Separating signal from noise in wastewater data: An algorithm to identify community-level COVID-19 surges in real time.

Wastewater monitoring has provided health officials with early warnings for new COVID-19 outbreaks, but to date, no approach has been validated to distinguish signal (sustained surges) from noise (background variability) in wastewater data to alert officials to the need for heightened public health response. We analyzed 62 wk of data from 19 sites participating in the North Carolina Wastewater Monitoring Network to characterize wastewater metrics around the Delta and Omicron surges. We found that wastewater data identified outbreaks 4 to 5 d before case data (reported on the earlier of the symptom start date or test collection date), on average. At most sites, correlations between wastewater and case data were similar regardless of how wastewater concentrations were normalized and whether calculated with county-level or sewershed-level cases, suggesting that officials may not need to geospatially align case data with sewershed boundaries to gain insights into disease transmission. Although wastewater trend lines captured clear differences in the Delta versus Omicron surge trajectories, no single wastewater metric (detectability, percent change, or flow-population normalized viral concentrations) reliably signaled when these surges started. After iteratively examining different combinations of these three metrics, we developed the Covid-SURGE (Signaling Unprecedented Rises in Groupwide Exposure) algorithm, which identifies unprecedented signals in the wastewater data. With a true positive rate of 82%, a false positive rate of 7%, and strong performance during both surges and in small and large sites, our algorithm provides public health officials with an automated way to flag community-level COVID-19 surges in real time.

Wastewater monitoring can anchor global disease surveillance systems.

To inform the development of global wastewater monitoring systems, we surveyed programmes in 43 countries. Most programmes monitored predominantly urban populations. In high-income countries (HICs), composite sampling at centralised treatment plants was most common, whereas grab sampling from surface waters, open drains, and pit latrines was more typical in low-income and middle-income countries (LMICs). Almost all programmes analysed samples in-country, with an average processing time of 2·3 days in HICs and 4·5 days in LMICs. Whereas 59% of HICs regularly monitored wastewater for SARS-CoV-2 variants, only 13% of LMICs did so. Most programmes share their wastewater data internally, with partnering organisations, but not publicly. Our findings show the richness of the existing wastewater monitoring ecosystem. With additional leadership, funding, and implementation frameworks, thousands of individual wastewater initiatives can coalesce into an integrated, sustainable network for disease surveillance-one that minimises the risk of overlooking future global health threats.

Lower Intent to Comply with COVID-19 Public Health Recommendations Correlates to Higher Disease Burden in Following 30 Days.

OBJECTIVES: We sought to determine whether self-reported intent to comply with public health recommendations correlates with future coronavirus disease 2019 (COVID-19) disease burden. METHODS: A cross-sectional, online survey of US adults, recruited by snowball sampling, from April 9 to July 12, 2020. Primary measurements were participant survey responses about their intent to comply with public health recommendations. Each participant's intent to comply was compared with his or her local COVID-19 case trajectory, measured as the 7-day rolling median percentage change in COVID-19 confirmed cases within participants' 3-digit ZIP code area, using public county-level data, 30 days after participants completed the survey. RESULTS: After applying raking techniques, the 10,650-participant sample was representative of US adults with respect to age, sex, race, and ethnicity. Intent to comply varied significantly by state and sex. Lower reported intent to comply was associated with higher COVID-19 case increases during the following 30 days. For every 3% increase in intent to comply with public health recommendations, which could be achieved by improving average compliance by a single point for a single item, we estimate a 9% reduction in new COVID-19 cases during the subsequent 30 days. CONCLUSIONS: Self-reported intent to comply with public health recommendations may be used to predict COVID-19 disease burden. Measuring compliance intention offers an inexpensive, readily available method of predicting disease burden that can also identify populations most in need of public health education aimed at behavior change.

Developing and testing an automated qualitative assistant (AQUA) to support qualitative analysis.

Qualitative research remains underused, in part due to the time and cost of annotating qualitative data (coding). Artificial intelligence (AI) has been suggested as a means to reduce those burdens, and has been used in exploratory studies to reduce the burden of coding. However, methods to date use AI analytical techniques that lack transparency, potentially limiting acceptance of results. We developed an automated qualitative assistant (AQUA) using a semiclassical approach, replacing Latent Semantic Indexing/Latent Dirichlet Allocation with a more transparent graph-theoretic topic extraction and clustering method. Applied to a large dataset of free-text survey responses, AQUA generated unsupervised topic categories and circle hierarchical representations of free-text responses, enabling rapid interpretation of data. When tasked with coding a subset of free-text data into user-defined qualitative categories, AQUA demonstrated intercoder reliability in several multicategory combinations with a Cohen's kappa comparable to human coders (0.62-0.72), enabling researchers to automate coding on those categories for the entire dataset. The aim of this manuscript is to describe pertinent components of best practices of AI/machine learning (ML)-assisted qualitative methods, illustrating how primary care researchers may use AQUA to rapidly and accurately code large text datasets. The contribution of this article is providing guidance that should increase AI/ML transparency and reproducibility.

Developing a Flexible National Wastewater Surveillance System for COVID-19 and Beyond.

BACKGROUND: Wastewater testing offers a cost-effective strategy for measuring population disease prevalence and health behaviors. For COVID-19, wastewater surveillance addresses testing gaps and provides an early warning for outbreaks. As U.S. federal agencies build a National Wastewater Surveillance System around the pandemic, thinking through ways to develop flexible frameworks for wastewater sampling, testing, and reporting can avoid unnecessary system overhauls for future infectious disease, chronic disease, and drug epidemics. OBJECTIVES: We discuss ways to transform a historically academic exercise into a tool for epidemic response. We generalize lessons learned by a global network of wastewater researchers around validation and implementation for COVID-19 and opioids while also drawing on our experience with wastewater-based epidemiology in the United States. DISCUSSION: Sustainable wastewater surveillance requires coordination between health and safety officials, utilities, labs, and researchers. Adapting sampling frequency, type, and location to threat level, community vulnerability, biomarker properties, and decisions that wastewater data will inform can increase the practical value of the data. Marketplace instabilities, coupled with a fragmented testing landscape due to specialization, may require officials to engage multiple labs to test for known and unknown threats. Government funding can stabilize the market, balancing commercial pressures with public good, and incentivize data sharing. When reporting results, standardizing metrics and contextualizing wastewater data with health resource data can provide insights into a community's vulnerability and identify strategies to prevent health care systems from being overwhelmed. If wastewater data will inform policy decisions for an entire community, comparing characteristics of the wastewater treatment plant's service population to those of the larger community can help determine whether the wastewater data are generalizable. Ethical protocols may be needed to protect privacy and avoid stigmatization. With data-driven approaches to sample collection, analysis, and interpretation, officials can use wastewater surveillance for adaptive resource allocation, pandemic management, and program evaluation. https://doi.org/10.1289/EHP8572.

Predictors and moderators of symptom change during cognitive-behavioral therapy or supportive psychotherapy for body dysmorphic disorder.

BACKGROUND: Research on predictors of treatment outcome in body dysmorphic disorder, a common and severe disorder, is very limited, and no prior studies have examined moderators of outcome. Because treatment is often but not always efficacious, it is important to identify who is more likely to benefit. We examined predictors and moderators of improvement with therapist-delivered cognitive-behavioral therapy versus supportive psychotherapy in the only study of these treatments for body dysmorphic disorder. This report presents secondary analyses from a study whose primary findings have previously been published (Wilhelm et al., 2019). METHODS: Participants (N=120) with DSM-IV body dysmorphic disorder were randomized to therapist-delivered weekly cognitive-behavioral therapy or supportive therapy for 24 weeks. Using reliable and valid measures, we tested baseline body dysmorphic disorder severity, insight/delusionality, and depression severity as predictors and moderators of overall and treatment modality-specific symptom change. We explored additional variables as predictors and moderators of outcome. RESULTS: Greater treatment credibility (p=0.02) and presence of obsessive-compulsive personality disorder (p=0.03) predicted greater improvement. Serotonin-reuptake inhibitor treatment at baseline (unchanged during the study) (p=0.01) predicted less improvement. No other variables predicted or moderated outcome (all p>0.05). LIMITATIONS: The study was not powered a priori to detect predictor or moderation effects, which limited our ability to detect them unless they were strong. CONCLUSIONS: Because greater treatment credibility predicted better outcomes, fostering credibility during therapy may maximize gains. Improvement was not impeded by more severe body dysmorphic disorder, depressive symptoms, or poorer insight. No variables moderated treatment-specific improvement.

Mechanisms of Change in Cognitive Behavioral Therapy for Body Dysmorphic Disorder.

Although cognitive-behavioral therapy (CBT) is highly efficacious for body dysmorphic disorder (BDD), not all patients benefit, and mechanisms underlying response remain unknown. In this first report of the mechanisms underlying improvement with CBT for BDD, we examined whether cognitive (maladaptive beliefs, perfectionism, schemas) and behavioral (checking, grooming, avoidance behaviors) changes mediate the effect of CBT on BDD symptom reduction. Forty-five participants with BDD who enrolled in a CBT for BDD treatment development study were included in two sets of analyses: (1) between-subject mediation of the effect of 12 weeks of CBT versus waitlist, and (2) within-subject mediation of longitudinal change in BDD symptom severity during 24 weeks of CBT. No significant mediators emerged in the between-subject analysis. Checking, grooming, avoidance behaviors, and maladaptive beliefs mediated within-subject improvements over time. Findings suggest that BDD symptom reduction occurs through the very mechanisms that have been hypothesized to maintain BDD in CBT models. Targeting certain cognitive (beliefs about appearance) and behavioral (checking, grooming, and avoidance behaviors) mechanisms in future treatment trials may enhance symptom improvement during CBT. National Clinical Trials Registration Identifier # NCT00106223.

Efficacy and Posttreatment Effects of Therapist-Delivered Cognitive Behavioral Therapy vs Supportive Psychotherapy for Adults With Body Dysmorphic Disorder: A Randomized Clinical Trial.

Importance: Cognitive behavioral therapy (CBT), the best-studied treatment for body dysmorphic disorder (BDD), has to date not been compared with therapist-delivered supportive psychotherapy, the most commonly received psychosocial treatment for BDD. Objective: To determine whether CBT for BDD (CBT-BDD) is superior to supportive psychotherapy in reducing BDD symptom severity and associated BDD-related insight, depressive symptoms, functional impairment, and quality of life, and whether these effects are durable. Design, Setting, and Participants: This randomized clinical trial conducted at Massachusetts General Hospital and Rhode Island Hospital recruited adults with BDD between October 24, 2011, and July 7, 2016. Participants (n = 120) were randomized to the CBT-BDD arm (n = 61) or the supportive psychotherapy arm (n = 59). Weekly treatments were administered at either hospital for 24 weeks, followed by 3- and 6-month follow-up assessments. Measures were administered by blinded independent raters. Intention-to-treat statistical analyses were performed from February 9, 2017, to September 22, 2018. Interventions: Cognitive behavioral therapy for BDD, a modular skills-based treatment, addresses the unique symptoms of the disorder. Supportive psychotherapy is a nondirective therapy that emphasizes the therapeutic relationship and self-esteem; supportive psychotherapy was enhanced with BDD-specific psychoeducation and treatment rationale. Main Outcomes and Measures: The primary outcome was BDD symptom severity measured by the change in score on the Yale-Brown Obsessive-Compulsive Scale Modified for BDD from baseline to end of treatment. Secondary outcomes were the associated symptoms and these were assessed using the Brown Assessment of Beliefs Scale, Beck Depression Inventory-Second Edition, Sheehan Disability Scale, and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form. Results: Of the 120 participants, 92 (76.7%) were women, with a mean (SD) age of 34.0 (13.1) years. The difference in effectiveness between CBT-BDD and supportive psychotherapy was site specific: at 1 site, no difference was detected (estimated mean [SE] slopes, -18.6 [1.9] vs -16.7 [1.9]; P = .48; d growth-modeling analysis change, -0.25), whereas at the other site, CBT-BDD led to greater reductions in BDD symptom severity, compared with supportive psychotherapy (estimated mean [SE] slopes, -18.6 [2.2] vs -7.6 [2.0]; P < .001; d growth-modeling analysis change, -1.36). No posttreatment symptom changes were observed throughout the 6 -months of follow-up (all slope P ≥ .10). Conclusions and Relevance: Body dysmorphic disorder severity and associated symptoms appeared to improve with both CBT-BDD and supportive psychotherapy, although CBT-BDD was associated with more consistent improvement in symptom severity and quality of life. Trial Registration: ClinicalTrials.gov identifier: NCT01453439.

Anxiety Symptoms Questionnaire (ASQ): development and validation.

BACKGROUND: The Anxiety Symptoms Questionnaire (ASQ) is a brief self-report questionnaire which measures frequency and intensity of symptoms and was developed to improve assessment of anxiety symptoms in a clinical setting. We examined the reliability and validity of the ASQ in patients with anxiety disorders and/or depression, non-clinical control subjects and college students. METHODS: 240 outpatients with generalised anxiety disorder, social anxiety disorder, panic disorder or major depressive disorder were administered the ASQ and additional questionnaires measuring depression and anxiety, as were 111 non-clinical control subjects and 487 college students. Factor analysis, Pearson's correlation coefficients and logistic regression were used to assess reliability and validity. Test-retest reliability of the ASQ was measured using a subset who were re-administered the ASQ after 4 weeks. RESULTS: Factor analysis revealed measurement of a single dimension by the ASQ. Internal consistency and test-retest reliability were strong. The ASQ total score also significantly distinguished patients with an anxiety disorder from the clinical controls above and beyond the clinician-rated Hamilton Anxiety Scale. CONCLUSIONS: The ASQ is a valid, reliable and effective self-rated measure of anxiety and may be a useful tool for screening and assessing anxiety symptoms in psychiatric as well as college settings.

Predictors of long-term recovery in anorexia nervosa and bulimia nervosa: Data from a 22-year longitudinal study.

OBJECTIVE: The objective of this study was to investigate predictors of long-term recovery from eating disorders 22 years after entry into a longitudinal study. METHOD: One hundred and seventy-six of the 228 surviving participants (77.2%) were re-interviewed 20-25 years after study entry using the Longitudinal Interval Follow-up Evaluation to assess ED recovery. The sample consisted of 100 women diagnosed with anorexia nervosa (AN) and 76 with bulimia nervosa (BN) at study entry. RESULTS: A comorbid diagnosis of major depression at the start of the study strongly predicted having a diagnosis of AN-Restricting type at the 22-year assessment. A higher body mass index (BMI) at study intake decreased the odds of being diagnosed with AN-Binge Purge type, relative to being recovered, 22 years later. The only predictor that increased the likelihood of having a diagnosis of BN at the 22-year assessment was the length of time during the study when the diagnostic criteria for BN were met. CONCLUSIONS: Together, these results indicate that the presence and persistence of binge eating and purging behaviors were poor prognostic indicators and that comorbidity with depression is particularly pernicious in AN. Treatment providers might pay particular attention to these issues in an effort to positively influence recovery over the long-term.

Examining the Role of Anxiety Sensitivity in Sleep Dysfunction Across Anxiety Disorders.

Anxiety Sensitivity (AS) has been associated with sleep difficulties in certain anxiety disorder populations, but no studies have examined cross-diagnostically the role of anxiety sensitivity in sleep dysfunction. Three hundred one participants with generalized anxiety disorder (GAD), social anxiety disorder (SAD), and panic disorder (PD) completed an ancillary questionnaire-based study. Linear regression was used to examine AS and sleep dysfunction, and mediation analyses were used to examine whether AS was a mediator of the effect of primary diagnosis on sleep. AS was associated with increased sleep dysfunction across anxiety disorders, and primary anxiety disorder diagnosis was significantly associated with sleep dysfunction. However, after controlling for AS, primary diagnosis was no longer significant. AS significantly mediated the effects of PD versus SAD and of PD versus GAD on sleep dysfunction, but did not significantly mediate the effect of GAD versus SAD on sleep dysfunction. Taken together, AS appears to be a more important predictor of sleep dysfunction overall, emphasizing the cross-diagnostic nature of AS and bolstering the RDoC initiative approach for treating psychological dysfunction.

Inflammatory cytokines in major depressive disorder: A case-control study.

INTRODUCTION: There is mixed evidence in the literature on the role of inflammation in major depressive disorder. Contradictory findings are attributed to lack of rigorous characterization of study subjects, to the presence of concomitant medical illnesses, to the small sample sizes, and to the limited number of cytokines tested. METHODS: Subjects aged 18-70 years, diagnosed with major depressive disorder and presenting with chronic course of illness, as well as matched controls ( n = 236), were evaluated by trained raters and provided blood for cytokine measurements. Cytokine levels in EDTA plasma were measured with the MILLIPLEX Multi-Analyte Profiling Human Cytokine/Chemokine Assay employing Luminex technology. The Wilcoxon rank-sum test was used to compare cytokine levels between major depressive disorder subjects and healthy volunteers, before (interleukin [IL]-1ß, IL-6, and tumor necrosis factor-α) and after Bonferroni correction for multiple comparisons (IL-1α, IL-2, IL-3, IL-4, IL-5, IL-7, IL-8, IL-10, IL-12(p40), IL-12(p70), IL-13, IL-15, IFN-γ-inducible protein 10, Eotaxin, interferon-γ, monotype chemoattractant protein-1, macrophage inflammatory protein-1α, granulocyte-macrophage colony-stimulating factor and vascular endothelial growth factor). RESULTS: There were no significant differences in cytokine levels between major depressive disorder subjects and controls, both prior to and after correction for multiple analyses (significance set at p ⩽ 0.05 and p ⩽ 0.002, respectively). CONCLUSION: Our well-characterized examination of cytokine plasma levels did not support the association of major depressive disorder with systemic inflammation. The heterogeneity of major depressive disorder, as well as a potential sampling bias selecting for non-inflammatory depression, might have determined our findings discordant with the literature.

Recovery From Anorexia Nervosa and Bulimia Nervosa at 22-Year Follow-Up.

OBJECTIVE: The course of eating disorders is often protracted, with fewer than half of adults achieving recovery from anorexia nervosa or bulimia nervosa. Some argue for palliative management when duration exceeds a decade, yet outcomes beyond 20 years are rarely described. This study investigates early and long-term recovery in the Massachusetts General Hospital Longitudinal Study of Anorexia and Bulimia Nervosa. METHODS: Females with DSM-III-R/DSM-IV anorexia nervosa or bulimia nervosa were assessed at 9 and at 20 to 25 years of follow-up (mean [SD] = 22.10 [1.10] years; study initiated in 1987, last follow-up conducted in 2013) via structured clinical interview (Longitudinal Interval Follow-Up Evaluation of Eating Disorders [LIFE-EAT-II]). Seventy-seven percent of the original cohort was re-interviewed, and multiple imputation was used to include all surviving participants from the original cohort (N = 228). Kaplan-Meier curves estimated recovery by 9-year follow-up, and McNemar test examined concordance between recovery at 9-year and 22-year follow-up. RESULTS: At 22-year follow-up, 62.8% of participants with anorexia nervosa and 68.2% of participants with bulimia nervosa recovered, compared to 31.4% of participants with anorexia nervosa and 68.2% of participants with bulimia nervosa by 9-year follow-up. Approximately half of those with anorexia nervosa who had not recovered by 9 years progressed to recovery at 22 years. Early recovery was associated with increased likelihood of long-term recovery in anorexia nervosa (odds ratio [OR] = 10.5; 95% CI, 3.77-29.28; McNemar χ²1 = 31.39; P < .01) but not in bulimia nervosa (OR = 1.0; 95% CI, 0.49-2.05; McNemar χ²1 = 0; P = 1.0). CONCLUSION: At 22 years, approximately two-thirds of females with anorexia nervosa and bulimia nervosa were recovered. Recovery from bulimia nervosa happened earlier, but recovery from anorexia nervosa continued over the long term, arguing against the implementation of palliative care for most individuals with eating disorders.

Pharmacotherapy Relapse Prevention in Body Dysmorphic Disorder: A Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: Body dysmorphic disorder is common, distressing, and often severely impairing. Serotonin reuptake inhibitors appear efficacious, but the few existing pharmacotherapy studies were short term (≤4 months), and no relapse prevention studies or continuation phase studies have been conducted to the authors' knowledge. The authors report results from the first relapse prevention study in body dysmorphic disorder. METHOD: Adults (N=100) with DSM-IV body dysmorphic disorder received open-label escitalopram for 14 weeks (phase 1); 58 responders were then randomized to double-blind continuation treatment with escitalopram versus switch to placebo for 6 months (phase 2). Reliable and valid outcome measures were utilized. RESULTS: In phase 1, 67.0% of treated subjects and 81.1% of subjects who completed phase 1 responded to escitalopram. Body dysmorphic disorder severity (in both the intent-to-treat and the completer groups) and insight, depressive symptoms, psychosocial functioning, and quality of life significantly improved from baseline to end of phase 1. In phase 2, time to relapse was significantly longer with escitalopram than with placebo treatment (hazard ratio=2.72, 95% CI=1.01-8.57). Phase 2 relapse proportions were 18% for escitalopram and 40% for placebo. Among escitalopram-treated subjects, body dysmorphic disorder severity significantly decreased over time during the continuation phase, with 35.7% of subjects showing further improvement. There were no significant group differences in body dysmorphic disorder severity or insight, depressive symptoms, psychosocial functioning, or quality of life. CONCLUSIONS: Continuation-phase escitalopram delayed time to relapse, and fewer escitalopram-treated subjects relapsed than did placebo-treated subjects. Body dysmorphic disorder severity significantly improved during 6 additional months of escitalopram treatment following acute response; more than one-third of escitalopram-treated subjects experienced further improvement.

Yoga for generalized anxiety disorder: design of a randomized controlled clinical trial.

Generalized anxiety disorder (GAD) is a common disorder associated with significant distress and interference. Although cognitive behavioral therapy (CBT) has been shown to be the most effective form of psychotherapy, few patients receive or have access to this intervention. Yoga therapy offers another promising, yet under-researched, intervention that is gaining increasing popularity in the general public, as an anxiety reduction intervention. The purpose of this innovative clinical trial protocol is to investigate the efficacy of a Kundalini Yoga intervention, relative to CBT and a control condition. Kundalini yoga and CBT are compared with each other in a noninferiority test and both treatments are compared to stress education training, an attention control intervention, in superiority tests. The sample will consist of 230 individuals with a primary DSM-5 diagnosis of GAD. This randomized controlled trial will compare yoga (N=95) to both CBT for GAD (N=95) and stress education (N=40), a commonly used control condition. All three treatments will be administered by two instructors in a group format over 12 weekly sessions with four to six patients per group. Groups will be randomized using permuted block randomization, which will be stratified by site. Treatment outcome will be evaluated bi-weekly and at 6month follow-up. Furthermore, potential mediators of treatment outcome will be investigated. Given the individual and economic burden associated with GAD, identifying accessible alternative behavioral treatments will have substantive public health implications.

Telomere length and telomerase in a well-characterized sample of individuals with major depressive disorder compared to controls.

BACKGROUND: Leukocyte telomere length (LTL) is a marker of cellular turnover and oxidative stress. Studies suggest major depressive disorder (MDD) is associated with oxidative stress, but examinations of MDD and LTL have yielded mixed results, likely because of differences in measurement methods and unmeasured confounding. This study examined LTL and telomerase activity in 166 individuals with MDD compared to 166 age- and gender-matched matched controls free of any psychiatric disorder, using well-validated assays and clinical assessment methods, and controlling for a range of potential confounders. METHODS: Subjects aged 18 to 70 were evaluated by trained raters and provided blood for LTL and telomerase activity measurement. LTL was assayed using Southern blot and replicated with qPCR, and telomerase activity was assayed with a repeat amplification protocol using a commercial kit. RESULTS: There was no significant difference in telomere length for individuals with MDD [mean (SD)=9.1 (3.0)kbp] compared to controls [mean(SD)=8.9(2.5)kbp] measured by Southern blot (p=0.65) or by confirmatory qPCR (p=0.91) assays. Controlling for potential confounders did not alter the results. Telomerase activity did not differ by MDD diagnosis overall (p=0.40), but the effect of MDD was significantly modified by gender (t(299)=2.67, p=0.0079) even after controlling for potential confounders, with telomerase activity significantly greater only in males with MDD versus controls. CONCLUSION: Our well-characterized, well-powered examination of concurrently assessed telomere length and telomerase activity in individuals with clinically significant, chronic MDD and matched controls failed to provide strong evidence of an association of MDD with shorter LTL, while telomerase activity was higher in men with MDD [corrected].