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BACKGROUND: Sleep problems are common in children with Tourette Syndrome (TS). However, research regarding their demographic and clinical profile is limited. METHODS: We examined characteristics of 114 children aged five to 17 years with a lifetime diagnosis of TS and compared children with sleep disorder (n = 32) and without sleep disorder (n = 82). Parent report from the 2014 National Survey of the Diagnosis and Treatment of ADHD and Tourette Syndrome provided demographics and clinical information, other diagnosed disorders, medication use, TS severity, and impairment. RESULTS: More children with TS with sleep disorder were from households with lower parental education (P

Tics peak in late childhood and decline during adolescence. Yet, for some with Tourettes disorder, tics persist into adulthood. We evaluated childhood predictors of adult tic severity and tic impairment, and change over time. Eighty adolescents/adults were evaluated 11 years following a randomized-controlled trial of behavior therapy. An independent evaluator rated tic severity and tic impairment at baseline, posttreatment, and long-term follow-up. At baseline, parents completed demographics/medical history, and youth tic, internalizing, and externalizing symptom ratings. Youth rated premonitory urge severity and family functioning. After controlling for prior tic treatment effects, female sex and higher tic severity predicted higher tic severity in adulthood; and female sex, no stimulant medication use, higher tic severity, and poorer family functioning predicted higher tic impairment. Higher tic severity and premonitory urge severity predicted smaller reductions in tic severity, whereas higher externalizing symptoms predicted greater reduction in tic severity. Female sex predicted smaller reduction in tic impairment, and externalizing symptoms predicted greater reduction in tic impairment. Female sex and childhood tic severity are important predictors of tic severity and tic impairment in adulthood. Family functioning, premonitory urge severity, and tic severity are important modifiable targets for early or targeted intervention to improve long-term outcomes.

BACKGROUND: Cognitive control processes are implicated in the behavioral treatment of Tourettes disorder (TD). However, the influence of these processes on treatment outcomes has received minimal attention. This study examined whether cognitive control processes and/or tic suppression predicted reductions in tic severity and treatment response to behavior therapy. METHOD: Fifty-three youth with TD or a pervasive tic disorder participated in a randomized wait list-controlled trial of behavior therapy. Following a baseline assessment to evaluate psychiatric diagnoses, tic severity, and cognitive control processes (e.g., response selection, inhibition, and suppression), youth were randomly assigned to receive eight sessions of behavior therapy (n = 23) or a wait list of equal duration (n = 28). Youth receiving immediate treatment completed a post-treatment assessment to determine improvement in tic severity. Meanwhile, youth in the wait list condition completed another assessment to re-evaluate tic severity and cognitive control processes, and subsequently received 8 sessions of behavior therapy followed by a post-treatment assessment to determine improvement. RESULTS: A multiple linear regression model found that pretreatment inhibition/switching on the Delis-Kaplan Executive Function System Color-Word Interference Test predicted reductions in tic severity after behavior therapy (β = -.36, t = -2.35, p = .025, ƞ2  = .15). However, other cognitive control processes and tic suppression did not predict treatment response and/or reductions in tic severity. Small nonsignificant effects were observed in cognitive control processes after behavior therapy. CONCLUSION: Cognitive control processes may influence tic severity reductions in behavior therapy. Notably, even when other cognitive control processes are impaired and youth are initially unable to voluntarily suppress their tics, youth with TD can still benefit from behavior therapy. Findings offer implications for clinical practice and research for TD.

This study describes impairment in academic, interpersonal, recreational, and family financial or occupational domains across children in three mutually exclusive diagnostic groups: ever diagnosed with Tourette syndrome (TS), attention-deficit/hyperactivity disorder (ADHD), and both disorders. In 2014, parents reported on impairment and diagnostic status of children aged 4-17 years (n = 3014). Weighted analysis and pairwise t-tests showed more children with ADHD (with or without TS) experienced impairment in overall school performance, writing, and mathematics, relative to children with TS but not ADHD. More children with TS and ADHD had problematic handwriting relative to children with ADHD but not TS. More children with TS and ADHD had problematic interpersonal relationships relative to those with ADHD but not TS. Children with TS and ADHD had higher mean impairment across domains than children with either TS or ADHD. Findings suggest assessing disorder-specific contributions to impairment could inform targeted interventions for TS and ADHD.

BackgroundIndividuals with Tourette Syndrome and Persistent Tic Disorders (collectively TS) often experience premonitory urges-aversive physical sensations that precede tics and are temporarily relieved by tic expression. The relationship between tics and premonitory urges plays a key role in the neurobehavioral treatment model of TS, which underlies first-line treatments such as the Comprehensive Behavioral Intervention for Tics (CBIT). Despite the efficacy of CBIT and related behavioral therapies, less than 40% of adults with TS respond to these treatments. Further examination of the relationship between premonitory urges, tic severity, and tic impairment can provide new insights into therapeutic targets to optimize behavioral treatment outcomes. This study examined whether urge intolerance-difficulty tolerating premonitory urges-predicted tic severity and tic-related impairment among adults with TS.MethodsParticipants were 80 adults with TS. Assessments characterized premonitory urge, distress tolerance, tic severity, and tic impairment. We used structural equation modeling (SEM) to examine the construct of urge intolerance-comprised of premonitory urge ratings and distress tolerance ratings. We first evaluated a measurement model of urge intolerance through bifactor modeling, including tests of the incremental value of subfactors that reflect premonitory urge severity and distress tolerance within the model. We then evaluated a structural model where we predicted clinician-rated tic severity and tic impairment by the latent variable of urge intolerance established in our measurement model.ResultsAnalyses supported a bifactor measurement model of urge intolerance among adults with TS. Consistent with theoretical models, higher levels of urge intolerance predicted greater levels of clinician-rated tic severity and tic impairment.ConclusionThis investigation supports the construct of urge intolerance among adults with TS and distinguishes it from subcomponents of urge severity and distress tolerance. Given its predictive relationship with tic severity and tic impairment, urge intolerance represents a promising treatment target to improve therapeutic outcomes in adults with TS.

BackgroundSleep disturbance is common among individuals with Tourette's Disorder (TD). Given that sleep is influenced by the circadian system, this study examined circadian rhythms and sleep in adults with TD, and explored the possible benefit of short-wavelength wearable morning light therapy.MethodsParticipants were 34 adults with TD (n = 14) and age- and sex-matched healthy controls (HC; n = 20). Participants were screened using clinician-rated diagnostic and tic severity interviews, and procedures lasted 3 consecutive weeks. Participants completed a baseline week of actigraphy. Adults with TD completed 2 weeks of Re-Timer™ morning light therapy and continued actigraphy monitoring. Dim light melatonin-onset (DLMO) phase assessment, tic severity interview, and measures of chronotype, sleep disturbance, daytime sleepiness, disability, depression, anxiety, and stress were completed at baseline and post-intervention.ResultsAdults with TD reported significantly greater eveningness and sleep disturbance relative to controls. Per wrist actigraphy, adults with TD exhibited significantly longer sleep-onset latency, lower sleep efficiency, and greater sleep fragmentation than HC. Following morning light therapy, there was a significant advance in DLMO phase, but not self-report or actigraphy sleep variables. There were small, statistically significant decreases in tic severity and impairment. There were also significant reductions in daytime sleepiness, and self-reported anxiety, but not depression, stress, or disability. Participants reported minimal side effects and rated light therapy as acceptable and comfortable.ConclusionsFindings showed some benefits following brief light therapy in TD; further exploration of the impact of spectral tuning the photic environment as part of treatment for TD subjects is warranted.

Decision makers face a nontrivial problem when evaluating how much time to invest in an uncertain future prospect. Un- conditional persistence is not always advantageous; rather, different levels of persistence are favored in environments with different temporal statistics. Previous studies using foraging- like decision-making tasks have found that people can rapidly recalibrate their persistence behavior—becoming either more or less willing to tolerate delay—after a short period of direct experience with the temporal statistics of a new environment. Furthermore, substantial individual variation is apparent both in baseline levels of persistence and in the flexibility of re- calibration across environments. However, it is unknown to what degree such variation reflects trait-like individual differences in contrast to session-specific measurement noise. Here we investigated the test-retest reliability of individual variation in behavioral persistence in a computerized decision-making task. We conducted an online experiment in which participants (n=141 after exclusions) performed the task on two occasions separated by a three-week interval. We evaluated the test- retest reliability of several behavior-derived indices, including: a descriptive estimate of overall willingness to wait, a contrast measure reflecting flexibility of recalibration across environments, and individual-level parameter estimates derived from a reinforcement learning model of adaptive persistence. The results showed strong evidence for stable, trait-like individual variation in multiple aspects of persistence-related decision- making behavior. Our findings establish a foundation for future investigations of associations between task-derived parameters of decision behavior and other cognitive and motivational traits.

Improving physical activity (PA) levels in autistic adults is an important population health goal. Limiting efforts to achieve this goal is an incomplete understanding of the barriers to PA in this high-risk group. This study utilized cross-sectional data collected via an electronic survey from 253 autistic adults aged 18-50 years to examine their perceived barriers to PA, how PA barriers differed by demographic factors, and the relationship between PA barriers and meeting PA guidelines. The Barriers to Physical Activity scale assessed the independent variable. Lack of motivation to exercise, perceiving exercise as boring, and lack of transportation were the most strongly endorsed barriers to PA. Participants who reported these barriers were significantly less likely ([less than or equal to] 50%) to meet PA guidelines.

Consistent with international reports,1 this group of Tourette syndrome (TS) experts has noticed a recent increase in adolescents presenting with tic-like symptoms that show a markedly atypical onset and course. These sudden-onset motor movements and vocalizations are often associated with significant impairment and disability, resulting in emergency department visits and hospitalizations for some affected youths.

Enrollment in metastatic breast cancer trials usually requires measurable lesions, but patients with invasive lobular carcinoma (ILC) tend to form diffuse disease. We found that the proportion of patients with metastatic ILC enrolled in clinical trials at our institution was significantly lower than that of patients with invasive ductal carcinoma (IDC). Possible links between requiring measurable disease and decreased enrollment of ILC patients require further study to ensure equitable trial access.

The present study investigated inhibitory control deficits in Tourette's Disorder (TD)-only, Attention Deficit/Hyperactivity Disorder (ADHD)-only, and TD+ADHD and explored the degree to which measures of inhibitory control, and tic and ADHD severity predicted objective tic suppressibility. Participants were youth ages 9 to 14 (M = 11.15) with TD-only (n = 24), TD+ADHD (n = 19), ADHD-only (n = 139), and typically-developing controls (n = 59) drawn from a larger study. Groups were compared on computer-based and paper and pencil neurocognitive inhibitory control tasks. Among youth with TD, neurocognitive measures of inhibitory control, subjective tic-suppressibility (Premonitory Urge for Tics Scale, item 10), and ADHD symptom severity were evaluated as predictors of objective tic suppressibility (i.e., laboratory-based tic suppression task), controlling for total tic severity. There were significant group differences on Color-Word inhibition/switching performance, though post-hoc comparisons yielded no significant pairwise group contrasts. Subjective tic suppressibility was the only significant predictor of objective tic suppressibility. The evident intact neurocognitive inhibitory control among youth with TD suggests that individuals with TD may use compensatory neural mechanisms to support typical speed and accuracy of response. The role of cognitive flexibility in mechanisms of tic suppression should also be further explored.

Behavior therapy is a first-line intervention for Tourette's Disorder (TD), and a key component is the practice of therapeutic skills between treatment visits (i.e., homework). This study examined the relationship between homework adherence during behavior therapy for TD and therapeutic outcomes, and explored baseline predictors of homework adherence during treatment. Participants included 119 individuals with TD (70 youth, 49 adults) who received behavior therapy in a clinical trial. After a baseline assessment of tic severity and clinical characteristics, participants received 8 sessions of behavior therapy. Therapists recorded homework adherence at each therapy session. After treatment, tic severity was re-assessed by independent evaluators masked to treatment condition. Greater overall homework adherence predicted tic severity reductions and treatment response across participants. Early homework adherence predicted therapeutic improvement in youth, whereas late adherence predicted improvement in adults. Baseline predictors of greater homework adherence in youth included lower hyperactivity/impulsivity and caregiver strain. Meanwhile in adults, baseline predictors of increased homework adherence included younger age, lower hyperactivity/impulsivity, obsessive-compulsive severity, anger, and greater work-related disability. Homework adherence is an integral component of behavior therapy and linked to therapeutic improvement. Strategies that improve homework adherence may optimize the efficacy of behavioral treatments and improve treatment outcomes.

ObjectiveTreatment guidelines for Tourette's Disorder (TD) are based on patients' degree of tic severity and impairment. However, clear benchmarks for determining tic severity and impairment have not been established. This study examined benchmarks of tic severity and tic impairment using the Yale Global Tic Severity Scale (YGTSS) and the Clinical Global Impression of Severity (CGI-S).MethodIndividuals with TD or another Tic Disorder (N = 519) recruited across nine sites were administered a diagnostic interview, the YGTSS, and the CGI-S. Correlations and trend analyses contrasted YGTSS scores across CGI-S ratings. A logistic regression model examined predictive benchmarks for tic severity, tic impairment, and global severity. Model classifications were compared against CGI-S ratings, and agreement was examined using kappa.ResultsSpearman correlations between the CGI-S and YGTSS scores ranged from 0.54 to 0.63 (p

Tourettes Disorder (TD) is characterized by tics that cause distress and impairment. While treatment guidelines recommend behavior therapy as a first-line intervention, patients with TD may exhibit limited therapeutic response. Given the need to improve treatment outcomes, this study examined the efficacy of augmenting behavior therapy with D-cycloserine (DCS) to reduce tic severity in a placebo-controlled quick-win/fast-fail trial. Twenty youth with TD completed a baseline assessment to characterize tic severity, premonitory urges, medical history, and psychiatric comorbidity. Youth were randomly assigned to receive a single session of habit reversal training (HRT) augmented by either 50 mg of DCS or placebo. Two bothersome tics on the Hopkins Motor/Vocal Tic Scale (HM/VTS) were targeted for treatment during HRT. One week after the HRT session, youth completed a posttreatment assessment to evaluate change in the severity of bothersome tics. All assessments were completed by independent evaluators masked to treatment group. There was a Treatment Group by Time Interaction in favor of DCS-augmented HRT (p

When learning about dynamic and uncertain environments, people should update their beliefs most strongly when new evidence is most informative, such as when the environment undergoes a surprising change or existing beliefs are highly uncertain. Here we show that modulations of surprise and uncertainty are encoded in a particular, temporally dynamic pattern of whole-brain functional connectivity, and this encoding is enhanced in individuals that adapt their learning dynamics more appropriately in response to these factors. The key feature of this whole-brain pattern of functional connectivity is stronger connectivity, or functional integration, between the fronto-parietal and other functional systems. Our results provide new insights regarding the association between dynamic adjustments in learning and dynamic, large-scale changes in functional connectivity across the brain.

BackgroundAlthough gemcitabine plus platinum chemotherapy is the established first-line regimen for advanced biliary cancer (ABC), there is no standard second-line therapy. This study evaluated current practice and outcomes for second-line chemotherapy in patients with ABC across 3 US academic medical centers.MethodsInstitutional registries were reviewed to identify patients who had received second-line chemotherapy for ABC from April 2010 to March 2015 along with their demographics, diagnoses and staging, treatment histories, and clinical outcomes. Overall survival from the initiation of second-line chemotherapy (OS2) was estimated with Kaplan-Meier methods.ResultsThis study identified 198 patients with cholangiocarcinoma (intrahepatic [61.1%] or extrahepatic [14.1%]) or gallbladder carcinoma (24.8%); 52% received at least 3 lines of systemic chemotherapy. The median OS2 was 11 months (95% confidence interval [CI], 8.8-13.1 months). The median OS2 for patients with intrahepatic cholangiocarcinoma was 13.4 months (95% CI, 10.7-17.8 months), which was longer than that for patients with extrahepatic cholangiocarcinoma (6.8 months; 95% CI, 5-10.6 months) or gallbladder carcinoma (9.4 months; 95% CI, 7.2-12.3 months; P = .018). The median time to second-line treatment failure was 2.2 months (95% CI, 1.8-2.7 months), and it was similar across tumor locations (P = .60).ConclusionsIn this large cohort of patients with ABC treated across 3 academic medical centers after the failure of first-line chemotherapy, the time to treatment failure on standard therapies was short, although the median OS2 was longer than has been reported previously, and more than half of the patients received additional lines of treatment. This multicenter collaboration represents the largest cohort studied to date of second-line chemotherapy for ABC and provides a contemporary benchmark for future clinical trials.

BackgroundA lack of diversity among clinical trial (CT) participants remains a critical problem. Few studies have examined recruitment variability in cancer treatment CTs by cancer type. Given the increasing organ-specific specialization of oncologic care, an understanding of this variability may affect institutional recruitment practices.MethodsThis study examines three data sources from 2010 through 2014. The analyzed sample includes 3,580 CT participants identified in the institutional Clinical Trials Management System (CTMS) database and 20,305 incident cases of invasive cancer within a Comprehensive Cancer Center (CCC) institutional catchment area. A total of 341,114 incident cases of primary invasive cancer were identified through the California Cancer Registry (CCR). The primary study measurements were sociodemographic characteristics of the three populations (age, sex, race/ethnicity, and health insurance).ResultsRacial/ethnic disparities were observed, with more incident cases of Whites seen in cancer center (68%) and enrolled in CTs (72%) compared to incident cases in catchment area (67%) (p

ObjectiveAlthough adult hoarding disorder is relatively common and often debilitating, few studies have examined the phenomenology of pediatric hoarding. We examined the clinical phenomenology and response to cognitive-behavioral therapy (CBT) treatment in youths with a diagnosis of obsessive-compulsive disorder (OCD) with and without hoarding symptoms. Age was tested as a moderator across analyses, given prior findings that the impact of hoarding symptoms may not become apparent until adolescence.MethodYouths (N = 215; aged 7-17 years) with OCD pursuing evaluation and/or treatment at a university-based specialty clinic participated in the current study. Presence of hoarding symptoms was assessed as part of a larger battery. Data from a subset of youths (n = 134) who received CBT were included in treatment response analyses.ResultsYouths with hoarding symptoms did not differ from those without hoarding symptoms with respect to overall OCD symptom severity and impairment. Youths with hoarding met criteria for more concurrent diagnoses, including greater rates of internalizing and both internalizing/externalizing, but not externalizing-only, disorders. Youths with and without hoarding symptoms did not significantly differ in rate of response to CBT. Age did not moderate any of these relationships, suggesting that the presence of hoarding symptoms was not associated with greater impairments across the clinical presentation of OCD or its response to treatment by age.ConclusionWe found no evidence that hoarding is associated with greater OCD severity or poorer treatment response in affected youth. Theoretical and clinical implications of these findings, including future directions for research on testing developmental models of hoarding across the lifespan, are discussed.

The incidence and patient survival rates of melanoma have increased over the last several decades, with a growing population of patients who develop multiple primary melanomas (MPMs). To determine risk factors for developing MPMs and compare the survival of patients with MPMs to those with single primary melanomas, a prospective, multidisciplinary database of patients with melanoma at a single tertiary care institution was retrospectively reviewed. From 1985 to 2013, 6,963 patients with single primary melanomas and 305 patients with MPMs were identified. Mean follow-up was 8.3 ± 6.3 years for patients with single primary melanomas and 8.8 ± 5.9 years for patients with MPMs. Risk of developing multiple melanomas increased with age at diagnosis of first melanoma (hazard ratio [HR] = 1.20 for a 10-year increase in age, 95% confidence interval [CI] = 1.11-1.29, P

Objective: Stimulant medication and behavior therapy are efficacious for youth with attention-deficit/hyperactivity disorder (ADHD). However, research suggests that stimulants may start and/or worsen sleep problems for youth. Further, the impact of behavior therapy for ADHD on sleep is unknown. This study examined the frequency of sleep problems and effects of stimulant medication, behavior therapy, and their combination on sleep problems in youth with ADHD. This study also explored the influence of dimensional baseline ratings of ADHD symptom subtype and psychiatric comorbidity on sleep outcomes. Methods: Participants were 576 children (aged 7-9 years) with ADHD-Combined type from the Multimodal Treatment of ADHD study that compared methylphenidate, behavior therapy, and their combination to community care. Before treatment, parents completed the Child Behavior Checklist used to derive a total sleep problems score. Parents also completed ratings of oppositionality and ADHD symptom severity, whereas youth completed ratings of depression and anxiety. These ratings were readministered after treatment. Results: General linear mixed-effects models were used to assess change in total sleep problems across treatment. The combined group exhibited a statistically significant reduction in total sleep problems (z = -5.81, p  0.99) did not reach statistical significance. Change in psychiatric symptoms did not significantly moderate change in total sleep problems by treatment assignment. Greater baseline oppositional defiant disorder severity predicted less reduction in total sleep problems, χ2(1) = 3.86, p

ObjectiveTo examine the internal consistency and distribution of the Yale Global Tic Severity Scale (YGTSS) scores to inform modification of the measure.MethodsThis cross-sectional study included 617 participants with a tic disorder (516 children and 101 adults), who completed an age-appropriate diagnostic interview and the YGTSS to evaluate tic symptom severity. The distributions of scores on YGTSS dimensions were evaluated for normality and skewness. For dimensions that were skewed across motor and phonic tics, a modified Delphi consensus process was used to revise selected anchor points.ResultsChildren and adults had similar clinical characteristics, including tic symptom severity. All participants were examined together. Strong internal consistency was identified for the YGTSS Motor Tic score (α = 0.80), YGTSS Phonic Tic score (α = 0.87), and YGTSS Total Tic score (α = 0.82). The YGTSS Total Tic and Impairment scores exhibited relatively normal distributions. Several subscales and individual item scales departed from a normal distribution. Higher scores were more often used on the Motor Tic Number, Frequency, and Intensity dimensions and the Phonic Tic Frequency dimension. By contrast, lower scores were more often used on Motor Tic Complexity and Interference, and Phonic Tic Number, Intensity, Complexity, and Interference.ConclusionsThe YGTSS exhibits good internal consistency across children and adults. The parallel findings across Motor and Phonic Frequency, Complexity, and Interference dimensions prompted minor revisions to the anchor point description to promote use of the full range of scores in each dimension. Specific minor revisions to the YGTSS Phonic Tic Symptom Checklist were also proposed.

This paper examined neurocognitive functioning and its relationship to behavior treatment response among youth with Tourette's Disorder (TD) in a large randomized controlled trial. Participants diagnosed with TD completed a brief neurocognitive battery assessing inhibitory functions, working memory, and habit learning pre- and post-treatment with behavior therapy (CBIT, Comprehensive Behavioral Intervention for Tics) or psychoeducation plus supportive therapy (PST). At baseline, youth with tics and Attention Deficit Hyperactivity Disorder (ADHD) exhibited some evidence of impaired working memory and simple motor inhibition relative to youth with tics without ADHD. Additionally, a small negative association was found between antipsychotic medications and youth's performance speed. Across treatment groups, greater baseline working memory and aspects of inhibitory functioning were associated with a positive treatment response; no between-group differences in neurocognitive functioning at post-treatment were identified. Within the behavior therapy group, pre-treatment neurocognitive status did not predict outcome, nor was behavior therapy associated significant change in neurocognitive functioning post-treatment. Findings suggest that co-occurring ADHD is associated with some impairments in neurocognitive functioning in youth with Tourette's Disorder. While neurocognitive predictors of behavior therapy were not found, participants who received behavior therapy exhibited significantly reduced tic severity without diminished cognitive functioning.

Functional magnetic resonance imaging (fMRI) is a powerful research tool to understand the neural underpinnings of human memory. However, as memory is known to be context-dependent, differences in contexts between naturalistic settings and the MRI scanner environment may potentially confound neuroimaging findings. Virtual reality (VR) provides a unique opportunity to mitigate this issue by allowing memories to be formed and/or retrieved within immersive, navigable, visuospatial contexts. This can enhance the ecological validity of task paradigms, while still ensuring that researchers maintain experimental control over critical aspects of the learning and testing experience. This mini-review surveys the growing body of fMRI studies that have incorporated VR to address critical questions about human memory. These studies have adopted a variety of approaches, including presenting research participants with VR experiences in the scanner, asking participants to retrieve information that they had previously acquired in a VR environment, or identifying neural correlates of behavioral metrics obtained through VR-based tasks performed outside the scanner. Although most such studies to date have focused on spatial or navigational memory, we also discuss the promise of VR in aiding other areas of memory research and facilitating research into clinical disorders.

This study assessed the psychometric properties of a parent-reported tic severity measure, the Parent Tic Questionnaire (PTQ), and used the scale to establish guidelines for delineating clinically significant tic treatment response. Participants were 126 children ages 9 to 17 who participated in a randomized controlled trial of Comprehensive Behavioral Intervention for Tics (CBIT). Tic severity was assessed using the Yale Global Tic Severity Scale (YGTSS), Hopkins Motor/Vocal Tic Scale (HMVTS) and PTQ; positive treatment response was defined by a score of 1 (very much improved) or 2 (much improved) on the Clinical Global Impressions - Improvement (CGI-I) scale. Cronbach's alpha and intraclass correlations (ICC) assessed internal consistency and test-retest reliability, with correlations evaluating validity. Receiver- and Quality-Receiver Operating Characteristic analyses assessed the efficiency of percent and raw-reduction cutoffs associated with positive treatment response. The PTQ demonstrated good internal consistency (α = 0.80 to 0.86), excellent test-retest reliability (ICC = .84 to .89), good convergent validity with the YGTSS and HM/VTS, and good discriminant validity from hyperactive, obsessive-compulsive, and externalizing (i.e., aggression and rule-breaking) symptoms. A 55% reduction and 10-point decrease in PTQ Total score were optimal for defining positive treatment response. Findings help standardize tic assessment and provide clinicians with greater clarity in determining clinically meaningful tic symptom change during treatment.

ObjectiveThis meta-analysis examined treatment efficacy, treatment response, and diagnostic remission effect sizes and moderators of D-cycloserine-augmented exposure treatment in randomized controlled trials (RCTs) of individuals with anxiety disorders, obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD).Data sources and study selectionThe terms D-cycloserine AND randomized controlled trial were used to search the PubMed (1965-May 2015), PsycINFO, and Scopus databases for randomized placebo-controlled trials of D-cycloserine-augmented exposure therapy for anxiety disorders, OCD, and PTSD.Data extractionClinical variables and effect sizes were extracted from 20 RCTs (957 participants). A random-effects model calculated the effect sizes for treatment efficacy, treatment response, and diagnostic remission using standardized rating scales. Subgroup analyses and meta-regression were used to examine potential moderators.ResultsA small, nonsignificant benefit of D-cycloserine augmentation compared to placebo augmentation was identified across treatment efficacy (g = 0.15), response (risk ratio [RR] = 1.08), and remission (RR = 1.109), with a moderately significant effect (P = .03) for anxiety disorders specifically (g = 0.33). At initial follow-up assessments, a small, nonsignificant effect size of D-cycloserine augmentation compared to placebo was found for treatment efficacy (g = 0.21), response (RR = 1.06), and remission (RR = 1.12). Specific treatment moderators (eg, comorbidity, medication status, gender, publication year) were found across conditions for both acute treatment and initial follow-up assessments.ConclusionsD-Cycloserine does not universally enhance treatment outcomes but demonstrates promise for anxiety disorders. Distinct treatment moderators may account for discrepant findings across RCTs and disorders. Future trials may be strengthened by accounting for identified moderators in their design, with ongoing research needed on the mechanisms of D-cycloserine to tailor treatment protocols and maximize its benefit.

Over the past six decades, behavior therapy has been a major contributor to the development of evidence-based psychotherapy treatments. However, a long-standing concern with behavior therapy among many nonbehavioral clinicians has been the potential risk for symptom substitution. Few studies have been conducted to evaluate symptom substitution in response to behavioral treatments, largely due to measurement and definitional challenges associated with treated psychiatric symptoms. Given the overt motor and vocal tics associated with Tourette's disorder, it presents an excellent opportunity to empirically evaluate the potential risk for symptom substitution associated with behavior therapy. The present study examined the possible presence of symptom substitution using four methods: (a) the onset of new tic symptoms, (b) the occurrence of adverse events, (c) change in tic medications, and (d) worsening of co-occurring psychiatric symptoms. Two hundred twenty-eight participants with Tourette's disorder or persistent motor or vocal tic disorders were randomly assigned to receive behavioral therapy or supportive therapy for tics. Both therapies consisted of eight sessions over 10 weeks. Results indicated that participants treated with behavior therapy were not more likely to have an onset of new tic symptoms, experience adverse events, increase tic medications, or have an exacerbation in co-occurring psychiatric symptoms relative to participants treated with supportive therapy. Further analysis suggested that the emergence of new tics was attributed with the normal waxing and waning nature of Tourette's disorder. Findings provide empirical support to counter the long-standing concern of symptom substitution in response to behavior therapy for individuals with Tourette's disorder.

This report examined the most frequently reported bothersome tics among individuals with chronic tic disorders and evaluated the improvement and remission of tics and their associated characteristics. Youths and adults (N = 240) were randomly assigned to receive the comprehensive behavioral intervention for tics (CBIT) or psychoeducation and supportive therapy (PST). At baseline, motor tics and tics with an urge were rated as more bothersome relative to vocal tics and tics without premonitory urges. The five most common bothersome tics included eye blinking, head jerks, sniffing, throat clearing, and other complex motor tics. While CBIT outperformed PST across tic type and urge presence, tics preceded by premonitory urges at baseline had higher severity at posttreatment across treatment condition. Six individual tic types had lower severity at posttreatment following CBIT relative to PST. Baseline urge presence was associated with tic remission for CBIT but not PST. Specific bothersome tics were more likely to remit with CBIT relative to PST. Findings suggest that individual tics respond and remit differently to CBIT relative to PST, with implications highlighting the negative reinforcement hypothesis in tic symptom maintenance. CLINICALTRIALS.Gov identifiersNCT00218777; NCT00231985.

Cluster analytic methods have examined the symptom presentation of chronic tic disorders (CTDs), with limited agreement across studies. The present study investigated patterns, clinical correlates, and treatment outcome of tic symptoms. 239 youth and adults with CTDs completed a battery of assessments at baseline to determine diagnoses, tic severity, and clinical characteristics. Participants were randomly assigned to receive either a comprehensive behavioral intervention for tics (CBIT) or psychoeducation and supportive therapy (PST). A cluster analysis was conducted on the baseline Yale Global Tic Severity Scale (YGTSS) symptom checklist to identify the constellations of tic symptoms. Four tic clusters were identified: Impulse Control and Complex Phonic Tics; Complex Motor Tics; Simple Head Motor/Vocal Tics; and Primarily Simple Motor Tics. Frequencies of tic symptoms showed few differences across youth and adults. Tic clusters had small associations with clinical characteristics and showed no associations to the presence of coexisting psychiatric conditions. Cluster membership scores did not predict treatment response to CBIT or tic severity reductions. Tic symptoms distinctly cluster with little difference across youth and adults, or coexisting conditions. This study, which is the first to examine tic clusters and response to treatment, suggested that tic symptom profiles respond equally well to CBIT. Clinical trials.gov. identifiers: NCT00218777; NCT00231985.

ObjectiveTo compare three statistical strategies for classifying positive treatment response based on a dimensional measure (Yale Global Tic Severity Scale [YGTSS]) and a categorical measure (Clinical Global Impression-Improvement [CGI-I] scale).MethodSubjects (N=232; 69.4% male; ages 9-69years) with Tourette syndrome or chronic tic disorder participated in one of two 10-week, randomized controlled trials comparing behavioral treatment to supportive therapy. The YGTSS and CGI-I were rated by clinicians blind to treatment assignment. We examined the percent reduction in the YGTSS-Total Tic Score (TTS) against Much Improved or Very Much Improved on the CGI-I, computed a signal detection analysis (SDA) and built a mixture model to classify dimensional response based on the change in the YGTSS-TTS.ResultsA 25% decrease on the YGTSS-TTS predicted positive response on the CGI-I during the trial. The SDA showed that a 25% reduction in the YGTSS-TTS provided optimal sensitivity (87%) and specificity (84%) for predicting positive response. Using a mixture model without consideration of the CGI-I, the dimensional response was defined by 23% (or greater) reduction on the YGTSS-TTS. The odds ratio (OR) of positive response (OR=5.68, 95% CI=[2.99, 10.78]) on the CGI-I for behavioral intervention was greater than the dimensional response (OR=2.86, 95% CI=[1.65, 4.99]).ConclusionA 25% reduction on the YGTSS-TTS is highly predictive of positive response by all three analytic methods. For trained raters, however, tic severity alone does not drive the classification of positive response. Clinicaltrials.gov identifiers: NCT00218777; NCT00231985.

BackgroundFibrolamellar carcinoma is a rare and poorly understood malignancy that affects the young in the absence of underlying liver disease. Despite reported small review series, the literature lacks large retrospective studies that may help in understanding this disease.MethodsMedical record review was undertaken for all patients histopathologically diagnosed with fibrolamellar carcinoma, seen at Memorial Sloan-Kettering Cancer Center, the University of California San Francisco, and Johns Hopkins Hospital from 1986 to 2011. Demographic, clinical, pathologic, and treatment data were recorded. Overall survival was estimated by using Kaplan-Meier methods. The impact of different clinicopathologic variables on survival was assessed with Cox regression models.ResultsNinety-five patients were identified. Median age was 22 years, 86% were Caucasian, and 50% presented with stage IV disease. There were more females than males (58% vs. 42%). Seventy-seven percent of the patients underwent surgical resection and/or liver transplantation; of these 31.5% received perioperative therapy. Patients with unresectable disease, including 8 patients treated in clinical trials, were treated with chemotherapy, occasionally given with interferon or biologic agents. Ten patients received sorafenib, and 7 received best supportive care. Median survival was 6.7 years. Factors significantly associated with poor survival were female sex, advanced stage, lymph node metastases, macrovascular invasion, and unresectable disease.ConclusionsThe clinicopathologic characteristics and survival outcomes from this dataset are consistent with those reported in the literature. Surgical resection and disease extent were confirmed as important predictors of survival. The possibility of a negative association between female sex and prognosis could represent a clue as to future therapeutic strategies.

The authors analyzed anesthetic management trends during ventricular tachycardia (VT) ablation, hypothesizing that (1) monitored anesthesia care (MAC) is more commonly used than general anesthesia (GA); (2) MAC uses significantly increased after release of the 2019 Expert Consensus Statement on Catheter Ablation of Ventricular Arrhythmias; and (3) anesthetic approach varies based on patient and hospital characteristics. Retrospective study. National Anesthesia Clinical Outcomes Registry data. Patients 18 years or older who underwent elective VT ablation between 2013 and 2021. None. Covariates were selected a priori within multivariate models, and interrupted time-series analysis was performed. Of the 15,505 patients who underwent VT ablation between 2013 and 2021, 9,790 (63.1%) received GA. After the 2019 Expert Consensus Statement on Catheter Ablation of Ventricular Arrhythmias supported avoidance of GA in idiopathic VT, no statistically significant increase in MAC was evident (immediate change in intercept post-consensus statement release adjusted odds ratio 1.41, p = 0.1629; change in slope post-consensus statement release adjusted odds ratio 1.06 per quarter, p = 0.1591). Multivariate analysis demonstrated that sex, American Society of Anesthesiologists physical status, age, and geographic location were statistically significantly associated with the anesthetic approach. GA has remained the primary anesthetic type for VT ablation despite the 2019 Expert Consensus Statement on Catheter Ablation of Ventricular Arrhythmias suggested its avoidance in idiopathic VT. Achieving widespread clinical practice change is an ongoing challenge in medicine, emphasizing the importance of developing effective implementation strategies to facilitate awareness of guideline release and subsequent adherence to and adoption of recommendations. [ABSTRACT FROM AUTHOR]