Nutrition biomarker assessment and exploration of the role of country foods to improve food security in the Sahtú Region, Canada.

Country foods (i.e. wild traditional food) are associated with improved nutrition for northern populations.

High genetic load without purging in caribou, a diverse species at risk.

High intra-specific genetic diversity is associated with adaptive potential, which is key for resilience to global change. However, high variation may also support deleterious alleles through genetic load, thereby increasing the risk of inbreeding depression if population sizes decrease. Purging of deleterious variation has been demonstrated in some threatened species.

Psychotherapies for Panic Disorder: A Tale of Two Sites.

Objective: To compare cognitive-behavioral therapy (CBT), panic-focused psychodynamic psychotherapy (PFPP), and applied relaxation training (ART) for primary DSM-IV panic disorder with and without agoraphobia in a 2-site randomized controlled trial.

Method: 201 patients were stratified for site and DSM-IV agoraphobia and depression and were randomized to CBT, PFPP, or ART (19-24 sessions) over 12 weeks in a 2:2:1 ratio at Weill Cornell Medical College (New York, New York) and University of Pennsylvania ("Penn"; Philadelphia, Pennsylvania). Any medication was held constant.

Bipolar CHOICE (Clinical Health Outcomes Initiative in Comparative Effectiveness): a pragmatic 6-month trial of lithium versus quetiapine for bipolar disorder.

Background: Bipolar disorder is among the 10 most disabling medical conditions worldwide. While lithium has been used extensively for bipolar disorder since the 1970s, second-generation antipsychotics (SGAs) have supplanted lithium since 1998. To date, no randomized comparative-effectiveness study has compared lithium and any SGA.

An exploratory study of responses to low-dose lithium in African Americans and Hispanics.

Objectives: Few prospective studies examine the impact of ethnicity or race on outcomes with lithium for bipolar disorder. This exploratory study examines differences in lithium response and treatment outcomes in Hispanics, African Americans, and non-Hispanic whites with bipolar disorder in the Lithium Treatment Moderate Dose Use Study (LiTMUS).

Methods: LiTMUS was a six-site randomized controlled trial of low-dose lithium added to optimized treatment (OPT; personalized, evidence-based pharmacotherapy) vs.

Clinical effectiveness of integrating depression care management into medicare home health: the Depression CAREPATH Randomized trial.

Importance: Among older home health care patients, depression is highly prevalent, is often inadequately treated, and contributes to hospitalization and other poor outcomes. Feasible and effective interventions are needed to reduce this burden of depression.

Objective: To determine whether, among older Medicare Home Health recipients who screen positive for depression, patients of nurses receiving randomization to an intervention have greater improvement in depressive symptoms during 1 year than patients receiving enhanced usual care.

The effect of personalized guideline-concordant treatment on quality of life and functional impairment in bipolar disorder.

Objectives: The aims of this study were to evaluate correlates and predictors of life functioning and quality of life in bipolar disorder during a comparative effectiveness trial of moderate doses of lithium.

Methods: In the Lithium treatment moderate-dose use study (LiTMUS), 283 symptomatic outpatients with bipolar disorder type I or II were randomized to receive lithium plus "optimal personalized treatment (OPT)", or OPT alone. Participants were assessed using structured diagnostic interviews, clinician-rated blinded assessments, and questionnaires.

A novel application of the Intent to Attend assessment to reduce bias due to missing data in a randomized controlled clinical trial.

Background: Missing data are unavoidable in most randomized controlled clinical trials, especially when measurements are taken repeatedly. If strong assumptions about the missing data are not accurate, crude statistical analyses are biased and can lead to false inferences. Furthermore, if we fail to measure all predictors of missing data, we may not be able to model the missing data process sufficiently.

Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder (Bipolar CHOICE): a pragmatic trial of complex treatment for a complex disorder.

Background: Classic and second-generation antipsychotic mood stabilizers are recommended for treatment of bipolar disorder, yet there are no randomized comparative effectiveness studies that have examined the 'real-world' advantages and disadvantages of these medications.

Purpose: We describe the strategic decisions in the design of the Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder (Bipolar CHOICE). This article outlines the key issues and solutions the investigators faced in designing a clinical trial that would maximize generalizability and inform real-world clinical treatment of bipolar disorder.

Use of treatment services in a comparative effectiveness study of bipolar disorder.

OBJECTIVE Bipolar disorder is a severe, chronic mental illness with a high incidence of medical and psychological comorbidities that make treatment and prevention of future episodes challenging. This study investigated the use of services among outpatients with bipolar disorder to further understanding of how to maximize and optimize personalization and accessibility of services for this difficult-to-treat population. METHODS The Lithium Treatment-Moderate Dose Use Study (LiTMUS) was a six-month multisite, comparative effectiveness trial that randomly assigned 283 individuals to receive lithium plus optimized care-defined as personalized, guideline-informed care-or optimized care without lithium.

The Medication Recommendation Tracking Form: a novel tool for tracking changes in prescribed medication, clinical decision making, and use in comparative effectiveness research.

This paper describes the development and use of the Medication Recommendation Tracking Form (MRTF), a novel method for capturing physician prescribing behavior and clinical decision making. The Bipolar Trials Network developed and implemented the MRTF in a comparative effectiveness study for bipolar disorder (LiTMUS). The MRTF was used to assess the frequency, types, and reasons for medication adjustments.

Defining a clinically meaningful effect for the design and interpretation of randomized controlled trials.

Objective: This article captures the proceedings of a meeting aimed at defining clinically meaningful effects for use in randomized controlled trials for psychopharmacological agents.

Design: Experts from a variety of disciplines defined clinically meaningful effects from their perspectives along with viewpoints about how to design and interpret randomized controlled trials.

Setting: The article offers relevant, practical, and sometimes anecdotal information about clinically meaningful effects and how to interpret them.

Subject-level matching for imbalance in cluster randomized trials with a small number of clusters.

In a cluster randomized controlled trial (RCT), the number of randomized units is typically considerably smaller than in trials where the unit of randomization is the patient. If the number of randomized clusters is small, there is a reasonable chance of baseline imbalance between the experimental and control groups. This imbalance threatens the validity of inferences regarding post-treatment intervention effects unless an appropriate statistical adjustment is used.

A controlled clinical treatment trial of interpersonal psychotherapy for depressed pregnant women at 3 New York City sites.

Objective: While treatment decisions for antepartum depression must be personalized to each woman and her illness, guidelines from the American Psychiatric Association and the American College of Obstetrics and Gynecology include the recommendation of psychotherapy for mild-to-moderate depression in pregnant women. Although we previously demonstrated the efficacy of interpersonal psychotherapy for antepartum depression in a sample of Hispanic women, this study provides a larger, more diverse sample of African American, Hispanic, and white pregnant women from 3 New York City sites in order to provide greater generalizability.

Method: A 12-week bilingual, parallel-design, controlled clinical treatment trial compared interpersonal psychotherapy for antepartum depression to a parenting education program control group.

Recovery from multiple episodes of bipolar I depression.

Objective: To describe the duration of bipolar I major and minor depressive episodes and factors associated with time to recovery.

Method: As part of the National Institute of Mental Health Collaborative Depression Study, 219 participants with bipolar I disorder based on Research Diagnostic Criteria analogs to DSM-IV-TR criteria were recruited at 5 academic medical centers from 1978 to 1981 and followed for up to 25 years with the Longitudinal Interval Follow-Up Evaluation. The probability of recovery over time from depressive episodes, the primary outcome measure, was examined with mixed-effects grouped-time survival models.

Lithium treatment moderate-dose use study (LiTMUS) for bipolar disorder: a randomized comparative effectiveness trial of optimized personalized treatment with and without lithium.

Objective: Lithium salts, once the mainstay of therapy for bipolar disorder, have tolerability issues at a higher dosage that often limit adherence. The authors investigated the comparative effectiveness of more tolerable dosages of lithium as part of optimized personalized treatment (OPT).

Method: The authors randomly assigned 283 bipolar disorder outpatients to 6 months of open, flexible, moderate dosages of lithium plus OPT or to 6 months of OPT alone.

Dysfunctional attitudes as a moderator of pharmacotherapy and psychotherapy for chronic depression.

Objective: Individuals with chronic depression exhibit heterogeneous responses to treatment. Important individual differences may therefore exist within this particularly difficult to treat population that act as moderators of treatment response.

Method: The present study examined whether pretreatment levels of dysfunctional attitudes (DA) moderated treatment response in a large sample of chronically depressed individuals.

Age of onset and the prospectively observed course of illness in bipolar disorder.

Background: To test the validity of age-of-onset grouping in bipolar disorder through the use of prospectively observed time in mood episodes.

Methods: Age-of-onset ranges from prior admixture analyses were used to divide 427 individuals with bipolar I or bipolar II disorders into early-, middle- and late- onset groups. These were compared by the proportions of weeks depressed and manic or hypomanic during a mean (SD) prospective follow-up of 17.

Performance of a propensity score adjustment in longitudinal studies with covariate-dependent representation.

Longitudinal observational studies provide rich opportunities to examine treatment effectiveness during the course of a chronic illness. However, there are threats to the validity of observational inferences. For instance, clinician judgment and self-selection play key roles in treatment assignment.

Independent data and safety monitoring in psychiatric intervention research.

A data and safety monitoring board (DSMB) is a multidisciplinary group of scientists that monitors a randomized clinical trial. Although DSMBs have been used for clinical trials in cardiology, oncology, and infectious disease for decades, it was not until the late 1990s that the National Institute of Mental Health (NIMH) initially required a DSMB for some of its larger trials. The NIMH mandate expanded during the succeeding decade to require DSMBs for many of the clinical trials in psychiatry.

A randomized controlled trial of supported employment among veterans with posttraumatic stress disorder.

Objective: Posttraumatic stress disorder (PTSD) is a potentially disabling mental illness that can cause occupational dysfunction. Although vocational rehabilitation is often prescribed for patients with PTSD, standard vocational services are far from adequate in helping them obtain and maintain competitive employment. This study is the first to examine the outcome of evidence-based supported employment for veterans with PTSD.