Fatigue is independently associated with disease activity assessed using the Physician Global Assessment but not the SLEDAI in patients with systemic lupus erythematosus

Objectives To analyse whether reported fatigue, one of the most challenging manifestations of systemic lupus erythematosus (SLE), may bias the assessment of disease activity in SLE according to the Physician Global Assessment (PGA). Methods Patients from the Lupus BioBank of the upper Rhein database, a cross-sectional multicentre collection of detailed clinical and biological data from patients with SLE, were included. Patients had to fulfil the 1997 American College of Rheumatology criteria for SLE and the PGA (0-3 scale) at the time of inclusion had to be available. Fatigue was assessed according to the Fatigue Scale for Motor and Cognitive Functions. Univariate and multivariate regression models were built to determine which variables were associated with the PGA. Results A total of 350 patients (89% female; median age: 42 years, IQR: 34-52) were included. The median Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score was 4 (IQR: 2-6). Of these 350 patients, 257 (73%) reported significant fatigue. The PGA (p=0.004) but not the SELENA-SLEDAI (p=0.43) was significantly associated with fatigue. Both fatigue and SELENA-SLEDAI were independently associated with the PGA in two different multivariate models. Conclusion Fatigue is independently associated with disease activity assessed using the PGA but not the SLEDAI. These findings highlight the fact that the PGA should capture only objectively active disease manifestations in order to improve its reliability

Cardiovascular, endocrine and behavioural responses to suckling and permanent separation in goats

<p>Abstract</p> <p>Background</p> <p>Suckling can be a peaceful or vulnerable event for goats and kids, whereas, separation is suggested as stressful. The aim of this study was to investigate physiology and behaviour in these two different situations in dairy goats.</p> <p>Methods</p> <p>Four studies were performed with seven goats kept with their first-born kid in individual boxes. The goats were videotaped and heart rate and arterial blood pressure were recorded every minute by telemetry from parturition until 24 hours after separation. One to two days after parturition, Study 1 was performed with analyses of heart rate and blood pressure around a suckling. In Study 2, performed 3-5 days after parturition, blood sampling was done before, during and after suckling. Study 3 was performed 4-6 days post partum, with blood sampling before and after a permanent goat and kid separation. In addition, vocalisations were recorded after separation. Blood samples were obtained from a jugular vein catheter and analysed for plasma cortisol, β-endorphin, oxytocin, and vasopressin concentrations. Study 4 was performed during the first (N1) and second nights (N2) after parturition and the nights after Study 2 (N3) and 3 (N4). Heart rate, blood pressure and time spent lying down were recorded.</p> <p>Results</p> <p>The kids suckled 2 ± 0.2 times per hour and each suckling bout lasted 43 ± 15 s. In Study 1, heart rate and blood pressure did not change significantly during undisturbed suckling. In Study 2, plasma cortisol (P ≤ 0.05 during suckling and P ≤ 0.01 five minutes after suckling) and β-endorphin (P ≤ 0.05) concentrations increased during suckling, but oxytocin and vasopressin concentrations did not change. In Study 3, the goats and kids vocalised intensively during the first 20 minutes after separation, but the physiological variables were not affected. In Study 4, heart rate and arterial blood pressure declined gradually after parturition and were lowest during N4 (P ≤ 0.05) when the goats spent longer time lying down than during earlier nights (P ≤ 0.01 during N1 and N3 and P ≤ 0.05 during N2).</p> <p>Conclusions</p> <p>Suckling elevated plasma cortisol and β-endorphin concentrations in the goats. The intensive vocalisation in the goats after separation, earlier suggested to indicate stress, was not accompanied by cardiovascular or endocrine responses.</p

The European Photon Imaging Camera on XMM-Newton: The MOS Cameras

The EPIC focal plane imaging spectrometers on XMM-Newton use CCDs to record the images and spectra of celestial X-ray sources focused by the three X-ray mirrors. There is one camera at the focus of each mirror; two of the cameras contain seven MOS CCDs, while the third uses twelve PN CCDs, defining a circular field of view of 30 arcmin diameter in each case. The CCDs were specially developed for EPIC, and combine high quality imaging with spectral resolution close to the Fano limit. A filter wheel carrying three kinds of X-ray transparent light blocking filter, a fully closed, and a fully open position, is fitted to each EPIC instrument. The CCDs are cooled passively and are under full closed loop thermal control. A radio-active source is fitted for internal calibration. Data are processed on-board to save telemetry by removing cosmic ray tracks, and generating X-ray event files; a variety of different instrument modes are available to increase the dynamic range of the instrument and to enable fast timing. The instruments were calibrated using laboratory X-ray beams, and synchrotron generated monochromatic X-ray beams before launch; in-orbit calibration makes use of a variety of celestial X-ray targets. The current calibration is better than 10% over the entire energy range of 0.2 to 10 keV. All three instruments survived launch and are performing nominally in orbit. In particular full field-of-view coverage is available, all electronic modes work, and the energy resolution is close to pre-launch values. Radiation damage is well within pre-launch predictions and does not yet impact on the energy resolution. The scientific results from EPIC amply fulfil pre-launch expectations.Comment: 9 pages, 11 figures, accepted for publication in the A&A Special Issue on XMM-Newto

ISGRI: the INTEGRAL Soft Gamma-Ray Imager

For the first time in the history of high energy astronomy, a large CdTe gamma-ray camera is operating in space. ISGRI is the low-energy camera of the IBIS telescope on board the INTEGRAL satellite. This paper details its design and its in-flight behavior and performances. Having a sensitive area of 2621 cm$^2$ with a spatial resolution of 4.6 mm, a low threshold around 12 keV and an energy resolution of $\sim$ 8% at 60 keV, ISGRI shows absolutely no signs of degradation after 9 months in orbit. All aspects of its in-flight behavior and scientific performance are fully nominal, and in particular the observed background level confirms the expected sensitivity of 1 milliCrab for a 10$^6$s observation.Comment: INTEGRAL A&A special issu

Neonatal Handling Affects Durably Bonding and Social Development

The neonatal period in humans and in most mammals is characterized by intense mother-young interactions favoring pair bonding and the adaptation of neonates to their new environment. However, in many post-delivery procedures, human babies commonly experience combined maternal separation and intense handling for about one hour post-birth. Currently, the effects of such disturbances on later attachment and on the development of newborns are still debated: clearly, further investigations are required. As animals present good models for controlled experimentation, we chose domestic horses to investigate this issue. Horses, like humans, are characterized by single births, long lactating periods and selective mother-infant bonds. Routine postnatal procedures for foals, as for human babies, also involve intense handling and maternal separation. In the present study, we monitored the behavior of foals from early stages of development to “adolescence”, in a normal ecological context (social groups with adults and peers). Experimental foals, separated from their mothers and handled for only 1 hour post-birth, were compared to control foals, left undisturbed after birth. Our results revealed short- and long-term effects of this unique neonatal experience on attachment and subsequent social competences. Thus, experimental foals presented patterns of insecure attachment to their mothers (strong dependence on their mothers, little play) and impaired social competences (social withdrawal, aggressiveness) at all ages. We discuss these results in terms of mother-young interactions, timing of interactions and relationships between bonding and subsequent social competences. Our results indicate that this ungulate species could become an interesting animal model. To our knowledge, this is the first clear demonstration that intervention just after birth affects bonding and subsequent social competences (at least until “adolescence”). It opens new research directions for studies on both humans and other animals

Predictors of disease worsening defined by progression of organ damage in diffuse systemic sclerosis: a European Scleroderma Trials and Research (EUSTAR) analysis.

Objectives Mortality and worsening of organ function are desirable endpoints for clinical trials in systemic sclerosis (SSc). The aim of this study was to identify factors that allow enrichment of patients with these endpoints, in a population of patients from the European Scleroderma Trials and Research group database. Methods Inclusion criteria were diagnosis of diffuse SSc and follow-up over 12\ub13 months. Disease worsening/organ progression was fulfilled if any of the following events occurred: new renal crisis; decrease of lung or heart function; new echocardiography-suspected pulmonary hypertension or death. In total, 42 clinical parameters were chosen as predictors for the analysis by using (1) imputation of missing data on the basis of multivariate imputation and (2) least absolute shrinkage and selection operator regression. Results Of 1451 patients meeting the inclusion criteria, 706 had complete data on outcome parameters and were included in the analysis. Of the 42 outcome predictors, eight remained in the final regression model. There was substantial evidence for a strong association between disease progression and age, active digital ulcer (DU), lung fibrosis, muscle weakness and elevated C-reactive protein (CRP) level. Active DU, CRP elevation, lung fibrosis and muscle weakness were also associated with a significantly shorter time to disease progression. A bootstrap validation step with 10 000 repetitions successfully validated the model. Conclusions The use of the predictive factors presented here could enable cohort enrichment with patients at risk for overall disease worsening in SSc clinical trial

Pain levels and associated factors in the Scleroderma Patient-centered Intervention Network (SPIN) cohort: a multicentre cross-sectional study

Background: Pain is an important and detrimental feature of systemic sclerosis but is often overlooked or deprioritised in research and clinical care. Raynaud's phenomenon, arthritis, and cutaneous ulcers are among the commonly reported disease manifestations of systemic sclerosis that could be associated with pain. We aimed to assess levels of pain intensity and interference and to evaluate disease factors associated with pain intensity and interference. Methods: In this multicentre cross-sectional study, participants from the Scleroderma Patient-centered Intervention Network cohort who completed pain intensity and interference measures (Patient Reported Outcomes Information System-29 profile, version 2·0) as part of baseline assessments were included. Patients were recruited from 46 centres in Australia, Canada, France, Mexico, Spain, the UK, and the USA between April 15, 2014, and Jan 7, 2020. Eligible patients included those aged 18 years or older who met the criteria for systemic sclerosis devised by the American College of Rheumatology and the European League Against Rheumatism. Associations of pain intensity and pain interference with systemic sclerosis-related variables and overlap syndromes, controlling for sociodemographic variables, were assessed with multiple linear regression. Continuous independent variables were standardised. Findings: Among 2157 participants with systemic sclerosis (268 [12%] males and 1889 [88%] females), 1870 (87%) reported mild, moderate, or severe pain (defined as ≥1 on a 0 to 10 scale), and 815 (38%) reported moderate or severe pain (defined as ≥5). Moreover, 757 (35%) participants reported moderate or severe pain interference. Greater pain intensity was independently associated with female sex (0·58 points [95% CI 0·26–0·90]), non-White race or ethnicity (0·50 points [0·21–0·79]), fewer years in formal education (0·30 points per SD [0·19–0·41]), country (reference: USA; Canada: 0·29 points [0·01–0·57] and UK: 0·58 points [0·21–0·95]), greater body-mass index (0·35 points per SD [0·24–0·45]); joint contractures (0·67 points [0·39–0·94]), digital ulcers (0·33 points [0·10–0·55]), gastrointestinal involvement (0·66 points [0·33–0·98]), skin involvement (measured using modified Rodnan skin score; 0·22 points per SD [0·10–0·35]), rheumatoid arthritis (0·96 points [0·50–1·43]), and Sjögren's syndrome (0·42 points [0·01–0·83]). Pain interference results were similar. Interpretation: Pain is common among people with systemic sclerosis. Controlling for sociodemographic variables, greater pain was associated with multiple systemic sclerosis-related manifestations, including joint contractures, digital ulcers, gastrointestinal involvement, skin involvement, and the presence of overlap syndromes. Health-care providers should work with patients to address pain, including identifying and addressing systemic sclerosis manifestations associated with their pain, and supporting behavioural approaches to minimise impact on function and quality of life. Funding: Canadian Institutes of Health Research, Arthritis Society, The Lady Davis Institute for Medical Research of the Jewish General Hospital, Jewish General Hospital Foundation, McGill University, Scleroderma Society of Ontario, Scleroderma Canada, Sclérodermie Québec, Scleroderma Manitoba, Scleroderma Atlantic, Scleroderma Association of BC, Scleroderma SASK, Scleroderma Australia, Scleroderma New South Wales, Scleroderma Victoria, and Scleroderma Queensland

Randomized controlled trial of an internet-based self-guided hand exercise program to improve hand function in people with systemic sclerosis: the Scleroderma Patient-centered Intervention Network Hand Exercise Program (SPIN-HAND) trial

BACKGROUND: Systemic sclerosis (scleroderma; SSc) is a rare autoimmune connective tissue disease. Functional impairment of hands is common. The Scleroderma Patient-centered Intervention Network (SPIN)-HAND trial compared effects of offering access to an online self-guided hand exercise program to usual care on hand function (primary) and functional health outcomes (secondary) in people with SSc with at least mild hand function limitations. METHODS: The pragmatic, two-arm, parallel-group cohort multiple randomized controlled trial was embedded in the SPIN Cohort. Cohort participants with Cochin Hand Function Scale (CHFS) scores ≥ 3 and who indicated interest in using the SPIN-HAND Program were randomized (3:2 ratio) to an offer of program access or to usual care (targeted N = 586). The SPIN-HAND program consists of 4 modules that address (1) thumb flexibility and strength; (2) finger bending; (3) finger extension; and (4) wrist flexibility and strength. The primary outcome analysis compared CHFS scores 3 months post-randomization between participants offered versus not offered the program. Secondary outcomes were CHFS scores 6 months post-randomization and functional health outcomes (Patient-Reported Outcomes Measurement Information System profile version 2.0 domain scores) 3 and 6 months post-randomization. RESULTS: In total, 466 participants were randomized to intervention offer (N = 280) or usual care (N = 186). Of 280 participants offered the intervention, 170 (61%) consented to access the program. Of these, 117 (69%) viewed at least one hand exercise instruction video and 77 (45%) logged into the program website at least 3 times. In intent-to-treat analyses, CHFS scores were 1.2 points lower (95% CI − 2.8 to 0.3) for intervention compared to usual care 3 months post-randomization and 0.1 points lower (95% CI − 1.8 to 1.6 points) 6 months post-randomization. There were no statistically significant differences in other outcomes. CONCLUSION: The offer to use the SPIN-HAND Program did not improve hand function. Low offer uptake, program access, and minimal usage among those who accessed the program limited our ability to determine if using the program would improve function. To improve engagement, the program could be tested in a group format or as a resource to support care provided by a physical or occupational therapist. TRIAL REGISTRATION: NCT03419208. Registered on February 1, 2018

Patterns of patient-reported symptoms and association with sociodemographic and systemic sclerosis disease characteristics: a scleroderma Patient-centered Intervention Network (SPIN) Cohort cross-sectional study

Background: Systemic sclerosis is a heterogenous disease in which little is known about patterns of patient-reported symptom clusters. We aimed to identify classes of individuals with similar anxiety, depression, fatigue, sleep disturbance, and pain symptoms and to evaluate associated sociodemographic and disease-related characteristics. Methods: This multi-centre cross-sectional study used baseline data from Scleroderma Patient-centered Intervention Network Cohort participants enrolled from 2014 to 2020. Eligible participants completed the PROMIS-29 v2.0 measure. Latent profile analysis was used to identify homogeneous classes of participants based on patterns of anxiety, depression, fatigue, sleep disturbance, and pain scores. Sociodemographic and disease-related characteristics were compared across classes. Findings: Among 2212 participants, we identified five classes, including four classes with “Low” (565 participants, 26%), “Normal” (651 participants, 29%), “High” (569 participants, 26%), or “Very High” (193 participants, 9%) symptom levels across all symptoms. Participants in a fifth class, “High Fatigue/Sleep/Pain and Low Anxiety/Depression” (234 participants, 11%) had similar levels of fatigue, sleep disturbance, and pain as in the “High” class but low anxiety and depression symptoms. There were significant and substantive trends in sociodemographic characteristics (age, education, race or ethnicity, marital or partner status) and increasing disease severity (diffuse disease, tendon friction rubs, joint contractures, gastrointestinal symptoms) across severity-based classes. Disease severity and sociodemographic characteristics of “High Fatigue/Sleep/Pain and Low Anxiety/Depression” class participants were similar to the “High” severity class. Interpretation: Most people with systemic sclerosis can be classified by levels of patient-reported symptoms, which are consistent across symptoms and highly associated with sociodemographic and disease-related variables, except for one group which reports low mental health symptoms despite high levels of other symptoms and substantial disease burden. Studies are needed to better understand resilience in systemic sclerosis and to identify and facilitate implementation of cognitive and behavioural strategies to improve coping and overall quality of life. Funding: National Institute of Nursing Research (F31NR019007), Canadian Institutes of Health Research, Arthritis Society Canada, the Lady Davis Institute for Medical Research, the Jewish General Hospital Foundation, McGill University, Scleroderma Society of Ontario, Scleroderma Canada, Sclérodermie Québec, Scleroderma Manitoba, Scleroderma Atlantic, Scleroderma Association of BC, Scleroderma SASK, Scleroderma Australia, Scleroderma New South Wales, Scleroderma Victoria, and Scleroderma Queensland