Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Comparing clinical characteristics and treatment outcomes between Veterans and non-Veterans with hoarding disorder

BackgroundBecause Veterans have higher rates of mental health conditions and both physical and mental health comorbidities are known to affect treatment outcomes, the purpose of this investigation was to compare the rates of risk factors for poor hoarding treatment outcomes between Veterans and non-Veterans with hoarding disorder (HD). This is the first study to investigate differences between Veterans and non-Veterans with HD.Material and methodsBaseline data were used from three different treatment studies of adults with hoarding disorder (n = 159). Demographic characteristics, baseline hoarding symptom severity, baseline medical and psychiatric comorbidities, and treatment attrition and response were compared between Veterans and non-Veterans.ResultsVeterans were significantly less likely to be employed than non-Veterans. Veterans did not report significantly more severe hoarding symptoms at baseline when compared to non-Veterans. Veterans reported having a greater mean number of overall medical and psychiatric comorbidities. Veterans were more likely than non-Veterans to meet criteria for major depressive disorder and post-traumatic stress disorder. There was no significant difference in the rate of attrition between Veterans and non-Veterans and Veterans were not significantly more likely to be classified as treatment responders.ConclusionMany similarities were observed between the two groups, including demographic characteristics, hoarding symptom severity, and rates of treatment response. Given that Veterans with HD may suffer from greater medical and psychiatric comorbidities, clinicians should ensure that their clients are receiving adequate medical care and that any other psychiatric comorbidities should be addressed in conjunction for treatment with HD

Group Cognitive Rehabilitation and Exposure/Sorting Therapy: A Pilot Program

While cognitive-behavioral therapy for hoarding disorder (HD) has resulted in significant reductions in symptoms, most individuals continue to have significant hoarding symptoms following treatment. This investigation sought to extend the literature on the behavioral treatments for hoarding by examining (1) group cognitive rehabilitation and exposure/sorting therapy (CREST) and (2) group exposure therapy (ET) for hoarding. Participants in both studies reported significant decreases in hoarding symptom severity from baseline to post-treatment on all primary outcome measures using mixed-effects linear regression models with the intent to treat sample. Participants who received group CREST reported statistically significant reductions in anxiety, depression, and overall severity at post-treatment, while participants who received group ET did not. Results provide preliminary evidence for both group CREST and group ET as effective treatments for hoarding disorder

Cognitive Rehabilitation and Exposure/Sorting Therapy (CREST) for Hoarding Disorder in Older Adults: A Randomized Clinical Trial.

ObjectiveTo compare the efficacy of Cognitive Rehabilitation and Exposure/Sorting Therapy (CREST) with geriatric case management (CM) in a sample of older adults meeting DSM-5 diagnostic criteria for hoarding disorder (HD).MethodsFifty-eight older adults with HD were enrolled in a randomized controlled trial between December 2011 and March 2014. Thirty-one participants received CREST, and 27 participants received CM. Both interventions consisted of 26 individual sessions over a period of 6 months and included several home visits by the study therapists (CREST) or nurses (CM). The Saving Inventory-Revised (SI-R) and the UCLA Hoarding Severity Scale (UHSS) were the main outcome measures.ResultsParticipants in the CREST condition had significantly greater improvement on the SI-R than participants in the CM group (group × time interaction: β = 3.95, SE = 1.81, P = .029), with participants who completed the CREST condition averaging a 38% decrease in symptoms and participants who completed the CM condition averaging a 25% decrease in symptoms. In contrast, there was not a significant group × time interaction effect on the UHSS (β = 1.23, SE = 0.84, P = .144), although participants did report greater improvement in symptoms in the CREST condition (35%) than in the CM condition (24%). Treatment gains were maintained at 6-month follow-up.ConclusionsCREST appears to be an efficacious treatment compared to CM for older adults, but CM also showed meaningful benefits.Trial registrationClinicalTrials.gov identifier: NCT01227057​

Recent Advances in Research on Hoarding

Purpose of reviewThe purpose of the following paper is to review recent literature trends and findings in hoarding disorder (HD). Our goal is to highlight recent research on etiology, associated features, and empirically based treatments.Recent findingsRecent literature has added support for cognitive differences as a risk factor for HD; however, there is evidence that individuals with HD may overestimate their level of cognitive impairment. Several associated features have been highlighted in recent studies, including emotion regulation, intolerance of uncertainty and distress intolerance, and attachment. Finally, several psychotherapeutic treatments for hoarding have been recently validated, including group-based therapy and treatments using the cognitive-behavioral model. Although recent research demonstrates that hoarding can be effectively treated with available psychotherapeutic modalities, the effectiveness of current treatments is not as robust as that for other psychiatric disorders and more work is needed in treatment precision

Implementation and evaluation of a community-based treatment for late-life hoarding

ObjectivesThe objective of this paper was to examine the implementation and effectiveness of a community-based intervention for hoarding disorder (HD) using Cognitive Rehabilitation and Exposure/Sorting Therapy (CREST).DesignThis was a mixed-method, pre-post quasi-experimental study informed by the Practical, Robust Implementation and Sustainability Model for implementation science.SettingProgram activities took place in San Diego County, mainly within clients' homes or community, with some activities in-office.ParticipantsParticipants were aged 60 years or older, met eligibility for Medi-Cal or were uninsured, and met criteria for HD.InterventionA manualized, mobile protocol that incorporated CREST was utilized.MeasurementsThe Clutter Image Rating and Hoarding Rating Scale were used as effectiveness outcomes. An investigator-created staff questionnaire was used to evaluate implementation.ResultsThirty-seven clients were reached and enrolled in treatment and 15 completed treatment during the initial 2 years of the program. There were significant changes in hoarding severity and clutter volume. Based on the initial 2 years of the program, funding was provided for expansion to cover additional San Diego County regions and hire more staff clinicians in year three.ConclusionPreliminary data suggest that the CREST intervention can be successfully implemented in a community setting with positive results for older adults with HD

Depressive symptoms and clinical status during the Treatment of Adolescent Suicide Attempters (TASA) Study

To examine the course of depression during the treatment of adolescents with depression who had recently attempted suicide. Adolescents (N = 124), ages 12 to 18 years, with a 90-day history of suicide attempt, a current diagnosis of depressive disorder (96.0% had major depressive disorder), and a Children's Depression Rating Scale-Revised (CDRS-R) score of 36 or higher, entered a 6-month treatment with antidepressant medication, cognitive-behavioral therapy focused on suicide prevention, or their combination (Comb), at five academic sites. Treatment assignment could be either random or chosen by study participants. Intent-to-treat, mixed effects regression models of depression and other relevant ratings were estimated. Improvement and remission rates were computed with the last observation carried forward. Most patients (n = 104 or 84%) chose treatment assignment, and overall, three fourths (n = 93) received Comb. In Comb, CDRS-R declined from a baseline adjusted mean of 49.6 (SD 12.3) to 38.3 (8.0) at week 12 and to 27.0 (10.1) at week 24 (p < .0001), with a Clinical Global Impression -defined improvement rate of 58.0% at week 12 and 72.2% at week 24 and a remission (CDRS-R ≤ 28) rate of 32.5% at week 12 and 50.0% at week 24. The CDRS-R and the Scale for Suicidal Ideation scores were correlated at baseline (r = 0.43, p < .0001) and declined in parallel. When vigorously treated with a combination of medication and psychotherapy, adolescents with depression who have recently attempted suicide show rates of improvement and remission of depression that seem comparable to those observed in nonsuicidal adolescents with depression