Background
Pediatric anxiety and depression are prevalent, impairing, and highly comorbid. Available evidence‐based treatments have an average response rate of 60%. One path to increasing response ...may be to identify likely non‐responders midway through treatment to adjust course prior to completing an episode of care. The aims of this study, thus, were to identify predictors of post‐intervention response assessing (a) mid‐treatment symptom severity, (b) session‐by‐session treatment process factors, and (c) a model optimizing the combination of these.
Method
Data were drawn from the treatment arm (N = 95, ages 8–16) of a randomized transdiagnostic intervention trial (Msessions = 11.2). Mid‐point measures of youth‐ and parent‐reported anxiety and depression were collected, and therapists rated homework completion, youth and parent engagement, and youth therapeutic alliance at each session. Logistic regression was used to predict response on the Clinical Global Impression Improvement Scale (CGI‐I ≤2) rated by independent evaluators masked to treatment condition.
Results
Mid‐point symptom measures were significant predictors of treatment response, as were therapist‐ratings of youth and parent engagement, therapeutic alliance, and homework completion. Therapist ratings were significant when tested as mean ratings summing across the first eight sessions of treatment (all ps < .004) and at individual session points (all ps <0.05). A combined prediction model included youth‐reported anxiety, parent‐reported depression, youth engagement at Session 2, and parent engagement at Session 8. This model correctly classified 76.5% of youth as non‐responders and 91.3% as responders at post‐treatment (Nagelkerke R2 = .59, χ2 (4, 80) = 46.54, p < .001).
Conclusion
This study provides initial evidence that response to transdiagnostic intervention for pediatric anxiety and depression may be reliably predicted by mid‐point. These data may serve as foundational evidence to develop adaptive treatment strategies to personalize intervention, correct treatment course, and optimize outcomes for youth with anxiety and depression.
Brief behavioral therapy (BBT) is an efficacious transdiagnostic intervention for pediatric anxiety and depression that targets behavioral avoidance as a key mechanism. It is unknown if change in ...avoidance mediates treatment effects, as theorized. Data on avoidance at baseline and Week 16 were available on 52 youth (ages 8–16 years) from a randomized controlled trial (Weersing, Jeffreys, et al., 2017) comparing BBT and assisted referral to community care (ARC). BBT had significant effects on youth-reported behavioral avoidance, and significant indirect effects on functioning and anxiety, statistically mediated through changes in youth-reported behavioral avoidance. Change in youth-reported avoidance was not a significant mediator of depression. Parent-report of avoidance was not impacted by treatment and was not a significant mediator. Overall, BBT appears to be an effective treatment for targeting behavioral avoidance, which in turn, may improve functioning and lessen anxiety.
https://clinicaltrials.gov; NCT01147614.
•Avoidance may be a key mechanism in the treatment of anxiety and depression.•TransDiagnostic behavioral therapy produces significant changes in youth avoidance.•Changes in avoidance mediate treatment effects on anxiety and functioning.
Assessment and counseling by healthcare providers can successfully increase physical activity; however, a valid instrument to effectively measure physical activity is needed. This study examines the ...validity of the Exercise Vital Sign tool by comparing Exercise Vital Sign data collected at Kaiser Permanente Northwest with accelerometry data.
Participants (n=521) completed accelerometer monitoring and had ≥1 Exercise Vital Sign measurement in their electronic medical record. Using accelerometry as the gold standard, the association between moderate-to-vigorous physical activity minutes per week estimated through Exercise Vital Sign and that estimated through accelerometry was examined using the Spearman correlation coefficient. Comparability of moderate-to-vigorous physical activity categories (inactive, lowly active, moderately active, sufficiently active) was assessed using simple and weighted κ statistics. Sensitivity, specificity, and positive and negative predictive values were calculated. The study was conducted in 2012–2015, with analysis in 2019–2020.
Average accelerometry-based moderate-to-vigorous physical activity was 212 minutes per week, and 57% of the participants were considered sufficiently active. Exercise Vital Sign‒based moderate-to-vigorous physical activity averaged 170 minutes per week, and 53% of the participants were active. There was a positive correlation between the moderate-to-vigorous physical activity minutes per week reported through Exercise Vital Sign and that reported through accelerometry (r =0.38, p<0.0001). A fair agreement was observed between Exercise Vital Sign‒ and accelerometry-based moderate-to-vigorous physical activity categories (weighted κ=0.29), with the highest agreement occurring for those with physical activity level ≥150 minutes per week. The positive correlation increased when moderate-to-vigorous physical activity was examined dichotomously (<150 or ≥150 minutes per week, κ=0.34). The sensitivity, specificity, positive predictive value, and negative predictive value for Exercise Vital Sign (when compared with those of accelerometry) were 67%, 68%, 61%, and 73%, respectively.
The Exercise Vital Sign is a useful physical activity assessment tool that correctly identifies the majority of adults who do and do not meet physical activity guidelines.
All families experience financial and time costs related to caring for their children's health. Understanding the economic burden faced by families of children with chronic health conditions (CHC) is ...crucial for designing effective policies to support families.
In this prospective study we used electronic health records to identify children between 3 and 17 years old with autism spectrum disorder (ASD), asthma, or neither (control) from three Kaiser Permanente regions and several community health centers in the OCHIN network. We oversampled children from racial and ethnic minority groups. Parent/guardian respondents completed surveys three times, approximately four months apart. The surveys included the Family Economic Impact Inventory (measuring financial, time, and employment costs of caring for a child's health), and standardized measures of children's quality of life, behavioral problems, and symptom severity for children with ASD or asthma. We also assessed parenting stress and parent physical and mental health. All materials were provided in English and Spanish.
Of the 1,461 families that enrolled (564 ASD, 468 asthma, 429 control), children were predominantly male (79%), with a mean age of 9.0 years, and racially and ethnically diverse (43% non-Hispanic white; 22% Hispanic; 35% Asian, Black, Native Hawaiian, or another race/ethnicity). The majority of survey respondents were female (86%), had a college degree (62%), and were married/partnered (79%). ASD group respondents were less likely to be employed (73%) than those in the asthma or control groups (both 80%; p = .023). Only 32% of the control group reported a household income ≤ $4,000/month compared with 41% of asthma and 38% of ASD families (p = .006).
Utilizing a novel measure assessing family economic burden, we successfully collected survey responses from a large and diverse sample of families. Drawing upon the conceptual framework, survey measures, and self-report data described herein we will conduct future analyses to examine the economic burdens related to CHC and the incremental differences in these burdens between health groups. This information will help policy makers to design more equitable health and social policies that could reduce the burden on families.
IMPORTANCE: Adolescents whose parents have a history of depression are at risk for developing depression and functional impairment. The long-term effects of prevention programs on adolescent ...depression and functioning are not known. OBJECTIVE: To determine whether a cognitive-behavioral prevention (CBP) program reduced the incidence of depressive episodes, increased depression-free days, and improved developmental competence 6 years after implementation. DESIGN, SETTING, AND PARTICIPANTS: A 4-site randomized clinical trial compared the effect of CBP plus usual care vs usual care, through follow-up 75 months after the intervention (88% retention), with recruitment from August 2003 through February 2006 at a health maintenance organization, university medical centers, and a community mental health center. A total of 316 participants were 13 to 17 years of age at enrollment and had at least 1 parent with current or prior depressive episodes. Participants could not be in a current depressive episode but had to have subsyndromal depressive symptoms or a prior depressive episode currently in remission. Analysis was conducted between August 2014 and June 2015. INTERVENTIONS: The CBP program consisted of 8 weekly 90-minute group sessions followed by 6 monthly continuation sessions. Usual care consisted of any family-initiated mental health treatment. MAIN OUTCOMES AND MEASURES: The Depression Symptoms Rating scale was used to assess the primary outcome, new onsets of depressive episodes, and to calculate depression-free days. A modified Status Questionnaire assessed developmental competence (eg, academic or interpersonal) in young adulthood. RESULTS: Over the 75-month follow-up, youths assigned to CBP had a lower incidence of depression, adjusting for current parental depression at enrollment, site, and all interactions (hazard ratio, 0.71 95% CI, 0.53-0.96). The CBP program’s overall significant effect was driven by a lower incidence of depressive episodes during the first 9 months after enrollment. The CBP program’s benefit was seen in youths whose index parent was not depressed at enrollment, on depression incidence (hazard ratio, 0.54 95% CI, 0.36-0.81), depression-free days (d = 0.34, P = .01), and developmental competence (d = 0.36, P = .04); these effects on developmental competence were mediated via the CBP program’s effect on depression-free days. CONCLUSIONS AND RELEVANCE: The effect of CBP on new onsets of depression was strongest early and was maintained throughout the follow-up period; developmental competence was positively affected 6 years later. The effectiveness of CBP may be enhanced by additional booster sessions and concomitant treatment of parental depression. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT00073671
To report on broad-based outcomes of the Brief Behavioral Therapy (BBT) trial for pediatric anxiety and depression. Secondary data analyses expand on previous reports by assessing diagnostic ...remission and independent functioning, impact on targeted psychopathology, and spillover effects on non-targeted outcomes.
Youth (N = 185; 8-16.9 years; 58% female; 78% White; 21% Hispanic) with anxiety and/or depression were eligible for this multi-site trial. Enrolled youth were randomly assigned to receive 8 to 12 sessions of BBT in primary care or assisted referral to outpatient care (ARC). Assessments were conducted 16 and 32 weeks post randomization.
BBT was superior to ARC on remission of all targeted diagnoses (week 16: 56.8% vs 28.2%, p < .001; week 32: 62.5% vs 38.9%, p = .004), clinician-rated independent functioning (week 16: 75.0% vs 45.7%, p < .001; week 32: 81.2% vs 55.7%, p < .001), and on measures of anxiety, depression, suicide items, total comorbid behavioral and emotional problems, and hyperactivity (d = 0.21-0.49). Moderation analyses revealed superior outcomes for Hispanic youth in BBT vs ARC for diagnostic remission, anxiety, emotional problems, and parent-child conflict. Youth depression at baseline moderated effects on peer problems and parent-child conflict, with effects favoring BBT. Significant main and moderated effects of BBT on change in non-targeted outcomes were largely mediated by change in anxiety (24.2%-49.3% of total effects mediated).
BBT has positive effects on youth, mediated by the strong impact of the intervention on anxiety. Analyses continue to support positive outcomes for Hispanic youth, suggesting that BBT is a broadly effective transdiagnostic treatment option for diverse populations.
Brief Cognitive Behavioral Therapy (CBT) for Pediatric Anxiety and Depression in Primary Care; https://clinicaltrials.gov; NCT01147614.
Health care providers have few alternatives for youth depression other than antidepressants. We examined whether brief cognitive behavioral therapy (CBT) is a viable alternative in primary care.
A ...total of 212 adolescents aged 12 to 18 with major depression who had recently declined or quickly discontinued new antidepressant treatment were randomized to self-selected treatment as usual (TAU) control condition or TAU plus brief individual CBT. Blinded evaluators followed youth for 2 years. The primary outcome was time to major depression diagnostic recovery.
CBT was superior to the control condition on the primary outcome of time to diagnostic recovery from major depression, with number needed to treat from 4 to 10 across follow-up. A similar CBT advantage was found for time to depression diagnosis response, with number needed to treat of 5 to 50 across time points. We observed a significant advantage for CBT on many secondary outcomes over the first year of follow-up but not the second year. Cohen's d effect sizes for significant continuous measures ranged from 0.28 to 0.44, in the small to medium effect range. Most TAU health care services did not differ across conditions, except for psychiatric hospitalizations, which occurred at a significantly higher rate in the control condition through the first year of follow-up.
Observed results were consistent with recent meta-analyses of CBT for youth depression. The initial year of CBT superiority imparted an important clinical benefit and may reduce the risk of future recurrent depression episodes.
A major bottleneck in the development of siRNA therapies is their delivery to the desired cell type or tissue, followed by effective passage across the cell membrane with subsequent silencing of the ...targeted mRNA. To address this problem, we describe the synthesis of core/shell hydrogel nanoparticles (nanogels) with surface-localized peptides that specifically target ovarian carcinoma cell lines possessing high expression levels of the Eph2A receptor. These nanogels are also demonstrated to be highly effective in the noncovalent encapsulation of siRNA and enable cell-specific delivery of the oligonucleotides in serum-containing medium. Cell toxicity and viability assays reveal that the nanogel construct is nontoxic under the conditions studied, as no toxicity or decrease in cell proliferation is observed following delivery. Importantly, a preliminary investigation of gene silencing illustrates that nanogel-mediated delivery of siRNA targeted to the EGF receptor results in knockdown of that receptor. Excellent protection of siRNA during endosomal uptake and endosomal escape of the nanogels is suggested by these results since siRNA activity in the cytosol is required for gene silencing.
Background
Initial and follow-up sexually transmitted infection (STI) and human immunodeficiency virus (HIV) testing are recommended when taking HIV preexposure prophylaxis (PrEP). We assessed STI ...services before and after PrEP initiation among persons 18 years or older.
Methods
We conducted this retrospective cohort study at a US integrated healthcare delivery system. We measured HIV/STI testing rates, STI prevalence and treatment at 3 time points: (1) at PrEP initiation, (2) at 120 days, and (3) at 210 days.
Results
Of 685 PrEP initiators, 67.2% continued PrEP use at 120 days and 49.5% at 210 days. Of PrEP users, HIV and STI testing were greater than 85% and greater than 80%, respectively, at all 3 time points. Prevalence for any chlamydia, rectal chlamydia, and any gonorrhea, rectal gonorrhea, or pharyngeal gonorrhea was always high at the 120 days and 210 days (eg, 6.9%, 10.5%, 6.7%, 5.0%, and 5.2%, respectively, at the 120 days for continuous PrEP users). Over 90% of all individuals who tested positive for chlamydia and gonorrhea received antibiotic pharmacy fills within 7 days at 120 and 210 days. Monthly PrEP-related pharmacy cost was about $2259 to $2659. The proportion of the total medical cost that was PrEP-related pharmacy was about 82% for PrEP continuous users.
Conclusions
Although HIV/STI testing rates were high, they can still be improved during HIV PrEP management. High STI prevalence after PrEP initiation in this study suggests that patients taking PrEP are at risk of acquiring an STI. Interventions to improve STI services during PrEP management are continuously needed.
Abstract A majority of ovarian cancer metastases result from the shedding of malignant cells from the primary tumor into the abdominal cavity. Free-floating cancer cells in serous effusions of ...late-stage ovarian cancer patients may spread to internal organs, making effective treatment extremely difficult. Selective removal of ovarian cancer cells from serous fluids may abate metastasis and improve long-term prognoses. We have already shown that superparamagnetic nanoparticles conjugated to an ephrin-A1 mimetic peptide with a high affinity for the EphA2 receptor can be used to capture and remove cultured human ovarian cancer cells from the peritonea of experimental mice. Here we demonstrate the potential clinical utility of the methodology by in vitro capture and isolation of cancer cells from the ascites fluid of ovarian cancer patients. From the Clinical Editor Ovarian cancer metastases usually are the result of shedding of malignant cells from the primary tumor into the abdominal cavity. In this paper, a novel nanotechnology-based method is demonstrated for the in vitro capture and isolation of cancer cells from the ascites fluid of ovarian cancer patients.
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