Pain during injections of botulinum toxin in children: Influence of the localization technique

Objective In this study, we consider two localization techniques used in injections of botulinium toxin in children: electrical stimulation and ultrasound. The hypothesis of this work was that injections performed without stimulation would be less painful. Patients and methods Monocentric prospective study, with 107 sessions of lower limb injections. Two groups of children were compared: localization by ultrasound only (60 children), detection by stimulation only or by stimulation combined with ultrasound (47 children). Pain assessment was performed by the child or an accompanying party using the Visual Analog Scale (VAS) and by a health care team using the Face, Legs, Activity, Cry, Consolability (FLACC). Results A significant difference between the two groups was found in both self-report and by means of the behavioral observational pain scale. Indeed, VAS average and FLACC average were significantly higher with detection by stimulation than with ultrasound alone: 4.5 cm ± 2.54 versus 2.7 cm ± 2.27; P < 0.001 for VAS scale and 3.7 ± 2.1 versus 2.7 ± 2.3; P < 0.05 for FLACC scale. Conclusion When compared to ultrasound detection, localization by electrostimulation appears to increase the overall pain caused during injections of botulinum toxin in children

Social Functioning and Self-Esteem in Young People with Disabilities Participating in Adapted Competitive Sport

Aims: The aim of this study was to investigate social functioning quality of life and self-esteem in young people with disabilities taking part in adapted competitive sport.Method: A sample of 496 athletes (mean age 16 years 4 months, range: 9 years to 20 years 9 months) was obtained from the 540 participants (91.8%) involved in a French national championship. The main outcome measurements were a social functioning inventory (PedsQL 4.0 social functioning) and a self-esteem inventory in physical areas (physical self inventory 6 PSI-6). Results: The mean PedsQL SF score was 74.6 (SD: 17.7). Comparisons of PedsQL SF according to gender, age, self mobility and training revealed no significant differences between the groups. PedsQL SF was weakly but significantly correlated with all subscales of the PSI-6 in the total population. PSI-6 scores were significantly different between boys and girls, with better self-esteem for boys on general self-esteem (7.7 vs. 6.9, p=0.018), physical condition (6.8 vs. 6.0, p=0.023) and attractive body subscores (6.5 vs. 5.1, p<0.001). Conclusion: Social functioning scores were significantly higher in this population than in the samples of young people with disabilities available in the literature. Interactions between self-concept, social functioning quality of life and participation in adapted sport activities require further studies

Intrathecal baclofen in cerebral palsy. A retrospective study of 25 wheelchair-assisted adults

ObjectiveTo study the efficacy and safety of intrathecal baclofen therapy (ITB) in wheelchair-dependent adults with cerebral palsy. Patients and methods A retrospective analysis and clinical examination of 25 wheelchair-assisted adults with cerebral palsy receiving ITB initiated between 1999 and 2009 in three different cities in western France. Results ITB improves spasticity and facilitates wheelchair comfort and nursing care. The therapy has an effect on motor disorders and pain. Eighty percent of the ITB patients were satisfied. Dissatisfaction was related to complications or adverse events and not lack of efficacy. Complications occurred in 32% of the patients and transient interruption of the treatment or surgical removal of the ITB pump was necessary in 16% of cases. Discussion and conclusion Wider use of ITB in this indication is likely and should lead to a better understanding of the drug\u27s pharmacological effects on motor disorders and pain. Use of the Goal Attainment Assessment Scale or Caregiver Questionnaire can help us

Measuring the Solar Radius from Space during the 2003 and 2006 Mercury Transits

The Michelson Doppler Imager (MDI) aboard the Solar and Heliospheric Observatory observed the transits of Mercury on 2003 May 7 and 2006 November 8. Contact times between Mercury and the solar limb have been used since the 17th century to derive the Sun's size but this is the first time that high-quality imagery from space, above the Earth's atmosphere, has been available. Unlike other measurements this technique is largely independent of optical distortion. The true solar radius is still a matter of debate in the literature as measured differences of several tenths of an arcsecond (i.e., about 500 km) are apparent. This is due mainly to systematic errors from different instruments and observers since the claimed uncertainties for a single instrument are typically an order of magnitude smaller. From the MDI transit data we find the solar radius to be 960".12 +/- 0".09 (696,342 +/- 65 km). This value is consistent between the transits and consistent between different MDI focus settings after accounting for systematic effects.Comment: Accepted for publication in The Astrophysical Journal (2012 March 5

Določanje benzodiazepinov v urinu preko benzofenonskih derivatov z uporabo tekočinske kromatografije sklopljene s tandemsko masno spektrometrijo

The aim of this study was to validate a new method for determining benzodiazepines in urine via their benzophenone derivatives, based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). Selected benzodiazepines were analysed after acid hydrolysis of urine and extraction by ethyl acetate in the presence of an internal standard. Samples were analysed using electrospray ionization LC-MS/MS in a multiple reaction monitoring mode. The chromatographic run time on a reversed phase C18 analytical column was set for 9 min. This method was validated in 21 patients receiving methadone. Benzodiazepines intake was established in two out of three patients. LC-MS/MS results were also compared with the rapid immunoassay and the methods showed good agreement. However, in three cases benzodiazepines were detected by LC-MS/MS, but not by the immunoassay. The sensitivity of the developed LC-MS/MS method is comparable to or even higher than of previously reported methods, which makes it suitable as a confi rmatory method.Razvili smo selektivno in občutljivo metodo za določanje nekaterih benzodiazepinov v urinu preko določanja njihovih benzofenonov. Metoda temelji na tekočinski kromatografi ji, sklopljeni s tandemsko masno spektrometrijo (LC-MS/MS). Izbrane benzodiazepine smo analizirali po kisli hidrolizi urinskih vzorcev in ekstrakciji z etilacetatom v prisotnosti internega standarda. Vzorce smo analizirali z elektrorazprševalno ionizacijo z MRM načinom detekcije. Čas kromatografske ločbe na reverznofazni (C18) analitski koloni je bil 9 min. Metoda je bila validirana in preizkušena na 21 pacientih, ki so prejemali metadonsko terapijo. Pri dveh tretjinah primerov je bil vnos benzodiazepinov tudi potrjen. Vzorce smo testirali tudi s hitro imunokemijsko metodo in rezultate primerjali z rezultati pridobljenimi z LC-MS/MS metodo. Ugotovili smo dobro ujemanje med rezultati pridobljenimi z obe a metodama. Kljub temu smo v treh primerih določili prisotnost benzodiazepinov z LC-MS/MS metodo, ki je z imunokemijsko metodo nismo. Občutljivost razvite metode je primerljiva ali celo boljša od predhodno opisanih metod, zato jo lahko uporabimo kot potrditveno metodo

Biomarker prevalence study and phase I trial of afatinib in children with malignant tumours

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Lenvatinib with etoposide plus ifosfamide in patients with refractory or relapsed osteosarcoma (ITCC-050): a multicentre, open-label, multicohort, phase 1/2 study

Background: Tyrosine kinase inhibitors have shown activity in osteosarcoma and might enhance the efficacy of chemotherapy. We aimed to determine the recommended phase 2 dose and antitumour activity of lenvatinib with etoposide plus ifosfamide in patients with refractory or relapsed osteosarcoma. // Methods: This multicentre, open-label, multicohort, phase 1/2 trial was done at 17 hospitals in six countries. Eligible patients were aged 2–25 years, had relapsed or refractory osteosarcoma, measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors version 1.1, Lansky play–performance score or Karnofsky performance score of 50% or higher, up to one previous VEGF or VEGF receptor-targeted therapy, and a life expectancy of at least 3 months. This study includes a combination dose-finding phase 1 part (cohort 3A) and a phase 2 combination expansion in patients with osteosarcoma (cohort 3B). Lenvatinib was administered orally at a starting dose of 11 mg/m2 per day, capped at 24 mg per day, and etoposide (100 mg/m2 per day) plus ifosfamide (3000 mg/m2 per day) were administered intravenously on days 1–3 of each 21-day cycle for a maximum of five cycles. Lenvatinib monotherapy continued after these five cycles until disease progression, toxic effects, or patient choice to discontinue. The phase 1 primary endpoint was to determine the recommended phase 2 dose by evaluating dose-limiting toxicity and the phase 2 primary endpoint was progression-free survival at 4 months. Progression-free survival was measured in the full analysis set, which included all patients enrolled for efficacy outcomes; safety was assessed in all patients who received any study drug. This study is registered with ClinicalTrials.gov, NCT02432274. // Findings: 30 patients were screened for enrolment into cohort 3A between May 9, 2016, and June 3, 2019, and 22 patients for enrolment into cohort 3B between Sept 13, 2018, and July 18, 2019. Eight patients from cohort 3A and two from cohort 3B were ineligible for enrolment in the study. In phase 1, dose-limiting toxicities were observed in three patients (one in the lenvatinib 11 mg/m2 combination group and two in the 14 mg/m2 combination group) and the recommended phase 2 dose was determined as lenvatinib 14 mg/m2 per day (with daily dose cap of 24 mg) and etoposide 100 mg/m2 per day plus ifosfamide 3000 mg/m2 per day administered intravenously on days 1–3 of each 21-day cycle for a maximum of five cycles. 35 patients from phase 1 (cohort 3A; n=15) and phase 2 (cohort 3B; n=20) were treated at the recommended phase 2 dose and their results were pooled. Progression-free survival at 4 months was 51% (95% CI 34–69) in 18 of 35 patients per the binomial estimate. The most common grade 3–4 treatment-emergent adverse events were neutropenia (27 [77%] of 35), thrombocytopenia (25 [71%]), anaemia (19 [54%]), and decreased white blood cell count (19 [54%]). 26 [74%] of 35 patients had serious treatment-emergent adverse events and no treatment-related deaths occurred. // Interpretation: Lenvatinib with etoposide plus ifosfamide shows promising antitumour activity with no new safety signals in patients with refractory and relapsed osteosarcoma. These findings warrant further investigation in an ongoing randomised phase 2 study (NCT04154189)

Phase I/II study of single-agent lenvatinib in children and adolescents with refractory or relapsed solid malignancies and young adults with osteosarcoma (ITCC-050)

Background: We report results from the phase I dose-finding and phase II expansion part of a multicenter, open-label study of single-agent lenvatinib in pediatric and young adult patients with relapsed/refractory solid tumors, including osteosarcoma and radioiodine-refractory differentiated thyroid cancer (RR-DTC) (NCT02432274). // Patients and methods: The primary endpoint of phase I was to determine the recommended phase II dose (RP2D) of lenvatinib in children with relapsed/refractory solid malignant tumors. Phase II primary endpoints were progression-free survival rate at 4 months (PFS-4) for patients with relapsed/refractory osteosarcoma; and objective response rate/best overall response for patients with RR-DTC at the RP2D. // Results: In phase I, 23 patients (median age, 12 years) were enrolled. With lenvatinib 14 mg/m2, three dose-limiting toxicities (hypertension, n = 2; increased alanine aminotransferase, n = 1) were reported, establishing 14 mg/m2 as the RP2D. In phase II, 31 patients with osteosarcoma (median age, 15 years) and 1 patient with RR-DTC (age 17 years) were enrolled. For the osteosarcoma cohort, PFS-4 (binomial estimate) was 29.0% [95% confidence interval (CI) 14.2% to 48.0%; full analysis set: n = 31], PFS-4 by Kaplan–Meier estimate was 37.8% (95% CI 20.0% to 55.4%; full analysis set) and median PFS was 3.0 months (95% CI 1.8-5.4 months). The objective response rate was 6.7% (95% CI 0.8% to 22.1%). The patient with RR-DTC had a best overall response of partial response. Some 60.8% of patients in phase I and 22.6% of patients in phase II (with osteosarcoma) had treatment-related treatment-emergent adverse events of grade ≥3. // Conclusions: The lenvatinib RP2D was 14 mg/m2. Single-agent lenvatinib showed activity in osteosarcoma; however, the null hypothesis could not be rejected. The safety profile was consistent with previous tyrosine kinase inhibitor studies. Lenvatinib is currently being investigated in osteosarcoma in combination with chemotherapy as part of a randomized, controlled trial (NCT04154189), in pediatric solid tumors in combination with everolimus (NCT03245151), and as a single agent in a basket study with enrollment ongoing (NCT04447755)

Bevacizumab, Irinotecan, or Topotecan Added to Temozolomide for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON-Neuroblastoma Trial

Purpose Outcomes for children with relapsed and refractory high-risk neuroblastoma (RR-HRNB) remain dismal. The BEACON Neuroblastoma trial (EudraCT 2012-000072-42) evaluated three backbone chemotherapy regimens and the addition of the antiangiogenic agent bevacizumab (B). Materials and Methods Patients age 1-21 years with RR-HRNB with adequate organ function and performance status were randomly assigned in a 3 × 2 factorial design to temozolomide (T), irinotecan-temozolomide (IT), or topotecan-temozolomide (TTo) with or without B. The primary end point was best overall response (complete or partial) rate (ORR) during the first six courses, by RECIST or International Neuroblastoma Response Criteria for patients with measurable or evaluable disease, respectively. Safety, progression-free survival (PFS), and overall survival (OS) time were secondary end points. Results One hundred sixty patients with RR-HRNB were included. For B random assignment (n = 160), the ORR was 26% (95% CI, 17 to 37) with B and 18% (95% CI, 10 to 28) without B (risk ratio [RR], 1.52 [95% CI, 0.83 to 2.77]; P = .17). Adjusted hazard ratio for PFS and OS were 0.89 (95% CI, 0.63 to 1.27) and 1.01 (95% CI, 0.70 to 1.45), respectively. For irinotecan ([I]; n = 121) and topotecan (n = 60) random assignments, RRs for ORR were 0.94 and 1.22, respectively. A potential interaction between I and B was identified. For patients in the bevacizumab-irinotecan-temozolomide (BIT) arm, the ORR was 23% (95% CI, 10 to 42), and the 1-year PFS estimate was 0.67 (95% CI, 0.47 to 0.80). Conclusion The addition of B met protocol-defined success criteria for ORR and appeared to improve PFS. Within this phase II trial, BIT showed signals of antitumor activity with acceptable tolerability. Future trials will confirm these results in the chemoimmunotherapy era

Exploring nitrogen use efficiency in Musa spp

Banana (Musa spp.) is an important staple crop, especially in developing countries where it ensures food security. However, optimal yields are not obtained due to both biotic and abiotic constraints. Low soil fertility is one of the limiting factors in the East African highlands, as the currently applied amount of organic (crop residues, animal manure, etc.) and inorganic fertilizers by smallholder farmers is not sufficient to maintain adequate soil fertility levels for optimal growth and production. This study, therefore, focuses specifically on the nitrogen (N) requirements of the banana plant and its genotypic differences. Genotypes with a high nitrogen use efficiency (NUE), that produce a high amount of dry mass per unit of nitrogen taken up, are thus of great importance. To get insight into the diversity of NUE among different genotypes, two hydroponics experiments were performed. First, four genotypes were exposed to four N treatments (0, 0.6, 1.3 and 7 mM). While all plants exposed to a N concentration of 1.3 mM or lower showed clear deficiency symptoms, the variability within the 0.6 mM treatment was mainly explained by the genotypes. This N treatment (0.6 mM) was, therefore, subsequently used to screen 16 genotypes in high-throughput and revealed genome-specific strategies to cope with limited N availability. AAA-EA genomes were least impacted by the limited N availability in both root and shoot. AAA genomes were most affected. Nevertheless, all N deficient plants invested in an absolute way more in roots than their shoot, resulting in significant larger root:shoot ratios. We conclude that a significant diversity exists in NUE among banana genomes and genotypes, and, therefore, encourage stakeholders to further investigate this genetic diversity