication management strategies that minimize burden without impacting quality of life during the patient’s final weeks and months. Until then, a more careful review of patients’ drug regimens at the time of hospice enrollment is warranted, including thoughtful consideration of the need to continue each medication in the context of its risks, benefits and the patient’s preferences and care goals

mPer1 and mPer2 mutant mice show regular spatial and contextual learning in standardized tests for hippocampus-dependent learning

Learning and memory, like most physiological processes, seem to be under the control of circadian rhythm. The recently cloned mPer1 and mPer2 genes play an important role in the regulation of the circadian rhythm. In this study, we tested mPer1 and mPer2 mutant mice in two different learning and memory paradigms, a water-maze place navigation task and contextual fear conditioning. In both learning tests, the hippocampus is critically involved. None of these learning types were affected by the mutations, suggesting that mPer1 and mPer2 do not play a major role in the regulation of hippocampus- dependent learning and memory

Revisiting nutritional support for allogeneic hematologic stem cell transplantation-a systematic review.

In 2009, the American Society of Parenteral and Enteral Nutrition and its European counterpart (Euopean Society for Parenteral and Enteral Nutrition) published guidelines regarding nutritional support of patients with hematologic stem cell transplantation. Our aim was to do an up-to-date literature review regarding benefit of nutritional interventions and treatment recommendations. We searched MEDLINE, EMBASE and Cochrane Library for interventional and observational clinical studies. We extracted data based on a predefined case report form and assessed bias. Out of 459 potential abstracts, 13 studies of mostly moderate quality with a total of 18 167 patients were included. Two very large trials reported negative associations of malnutrition and survival, transplant-related mortality and relapse risk. Some trials found enteral nutrition (EN) to be as effective as parenteral nutrition (PN) with lower complication rates. In addition, EN was associated with better survival, less acute GvHD and faster neutrophil recovery. A neutropenic diet was not superior regarding overall survival, but in contrast resulted in higher infection risk. Current moderate quality studies show negative associations of malnutrition and clinical outcomes, with EN being superior to PN. There was no benefit of neutropenic diets. Large, randomized controlled studies are needed to better understand optimal nutritional support in this patient population