Publications by authors named "Paul Arnold"

393 Publications

Integration of clinical perspective into biomimetic bioreactor design for orthopedics.

J Biomed Mater Res B Appl Biomater 2021 Sep 12. Epub 2021 Sep 12.

Bioengineering Program, University of Kansas, Lawrence, Kansas, USA.

The challenges to accommodate multiple tissue formation metrics in conventional bioreactors have resulted in an increased interest to explore novel bioreactor designs. Bioreactors allow researchers to isolate variables in controlled environments to quantify cell response. While current bioreactor designs can effectively provide either mechanical, electrical, or chemical stimuli to the controlled environment, these systems lack the ability to combine all these stimuli simultaneously to better recapitulate the physiological environment. Introducing a dynamic and systematic combination of biomimetic stimuli bioreactor systems could tremendously enhance its clinical relevance in research. Thus, cues from different tissue responses should be studied collectively and included in the design of a biomimetic bioreactor platform. This review begins by providing a summary on the progression of bioreactors from simple to complex designs, focusing on the major advances in bioreactor technology and the approaches employed to better simulate in vivo conditions. The current state of bioreactors in terms of their clinical relevance is also analyzed. Finally, this review provides a comprehensive overview of individual biophysical stimuli and their role in establishing a biomimetic microenvironment for tissue engineering. To date, the most advanced bioreactor designs only incorporate one or two stimuli. Thus, the cell response measured is likely unrelated to the actual clinical performance. Integrating clinically relevant stimuli in bioreactor designs to study cell response can further advance the understanding of physical phenomenon naturally occurring in the body. In the future, the clinically informed biomimetic bioreactor could yield more efficiently translatable results for improved patient care.
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http://dx.doi.org/10.1002/jbm.b.34929DOI Listing
September 2021

Management of single-level thoracic disc herniation through a modified transfacet approach: A review of 86 patients.

Surg Neurol Int 2021 6;12:338. Epub 2021 Jul 6.

Department of Neurosurgery, Carle Neuroscience Institute, Urbana, Illinois, United States.

Background: Symptomatic thoracic disc herniation (TDH) is rare and does not typically resolve with conservative management. Traditional surgical management is the transthoracic approach; however, this approach can carry significant risk. Posterolateral approaches are less invasive, but no single approach has proven to be more effective than the other results are often dependent on surgeon experience with a particular approach, as well as the location and characteristics of the disc herniation.

Methods: This was retrospective review of a prospectively collected database. Eighty-six patients with TDH treated surgically through the modified transfacet approach were reviewed and evaluated for pain improvement, Nurick grade, and neurological symptoms. Patients were followed for 12 months postoperatively; estimated blood loss, length of hospital stay, hospital course, and postoperative complications were also assessed.

Results: All attempts at disc resection were successful. Most patients reported improvement in pain, sensory involvement, and strength. Seventy-nine patients had complete resolution of their symptoms while four patients had unchanged symptoms. Three patients experienced mild neurologic worsening postoperatively, but this resolved back to baseline. One patient experienced myelopathy during the postoperative period that resolved with steroid administration. The procedure was well tolerated with minimal complications.

Conclusion: TDH can be managed surgically through a variety of approaches. The selection of approach is dependent on surgeon experience with an approach, the patient's health, and the location and type of disc. The transfacet approach is safe and efficacious.
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http://dx.doi.org/10.25259/SNI_94_2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326068PMC
July 2021

Correlation Between the Spinal Instability Neoplastic Score (SINS) and Patient Reported Outcomes.

Global Spine J 2021 Jul 26:21925682211033591. Epub 2021 Jul 26.

Research Department, AO Spine International, Davos, Switzerland.

Study Design: International multicenter prospective observational cohort study on patients undergoing radiation +/- surgical intervention for the treatment of symptomatic spinal metastases.

Objectives: To investigate the association between the total Spinal Instability Neoplastic Score (SINS), individual SINS components and PROs.

Methods: Data regarding patient demographics, diagnostics, treatment, and PROs (SF-36, SOSGOQ, EQ-5D) was collected at baseline, 6 weeks, and 12 weeks post-treatment. The SINS was assessed using routine diagnostic imaging. The association between SINS, PRO at baseline and change in PROs was examined with the Spearmans rank test.

Results: A total of 307 patients, including 174 patients who underwent surgery+/- radiotherapy and 133 patients who underwent radiotherapy were eligible for analyses. In the surgery+/- radiotherapy group, 18 (10.3%) patients with SINS score between 0-6, 118 (67.8%) with a SINS between 7-12 and 38 (21.8%) with a SINS between 13-18, as compared to 55 (41.4%) SINS 0-6, 71(53.4%) SINS 7-12 and 7 (5.2%) SINS 13-18 in the radiotherapy alone group. At baseline, the total SINS and the presence of mechanical pain was significantly associated with the SOSGOQ pain domain (r = -0.519, < 0.001) and the NRS pain score (r = 0.445, < 0.001) for all patients. The presence of mechanical pain demonstrated to be moderately associated with a positive change in PROs at 12 weeks post-treatment.

Conclusion: Spinal instability, as defined by the SINS, was significantly correlated with PROs at baseline and change in PROs post-treatment. Mechanical pain, as a single SINS component, showed the highest correlations with PROs.
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http://dx.doi.org/10.1177/21925682211033591DOI Listing
July 2021

Protocol for Testing Yoga to Reduce Post-Lumbar Spine Surgery Pain: A Methodology Article.

Int J Yoga Therap 2021 Jul 19. Epub 2021 Jul 19.

Department of Physical Therapy and Rehabilitation Science, School of Health Professions, University of Kansas Medical Center, Kansas City.

Currently, acute postoperative pain during hospitalization is primarily managed by medications, and patients must adhere to restrictive postoperative precautions for 3 months following lumbar spine surgeries. Yoga can be an alternative approach to assist in acute and subacute postoperative pain management, anxiety, and return to function. The purpose of the present work was to develop and test the feasibility and explore the effectiveness of a tailored yoga program, delivered in-person during the hospital stay and electronically after hospital discharge, as a potential new avenue for postoperative care. This pilot study will use a crossover randomized controlled design. Individuals aged between 40 and 80 years who are scheduled for lumbar laminectomy and/or fusion, and who have not practiced regular yoga within the past 6 months at the time of enrollment, will be recruited and randomized to either a tailored yoga program (intervention group) or usual care (control group) during the hospital stay (phase one). Bearing in mind postoperative precautions, all subjects will be instructed to perform a home-based tailored yoga program delivered electronically via YouTube links for 8 weeks post-hospital discharge (phase two). The primary outcome measures assessing feasibility are adherence/compliance. Secondary outcome measures include pain, anxiety, function, sleep, perceived stress, and pain-catastrophizing behavior. Length of hospital stay and pain medication use, gait distance, and overall physical activity during hospitalization will also be collected. Finally, a qualitative interview will be obtained after completion of the hospital and home-based programs. This study will determine the feasibility of a tailored yoga program for acute and subacute postoperative lumbar spine surgery pain, anxiety, and functional outcomes.
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http://dx.doi.org/10.17761/2021-D-20-00016DOI Listing
July 2021

Developing a provincial patient support network for children and families affected by Tourette syndrome and/or obsessive-compulsive disorder: results of a stakeholder consultation.

Child Adolesc Psychiatry Ment Health 2021 Jun 16;15(1):29. Epub 2021 Jun 16.

Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Canada.

Background: Tourette syndrome and OCD are disorders that frequently occur in children and cause a high level of disability. In Alberta there is a huge delivery gap in providing healthcare services for children with TS and OCD. A stakeholder consultation was performed to ascertain how service delivery could be improved across the province and to inform the development of a provincial information and support organization, the Tourette OCD Alberta Network.

Methods: A mixed-methods study was employed: 10 parents were recruited for interview and 140 parents responded to a survey.

Results: Qualitative data showed there was often an absence of a clear pathway to access healthcare for people with TS and OCD. The negative impact of not receiving treatment, information, and resources in a timely and prompt manner was also revealed. Good clinical practice existed across the province but too often it was hindered by a shortage of knowledge about TS and OCD. In schools, learning for students with TS and OCD was also impaired by educators' lack of knowledge and preparedness in relation to the disorders.

Conclusions: This study identified ways that challenges with healthcare access, school learning, and seeking information can be overcome. Skills-based training webinars, educational outreach in schools, and peer support were recognized as actions for improving healthcare outcomes for people with TS and OCD. The aim of the Tourette OCD Alberta Network is to provide services and support that directly address the healthcare service delivery shortfalls shown in this study.
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http://dx.doi.org/10.1186/s13034-021-00383-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208059PMC
June 2021

Cross-Diagnosis Structural Correlates of Autistic-Like Social Communication Differences.

Cereb Cortex 2021 Jun 3. Epub 2021 Jun 3.

Autism Research Centre, Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Ontario M4G 1R8, Canada.

Social communication differences are seen in autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and obsessive-compulsive disorder (OCD), but the brain mechanisms contributing to these differences remain largely unknown. To address this gap, we used a data-driven and diagnosis-agnostic approach to discover brain correlates of social communication differences in ASD, ADHD, and OCD, and subgroups of individuals who share similar patterns of brain-behavior associations. A machine learning pipeline (regression clustering) was used to discover the pattern of association between structural brain measures (volume, surface area, and cortical thickness) and social communication abilities. Participants (n = 416) included children with a diagnosis of ASD (n = 192, age = 12.0[5.6], 19% female), ADHD (n = 109, age = 11.1[4.1], 18% female), or OCD (n = 50, age = 12.3[4.2], 42% female), and typically developing controls (n = 65, age = 11.6[7.1], 48% female). The analyses revealed (1) associations with social communication abilities in distributed cortical and subcortical networks implicated in social behaviors, language, attention, memory, and executive functions, and (2) three data-driven, diagnosis-agnostic subgroups based on the patterns of association in the above networks. Our results suggest that different brain networks may contribute to social communication differences in subgroups that are not diagnosis-specific.
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http://dx.doi.org/10.1093/cercor/bhab142DOI Listing
June 2021

COVID-19 and Student Well-Being: Stress and Mental Health during Return-to-School.

Can J Sch Psychol 2021 Jun 18;36(2):166-185. Epub 2021 Mar 18.

University of Calgary, AB, Canada.

Students have been multiply impacted by the COVID-19 pandemic: threats to their own and their family's health, the closure of schools, and pivoting to online learning in March 2020, a long summer of physical distancing, and then the challenge of returning to school in fall 2020. As damaging as the physical health effects of a global pandemic are, much has been speculated about the "second wave" of mental health crises, particularly for school-aged children and adolescents. Yet, few studies have asked students about their experiences during the pandemic. The present study engaged with over two thousand ( = 2,310; 1,288 female;  = 14.5) 12- to 18-year-old Alberta students during their first few weeks of return-to-school in fall 2020. Students completed an online survey that asked about their perceptions of COVID-19, their fall return-to-school experiences (84.9% returned in-person), their self-reported pandemic-related stress, and their behavior, affect, and cognitive functioning in the first few weeks of September. The majority of students (84.9%) returned to school in person. Students reported moderate and equal concern for their health, family confinement, and maintaining social contact. Student stress levels were also above critical thresholds for 25% of the sample, and females and older adolescents (age 15-18 years) generally reported higher stress indicators as compared to males and younger (age 12-14 years) adolescents. Multivariate analysis showed that stress indicators were positively and significantly correlated with self-reported behavioral concerns (i.e., conduct problems, negative affect, and cognitive/inattention), and that stress arousal (e.g., sleep problems, hypervigilance) accounted for significant variance in behavioral concerns. Results are discussed in the context of how schools can provide both universal responses to students during COVID-19 knowing that most students are coping well, while some may require more targeted strategies to address stress arousal and heightened negative affect.
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http://dx.doi.org/10.1177/08295735211001653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114331PMC
June 2021

Visuomotor Activation of Inhibition-Processing in Pediatric Obsessive Compulsive Disorder: A Magnetoencephalography Study.

Front Psychiatry 2021 29;12:632736. Epub 2021 Apr 29.

Neuroscience and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada.

Response inhibition engages the cortico-striato-thalamo-cortical (CSTC) circuit, which has been implicated in children, and youth with obsessive compulsive disorder (OCD). This study explored whether CSTC engagement during response inhibition, measured using magnetoencephalography (MEG), differed in a sample of medication-naïve youth with OCD, compared to typically developing controls (TDC). Data was analyzed in 17 medication-naïve children and youth with OCD (11.7 ± 2.2 SD years) and 13 TDC (12.6 ± 2.2 SD years). MEG was used to localize and characterize neural activity during a Go/No-Go task. Task performance on Go/No-Go conditions and regional differences in amplitude of activity during Go and No-Go condition between OCD vs. TDC were examined using two-sample tests. analysis with Bayesian tests was used to estimate the certainty of outcomes. No differences in Go/No-Go performance were found between OCD and TDC groups. In response to the visual cue presented during the Go condition, participants with OCD showed significantly increased amplitude of activity in the primary motor (MI) cortex compared to TDC. In addition, significantly reduced amplitude of PCu was found following successful stopping to No-Go cues in OCD vs. TDC during No-Go task performance. Bayesian tests indicated high probability and large effect sizes for the differences in MI and PCu amplitude found between groups. Our preliminary study in a small medication-naïve sample extends previous work indicating intact response inhibition in pediatric OCD. While altered neural response in the current study was found during response inhibition performance in OCD, differences localized to regions outside of the CSTC. Our findings suggest that additional imaging research in medication-naïve samples is needed to clarify regional differences associated with OCD vs. influenced by medication effects, and suggest that MEG may be sensitive to detecting such differences.
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http://dx.doi.org/10.3389/fpsyt.2021.632736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116532PMC
April 2021

Cost-Effectiveness of Adult Spinal Deformity Surgery.

Global Spine J 2021 Apr 14;11(1_suppl):73S-78S. Epub 2020 Oct 14.

8100Carle Clinic, Urbana, IL, USA.

Study Design: Review article.

Objective: A review of the literature evaluating the cost-effectiveness of undergoing adult spinal deformity surgery and potential avenues for reducing costs.

Methods: A review of the current literature and synthesis of data to provide an update on the cost effectiveness of undergoing adult spinal deformity surgery.

Results: Compared with nonoperative management, operative management for adult spinal deformity is associated with improved patient-reported outcomes and quality of life; however, it is associated with significant financial and resource use.

Conclusion: Operative management for adult spinal deformity has been shown to be effective but is associated with significant cost and resource utilization. The optimal operative treatment is highly dependent on the patients' symptomatology and is surgeon dependent. Maximizing preoperative surgical health and minimizing postoperative complications are key measures in reducing the cost and resource utilization of adult spinal deformity surgery. Future studies are needed to evaluate how to optimize the cost-effectiveness.
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http://dx.doi.org/10.1177/2192568220964098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076806PMC
April 2021

Commentary: Smoking Is an Independent Risk Factor for 90-Day Readmission and Reoperation Following Posterior Cervical Decompression and Fusion.

Neurosurgery 2021 06;89(1):E70-E71

The Grainger College of Engineering, University of Illinois Urbana-Champaign, Urbana, Illinois, USA.

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http://dx.doi.org/10.1093/neuros/nyab101DOI Listing
June 2021

Four-level Anterior Cervical Discectomy and Fusions: Results Following Multilevel Cervical Fusion With a Minimum 1-Year Follow-up.

Clin Spine Surg 2021 05;34(4):E243-E247

Departments of Neurosurgery.

Study Design: A retrospective review of prospectively collected case series.

Objective: This is a retrospective review of prospectively collected data regarding the clinical outcomes, complications, and fusion rates of patients who underwent a 4-level (C3-C7) anterior cervical discectomy and fusion (ACDF).

Summary Of Background: The use of multilevel ACDF for cervical spondylosis has been controversial. The literature regarding fusion rates and outcomes have been variable. This study intends to evaluate the outcomes following multilevel ACDF in a large cohort of patients.

Clinical Materials And Methods: Between 1994 and 2011, 60 patients underwent a 4-level ACDF by a single surgeon. All patients were followed for a minimum of 12 months, and outcome measures included neurological findings, presence or absence of radiographic fusion, and complication rates. All patients had radiographic documentation of spinal cord stenosis at 4 consecutive cervical levels as well as myelopathy and/or radiculopathy symptoms.

Results: Forty-eight patients underwent a single anterior procedure, only 5 patients underwent concurrent anterior and posterior fusion, and 7 patients required a second posterior surgery due to new-onset or residual symptoms or hardware complications after undergoing ACDF. Patients most commonly presented with paresthesias and were diagnosed with cervical stenosis. Overall, 18.3% reported early postoperative dysphagia; however, only 2 patients continued to have mild dysphagia symptoms on long-term follow-up. Other complications included hardware failure (11), residual neck pain (7), residual paresthesias (6), new-onset weakness (3), neck hematoma (1), cellulitis (1), and C5 radiculopathy (1). Overall, 88.3% of patients reported improvement in initial symptoms. Nurick scores were significantly lower following 4-level ACDF. The radiographic fusion rate for all levels was 95%. No patients required reoperation for pseudarthrosis.

Conclusion: In appropriate patients, 4-level ACDF is a safe, efficacious method for treating multilevel cervical spinal cord compression, with acceptable complication rates and the ability to achieve neurological improvement and high fusion rates.
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http://dx.doi.org/10.1097/BSD.0000000000001116DOI Listing
May 2021

Harmonized outcome measures for use in degenerative lumbar spondylolisthesis patient registries and clinical practice.

J Neurosurg Spine 2021 Mar 19:1-9. Epub 2021 Mar 19.

3OM1, Inc., Boston, Massachusetts.

Objective: The development of new treatment approaches for degenerative lumbar spondylolisthesis (DLS) has introduced many questions about comparative effectiveness and long-term outcomes. Patient registries collect robust, longitudinal data that could be combined or aggregated to form a national and potentially international research data infrastructure to address these and other research questions. However, linking data across registries is challenging because registries typically define and capture different outcome measures. Variation in outcome measures occurs in clinical practice and other types of research studies as well, limiting the utility of existing data sources for addressing new research questions. The purpose of this project was to develop a minimum set of patient- and clinician-relevant standardized outcome measures that are feasible for collection in DLS registries and clinical practice.

Methods: Nineteen DLS registries, observational studies, and quality improvement efforts were invited to participate and submit outcome measures. A stakeholder panel was organized that included representatives from medical specialty societies, health systems, government agencies, payers, industries, health information technology organizations, and patient advocacy groups. The panel categorized the measures using the Agency for Healthcare Research and Quality's Outcome Measures Framework (OMF), identified a minimum set of outcome measures, and developed standardized definitions through a consensus-based process.

Results: The panel identified and harmonized 57 outcome measures into a minimum set of 10 core outcome measure areas and 6 supplemental outcome measure areas. The measures are organized into the OMF categories of survival, clinical response, events of interest, patient-reported outcomes, and resource utilization.

Conclusions: This effort identified a minimum set of standardized measures that are relevant to patients and clinicians and appropriate for use in DLS registries, other research efforts, and clinical practice. Collection of these measures across registries and clinical practice is an important step for building research data infrastructure, creating learning healthcare systems, and improving patient management and outcomes in DLS.
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http://dx.doi.org/10.3171/2020.9.SPINE20437DOI Listing
March 2021

White matter microstructure and its relation to clinical features of obsessive-compulsive disorder: findings from the ENIGMA OCD Working Group.

Transl Psychiatry 2021 03 17;11(1):173. Epub 2021 Mar 17.

Department of Psychiatry, Oxford University, Oxford, UK.

Microstructural alterations in cortico-subcortical connections are thought to be present in obsessive-compulsive disorder (OCD). However, prior studies have yielded inconsistent findings, perhaps because small sample sizes provided insufficient power to detect subtle abnormalities. Here we investigated microstructural white matter alterations and their relation to clinical features in the largest dataset of adult and pediatric OCD to date. We analyzed diffusion tensor imaging metrics from 700 adult patients and 645 adult controls, as well as 174 pediatric patients and 144 pediatric controls across 19 sites participating in the ENIGMA OCD Working Group, in a cross-sectional case-control magnetic resonance study. We extracted measures of fractional anisotropy (FA) as main outcome, and mean diffusivity, radial diffusivity, and axial diffusivity as secondary outcomes for 25 white matter regions. We meta-analyzed patient-control group differences (Cohen's d) across sites, after adjusting for age and sex, and investigated associations with clinical characteristics. Adult OCD patients showed significant FA reduction in the sagittal stratum (d = -0.21, z = -3.21, p = 0.001) and posterior thalamic radiation (d = -0.26, z = -4.57, p < 0.0001). In the sagittal stratum, lower FA was associated with a younger age of onset (z = 2.71, p = 0.006), longer duration of illness (z = -2.086, p = 0.036), and a higher percentage of medicated patients in the cohorts studied (z = -1.98, p = 0.047). No significant association with symptom severity was found. Pediatric OCD patients did not show any detectable microstructural abnormalities compared to controls. Our findings of microstructural alterations in projection and association fibers to posterior brain regions in OCD are consistent with models emphasizing deficits in connectivity as an important feature of this disorder.
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http://dx.doi.org/10.1038/s41398-021-01276-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969744PMC
March 2021

Effect of Ventral vs Dorsal Spinal Surgery on Patient-Reported Physical Functioning in Patients With Cervical Spondylotic Myelopathy: A Randomized Clinical Trial.

JAMA 2021 03;325(10):942-951

Neurosurgery, Cleveland Clinic Foundation, Cleveland, Ohio.

Importance: Cervical spondylotic myelopathy is the most common cause of spinal cord dysfunction worldwide. It remains unknown whether a ventral or dorsal surgical approach provides the best results.

Objective: To determine whether a ventral surgical approach compared with a dorsal surgical approach for treatment of cervical spondylotic myelopathy improves patient-reported physical functioning at 1 year.

Design, Setting, And Participants: Randomized clinical trial of patients aged 45 to 80 years with multilevel cervical spondylotic myelopathy enrolled at 15 large North American hospitals from April 1, 2014, to March 30, 2018; final follow-up was April 15, 2020.

Interventions: Patients were randomized to undergo ventral surgery (n = 63) or dorsal surgery (n = 100). Ventral surgery involved anterior cervical disk removal and instrumented fusion. Dorsal surgery involved laminectomy with instrumented fusion or open-door laminoplasty. Type of dorsal surgery (fusion or laminoplasty) was at surgeon's discretion.

Main Outcomes And Measures: The primary outcome was 1-year change in the Short Form 36 physical component summary (SF-36 PCS) score (range, 0 [worst] to 100 [best]; minimum clinically important difference = 5). Secondary outcomes included 1-year change in modified Japanese Orthopaedic Association scale score, complications, work status, sagittal vertical axis, health resource utilization, and 1- and 2-year changes in the Neck Disability Index and the EuroQol 5 Dimensions score.

Results: Among 163 patients who were randomized (mean age, 62 years; 80 [49%] women), 155 (95%) completed the trial at 1 year (80% at 2 years). All patients had surgery, but 5 patients did not receive their allocated surgery (ventral: n = 1; dorsal: n = 4). One-year SF-36 PCS mean improvement was not significantly different between ventral surgery (5.9 points) and dorsal surgery (6.2 points) (estimated mean difference, 0.3; 95% CI, -2.6 to 3.1; P = .86). Of 7 prespecified secondary outcomes, 6 showed no significant difference. Rates of complications in the ventral and dorsal surgery groups, respectively, were 48% vs 24% (difference, 24%; 95% CI, 8.7%-38.5%; P = .002) and included dysphagia (41% vs 0%), new neurological deficit (2% vs 9%), reoperations (6% vs 4%), and readmissions within 30 days (0% vs 7%).

Conclusions And Relevance: Among patients with cervical spondylotic myelopathy undergoing cervical spinal surgery, a ventral surgical approach did not significantly improve patient-reported physical functioning at 1 year compared with outcomes after a dorsal surgical approach.

Trial Registration: ClinicalTrials.gov Identifier: NCT02076113.
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http://dx.doi.org/10.1001/jama.2021.1233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944378PMC
March 2021

Mostly worse, occasionally better: impact of COVID-19 pandemic on the mental health of Canadian children and adolescents.

Eur Child Adolesc Psychiatry 2021 Feb 26. Epub 2021 Feb 26.

Department of Psychiatry, Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, 686 Bay Street, 6th Floor, Toronto, On, M5G 0A4, Canada.

This large cross-sectional study examined the impact of COVID-19 emergency measures on child/adolescent mental health for children/adolescents with and without pre-existing psychiatric diagnoses. Using adapted measures from the CRISIS questionnaire, parents of children aged 6-18 (N = 1013; 56% male; 62% pre-existing psychiatric diagnosis) and self-reporting children/adolescents aged 10-18 (N = 385) indicated changes in mental health across six domains: depression, anxiety, irritability, attention, hyperactivity, and obsessions/compulsions. Changes in anxiety, irritability, and hyperactivity were calculated for children aged 2-5 years using the Strengths and Difficulties Questionnaire. COVID-19 exposure, compliance with emergency measures, COVID-19 economic concerns, and stress from social isolation were measured with the CRISIS questionnaire. Prevalence of change in mental health status was estimated for each domain; multinomial logistic regression was used to determine variables associated with mental health status change in each domain. Depending on the age group, 67-70% of children/adolescents experienced deterioration in at least one mental health domain; however, 19-31% of children/adolescents experienced improvement in at least one domain. Children/adolescents without and with psychiatric diagnoses tended to experience deterioration during the first wave of COVID-19. Rates of deterioration were higher in those with a pre-exiting diagnosis. The rate of deterioration was variable across different age groups and pre-existing psychiatric diagnostic groups: depression 37-56%, anxiety 31-50%, irritability 40-66%, attention 40-56%, hyperactivity 23-56%, obsessions/compulsions 13-30%. Greater stress from social isolation was associated with deterioration in all mental health domains (all ORs 11.12-55.24). The impact of pre-existing psychiatric diagnosis was heterogenous, associated with deterioration in depression, irritability, hyperactivity, obsession/compulsions for some children (ORs 1.96-2.23) but also with improvement in depression, anxiety, and irritability for other children (ORs 2.13-3.12). Economic concerns were associated with improvement in anxiety, attention, and obsessions/compulsions (ORs 3.97-5.57). Children/adolescents with and without pre-existing psychiatric diagnoses reported deterioration. Deterioration was associated with increased stress from social isolation. Enhancing social interactions for children/adolescents will be an important mitigation strategy for current and future COVID-19 waves.
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http://dx.doi.org/10.1007/s00787-021-01744-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909377PMC
February 2021

Clinical and Radiologic Outcomes of Thoracolumbar Fusions Using Intraoperative CT Guidance and Stereotactic Navigation in a Spinal Trauma Population: An Analysis of 58 Patients.

Clin Spine Surg 2021 03;34(2):E80-E85

Department of Neurosurgery, Carle Illinois College of Medicine, Champaign, IL.

Study Design: Retrospective review of prospectively collected single-institution database.

Objective: To analyze the clinical and radiographic outcomes of posterior thoracolumbar fusions using intraoperative computed tomography (CT)-guidance and stereotactic navigation in thoracolumbar spinal trauma.

Summary Of Background Data: Pedicle screw instrumentation is utilized for stabilization in thoracolumbar fusions. Suboptimal placement may lead to neurovascular complications, pseudarthrosis, postoperative pain, and the need for revision surgery. Image-guided spinal surgery is commonly used to improve accuracy, particularly for complex anatomy such as encountered with traumatic fractures.

Methods: We retrospectively identified 58 patients undergoing posterior thoracolumbar fusions using intraoperative CT and stereotactic navigation for traumatic fractures from 2010 to 2017 at a single institution. Pedicle screw accuracy, realignment, clinical outcomes, and ease of use were retrospectively reviewed. Accuracy was assessed on postplacement or postoperative CT. Breach grades included: grade 1 (<2 mm), grade 2 (2-4 mm), and grade 3 (>4 mm).

Results: A total of 58 patients were identified having undergone 58 operations, which involved placement of 519 pedicle screws. Traumatic fracture patterns and levels of injury were varied. Accurate pedicle screw placement was found in 95.8% and was stable over time. Breach included: grade 1 in 19 screws, grade 2 in 2 screws, and grade 3 in 1 screw. No neurovascular complications were noted. No revision surgery was performed for misplacement. A subgroup of 6 ankylosing spondylitis patients were identified having undergone 6 operations with 63 pedicle screws. Accurate pedicle screw placement was found in 93.7%.

Conclusion: Intraoperative CT-guidance and stereotactic navigation can overcome the difficulty associated with thoracolumbar trauma resulting in complex anatomy with malalignment and unpredictable trajectories. Intraoperative CT can be used with stereotactic guidance or for intraoperative verification of free-hand screw placement with repositioning as needed. CT-guidance maintains the benefit of reduced fluoroscopic exposure while improving accuracy of instrumentation and reducing reoperation for screw malposition.
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http://dx.doi.org/10.1097/BSD.0000000000001054DOI Listing
March 2021

Genome-wide association study of pediatric obsessive-compulsive traits: shared genetic risk between traits and disorder.

Transl Psychiatry 2021 02 2;11(1):91. Epub 2021 Feb 2.

Genetics and Genome Biology Hospital for Sick Children, Toronto, Canada.

Using a novel trait-based measure, we examined genetic variants associated with obsessive-compulsive (OC) traits and tested whether OC traits and obsessive-compulsive disorder (OCD) shared genetic risk. We conducted a genome-wide association analysis (GWAS) of OC traits using the Toronto Obsessive-Compulsive Scale (TOCS) in 5018 unrelated Caucasian children and adolescents from the community (Spit for Science sample). We tested the hypothesis that genetic variants associated with OC traits from the community would be associated with clinical OCD using a meta-analysis of all currently available OCD cases. Shared genetic risk was examined between OC traits and OCD in the respective samples using polygenic risk score and genetic correlation analyses. A locus tagged by rs7856850 in an intron of PTPRD (protein tyrosine phosphatase δ) was significantly associated with OC traits at the genome-wide significance level (p = 2.48 × 10). rs7856850 was also associated with OCD in a meta-analysis of OCD case/control genome-wide datasets (p = 0.0069). The direction of effect was the same as in the community sample. Polygenic risk scores from OC traits were significantly associated with OCD in case/control datasets and vice versa (p's < 0.01). OC traits were highly, but not significantly, genetically correlated with OCD (r = 0.71, p = 0.062). We report the first validated genome-wide significant variant for OC traits in PTPRD, downstream of the most significant locus in a previous OCD GWAS. OC traits measured in the community sample shared genetic risk with OCD case/control status. Our results demonstrate the feasibility and power of using trait-based approaches in community samples for genetic discovery.
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http://dx.doi.org/10.1038/s41398-020-01121-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870035PMC
February 2021

Safety and efficacy of riluzole in patients undergoing decompressive surgery for degenerative cervical myelopathy (CSM-Protect): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial.

Lancet Neurol 2021 02 22;20(2):98-106. Epub 2020 Dec 22.

Department of Health Services, University of Washington, Seattle, WA, USA.

Background: Degenerative cervical myelopathy represents the most common form of non-traumatic spinal cord injury. This trial investigated whether riluzole enhances outcomes in patients undergoing decompression surgery for degenerative cervical myelopathy.

Methods: This multicentre, double-blind, placebo-controlled, randomised, phase 3 trial was done at 16 university-affiliated centres in Canada and the USA. Patients with moderate-to-severe degenerative cervical myelopathy aged 18-80 years, who had a modified Japanese Orthopaedic Association (mJOA) score of 8-14, were eligible. Patients were randomly assigned (1:1) to receive either oral riluzole (50 mg twice a day for 14 days before surgery and then for 28 days after surgery) or placebo. Randomisation was done using permuted blocks stratified by study site. Patients, physicians, and outcome assessors remained masked to treatment group allocation. The primary endpoint was change in mJOA score from baseline to 6 months in the intention-to-treat (ITT) population, defined as all individuals who underwent randomisation and surgical decompression. Adverse events were analysed in the modified intention-to-treat (mITT) population, defined as all patients who underwent randomisation, including those who did not ultimately undergo surgical decompression. This study is registered with ClinicalTrials.gov, NCT01257828.

Findings: From Jan 31, 2012, to May 16, 2017, 408 patients were screened. Of those screened, 300 were eligible (mITT population); 290 patients underwent decompression surgery (ITT population) and received either riluzole (n=141) or placebo (n=149). There was no difference between the riluzole and placebo groups in the primary endpoint of change in mJOA score at 6-month follow-up: 2·45 points (95% CI 2·08 to 2·82 points) versus 2·83 points (2·47 to 3·19), difference -0·38 points (-0·90 to 0·13; p=0·14). The most common adverse events were neck or arm or shoulder pain, arm paraesthesia, dysphagia, and worsening of myelopathy. There were 43 serious adverse events in 33 (22%) of 147 patients in the riluzole group and 34 serious adverse events in 29 (19%) of 153 patients in the placebo group. The most frequent severe adverse events were osteoarthrosis of non-spinal joints, worsening of myelopathy, and wound complications.

Interpretation: In this trial, adjuvant treatment for 6 weeks perioperatively with riluzole did not improve functional recovery beyond decompressive surgery in patients with moderate-to-severe degenerative cervical myelopathy. Whether riluzole has other benefits in this patient population merits further study.

Funding: AOSpine North America.
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http://dx.doi.org/10.1016/S1474-4422(20)30407-5DOI Listing
February 2021

Neuroimaging the emotional modulation of urge inhibition in Tourette Syndrome.

Cortex 2021 02 1;135:341-351. Epub 2020 Nov 1.

Tourette Syndrome Neurodevelopmental Clinic, Toronto Western Hospital, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Division of Child Psychiatry, Department of Psychiatry, Youthdale Treatment Centers, Toronto, Ontario, Canada. Electronic address:

Tourette Syndrome (TS) is a neuropsychiatric condition characterized by tics that are typically preceded by uncomfortable urges that build until the tic is performed. Both tics and their associated urges are commonly exacerbated during states of heightened emotion. However, the neural substrates that are responsible for the development of urges have not been fully elucidated, particularly with regards to the influence of emotion. In this study, we investigate the brain areas associated with the development of urges and their modulation by emotion in patients with TS. Moreover, we explore the influence of obsessive-compulsive symptoms (OCS) which are commonly comorbid in TS. Forty patients with TS and 20 healthy controls completed an emotional blink suppression paradigm while undergoing functional magnetic resonance imaging. For the paradigm, participants completed alternating blocks of blink inhibition and free blinking while viewing pictures of angry and neutral facial expressions. Compared to controls, patients exhibited greater activity in the superior temporal gyrus and midcingulate during the inhibition of urges. Within the patient group, tic severity was associated with activity in the superior frontal gyrus during the angry inhibition contrast as compared to neutral; greater premonitory urge severity was associated with greater activity in the hippocampus, middle temporal gyrus and in the subcortex; blink inhibition ability was negatively associated with activity in the thalamus and insula. There were no significant associations with OCS severity for the emotion-related contrasts. The observed activated regions may represent a network that produces urges in patients, or alternatively, could represent compensatory cortical activity needed to keep urges and tics under control during emotional situations. Additionally, our findings suggest that OCS in the context of TS is similar to traditional obsessive-compulsive disorder and is neurobiologically dissociable from tics.
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http://dx.doi.org/10.1016/j.cortex.2020.10.010DOI Listing
February 2021

An association of Myelin Oligodendrocyte Glycoprotein (MOG) gene variants with white matter volume in pediatric obsessive-compulsive disorder.

Psychiatry Res Neuroimaging 2021 01 21;307:111231. Epub 2020 Nov 21.

Tanenbaum Centre for Pharmacogenetics, Molecular Brain Science Department, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada; Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada; Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.

An increasing number of neuroimaging studies have implicated alterations of white matter in obsessive-compulsive disorder (OCD). The myelin oligodendrocyte glycoprotein (MOG) gene plays a major role in myelination, and has previously demonstrated significant association with this disorder, thus variations in this gene may contribute to observed white matter alterations. The purpose of this study is to examine the relationship between white matter volume in OCD and genetic variations in the MOG gene. Two polymorphisms in the MOG gene, MOG(C1334T) and MOG(C10991T), were investigated for association with total white matter volume as measured using volumetric magnetic resonance imaging in 37 pediatric OCD patients. We compared white matter volumes between allele and genotype groups for each polymorphism using ANCOVA. A significant relationship was detected between genotype C/C of MOG(C10991T) and decreased total white matter volume (P = 0.016). Our results showed an association between a MOG genetic variant and white matter volume. This finding is intriguing in light of the posited role of white matter alteration in the etiology of at least some cases of childhood-onset OCD. Further investigation with larger samples and sub-regional white matter volume phenotypes is warranted.
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http://dx.doi.org/10.1016/j.pscychresns.2020.111231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775903PMC
January 2021

Characterization of mice bearing humanized androgen receptor genes (h/mAr) varying in polymorphism length.

Neuroimage 2021 02 26;226:117594. Epub 2020 Nov 26.

Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Wellcome Centre for Integrative Neuroimaging (WIN), FMRIB, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, United Kingdom.

The androgen receptor (AR) is known for masculinization of behavior and brain. To better understand the role that AR plays, mice bearing humanized Ar genes with varying lengths of a polymorphic N-terminal glutamine (Q) tract were created (Albertelli et al., 2006). The length of the Q tract is inversely proporitional to AR activity. Biological studies of the Q tract length may also provide a window into potential AR contributions to sex-biases in disease risk. Here we take a multi-pronged approach to characterizing AR signaling effects on brain and behavior in mice using the humanized Ar Q tract model. We first map effects of Q tract length on regional brain anatomy, and consider if these are modified by gonadal sex. We then test the notion that spatial patterns of anatomical variation related to Q tract length could be organized by intrinsic spatiotemporal patterning of AR gene expression in the mouse brain. Finally, we test influences of Q tract length on four behavioral tests.Altering Q tract length led to neuroanatomical differences in a non-linear dosage-dependent fashion. Gene expression analyses indicated that adult neu- roanatomical changes due to Q tract length are only associated with neurode- velopment (as opposed to adulthood). No significant effect of Q tract length was found on the behavior of the three mouse models. These results indicate that AR activity differentially mediates neuroanatomy and behavior, that AR activity alone does not mediate sex differences, and that neurodevelopmen- tal processes are associated with spatial patterns of volume changes due to Q tract length in adulthood. They also indicate that androgen sensitivity in adulthood is not likely to lead to autism-related behaviors or neuroanatomy, although neurodevelopmental processes may play a role earlier. Further study into sex differences, development, other behaviors, and other sex-specific mech- anisms are needed to better understand AR sensitivity, neurodevelopmental disorders, and the sex difference in their prevalence.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117594DOI Listing
February 2021

Beyond diagnosis: Cross-diagnostic features in canonical resting-state networks in children with neurodevelopmental disorders.

Neuroimage Clin 2020 27;28:102476. Epub 2020 Oct 27.

Autism Research Centre, Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada; Department of Paediatrics, University of Toronto, Toronto, ON, Canada.

Children with neurodevelopmental disorders (NDDs) share common behavioural manifestations despite distinct categorical diagnostic criteria. Here, we examined canonical resting-state network connectivity in three diagnostic groups (autism spectrum disorder, attention-deficit/hyperactivity disorder and paediatric obsessive-compulsive disorder) and typically developing controls (TD) in a large single-site sample (N = 407), applying diagnosis-based and dimensional approaches to understand underlying neurobiology across NDDs. Each participant's functional network graphs were computed using five graph metrics. In diagnosis-based comparisons, an analysis of covariance was performed to compare all NDDs to TD, followed by pairwise comparisons between NDDs. In the dimensional approach, participants' functional network graphs were correlated with continuous behavioural measures, and a data-driven k-means clustering analysis was applied to determine if subgroups of participants were seen, without diagnostic information having been included. In the diagnosis-based comparisons, children with NDDs did not differ significantly from the TD group and the NDD categorical groups also did not differ significantly from each other, across all graph metrics. In the dimensional, diagnostic-independent approach, however, subcortical functional connectivity was significantly correlated with participants' general adaptive functioning across all participants. The clustering analysis identified an optimal solution of two clusters, and participants assigned in the same data-driven cluster were highly heterogeneous in diagnosis. Neither cluster exclusively contained a specific diagnostic group, nor did NDDs separate cleanly from TDs. Each participant's distance ratio between the two clusters was significantly correlated with general adaptive functioning, social deficits and attentional problems. Our results suggest the neurobiological similarity and dissimilarity between NDDs need to be investigated beyond DSM/ICD-based, behaviourally-defined diagnostic categories.
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http://dx.doi.org/10.1016/j.nicl.2020.102476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649647PMC
June 2021

Integration of brain and behavior measures for identification of data-driven groups cutting across children with ASD, ADHD, or OCD.

Neuropsychopharmacology 2021 02 9;46(3):643-653. Epub 2020 Nov 9.

Department of Psychiatry, University of Toronto, Toronto, ON, Canada.

Autism spectrum disorder (ASD), obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) are clinically and biologically heterogeneous neurodevelopmental disorders (NDDs). The objective of the present study was to integrate brain imaging and behavioral measures to identify new brain-behavior subgroups cutting across these disorders. A subset of the data from the Province of Ontario Neurodevelopmental Disorder (POND) Network was used including participants with different NDDs (aged 6-16 years) that underwent cross-sectional T1-weighted and diffusion-weighted magnetic resonance imaging (MRI) scanning on the same 3T scanner, and behavioral/cognitive assessments. Similarity Network Fusion was applied to integrate cortical thickness, subcortical volume, white matter fractional anisotropy (FA), and behavioral measures in 176 children with ASD, ADHD or OCD with complete data that passed quality control. Normalized mutual information was used to determine top contributing model features. Bootstrapping, out-of-model outcome measures and supervised machine learning were each used to examine stability and evaluate the new groups. Cortical thickness in socio-emotional and attention/executive networks and inattention symptoms comprised the top ten features driving participant similarity and differences between four transdiagnostic groups. Subcortical volumes (pallidum, nucleus accumbens, thalamus) were also different among groups, although white matter FA showed limited differences. Features driving participant similarity remained stable across resampling, and the new groups showed significantly different scores on everyday adaptive functioning. Our findings open the possibility of studying new data-driven groups that represent children with NDDs more similar to each other than others within their own diagnostic group. Future work is needed to build on this early attempt through replication of the current findings in independent samples and testing longitudinally for prognostic value.
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http://dx.doi.org/10.1038/s41386-020-00902-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027842PMC
February 2021

Emotional face processing across neurodevelopmental disorders: a dynamic faces study in children with autism spectrum disorder, attention deficit hyperactivity disorder and obsessive-compulsive disorder.

Transl Psychiatry 2020 11 2;10(1):375. Epub 2020 Nov 2.

Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Canada.

Autism spectrum disorder (ASD) is classically associated with poor face processing skills, yet evidence suggests that those with obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) also have difficulties understanding emotions. We determined the neural underpinnings of dynamic emotional face processing across these three clinical paediatric groups, including developmental trajectories, compared with typically developing (TD) controls. We studied 279 children, 5-19 years of age but 57 were excluded due to excessive motion in fMRI, leaving 222: 87 ASD, 44 ADHD, 42 OCD and 49 TD. Groups were sex- and age-matched. Dynamic faces (happy, angry) and dynamic flowers were presented in 18 pseudo-randomized blocks while fMRI data were collected with a 3T MRI. Group-by-age interactions and group difference contrasts were analysed for the faces vs. flowers and between happy and angry faces. TD children demonstrated different activity patterns across the four contrasts; these patterns were more limited and distinct for the NDDs. Processing happy and angry faces compared to flowers yielded similar activation in occipital regions in the NDDs compared to TDs. Processing happy compared to angry faces showed an age by group interaction in the superior frontal gyrus, increasing with age for ASD and OCD, decreasing for TDs. Children with ASD, ADHD and OCD differentiated less between dynamic faces and dynamic flowers, with most of the effects seen in the occipital and temporal regions, suggesting that emotional difficulties shared in NDDs may be partly attributed to shared atypical visual information processing.
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http://dx.doi.org/10.1038/s41398-020-01063-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608673PMC
November 2020

Health related quality of life outcomes following surgery and/or radiation for patients with potentially unstable spinal metastases.

Spine J 2021 03 22;21(3):492-499. Epub 2020 Oct 22.

Research Department, AOSpine International, Davos, Switzerland.

Background: Currently there is no prospective pain and health related quality of life (HRQOL) data of patients with potentially unstable spinal metastases who were treated with surgery ± radiation or radiation alone.

Methods: An international prospective cohort multicenter study of patients with potentially unstable spinal metastases, defined by a SINS score 7 to 12, treated with surgery ± radiation or radiotherapy alone was conducted. HRQOL was evaluated with the numeric rating scale (NRS) pain score, the SOSGOQ2.0, the SF-36, and the EQ-5D at baseline and 6, 12, 26, and 52 weeks after treatment.

Results: A total of 136 patients were treated with surgery ± radiotherapy and 84 with radiotherapy alone. At baseline, surgically treated patients were more likely to have mechanical pain, a lytic lesion, a greater median Spinal Instability Neoplastic score, vertebral compression fracture, lower performance status, HRQOL, and pain scores. From baseline to 12 weeks post-treatment, surgically treated patients experienced a 3.0-point decrease in NRS pain score (95% CI -4.1 to -1.9, p<.001), and a 12.7-point increase in SOSGOQ2.0 score (95% CI 6.3-19.1, p<.001). Patients treated with radiotherapy alone experienced a 1.4-point decrease in the NRS pain score (95% CI -2.9 to 0.0, p=.046) and a 6.2-point increase in SOSGOQ2.0 score (95% CI -2.0 to 14.5, p=.331). Beyond 12 weeks, significant improvements in pain and HRQOL metrics were maintained up to 52-weeks follow-up in the surgical cohort, as compared with no significant changes in the radiotherapy alone cohort.

Conclusions: Patients treated with surgery demonstrated clinically and statistically significant improvements in pain and HRQOL up to 1-year postsurgery. Treatment with radiotherapy alone resulted in improved pain scores, but these were not sustained beyond 3 months and HRQOL outcomes demonstrated nonsignificant changes over time. Within the SINS potentially unstable group, distinct clinical profiles were observed in patients treated with surgery or radiotherapy alone.
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http://dx.doi.org/10.1016/j.spinee.2020.10.017DOI Listing
March 2021

and Antipsychotic Treatment Outcomes in Children and Youth: A Systematic Review.

J Child Adolesc Psychopharmacol 2021 02 19;31(1):33-45. Epub 2020 Oct 19.

The Mathison Centre for Mental Health Research and Education, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada.

To systematically review the impact of genetic variation on antipsychotic pharmacokinetics, efficacy, and adverse drug reactions among children and youth. The published literature was systematically searched in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations and critically evaluated using standardized tools and consensus criteria. A total of 20 eligible studies comprising 1078 children and youth were evaluated. The included studies were of fair to moderate quality and included mostly males, individuals of European ancestry, and those treated with risperidone. CYP2D6 poor metabolizers (PMs) were consistently shown to have increased concentrations of risperidone relative to normal metabolizers (NMs). PMs were also consistently shown to have a greater propensity to experience antipsychotic (primarily risperidone) associated adverse drug reactions relative to NMs. However, robust evidence for an association between and efficacy was less apparent. The current knowledge base suggests that genetic variation has an appreciable impact on antipsychotic pharmacokinetics and the propensity for adverse drug reactions, particularly among children receiving risperidone treatment. However, several limitations with the current literature (e.g., sample sizes, study design, sample heterogeneity) should be addressed in future studies. Assuming that future studies support the link between genetic variation and antipsychotic outcomes, we would anticipate an increase in the implementation of -guided antipsychotic drug selection and dose optimization in child and adolescent psychiatric services.
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http://dx.doi.org/10.1089/cap.2020.0093DOI Listing
February 2021

Evoking network profiles of the dorsal anterior cingulate in youth with Obsessive-Compulsive Disorder during motor control and working memory.

J Psychiatr Res 2021 01 8;132:72-83. Epub 2020 Oct 8.

Department of Psychiatry and Behavioral Neurosciences, Brain Imaging Research Division, Wayne State University School of Medicine, 3901 Chrysler Service Dr, Suite 5B, Tolan Park Medical Bldg, Detroit, MI, 48201, USA. Electronic address:

Interest in the pathology of Obsessive-Compulsive Disorder\has focused on brain network profiles of the dorsal Anterior Cingulate Cortex (dACC), given its role as a principal control region. Both motor control and working memory tasks induce dysfunctional dACC profiles in OCD. H H We contrasted dACC network profiles in OCD and age-comparable controls during both tasks (from data collected in the same participants). The motor task required participants to tap their right forefinger in response to a flashing white probe; the memory task was a standard n-back (2-Back) requiring participants to identify if a current stimulus was identical to the one presented two items before it in the sequence. Network interactions were modeled using Psychophysiological Interactions (PPI), a model of directional functional connectivity. Inter-group analyses indicated a) that the motor control task evoked greater dACC modulation than the working memory task, and b) that the modulatory effect was significantly greater in the OCD group. We also investigated the relationship between OCD symptom dimensions (lifetime obsession and lifetime compulsion measured using the CY-BOCS) and dACC network profiles in OCD. This analysis revealed a dichotomy between Obsessive-Compulsive symptom dimensions and the degree of dACC modulation: primarily increased obsessions predicted increased modulation during the motor control task, but primarily increased compulsions predicted increased modulation during the working memory task. These results re-emphasize the salience of the dACC in OCD, and the primacy of tasks of motor control in evoking dACC pathology in the disorder.
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http://dx.doi.org/10.1016/j.jpsychires.2020.09.028DOI Listing
January 2021
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