An examination of a modified Yo-Yo test to measure intermittent running performance in rugby players

This is an Accepted Manuscript of an article published by Taylor & Francis in European Journal of Sport Science on 17/06/2018, available online: https://doi.org/10.1080/17461391.2018.1475509This study examined how starting each shuttle in the prone position altered the internal, external and perceptual responses to the Yo-Yo Intermittent Recovery Test Level 1. Using a randomized crossover design, 17 male rugby players completed the Yo-Yo IR1 and prone Yo-Yo IR1 on two separate occasions. External loads (via microtechnology), V ̇O2, heart rate (HR), rating of perceived exertion (RPE) were measured at 160, 280 and 440 m (sub-maximal) and when the test was terminated (peak). The pre-to-post change in blood lactate concentration (∆[La]b) was determined for both tests. All data were analysed using effect sizes and magnitude-based inferences. Between-trial differences (ES 90%CL) indicated total distance was most likely lower (-1.87 0.19), whereas other measures of peak external load were likely to very likely higher during the prone Yo-Yo IR1 (0.62-1.80). Sub-maximal RPE was likely to most likely higher (0.40-0.96) and peak RPE very likely higher (0.63 0.41) in the prone Yo-Yo IR1. The change in [La]b was likely higher after the prone Yo-Yo IRl. Mean HR was possibly lower at 440 m (-0.25 0.29) as was peak HR (-0.26 0.25) in the prone Yo-Yo IR1. "V" ̇E, "V" ̇O2 and "V" ̇CO2 were likely to very likely higher at 280 and 440 m (ES = 0.36-1.22), while peak values were possibly to likely higher (ES = 0.23-0.37) in the prone Yo-Yo IR1. Adopting a prone position during the Yo-Yo IR1 increases the internal, perceptual and external responses, placing greater emphasis on metabolically demanding actions typical of rugby

The influence of music genre on explosive power, repetitions to failure and mood responses during resistance exercise

Objectives: To investigate the influence of different music genres on the psychological, psychophysical and psychophysiological responses during power-based and strength-based resistance exercises. Design: Repeated-measures counterbalanced design. Method: Sixteen resistance-trained participants completed an explosive power test in the squat and bench exercises at 30% 1RM across no music, electronic dance music, metal and self-selected conditions. Peak and mean values were recorded for power and velocity. A progressive loading protocol assessed the impact of condition on repetitions to failure at 60, 70 and 80% 1RM in the squat and bench exercises. For all tests, recording of heart rate and rating of perceived exertion were completed after every set, blood lactate after protocol completion, and mood states before and after. Results: Using magnitude-based inferences, music either had no effect or a small detrimental effect on power and velocity, depending on the exercise. Repetitions to failure increased by a small to moderate amount for all music conditions compared to no music at low but not high intensities. Self-selected music provided additional small benefits in repetitions than other music conditions. Rating of perceived exertion was similar between self-selected, metal and no music conditions, whereas electronic dance music revealed higher responses. Vigour increased after all music conditions but remained unchanged in no music. Conclusions: Explosive power exercises either remain unchanged or are disadvantaged when completed to music. Various music genres could improve repetition to failure training at low to moderate intensities, although individuals might expect greatest improvements using self-selected music, without concomitant increases in perceived effort

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Azithromycin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19. Methods: In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospital with COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once per day by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatment groups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment and were twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants and local study staff were not masked to the allocated treatment, but all others involved in the trial were masked to the outcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) were eligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was 65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomly allocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall, 561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days (rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median 10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, no significant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24). Interpretation: In patients admitted to hospital with COVID-19, azithromycin did not improve survival or other prespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restricted to patients in whom there is a clear antimicrobial indication. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Mammographic surveillance in women younger than 50 years who have a family history of breast cancer: tumour characteristics and projected effect on mortality in the prospective, single-arm, FH01 study.

BACKGROUND: Evidence supports a reduction in mortality from breast cancer with mammographic screening in the general population of women aged 40-49 years, but the effect of family history is not clear. We aimed to establish whether screening affects the disease stage and projected mortality of women younger than 50 years who have a clinically significant family history of breast cancer. METHODS: In the single-arm FH01 study, women at intermediate familial risk who were younger than 50 years were enrolled from 76 centres in the UK, and received yearly mammography. Women with BRCA mutations were not explicitly excluded, but would be rare in this group. To compare the FH01 cohort with women not receiving screening, two external comparison groups were used: the control group of the UK Age Trial (106,971 women aged 40-42 years at recruitment, from the general population [ie, average risk], followed up for 10 years), and a Dutch study of women with a family history of breast cancer (cancer cases aged 25-77 years, diagnosed 1980-2004). Study endpoints were size, node status, and histological grade of invasive tumours, and estimated mortality calculated from the Nottingham prognostic index (NPI) score, and adjusted for differences in underlying risk between the FH01 cohort and the control group of the UK Age Trial. This study is registered with the National Research Register, number N0484114809. FINDINGS: 6710 women were enrolled between Jan 16, 2003, and Feb 28, 2007, and received yearly mammography for a mean of 4 years (SD 2) up until Nov 30, 2009; surveillance and reporting of cancers is still underway. 136 women were diagnosed with breast cancer: 105 (77%) at screening, 28 (21%) symptomatically in the interval between screening events, and three (2%) symptomatically after failing to attend their latest mammogram. Invasive tumours in the FH01 study were significantly smaller (p=0·0094), less likely to be node positive (p=0·0083), and of more favourable grade (p=0·0072) than were those in the control group of the UK Age Trial, and were significantly less likely to be node positive than were tumours in the Dutch study (p=0·012). Mean NPI score was significantly lower in the FH01 cohort than in the control group of the UK Age Trial (p=0·00079) or the Dutch study (p<0·0001). After adjustment for underlying risk, predicted 10-year mortality was significantly lower in the FH01 cohort (1·10%) than in the control group of the UK Age Trial (1·38%), with relative risk of 0·80 (95% CI 0·66-0·96; p=0·022). INTERPRETATION: Yearly mammography in women with a medium familial risk of breast cancer is likely to be effective in prevention of deaths from breast cancer

Follow-on rifaximin for the prevention of recurrence following standard treatment of infection with clostridium fifficile (RAPID): a randomised placebo controlled trial

©2018 The Authors. Published by BMJ. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: http://dx.doi.org/10.1136/gutjnl-2018-316794Background Clostridium difficile infection (CDI) recurs after initial treatment in approximately one in four patients. A single-centre pilot study suggested that this could be reduced using ’follow-on’ rifaximin treatment. We aimed to assess the efficacy of rifaximin treatment in preventing recurrence. Methods A multisite, parallel group, randomised, placebo controlled trial recruiting patients aged ≥18 years immediately after resolution of CDI through treatment with metronidazole or vancomycin. Participants received either rifaximin 400mg three times a day for 2weeks, reduced to 200mg three times a day for a further 2weeks or identical placebo. The primary endpoint was recurrence of CDI within 12 weeks of trial entry. Results Between December 2012 and March 2016, 151 participants were randomised to either rifaximin or placebo. Primary outcome data were available on 130. Mean age was 71.9 years (SD 15.3). Recurrence within 12 weeks was 29.5% (18/61) among participants allocated to placebo compared with 15.9% (11/69) among those allocated to rifaximin, a difference between groups of 13.7% (95% CI −28.1% to 0.7%, p=0.06). The risk ratio was 0.54 (95% CI 0.28 to 1.05, p=0.07). During 6-month safety follow-up, nine participants died in each group (12%). Adverse event rates were similar between groups. Conclusion While ’follow-on’ rifaximin after CDI appeared to halve recurrence rate, we failed to reach our recruitment target in this group of frail elderly patients, so the estimated effect of rifaximin lacks precision. A meta-analysis including a previous trial suggests that rifaximin may be effective; however, further, larger confirmatory studies are needed.The trial was sponsored by the University of Nottingham, was coordinated from the Nottingham Clinical Trials Unit and was supported by the National Institute for Health Research Clinical Research Network