The model of access to speech-language pathology services.

PURPOSE: Within Australia, some families face challenges in accessing paediatric speech-language pathology services. This research sought to investigate the factors that impact access to paediatric speech-language pathology services within Western Australia. METHOD: Researchers used constructivist grounded theory to investigate the construct of access, as experienced and perceived by service decision-makers, namely caregivers of children with communication needs and speech-language pathologists who provide communication services. Eleven speech-language pathologists and 16 caregivers took part in 32 semi-structured in-depth interviews. Researchers used layers of coding of interviews transcripts and the constant comparative method to investigate data. RESULT: Findings outline the factors that impact access to speech-language pathology services, as organised into the seven categories of the Model of Access to Speech-Language Pathology Services (MASPS). The categories and properties of this model are grounded within experiences and perspectives that participants contributed to the dataset. CONCLUSION: MASPS provides a theoretical structure that has been constructed using inductive and abductive reasoning. This model can be used by service designers and decision-makers to reflect upon and improve experiences of service for a range of consumers. MASPS can also be used as a basis for further investigation into aspects of service access.

The LTAR cropland common experiment in the Lower Mississippi River Basin.

The Lower Mississippi River Basin-Long-Term Agroecosystem Research Site (LMRB-LTAR) encompasses six states from Missouri to the Gulf of Mexico and is coordinated by the USDA-ARS National Sedimentation Laboratory, Oxford, MS. The overarching goal of LTAR is to assess regionally diverse and geographically scalable farming practices for enhanced sustainability of agroecosystem goods and services under changing environment and resource-use conditions. The LMRB-LTAR overall goal is to assess sustainable row crop agricultural production systems that integrate regional environmental and socioeconomic needs. Primary row crops in the region include soybeans, corn, cotton, rice, and sugarcane with crop rotations influenced by commodity crop price and other factors. The field-scale common experiment (CE) includes four row crop farms (26-101 ha) established in 2021 and 2023. Three fields are managed with alternative practices, including reduced tillage, cover crops, and automated prescription irrigation, and three fields are managed with prevailing farming practices, consisting of conventional tillage, no cover crop, and nonprescription irrigation. Treatment effects on crop productivity, soil quality, water use efficiency, water quality, and carbon storage are assessed. Research from the LMRB CE will deliver outcomes linked to overarching LTAR network goals, including innovative agricultural systems, strengthened partnerships, data management technologies, and precision environmental tools.

Non-pharmacological interventions to support coronary artery bypass graft (CABG) patient recovery following discharge: protocol for a scoping review.

BACKGROUND: In Canada, approximately 15 000 people undergo coronary artery bypass grafting (CABG) each year. However, 9.5% of these patients are urgently readmitted to hospital within 30 days of surgery. Postoperative interventions following discharge play an important role in reducing readmissions and improving CABG patient outcomes. Therefore, it is important to determine effective interventions available to enhance CABG patient recovery following postoperative discharge. OBJECTIVES: Our scoping review aims to identify non-pharmacological interventions available to support recovery of patients who are discharged after CABG in the community setting. METHODS: The methodological framework described by Arksey and O'Malley will be applied to this review. Our search strategy will include electronic databases (Medline, Embase, Cochrane Library and CINAHL), and studies will be screened and reviewed by two independent reviewers. Studies looking at non-pharmacological interventions targeting patients who are discharged after CABG will be included. Preliminary searches were conducted March 2022 and following abstract screening, full-text screening was completed May 2023. Data extraction is planned to begin September 2023 with an expected finish date of October 2023. The study is expected to be completed by January 2024. ETHICS AND DISSEMINATION: This scoping review will retrieve and analyse previously published studies in which informed consent was obtained by primary investigators. Therefore, no ethical review or approval will be required. This scoping review aims to enumerate available non-pharmacological interventions to support recovery of patients who are discharged after CABG and identify gaps in postoperative recovery after discharge to support the development of innovative and targeted interventions. On completion of this review, we will ensure broad dissemination of our findings through peer-reviewed, open-access journals, conference presentations and hold meetings to engage stakeholders, including clinicians, policy makers and others.

Influence of placement stability on developmental outcomes of children and young people in out-of-home care: Findings from the Pathways of Care Longitudinal Study.

BACKGROUND: Placement stability is an important indicator of the functioning of an out-of-home care system. Previous research suggests that frequent placement changes have a negative impact on the outcomes for children and young people in out-of-home care. OBJECTIVE: This paper examines the association between placement stability in out-of-home care and children's socio-emotional, cognitive and physical health outcomes. PARTICIPANT AND SETTING: The Pathways of Care Longitudinal Study (POCLS) is the first large-scale prospective longitudinal study of children in out-of-home care in Australia. The sample consists of any study child who participated in any of the first three waves of the POCLS interview. METHODS: Unweighted data from the first three waves of the POCLS interview and administrative data was used. A measure of placement stability was developed that accounted for both number of placements and length of time in care. Mixed effect modelling was used to examine the link between placement stability and children's developmental outcomes. RESULTS: Placement stability was found to have a significant association with socio-emotional, cognitive (non-verbal) and physical health (gross and fine motor skill) development. A number of other factors were also found to be associated with positive development. CONCLUSIONS: The findings support the existing evidence that placement stability is an important factor for children's development. Other factors including placement type, carer wellbeing and carer support are also important for positive development. Appropriate policy and practice intervention to support children and families to improve placement stability is fundamental to achieving positive developmental outcomes for children in out-of-home care.

E-prescribing and medication safety in community settings: A rapid scoping review.

Background: Medication prescribing is essential for the treatment, curing, maintenance, and/or prevention of an illness and disease, however, medication errors remain common. Common errors including prescribing and administration, pose significant risk to patients. Electronic prescribing (e-prescribing) is one intervention used to enhance the safety and quality of prescribing by decreasing medication errors and reducing harm. E-prescribing in community-based settings has not been extensively examined. Objective: To map and characterize the current evidence on e-prescribing and medication safety in community pharmacy settings. Methods: We conducted a rapid scoping review of quantitative, qualitative, and mixed methods studies reporting on e-prescribing and medication safety. MEDLINE All (OVID), Embase (Elsevier), CINAHL Full Text (EBSCOHost), and Scopus (Elsevier) databases were searched December 2022 using keywords and MeSH terms related to e-prescribing, medication safety, efficiency, and uptake. Articles were imported to Covidence and screened by two reviewers. Data were extracted by a single reviewer and verified by a second reviewer using a standardized data extraction form. Findings are reported in accordance with JBI Manual for Evidence Synthesis following thematic analysis to narratively describe results. Results: Thirty-five studies were included in this review. Most studies were quantitative (n = 22), non-experimental study designs (n = 16) and were conducted in the United States (n = 18). Half of included studies reported physicians as the prescriber (n = 18), while the remaining reported a mix of nurse practitioners, pharmacists, and physician assistants (n = 6). Studies reported on types of errors, including prescription errors (n = 20), medication safety errors (n = 9), dispensing errors (n = 2), and administration errors (n = 1). Few studies examined patient health outcomes, such as adverse drug events (n = 5). Conclusions: Findings indicate that most research is descriptive in nature and focused primarily on rates of prescription errors. Further research, such as experimental, implementation, and evaluation mixed-methods research, is needed to investigate the effects of e-prescribing on reducing error rates and improving patient and health system outcomes.

Guided self-help for anxiety among Huntington's disease gene expansion carriers (GUIDE-HD) compared to treatment as usual: a randomised controlled feasibility trial.

BACKGROUND: Huntington's disease (HD) is an adult-onset genetic neurodegenerative condition associated with cognitive decline, motor impairments, and emotional difficulties. Anxiety affects up to 71% of HD gene expansion carriers (i.e., those with the version of the gene that causes HD) and can negatively impact quality of life, worsen other HD symptoms, and increase suicide risk. Therefore, helping people with their anxiety should be a clinical priority. A significant evidence base now exists for low-cost talking therapies for anxiety, such as guided self-help, and with people with other neurodegenerative conditions (e.g., Parkinson's disease). However, this type of intervention has not been specifically assessed with HD gene expansion carriers. METHODS: This protocol describes an exploratory randomised controlled feasibility study of a psychological intervention for anxiety for HD gene expansion carriers. The 10 session guided self-help intervention ('GUIDE-HD') is based on a blend of second and third wave cognitive behavioural models of anxiety (cognitive behaviour therapy [CBT] and acceptance and commitment therapy [ACT]) and is adapted to meet the specific needs of an HD population. This study will compare guided self-help with treatment as usual (TAU), with 15 HD gene expansion carriers randomly allocated to each group. Participants will be recruited across the UK. Quantitative data will be collected pre-intervention, immediately post-intervention, 3-month post-intervention and 6-month post-intervention. Qualitative data will be collected at one month post-intervention from participants, including HD carers. The data will be analysed to assess whether the current intervention and study design are feasible to progress to a larger randomised controlled trial. Feasibility has been defined in terms of recruitment rate, retention rate to both trial arms, intervention adherence, and acceptability of the intervention and measurement tools. DISCUSSION: Given the lack of evidenced interventions to date to support the wellbeing of people with the expanded Huntington's gene, this study will assess the feasibility of progressing this particular intervention to a full trial. To try and increase the acceptability of the intervention, a number of stakeholders, including those affected by HD and in caring roles, have been fundamental to the creation of the intervention (e.g., therapy manual, planned therapy process) to date. TRIAL REGISTRATION: Trial ID: ISRCTN47330596 . Date registered: 28/09/2022. Protocol version and date: Version 2, 09/06/22. Trial sponsor organisation and contact: Leicestershire Partnership NHS Trust (Dave Clarke). Role of sponsor: Overall responsibility for the conduct and governance of the trial. Role of funder: Review of initial research proposal.

CD98hc is a target for brain delivery of biotherapeutics.

Brain exposure of systemically administered biotherapeutics is highly restricted by the blood-brain barrier (BBB). Here, we report the engineering and characterization of a BBB transport vehicle targeting the CD98 heavy chain (CD98hc or SLC3A2) of heterodimeric amino acid transporters (TVCD98hc). The pharmacokinetic and biodistribution properties of a CD98hc antibody transport vehicle (ATVCD98hc) are assessed in humanized CD98hc knock-in mice and cynomolgus monkeys. Compared to most existing BBB platforms targeting the transferrin receptor, peripherally administered ATVCD98hc demonstrates differentiated brain delivery with markedly slower and more prolonged kinetic properties. Specific biodistribution profiles within the brain parenchyma can be modulated by introducing Fc mutations on ATVCD98hc that impact FcγR engagement, changing the valency of CD98hc binding, and by altering the extent of target engagement with Fabs. Our study establishes TVCD98hc as a modular brain delivery platform with favorable kinetic, biodistribution, and safety properties distinct from previously reported BBB platforms.

Outcomes of Ultrasound Guided Peripheral Intravenous Catheters Placed in the Emergency Department and Factors Associated with Survival.

Background: Patients with difficult peripheral intravenous (IV) access are common in emergency departments (EDs). Ultrasound-guided peripheral intravenous catheters (USIVs) are frequently used in this population; however, information regarding the effect of patient and IV characteristics on the dwell time (DT) and survival probability (SP) of USIVs is limited. Objective: Our study aimed to evaluate for associations between patient or IV characteristics and the DT and SP of USIVs. Methods: Retrospective analysis was performed on a database from an ED nurse (RN) USIV training program at an urban, academic hospital. Patients over 18 years with an USIV placed during the study period were included. Subject demographics, history, IV characteristics, insertion, and removal times were collected. Data were analyzed using descriptive statistics and univariable and multivariable Cox regression. USIV survival times for variates of interest were estimated using Kaplan-Meier curves for three censoring points. Results: The final analysis cohort was 388 patients. Mean age was 56.6 years, 66.5% were female, mean BMI was 29.9 kg/m2, and 42.5% were obese (BMI ≥30). Median DT was 40.3 hours in admitted patients (N=340). SP for USIVs at 96 hours was 87.8%. A total of 21 of 340 (6.2%) USIVs failed. USIV location conferred a difference on DT in obese patients when dichotomized into upper arm versus antecubital fossa and forearm together (38.6 hours vs 44.6 hours, p=0.03). No factors were associated with a difference in USIV SP. Conclusion: Median USIV DT of 40.3 hours for admitted patients was higher than in previous studies. Only 7% of USIVs in our study failed. Overall, catheters survived longer than expected.

Effect of Experiential Communication Skills Education on Graduate Medical Education Trainees' Communication Behaviors: A Systematic Review.

PURPOSE: A better understanding of how communication skills education impacts trainees' communication skills is important for continual improvement in graduate medical education (GME). Guided by the Kirkpatrick Model, this review focused on studies that measured communication skills in either simulated or clinical settings. The aim of this systematic review was to examine the effect of experiential communication skills education on GME trainees' communication behaviors. METHOD: Five databases were searched for studies published between 2001 and 2021 using terms representing the concepts of medical trainees, communication, training, and skills and/or behaviors. Included studies had an intervention design, focused only on GME trainees as learners, used experiential methods, and had an outcome measure of communication skills behavior that was assessed by a simulated or standardized patient (SP), patient, family member, or outside observer. Studies were examined for differences in outcomes based on study design; simulated versus clinical evaluation setting; outside observer versus SP, patient, or family member evaluator; and length of training. RESULTS: Seventy-seven studies were ultimately included. Overall, 54 (70%) studies reported some positive findings (i.e., change in behavior). There were 44 (57%) single-group pre-post studies, 13 (17%) nonrandomized control studies, and 20 (26%) randomized control studies. Positive findings were frequent in single-group designs (80%) and were likely in nonrandomized (62%) and randomized (55%) control trials. Positive findings were likely in studies evaluating communication behavior in simulated (67%) and clinical (78%) settings as well as in studies with outside observer (63%) and SP, patient, and family member (64%) evaluators. CONCLUSIONS: This review demonstrates strong support that experiential communication skills education can impact GME trainees' communication behaviors. Marked heterogeneity in communication trainings and evaluation measures, even among subgroups, did not allow for meta-analysis or comparative efficacy evaluation of different studies. Future studies would benefit from homogeneity in curricular and evaluation measures.

Symptom and Illness Experience for English and Spanish-Speaking Children with Advanced Cancer: Child and Parent Perspective.

Understanding the symptom and illness experience of children with advanced cancer facilitates quality care; yet, obtaining this understanding is complicated by the child's developmental level and physical and psychological health factors that affect communication. The purpose of this study was to describe the symptom and illness experience of English- and Spanish-speaking children with advanced cancer as described by the child and parent. We conducted hermeneutic phenomenological, descriptive, and interpretive interviews with eligible children and parents. The interdisciplinary research team analyzed transcripts hermeneutically until consensus on theme labels was reached. Four themes and associated subthemes were identified from the interviews of the 10 child-parent dyads: 1. symptoms disrupt life (path to diagnosis, life is disrupted), 2. isolation (lack of understanding, family separations/relationships), 3. protection, and 4. death is not for children. Children and parents readily described the impact symptoms and cancer treatment had on their lives and relationships. These findings underscore the salient aspects of daily life disrupted by cancer. With a deeper understanding of symptom burden and its interference, relationship and communication implications, and anticipatory grief, the treating team may better optimize care for children and their families living with advanced cancer.

Brain delivery and activity of a lysosomal enzyme using a blood-brain barrier transport vehicle in mice.

Most lysosomal storage diseases (LSDs) involve progressive central nervous system (CNS) impairment, resulting from deficiency of a lysosomal enzyme. Treatment of neuronopathic LSDs remains a considerable challenge, as approved intravenously administered enzyme therapies are ineffective in modifying CNS disease because they do not effectively cross the blood-brain barrier (BBB). We describe a therapeutic platform for increasing the brain exposure of enzyme replacement therapies. The enzyme transport vehicle (ETV) is a lysosomal enzyme fused to an Fc domain that has been engineered to bind to the transferrin receptor, which facilitates receptor-mediated transcytosis across the BBB. We demonstrate that ETV fusions containing iduronate 2-sulfatase (ETV:IDS), the lysosomal enzyme deficient in mucopolysaccharidosis type II, exhibited high intrinsic activity and degraded accumulated substrates in both IDS-deficient cell and in vivo models. ETV substantially improved brain delivery of IDS in a preclinical model of disease, enabling enhanced cellular distribution to neurons, astrocytes, and microglia throughout the brain. Improved brain exposure for ETV:IDS translated to a reduction in accumulated substrates in these CNS cell types and peripheral tissues and resulted in a complete correction of downstream disease-relevant pathologies in the brain, including secondary accumulation of lysosomal lipids, perturbed gene expression, neuroinflammation, and neuroaxonal damage. These data highlight the therapeutic potential of the ETV platform for LSDs and provide preclinical proof of concept for TV-enabled therapeutics to treat CNS diseases more broadly.

Brain delivery of therapeutic proteins using an Fc fragment blood-brain barrier transport vehicle in mice and monkeys.

Effective delivery of protein therapeutics to the central nervous system (CNS) has been greatly restricted by the blood-brain barrier (BBB). We describe the development of a BBB transport vehicle (TV) comprising an engineered Fc fragment that exploits receptor-mediated transcytosis for CNS delivery of biotherapeutics by binding a highly expressed brain endothelial cell target. TVs were engineered using directed evolution to bind the apical domain of the human transferrin receptor (hTfR) without the use of amino acid insertions, deletions, or unnatural appendages. A crystal structure of the TV-TfR complex revealed the TV binding site to be away from transferrin and FcRn binding sites, which was further confirmed experimentally in vitro and in vivo. Recombinant expression of TVs fused to anti-ß-secretase (BACE1) Fabs yielded antibody transport vehicle (ATV) molecules with native immunoglobulin G (IgG) structure and stability. Peripheral administration of anti-BACE1 ATVs to hTfR-engineered mice and cynomolgus monkeys resulted in substantially improved CNS uptake and sustained pharmacodynamic responses. The TV platform readily accommodates numerous additional configurations, including bispecific antibodies and protein fusions, yielding a highly modular CNS delivery platform.

Sustained molecular response following a failed attempt of tyrosine kinase inhibitor discontinuation & the effects on growth in a child with chronic myeloid leukemia: not always a short story.

We report a patient who developed chronic myelogenous leukemia (CML) at 12 months of age. She was treated aggressively with stem cell transplant (SCT), interferon, donor lymphocytes and imatinib, with subsequent molecular progression. She received dasatinib, achieving a complete molecular response. Dasatinib was discontinued at 3 years but she had a molecular recurrence. Dasatinib was restarted and continued for 5 additional years with a second major molecular remission (MMR). While on dasatinib therapy she suffered growth failure and was treated with concurrent growth hormone (GH). After discontinuing dasatinib and GH, catch-up growth continues and she remains in MMR. Discontinuation of TKI therapy and the toxicity of long-term TKI therapy is discussed.

Author Correction: Cancer Testis Antigen Promotes Triple Negative Breast Cancer Metastasis and is Traceable in the Circulating Extracellular Vesicles.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Contrast Extravasation as a Complication of Emergency Nurse-Performed Ultrasound-Guided Peripheral Intravenous Catheter Placement.

INTRODUCTION: Vascular access procedures are among the most commonly performed procedures in the emergency department. The objective of the current study was to compare the contrast extravasation rate for ultrasound-guided peripheral intravenous (USGPIV) catheter placement by emergency nurses with peripheral intravenous catheters placed by standard landmark techniques. METHODS: A retrospective chart review of all ED patients at our urban tertiary-care institution who underwent contrasted computed tomography examination and suffered contrast extravasation events was performed. A logbook of all ED patients who underwent USGPIV placement and an institution-wide electronic patient safety incident-reporting system was reviewed for all contrast extravasation events between May 2014, and February 2017. Data were analyzed using descriptive statistics, Student t-tests for continuous data, and χ2 or Fisher's exact test for categorical data. RESULTS: One thousand five hundred USGPIV catheters were placed by 27 emergency nurses. Contrast material was administered 29,508 times, and, of these, 291 were administered via USGPIV placement. There were 74 peripheral IV lines with documented contrast extravasations (0.25%) as reported in the safety-event database; 12 (4.1%) were from the USGPIV population, and 62 (0.21%) occurred in the standard landmark technique population. Relative risk of contrast extravasation events with USGPIV placement was 19.4 (95% confidence interval [CI], 10.6-35.6), and the absolute risk difference was 3.9% (95% CI 1.6%-6.2%). DISCUSSION: USGPIV placement by trained emergency nurses has higher rates of contrast extravasation than with standard landmark technique placement.

Cancer Testis Antigen Promotes Triple Negative Breast Cancer Metastasis and is Traceable in the Circulating Extracellular Vesicles.

Triple negative breast cancer (TNBC) has poor survival, exhibits rapid metastases, lacks targeted therapies and reliable prognostic markers. Here, we examined metastasis promoting role of cancer testis antigen SPANXB1 in TNBC and its utility as a therapeutic target and prognostic biomarker. Expression pattern of SPANXB1 was determined using matched primary cancer, lymph node metastatic tissues and circulating small extracellular vesicles (sEVs). cDNA microarray analysis of TNBC cells stably integrated with a metastasis suppressor SH3GL2 identified SPANXB1 as a potential target gene. TNBC cells overexpressing SH3GL2 exhibited decreased levels of both SPANXB1 mRNA and protein. Silencing of SPANXB1 reduced migration, invasion and reactive oxygen species production of TNBC cells. SPANXB1 depletion augmented SH3GL2 expression and decreased RAC-1, FAK, A-Actinin and Vinculin expression. Phenotypic and molecular changes were reversed upon SPANXB1 re-expression. SPANXB1 overexpressing breast cancer cells with an enhanced SPANXB1:SH3GL2 ratio achieved pulmonary metastasis within 5 weeks, whereas controls cells failed to do so. Altered expression of SPANXB1 was detected in the sEVs of SPANXB1 transduced cells. Exclusive expression of SPANXB1 was traceable in circulating sEVs, which was associated with TNBC progression. SPANXB1 represents a novel and ideal therapeutic target for blocking TNBC metastases due to its unique expression pattern and may function as an EV based prognostic marker to improve TNBC survival. Uniquely restricted expression of SPANXB1 in TNBCs, makes it an ideal candidate for targeted therapeutics and prognostication.

Development of acute lymphoblastic leukemia following treatment for acute myeloid leukemia in children with Down syndrome: A case report and retrospective review of Children's Oncology Group acute myeloid leukemia trials.

Children with Down syndrome have a 150-fold increased risk of developing acute myeloid leukemia (AML) and 20-fold increased risk of developing acute lymphoblastic leukemia (ALL). Although the risk of developing AML and ALL is significantly increased in children with Down syndrome, the development of both malignancies in the same patient is very rare. We describe a patient with Down syndrome who developed ALL 6 years after being diagnosed with AML. We performed a literature review and Children's Oncology Group query and discovered eight published cases and five cases of ALL following AML in pediatric patients with Down syndrome, as well as six cases of ALL following AML in non-Down syndrome patients. There was a similar cumulative incidence of ALL after treatment for AML in the Down syndrome and non-Down syndrome populations. Overall survival in patients with Down syndrome who developed ALL after treatment for AML was comparable to overall survival for patients with Down syndrome with de novo ALL with an average follow-up of 7 years after ALL diagnosis. Clinical data collected were used to discuss whether this phenomenon represents a secondary leukemia, second primary cancer, or mixed-lineage leukemia.

The Effects of Avatars' Age on Older Adults' Self-Disclosure and Trust.

Older adults are increasingly interacting with other people online via virtual avatars, yet little is known about how avatars affect older adults' behavior. This study examines how interacting avatars' age affects older adult's self-disclosure and trust in a relation-building context. Previous studies have found that users can take on behaviors consistent with characteristics of the avatars. In social interactions, people also assess their avatar in relation to other avatars for similarity or differences. We conducted a 2 (self-avatar: old vs. young) × 2 (other's avatar: old vs. young) experiment with older-adult participants aged 60+ (n = 95). The findings show that using younger avatars did not increase self-disclosure. However, the older-adult participants disclosed more information when their avatar's age matched their partner avatar's age (i.e., old to old, young to young). They also trust their partners more when the interacting avatars shared similar age. This study provides theoretical insights into the role of avatars in online relationship-building and extends our understanding of the avatar effects on older adults.

Modifying bone mineral density, physical function, and quality of life in children with acute lymphoblastic leukemia.

BACKGROUND: The early effects of childhood acute lymphoblastic leukemia (ALL) include decreased physical function, bone mineral density (BMD/g/cm2 ), and health-related quality of life (HRQL). We assessed the capacity of a physical therapy and motivation-based intervention, beginning after diagnosis and continuing through the end of treatment, to positively modify these factors. PROCEDURE: A 2.5-year randomized controlled trial of 73 patients aged 4-18.99 years within 10 days of ALL diagnosis assessed BMD at baseline (T0 ) and end of therapy (T3 ), strength, range of motion, endurance, motor skills, and HRQL at baseline (T0 ), 8 (T1 ), 15 (T2 ), and 135 (T3 ) weeks. RESULTS: There were no significant changes between groups (intervention, n = 33; usual care, n = 40) in BMD (P = 0.059) at T3 or physical function and HRQL at T0 -T3 . While BMD declined in both the intervention (T0  = -0.21, T3  = -0.55) and usual care (T0  = -0.62, T3  = -0.78) groups, rates of decline did not differ between groups (P = 0.56). Univariate analysis (n = 73) showed associations of higher T3 bone density with body mass index T1 (P = 0.01), T2 (P = <0.0001), T3 (P = 0.01), T3 ankle flexibility/strength (P = 0.001), and T2 parent (P = 0.02)/T0 child (P = 0.03) perceptions of less bodily pain. CONCLUSIONS: The intervention delivered during treatment was not successful in modifying BMD, physical function, or HRQL. Physical activity, at the level and intensity required to modify these factors, may not be feasible during early treatment owing to the child's responses to the disease and treatment. Future studies will consider intervention implementation during late maintenance therapy, extending into survivorship.