Background
This is an update of the original Cochrane Review published in Issue 4, 2011.
Attention deficit hyperactivity disorder (ADHD) is the most prevalent of the comorbid psychiatric disorders ...that complicate tic disorders. Medications commonly used to treat ADHD symptoms include stimulants such as methylphenidate and amphetamine; non‐stimulants, such as atomoxetine; tricyclic antidepressants; and alpha agonists. Alpha agonists are also used as a treatment for tics. Due to the impact of ADHD symptoms on the child with tic disorder, treatment of ADHD is often of greater priority than the medical management of tics. However, for many decades, clinicians have been reluctant to use stimulants to treat children with ADHD and tics for fear of worsening their tics.
Objectives
To assess the effects of pharmacological treatments for ADHD in children with comorbid tic disorders on symptoms of ADHD and tics.
Search methods
In September 2017, we searched CENTRAL, MEDLINE, Embase, and 12 other databases. We also searched two trial registers and contacted experts in the field for any ongoing or unpublished studies.
Selection criteria
We included randomized, double‐blind, controlled trials of any pharmacological treatment for ADHD used specifically in children with comorbid tic disorders. We included both parallel‐group and cross‐over study designs.
Data collection and analysis
We used standard methodological procedures of Cochrane, in that two review authors independently selected studies, extracted data using standardized forms, assessed risk of bias, and graded the overall quality of the evidence by using the GRADE approach.
Main results
We included eight randomized controlled trials (four of which were cross‐over trials) with 510 participants (443 boys, 67 girls) in this review. Participants in these studies were children with both ADHD and a chronic tic disorder. All studies took place in the USA and ranged from three to 22 weeks in duration. Five of the eight studies were funded by charitable organizations or government agencies, or both. One study was funded by the drug manufacturer. The other two studies did not specify the source of funding. Risk of bias of included studies was low for blinding; low or unclear for random sequence generation, allocation concealment, and attrition bias; and low or high for selective outcome reporting. We were unable to combine any of the studies in a meta‐analysis due to important clinical heterogeneity and unit‐of‐analysis issues.
Several of the trials assessed multiple agents. Medications assessed included methylphenidate, clonidine, desipramine, dextroamphetamine, guanfacine, atomoxetine, and deprenyl. There was low‐quality evidence for methylphenidate, atomoxetine, and clonidine, and very low‐quality evidence for desipramine, dextroamphetamine, guanfacine and deprenyl in the treatment of ADHD in children with tics. All studies, with the exception of a study using deprenyl, reported improvement in symptoms of ADHD. Tic symptoms also improved in children treated with guanfacine, desipramine, methylphenidate, clonidine, and a combination of methylphenidate and clonidine. In one study, tics limited further dosage increases of methylphenidate. High‐dose dextroamphetamine appeared to worsen tics in one study, although the length of this study was limited to three weeks. There was appetite suppression or weight loss in association with methylphenidate, dextroamphetamine, atomoxetine, and desipramine. There was insomnia associated with methylphenidate and dextroamphetamine, and sedation associated with clonidine.
Authors' conclusions
Following an updated search of potentially relevant studies, we found no new studies that matched our inclusion criteria and thus our conclusions have not changed.
Methylphenidate, clonidine, guanfacine, desipramine, and atomoxetine appear to reduce ADHD symptoms in children with tics though the quality of the available evidence was low to very low. Although stimulants have not been shown to worsen tics in most people with tic disorders, they may, nonetheless, exacerbate tics in individual cases. In these instances, treatment with alpha agonists or atomoxetine may be an alternative. Although there is evidence that desipramine may improve tics and ADHD in children, safety concerns will likely continue to limit its use in this population.
Parkinson's disease (PD) is a common neurodegenerative disorder. Epidemiological studies on the incidence of PD are important to better understand the risk factors for PD and determine the ...condition's natural history.
This systematic review and meta-analysis examine the incidence of PD and its variation by age and gender.
We searched MEDLINE and EMBASE for epidemiologic studies of PD from 2001 to 2014, as a previously published systematic review included studies published until 2001. Data were analyzed separately for age group and gender, and meta-regression was used to determine whether a significant difference was present between groups.
Twenty-seven studies were included in the analysis. Meta-analysis of international studies showed rising incidence with age in both men and women. Significant heterogeneity was observed in the 80+ group, which may be explained by methodological differences between studies. While males had a higher incidence of PD in all age groups, this difference was only statistically significant for those in the age range 60-69 and 70-79 (p < 0.05).
PD incidence generally increases with age, although it may stabilize in those who are 80+.
Abstract This study evaluated the prevalence of tic disorders. MEDLINE and EMBASE databases were searched, using terms specific to Tourette syndrome and tic disorders, for studies of incidence, ...prevalence, and epidemiology. Thirty-five studies reporting data from 1985-2011 on the incidence or prevalence of tic disorders in a defined population were included. One reported incidence, and 34 reported prevalence. Meta-analysis of 13 studies of children yielded a prevalence of Tourette syndrome at 0.77% (95% confidence interval, 0.39-1.51%). Prevalence is higher in boys: 1.06% of boys were affected (95% confidence interval, 0.54-2.09%) vs 0.25% of girls (95% confidence interval, 0.05-1.20%). Transient tic disorder comprised the most common tic disorder in children, affecting 2.99% (95% confidence interval, 1.60-5.61%). Meta-analysis of two studies assessing adults for Tourette syndrome revealed a prevalence of 0.05% (95% confidence interval, 0.03-0.08%). The prevalence of tic disorders was higher in all studies performed in special education populations. Tic disorders are more common in children than adults, in boys than girls, and in special education populations. Parents, educators, healthcare professionals, and administrators should be aware of the frequency with which tic disorders occur, and ensure proper access to appropriate care.
Objective
Tourette syndrome (TS) is a neuropsychiatric disorder presenting with tics and a constellation of nonmotor symptoms that includes attention deficit hyperactivity disorder, ...obsessive–compulsive disorder, and impulse control disorders. Accumulated evidence from pharmacological trials and postmortem analyses suggests that abnormalities of dopaminergic neurotransmission play a key role in the pathogenesis of TS. A substantial body of evidence has also accrued to implicate regions outside the striatum in the generation of tics.
Methods
We initiated an 11CFLB 457 positron emission tomography study in conjunction with an amphetamine challenge to evaluate extrastriatal dopamine (DA) D2/D3 receptor binding and DA release in a group of treatment‐naive, adult TS patients compared with a group of age‐ and sex‐matched controls.
Results
At baseline, TS patients showed decreased 11CFLB 457 binding potentials bilaterally in cortical and subcortical regions outside the striatum, including the cingulate gyrus, middle and superior temporal gyrus, occipital cortex, insula, and thalamus. Amphetamine challenge induced DA release in both control and TS subjects bilaterally in many cortical regions; however, in TS patients, regions of increased DA release were significantly more widespread and extended more anteriorly to involve anterior cingulate and medial frontal gyri. Conversely, and in contrast to healthy controls, no significant DA release was noted in the thalami of TS patients.
Interpretation
These abnormalities of dopaminergic function localize to brain regions previously implicated in TS and suggest a mechanism for the hyperexcitability of thalamocortical circuits that has been documented in the disorder. ANN NEUROL 2010;67:170–181
Purpose The purpose of this retrospective study was to determine the prevalence of surgical site infection (SSI) after orthognathic surgery at the Department of Oral and Maxillofacial Surgery of ...Capital Health and Dalhousie University (Halifax, NS, Canada). Patients and Methods A retrospective chart review of all patients undergoing orthognathic surgery from October 2005 through April 2013 was performed. The outcome variable was SSI. The primary predictor variable was the antibiotic used for prophylaxis. The secondary predictor variables were patient demographics, such as age, gender, medical comorbidities, and smoking status; duration of surgery; wisdom teeth extractions; single-jaw or bimaxillary surgery; and type of surgery. Data also were gathered on the diagnosis of SSIs and the treatment to resolve these infections. Results In total, 2,521 patients underwent surgery, and 253 patients did not meet the inclusion criteria; therefore, the charts of 2,268 patients were reviewed (mean ± standard deviation, 26.9 ± 11.7 yr of age). Eight percent of patients developed an SSI. None of the patient demographics was associated with an increased risk for infection. Most initial infections (62%) and most recurrent infections (78%) occurred in the mandible. Twenty-six percent of patients who developed SSIs had recurrent infections after antibiotic treatment. SSIs necessitated hardware removal for 14% of patients. Adverse effects from the antibiotics were seen in 4.2% of patients. Infection was most frequently diagnosed 11 to 15 days postoperatively. The average length of surgery for patients who did not have an SSI was 136 minutes compared with an average of 157 minutes for patients who had an SSI (odds ratio = 1.0051; 95% confidence interval, 1.0026 to 1.0076; P < .001). Wisdom teeth were extracted in 49.6% of the 2,268 cases. The mean SSI prevalence for multiple jaw procedures (9.2%) was significantly higher than that for single surgical procedures (5.3%; P = .0013). Isolated Le Fort surgeries had a significantly lower prevalence of infection compared with the mean prevalence (3.9%; P = .02), whether they were single piece or segmented (3.5 and 4.3%, respectively; P = .98). The prevalence of infection was significantly lower in the cefazolin group (6.2%) compared with the penicillin (14.3%; P < .0001) and clindamycin (10.4%; P < .02) groups. Conclusions The prophylactic use of first-generation cephalosporins, such as cefazolin, appears to be more effective than penicillin and clindamycin for preventing SSIs in orthognathic surgery. In addition, bimaxillary surgery, mandibular procedures, and duration of surgery might demand antibiotic prophylaxis that is more effective. The presence of third molars and patient demographics are not risk factors for SSIs. A prospective randomized controlled study is underway to investigate the findings of this study.
Objective
Neuropsychiatric symptoms (NPS) are prevalent in neurodegenerative disorders, however, their frequency and impact on function across different disorders is not well understood. We compared ...the frequency and severity of NPS across Alzheimer's disease (AD) (either with mild cognitive impairment or dementia), Cerebrovascular disease (CVD), Parkinson's disease (PD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), and explored the association between NPS burden and function.
Methods
We obtained data from Ontario Neurodegenerative Disease Research Initiative (ONDRI) that included following cohorts: AD (N = 111), CVD (N = 148), PD (N = 136), FTD (N = 50) and ALS (N = 36). We compared the frequency and severity of individual NPS (assessed by the neuropsychiatric inventory questionnaire) across cohorts using generalized estimating equations and analysis of variance. Second, we assessed the relationship of NPS burden with instrumental (iADLs) and basic (ADLs) activities of living across cohorts using multivariate linear regression while adjusting for relevant demographic and clinical covariates.
Results
Frequency of NPS varied across cohorts (χ2(4) = 34.4, p < .001), with post-hoc tests showing that FTD had the greatest frequency as compared to all other cohorts. The FTD cohort also had the greatest severity of NPS (H(4) = 34.5, p < .001). Further, there were differences among cohorts in terms of the association between NPS burden and ADLs (F(4,461) = 3.1, p = 0.02). Post-hoc comparisons suggested that this finding was driven by the FTD group, however, the differences did not remain significant following Bonferroni correction. There were no differences among cohorts in terms of the association between NPS burden and IADLs.
Conclusions
NPS frequency and severity are markedly greater in FTD as compared to other neurodegenerative diseases. Further, NPS burden appears to be associated differently with function across neurodegenerative disorders, highlighting the need for individualized clinical interventions.
The purpose of this study was to determine the effect of a 3- versus 1-day antibiotic regimen on the rate of surgical site infection (SSI) in patients undergoing orthognathic surgery at a department ...of oral and maxillofacial surgery in Halifax, Nova Scotia, Canada.
A prospective, randomized controlled trial was conducted. All patients received 1 day of intravenous antibiotics after surgery. Then, patients were randomly distributed into groups that received 2 days of additional antibiotics (group A) or placebo (group B). The primary outcome measured was the presence of SSI. The operating surgeon, concomitant extraction of teeth, surgical procedures performed, duration of intermaxillary fixation, and length of hospital stay were analyzed for an effect on SSI. Patients were followed for 1 year after surgery to identify SSIs that might have been diagnosed outside the hospital.
The trial started with 288 patients, and 117 patients were lost to follow-up. Statistical analyses were ultimately performed on those 171 patients who were adherent to the study medication regimen. Group A (n = 86) and B (n = 85) SSI rates were 7.0 and 17.6% (number needed to treat = 10; P = .04), respectively. Mandibular bilateral sagittal split osteotomy (BSSO) was involved in 71% of SSIs. Intra- and postoperative surgical variables did not have a relevant effect on the SSI rate. Patients were followed for 1 year after surgery, and group A (n = 46) and group B (n = 44) had SSI rates of 4 and 25% (P < .05), respectively.
Three days of postoperative cefazolin and cephalexin markedly decreases SSI rates compared with 1 day. However, the number needed to treat of 10 suggests that the benefits of the extended regimen might not outweigh the risks. The high prevalence of SSIs at the mandibular BSSO incisions might have been caused by contamination, with more saliva and reception of a lower blood supply, than maxillary Le Fort I incisions. Mandibular osteotomies could benefit from an extended antibiotic regimen to minimize SSIs and associated complications. Other surgical variables might not require special consideration for antibiotic therapy.
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