An Exploratory Study of Long-Term Outcome Measures in Critical Illness Survivors: Construct Validity of Physical Activity, Frailty, and Health-Related Quality of Life Measures.

OBJECTIVE: Functional capacity is commonly impaired after critical illness. We sought to clarify the relationship between objective measures of physical activity, self-reported measures of health-related quality of life, and clinician reported global functioning capacity (frailty) in such patients, as well as the impact of prior chronic disease status on these functional outcomes. DESIGN: Prospective outcome study of critical illness survivors. SETTING: Community-based follow-up. PATIENTS: Participants of the Musculoskeletal Ultrasound Study in Critical Care: Longitudinal Evaluation Study (NCT01106300), invasively ventilated for more than 48 hours and on the ICU greater than 7 days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Physical activity levels (health-related quality of life [36-item short-form health survey] and daily step counts [accelerometry]) were compared to norm-based or healthy control scores, respectively. Controls for frailty (Clinical Frailty Score) were non-morbid, age- and gender-matched to survivors. Ninety-one patients were recruited on ICU admission: 41 were contacted for post-discharge assessment, and data were collected from 30 (14 female; mean age, 55.3 yr [95% CI, 48.3-62.3]; mean post-discharge, 576 d [95% CI, 539-614]). Patients' mean daily step count (5,803; 95% CI, 4,792-6,813) was lower than that in controls (11,735; 95% CI, 10,928-12,542; p < 0.001), and lower in those with preexisting chronic disease than without (2,989 [95% CI, 776-5,201] vs 7,737 [95% CI, 4,907-10,567]; p = 0.013). Physical activity measures (accelerometry, health-related quality of life, and frailty) demonstrated good construct validity across all three tools. Step variability (from SD) was highly correlated with daily steps (r = 0.67; p < 0.01) demonstrating a potential boundary constraint. CONCLUSIONS: Subjective and objective measures of physical activity are all informative in ICU survivors. They are all reduced 18 months post-discharge in ICU survivors, and worse in those with pre-admission chronic disease states. Investigating interventions to improve functional capacity in ICU survivors will require stratification based on the presence of premorbidity.

Arthroplasty in the Valgus Knee: Comparison and Discussion of Lateral vs Medial Parapatellar Approaches and Implant Selection.

Constrained implants are frequently used for primary total knee arthroplasty (TKA) in patients with moderate and severe genu-valgum (>10˚). This deformity presents corrective challenges for ligament release. The lateral-parapatellar approach has been advocated as an alternative to the traditional medial-parapatellar approach. Claimed advantages include better access for release of tight ligamentous structures, without requirement for release of the medial-collateral ligament. We present our comparative experience of the use of an unconstrained knee-replacement prosthesis inserted by the lateral-parapatellar approach in comparison to a constrained-knee prosthesis inserted via the medial-parapatellar approach. 49 primary total knee-replacements in 48 (6 males, 42 females) patients were performed; 32 through a lateral-parapatellar approach (group L) using an unconstrained-prosthesis and 17 through a medial-parapatellar approach more often requiring a constrained-prosthesis (group M). Mean preoperative valgus angle was 18.5 (range 11-34˚). Patient demographics (p=0.7) and valgus correctability were similar between the two groups. There was no significant difference in the mean post-operative valgus angle. This was 4.2˚ (range 1-9.5˚) using the lateral-parapatellar approach and 5.3˚ (range 0.3-10˚), p=0.12, using the medial-parapatellar approach. Transient common peroneal injury occurred in 2 patients, both group L, in the presence of valgus angles of greater than 20˚. To date no joints have been revised, or are unstable. The use of a lateral-parapatellar approach, appropriate soft tissue release, and an unconstrained PCL-preserving implant, yielded in all cases a stable, well aligned knee arthroplasty. This represents a viable alternative to the constrained-prosthesis using a medial-parapatellar approach in patients with moderate and severe genu-valgum.

The relationship between lower limb bone and muscle in military recruits, response to physical training, and influence of smoking status.

UNLABELLED: The relationship between bone and skeletal muscle mass may be affected by physical training. No studies have prospectively examined the bone and skeletal muscle responses to a short controlled exercise-training programme. We hypothesised that a short exercise-training period would affect muscle and bone mass together. METHODS: Femoral bone and Rectus femoris Volumes (RFVOL) were determined by magnetic resonance imaging in 215 healthy army recruits, and bone mineral density (BMD) by Dual X-Ray Absorptiometry (DXA) and repeated after 12 weeks of regulated physical training. RESULTS: Pre-training, RFVOL was smaller in smokers than non-smokers (100.9 ± 20.2 vs. 108.7 ± 24.5, p = 0.018; 96.2 ± 16.9 vs. 104.8 ± 21.3, p = 0.002 for dominant/non-dominant limbs), although increases in RFVOL with training (of 14.2 ± 14.5% and 13.2 ± 15.6%] respectively, p < 0.001) were independent of prior smoking status. Pre-training RFVOL was related to bone cortical volume (r(2) = 0.21 and 0.30, p < 0.001 for dominant and non-dominant legs), and specifically to periosteal (r(2) = 0.21 and 0.23, p < 0.001) volume. Pre-training dominant RFVOL was independently associated with Total Hip BMD (p < 0.001). Training-related increases in RFVOL and bone volumes were related. Whilst smokers demonstrated lower muscle mass than non-smokers, differences were abolished with training. Training-related increases in muscle mass were related to increases in periosteal bone volume in both dominant and non-dominant legs.

Genetic influences in sport and physical performance.

The common inheritance of approximately 20 000 genes defines each of us as human. However, substantial variation exists between individual human genomes, including 'replication' of gene sequences (copy number variation, tandem repeats), or changes in individual base pairs (mutations if <1% frequency and single nucleotide polymorphisms if >1% frequency). A vast array of human phenotypes (e.g. muscle strength, skeletal structure, tendon elasticity, and heart and lung size) influences sports performance, each itself the result of a complex interaction between a myriad of anatomical, biochemical and physiological systems. This article discusses the role for genetic influences in influencing sporting performance and injury, offering specific exemplars where these are known. Many of these preferable genotypes are uncommon, and their combination even rarer. In theory, the chances of an individual having a perfect sporting genotype are much lower than 1 in 20 million - as the number of associated polymorphisms increase, the odds decrease correspondingly. Many recently discovered polymorphisms that may affect sports performance have been described in animal or other human based models, and have been included in this review if they may apply to athletic populations. Muscle performance is heavily influenced by basal muscle mass and its dynamic response to training. Genetic factors account for approximately 50-80% of inter-individual variation in lean body mass, with impacts detected on both 'training-naive' muscle mass and its growth response. Several cytokines such as interleukin-6 and -15, cilliary neurotrophic factor and insulin-like growth factor (IGF) have myoanabolic effects. Genotype-associated differences in endocrine function, necessary for normal skeletal muscle growth and function, may also be of significance, with complex interactions existing between thyroxine, growth hormone and the downstream regulators of the anabolic pathways (such as IGF-1 and IGF-2). Almost 200 polymorphisms are known to exist in the vitamin D receptor (VDR) gene. VDR genotype is associated with differences in strength in premenopausal women. VDR expression decreases with age and VDR genotype is associated with fat-free mass and strength in elderly men and women. Muscle fibre type determination is complex. Whilst initial composition is likely to be strongly influenced by genetic factors, training has significant effects on fibre shifts. Polymorphisms of the peroxisome proliferator-activated receptor α (PPARα) gene and R577x polymorphism of the ACTN3 gene are both associated with specific fibre compositions. Alterations in cardiac size have been associated with both increased performance and excess cardiovascular mortality. PPARα is a ligand-activated transcription factor that regulates genes involved in fatty acid uptake and oxidation, lipid metabolism and inflammation. Psychology plays an important role in training, competition, tolerance of pain and motivation. However, the role of genetic variation in determining psychological state and responses remains poorly understood; only recently have specific genes been implicated in motivational behaviour and maintenance of exercise. Thyroid hormone receptors exist within the brain and influence both neurogenesis and behaviour. With the current state of knowledge, the field of genetic influences on sports performance remains in its infancy, despite over a decade of research.

The ACE gene and human performance: 12 years on.

Some 12 years ago, a polymorphism of the angiotensin I-converting enzyme (ACE) gene became the first genetic element shown to impact substantially on human physical performance. The renin-angiotensin system (RAS) exists not just as an endocrine regulator, but also within local tissue and cells, where it serves a variety of functions. Functional genetic polymorphic variants have been identified for most components of RAS, of which the best known and studied is a polymorphism of the ACE gene. The ACE insertion/deletion (I/D) polymorphism has been associated with improvements in performance and exercise duration in a variety of populations. The I allele has been consistently demonstrated to be associated with endurance-orientated events, notably, in triathlons. Meanwhile, the D allele is associated with strength- and power-orientated performance, and has been found in significant excess among elite swimmers. Exceptions to these associations do exist, and are discussed. In theory, associations with ACE genotype may be due to functional variants in nearby loci, and/or related genetic polymorphism such as the angiotensin receptor, growth hormone and bradykinin genes. Studies of growth hormone gene variants have not shown significant associations with performance in studies involving both triathletes and military recruits. The angiotensin type-1 receptor has two functional polymorphisms that have not been shown to be associated with performance, although studies of hypoxic ascent have yielded conflicting results. ACE genotype influences bradykinin levels, and a common gene variant in the bradykinin 2 receptor exists. The high kinin activity haplotye has been associated with increased endurance performance at an Olympic level, and similar results of metabolic efficiency have been demonstrated in triathletes. Whilst the ACE genotype is associated with overall performance ability, at a single organ level, the ACE genotype and related polymorphism have significant associations. In cardiac muscle, ACE genotype has associations with left ventricular mass changes in response to stimulus, in both the health and diseased states. The D allele is associated with an exaggerated response to training, and the I allele with the lowest cardiac growth response. In light of the I-allele association with endurance performance, it seems likely that other regulatory mechanisms exist. Similarly in skeletal muscle, the D allele is associated with greater strength gains in response to training, in both healthy individuals and chronic disease states. As in overall performance, those genetic polymorphisms related to the ACE genotype, such as the bradykinin 2 gene, also influence skeletal muscle strength. Finally, the ACE genotype may influence metabolic efficiency, and elite mountaineers have demonstrated an excess of I alleles and I/I genotype frequency in comparison to controls. Interestingly, this was not seen in amateur climbers. Corroboratory evidence exists among high-altitude settlements in both South America and India, where the I allele exists in greater frequency in those who migrated from the lowlands. Unfortunately, if the ACE genotype does influence metabolic efficiency, associations with peak maximal oxygen consumption have yet to be rigorously demonstrated. The ACE genotype is an important but single factor in the determinant of sporting phenotype. Much of the mechanisms underlying this remain unexplored despite 12 years of research.