Functional Impact of Telehealth Physical Therapy Services on Patients Post Hematopoietic Stem Cell Transplant

BACKGROUND AND PURPOSE: Stem cell transplantation (SCT) in patients with hematological cancers results in longstanding physical changes. Commonly reported symptoms include chronic fatigue, global weakness, interference with activities of daily living (ADLs) and aerobic deconditioning. Aside from the sequela of symptoms experienced post SCT, these patients remain in an immunosuppressed state for several months following discharge from the hospital. Patients are often advised by their medical team to isolate themselves unless to attend follow-up outpatient clinic appointments. With the COVID-19 pandemic, this functional gap in the continuum of care worsened. As a result, SCT patients are both hesitant and discouraged to pursue outpatient or home health physical therapy even when these services are warranted. Thus, there is great need for options to safely optimize function for people post-SCT that are suitable in today's ever-changing environment. The purpose of this case series is to describe the functional impact of incorporating telehealth into the continuum of care for post SCT patients. CASE DESCRIPTION: 9 patients post inpatient admission for SCT were triaged to telehealth PT based on their scores on the Short Physical Performance Battery (SPPB) and the Activity Measure for Post Acute Care (AM-PAC) at the time of discharge from inpatient care. Scores on the SPPB ranged from 5-11, and AMPAC scores ranged from 21-24, demonstrating physical impairment. Patients were scheduled to receive telehealth twice a week. Sessions consisted of therapeutic exercises monitored via secure video software. Lab values were monitored via electronic medical record to assess appropriateness for therapy prior to each session. Rating of perceived exertion (RPE) scale and patientowned pulse oximeter were used to monitor patient fatigue levels. Patients' progress was assessed via Lower Extremity Functional Scale (LEFS), Brief Fatigue Inventory (BFI) and 5-times sit to stand (5xSTS) scores. OUTCOME(S): One year post telehealth implementation, patients reported improved independence and achievement of selfselected goals. Notable patient quotes include, "I feel less fearful in climbing up and down the stairs, and I feel more independent with laundry and cooking.which was very important for me." Additionally, patients reported a decrease in LEFS and BFI scores. Initial LEFS scores averaged 40% and dropped to 20% by discharge. Similarly, BFI scores dropped by 2 points at discharge, reflecting improved self-reported functional performance and a return to pre transplant fatigue levels. 5xSTS scores decreased by greater than 3 seconds in 6 of 9 patients, with one patient performing where previously unable. DISCUSSION: Telehealth services provide an additional method of care delivery to those unable to seek it in the traditional sense. For the severely immunocompromised, physical therapy via telehealth provides direct connection to providers trained in oncology rehabilitation serving as a feasible bridge between inpatient and outpatient care for amelioration of side effects associated with SCT.

Physical Therapy Management of Postacute Sequelae of COVID-19 in Outpatient Settings: A Scoping Review

Purpose:The devasting effects of the coronavirus disease 2019 (COVID-19) pandemic have warranted the rapid development of evidence surrounding the physical therapy (PT) management of the disease within inpatient settings. However, the medical community is still working to define the long-term effects of COVID-19, referred to as Postacute Sequalae of SARS-CoV-2 (PASC), and ways for physical therapists to manage them in outpatient settings. The primary objective of this review was to summarize the available evidence related to the PT management of PASC in outpatient settings. Method(s):A systematic search in PubMed, Cumulative Index to Nursing and Allied Health Literature, Cochrane CENTRAL, Academic Search Complete, and MedLine yielded systematic and scoping reviews and randomized controlled trials, among others. Data extraction was performed independently by 2 reviewers with 8 studies included. Result(s):Only 3 publications were specific to the outpatient setting area, with 5 more studies that focused on outpatient practice as part of a multisetting study, or the postacute setting. Although the limited number and quality of publications creates challenges applying the interventions provided across a population, each were specific to PASC. Conclusion(s):This review supports the need for further research focused on the PT management of patients who are experiencing PASC in outpatient settings.Copyright © Cardiovascular and Pulmonary Section, APTA.

Muscle volume, functionality and metabolic resilience during recovery following severe COVID-19

Introduction: Following hospitalisation with SARS-Cov2 infection a large proportion of individuals report fatigue as a persisting symptom. Here, we performed a detailed study of the muscle for insight into underlying mechanisms. Method(s): Adults were recruited at 5-7 months following hospital discharge for severe SARS-Cov2 infection (n=21), along with control volunteers (n=10) of a similar age, gender, ethnicity and body mass. Perceived fatigue was estimated using the fatigue severity scale. The short physical performance battery test determined habitual functionality, alongside isometric quadriceps strength normalised for appendicular mass and isokinetic force loss during 20 knee extensions (Cybex Norm dynamometer). Leg muscle volume, and phosphocreatine (PCr) resynthesis during recovery from ischemic plantar flexion exercise (an index of muscle metabolic resilience) were quantified using MRI and 31P MRS. Student t-test was used to detect differences between groups and all data are mean (SD). Result(s): Patients (P) reported greater perception of fatigue and demonstrated worse habitual functionality compared to controls (C). However, leg volume [P: 2,578 (303) cm3/m2 vs C: 2,384 (289) cm3/m2, p=0.1], strength [P: 21.8 (4.1) Nm/kg vs C: 21.1 (4.5) Nm/kg, p=0.7], force loss [P: 25% (6) vs C: 21% (10), p=0.1] and PCr recovery kinetics (Qmax) [P: 25.8 (11.3) vs C: 22.8 (8.7), p=0.5] were not different. Conclusion(s): Despite greater perception of fatigue and lower habitual functionality, patients recovering from severe COVID-19 infection did not have altered muscle volume, strength, fatiguability or metabolic resilience compared to controls.

Short-term impact of COVID-19 on health-related physical fitness in hospitalized and home-treated patients

Assessment of health-related physical fitness (PF) and body composition (BC) may yield relevant information on body function in patients who have been affected by Coronavirus disease-2019 (COVID-19). Aim of our study was to evaluate the short-term effects of COVID-19 on physical fitness in a real-life cohort of outpatients including hospitalized and home-treated patients. Sixty-four patients (M=36;mean age 56+/-13.5 yrs) previously affected by COVID-19 (25 hospitalized vs. 39 hometreated) in the 3-6 months preceding the study measurements were enrolled. PF was evaluated with the following tests: handgrip strength (HGS), gait speed (GAIT), sit-to-stand (STS), timed up and go (TUG) and Short physical performance battery (SPPB). Phase angle (PhA) was measured by bioelectrical impedance analysis (BIA) as a proxy marker of fat-free mass composition in terms of body cell mass and cell integrity. Poor PF performance was observed in 38% of subjects for HGS, 55% for GAIT, 30% for STS, 38% for TUG, and 70% for SPPB, while low values of PA were observed in 42% of the study sample in comparison with international cut-offs. The presence of 3-5 impaired values out of five was observed in 38% of patients. All PF tests (and even more the number of abnormal PF tests) consistently correlated with PhA. No differences were reported between hospitalized and home-treated patients. In the short-run, COVID-19 causes a worsening of physical fitness regardless of baseline disease severity. More research is required to systematically measure the extent of functional impairments in COVID-19 and to address whether and how rehabilitation can promote post-infection recovery.

THE 2-YEAR IMPACT of COVID-19 PANDEMIC on MUSCLE STRENGTH and PHYSICAL PERFORMANCE in PATIENTS with SYSTEMIC SCLEROSIS: A COHORT STUDY

Background: Systemic sclerosis (SSc) patients are particularly prone to developing loss of muscle strength and worsening of physical performance due to decreased physical activity1. The lifestyle changes imposed by the SARS-CoV-2 outbreak have increased the incidence of sarcopenia in at-risk individuals2. However, the literature is scarce on the impacts of the COVID-19 pandemic on muscle strength and physical performance of SSc patients. Objectives: (1) To assess the impact of the COVID-19 pandemic on muscle strength and physical performance of SSc patients and (2) to verify the associations of muscle strength and physical performance with infammatory markers in a cohort study. Methods: SSc patients who met the ACR/EULAR 2013 classifcation criteria were included. Patients followed between 2019 and 2021. Muscle strength was measured by handgrip strength (kg) and sit and stand (SST, seconds) tests. Physical performance was measured by timed up and go (TUG, seconds) and short physical performance battery (SPPB, points). Infammatory markers were measured by C-reactive protein (CRP). T test for independent samples, Mann-Whitney U test of independent samples and Spearman's correlation coef-fcients were explored. The signifcance level was set at p ≤ 0.05 for all analyses. Results: Forty SSc patients concluded this study. At baseline, the mean age was 59 ± 11. 1 years old and the median disease duration was 13.1 (6.4-19.2) years. Patients had a median of 4.5 clinic visits (3.0-6.0) over the 2 years. The majority of patients were women (37, 92.5%). Te n patients (25%) had diffuse cutaneous disease, 30 patients (75%) non-diffuse cutaneous disease [25 patients (62.5%) had limited cutaneous disease, and 5 (12.5%) had sine scleroderma SSc]. The median of CRP was 2.9 (1.2-5.3). The median of handgrip strength was 20.0 (10.3-25.8) kg to the right hand and 19.0 (12.0-22.8) kg to the left hand. The median of SST was 14.4 (11.9-18.7) seconds. The median of TUG was 8.6 (7.7-9.5) seconds and the median of SPPB was 9.8 (9.0-11.0) points. The CRP was positively associated with SST (r=0.3, p=0.047) and TUG (r=0.3, p=0.029), and negatively with SPPB (r=-0.4, p=0.016). After 2 years of follow-up, the patients showed improvement in the left handgrip strength test (p=0.049) and SST (p=0.001). In physical performance, they showed improvement in the TUG test (p=0.005) and SPPB (p=0.001). The CRP was associated positively with TUG (r=0.4, p=0.033), no other associations were found. Conclusion: Despite the COVID-19 pandemic and the restrictions imposed, in this population of patients with SSc, we did not detect any worsening in muscle strength and physical performance. Some of these parameters of muscle strength and physical performance were associated with the infammatory marker CRP. More investigations are needed to assess the actual impact and possible associations.

Metabolomic Biomarkers Measured at Patient Discharge Predict Long- Term Physical Function in Survivors of Acute Respiratory Failure

RATIONALE: Long-term quality of life is a significant concern for survivors of sepsis and acute respiratory failure (ARF). Financial burdens await as many patients never return to work. Notably, the duration of the ICU stay significantly correlates with the severity of physical impairment and up to 25% of skeletal muscle is lost within one week in the ICU. The recent pandemic due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) is likely to exacerbate these issues. We have previously reported that metabolites related to mitochondrial bioenergetics status can predict acute patient outcomes. Here, we propose that these same metabolomic and mitochondrial biomarkers of mortality also predict physical function in survivors. METHODS: To test this hypothesis, we performed a retrospective analysis of metabolomic changes in ARF survivors using ultrahigh performance liquid chromatography mass spectrometry. Six months after ICU admission, physical function was determined by the short physical performance battery (SPPB), an objective physical function measurement assessing gait speed, balance and lower extremity strength. A total of 70 consecutively enrolled patients were selected, of which 35 had good physical function (SPPB ≥ 7) and 35 had poor physical function (SPPB ≤6). The patients were matched for age, race and sex. Metabolomic analysis of patient's serum was measured at ICU admittance (n=70), 5d-post admittance (n=20) and discharge (n=20). RESULTS: More than 1250 named compounds were identified. There were only 19 metabolites that were significantly different at admittance (ANOVA;p < 0.05), of which seven were bile acids. However at discharge, despite less patient samples tested, 151 metabolites were significantly different (ANOVA;p < 0.05). Specifically, we found that 10 lysophospholipids, eight bile acids, three TCA cycle metabolites, eight kynurenine-related metabolites and nine urea cycle metabolites were significantly different. Many of these pathways have previously been shown to be altered in nonsurvivors of sepsis and ARF. CONCLUSIONS: Findings suggest that bioenergetic abnormalities arising during the acute phase of recovery may be persistent and predict longer-term decrements of physical function in survivors of ARF. Larger retrospective and prospective studies are needed to confirm these preliminary findings;however, predicting poor physical function in survivors as well as identifying the affected metabolic pathways may lead to improved therapies and long-term patient outcomes.

BIOPHYTIS BIO101 IN SARCOPENIA: RESULTS OF THE PHASE 2 SARA-INT STUDY

Backgrounds: Sarcopenia is a geriatric condition characterized by a progressive loss of muscle mass and function, having high personal, social and economic burdens when untreated. Sarcopenia increases risk of falls and fractures;impairs ability to perform activities of daily living;is associated with cardiac and respiratory disease and cognitive impairment;leads to mobility disorders;and contributes to lowered quality of life, loss of independence or need for long-term care placement, and death. It is recognized as one of the five pillars of frailty. As of today, to our knowledge, only exercise and nutrition interventions seem somewhat effective interventions. Objectives: SARA-INT study is a Phase 2 study to develop a viable option to treat community-dwelling seniors suffering from age-related sarcopenia, including sarcopenic obesity. Methods: SARA-INT is a randomized double-blind three-arm study (BIO101 175 mg bid / BIO101 350 mg bid / placebo) with planned treatment duration of 6 Months;due to COVID-related measures, 49 patients continued up to 9 months of treatment. Main eligibility criteria for sarcopenia were meeting FNIH criteria and Short Physical Performance Battery (SPPB) score ≤ 8/12 in men and women aged ≥ 65 years. Primary analysis was the gait speed from the 400-meter walking test (400MWT) at month 6/9 in the FAS with secondary analyses at other timepoints, secondary endpoints were other physical activity assessments, muscle strength, muscle mass and Patient Reported Outcomes (PROs). Results: 233 participants were randomized in the study, 232 and 156 participants were included in the Full Analysis Set (FAS) and Per-Protocol (PP) populations, respectively. Due to COVID-19 pandemic, end-of-treatment assessments are missing for approximately half of the participants, impacting the treatment effect detection. In the primary analysis (at month 6/9 in the FAS population) of the primary parameter, the improvement in 400MWT compared to placebo was not statistically significant (0.0363 (0.03098) m/s and 0.0385 (0.02985) m/s in the BIO101 175 mg and 350 mg groups, p=0.2437 and p=0.2000, respectively). BIO101 350 mg bid treatment after 6 months showed a clinically relevant improvement in the 400MWT of 0.07 m/s in the FAS population (not significant) and of 0.09 m/s in the PP population (nominally statistically significant, p=0.008);this is close to the Minimal Clinically Important Difference (MCID) in sarcopenia (0.1 m/s). BIO101 350mg bid treatment effect on the 400MWT is confirmed in pre-defined sub-populations at higher risk of mobility disability such as slow walkers, obese and those with chair stand sub-score ≤2 from SPPB;trends were observed with other independent endpoints. BIO101 showed no difference in adverse events or safety laboratory parameters versus placebo (), and no severe adverse event associated with BIO101 treatment. Conclusions: After 6 to 9 months of treatment, BIO101 at 350 mg bid showed promising results with a clinically relevant improvement in the 400MWT gait speed, the primary endpoint of the study, confirmed in sub-populations at higher risk of mobility disability. BIO101 showed a very good safety profile at the doses of 175 and 350 mg bid. Biophytis is preparing to start a phase 3 program with BIO101 at 350 mg bid in 2022, targeting a similar patient population. Conflicts of interests: CT, WD, CM, RL, PD, RvM and SV are employees of Biophytis SA, AZ, and SA are employees of Biophytis Inc., JM is president of the Scientific Advisory Board of Biophytis, SDS is employee of BlueCompanion Ltd.

Effects of neuromuscular electrical stimulation therapy on physical function in patients with COVID-19 associated pneumonia: Study protocol of a randomized controlled trial.

PURPOSE: Neuromuscular electrical stimulation (NMES) has been considered as a promising approach for the early rehabilitation of patients during and/or after intensive care unit (ICU) stay. The overall objective of this study is to evaluate the NMES effectiveness to counteract the post-ICU impairment in physical function of COVID-19 patients. The specific aim of this manuscript is to describe the study design, protocol, content of interventions, primary and secondary outcomes and to discuss the clinical rehabilitation impact of the expected experimental results. METHODS: This prospective, randomized, controlled, parallel-group, single-blind trial will include 80 patients who had undergone mechanical or non-invasive ventilation following pneumonia-induced respiratory failure. Patients are randomized to a control group (routine physical therapy for 3 weeks) or a NMES group (routine physical therapy plus NMES of quadriceps and gastrocnemius muscles for 3 weeks). The primary outcome is physical performance assessed through the Short Physical Performance Battery (SPPB). Secondary outcomes include independence level, perceived fatigue, muscle strength, rectus femoris thickness, and walking performance. The SPBB and walking performance are assessed once (after the intervention), while all other outcomes are assessed twice (before and after the intervention). CONCLUSION: NMES is a simple and non-invasive technique for muscle strengthening that is usually well tolerated, does not produce adverse effects, requires no or little cooperation from patients and is quite inexpensive. Therefore, proving the effectiveness of NMES therapy for physical and muscle function in COVID-19 patients could support its systematic incorporation in post-ICU rehabilitation protocols of patients presenting with post-intensive care syndrome.