Training and match load in professional rugby union: Do contextual factors influence the training week?

Background: Rugby union demands a multifaceted approach to training, given the multiple physical and technical attributes required to play the sport. Objectives: The aim of this study is to describe the distribution of training throughout the week and investigate how this may be influenced by match-related factors. Methods: Training load data (session Rating of Perceived Exertion [sRPE], total distance and high-speed running [HSR]) were collected from six professional English rugby teams during the 2017/18 season. Five contextual factors were also recorded including: standard of opposition, competition type, result of previous fixture, surface type, and match venue. Results: The day prior to matches demonstrated the lowest training load (101 AU (95% CIs: 0-216 AU), 1 047 m (95% CIs:1 128-1 686 m) and 59 m (95% CIs: 0-343 m), respectively), while four days prior to the match demonstrated the highest training load (464 AU (95% CIs: 350-578), 2 983 m (95% CIs: 2 704-3 262m) and 234m (95% CIs: 0-477m), respectively). Of the five contextual factors, competition type was the only variable that demonstrated greater than trivial findings, with training before European fixtures the lowest stimulus across the four different competition types. Standard of opposition, previous result, surface type and venue had only trivial effects on training load (effect sizes = -0.13 to 0.15). Conclusion: Future studies should outline the distribution of other training metrics, including contact and collision training. This study provides a multi-club evaluation that demonstrates the variety of loading strategies prior to competitive match play and highlights competition type as the most influential contextual factor impacting the average training load.

Strategies used by professional rugby union clubs to manage players for artificial turf exposure.

Background: The use of artificial turf on rugby pitches is increasingly commonplace but there is limited evidence around its effects on injury, recovery, and performance. It is unclear whether this uncertainty influences player management strategies in professional clubs. Objectives: To understand how professional rugby union clubs in England approach player management for artificial turf, to explore how the beliefs of medical and strength/conditioning staff influence these decisions, and to determine whether differences exist between clubs with different levels of exposure to artificial surfaces. Methods: The study was a cross-sectional mixed methods study. Twenty-three medical and strength/conditioning staff members from 12 English Premiership Rugby Union clubs completed two bespoke questionnaires and participated in a semi-structured interview. Results: Two-thirds of the participants described formal club-level approaches to artificial turf. All participants from low-exposure clubs (<50% training and match time on artificial pitches) reported adjusting player recovery strategies following games on artificial turf to mitigate elevated muscle soreness and fatigue. Clubs with artificial surfaces at their home venues were less likely to adapt recovery than clubs with natural turf pitches. Regardless of exposure participants believed switching between surface types was a risk factor for injury. Medics reported that acute injuries associated with artificial turf exposure typically occurred at the foot or ankle, whereas abrasions and overuse injuries were more common and often affected the knees, hips and lower back. Players with compromised joints were less likely to be selected for matches on artificial surfaces. Conclusion: Player management around artificial turf is a focus for staff at professional rugby union clubs. Club practices vary by exposure and may consequently influence injury risk estimates.

Differences and similarities between ankylosing spondylitis and rheumatoid arthritis: epidemiology.

Ankylosing spondylitis (AS) and rheumatoid arthritis (RA) are among the most common rheumatic diseases. The epidemiology of these diseases highlights both similarities and differences. Prevalence rates of approximately 0.2-1% have been reported for the diseases, but the rate for AS is increasing while RA is declining. Geographical variations exist in the incidence and prevalence of the diseases, although the majority of studies have been conducted in northern Europe and North America. AS is a predominantly a male disorder, whereas more females are affected by RA. Both diseases result in increased disability, reduced work productivity, and increased mortality rates. These similarities and differences may give us important clues as to the aetiology of both diseases.

Costs and outcomes of total hip and knee joint replacement for rheumatoid arthritis.

The objective of the study was to ascertain costs and outcomes of total joint replacement surgery for rheumatoid arthritis (RA) in Australia from the patients' perspective and to explore whether costs were affected by health status pre- or postsurgery. RA patients, scheduled for primary unilateral total knee replacement (TKR) or total hip replacement (THR) surgery at five Sydney hospitals, were approached. Preoperatively, patients retrospectively recorded expenses incurred over the previous 3 months and the health assessment questionnaire (HAQ). Postoperatively, patients completed detailed prospective cost diaries, short form (SF) 36, and HAQ every 3 months during the first postoperative year. In addition, patients were asked to complete a visual analogue measure for pain at 12 months postsurgery. Arthritis-specific cost information included prescription and nonprescription medication, visits to health professionals, tests, special equipment, alterations to the house, and use of private or community services. Thirty-one TKR and 11 THR patients provided cost data for the first postoperative year. Out-of-pocket costs and service utilization decreased over the first postoperative year for both TKR and THR patients. In addition, there was an improvement in the health status as measured by SF-36 but not the HAQ at 3 and 12 months postoperatively. The small sample size of this analysis is reflective of the current national trends of RA joint replacement surgery. Despite the low incidence of RA joint replacement surgery, it was substantiated that patients consider the positive impact on health outcomes and costs important. The generic SF-36 detected improvements in the health status of these RA patients, while total HAQ scores failed to do so. HAQ was found to be insensitive in reflecting improvements following lower limb replacement surgery. Patient out-of-pocket costs significantly decreased postoperatively; however, these costs remain substantial compared to osteoarthritis total joint replacement patients.

Stimulation of actin stress fibre formation mediated by activation of phospholipase D.

BACKGROUND: Agonist-stimulated phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine, generating the putative messenger phosphatidate (PA). Proposed functions for PA, and hence for PLD, include kinase activation, the regulation of small molecular weight GTP-binding proteins, actin polymerization and secretion. It has not been possible to define a physiological function for PLD activation as it is generally stimulated together with other signalling pathways, such as those involving phospholipases A2 and C, phosphatidylinositide (PI) 3-kinase and the p21(ras)/mitogen-activated protein (MAP) kinase cascade. RESULTS: We report that, in porcine aortic endothelial (PAE) cells, lysophosphatidic acid (LPA) stimulated PLD activity and rapidly generated PA in the absence of other phospholipase, PI 3-kinase or MAP kinase activities. PLD activation was controlled by a tyrosine kinase-regulated pathway. LPA also stimulated actin stress fibre formation, but was inhibited by butan-1-ol; the alcohol also reduced the accumulation of PA. The addition of PA to cells did not stimulate PLD activity, but did cause stress fibre formation in a manner that was insensitive to butan-1-ol. Stimulation of stress fibre formation by LPA and PA was sensitive to genistein, and was inhibited by micro-injection of the Rho-inhibiting C3 exotoxin into PAE cells. CONCLUSIONS: This study provides the first clear demonstration of a physiological role for PLD activity. In PAE cells, the stimulation of actin stress fibre formation was a consequence of PA generation and, therefore, PLD activation. The results suggest that PA generation is upstream of Rho activation, and imply a role for PLD in the regulation of Rho-mediated pathways.

G protein-coupled receptor-mediated mitogen-activated protein kinase activation through cooperation of Galpha(q) and Galpha(i) signals.

G protein-coupled receptors (GPCRs) have been shown to stimulate extracellular regulated kinases (ERKs) through a number of linear pathways that are initiated by G(q/11) or G(i) proteins. We studied signaling to the ERK cascade by receptors that simultaneously activate both G protein subfamilies. In HEK293T cells, bradykinin B(2) receptor (B(2)R)-induced stimulation of ERK2 and transcriptional activity of Elk1 are dependent on Galpha(q)-mediated protein kinase C (PKC) and on Galpha(i)-induced Ras activation, while they are independent of Gbetagamma subunits, phosphatidylinositol 3-kinase, and tyrosine kinases. Similar results were obtained with m(1) and m(3) muscarinic receptors in HEK293T cells and with the B(2)R in human and mouse fibroblasts, indicating a general mechanism in signaling toward the ERK cascade. Furthermore, the bradykinin-induced activation of ERK is strongly reduced in Galpha(q/11)-deficient fibroblasts. In addition, we found that constitutively active mutants of Galpha(q/11) or Galpha(i) proteins alone poorly stimulate ERK2, whereas a combination of both led to synergistic effects. We conclude that dually coupled GPCRs require a cooperation of Galpha(i)- and G(q/11)-mediated pathways for efficient stimulation of the ERK cascade. Cooperative signaling by multiple G proteins thus might represent a novel concept implicated in the regulation of cellular responses by GPCRs.

Osteochondritis dissecans of the knee; long-term clinical outcome following arthroscopic debridement.

We reviewed 32 knees in 26 patients who had previously undergone arthroscopic debridement for symptomatic osteochondritis dissecans (OCD) of the knee. The patients were followed up at a minimum of 11 years following surgery and were evaluated clinically using the American Knee Society Clinical Rating Score. Additional evaluation was performed using the Hughston Scale to include radiographic assessment. The mean American Knee Society Score was 179 (out of 200), indicating good clinical function. Radiographically, however, only 29% scored excellent or good on the Hughston Scale. Younger patients with a small, stable (and therefore preserved), medial femoral condyle lesion had the best prognosis. Whilst more novel and complex options such as chondrocyte implantation are being assessed for the treatment of OCD, it is clear that within this study group careful debridement with removal of loose tissue can achieve good clinical results in the long term. There was however radiographic evidence of early degenerative joint disease in 17/24 (71%) of patients reviewed. Patients undergoing excision of OCD fragments did worse than those in whom the fragment was preserved, however the risk of further surgery is raised if a fragment is left in situ at initial surgery.

Five- to 12-year follow-up of a hydroxyapatite-coated, cementless total knee replacement in young, active patients.

We carried out a prospective study of 118 hydroxyapatite-coated, cementless total knee replacements in patients who were

A comparison of bilateral uncemented total knee arthroplasty: simultaneous or staged?

In a series of 1304 patients (1867 knees), the results of simultaneous and staged bilateral total knee arthroplasty were compared with each other and with unilateral total knee arthroplasty. The bilateral procedures had a significantly higher rate of complications than unilateral procedures, almost entirely because of thromboembolic problems. However, this did not correspond to an increase in mortality. If a bilateral procedure was indicated, then a simultaneous procedure had no increased risk over a staged procedure. There was no increase in cardiovascular complications, the rate of deep-vein thrombosis or pulmonary embolism or mortality. The rate of infection was lower with a bilateral procedure and the overall revision rate was less than 1% in all groups. The prosthesis functioned as well in all groups in the medium and longer term periods. We feel that simultaneous bilateral total knee arthroplasty is a safe and successful procedure when compared with a staged bilateral procedure. It also has the added benefit of single anaesthetic, reduced costs and decreased total recovery time when compared to a staged bilateral procedure. For these reasons it should be considered as an option in the presence of bilateral knee joint disease.

Inhibition of phospholipid signalling and proliferation of Swiss 3T3 cells by the wortmannin analogue demethoxyviridin.

Growth factors and certain oncogenes activate a range of phospholipid-mediated signal transduction pathways resulting in cell proliferation. Demethoxyviridin (DMV), a structural analogue of wortmannin and recently reported as a potent inhibitor of phosphoinositide-3-kinase, inhibited bombesin plus insulin-stimulated increase in cell number in Swiss 3T3 cells, a model of cell proliferation. The drug produced cytostatic effects at concentrations below 1 microM and cytotoxic effects at 10 microM. In intact Swiss 3T3 cells DMV inhibited insulin-stimulated PI 3- and 4-kinases and bombesin-stimulated phospholipases C, D and A2 in the nanomolar range. DMV also inhibited bombesin-stimulated tyrosine phosphorylation of a range of proteins at nM concentrations. This study shows that DMV inhibited multiple stimulated signalling pathways which lead to increased Swiss 3T3 cell proliferation. A stable analogue of DMV may have chemotherapeutic potential.

FGF and VEGF function in angiogenesis: signalling pathways, biological responses and therapeutic inhibition.

Angiogenic growth factors such as fibroblast growth factors (FGFs) and vascular endothelial growth factors (VEGFs) are currently targets of intense efforts to inhibit deregulated blood vessel formation in diseases such as cancer. FGFs and VEGFs exert their effects via specific binding to cell surface-expressed receptors equipped with tyrosine kinase activity. Activation of the receptor kinase activity allows coupling to downstream signal transduction pathways that regulate proliferation, migration and differentiation of endothelial cells. Inhibitors of FGF and VEGF signalling are currently in clinical trials. In this article, the current knowledge of FGF- and VEGF-induced signal transduction that leads to specific biological responses will be summarized. Furthermore, the manner in which this knowledge is being exploited to regulate angiogenesis will be discussed.

A hydroxyapatite-coated total knee replacement: prospective analysis of 1000 patients.

We prospectively reviewed 1000 consecutive patients who underwent a cementless, hydroxyapatite-coated, stemless, total knee replacement over a period of nine years. Regular post-operative clinical follow-up was performed using the Knee Society score. The mean pre-operative score was 96, improving to 182 and 180 at five and ten years, respectively. To date, there have been seven (0.5%) cases which required revision, primarily for septic loosening (four cases), with low rates of other post-operative complications. The cumulative survival at ten years with revision as the end-point, was 99.14% (95% confidence interval 92.5 to 99.8). These results support the use of hydroxyapatite in a cementless total knee replacement since it can give reliable fixation with an excellent clinical and functional outcome.

Results of open arthrolysis for the treatment of stiffness after total knee replacement.

Stiffness is an uncommon but potentially debilitating complication following total knee replacement (TKR). The treatment of this condition remains difficult and controversial. We present the results of 13 patients who underwent open arthrolysis for stiffness. The mean time between TKR and arthrolysis was 14 months. The mean follow-up was 7.2 years (2 to 10). The mean range of movement prior to arthrolysis was 55 degrees . This increased to 91 degrees , six months after arthrolysis (p < 0.005). The improved range of movement was maintained during the follow-up period. No patient has required revision of their components. We have found arthrolysis to be a useful and successful approach to post-TKR stiffness.

The Impact of Fracture Incidence on Health Related Quality of Life among Community-Based Postmenopausal Women.

This prospective study aimed to examine the impact of fracture incidence on health-related quality of life (HRQOL) among postmenopausal women. Study subjects were Australian female community-dwellers in the Global Longitudinal Study of Osteoporosis in Women (GLOW). Self-administered questionnaires were collected annually from 2007 to 2010. Outcomes were the Medical Outcomes Study Short Form-36 (SF-36 physical function (SF36PFS) and vitality (SF36VS) scores), European Quality of Life (EQ-5D), and self-reported general health (GH) of excellent/good. Questionnaires were divided into prior to, the 1st, the 2nd, and the 3rd year after incident fracture assessments. Generalized linear models with generalised estimating equations (GEE) were employed for the analysis. The 2,872 participants (age: median 65; interquartile range 60-73 years) provided a total of 10,436 assessments including 266, 165 and 76 assessments for the 1st, the 2nd, and the 3rd year after incident fracture, respectively. Multivariate adjustments showed reductions in HRQOL measures peaking at the 1st year for SF36VS (coefficient -3.0; 95% CI: -5.1, -0.8) and EQ-5D (coefficient -0.03; 95% CI: -0.06, -0.00) and at the 2nd year for SF36PFS (coefficient -3.0; 95% CI: -5.6, -0.5) and GH (odds ratio 0.92; 95% CI: 0.70, 1.19). Fracture incidence reduced HRQOL including vitality and physical function among relatively young, healthy postmenopausal women and the reduction in European Quality of Life measure was clinically important.

Physiological, pharmacological and toxicological considerations of drug-induced structural cardiac injury.

The incidence of drug-induced structural cardiotoxicity, which may lead to heart failure, has been recognized in association with the use of anthracycline anti-cancer drugs for many years, but has also been shown to occur following treatment with the new generation of targeted anti-cancer agents that inhibit one or more receptor or non-receptor tyrosine kinases, serine/threonine kinases as well as several classes of non-oncology agents. A workshop organized by the Medical Research Council Centre for Drug Safety Science (University of Liverpool) on 5 September 2013 and attended by industry, academia and regulatory representatives, was designed to gain a better understanding of the gaps in the field of structural cardiotoxicity that can be addressed through collaborative efforts. Specific recommendations from the workshop for future collaborative activities included: greater efforts to identify predictive (i) preclinical; and (ii) clinical biomarkers of early cardiovascular injury; (iii) improved understanding of comparative physiology/pathophysiology and the clinical predictivity of current preclinical in vivo models; (iv) the identification and use of a set of cardiotoxic reference compounds for comparative profiling in improved animal and human cellular models; (v) more sharing of data (through publication/consortia arrangements) on target-related toxicities; (vi) strategies to develop cardio-protective agents; and (vii) closer interactions between preclinical scientists and clinicians to help ensure best translational efforts.

Role and regulation of phospholipase D activity in normal and cancer cells.

PLD is regulated by the small GTP binding proteins Rho and Arf, though predominantly by the latter. The PA product of PLD activation is an activator of Rho-regulated actin stress fibre formation and in invasive cells of MMP-9 synthesis and activation. Together this may explain the increased invasion of cells in response to PA.

Subareolar injection is a better technique for sentinel lymph node biopsy.

BACKGROUND: Numerous techniques and materials show accuracy in localizing the sentinel lymph node (SLN). We hypothesized that subareolar injection of material would localize the SLN as effectively as peritumoral injection. METHODS: Thirty-eight patients were injected with technetium-99 sulfur colloid either peritumorally or subareolarly in addition to the injection of blue dye around the tumor. Radioactive SLNs were localized using a hand-held gamma probe. RESULTS: Nineteen patients were included in each of the two groups, peritumoral and subareolar. SLNs were found in all patients injected subareolarly and in 18 of 19 injected peritumorally. The false-negative rate was 20% for peritumoral injection and 0% for subareolar injection. CONCLUSION: The results suggest that subareolar injection was as accurate, if not more accurate, than peritumoral injection for localizing the SLN. This technique is simpler than peritumoral injection and does not require injection under image guidance for nonpalpable lesions.

New horizons in the diagnosis and treatment of breast cancer using magnetic resonance imaging.

A new nuclear magnetic resonance imaging (MRI) technique, Rotating Delivery of Excitation Off-resonance (RODEO), has been developed to assist surgeons in the diagnosis and treatment of breast cancer. A nonrandomized, prospective study of 100 patients with a high suspicion of breast cancer was conducted; these patients were examined by RODEO and conventional breast imaging, including mammography. Forty-one breasts were removed by mastectomy; each pathologic specimen was examined by sectional analysis. This study was undertaken to determine the extent that RODEO can aid in detecting breast tumors (including multicentric disease) and in evaluating candidates for conservative breast surgery. RODEO detected 85 pathologically confirmed lesions, 64 of which proved to be malignant. RODEO had a sensitivity of 95%, compared with a sensitivity of 58% for conventional imaging. More study is needed to determine distinguishing MRI characteristics that are suspicious for malignancy. RODEO may be used clinically to assess multicentricity and response to chemotherapy.

Classification of knee ligament instabilities. Part I. The medial compartment and cruciate ligaments.

Based on the clinical and operative findings in sixty-eight knees with acute tears of the medial compartment and cruciate ligaments, a standardized terminology and classification of knee ligament instability is presented. With an intact posterior cruciate ligament, anteromedial, anterolateral, or posterolateral rotatory instability may occur, but not true posteromedial rotatory instability. With the posterior cruciate ligament ruptured, straight anterior, posterior, medial, or lateral instability may be found.

Classification of knee ligament instabilities. Part II. The lateral compartment.

Lateral instability of the knee is less frequent but more disabling than medial instability of a comparable amount. At the same time the diagnostic tests for lateral instability are more subtle and more frequently misinterpreted. Posterolateral rotatory subluxation is demonstrated by an apparently positive posterior drawer test with the tibia in neutral rotation or by the external rotation-recurvatum test with the knee in extension. Anterolateral rotatory subluxation is present when the anterior drawer test with the tibia in neutral rotation demonstrates that the lateral tibial condyle appears to become more prominent or that both condyles appear to become equally prominent.