Browsing by Subject "ASD"
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Item Open Access Calibration of a comprehensive predictive model for the development of proximal junctional kyphosis and failure in adult spinal deformity patients with consideration of contemporary goals and techniques.(Journal of neurosurgery. Spine, 2023-06) Tretiakov, Peter S; Lafage, Renaud; Smith, Justin S; Line, Breton G; Diebo, Bassel G; Daniels, Alan H; Gum, Jeffrey; Protopsaltis, Themistocles; Hamilton, D Kojo; Soroceanu, Alex; Scheer, Justin K; Eastlack, Robert K; Mundis, Gregory; Nunley, Pierce D; Klineberg, Eric O; Kebaish, Khaled; Lewis, Stephen; Lenke, Lawrence; Hostin, Richard; Gupta, Munish C; Ames, Christopher P; Hart, Robert A; Burton, Douglas; Shaffrey, Christopher I; Schwab, Frank; Bess, Shay; Kim, Han Jo; Lafage, Virginie; Passias, Peter GObjective
The objective of this study was to calibrate an updated predictive model incorporating novel clinical, radiographic, and prophylactic measures to assess the risk of proximal junctional kyphosis (PJK) and failure (PJF).Methods
Operative patients with adult spinal deformity (ASD) and baseline and 2-year postoperative data were included. PJK was defined as ≥ 10° in sagittal Cobb angle between the inferior uppermost instrumented vertebra (UIV) endplate and superior endplate of the UIV + 2 vertebrae. PJF was radiographically defined as a proximal junctional sagittal Cobb angle ≥ 15° with the presence of structural failure and/or mechanical instability, or PJK with reoperation. Backstep conditional binary supervised learning models assessed baseline demographic, clinical, and surgical information to predict the occurrence of PJK and PJF. Internal cross validation of the model was performed via a 70%/30% cohort split. Conditional inference tree analysis determined thresholds at an alpha level of 0.05.Results
Seven hundred seventy-nine patients with ASD (mean 59.87 ± 14.24 years, 78% female, mean BMI 27.78 ± 6.02 kg/m2, mean Charlson Comorbidity Index 1.74 ± 1.71) were included. PJK developed in 50.2% of patients, and 10.5% developed PJF by their last recorded visit. The six most significant demographic, radiographic, surgical, and postoperative predictors of PJK/PJF were baseline age ≥ 74 years, baseline sagittal age-adjusted score (SAAS) T1 pelvic angle modifier > 1, baseline SAAS pelvic tilt modifier > 0, levels fused > 10, nonuse of prophylaxis measures, and 6-week SAAS pelvic incidence minus lumbar lordosis modifier > 1 (all p < 0.015). Overall, the model was deemed significant (p < 0.001), and internally validated receiver operating characteristic analysis returned an area under the curve of 0.923, indicating robust model fit.Conclusions
PJK and PJF remain critical concerns in ASD surgery, and efforts to reduce the occurrence of PJK and PJF have resulted in the development of novel prophylactic techniques and enhanced clinical and radiographic selection criteria. This study demonstrates a validated model incorporating such techniques that may allow for the prediction of clinically significant PJK and PJF, and thus assist in optimizing patient selection, enhancing intraoperative decision making, and reducing postoperative complications in ASD surgery.Item Open Access Caregiver Descriptions of Joint Activity Routines and Perceptions of Acceptability of a Caregiver Coaching Approach to Early Autism Spectrum Disorder Intervention in South Africa(2018) Ramseur II, Kevin ChristopherBackground: Early detection and early intervention for autism spectrum disorder (ASD) is critical because it can reduce the severity of core ASD symptoms, and result in significant long-term improvements in language acquisition, social skills, cognitive abilities, and adaptive behaviors. Involving caregivers in the delivery of early ASD intervention is becoming increasingly important, particularly in low-resource settings, due to limited access to specialist ASD services. Currently, there is no published research on early ASD intervention in South Africa or sub-Saharan Africa (SSA). In addition, there are no published descriptions of caregiver-child joint activity routines, in which early intervention techniques can be embedded, or perceptions of the acceptability of a caregiver coaching approach.
Study Aims: This study aimed to elicit qualitative descriptions of caregiver-child joint activity routines in order to understand how the Early Start Denver Model (ESDM), an evidence-based early ASD intervention, could fit in a low resource South African setting. It also aimed to gauge the acceptability of a caregiver coaching intervention from South African caregivers of young children with ASD who received two taster sessions of caregiver coaching.
Methods: Participants were recruited from the Western Cape Education Department autism waiting list through convenience sampling. Four focus group discussions were conducted with 22 caregivers of young children with ASD, which gathered data on caregiver-child joint activity routines. Four additional families were recruited to participate in two caregiver coaching sessions each. Four in-depth interviews were subsequently conducted with the six caregivers from these families, which gathered data on joint activity routines and acceptability of a caregiver coaching intervention. Data were analyzed through a qualitative content analysis approach, which used a combination of inductive and deductive methods to determine the salient themes and subthemes within the data.
Results: Caregiver descriptions of joint activity routines aligned with ESDM themes of object-based play, sensory social routines, and family routines. In object-based play caregivers reported engaging in turn-taking with their children, teaching skills across developmental domains, embracing child-directed activities, and managing challenges related to play in resource limited settings. In sensory social routines, caregivers described physical play, an awareness of the child’s affect and engagement, increased child expressive communication, and willingness of the child to engage with different play partners. In family routines, caregivers reported child participation in meals and bath time. Caregivers reported that a caregiver coaching approach was acceptable and that they had acquired a variety of skills, including strategies to enhance their child’s social communication. Caregivers preferred receiving coaching in their homes as opposed to in a clinic setting; however, limitations in physical space and financial resources were important considerations.
Conclusion: Training caregiver coaches and non-specialist workers narrows the treatment gap by providing access to children in need of early ASD intervention. This is essential, because of the scarcity of psychologists and psychiatrists working in mental health in low and middle-income countries (LMIC). Descriptions from South African caregivers of caregiver-child joint activity routines and acceptability of the caregiver coaching approach contextualize the caregiver coaching intervention. These data will inform the adaptation and piloting of an early ASD intervention within a low-resource South African setting.
Item Open Access SHANK3 Deficiency Impairs Heat Hyperalgesia and TRPV1 Signaling in Primary Sensory Neurons.(Neuron, 2016-12-21) Han, Qingjian; Kim, Yong Ho; Wang, Xiaoming; Liu, Di; Zhang, Zhi-Jun; Bey, Alexandra L; Lay, Mark; Chang, Wonseok; Berta, Temugin; Zhang, Yan; Jiang, Yong-Hui; Ji, Ru-RongAbnormal pain sensitivity is commonly associated with autism spectrum disorders (ASDs) and affects the life quality of ASD individuals. SHANK3 deficiency was implicated in ASD and pain dysregulation. Here, we report functional expression of SHANK3 in mouse dorsal root ganglion (DRG) sensory neurons and spinal cord presynaptic terminals. Homozygous and heterozygous Shank3 complete knockout (Δe4-22) results in impaired heat hyperalgesia in inflammatory and neuropathic pain. Specific deletion of Shank3 in Nav1.8-expressing sensory neurons also impairs heat hyperalgesia in homozygous and heterozygous mice. SHANK3 interacts with transient receptor potential subtype V1 (TRPV1) via Proline-rich region and regulates TRPV1 surface expression. Furthermore, capsaicin-induced spontaneous pain, inward currents in DRG neurons, and synaptic currents in spinal cord neurons are all reduced after Shank3 haploinsufficiency. Finally, partial knockdown of SHANK3 expression in human DRG neurons abrogates TRPV1 function. Our findings reveal a peripheral mechanism of SHANK3, which may underlie pain deficits in SHANK3-related ASDs.Item Open Access The effects of aging on the BTBR mouse model of autism spectrum disorder.(Front Aging Neurosci, 2014) Jasien, Joan M; Daimon, Caitlin M; Wang, Rui; Shapiro, Bruce K; Martin, Bronwen; Maudsley, StuartAutism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental disorder characterized by alterations in social functioning, communicative abilities, and engagement in repetitive or restrictive behaviors. The process of aging in individuals with autism and related neurodevelopmental disorders is not well understood, despite the fact that the number of individuals with ASD aged 65 and older is projected to increase by over half a million individuals in the next 20 years. To elucidate the effects of aging in the context of a modified central nervous system, we investigated the effects of age on the BTBR T + tf/j mouse, a well characterized and widely used mouse model that displays an ASD-like phenotype. We found that a reduction in social behavior persists into old age in male BTBR T + tf/j mice. We employed quantitative proteomics to discover potential alterations in signaling systems that could regulate aging in the BTBR mice. Unbiased proteomic analysis of hippocampal and cortical tissue of BTBR mice compared to age-matched wild-type controls revealed a significant decrease in brain derived neurotrophic factor and significant increases in multiple synaptic markers (spinophilin, Synapsin I, PSD 95, NeuN), as well as distinct changes in functional pathways related to these proteins, including "Neural synaptic plasticity regulation" and "Neurotransmitter secretion regulation." Taken together, these results contribute to our understanding of the effects of aging on an ASD-like mouse model in regards to both behavior and protein alterations, though additional studies are needed to fully understand the complex interplay underlying aging in mouse models displaying an ASD-like phenotype.Item Open Access Use of multiple rods and proximal junctional kyphosis in adult spinal deformity surgery.(Journal of neurosurgery. Spine, 2023-06) Ye, Jichao; Gupta, Sachin; Farooqi, Ali S; Yin, Tsung-Cheng; Soroceanu, Alex; Schwab, Frank J; Lafage, Virginie; Kelly, Michael P; Kebaish, Khaled; Hostin, Richard; Gum, Jeffrey L; Smith, Justin S; Shaffrey, Christopher I; Scheer, Justin K; Protopsaltis, Themistocles S; Passias, Peter G; Klineberg, Eric O; Kim, Han Jo; Hart, Robert A; Hamilton, D Kojo; Ames, Christopher P; Gupta, Munish CObjective
Multiple rods are utilized in adult spinal deformity (ASD) surgery to increase construct stiffness. However, the impact of multiple rods on proximal junctional kyphosis (PJK) is not well established. This study aimed to investigate the impact of multiple rods on PJK incidence in ASD patients.Methods
ASD patients from a prospective multicenter database with a minimum follow-up of 1 year were retrospectively reviewed. Clinical and radiographic data were collected preoperatively, at 6 weeks postoperatively, at 6 months postoperatively, at 1 year postoperatively, and at every subsequent year postoperatively. PJK was defined as a kyphotic increase of > 10° in the Cobb angle from the upper instrumented vertebra (UIV) to UIV+2 as compared with preoperative values. Demographic data, radiographic parameters, and PJK incidence were compared between the multirod and dual-rod patient cohorts. PJK-free survival analysis was performed using Cox regression to control for demographic characteristics, comorbidities, level of fusion, and radiographic parameters.Results
Overall, 307/1300 (23.62%) cases utilized multiple rods. Cases with multiple rods were more likely to be revisions (68.4% vs 46.5%, p < 0.001), to be posterior only (80.7% vs 61.5%, p < 0.001), involve more levels of fusion (mean 11.73 vs 10.60, p < 0.001), and include 3-column osteotomy (42.9% vs 17.1%, p < 0.001). Patients with multiple rods also had greater preoperative pelvic retroversion (mean pelvic tilt 27.95° vs 23.58°, p < 0.001), greater thoracolumbar junction kyphosis (-15.9° vs -11.9°, p = 0.001), and more severe sagittal malalignment (C7-S1 sagittal vertical axis 99.76 mm vs 62.23 mm, p < 0.001), all of which corrected postoperatively. Patients with multiple rods had similar incidence rates of PJK (58.6% vs 58.1%) and revision surgery (13.0% vs 17.7%). The PJK-free survival analysis demonstrated equivalent PJK-free survival durations among the patients with multiple rods (HR 0.889, 95% CI 0.745-1.062, p = 0.195) after controlling for demographic and radiographic parameters. Further stratification based on implant metal type demonstrated noninferior PJK incidence rates with multiple rods in the titanium (57.1% vs 54.6%, p = 0.858), cobalt chrome (60.5% vs 58.7%, p = 0.646), and stainless steel (20% vs 63.7%, p = 0.008) cohorts.Conclusions
Multirod constructs for ASD are most frequently utilized in revision, long-level reconstructions with 3-column osteotomy. The use of multiple rods in ASD surgery does not result in an increased incidence of PJK and is not affected by rod metal type.