Lower Likelihood Of Remission Research Articles

Ustekinumab Drug Clearance Is Better Associated with Disease Control than Serum Trough Concentrations in a Prospective Cohort of Inflammatory Bowel Disease

Background/Objectives: This study aimed to compare the association of ustekinumab (UST) drug clearance (CL) and trough drug concentrations with disease activity in patients with inflammatory bowel diseases (IBDs). Methods: A prospective cohort of 83 patients with IBD receiving maintenance therapy with 90 mg subcutaneous UST was analyzed using Bayesian PK modeling. UST concentrations and antibodies to UST (ATU) were collected at the trough and measured using a drug-tolerant homogenous mobility shift assay (HMSA). CL was estimated using Bayesian estimation methods with priors from a previous population pharmacokinetic study specifically reparametrized using HMSA. Outcomes were combined clinical and biochemical remission and endoscopic healing index (EHI) score, a validated marker of endoscopic active disease in IBD. Statistical analysis consisted of linear and nonlinear mixed effect models for repeated time-to-event analysis. Results: A total of 83 patients with IBD were enrolled (median age 42 years, 52% female) and evaluated across 312 dose cycles (median follow-up: 279 days, median of 3 cycles/patient). Median concentrations and CL were 5.0 µg/mL and 0.157 L/day, respectively. Most patients (89%) were exposed to other biologics before starting UST, which was associated with lower rates of clinical and biochemical remission (p = 0.01). Longitudinal changes in concentrations were not associated with remission (p = 0.53). Conversely, higher CL was associated with a lower likelihood of remission (p < 0.01). EHI > 50 points (endoscopic active disease, n = 303 cycles) was associated with higher UST CL (p < 0.01). Conclusions: UST CL was more strongly associated with clinical and biochemical outcomes than trough concentrations, highlighting its potential role in therapy optimization.

The effectiveness of vedolizumab in advanced therapy-experienced ulcerative colitis patients: Real world data from the Inflammatory Bowel Disease of the Middle East (IBD-ME) Registry group.

Vedolizumab is an approved ulcerative colitis (UC) treatment. Multiple large randomized clinical trials have demonstrated the drug's efficacy and safety. However, real-world data from Middle Eastern countries are spare. The study aims to evaluate the clinical efficacy of vedolizumab (VDZ) therapy in advanced therapy experienced UC patients. A retrospective electronic chart review of a cohort study of 153 moderately to severely active UC patients who failed or were intolerant to TNF antagonists and received vedolizumab from two large tertiary care centers was performed. Rates of clinical response and remission were retrospectively evaluated at 3,6, and 12 months post VDZ therapy using Patient Simple Clinical Colitis Activity Index (P-SCCAI); clinical response was defined as a decrease in P-SCCAI ≥3, and clinical remission was defined as a P-SCCAI score of ≤3 points. Logistic regression analysis was used to identify predictors of response to vedolizumab. A total of 153 UC patients had sufficient data for analysis. Clinical remission rates were 61.9% for patients on vedolizumab every 8 weeks and 89.3% for those receiving every 4 (Q4) weeks dosing. A significant reduction in CRP and improvement of albumin post vedolizumab treatment were observed, and corticosteroids were stopped in most patients. In a multiple logistic regression analysis, several factors were found to influence the clinical effectiveness of VDZ in inducing remission. Female gender was associated with a higher likelihood of remission [OR =3.09, 95% CI = (1.05-9.13), P = 0.04]. Conversely, a greater number of biologics used prior to VDZ treatment was associated with a lower likelihood of remission [OR =0.418, 95% CI = (0.203-0.859), P = 0.017]. Patients with extensive disease (E3) had an increased likelihood of remission [OR =3.81, 95% CI = (1.32-10.97), P = 0.0129]. Additionally, a VDZ dosing frequency of Q4 weeks was associated with a significantly higher likelihood of remission [OR =6.08, 95% CI = (1.73-21.39), P = 0.0049]. No significant safety signals were reported. In this current real-world study, vedolizumab effectively achieved clinical response and remission in most advanced therapy experienced UC patients treated for up to 12 months. Future studies with larger sample sizes and more robust study designs should be conducted to further validate the results of this study.

A comparison of self- and observer-rated scales for detecting clinical improvement during repetitive transcranial stimulation (rTMS) treatment of depression

Clinical outcomes of repetitive Transcranial Magnetic Stimulation (rTMS) for treatment of Major Depressive Disorder (MDD) vary widely, and no single mood rating scale is standard for assessing rTMS outcomes. This study of 708 subjects undergoing clinical rTMS compared the performance of four scales in measuring symptom change during rTMS treatment. Self-report and observer ratings were examined weekly with the Inventory of Depressive Symptomatology 30-item (IDS), Patient Health Questionnaire 9-item (PHQ), Profile of Mood States 30-item (POMS), and Hamilton Depression Rating Scale 17-item (HDRS). While all scales were correlated and detected significant improvement, the degree of improvement over time as well as response (33–50%) and remission (20–24%) rates varied significantly. Higher baseline severity was associated with lower likelihood of remission, and greater improvement by sessions 5 and 10 predicted response across all scales. Use of only a single scale to assess outcome conferred 14–36% risk of failing to detect response/remission indicated by another scale. The PHQ was most likely to indicate improvement and least likely to miss response or remission. These findings indicate that assessment of symptom burden during rTMS treatment may be most accurately assessed through use of multiple instruments.

Major depressive disorders in patients with inflammatory bowel disease and rheumatoid arthritis.

Various immune-mediated inflammatory diseases consisting of inflammatory bowel disease (IBD) and rheumatoid arthritis (RA), are found to have a substantial societal burden, increased healthcare costs, and progressive disability. Studies suggest that patients with vs without comorbid depression have a more significant disability, a lower likelihood of remission, and reduced adherence to therapy. Elevated interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 contribute to developing depression by the impaired physiological responses to stress, resulting in increased pain, fever, fatigue, and lack thereof of interest, and thus poor long-term outcomes. This study emphasizes the timely recognition of the prevalence of major depressive disorder (MDD) in patients with RA and IBD combined, thus preventing disability. To identify the prevalence level and temporal trends of depression in hospitalized IBD-RA patients. All adult hospitalized patients from January 2000 to December 2019 in the nationwide inpatient sample (NIS) were captured. The study population included all patients with a primary or secondary IBD-RA overlap disease using corresponding international classification of diseases (ICD)-9 and ICD-10 codes. IBD includes Crohn's disease and ulcerative colitis. The study population was divided into IBD-RA without MDD (controls) and IBD-RA with MDD (cases). For group comparison between MDD vs no MDD, we used Student's t-test for continuous variables and Rao-Scott Chi-square tests for categorical variables. For univariate analyses, we used logistic regression, and for multivariate analysis, we used a weighted multi-level mixed-effects model. We attested all hypotheses with two-tailed significance level of 0.05 (P < 0.05 was considered significant). The outcome is to examine the temporal trends and prevalence of depression in patients with IBD-RA by gender, race, and age. A total of 133315 records were identified with IBD-RA overlap, of which 26155 patients (19.62%) had MDD. Among the IBD-RA patients, those who had MDD were younger [mean age of 56 years (SD ± 15)] to IBD-RA without MDD patients with a P < 0.0001, more females (80% among cases vs 73% among controls) than males with a P < 0.0001, frequent in the white race (79% among cases vs 73% among controls) than black race. Over the 19 years, the number of patients with MDD in IBD-RA increased from 153 (the year 2000) to 2880 (the year 2019) in weighted NIS, representing a 1782% increase compared to the year 2000 with a P < 0.001. Factors associated with higher MDD included younger age, female gender, white race, alcohol, opioids, esophageal disorders, peptic ulcer disease, chronic pancreatitis, paralysis, dementia, menopausal disorders, obesity, nutritional deficiencies, diabetes mellitus with chronic complications, and osteoarthritis. There is a rise in the prevalence of depression in younger patients with IBD-RA combined compared to their counterparts. These patients are also at higher risk for the increased cost of care and poor treatment compliance. It is crucial to educate the involved clinicians to identify the early signs and symptoms of depression in patients with IBD or RA or IBD-RA combined and treat them to have a better overall prognosis.

Association Between Asthma Control Trajectories in Preschoolers and Disease Remission

In few studies have researchers characterized the relationship between the frequency (and severity) of early events and long-term disease evolution in preschoolers with asthma. The purpose of this study was to investigate if asthma control trajectories 2 years postdiagnosis in preschoolers were associated with subsequent disease remission and recurrence.The study included a population cohort in 4 Canadian provinces consisting of 48 687 children with asthma diagnosed before 5 years of age and born between 1990 and 2013 who had prolonged disease activity postdiagnosis.Prolonged disease activity was defined as ≥1 medical visits or medications for asthma every 6-month period for at least 4 of the 6 periods postdiagnosis. Remission was defined as 2 consecutive years without drug claims or medical visits for asthma. Asthma control trajectories were classified by using the validated Pharmacoepidemiologic Pediatric Asthma Control Index. Cox regression models within each Canadian province were used to estimate associations between asthma control trajectories and time to remission or recurrence, with children controlled 2 years postdiagnosis as a reference control category. Province specific hazard ratios (HRs) and 95% confidence intervals (CIs) were summarized by using random-effects meta-analysis.All suboptimal control trajectories were associated with a lower likelihood of remission, compared with that of children who were controlled throughout, with a pooled adjusted HR for remission of 0.51 (95% CI: 0.45 to 0.59) for those out of control throughout. An older age at diagnosis, atopy, and asthma diagnosis on the basis of hospitalization outside of the winter season were associated with a lower likelihood of remission. Suboptimal control trajectories were also associated with a higher likelihood of recurrence (HR: 1.17; 95% CI: 1.11 to 1.24), compared with children controlled throughout. Stratifying by sex or atopy did not significantly alter estimated HRs between trajectories. Girls in the study had higher recurrence rates than boys did. Children without atopy in early life were more likely to experience recurrence, compared with atopic children.In the 2 years after an asthma diagnosis in preschoolers, worse asthma control trajectories were associated with incrementally lower likelihoods of remission.With this study, the authors are the first to investigate the association between asthma control trajectories after a preschool diagnosis and remission. The asthma control trajectory in the 2 years after diagnosis in preschoolers appears to be an important predictor of both remission and recurrence, with poorer control associated with a lower likelihood of remission. With the study, the authors support previous studies in which researchers reported potential predictors of persistence, including older age at diagnosis, male sex, and diagnosis in a season other than winter.

Impact of Duration of Untreated Psychosis on Cognitive Function in Schizophrenia

Background: Schizophrenia is a chronic and serious clinical syndrome with very aggravating psychopathology involving perception, cognition, emotion, and behaviour. Currently, cognitive dysfunction is seen as a core disorder of schizophrenia. Duration of Untreated Psychosis (DUP) refers to the period from the onset of psychotic symptoms to the first adequate administration of antipsychotics.Aims: This review aims to analyse the impact of DUP on cognitive function in schizophrenia.Methods: PubMed and Google Scholar were searched using the following keyword: (cognitive function) and (neurodevelopmental OR neurotoxicity hypothesis) and (duration of untreated psychosis or DUP) and (schizophrenia or psychosis or psychotic) using the journal publication filter for the 2014-2020 issue. We also used textbooks published in the last 10 years and were related to writing themes.Review: There are two different opinions about the impact of DUP on the cognitive function of schizophrenic patients: (1) the neurodevelopmental hypothesis says there is no impact of the length of DUP on the cognitive function of schizophrenic patients; (2) the neurotoxicity hypothesis says the length of the DUP will impact the patient's cognitive function. Despite differences of opinion about the impact of DUP on cognitive function in schizophrenia, early intervention in schizophrenic patients is important because DUP is associated with worse general disease symptoms, lower likelihood of remission, more severe positive and negative symptoms, and worse social functioning and overall outcomes.Summary: There are differences of opinion about the impact of DUP on cognitive function in schizophrenic patients.

Preliminary Evidence That Cortical Amyloid Burden Predicts Poor Response to Antidepressant Medication Treatment in Cognitively Intact Individuals With Late-Life Depression

Amyloid accumulation, the pathological hallmark of Alzheimer's disease, may predispose some older adults to depression and cognitive decline. Deposition of amyloid also occurs prior to the development of cognitive decline. It is unclear whether amyloid influences antidepressant outcomes in cognitively intact depressed elders. A pharmacoimaging trial utilizing florbetapir (18F) PET scanning followed by 2 sequential 8-week antidepressant medication trials. Twenty-seven depressed elders who were cognitively intact on screening. After screening, diagnostic testing, assessment of depression severity and neuropsychological assessment, participants completed florbetapir (18F) PET scanning. They were then randomized to receive escitalopram or placebo for 8 weeks in a double-blinded two-to-one allocation rate. Individuals who did not respond to initial treatment transitioned to a second open-label trial of bupropion for another 8 weeks. Compared with 22 amyloid-negative participants, 5 amyloid-positive participants exhibited significantly less change in depression severity and a lower likelihood of remission. In the initial blinded trial, 4 of 5 amyloid-positive participants were nonremitters (80%), while only 18% (4 of 22) of amyloid-negative participants did not remit (p = 0.017; Fisher's Exact test). In separate models adjusting for key covariates, both positive amyloid status (t = 3.07, 21 df, p = 0.003) and higher cortical amyloid binding by standard uptake value ratio (t = 2.62, 21 df, p = 0.010) were associated with less improvement in depression severity. Similar findings were observed when examining change in depression status across both antidepressant trials. In this preliminary study, amyloid status predicted poor antidepressant response to sequential antidepressant treatment. Alternative treatment approaches may be needed for amyloid-positive depressed elders.

PRESENCE OF OPTIMISM AND ANTIDEPRESSANT REMISSION RATES IN LATE-LIFE DEPRESSION

Introduction Interest in personality traits and their relationship to depression has grown in recent years. The Big Five model of personality is often used as the standard framework in which personality constructs can be better understood. The model includes: (1) Extraversion/Positive Emotionality, (2) Agreeableness, (3) Conscientiousness, (4) Emotional Stability versus Neuroticism, and (5) Openness/Intellect. However, there is growing interest in optimism since it has been linked to low Neuroticism and high Extraversion/Positive Emotionality (Sharpe et al 2011). Optimism, defined as the extent to which people hold generalized favorable expectancies for their future, is also inversely related to hopelessness, a risk factor for depressive disorders. Prior research suggests that optimists tend to have high Emotional Stability, Extraversion, Agreeableness, and Conscientiousness, resulting in a tendency toward better mental and physical health, adaptive behavior, and even lower mortality rates (Achat et al 2000 and Armbruster et al 2015). Optimism remains understudied in older adults, particularly as most of the prior research has explored optimism as a construct of Neuroticism and Extraversion in younger and middle-aged adults (Armbruster et al 2015). We aimed to examine the effects of optimism on acute treatment outcome in a group of older depressed adults initially treated with the antidepressant sertraline in an open-label fashion as part of Neurobiology of Late-Life Depression (NBOLD), a US National Institute of Mental Health (NIMH)- supported study at the University of Connecticut (UConn). We hypothesized that presence of high optimism would be associated with lower 12-week remission rates in older depressed sertraline-treated patients. Methods In this longitudinal cohort study, all subjects were enrolled in NBOLD and recruited from clinic referrals and newspaper advertisements. Inclusion criteria for depressed subjects were age 60 or above, ability to read and write English, Mini- Mental State Examination (MMSE) score 25 or greater and meeting criteria for major depression, single episode, or recurrent (DSM-IV-TR). A total of 74 subjects were included and were administered the Montgomery–Ǻsberg Depression Rating Scale (MADRS) and Cumulative Illness Rating Scale (CIRS), as modified for geriatric patients. Each subject completed several self-report measures, including the Life Orientation Test- Revised (LOT-R, Scheier et al 1994), which measures total optimism. We used regression analyses to examine factors related to 12-week remission of depression (MADRS score Results We found that higher total optimism was not associated with lower likelihood of remission among both the intention-to-treat group and sertraline completers after controlling for baseline MADRS and CIRS score. Additional regression analyses of optimism, neuroticism and apathy were also examined, but were not associated with lower likelihood of remission. Conclusions Our results do not support that optimism alone can predict depression outcomes in older adults. Although optimism has been shown to have predictive value in younger and middle-aged adults, there may be other medical comorbidities such as somatic illness, as well as increasing psychosocial stressors, contributing to the development of late life depression that override the effects of optimism. This may explain why optimism, although important in older age, may not have strong predictive accuracy for health-related outcomes. Our findings are consistent with a prior study examining optimism and depression outcomes in younger vs older adults in which predictive accuracy decreases with age (Armbruster et al 2015). This research was funded by: Neurobiology of Late-Life Depression (NBOLD), a US National Institute of Mental Health (NIMH)- supported study at the University of Connecticut (UConn)

Increase in pharmacodynamic tolerance after repeated antidepressant trials in treatment-responsive bipolar I depressed subjects: An exploratory study.

This study examined the presence of increased pharmacodynamic tolerance with reduced effectiveness following repeated antidepressant trials over the course of the affective illness in subjects with treatment-responsive bipolar II depression. Data were derived from the open-label phase of a prospective, randomized, placebo-controlled trial of long-term fluoxetine versus lithium monotherapy in 148 subjects >=18 years old with treatment-responsive bipolar II depression, who were initially administered open-label fluoxetine monotherapy for 12 weeks. Response was defined as >=50% reduction in baseline Hamilton Rating Scale for Depression (HRSD) score, and remission was defined as a final HRSD score =<8. Subjects reported a mean (SD) total of 1.61 (1.85) (range: 0-9) prior adequate, antidepressant trials over the course of their affective illness, before study enrollment. There was a 25% reduction in the likelihood of fluoxetine response (p < 0.01) and a 22% lower likelihood of remission (p = 0.02), respectively, with each increase in the number of prior antidepressant treatment trials over the illness course. There was no clinically meaningful correlation between fluoxetine response or remission and any other baseline clinical or demographic variable. Thus, only the number of prior antidepressant trials meaningfully impacted the likelihood of fluoxetine response or remission. Limitations. This was an exploratory study of post hoc, analyses, and the trial was not specifically powered to test the development of increased pharmacodynamic tolerance. Disease heterogeneity or inter-individual differences in antidepressant responsiveness may have influenced fluoxetine effectiveness. Conclusion. These results confirm prior observations of an increased pharmacodynamic tolerance after repeated antidepressant administration, resulting in a step-wise loss of antidepressant effectiveness over the course of the illness.

Impact of Personality Disorder Cluster on Depression Outcomes Within Collaborative Care Management Model of Care.

Background: Previous studies have suggested that having a comorbid personality disorder (PD) along with major depression is associated with poorer depression outcomes relative to those without comorbid PD. However, few studies have examined the influence of specific PD cluster types. The purpose of the current study is to compare depression outcomes between cluster A, cluster B, and cluster C PD patients treated within a collaborative care management (CCM), relative to CCM patients without a PD diagnosis. The overarching goal was to identify cluster types that might confer a worse clinical prognosis. Methods: This retrospective chart review study examined 2826 adult patients with depression enrolled in CCM. The cohort was divided into 4 groups based on the presence of a comorbid PD diagnosis (cluster A/nonspecified, cluster B, cluster C, or no PD). Baseline clinical and demographic variables, along with 6-month follow-up Patient Health Questionnaire–9 (PHQ-9) scores were obtained for all groups. Depression remission was defined as a PHQ-9 score <5 at 6 months, and persistent depressive symptoms (PDS) was defined as a PHQ-9 score ≥10 at 6 months. Adjusted odds ratios (AORs) were determined for both remission and PDS using logistic regression modeling for the 6-month PHQ-9 outcome, while retaining all study variables. Results: A total of 59 patients (2.1%) had a cluster A or nonspecified PD diagnosis, 122 patients (4.3%) had a cluster B diagnosis, 35 patients (1.2%) had a cluster C diagnosis, and 2610 patients (92.4%) did not have any PD diagnosis. The presence of a cluster A/nonspecified PD diagnosis was associated with a 62% lower likelihood of remission at 6 months (AOR = 0.38; 95% CI 0.20-0.70). The presence of a cluster B PD diagnosis was associated with a 71% lower likelihood of remission at 6 months (AOR = 0.29; 95% CI 0.18-0.47). Conversely, having a cluster C diagnosis was not associated with a significantly lower likelihood of remission at 6 months (AOR = 0.83; 95% CI 0.42-1.65). Increased odds of having PDS at 6-month follow-up were seen with cluster A/nonspecified PD patients (AOR = 3.35; 95% CI 1.92-5.84) as well as cluster B patients (AOR = 3.66; 95% CI 2.45-5.47). However, cluster C patents did not have significantly increased odds of experiencing persistent depressive symptoms at 6-month follow-up (AOR = 0.95; 95% CI 0.45-2.00). Conclusions: Out of the 3 clusters, the presence of a cluster B PD diagnosis was most significantly associated with poorer depression outcomes at 6-month follow-up, including reduced remission rates and increased risk for PDS. The cluster A/nonspecified PD group also showed poor outcomes; however, the heterogeneity of this subgroup with regard to PD features must be noted. The development of novel targeted interventions for at-risk clusters may be warranted in order to improve outcomes of these patients within the CCM model of care.

Pain Remission at One-Year Follow-Up With Spinal Cord Stimulation

Spinal Cord Stimulation (SCS) is an effective treatment for chronic pain. How often pain remission follows SCS has not been evaluated. This is a retrospective analysis of patients who underwent an implantation of spinal cord stimulators for various chronic pain conditions. The objective of the study was to elucidate characteristics and features of patients with pain relief greater than 80% after one year of treatment. A total of 86 patients with thoracic SCS and 12-month follow-up data were identified. Patients were divided into a remission group (>80% improvement in Numeric Pain Rating Scale [NRS] pain scale), average responders (20-80% improvement) and a non-responder group (less than 20% improvement). These patient groups were compared via the following outcome measures: NRS, Oswestry Disability Index (ODI), Pain Catastrophizing Scale (PCS), McGill Pain Questionnaire (MPQ), and Insomnia Severity Index (ISI). Correlations with age, body mass index (BMI), tobacco and alcohol usage, patient satisfaction with SCS, disability status, and opioid usage were assessed. Nineteen of 86 patients (22%) were remitters at one year follow-up, including 17 patients who had an NRS = 0 at that time. Upon analyzing the three patient groups (non-responders, average responders, and remitters), remitter patients showed the greatest change over the one-year post-operative period in ODI (F(2) = 8.101, p < 0.01) and PCS (F(2) = 7.607, p < 0.01). Moreover, remission was less likely when the patients were on disability prior to implant (χ2 (2) = 6.469, p < 0.05) and on opioids pre-operatively (χ2 (2) = 17.688, p < 0.01). Our study demonstrates a remission rate of 22% with SCS at one-year follow with a total of 19.8% of our total patient cohort having an NRS of 0. Greater decreases in PCS and ODI correlate with remission. Further, pre-operative disability and opioid use correlate with lower likelihood of remission.

High burden of adverse events is associated with reduced remission rates in early rheumatoid arthritis.

Adverse events (AEs) are common during disease-modifying antirheumatic drug (DMARD) treatment, but their influence on treatment results is unclear. We studied AEs in relation to disease activity in early rheumatoid arthritis (RA). Ninety-nine patients started intensive treatment with three conventional synthetic DMARDs (csDMARDs) and oral prednisolone, and were randomized to a 6-month induction treatment with infliximab or placebo. All AEs during the first 12months of treatment were recorded. We scored each AE based on severity (scale 1-4) and defined the burden of AEs as the sum of these scores. Patients were divided into tertiles according to the burden of AEs. As outcomes, we assessed 28-joint disease activity score (DAS28) levels and remission rates at 12 and 24months. Three hundred thirty-one AEs in 99 patients were reported, and 27 (8%) were categorized as severe or serious. Mean burden of AEs per patient was 5.4 ± 4.3. Seventy-nine AEs (24%) led to temporary (n = 52) or permanent (n = 27) csDMARD discontinuation. Of discontinuations, 1, 21, and 57 were detected in the first, second, and third tertiles, respectively. DAS28 remission rates decreased across tertiles at 12months (94, 94, and 76%; p for linearity 0.029) and at 24months (90, 86, and 70%; p for linearity 0.021). Mean DAS28 levels increased across tertiles at 12months (1.5 ± 1.0, 1.7 ± 0.9, and 1.9 ± 1.2; p for linearity 0.021) and at 24months (1.4 ± 0.8, 1.6 ± 1.0, and 1.9 ± 1.1; p for linearity 0.007). High burden of AEs is associated with higher disease activity and lower likelihood of remission in early RA.

Presence of neuroticism and antidepressant remission rates in late-life depression: results from the Neurobiology of Late-Life Depression (NBOLD) study.

ABSTRACTNeuroticism in older adults is common yet understudied, particularly its effects on depression treatment outcomes. We hypothesized that presence of high neuroticism would be associated with lower 12-week remission rates in older depressed sertraline-treated patients. In this longitudinal cohort study, 43 depressed older adults completed the Revised NEO Personality Inventory (NEO PI-R). A study psychiatrist administered the Montgomery Ǻsberg Depression Rating Scale (MADRS), and the Cumulative Illness Rating Scale (CIRS, a measure of medical burden) at baseline, and the MADRS at each clinical visit. All subjects began open-label sertraline treatment and were followed over 12 weeks with clinically indicated flexible dosing and an option to switch antidepressants. We used regression analyses to examine factors related to 12-week remission of depression (MADRS score < 8) and final MADRS score. We found that higher total neuroticism (odds ratio (OR) = 0.963, 95% confidence interval (CI) = 0.928-1.000) and a neuroticism subscale, stress vulnerability (OR = 0.846, 95% CI = 0.728-0.983), were associated with lower likelihood of remission among both the intention-to-treat group and sertraline completers. Findings remained significant after controlling for baseline MADRS and CIRS score. In conclusion, assessment of personality, particularly features of neuroticism, may be important in management of late-life depression. Future studies should determine if depressed patients high in neuroticism may benefit from psychotherapy focusing on emotional regulation and stress management.

Personality Disorders in Primary Care: Impact on Depression Outcomes Within Collaborative Care.

Background:Individuals with personality disorders (PDs) are high utilizers of primary care and mental health services; however, they struggle to utilize the care effectively and studies have shown a strong association between having a PD and higher impairment in social role functioning. This is especially important because PDs are highly comorbid with a wide range of other mental health disorders. The collaborative care model (CCM) for depression was developed with an emphasis on patient engagement and aimed to reduce health care utilization, while improving treatment outcomes in primary care. We hypothesized that the diagnosis of a personality disorder in primary care patients will negatively affect 6-month depression outcomes after enrollment into a CCM. Methods: This retrospective chart review study was conducted on patients enrolled into CCM over a period of 7 years with collection of 6-month follow-up data. A total of 2826 patients were enrolled into CCM with a clinical diagnosis of depression and a baseline Patient Health Questionnaire–9 (PHQ-9) ≥10 were included in the study cohort. Using the depression database, baseline and 6-month follow-up data were obtained. Adjusted odds ratios (AORs) were determined for both remission and persistent depressive symptoms using logistic regression modeling for the 6-month PHQ-9 outcome; while retaining all the study variables. Results: Of the 2826 CCM patients with depression in our study, 216 (7.6%) were found to have a PD. Patients with PD were younger (37.7 vs 42.5 years, P < .001) and more likely to be unmarried (36.1% vs 55.6%, P < .001) than patients without a PD. While age, marital status, clinical diagnosis, and Mood Disorders Questionnaire (MDQ) score were significant predictors of remission; anxiety symptoms, gender, and race were not. The presence of a PD diagnosis was associated with a 60% lower likelihood of remission at 6 months (AOR = 0.39; 95% CI 0.28-0.54). Conversely, patients without a PD were 2.5 times as likely to experience remission at 6-month remission compared to patients with PD (AOR =2.57; 95% CI 1.85-3.56). Conclusion: Patients with a personality disorder were more likely to have a recurrent depressive disorder diagnosis, an abnormal MDQ score, increased anxiety symptoms, and higher baseline PHQ-9 score. Patients with PD had worse CCM outcomes at 6 months with only 25.0% able to achieve remission versus 54.3% (P < .001) without a PD. The presence of a PD with depression was associated with poor outcomes (reduced remission rates and increased persistent depressive symptoms rates) in comparison to patients without a diagnosis of PD, while treated within CCM.

Chronotype and Improved Sleep Efficiency Independently Predict Depressive Symptom Reduction after Group Cognitive Behavioral Therapy for Insomnia.

Cognitive behavioral therapy for insomnia (CBT-I) has been shown to improve both sleep and depressive symptoms, but predictors of depression outcome following CBT-I have not been well examined. This study investigated how chronotype (i.e., morningness-eveningness trait) and changes in sleep efficiency (SE) were related to changes in depressive symptoms among recipients of CBT-I. Included were 419 adult insomnia outpatients from a sleep disorders clinic (43.20% males, age mean ± standard deviation = 48.14 ± 14.02). All participants completed the Composite Scale of Morningness and attended at least 4 sessions of a 6-session group CBT-I. SE was extracted from sleep diary; depressive symptoms were assessed using the Beck Depression Inventory (BDI) prior to (Baseline), and at the end (End) of intervention. Multilevel structural equation modeling revealed that from Baseline to End, SE increased and BDI decreased significantly. Controlling for age, sex, BDI, and SE at Baseline, stronger evening chronotype and less improvement in SE significantly and uniquely predicted less reduction in BDI from Baseline to End. Chronotype did not predict improvement in SE. In an insomnia outpatient sample, SE and depressive symptoms improved significantly after a CBT-I group intervention. All chronotypes benefited from sleep improvement, but those with greater eveningness and/or less sleep improvement experienced less reduction in depressive symptom severity. This suggests that evening preference and insomnia symptoms may have distinct relationships with mood, raising the possibility that the effect of CBT-I on depressive symptoms could be enhanced by assessing and addressing circadian factors.

AB0405 Baseline Predictors of Remission Rates during Golimumab Treatment for Rheumatoid Arthritis in the GO-MORE Study

BackgroundIn patients with rheumatoid arthritis (RA), current treatment strategies aim for clinical remission. Knowing which patients are likely to respond to biologic treatment is helpful when considering treatment options.ObjectivesTo evaluate...

Treatment of childhood nephrotic syndrome with long-term, low-dose tacrolimus

Children with steroidresistant (SR) and steroid-dependent (SD) nephrotic syndrome (NS) pose a treatment challenge. Literature on the use of tacrolimus (TAC), a calcineurin inhibitor, for maintenance treatment of NS is sparse. We aimed to evaluate the efficacy and safety of low-dose, long-term TAC for inducing and sustaining remission in children with SD/SR NS. Data from patients treated at our center from 1999 to 2009 were analyzed. 40 patients with NS were treated with TAC for 3 - 80-month periods (median 25.2 months). Diagnoses included focal segmental glomerulosclerosis (FSGS) (60%), IgM nephropathy (15%), minimal change disease (20%) and membrano-proliferative glomerulonephritis (MPGN) (5%). 58% of patients had been previously treated with alternate agents. After 1, 2, and 3 years on TAC, complete remission was achieved in 26%, 48%, and 29% of patients; complete or partial remission was achieved in 85%, 100%, and 86%, respectively (p < 0.05). Median time to remission was 41 days (range: 10 - 270 days). FSGS and SR diseases were associated with lower likelihood of remission (p < 0.05). Remission was equally likely in both treatment naïve patients and those who had received prior second-line agents. Our results demonstrate that TAC treatment for children with SR/SD NS is associated with high rates of sustained remission, even when prior second-line agents failed.

Mo1095 Racial/Ethnic Differences in Inflammatory Bowel Disease Risk Factors Medication Compliance and Outcomes At a Tertiary Care Academic Medical Center

Background: Inflammatory bowel disease (IBD) including Crohn's disease and ulcerative colitis (UC) is increasingly recognized in minority patients. Prior studies suggest that African American and Hispanic patients with IBD tend to have worse outcomes compared to nonHispanic white patients. Aims: To compare the racial/ethnic differences in risk factors for IBD flare, medication compliance, and symptom-free remission among African American, Hispanic and non-Hispanic white IBD patients at a tertiary care academic medical center. Data andMethods: A list of all inpatient and outpatient visits with attending gastroenterologists and an ICD-9 diagnosis code for IBD (Crohn's disease 555.x; UC 556.x) between 01/2011 and 10/2012 were provided by the Health Information Management Department. Chart review was performed to verify IBD diagnosis and to obtain patient demographics including race/ ethnicity, IBD phenotype (Montreal classification for Crohn's; extent of UC), risk factors (primary sclerosing cholangitis, family history of IBD, smoking, previous bowel surgery, use of steroids, narcotics, or non-steroidal anti-inflammatory drugs), compliance with IBD medications, and presence of symptom-free remission. Both medication compliance and remission were based on assessment of the attending gastroenterologist at the most recent visit. The chi-square test or Fisher's exact test and the multivariate logistic model were used in statistical analysis. Results: There were a total of 502 IBD patients in our study sample, including 86 African Americans (47 Crohn's; 39 UC), 43 Hispanics (23 Crohn's; 20 UC), and 373 non-Hispanic whites (154 Crohn's; 219 UC). Compared with non-Hispanic whites, narcotic use was higher among minorities (African Americans 15.3%, Hispanics 20.9%, Whites 8.4%; both p,0.05). Racial/ethnic differences in the other risk factors were insignificant. Compared with non-Hispanic whites, both medication compliance (African Americans 81.9%, Hispanics 82.9%, Whites 91.7%) and symptom-free remission (African Americans 10.5%, Hispanics 20.9%, Whites 27.1%) were lower among minorities (both p ,0.05). In multivariate logistic regression, African American (odds ratio [OR]: 0.323, 95% confidence interval [CI]: 0.142-0.735 vs. non-Hispanic white) and family history of IBD (OR: 0.409, 95% CI: 0.168-0.994) were negative predictors of symptom-free remission (both p,0.05). Conclusions: More narcotic use and lower medication compliance among minorities might contribute to racial/ethnic differences in IBD outcomes. African American race and family history of IBD were associated with a lower likelihood of remission. Whether some of the racial/ethnic differences in IBD outcomes can be explained by differences in socioeconomic status, risk factors for disease flare and medication compliance is an important question for future research.

1606 – Temperament in individuals with psychotic disorders before and after the onset of illness

Introduction The Temperament and Character Inventory (TCI) is used to measure novelty seeking (NS), harm avoidance (HA), reward dependence RD), and persistence (P). Objectives We will study temperament in individuals with psychosis and healthy controls. Aim We aim to study the stability of temperament in individuals with psychotic disorders (with onset of illness before and after first follow-up) and in healthy controls. Methods As part of the 31-year follow-up survey of the prospective population based Northern Finland 1966 Birth Cohort, the TCI was filled by a large sample of individuals. A subsample of psychotic individuals, with the onset of illness before (n=16) or after (n=15) the 31-year follow-up, and healthy controls (n=117) filled in these scales again at the age of 43. We studied also the association between psychotic symptoms and premorbid temperament. Results The 31-year and 43-year temperament scores correlated strongly among controls (Pearson's r: NS 0.68, HA 0.60, RD 0.56, P 0.54), whereas correlations among psychotic individuals with the onset of psychosis before first follow-up were weaker (NS 0.38, HA 0.50, RD 0.17, P 0.53). High HA before the onset of illness (at age of 31 years) associated significantly with a lower likelihood of remission and with more negative, disorganization and total symptoms in the PANSS. High NS before illness associated with a higher likelihood of remission according to the PANSS. Conclusions Temperament was stable among controls, and more unstable in individuals with psychoses. Premorbid harm avoidance and novelty seeking predicts the clinical outcome in schizophrenia.

Methylene blue‐photoinactivated plasma versus quarantine fresh frozen plasma in thrombotic thrombocytopenic purpura: a multicentric, prospective cohort study

Plasma exchange (PE) with plasma infusion is the treatment of choice for thrombotic thrombocytopenic purpura (TTP) but doubts remain as to whether all kinds of plasma are equally effective. A multicentric cohort study was conducted to compare methylene blue-photoinactivated plasma (MBPIP) with quarantine fresh frozen plasma (qFFP) in the treatment of TTP. One hundred and two episodes of idiopathic TTP were included; MBPIP was used in 63 and qFFP in 39. The treatment schedule consisted of daily PE and costicosteroids, and the main end-point was remission status on day 8. Patients treated with MBPIP required more PEs (median: 11 vs. 5, P = 0.002) and a larger volume of plasma (median: 485 ml/kg vs. 216 ml/kg, P = 0.007) to achieve a remission, and presented more recrudescences while on PE therapy (29 of 63 vs. 8 of 39, P = 0.02) than those receiving qFFP. After adjustment for possible confounding factors, the use of MBPIP was associated with a lower likelihood of remission on day 8 [Odds ratio (OR): 0.17; 95% confidence interval (CI): 0.06-0.47] and a higher risk of recrudescence while on treatment (OR: 4.2; 95% CI: 1.6-10.8). In conclusion, MBPIP is less effective than qFFP in the treatment of TTP.