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Although relative age effects in sports have been studied worldwide, the underlying mechanisms are still under debate. This study adds to the existing knowledge by providing a further exploration of the within-year and between-year effects and their possible interaction in an individual skill/technique based sport: table tennis. Data of male and female elite players across ages (U15, U18, U21, and senior) were collected from the ranking lists in international (world and Europe) and national contexts (France and the Netherlands). A multi-way frequency analysis per subsample revealed (1) no interaction effects; (2) significant within-year and between-year effects for the U15 players in the international context and male French players; (3) a significant within-year effect in the French U18 category; (4) a significant within-year effect in female European U21; and (5) no within-year effects in the senior category. Table tennis seems to be at risk for within-year and between-year effects specifically within the context of high competitive level for younger players (U15, males, and females), but not for interactions between these effects. Future research should reveal the development of the RAEs over time in a longitudinal study, evaluate influencing constraints, and innovative prevention solutions in a more comprehensive way.

The phase 3 NCT00793962 trial demonstrated that postmastectomy hypofractionated radiation therapy (HFRT) was noninferior to conventional fractionated radiation therapy (CFRT) in patients with high-risk breast cancer. This study assessed the cost-effectiveness of postmastectomy HFRT vs CFRT based on the NCT00793962 trial. A Markov model was adopted to synthesize the medical costs and health benefits of patients with high-risk breast cancer based on data from the NCT00793962 trial. Main outcomes were discounted lifetime costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). We employed a time-dependent horizon from Chinese, French and USA payer perspectives. Model robustness was evaluated with one-way and probabilistic sensitivity analyses. Patients receiving CFRT versus HFRT gained an incremental 0.0163 QALYs, 0.0118 QALYs and 0.0028 QALYs; meanwhile an incremental cost of $2351.92, $4978.34 and $8812.70 from Chinese, French and USA payer perspectives, respectively. Thus CFRT versus HFRT yielded an ICER of $144,281.47, $420,636.10 and $3,187,955.76 per QALY from Chinese, French and USA payer perspectives, respectively. HFRT could maintain a trend of >50% probabilities of cost-effectiveness below a willingness-to-pay (WTP) of $178,882.00 in China, while HFRT was dominant relative to CFRT, regardless of the WTP values in France and the USA. Sensitivity analyses indicated that the ICERs were most sensitive to the parameters of overall survival after radiotherapy. Postmastectomy HFRT could be used as a cost-effective substitute for CFRT in patients with high-risk breast cancer and should be considered in appropriately selected patients. • HFRT is a cost-effective substitute for CFRT for women with high-risk breast cancer. • The incremental cost-effectiveness ratio varied in a time-dependent manner and increased with the time horizon. • Overall survival were the most influential parameter on the incremental cost-effectiveness ratio. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus remains a common cause of ventilator-associated pneumonia, with little change in incidence over the past 15 years. We aimed to evaluate the efficacy of suvratoxumab, a monoclonal antibody targeting the α toxin, in reducing the incidence of S aureus pneumonia in patients in the intensive care unit (ICU) who are on mechanical ventilation., Methods: We did a multicentre, randomised, double-blind, placebo-controlled, parallel-group, phase 2 pilot trial at 31 hospitals in Belgium, the Czech Republic, France, Germany, Greece, Hungary, Portugal, Spain, and Switzerland. Eligible patients were in the ICU, aged ≥18 years, were intubated and on mechanical ventilation, were positive for S aureus colonisation of the lower respiratory tract, as assessed by quantitative PCR (qPCR) analysis of endotracheal aspirate, and had not been diagnosed with new-onset pneumonia. Patients were excluded if they had confirmed or suspected acute ongoing staphylococcal disease; had received antibiotics for S aureus infection for more than 48 h within 72 h of randomisation; had a Clinical Pulmonary Infection Score of 6 or higher; had an acute physiology and chronic health evaluation II score of 25 or higher with a Glasgow coma scale (GCS) score of more than 5, or an acute physiology and chronic health evaluation II score of at least 30 with a GCS score of 5 or less; had a Sequential Organ Failure Assessment score of 9 or higher; or had active pulmonary disease that would impair the ability to diagnose pneumonia. Colonised patients were randomly assigned (1:1:1), by use of an interactive voice or web response system, to receive either a single intravenous infusion of suvratoxumab 2000 mg, suvratoxumab 5000 mg, or placebo. Randomisation was done in blocks of size four, stratified by country and by whether patients had received systemic antibiotics for S aureus infection. Patients, investigators, and study staff involved in the treatment or clinical evaluation of patients were masked to patient assignment. The primary efficacy endpoint was the incidence of S aureus pneumonia at 30 days, as determined by a masked independent endpoint adjudication committee, in all patients who received their assigned treatment (modified intention-to-treat [ITT] population). Primary safety endpoints were the incidence of treatment-emergent adverse events at 30 days, 90 days, and 190 days after treatment, and the incidence of treatment-emergent serious adverse events, adverse events of special interest, and new-onset chronic disease at 190 days after treatment. All primary safety endpoints were assessed in the modified ITT population. This trial is registered with ClinicalTrials.gov (NCT02296320) and the EudraCT database (2014-001097-34)., Findings: Between Oct 10, 2014, and April 1, 2018, 767 patients were screened, of whom 213 patients with confirmed S aureus colonisation of the lower respiratory tract were randomly assigned to the suvratoxumab 2000 mg group (n=15), the suvratoxumab 5000 mg group (n=96), or the placebo group (n=102). Two patients in the placebo group did not receive treatment after randomisation because their clinical conditions changed and they no longer met the eligibility criteria for dosing. As adjudicated by the data monitoring committee at an interim analysis, the suvratoxumab 2000 mg group was discontinued on the basis of predefined pharmacokinetic criteria. At 30 days after treatment, 17 (18%) of 96 patients in the suvratoxumab 5000 mg group and 26 (26%) of 100 patients in the placebo group had developed S aureus pneumonia (relative risk reduction 31·9% [90% CI -7·5 to 56·8], p=0·17). The incidence of treatment-emergent adverse events at 30 days were similar between the suvratoxumab 5000 mg group (87 [91%]) and the placebo group (90 [90%]). The incidence of treatment-emergent serious adverse events at 30 days were also similar between the suvratoxumab 5000 mg group (36 [38%]) and the placebo group (32 [32%]). No significant difference in the incidence of treatment-emergent adverse events between the two groups at 90 days (89 [93%] in the suvratoxumab 5000 mg group vs 92 [92%] in the placebo group) and at 190 days (93 [94%] vs 93 [93%]) was observed. 40 (40%) patients in the placebo group and 50 (52%) in the suvratoxumab 5000 mg group had a serious adverse event at 190 days. In the suvratoxumab 5000 mg group, one (1%) patient reported at least one treatment-emergent serious adverse event related to treatment, two (2%) patients reported an adverse event of special interest, and two (2%) reported a new-onset chronic disease., Interpretation: In patients in the ICU receiving mechanical ventilation with qPCR-confirmed S aureus colonisation of the lower respiratory tract, the incidence of S aureus pneumonia at 30 days was not significantly lower following treatment with 5000 mg suvratoxumab than with placebo. Despite these negative results, monoclonal antibodies still represent one promising therapeutic option to reduce antibiotic consumption that require further exploration and studies., Funding: AstraZeneca, with support from the Innovative Medicines Initiative Joint Undertaking., Competing Interests: Declaration of interests BF reports personal fees from AM-Pharma, Aridis, Ashai-Kasai, Biomérieux, Enlivex, Ferring, Inotrem, Polyphor, and Transgene, outside the submitted work. JC reports personal fees from Combacte Magnet during the conduct of the study; personal fees from Bayer, Inotrem, Shionogi, and TiGenix (Takeda) outside the submitted work; and grants from Medimmune (AstraZeneca) outside the submitted work. PE reports personal fees from the COMBACTE-MAGNET Consortium during the conduct of the study. P-FD reports personal fees from the Associations pour la Promotion de la Réanimation Médicale, University Hospital, Tours, France during the conduct of the study. MJB reports grants from Jansen Vaccines, Merck, and Sanofi outside the submitted work; consultancy fees from Jansen Vaccines outside the submitted work; and Data and Safety Monitoring Board fees from Merck (all paid to the University Medical Center Utrecht) outside the submitted work. HSJ, OA, KS, PR, AR, VP, MTE, FD, YW, SC, and TBe report being employees of AstraZeneca. HSJ, OA, KS, PR, AR, VP, MTE, FD, YW, and SC report holding stock in AstraZeneca. HSJ, OA, KS, PR, AR, VP, MTE, FD, YW, SC report holding stock options in AstraZeneca. OA was an employee of AstraZeneca during the conduct of the study, and is now an employee of and holds stock options in Viela Bio. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)