Search

Objectives: Approximately 10 million Americans experience acts of physical violence by an intimate partner (IPV). Ocular injuries can present as a symptom of IPV in the emergency department, but IPV remains underreported in the literature. Understanding the incidence and trends in IPV-associated ocular injuries in the emergency department could increase the detection of at-risk patients otherwise overlooked., Design: Retrospective chart review., Participants: Emergency department patients evaluated for traumatic ocular injuries between January 2018 and April 2023 at a large tertiary care health system., Methods: The study population was identified by ICD-10 code and their responses to being screened at triage for home safety and any nursing concerns for abuse or neglect. Patient screening consisted of a 2-part questionnaire inquiring first about whether the patient feels safe at home ("Yes" or "No") and second regarding nurses' concerns for abuse, neglect, domestic violence, sexual assault, or human trafficking., Results: There were 2,653,993 emergency department visits and 16,737 traumatic ocular injuries in the study period. Of them, 1.1% of patients (154 of 14,457) responded "No" to feeling safe at home. In only 0.6% of patients (82 of 14,457), a nursing concern was documented. Patients responding "No" to feeling safe at home presented with more severe ocular injuries such as maxillary fractures. On regression analysis, married, divorced, and widowed patients as well as patients on private insurance were less likely to report feeling unsafe at home than single patients on public insurance (p < 0.05)., Conclusion: Traumatic ocular injuries in emergency departments should raise concerns about IPV. Opportunity exists to improve education, screening, and management of these patients., (Copyright © 2023 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Background: Participants who received ketamine at the NIMH were among the first to receive ketamine for depression in controlled clinical trials, providing a unique opportunity to assess long-term outcomes. This analysis evaluated the relationship between participating in a ketamine clinical trial and subsequent ketamine/esketamine use after leaving the research setting., Methods: Participants seen within the NIMH Experimental Therapeutics and Pathophysiology Branch from 2002 to 2022 (n = 1000) were contacted for follow-up assessment. Participants reported whether they had used ketamine/esketamine, sought non-prescribed ketamine, attempted suicide, or been psychiatrically hospitalized since discharge. Information regarding their recent depressive symptoms, dissociative symptoms, and hallucinations was also collected., Results: Of the 203 participants in follow-up assessments (55 % female, average time since leaving NIMH = 9.04 years), 52 (25.6 %) had originally received ketamine at the NIMH, and the rest had participated in non-ketamine studies. Individuals who had received ketamine at the NIMH were more likely to have received ketamine/esketamine post-discharge than those who did not receive ketamine at the NIMH (OR = 0.25, p < .001). Participants who reported using ketamine/esketamine post-discharge reported more depressive symptoms than those who had not (p < .001). Receiving ketamine at the NIMH was not associated with differences in suicide attempts, psychiatric hospitalizations, dissociation, hallucinations, or attempt to obtain non-prescribed ketamine., Limitations: Low follow-up study participation rate; varying time since discharge., Conclusions: Participants who received ketamine in an NIMH clinical trial were more likely to receive ketamine/esketamine post-discharge, but none reported symptoms indicating abuse. Results underscore the critical need for long-term follow-up of individuals receiving these and other rapid-acting antidepressants., Clinical Trials Identifier: NCT04877977., Competing Interests: Declaration of competing interest Dr. Zarate is listed as a co-inventor on a patent for the use of ketamine in major depression and suicidal ideation; as a co-inventor on a patent for the use of (2R,6R)-hydroxynorketamine, (S)-dehydronorketamine, and other stereoisomeric dehydroxylated and hydroxylated metabolites of (R,S)-ketamine metabolites in the treatment of depression and neuropathic pain; and as a co-inventor on a patent application for the use of (2R,6R)-hydroxynorketamine and (2S,6S)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorders. He has assigned his patent rights to the U.S. government but will share a percentage of any royalties that may be received by the government. All other authors have no conflict of interest to disclose, financial or otherwise., (Published by Elsevier B.V.)

Objectives: This study aims to compare emergency department (ED) utilization and admission rates for patients with a history of mental health (MH) disorders, substance use disorders (SUDs), and social determinants of health (SDOH) before and after implementing COVID-19 shelter-in-place (SIP) orders., Methods: This was a retrospective, multicenter study leveraging electronic medical record (EMR) data from 20 EDs across a large Midwest integrated healthcare system from 5/2/2019 to 12/31/2019 (pre-SIP) and from 5/2/2020 to 12/31/2020 (post-SIP). Diagnoses were documented in the patient's medical records. Poisson and logistic regression models were used to evaluate ED utilization and admission rate changes., Results: A total of 871,020 ED encounters from 487,028 unique patients were captured. Overall, 2,572 (0.53%) patients had a documented Z code for SDOH. Patients with previously diagnosed MH disorders or SUDs were more likely to seek ED care after the SIP orders were implemented (risk ratio (RR): 1.20, 95% confidence interval (CI): 1.18-1.22, p<0.001), as were patients with SDOH (RR: 2.37, 95% CI: 2.19-2.55, p<0.001). Patients with both previously diagnosed MH disorders or SUDs and a documented SDOH had even higher ED utilization (RR: 3.31, 95% CI: 2.83-3.88, p<0.001) than those with either condition alone. Patients with MH disorders and SUDs (OR: 0.89, 95% CI: 0.86-0.92, p<0.001) or SDOH (OR: 0.67, 95% CI: 0.54-0.83, p<0.001) were less likely to be admitted post-SIP orders, while patients with a history of diseases of physiologic systems were more likely to be admitted., Conclusion: Vulnerable populations with a history of MH disorders, SUDs, and SDOH experienced increased ED utilization but a lower rate of hospital admissions after the implementation of SIP orders. The findings highlight the importance of addressing these needs to mitigate the impact of public health crises on these populations., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Wang et al.)

Introduction: Behavioral measurement-based care (MBC) can improve patient outcomes and has also been advanced as a critical learning health system (LHS) tool for identifying and mitigating potential disparities in mental health treatment. However, little is known about the uptake of remote behavioral MBC in safety net settings, or possible disparities occurring in remote MBC implementation., Methods: This study uses electronic health record data to study variation in completion rates at the clinic and patient level of a remote MBC symptom measure tool during the first 6 months of implementation at three adult outpatient psychiatry clinics in a safety net health system. Provider-reported barriers to MBC adoption were also measured using repeated surveys at one of the three sites., Results: Out of 1219 patients who were sent an MBC measure request, uptake of completing at least one measure varied by clinic: General Adult Clinic, 38% (n = 262 of 696); Substance Use Clinic, 28% (n = 73 of 265); and Transitions Clinic, 17% (n = 44 of 258). Compared with White patients, Black and Portuguese or Brazilian patients had lower uptake. Older patients also had lower uptake. Spanish language of care was associated with much lower uptake at the patient level. Significant patient-level disparities in uptake persisted after adjusting for the clinic, mental health diagnoses, and number of measure requests sent. Providers cited time within visits and bandwidth in their workflow as the greatest consistent barriers to discussing MBC results with patients., Conclusions: There are significant disparities in MBC uptake at the patient and clinic level. From an LHS data infrastructure perspective, safety net health systems may need to address the need for possible ways to adapt MBC to better fit their populations and clinical needs, or identify targeted implementation strategies to close data gaps for the identified disparity populations., Competing Interests: The authors have no conflicts of interest with the work described., (© 2024 The Authors. Learning Health Systems published by Wiley Periodicals LLC on behalf of University of Michigan.)

Background: Hospitalization and mortality in patients with alcohol-associated hepatitis (AH), a severe form of liver disease, continue to increase over time. Given the severity of the illness, most hospitalized patients with AH are admitted from the emergency department (ED). However, there are no data on ED utilization by patients with AH. Thus, the Nationwide Emergency Department Sample (NEDS) dataset was analyzed to determine the ED utilization for AH., Methods: Temporal trends (2016-2019) and outcomes of ED visits for AH were determined. Primary or secondary AH diagnoses were based on coding priority. Numbers of patients evaluated in the ED, severity of disease, complications of liver disease, and discharge disposition were analyzed. Crude and adjusted rates were examined, and temporal trends evaluated using logistic regression with orthogonal polynomial contrasts for each year., Results: There were 466,014,370 ED visits during 2016-2019, of which 448,984 (0.096%) were for AH, 85.0% of which required hospitalization. The rate of visits for AH (primary and secondary) between 2016 and 2019 increased from 85 to 106.8/100,000 ED visits. The rate of secondary AH increased more than the rate of primary AH (from 68.6 to 86.5 vs. from 16.4 to 20.3/100,000 ED visits). Patients aged 45-64 years had the highest rate of ED visits for AH, which decreased during the study period, while the rate of ED visits for AH increased in those aged 25-44 years (from 38.5% to 42.9%). The severity of disease (ascites, hepatic encephalopathy, and acute kidney injury) also increased over time. Medicaid and private insurance were the most common payors for patients seeking care in the ED for AH., Conclusions: Temporal trends show an overall increase in ED utilization rates for AH, more patients requiring hospitalization, and an increase in the proportion of younger patients presenting to the ED with AH., (© 2023 Research Society on Alcohol.)

Objectives: Little contemporary research has explored phencyclidine (PCP) use in people with alcohol use disorder. Therefore, we sought to determine the prevalence of PCP positivity on urine toxicology screening among patients admitted for alcohol withdrawal, identify correlates of PCP positivity, and investigate PCP positivity's relationship to length of stay (LOS) and risk of facility readmission., Methods: This was a retrospective study of patients admitted to a dual-diagnosis medically assisted withdrawal unit for alcohol withdrawal from 2014 to 2019. Univariate tests and logistic regression were used to investigate potential correlates of PCP positivity on admission toxicology screening (primary outcome). Multivariable linear regression models and survival analyses analyzing LOS and risk of readmission (secondary outcomes) were also developed., Results: Ninety of 3731 patients (2.4%) screened positive for PCP. There were significant associations on univariate testing between PCP positivity and age, race, homeless status, and urine toxicology positivity for amphetamines, benzodiazepines, barbiturates, cocaine, tetrahydrocannabinol, and oxycodone. On multivariate logistic regression, only tetrahydrocannabinol, barbiturates, and cocaine positivity were associated with PCP positivity. Multivariate logistic regression and survival analysis found no statistically significant associations between PCP positivity and LOS or risk of readmission., Conclusions: This study provides rare analysis of contemporary data on PCP use among patients undergoing medically assisted alcohol withdrawal. Phencyclidine positivity was uncommon, but use appears considerably higher among this patient population than the general population. There was no significant association between PCP positivity and LOS or readmission risk., Competing Interests: BSB is on the advisory board of CB Therapeutics and has stock options. He has also received monetary compensation for editorial work for DynaMed Plus (EBSCO Industries, Inc.) and consulting for Cerebral. The other authors report no potential conflicts of interest., (Copyright © 2023 American Society of Addiction Medicine.)

Background: The COVID-19 pandemic involved a prolonged period of collective trauma and stress during which substantial increases in mental health concerns, like depression and anxiety, were observed across the population. In this context, CHAMindWell was developed as a web-based intervention to improve resilience and reduce symptom severity among a public health care system's patient population., Objective: This program evaluation was conducted to explore participants' engagement with and outcomes from CHAMindWell by retrospectively examining demographic information and mental health symptom severity scores throughout program participation., Methods: We examined participants' symptom severity scores from repeated, web-based symptom screenings through Computerized Adaptive Testing for Mental Health (CAT-MH) surveys, and categorized participants into symptom severity-based tiers (tier 1=asymptomatic to mild; tier 2=moderate; and tier 3=severe). Participants were provided tier-based mindfulness resources, treatment recommendations, and referrals. Logistic regressions were conducted to evaluate associations between demographic variables and survey completion. The McNemar exact test and paired sample t tests were performed to evaluate changes in the numbers of participants in tier 1 versus tier 2 or 3 and changes in depression, anxiety, and posttraumatic stress disorder severity scores between baseline and follow-up., Results: The program enrolled 903 participants (664/903, 73.5% female; 556/903, 61.6% White; 113/903, 12.5% Black; 84/903, 9.3% Asian; 7/903, 0.8% Native; 36/903, 4% other; and 227/903, 25.1% Hispanic) between December 16, 2020, and March 17, 2022. Of those, 623 (69%) completed a baseline CAT-MH survey, and 196 completed at least one follow-up survey 3 to 6 months after baseline. White racial identity was associated with completing baseline CAT-MH (odds ratio [OR] 1.80, 95% CI 1.14-2.84; P=.01). Participants' odds of having symptom severity below the clinical threshold (ie, tier 1) were significantly greater at follow-up (OR 2.60, 95% CI 1.40-5.08; P=.001), and significant reductions were observed across symptom domains over time., Conclusions: CHAMindWell is associated with reduced severity of mental health symptoms. Future work should aim to address program engagement inequities and attrition and compare the impacts of CHAMindWell to a control condition to better characterize its effects., (©Joseph A Rosansky, Kayley Okst, Miriam C Tepper, Ana Baumgart Schreck, Carl Fulwiler, Philip S Wang, Zev Schuman-Olivier. Originally published in JMIR Mental Health (https://mental.jmir.org), 26.10.2023.)

Background: Approximately one third of individuals with major depressive disorder have treatment-resistant depression (TRD). Glutamatergic modulators such as the N -methyl- d -aspartate receptor antagonist ketamine have rapid and robust antidepressant effects, but their use has been limited by accessibility and route of administration. This open-label pilot study assessed the adjunctive antidepressant efficacy of dextromethorphan/quinidine (DM/Q) in TRD., Methods: Inpatients with TRD (n = 17, 40.8 ± 12.3 years; 9 females/8 males) received adjunctive open-label DM/Q (20 mg/10 mg) up to 3 times daily. The study had no set endpoint; participants were followed until they discontinued DM/Q or were discharged. Montgomery-Asberg Depression Rating Scale (MADRS) scores were obtained at baseline (before DM/Q administration) and regularly during hospitalization. Full response was defined as a ≥50% reduction in baseline MADRS score, partial response as a 25% to 50% decrease in baseline MADRS score, and nonresponse as a <25% reduction or an increase in baseline MADRS score., Results: The 17 inpatients received open-label DM/Q for 5.1 ± 2.7 weeks. Forty-seven percent of participants responded to DM/Q-12% achieved a full response and 35% achieved a partial response. The largest MADRS difference observed at any time point was -6.4 ± 8.4 (-21.0% ± 29.9%), and the MADRS difference observed at time of DM/Q discontinuation or hospital discharge was -4.8 ± 8.4 (-15.9% ± 29.7%). Twenty-four percent of participants experienced a nonserious adverse event; none experienced a serious adverse event., Conclusions: In this open-label pilot study, 47% of participants responded to adjunctive DM/Q, which was well tolerated. Larger placebo-controlled trials are needed to determine the real-world efficacy of DM/Q., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Achieving population behavioral health is urgently needed. The mental health system struggles with enormous challenges of providing access to mental health services, improving quality and equitability of care, and ensuring good health outcomes across subpopulations. Little data exists about increasing access within highly constrained resources, staging/sequencing treatment along care pathways, or personalizing treatments. The conceptual model of the learning healthcare system offers a potential paradigm shift for addressing these challenges. In this article we present an overview of how the three constructs of population health, learning health systems, and measurement-based care are inter-related, and we provide an example of how one academic, community-based, safety net health system is approaching integrating these paradigms into its service delivery system. Implementation outcomes will be described in a subsequent publication. We close by discussing how ultimately, to meaningfully improve population behavioral health, a learning healthcare system could expand into a learning health community in order to target critical points of prevention and intervention., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Comorbidity of psychiatric and medical illnesses among older adult populations is highly prevalent and associated with adverse outcomes. Care management is a common form of outpatient support for both psychiatric and medical conditions in which assessment, care planning, and care coordination are provided. Although care management is often remote and delivered by telephone, the evidence supporting this model of care is uncertain., Objective: To perform a systematic review of the literature on remote care management programs for older adult populations with elevated prevalence of depression or anxiety and comorbid chronic medical illness., Methods: A systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A multidatabase search was performed. Articles were included for review if they studied fully remote care management for older adult populations with elevated prevalence of depression or anxiety and chronic medical illness or poor physical health. A narrative synthesis was performed., Results: A total of 6 articles representing 6 unique studies met inclusion criteria. The 6 studies included 4 randomized controlled trials, 1 case-matched retrospective cohort study, and 1 pre-post analysis. Two studies focused on specific medical conditions. All interventions were entirely telephonic. Five of 6 studies involved an intervention that was 3 to 6 months in duration. Across the 6 studies, care management demonstrated mixed results in terms of impact on psychiatric outcomes and limited impact on medical outcomes. No studies demonstrated a statistically significant impact on health care utilization or cost., Conclusions: Among older adult populations with elevated prevalence of depression or anxiety and comorbid chronic medical illness, remote care management may have favorable impact on psychiatric symptoms, but impact on physical health and health care utilization is uncertain. Future research should focus on identifying effective models and elements of remote care management for this population, with a particular focus on optimizing medical outcomes., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Psychiatric and medical comorbidities are common among adults in the United States. Due to the complex interplay between medical and psychiatric illness, comorbidities result in substantial disparities in morbidity, mortality, and health care costs. There is, thus, both an ethical and fiscal imperative to develop care management programs to address the needs of individuals with comorbid conditions. Although there is substantial evidence supporting the use of care management for improving health outcomes for patients with chronic diseases, the majority of interventions described in the literature are condition-specific. Given the prevalence of comorbidities, the authors of this article reviewed the literature and drew on their clinical expertise to guide the development of future multimorbidity care management programs. Their review yielded one study of multimorbidity care management and two studies of multimorbidity collaborative care. The authors supplemented their findings by describing three key pillars of effective care management, as well as specific interventions to offer patients based on their psychiatric diagnoses and illness severity. The authors proposed short-, medium-, and long-term indicators to measure and track the impact of care management programs on disparities in care. Future studies are needed to identify which elements of existing multimorbidity collaborative care models are active ingredients, as well as which of the suggested supplemental interventions offer the greatest value.

Background: Both traumatic and nontraumatic ocular issues often present to the emergency department. Understanding the epidemiology of ocular presentations to the emergency department not only informs current resource allocation, but also provides opportunities to evaluate the efficacy of prior healthcare access interventions., Purpose: To characterize emergency department utilization in the United States for ophthalmic encounters between 2010 and 2018., Methods: Cross-sectional analysis of the National Hospital Ambulatory Medical Care Survey database, a nationally representative sample of United States emergency department visits. 4284 deidentified emergency department patient encounters with an ICD-10 ophthalmic diagnosis from 2010 to 2018 were analyzed. The main outcome measures were the composition and characteristics of ophthalmic emergency department encounters over time., Main Findings: 4284 ophthalmic visits were identified which represented an estimated 23.1 million visits (95% CI, 20.8 million-25.5 million). 31.6% (95% CI, 29.6-33.8) of ophthalmic visits were traumatic. Conjunctivitis was the most common non-traumatic diagnosis (32.8%, 95% CI, 30.7-35.0), while superficial injury of the cornea was the most common traumatic diagnosis (13.9%, 95% CI, 12.5-15.3). A greater proportion of emergency department visits involving the sclera and cornea were made by men (58.7%, 95% CI, 53.7%-63.6%; P = 0.02), whereas more women visited for visual disturbances (57.8%, 95% CI, 51.3%-64.4%; P = 0.01). Longitudinal trends of ophthalmic visits revealed an increase in public insurance payers in 2014, which corresponds to Medicaid expansion and implementation of mandated coverage for pediatric vision care. After stratification, this increase continued to be present in nontraumatic visits, but not traumatic ones., Conclusions: Ophthalmic emergency department visits in the United States between 2010 and 2018 were typically for non-traumatic eye issues. Diagnoses varied greatly by patient demographics, such as age and gender. Understanding these variations is valuable for preparing emergency departments for ocular presentations and providing guidance for future practice., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The COVID-19 pandemic has been expected to lead to substantial increases in need for behavioral health care. A population health framework can facilitate the development of interventions and policies to promote the equitable distribution of care across the population. This column describes the application of population behavioral health principles in a safety-net health system during the pandemic. The approach includes stepped models of care, interventions to target individuals at high behavioral health risk, and measurement-based care. Early data suggest that these strategies have resulted in expanded behavioral health care capacity.

Objectives: Determine whether D-dimer concentration in the absence of imaging can differentiate patients that require anti-coagulation from patients who do not require anti-coagulation., Methods: Data was obtained retrospectively from 366 hemodynamically stable adult ED patients with suspected pulmonary embolism (PE). Patients were categorized by largest occluded artery and aggregated into: 'Require anti-coagulation' (main, lobar, and segmental PE), 'Does not require anti-coagulation' (sub-segmental and No PE), 'High risk of deterioration' (main and lobar PE), and 'Not high risk of deterioration' (segmental, sub-segmental, and No PE) groups. Wilcoxon rank-sum test was used for 2 sample comparisons of median D-dimer concentrations. Receiver operating characteristic (ROC) curve analysis was utilized to determine a D-dimer cut-off that could differentiate 'Require anti-coagulation' from 'Does not require anti-coagulation' and 'High risk of deterioration' from 'Low risk of deterioration' groups., Results: The 'Require anti-coagulation' group had a maximum area under the curve (AUC) of 0.92 at an age-adjusted D-dimer cut-off of 1540 with a specificity of 86% (95% CI, 81-91%), and sensitivity of 84% (79-90%). The 'High risk of deterioration' group had a maximum AUC of 0.93 at an age-adjusted D-dimer cut-off of 2500 with a specificity of 90% (85-93%) and sensitivity of 83% (77-90%)., Conclusions: An age-adjusted D-dimer cut-off of 1540 ng/mL differentiates suspected PE patients requiring anti-coagulation from those not requiring anti-coagulation. A cut-off of 2500 differentiates those with high risk of clinical deterioration from those not at high risk of deterioration. When correlated with clinical outcomes, these cut-offs can provide an objective method for clinical decision making when imaging is unavailable., Competing Interests: Declaration of competing interest All authors report no conflict of interest., (Copyright © 2020. Published by Elsevier Inc.)

Patient-derived tumor xenografts (PDXs) are considered the most predictive preclinical models, largely believed to be driven by cancer stem cells (CSC) for conventional cancer drug evaluation. A large library of PDXs is reflective of the diversity of patient populations and thus enables population based preclinical trials ("Phase II-like mouse clinical trials"); however, PDX have practical limitations of low throughput, high costs and long duration. Tumor organoids, also being patient-derived CSC-driven models, can be considered as the in vitro equivalent of PDX, overcoming certain PDX limitations for dealing with large libraries of organoids or compounds. This study describes a method to create PDX-derived organoids (PDXO), thus resulting in paired models for in vitro and in vivo pharmacology research. Subcutaneously-transplanted PDX-CR2110 tumors were collected from tumor-bearing mice when the tumors reached 200-800 mm 3 , per an approved autopsy procedure, followed by removal of the adjacent non-tumor tissues and dissociation into small tumor fragments. The small tumor fragments were washed and passed through a 100 µm cell strainer to remove the debris. Cell clusters were collected and suspended in basement membrane extract (BME) solution and plated in a 6-well plate as a solid droplet with surrounding liquid media for growth in a CO2 incubator. Organoid growth was monitored twice weekly under light microscopy and recorded by photography, followed by liquid medium change 2 or 3 times a week. The grown organoids were further passaged (7 days later) at a 1:2 ratio by disrupting the BME embedded organoids using mechanical shearing, aided by addition of trypsin and the addition of 10 µM Y-27632. Organoids were cryopreserved in cryo-tubes for long-term storage, after release from BME by centrifugation, and also sampled (e.g., DNA, RNA and FFPE block) for further characterization.

Objective: The study objective was to describe trends in the medical management of migraine in the emergency department (ED) using the 2010-2017 National Hospital Ambulatory Medical Care Survey (NHAMCS) datasets., Methods: Using the 2010-2017 NHAMCS datasets, we analyzed visits with a discharge diagnosis of migraine. Drug prescription frequencies between years were compared with the Rao-Scott chi-squared test. Adjusted odds ratios of opioid administration from 2010 to 2017 were calculated using weighted multivariable logistic regression with sex, age, race/ethnicity, pain-score, primary expected source of payment, and year as predictor variables., Results: Our analysis captured 1846 ED visits with a diagnosis of migraine from 2010 to 2017, representing a weighted average of 1.2 million US ED visits per year. Parenteral opioids were prescribed in 49% (95% CI: 40, 58) of visits in 2010 and 28% (95% CI: 15, 45) of visits in 2017 (p = 0.03). From 2010 to 2017, there was a 10% yearly decrease in opioid prescriptions. Metoclopramide and ketorolac were prescribed more frequently in years 2015 through 2017 than in 2010. Increased opioid administration was associated with female sex, older age, white race, higher pain score, and having Medicare or private insurance as the primary expected source of payment for all years., Conclusion: Opioid administration for migraine in EDs across the US declined 10% annually between 2010 and 2017, demonstrating improved adherence to migraine guidelines recommending against opioids. We identified several factors associated with opioid administration for migraine, identifying groups at higher risk for unnecessary opioids in the ED setting., Competing Interests: Declaration of Competing Interest The authors, to the best of our knowledge, have no conflicts of interest, financial or otherwise, to declare related to this manuscript., (Copyright © 2021 Elsevier Inc. All rights reserved.)

We investigate the mechanical response of jammed packings of repulsive, frictionless spherical particles undergoing isotropic compression. Prior simulations of the soft-particle model, where the repulsive interactions scale as a power law in the interparticle overlap with exponent α, have found that the ensemble-averaged shear modulus 〈G(P)〉 increases with pressure P as ∼P^{(α-3/2)/(α-1)} at large pressures. 〈G〉 has two key contributions: (1) continuous variations as a function of pressure along geometrical families, for which the interparticle contact network does not change, and (2) discontinuous jumps during compression that arise from changes in the contact network. Using numerical simulations, we show that the form of the shear modulus G^{f} for jammed packings within near-isostatic geometrical families is largely determined by the affine response G^{f}∼G&#95;{a}^{f}, where G&#95;{a}^{f}/G&#95;{a0}=(P/P&#95;{0})^{(α-2)/(α-1)}-P/P&#95;{0}, P&#95;{0}∼N^{-2(α-1)} is the characteristic pressure at which G&#95;{a}^{f}=0, G&#95;{a0} is a constant that sets the scale of the shear modulus, and N is the number of particles. For near-isostatic geometrical families that persist to large pressures, deviations from this form are caused by significant nonaffine particle motion. We further show that the ensemble-averaged shear modulus 〈G(P)〉 is not simply a sum of two power laws, but 〈G(P)〉∼(P/P&#95;{c})^{a}, where a≈(α-2)/(α-1) in the P→0 limit and 〈G(P)〉∼(P/P&#95;{c})^{b}, where b≳(α-3/2)/(α-1), above a characteristic pressure that scales as P&#95;{c}∼N^{-2(α-1)}.

Major depressive disorder is a common mental health condition that affects an estimated 16.2 million adults and 3.1 million adolescents in the United States. Yet, a lack of uniformity remains in measurements and monitoring for depression both in clinical practice and in research settings. This project aimed to develop a minimum set of standardized outcome measures relevant to both patients and clinicians that can be collected in depression registries and clinical practice. Twenty-nine depression registries and related data collection efforts were identified and invited to submit outcome measures. Additional measures were identified through literature searches and reviews of quality measures. A multistakeholder panel representing clinicians; payers; government agencies; industry; and medical specialty, health care quality, and patient advocacy organizations categorized the 27 identified measures using the Agency for Healthcare Research and Quality's supported Outcome Measures Framework. The panel identified 10 broadly relevant measures and harmonized definitions for these measures through in-person and virtual meetings. The harmonized measures represent a minimum set of outcomes that are relevant to clinicians and patients and appropriate for use in depression research and clinical practice. Routine and consistent collection of these measures in registries and other systems would support creation of a national research infrastructure to efficiently address new questions, improve patient management and outcomes, and facilitate care coordination.

Carotenoids are well known for their contribution to the vibrant coloration of many animals and have been hypothesized to be important antioxidants. Surprisingly few examples of carotenoids acting as biologically relevant antioxidants in vivo exist, in part because experimental designs often employ carotenoid doses at levels that are rarely observed in nature. Here, we used an approach that reduces carotenoid content from wild-type levels to test for the effect of carotenoids as protectants against an oxidative challenge. We used the marine copepod Tigriopus californicus reared on a carotenoid-free or a carotenoid-restored diet of nutritional yeast and then exposed them to a pro-oxidant. We found that carotenoid-deficient copepods not only accumulated more damage but also were more likely to die during an oxidative challenge than carotenoid-restored copepods. We suggest that carotenoid reduction, and not supplementation, better tests the proposed roles of carotenoids in other physiological functions in animals., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

With thousands of smartphone apps targeting mental health, it is difficult to ignore the rapidly expanding use of apps in the treatment of psychiatric disorders. Patients with psychiatric conditions are interested in mental health apps and have begun to use them. That does not mean that clinicians must support, endorse, or even adopt the use of apps, but they should be prepared to answer patients' questions about apps and facilitate shared decision making around app use. This column describes an evaluation framework designed by the American Psychiatric Association to guide informed decision making around the use of smartphone apps in clinical care.

Objective: Lack of access to mental health treatment remains a significant problem in the United States, even after implementation of mental health parity legislation. This study examined availability of psychiatrists listed in insurance carrier network provider databases in the Washington, D.C., area., Methods: Contact information was obtained for 1,184 psychiatrists listed in online directories for three of the largest insurance carriers serving the Washington, D.C., area. The "mystery shopper" method was used to assess the accuracy of listed contact information, new outpatient appointment availability, and average wait times for 50 psychiatrists randomly selected from each insurance directory., Results: Most (77%) physicians were successfully contacted, meaning that someone answered the phone or returned a voice mail message, and 51% of the psychiatrists had working telephone numbers verified to be correct. Fifteen percent of the psychiatrists were accepting new outpatients with the target insurance, with average wait times of 19 days; only 7% were able to schedule an appointment within two weeks., Conclusions: Inaccuracy of insurance provider directories significantly affected the ability of patients to obtain timely mental care.

Translational science is an emerging field that holds great promise to accelerate the development of novel medical interventions. As the field grows, so does the demand for highly trained biomedical scientists to fill the positions that are being created. Many graduate and postdoctorate training programs do not provide their trainees with sufficient education to take advantage of this growing employment sector. To help better prepare the trainees at the National Institutes of Health for possible careers in translation, we have created the Translational Science Training Program (TSTP). The TSTP is an intensive 2- to 3-day training program that introduces NIH postdoctoral trainees and graduate students to the science and operation of turning basic research discoveries into a medical therapeutic, device or diagnostic, and also exposes them to the variety of career options in translational science. Through a combination of classroom teaching from practicing experts in the various disciplines of translation and small group interactions with pre-clinical development teams, participants in the TSTP gain knowledge that will aid them in obtaining a career in translational science and building a network to make the transition to the field. © 2016 by The International Union of Biochemistry and Molecular Biology, 45(1):13-24, 2017., (© 2016 The International Union of Biochemistry and Molecular Biology.)

We previously reported that remote limb ischemic conditioning (RLIC; PERconditioning) during acute stroke confers neuroprotection, possibly due to increased cerebral blood flow (CBF). Vascular cognitive impairment (VCI) is a growing threat to public health without any known treatment. The bilateral common carotid artery stenosis (BCAS) mouse model is regarded as the most valid model for VCI. We hypothesized that RLIC (postconditioning; RIPostC) will augment CBF during chronic cerebral hypoperfusion (CCH) and prevent cognitive impairment in the BCAS model. BCAS using customized microcoil was performed in C57/B6 male mice to establish CCH. A week after the BCAS surgery, mice were treated with RIPostC-therapy once daily for 2 weeks. CBF was measured with laser speckle contrast imager at different time points. Cognitive testing was performed at 4-week post-BCAS, and brain tissue was harvested for biochemistry. BCAS led to chronic hypoperfusion resulting into impaired cognitive function as tested by novel object recognition (NOR). Histological examinations revealed that BCAS triggered inflammatory responses and caused frequent vacuolization and cell death. BCAS also increased the generation and accumulation of amyloid beta protein (Aβ), resulting into the loss of white matter (WM) and myelin basic protein (MBP). RIPostC-therapy showed both acute increase as well as sustained improvement in CBF even after the cessation of therapy for a week. RIPostC improved cognitive function, inhibited inflammatory responses, prevented the cell death, reduced the generation and accumulation of Aβ, and protected WM integrity. RIPostC is effective in the BCAS model and could be an attractive low-cost conventional therapy for aged individuals with VCI. The mechanisms by which RIPostC improves CBF and attenuates tissue damage need to be investigated in the future.

Learning to maintain standing balance in the presence of a paretic limb is an important recovery process for many stroke survivors. In this study, we used a robotic balance simulator to investigate whether manipulating medial-lateral or anterior-posterior torque contributions (i.e. input gains) could shift the control of balance toward a targeted lower limb in healthy controls. Manipulation of medial-lateral (ML) torque gains shifted the vertical load distribution toward the virtually weakened limb, but did not result in a significant shift in anterior-posterior (AP) torque control. Instead individual participants were observed to shift AP torque control in either direction, although participants more often shifted control toward the virtually weakened limb at larger ML asymmetries. In contrast, manipulation of AP torque gains did not produce any observable changes in measured torque signals. The shift in torque contributions during ML manipulations shows promise as an implicit training method for reducing weight-bearing asymmetry. However, further work is required to ensure both vertical load and AP torque control shift in the desired direction as well as to determine the applicability of the protocol in a patient population.

Synaptic adhesion-like molecules (SALMs) are a family of cell adhesion molecules involved in neurite outgrowth and synapse formation. Of the five family members, only SALM1, -2, and -3 contain a cytoplasmic C-terminal PDZ-binding motif. We have found that SALM1 is unique among the SALMs because deletion of its PDZ-binding motif (SALM1ΔPDZ) blocks its surface expression in heterologous cells. When expressed in hippocampal neurons, SALM1ΔPDZ had decreased surface expression in dendrites and the cell soma but not in axons, suggesting that the PDZ-binding domain may influence cellular trafficking of SALMs to specific neuronal locations. Endoglycosidase H digestion assays indicated that SALM1ΔPDZ is retained in the endoplasmic reticulum (ER) in heterologous cells. However, when the entire C-terminal tail of SALM1 was deleted, SALM1 was detected on the cell surface. Using serial deletions, we identified a region of SALM1 that contains a putative dileucine ER retention motif, which is not present in the other SALMs. Mutation of this DXXXLL motif allowed SALM1 to leave the ER and enhanced its surface expression in heterologous cells and neurons. An increase in the number of protrusions at the dendrites and cell body was observed when this SALM1 mutant was expressed in hippocampal neurons. With electron microscopy, these protrusions appeared to be irregular, enlarged spines and filopodia. Thus, enrichment of SALM1 on the cell surface affects dendritic arborization, and intracellular motifs regulate its dendritic versus axonal localization.

NMDA receptors (NMDARs) are critical to the development of the nervous system, although their roles at axonal growth cones are unclear. We examined NMDAR localization and function at axonal growth cones of young hippocampal neurons. Our immunocytochemical data showed that native and transfected NMDAR subunits are expressed in axons and growth cones of young (days in vitro 3-6) hippocampal rat neurons. Moreover, immunogold electron microscopy showed that NR1 is expressed in growth cones of postnatal day 2 rat hippocampus. Local application of NMDAR agonists to growth cones of voltage-clamped neurons evoked inward currents that were blocked by bath application of an NMDAR antagonist (dl-APV), indicating that these NMDARs are functional. In addition, calcium imaging experiments indicated that NMDARs present in growth cones mediate calcium influx. Calcium transients in growth cones persisted despite pharmacological blockade of voltage-sensitive calcium channels and depletion of intracellular calcium stores. Our findings reveal the presence of functional NMDARs in axons and growth cones of young neurons, suggesting a role for these receptors in axonal guidance and synapse formation during neuronal development.

Context: Suicidal behavior has gained attention as an adverse outcome of prescription drug use. Hospitalizations for intentional self-harm, including suicide, can be identified in administrative claims databases using external cause of injury codes (E-codes). However, rates of E-code completeness in US government and commercial claims databases are low due to issues with hospital billing software., Objective: To develop an algorithm to identify intentional self-harm hospitalizations using recorded injury and psychiatric diagnosis codes in the absence of E-code reporting., Methods: We sampled hospitalizations with an injury diagnosis (ICD-9 800-995) from two databases with high rates of E-coding completeness: 1999-2001 British Columbia, Canada data and the 2004 US Nationwide Inpatient Sample. Our gold standard for intentional self-harm was a diagnosis of E950-E958. We constructed algorithms to identify these hospitalizations using information on type of injury and presence of specific psychiatric diagnoses., Results: The algorithm that identified intentional self-harm hospitalizations with high sensitivity and specificity was a diagnosis of poisoning, toxic effects, open wound to elbow, wrist, or forearm, or asphyxiation; plus a diagnosis of depression, mania, personality disorder, psychotic disorder, or adjustment reaction. This had a sensitivity of 63%, specificity of 99% and positive predictive value (PPV) of 86% in the Canadian database. Values in the US data were 74, 98, and 73%. PPV was highest (80%) in patients under 25 and lowest those over 65 (44%)., Conclusions: The proposed algorithm may be useful for researchers attempting to study intentional self-harm in claims databases with incomplete E-code reporting, especially among younger populations., (Copyright © 2010 John Wiley & Sons, Ltd.)

There exists a divide between findings from integrative neuroscience and clinical research focused on mechanisms of psychopathology. Specifically, a clear correspondence does not emerge between clusters of complex clinical symptoms and dysregulated neurobiological systems, with many apparent redundancies. For instance, many mental disorders involve multiple disruptions in putative mechanistic factors (e.g., excessive fear, deficient impulse control), and different disrupted mechanisms appear to play major roles in many disorders. The Research Domain Criteria (RDoC) framework is a heuristic to facilitate the incorporation of behavioral neuroscience in the study of psychopathology. Such integration might be achieved by shifting the central research focus of the field away from clinical description to more squarely examine aberrant mechanisms. RDoC first aims to identify reliable and valid psychological and biological mechanisms and their disruptions, with an eventual goal of understanding how anomalies in these mechanisms drive psychiatric symptoms. This approach will require new methods to ascertain samples, relying on hypothesized psychopathological mechanisms to define experimental groups instead of traditional diagnostic categories. RDoC, by design, uncouples research efforts from clinically familiar categories to focus directly on fundamental mechanisms of psychopathology. RDoC proposes a matrix of domains and levels of analyses and invites the field to test and refine the framework. If RDoC is successful, the domains will ultimately relate to familiar psychopathologies in ways that promote new knowledge regarding etiology and more efficient development of new preventive and treatment interventions., (PsycINFO Database Record (c) 2010 APA, all rights reserved)

Objective: The objective of this study was to assess the risk of suicide attempts and suicides after initiation of antidepressant medication use by children and adolescents, for individual agents., Methods: We conducted a 9-year cohort study by using population-wide data from British Columbia. We identified new users of antidepressants who were 10 to 18 years of age with a recorded diagnosis of depression. Study outcomes were hospitalization attributable to intentional self-harm and suicide death., Results: Of 20,906 children who initiated antidepressant therapy, 16,774 (80%) had no previous antidepressant use. During the first year of use, we observed 266 attempted and 3 completed suicides, which yielded an event rate of 27.04 suicidal acts per 1000 person-years (95% confidence interval [CI]: 23.9-30.5 suicidal acts per 1000 person-years). There were no meaningful differences in the rate ratios (RRs) comparing fluoxetine with citalopram (RR: 0.97 [95% CI: 0.54-1.76]), fluvoxamine (RR: 1.05 [95% CI: 0.46-2.43]), paroxetine (RR: 0.80 [95% CI: 0.47-1.37]), and sertraline (RR: 1.02 [95% CI: 0.56-1.84]). Tricyclic agents showed risks similar to those of selective serotonin reuptake inhibitors (RR: 0.92 [95% CI: 0.43-2.00])., Conclusion: Our finding of equal event rates among antidepressant agents supports the decision of the Food and Drug Administration to include all antidepressants in the black box warning regarding potentially increased suicidality risk for children and adolescents beginning use of antidepressants.

Context: A US Food and Drug Administration advisory has warned that antidepressants may be associated with an increased risk of suicidal thoughts and behaviors in adolescents. This prompted a meta-analysis of trials in adults that found no overall increase in risk, but individual agents could not be studied., Objective: To assess the risk of suicide and suicide attempts associated with individual antidepressant agents., Design: Cohort study of incident users of antidepressant agents., Setting: Population-based health care utilization data of all residents of British Columbia, Canada, aged 18 years and older between January 1, 1997, and December 31, 2005., Patients: British Columbia residents who had antidepressant therapy initiated and had a recorded diagnosis of depression., Intervention: Initiation of various antidepressant medications., Main Outcome Measures: Combined suicide death or hospitalization due to self-harm., Results: In a population of 287,543 adults aged 18 years and older with antidepressant therapy initiated, we observed outcome rates ranging from 4.41/1000 person-years to 9.09/1000 person-years. Most events occurred in the first 6 months after treatment initiation. After extensive propensity score adjustment, we found no clinically meaningful variation in the risk of suicide and suicide attempt between antidepressant agents compared with fluoxetine hydrochloride initiation: citalopram hydrobromide, hazard ratio = 1.00 (95% confidence interval, 0.63-1.57); fluvoxamine maleate, hazard ratio = 0.98 (95% confidence interval, 0.63-1.51); paroxetine hydrochloride, hazard ratio = 1.02 (95% confidence interval, 0.77-1.35); and sertraline hydrochloride, hazard ratio = 0.75 (95% confidence interval, 0.53-1.05). Compared with selective serotonin reuptake inhibitors as a drug class, other classes including serotonin-norepinephrine reuptake inhibitors, tricyclic agents, and other newer and atypical agents had a similar risk. Restriction to patients with no antidepressant use in the past 3 years further reduced apparent differences between groups., Conclusions: Our finding of equal event rates across antidepressant agents supports the US Food and Drug Administration's decision to treat all antidepressants alike in their advisory. Treatment decisions should be based on efficacy, and clinicians should be vigilant in monitoring after initiating therapy with any antidepressant agent.

Background: Depression imposes enormous burdens on the elderly. Despite this, rates of initiation of and adherence to recommended pharmacotherapy are frequently low in this population. Although initiatives such as the Medicare Modernization Act (MMA) have improved seniors' access to antidepressants, there are concerns that the patient cost-sharing incorporated in the MMA may have unintended consequences if it reduces essential drug use. Age-related pharmacokinetic and pharmacodynamic changes could make seniors particularly vulnerable to antidepressant regimens used inappropriately to save costs, increasing their risks of morbidity, hospitalizations, and nursing home placements. Two sequential large-scale "natural experiments'' in British Columbia provide a unique opportunity to evaluate the effect of cost sharing on outcomes and mental health service use among seniors. In January 2002 the province introduced a CAD 25 copay (CAD10 for low-income seniors). In May 2003 this copay policy was replaced by a second policy consisting of an income-based deductible, 25% coinsurance once the deductible was met, and full coverage once an out-of-pocket ceiling was met. The transition between the two policies is analogous to what many U.S. seniors experience when they transition from private insurance requiring copays to Medicare Part D requiring deductibles and coinsurance., Aims: To evaluate whether declines in antidepressant initiation after the introduction of two drug cost-sharing policies in British Columbia were associated with increased use of physician services, hospitalizations, and nursing home admissions among all British Columbia residents aged 65+., Methods: Records of physician service use, inpatient hospitalizations, and residential care admissions were obtained from administrative databases. Population-level patterns over time were plotted, and effects of implementing the cost-sharing policies examined in segmented linear regression models., Results: Neither policy affected the rates of visits to physicians or psychiatrists for depression, hospitalizations with a depression diagnosis, or long-term care admissions., Discussion: The cost-sharing policies studied may have contained non-essential antidepressant use without substantially increasing mental health service utilization. However, it is possible that the policies had effects that we were unable to detect, such as increasing rates of visits to social workers or psychologists or forcing patients to reduce other spending. Further, the sequential implementation of the policy changes, makes it difficult to estimate the effect of a direct change from full coverage to a coinsurance/income-based deductible policy., Implications for Health Policies: It may be possible to design policies to contain non-essential antidepressant use without substantially increasing other service utilization or adverse events. However, because undertreatment remains a serious problem among depressed elderly, well-designed prescription drug policies should be coupled with interventions to address under-treatment.

Background: We report the lifetime and 12-month prevalence and associations of mental health treatment among Mexican adolescents with suicide-related outcomes (SROs; including ideation, plans, gestures and attempts)., Methods: A representative multistage probability household survey of 3005 adolescents aged 12 to 17 years residing in the Mexico City Metropolitan Area was carried out in 2005. Discrete-time survival analyses were used to assess the relationships between SROs and receiving treatment for emotional, alcohol, or drug problems., Results: The prevalence of lifetime service use among respondents with SROs was 35% for those with ideation only, 44% for those with ideation and plan, 49% for those with gesture and 50% for those with attempt; the prevalence of 12-month service use was 10%, 24%, 6% and 21%, respectively. Timing between onset of SRO and receiving treatment for emotional, alcohol, or drug problems showed that about 50% of adolescents will have contact with a service provider before developing any SRO. Healthcare professionals were the most likely to be consulted, followed by school-based programs., Limitations: This survey was limited to adolescents living in one of the largest metropolitan areas in the world and the analyses used data on retrospectively reported ages of onset that are subject to recall errors., Conclusions: Most suicidal adolescents do not receive treatment, and many adolescents develop their suicidality in spite of prior contacts with service providers. Interventions to increase treatment, prevention, and monitoring are sorely needed for this vulnerable population.

Introduction: In 2003, more intense monitoring of patients initiating antidepressants was advised because of emerging concerns of suicidality. We sought to identify patterns of patient monitoring after antidepressant initiation in British Columbia before and after issuance of health advisories., Materials and Methods: We conducted a cohort study of antidepressant initiators between 1999 and 2005 using healthcare utilization data of all British Columbia residents. For the periods before (1999-2001) and after (2004-2005), health advisories concerning suicidality associated with antidepressants, we assessed monitoring intensity by calculating weekly physician and psychotherapy visit rates since antidepressant initiation. We also estimated monitoring patterns as the proportion of individuals who received weekly in-person contact during the first 4 weeks of treatment, then biweekly visits for 4 weeks, and then a visit at 12 weeks, as a proxy for intensive monitoring., Results: Patterns of monitoring intensity were similar before and after the health advisories, but the level of intensity was lower after the advisory period. Overall, monitoring intensity peaked in the 4 weeks after antidepressant initiation. Weekly numbers of visits per subject during these 4 weeks were between 0.44 and 0.49 before the advisory and from 0.39 to 0.44 after the advisory. Among all initiators stratified by year of initiation, between 21% and 25% received intensive monitoring, and this proportion generally decreased on a yearly basis., Discussion: Monitoring intensity for patients with depression initiating antidepressants decreased after the period of emergence and greater awareness of the association between antidepressants and suicidality.

STAR*D (Sequenced Treatment Alternatives to Relieve Depression) continues to stimulate debate. The landmark trial demonstrated the feasibility of large-scale, community-based studies conducted without pharmaceutical company support. The results provided insight into nonresponse to initial treatment with selective serotonin reuptake inhibitors and alternatives for second- and third-line treatment options and suggested opportunities for personalized approaches to depression care. However, initial and one-year remission rates (28% and 70%, respectively) suggest that important goals for treatment of this disabling disease remain out of reach and that the bar for antidepressants has been set far too low.

Objective: This study sought to determine whether previously reported poor outcomes among patients of low socioeconomic status who have depression and anxiety could result from not receiving mental health treatment or from receiving minimally adequate treatment., Methods: The study sample consisted of 1,772 participants in the National Comorbidity Survey Replication (NCS-R) who met criteria for a mood or anxiety disorder. Bivariate and multivariate logistic regression analyses were used to examine associations between education, income, and assets and receipt of treatment and quality of treatment (minimally adequate treatment) for mood and anxiety disorders in sectors with the capacity to deliver evidence-based treatments (the general medical and mental health specialty sectors). Multivariate analyses controlled for age, gender, race-ethnicity, marital status, health insurance, and urbanicity., Results: Age, gender, marital status, and race-ethnicity were strong and fairly consistent predictors of mental health services use, with some modest variations by sector. In contrast, in bivariate and multivariate analyses, education, income, and assets were minimally related to use of mental health care and to receipt of minimally adequate care in both general medical and mental health specialty sectors., Conclusions: Socioeconomic status does not appear to play a major role in determining aspects of treatment for depression and anxiety disorders. Poor outcomes of depressed and anxious patients with low socioeconomic status may be due to differences in quality of care beyond the minimally adequate level assessed in this study or to factors unrelated to quality of care that could counteract effective treatments, such as the presence of ongoing chronic stress.

The potential of personalized medicine to transform the treatment of mood disorders has been widely touted in psychiatry, but has not been quantified. We estimated the costs and benefits of a putative pharmacogenetic test for antidepressant response in the treatment of major depressive disorder (MDD) from the societal perspective. Specifically, we performed cost-effectiveness analyses using state-transition probability models incorporating probabilities from the multicenter STAR*D effectiveness study of MDD. Costs and quality-adjusted life years (QALYs) were compared for sequential antidepressant trials, with or without guidance from a pharmacogenetic test for differential response to selective serotonin reuptake inhibitors (SSRIs). Likely SSRI responders received an SSRI, whereas likely nonresponders received the norepinephrine/dopamine reuptake inhibitor bupropion. For a 40-year old with MDD, applying the pharmacogenetic test and using the non-SSRI bupropion for those at higher risk for nonresponse cost $93,520 per additional QALY compared with treating all patients with an SSRI first and switching sequentially in the case of nonremission. Cost per QALY dropped below $50,000 for tests with remission rate ratios as low as 1.5, corresponding to odds ratios approximately 1.8-2.0. Tests for differential antidepressant response could thus become cost effective under certain circumstances. These circumstances, particularly availability of alternative treatment strategies and test effect sizes, can be estimated and should be considered before these tests are broadly applied in clinical settings.

Making decisions about medical treatments based upon valid evidence is critical to improve health-care quality, outcomes, and value. Although such research commonly connotes the use of randomized controlled trials, experimental methods are not always feasible, and research using observational, quasi-experimental, and other nonexperimental methods may also be important. At the same time, nonexperimental methods are inherently susceptible to various types of bias and thus present special challenges in the search for valid and generalizable evidence. The study by Gardarsdottir et al. (Am J Epidemiol. 2009;170(3):280-285), on which this commentary is based, addresses a key potential source of bias -- mismeasurement of patients' duration of treatment -- in previous research on pharmacotherapy for depression. However, the authors' study is unlikely to address other potential sources of bias, which may make interpretation of their findings more difficult.

Objective: Although mental health treatment dropout is common, patterns and predictors of dropout are poorly understood. This study explored patterns and predictors of mental health treatment dropout in a nationally representative sample., Methods: Data were from the National Comorbidity Survey Replication, a nationally representative household survey. Respondents who had received mental health treatment in the 12 months before the interview (N=1,664) were asked about dropout, which was defined as quitting treatment before the provider wanted them to stop. Cross-tabulation and discrete-time survival analyses were used to identify predictors., Results: Approximately one-fifth (22%) of patients quit treatment prematurely. The highest dropout rate was from treatment received in the general medical sector (32%), and the lowest was from treatment received by psychiatrists (15%). Dropout rates were intermediate from treatment in the human services sector (20%) and among patients seen by nonpsychiatrist mental health professionals (19%). Over 70% of all dropout occurred after the first or second visits. Mental health insurance was associated with low odds of dropout (odds ratio=.6, 95% confidence interval=.4-.9). Psychiatric comorbidity was associated with a trend toward dropout. Several patient characteristics differentially predicted dropout across treatment sectors and in early and later phases of treatment., Conclusions: Roughly one-fifth of adults in mental health treatment dropped out before completing the recommended course of treatment. Dropout was most common in the general medical sector and varied by patient characteristics across treatment sectors. Interventions focused on high-risk patients and sectors that have higher dropout rates will likely be required to reduce the large proportion of patients who prematurely terminate treatment.

There is a pressing need for comparative effectiveness research to improve mental health treatments. Although U.S. mental health spending has increased dramatically, mainly because of the rapid adoption of newer psychotropic medications, fewer than a quarter of people with serious mental illnesses receive appropriate care. Because of a general lack of information on the relative effectiveness of different treatments, payers are uncertain about the value of current spending, which in turn may deter new investments to reduce unmet need. We use several recent comparative effectiveness trials to illustrate the potential value of such research for improving practice and policy.

Background: Nonrandomised studies on the causal effects of psychotropic medications may be biased by patient characteristics that are not fully adjusted., Objective: Studies using linked claims databases found that typical antipsychotic medications were associated with increased short-term mortality compared with atypical antipsychotics. It has been suggested that such results may be due to residual confounding by factors that cannot be measured in claims databases. Using detailed survey data we identified the direction and magnitude of such residual confounding., Design: Cross-sectional survey data., Participants: 17 776 participants aged > or =65 years from the Medicare Current Beneficiary Survey (MCBS)., Measurements: To determine the association between typical antipsychotic use and potential confounding factors we assessed five factors not measured in Medicare claims data but in the MCBS, i.e. body mass index, smoking, activities of daily living (ADL) score, cognitive impairment and Rosow-Breslau physical impairment scale. We estimated adjusted associations between these factors and antipsychotic use. Combined with literature estimates of the independent effect of confounders on death, we computed the extent of residual confounding caused by a failure to adjust for these factors., Results: Comparing typical antipsychotic users with atypical antipsychotic users, we found that not adjusting for impairments in the ADL score led to an underestimation of the association with death (-13%), as did a failure to adjust for cognitive impairment (-7%). The combination of all five unmeasured confounders resulted in a net confounding of -5% (range -19% to +2%). After correction, the reported association between typical antipsychotic use and death compared with atypical antipsychotic use was slightly increased from a relative risk (RR) of 1.37 to 1.44 (95% CI 1.33, 1.56). Comparing any antipsychotic use with non-users would result in overestimations of >50% if cognitive impairment remained unadjusted., Conclusion: Claims data studies tend to underestimate the association of typical antipsychotics with death compared with atypical antipsychotics because of residual confounding by measures of frailty. Studies comparing antipsychotic use with non-users may substantially overestimate harmful effects of antipsychotics.

Aims: The paper reviews recent findings from the WHO World Mental Health (WMH) surveys on the global burden of mental disorders., Methods: The WMH surveys are representative community surveys in 28 countries throughout the world aimed at providing information to mental health policy makers about the prevalence, distribution, burden, and unmet need for treatment of common mental disorders., Results: The first 17 WMH surveys show that mental disorders are commonly occurring in all participating countries. The inter-quartile range (IQR: 25th-75th percentiles) of lifetime DSM-IV disorder prevalence estimates (combining anxiety, mood, externalizing, and substance use disorders) is 18.1-36.1%. The IQR of 12-month prevalence estimates is 9.8-19.1%. Prevalence estimates of 12-month Serious Mental Illness (SMI) are 4-6.8% in half the countries, 2.3-3.6% in one-fourth, and 0.8-1.9% in one-fourth. Many mental disorders begin in childhood-adolescence and have significant adverse effects on subsequent role transitions in the WMH data. Adult mental disorders are found to be associated with such high role impairment in the WMH data that available clinical interventions could have positive cost-effectiveness ratios., Conclusions: Mental disorders are commonly occurring and often seriously impairing in many countries throughout the world. Expansion of treatment could be cost-effective from both employer and societal perspectives.