Background
Currently, there are no standardized approaches to care or evaluation for tone dysfunction in Canada. The study authors hypothesize that there is significant practice variation across the ...country. This environmental scan is aimed to describe the current practice for management of paediatric patients with hypertonia across Canada.
Methods
A web‐based survey was developed by the authors with a multi‐disciplinary approach and sent to representative paediatric rehabilitation sites in each province in Canada. Disciplines at the rehabilitation sites surveyed included all or some of the following disciplines: physiatry, neurology, neurosurgery, plastic surgery, orthopaedic surgery, physiotherapy and occupational therapy. All statistical analyses were performed using the R statistical software version 4.0. Fifteen rehabilitation sites were contacted, and 12 sites were used for the final analysis.
Results
Cerebral palsy was found to be the most common diagnosis for tone dysfunction, with 58% of sites diagnosing greater than 20 new patients per year. In 67% of sites, patients were seen within a formal multidisciplinary clinic to manage hypertonia. All 12 sites utilized oral baclofen and gabapentin, and 92% of sites utilized trihexyphenidyl. Botulinum toxin injections were offered at 50% of sites. Upper and lower extremity surgical procedures were offered in 83% of the sites.
Conclusion
The information gained from this study provides some insight into the current practice across Canada for children with hypertonia. This study may assist in the development of a national, standardized strategy to tone management, potentially facilitating more equitable access to care for patients.
PurposeHemiplegia is a subtype of cerebral palsy (CP) in which one side of the body is affected. Our earlier study of unselected children with CP demonstrated de novo and clinically relevant rare ...inherited genomic copy-number variations (CNVs) in 9.6% of participants. Here, we examined the prevalence and types of CNVs specifically in hemiplegic CP.MethodsWe genotyped 97 unrelated probands with hemiplegic CP and their parents. We compared their CNVs to those of 10,851 population controls, in order to identify rare CNVs (<0.1% frequency) that might be relevant to CP. We also sequenced exomes of "CNV-positive" trios.ResultsWe detected de novo CNVs and/or sex chromosome abnormalities in 7/97 (7.2%) of probands, impacting important developmental genes such as GRIK2, LAMA1, DMD, PTPRM, and DIP2C. In 18/97 individuals (18.6%), rare inherited CNVs were found, affecting loci associated with known genomic disorders (17p12, 22q11.21) or involving genes linked to neurodevelopmental disorders.ConclusionWe found an increased rate of de novo CNVs in the hemiplegic CP subtype (7.2%) compared to controls (1%). This result is similar to that for an unselected CP group. Combined with rare inherited CNVs, the genomic data impacts the understanding of the potential etiology of hemiplegic CP in 23/97 (23.7%) of participants.
Aims: To compare changes in gross motor skills and functional mobility between ambulatory children with cerebral palsy who underwent a 1-week clinic-based virtual reality intervention (VR) followed ...by a 6-week, therapist-monitored home active video gaming (AVG) program and children who completed only the 6-week home AVG program. Methods: Pilot non-randomized controlled trial. Five children received 1 hour of VR training for 5 days followed by a 6-week home AVG program, supervised online by a physical therapist. Six children completed only the 6-week home AVG program. The Gross Motor Function Measure Challenge Module (GMFM-CM) and Six Minute Walk Test (6MWT) evaluated change. Results: There were no significant differences between groups. The home AVG-only group demonstrated a statistically and clinically significant improvement in GMFM-CM scores following the 6-week AVG intervention (median difference 4.5 points, interquartile range IQR 4.75, p = 0.042). The VR + AVG group demonstrated a statistically and clinically significant decrease in 6MWT distance following the intervention (median decrease 68.2 m, IQR 39.7 m, p = 0.043). All 6MWT scores returned to baseline at 2 months post-intervention. Conclusion: Neither intervention improved outcomes in this small sample. Online mechanisms to support therapist-child communication for exercise progression were insufficient to individualize exercise challenge.
Longevity Genes: From Primitive Organisms to Humans Butler, Robert N.; Austad, Steven N.; Barzilai, Nir ...
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences,
07/2003, Letnik:
58, Številka:
7
Conference Proceeding, Journal Article
Recenzirano
Odprti dostop
Butler et al suggest that longevity genes can be sorted into distinct theoretical categories. Seven categories are described. Lessons from invertebrate model systems, such as nematodes and fruit ...flies, lessons from a mammalian model system, and the transition from models to humans are discussed.
To compare visualization of first trimester fetal anatomic transvaginal ultrasound (TVUS) to the second trimester transabdominal anatomic ultrasound (TAU) in normal weight and obese patients.
In a ...prospective cross-sectional study design, 25 women underwent a TVUS between 12 and 14 weeks, and a TAU at 18-22 weeks. For each anatomic structure, the percentage of patients achieving optimal visualization was recorded. Risk ratios for visualizing a structure in the second trimester versus the first were calculated.
Twenty-five patients underwent a TVUS and 24 completed the TAU. The average BMI in the obese and nonobese groups was 34 kg/m
and 23 kg/m
, respectively. All structures were more consistently visualized during the TAU for the both groups. The cardiac views, hands and feet were more difficult to visualize in all the patients at both scan times but were more frequently visualized in the TAU. For the obese patients, hands, feet, cardiac and spine views were less frequently visualized in both the scans. The posterior fossa and profile views were more difficult to obtain in the TVUS.
The first trimester TVUS detects many of the structures assessed during an anatomic survey; however, it is not superior to the second trimester TAU in normal weight and obese patients.
To determine the stability of Gross Motor Function Classification System (GMFCS) levels between approximately 12 years of age and adulthood (i.e. > 16y) using a matched chart review. Adult health ...records from the Ottawa Rehabilitation Centre were matched with childhood health records from the Ottawa Children's Treatment Centre (OCTC). Health records were available for 103 adults (52 males, 51 females) with cerebral palsy (CP; age range 17–38y; mean age 22y SD 4y) who had also been seen at the OCTC at a mean age of 12 years (SD 1y). GMFCS levels as adults were: Level I, n= 10; Level II, n= 24; Level III, n= 21; Level IV, n= 30; and Level V, n= 18. Adult participants were classified using the GMFCS at the time they were last seen by a rehabilitation specialist, sometime between June 2002 and June 2005. Corresponding paediatric charts were reviewed and classified by two independent raters blinded to the adult GMFCS levels. GMFCS levels around age 12 were: Level I, n= 20; Level II, n= 13; Level III, n= 22; Level IV, n= 35; and Level V, n= 13. Interrater reliability for childhood health records was determined with a quadratic weighted kappa and was 0.978. Stability of GMFCS levels was also assessed using the quadratic weighted kappa and was 0.895. The positive predictive value of the GMFCS at 12 years of age to predict walking without mobility aids by adulthood is 0.88. If the child is a wheelchair user at around age 12 years, the positive predictive value is 0.96 that the individual will still be a wheelchair user as an adult. This study supports previous findings that interrater reliability when using the GMFCS is very high. It also shows that the GMFCS level observed around the age of 12 years is highly predictive of adult motor function. This provides important information for individuals with CP, their families, and care providers as they plan for future care needs and rehabilitation intervention.
We performed whole-genome sequencing (WGS) in 327 children with cerebral palsy (CP) and their biological parents. We classified 37 of 327 (11.3%) children as having pathogenic/likely pathogenic ...(P/LP) variants and 58 of 327 (17.7%) as having variants of uncertain significance. Multiple classes of P/LP variants included single-nucleotide variants (SNVs)/indels (6.7%), copy number variations (3.4%) and mitochondrial mutations (1.5%). The COL4A1 gene had the most P/LP SNVs. We also analyzed two pediatric control cohorts (n = 203 trios and n = 89 sib-pair families) to provide a baseline for de novo mutation rates and genetic burden analyses, the latter of which demonstrated associations between de novo deleterious variants and genes related to the nervous system. An enrichment analysis revealed previously undescribed plausible candidate CP genes (SMOC1, KDM5B, BCL11A and CYP51A1). A multifactorial CP risk profile and substantial presence of P/LP variants combine to support WGS in the diagnostic work-up across all CP and related phenotypes.
Acute myeloid leukaemia (AML) is an aggressive cancer with 50-75% of patients relapsing even after successful chemotherapy. The role of the bone marrow microenvironment (BMM) in protecting AML cells ...from chemotherapeutics and causing consequent relapse is increasingly recognised. However the role that the anti-apoptotic Bcl-2 proteins play as effectors of BMM-mediated drug resistance are less understood. Here we show that bone marrow mesenchymal stromal cells (BMSC) provide resistance to AML cells against BH
-mimetics, cytarabine and daunorubicin, but this is not mediated by Bcl-2 and/or Bcl-X
as previously thought. Instead, BMSCs induced Mcl-1 expression over Bcl-2 and/or Bcl-X
in AML cells and inhibition of Mcl-1 with a small-molecule inhibitor, A1210477, or repressing its expression with the CDC7/CDK9 dual-inhibitor, PHA-767491 restored sensitivity to BH
-mimetics. Furthermore, combined inhibition of Bcl-2/Bcl-X
and Mcl-1 could revert BMSC-mediated resistance against cytarabine + daunorubicin. Importantly, the CD34
/CD38
leukemic stem cell-encompassing population was equally sensitive to the combination of PHA-767491 and ABT-737. These results indicate that Bcl-2/Bcl-X
and Mcl-1 act in a redundant fashion as effectors of BMM-mediated AML drug resistance and highlight the potential of Mcl-1-repression to revert BMM-mediated drug resistance in the leukemic stem cell population, thus, prevent disease relapse and ultimately improve patient survival.
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