Resting state fMRI scanner instabilities revealed by longitudinal phantom scans in a multi-center study.

Quality assurance (QA) is crucial in longitudinal and/or multi-site studies, which involve the collection of data from a group of subjects over time and/or at different locations. It is important to regularly monitor the performance of the scanners over time and at different locations to detect and control for intrinsic differences (e.g., due to manufacturers) and changes in scanner performance (e.g., due to gradual component aging, software and/or hardware upgrades, etc.). As part of the Ontario Neurodegenerative Disease Research Initiative (ONDRI) and the Canadian Biomarker Integration Network in Depression (CAN-BIND), QA phantom scans were conducted approximately monthly for three to four years at 13 sites across Canada with 3T research MRI scanners. QA parameters were calculated for each scan using the functional Biomarker Imaging Research Network's (fBIRN) QA phantom and pipeline to capture between- and within-scanner variability. We also describe a QA protocol to measure the full-width-at-half-maximum (FWHM) of slice-wise point spread functions (PSF), used in conjunction with the fBIRN QA parameters. Variations in image resolution measured by the FWHM are a primary source of variance over time for many sites, as well as between sites and between manufacturers. We also identify an unexpected range of instabilities affecting individual slices in a number of scanners, which may amount to a substantial contribution of unexplained signal variance to their data. Finally, we identify a preliminary preprocessing approach to reduce this variance and/or alleviate the slice anomalies, and in a small human data set show that this change in preprocessing can have a significant impact on seed-based connectivity measurements for some individual subjects. We expect that other fMRI centres will find this approach to identifying and controlling scanner instabilities useful in similar studies.

The effect of remission status on work functioning in employed patients treated for major depressive disorder.

BACKGROUND: The ability to function at work is impaired in patients with major depressive disorder (MDD) but few clinical trials include occupational outcome assessments. This study examined whether symptom remission following treatment for MDD is associated with work functioning improvement. METHODS: We conducted a secondary analysis of a 12-week randomized clinical trial comparing escitalopram with or without telephone-administered cognitive therapy in employed patients with MDD (N = 86). Outcomes included the Montgomery-Åsberg Depression Rating Scale (MADRS) and validated, self-rated work functioning scales including the Lam Employment Absence and Productivity Scale (LEAPS), Work Performance Questionnaire (HPQ), and Sheehan Disability Scale (SDS). Remission was defined as MADRS score ≤10 at 12 weeks. Data were evaluated using analysis of covariance with baseline score as covariates. RESULTS: Remission status was associated with significant improvement in work performance as assessed by the LEAPS productivity subscale, HPQ overall performance, and the SDS work/school item; a trend (P = .08) was observed with the HPQ productivity subscale. The effect sizes (d = 0.23, 0.51, 0.36, and 0.43, respectively) indicate small to medium effects that are likely clinically significant. CONCLUSIONS: The results of our study confirm that symptom remission following treatment is associated significantly with improvement in work performance and productivity, as measured by validated work functioning scales. Measurement-based care for MDD should include both symptom and functional outcome assessments.

Long-term neuropsychological safety of subgenual cingulate gyrus deep brain stimulation for treatment-resistant depression.

Deep brain stimulation (DBS) of the subgenual cingulate gyrus (SCG) is a promising investigational intervention for treatment-resistant depression (TRD), but long-term outcome data are limited. Serial neuropsychological evaluations, using a comprehensive battery, were conducted on four subjects with TRD prior to surgery, and up to 42 months post-operatively. Reliable change methodology suggested general stability and/or select statistically reliable improvement in cognitive abilities over time. This is the first known set of multi-year neuropsychological follow-up data for SCG DBS for TRD. Observed improvements are likely attributable to reduced depressive symptomatology, recovery of functional capacities, and/or specific practice effects of repeated assessment.

Relationship between work functioning and self-reported cognitive complaints in patients with major depressive disorder treated with desvenlafaxine.

Patients with major depressive disorder (MDD) often report that cognitive difficulties, such as memory problems or poor concentration, interfere with their work functioning. We examined the association between self-reported cognitive complaints and work functioning in employed patients with MDD treated with desvenlafaxine. A sample of 36 adult outpatients with MDD completed subjective cognition (British Columbia Cognitive Complaints Inventory [BC-CCI]) and functioning scales (Sheehan Disability Scale [SDS]; Lam Employment Absence and Productivity Scale [LEAPS]; and Health and Work Performance Questionnaire [HPQ]) before and after 8 weeks of open-label treatment with flexibly-dosed desvenlafaxine (50-100 mg/day). Multiple regression analyses were used to assess the relationship between subjective cognitive measures and work functioning scales. Patients showed significant improvements in clinical, cognitive, and work functioning measures following treatment with desvenlafaxine. A predictive association was found between the BC-CCI and both the SDS and LEAPS, but not with the HPQ, when adjusted for depression severity. Self-report cognitive questionnaires can provide useful information to monitor changes in cognitive functioning over time and to predict improvement in work functioning outcomes.

The impact of fatigue and energy on work functioning and impairment in patients with major depressive disorder treated with desvenlafaxine.

Fatigue and low energy are cardinal symptoms of major depressive disorder (MDD) that have an impact on work functioning. Antidepressants with noradrenergic activity have been hypothesized to improve symptoms of fatigue and low energy. We examined the impact of these symptoms on work functioning in patients with MDD treated with the serotonin and noradrenaline reuptake inhibitor, desvenlafaxine. A secondary analysis was carried out from a study of employed adult outpatients (n=35) with MDD and subjective cognitive complaints treated with desvenlafaxine 50-100 mg/day for 8 weeks. Multiple regression analyses modeled improvement in work functioning measures (Lam Employment Absence and Productivity Scale, Health and Work Performance Questionnaire, Sheehan Disability Scale) with measures of fatigue (Patient-Reported Outcomes Measurement Information System Fatigue scale and 20-item Hopkins Symptom Check List Energy scale). Patients showed a significant improvement in Montgomery-Åsberg Depression Rating Scale scores as well as in fatigue and work functioning measures following treatment. Fatigue measures were significantly associated with improvement in some (Lam Employment Absence and Productivity Scale, Sheehan Disability Scale), but not all (Health and Work Performance Questionnaire) work functioning measures, independent of improvement in overall depressive symptoms. The limitations of this study include the small sample size and the lack of a placebo or a comparison group. Fatigue and low energy are important symptoms that are associated with occupational impairment in MDD. Treatments that improve these symptoms are likely to improve work functioning.

The Effects of Newer Antidepressants on Occupational Impairment in Major Depressive Disorder: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVES: A substantial proportion of the disease burden of major depressive disorder (MDD) results from impairments in occupational functioning, including disability and reduced productivity. Accumulating evidence suggests that antidepressants can improve functional as well as symptomatic outcomes in patients with MDD. We examined the treatment effects of newer antidepressants on occupational impairment in MDD, based on a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: We searched MEDLINE, EMBASE, and ClinicalTrials.gov for the period 1 January 1992 to 15 June 2015 to identify RCTs of newer antidepressants (excluding tricyclic antidepressants and monoamine oxidase inhibitors), with or without a placebo condition, that included a validated measure of occupational functioning in patients with MDD. Abstracts were scanned for eligibility by two independent reviewers and investigators of unpublished studies were contacted to obtain data. Study data were extracted and double-entered for accuracy. We selected the Sheehan Disability Scale Work/School subscale (SDS-Work) for the meta-analysis because it was the most consistently used assessment of occupational impairment. Analysis employed a random-effects model. RESULTS: The systematic review initially identified 42 RCTs but only 28 (67 %) had data on occupational outcomes that were published or obtained from investigators. The SDS-Work subscale was used in 25 of 28 trials; five other assessments of occupational functioning were used in seven trials. Data were synthesized from 17 placebo-controlled studies (n = 7031) that used the SDS-Work subscale. Antidepressants (n = 4722) were significantly superior to placebo (n = 2309) in improving SDS-Work scores at 8 weeks, with a mean difference of 0.73 [95 % confidence interval (CI) 0.60-0.86] and a standardized mean difference of 0.28 (95 % CI 0.23-0.33), representing small effects. LIMITATIONS: Few included trials reported on the employment status of their samples, and most trials were of short-term treatment duration (8-12 weeks). Several RCTs that collected data on occupational outcomes were also excluded from the review and meta-analysis because their data were unpublished and unobtainable. CONCLUSIONS: Our meta-analysis suggests that newer antidepressants have a small, positive impact on occupational impairment in the short-term, but the clinical significance of this impact is questionable. To improve assessment of this important outcome, future research studies should use more comprehensive measures of occupational functioning, productivity and impairment, and longer treatment durations.

The effects of desvenlafaxine on neurocognitive and work functioning in employed outpatients with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is associated with staggering personal and economic costs, a major proportion of which stem from impaired psychosocial and occupational functioning. Few studies have examined the impact of depression-related cognitive dysfunction on work functioning. We examined the association between neurocognitive and work functioning in employed patients with MDD. METHODS: Employed adult outpatients (n=36) with MDD of at least moderate severity (≥23 on the Montgomery Asberg Depression Rating Scale, MADRS) and subjective cognitive complaints completed neurocognitive tests (CNS Vital Signs computerized battery) and validated self-reports of their work functioning (LEAPS, HPQ) before and after 8 weeks of open-label treatment with flexibly-dosed desvenlafaxine 50-100mg/day. Relationships between neurocognitive tests and functional measures were examined using bivariate correlational and multiple regression analyses, as appropriate. An ANCOVA model examined whether significant change in neurocognitive performance, defined as improvement of ≥1SD in the Neurocognition Index (NCI) from baseline to post-treatment, was associated with improved outcomes. RESULTS: Patients showed significant improvements in depressive symptom, neurocognitive, and work functioning measures following treatment with desvenlafaxine (e.g., MADRS response=77% and MADRS remission=49%). There were no significant correlations between changes in NCI or cognitive domain subscales and changes in MADRS, LEAPS, or HPQ scores. However, patients demonstrating significant improvement in NCI scores (n=11, 29%) had significantly greater improvement in clinical and work functioning outcomes compared to those without NCI improvement. LIMITATIONS: The limitations of this study include small sample size, lack of a placebo control group, and lack of a healthy comparison group. Our sample also had more years of education and higher premorbid intelligence than the general population. CONCLUSIONS: There were no significant correlations between changes in neurocognitive and work functioning measures in this study. However, meaningful improvement in neurocognitive functioning with desvenlafaxine was associated with greater improvement in both mood and occupational outcomes. This suggests that addressing cognitive dysfunction may improve clinical and occupational outcomes in employed patients with MDD. However, the relationship between neurocognitive and work functioning in MDD is complex and requires further study.

The relationship between burnout and depressive symptoms in patients with depressive disorders.

BACKGROUND: Burnout - physical or psychological fatigue in the personal, work and client-related work domains - appears to share numerous overlapping characteristics with major depressive episodes. However, whether burnout and depression are in fact separate conditions is still ambiguous. Our aim was to examine burnout in a clinically depressed patient sample. METHODS: Outpatients with a DSM-IV depressive episode (major depressive episode and dysthymic disorder) completed the Copenhagen Burnout Inventory (CBI) and the Quick Inventory for Depressive Symptomatology, Self-Rated (QIDS-SR). The relationship between CBI-defined burnout and depressive symptoms was examined using correlation and hierarchical multiple regression analyses. RESULTS: Depressed patients had high rates of CBI-defined burnout as well as significant correlations between burnout scores and overall depression severity scores. Individual depressive symptoms were significantly higher between patients with and without burnout, and significantly correlated with burnout scores, with the exception of guilt/worthlessness. Multiple regression analysis identified changes in sleep and fatigue as significant predictors of burnout. LIMITATIONS: The main limitations of the study were the sample size, the broad definition of depression, and the cross-sectional design. CONCLUSIONS: The high burnout scores and correlations between burnout and depression severity observed in this study highlight the importance of understanding burnout in depressed patients. Despite the significant overlap between burnout and depression, the relationship between these two concepts still requires further clarification.

Evaluation of a depression health management program to improve outcomes in first or recurrent episode depression.

OBJECTIVES: To evaluate the impact of telephone counseling and educational materials on medication adherence and persistency among members with newly diagnosed depression enrolled in a pharmacy benefit management-sponsored disease management program. STUDY DESIGN: Longitudinal cohort observation. METHODS: The study population comprised 505 members with a new or recurrent episode of depression who consented and enrolled in a depression disease management program. After written consent was obtained, program participants received up to 4 telephone-counseling calls and 5 educational mailings focused on the importance of medication compliance, barriers to medication compliance, quality of life, symptoms, and satisfaction with the program. A control group of 3744 members was selected from client companies that opted not to offer the depression program. Measures of medication adherence, persistency with prescription drug therapy, and patient refill timeliness were computed for both groups and compared. RESULTS: Patients enrolled in the depression disease management program were significantly more likely to adhere to their medication regimen during acute (89.0% vs 67.7%, P < .001) and continuation treatment phases (81.1% vs 57.6%, P < .001). In addition, members enrolled in the program were significantly more likely to continue their therapy after 7 months (77.8% vs 49.5%, P < .001) and refilled their prescriptions on a more timely basis (0 vs 18 days, P < .001). CONCLUSIONS: A pharmacy benefit management-sponsored health management depression program succeeded in encouraging patients with new or recurrent depression to stay on antidepressant medication and to reach treatment goals outlined by best practice guidelines.

The prevalence and impact of depression in self-referred clients attending an employee assistance program.

OBJECTIVE: To determine the prevalence and characteristics of clients with depression attending an employee assistance program (EAP). METHODS: Anonymized data were obtained from 10,794 consecutive clients, including 9105 employees, self-referred to PPC Canada, a large, external EAP. Assessment measures included the self-rated nine-item Patient Health Questionnaire (PHQ-9). Clinical characteristics of depressed clients (PHQ-9 score ≥ 10) were compared with those of nondepressed clients. RESULTS: Thirty-seven percent of the employee sample met PHQ-9 criteria for clinically significant depression. Compared with clients without depression, they had significantly higher rates of anxiety, psychotropic medication use, problem substance use, global problems with functioning, absenteeism, impairment in work-related tasks, and low job satisfaction. CONCLUSIONS: A large proportion of EAP clients were clinically depressed with associated negative effects on personal and occupational functioning.

Pediatric eye disease investigator group amblyopia treatment review.

INTRODUCTION: The Pediatric Eye Disease Investigator Group (PEDIG), formed in 1997, has been dedicated to clinical research of eye diseases affecting children. Over the last three years, PEDIG has studied the efficacy of amblyopia treatment regimes, and has followed the long-term outcomes of these regimes. These studies are known as the Amblyopia Treatment Studies (ATS) and have been sorted into eight categories. Four of these have been published and four are still awaiting publication. METHOD: A survey of ophthalmologists and orthoptists attending a seminar in British Columbia, Canada. They were questioned as to how they treat amblyopia in light of the PEDIG studies. RESULTS: Ninety percent continue to use patching as their first method of treatment in moderate amblyopia. Over 50% will patch four hours/day or more to begin treatment and 83% will use near exercises to augment the patching. Two thirds will begin patching six or more hours/day in patients with severe amblyopia. Those that use atropine, use it daily rather than on weekends. Most felt that amblyopia could be treated to age 12 years and some thought it could be treated to 14 years. CONCLUSION: Most ophthalmologists and orthoptists taking the survey have not significantly changed their approach to amblyopia treatment in light of the recent PEDIG studies.