Mediators of Ethnic Differences in Dropout Rates From a Randomized Controlled Treatment Trial Among Latinx and Non-Latinx White Primary Care Patients With Anxiety Disorders.

ABSTRACT: Disparities in treatment engagement and adherence based on ethnicity have been widely recognized but are inadequately understood. Few studies have examined treatment dropout among Latinx and non-Latinx White (NLW) individuals. Using Andersen's Behavioral Model of Health Service Use (A behavioral model of families' use of health services. 1968; J Health Soc Behav. 1995; 36:1-10) as a framework, we examine whether pretreatment variables (categorized as predisposing, enabling, and need factors) mediate the relationship between ethnicity and premature dropout in a sample of Latinx and NLW primary care patients with anxiety disorders who participated in a randomized controlled trial (RCT) of cognitive behavioral therapy. Data from a total of 353 primary care patients were examined; 96 Latinx and 257 NLW patients participated. Results indicated that Latinx patients dropped out of treatment more often than NLW patients, resulting in roughly 58% of Latinx patients failing to complete treatment compared with 42% of NLW, and approximately 29% of Latinx patients dropping out before engaging in modules related to cognitive restructuring or exposure, relative to 11% of NLW patients. Mediation analyses suggest that social support and somatization partially explained the relationship between ethnicity and treatment dropout, highlighting the importance of these variables in understanding treatment disparities.

Childhood Trauma, DNA Methylation of Stress-Related Genes, and Depression: Findings From Two Monozygotic Twin Studies.

OBJECTIVE: DNA methylation has been associated with both early life stress and depression. This study examined the combined association of DNA methylation at multiple CpG probes in five stress-related genes with depressive symptoms and tested whether these genes methylation mediated the association between childhood trauma and depression in two monozygotic (MZ) twin studies. METHODS: The current analysis comprised 119 MZ twin pairs (84 male pairs [mean = 55 years] and 35 female pairs [mean = 36 years]). Peripheral blood DNA methylation of five stress-related genes (BDNF, NR3C1, SLC6A4, MAOA, and MAOB) was quantified by bisulfite pyrosequencing or 450K BeadChip. We applied generalized Poisson linear-mixed models to examine the association between each single CpG methylation and depressive symptoms. The joint associations of multiple CpGs in a single gene or all five stress-related genes as a pathway were tested by weighted truncated product method. Mediation analysis was conducted to test the potential mediating effect of stress gene methylation on the relationship between childhood trauma and depressive symptoms. RESULTS: Multiple CpG probes showed nominal individual associations, but very few survived multiple testing. Gene-based or gene-set approach, however, revealed significant joint associations of DNA methylation in all five stress-related genes with depressive symptoms in both studies. Moreover, two CpG probes in the BDNF and NR3C1 mediated approximately 20% of the association between childhood trauma and depressive symptoms. CONCLUSIONS: DNA methylation at multiple CpG sites are jointly associated with depressive symptoms and partly mediates the association between childhood trauma and depression. Our results highlight the importance of testing the combined effects of multiple CpG loci on complex traits and may unravel a molecular mechanism through which adverse early life experiences are biologically embedded.

High expectancy and early response produce optimal effects in sertraline treatment for post-traumatic stress disorder.

BACKGROUND: Better indicators of prognosis are needed to personalise post-traumatic stress disorder (PTSD) treatments.AimsWe aimed to evaluate early symptom reduction as a predictor of better outcome and examine predictors of early response. METHOD: Patients with PTSD (N = 134) received sertraline or prolonged exposure in a randomised trial. Early response was defined as 20% PTSD symptom reduction by session two and good end-state functioning defined as non-clinical levels of PTSD, depression and anxiety. RESULTS: Early response rates were similar in prolonged exposure and sertraline (40 and 42%), but in sertraline only, early responders were four times more likely to achieve good end-state functioning at post-treatment (Number Needed to Treat = 1.8, 95% CI 1.28-3.00) and final follow-up (Number Needed to Treat = 3.1, 95% CI 1.68-16.71). Better outcome expectations of sertraline also predicted higher likelihood of early response. CONCLUSIONS: Higher expectancy of sertraline coupled with early response may produce a cascade-like effect for optimal conditions for long-term symptom reduction. Therefore, assessing expectations and providing clear treatment rationales may optimise sertraline effects. DECLARATION OF INTEREST: None.

Study Design and Rationale for the Mood and Methylation Study: A Platform for Multi-Omics Investigation of Depression in Twins.

Major depression is a complex disorder with no single, direct causal mechanism. Morbidity has been linked to genetic processes, developmental history, and unique environmental exposures. Epigenetic mechanisms, especially DNA methylation, are also likely important factors in the pathogenesis of major depressive disorder (MDD). A community-based twin sample has many advantages for epigenetic studies, given the shared genetic and developmental histories of same-sex twin pairs. This article describes the rationale and study design for the Mood and Methylation Study in which 133 twin pairs (101 monozygotic and 32 dizygotic), both discordant and concordant for lifetime history of MDD, were evaluated on a large number of variables related to MDD. The twins also provided blood samples for an epigenome-wide association study of differentially methylated regions (DMR) relevant to MDD. Although MDD is typically considered a disorder of the central nervous system, it is unfeasible to obtain a large sample of brain tissues. However, epigenetic variation is not limited to the affected tissue but can also be detected in peripheral blood leukocytes. Thus, this study focused on monocytes for the major analyses. Additional plans for the study include gene expression analysis from the same set of twins using RNA-seq and validation of significant DMRs in postmortem brain tissues from a separate sample. Moreover, sufficient samples have been collected to perform future 'multi-omic' analyses, including metabolome, microbiome, and transcriptome. Our long-term goal is to understand how epigenomic and other 'omic' factors can be manipulated for diagnostic, preventive, and therapeutic purposes for MDD and its related conditions.

Age Differences in Death and Suicidal Ideation in Anxious Primary Care Patients.

OBJECTIVES: The objective of this study was to examine age differences in the likelihood of endorsing of death and suicidal ideation in primary care patients with anxiety disorders. METHOD: Participants were drawn from the Coordinated Anxiety Learning and Management (CALM) Study, an effectiveness trial for primary care patients with panic disorder (PD), generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), and/or social anxiety disorder (SAD). RESULTS: Approximately one third of older adults with anxiety disorders reported feeling like they were better off dead. Older adults with PD and SAD were more likely to endorse suicidal ideation lasting at least more than half the prior week compared with younger adults with these disorders. Older adults with SAD endorsed higher rates of suicidal ideation compared with older adults with other anxiety disorders. Multivariate analyses revealed the importance of physical health, social support, and comorbid MDD in this association. CONCLUSIONS: Suicidal ideation is common in anxious, older, primary care patients and is particularly prevalent in socially anxious older adults. Findings speak to the importance of physical health, social functioning, and MDD in this association. CLINICAL IMPLICATIONS: When working with anxious older adults it is important to conduct a thorough suicide risk assessment and teach skills to cope with death and suicidal ideation-related thoughts.

Improving outcomes for patients with medication-resistant anxiety: effects of collaborative care with cognitive behavioral therapy.

BACKGROUND: Many patients with anxiety disorders remain symptomatic after receiving evidence-based treatment, yet research on treatment-resistant anxiety is limited. We evaluated effects of cognitive behavioral therapy (CBT) on outcomes of patients with medication-resistant anxiety disorders using data from the Coordinated Anxiety Learning and Management (CALM) trial. METHODS: Primary care patients who met study entry criteria (including DSM-IV diagnosis of generalized anxiety disorder, panic disorder, posttraumatic stress disorder, or social anxiety disorder) despite ongoing pharmacotherapy of appropriate type, dose, and duration were classified as medication resistant (n = 227). Logistic regression was used to estimate effects of CALM's CBT program (CALM-CBT; chosen by 104 of 117 medication-resistant patients randomized to CALM) versus usual care (UC; n = 110) on response [≥ 50% reduction of 12-item Brief Symptom Inventory (BSI-12) anxiety and somatic symptom score] and remission (BSI-12 < 6) at 6, 12, and 18 months. Within-group analyses examined outcomes by treatment choice (CBT vs. CBT plus medication management) and CBT dose. RESULTS: Approximately 58% of medication-resistant CALM-CBT patients responded and 46% remitted during the study. Relative to UC, CALM-CBT was associated with greater response at 6 months (AOR = 3.78, 95% CI 2.02-7.07) and 12 months (AOR = 2.49, 95% CI 1.36-4.58) and remission at 6, 12, and 18 months (AORs = 2.44 to 3.18). Patients in CBT plus medication management fared no better than those in CBT only. Some evidence suggested higher CBT dose produced better outcomes. CONCLUSIONS: CBT can improve outcomes for patients whose anxiety symptoms are resistant to standard pharmacotherapy.

The Association of Panic Disorder, Posttraumatic Stress Disorder, and Major Depression With Smoking in American Indians.

INTRODUCTION: Rates of cigarette smoking are disproportionately high among American Indian populations, although regional differences exist in smoking prevalence. Previous research has noted that anxiety and depression are associated with higher rates of cigarette use. We asked whether lifetime panic disorder, posttraumatic stress disorder, and major depression were related to lifetime cigarette smoking in two geographically distinct American Indian tribes. METHODS: Data were collected in 1997-1999 from 1506 Northern Plains and 1268 Southwest tribal members; data were analyzed in 2009. Regression analyses examined the association between lifetime anxiety and depressive disorders and odds of lifetime smoking status after controlling for sociodemographic variables and alcohol use disorders. Institutional and tribal approvals were obtained for all study procedures, and all participants provided informed consent. RESULTS: Odds of smoking were two times higher in Southwest participants with panic disorder and major depression, and 1.7 times higher in those with posttraumatic stress disorder, after controlling for sociodemographic variables. After accounting for alcohol use disorders, only major depression remained significantly associated with smoking. In the Northern Plains, psychiatric disorders were not associated with smoking. Increasing psychiatric comorbidity was significantly linked to increased smoking odds in both tribes, especially in the Southwest. CONCLUSIONS: This study is the first to examine the association between psychiatric conditions and lifetime smoking in two large, geographically diverse community samples of American Indians. While the direction of the relationship between nicotine use and psychiatric disorders cannot be determined, understanding unique social, environmental, and cultural differences that contribute to the tobacco-psychiatric disorder relationship may help guide tribe-specific commercial tobacco control strategies.

Suicide risk and associated demographic and clinical correlates among primary care patients with recent drug use.

BACKGROUND: There is an increased need to prepare primary care clinicians to effectively gauge the risk of suicidal behavior occurring within primary care patients who may abuse drugs, especially those served in safety-net settings. OBJECTIVES: The objectives of this paper were to explore suicide risk in a population of individuals endorsing recent drug use, and to describe patient demographic, medical, psychiatric, social, and substance use characteristics across different levels of suicide risk. METHODS: A total of 867 primary care patients with reported drug use in the previous 90 days were studied. Based upon their responses to two Addiction Severity Index questions, four suicide risk categories were constructed: (1) low risk; (2) moderate-low (suicidal ideation in the past 30 days); (3) moderate-high (history of a lifetime suicide attempt); and (4) high risk (history of a lifetime suicide attempt and suicidal ideation in the past 30 days). The association between suicide risk groups and demographic and clinical variables were assessed. RESULTS: A total of 40% of primary care patients endorsing recent drug use reported a lifetime suicide attempt. Compared to individuals in other suicide risk groups, individuals at high suicide risk had higher rates of substance use severity, recently used two or more substances, and were more likely to have a comorbid psychiatric condition. CONCLUSION: These findings indicate that the percentage of patients with suicide risk may be higher among patients with recent drug use. Primary care clinicians should be aware that they may be encountering patients with suicide risk among those with recent drug use.

Barriers and Facilitators to Coordinating Care With High-Risk, High-Cost Disabled Medicaid Beneficiaries: Perspectives of Frontline Staff and Participating Clients.

This evaluation was designed to examine the perspectives of 15 frontline staff who implemented a managed care program and 154 high-risk, high-cost disabled Medicaid clients who were participants in the program. Results indicated that positive relationships between staff and clients played a key role in facilitating program implementation. Challenges included finding ways to provide a wide breadth of services including food, shelter, and transportation; handling difficulties following from staff turnover; and creating transitions of care for clients to community health clinics. Staff identified training in motivational interviewing and having both nurse care managers and social workers collaboratively deliver the intervention as among the most powerful components of the program. Staff and clients expressed high levels of satisfaction with the program, and clients believed they were experiencing positive impacts of the program. Lessons learned from this study may inform the design of services as the Affordable Care Act continues to unfold.

Self-reported Usual Care for Self-directed Violence During the 6 Months Before Emergency Department Admission.

BACKGROUND: The literature describing the health services individuals receive before and following self-directed violence (SDV) is limited. OBJECTIVES: This study examines services received for the 6 months preceding admission to an urban county medical center emergency department (ED) for SDV. We predicted that individuals with at least 1 prior act of SDV in the past 6 months would have received more services than those for whom the index admission was their only recent act. METHODS: Participants were recruited from ED admissions during shifts selected to maximize representativeness. Participants (n=202) were interviewed using the Suicide Attempt Self-Injury Interview, Suicide Attempt Self-Injury Count, Treatment History Interview, Mini International Neuropsychiatric Interview, Brief Symptom Index, and SF-12. RESULTS: The majority of index acts of SDV (79%) were suicide attempts. The participants were characterized by low socioeconomic status, substantial symptomatology, low physical and mental health functioning, and multiple psychiatric diagnoses. In the preceding 6 months, 34% were admitted to a hospital and 56% received crisis services (including 44% in the ED). Although three quarters (76%) had seen an outpatient medical provider and most (70%) received psychotropic medications, less than half of the sample received psychiatric services (40%) or outpatient psychosocial treatment (48%). As predicted, utilization for most types of usual care was higher for those engaging in SDV in the 6 months preceding the index admission. CONCLUSION: Individuals admitted to this ED for SDV received inadequate outpatient psychosocial and psychiatric services despite severe illness and disability.

Are medical marijuana users different from recreational users? The view from primary care.

BACKGROUND AND OBJECTIVES: Marijuana is currently approved for medical use in 23 states. Both clinicians and the lay public have questioned whether users of marijuana for medical purposes are different from users of marijuana for recreational purposes. This study examined similarities and differences in important clinical characteristics between users of medical marijuana and users of recreational marijuana. METHODS: The sample consisted of 868 adult primary care patients in Washington State, who reported use of medical marijuana (n = 131), recreational marijuana (n = 525), or drugs other than marijuana (n = 212). Retention was over 87% at 3-, 6-, 9-, and 12-month assessments. RESULTS: The majority of medical, psychiatric, substance use, and service utilization characteristic comparisons were not significant. However, medical marijuana users had significantly more medical problems, a significantly larger proportion reported >15 days medical problems in the past month, and significantly smaller proportions reported no pain and no mobility limitations (p < .001). Medical marijuana users also had significantly lower drug problem severity, lower alcohol problem severity, and significantly larger proportions reported using marijuana alone and concomitant opioid use only (p < .001). There was no significant difference between medical and recreational users in the percentage using marijuana with at least two additional substances (48% vs. 58%, respectively, p = .05). CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Although our results suggest that there are few distinct differences between medical and recreational users of marijuana, the differences observed, while mostly very small in effect size (<.2), are consistent with at least some medical users employing marijuana to relieve symptoms and distress associated with medical illness.

Transcranial magnetic stimulation in the treatment of chronic widespread pain: a randomized controlled study.

OBJECTIVE: Our objective was to assess transcranial magnetic stimulation (TMS) in the treatment of chronic widespread pain. METHODS: Nineteen participants were randomized into 2 groups: one group receiving active TMS (n = 7) and another group receiving sham stimulation (n = 11) applied to the left dorsolateral prefrontal cortex. During sham stimulation, subjects heard a sound similar to the sound heard by those receiving the active treatment and received an active electrical stimulus to the scalp. The stimulation protocol consisted of 15 sessions completed within a 4-week period. Blind assessments were done at baseline and after each 5 sessions followed by blind assessments at 1 week, 1 month, and 3 months after the last TMS sessions. The primary outcome variable was a pain measure, the Gracely Box Intensity Scale (BIRS). RESULTS: The percentage of subjects who guessed that they were receiving TMS was similar in the 2 groups. Both the TMS group and the sham group showed a statistically significant reduction in the BIRS scores from baseline during the acute phase of treatment and the follow-up phase. However, the TMS and sham groups did not differ in the change in the BIRS scores. DISCUSSION: Although some previous clinical studies and basic science studies of TMS in treating pain are promising, this study found no difference in the analgesic effect of TMS and sham stimulation. Future studies should use a sham condition that attempts to simulate the sound and sensation of the TMS stimulation. Stimulus location and other stimulus parameters should be explored in future studies.

Perceived social support mediates anxiety and depressive symptom changes following primary care intervention.

BACKGROUND: The current study tested whether perceived social support serves as a mediator of anxiety and depressive symptom change following evidence-based anxiety treatment in the primary care setting. Gender, age, and race were tested as moderators. METHODS: Data were obtained from 1004 adult patients (age M = 43, SD = 13; 71% female; 56% White, 20% Hispanic, 12% Black) who participated in a randomized effectiveness trial (coordinated anxiety learning and management [CALM] study) comparing evidence-based intervention (cognitive-behavioral therapy and/or psychopharmacology) to usual care in the primary care setting. Patients were assessed with a battery of questionnaires at baseline, as well as at 6, 12, and 18 months following baseline. Measures utilized in the mediation analyses included the Abbreviated Medical Outcomes (MOS) Social Support Survey, the Brief Symptom Index (BSI)-Somatic and Anxiety subscales, and the Patient Health Questionnaire (PHQ-9). RESULTS: There was a mediating effect over time of perceived social support on symptom change following treatment, with stronger effects for 18-month depression than anxiety. None of the mediating pathways were moderated by gender, age, or race. CONCLUSIONS: Perceived social support may be central to anxiety and depressive symptom changes over time with evidence-based intervention in the primary care setting. These findings possibly have important implications for development of anxiety interventions.

Changes in self-efficacy and outcome expectancy as predictors of anxiety outcomes from the CALM study.

BACKGROUND: Although self-efficacy (SE) and outcome expectancy (OE) have been well researched as predictors of outcome, few studies have investigated changes in these variables across treatments. We evaluated changes in OE and SE throughout treatment as predictors of outcomes in a large sample with panic disorder, generalized anxiety disorder, social anxiety disorder, or posttraumatic stress disorder. We hypothesized that increases in SE and OE would predict reductions in anxiety and depression as well as improvement in functioning. METHODS: Participants (mean age = 43.3 years, SD = 13.2, 71.1% female, 55.5% white) were recruited from primary care centers throughout the United States and were randomized to receive either Coordinated Anxiety Learning and Management (CALM) treatment - composed of cognitive behavioral therapy, psychotropic medication, or both - or usual care. SE and OE ratings were collected at each session for participants in the CALM treatment (n = 482) and were entered into a structural equation model as predictors of changes in Brief Symptom Inventory, Anxiety Sensitivity Index, Patient Health Questionnaire (PHQ), and Sheehan Disability Scale outcomes at 6, 12, and 18 months after baseline. RESULTS: The best-fitting models predict symptom levels from OE and SE and not vice versa. The slopes and intercept of OE significantly predicted change in each outcome variable except PHQ-8. The slope and intercept of SE significantly predicted change in each outcome variable. CONCLUSION: Over and above absolute level, increases in SE and OE were significant predictors of decreases in symptoms and increases in functioning. Implications for treatment are discussed, as well as future directions of research.

No change in neuropsychological functioning after receiving repetitive transcranial magnetic stimulation treatment for major depression.

Early studies of transcranial magnetic stimulation (TMS) have shown no adverse effects on neuropsychological function. However, further research using higher TMS intensities as well as a greater number of TMS pulses and with larger sample sizes is needed. We studied 68 patients with major depressive disorder who were randomized to receive either 15 sessions of sham or real TMS at 110% of the estimated prefrontal cortex threshold to the left dorsolateral prefrontal cortex. Each session consisted of 32 5-second trains of 10-Hz repetitive TMS at 110% adjusted motor threshold. A total of 24,000 pulses were given. Neuropsychological function was assessed before and immediately after TMS treatment with a battery of 8 tests. Using a higher TMS intensity as well as a greater number of pulses and having a larger sample size compared with most previous studies, this study found no negative neuropsychological effects of TMS. Changes in neuropsychological function were unrelated to changes in depression.

Brief intervention for problem drug use in safety-net primary care settings: a randomized clinical trial.

IMPORTANCE: Although brief intervention is effective for reducing problem alcohol use, few data exist on its effectiveness for reducing problem drug use, a common issue in disadvantaged populations seeking care in safety-net medical settings (hospitals and community health clinics serving low-income patients with limited or no insurance). OBJECTIVE: To determine whether brief intervention improves drug use outcomes compared with enhanced care as usual. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial with blinded assessments at baseline and at 3, 6, 9, and 12 months conducted in 7 safety-net primary care clinics in Washington State. Of 1621 eligible patients reporting any problem drug use in the past 90 days, 868 consented and were randomized between April 2009 and September 2012. Follow-up participation was more than 87% at all points. INTERVENTIONS: Participants received a single brief intervention using motivational interviewing, a handout and list of substance abuse resources, and an attempted 10-minute telephone booster within 2 weeks (n = 435) or enhanced care as usual, which included a handout and list of substance abuse resources (n = 433). MAIN OUTCOMES AND MEASURES: The primary outcomes were self-reported days of problem drug use in the past 30 days and Addiction Severity Index-Lite (ASI) Drug Use composite score. Secondary outcomes were admission to substance abuse treatment; ASI composite scores for medical, psychiatric, social, and legal domains; emergency department and inpatient hospital admissions, arrests, mortality, and human immunodeficiency virus risk behavior. RESULTS: Mean days used of the most common problem drug at baseline were 14.40 (SD, 11.29) (brief intervention) and 13.25 (SD, 10.69) (enhanced care as usual); at 3 months postintervention, means were 11.87 (SD, 12.13) (brief intervention) and 9.84 (SD, 10.64) (enhanced care as usual) and not significantly different (difference in differences, ß = 0.89 [95% CI, -0.49 to 2.26]). Mean ASI Drug Use composite score at baseline was 0.11 (SD, 0.10) (brief intervention) and 0.11 (SD, 0.10) (enhanced care as usual) and at 3 months was 0.10 (SD, 0.09) (brief intervention) and 0.09 (SD, 0.09) (enhanced care as usual) and not significantly different (difference in differences, ß = 0.008 [95% CI, -0.006 to 0.021]). During the 12 months following intervention, no significant treatment differences were found for either variable. No significant differences were found for secondary outcomes. CONCLUSIONS AND RELEVANCE: A one-time brief intervention with attempted telephone booster had no effect on drug use in patients seen in safety-net primary care settings. This finding suggests a need for caution in promoting widespread adoption of this intervention for drug use in primary care. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00877331.

Reciprocal and Indirect Effects Among Intervention, Perceived Social Support, and Anxiety Sensitivity Within a Randomized Controlled Trial for Anxiety Disorders.

Social support may facilitate adaptive reappraisal of stressors, including somatic symptoms. Anxiety sensitivity refers to negative beliefs about somatic symptoms of anxiety, which may influence one's perception of social support. Evidence-based treatment may impact these associations. The current longitudinal study evaluated reciprocal relationships between perceived social support and anxiety sensitivity, and explored indirect intervention effects, in a randomized controlled trial for anxiety disorders that compared cognitive behavioral therapy with or without medications (CALM) to usual care. Data collected over 18 months from 940 primary care patients were examined in random intercept cross-lagged panel models. There were significant reciprocal associations between perceived social support increases and anxiety sensitivity decreases over time. There were significant indirect effects from intervention to perceived social support increases through anxiety sensitivity decreases and from intervention to anxiety sensitivity decreases through perceived social support increases. These data suggest that, relative to usual care, CALM predicted changes in one construct, which predicted subsequent changes in the other. Secondary analyses revealed an influence of anxiety and depressive symptoms on reciprocal associations and indirect effects. Findings suggest that future treatments could specifically address perceived social support to enhance reappraisal of somatic symptoms, and vice versa.

Effects of medical comorbidity on anxiety treatment outcomes in primary care.

OBJECTIVE: To evaluate the effects of medical comorbidity on anxiety treatment outcomes. METHODS: Data were analyzed from 1004 primary care patients enrolled in a trial of a collaborative care intervention for anxiety. Linear-mixed models accounting for baseline characteristics were used to evaluate the effects of overall medical comorbidity (two or more chronic medical conditions [CMCs] versus fewer than two CMCs) and specific CMCs (migraine, asthma, and gastrointestinal disease) on anxiety treatment outcomes at 6, 12, and 18 months. RESULTS: At baseline, patients with two or more CMCs (n = 582; 58.0%) reported more severe anxiety symptoms (10.5 [95% confidence interval {CI} = 10.1-10.9] versus 9.5 [95% CI = 9.0-10.0], p = .003) and anxiety-related disability (17.6 [95% CI = 17.0-18.2] versus 16.0 [95% CI = 15.3-16.7], p = .001). However, their clinical improvement was comparable to that of patients with one or zero CMCs (predicted change in anxiety symptoms = -3.9 versus -4.1 at 6 months, -4.6 versus -4.4 at 12 months, -4.9 versus -5.0 at 18 months; predicted change in anxiety-related disability = -6.4 versus -6.9 at 6 months, -6.9 versus -7.3 at 12 months, -7.3 versus -7.5 at 18 months). The only specific CMC with a detrimental effect was migraine, which was associated with less improvement in anxiety symptoms at 18 months (predicted change = -4.1 versus -5.3). CONCLUSIONS: Effectiveness of the anxiety intervention was not significantly affected by the presence of multiple CMCs; however, patients with migraine displayed less improvement at long-term follow-up. Trial Registration ClinicalTrials.com Identifier: NCT00347269.

Collaborative care at the crossroads.

Collaborative care is a well-studied and effective model of integrating behavioural healthcare into primary care medical settings. Despite evidence of its effectiveness, it has been difficult to implement into the US healthcare system. The upcoming reorganisation of US healthcare will rely heavily on adaptations of this model to improve its uptake and cost-effectiveness.