There have been more than 425 million COVID-19 infections worldwide. Post-COVID illness has become a common, disabling complication of this infection. Therefore, it presents a significant challenge ...to global public health and economic activity.
Comprehensive clinical assessment (symptoms, WHO performance status, cognitive testing, CPET, lung function, high-resolution CT chest, CT pulmonary angiogram and cardiac MRI) of previously well, working-age adults in full-time employment was conducted to identify physical and neurocognitive deficits in those with severe or prolonged COVID-19 illness.
205 consecutive patients, age 39 (IQR30.0-46.7) years, 84% male, were assessed 24 (IQR17.1-34.0) weeks after acute illness. 69% reported ≥3 ongoing symptoms. Shortness of breath (61%), fatigue (54%) and cognitive problems (47%) were the most frequent symptoms, 17% met criteria for anxiety and 24% depression. 67% remained below pre-COVID performance status at 24 weeks. One third of lung function tests were abnormal, (reduced lung volume and transfer factor, and obstructive spirometry). HRCT lung was clinically indicated in <50% of patients, with COVID-associated pathology found in 25% of these. In all but three HRCTs, changes were graded 'mild'. There was an extremely low incidence of pulmonary thromboembolic disease or significant cardiac pathology. A specific, focal cognitive deficit was identified in those with ongoing symptoms of fatigue, poor concentration, poor memory, low mood, and anxiety. This was notably more common in patients managed in the community during their acute illness.
Despite low rates of residual cardiopulmonary pathology, in this cohort, with low rates of premorbid illness, there is a high burden of symptoms and failure to regain pre-COVID performance 6-months after acute illness. Cognitive assessment identified a specific deficit of the same magnitude as intoxication at the UK drink driving limit or the deterioration expected with 10 years ageing, which appears to contribute significantly to the symptomatology of long-COVID.
There is growing evidence to support the use of low-load blood flow restriction (LL-BFR) exercise in musculoskeletal rehabilitation.
The purpose of this study was to evaluate the efficacy and ...feasibility of low-load blood flow restricted (LL-BFR) training versus conventional high mechanical load resistance training (RT) on the clinical outcomes of patient's undergoing inpatient multidisciplinary team (MDT) rehabilitation.
A single-blind randomized controlled study.
Twenty-eight lower-limb injured adults completed a 3-week intensive MDT rehabilitation program. Participants were randomly allocated into a conventional RT (3-days/week) or twice-daily LL-BFR training group. Outcome measurements were taken at baseline and 3-weeks and included quadriceps and total thigh muscle cross-sectional area (CSA) and volume, muscle strength five repetition maximum (RM) leg press and knee extension test, isometric hip extension, pain and physical function measures (Y-balance test, multistage locomotion test-MSLT).
A two-way repeated measures analysis of variance revealed no significant differences between groups for any outcome measure post-intervention (
> 0.05). Both groups showed significant improvements in mean scores for muscle CSA/volume, 5-RM leg press, and 5-RM knee extension (
< 0.01) after treatment. LL-BFR group participants also demonstrated significant improvements in MSLT and Y-balance scores (
< 0.01). The Pain scores during training reduced significantly over time in the LL-BFR group (
= 0.024), with no adverse events reported during the study.
Comparable improvements in muscle strength and hypertrophy were shown in LL-BFR and conventional training groups following in-patient rehabilitation. The LL-BFR group also achieved significant improvements in functional capacity. LL-BFR training is a rehabilitation tool that has the potential to induce positive adaptations in the absence of high mechanical loads and therefore could be considered a treatment option for patients suffering significant functional deficits for whom conventional loaded RT is contraindicated.
ISRCTN Reference: ISRCTN63585315, dated 25 April 2017.
Muscle atrophy, muscle weakness and localised pain are commonly reported following musculoskeletal injury (MSKI). To mitigate this risk and prepare individuals to return to sport or physically ...demanding occupations, resistance training (RT) is considered a vital component of rehabilitation. However, to elicit adaptations in muscle strength, exercise guidelines recommend lifting loads ≥ 70% of an individual's one repetition maximum (1-RM). Unfortunately, individuals with persistent knee pain are often unable to tolerate such high loads and this may negatively impact the duration and extent of their recovery. Low load blood flow restriction (LL-BFR) is an alternative RT technique that has demonstrated improvements in muscle strength, hypertrophy, and pain in the absence of high mechanical loading. However, the effectiveness of high-frequency LL-BFR in a residential rehabilitation environment remains unclear. This study will compare the efficacy of high frequency LL-BFR to 'conventional' heavier load resistance training (HL-RT) on measures of physical function and pain in adults with persistent knee pain.
This is a multicentre randomised controlled trial (RCT) of 150 UK service personnel (aged 18-55) admitted for a 3-week residential rehabilitation course with persistent knee pain. Participants will be randomised to receive: a) LL-BFR delivered twice daily at 20% 1-RM or b) HL-RT three-times per week at 70% 1-RM. Outcomes will be recorded at baseline (T1), course discharge (T2) and at three-months following course (T3). The primary outcome will be the lower extremity functional scale (LEFS) at T2. Secondary outcomes will include patient reported perceptions of pain, physical and occupational function and objective measures of muscle strength and neuromuscular performance. Additional biomechanical and physiological mechanisms underpinning both RT interventions will also be investigated as part of a nested mechanistic study.
LL-BFR is a rehabilitation modality that has the potential to induce positive clinical adaptations in the absence of high mechanical loads and therefore could be considered a treatment option for patients suffering significant functional deficits who are unable to tolerate heavy load RT. Consequently, results from this study will have a direct clinical application to healthcare service providers and patients involved in the rehabilitation of physically active adults suffering MSKI.
ClinicalTrials.org reference number, NCT05719922.
To evaluate the functional and mental health status of severely injured traumatic amputees from the United Kingdom military at the completion of their rehabilitation pathway and to compare these data ...with the published normative data.
Retrospective independent group comparison of descriptive rehabilitation data recorded postrehabilitation.
A military complex trauma rehabilitation center.
Amputees (N=65; mean age, 29±6y) were evaluated at the completion of their rehabilitation pathway; of these, 54 were operationally (combat) injured (23 unilateral, 23 bilateral, 8 triple) and 11 nonoperationally injured (all unilateral).
Continuous ∼4-week inpatient, physician-led, interdisciplinary rehabilitation followed by ∼4-weeks of patient-led, home-based rehabilitation.
The New Injury Severity Score at the point of injury was used as the baseline reference. The 6-minute walk test, Amputee Mobility Predictor with Prosthesis, Special Interest Group in Amputee Medicine, Defence Medical Rehabilitation Centre mobility and activity of daily living scores as well as depression (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder Scale-7), mental health support, and pain scores were recorded at discharge and compared with the published normative data.
The mean New Injury Severity Score was 40±15. After 34±14 months of rehabilitation, amputees achieved a mean 6-minute walk distance of 489±117m compared with age-matched normative distances of 459 to 738m. The 2 unilateral groups walked (544m) significantly further (P>.05) than did the bilateral amputee (445±104m) and triple amputee (387±99m) groups. All groups demonstrated mean functional mobility scores consistent with scores of either active adults or community ambulators with limb loss. In total, 85% could walk/run independently and 95% could walk and perform activities of daily living independently with an aid/adaptation. No significant difference in mental health outcome was reported between the groups (P>.05). At discharge, 98% of patients were able to control their pain.
Severely injured military amputees who completed intensive interdisciplinary rehabilitation achieved levels of physical function comparable with those in age-matched healthy adults. Mental health outcomes were indicative of preparedness for full integration back into society.
To assess the influence of the anatomical placement of a tri-axial accelerometer on the prediction of physical activity energy expenditure (PAEE) in traumatic lower-limb amputees during walking and ...to develop valid population-specific prediction algorithms.
Thirty participants, consisting of unilateral (n = 10), and bilateral (n = 10) amputees, and non-injured controls (n = 10) volunteered to complete eight activities; resting in a supine position, walking on a flat (0.48, 0.67, 0.89, 1.12, 1.34 m.s-1) and an inclined (3 and 5% gradient at 0.89 m.s-1) treadmill. During each task, expired gases were collected and an Actigraph GT3X+ accelerometer was worn on the right hip, left hip and lumbar spine. Linear regression analyses were conducted between outputs from each accelerometer site and criterion PAEE (indirect calorimetry). Mean bias ± 95% limits of agreement were calculated. Additional covariates were incorporated to assess whether they improved the prediction accuracy of regression models. Subsequent mean absolute error statistics were calculated for the derived models at all sites using a leave-one out cross-validation analysis.
Predicted PAEE at each anatomical location was significantly (P< 0.01) correlated with criterion PAEE (P<0.01). Wearing the GT3X+ on the shortest residual limb demonstrates the strongest correlation (unilateral; r = 0.86, bilateral; r = 0.94), smallest ±95% limits of agreement (unilateral; ±2.15, bilateral ±1.99 kcal·min-1) and least absolute percentage error (unilateral; 22±17%, bilateral 17±14%) to criterion PAEE.
We have developed accurate PAEE population specific prediction models in lower-limb amputees using an ActiGraph GT3X+ accelerometer. Of the 3 anatomical locations considered, wearing the accelerometer on the side of the shortest residual limb provides the most accurate prediction of PAEE with the least error in unilateral and bilateral traumatic lower-limb amputees.
To assess the validity of a derived algorithm, combining tri-axial accelerometry and heart rate (HR) data, compared to a research-grade multi-sensor physical activity device, for the estimation of ...ambulatory physical activity energy expenditure (PAEE) in individuals with traumatic lower-limb amputation.
Twenty-eight participants unilateral (n = 9), bilateral (n = 10) with lower-limb amputations, and non-injured controls (n = 9) completed eight activities; rest, ambulating at 5 progressive treadmill velocities (0.48, 0.67, 0.89, 1.12, 1.34m.s-1) and 2 gradients (3 and 5%) at 0.89m.s-1. During each task, expired gases were collected for the determination of Formula: see text and subsequent calculation of PAEE. An Actigraph GT3X+ accelerometer was worn on the hip of the shortest residual limb and, a HR monitor and an Actiheart (AHR) device were worn on the chest. Multiple linear regressions were employed to derive population-specific PAEE estimated algorithms using Actigraph GT3X+ outputs and HR signals (GT3X+HR). Mean bias±95% Limits of Agreement (LoA) and error statistics were calculated between criterion PAEE (indirect calorimetry) and PAEE predicted using GT3X+HR and AHR.
Both measurement approaches used to predict PAEE were significantly related (P<0.01) with criterion PAEE. GT3X+HR revealed the strongest association, smallest LoA and least error. Predicted PAEE (GT3X+HR; unilateral; r = 0.92, bilateral; r = 0.93, and control; r = 0.91, and AHR; unilateral; r = 0.86, bilateral; r = 0.81, and control; r = 0.67). Mean±SD percent error across all activities were 18±14%, 15±12% and 15±14% for the GT3X+HR and 45±20%, 39±23% and 34±28% in the AHR model, for unilateral, bilateral and control groups, respectively.
Statistically derived algorithms (GT3X+HR) provide a more valid estimate of PAEE in individuals with traumatic lower-limb amputation, compared to a proprietary group calibration algorithm (AHR). Outputs from AHR displayed considerable random error when tested in a laboratory setting in individuals with lower-limb amputation.
Post-traumatic OA (PTOA) can occur within 5 years after a significant injury and is a valuable paradigm for identifying biomarkers. This systematic review aims to summarise published literature in ...human studies on the associations of known serum and synovial fluid biomarkers at least a year from injury to structural, symptomatic changes and underlying PTOA processes.
A systematic review was performed using PRISMA guidelines, prospectively registered on PROSPERO (CRD42022371838), for all ‘wet’ biomarkers a year or more post-injury in 18-45-year-old participants. Three independent reviewers screened search results, extracted data, and performed risk of bias assessments (Newcastle-Ottawa Scale). Study heterogeneity meant a narrative synthesis was required utilising SWiM guidelines.
952 studies were identified, 664 remaining after deduplication. Following first-round screening, 53 studies underwent second-round screening against pre-determined criteria. Eight studies, with 879 participants (49% male), were included, measuring serum (n=7), synovial fluid (SF, n=6), or both (n=5). The pooled participant mean age was 29.1(±4). 51 biomarkers were studied (serum=38, SF=13), with no correlation between paired serum and SF samples. One serum biomarker, cartilage oligomeric matrix protein (COMP), and four SF biomarkers, interleukin (IL)-1β, IL-6, tumour necrosis factor (TNF), and COMP, were measured in multiple studies.
Associations were described between 10 biomarkers related to catabolism (n=4), anabolism (n=2), inflammation (n=3) and non-coding RNA (n=1), with OA imaging changes (X-ray and MRI), pain, quality of life and function. Widespread differences in study design and methodology prevented meta-analysis, and evidence was generally weak. A unified approach is required before widespread research and clinical biomarker use.
Mobility limitations in old age can greatly reduce quality of life, generate substantial health and social care costs, and increase mortality. Through the Retirement in Action (REACT) trial, we aimed ...to establish whether a community-based active ageing intervention could prevent decline in lower limb physical functioning in older adults already at increased risk of mobility limitation.
In this pragmatic, multicentre, two-arm, single-blind, parallel-group, randomised, controlled trial, we recruited older adults (aged 65 years or older and who are not in full-time employment) with reduced lower limb physical functioning (Short Physical Performance Battery SPPB score 4–9) from 35 primary care practices across three sites (Bristol and Bath; Birmingham; and Devon) in England. Participants were randomly assigned to receive brief advice (three healthy ageing education sessions) or a 12-month, group-based, multimodal physical activity (64 1-h exercise sessions) and behavioural maintenance (21 45-min sessions) programme delivered by charity and community or leisure centre staff in local communities. Randomisation was stratified by site and adopted a minimisation approach to balance groups by age, sex, and SPPB score, using a centralised, online, randomisation algorithm. Researchers involved in data collection and analysis were masked but participants were not because of the nature of the intervention. The primary outcome was change in SPPB score at 24 months, analysed by intention to treat. This trial is registered with ISRCTN, ISRCTN45627165.
Between June 20, 2016, and Oct 30, 2017, 777 participants (mean age 77·6 SD 6·8 years; 66% female; mean SPPB score 7·37 1·56) were randomly assigned to the intervention (n=410) and control (n=367) groups. Primary outcome data at 24 months were provided by 628 (81%) participants (294 in the control group and 334 in the intervention group). At the 24-month follow-up, the SPPB score (adjusted for baseline SPPB score, age, sex, study site, and exercise group) was significantly greater in the intervention group (mean 8·08 SD 2·87) than in the control group (mean 7·59 2·61), with an adjusted mean difference of 0·49 (95% CI 0·06–0·92; p=0·014), which is just below our predefined clinically meaningful difference of 0·50. One adverse event was related to the intervention; the most common unrelated adverse events were heart conditions, strokes, and falls.
For older adults at risk of mobility limitations, the REACT intervention showed that a 12-month physical activity and behavioural maintenance programme could help prevent decline in physical function over a 24-month period.
National Institute for Health Research Public Health Research Programme (13/164/51).
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Osteoarthritis (OA) results from various aetiologies, including joint morphology, biomechanics, inflammation, and injury. The latter is implicated in post-traumatic OA, which offers a paradigm to ...identify potential biomarkers enabling early identification and intervention. This review aims to describe imaging features associated with structural changes or symptoms at least one year following injury.
A systematic review was conducted using PRISMA guidance, prospectively registered on PROSPERO (CRD42022371838). Three independent reviewers screened titles and abstracts, followed by full-texts, performed data extraction, and risk of bias assessments (Newcastle-Ottawa Scale). Inclusion criteria included imaging studies involving human participants aged 18–45 who had sustained a significant knee injury at least a year previously. A narrative synthesis was performed using synthesis without meta-analysis methodology.
Six electronic databases and conference proceedings were searched, identifying 11 studies involving 776 participants. All studies included participants suffering an anterior cruciate ligament (ACL) injury and utilised MRI. Different, and not directly comparable, techniques were used. MRI features could be broadly divided into structural, including joint position and morphology, and compositional. Promising biomarkers for diagnosing and predicting osteoarthritis include T1rho and T2 relaxation time techniques, bone morphology changes and radiomic modelling.
As early as 12 months after injury, differences in tibia position, bone morphology, presence of effusion and synovitis, and cartilage/subchondral bone composition can be detected, some of which are linked with worse patient-reported or radiological progression. Standardisation, including MR strength, position, sequence, scoring and comparators, is required to utilise clinical and research OA imaging biomarkers fully.
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