Impact of adapted bicycle riding on outcomes for children and adolescents with disabilities: A systematic review.

AIM: To review the evidence for the effects of adapted bicycle riding on body structures and functions, activity, participation, and quality of life outcomes in children with disabilities, along with family-level participation outcomes. METHOD: A systematic review with searches of nine electronic databases to identify studies involving participants with a developmental disability aged 4 to 18 years who used a dynamic adapted bicycle was completed in August 2021. Risk of bias was assessed based on individual study designs. A narrative synthesis integrated the findings of the included studies. Certainty of evidence was synthesized using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Ten studies were included with 234 participants. Five studies reported outcomes at the body structures and functions level, ten reported activity-level outcomes, two reported participation-related outcomes, and none assessed quality of life or family participation in social and recreational activities. INTERPRETATION: Adapted bicycle riding interventions may improve gross motor function, enhance lower-limb muscle strength, and promote physical activity; however, certainty of evidence of effects was rated very low using GRADE. Further research is required to understand the impact of adapted bicycle riding on the participation outcomes of children and adolescents with disabilities and on family-level participation in social and recreational activities. WHAT THIS PAPER ADDS: Adapted bicycle riding interventions may improve motor functions and physical activity. Evidence about participation outcomes after adapted bicycle riding is limited. Research on adapted bicycle riding interventions in natural settings is needed.

Stakeholder consensus for decision making in eye-gaze control technology for children, adolescents and adults with cerebral palsy service provision: findings from a Delphi study.

BACKGROUND: Limited research exists to guide clinical decisions about trialling, selecting, implementing and evaluating eye-gaze control technology. This paper reports on the outcomes of a Delphi study that was conducted to build international stakeholder consensus to inform decision making about trialling and implementing eye-gaze control technology with people with cerebral palsy. METHODS: A three-round online Delphi survey was conducted. In Round 1, 126 stakeholders responded to questions identified through an international stakeholder Advisory Panel and systematic reviews. In Round 2, 63 respondents rated the importance of 200 statements generated by in Round 1. In Round 3, 41 respondents rated the importance of the 105 highest ranked statements retained from Round 2. RESULTS: Stakeholders achieved consensus on 94 of the original 200 statements. These statements related to person factors, support networks, the environment, and technical aspects to consider during assessment, trial, implementation and follow-up. Findings reinforced the importance of an individualised approach and that information gathered from the user, their support network and professionals are central when measuring outcomes. Information required to support an application for funding was obtained. CONCLUSION: This Delphi study has identified issues which are unique to eye-gaze control technology and will enhance its implementation with people with cerebral palsy.

The Dyskinetic Cerebral Palsy Functional Impact Scale: development and validation of a new tool.

AIM: To outline the development and examine the content and construct validity of a new tool, the Dyskinetic Cerebral Palsy Functional Impact Scale (D-FIS), which measures the impact of dyskinesia on everyday activities in children with cerebral palsy (CP). METHOD: D-FIS content was informed by a systematic review of dyskinesia outcome measures, in collaboration with children with dyskinetic CP, parents, caregivers, and expert clinicians. The D-FIS uses parent proxy to rate impact of dyskinesia on everyday activities. Construct validity was determined by examining internal consistency; known groups validity with the Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS), Communication Function Classification System (CFCS), and Eating and Drinking Ability Classification System (EDACS); and convergent validity with the Barry-Albright Dystonia Scale (BADS). RESULTS: Fifty-seven parents of children (29 males, 28 females, mean [SD] age 11y 8mo [4y 4mo], range 2y 6mo-18y) completed the D-FIS. Correlation between D-FIS and GMFCS was r=0.86 (95% confidence interval [CI]: 0.77-0.91, p<0.001); MACS r=0.84 (95% CI: 0.73-0.90, p<0.001); CFCS r=0.80 (95% CI: 0.67-0.88, p<0.001); and EDACS r=0.78 (95% CI: 0.66-0.87). Correlation between D-FIS and BADS was r=0.77 (95% CI: 0.64-0.86, p<0.001). Cronbach's alpha was 0.96. INTERPRETATION: The D-FIS demonstrates good construct validity and high internal consistency. The D-FIS will be useful for identifying priorities for intervention. It adds to the measurement tool kit for children with dyskinetic CP by addressing functional impact of dyskinetic movements and postures. What this paper adds The Dyskinetic Cerebral Palsy Functional Impact Scale (D-FIS) assesses the perceived impact of dyskinesia on daily activities in children with cerebral palsy (CP). The D-FIS demonstrates good construct validity and high internal consistency. The D-FIS is a clinically feasible, family-centred tool that fills a current gap in the dyskinetic CP assessment toolkit.

Brain magnetic resonance imaging is a predictor of bimanual performance and executive function in children with unilateral cerebral palsy.

AIM: To examine the association between brain magnetic resonance imaging (MRI) characteristics and executive function and bimanual performance in children with unilateral cerebral palsy (CP). METHOD: Clinical MRI brain scans were classified as: (1) predominant pathological pattern (normal, white matter injury [WMI]; grey matter injury; focal vascular insults [FVI]; malformations; or miscellaneous); and (2) focal lesions (frontal, basal ganglia, and/or thalamus). Assessments included: (1) bimanual performance; (2) unimanual dexterity; and (3) executive function tasks (information processing, attention control, cognitive flexibility, and goal setting) and behavioural ratings (parent). RESULTS: From 131 recruited children, 60 were ineligible for analysis, leaving 71 children (47 males, 24 females) in the final sample (mean age 9y [SD 2y], 6y-12y 8mo). Brain MRIs were WMI (69%) and FVI (31%); and frontal (59%), thalamic (45%), basal ganglia (37%), and basal ganglia plus thalamic (21%). Bimanual performance was lower in FVI versus WMI (p<0.003), and with frontal (p=0.36), basal ganglia (p=0.032), and thalamic/basal ganglia lesions (p=0.013). Other than information processing, executive function tasks were not associated with predominant pattern. Frontal lesions predicted attention control (p=0.049) and cognitive flexibility (p=0.009) but not goal setting, information processing, or behavioural ratings. INTERPRETATION: Clinical brain MRI predicts cognitive and motor outcomes when focal lesions and predominate lesion patterns are considered. What this paper adds Early brain magnetic resonance imaging (MRI) predicts bimanual performance and cognitive outcomes. Brain MRI may identify children requiring targeted interventions. Basal ganglia with/without thalamic lesions predicted bimanual performance. Frontal lesions were associated with attention control and cognitive flexibility. Brain MRI predominant patterns predicted motor, not cognitive outcomes, other than information processing.

La resonancia magnética cerebral es un predictor del rendimiento bimanual y la función ejecutiva en niños con parálisis cerebral unilateral OBJETIVO: Examinar la asociación entre las características de la resonancia magnética cerebral (RMN) y la función ejecutiva y el rendimiento bimanual en niños con parálisis cerebral unilateral (PC). MÉTODO: Los escáneres cerebrales de resonancia magnética clínica se clasificaron como: (1) patrón patológico predominante (normal, lesión de la sustancia blanca [WMI]; lesión de la materia gris; lesiones vasculares focales [FVI]; malformaciones; o varios); y (2) lesiones focales (ganglios frontales, basales y / o tálamo). Las evaluaciones incluyeron: (1) desempeño bimanual; (2) destreza unimanual; y (3) tareas de funciones ejecutivas (procesamiento de información, control de atención, flexibilidad cognitiva y fijación de objetivos) y calificaciones de comportamiento (padres). RESULTADOS: De 131 niños reclutados, 60 no fueron elegibles para el análisis, dejando 71 niños (47 varones, 24 mujeres) en la muestra final (edad media 9 años [DE 2 años], 6 años - 12 años 8 meses). Las RMN cerebrales fueron WMI (69%) y FVI (31%); y frontal (59%), talámico (45%), ganglios basales (37%) y ganglios basales más talámico (21%). El rendimiento bimanual fue menor en FVI versus WMI (p <0,003), y con lesiones frontales (p = 0,36), ganglios basales (p = 0,032) y talámicas / ganglios basales (p = 0,013). Aparte del procesamiento de la información, las tareas de la función ejecutiva no se asociaron con el patrón predominante. Las lesiones frontales predijeron el control de la atención (p = 0,049) y la flexibilidad cognitiva (p = 0,009) pero no el establecimiento de objetivos, el procesamiento de la información o las clasificaciones de comportamiento. INTERPRETACIÓN: La resonancia magnética cerebral clínica predice los resultados cognitivos y motores cuando se consideran las lesiones focales y los patrones de lesiones predominantes.

Imagem por ressonância magnética do cérebro como preditora do desempenho bimanual e função executiva de crianças com paralisia cerebral unilateral OBJETIVO: Examinar a associação entre as características do exame de imagem por ressonância magnética (IRM) e a função executiva e desempenho bimanual em crianças com paralisia cerebral (PC) unilateral. MÉTODO: Escaneamentos clínicos de IRM cerebrais foram classificados como: 1) padrão patológico predominante (normal, lesão da substância branca [LSB]; lesão da substância cinzenta; insultos vasculares focais [IVF]; malformações; ou outro); e (2) lesões focais (frontal, gânglios basais, e/ou tálamo). As avaliações incluíram: (1) desempenho bimanual; (2) destreza unimanual; e (3) tarefas de função executiva (processamento de informações, controle da atenção, flexibilidade cognitiva, e estabelecimento de metas) e pontuações comportamentais (pais). RESULTADOS: De 131 crianças recrutadas, 60 eram inelegíveis para análise, restando 71 crianças (47 do sexo masculino, 24 do sexo feminino) na amostra final (média de idade 9a [DP 2a], 6a-12a 8m). IRMs cerebrais eram do tipo LSB (69%) e IVFs (31%); e frontais (59%), talâmicas (45%), de gânglios da base (37%), e de gânglios da base mais talâmicas (21%). O desempenho bimanual foi menor em IVF versus LSB (p<0,003), e com lesões frontais (p=0,36), gânglios da base (p=0,032), e talâmicas/gânglios da base (p=0,013). Com exceção do processamento de informações, as tarefas da função executiva não foram associadas com o padrão predominante. Lesões frontais foram preditivas do controle da atenção (p=0,049) e flexibilidade cognitiva (p=,.009) mas não do estabelecimento de metas, processamento de informações, e pontuações comportamentais. INTERPRETAÇÃO: A IRM cerebral clínica prediz resultados cognitivos e motores quando lesões focais e padrões predominantes de lesão são considerados.

Are boys and girls just different? Gender differences in the Movement Assessment Battery for Children, 2nd edition (M ABC-2) suggests that they are.

INTRODUCTION: The second edition of the Movement Assessment Battery for Children (M ABC-2) is a standardised, norm referenced assessment that is frequently used by therapists to identify children with motor difficulties. The norms for the M ABC-2 were derived from a sample of children in the United Kingdom (UK) and are combined across the age groups for boys and girls. The aims of this research were to investigate gender differences in the performance of 8- and 9-year-old Australian children and if the norms in our cohort differed from UK-based M ABC-2 norms. METHODS: Children aged 8 or 9 years of age who underwent major neonatal cardiac or non-cardiac surgery and healthy controls were assessed using the M ABC-2 as part of the Development After Infant Surgery (DAISy) study. RESULTS: There were statistically significant differences in the scores for boys and girls aged 8- and 9-years old on the M ABC-2. Girls performed better than boys in manual dexterity and on total standard scores. Our control group compared to the assessment norms scored significantly poorer in manual dexterity, aiming and catching and total standard scores. CONCLUSION: Caution should be used when interpreting the results of the M ABC-2 for Australian 8- and 9-year olds. Contemporary Australian, gender-specific M ABC-2 norms should be considered. Further research is required to investigate gender differences and differences in performance of Australian children compared to the assessment norms in other age groups on the M ABC-2.

Constraint-induced movement therapy in children with unilateral cerebral palsy.

BACKGROUND: Unilateral cerebral palsy (CP) is a condition that affects muscle control and function on one side of the body. Children with unilateral CP experience difficulties using their hands together secondary to disturbances that occur in the developing fetal or infant brain. Often, the more affected limb is disregarded. Constraint-induced movement therapy (CIMT) aims to increase use of the more affected upper limb and improve bimanual performance. CIMT is based on two principles: restraining the use of the less affected limb (for example, using a splint, mitt or sling) and intensive therapeutic practice of the more affected limb. OBJECTIVES: To evaluate the effect of constraint-induced movement therapy (CIMT) in the treatment of the more affected upper limb in children with unilateral CP. SEARCH METHODS: In March 2018 we searched CENTRAL, MEDLINE, Embase, CINAHL, PEDro, OTseeker, five other databases and three trials registers. We also ran citation searches, checked reference lists, contacted experts, handsearched key journals and searched using Google Scholar. SELECTION CRITERIA: Randomised controlled trials (RCTs), cluster-RCTs or clinically controlled trials implemented with children with unilateral CP, aged between 0 and 19 years, where CIMT was compared with a different form of CIMT, or a low dose, high-dose or dose-matched alternative form of upper-limb intervention such as bimanual intervention. Primarily, outcomes were bimanual performance, unimanual capacity and manual ability. Secondary outcomes included measures of self-care, body function, participation and quality of life. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts to eliminate ineligible studies. Five review authors were paired to extract data and assess risk of bias in each included study. GRADE assessments were undertaken by two review authors. MAIN RESULTS: We included 36 trials (1264 participants), published between 2004 and 2018. Sample sizes ranged from 11 to 105 (mean 35). Mean age was 5.96 years (standard deviation (SD) 1.82), range three months to 19.8 years; 53% male and 47% participants had left hemiplegia. Fifty-seven outcome measures were used across studies. Average length of CIMT programs was four weeks (range one to 10 weeks). Frequency of sessions ranged from twice weekly to seven days per week. Duration of intervention sessions ranged from 0.5 to eight hours per day. The mean total number of hours of CIMT provided was 137 hours (range 20 to 504 hours). The most common constraint devices were a mitt/glove or a sling (11 studies each).We judged the risk of bias as moderate to high across the studies. KEY RESULTS: Primary outcomes at primary endpoint (immediately after intervention)CIMT versus low-dose comparison (e.g. occupational therapy)We found low-quality evidence that CIMT was more effective than a low-dose comparison for improving bimanual performance (mean difference (MD) 5.44 Assisting Hand Assessment (AHA) units, 95% confidence interval (CI) 2.37 to 8.51).CIMT was more effective than a low-dose comparison for improving unimanual capacity (Quality of upper extremity skills test (QUEST) - Dissociated movement MD 5.95, 95% CI 2.02 to 9.87; Grasps; MD 7.57, 95% CI 2.10 to 13.05; Weight bearing MD 5.92, 95% CI 2.21 to 9.6; Protective extension MD 12.54, 95% CI 8.60 to 16.47). Three studies reported adverse events, including frustration, constraint refusal and reversible skin irritations from casting.CIMT versus high-dose comparison (e.g. individualised occupational therapy, bimanual therapy)When compared with a high-dose comparison, CIMT was not more effective for improving bimanual performance (MD -0.39 AHA Units, 95% CI -3.14 to 2.36). There was no evidence that CIMT was more effective than a high-dose comparison for improving unimanual capacity in a single study using QUEST (Dissociated movement MD 0.49, 95% CI -10.71 to 11.69; Grasp MD -0.20, 95% CI -11.84 to 11.44). Two studies reported that some children experienced frustration participating in CIMT.CIMT versus dose-matched comparison (e.g. Hand Arm Bimanual Intensive Therapy, bimanual therapy, occupational therapy)There was no evidence of differences in bimanual performance between groups receiving CIMT or a dose-matched comparison (MD 0.80 AHA units, 95% CI -0.78 to 2.38).There was no evidence that CIMT was more effective than a dose-matched comparison for improving unimanual capacity (Box and Blocks Test MD 1.11, 95% CI -0.06 to 2.28; Melbourne Assessment MD 1.48, 95% CI -0.49 to 3.44; QUEST Dissociated movement MD 6.51, 95% CI -0.74 to 13.76; Grasp, MD 6.63, 95% CI -2.38 to 15.65; Weightbearing MD -2.31, 95% CI -8.02 to 3.40) except for the Protective extension domain (MD 6.86, 95% CI 0.14 to 13.58).There was no evidence of differences in manual ability between groups receiving CIMT or a dose-matched comparison (ABILHAND-Kids MD 0.74, 95% CI 0.31 to 1.18). From 15 studies, two children did not tolerate CIMT and three experienced difficulty. AUTHORS' CONCLUSIONS: The quality of evidence for all conclusions was low to very low. For children with unilateral CP, there was some evidence that CIMT resulted in improved bimanual performance and unimanual capacity when compared to a low-dose comparison, but not when compared to a high-dose or dose-matched comparison. Based on the evidence available, CIMT appears to be safe for children with CP.

Cognition and bimanual performance in children with unilateral cerebral palsy: protocol for a multicentre, cross-sectional study.

BACKGROUND: Motor outcomes of children with unilateral cerebral palsy are clearly documented and well understood, yet few studies describe the cognitive functioning in this population, and the associations between the two is poorly understood. Using two hands together in daily life involves complex motor and cognitive processes. Impairment in either domain may contribute to difficulties with bimanual performance. Research is yet to derive whether, and how, cognition affects a child's ability to use their two hands to perform bimanual tasks. METHODS/DESIGN: This study will use a prospective, cross-sectional multi-centre observational design. Children (aged 6-12 years) with unilateral cerebral palsy will be recruited from one of five Australian treatment centres. We will examine associations between cognition, bimanual performance and brain neuropathology (lesion type and severity) in a sample of 131 children. The primary outcomes are: Motor - the Assisting Hand Assessment; Cognitive - Executive Function; and Brain - lesion location on structural MRI. Secondary data collected will include: Motor - Box and Blocks, ABILHAND- Kids, Sword Test; Cognitive - standard neuropsychological measures of intelligence. We will use generalized linear modelling and structural equation modelling techniques to investigate relationships between bimanual performance, executive function and brain lesion location. DISCUSSION: This large multi-centre study will examine how cognition affects bimanual performance in children with unilateral cerebral palsy. First, it is anticipated that distinct relationships between bimanual performance and cognition (executive function) will be identified. Second, it is anticipated that interrelationships between bimanual performance and cognition will be associated with common underlying neuropathology. Findings have the potential to improve the specificity of existing upper limb interventions by providing more targeted treatments and influence the development of novel methods to improve both cognitive and motor outcomes in children with unilateral cerebral palsy. TRIAL REGISTRATION: ACTRN12614000631606 ; Date of retrospective registration 29/05/2014.

Comparison of the Properties of the Handwriting Speed Test (HST) and Detailed Assessment of Speed of Handwriting (DASH): An Exploratory Study.

BACKGROUND: Handwriting speed is an important component of students' ability to adequately express their ideas, knowledge and creativity in a timely and effective manner. AIMS: Psychometric properties of the Handwriting Speed Test (HST) and Detailed Assessment of Speed of Handwriting (DASH) and accuracy of the norms for identifying current Australian students with handwriting speed difficulties were examined. METHODS: An exploratory, cross-sectional study was conducted involving students, with and without handwriting difficulties, in Years 3-12 (mean age: 12.0 yrs, SD = 3.0 yrs; range = 7 to 18 yrs) in New South Wales (NSW; Australia). Participants were recruited through occupational therapists and schools. Students completed the HST and all DASH subtests. RESULTS: Thirty-two students with, and 139 students without, handwriting difficulties participated. Intra-rater and inter-rater reliability were found to be excellent; sensitivity was low and specificity high for the HST and DASH. No significant differences were found between test scores and normative data for students without handwriting difficulties (year/age groups with n > 10). CONCLUSIONS: The HST and DASH are reliable assessments of handwriting speed. Further research is required into discriminant validity of the HST and DASH and need for updated norms.

Minimising impairment: Protocol for a multicentre randomised controlled trial of upper limb orthoses for children with cerebral palsy.

BACKGROUND: Upper limb orthoses are frequently prescribed for children with cerebral palsy (CP) who have muscle overactivity predominantly due to spasticity, with little evidence of long-term effectiveness. Clinical consensus is that orthoses help to preserve range of movement: nevertheless, they can be complex to construct, expensive, uncomfortable and require commitment from parents and children to wear. This protocol paper describes a randomised controlled trial to evaluate whether long-term use of rigid wrist/hand orthoses (WHO) in children with CP, combined with usual multidisciplinary care, can prevent or reduce musculoskeletal impairments, including muscle stiffness/tone and loss of movement range, compared to usual multidisciplinary care alone. METHODS/DESIGN: This pragmatic, multicentre, assessor-blinded randomised controlled trial with economic analysis will recruit 194 children with CP, aged 5-15 years, who present with flexor muscle stiffness of the wrist and/or fingers/thumb (Modified Ashworth Scale score ≥1). Children, recruited from treatment centres in Victoria, New South Wales and Western Australia, will be randomised to groups (1:1 allocation) using concealed procedures. All children will receive care typically provided by their treating organisation. The treatment group will receive a custom-made serially adjustable rigid WHO, prescribed for 6 h nightly (or daily) to wear for 3 years. An application developed for mobile devices will monitor WHO wearing time and adverse events. The control group will not receive a WHO, and will cease wearing one if previously prescribed. Outcomes will be measured 6 monthly over a period of 3 years. The primary outcome is passive range of wrist extension, measured with fingers extended using a goniometer at 3 years. Secondary outcomes include muscle stiffness, spasticity, pain, grip strength and hand deformity. Activity, participation, quality of life, cost and cost-effectiveness will also be assessed. DISCUSSION: This study will provide evidence to inform clinicians, services, funding agencies and parents/carers of children with CP whether the provision of a rigid WHO to reduce upper limb impairment, in combination with usual multidisciplinary care, is worth the effort and costs. TRIAL REGISTRATION: ANZ Clinical Trials Registry: U1111-1164-0572 .

Caregiver perspectives of scoliosis surgery for children with cerebral palsy: a qualitative study.

PURPOSE: To explore the perspectives of primary caregivers of children with cerebral palsy (CP) who had spinal surgery for scoliosis. MATERIALS AND METHODS: A qualitative study was conducted using semi-structured interviews and guided by qualitative description methodology. Participants were caregivers of children with CP aged 5-18, who had undergone spinal surgery for scoliosis in Australia. The research team included a parent with lived experience. RESULTS: Fourteen participants (8 biological mothers), aged 40-49 years, completed online semi-structured interviews. Four themes were identified emerged. Life with a child with CP underpinned all experiences which were founded on familiarity with their child, medical procedures, and hospitalisation. Three subthemes were parents are the experts in knowing their child, children are vulnerable, and impact on caregivers. Theme 2 involved the significance of decision making to proceed with surgery. Theme 3 underscored a need to be prepared for the surgical journey and, in Theme 4, participants spoke of needing to expect the unexpected. CONCLUSION: The findings highlight the importance of understanding caregiver experiences and can help inform health professionals and other families in the decision-making process, preparing for and navigating spinal surgery.

Spinal surgery for scoliosis in children with cerebral palsy is a major surgery and poses substantial challenges for the family.Understanding the magnitude of the decision for families to proceed with surgery will equip health professionals to adequately support and partner with families.Detailed information and extensive preparation are necessary for families to proceed with and navigate surgery, the hospital stay and to return home and to the community.

Exosomes as an Emerging Plasmid Delivery Vehicle for Gene Therapy.

Despite its introduction more than three decades ago, gene therapy has fallen short of its expected potential for the treatment of a broad spectrum of diseases and continues to lack widespread clinical use. The fundamental limitation in clinical translatability of this therapeutic modality has always been an effective delivery system that circumvents degradation of the therapeutic nucleic acids, ensuring they reach the intended disease target. Plasmid DNA (pDNA) for the purpose of introducing exogenous genes presents an additional challenge due to its size and potential immunogenicity. Current pDNA methods include naked pDNA accompanied by electroporation or ultrasound, liposomes, other nanoparticles, and cell-penetrating peptides, to name a few. While the topic of numerous reviews, each of these methods has its own unique set of limitations, side effects, and efficacy concerns. In this review, we highlight emerging uses of exosomes for the delivery of pDNA for gene therapy. We specifically focus on bovine milk and colostrum-derived exosomes as a nano-delivery "platform". Milk/colostrum represents an abundant, scalable, and cost-effective natural source of exosomes that can be loaded with nucleic acids for targeted delivery to a variety of tissue types in the body. These nanoparticles can be functionalized and loaded with pDNA for the exogenous expression of genes to target a wide variety of disease phenotypes, overcoming many of the limitations of current gene therapy delivery techniques.

Milk/colostrum exosomes: A nanoplatform advancing delivery of cancer therapeutics.

Chemotherapeutics continue to play a central role in the treatment of a wide variety of cancers. Conventional chemotherapy involving bolus intravenous doses results in severe side effects - in some cases life threatening - delayed toxicity and compromised quality-of-life. Attempts to deliver small drug molecules using liposomes, polymeric nanoparticles, micelles, lipid nanoparticles, etc. have produced limited nanoformulations for clinical use, presumably due to a lack of biocompatibility of the material, costs, toxicity, scalability, and/or lack of effective administration. Naturally occurring small extracellular vesicles, or exosomes, may offer a solution and a viable system for delivering cancer therapeutics. Combined with their inherent trafficking ability and versatility of cargo capacity, exosomes can be engineered to specifically target cancerous cells, thereby minimizing off-target effects, and increasing the efficacy of cancer therapeutics. Exosomal formulations have mitigated the toxic effects of several drugs in murine cancer models. In this article, we review studies related to exosomal delivery of both small molecules and biologics, including siRNA to inhibit specific gene expression, in the pursuit of effective cancer therapeutics. We focus primarily on bovine milk and colostrum exosomes as the cancer therapeutic delivery vehicles based on their high abundance, cost effectiveness, scalability, high drug loading, functionalization of exosomes for targeted delivery, and lack of toxicity. While bovine milk exosomes may provide a new platform for drug delivery, extensive comparison to other nanoformulations and evaluation of long-term toxicity will be required to fully realize its potential.

Implications of providing wrist-hand orthoses for children with cerebral palsy: evidence from a randomised controlled trial.

PURPOSE: To investigate the effects of providing rigid wrist-hand orthoses plus usual multidisciplinary care, on reducing hand impairments in children with cerebral palsy. METHODS: A pragmatic, multicentre, assessor-blinded randomised controlled trial aimed to enrol 194 children aged 5-15 years, with wrist flexor Modified Ashworth Scale score ≥1. Randomisation with concealed allocation was stratified by study site and passive wrist range. The treatment group received a rigid wrist-hand orthosis, to wear ≥6 h per night for 3 years. Analysis included repeated measures mixed-effects linear regression models, using intention-to-treat principles. RESULTS: The trial stopped early due to insufficient recruitment: 74 children, across all Manual Ability Classification System levels, were randomised (n = 38 orthosis group; n = 36 control). Mean age was 10.2 (SD 3.1) years (orthosis group) and 9.1 (SD 2.8) years (control). Data showed some evidence that rigid wrist-hand orthosis impacted passive wrist extension with fingers extended in the first year [mean difference between-groups at 6 months: 13.15° (95%CI: 0.81-25.48°, p = 0.04); 12 months: 20.94° (95%CI: 8.20-33.69°, p = 0.001)]. Beyond 18 months, participant numbers were insufficient for conclusive findings. CONCLUSION: The study provided detailed data about short- and long-term effects of the wrist-hand orthosis and highlighted challenges in conducting large randomised controlled trials with this population. Trial Registration: Australia and New Zealand Clinical Trials Registry: U1111-1164-0572 IMPLICATIONS FOR REHABILITATIONThere may be incremental benefit, for children with cerebral palsy, at 6 and 12 months on passive wrist range from wearing a rigid wrist-hand orthosis designed according to this protocol.The rigid-wrist-hand orthosis evaluated in this study, which allowed for some tailoring for individual children's presentations, differed in design from past recommendations for "resting hand" positioning.Longitudinal follow up of children with cerebral palsy prescribed a rigid wrist-hand orthosis is essential to monitor any benefit.Minor adverse events were commonly experienced when wearing the orthosis and should be discussed prior to prescription of a rigid wrist-hand orthosis.

Consumer involvement in research - parent perceptions of partnership in cerebral palsy research: a qualitative study.

PURPOSE: Identify perceptions of parents and caregivers of children with cerebral palsy about being consumer research partners and identify strategies to inform involvement of parents in cerebral palsy research. MATERIALS AND METHODS: Twenty-two parents in New South Wales and Victoria (Australia) participated in this qualitative study. Seven interviews and three focus groups were completed. Interpretive description guided data analysis. Methodological rigor was enhanced through involving two consumer investigators in the research team, member checking, and multiple researchers completing data analysis and theme generation. RESULTS: Participants identified a range of factors that may influence their involvement in research partner roles. Main topics emerging from the data included "Research Is Better with Parents" and "Parents Benefit from Being Research Partners." A third, "Parents as Research Partners," contained the themes "Flexible Involvement," "Starting Partnerships," and "Building and Sustaining Partnerships." CONCLUSION: This study has provided a rich insight into how parents perceive and describe engaging as research partners. Parent-identified guidance will inform future partnerships aiming to enhance the quality of cerebral palsy research and outcomes for people with cerebral palsy and their families. The involvement of consumer investigators in this study was considered valuable for enhancing the quality and applicability of the research.IMPLICATIONS FOR REHABILITATIONParents believed that parent partnership in research has benefits for the research and for the consumers involved.Parents provided guidance about the importance of starting, building and sustaining relationships in involving parents as research partners.Understanding the parent context, investing in relationships and acknowledgement of, and recognition for, contributions were considered important for building and sustaining effective partnerships.Flexible approaches to supporting parents as research partners was considered necessary for effective partnership.

Does exercise affect quality of life and participation of adolescents and adults with cerebral palsy: a systematic review.

PURPOSE: Investigate the effect of exercise for adults with cerebral palsy (CP) on quality of life, participation (attendance and involvement in life situations), functional mobility, pain, fatigue, mood, and self-efficacy. METHODS: A systematic review was completed. Twelve databases were searched from inception to August 2022 for studies including participants (≥16 years) with cerebral palsy, and that evaluated an exercise intervention. Two reviewers independently assessed eligibility, risk of bias, and extracted data. RESULTS: Seventeen studies (total n = 532) were included: 12 randomised control trials, four non-randomised trials, and one single case experimental design. Interventions studied were predominantly strength, aerobic or treadmill training, dance, and swimming. No study assessed participation, pain or mood. Of two studies that assessed quality of life, one reported a positive effect on an aspect of mental health immediately after the programme finished. All studies assessed functional mobility, but only one reported a positive effect. One study assessed self-efficacy and found no effect, and another assessed fatigue and reported conflicting results. CONCLUSIONS: The effect of exercise for adults with CP, on outcomes that adults report as important to them - quality of life, participation, pain, mood, and fatigue - are unknown.IMPLICATIONS FOR REHABILITATIONTo address outcomes important to adults with cerebral palsy (CP), it is important to understand how exercise affects participation and quality of life.All modes of exercise reviewed appear safe for adults with CP and choice should be based on the client's preferences, access to services, and convenience.Addressing any needed accommodations in the environment and context is likely more important than exercise prescription parameters when tailoring exercise to meet the needs of adults with CP and sustain participation.

Effects of neoprene wrist/hand splints on handwriting for students with joint hypermobility syndrome: a single system design study.

PURPOSE: Pain associated with hypermobility of wrist and hand joints can contribute to decreased handwriting output. This study examined the effectiveness of a neoprene wrist/hand splint in reducing pain and increasing handwriting speed and endurance for students with joint hypermobility syndrome. METHODS: Multiple baseline, single system design (SSD) methodology was used. Four ninth grade students with handwriting difficulties because of joint hypermobility syndrome participated in this study. RESULTS: Visual and statistical (two standard deviation band method) analyses indicated a significant decrease in handwriting speed when using the splint for three out of four participants. No significant change in pain or endurance was noted during intervention. There was a significant decrease in pain following withdrawal of the splint for three participants. CONCLUSION: Evidence from this study does not support use of this particular splint for decreasing pain and increasing handwriting speed and endurance for ninth grade students with joint hypermobility syndrome.

Validity of the fine motor area of the 12-month ages and stages questionnaire in infants following major surgery.

The Ages and Stages Questionnaires (ASQ) are parent-report screening tools to identify infants at risk of developmental difficulties. The purpose of this study was to examine validity and internal reliability of the fine motor developmental area of the ASQ, 2nd edition (ASQ2-FM) for screening 12-month-old infants following major surgery. The ASQ2-FM was completed by caregivers of 74 infants who had cardiac surgery in the first 90 days of life, 104 infants who had noncardiac surgery in the first 90 days of life, and a control group of 154 infants. The Rasch item response analysis revealed that the ASQ2-FM had poor ability to discriminate among levels of fine motor ability. Sensitivity was poor (20%) and specificity was good (98%) when compared with the scores for the fine motor subscale of the Bayley Scales of Infant and Toddler Development. The ASQ2-FM under-identified infants at risk for fine motor delay; internal reliability and construct validity do not support use as a screening tool of fine motor development of infants aged 12 months who have undergone major surgery.

Canadian Occupational Performance Measure: impact of blinded parent-proxy ratings on outcome.

BACKGROUND: There is potential for unintended effects on intervention outcome when using the Canadian Occupational Performance Measure (COPM) in intervention studies. PURPOSE: To determine the effect of blinded parent-proxy ratings of the COPM on outcomes at later endpoints. METHODS: Data were drawn from a randomized trial of 50 children with hemiplegic cerebral palsy aged 19 months to seven years. Outcomes were measured at baseline, post-intervention, and six months. Parents of 36 children were randomly allocated to complete six-month COPM proxy ratings blinded or unblinded to previous ratings. A group of 32 parents rated the six-month COPM blinded and then re-rated it after access to previous ratings. FINDINGS: There was no statistically significant difference in ratings between those completing the COPM blinded compared to unblinded. IMPLICATIONS: The COPM should continue to be rated blinded at post-intervention endpoints in the absence of further research to the contrary.