2 research outputs found
THE BIOMECHANICAL IMPACT OF WEIGHT ON THE LOWER EXTREMITY
Background: Obesity is a chronic disease characterized by a body mass index (BM1) of ≥ 30 kg/m2 which negatively impacts the musculoskeletal system and has been found to be a major contributing factor to obesity-induced biomechanical alterations during activities of daily living (ADLs). A certain level of mobility is required for all populations to maintain independence and a good quality of life becomes more difficult with excess weight. Using a reduced weight-bearing activity, such as the Alter Gravity treadmill, would be beneficial in an obese population to reduce the load on the joints and potentially decrease the risk of weight bearing injury while maintaining normal gait mechanics. The purpose of this dissertation was to determine the biomechanical effects of excess weight and weight distribution on ADLs. To address this, two different weight gain models were created to simulate central (CL) and peripheral (PL) weight gain compared to an obese group (OW), and normal weight group (UL) during different activities of daily living (ADLs). The purpose of the third study was to compare lower extremity joint kinematics and muscle activation patterns between obese and normal individuals at different levels of body support (100, 75, and 50%) while walking in the AlterG treadmill.
Methods: 14 normal weight (BMI: 22.4 ± 1.8 kg/m2, age: 23.4 ± 3.6 yrs) and 17 obese (BMI: 33.2 ± 2.3 kg/m2, age: 31.6 ± 8.0 years) adults participated in different ADLs (gait and descending a set of stairs). Normal weight participants were loaded with two different external loads sufficient to increase their BMI by 5 kg/m2 (~22.6% body mass).
Kinematic and kinetic data were collected with 3D motion analysis. Frontal plane hip and knee angles and moments were calculated.
Results: During gait, the obese group walked at a significantly slower velocity compared to UL. Step length was 8.7% longer in UL and 7.4% longer in the CL compared to the OW. PL more closely mirrored the OW group in step length, flexion moment and extension moment and the CL more closely mirrored the obese group in sagittal plane knee and hip excursion, and peak hip flexion moment and extension moment during gait
During the transition from descending stair walking to level gait, it was found that the PL, but not CL, decreased step length, increased step width, and increased proportion of the gait cycle spent in stance. During the transition from walking down the stairs to level gait it was found that CL and PL affect temporal spatial variables differently. PL also reduced peak hip adduction angle, increased peak hip flexion moment, decreased peak hip extension, decreased sagittal plane hip excursion, and decreased frontal plane hip excursion. Conversely, CL reduced peak hip flexion moment and trended to reduce peak hip extension moment.
To determine the effects of reduced body mass per se on improved biomechanics, we needed a model that would prevent associated changes in segmental volume. Therefore, using an AlterG treadmill facilitated this method. At 100 % BW support, mean ST and VM EMG activity were significantly higher in the obese compared to the normal weight groups. There were also differences found at 75 % BW support in ST in the obese being greater than the normal.
Conclusions: Combined, the overall results of this dissertation suggest that weight gain is able to be modeled but is variable and task specific. The CL has proven to be the weight gain model that which elicits a better biomechanical obese response when normal weight individuals are loaded. Further work is needed to understand how to truly mimic obesity with an external load
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Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial
We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19.
In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978.
Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50–72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74–1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67–1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74–1·58]; BRII-196 plus BRII-198 1·00 [0·68–1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91–1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88–1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90.
Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19.
US National Institutes of Health and Operation Warp Spee