Cognitive-Behavioral Therapy Augmentation of SSRI Reduces Cortisol Levels in Older Adults with Generalized Anxiety Disorder: A Randomized Clinical Trial

Objectives: Elevated cortisol in stress and aging, such as has been seen in late-life anxiety disorders, is postulated to accelerate cognitive and physiological decline in this large and increasing population. Selective serotonin-reuptake inhibitors (SSRIs) and cognitive behavior therapy (CBT) are both effective treatments for Generalized Anxiety Disorder (GAD) in older adults. On the other hand, there is very little research examining the effect of combining these therapies on peak cortisol levels. For the current analyses, we examined the effectiveness of CBT augmentation on peak cortisol levels in older adults diagnosed with GAD. Methods: The sample consisted of 42 individuals with late-life GAD who received an acute course of the SSRI escitalopram and then entered a 16-week randomized phase. Twenty-one participants were randomized to receive 16 sessions of CBT in addition to continuing escitalopram and the remaining 21 participants continued on escitalopram without CBT. Generalized Estimating Equations were performed to assess the effectiveness of CBT augmentation on peak cortisol levels (30 minutes after waking). Results: Older adults with GAD who received both escitalopram and CBT demonstrated a significant reduction in peak cortisol levels at post-treatment compared to the group who received escitalopram without CBT augmentation. Conclusions: CBT augmentation of SSRI treatment reduced peak cortisol levels for older adults with GAD. Since persistently high cortisol levels in aging are thought to increase age-related cognitive and medical problems, our findings suggest that there may be a benefit to health and cognition of CBT augmentation for late-life anxiety disorders

Cellular senescence predicts treatment outcome in metastasised colorectal cancer

Background: Cellular senescence is a terminal cell-cycle arrest that occurs in response to activated oncogenes and DNA-damaging chemotherapy. Whether cancer cell senescence at diagnosis might be predictive for treatment outcome is unknown. Methods: A senescence index (SI) was developed and used to retrospectively correlate the treatment outcome of 30 UICC stage IV colorectal cancer (CRC) patients with their SI at diagnosis. Results: 5-Fluorouracil/leucovorin-treated CRC patients achieved a significantly longer progression-free survival when presenting with SI-positive tumours before therapy (median 12.0 vs 6.0 months; P=0.044). Conclusion: Cancer cell senescence predicts treatment outcome in metastasised CRC. Prospective analyses of larger patient cohorts are needed

Elevating Voices, Addressing Depression, Toxic Stress, and Equity through Group Prenatal Care: A pilot study

INTRODUCTION: Elevating Voices, Addressing Depression, Toxic Stress and Equity (EleVATE) is a group prenatal care (GC) model designed to improve pregnancy outcomes and promote health equity for Black birthing people. This article outlines the foundational community-engaged process to develop EleVATE GC and pilot study results. METHODS: We used community-based participatory research principles and the Ferguson Commission Report to guide creation of EleVATE GC. The intervention, designed by and for Black birthing people, centers trauma-informed care, antiracism, and integrates behavioral health strategies into group prenatal care to address unmet mental health needs. Using a convenience sample of patients seeking care at one of three safety-net health care sites, we compared preterm birth, small for gestational age, depression scores, and other pregnancy outcomes between patients in individual care (IC), CenteringPregnancy™ (CP), and EleVATE GC. RESULTS: Forty-eight patients enrolled in the study ( DISCUSSION: Our findings model a systematic approach to design a feasible, patient-centered, community-based, trauma-informed, antiracist intervention. Further study is needed to determine whether EleVATE GC improves perinatal outcomes and promotes health equity

Gene conversion in human rearranged immunoglobulin genes

Over the past 20 years, many DNA sequences have been published suggesting that all or part of the V<sub>H</sub> segment of a rearranged immunoglobulin gene may be replaced in vivo. Two different mechanisms appear to be operating. One of these is very similar to primary V(D)J recombination, involving the RAG proteins acting upon recombination signal sequences, and this has recently been proven to occur. Other sequences, many of which show partial V<sub>H</sub> replacements with no addition of untemplated nucleotides at the V<sub>H</sub>–V<sub>H</sub> joint, have been proposed to occur by an unusual RAG-mediated recombination with the formation of hybrid (coding-to-signal) joints. These appear to occur in cells already undergoing somatic hypermutation in which, some authors are convinced, RAG genes are silenced. We recently proposed that the latter type of V<sub>H</sub> replacement might occur by homologous recombination initiated by the activity of AID (activation-induced cytidine deaminase), which is essential for somatic hypermutation and gene conversion. The latter has been observed in other species, but not in human Ig genes, so far. In this paper, we present a new analysis of sequences published as examples of the second type of rearrangement. This not only shows that AID recognition motifs occur in recombination regions but also that some sequences show replacement of central sections by a sequence from another gene, similar to gene conversion in the immunoglobulin genes of other species. These observations support the proposal that this type of rearrangement is likely to be AID-mediated rather than RAG-mediated and is consistent with gene conversion

Effect of physical activity, social support, and skills training on late-life emotional health: a systematic literature review and implications for public health research

Purpose: Given that emotional health is a critical component of healthy aging, we undertook a systematic literature review to assess whether current interventions can positively affect older adults’ emotional health. Methods: A national panel of health services and mental health researchers guided the review. Eligibility criteria included community-dwelling older adult (aged ≥ 50 years) samples, reproducible interventions, and emotional health outcomes, which included multiple domains and both positive (well-being) and illness-related (anxiety) dimensions. This review focused on three types of interventions – physical activity, social support, and skills training – given their public health significance and large number of studies identified. Panel members evaluated the strength of evidence (quality and effectiveness). Results: In all, 292 articles met inclusion criteria. These included 83 exercise/physical activity, 25 social support, and 40 skills training interventions. For evidence rating, these 148 interventions were categorized into 64 pairings by intervention type and emotional health outcome, e.g., strength training targeting loneliness or social support to address mood. 83% of these pairings were rated at least fair quality. Expert panelists found sufficient evidence of effectiveness only for skills training interventions with health outcomes of decreasing anxiety and improving quality of life and self-efficacy. Due to limitations in reviewed studies, many intervention–outcome pairings yielded insufficient evidence. Conclusion: Skills training interventions improved several aspects of emotional health in community-dwelling older adults, while the effects for other outcomes and interventions lacked clear evidence. We discuss the implications and challenges in moving forward in this important area

D-cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders: a systematic review and meta-analysis of individual participant data

Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance: D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.2018-05-0

Evaluation of pathologic staging using number of nodes in p16-negative head and neck cancer

Objectives: The 8th edition AJCC staging guidelines for head and neck squamous cell carcinoma (HNSCC) recently introduced pathologic staging criteria for nodal disease among p16-positive patients. In this study we evaluate pathologic staging in p16-negative HNSCC. Materials and Methods: We compared pathologic staging to the 7th and 8th edition AJCC staging systems using a statewide population-based cohort. All M0 p16-negative surgical patients were included. The outcome was five-year overall survival. Results: Of 304 patients identified, 113 were N0, 157 had 1–4 positive nodes, and 34 had ≥4 nodes. Survival was 71% (95% CI 61–78%) with no nodes, 48% (36%−60%) for 1–4 nodes, and 24% (11 – 39%) for > 4 nodes. When compared to the AJCC systems, the pathologic staging yielded a larger total survival gradient, more montonic survival, better consistency across primary sites, and a slightly lower Bayesian information criterion (1510 vs 1538). After adjusting for disease characteristics, demographics, and tobacco use, hazard ratios for survival were similar using pathologic and AJCC criteria. Conclusion: In this cohort, pathological staging was more prognostic than AJCC staging. This is the first study to evaluate pathologic staging in p16-negative cancer; if these findings are verified, a universal nodal staging system could be introduced

Socioeconomic status, access to care, risk factor patterns, and stage at diagnosis for head and neck cancer among black and white patients

Background: Little is known about how factors combine to influence progression of squamous cell carcinoma of the head and neck (HNSCC). We aimed to evaluate multidimensional influences of factors associated with HNSCC stage by race. Methods: Using retrospective data, patients with similar socioeconomic status (SES), access to care (travel time/distance), and behavioral risk factors (tobacco/alcohol use and dental care) were grouped by latent class analysis. Relative frequency differences (RFD) were calculated to evaluate latent classes by stage, race, and p16 status. Results: We identified three latent classes. Advanced T-stage was higher for black (RFD = +20.2%; 95% CI: −4.6 to 44.9) than white patients (RFD = +10.7%; 95% CI: 2.1–19.3) in the low-SES/high-access/high-behavioral risk class and higher for both black (RFD = +29.6%; 95% CI: 4.7–54.5) and white patients (RFD = +23.9%; 95% CI: 15.2–32.6) in the low-SES/low-access/high-behavioral risk class. Conclusion: Results suggest that SES, access to care, and behavioral risk factors combine to underly the association with advanced T-stage. Additionally, differences by race warrant further investigation