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BACKGROUND: Quetiapine is an antipsychotic that is widely prescribed off-label by family physicians despite evidence that safer alternatives exist. The aim of this research was to explore, in-depth, family physicians' reasons for this behaviour. METHODS: We conducted qualitative interviews with 15 urban family physicians in Alberta between October 2015 and April 2016. Participants were purposively selected based on sex, years of experience and practice type. Interviews explored participants' experiences prescribing quetiapine. Interviews were recorded, transcribed verbatim and coded with the use of thematic analysis. RESULTS: A wish to support day-to-day function of patients with complex psychosocial needs without causing benzodiazepine addiction motivated participants to prescribe quetiapine. The indications were varied and included incomplete symptom resolution, unclear or multiple mental health diagnoses, and complicated psychosocial problems. Family physicians benchmarked their prescribing against peers and were reluctant to stop medication started by colleagues. Limited knowledge of quetiapine's adverse effects led prescribers to choose low dosages. INTERPRETATION: Quetiapine helped family physicians treat patients with complex mental health problems without prescribing benzodiazepines, but awareness of quetiapine's adverse effects was poor. Education about quetiapine should combine psychopharmacology with multidisciplinary educational initiatives that focus on symptom resolution, comorbidity and nondrug options to promote more appropriate prescribing.

RÉSUMÉNotre principal objectif était de comprendre les barrières et les facilitateurs associés à l’application de guides de pratique clinique (GPC) de haute qualité pour la dépression et l’anxiété chez les patients atteint de démence ou de la maladie de Parkinson (MP). Des groupes de discussion et des entrevues ont été réalisés avec des participants atteints de démence ou de la MP, leurs soignants et les médecins impliqués dans les soins de ces patients à Calgary (Alberta). Le cadre conceptuel des domaines théoriques et le Behaviour Change Wheel ont été utilisés pour guider la collecte des données et l’analyse du cadre conceptuel. Au total, 33 médecins, 7 patients et leurs aidants ont participé à l’étude. Les barrières et les facilitateurs pour l’application des recommandations des GPC liées au diagnostic, à la gestion et à l’utilisation des lignes directrices ont été rapportés. L’insuffisance des données concernant les troubles anxieux et dépressifs dans la démence et la MP constituaient un thème dominant dans les résultats. Ce constat était particulièrement évident en matière de troubles anxieux. Les patients ont aussi mentionné des difficultés à communiquer leurs symptômes et à accéder aux services. Bien que des guides de pratiques soient disponibles, les médecins éprouvent quelques difficultés dans l’application de certaines recommandations, ces difficultés étant surtout dues au manque de données probantes disponibles.

Background:Akathisia is a common and distressing neuropsychiatric syndrome associated with antipsychotic medication, characterised by subjective and objective psychomotor restlessness. The goal of this guideline is to provide clinicians with recommendations on the assessment and treatment of akathisia.Methods:We performed a systematic review of therapeutic studies assessing the treatment of antipsychotic-induced extrapyramidal symptoms. Forty studies on akathisia and 4 systematic reviews evaluating the adverse effects of antipsychotics were used in the formulation of recommendations. Studies were rated for methodological quality using the American Academy of Neurology Risk of Bias Classification system. The overall level of evidence classifications and grades of recommendation were made using the Scottish Intercollegiate Guidelines Network framework.Results:As a good practice point, clinicians should systematically assess akathisia with a validated scale before starting antipsychotics and during antipsychotic dosage titration. For the management of akathisia, there was adequate evidence to allow recommendations regarding antipsychotic dose reduction, antipsychotic polypharmacy, switching antipsychotic medication, and the use of adjuvant medications including beta-blockers, anticholinergics, 5HT2Aantagonists, benzodiazepines, and vitamin B6.Conclusion:The treatment of antipsychotic-induced akathisia should be personalised, with consideration of antipsychotic dose reduction, cessation of antipsychotic polypharmacy, and switching to an antipsychotic with a perceived lower liability for akathisia, before the use of adjuvant medications. The choice of adjuvant medications should favour the more established treatments, with careful consideration of contraindications and side effects. Limitations in the evidence should be acknowledged and prompt cautious prescribing, particularly with respect to the duration of use of adjuvant medications, is warranted.

Background Hydrocephalus is a debilitating disorder, affecting all age groups. Evaluation of its global epidemiology is required for healthcare planning and resource allocation. Objectives To define age-specific global prevalence and incidence of hydrocephalus. Methods Population-based studies reporting prevalence of hydrocephalus were identified (MEDLINE, EMBASE, Cochrane, and Google Scholar (1985-2017)). Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Two authors reviewed abstracts, full text articles and abstracted data. Metanalysis and meta-regressions were used to assess associations between key variables. Heterogeneity and publication bias were assessed. Main outcome of interest was hydrocephalus prevalence among pediatric (≤ 18 years), adults (19-64 years), and elderly (≥ 65) patients. Annual hydrocephalus incidence stratified by country income level and folate fortification requirements were obtained (2003-2014) from the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR). Results Of 2,460 abstracts, 52 met review eligibility criteria (aggregate population 171,558,651). Mean hydrocephalus prevalence was 85/100,000 [95% CI 62, 116]. The prevalence was 88/100,000 [95% CI 72, 107] in pediatrics; 11/100,000 [95% CI 5, 25] in adults; and 175/100,000 [95% CI 67, 458] in the elderly. The ICBDSR-based incidence of hydrocephalus diagnosed at birth remained stable over 11 years: 81/100,000 [95% CI 69, 96]. A significantly lower incidence was identified in high-income countries. Conclusion This systematic review established age-specific global hydrocephalus prevalence. While high-income countries had a lower hydrocephalus incidence according to the ICBDSR registry, folate fortification status was not associated with incidence. Our findings may inform future healthcare resource allocation and study.

The management of Tourette syndrome (TS) and other chronic tic disorders occurs in multiple stages and begins with comprehensive assessment and complex psychoeducation. Behavioral and pharmacological interventions (second stage) are needed when tics cause physical or psychosocial impairment. Deep brain stimulation surgery or experimental therapies represent the third stage. Areas covered: Discussed are recent advances in assessment and therapy of chronic tic disorders, encompassing the three stages of intervention, with the addition of experimental, non-invasive brain stimulation strategies. A PubMed search was performed using as keywords: 'tic disorders', 'Tourette syndrome', 'assessment', 'rating scales', 'behavioral treatment', 'pharmacological treatment', 'deep brain stimulation', 'transcranial magnetic (or current) stimulation', and 'transcranial current stimulation'. More than 300 peer-reviewed articles were evaluated. The studies discussed have been selected on the basis of novelty and impact. Expert commentary: Comprehensive assessment of tic disorders and psychoeducation are crucial to a correct active management approach. Behavioral treatments represent first line of active interventions, with increasing potential offered by telehealth. Antipsychotics and alpha agonists remain first line pharmacological interventions for tics, although VMAT-2 inhibitors appear promising. Deep brain stimulation is a potential option for medically refractory, severely disabled patients with tics, but age and target selection require further investigation.

Background:The muscular dystrophies are a heterogeneous group of genetic muscle diseases with variable distribution of weakness and mode of inheritance.Methods:We previously performed a systematic review of worldwide population-based studies on Duchenne and Becker muscular dystrophies; the current study focused on the epidemiology of other muscular dystrophies using Medline and EMBASE databases. Two reviewers independently reviewed all abstracts, full-text articles, and abstracted data from 1985 to 2011. Pooling of prevalence estimates was performed using random-effect models.Results:A total of 1104 abstracts and 167 full-text articles were reviewed. Thirty-one studies met all eligibility criteria and were included in the final analysis. The overall pooled prevalence of combined muscular dystrophies was 16.14 (confidence interval [CI], 11.21-23.23) per 100,000. The prevalence estimates per 100,000 were 8.26 (CI, 4.99-13.68) for myotonic dystrophy, 3.95 (CI, 2.89-5.40) for facioscapulohumeral dystrophy, 1.63 (CI, 0.94-2.81) for limb girdle muscular dystrophy, and 0.99 (CI, 0.62-1.57) for congenital muscular dystrophies.Conclusions:The studies differed widely in their approaches to case ascertainment, and substantial gaps remain in the global estimates of many other types of muscular dystrophies. Additional epidemiological studies using standardized diagnostic criteria as well as multiple sources of case ascertainment will help address the economic impact and health care burden of muscular dystrophies worldwide.

BACKGROUND Successful management of chronic cough has varied in the primary research studies in the reported literature. One of the potential reasons relates to a lack of intervention fidelity to the core elements of the diagnostic and/or therapeutic interventions that were meant to be used by the investigators. METHODS We conducted a systematic review to summarize the evidence supporting intervention fidelity as an important methodologic consideration in assessing the effectiveness of clinical practice guidelines used for the diagnosis and management of chronic cough. We developed and used a tool to assess for five areas of intervention fidelity. Medline (PubMed), Scopus, and the Cochrane Database of Systematic Reviews were searched from January 1998 to May 2014. Guideline recommendations and suggestions for those conducting research using guidelines or protocols to diagnose and manage chronic cough in the adult were developed and voted upon using CHEST Organization methodology. RESULTS A total of 23 studies (17 uncontrolled prospective observational, two randomized controlled, and four retrospective observational) met our inclusion criteria. These articles included 3,636 patients. Data could not be pooled for meta-analysis because of heterogeneity. Findings related to the five areas of intervention fidelity included three areas primarily related to the provider and two primarily related to the patients. In the area of study design , 11 of 23 studies appeared to be underpinned by a single guideline/protocol; for training of providers , two of 23 studies reported training, and zero of 23 reported the use of an intervention manual; and for the area of delivery of treatment , when assessing the treatment of gastroesophageal reflux disease, three of 23 studies appeared consistent with the most recent guideline/protocol referenced by the authors. For receipt of treatment , zero of 23 studies mentioned measuring concordance of patient-interventionist understanding of the treatment recommended, and zero of 23 mentioned measuring enactment of treatment , with three of 23 measuring side effects and two of 23 measuring adherence. The overall average intervention fidelity score for all 23 studies was poor (20.74 out of 48). CONCLUSIONS Only low-quality evidence supports that intervention fidelity strategies were used when conducting primary research in diagnosing and managing chronic cough in adults. This supports the contention that some of the variability in the reporting of patients with unexplained or unresolved chronic cough may be due to lack of intervention fidelity. By following the recommendations and suggestions in this article, researchers will likely be better able to incorporate strategies to address intervention fidelity, thereby strengthening the validity and generalizability of their results that provide the basis for the development of trustworthy guidelines.

BACKGROUND We conducted a systematic review on the management of psychogenic cough, habit cough, and tic cough to update the recommendations and suggestions of the 2006 guideline on this topic. METHODS We followed the American College of Chest Physicians (CHEST) methodologic guidelines and the Grading of Recommendations, Assessment, Development, and Evaluation framework. The Expert Cough Panel based their recommendations on data from the systematic review, patients' values and preferences, and the clinical context. Final grading was reached by consensus according to Delphi methodology. RESULTS The results of the systematic review revealed only low-quality evidence to support how to define or diagnose psychogenic or habit cough with no validated diagnostic criteria. With respect to treatment, low-quality evidence allowed the committee to only suggest therapy for children believed to have psychogenic cough. Such therapy might consist of nonpharmacologic trials of hypnosis or suggestion therapy, or combinations of reassurance, counseling, and referral to a psychologist, psychotherapy, and appropriate psychotropic medications. Based on multiple resources and contemporary psychologic, psychiatric, and neurologic criteria ( Diagnostic and Statistical Manual of Mental Disorders , 5th edition and tic disorder guidelines), the committee suggests that the terms psychogenic and habit cough are out of date and inaccurate. CONCLUSIONS Compared with the 2006 CHEST Cough Guidelines, the major change in suggestions is that the terms psychogenic and habit cough be abandoned in favor of somatic cough syndrome and tic cough, respectively, even though the evidence to do so at this time is of low quality.

BACKGROUND Patients with suspected thiamine deficiency should receive treatment with parenteral thiamine to achieve the high serum thiamine levels necessary to reverse the effects of deficiency and to circumvent problems with absorption common in the medically ill. OBJECTIVE To quantify rates of parenteral administration of thiamine across university-affiliated hospitals and to identify factors associated with higher rates of parenteral prescribing. DESIGN Multicenter, retrospective observational study of thiamine prescriptions. METHODS Prescriptions for thiamine were captured from computerized pharmacy information systems across participating centers, providing information concerning dose, route, frequency, and duration of thiamine prescribed from January 2010 to December 2011. SETTING Fourteen university-affiliated tertiary care hospitals geographically distributed across Canada, including 48,806 prescriptions for thiamine provided to 32,213 hospitalized patients. RESULTS Parenteral thiamine accounted for a statistically significant majority of thiamine prescriptions (57.6%, P

Objective: Children with attention-deficit hyperactivity disorder (ADHD) may have oppositional behaviour, conduct problems, and aggression. These symptoms vary in severity, and may be related to a comorbid diagnosis of oppositional defiant disorder (ODD) or conduct disorder (CD). Critical evaluation of the efficacy of ADHD medications may guide the clinician regarding the usefulness of medications for these symptoms. Method: We performed a systematic review and meta-analysis of psychostimulants, alpha-2 agonists, and atomoxetine for oppositional behaviour, conduct problems, and aggression in youth with ADHD, ODD, and CD. The quality of evidence for medications was rated using the Grading of Recommendations Assessment, Development and Evaluation approach. Results: Two systematic reviews and 20 randomized controlled trials were included. There is high-quality evidence that psychostimulants have a moderate-to-large effect on oppositional behaviour, conduct problems, and aggression in youth with ADHD, with and without ODD or CD. There is very-low-quality evidence that clonidine has a small effect on oppositional behaviour and conduct problems in youth with ADHD, with and without ODD or CD. There is moderate-quality evidence that guanfacine has a small-to-moderate effect on oppositional behaviour in youth with ADHD, with and without ODD. There is high-quality evidence that atomoxetine has a small effect on oppositional behaviour in youth with ADHD, with and without ODD or CD. Conclusions: Evidence indicates that psychostimulants, alpha-2 agonists, and atomoxetine can be beneficial for disruptive and aggressive behaviours in addition to core ADHD symptoms; however, psychostimulants generally provide the most benefit.

Objective:To develop evidence-based guidelines on pharmacotherapy for severe disruptive and aggressive behaviour in children and adolescents with attention-deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), or conduct disorder (CD). The guidelines assume that psychosocial interventions have been pursued but did not achieve sufficient improvement.Method:A multidisciplinary consensus group used the Grading of Recommendations Assessment, Development and Evaluation approach for rating evidence quality and for grading recommendations. We conducted a systematic review of medications studied in placebo-controlled trials for treating disruptive and aggressive behaviour in children and adolescents with ADHD, ODD, or CD. We followed consensus procedures to make 1 of 4 recommendations for each medication: strong, in favour (↑↑); conditional, in favour (↑?); conditional, against (↓?); and strong, against (↓↓).Results:For children and adolescents with disruptive or aggressive behaviour associated with ADHD, psychostimulants received a strong recommendation in favour of use, while atomoxetine and alpha-2 agonists received a conditional recommendation in favour of use. If these patients do poorly with ADHD medications, the medication with the most evidence is risperidone. Risperidone also has the most evidence for treating disruptive or aggressive behaviour in the absence of ADHD. However, given risperidone's major adverse effects, it received only a conditional recommendation in favour of use. We recommended against using quetiapine, haloperidol, lithium, or carbamazepine because of the poor quality of evidence and their major adverse effects.Conclusion:When severe disruptive or aggressive behaviour occurs with ADHD, medications for ADHD should be used first. Other medications have major adverse effects and, with the exception of risperidone, very limited evidence to support their use.

Bronchopulmonary C-fibers and a subset of mechanically sensitive, acid-sensitive myelinated sensory nerves play essential roles in regulating cough. These vagal sensory nerves terminate primarily in the larynx, trachea, carina, and large intrapulmonary bronchi. Other bronchopulmonary sensory nerves, sensory nerves innervating other viscera, as well as somatosensory nerves innervating the chest wall, diaphragm, and abdominal musculature regulate cough patterning and cough sensitivity. The responsiveness and morphology of the airway vagal sensory nerve subtypes and the extrapulmonary sensory nerves that regulate coughing are described. The brainstem and higher brain control systems that process this sensory information are complex, but our current understanding of them is considerable and increasing. The relevance of these neural systems to clinical phenomena, such as urge to cough and psychologic methods for treatment of dystussia, is high, and modern imaging methods have revealed potential neural substrates for some features of cough in the human.

Purpose/background Antipsychotics are efficacious for tics and are increasingly prescribed to children with behavioral disorders. Antipsychotics have important adverse effects, and systematic monitoring of drug safety is infrequently performed. The objectives of this study were to determine the feasibility of antipsychotic safety monitoring in children with Tourette Syndrome using a defined protocol and to evaluate the risk of adverse effects with chronic use. Methods/procedures A prospective longitudinal study of children prescribed antipsychotics was performed. Children were monitored for extrapyramidal, metabolic, and hormonal adverse effects using the Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotic Medications guidelines. This included the measurement of height, weight, waist circumference, the Extrapyramidal Symptom Rating Scale, and laboratory tests of lipids, glucose, insulin, and prolactin at prespecified time points. Findings/results Fifty-seven children who started on risperidone or aripiprazole were monitored for a mean of 10 months 3 days. Significant increases in body mass index (BMI) and waist circumference percentiles occurred with time. There was a significant time by drug interaction, with children on aripiprazole having smaller changes in BMI initially, followed by a faster rate of increase than with risperidone. There was a significant difference between Extrapyramidal Symptom Rating Scale scores on versus before starting antipsychotics and significant increases in insulin and prolactin. Change from a healthy to overweight or obese BMI percentile occurred in 26%. Extrapyramidal symptoms occurred in 35%. Medication was discontinued because of metabolic effects in 19%, and extrapyramidal symptoms in 7%. Implications/conclusions Monitoring of antipsychotic safety in children is feasible and recommended to inform treatment decisions.

Objective: Schizophrenia spectrum and other psychotic disorders often have their onset in adolescence. The sequelae of these illnesses can negatively alter the trajectory of emotional, cognitive, and social development in children and youth if left untreated. Early and appropriate interventions can improve outcomes. This article aims to identify best practices in the pharmacotherapy management of children and youth with schizophrenia spectrum disorders. Methods: A systematic search was conducted for published guidelines for schizophrenia and schizophrenia spectrum disorders in children and youth (under age 18 years). Recommendations were drawn from the National Institute for Health and Care Excellence guidelines on psychosis and schizophrenia in children and youth (2013 and 2015 updates). Current guidelines were adopted using the ADAPTE process, which includes consensus ratings by a panel of experts. Results: Recommendations identified covered a range of issues in the pharmacotherapy management of children and youth with schizophrenia spectrum disorders. Further work in this area is warranted as we continue to further understand their presentation in the developing brain. Conclusions: Canadian guidelines for the pharmacotherapy management of children and youth with schizophrenia spectrum disorders are essential to assist clinicians in treating this vulnerable population. Ongoing work in this area is recommended.

Background: While antipsychotic medications are the mainstay of therapy for individuals with schizophrenia and psychotic disorders, their use is associated with adverse effects on physical health that require the attention and care of prescribers. Methods: We used the ADAPTE process to adapt existing guideline recommendations from the National Institute for Health and Care Excellence (NICE) and Scottish Intercollegiate Guidelines Network (SIGN) guidelines on the dosing of antipsychotics and antipsychotic polypharmacy, screening for adverse effects of antipsychotics, and management of metabolic and extrapyramidal side effects to the Canadian context. Results: Prescribers are encouraged to use the lowest effective dose and to avoid the routine use of multiple antipsychotics. Scheduled monitoring of body mass index, waist circumference, blood pressure, glucose, lipids, prolactin, electrocardiograms, and extrapyramidal symptoms is recommended. Lifestyle interventions are recommended to mitigate antipsychotic-induced weight gain. Prescribers should follow Canadian guidelines on the treatment of obesity, dyslipidemia, and diabetes. Recommendations on antipsychotic drug choice are made for users particularly concerned about extrapyramidal symptoms. Conclusion: Careful monitoring and attention by prescribers may mitigate adverse effects associated with antipsychotic medications.

ObjectiveTo review evidence on starting, switching, and stopping disease-modifying therapies (DMTs) for multiple sclerosis (MS) in clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and progressive MS forms.MethodsRelevant, peer-reviewed research articles, systematic reviews, and abstracts were identified (MEDLINE, CENTRAL, EMBASE searched from inception to November 2016). Studies were rated using the therapeutic classification scheme. Prior published Cochrane reviews were also used.ResultsTwenty Cochrane reviews and an additional 73 full-text articles were selected for data extraction through an updated systematic review (completed November 2016). For people with RRMS, many DMTs are superior to placebo (annualized relapses rates [ARRs], new disease activity [new MRI T2 lesion burden], and in-study disease progression) (see summary and full text publications). For people with RRMS who experienced a relapse on interferon-β (IFN-β) or glatiramer acetate, alemtuzumab is more effective than IFN-β-1a 44 μg subcutaneous 3 times per week in reducing the ARR. For people with primary progressive MS, ocrelizumab is probably more effective than placebo (in-study disease progression). DMTs for MS have varying adverse effects. In people with CIS, glatiramer acetate and IFN-β-1a subcutaneous 3 times per week are more effective than placebo in decreasing risk of conversion to MS. Cladribine, immunoglobulins, IFN-β-1a 30 μg intramuscular weekly, IFN-β-1b subcutaneous alternate day, and teriflunomide are probably more effective than placebo in decreasing risk of conversion to MS. Suggestions for future research include studies considering comparative effectiveness, usefulness of high-efficacy treatment vs stepped-care protocols, and research into predictive biomarkers.

BackgroundPersons with multiple sclerosis (MS) may now choose from a broad array of approved disease-modifying treatments (DMTs). The priority that patients and practitioners assign to specific clinical outcomes is likely to influence the MS DMT selection process.MethodsWe invited 9,126 participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry and 18 members of the American Academy of Neurology MS DMT guideline development panel to complete a brief survey prioritizing outcomes of importance to MS DMT selection. The frequency of outcomes ranked as first, second, or third priority by respondents were compared across groups.ResultsA total of 2,056 of 9,126 (23.6%) NARCOMS participants and all 18 members of the MS DMT guideline development panel (100%) completed the survey. Reduced disability progression was identified as a priority by a majority of respondents in both groups. Guideline panelists tended to be more likely than persons with MS to prioritize relapse rate reduction (p = 0.055). Respondents from both groups commonly cited the “selection of therapies most likely to lead to improvements in quality of life measures, MS symptoms, and preservation of cognition” as top priorities in DMT selection; however, these priority outcomes were reported in fewer than 20% of clinical trials used to inform MS DMT guideline development.ConclusionSpecific outcomes were defined by similar proportions of persons with MS and guideline panelists as priority outcomes influencing MS DMT selection. Several of these priority outcomes were not routinely reported in clinical trials, identifying areas for future evidence development.

Systematic reviews were conducted to identify risk factors associated with the onset and progression of 14 neurological conditions, prioritized as a component of the National Population Health Study of Neurological Conditions. These systematic reviews provided a basis for evaluating the weight of evidence of evidence for risk factors for the onset and progression of the 14 individual neurological conditions considered. A number of risk factors associated with an increased risk of onset for more than one condition, including exposure to pesticides (associated with an increased risk of AD, amyotrophic lateral sclerosis, brain tumours, and PD; smoking (AD, MS); and infection (MS, Tourette syndrome). Coffee and tea intake was associated with a decreased risk of onset of both dystonia and PD. Further understanding of the etiology of priority neurological conditions will be helpful in focusing future research initiatives and in the development of interventions to reduce the burden associated with neurological conditions in Canada and internationally.

While attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder have been shown to have major impacts on quality of life in individuals with Tourette syndrome, there is comparatively little data on how the presence of these comorbidities influence tic severity and treatment. 114 children (mean age 10.25 years) were extensively clinically phenotyped at a single specialty clinic. While there was no difference in Yale Global Tic Severity Scale (YGTSS) scores in children with versus without ADHD, children with obsessive compulsive behaviors had significantly higher YGTSS scores (p = 0.008). There was a significant correlation between YGTSS scores and age (r = 0.344, p

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by chorea, behavioural and psychiatric manifestations, and dementia, caused by a CAG triplet repeat expansion in the huntingtin gene. Systematic review of the literature was conducted to determine the risk factors for the onset and progression of HD. Multiple databases were searched, using terms specific to Huntington disease and to studies of aetiology, risk, prevention and genetics, limited to studies on human subjects published in English or French between 1950 and 2010. Two reviewers independently screened the abstracts and identified potentially relevant articles for full-text review using predetermined inclusion criteria. Three major categories of risk factors for onset of HD were identified: CAG repeat length in the huntingtin gene, CAG instability, and genetic modifiers. Of these, CAG repeat length in the huntingtin gene is the most important risk factor. For the progression of HD: genetic, demographic, past medical/clinical and environmental risk factors have been studied. Of these factors, genetic factors appear to play the most important role in the progression of HD. Among the potential risk factors, CAG repeat length in the mutant allele was found to be a relatively consistent and significant risk factor for the progression of HD, especially in motor, cognitive, and other neurological symptom deterioration. In addition, there were many consistent results in the literature indicating that a higher number of CAG repeats was associated with shorter survival, faster institutionalization, and earlier percutaneous endoscopic gastrostomy.

The clinical surveillance and active management of Tourette syndrome (TS) and other primary chronic tic disorders cannot be limited to tics, as these patients manifest a spectrum of sensory-, behavioral-, cognitive-, and sleep-related problems that have a major impact on their functioning and quality of life, influencing enormously clinical decision making on a routine basis. The sensory phenomena of primary tic disorders consist of premonitory urges and heightened sensitivity to external somatosensory and interoceptive stimuli. Recent evidence suggests that raised interoceptive awareness may be related to the classical premonitory urges associated with tics. The burden of behavioral comorbidities is very important in determining the degree of disability of patients with primary tic disorders. Only 10%-15% of these patients presents exclusively with a tic disorder. Obsessive-compulsive disorder (OCD) are common in TS, and the clinical distinction between compulsions and complex tics may be difficult in some cases. "Tic-related OCD" represents a phenomenologically characteristic subtype of OCD, also associated with "just right" phenomena. Probably the presence of comorbid attention deficit/hyperactivity disorder is the main determinant of cognitive dysfunction in TS patients and influences heavily also the risk of developing disruptive behaviors. Mood and anxiety disorders, impulse control disorders, rage attacks, "impulsive" tic-like behaviors (e.g., nonobscene socially inappropriate behaviors, and self-injurious behaviors), and autism spectrum disorders complete the wide psychopathological spectrum of primary chronic tic disorders. Moreover, specific sleep abnormalities have been reported in TS patients, although more research is needed on this specific clinical problem. As in other areas of clinical neuroscience, a comprehensive approach to both motor and nonmotor aspects of this group of disorders will help personalizing treatment interventions and, ultimately, improve quality of care.

BACKGROUND This series of guidance documents on cough, which will be published over time, is a hybrid of two processes: (1) evidence-based guidelines and (2) trustworthy consensus statements based on a robust and transparent process. METHODS The CHEST Guidelines Oversight Committee selected a nonconflicted Panel Chair and jointly assembled an international panel of experts in each clinical area with few, if any, conflicts of interest. PICO (population, intervention, comparator, outcome)-based key questions and parameters of eligibility were developed for each clinical topic to inform the comprehensive literature search. Existing guidelines, systematic reviews, and primary studies were assessed for relevance and quality. Data elements were extracted into evidence tables and synthesized to provide summary statistics. These, in turn, are presented to support the evidence-based graded recommendations. A highly structured consensus-based Delphi approach was used to provide expert advice on all guidance statements. Transparency of process was documented. RESULTS Evidence-based guideline recommendations and consensus-based suggestions were carefully crafted to provide direction to health-care providers and investigators who treat and/or study patients with cough. Manuscripts and tables summarize the evidence in each clinical area supporting the recommendations and suggestions. CONCLUSIONS The resulting guidance statements are based on a rigorous methodology and transparency of process. Unless otherwise stated, the recommendations and suggestions meet the guidelines for trustworthiness developed by the Institute of Medicine and can be applied with confidence by physicians, nurses, other health-care providers, investigators, and patients.

Primary brain tumors are a heterogeneous group of benign and malignant tumors arising from the brain parenchyma and its surrounding structures. These tumors are an important cause of morbidity and mortality in both adults and children, often generating severe disabilities and producing high burden in both families and health care systems.1,2 The epidemiology of these tumors is poorly understood, as there is a paucity of data published on their incidence and prevalence across the globe. A solid understanding of the incidence and prevalence of primary brain tumors can help with better planning in the allocation of health resources and a better understanding of geographical differences. Only one systematic review on the worldwide incidence of brain tumors has been published within the last 20 years.3 The paper, published in 1998, reviewed the methodology and results of studies including not only primary, but also secondary intracranial tumors. The world age-standardized incidence rate for all primary brain tumors reported in this review ranged from 4.3 to 18.6 per 100 000 per year. Unfortunately, this review had methodological limitations. The authors searched only English-language papers published from 1966 to 1995 (including data collected from 1935 to 1991) and included studies that were not population based in the review, which could result in biased estimates. Only one bibliographical database (Medline) was used for the search, and a formal meta-analysis of incidence rates was not performed. There was also marked heterogeneity in the methodology and results of the different studies included in the review. There is a lack of a comprehensive and up-to-date systematic review of the global incidence and prevalence of brain tumors in the literature. The goal of our study was to systematically review the latest literature on incidence and prevalence of primary brain tumors.

This overview will demonstrate that cough is a common and potentially expensive health-care problem. Improvement in the quality of care of those with cough has been the focus of study for a variety of disciplines in medicine. The purpose of the Cough Guideline and Expert Panel is to synthesize current knowledge in a form that will aid clinical decision-making for the diagnosis and management of cough across disciplines and also identify gaps in knowledge and treatment options.

Patient registries represent an important platform across geographical areas that can provide critical epidemiological data and information on the effectiveness of therapies or devices within a given disease group. Neurological patient registries represent an exciting opportunity to directly impact patient care and clinical trial readiness. Neurological registries also aid in the formulation of investigator networks and support translational research pipelines enhancing collaboration and cost–effectiveness of clinical research. Registries collecting high-quality data with near complete to complete ascertainment have the ability to generate useful knowledge about diseases, which is more generalizable to larger disease populations.

BACKGROUND Several pharmacologic and nonpharmacologic therapeutic options have been used to treat cough that is not associated with a pulmonary or extrapulmonary etiology. METHODS We conducted a systematic review to summarize the evidence supporting different cough management options in adults and children with psychogenic, tic, and habit cough. Medline, EMBASE, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus were searched from the earliest inception of each database to September 2013. Content experts were contacted, and we searched bibliographies of included studies to identify additional references. RESULTS A total of 18 uncontrolled studies were identified, enrolling 223 patients (46% male subjects, 96% children and adolescents). Psychogenic cough was the most common descriptive term used (90% of the studies). Most of the patients (95%) had no cough during sleep; barking or honking quality of cough was described in only eight studies. Hypnosis (three studies), suggestion therapy (four studies), and counseling and reassurance (seven studies) were the most commonly used interventions. Hypnosis was effective in resolving cough in 78% of the patients and improving it in another 5%. Suggestion therapy resolved cough successfully in 96% of the patients. The greatest majority of improvements noted with these forms of therapy occurred in the pediatric age group. The quality of evidence is low due to the lack of control groups, the retrospective nature of all the studies, heterogeneity of definitions and diagnostic criteria, and the high likelihood of reporting bias. CONCLUSIONS Only low-quality evidence exists to support a particular strategy to define and treat psychogenic, habit, and tic cough. Patient values, preferences, and availability of potential therapies should guide treatment choice.

Parkinson's Disease (PD) is a common neurodegenerative disorder. We sought to synthesize studies on the prevalence of PD to obtain an overall view of how the prevalence of this disease varies by age, by sex, and by geographic location. We searched MEDLINE and EMBASE for epidemiological studies of PD from 1985 to 2010. Data were analyzed by age group, geographic location, and sex. Geographic location was stratified by the following groups: 1) Asia, 2) Africa, 3) South America, and 4) Europe/North America/Australia. Meta-regression was used to determine whether a significant difference was present between groups. Forty-seven studies were included in the analysis. Meta-analysis of the worldwide data showed a rising prevalence of PD with age (all per 100,000): 41 in 40 to 49 years; 107 in 50 to 59 years; 173 in 55 to 64 years; 428 in 60 to 69 years; 425 in 65 to 74 years; 1087 in 70 to 79 years; and 1903 in older than age 80. A significant difference was seen in prevalence by geographic location only for individuals 70 to 79 years old, with a prevalence of 1,601 in individuals from North America, Europe, and Australia, compared with 646 in individuals from Asia (P

Objectives Studies of multiple sclerosis (MS) incidence and prevalence from Africa, Asia, Australia and New Zealand are relatively scarce. We systematically reviewed MS incidence and prevalence in these regions including a standardized evaluation of study quality. Methods We searched MEDLINE and EMBASE databases for studies of MS prevalence or incidence in Africa, Asia, Australia and New Zealand published in English or French between January 1, 1985 and January 31, 2011. Study quality was assessed using a standardized tool. All steps of the review were performed in duplicate. Results Of 3925 citations identified, 28 studies met inclusion criteria and 21 of these were from Asia. Quality scores ranged from 1/8 to 8/8; the lowest scores were observed in studies from Asia (median 4/8, IQR 3,6). Prevalence was lowest in South African Blacks (0.22/100,000) and highest amongst Australian-born individuals in Australia (125/100,000). Prevalence increased over time in many countries. MS prevalence increased with increasing latitude only in some regions, and prevalence varied significantly with ethnicity. Eight studies reported incidence, which ranged from 0.67/100,000/year in Taiwan to 3.67/100,00/year in Australia. Conclusions This comprehensive study provides an update of MS epidemiology in Africa, Asia, Australia, and New Zealand. Incidence and prevalence were lowest in Africa and Asia and highest in Australia, but many Asian studies were of poor quality. Use of consistent case ascertainment methods, standardized data collection tools, and similar outcomes would all improve study quality and comparability. The underlying basis of observed ethnic differences is an important area for future study.

A 12-year-old girl was referred for treatment-refractory obsessive–compulsive disorder (OCD). She had a history from age 6 of tics showing a waxing and waning pattern. Tic-related disability was minimal and had not warranted medical intervention. The patient presented initially for medical

IntroductionTourette syndrome is a common childhood-onset neuropsychiatric disorder, with tics that wax and wane in frequency and severity over time. The purpose of the proposed scoping review is to map the types of evidence available pertaining to the effect of diet, sleep and exercise on tic severity and identify key concepts and gaps in research.MethodsOur scoping review will use the six-step framework recommended by Arksey and O’Malley, with enhancements from Levacet aland Joanna Briggs Institute. We will attempt to identify all the relevant literature regardless of study design. We will search six electronic databases, the reference lists of all selected studies and the grey literature for studies examining an association between dietary factors, sleep or physical exercise and tics, or studies of interventions targeting diet, sleep or exercise to reduce tics. Our analysis plan includes description of the reported associations among dietary factors, sleep and physical exercise and tics, the effects of interventions, the research methodologies and how outcomes are measured.Ethics and disseminationAn approval from a recognised committee is not required to conduct the proposed review, as the study entails secondary analysis of the literature available publicly. For dissemination of the study, the results will be submitted for publication to peer-reviewed scientific journals and presented at relevant public forums and conferences.

Objectives:To provide an overview of the objectives and target population of the guideline, and to review the general principles of acute pharmacological migraine therapy.Methods:A general literature review and several consensus groups were used to formulate an expert consensus for the general use of acute migraine medications.Results:The objective of the guideline is to assist the physician in choosing an appropriate acute migraine medication for an individual with migraine, and thereby to reduce migraine-related disability. The target population includes adults with episodic migraine (patients with migraine headache < 15 days/month). This guideline is intended primarily for physicians who treat patients with migraine. Other health professionals may also find this guideline helpful. Acute migraine therapy should be considered for the great majority of patients with migraine. A specific acute medication is chosen based on evidence for efficacy, tolerability, migraine attack severity, patient preference, and on the presence of co-existing disorders. General principles of acute migraine therapy include that the response of a patient to any given medication cannot be predicted with certainty, and that treatment early in the attack is generally more effective than treatment later once the migraine attack is fully developed. A suitable treatment approach (stratified or stepped approaches) and drug formulation (injection, tablet, wafer, powdered formulation, or nasal spray) should be chosen based on patient clinical features. Excessively frequent use of acute medications (medication overuse) should be avoided. Two or more acute medications can be combined if necessary.Conclusions:This guideline provides evidence-based advice on the use of acute medications for migraine, and should provide useful guidance for acute migraine therapy to both health professionals and patients.

Background:In our targeted review (Section 2), 12 acute medications received a strong recommendation for use in acute migraine therapy while four received a weak recommendation for use. Strong recommendations were made to avoid use of two other medications, except for exceptional circumstances. Two anti-emetics received strong recommendations for use as needed.Objective:To organize the available acute migraine medications into acute migraine treatment strategies in order to assist the practitioner in choosing a specific medication(s) for an individual patient.Methods:Acute migraine treatment strategies were developed based on the targeted literature review used for the development of this guideline (Section 2), and a general literature review. Expert consensus groups were used to refine and validate these strategies.Results:Based on evidence for drug efficacy, drug side effects, migraine severity, and coexistent medical disorders, our analysis resulted in the formulation of eight general acute migraine treatment strategies. These could be grouped into four categories: 1) two mild-moderate attack strategies, 2) two moderate-severe attack or NSAID failure strategies, 3) three refractory migraine strategies, and 4) a vasoconstrictor unresponsive-contraindicated strategy. In addition, strategies were developed for menstrual migraine, migraine during pregnancy, and migraine during lactation. The eight general treatment strategies were coordinated with a “combined acute medication approach” to therapy which used features of both the “stratified” and the “step care across attacks” approaches to acute migraine management.Conclusions:The available medications for acute migraine treatment can be organized into a series of strategies based on patient clinical features. These strategies may help practitioners make appropriate acute medication choices for patients with migraine.

Objective:To assess the evidence base for drugs used for acute treatment of episodic migraine (headache on < 14 days a month) in Canada.Methods:A detailed search strategy was employed to find relevant published clinical trials of drugs used in Canada for the acute treatment of migraine in adults. Primarily meta-analyses and systematic reviews were included. Where these were not available for a drug or were out of date, individual clinical trial reports were utilized. Only double-blind randomized clinical trials with placebo or active drug controls were included in the analysis. Recommendations and levels of evidence were graded according to the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group, using a consensus group.Results:Eighteen acute migraine medications and two adjunctive medications were evaluated. Twelve acute medications received a strong recommendation with supporting high quality evidence for use in acute migraine therapy (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan, ASA, ibuprofen, naproxen sodium, diclofenac potassium, and acetaminophen). Four acute medications received a weak recommendation for use with low or moderate quality evidence (dihydroergotamine, ergotamine, codeine-containing combination analgesics, and tramadol-containing combination analgesics). Three of these medications were NOT recommended for routine use (ergotamine, and codeine- and tramadol-containing medications), and strong recommendations were made to avoid use of butorphanol and butalbital-containing medications. Both metoclopramide and domperidone received a strong recommendation for use with acute migraine attack medications where necessary.Conclusion:Our targeted review formulated recommendations for the available acute medications for migraine treatment according to the GRADE method. This should be helpful for practitioners who prescribe medications for acute migraine treatment.

When tics caused by Tourette Syndrome cause meaningful impairment for patients, a comprehensive treatment approach includes education of patients, peers, and family, treatment of comorbid behavioral disorders if present, and consideration of behavior therapy and pharmacotherapy for tics themselves. This systematic review and meta-analysis demonstrates that behavior therapies based on Habit Reversal Therapy, including the Comprehensive Behavioral Intervention for Tics are effective in reducing tic severity when compared with supportive psychotherapy. When these behavior therapies are unavailable, Exposure with Response Prevention may also be effective. Both face-to-face and telehealth delivery methods for behavior therapy improve tic severity, and broader distribution of behavior therapy through increased training or telehealth methods is encouraged. High-quality randomized trials comparing behavior therapies for tics with pharmacotherapy are needed.

The aim of this study was to describe the frequency and trends in prescriptions and recommendations for selective serotonin reuptake inhibitors (SSRIs) for mental health disorders in children and adolescents in Canada from 2005 to 2009. Data were extracted from databases supplied by IMS Brogan (IMS), a proprietary source of pharmacoepidemiologic data. Analyses were performed to obtain descriptive statistics on SSRI prescriptions dispensed, SSRI drug recommendation frequency, reasons for drug recommendations (therapeutic indication), and median duration of use of SSRIs in Canadian children. Canadian census data were used to assess whether changes in SSRI use were related to changes in the number of children in Canada over the time period studied. SSRI prescriptions written by pediatricians increased by 39 %, while SSRI drug recommendations by all specialists for children and adolescents increased by 44 % over the 5-year interval. Over the 5-year period studied, fluoxetine was the most commonly recommended and dispensed SSRI. The use of escitalopram has increased while the use of paroxetine has declined. Between 2005 and 2009, the two most common therapeutic indications for SSRI recommendations were mood disorder (50 %) and anxiety disorder (25 %). Median treatment duration was less than 1 year, with duration generally increasing with patient age. The increase in use of SSRIs in Canadian children and adolescents from 2005 to 2009 suggests that the effects of public health warnings concerning suicidal thinking and behavior associated with these drugs are now dissipating. This may be attributable to the FDA’s pediatric approvals for fluoxetine and escitalopram, the growing comfort of clinicians with using SSRIs in children, limited availability of psychosocial treatments, and the influence of marketing. The use of paroxetine has continued to decline, likely because of specific warnings directed toward this agent and limited evidence supporting its efficacy.

Objective: The use of second-generation antipsychotics (SGAs) in youth has increased considerably. Increases are mainly attributable to treatment of disruptive behaviour disorders (DBDs). Our objective was to review the evidence regarding the efficacy of SGAs for DBDs in youth. Method: We performed a systematic review of all randomized controlled trials (RCTs) of SGAs and placebo for the treatment of DBDs in youth, focusing on efficacy data. Results: Eight RCTs in youth with DBDs were included. Five RCTs evaluated the use of risperidone in youth with the combination of subaverage-borderline IQ and disruptive behaviour-aggression. Single RCTs evaluated the use of risperidone for treatment-resistant aggression in attention-deficit hyperactivity disorder and for the treatment of conduct disorder (CD), and a single RCT evaluated the use of quetiapine for adolescent CD. The efficacy results of each of these studies are described. Conclusion: Four placebo-controlled studies support the short-term efficacy of low-dose risperidone in youth with a subaverage IQ. Placebo-controlled evidence is weak or nonexistent for SGAs other than risperidone, and is weak in youth with an average IQ. Multiple factors likely account for the disconnect between this limited evidence base and the frequent use of SGAs for DBDs in clinical practice. These include extrapolation from studies in youth with autism or a subaverage IQ to normally developing youth; ease of SGA titration and the mistaken perception that little monitoring is required; unavailability of psychosocial treatments; limited familiarity with other pharmacological options; clinical and cultural norms; and the influence of the pharmaceutical industry.

A 32-year-old woman presents to her primary care physician about a headache she experienced a week ago. She states that the pain began behind one eye and was accompanied by nausea and photophobia. Over a few hours, the pain spread to involve the temple and occiput unilaterally. It also intensified

BACKGROUND Patients with Parkinson's disease (PD) and/or Parkinsonism are affected by a complex burden of comorbidity. Many ultimately require institutional care, where they may be subject to the application of physical restraints or the prescription of antipsychotic medications, making them more vulnerable to adverse outcomes. OBJECTIVES The objectives of this paper are to: 1) describe the clinical complexity of older institutionalized persons with PD; and 2) examine patterns and predictors of restraint use and prescription of antipsychotics in this population. METHODS Population-based cross-sectional cohort study. Residents with PD and/or Parkinsonism living in long-term care (LTC) facilities in 6 Canadian provinces and 1 Northern Territory and Complex Continuing Care (CCC) facilities in Manitoba and Ontario, Canada. The RAI MDS 2.0 instrument was used to assess all LTC residents and CCC residents. Clinical characteristics and the prevalence of major comorbidities were examined. Multivariate modeling was used to identify the characteristics of PD residents most associated with the prescription of antipsychotics and the use of restraints in LTC and CCC facilities. RESULTS Residents with PD in LTC and CCC exhibit a high prevalence of dementia, major psychiatric disorders, stroke, heart failure, chronic obstructive pulmonary disease and diabetes mellitus. More than 90% of LTC and CCC residents with PD had cognitive impairment; with more than half having moderate to severe impairment. Residents with PD were more likely to receive antipsychotics than those without PD. Antipsychotic use was associated with psychosis and aggressive behaviours, but also with unsteady gait and higher comorbidity and medication count. Similarly, although more common in CCC than LTC facilities, both psychosis and aggressive behaviours were associated with restraint use, as was greater cognitive and functional impairment, and urinary incontinence. Younger age, male gender, and lower physician access were all associated with greater antipsychotic and restraint use. CONCLUSIONS LTC and CCC residents with PD are very complex medically. Use of antipsychotics and restraints is common, and their use is often associated with factors other than psychosis or aggression.

This paper presents an overview of genetic variation associated with the onset and progression of 14 neurological disorders, focusing primarily on association studies. The 14 disorders are heterogeneous in terms of their frequency, age of onset, etiology and progression. There is substantially less evidence on progression than onset. With regard to onset, the conditions are diverse in terms of their epidemiology and patterns of familial aggregation. While the muscular dystrophies and Huntington’s disease are monogenic diseases, for the other 12 conditions only a small proportion of cases is associated with specific genetic syndromes or mutations. Excluding these, some familial aggregation remains for the majority of cases. There is considerable variation in the volume of evidence by condition, and by gene within condition. The volume of evidence is greatest for Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and amyotrophic lateral sclerosis. As for common complex chronic diseases, genome wide association studies have found that validated genomic regions account for a low proportion of heritability. Apart from multiple sclerosis, which shares several susceptibility loci with other immune-related disorders, variation at HLA-DRB5 being associated both with Parkinson’s disease and Alzheimer’s disease, and the association of the C9orf72 repeat expansion with ALS and frontotemporal degeneration, there was little evidence of gene loci being consistently associated with more than one neurological condition or with other conditions. With the exception of spina bifida, for which maternal MTHFR genotype is associated with risk in the offspring, and corroborates other evidence of the importance of folate in etiology, there was little evidence that the pathways influenced by genetic variation are related to known lifestyle or environmental exposures.