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

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

Evaluation of Measurement Properties and Differential Item Functioning in the English and French Versions of the University of California, Los Angeles, Loneliness Scale-6: A Scleroderma Patient-Centered Intervention Network (SPIN) Study

Objective: Loneliness has been associated with poorer health-related quality of life but has not been studied in patients with systemic sclerosis (SSc). The current study was undertaken to examine and compare the psychometric properties of the English and French versions of the University of California, Los Angeles, Loneliness Scale-6 (ULS-6) in patients with SSc during the COVID-19 pandemic. Methods: This study used baseline cross-sectional data from 775 adults enrolled in the Scleroderma Patient-Centered Intervention Network (SPIN) COVID-19 Cohort. Reliability and validity of ULS-6 scores overall and between languages were evaluated using confirmatory factor analysis (CFA), differential item functioning (DIF) through the multiple-indicator multiple-cause (MIMIC) model, omega/alpha calculation, and correlations of hypothesized convergent relationships. Results: CFA for the total sample supported the single-factor structure (comparative fit index [CFI] 0.96, standardized root mean residual [SRMR] 0.03), and all standardized factor loadings for items were large (0.60–0.86). The overall MIMIC model with language as a covariate fit well (CFI 0.94, SRMR 0.04, root mean square error of approximation 0.11). Statistically significant DIF was found for 3 items across language (βitem2 = 0.14, P < 0.001; βitem4 = –0.07, P = 0.01; βitem6 = 0.13, P < 0.001), but these small differences were without practical measurement implications. Analyses demonstrated high internal consistency with no language-based convergent validity differences. Conclusion: Analyses demonstrated evidence of acceptable reliability and validity of ULS-6 scores in English- and French-speaking adults with SSc. DIF analysis supported use of the ULS-6 to examine comparative experiences of loneliness without adjusting for language

Association between D-Dimer levels and mortality in patients with coronavirus disease 2019 (COVID-19): a systematic review and pooled analysis

International audienceBackground: Several observational studies have reported elevated baseline D-dimer levels in patients hospitalized for moderate to severe coronavirus disease 2019 (COVID-19). These elevated baseline D-dimer levels have been associated with disease severity and mortality in retrospective cohorts.Objectives: To review current available data on the association between D-Dimer levels and mortality in patients admitted to hospital for COVID-19.Methods: We performed a systematic review of published studies using MEDLINE and EMBASE through 13 April 2020. Two authors independently screened all records and extracted the outcomes. A random effects model was used to estimate the standardized mean difference (SMD) with 95% confidence intervals (CI).Results: Six original studies enrolling 1355 hospitalized patients with moderate to critical COVID-19 (391 in the non-survivor group and 964 in the survivor group) were considered for the final pooled analysis. When pooling together the results of these studies, D-Dimer levels were found to be higher in non-survivors than in-survivors. The SMD in D-Dimer levels between non-survivors and survivors was 3.59μg/L (95% CI 2.79-4.40μg/L), and the Z-score for overall effect was 8.74 (P<0.00001), with a high heterogeneity across studies (I2=95%).Conclusions: Despite high heterogeneity across included studies, the present pooled analysis indicates that D-Dimer levels are significantly associated with the risk of mortality in COVID-19 patients. Early integration of D-Dimer testing, which is a rapid, inexpensive, and easily accessible biological test, can be useful to better risk stratification and management of COVID-19 patients

Heart Rate and Mortality in Patients With Acute Symptomatic Pulmonary Embolism

Background: The association between heart rate (HR) and pulmonary embolism (PE) outcomes has not been well studied. Furthermore, optimal cutoffs to identify low-risk and intermediate- to high-risk patients are not well known. Research Question: Does an association exist between baseline HR and PE outcome across the continuum of HR values? Study Design and Methods: The current study included 44,331 consecutive nonhypotensive patients with symptomatic PE from the Registro Informatizado de la Enfermedad TromboEmbólica registry between 2001 and 2021. Outcomes included 30-day all-cause and PE-specific mortality. We used hierarchical logistic regression to assess the association between admission HR and outcomes. Results: A positive relationship was found between admission HR and 30-day all-cause and PE-related mortality. Considering an HR of 80 to 99 beats/min as a reference, patients in the higher HR strata showed higher rates of all-cause death (adjusted OR, 1.5 for HR of 100-109 beats/min; adjusted OR, 1.7 for HR of 110-119 beats/min; adjusted OR, 1.9 for HR of 120-139 beats/min; and adjusted OR, 2.4 for HR of ≥ 140 beats/min). Patients in the lower strata of HR showed significantly lower rates of 30-day all-cause mortality compared with the same reference group (adjusted OR, 0.6 for HR of 60-79 beats/min; and adjusted OR, 0.5 for HR of < 60 beats/min). The findings for 30-day PE-related mortality were similar. For identification of low-risk patients, a cutoff value of 80 beats/min (vs 110 beats/min) increased the sensitivity of the simplified Pulmonary Embolism Severity Index (sPESI) from 93.4% to 98.8%. For identification of intermediate- to high-risk patients, a cutoff value of 140 beats/min (vs 110 beats/min) increased the specificity of the Bova score from 93.2% to 98.0%. Interpretation: In nonhypotensive patients with acute symptomatic PE, a high HR portends an increased risk of all-cause and PE-related mortality. Modifying the HR cutoff in the sPESI and the Bova score improves prognostication of patients with PE

2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19

The International Initiative on Thrombosis and Cancer is an independent academic working group of experts aimed at establishing global consensus for the treatment and prophylaxis of cancer-associated thrombosis. The 2013, 2016, and 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines have been made available through a free, web-based mobile phone application. The 2022 clinical practice guidelines, which are based on a literature review up to Jan 1, 2022, include guidance for patients with cancer and with COVID-19. Key recommendations (grade 1A or 1B) include: (1) low-molecular-weight heparins (LMWHs) for the initial (first 10 days) treatment and maintenance treatment of cancer-associated thrombosis; (2) direct oral anticoagulants for the initial treatment and maintenance treatment of cancer-associated thrombosis in patients who are not at high risk of gastrointestinal or genitourinary bleeding, in the absence of strong drug–drug interactions or of gastrointestinal absorption impairment; (3) LMWHs or direct oral anticoagulants for a minimum of 6 months to treat cancer-associated thrombosis; (4) extended prophylaxis (4 weeks) with LMWHs to prevent postoperative venous thromboembolism after major abdominopelvic surgery in patients not at high risk of bleeding; and (5) primary prophylaxis of venous thromboembolism with LMWHs or direct oral anticoagulants (rivaroxaban or apixaban) in ambulatory patients with locally advanced or metastatic pancreatic cancer who are treated with anticancer therapy and have a low risk of bleeding

Real-Time Dissemination of Aggregate Data on Presentation and Outcomes of Patients With Venous Thromboembolism: The RIETE Infographics Project

In the current era of patient empowerment and precision medicine, access to timely information is critical to decision-making. Unfortunately, we currently lack patient-specific, real-time data about clinical presentation, risk of thrombotic or hemorrhagic events, key risk factors, and adverse outcomes in patients with venous thromboembolism (VTE). Accordingly, the Registro Informatizado Enfermedad TromboEmb\uf3lica (RIETE) investigators developed a tool to provide an open-source, real-time graphic representation of VTE-related data derived from over 90 000 patients with confirmed VTE. This information is intended to facilitate discussion in the informed decision-making process. The current article describes the aims, rationale, methods, and ongoing and future efforts of the real-time VTE infographics developed by the RIETE registry collaborators

Liver status and outcomes in patients without previous known liver disease receiving anticoagulant therapy for venous thromboembolism

The association between elevated liver enzymes or FIB-4 (fibrosis index 4) and outcome in patients with venous thromboembolism (VTE) has not been evaluated. Data from patients in RIETE (Registro Informatizado Enfermedad TromboEmbólica) were used to assess the association between elevated liver enzymes or FIB-4 levels and the rates of major bleeding or death in apparent liver disease-free patients with acute VTE under anticoagulation therapy. A total of 6206 patients with acute VTE and without liver disease were included. Of them, 92 patients had major bleeding and 168 died under anticoagulation therapy. On multivariable analysis, patients with elevated liver enzymes were at increased mortality risk (HR: 1.58; 95% CI: 1.10–2.28), while those with FIB-4 levels > 2.67 points were at increased risk for major bleeding (HR: 1.69; 95% CI: 1.04–2.74). Evaluation of liver enzymes and FIB-4 index at baseline in liver disease-free patients with VTE may provide additional information on the risk for major bleeding or death during anticoagulation