Publications by authors named "Tamara Pringsheim"

188 Publications

Cerebellar Brain Inhibition Is Associated With the Severity of Cervical Dystonia.

J Clin Neurophysiol 2021 Jul 27. Epub 2021 Jul 27.

Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, Calgary, AB, Canada; Department of Biology, Faculty of Science and Technology, Mount Royal University, Calgary, AB, Canada; Department of Psychiatry, Pediatrics and Community Healthy Sciences, University of Calgary, Calgary, AB, Canada; Department of Experimental Medicine, Section of Human Physiology, University of Genoa, Genoa, Italy; and IRCCS Policlinico, San Martino, Genova.

Purpose: Cerebellar connectivity is thought to be abnormal in cervical dystonia (CD) and other dystonia subtypes, based on evidence from imaging studies and animal work. The authors investigated whether transcranial magnetic stimulation-induced cerebellar brain inhibition (CBI), a measure of cerebellar efficiency at inhibiting motor outflow, is abnormal in patients with CD and/or is associated with clinical features of CD. Because of methodological heterogeneity in CBI reporting, the authors deployed additional controls to reduce potential sources of variability in this study.

Methods: Cerebellar brain inhibition was applied in 20 CD patients and 14 healthy control subjects. Cerebellar brain inhibition consisted of a cerebellar conditioning stimulus delivered at four different interstimulus intervals (ISIs) before a test stimulus delivered to hand muscle representation in the motor cortex. The average ratio of conditioned to unconditioned motor evoked potential was computed for each ISI. Cervical dystonia clinical severity was measured using the Toronto Western Spasmodic Torticollis Rating Scale. Control experiments involved neuronavigated transcranial magnetic stimulation, neck postural control in patients, and careful screening for noncerebellar pathway inhibition via cervicomedullary evoked potentials.

Results: There was no difference between CBI measured in healthy control subjects and CD patients at any of the four ISIs; however, CBI efficiency was significantly correlated with worsening CD clinical severity at the 5 ms ISI.

Conclusions: Cerebellar brain inhibition is a variable measure in both healthy control subjects and CD patients; much of this variability may be attributed to experimental methodology. Yet, CD severity is significantly associated with reduced CBI at the 5 ms ISI, suggestive of cerebello-thalamo-cortical tract dysfunction in this disorder.
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http://dx.doi.org/10.1097/WNP.0000000000000884DOI Listing
July 2021

Non-pharmacologic interventions to treat apathy in Parkinson's disease: A realist review.

Clin Park Relat Disord 2021 25;4:100096. Epub 2021 May 25.

Department of Community Health Sciences, University of Calgary, 3D10, 3280 Hospital Drive NW, Calgary, Alberta T2N 4Z6, Canada.

Introduction: There is a diverse body of evidence investigating non-pharmacological treatment options for apathy in Parkinson's disease (PD). We aimed to better understand the context and mechanisms by which non-pharmacological interventions may improve apathy in persons with PD.

Methods: We conducted a realist review of the body of evidence investigating treatment options for apathy in PD. Study authors used findings from a preceding scoping review to identify initial program theory. We then update the scoping review, which was originally conducted in 2017. Two authors independently reviewed and extracted data from studies that discussed non-pharmacological treatment options for apathy in PD. Any data concerning context, mechanisms, and outcomes of interventions for apathy in PD were extracted, synthesized, and analyzed.

Results: Our review included nine studies. We categorized studies into two categories, exercise and mindfulness. There were seven exercise interventions included. Exercise interventions evaluated group exercise compared to individual exercise, aerobic exercise, dance, Nordic walking, and an equine program. There were two mindfulness interventions.

Conclusion: Exercise interventions work best for persons with PD and apathy who are not significantly physically or cognitively impaired, and who have access to transportation, adapted programs, and specialized coaches. Exercise may improve apathy through goal-directed behaviour change and engagement in social interactions. Mindfulness interventions work best for persons with PD and apathy who are not significantly cognitively impaired, have caregiver support, and may improve apathy by targeting the emotional, cognitive, and goal-directed domains that define apathy.
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http://dx.doi.org/10.1016/j.prdoa.2021.100096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299975PMC
May 2021

Inhibitory Control Deficits in Children with Tic Disorders Revealed by Object-Hit-and-Avoid Task.

Neural Plast 2021 1;2021:8825091. Epub 2021 Jul 1.

Department of Clinical Neurosciences, Psychiatry, Pediatrics and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.

Background: Tic disorders may reflect impaired inhibitory control. This has been evaluated using different behavioural tasks, yielding mixed results. Our objective was to test inhibitory control in children with tics through simultaneous presentation of multiple, mobile stimuli.

Methods: Sixty-four children with tics (mean age 12.4 years; 7.5-18.5) were evaluated using a validated robotic bimanual exoskeleton protocol (Kinarm) in an object-hit-and-avoid task, in which target and distractor objects moved across a screen and participants aimed to hit only the targets while avoiding distractors. Performance was compared to 146 typically developing controls (mean age 13 years; 6.1-19.9). The primary outcome was the percentage of distractors struck.

Results: ANCOVA (age as covariate) showed participants struck significantly more distractors (participants without comorbid ADHD, 22.71% [SE 1.47]; participants with comorbid ADHD, 23.56% [1.47]; and controls, 15.59% [0.68]). Participants with comorbid ADHD struck significantly fewer targets (119.74 [2.77]) than controls, but no difference was found between participants without comorbid ADHD (122.66 [2.77]) and controls (127.00 [1.28]). Participants and controls did not differ significantly in movement speed and movement area. Just over 20% of participants with tics fell below the age-predicted norm in striking distractors, whereas fewer than 10% fell outside age-predicted norms in other task parameters.

Conclusions: In children with tics (without comorbid ADHD), acting upon both targets and distractors suggests reduced ability to suppress responses to potential triggers for action. This may be related to increased sensorimotor noise or abnormal sensory gating.
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http://dx.doi.org/10.1155/2021/8825091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270726PMC
July 2021

Rapid onset of functional tic-like behaviours in young adults during the COVID-19 pandemic.

Eur J Neurol 2021 Jul 22. Epub 2021 Jul 22.

Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.

Background And Purpose: Clinicians have reported an increase in functional tic-like behaviours in children and youth during the COVID-19 pandemic. We describe adults developing rapid onset of functional tic-like behaviours between May 2020 and June 2021.

Methods: Data were analysed from the Adult Tic Disorders Registry, a single-site,12-month prospective cohort study that began enrolment in January 2021. We compared clinical features of participants with Tourette syndrome or persistent motor/vocal tic disorder to participants with rapid onset tic-like behaviours.

Results: Thirty-three participants registered between January and June of 2021; nine had rapid onset tic-like behaviours, and 24 had Tourette syndrome or persistent motor tic disorder. Participants with rapid onset tic-like behaviours were younger (19.9 vs. 38.6 years, p = 0.003), had older age at onset (15.3 vs. 10.1, p = 0.0009), and were more likely female (p < 0.0001). They had higher motor and vocal tic severity and impairment scores (all p < 0.01) and were more likely to have complex arm/hand motor tics (p < 0.0001), complex vocal tics (p < 0.0001), and coprolalia (p = 0.004). They had significantly higher scores on all mental health symptom self-report measures (all p < 0.05) and were significantly more likely to be diagnosed with depression (p = 0.03).

Conclusions: The clinical features that help differentiate rapid onset tic-like behaviours from Tourette syndrome or persistent motor tic disorder include their phenomenology, onset age, and clinical course. Rapid onset tic-like behaviours are a distinct subtype of functional neurological disorder that has emerged during the COVID-19 pandemic in young people and appears to be strongly socially influenced.
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http://dx.doi.org/10.1111/ene.15034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444872PMC
July 2021

Working with parents of children with complex mental health issues to improve care: A qualitative inquiry.

J Child Health Care 2021 Jun 28:13674935211028694. Epub 2021 Jun 28.

Departments of Paediatrics and Community Health Sciences, Cumming School of Medicine, 70401University of Calgary, Calgary, AB Canada.

The study objective was to explore the experiences of parents of children (6-17 years) with complex mental healthcare needs in accessing healthcare services in Alberta, Canada. Parents were interviewed using a semi-structured guide with open-ended and probing questions. Interviews were audio recorded and transcribed verbatim. Thematic analysis revealed three main themes: (1) profoundly impacted participants' experience of mental health care due to (a) a lack of a collaborative approach across disciplines in the healthcare system; (b) unavailability of information related to mental health care and (c) a lack of patient-centred care. (2) was difficult due to fragmented services and was hindered by gaps in accessing and receiving care, lack of continuity of care and lack of resources. (3) discussed the emotional challenges, financial burdens, self-advocacy and stigma they experienced in navigating the system. Parents offered insights into potential solutions to these gaps. Parents recommended the creation of a one-stop shop service with a team approach led by a navigator to facilitate and support navigations across healthcare services that work collaboratively across disciplines among healthcare services and across sectors inclusive of social services, education, policing and community programmes.
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http://dx.doi.org/10.1177/13674935211028694DOI Listing
June 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

Microstructural Abnormalities of the Dentatorubrothalamic Tract in Cervical Dystonia.

Mov Disord 2021 Sep 28;36(9):2192-2198. Epub 2021 May 28.

Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.

Background: The dentatorubrothalamic tract (DRTT) remains understudied in idiopathic cervical dystonia (CD), despite evidence that the pathway is relevant in the pathophysiology of the disorder.

Objective: The aim of this study was to examine the DRTT in patients with CD using diffusion tensor imaging (DTI)-based tractography.

Methods: Magnetic resonance imaging scans from 67 participants were collected to calculate diffusion tractography metrics using a binary tractography-based DRTT template. Fractional anisotropy and diffusivity measures of left and right DRTT were computed and compared between 32 subjects with CD and 35 age-matched healthy volunteers.

Results: Fractional anisotropy of right DRTT and mean and axial diffusivity of left DRTT were significantly reduced in patients with CD. Similar abnormalities were observed in patients with focal CD and patients with CD without tremor. DTI metrics did not correlate with disease duration or severity.

Conclusions: Significant reductions in DTI measures suggest microstructural abnormalities within the DRTT in CD, characterized by a tractography pattern consistent with decreased axonal integrity. © 2021 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28649DOI Listing
September 2021

Teaching Video NeuroImage: Paroxysmal Nocturnal Dyskinesias: A Characteristic Feature of Mutation.

Neurology 2021 09 7;97(10):e1062. Epub 2021 Apr 7.

From the Department of Clinical Neurosciences (T.M.P., N.C.), University of Calgary, Canada; and Department of Neurology (E.R.), Pitié-Salpêtrière Hospital, Sorbonne University and the Assistance Publique-Hôpitaux de Paris, France.

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http://dx.doi.org/10.1212/WNL.0000000000011920DOI Listing
September 2021

The prevalence of depression in adult onset idiopathic dystonia: Systematic review and metaanalysis.

Neurosci Biobehav Rev 2021 06 1;125:221-230. Epub 2021 Mar 1.

Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Mathison Centre for Mental Health Research and Education, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada. Electronic address:

Adult onset idiopathic dystonia (AOID) is the third most common movement disorder in adults. Co-existing depressive symptoms and disorders represent major contributors of disability and quality of life in these patients, but their prevalence remains unclear. We investigated the point prevalence of supra-clinical threshold depressive symptoms/depressive disorders in AOID in a systematic review with qualitative synthesis and meta-analysis. Our search identified 60 articles suitable for qualitative synthesis and 54 for meta-analysis. The overall pooled prevalence of either supra-clinical threshold depressive symptoms or depressive disorders was 31.5 % for cervical dystonia, 29.2 % for cranial dystonia, and 33.6 % for clinical samples with mixed forms of AOID. Major depressive disorder was more prevalent than dysthymia in cervical dystonia, whereas dysthymia was more prevalent in cranial dystonia. In cervical dystonia, the prevalence of supra-clinical threshold depressive symptoms screened by rating scales was higher than that of depressive disorders diagnosed with structured interviews. Prevalence studies using rating scales yielded higher heterogeneity. More research is warranted to standardize screening methodology and characterization of mood disorders in AOID.
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http://dx.doi.org/10.1016/j.neubiorev.2021.02.036DOI Listing
June 2021

Bilateral transcranial magnetic stimulation of the supplementary motor area in children with Tourette syndrome.

Dev Med Child Neurol 2021 07 25;63(7):808-815. Epub 2021 Feb 25.

Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

Aim: To explore the feasibility and possible effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) delivered to the supplementary motor area (SMA) on tic severity and motor system neurophysiology in children with Tourette syndrome.

Method: Ten children with Tourette syndrome (eight males, two females; 9-15y) participated in this open-label, phase 1 clinical trial. Treatment consisted of 1800 low-frequency (1Hz) neuronavigated robotic rTMS (100% resting motor threshold) to the SMA, bilaterally for 15 sessions. The primary outcome was a change in Yale Global Tic Severity Scale (YGTSS) total score from baseline to posttreatment. Secondary outcome measures included changes in magnetic resonance spectroscopy metabolite concentrations, TMS neurophysiology measures, TMS motor maps, and clinical assessments (anxiety, depression) from baseline to the end of treatment.

Results: The YGTSS score decreased from baseline after treatment (p<0.001; Cohen's d=2.9). All procedures were well-tolerated.

Interpretation: Robot-driven, neuronavigated bilateral rTMS of the SMA is feasible in children with Tourette syndrome and appears to reduce tic severity. What this paper adds Repetitive transcranial magnetic stimulation (rTMS) is feasible to use in children with Tourette syndrome. rTMS is tolerated by children with Tourette syndrome. Precise targeting of the supplementary motor area using functional magnetic resonance imaging is also feasible in these children.
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http://dx.doi.org/10.1111/dmcn.14828DOI Listing
July 2021

The 5 Pillars in Tourette Syndrome Deep Brain Stimulation Patient Selection: Present and Future.

Neurology 2021 04 16;96(14):664-676. Epub 2021 Feb 16.

From the Department of Clinical Neurosciences (D.M., T.M.P.), Cumming School of Medicine, University of Calgary, Calgary AB, Canada; Hotchkiss Brain Institute (D.M., T.M.P.), University of Calgary, Calgary AB, Canada; Alberta Children's Hospital Research Institute (D.M.), University of Calgary, Calgary AB, Canada; Mathison Centre for Mental Health Research and Education (D.M., T.M.P.), Calgary, AB, Canada; UMass Memorial Medical Center and UMass Medical School (W.D.), Worcester, MA, United States; Department of Neurology (J.J.-S.), Icahn School of Medicine at Mount Sinai, New York, NY, United States; Department of Neurology (I.M., M.S.O.), Norman Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville, FL, United States; Department of Psychiatry (T.M.P.), Pediatrics and Community Health Sciences, University of Calgary, AB, Canada; Edmond J. Safra Program in Parkinson's Disease (A.F.), Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, Toronto, Ontario, Canada; Division of Neurology, University of Toronto, Toronto, Ontario, Canada; Krembil Brain Institute (A.F.), Toronto, Ontario, Canada; CenteR for Advancing Neurotechnological Innovation to Application (CRANIA) (A.F.), Toronto, ON, Canada; Movement Disorders and Neuromodulation Unit (C.G.), Charité, University Medicine Berlin, Department of Neurology, Berlin, Germany; and Strategic Regulatory Partners (W.W.), LLC.

The selection of patients with Tourette syndrome (TS) for deep brain stimulation (DBS) surgery rests on 5 fundamental pillars. However, the operationalization of the multidisciplinary screening process to evaluate these pillars remains highly diverse, especially across sites. High tic severity and tic-related impact on quality of life (first 2 pillars) require confirmation from objective, validated measures, but malignant features of TS should per se suffice to fulfill this pillar. Failure of behavioral and pharmacologic therapies (third pillar) should be assessed taking into account refractoriness through objective and subjective measures supporting lack of efficacy of all interventions of proven efficacy, as well as true lack of tolerability, adherence, or access. Educational interventions and use of remote delivery formats (for behavioral therapies) play a role in preventing misjudgment of treatment failure. Stability of comorbid psychiatric disorders for 6 months (fourth pillar) is needed to confirm the predominant impact of tics on quality of life, to prevent pseudo-refractoriness, and to maximize the future DBS response. The 18-year age limit (fifth pillar) is currently under reappraisal, considering the potential impact of severe tics in adolescence and the predictive effect of tic severity in childhood on tic severity when transitioning into adulthood. Future advances should aim at a consensus-based definition of failure of specific, noninvasive treatment strategies for tics and of the minimum clinical observation period before considering DBS treatment, the stability of behavioral comorbidities, and the use of a prospective international registry data to identify predictors of positive response to DBS, especially in younger patients.
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http://dx.doi.org/10.1212/WNL.0000000000011704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105965PMC
April 2021

Children with Tic Disorders Show Greater Variability in an Arm-Position-Matching Proprioceptive Task.

Mov Disord 2021 03 7;36(3):782-784. Epub 2020 Dec 7.

Department of Clinical Neurosciences, Psychiatry, Pediatrics and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.

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http://dx.doi.org/10.1002/mds.28413DOI Listing
March 2021

Transitional Care for Young People with Neurological Disorders: A Scoping Review with A Focus on Patients with Movement Disorders.

Mov Disord 2021 06 17;36(6):1316-1324. Epub 2020 Nov 17.

Department of Neurology, Salpêtrière Hospital, Sorbonne University and Assistance Publique - Hôpitaux de Paris, Paris, France.

Childhood-onset movement disorders represent a heterogenous group of conditions. Given the complexity of these disorders, the transition of care from pediatric to adult medicine is an important consideration. We performed a scoping review of the literature on transitional care in chronic neurological disease, exploring key transitional issues and proposed transitional care models. Our aim was to describe the current knowledge and gaps about the transition process of young adults with chronic neurological disorders, paying special attention to childhood onset movement disorders. A total of 64 articles were included in the qualitative synthesis; 56 articles reported on transitional care issues, and 8 articles reported on transitional care models. Only 2 articles included patients with movement disorders. The following 4 main transitional issues were identified following synthesis of the available literature: (1) inadequate preparation for the transition process, (2) inappropriate and inconsistent transition practices, (3) inadequate adult services, and (4) heightened emotional response surrounding transition. Of the reported transitional care models, multidisciplinary ambulatory care was the most common approach. In studies evaluating patient-related outcomes, positive health, educational, and vocational outcomes were found. The available literature provides insights on issues that can arise during transition that should be addressed to improve patient and caregiver comfort and satisfaction with care. Further research is needed to evaluate how transitional care programs affect outcomes and their cost effectiveness. More studies are required to determine the needs and outcomes specific to patients with childhood onset movement disorders. © 2020 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28381DOI Listing
June 2021

Diagnosis, treatment and management of apathy in Parkinson's disease: a scoping review.

BMJ Open 2020 09 9;10(9):e037632. Epub 2020 Sep 9.

Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.

Objective: To conduct a scoping review of the literature on apathy in Parkinson's disease (PD), to better understand how apathy in Parkinson's disease is diagnosed, treated and managed.

Methods: MEDLINE, Embase, PsycINFO, CINAHL, Cochrane Central Register of Control Trials and Cochrane Database of Systematic Reviews were searched to 17 May 2017. An updated review was run from 17 May 2017 to 28 January 2019. The grey literature was searched using the CADTH Grey Matters tool. Original peer-reviewed research was included if it included individuals with PD and apathy. Non-original data was only included if it was in the form of meta-analysis. All information regarding diagnosis, treatment and management of PD was extracted. Citation screening and extraction were performed in duplicate.

Results: From 11 375 citations, 362 articles were included in the final review. The majority of included studies focussed on prevalence, with few studies examining treatment. Twenty screening tools for apathy were identified. Fifty per cent of treatment studies were randomised control trials (RCTs). RCTs applied treatment methods including: exercise, mindfulness, rotigotine (Neupro) transdermal patch and rivastigmine (Exelon).

Conclusions: This review identified a large body of literature describing current knowledge on diagnosing, treating and managing apathy in PD. Future research should aim to detect an ideal screening tool for apathy in PD, to identify the best treatment options for apathy and the variety of comorbidities it may present with and finally aim to better understand postoperative apathy in those with deep brain stimulation.
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http://dx.doi.org/10.1136/bmjopen-2020-037632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482451PMC
September 2020

Barriers and Facilitators Associated with the Management of Aggressive and Disruptive Behaviour in Children: A Qualitative Study with Pediatricians.

J Can Acad Child Adolesc Psychiatry 2020 Aug 1;29(3):177-187. Epub 2020 Aug 1.

Associate Professor, Department of Clinical Neurosciences, Psychiatry, Pediatrics and Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta.

Background: Aggressive and disruptive behaviours are frequently observed in children. Short-term use of antipsychotics with monitoring for adverse effects is recommended when first-line interventions fail (e.g. psychosocial therapies and psychostimulants for ADHD). This study aimed to understand the barriers and facilitators to behavioural change for the management of aggressive and disruptive behaviours by pediatricians.

Methods: This was a qualitative study with twenty community-based pediatricians. An interview guide was developed to elicit beliefs associated with practice behaviours. We used thematic content analysis with the Theoretical Domains Framework to inform knowledge translation interventions, by helping to determine what behavioural barriers and facilitators to practice exist. Key domains which influenced behaviour were identified by evaluating the frequency of beliefs across interviews, conflicting beliefs, and the strength of beliefs impacting behaviour.

Results: Pediatricians described evaluating the impact of aggressive and disruptive behaviours, attempting to determine their cause, and using an approach that prioritized psychosocial therapies and psychostimulants. Pediatricians reported that antipsychotics were effective but that they experienced anxiety about harms, and there was a need to accept the adverse effects as a trade-off for improved function. Discontinuing antipsychotics was problematic. Despite awareness of antipsychotic-induced movement disorders and metabolic effects, there were limitations in physician skills, knowledge and resources and social influences that were a barrier to routine implementation of recommended monitoring procedures.

Conclusions: This study identifies barriers and facilitators to evidence-based practice that can be used for knowledge translation interventions to ensure a high standard of care for children prescribed antipsychotics.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391873PMC
August 2020

Barriers and Facilitators Associated with the Management of Aggressive and Disruptive Behaviour in Children: A Qualitative Study with Pediatricians.

J Can Acad Child Adolesc Psychiatry 2020 Aug 1;29(3):177-187. Epub 2020 Aug 1.

Associate Professor, Department of Clinical Neurosciences, Psychiatry, Pediatrics and Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta.

Background: Aggressive and disruptive behaviours are frequently observed in children. Short-term use of antipsychotics with monitoring for adverse effects is recommended when first-line interventions fail (e.g. psychosocial therapies and psychostimulants for ADHD). This study aimed to understand the barriers and facilitators to behavioural change for the management of aggressive and disruptive behaviours by pediatricians.

Methods: This was a qualitative study with twenty community-based pediatricians. An interview guide was developed to elicit beliefs associated with practice behaviours. We used thematic content analysis with the Theoretical Domains Framework to inform knowledge translation interventions, by helping to determine what behavioural barriers and facilitators to practice exist. Key domains which influenced behaviour were identified by evaluating the frequency of beliefs across interviews, conflicting beliefs, and the strength of beliefs impacting behaviour.

Results: Pediatricians described evaluating the impact of aggressive and disruptive behaviours, attempting to determine their cause, and using an approach that prioritized psychosocial therapies and psychostimulants. Pediatricians reported that antipsychotics were effective but that they experienced anxiety about harms, and there was a need to accept the adverse effects as a trade-off for improved function. Discontinuing antipsychotics was problematic. Despite awareness of antipsychotic-induced movement disorders and metabolic effects, there were limitations in physician skills, knowledge and resources and social influences that were a barrier to routine implementation of recommended monitoring procedures.

Conclusions: This study identifies barriers and facilitators to evidence-based practice that can be used for knowledge translation interventions to ensure a high standard of care for children prescribed antipsychotics.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391873PMC
August 2020

The cognitive neuropsychiatry of Tourette syndrome.

Cogn Neuropsychiatry 2020 07 6;25(4):254-268. Epub 2020 May 6.

School of Life and Health Sciences, Aston Brain Centre, Aston University, Birmingham, United Kingdom.

Converging evidence from both clinical and experimental studies has shown that Tourette syndrome (TS) is not a unitary condition, but a cluster of multiple phenotypes, which encompass both tics and specific behavioural and cognitive symptoms (mainly attention-deficit and hyperactivity disorder and obsessive-compulsive disorder). We conducted a narrative review of the recent literature on the cognitive neuropsychiatry of TS. Although clinical research has shown that TS is not associated with cognitive deficits per se, the findings of recent studies have suggested the presence of subtle alterations in specific cognitive functions. A promising line of research on imitative behaviour could provide a common background for the alterations in executive control and social cognition observed in TS. Two different (but not mutually exclusive) neurocognitive theories have recently suggested that TS could originate from altered perception-action binding and social decision-making dysfunction, respectively. Since the presence of behavioural comorbidities influences individualised treatment approaches, it is likely that a more precise characterisation of TS phenotypes, including cognitive aspects, will result in improved levels of care for patients with tic disorders.
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http://dx.doi.org/10.1080/13546805.2020.1760812DOI Listing
July 2020

Physical activity, sleep and neuropsychiatric symptom severity in children with tourette syndrome.

Eur Child Adolesc Psychiatry 2021 May 5;30(5):711-719. Epub 2020 May 5.

Department of Clinical Neurosciences, University of Calgary, Calgary, Canada.

The purpose of this study was to examine associations between physical activity, sleep and symptom severity in children with tic disorders. Children with tic disorders wore the GeneActiv device, a wrist-worn accelerometer that measures physical activity intensity and sleep/wake parameters continuously for seven days, and completed questionnaires on sleep quality, exercise and severity of tics, ADHD, obsessive-compulsive behaviours, anxiety and depression. 110 children participated in the study. Children with more severe tics had significantly more frequent comorbid diagnoses, greater impairment in subjective sleep measures, greater sedentary activity time and less light, moderate and vigorous activity time (all p < 0.05). There was a significant negative correlation between light, moderate and vigorous physical activity and the severity of tics (- 0.22, p = 0.04), obsessive compulsive behaviours (- 0.22, p = 0.03), anxiety (- 0.35, p = 0.0005) and depression (- 0.23, p = 0.03). There was no correlation between objective sleep time, sleep efficiency and symptom severity. Subjective sleep quality was positively correlated with all symptom severity measures, with the strongest correlation with ADHD severity (0.42, p < 0.00001). The results of this observational study indicate a small, but significant relationship between activity and sleep measures and the severity of the main symptom domains present in tic disorders.
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http://dx.doi.org/10.1007/s00787-020-01552-1DOI Listing
May 2021

Current pharmacotherapy for tic disorders.

Expert Opin Pharmacother 2020 Apr 14;21(5):567-580. Epub 2020 Apr 14.

Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary and Hotchkiss Brain Institute, Calgary, Alberta, Canada.

: Though many unanswered questions about the pathophysiology of Tourette Syndrome remain, several pharmacotherapies for tics have been studied, with varying results in terms of efficacy and the strength of evidence.: This literature review encompasses pharmacotherapies for tics. The pharmacotherapies discussed in this review include: alpha agonists, antipsychotics, topiramate, botulinum toxin, and dopamine depleters.: Once the presence of tics is confirmed and psychoeducation and support are provided to patients and caregivers, one must examine the degree of tic-related impairment and the presence of psychiatric comorbidities. These factors influence treatment decisions as the presence of comorbidity and related impairment may shift the treatment target. When selecting a medication for tics, the presence of ADHD (the most frequent comorbidity) strengthens the case for choosing an alpha agonist. The case for antipsychotic medications is strongest when tic-related impairment is severe and/or the tics are refractory to more conservative measures. All medications require drug safety monitoring procedures and reevaluation over time.
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http://dx.doi.org/10.1080/14656566.2020.1721465DOI Listing
April 2020

Cannabis Use and Internalizing/Externalizing Symptoms in Youth: A Canadian Population-Based Study.

J Adolesc Health 2020 07 27;67(1):26-32. Epub 2020 Feb 27.

Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada; Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada.

Purpose: With the recent legalization of cannabis for nonmedicinal purposes in Canada, it is becoming increasingly important to understand the potential mental health risks that cannabis may present. The objective of this study was to estimate associations between the frequency of cannabis use and the presence of elevated internalizing (e.g., anxiety and depression) and externalizing (e.g., conduct disorder and attention deficit hyperactivity disorder) symptoms within Ontario youth aged 12-17 years.

Methods: The 2014 Ontario Child Health Study included Emotional and Behavioural Scales used to assess internalizing and externalizing symptoms. To assess associations between internalizing/externalizing symptoms and cannabis use, the Ontario Child Health Study-Emotional and Behavioural Scales were dichotomized using the upper quintile (those with the most severe symptoms). Logistic regression was used to estimate odds ratios (ORs) to quantify the association between the frequency of cannabis use and the presence of elevated internalizing and externalizing symptoms. Estimates used a recommended procedure (replicate bootstrap weighting) to address design effects.

Results: A significant association between frequent cannabis use and elevated externalizing symptoms was observed with an OR of 2.17 (1.80-2.62) in males and 5.13 (4.24-6.21) in females. Similar significant associations were also observed between frequent cannabis use and elevated internalizing symptoms with an OR of 2.07 (1.74-2.47) in males and an OR of 3.40 (2.73-4.24) in females. These associations were still present after adjusting for age, binge drinking, smoking, and negative/positive parenting.

Conclusions: Cannabis use, especially in females and frequent users, is associated with elevated levels of internalizing and externalizing symptoms.
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http://dx.doi.org/10.1016/j.jadohealth.2020.01.015DOI Listing
July 2020

Practice guideline: Treatment for insomnia and disrupted sleep behavior in children and adolescents with autism spectrum disorder: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

Neurology 2020 03 12;94(9):392-404. Epub 2020 Feb 12.

From the Pediatrics and Developmental Neuroscience Branch (A.W.B., T.G., R.K., A.T.), National Institute of Mental Health, NIH, Bethesda, MD; Department of Neurological Sciences (D.H.), University of Vermont Medical Center, Burlington; Department of Pediatric Neurology (M.O.), McGill University Health Centre, Montréal, Canada; Department of Neurology (M.J.A.), University of Florida College of Medicine, Gainesville; Developmental Pediatrics (A.B.), Our Special Kids Pediatric Care, Los Angeles, CA; Division of Developmental Medicine (C.B.) and Center for Pediatric Sleep Disorders (J.O.), Boston Children's Hospital, MA; Departments of Pediatrics and Psychiatry (D.C.), The Ohio State University College of Medicine, Columbus; Duke Center for Autism and Brain Development (G.D., L.S.), Duke University School of Medicine, Durham, NC; Northern Michigan Neurology (D.D.), Traverse City; Department of Child and Behavioral Sciences (R.L.F.), Johns Hopkins University, Baltimore, MD; Department of Neurology (D.G.), Charleston Area Medical Center, WV; Department of Neurology (G.G.), Kansas University Medical Center, Kansas City; American Academy of Neurology (S.M.), Minneapolis, MN; Division of Pediatric Neurology, Department of Pediatrics (D.M., S.A.), Loma Linda University School of Medicine, CA; Department of Clinical Neurosciences (T.P.), University of Calgary, Alberta, Canada; Department of Psychiatry and Behavioral Science and MIND Institute (A.S.), University of California, Davis; Division of Neurology (R.T.), Nicklaus Children's Hospital and Miami Children's Hospital, FL; Treatment and Research Institute for Autism Spectrum Disorders (Z.W.), Vanderbilt Kennedy Center, Nashville, TN; Autism Institute, College of Medicine (A.W.), Florida State University, Tallahassee; and Division of Neurology (M.W.), Rainbow Babies & Children's Hospital, Cleveland, OH.

Objective: To review pharmacologic and nonpharmacologic strategies for treating sleep disturbances in children and adolescents with autism spectrum disorder (ASD) and to develop recommendations for addressing sleep disturbance in this population.

Methods: The guideline panel followed the American Academy of Neurology 2011 guideline development process, as amended. The systematic review included studies through December 2017. Recommendations were based on evidence, related evidence, principles of care, and inferences.

Major Recommendations Level B: For children and adolescents with ASD and sleep disturbance, clinicians should assess for medications and coexisting conditions that could contribute to the sleep disturbance and should address identified issues. Clinicians should counsel parents regarding strategies for improved sleep habits with behavioral strategies as a first-line treatment approach for sleep disturbance either alone or in combination with pharmacologic or nutraceutical approaches. Clinicians should offer melatonin if behavioral strategies have not been helpful and contributing coexisting conditions and use of concomitant medications have been addressed, starting with a low dose. Clinicians should recommend using pharmaceutical-grade melatonin if available. Clinicians should counsel children, adolescents, and parents regarding potential adverse effects of melatonin use and the lack of long-term safety data. Clinicians should counsel that there is currently no evidence to support the routine use of weighted blankets or specialized mattress technology for improving disrupted sleep. If asked about weighted blankets, clinicians should counsel that the trial reported no serious adverse events with blanket use and that blankets could be a reasonable nonpharmacologic approach for some individuals.
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http://dx.doi.org/10.1212/WNL.0000000000009033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238942PMC
March 2020

Antidepressant Prescriptions, Including Tricyclics, Continue to Increase in Canadian Children.

J Child Adolesc Psychopharmacol 2020 07 31;30(6):381-388. Epub 2019 Dec 31.

Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

Few studies have longitudinally followed trends in antidepressant prescribing for Canadian children following the Black Box warning issued in 2004. Using a national data source, we aim to describe trends in antidepressant recommendations for Canadian children ages 1-18 during 2012 to 2016. A database called the Canadian Disease and Therapeutic Index (CDTI), provided by IQVIA, was used to conduct analyses. The CDTI dataset collects a quarterly sample of pediatric antidepressant recommendations, projected using a weight procedure from a dynamic sample of 652 Canadian office-based physicians. The term "recommendations" is used because nonprescription drugs may be recommended and there is no confirmation in the database that the prescriptions were filled or medications taken. The data were collected from 2012 to 2016 and the sample population was projected by IQVIA to be representative of the entire Canadian pediatric population. The total number of projected antidepressant recommendations for children increased from 2012 to 2016. Selective serotonin reuptake inhibitors were the most recommended class of antidepressants. Analysis indicated that fluoxetine was the most frequently recommended drug. Findings also suggest that recommendations for tricyclic antidepressants (TCAs) are increasing, but predominantly for reasons other than treatment of depression. Overall, antidepressant use in Canadian children increased over the study period. Unsurprisingly, fluoxetine was the most recommended antidepressant for Canadian children. However, the observed increase in TCA use for a pediatric population is unexpected. The data source is descriptive and lacks detailed measures supporting comprehensive explanation of the findings, therefore, further research is required.
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http://dx.doi.org/10.1089/cap.2019.0121DOI Listing
July 2020

Rebuttal From Dr Pringsheim.

Chest 2019 11;156(5):824

Department of Clinical Neurosciences, Psychiatry, Pediatrics and Community Health Sciences, University of Calgary, Calgary, AB, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.chest.2019.06.027DOI Listing
November 2019

POINT: Is the Term Habit Cough an Inaccurate Use of a Term? Yes.

Chest 2019 11;156(5):820-821

Department of Clinical Neurosciences, Psychiatry, Pediatrics and Community Health Sciences, University of Calgary, Calgary, AB, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.chest.2019.06.024DOI Listing
November 2019

Practice guideline update summary: Acute treatment of migraine in children and adolescents: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Headache Society.

Headache 2019 09;59(8):1158-1173

Department of Neurology, Mayo Clinic, Rochester, MN.

Objective: To provide evidence-based recommendations for the acute symptomatic treatment of children and adolescents with migraine.

Methods: We performed a systematic review of the literature and rated risk of bias of included studies according to the American Academy of Neurology classification of evidence criteria. A multidisciplinary panel developed practice recommendations, integrating findings from the systematic review and following an Institute of Medicine-compliant process to ensure transparency and patient engagement. Recommendations were supported by structured rationales, integrating evidence from the systematic review, related evidence, principles of care, and inferences from evidence.

Results: There is evidence to support the efficacy of the use of ibuprofen, acetaminophen (in children and adolescents), and triptans (mainly in adolescents) for the relief of migraine pain, although confidence in the evidence varies between agents. There is high confidence that adolescents receiving oral sumatriptan/naproxen and zolmitriptan nasal spray are more likely to be headache free at 2 hours than those receiving placebo. No acute treatments were effective for migraine-related nausea or vomiting; some triptans were effective for migraine-related phonophobia and photophobia.

Recommendations: Recommendations for the treatment of acute migraine in children and adolescents focus on the importance of early treatment, choosing the route of administration best suited to the characteristics of the individual migraine attack, and providing counselling on lifestyle factors that can exacerbate migraine, including trigger avoidance and medication overuse.
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http://dx.doi.org/10.1111/head.13628DOI Listing
September 2019

Practice guideline update summary: Pharmacologic treatment for pediatric migraine prevention: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Headache Society.

Headache 2019 09;59(8):1144-1157

Division of Behavioral Medicine & Clinical Psychology, Cincinnati Children's Hospital Medical Center, OH.

Objective: To provide updated evidence-based recommendations for migraine prevention using pharmacologic treatment with or without cognitive behavioral therapy in the pediatric population.

Methods: The authors systematically reviewed literature from January 2003 to August 2017 and developed practice recommendations using the American Academy of Neurology 2011 process, as amended.

Results: Fifteen class I-III studies on migraine prevention in children in adolescents met inclusion criteria. There is insufficient evidence to determine if children and adolescents receiving divalproex, onabotulinumtoxinA, amitriptyline, nimodipine and flunarizine are more or less likely than those receiving placebo to have a reduction in headache frequency. Children with migraine receiving propranolol are possibly more likely than those receiving placebo to have an at least 50% reduction in headache frequency. Children and adolescents receiving topiramate and cinnarizine are probably more likely than those receiving placebo to have a decrease in headache frequency. Children with migraine receiving amitriptyline plus cognitive behavioral therapy are more likely than those receiving amitriptyline plus headache education to have a reduction in headache frequency. Recommendations The majority of randomized controlled trials studying the efficacy of preventive medications for pediatric migraine fail to demonstrate superiority to placebo. Recommendations for the prevention of migraine in children include counseling on lifestyle and behavioral factors that influence headache frequency, and assessment and management of comorbid disorders associated with headache persistence. Clinicians should engage in shared decision making with patients and caregivers regarding the use of preventive treatments for migraine, including discussion of the limitations in the evidence to support pharmacologic treatments.
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http://dx.doi.org/10.1111/head.13625DOI Listing
September 2019

Treatment Patterns, Health Care Resource Utilization, and Health Care Cost Associated with Atypical Antipsychotics or Guanfacine Extended Release in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder in Quebec, Canada.

J Child Adolesc Psychopharmacol 2019 12 17;29(10):730-739. Epub 2019 Sep 17.

Center for Pediatric Excellence, Ottawa, Ontario, Canada.

To assess treatment patterns, health care resource utilization, and health care costs associated with use of atypical antipsychotics (AAPs) or the nonstimulant guanfacine extended release (GXR) after stimulant therapy for attention-deficit/hyperactivity disorder (ADHD). In Canada, GXR is approved as a monotherapy for children and adolescents with ADHD or as an adjunct to stimulants, and AAPs are commonly used off-label as an adjunct to stimulants. Health care claims data (January 1, 2007 to March 31, 2016) from Quebec's provincial health plan were assessed for individuals with ADHD, 6-17 years of age, who received ≥1 stimulant followed by a first AAP or GXR prescription (index medication), without a diagnosis for which AAPs are indicated. Overall, 1327 individuals were included (AAPs, 1098; GXR, 229). Rates of discontinuation, augmentation, or switching of the index medication did not differ between AAPs and GXR during the first follow-up year. Discontinuation rates were significantly lower with GXR than with AAPs during the second year (22.0% vs. 35.9%;  = 0.03). GXR and AAPs resulted in similar increases in total health care cost. In GXR users, the increase in prescription drug cost after 6 months was higher than in AAP users, whereas the increase in overall medical cost was higher with AAPs than GXR, owing to more psychiatric department visits. In children and adolescents with ADHD who used AAPs or GXR after stimulants, secondary treatment changes were similar with both treatments after 1 year, but discontinuation rates were significantly lower with GXR than with AAPs in the second year. The greater increase in prescription cost with GXR was balanced by a greater increase in overall medical costs with AAPs, resulting in no overall difference in total health care cost between the two treatments.
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http://dx.doi.org/10.1089/cap.2019.0097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885769PMC
December 2019

Prescriptions for Alpha Agonists and Antipsychotics in Children and Youth with Tic Disorders: A Pharmacoepidemiologic Study.

Tremor Other Hyperkinet Mov (N Y) 2019 15;9. Epub 2019 Jul 15.

Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary and Hotchkiss Brain Institute, Foothills Hospital, Calgary, AB, CA.

Background: Trends in the use of antipsychotics and alpha agonists for the treatment of tic disorders in Canadian children, and how closely these trends align with evidence-based guidelines on the pharmacotherapy of tic disorders, have not been explored.

Methods: IQVIA's Canadian Disease and Therapeutic Index, a survey-based data set, was used to identify prescription patterns by physicians. Respondents recorded all patient visits during a 48-hour period in each quarter of the year, including patient age, gender, drug recommendation and therapeutic indication. Recommendations for alpha agonists and antipsychotics from 2012 to 2016 were analysed for children and adolescents with tic disorders.

Results: Risperidone and clonidine were the most commonly recommended medications for tic disorders over the study period, with 36,868 and 35,500 recommendations in 2016, respectively. Recommendations for clonidine increased over the study period, whereas those for risperidone decreased. Guanfacine (approved in Canada in 2013) was used less frequently than clonidine. Clonidine was more frequently recommended than antipsychotics in children younger than 6, in whom antipsychotic recommendations were uncommon. Aripiprazole was the second most commonly recommended antipsychotic for tic disorders, with 22,892 recommendations in 2016. Of the first-generation antipsychotics, pimozide was most commonly recommended (11,334 recommendations in 2016); haloperidol was infrequently recommended.

Discussion: The trends observed are in line with guideline recommendations reflected in the decreasing use of risperidone, and the growing use of clonidine and guanfacine. The growing use of aripiprazole is likely due to emerging evidence from clinical trials supporting its efficacy for tics. Recommendations for pimozide and haloperidol were limited, likely due to the greater adverse effects associated with these medications.
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http://dx.doi.org/10.7916/tohm.v0.645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691607PMC
January 2020
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