Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Measuring walking-related performance fatigability in clinical practice : a systematic review

INTRODUCTION: Fatigability, a change in performance according to tasks and circumstances, can contribute to walking limitations in daily life. Walking-related fatigability (WF) has been assessed subjectively, but current knowledge on best objective measurement methods is limited. The aim of this study was to provide an overview of objective clinical measurement methods assessing WF in different populations. EVIDENCE ACQUISITION: Articles were searched in Pubmed and Web Of Science by two independent raters. Studies were included when meeting inclusion criteria of measuring WF objectively in a clinical setting, with no exclusion towards any population. Case studies and reviews were not included in the review (systematic review registration number: PROSPERO - CRD42017074121). In total, 28 articles were included. The study populations were older adults (N.=7), multiple sclerosis (N.=14), spinal muscle atrophy (N.=3), osteoarthritis (N.=3), interstitial lung diseases (N.=1), and myasthenia gravis (N.=1). Data about patient characteristics, walking task, WF formula and interpretation (cut-off values and/or psychometric properties) got extracted from included literature. Every included article got checked for quality and risk of bias. EVIDENCE SYNTHESIS: WF was mostly measured during longer walking test such as six-minute walking test (6MWT) and 500 or 400-m walking test, by comparing the first and last minute or lap for spatiotemporal or kinematic changes in well-defined formulas. No gold standard is however available yet given different tasks or outcome measures across study populations. CONCLUSIONS: Longer walking test were most often used, with a preference towards the 6MWT, thereby comparing the changes over the last and first part of the test. Psychometric properties need more documentation before inclusion as experimental outcome

Feasibility study of a 10-week community -based program using the WalkWithMe application on physical activity, walking, fatigue and cognition in persons with Multiple Sclerosis

Background: People with Multiple Sclerosis (pwMS) show diverse symptoms, such as fatigue and decline in motor and cognitive function. Physical activity shows to have a positive impact on many of these symptoms. However, many pwMS lead sedentary lives. Objectives of this study were to evaluate the feasibility of prolonged use of the WalkWithMe, a personalized mobile application that supports pwMS in walking at home, and its e ffect on physical activity, walking, fatigue and cognition in persons with MS. Methods: Nineteen pwMS were enrolled in a 10 -week home -based intervention with the WalkWithMe applica- tion after setting personal goals based on baseline testing values, where twelve patients completed the program. Before and after the intervention, motor (6MWT, T25FW, 5 -STS, NHPT) and cognitive function (PASAT and SDMT) were evaluated, together with the patient reported impact on walking, physical activity, quality of life and fatigue by MSWS-12, IPAQ, SF -36, MSIS-29, MFIS and FSS, respectively. Results: Signi ficant improvement was seen for some parts of self -reported physical activity and quality of life (IPAQ: walking, p = 0.04, leisure, p = 0.02; SF -36: physical functioning, p = 0.02), cognition (SDMT, p = 0.01), cognitive fatigability (PASAT, p = 0.05), lower limb strength (5 -STS, p = 0.05) and dominant hand function (NHPT, p = 0.002). Conclusion: This feasibility study was successful at improving categories of self -reported physical activity, lower limb functional strength, hand function and cognition, but results need to be interpreted with caution, given the small and not always clinically relevant changes. Larger sample sizes in a controlled experimental design are needed to con firm these results

Rhythmic interlimb coordination of the lower limbs in multiple sclerosis during auditory pacing to three different frequencies

Background: Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system with heterogeneous symptoms. Persons with MS (PwMS) show reduced walking capacity with changes in their gait pattern. It is unknown to which extent coordination deficits are present in PwMS, which can be measured by seated lower leg interlimb coordination tasks, and to which extent they are related to motor and cognitive function. Research question: How is the control of interlimb coordination of the lower limbs characterized in PwMS compared to healthy controls (HC) during a seated rhythmical coordination task and what is the relationship between interlimb coordination, motor or cognitive function? Methods: Rhythmical interlimb coordination was assessed during a single session in 38 PwMS and 13 HC, using a seated rhythmical coordination task, comprising of antiphase flexion-extension of the lower limbs, to metronomes at 0.75 Hz, 1.00 Hz, 1.50 Hz. Outcomes were phase coordination index (PCI), movement amplitude and movement frequency. Correlations between interlimb coordination, motor, and cognitive function were examined. Results: PwMS showed impaired walking capacity but preserved cognitive function. Mixed model analysis revealed a significant effect of group and metronome frequency for PCI, attenuated by the variability in generating knee (antiphase flexion-extension) movements. Movement amplitude was highest at metronome frequency 1.00 Hz. In PwMS significant correlations were found between PCI and cognitive function when performing the task at metronome frequencies 0.75 Hz and 1.50 Hz, as well as motor function at 1.50 Hz. Significance: PwMS had a higher variability in interlimb coordination compared to HC. The most stable interlimb antiphase coordination mode was performed at 1.00 Hz. Significant correlations support the existence of a relationship between information processing speed, as well as walking impairment, with interlimb coordination. While cognitive and motor control are always needed for interlimb coordination movements, associations are strongest in the deviant higher and lower metronome rhythms

Flambement lineaire d'une coque mince elastique de forme generale

Programme 6 : calcul scientifique, modelisation et logiciels numeriquesSIGLEAvailable at INIST (FR), Document Supply Service, under shelf-number : 14802 E, issue : a.1991 n.1435 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Interlimb coordination performance in seated position in persons with multiple sclerosis : reduced amplitude over 6 min and higher coordination variability in persons with walking fatigability

Background: Walking fatigability is prevalent in MS and can be measured by a percentage distance decline during a 6-min walking test. Walking is characterized by an accurate and consistent interlimb antiphase coordination pattern. A decline in coordination each minute during a 6-min walking test is observed in persons with MS (pwMS). Measuring coordination during a 6-min seated coordination task with minimized balance and strength requirements, is assumed to examine a more fundamental interlimb antiphase coordination pattern in pwMS. This research aimed to answer the following research question: How does interlimb antiphase coordination pattern change during a seated coordination task in pwMS with walking fatigability (WF), non-walking fatigability (NWF) and Healthy Controls (HC)? Methods: Thirty-five pwMS and 13 HC participated. Interlimb coordination was assessed by a seated 6-min coordination task (6MCT) with the instruction to perform antiphase lower leg movements as fast as possible. Outcomes were Phase Coordination Index (PCI) and movement parameters (amplitude, frequency). Results: Mixed models revealed a significant effect of time for the the variability of generating interlimb movements, with a difference in mean values between WF and HC. A significant group∗time interaction effect was found for movement amplitude, represented by a significant decrease in movement amplitude in the WF group from minute 1 to the end of the task. Conclusion: The higher variability in interlimb coordination and decrease in movement amplitude over time during the 6MCT in the WF group could be an indicator of decreased control of fundamental antiphase coordination pattern in pwMS with walking fatigability

Continuous 12 min walking to music, metronomes and in silence : auditory-motor coupling and its effects on perceived fatigue, motivation and gait in persons with multiple sclerosis

Background: In Persons with Multiple Sclerosis (PwMS), coupling walking to beats/pulses in short bursts is reported to be beneficial for cadence and perceived fatigue. However it is yet to be investigated if coupling and its effects can be sustained for longer durations, required for task-oriented training strategy in PwMS. Aims: To investigate if PwMS compared to healthy controls (HC) sustain synchronization for 12 min when walking to music and metronome, and its effects on perceived physical and cognitive fatigue, motivation and gait compared to walking in silence. Methods: Participants walked for 12 min in three conditions (music, metronome and silence). The tempo of the auditory conditions was individualized. Auditory-motor coupling and spatio-temporal gait parameters were measured during walking. The visual analogue scale was used for perceived fatigue, and the Likert scale for motivation. Results: 27 PwMS and 28 HC participated. All participants synchronized to both stimuli, yet PwMS synchronized better to music. Overall, participants had lower cadence, speed and stride length when over time all conditions, with an exception of HC, with increasing cadence during the music condition. PwMS perceived less cognitive fatigue, no difference in perceived physical fatigue and a higher motivation walking to music compared to metronomes and silence. Conclusion: 12 min of uninterrupted walking was possible in PwMS in all conditions, while better synchronization, low perception of cognitive fatigue and high motivation occurred with music compared to other conditions. Coupling walking to music could offer novel paradigms for motor task-oriented training in PwMS

The Global Retinoblastoma Outcome Study: a prospective, cluster-based analysis of 4064 patients from 149 countries

Background Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. Methods We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1,2017, and Dec 31,2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. Findings The cohort included 4064 children from 149 countries. The median age at diagnosis was 23.2 months (IQR 11.0-36.5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0.8%) of 636 children from high-income countries, 55 (5.4%) of 1027 children from upper-middle-income countries, 342 (19. 7%) of 1738 children from lower-middle-income countries, and 196 (42.9%) of 457 children from low-income countries. Enudeation surgery was available for all children and intravenous chemotherapy was available for 4014 (98.8%) of 4064 children. The 3-year survival rate was 99.5% (95% CI 98.8-100.0) for children from high-income countries, 91.2% (89.5-93.0) for children from upper-middle-income countries, 80.3% (78.3-82.3) for children from lower-middle-income countries, and 57.3% (524-63-0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16.67; 95% CI 4.76-50.00), cT4 advanced tumour compared to cT1 (8.98; 4.44-18.18), and older age at diagnosis in children up to 3 years (1.38 per year; 1.23-1.56). For children aged 3-7 years, the mortality risk decreased slightly (p=0.0104 for the change in slope). Interpretation This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.Y

Global Retinoblastoma Presentation and Analysis by National Income Level

This cross-sectional analysis reports the retinoblastoma stage at diagnosis across the world during a single year, investigates associations between clinical variables and national income level, and investigates risk factors for advanced disease at diagnosis. Key PointsQuestionIs the income level of a country of residence associated with the clinical stage of presentation of patients with retinoblastoma? FindingsIn this cross-sectional analysis that included 4351 patients with newly diagnosed retinoblastoma, approximately half of all new retinoblastoma cases worldwide in 2017, 49.1\% of patients from low-income countries had extraocular tumor at time of diagnosis compared with 1.5\% of patients from high-income countries. MeaningThe clinical stage of presentation of retinoblastoma, which has a major influence on survival, significantly differs among patients from low-income and high-income countries, which may warrant intervention on national and international levels. ImportanceEarly diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. ObjectivesTo report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and ParticipantsA total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and MeasuresAge at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. ResultsThe cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4\%) were female. Most patients (n=3685 {[}84.7\%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n=2638 {[}62.8\%]), followed by strabismus (n=429 {[}10.2\%]) and proptosis (n=309 {[}7.4\%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5\%) patients having intraocular retinoblastoma and 2 (0.3\%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1\%) having extraocular retinoblastoma and 94 of 498 (18.9\%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 {[}95\% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 {[}95\% CI, 4.30-7.68]). Conclusions and RelevanceThis study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs