Abstract Objective: Patients with Tourette syndrome (TS) often report characteristic sensory experiences, also called premonitory urges (PUs), which precede tic expression and have high diagnostic ...relevance. This study investigated the usefulness of a scale developed and validated in children and adolescents–the Premonitory Urge for Tics Scale (PUTS, Woods et al., 2005 13)–for the assessment of PUs in adult patients with TS. Method: Standard statistical methods were applied to test the psychometric properties of the PUTS in 102 adult TS outpatients recruited from two specialist clinics in the United Kingdom. Results: The PUTS showed good acceptability and endorsement rates, with evenly distributed scores and low floor and ceiling effects. Item-total correlations were moderate to strong; PUTS total scores were significantly correlated with quantitative measures of TS severity. The PUTS showed excellent internal consistency reliability (Cronbach’s alpha = 0.85) and Spearman’s correlations demonstrated satisfactory convergent and discriminant validity. Conclusions: Although originally devised to assess urges to tic in young patients with TS, the PUTS demonstrated good psychometric properties in a large sample of adults recruited at specialist TS clinics. This instrument is therefore recommended for use across the life span as a valid and reliable self-report measure of sensory experiences accompanying tic expression.
The Warburg effect has been found in a wide spectrum of human cancers, however the underlying mechanisms are still unclear. This study aims to explore the role of cellular oxidative stress in ...relation to glycolysis and the Warburg effect in hepatoma cells.
Various cell lines combining environmental hypoxia was used as an in vitro model to mimic tumor microenvironment in vivo. Superoxide dismutases (SOD) and xanthine oxidase (XO) gene transfection were used to produce various cellular redox levels. 2',7'-dichlorofluorescin (DCF) fluorescence and ESR spectrum were used to detect cellular reactive oxygen species (ROS).
We found that endogenous or exogenous interference with the cellular oxidative stress can sensitively regulate glycolysis and the Warburg effect in hepatoma cells. Hepatoma cells displayed a high level of free radicals compared to immortalized normal hepatocyte cells. Increasing the level of ROS stress in hepatoma cells can directly upregulate HIF-1 and activate glycolysis without requirement of a hypoxic condition. This explains the mechanism whereby aerobic glycolysis, i.e. the Warburg effect arises. Either endogenously upregulating SOD or exogenously administration with antioxidant can, through downregulating ROS level, effectively regulate energy pathways in hepatoma cells and can inhibit the growth of tumor cells and xenograft tumors.
This study suggests that the Warburg effect was related to an inherently high level of cellular ROS and HIF-1. Hepatoma cells adaptation to hypoxia for survival and rapid growth exploits oxidative stress ectopically activated glycolysis to compensate the energy supply. This specific mechanism in which tumor cells through cellular oxidative stress activate glycolysis to meet their energy metabolism requirement could be exploited to selectively kill tumor cells.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In 2011, the European Society for the Study of Tourette Syndrome (ESSTS) published the first European guidelines for Tourette Syndrome (TS). We now present an update of the part on pharmacological ...treatment, based on a review of new literature with special attention to other evidence-based guidelines, meta-analyses, and randomized double-blinded studies. Moreover, our revision took into consideration results of a recent survey on treatment preferences conducted among ESSTS experts. The first preference should be given to psychoeducation and to behavioral approaches, as it strengthens the patients’ self-regulatory control and thus his/her autonomy. Because behavioral approaches are not effective, available, or feasible in all patients, in a substantial number of patients pharmacological treatment is indicated, alone or in combination with behavioral therapy. The largest amount of evidence supports the use of dopamine blocking agents, preferably aripiprazole because of a more favorable profile of adverse events than first- and second-generation antipsychotics. Other agents that can be considered include tiapride, risperidone, and especially in case of co-existing attention deficit hyperactivity disorder (ADHD), clonidine and guanfacine. This view is supported by the results of our survey on medication preference among members of ESSTS, in which aripiprazole was indicated as the drug of first choice both in children and adults. In treatment resistant cases, treatment with agents with either a limited evidence base or risk of extrapyramidal adverse effects might be considered, including pimozide, haloperidol, topiramate, cannabis-based agents, and botulinum toxin injections. Overall, treatment of TS should be individualized, and decisions based on the patient’s needs and preferences, presence of co-existing conditions, latest scientific findings as well as on the physician’s preferences, experience, and local regulatory requirements.
Background
Tourette syndrome (TS) and chronic tic disorder (CTD) affect 1–2% of children and young people, but the most effective treatment is unclear. To establish the current evidence base, we ...conducted a systematic review of interventions for children and young people.
Methods
Databases were searched from inception to 1 October 2014 for placebo‐controlled trials of pharmacological, behavioural, physical or alternative interventions for tics in children and young people with TS or CTD. Certainty in the evidence was assessed with the GRADE approach.
Results
Forty trials were included pharmacological (32), behavioural (5), physical (2), dietary (1). For tics/global score there was evidence favouring the intervention from four trials of α2‐adrenergic receptor agonists clonidine and guanfacine, standardised mean difference (SMD) = −0.71; 95% CI −1.03, −0.40; N = 164 and two trials of habit reversal training (HRT)/comprehensive behavioural intervention (CBIT) (SMD = −0.64; 95% CI −0.99, −0.29; N = 133). Certainty in the effect estimates was moderate. A post hoc analysis combining oral clonidine/guanfacine trials with a clonidine patch trial continued to demonstrate benefit (SMD = −0.54; 95% CI −0.92, −0.16), but statistical heterogeneity was high. Evidence from four trials suggested that antipsychotic drugs improved tic scores (SMD = −0.74; 95% CI −1.08, −0.40; N = 76), but certainty in the effect estimate was low. The evidence for other interventions was categorised as low or very low quality, or showed no conclusive benefit.
Conclusions
When medication is considered appropriate for the treatment of tics, the balance of clinical benefits to harm favours α2‐adrenergic receptor agonists (clonidine and guanfacine) as first‐line agents. Antipsychotics are likely to be useful but carry the risk of harm and so should be reserved for when α2‐adrenergic receptor agonists are either ineffective or poorly tolerated. There is evidence that HRT/CBIT is effective, but there is no evidence for HRT/CBIT alone relative to combining medication and HRT/CBIT. There is currently no evidence to suggest that the physical and dietary interventions reviewed are sufficiently effective and safe to be considered as treatments.
Tourette syndrome (TS) is a common neurodevelopmental condition affecting approximately 1% of children and young people (c. 70,000 people age 7–17 years in England) which if untreated has a major adverse impact on mental health, social functioning and quality of life. Despite the prevalence of TS in young people being greater than diabetes and epilepsy, it remains a frequently misunderstood condition and its seriousness at a population level is typically overlooked, as evidenced by the absence of evidence‐based clinical guidelines. TS is characterised by persistent and impairing motor and vocal tics which typically emerge in childhood, run a waxing and waning course and carry on into adult life in about 30% of young people. Tics can be highly stigmatising, especially for teenagers, and often lead to bullying, peer victimisation, social exclusion, depression and self‐harm. TS is associated and frequently coexists with other neurodevelopmental and mental health conditions including ADHD (60%), anxiety disorder (40%), OCD (30%) and ASD (20%) which add to the complexity of clinical management. Evidence from this major systematic review and meta‐analysis shows that clinically effective treatments for tics in children and young people exist and include medication (e.g. α2‐noradrenergic agonists and antipsychotics) and behavioural interventions, including exposure and response prevention, habit reversal training (HRT) and the comprehensive behavioural intervention for tics programme which combines psychoeducation with HRT. The results of this review suggest that both medication and behavioural interventions have similar efficacy (moderate effect size) in treating tics, with behavioural interventions having a more favourable adverse effect profile. When considering medication, the more favourable adverse effect profile of α2‐noradrenergic agonists suggests that these agents should be offered before antipsychotics. However, psychoeducation and behavioural interventions are generally the preferred treatment option, particularly as first‐line interventions, by young people and their parents. Despite demonstrated efficacy, access in most healthcare systems to evidence‐based behavioural interventions for tics is extremely poor. Therefore, given the healthcare challenge of delivering behavioural interventions at scale with existing numbers of therapists and the traditional model of face‐to‐face delivery there is a pressing need to develop and evaluate digitally delivered interventions for young people with tics using a stepped‐care model of therapist support.
In 2011 a working group of the European Society for the Study of Tourette Syndrome (ESSTS) has developed the first European assessment guidelines for Tourette syndrome (TS). Now, we present an ...updated version 2.0 of these European clinical guidelines for Tourette syndrome and other tic disorders, part I: assessment. Therefore, the available literature has been thoroughly screened, supplemented with national guidelines across countries and discussions among ESSTS experts. Diagnostic changes between DSM-IV and DSM-5 classifications were taken into account and new information has been added regarding differential diagnoses, with an emphasis on functional movement disorders in both children and adults. Further, recommendations regarding rating scales to evaluate tics, comorbidities, and neuropsychological status are provided. Finally, results from a recently performed survey among ESSTS members on assessment in TS are described. We acknowledge that the Yale Global Tic Severity Scale (YGTSS) is still the gold standard for assessing tics. Recommendations are provided for scales for the assessment of tics and psychiatric comorbidities in patients with TS not only in routine clinical practice, but also in the context of clinical research. Furthermore, assessments supporting the differential diagnosis process are given as well as tests to analyse cognitive abilities, emotional functions and motor skills.
Previous research has reported that aspects of social cognition such as nonliteral language comprehension are impaired in adults with Tourette's syndrome (TS), but little is known about social ...cognition in children and adolescents with TS. The present study aims to evaluate a measure of sarcasm comprehension suitable for use with children and adolescents (Experiment 1), and to examine sarcasm comprehension in children and adolescents with TS-alone or TS and attention deficit hyperactivity disorder (ADHD; Experiment 2). In Experiment 1, the measure of sarcasm comprehension was found to be sensitive to differences in nonliteral language comprehension for typically-developing children aged 10 to 11 years old compared to children aged 8 to 9 years old; the older group performed significantly better on the comprehension of scenarios ending with either direct or indirect sarcastic remarks, whereas the two age groups did not differ on the comprehension of scenarios ending with sincere remarks. In Experiment 2, both the TS-alone and TS+ADHD groups performed below the level of the control participants on the comprehension of indirect sarcasm items but not on the comprehension of direct sarcasm items and sincere items. Those with TS+ADHD also performed below the level of the control participants on measures of interference control and fluency. The findings are discussed with reference to the possible contribution of executive functioning and mentalizing to the patterns of performance.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Tourette syndrome (TS) is a neurodevelopmental condition characterised by chronic motor and vocal tics affecting up to 1% of school-age children and young people and is associated with significant ...distress and psychosocial impairment.
To conduct a systematic review of the benefits and risks of pharmacological, behavioural and physical interventions for tics in children and young people with TS (part 1) and to explore the experience of treatment and services from the perspective of young people with TS and their parents (part 2).
For the systematic reviews (parts 1 and 2), mainstream bibliographic databases, The Cochrane Library, education, social care and grey literature databases were searched using subject headings and text words for tic* and Tourette* from database inception to January 2013.
For part 1, randomised controlled trials and controlled before-and-after studies of pharmacological, behavioural or physical interventions in children or young people (aged < 18 years) with TS or chronic tic disorder were included. Mixed studies and studies in adults were considered as supporting evidence. Risk of bias associated with each study was evaluated using the Cochrane tool. When there was sufficient data, random-effects meta-analysis was used to synthesize the evidence and the quality of evidence for each outcome was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. For part 2, qualitative studies and survey literature conducted in populations of children/young people with TS or their carers or in health professionals with experience of treating TS were included in the qualitative review. Results were synthesized narratively. In addition, a national parent/carer survey was conducted via the Tourettes Action website. Participants included parents of children and young people with TS aged under 18 years. Participants (young people with TS aged 10-17 years) for the in-depth interviews were recruited via a national survey and specialist Tourettes clinics in the UK.
For part 1, 70 studies were included in the quantitative systematic review. The evidence suggested that for treating tics in children and young people with TS, antipsychotic drugs standardised mean difference (SMD) -0.74, 95% confidence interval (CI) -1.08 to -0.41; n = 75 and noradrenergic agents clonidine (Dixarit(®), Boehringer Ingelheim) and guanfacine: SMD -0.72, 95% CI -1.03 to -0.40; n = 164 are effective in the short term. There was little difference among antipsychotics in terms of benefits, but adverse effect profiles do differ. Habit reversal training (HRT)/comprehensive behavioural intervention for tics (CBIT) was also shown to be effective (SMD -0.64, 95% CI -0.99 to -0.29; n = 133). For part 2, 295 parents/carers of children and young people with TS contributed useable survey data. Forty young people with TS participated in in-depth interviews. Four studies were in the qualitative review. Key themes were difficulties in accessing specialist care and behavioural interventions, delay in diagnosis, importance of anxiety and emotional symptoms, lack of provision of information to schools and inadequate information regarding medication and adverse effects.
The number and quality of clinical trials is low and this downgrades the strength of the evidence and conclusions.
Antipsychotics, noradrenergic agents and HRT/CBIT are effective in reducing tics in children and young people with TS. The balance of benefits and harms favours the most commonly used medications: risperidone (Risperdal(®), Janssen), clonidine and aripiprazole (Abilify(®), Otsuka). Larger and better-conducted trials addressing important clinical uncertainties are required. Further research is needed into widening access to behavioural interventions through use of technology including mobile applications ('apps') and video consultation.
This study is registered as PROSPERO CRD42012002059.
The National Institute for Health Research Health Technology Assessment programme.
To develop a European guideline on pharmacologic treatment of Tourette syndrome (TS) the available literature was thoroughly screened and extensively discussed by a working group of the European ...Society for the Study of Tourette syndrome (ESSTS). Although there are many more studies on pharmacotherapy of TS than on behavioral treatment options, only a limited number of studies meets rigorous quality criteria. Therefore, we have devised a two-stage approach. First, we present the highest level of evidence by reporting the findings of existing Cochrane reviews in this field. Subsequently, we provide the first comprehensive overview of all reports on pharmacological treatment options for TS through a MEDLINE, PubMed, and EMBASE search for all studies that document the effect of pharmacological treatment of TS and other tic disorders between 1970 and November 2010. We present a summary of the current consensus on pharmacological treatment options for TS in Europe to guide the clinician in daily practice. This summary is, however, rather a status quo of a clinically helpful but merely low evidence guideline, mainly driven by expert experience and opinion, since rigorous experimental studies are scarce.
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