ObjectiveTo make recommendations on the assessment and management of tics in people with Tourette syndrome and chronic tic disorders. MethodsA multidisciplinary panel consisting of 9 physicians, 2 psychologists, and 2 patient representatives developed practice recommendations, integrating findings from a 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. ResultsForty-six recommendations were made regarding the assessment and management of tics in individuals with Tourette syndrome and chronic tic disorders. These include counseling recommendations on the natural history of tic disorders, psychoeducation for teachers and peers, assessment for comorbid disorders, and periodic reassessment of the need for ongoing therapy. Treatment options should be individualized, and the choice should be the result of a collaborative decision among patient, caregiver, and clinician, during which the benefits and harms of individual treatments as well as the presence of comorbid disorders are considered. Treatment options include watchful waiting, the Comprehensive Behavioral Intervention for Tics, and medication; recommendations are provided on how to offer and monitor these therapies. Recommendations on the assessment for and use of deep brain stimulation in adults with severe, treatment-refractory tics are provided as well as suggestions for future research.Glossary AAN = American Academy of Neurology; ADHD = attention-deficit/hyperactivity disorder; CBD = cannabidiol; CBIT = Comprehensive Behavioral Intervention for Tics; CBT = cognitive behavioral therapy; DBS = deep brain stimulation; DSM-5 = Diagnostic and Statistical Manual of Mental Disorders, 5th edition; EVID = evidence-based conclusions from the systematic review; HRT = habit reversal training; INFER = deductive inferences from other premises; OCD = obsessive-compulsive disorder; PRIN = generally accepted principles of care; RELA = strong evidence from related conditions; THC = δ-9tetrahydrocannabinol; TS = Tourette syndrome; VMAT2 = vesicular monoamine transporter type 2. Recommendation 3aClinicians should ensure an assessment for comorbid ADHD is performed in people with tics (Level B). Recommendation 3bClinicians should evaluate the burden of ADHD symptoms in people with tics (Level B). Recommendation 3cIn people with tics and functionally impairing ADHD, clinicians should ensure appropriate ADHD treatment is provided (Level B).Share your own best practices. Read commentary with expert opinion.Explore results on an interactive world map. NPub.org/NCP/practicecurrentNeurology ® Clinical Practice Now Accepting Applications for Emerging Leaders ProgramApplications are now open for the prestigious Emerging Leaders program, designed to identify, engage, and mentor talent among early-career members interested in future leadership ro...
Methuosis is a novel caspase-independent form of cell death in which massive accumulation of vacuoles derived from macropinosomes ultimately causes cells to detach from the substratum and rupture. We recently described a chalcone-like compound, 3-(2-methyl-1H indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one (i.e. MIPP), which can induce methuosis in glioblastoma and other types of cancer cells. Herein we describe the synthesis and structure-activity relationships of a directed library of related compounds, providing insights into the contributions of the two aryl ring systems and highlighting a potent derivative, 3-(5-methoxy, 2-methyl-1H-indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one (i.e. MOMIPP) that can induce methuosis at low μM concentrations. We have also generated biologically active azide derivatives that may be useful for future studies aimed at identifying the protein targets of MOMIPP by photoaffinity labeling techniques. The potential significance of these studies is underscored by the finding that MOMIPP effectively reduces the growth and viability of temozolomide-resistant glioblastoma and doxorubicin-resistant breast cancer cells. Thus, it may serve as a prototype for drugs that could be used to trigger death by methuosis in cancers that are resistant to conventional forms of cell death (e.g. apoptosis).
Thirty-three New Zealand women aged 18–23 years received daily for 32 weeks, 200 μg Se as Seenriched yeast (selenomethionine), or brewer's yeast mixed with selenate, or no added Se (placebo) in a double-blind trial. Se supplementation raised (P= 0.001), platelet glutathione peroxidase (EC1.11.1.9; GSHPx) activity, and also Se and GSHPx in whole blood, erythrocytes and plasma. Selenomethionine was more effective in raising blood Se concentrations than selenate, but both were equally effective in raising GSHPx activities in whole blood, erythrocytes and plasma, indicating a similar bioavailability for the two forms. These observations and those of gel filtration studies of erythrocytes and plasma proteins reported elsewhere (Butleret al.1991) are consistent with the incorporation of Se from selenomethionine into a general tissue protein pool while selenate is directly available for GSHPx synthesis, and explain the poorer correlation between Se and GSHPx in individuals with higher Se status. However, selenate raised platelet GSHPx activities to a greater extent than did selenomethionine suggesting some other effect of selenate on platelets which needs further investigation. A response of GSHPx activity in these New Zealand subjects indicates that their dietary Se intake is insufficient to meet recommended intakes based on the criterion of saturation of GSHPx activity, and could reflect a marginal Se status. The level of blood Se necessary for saturation of GSHPx of about 100 ng Se/ml whole blood confirms observations in earlier studies.
ObjectiveTo systematically evaluate the efficacy of treatments for tics and the risks associated with their use. MethodsThis project followed the methodologies outlined in the 2011 edition of the American Academy of Neurology's guideline development process manual. We included systematic reviews and randomized controlled trials on the treatment of tics that included at least 20 participants (10 participants if a crossover trial), except for neurostimulation trials, for which no minimum sample size was required. To obtain additional information on drug safety, we included cohort studies or case series that specifically evaluated adverse drug effects in individuals with tics. ResultsThere was high confidence that the Comprehensive Behavioral Intervention for Tics was more likely than psychoeducation and supportive therapy to reduce tics. There was moderate confidence that haloperidol, risperidone, aripiprazole, tiapride, clonidine, onabotulinumtoxinA injections, 5-ling granule, Ningdong granule, and deep brain stimulation of the globus pallidus were probably more likely than placebo to reduce tics. There was low confidence that pimozide, ziprasidone, metoclopramide, guanfacine, topiramate, and tetrahydrocannabinol were possibly more likely than placebo to reduce tics. Evidence of harm associated with various treatments was also demonstrated, including weight gain, drug-induced movement disorders, elevated prolactin levels, sedation, and effects on heart rate, blood pressure, and ECGs. ConclusionsThere is evidence to support the efficacy of various medical, behavioral, and neurostimulation interventions for the treatment of tics. Both the efficacy and harms associated with interventions must be considered in making treatment recommendations. Glossary AAN = American Academy of Neurology; ADHD = attention-deficit/hyperactivity disorder; CI = confidence interval; COI = conflict of interest; DBS = deep brain stimulation; GDDI = Guideline Development, Dissemination, and Implementation; rTMS = repetitive transcranial magnetic stimulation; SMD = standardized mean difference; TS = Tourette syndrome; YGTSS = Yale Global Tic Severity Scale. c Riluzole, SMD 0.17 (95% CI −0.91 to 1.25), 1 Class I study 56 ; confidence in evidence downgraded due to imprecision (children only)
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