Step Number and Aerobic Minute Exercise Prescription and Progression in Stroke: A Roadmap

Background While higher therapeutic intensity improves motor recovery after stroke, translating findings from successful studies is challenging without clear exercise intensity targets. We show in the DOSE trial 1 more than double the steps and aerobic minutes within a session can be achieved compared with usual care and translates to improved long-term walking outcomes. Objective We modeled data from this successful higher intensity multi-site RCT to develop targets for prescribing and progressing exercise for varying levels of walking impairment after stroke. Methods In twenty-five individuals in inpatient rehabilitation, twenty sessions were monitored for a total of 500 one-hour physical therapy sessions. For the 500 sessions, step number and aerobic minute progression were modeled using linear mixed effects regression. Using formulas from the linear mixed effects regression, targets were calculated. Results The model for step number included session number and baseline walking speed, and for aerobic minutes, session number and age. For steps, there was an increase of 73 steps per session. With baseline walking speed, for every 0.1 m/s increase, a corresponding increase of 302 steps was predicted. For aerobic minutes, there was an increase of .56 minutes of aerobic activity (ie, 34 seconds) per session. For every year increase in age, a decrease of .39 minutes (ie, 23 seconds) was predicted. Conclusions Using data associated with better walking outcomes, we provide step number and aerobic minute targets that future studies can cross-validate. As walking speed and age are collected at admission, these models allow for uptake of routine measurement of therapeutic intensity. Registration: www.clinicaltrials.gov ; NCT01915368.

SOFA Score as a Reliable Tool to Detect High Risk for Venous Thrombosis in Patients With Critical Stage SARS-CoV-2

Background: Severe acute respiratory syndrome from coronavirus-2 (SARS-CoV-2) has been associated with an increased risk of venous thromboembolism (VTE). Different anticoagulation protocols have been applied in several studies in the absence of clear evidence. A reliable deep venous thrombosis (DVT) indicator in critical patients with SARS-CoV-2 could guide the anticoagulation treatment; however, it has not yet been identified, and clinical applicability of the most common markers is debatable. The aim of our study was to determine the actual incidence of DVT in critically ill SARS-CoV-2 patients and to find a reliable tool to identify patients who might benefit from therapeutic-intensity anticoagulation.Methods: From March 1, 2020 to May 31, 2020, all patients admitted to the intensive care unit (ICU) for SARS-CoV-2 at Ospedale Regionale di Locarno, Locarno, Switzerland, were prospectively enrolled and screened daily with ultrasound for DVT. Following international consensus, a higher-intensity thromboprophylaxis was administered to all patients who were not at increased risk for bleeding. Sepsis-induced coagulopathy (SIC) and sequential organ failure assessment (SOFA) scores were calculated and time-to-DVT event in a COX proportional-hazard regression model was performed. A receiver operating characteristic (ROC) curve was used to determine sensitivity and specificity and the Youden's Index to establish the best threshold.Results: A total of 96 patients were enrolled. Deep venous thrombosis was detected in 37% of patients. Sepsis-induced coagulopathy and SOFA scores were both correlated to DVT. A SIC score of 1 vs. ≥2 showed a close association with DVT, with sensitivity, specificity, and positive and negative predictive values of 90.0, 48.1, and 49.1, and 89.7%, respectively. Most significantly though, a SOFA score of 1 or 2 points was shown to be the most accurate value in predicting the absence of DVT, indicating no need for therapeutic-intensity anticoagulation. Its sensitivity, specificity, and positive and negative predictive values were 87.9, 100, and 100, and 93.7%, respectively. The D-dimer test showed lower sensitivity and specificity whereas platelet count and aPTT were not found to be correlated to DVT.Conclusions: Patients with SOFA scores of 1 or 2 are at low risk of developing DVT and do not require therapeutic-intensity anticoagulation. Conversely, patients with scores ≥3 are at high risk of developing DVT.

American Society of Hematology 2021 guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19

Background: Coronavirus disease 2019 (COVID-19)–related critical illness and acute illness are associated with a risk of venous thromboembolism (VTE). Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for thromboprophylaxis for patients with COVID-19–related critical illness and acute illness who do not have confirmed or suspected VTE. Methods: ASH formed a multidisciplinary guideline panel and applied strict management strategies to minimize potential bias from conflicts of interest. The panel included 3 patient representatives. The McMaster University GRADE Centre supported the guideline-development process, including performing systematic evidence reviews (up to 19 August 2020). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment. Results: The panel agreed on 2 recommendations. The panel issued conditional recommendations in favor of prophylactic-intensity anticoagulation over intermediate-intensity or therapeutic-intensity anticoagulation for patients with COVID-19–related critical illness or acute illness who do not have confirmed or suspected VTE. Conclusions: These recommendations were based on very low certainty in the evidence, underscoring the need for high-quality, randomized controlled trials comparing different intensities of anticoagulation. They will be updated using a living recommendation approach as new evidence becomes available.

Older patients with mantle cell lymphoma (MCL): Practice patterns and predictors of survival in the rituximab era.

e20064 Background: Therapeutic intensity poses a challenge for older or medically unfit pts with untreated MCL. We assessed clinical outcomes and predictors of survival in older MCL pts treated in the rituximab era. Methods: We included pts ≥ 65 yrs of age with newly diagnosed MCL treated between 2000 and 2015. The primary objective was to characterize practice patterns and survival outcomes in older pts and secondarily to assess predictive factors of survival. Results: Data were collected from 12 centers for 1168 pts. For 465 pts ≥ 65 yrs of age (median 70; range 65-100), variable denominators indicate missing data: 305 of 444 pts (69%) were male; 23 (8%), 110 (39%) and 148 (53%) of 281 pts had low, intermediate and high-risk MIPI respectively. Median time from diagnosis to first treatment was 31 days (range 0-2611 days). In 407 older pts with initial treatment data, 148 (36%) received BR, 65 (16%) a cytarabine containing regimen, 9 (2%) lenalidomide, and 92 (23%) other treatments that excluded BTK inhibitors (BTKi). 68 of 365 pts (19%) were enrolled on clinical trial for initial therapy, 88 of 369 pts (24%) received autologous transplant (AHCT) in first remission, and 155 of 351 pts (44%) received maintenance rituximab (MR). Median f/u was 2.7 yrs. 41 of 465 pts (9%) had primary refractory disease (POD6); 107 (23%) progressed within 24 months (POD24). Treatment data were available for 157 relapsing pts: 58 (37%) were treated with BTKi/BTKi combinations. PFS and OS rates were compared across young and older age cohorts: 2 yr PFS rates were 79%, 69%, and 66% and 2 yr OS rates were 92%, 87%, and 84% for age < 65, age 65-69, and age ≥ 70 respectively (p < 0.001). In the older cohort: on UVA, ECOG ≥2, BM involvement, blastoid histology, > 3 cytogenetic abnormalities and lack of MR were associated with inferior PFS and OS (p = 0.012 – < 0.001). POD6 and POD24 were associated with decreased OS (p < 0.001). AHCT in first remission did not impact PFS or OS. After MVA, MR remained significantly associated with improved PFS and OS (p < 0.001). 2 yr PFS rates were 81% and 58% and 2 yr OS rates were 96% and 80% with and without MR respectively (p < 0.001). Conclusions: In this large cohort of older pts in the rituximab era, survival outcomes remain inferior to younger pts. MR is associated with improved PFS and OS but AHCT does not yield better survival. A small number of pts received BTKi salvage therapy. As such, our data does not reliably reflect the potential advancements in survival achieved with the introduction of BTKis. Focused clinical trials are necessary to identify effective therapeutics in this population.