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Emily OC Palmer,1 Sheryl Ker,2 Miguel E Rentería,3 Thomas Carmody,4 A John Rush5,6 1Holmusk Europe Ltd, London, UK; 2KKT Technologies, Pte. Ltd, Singapore; 3QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; 4Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA; 5Duke University School of Medicine, Duke University School of Medicine, Durham, NC, USA; 6Clinical sciences, Duke-National University of Singapore, SingaporeCorrespondence: Emily OC Palmer, Holmusk Europe Ltd, 414 Linen Hall, 162-168 Regent St, London, W1B 5TE, UK, Email emily.palmer@holmusk.comPurpose: Major depressive disorder (MDD) is a leading cause of disability worldwide. An accurate assessment of depressive symptomology is crucial for clinical management and research. This study assessed the convergent validity, reliability, and total scale score interconversion across the 9-item Patient Health Questionnaire (PHQ-9) self-report, the 16-item Quick Inventory of Depressive Symptomatology-clinician report (QIDS-C) (two widely used clinical ratings) and the 5-item Very Brief Quick Inventory of Depressive Symptoms-clinician report (VQIDS-C), which evaluate the core features of MDD.Patients and Methods: This study leveraged electronic health record (EHR)-derived, de-identified data from the NeuroBlu Database (Version 23R1), a longitudinal behavioural health real-world platform. Classical Test Theory (CTT) and Item Response Theory (IRT) analyses were used to evaluate the reliability, validity of, and conversions between the scales. The Test Information Function (TIF) was calculated for each scale, with greater test information reflecting higher precision and reliability in measuring depressive symptomology. IRT was also used to generate conversion tables so that total scores on each scale could be compared to the other.Results: The study sample (n = 2,156) had an average age of 36.4 years (standard deviation [SD] = 13.0) and 59.7% were female. The mean depression scores for the PHQ-9, QIDS-C, and VQIDS-C were 12.9 (SD = 6.6), 12.0 (SD = 4.9), and 6.18 (SD = 3.2), respectively. The Cronbach’s alpha coefficients for PHQ-9, QIDS-C, and VQIDS-C were 0.9, 0.8, and 0.7, respectively, suggesting acceptable internal consistency. PHQ-9 (TIF = 30.3) demonstrated the best assessment of depressive symptomology, followed by QIDS-C (TIF = 25.8) and VQIDS-C (TIF = 17.7).Conclusion: Overall, PHQ-9, QIDS-C, and VQIDS-C appear to be reliable and convertible measures of MDD symptomology within a US-based adult population in a real-world clinical setting.Keywords: psychometrics, linking, patient health questionnaire, quick inventory of depressive symptoms, depression, real-world data

Charlotte L Haley,1 Betsy D Kennard,1,2 David W Morris,1 Ira H Bernstein,3 Thomas Carmody,4 Graham J Emslie,1,2 Taryn L Mayes,1 A John Rush5– 7 1Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA; 2Children’s Health, Children’s Medical Center of Dallas, Dallas, TX, USA; 3Department of Psychology, The University of Texas at Arlington, Arlington, TX, USA; 4Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA; 5Department of Psychiatry and Clinical Sciences, Duke-National University of Singapore, Singapore, Singapore; 6Department of Psychiatry and Behavioral Sciences, Texas Tech University – Health Sciences Center, Permian Basin, TX, USA; 7Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USACorrespondence: Betsy D Kennard, University of Texas Southwestern Medical Center, Child Psychiatry, 5323 Harry Hines Blvd, Dallas, TX, 75390-8589, USA, Tel +1 214.645.8680, Fax +1 214.648.3914, Email beth.kennard@utsouthwestern.eduObjective: The current study aimed to evaluate the psychometric features of the Quick Inventory of Depressive Symptomatology, Adolescent version (QIDS-A17) and the clinician-rated Children’s Depression Rating Scale-Revised (CDRS-R).Methods: Altogether, 103 outpatients (8 to 17 years) completed the self-report QIDS-A17-SR. Clinician interviews of adolescents (QIDS-A17-C (Adolescent)) and of parents (QIDS-A17-C (Parent)) were combined to create the QIDS-A17-C(Composite) and the CDRS-R.Results: All QIDS-A17 measures and the CDRS-R evidenced high total score correlations and internal consistency. Factor analysis found all four measures to be unidimensional. Item Response Theory (IRT) analysis found results that complemented the reliability results found in CTT. All four also demonstrated discriminant diagnostic validity based on logistic regression and ANOVA analyses.Conclusion: The psychometric properties of the self-report and composite versions of the QIDS-A17 suggest acceptability as a measure of depression in adolescents either as a measure of depressive symptoms or severity of illness in adolescents. The self-report version may be a helpful tool in busy clinical practices.Keywords: pediatric depression, rating scale, psychometric properties, self-report measures

Soon Nan Wee,1,* Christian Liman,1,* Heidi C Waters,2 Christy R Houle,3 Miguel Renteria,1 Sankha S Mukherjee,1 Subina Surendran,1 Joshua Marcovici,1 Malaak Brubaker,2 Stine Rasmussen Meehan,4 Anne de Jong-Laird,2 A John Rush,5– 7 Joydeep Sarkar1 1Holmusk Technologies, Inc, New York, NY, USA; 2Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, NJ, USA; 3Lundbeck, Deerfield, IL, USA; 4H. Lundbeck A/S, Valby, Denmark; 5Department of Psychiatry, Duke-National University of Singapore, Singapore, Singapore; 6Department of Psychiatry, Duke University School of Medicine, Durham, NC, USA; 7Health Sciences Center, Texas Tech University, Odessa, TX, USA*These authors contributed equally to this workCorrespondence: Heidi C Waters, Otsuka Pharmaceutical Development & Commercialization, Inc, 508 Carnegie Center Drive, Princeton, NJ, 08540, USA, Tel +1 609 535 9626, Email heidi.waters@otsuka-us.comPurpose: Life engagement encompasses concepts such as life fulfillment, well-being, and participation in meaningful activities, encompassing cognitive, physical, social, and emotional dimensions. Patients with MDD experience impaired functioning across multiple domains of life engagement and have ranked concepts related to life engagement and fulfillment as important predictors of treatment success. Post-hoc analyses of three clinical trials of patients with MDD treated adjunctively with brexpiprazole have reported a significantly greater improvement in life engagement. This study investigated improvements in life engagement among patients with MDD following initiation of brexpiprazole treatment using a real-world dataset.Patients and Methods: Information was extracted from semi-structured clinical notes of the Mental Status Examination (MSE) of patients in a real-world setting to develop an outcome measure for quantifying life engagement of psychiatric patients. Measures of life engagement and its four sub-domains (emotional, physical, social, and cognitive) were calculated at each clinical visit for 624 adult patients with MDD during the 6 months following brexpiprazole initiation. Paired t-tests assessed differences between the index event and time periods within 6 months of the index event. Kaplan–Meier survival analyses were used to quantify the improvement in life engagement scores following brexpiprazole initiation.Results: The study identified 54 clinical features associated with life engagement. Statistically significant improvements were observed from as early as 1 month following brexpiprazole initiation, with 20.6%, 37.9%, and 53.9% of the patients demonstrating improved life engagement scores within 1, 3, and 6 months, respectively. The improvements were particularly apparent for the emotional and social sub-domains.Conclusion: The results of this study provide evidence of improved life engagement following brexpiprazole initiation in a real-world dataset.Keywords: brexpiprazole, major depressive disorder, real-world evidence, mental status examination, life engagement

A John Rush,1– 3 Nancy D Madia,4 Thomas Carmody,5 Madhukar H Trivedi6,7 1Department of Psychiatry, Texas Tech University Health Science Center, Midland, TX, USA; 2Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA; 3Duke-National University of Singapore, Singapore; 4Texas Tech University Health Sciences Center Permian Basin, Odessa, TX, USA; 5Department of Population and Data Science, University of Texas Southwestern Medical Center, Dallas, TX, USA; 6Peter O’Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA; 7Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USACorrespondence: Madhukar H Trivedi, Center for Depression Research and Clinical Care, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, 75390-9119, USA, Tel +1 214-648-0188, Fax +1 214-648-0167, Email madhukar.trivedi@utSouthwestern.eduPurpose: Evaluate the psychometric properties of the 5-item Very Quick Inventory of Depressive Symptomatology self-report and clinician-rated versions (VQIDS-SR5/VQIDS-C5), compare their relative performance, create crosswalks between their total scores and other accepted depressive symptom ratings, and define clinically relevant depressive symptom severity thresholds and categorical outcomes for both versions.Patients and Methods: The Sequenced Treatment Alternatives to Relieve Depression trial obtained baseline and exit 17-item Hamilton Rating Scale for Depression (HRSD17) and 30-item Inventory of Depressive Symptomatology – Clinician-rated scores, and baseline and visit-wise QIDS-SR16 and QIDS-C16 ratings from the first treatment step (citalopram). The VQIDS-C5 and the VQIDS-SR5 items (sad mood, self-outlook, involvement, fatigue, psychomotor slowing) (each rated 0– 3), extracted from the corresponding 16-item ratings, were selected to best reflect the 6-item HRSD (HRSD6) (exclusive of anxiety). Classical Test Theory (CTT) and Item-Response Theory (IRT) analyses assessed psychometric features. IRT analyses produced total score crosswalks between the VQIDS5, QIDS-C16, QIDS-SR16 and HRSD6. Clinically relevant VQIDS symptom severity thresholds and treatment outcomes were estimated based on cross-walks from the parent QIDS16 ratings.Results: Both VQIDS versions were unifactorial with acceptable internal consistencies (Cronbach’s alphas > 0.80), item-total correlations (0.57– 0.74) by CCT, and strong IRT item performance. Based on QIDS16 severity thresholds (none 0– 5; mild 6– 10; moderate 11– 15; severe 16– 20; and very severe 21– 27), comparable thresholds were 0– 2; 3– 5; 6– 9; 9– 12; and > 12 for VQIDS-C5, and 0– 2; 2– 5; 6– 8; 9– 12; and > 12 for VQIDS-SR5. Kappa values were acceptable in comparing categories of outcomes (eg, no benefit, remission, etc) based on VQIDS and corresponding QIDS categories.Conclusion: The VQIDS-C5 and VQIDS-SR5 assess selected core depressive symptoms with psychometrically acceptable properties. Theelf-report and clinician-rated versions provide virtually identical information, symptom severity thresholds and symptom change categories. Both are as sensitive to change as the corresponding QIDS16, making them suitable for use in busy practices.Keywords: depression, self-report, psychometrics, rating scales, QIDS, symptoms

Sheryl Ker,1,* Jennifer Hsu,2,* Anisha Balani,1,* Sankha Subhra Mukherjee,1 A John Rush,3– 5 Mehreen Khan,2 Sara Elchehabi,2 Seth Huffhines,2 Dustin DeMoss,2,6 Miguel E Rentería,1 Joydeep Sarkar1 1Holmusk Technologies, Inc., New York, NY, USA; 2John Peter Smith Health Network, Fort Worth, TX, USA; 3Department of Psychiatry, Duke-National University of Singapore (NUS), Singapore; 4Duke University School of Medicine, Durham, NC, USA; 5Texas Tech Health Sciences Center, Odessa, TX, USA; 6University of North Texas Health Science Center/Texas Christian University, Fort Worth, TX, USA*These authors contributed equally to this workCorrespondence: Miguel E Rentería; Joydeep SarkarHolmusk Technologies, Inc., 4th Floor, 54 Thompson St, New York, NY, 10012, USAEmail miguel.renteria@holmusk.com; joydeep.sarkar@holmusk.comPurpose: To describe attrition patterns of opioid use disorder (OUD) patients treated with buprenorphine (BUP) and to assess how clinical, sociodemographic, or BUP medication dosing features are associated with attrition.Patients and Methods: Electronic health records of adults (16+ year-olds) with OUD treated with BUP from 23 different substance use or mental health care programs across 11 US states were examined for one year following BUP initiation in inpatient (IP), intensive outpatient (IOP), or outpatient (OP) settings. Treatment attrition was declared at > 37 days following the last recorded visit. Survival analyses and predictive modelling were used.Results: Retention was consistently 2– 3 times higher following BUP initiation in OP (n = 2409) than in IP/IOP (n = 2749) settings after 2 (50% vs 25%), 6 (27% vs 9%) and 12 months (14% vs 4%). Retention was higher for females, whites (vs blacks), and those with less severe OUD, better global function, or not using non-psychotropic medications. Comorbid substance use, other psychiatric disorders, and the number of psychotropic medications were variously related to retention depending on the setting in which BUP was initiated. Predictive modelling revealed that a higher global assessment of functioning and a smaller OUD severity based on the Clinical Global Impression – Severity led to longer retentions, a higher initial BUP dose led to higher retention in a few cases, an OP setting of BUP initiation led to longer retentions, and a lower total number of psychotropic and non-psychotropic medications led to longer retentions. These were the most important parameters in the model, which identified 75.2% of patients who left BUP treatment within three months post-initiation, with a precision of 90.5%.Conclusion: Of all the OUD patients who began BUP, 50– 75% left treatment within three months, and most could be accurately identified. This could facilitate patient-centered management to better retain OUD patients in BUP treatment.Keywords: opioids, buprenorphine, buprenorphine dosing, treatment engagement, treatment retention, treatment dropout, predictors

Augustus John Rush, 1– 3 Charles South, 4 Shailesh Jain, 1 Raafae Agha, 1 Mingxu Zhang, 1 Shristi Shrestha, 1 Zershana Khan, 1 Mudasar Hassan, 1 Madhukar H Trivedi 5 1Department of Psychiatry, Texas Tech University Health Science Center, Midland, TX, USA; 2Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA; 3Professor Emeritus, Duke-National University of Singapore, Singapore; 4Department of Statistical Science, Southern Methodist University, Dallas, TX, USA; 5Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USACorrespondence: Madhukar H TrivediDepartment of Psychiatry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-9119, USATel +1 214-648-0188Fax +1 214-648-0167Email madhukar.trivedi@utsouthwestern.eduObjective: To develop clinically meaningful improvement thresholds in both the 17-item and the 6-item Hamilton Rating Scale for Depression (HRSD) total scores in depressed outpatients.Methods: The post-hoc analysis included all adult outpatients with non-psychotic major depressive disorder in the STAR*D trial who entered and exited the first treatment step (up to 14 weeks of citalopram) with a complete set of study measures at baseline and exit and at least one post-baseline measure. Within-patient change and linear regression anchor-based analyses were conducted to define meaningful and substantial changes in the HRSD 17 and HRSD 6 using three patient-reported outcomes [Work and Social Adjustment Scale (WSAS), Quality of Life Enjoyment and Satisfaction-Short Form (Q-LES-Q-SF); Mini-Q-LES-Q] obtained at baseline and exit from the first treatment step in STAR*D.Results: Linear regression analyses identified a meaningful change threshold for the HRSD 17 as 3.9 [3.7– 4.1] [lower, upper 95% CI] and a substantial change as 7.8 [7.4– 8.3] with the WSAS. Analogous thresholds based on the Q-LES-Q-SF were 5.8 [5.5– 6.1] and 11.6 [11.0– 12.2], respectively, and 4.9 [4.7– 5.2] and 9.9 [9.3– 10.4] for the Mini-QLES-Q, respectively. For the HRSD 6, linear regression analyses with the WSAS identified a meaningful change as 2.2 [2.1– 2.4], while a substantial change was 4.5 [4.2– 4.7]. Analogous figures based on the Q-LES-Q-SF were 3.2 [3.0– 3.4] and 6.4 [6.1– 6.8]. Similarly, based on the Mini-QLESQ, results were 2.8 [2.6– 2.9] and 5.6 [5.3– 5.9]. For both the HRSD 17 and the HRSD 6, within-patient analyses produced less precise estimates of the same change thresholds with substantial overlap between groups. Based on the WSAS, a clinically meaningful change in the HRSD 17 total score was 9.6 (SD = 6.5), while a substantial change was 15.0 (SD = 6.7). Analogous change thresholds based on the Q-LESQ-SF were 12.9 (SD = 6.2) and 16.8 (SD = 6.4), respectively. For the Mini-Q-LES-Q, thresholds were 10.9 (SD = 6.5) and 16.1 (SD = 6.2).Conclusion: A 4– 6 point change in the HRSD 17 is clinically meaningful; a 7– 12 point change is clinically substantial. For the HRSD 6, analogous estimates were 2– 3 and 4– 7 point changes, respectively.Keywords: depression ratings, patient-reported outcomes, meaningful change

Kristin Martin-Cook,1 Lucy Palmer,1 Larry Thornton,1 A John Rush,2 Carol A Tamminga,1 Hicham M Ibrahim1 1Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA; 2National University of Singapore, Singapore; Department of Psychiatry, Duke University School of Medicine, Durham, NC, USA; Department of Psychiatry, Texas Tech Health Sciences Center, Midland, TX, USACorrespondence: Kristin Martin-CookDepartment of Psychiatry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75235, USATel +1-214-648-1983Fax +1-214-648-4947Email Kristin.Martin-Cook@UTSouthwestern.eduAbstract: Measurement-based care (MBC) involves the systematic use of standardized measurements to inform treatment decisions. MBC can enhance clinical decision-making and quality of care by prompting personalized changes in treatment based on measured patient outcomes. MBC can also promote more precise communications between patients and clinicians around individual patient care. While commonly employed in psychiatric clinical research, the use of MBC in everyday practice can be complicated by clinic operations and variability across patients. We implemented MBC in the UT Southwestern Psychiatry Multispecialty Outpatient Clinic during the expansion of our general psychiatry clinic and subspecialty targeted programs. This article describes the top 10 lessons we learned as we confronted practical obstacles around implementing the ideals of MBC into a pre-existing, busy psychiatric clinical practice and how doing so impacts care, provider engagement, patient engagement, and research opportunity.Keywords: measurement-based care, clinic operations, quality improvement, quality care, screening, outpatient

Fang Liu-Walsh,1 Neena K Tierney,1 James Hauschild,2 Allison K Rush,1 John Masucci,3 Gregory C Leo,3 Kimberly A Capone1 1Johnson & Johnson Consumer Inc., Skillman, NJ, USA; 2Johnson & Johnson Microbiological Quality & Sterility Assurance, Johnson & Johnson Inc., Raritan, NJ, USA; 3Janssen R&D Companies of Johnson & Johnson, Springhouse, PA, USACorrespondence: Fang Liu-Walsh; Kimberly A CaponeJohnson & Johnson Consumer Inc., 199 Grandview Road, Skillman, NJ 08558-9418, USAEmail fliuwals@ITS.JNJ.com; KCapone@its.jnj.comBackground: Multiple skin conditions have been associated with alterations in the diversity and composition of the skin microbiome, including dry skin and atopic dermatitis. In these conditions, a number of commensal skin bacteria have been implicated in supporting a healthy skin barrier, including Staphylococcus epidermidis. Recent clinical studies in patients with mild-to-moderate atopic dermatitis and dry/itchy skin have shown significantly improved skin barrier function and microbial diversity upon treatment with moisturizers containing 1% colloidal oat. We hypothesized that direct use of colloidal oat by skin microbes contributes to these therapeutic benefits.Methods: Skin bacterial growth was assessed using the BacT/ALERT system. Staphylococcus aureus and S. epidermidis growth rates and metabolism were compared in an in vitro competition assay. The effect of a 1% colloidal oat–containing moisturizer on lactic acid content of the stratum corneum was clinically assessed in subjects with moderate-to-severe dry skin. S. epidermidis gene expression was evaluated by next-generation mRNA sequencing. Short-chain fatty acids were quantified in bacterial culture supernatants.Results: In vitro, colloidal oat increased the growth rate of S. epidermidis vs S. aureus, as well as the metabolism of S. epidermidis. Colloidal oat also significantly increased lactic acid concentrations in supernatants of both strains and decreased pH, consistent with clinical findings that 6-week use of a 1% colloidal oat–containing lotion significantly increased lactic acid on dry skin. Further analyses suggest that colloidal oat alters the gene expression profile of S. epidermidis.Conclusion: Colloidal oat directly affects the growth, metabolism, lactic acid production, and gene expression of skin commensal bacteria, as shown via in vitro studies. The increased production of lactic acid reflects clinical observations with colloidal oat–containing skin moisturizers. Our findings suggest a new mechanism for colloidal oat as a skin prebiotic, which may contribute to improvements in skin and microbiome diversity in various skin conditions, including dry/itchy skin and atopic dermatitis.Keywords: atopic dermatitis, dry skin, colloidal oat, skin barrier function, skin microbiome, skin moisturizer, S. epidermidis

PURPOSE: To describe clinical outcomes among patients with benign prostatic hyperplasia (BPH) 24 months following prostatic artery embolization (PAE). MATERIALS AND METHODS: This was an international, multicenter, prospective trial of males with BPH with lower urinary tract symptoms (LUTS) or acute urinary retention (AUR) treated with PAE. The primary outcome was the 12 month change in the International Prostate Symptom Score (IPSS) for patients referred for bothersome LUTS, or urinary catheter independence for patients treated for AUR. Secondary outcome measures included changes in IPSS at 3 and 24 months, changes in quality of life (QoL), changes in the Sexual Health Inventory for Men (SHIM) questionnaire, technical success rate, and adverse events (AEs). Data were summarized using descriptive statistics. RESULTS: Four hundred seventy-eight consecutive patients underwent PAE (bothersome LUTS: N = 405; AUR: N = 73), mean age was 70 years. For patients treated for bothersome LUTS, mean total IPSS at baseline was 21.8 and decreased to 9.3, 10.6, and 11.2 at 3, 12, and 24 months following PAE, respectively (all p

Harold A Sackeim,1 Maxine Dibué,2,3 Mark T Bunker,4 A John Rush5– 7 1Departments of Psychiatry and Radiology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA; 2Department of Neurosurgery, Heinrich Heine University, Düsseldorf, Germany; 3Medical Affairs Europe, LivaNova Deutschland GmbH, Munich, Germany; 4LivaNova USA PLC, Houston, TX, USA; 5Duke-NUS Medical School, Singapore; 6Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA; 7Department of Psychiatry, Texas Tech University, Permian Basin, TX, USACorrespondence: Harold A SackeimDepartments of Psychiatry and Radiology, Vagelos College of Physicians and Surgeons, Columbia University, 2124 Moselem Springs Road, Fleetwood, PA 10522, USATel +1 917 273-5379Email has1@columbia.eduPurpose: The Vagus Nerve Stimulation (VNS) Therapy System has been studied for more than 20 years in patients with severe, treatment-resistant, chronic mood disorder, i.e., difficult-to-treat depression (DTD). This review distills some of the implications of this research for future therapeutic trials in this population.Methods: A narrative review is provided on VNS in DTD. Protocols for a new, large, sham-controlled trial and a global, longitudinal observational study are described.Results: Following encouraging results in open studies, a randomized, masked, sham-controlled trial of VNS for DTD failed to demonstrate an effect on the primary outcome. The negative results may have been partly due to inadequate treatment duration (10 weeks). In long-term observational studies, adjunctive VNS, combined with treatment-as-usual (VNS+TAU), was administered to more than 1100 DTD patients and compared with TAU alone in more than 400 patients. VNS+TAU had superior antidepressant effects, but maximal symptom reduction was often observed after 12 months or longer of stimulation. VNS+TAU had also marked superiority in durability of benefit. Sustained levels of symptom reduction below the traditional cutoff for response (i.e. < 50%) were associated with improved quality of life.Limitations: Most comparisons of VNS+TAU and TAU were derived from observational, open label studies.Conclusion: The history of VNS in DTD has implications for interventional studies in this population, and perhaps other chronic medical disorders. The slow onset of benefit with VNS necessitates considerably longer controlled observation periods to establish efficacy. Durability of benefit should be routinely incorporated in efficacy assessment. New outcome metrics are needed to both categorically identify clinically meaningful benefit and to integrate information on symptom burden over time.Keywords: vagus nerve stimulation, major depressive episode, difficult-to-treat depression, treatment-resistant depression, antidepressant, efficacy, regulatory process

Youth purpose was investigated using a two-phase embedded design with youth participating in Scouts BSA (N = 3,943), ages 9-20 (M = 14.0, SD = 1.9). Participating Scouts were mostly White (91%) and male (98%). In Phase 1, we conducted a two-step cluster analysis on Scouts' survey responses to three purpose dimensions (personal meaning, goal-directedness, beyond-the-self orientation). Four clusters emerged: "Purposeful", "Explorers", "Dreamers", "Nonpurposeful." In Phase 2, we explored qualities of purpose within each cluster and programmatic features and relationships within the scouting context fostering youth purpose with a Scout subsample (N = 30) who completed semi-structured interviews. Results demonstrated that adults supporting scouting, inspiration from older peers, and opportunities to help others and explore new activities supported youth purpose.

Arun Kumar,1 Mark T Bunker,1 Scott T Aaronson,2 Charles R Conway,3 Anthony J Rothschild,4,5 Giacomo Mordenti,6 Augustus J Rush7,8 1LivaNova USA PLC, Houston, TX, USA; 2Department of Clinical Research, Sheppard Pratt Health System, Baltimore, MD, USA; 3Department of Psychiatry, Washington University School of Medicine in St Louis, St Louis, MO, USA; 4Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA, USA; 5Department of Psychiatry, UMass Memorial Medical Center, Worcester, MA, USA; 6LivaNova PLC, London, UK; 7Department of Psychiatry and Behavioral Sciences, National University of Singapore, Singapore; 8Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA Objective: To compare the durations of response achieved with adjunctive vagus nerve stimulation (VNS + TAU) vs treatment as usual (TAU) alone in treatment-resistant depression (TRD) over a 5-year period in the TRD registry. Materials and methods: Data from 271 participants on TAU and 328 participants on VNS + TAU were analyzed. Response was defined as ≥50% decrease in baseline Montgomery–Åsberg Depression Rating Scale (MADRS) score at postbaseline visit and was considered retained until the decrease was