VISUAL FLOW DOES NOT ALTER MUSCLE ACTIVITY DURING TREADMILL WALKING OR RUNNING

The current study examined the effect of visual flow (patterns of visual movement of surroundings) on muscle activity during treadmill walking and running. Participants (n=14 walked (1 -39 m-s4) and ran (2.78 msl) in visual flow and control conditions. Activity of the vastus medalis (VM), biceps fernoris (BF), gluteus maximus (GM ), gastrocnemius (GA), tibialis anterior (TA), erector spinae (ES), mtus abdominis (RA), and C4 paraspinal (C4) were assessed via electromyography (EMG) during each condition. Repeated Measures ANOVA revealed EMG differences (p < 0.05) between walking and running for RA, VM, GM, and BF. There were no differences in speeds for the other muscles, or across the visual conditions for any of the muscles. Visual flow does not alter muscle activity during walking or running

Long-term, Real-world Safety of Adalimumab in Rheumatoid Arthritis: Analysis of a Prospective US-Based Registry

OBJECTIVE: To assess long-term safety in a US cohort of rheumatoid arthritis (RA) patients treated with adalimumab in real-world clinical care settings. METHODS: This observational study analyzed the long-term incidence of safety outcomes among RA patients initiating adalimumab using data from the Corrona RA registry. Patients were adults ( \u3e /=18 years) who initiated adalimumab treatment between January 2008 and June 2017, and who had at least 1 follow-up visit. RESULTS: In total, 2798 adalimumab initiators were available for analysis, with a mean age of 54.5 years, 77% female, and mean duration of disease of 8.3 years. Nearly half (48%) were biologic naive, and 9% were using prednisone \u3e /=10 mg at adalimumab initiation. The incidence rates per 100 person-years for serious infections, congestive heart failure requiring hospitalization, malignancy (excluding nonmelanoma skin cancer), and all-cause mortality were 1.86, 0.15, 0.64, and 0.33, respectively. The incidence of serious infections was higher in the first year of therapy (3.44 [95% confidence interval: 2.45-4.84]) than subsequent years, while other measured AEs did not vary substantially by duration of exposure. The median time to adalimumab discontinuation was 11 months, while the median time to first serious infection among those experiencing a serious infection event was 12 months. CONCLUSION: Analysis of long-term data from this prospective real-world registry demonstrated a safety profile consistent with previous studies in patients with RA. This analysis did not identify any new safety signals associated with adalimumab treatment and provides valuable guidance for physicians prescribing adalimumab for extended periods of time

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&nbsp;mg, placebo, or adalimumab 40&nbsp;mg every other week through 56&nbsp;weeks. At week 24, placebo-assigned patients were rerandomized to upadacitinib 15 or 30&nbsp;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 &lt; 0.05). Improvements in PtGA, pain, and HAQ-DI were reported as early as week 2. At week 12, significantly (nominal p &lt; 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 &lt; 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

Machine learning for non‐invasive sensing of hypoglycaemia while driving in people with diabetes

Aim: To develop and evaluate the concept of a non-invasive machine learning (ML) approach for detecting hypoglycaemia based exclusively on combined driving (CAN) and eye tracking (ET) data. Materials and Methods: We first developed and tested our ML approach in pronounced hypoglycaemia, and then we applied it to mild hypoglycaemia to evaluate its early warning potential. For this, we conducted two consecutive, interventional studies in individuals with type 1 diabetes. In study 1 (n = 18), we collected CAN and ET data in a driving simulator during euglycaemia and pronounced ypoglycaemia (blood glucose [BG] 2.0-2.5 mmol L-1). In study 2 (n = 9), we collected CAN and ET data in the same simulator but in euglycaemia and mild hypoglycaemia (BG 3.0-3.5 mmol L-1). Results: Here, we show that our ML approach detects pronounced and mild hypoglycaemia with high accuracy (area under the receiver operating characteristics curve 0.88 ± 0.10 and 0.83 ± 0.11, respectively). Conclusions: Our findings suggest that an ML approach based on CAN and ET data, exclusively, enables detection of hypoglycaemia while driving. This provides a promising concept for alternative and non-invasive detection of hypoglycaemia

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

Association of Nutritional Parameters with Clinical Outcomes in Patients with Acute Myeloid Leukemia Undergoing Haematopoietic Stem Cell Transplantation.

INTRODUCTION In acute myeloid leukemia (AML) patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT), there is uncertainty about the extent of influence nutritional parameters have on clinical outcomes. In this study, we investigated the association between initial body mass index (BMI) and weight loss during HSCT on clinical outcomes in a well-characterised cohort of AML patients. METHODS We analysed data of the Basel stem-cell transplantation registry ('KMT Kohorte') including all patients with AML undergoing first allogeneic HSCT from January 2003 to January 2014. We used multivariable regression models adjusted for prognostic indicators (European Group for Blood and Marrow Transplantation risk score and cytogenetics). RESULTS Mortality in the 156 AML patients (46% female, mean age 46 years) over the 10 years of follow-up was 57%. Compared to patients with a baseline BMI (kg/m2) of 20-25, a low BMI 7 vs. <2%) was associated with higher risk for bacterial infections (52 vs. 28%, OR 2.8, 95% CI 0.96-8.18, p = 0.059) and fungal infections (48 vs. 23%, OR 3.37, 95% CI 1.11-10.19, p = 0.032), and longer hospital stays (64 vs. 38 days, adjusted mean difference 25.6 days (15.7-35.5), p < 0.001). CONCLUSION In patients with AML, low initial BMI and more pronounced weight loss during HSCT are strong prognostic indicators associated with lower survival and worse disease outcomes. Intervention research is needed to investigate whether nutritional therapy can reverse these associations

The effect of a single 2h bout of aerobic exercise on ectopic lipids in skeletal muscle, liver and the myocardium

Aims/hypothesis: Ectopic lipids are fuel stores in non-adipose tissues (skeletal muscle [intramyocellular lipids; IMCL], liver [intrahepatocellular lipids; IHCL] and heart [intracardiomyocellular lipids; ICCL]). IMCL can be depleted by physical activity. Preliminary data suggest that aerobic exercise increases IHCL. Data on exercise-induced changes on ICCL is scarce. Increased IMCL and IHCL have been related to insulin resistance in skeletal muscles and liver, whereas this has not been documented in the heart. The aim of this study was to assess the acute effect of aerobic exercise on the flexibility of IMCL, IHCL and ICCL in insulin-sensitive participants in relation to fat availability, insulin sensitivity and exercise capacity. Methods: Healthy physically active men were included. V ⋅ O 2 max $$\overset{\cdot }{V}{\mathrm{O}}_{2 \max }$$ was assessed by spiroergometry and insulin sensitivity was calculated using the HOMA index. Visceral and subcutaneous fat were separately quantified by MRI. Following a standardised dietary fat load over 3days, IMCL, IHCL and ICCL were measured using MR spectroscopy before and after a 2h exercise session at 50-60% of V ⋅ O 2 max $$\overset{\cdot }{V}{\mathrm{O}}_{2 \max }$$ . Metabolites were measured during exercise. Results: Ten men (age 28.9 ± 6.4years, mean ± SD; V ⋅ O 2 max $$\overset{\cdot }{V}{\mathrm{O}}_{2 \max }$$ 56.3 ± 6.4mlkg−1min−1; BMI 22.75 ± 1.4kg/m2) were recruited. A 2h exercise session resulted in a significant decrease in IMCL (−17 ± 22%, p = 0.008) and ICCL (−17 ± 14%, p = 0.002) and increase in IHCL (42 ± 29%, p = 0.004). No significant correlations were found between the relative changes in ectopic lipids, fat availability, insulin sensitivity, exercise capacity or changes of metabolites during exercise. Conclusions/interpretation: In this group, physical exercise decreased ICCL and IMCL but increased IHCL. Fat availability, insulin sensitivity, exercise capacity and metabolites during exercise are not the only factors affecting ectopic lipids during exercise

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