Factors associated with satisfaction with physical therapy services - a survey of patients with musculoskeletal pain at a federally qualified health center.

PURPOSE: The objective of this cross-sectional survey-based study was to assess factors associated with patient satisfaction with physical therapy (PT) services received at a Federally Qualified Health Center (FQHC) in the United States (US) located near the US-Mexico border. METHODS: Patients > 18 years of age, English or Spanish speakers, referred to PT were invited to complete an online survey. Factors that may influence PT satisfaction were examined for patients who attended PT. Variables associated with PT satisfaction from bivariate analyses (p < .15) were included in three separate ordinal logistic regression models. RESULTS: Patients (N = 231) who reported more confidence that PT could help relieve their pain were more likely to have higher levels of satisfaction with PT communication, treatment, and outcomes than those who reported low confidence (p < .05). Patients who reported having more support from family and friends were more likely to have higher levels of satisfaction with PT communication and treatment than those with less support (p < .01). Patients with occasional or frequent pain after ending PT treatment were more likely to have lower satisfaction with PT outcomes than those reporting no pain (p < .05). CONCLUSIONS: Findings suggest that addressing confidence in PT and promoting health support from family and friends may be important for satisfaction with PT. Additionally, PTs may consider addressing gaps between expected and achieved outcomes to improve PT satisfaction.

Long-term outcomes of symptomatic optic pathway glioma: 32-year experience at a single Western Australian tertiary pediatric oncology center.

Introduction: Optic pathway gliomas (OPGs) are associated with significant risk of visual and endocrine morbidity, but data on long-term outcomes in symptomatic patients is sparse. This study reviews the clinical course, disease progression, survival outcomes and long-term sequelae in pediatric patients with symptomatic OPGs in our institution over three decades. Methods: Retrospective review of patients with symptomatic OPG treated in a single tertiary pediatric oncology center from 1984 to 2016. Results: A total of 37 patients were diagnosed with symptomatic OPG. Decreased visual acuity was the commonest presenting symptom (75.7%). Surgical intervention was performed in 62.2%; 56.5% underwent biopsy, 26.1% surgical debulking and 17.4% had orbital decompression with cystic fenestration and cosmetic optic nerve excision at different treatment intervals. CSF diversion was performed in 47.8% patients. Histopathologic examination confirmed 86% to be pilocytic astrocytoma and 1 ganglioglioma. 46% received chemotherapy and 48% had radiotherapy, at different intervals. Median follow-up was 13.74 years. In NF1 patients, overall survival (OS) was 100% at 5 years and 55.6 ± 24.8% at 25 years while progression-free-survival (PFS) was 50 ± 15.8% at 5 and 20 years. In non-NF1 patients, OS was 96.2 ± 3.8% at 5 years and 87.4 ± 9% at 25-years. 5-year PFS was 53.8 ± 9.8% and 25-year PFS was 49.0 ± 10%. Cumulative PFS was 53 ± 8.3% at 5 years and 49.7 ± 8.4% at 20 years while cumulative OS was 97.2 ± 2.7% at 5 years and 77.5 ± 10.8% at 25 years. 59.5% patients developed post-operative endocrinopathy. Long-term vision was normal in 8.1%, improved in 13.5%, stabilized in 40.5% but worsened in 37.8% patients. Three patients treated with radiotherapy developed second brain tumors. Conclusion: 25-year OS in this cohort was 77.5% but survivorship carried significant long-term morbidities including radiation-induced second malignant brain tumors.

Implementation of DNA Methylation Array Profiling in Pediatric Central Nervous System Tumors: The AIM BRAIN Project: An Australian and New Zealand Children's Haematology/Oncology Group Study.

DNA methylation array profiling for classifying pediatric central nervous system (CNS) tumors is a valuable adjunct to histopathology. However, unbiased prospective and interlaboratory validation studies have been lacking. The AIM BRAIN diagnostic trial involving 11 pediatric cancer centers in Australia and New Zealand was designed to test the feasibility of routine clinical testing and ran in parallel with the Molecular Neuropathology 2.0 (MNP2.0) study at Deutsches Krebsforschungszentrum (German Cancer Research Center). CNS tumors from 269 pediatric patients were prospectively tested on Illumina EPIC arrays, including 104 cases co-enrolled on MNP2.0. Using MNP classifier versions 11b4 and 12.5, we report classifications with a probability score ≥0.90 in 176 of 265 (66.4%) and 213 of 269 (79.2%) cases, respectively. Significant diagnostic information was obtained in 130 of 176 (74%) for 11b4, and 12 of 174 (7%) classifications were discordant with histopathology. Cases prospectively co-enrolled on MNP2.0 gave concordant classifications (99%) and score thresholds (93%), demonstrating excellent test reproducibility and sensitivity. Overall, DNA methylation profiling is a robust single workflow technique with an acceptable diagnostic yield that is considerably enhanced by the extensive subgroup and copy number profile information generated by the platform. The platform has excellent test reproducibility and sensitivity and contributes significantly to CNS tumor diagnosis.

Protocol for a Parallel Group Randomized Clinical Trial Comparing a Culturally Adapted Cognitive Behavioral Telerehabilitation Intervention to Usual Physical Therapy for Latino Patients With Chronic Spine Pain.

OBJECTIVE: Disparities exist in health care access, diagnosis, and treatment of chronic pain in Latino populations and other minority populations. Cognitive behavioral-based physical therapy (CBPT) interventions have been shown to be effective in predominantly non-Hispanic white populations with chronic spine pain. However, there is a need for culturally adapted CBPT interventions that focus on the conservative management of chronic spine pain. The primary purpose of the study described in this protocol is to test the efficacy of an adapted cognitive behavioral-based hybrid telerehabilitation intervention for Latino patients with chronic spine pain. METHODS: A single-blind, 2-arm parallel group, superiority randomized clinical trial is planned to compare an adapted CBPT intervention to Usual Care physical therapy. Goal Oriented Activity for Latinos with chronic Spine pain (GOALS/Metas) is an 8-week hybrid telerehabilitation intervention that integrates guideline-based physical therapy and pain management interventions using cognitive behavioral approaches and has been adapted for Latino patients with chronic spine pain. Usual Care physical therapy will be administered based on institutional standards at the referring health center. Outcome measures will be evaluated preintervention and at 1-week, 3-months, and 6-months postintervention. The primary outcome is pain-related disability 1-week postintervention using the Brief Pain Inventory Pain Interference subscale. Secondary outcome measures include behavioral measures of functional activity, social participation, physical activity, and sleep. Determinants of treatment effect, including pain-related psychological measures, posture and movement, self-efficacy, treatment expectancy, and therapeutic alliance, will be included in the secondary moderation and mediation analyses. IMPACT: This clinical trial will provide information on the extent to which an adapted CBPT hybrid telerehabilitation intervention is effective in reducing pain-related disability for Latino patients with chronic spine pain. This information will be useful for clinicians to integrate in their practice, given the growing population of Latino patients who experience disparities in health care management of chronic pain.

In vivo loss of tumorigenicity in a patient-derived orthotopic xenograft mouse model of ependymoma.

Introduction: Ependymomas (EPN) are the third most common malignant brain cancer in children. Treatment strategies for pediatric EPN have remained unchanged over recent decades, with 10-year survival rates stagnating at just 67% for children aged 0-14 years. Moreover, a proportion of patients who survive treatment often suffer long-term neurological side effects as a result of therapy. It is evident that there is a need for safer, more effective treatments for pediatric EPN patients. There are ten distinct subgroups of EPN, each with their own molecular and prognostic features. To identify and facilitate the testing of new treatments for EPN, in vivo laboratory models representative of the diverse molecular subtypes are required. Here, we describe the establishment of a patient-derived orthotopic xenograft (PDOX) model of posterior fossa A (PFA) EPN, derived from a metastatic cranial lesion. Methods: Patient and PDOX tumors were analyzed using immunohistochemistry, DNA methylation profiling, whole genome sequencing (WGS) and RNA sequencing. Results: Both patient and PDOX tumors classified as PFA EPN by methylation profiling, and shared similar histological features consistent with this molecular subgroup. RNA sequencing revealed that gene expression patterns were maintained across the primary and metastatic tumors, as well as the PDOX. Copy number profiling revealed gains of chromosomes 7, 8 and 19, and loss of chromosomes 2q and 6q in the PDOX and matched patient tumor. No clinically significant single nucleotide variants were identified, consistent with the low mutation rates observed in PFA EPN. Overexpression of EZHIP RNA and protein, a common feature of PFA EPN, was also observed. Despite the aggressive nature of the tumor in the patient, this PDOX was unable to be maintained past two passages in vivo. Discussion: Others who have successfully developed PDOX models report some of the lowest success rates for EPN compared to other pediatric brain cancer types attempted, with loss of tumorigenicity not uncommon, highlighting the challenges of propagating these tumors in the laboratory. Here, we discuss our collective experiences with PFA EPN PDOX model generation and propose potential approaches to improve future success in establishing preclinical EPN models.

Diffuse paediatric cerebellar glioma: two identical imaging phenotypes of an extremely rare entity with disparate pathology.

Although the posterior fossa is a common location for paediatric brain tumours [1], diffuse glioma isolated to the cerebellum is an extremely rare imaging entity. Only two cases of isolated diffuse paediatric cerebellar glioma have been reported in the English language to the best of our knowledge [2, 3], and only one of these cases had a similar imaging phenotype to our cases [3]. Although somewhat similar to Lhermitte-Duclos (dysplastic gangliocytoma of the cerebellum), the appearances are distinct from other neoplastic entities of the paediatric posterior fossa. Clinical presentation and neurological examination findings are vital however to help differentiate other diffuse pathologies involving the cerebellum such as rhombencephalitis. Presented here are two diffuse cerebellar gliomas in children under the age of 3 with near identical imaging phenotypes demonstrating differing histological and molecular genetic profiles.

Epilepsy surgery in PCDH 19 related developmental and epileptic encephalopathy: A case report.

We report a female child with PCDH19 related developmental and epileptic encephalopathy with drug-resistant seizures, cognitive and language impairment, autism spectrum disorder and sleep dysfunction. Her seizures, which started at 10 months of age, were resistant to multiple anti-seizure medications. Developmental stagnation followed by regression occurred after the onset of recurrent seizures. Her ictal EEGS suggested left temporal lobe origin for her recorded seizures. MRI upon expert re-review showed a subtle abnormality in the left temporal lobe. In view of the severe nature and frequency of her seizures, a left temporal lobectomy was undertaken at the age of 2 years and 3 months. Though her seizure outcome was Engel class 3, her seizure frequency and severity were significantly reduced. She has been seizure-free for 10 months at her last outpatient assessment when she was 4 years and 8 months of age (2 years and 5 months after epilepsy surgery). However she recently had an admission for COVID19 infection, with a breakthrough cluster of seizures. Her developmental trajectory changed, though she is making good progress with her cognitive and language skills.

Intramolecular Proton Transfer in the Hydrogen Oxalate Anion and the Cooperativity Effects of the Low-Frequency Vibrations: A Driven Molecular Dynamics Study.

We report first-principles molecular dynamics (MD) and dipole-driven molecular dynamics (µ-DMD) simulations of the hydrogen oxalate anion at the MP2/aug-cc-pVDZ level of theory. We examine the role of vibrational coupling between the OH stretching bands, that is, the fundamental and a few combination bands spanning the 2900-3100 cm-1 range, and several of the low-frequency bending and stretching fundamental modes. The low-frequency modes between 300 and 825 cm-1 play a crucial role in the proton-transfer motion. Strong involvement of CO2 and CCO bending and the CC stretching vibrations indicate that these large amplitude motions cause the shortening of the O···O distance and thus promote H+ transfer to the other oxygen by bringing it over the 3.4 kcal/mol barrier. Analysis of resonant µ-DMD trajectories shows that the complex spectral feature near 825 cm-1, closely corresponding to both an overtone of two quanta of 425 cm-1 and a combination band of low-frequency CO2 rocking (300 cm-1) and CCO bending (575 cm-1) modes, is involved in the proton transfer. µ-DMD shows that exciting the system at these mode combinations leads to faster barrier activation than exciting at the OH fundamental mode.

Application of multiplex ligation-dependent probe amplification (MLPA) and low pass whole genome sequencing (LP-WGS) to the classification / characterisation of low grade glioneuronal tumours.

AIMS: Glioneuronal tumours, although rare, are an important cause of treatment-resistant epilepsy. Differential diagnosis of glioneuronal tumour subtypes is complicated by their variable histological appearance and the lack of pathognomonic histological or molecular biomarkers. In this study we have applied techniques available in a diagnostic laboratory setting to characterise molecular and cytogenetic abnormalities in a single institution cohort of glioneuronal tumours. METHODS: A cohort of 29 glioneuronal tumours that included 21 gangliogliomas and 5 dysembryoplastic neuroepithelial tumours (DNETs) was analysed using low pass whole genome sequencing (WGS) and 2 multiplex ligation-dependent probe amplification (MLPA) central nervous system (CNS) tumour probesets. RESULTS: Low pass WGS identified chromosomal or subchromosomal alterations in 15 specimens. The most common chromosomal alterations were gains of chromosome 7 (n = 8) and chromosome 16 (n = 3). The BRAFV600E mutation was detected by MLPA in 9/21 (42.9%) gangliogliomas and 2/2 pleomorphic xanthoastrocytomas (PXAs). Chromosome 7 gains detected by WGS were reflected in MLPAs by overall gains of chromosome 7 gene probes, including those for BRAF, KIAA1549 and EGFR, while an internal BRAF/MKRN1 duplication was detected in a single ganglioglioma. Homozygous CDKN2A/B loss was detected by MLPA in 3 gangliogliomas, with p16 immunohistochemistry supporting these results. CONCLUSIONS: The combination of low pass WGS and MLPA identifies multiple, diverse genetic and chromosomal alterations in glioneuronal tumours, irrespective of histological tumour grade.

Discordant electroencephalogram epileptiform activity and hemispherectomy in children with refractory epilepsy and encephaloclastic lesions: a case series.

This is a case series of six children with unilateral cerebral palsy and hemispheric encephaloclastic lesions who were evaluated for epilepsy surgery. Seizure onset was in the neonatal period in three children, at 17 months in two, and at 5 years in one. Their ictal and interictal electroencephalogram (EEG) abnormalities showed paradoxical lateralization to the incorrect/'normal' hemisphere or showed bilateral abnormalities. After cautious discussion regarding the discordant electroclinical profile and implications for outcome, they proceeded to a functional hemispherectomy (between ages 4-11y) with good outcomes (at 1-10y follow-up). Their clinical details, EEG findings, electrocorticography, neuroimaging, and histology are reported. Possible surgical candidacy should be evaluated early in children with refractory epilepsy, even those with complex profiles and discordant data from the different investigations. Contralateral or bilateral EEG abnormalities should not preclude consideration of hemispherectomy in children with refractory epilepsy, hemiparesis, and uniclastic lesions.

Case report: congenital intraventricular meningioma demonstrated with fetal MRI.

Congenital intracranial meningiomas are rare lesions. We present a case of congenital intraventricular cystic meningioma, initially characterized with fetal MRI and confirmed postnatally with histopathology. To our knowledge, this is the first in vivo description of a congenital meningioma with fetal MRI. The fetal MRI was able to characterize the lesion as an atypical intraventricular mass which was separate from the choroid plexus, differentiating the mass from a choroid plexus neoplasm. An intraventricular location of the meningioma is more commonly described in pediatric than in adult patients. Meningioma should be considered in the differential for an intraventricular congenital lesion, and fetal MRI is advocated for lesion characterization.

A case of subependymal giant cell astrocytoma without tuberous sclerosis complex and review of the literature.

Subependymal giant cell astrocytoma (SEGA) is a World Health Organization (WHO) grade I tumor most commonly seen in the context of the underlying tuberous sclerosis complex (TSC). SEGA in the absence of TSC is exceedingly rare. We report the youngest known case of SEGA in the absence of genetic or phenotypic evidence of TSC with a 10-year follow-up. We discuss the literature surrounding isolated SEGA including an approach to diagnosis, management, and prognosis.

A Novel Orthotopic Patient-Derived Xenograft Model of Radiation-Induced Glioma Following Medulloblastoma.

Radiation-induced glioma (RIG) is a highly aggressive brain cancer arising as a consequence of radiation therapy. We report a case of RIG that arose in the brain stem following treatment for paediatric medulloblastoma, and the development and characterisation of a matched orthotopic patient-derived xenograft (PDX) model (TK-RIG915). Patient and PDX tumours were analysed using DNA methylation profiling, whole genome sequencing (WGS) and RNA sequencing. While initially thought to be a diffuse intrinsic pontine glioma (DIPG) based on disease location, results from methylation profiling and WGS were not consistent with this diagnosis. Furthermore, clustering analyses based on RNA expression suggested the tumours were distinct from primary DIPG. Additional gene expression analysis demonstrated concordance with a published RIG expression profile. Multiple genetic alterations that enhance PI3K/AKT and Ras/Raf/MEK/ERK signalling were discovered in TK-RIG915 including an activating mutation in PIK3CA, upregulation of PDGFRA and AKT2, inactivating mutations in NF1, and a gain-of-function mutation in PTPN11. Additionally, deletion of CDKN2A/B, increased IDH1 expression, and decreased ARID1A expression were observed. Detection of phosphorylated S6, 4EBP1 and ERK via immunohistochemistry confirmed PI3K pathway and ERK activation. Here, we report one of the first PDX models for RIG, which recapitulates the patient disease and is molecularly distinct from primary brain stem glioma. Genetic interrogation of this model has enabled the identification of potential therapeutic vulnerabilities in this currently incurable disease.

Does early physical therapy intervention reduce opioid burden and improve functionality in the management of chronic lower back pain?

INTRODUCTION: Chronic lower back pain is a leading cause of disability in US adults. Opioid use continues to be controversial despite the Centers for Disease Control and Prevention guidance on chronic pain management to use nonpharmacologic and nonopioid pharmacologic interventions. The objectives of the study were to assess the impact of early physical therapy (PT) intervention on improving functionality and reducing opioid burden in patients with chronic lower back pain. METHODS: A single-center, retrospective chart review of patients receiving ≥6 PT visits and treated with either opioids first (OF) or PT first (PTF) therapy for chronic lower back pain were evaluated. Concomitant use of nonopioid and nonpharmacologic therapy was permitted. The Oswestry Disability Index (ODI), a survey measuring functionality, was recorded for PTF group. Pain scores and medication use including opioids were collected at treatment initiation and completion. RESULTS: One hundred and eighty patients were included in three groups: OF group (n = 60), PTF group (n = 60), and PTF + ODI group (n = 60). The PTF + ODI group had mean ODI reduction of 11.9% (P < .001). More OF patients were lost to follow up (68.3%) or failed PT (60%) compared to the PTF group, 38.3% and 3.3% (P < .001). Reduction in both opioid and nonopioid medications as well as pain scores were observed but not statistically significant. DISCUSSION: Early PT resulted in improved functionality, decreased pain, and reduced medication use upon PT completion. These findings suggest PT, along with nonopioid modalities, are a viable first-line option for the management of chronic lower back pain.

Polyarteritis nodosa isolated to muscles-A case series with a review of the literature.

Muscular polyarteritis nodosa where disease is isolated to skeletal muscle is a rare and often poorly recognised clinical entity. Patients typically present with fever and severe muscle pain limiting ability to ambulate without rise in creatine kinase. Often there is a significant delay between presentation and diagnosis, which requires histological confirmation. Musculoskeletal MRI is a sensitive investigation that can lead to timely biopsy and improve diagnostic yield. Early diagnosis of this condition is essential as patients typically respond favourably to corticosteroid treatment. Here we report 4 cases of muscular polyarteritis nodosa and review the reported literature.

Normative data of muscle fiber diameter of vastus lateralis during childhood: a field test.

INTRODUCTION: Currently, our knowledge of standard data for muscle morphology in children is largely limited to the 1969 article by Brooke and Engel (BE). In 2016, we reported normal muscle morphology from vastus lateralis biopsies in ambulant children with cerebral palsy (CP). This report compares our normal biopsy results against BE standard value criteria. METHODS: Single-blind prospective cross-sectional study design. RESULTS: Results of biopsies taken in ambulant children with CP were normal according to morphometry and light and electron microscopy; however, only 5 of 10 fulfilled the BE standard value criteria. DISCUSSION: This short report highlights the requirement for contemporary age-specific normative data from a larger number of biopsies, including typically developing children. Review of the literature suggests that biopsy material may be available from typically developing children who were control patients in research trials. This morphometric data could contribute to expanding the normative data set. Muscle Nerve 59:590-590, 2019.

Sporadic late onset nemaline myopathy (SLONM) in an adult presenting with progressive muscle weakness.

Sporadic late onset nemaline myopathy (SLONM) is a rare, intractable acquired myopathy that is characterised by progressive muscle weakness and the presence of nemaline rods in myofibres. Unlike the congenital form of nemaline myopathy (NM), there are only few case reports and series on SLONM in the scientific literature. We present a case report of SLONM in a 62-year-old male from a rural town in Western Australia, without any of the conditions often associated with SLONM such as monoclonal gammopathy of uncertain significance or HIV infection. SLONM should be considered in the differential diagnosis of progressive proximal muscle weakness in an adult.

Investigation of Dopamine Analogues: Synthesis, Mechanistic Understanding, and Structure-Property Relationship.

Dopamine, perhaps the simplest molecule that covalently links catechol and amine, together with its derivatives, has shown impressive adhesive and coating properties with its polymers. However, the scope of the molecules is rather limited, and the polymerization mechanisms are still elusive. We designed a general synthetic scheme and successfully synthesized a series of dopamine analogues with different alkyl chain lengths between the catechol and amine. Taking these new dopamine analogues, together with the molecular systems that have separate catechol and alkyl amine, we show that having both catechol and amine in the molecular system, whether covalently linked via an alkyl chain or not, is sufficient to polymerize under a similar reaction condition to that of dopamine polymerization. However, the time-dependent UV-vis characterization of the individual polymerization indicates that the polymerization for individual molecular systems likely proceeds via different reaction intermediates, depending on the length of the alkyl chain and whether there is a covalent linkage. Interestingly, whereas the covalent linkage via an alkyl chain is not necessary for showing the adhesive property, it is required to achieve the impressive coating property. Our results offer new insights into the design and synthesis of dopamine analogues for future applications, as well as a further mechanistic understanding of the polymerization of these dopamine analogues.

The role of temperature in forming sol-gel biocomposites containing polydopamine.

To further improve the physical strength and biomedical applicability of bioceramicsbuilt on hydroxyapatite-gelatin (HAp-Gel) and siloxane sol-gel reactions, we incorporated mussel adhesive inspired polydopamine (PD) into our original composite based on HAp-Gel cross-linked with siloxane. Surprisingly, with the addition of PD, we observed that the processing conditions and temperatures play an important role in the structure and performance of these materials. A systematic study to investigate this temperature dependence behavior discloses that the rate of crosslinking of silane during the sol-gel process is significantly influenced by the temperature, whereas the polymerization of the dopamine only shows minor temperature dependence. With this discovery, we report an innovative thermal process for the design and application of these biocomposites.