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Background Severely delayed elimination of methotrexate (MTX) is difficult to predict in patients treated with high‐dose MTX (HD‐MTX), but it may cause life‐threatening toxicity. It has not been defined how an increase in plasma creatinine can be best used as a predictor for severely delayed MTX elimination, thus providing a guide for therapeutic interventions to minimize renal toxicity. Methods Pharmacokinetic data were retrospectively collected on 218 Danish children with acute lymphoblastic leukemia treated with HD‐MTX 5 or 8 g/m2 on the NOPHO2000 protocol. Moderately delayed MTX elimination was defined as 42‐hour plasma MTX ≥ 4.0–9.9 μM, and severely delayed elimination was defined as 42‐hour plasma MTX ≥ 10 μM. Results Median 42‐hour plasma MTX was 0.61 μM (interquartile range, 0.4–1.06 μM). Of 1295 MTX infusions with 5 g/m2 (n = 140 patients) or 8 g/m2 (n = 78 patients), 5.1% were severely (1.5%) or moderately (3.6%) delayed. The risk of having delayed elimination was highest in the first of eight infusions with MTX 5 g/m² (7.4% vs 0.0 to 4.1% for subsequent MTX infusions) (P < 0.02). A 25 μM increase or a 1.5‐fold increase in plasma creatinine within 36 hours from start of the MTX infusion had a sensitivity of 92% (95% CI, 82%–97%) and a specificity of 85% (95% CI, 83%–87%) for predicting 42‐hour MTX ≥4.0 μM. Conclusions A 25 μM increase or a 1.5‐fold in plasma creatinine within 36 hours after start of an HD‐MTX infusion can predict delayed MTX elimination, thus allowing intensification of hydration and alkalization to avoid further renal toxicity and promote the elimination of MTX.

It is not known how effective specific types of motor-enriched activities are at improving academic learning and early reading skills in children. The aim of this study was to investigate whether fine or gross motor enrichment during a single session of recognizing letters "b"/"d" can improve within-session performance or delayed retention the following day in comparison to letter recognition practice without movement. Furthermore, the aim was to investigate children's motivation to perform the specific tasks. We used a randomized controlled intervention study-design to investigate the effect of 10-min motor-enriched "b"/"d" letter training on children's ability to recognize the letters "b" and "d" (n = 127, mean age = 7.61 ± SD = 0.44 years) acutely, and in a delayed retention test. Three groups were included: a fine motor-enriched group (FME), a gross motor-enriched group (GME), that received 10 min of "b" and "d" training with enriched gestures (fine or gross motor movements, respectively), and a control group (CON), which received non motor-enriched "b"/"d" training. The children's ability to recognize "b" and "d" were tested before (T0), immediately after (T1), and one day after the intervention (T2) using a "b"/"d" Recognition Test. Based on a generalized linear mixed model a significant group-time interaction was found for accuracy in the "b"/"d" Recognition Test. Specifically, FME improved their ability to recognize "b"/"d" at post intervention (T0→T1, p = 0.008) and one-day retention test (T0→T2, p < 0.001) more than CON. There was no significant difference in change between GME and CON. For reaction time there were no significant global interaction effects observed. However, planned post hoc comparisons revealed a significant difference between GME and CON immediately after the intervention (T0→T1, p = 0.03). The children's motivation-score was higher for FME and GME compared to CON (FME-CON: p = 0.01; GME-CON: p = 0.01). The study demonstrated that fine motor-enriched training improved children's letter recognition more than non motor activities. Both types of motor training were accompanied by higher intrinsic motivation for the children compared to the non motor training group. The study suggests a new method for motor-enriched letter learning and future research should investigate the underlying mechanisms.

Background Results from previous studies suggest that bodily movements, spanning from gestures to whole-body movements, integrated into academic lessons may benefit academic learning. However, only few studies have investigated the effects of movement integrated into reading practice. The PLAYMORE study aims to investigate the effects of two interventions focusing on a close and meaningful coupling between bodily movement and academic content on early pre-reading and word recognition skills in children. Further, the study aims to compare two interventions involving either hand movements (i.e. using arms and hands) or whole-body movements (i.e. using the whole body). Potential mediating factors underlying the link between bodily movement on early pre-reading and word recognition skills will be explored. Methods/design The PLAYMORE study will be conducted as a three-armed randomized controlled trial including children aged five to six years recruited from four schools in the Copenhagen area, Denmark. Stratified by class, children will be randomly allocated to one of three 8-week intervention/control periods: 1) teaching involving whole-body movements, 2) teaching involving hand movements (i.e. arms and hands) or 3) teaching involving minimal motor movements (i.e. seated on a chair using paper and pencil). Outcome measurements, including pre-reading and word recognition skills, will be collected before and after the intervention period to assess the intervention effects. This study protocol follows the SPIRIT guidelines. Discussion The PLAYMORE study will add to the current knowledge concerning the link between bodily movement and academic performance with important details about pre-reading and word recognition skills in preschool children. If effective, evaluation of the implementation of the PLAYMORE program should be conducted in order to investigate whether the effects can be transferred into standard school settings. The PLAYMORE study will lay the foundation for future research that have the potential to inform the political and scientific debate and importantly, to provide teachers with detailed information of how to implement movements effectively during teaching in order to support and motivate children in the process of learning to read. Trial registration The study was retrospectively registered in ClinicalTrials.gov (NCT04618822) the 5th of November 2020.

The aim of this study was to investigate the effects of embodied learning on children’s pre-reading and word reading skills. We conducted a three-armed randomized controlled trial including two intervention groups and one control group. One hundred forty-nine children from grade 0 (5–6 years old) who had just started school were recruited from 10 different classes from four elementary schools. Within each class, children were randomly assigned to receive teaching of letter-sound couplings and word decoding either with whole-body movements (WM), hand movements (HM), or no movements (CON) over an 8-week period. Children were evaluated on pre-reading, word reading, and motor skills before (T1), immediately after (T2), and after 17–22 weeks of retention period (T3) following the intervention. Between-group analysis showed a significant improvement in children’s ability to name letter-sounds correctly from T1 to T2 (p < 0.001) and from T1 to T3 (p < 0.05) for WM compared to CON. HM and WM improved significantly in naming conditional letter-sounds from T1 to T2 (p < 0.01, p < 0.01) compared to CON and from T1 to T3 for the HM group compared to CON (p < 0.05). We did not find an effect on word reading or a correlation between motor skill performance and reading. Results from the present study suggest that there are beneficial effects of using whole-body movements for children. Hand motor movements indeed also had a performance effect on letter-sound knowledge; however, the whole-body movements had longer-lasting effects. We do not see an effect on whole word reading.