Experiential learning through Program Evaluation: Assessing external barriers to Bridgehaven attendance.

This cross-sectional study was conducted as an experiential project in a graduate Program Evaluation class. We worked together as a team to solve difficulties that occurred when evaluating a program for the first time, including overcoming initial fears and identifying the appropriate focus. The goal of this study was to identify the most common barriers to attendance at Bridgehaven Mental Health Services, a community-based outpatient program tailored to aid in the transition from hospitals to community living. External barriers to attendance were examined by an adapted version of the Structural Barriers to Clinic Attendance Scale (SCBA) and a researcher-created qualitative measure. Between-group t-tests and non-parametric analyses indicated that a far walk from the bus stop and negative perceptions of staff behavior were significant external barriers to Bridgehaven attendance among 42 adult members with severe mental illness. Additionally, themes from the qualitative data revealed that 74.7% of members viewed other obligations and appointments as barriers to their attendance. About half of the members surveyed indicated the positive impact of groups on attendance. Overall findings revealed the importance of considering external barriers, particularly issues related to transportation, scheduling, and social perceptions when identifying solutions to declining attendance rates. Through the process of conducting this study, we learned invaluable skills (e.g., problem-solving, teamwork, collaboration, and flexibility) that will carry with us as we evaluate programs in the future.

Capecitabine for Salvage Treatment of Patients With Heavily Pretreated Human Papillomavirus-Associated Oropharynx Cancer With Distant Metastases.

Background: Patients with metastatic human papillomavirus-associated oropharyngeal cancer (HPV-OPC) have a median overall survival exceeding 2 years and are often candidates for multiple lines of palliative therapy. With the approval of immunotherapy as first-line treatment, salvage therapeutic options are limited. We describe our experience using capecitabine as salvage therapy for patients with recurrent or metastatic (R/M) HPV-OPC. Methods: We performed a retrospective study of patients with R/M HPV-OPC with distant metastatic disease. Eligible patients were identified from a medical oncology clinical database. Demographic and clinical data were abstracted from the medical record. Survival probabilities were estimated with the Kaplan-Meier method. Results: 10 patients were identified. Sites of metastatic disease included lung, liver, mediastinal lymph nodes, bone, abdominal lymph nodes, and soft tissue. Most patients received capecitabine as fourth-line treatment. The median duration from start of capecitabine therapy until death was 10.5 months. Best treatment response was as follows: partial responses (PR) were seen in 4 of 10 (40%), stable disease (SD) in 3 of 10 (30%), and progressive disease (PD) in 2 of 10 (20%). The clinical benefit rate (CR + PR + SD) was 70%. Reasons for discontinuation included disease progression (n = 8) and side effects (n = 2). One patient notably had prolonged benefit from capecitabine and continued to be on treatment for 34 months total. Conclusions: Capecitabine is a potential salvage treatment for heavily pretreated patients with R/M HPV-OPC, with some patients experiencing prolonged response. Clinical or molecular predictors of response would be helpful to identify patients likely to benefit; a larger prospective study would be useful to confirm efficacy in this patient population.

Fatigue Following Pediatric Arterial Ischemic Stroke: Prevalence and Associated Factors.

Background and Purpose: The aims of this study were to assess the prevalence of multidimensional fatigue symptoms 5 years after pediatric arterial ischemic stroke and identify factors associated with fatigue. Methods: Thirty-one children (19 males) with pediatric arterial ischemic stroke, participating in a larger prospective, longitudinal study, were recruited to this study at 5 years poststroke. Parent- and self-rated PedsQL Multidimensional Fatigue Scale scores were compared with published normative data. Associations between parent-rated PedsQL Multidimensional Fatigue Scale, demographics, stroke characteristics, and concurrent outcomes were examined. Results: Parent-rated total, general and cognitive fatigue were significantly poorer than population norms, with more than half of all parents reporting fatigue symptoms in their children. One-third of children also reported experiencing fatigue symptoms, but their ratings did not differ significantly from normative expectations, as such, all further analyses were on parent ratings of fatigue. Older age at stroke and larger lesion size predicted greater general fatigue; older age, female sex, and higher social risk predicted more sleep/rest fatigue. No significant predictors of cognitive fatigue were identified and only older age at stroke predicted total fatigue. Greater fatigue was associated with poorer adaptive functioning, motor skills, participation, quality of life, and behavior problems but not attention. Conclusions: Fatigue is a common problem following pediatric arterial ischemic stroke and is associated with the functional difficulties often seen in this population. This study highlights the importance of long-term monitoring following pediatric arterial ischemic stroke and the need for effective interventions to treat fatigue in children.

Social Cognitive Dysfunction Following Pediatric Arterial Ischemic Stroke: Evidence From a Prospective Cohort Study.

Background and Purpose: Childhood and adolescence coincide with rapid maturation of distributed brain networks supporting social cognition; however, little is known about the impact of early ischemic brain insult on the acquisition of these skills. This study aimed to examine the influence of arterial ischemic stroke (AIS) on facial emotion recognition and theory of mind (ToM) abilities of children and adolescents initially recruited to a single-center, prospective longitudinal study of recovery following AIS. Methods: The study involved 67 participants, including 30 children with AIS (mean time since stroke=5 years) and 37 age-matched typically developing controls who were assessed on measures of cognitive ToM, facial emotion recognition, and affective ToM. Acute clinical magnetic resonance imaging, including diffusion-weighted imaging sequences, were used to evaluate prospective structure-function relationships between acute lesion characteristics (size, location, and arterial territories affected) and long-term social cognitive abilities. Results: Relative to age-matched typically developing controls, children with AIS showed significantly worse performance on measures of basic facial emotion processing, cognitive ToM, and affective ToM. In univariate models, poorer ToM was associated with larger infarcts, combined cortical-subcortical pathology, and involvement of multiple arterial territories. In multivariate analyses, larger lesions and multiterritory infants were predictive of ToM processing but not facial emotion recognition. Poorer cognitive ToM predicted less frequent prosocial behavior and increased peer problems. Conclusions: Social cognitive skills appear vulnerable to disruption from early ischemic brain insult. In the first study to examine social cognition in a prospective cohort of children with AIS, our findings suggest that acute magnetic resonance imaging-based lesion characteristics may have predictive value for long-term social cognitive outcomes and may assist to identify children at elevated risk for social cognitive dysfunction.

Multi-focal Lytic Lesions in a Patient with Myelofibrosis: A Case Report.

Myelofibrosis is a rare disorder that is classified as one of the myeloproliferative disorders. This particular disorder results in the abnormal proliferation of hematopoietic stem cells in the bone marrow. In some cases, such as ours, pathologic fractures can occur due to skeletal manifestations. We report on a rare finding of rapidly progressive lytic lesions in multiple regions throughout the body. This presentation of myelofibrosis behaving in a metastatic-like fashion has not been previously described.

Pediatric Sarcoma Patients with Worse Physical Function but Better Peer Relationships and Depressive Symptoms than U.S. Pediatric Population as Measured by PROMIS®.

Background Pediatric patients with sarcomas are at risk of poor quality of life outcomes. The National Institutes of Health (NIH)-funded Patient-reported Outcomes Measurement Information System (PROMIS®) improves our ability to capture patient-reported outcomes. Do physical function, social, and mental health PROMIS outcomes for pediatric patients with non-metastatic malignant sarcomas differ from the U.S. pediatric population? Methods Six pediatric PROMIS short forms were collected for patient visits to orthopedic oncology at a tertiary referral center from September 1, 2016, to March 31, 2017. Mean T-scores differed from the reference population by a one-sample t-test. Results Of the 30 eligible patients, five had soft-tissue sarcomas and 25 (83%) had bone sarcomas. The mean age of the cohort was 13 years (5-17). The study cohort had a mean physical function T-score of 39.8 (SD 9.8), which was worse than the reference population. In contrast, the mean peer relationship T-score of 54.3 (SD 8.8) and mean depression T-score of 42.0 (SD 9.1) were better than the reference population. Conclusions Pediatric patients with non-metastatic sarcomas had a worse physical function but a better peer relationship and depression scores than the U.S. PROMIS reference population. Ceiling and flooring effects were reported. The level of evidence was III.

Cognitive resilience following paediatric stroke: Biological and environmental predictors.

Little is known about resilience after paediatric stroke (PS), or the factors that contribute to better outcomes. Rather, research emphasis has been on impairment, measured through cross-sectional or retrospective designs, often heavily weighted to children presenting for clinical or rehabilitation follow-up. Implementing a resilience framework, this study aimed to investigate cognitive recovery post-stroke and factors that contribute to cognitive resilience at 12 months following PS. In a single site, prospective, longitudinal study (baseline, 1, 6, 12 months post-stroke), 61 children (55.7% male) aged 0-18 years, with a diagnosis of acute arterial ischemic stroke were recruited. Neurological status, lesion and child characteristics were collected at diagnosis. Cognitive, language and motor skills were assessed directly using age-appropriate, standardised tools. Parents rated their mental health, and child social and adaptive abilities. Participants were classified as 'resilient' (74%) or 'vulnerable' based on 12-month cognitive scores. The resilient group demonstrated more intact acute neurological status and higher language and adaptive abilities 1-month post-stroke; 88% of the vulnerable group had strokes involving both cortical and subcortical regions. Neonatal stroke, large lesions, cortical-only lesions, and middle cerebral artery involvement were associated with poorer cognition over the 12 months post-stroke. Absence of seizures and older age at stroke predicted better cognitive outcomes. In summary, most children surviving PS are cognitively resilient at 12 months post-insult. Risk and protective factors identified may guide targeted clinical intervention for more vulnerable children. Future research is needed to explore cognitive resilience trajectories beyond 12 months post-stroke.

Evaluation of Planned versus Unplanned Soft-Tissue Sarcoma Resection Using PROMIS Measures.

BACKGROUND: The Patient Reported Outcomes Measurement Information System (PROMIS) is a tool developed by the National Institutes of Health that allows comparisons across conditions or even the United States (U.S.) general population. OBJECTIVES: Our purpose was to compare PROMIS outcomes between patients who underwent a planned resection to those who underwent an initial unplanned excision of their sarcoma followed by a definitive oncologic resection. We then compared these groups to the U.S. general population. METHODS: Eighty-five patients were included and were divided into those who underwent an initial planned resection (67) and unplanned excision (18). These patients were then further categorized based on the length of follow-up since their last surgery, either early (<12 months) or late (>12 months). RESULTS: We evaluated seven PROMIS domains and found no differences between patients who underwent planned resection versus those who underwent an initial unplanned excision followed by a wide resection of the previous wound bed. When compared to the U.S. population, both cohorts demonstrated significantly improved scores in several emotional health domains. CONCLUSIONS: Patients who undergo an unplanned excision followed by a definitive oncologic procedure have similar PROMIS scores compared to patients who undergo an initial planned resection.

A Comparison of Limb Salvage Versus Amputation for Nonmetastatic Sarcomas Using Patient-reported Outcomes Measurement Information System Outcomes.

INTRODUCTION: The Patient-reported Outcomes Measurement Information System (PROMIS) is a scoring tool that allows comparisons between patients with rare conditions and more common ailments, or the general US population. PROMIS outcomes were compared between the limb salvage and amputee patients for nonmetastatic sarcomas to the US population. METHODS: One hundred thirty-eight patients were included in the analysis. Patients were divided into the limb salvage and amputee cohorts, as well as based on the follow-up (1 to 11 or 12+ months). RESULTS: Seven PROMIS domains were evaluated, and higher scores were found in both the limb salvage group and patients >12 months from surgery. The limb salvage group also had improved emotional health compared with the US population. DISCUSSION: Improvements in PROMIS values are observed in limb salvage patients and in patients >12 months from surgery. Limb salvage patients demonstrate improved emotional health compared with the US population.

An Evaluation of PROMIS Health Domains in Sarcoma Patients Compared to the United States Population.

BACKGROUND: The Patient Reported Outcomes Measurement Information System (PROMIS) is a patient-directed system that allows comparisons across medical conditions. With this tool, comparisons can now be made between rare conditions, such as sarcomas, and more common ailments, of the United States general population. This allows comparisons between rare conditions, such as sarcomas, to more common ailments, or even the United States (US) general population. OBJECTIVES: Our purpose was to use PROMIS to compare outcomes in patients that had undergone resection of a nonmetastatic sarcoma to the US population. METHODS: One hundred thirty-eight patients were included in the analysis. These patients were divided into early (<2 years) and late follow-up (>2 years). RESULTS: We evaluated results from seven health domains and found significantly lower scores in the physical function and depression domains. These differences were present in both the early and late cohorts when compared to the US population. CONCLUSION: While physical function was found to be worse in the sarcoma cohorts, we observed significantly improved levels of depression in these patients when compared to the US population. This finding was maintained over time and is an important reminder that a patient's goals and desires change following a cancer diagnosis and must be taken into consideration when planning treatment and determining a successful outcome.

Motor function daily living skills 5 years after paediatric arterial ischaemic stroke: a prospective longitudinal study.

AIM: To describe 5-year motor and functional outcomes after paediatric arterial ischaemic stroke (AIS) and to explore factors associated with poorer long-term outcome. METHOD: Thirty-three children (21 males, 12 females) with AIS were recruited to a single-site, cross-sectional study, from a previously reported prospective longitudinal stroke outcome study. Children were stratified according to age at diagnosis: neonates (≤30d), preschool (>30d-5y), and school age (≥5y). Motor and functional outcomes were measured at 5 years after stroke. Neurological outcomes were evaluated using the Pediatric Stroke Outcome Measure (PSOM) at 1 month and more than 4 years after stroke. RESULTS: At 5 years after stroke, motor function, quality of life, fatigue, adaptive behaviour, activities of daily living, and handwriting speed were significantly poorer than age expectations. The preschool group had the highest percentage of fine and gross motor impairment. Poorer fine motor skills were associated with subcortical-only lesions and large lesion size. Poorer gross motor outcomes correlated with preschool age, bilateral lesions, and PSOM impairment at 1 month. INTERPRETATION: Children are at elevated risk for motor and functional impairments after AIS, with the preschool age group most vulnerable. Identifying early predictors of poorer outcomes facilitates targeted early intervention and long-term rehabilitation. WHAT THIS PAPER ADDS: Following paediatric stroke, children are at elevated risk of motor and functional difficulties. Stroke occurring between 30 days and 5 years of age may result in poorer motor and functional outcomes.

Long-Term Functional Outcomes of Distal Femoral Replacements Compared to Geographic Resections for Parosteal Osteosarcomas of the Distal Femur.

Background: Parosteal osteosarcoma is a rare tumor with increased survival compared to conventional high-grade osteosarcoma. Due to this increased survival comes the need for reconstructive options that provide good long-term functional results. Current treatment methods include geographic resection with allograft reconstruction versus resection and reconstruction with a distal femoral replacement. Purpose: Our purpose was to compare the long-term functional outcomes of distal femoral replacements to allograft reconstructions, using the musculoskeletal tumor society (MSTS) scoring system. Methods: After querying our database, 12 patients were identified and completed a MSTS questionnaire. Results: There was no difference in functional outcomes between the cohorts at an average of 14 years follow up for the endoprosthetic group and 25 years of follow up for the geographic resection group. Conclusion: At long-term follow-up, patients who undergo a distal femoral replacement for a parosteal osteosarcoma have no difference in functional outcomes compared to those who undergo an allograft reconstruction.Level of Evidence: IV.

Radiosynthesis and in vivo evaluation of [11C]MOV as a PET imaging agent for COX-2.

Radiosynthesis and in vivo evaluation of [11C]4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (methoxy analogue of valdecoxib, [11C]MOV), a COX-2 inhibitor, was conducted in rat and baboon. Synthesis of the reference standard MOV (3), and its desmethyl precursor 2 for radiolabeling were performed using 1,2-diphenylethan-1-one as the starting material in five steps with 15% overall yield. Radiosynthesis of [11C]MOV was accomplished in 40 ±â€¯10% yield and >99% radiochemical purity by reacting the precursor 2 in dimethyl formamide (DMF) with [11C]CH3I followed by removal of the dimethoxytrityl (DMT) protective group using trifluroacetic acid. PET studies in anesthetized baboon showed very low uptake and homogeneous distribution of [11C]MOV in brain. The radioligand underwent rapid metabolism in baboon plasma. MicroPET studies in male Sprague Dawley rats revealed [11C]MOV binding in lower thorax. The tracer binding in rats was partially blocked in heart and duodenum by the administration of 1 mg/kg oral dose of COX-2 inhibitor valdecoxib.

Reverse-reamed Intercalary Allograft: A Surgical Technique.

Allograft reconstruction of large segmental intercalary bone defects after tumor resection is a well-accepted surgical technique. Although results generally have been satisfactory, nonunion at the allograft-host bone junction site remains a notable concern. Various reports have described attempts to enhance junctional healing with a variety of complex osteotomies, often complicating an already complex procedure. The use of an innovative reverse reaming technique can decrease the level of intraoperative difficulty mating the allograft-host junction and theoretically may improve junctional healing by enhancing stability and increasing the contact surface area.

Social functioning following pediatric stroke: contribution of neurobehavioral impairment.

Pediatric stroke can result in long-term neurobehavioral impairments including cognitive, language, and motor deficits, all of which may disrupt the normal development of social skills. This study aimed to examine specific components of social function at 5-year poststroke at a group and individual level and explore the contribution of neurobehavioral impairment. Thirty-one children with arterial ischemic stroke participated in the study. Assessment included parent-rated questionnaires measuring social adjustment and social participation as well as behavior and fatigue. Children underwent testing of social cognition and neurobehavioral abilities (intellectual function, attention, pragmatic language, motor function, and neurological impairment). Group means for social function were generally within the normal range, with social adjustment poorer than normative expectations. Examination of impairment rates showed a significant proportion of children had impaired function across social domains. Childhood stroke was associated with poorer social adjustment and a range of neurobehavioral outcomes, compared to neonatal stroke. Social function was found to be impacted by fatigue and intellectual function, but not by attention, pragmatic language, behavior, motor function, or neurological impairment.

Alkyl indole-based cannabinoid type 2 receptor tools: Exploration of linker and fluorophore attachment.

Cannabinoid type 2 (CB2) receptor continues to emerge as a promising drug target for many diseases and conditions. New tools for studying CB2 receptor are required to further inform how this receptor functions in healthy and diseased states. The alkyl indole scaffold is a well-recognised ligand for cannabinoid receptors, and in this study the indole C5-7 positions were explored for linker and fluorophore attachment. A new high affinity, CB2 receptor selective inverse agonist was identified (16b) along with a general trend of C5-substituted indoles acting as agonists versus C7-substituted indoles acting as inverse agonists. The indole C7 position was found to be the most tolerant to linker extension and resulted in a high affinity inverse agonist with a medium length linker (19). Although a high affinity fluorescent ligand for CB2 receptor was not identified in this study, the indole C7 position shows great promise for fluorophore or probe attachment.

The Pediatric Stroke Outcome Measure: A predictor of outcome following arterial ischemic stroke.

OBJECTIVE: To evaluate the relationship between neurologic outcome at 1 month following diagnosis of pediatric arterial ischemic stroke (AIS) and motor and adaptive behavior outcomes at 12 months. METHODS: This prospective longitudinal observational cohort study recruited children from a single tertiary children's hospital diagnosed with first AIS between December 2007 and November 2013. Neurologic impairment was evaluated at 4 time points using the Pediatric Stroke Outcome Measure (PSOM) or Recovery and Recurrence Questionnaire following diagnosis of AIS (acute, 1, 6, and 12 months). Motor function and adaptive behavior were assessed at 12 months using standardized measures. Children were grouped for analysis, according to age at diagnosis (neonates vs preschool vs school-aged). The relationship between neurologic impairment and 12-month functional outcomes were examined. RESULTS: Sixty-four children were recruited (27 neonates, 19 preschool-aged, and 18 school-aged). Presence of impairment on the PSOM at 1 month was associated with lower 12-month fine motor z scores (p = 0.004), gross motor z scores (p = 0.001), and adaptive behavior standard scores (p = 0.004). One-month PSOM impairment score was more predictive than age group or lesion size of 12-month motor and adaptive behavior outcome. CONCLUSIONS: The PSOM has value as a predictive tool when used at 1 month after first AIS diagnosed acutely in relation to motor and adaptive behavior, with variation according to age group.

Development of selective, fluorescent cannabinoid type 2 receptor ligands based on a 1,8-naphthyridin-2-(1H)-one-3-carboxamide scaffold.

Cannabinoid type 2 (CB2) receptor has been implicated in several diseases and conditions, however no CB2 receptor selective drugs have made it to market. The aim of this study was to develop fluorescent ligands as CB2 receptor tools, to enable an increased understanding of CB2 receptor expression and signalling and thereby accelerate drug discovery. Fluorescent ligands have been successfully developed for other receptors, however none with adequate subtype selectivity or imaging properties have been reported for CB2 receptor. A series of 1,8-naphthyridin-2-(1H)-one-3-carboxamides with linkers and fluorophores appended in the N1 and C3-positions were developed. Molecular modelling indicated the C3 cis-cyclohexanol-linked compounds directed the linker out of the CB2 receptor between transmembrane helices 1 and 7. Herein we report fluorescent ligand 32 (hCB2 pK i = 6.33 ± 0.02) as one of the highest affinity, selective CB2 receptor fluorescent ligands reported. Despite 32 displaying poor specific labelling of CB2 receptor, the naphthyridine scaffold with this linker remains highly promising for future development of CB2 receptor tools.

Early predictors of psychosocial functioning 5 years after paediatric stroke.

AIM: Little is known about psychological and social outcomes after paediatric stroke. This study aimed to evaluate psychosocial outcomes in children 5 years after paediatric stroke and explore the contribution of early presenting factors. METHOD: Thirty-one children (19 males, 12 females) with arterial ischemic stroke were involved in this prospective, longitudinal study. Children underwent intellectual assessment at 12 months poststroke and parents completed questionnaires rating their own mental health and their child's functioning at 12 months and 5 years poststroke. RESULTS: At 5-year follow-up, psychological and social function were significantly poorer than normative expectations. Exploration of early predictive factors showed poorer cognitive and psychological function at 12 months poststroke and older age at stroke onset was associated with poorer psychosocial function at 5 years. Larger lesion size was also associated with poorer psychological function at 5 years poststroke. INTERPRETATION: These early predictors of poorer psychosocial outcome suggest that screening children within the first year after stroke may identify children most at risk of later problems and facilitate early intervention.