Stephen R Wisniewski

University of Pittsburgh, Pittsburgh, Pennsylvania, United States

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Publications (362)1938.4 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To explore relationships between baseline and changes in fatigue during treatment with outcomes in patients with major depressive disorder (MDD) receiving citalopram monotherapy. Research design and methods: Secondary analyses of data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Level 1 treatment phase (≤14 weeks citalopram monotherapy). Fatigue was assessed with item 14 on energy level from the 16-item Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR16; scored 0–3: 0 = no fatigue, 3 = maximal fatigue); prospective fatigue: assessment of fatigue at Level 1 entry and exit (no fatigue, treatment-emergent fatigue, remitted fatigue, or residual fatigue). Clinical trial registration: Http://clinicaltrials.gov, NCT00021528. Main outcome measures: Remission of depressive symptoms (17-item Hamilton Rating Scale for Depression ≤7 or QIDS-SR16 ≤5); Quality of Life Enjoyment and Satisfaction Questionnaire–Short Form; Short-Form Health Survey Mental and Physical subscales; and Work and Social Adjustment Scale (WSAS). Results: At baseline, of 2868 patients included in the analyses, 5.5% had a QIDS-SR16 item 14 score of 0; 22.9%, a score of 1; 53.6%, a score of 2; and 18.0%, a score of 3. During Level 1 treatment, 3.5% of patients had no prospective fatigue, 2.1% had treatment-emergent fatigue, 33.6% had fatigue remitting during treatment, and 60.8% had residual fatigue. Female gender, unemployment, fewer years of education, and lower monthly income were significantly associated with higher rates of baseline fatigue (all P < 0.0001). Higher levels of baseline or prospective fatigue were associated with reduced likelihood of remission, decreased overall satisfaction (P < 0.0001), and reduced mental and physical function at outcome (P ≤ 0.05). Patients with higher baseline or prospective fatigue reported higher WSAS total scores (P < 0.0001), indicative of more severe functional impairment. Conclusions: Lower baseline fatigue and remission of fatigue during antidepressant treatment in patients with MDD are associated with higher rates of remission of depressive symptoms and better function and quality of life. Study limitations include use of the STAR*D Level 1 sample (citalopram as only antidepressant), use of a proxy measure of energy/fatigue (item 14 from the QIDS-SR16), and the secondary post-hoc analysis design.
    Current Medical Research and Opinion 07/2014; · 2.26 Impact Factor
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    ABSTRACT: Abstract Objective: To explore relationships between baseline and changes in fatigue during treatment with outcomes in patients with major depressive disorder (MDD) receiving citalopram monotherapy. Research design and methods: Secondary analyses of data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Level 1 treatment phase (≤14 weeks citalopram monotherapy). Fatigue was assessed with item 14 on energy level from the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16; scored 0-3: 0=no fatigue, 3=maximal fatigue); prospective fatigue: assessment of fatigue at Level 1 entry and exit (no fatigue, treatment-emergent fatigue, remitted fatigue, or residual fatigue). Clinical trial registration: http://clinicaltrials.gov, NCT00021528 Main outcome measures: Remission of depressive symptoms (17-item Hamilton Rating Scale for Depression ≤7 or QIDS-SR16 ≤5); Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form; Short-Form Health Survey Mental and Physical subscales; and Work and Social Adjustment Scale (WSAS). Results: At baseline, of 2,868 patients included in the analyses, 5.5% had a QIDS-SR16 item 14 score of 0; 22.9%, a score of 1; 53.6%, a score of 2; and 18.0%, a score of 3. During Level 1 treatment, 3.5% of patients had no prospective fatigue, 2.1% had treatment-emergent fatigue, 33.6% had fatigue remitting during treatment, and 60.8% had residual fatigue. Female gender, unemployment, fewer years of education, and lower monthly income were significantly associated with higher rates of baseline fatigue (all P<.0001). Higher levels of baseline or prospective fatigue were associated with reduced likelihood of remission, decreased overall satisfaction (P<.0001), and reduced mental and physical function at outcome (P≤.05). Patients with higher baseline or prospective fatigue reported higher WSAS total scores (P<.0001), indicative of more severe functional impairment. Conclusions: Lower baseline fatigue, or remission of fatigue during antidepressant treatment in patients with MDD, are associated with higher rates of remission of depressive symptoms and better function and quality of life. Study limitations include use of the STAR*D Level 1 sample (citalopram as only antidepressant), use of a proxy measure of energy/fatigue (item 14 from the QIDS-SR16), and the secondary post-hoc analysis design.
    Current Medical Research and Opinion 06/2014; · 2.26 Impact Factor
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    ABSTRACT: Respiratory tract infections are a major cause of outpatient visits, yet only a portion is tested to determine the etiologic organism. Multiplex reverse transcriptase polymerase chain reaction (MRT-PCR) assays for detection of multiple viruses are being used increasingly in clinical settings.
    Influenza and Other Respiratory Viruses 05/2014; · 1.47 Impact Factor
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    ABSTRACT: Background. We analyzed the public STAR*D database to better characterize the baseline clinical characteristics and functional outcomes of patients with major depressive disorder (MDD) who experienced partial response in order to better understand the burden associated with this outcome. Method. Patients (n=2,876) received treatment with citalopram. The last available Quick Inventory of Depressive Symptoms (QIDS-SR) from the 12-week treatment period was used to assign subjects to one of three groups: remitters QIDS-SR≤5; non-responders QIDS-SR >5 and <25% reduction from baseline; and partial responders QIDS-SR >5 and ≥25% reduction from baseline. Baseline sociodemographic and clinical characteristics were compared across groups, as well as functional outcomes at Level 1 exit. Results. Of the 2,876 patients, 943 patients (33%) were classified as remitters, 1069 (37%) as partial responders, and 854 (30%) as non-responders. The groups differed on a number of pre-treatment course of illness variables and comorbidities. In addition, remitters, partial responders, and non-responders all separated on posttreatment quality of life and functional outcomes at Level 1 exit. Conclusion. Partial responders demonstrated significant functional impairment at Level 1 exit, differing significantly from the patients who remitted on quality of life, mental and physical functioning, and social and work-related impairment. Adjusted outcomes showed similar differences. Differences in baseline rates of suicidality, comorbidity, and atypical presentations of depression were also observed between outcome groups. Given the substantial clinical and economic burden associated with functional impairment in depression, the need to fully treat partially responding patients to achieve depression remission and restoration of functioning is highlighted by this work. (Journal of Psychiatric Practice 2014;20:178-187).
    Journal of Psychiatric Practice 05/2014; 20(3):178-87. · 1.29 Impact Factor
  • Journal of Psychiatric Practice 05/2014; 20(3):178-187. · 1.29 Impact Factor
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    ABSTRACT: To evaluate energy expenditure in a cohort of children with severe traumatic brain injury. A prospective observational study. A pediatric neurotrauma center within a tertiary care institution. Mechanically ventilated children admitted with severe traumatic brain injury (Glasgow Coma Scale < 9) with a weight more than 10 kg were eligible for study. A subset of children was co-enrolled in a phase 3 study of early therapeutic hypothermia. All children were treated with a comprehensive neurotrauma protocol that included sedation, neuromuscular blockade, temperature control, antiseizure prophylaxis, and a tiered-based system for treating intracranial hypertension. Within the first week after injury, indirect calorimetry measurements were performed daily when the patient's condition permitted. Data from 13 children were analyzed (with a total of 32 assessments). Measured energy expenditure obtained from indirect calorimetry was compared with predicted resting energy expenditure calculated from Harris-Benedict equation. Overall, measured energy expenditure/predicted resting energy expenditure averaged 70.2% ± 3.8%. Seven measurements obtained while children were hypothermic did not differ from normothermic values (75% ± 4.5% vs 68.9% ± 4.7%, respectively, p = 0.273). Furthermore, children with favorable neurologic outcome at 6 months did not differ from children with unfavorable outcome (76.4% ± 6% vs 64.7% ± 4.7% for the unfavorable outcome, p = 0.13). Contrary to previous work from several decades ago that suggested severe pediatric traumatic brain injury is associated with a hypermetabolic response (measured energy expenditure/predicted resting energy expenditure > 110%), our data suggest that contemporary neurocritical care practices may blunt such a response. Understanding the metabolic requirements of children with severe traumatic brain injury is the first step in development of rational nutritional support goals that might lead to improvements in outcome.
    Pediatric Critical Care Medicine 01/2014; · 2.35 Impact Factor
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    ABSTRACT: Background Most depression rating scales are multidimensional and the resulting heterogeneity may impede identification of coherent biomarkers. The aim of this study was to compare the psychometric performance of the multidimensional 17-item Hamilton Depression Rating Scale (HAM-D17) and the 30-item Inventory of Depressive Symptomatology (IDS-C30) to that of their unidimensional six-item melancholia subscales (HAM-D6 and IDS-C6). Methods A total of 2,242 subjects from level 1 (citalopram) of the Sequenced Treatment Alternatives to Relieve Depression (STAR⁎D) study were included in the analysis. Symptom change, response and remission rates were compared for HAM-D6 versus HAM-D17 and for IDS-C6 versus IDS-C30. The changes in total scores on these scales were compared to the change in Quality of Life Enjoyment and Satisfaction Questionnaire (QLES-Q) score using correlation analysis. Results The response to treatment was significantly greater according to the HAM-D6 and IDS-C6. Furthermore, the correlation of changes in depression-ratings with changes in QLES-Q scores were comparable for the subscales and full scales. Limitations STAR⁎D was not designed to answer the research questions addressed in this analysis. Conclusions Our findings indicate that the HAM-D6 and IDS-C6 melancholia scales capture a coherent construct in depression. The syndrome reflected in these scales is unidimensional, sensitive to specific pharmacological intervention, and therefore likely to have biological validity. We therefore believe that “melancholia” thus defined could be a valuable construct under the Research Domain Criteria (RDoC), which specifically aims at identifying the neurobiology underlying mental disorders and provide drugable targets. Clinical trial registration NCT00021528
    Journal of Affective Disorders. 01/2014;
  • American Journal of Psychiatry 11/2013; 170(11):1364-5. · 14.72 Impact Factor
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    ABSTRACT: Background/Purpose: C reactive protein (CRP) levels have been used extensively to model disease activity in rheumatoid arthritis (RA). However, TNF antagonist therapy (and likely therapy with other biologics) reduce CRP levels, even without associated reductions in RA disease activity. Serum amyloid A (SAA) also models RA disease activity and has been suggested as a better biomarker for RA disease activity. We previously showed that TNF antagonist therapy lowered both SAA and CRP levels to a greater extent than oral disease modifying anti-rheumatic drugs (DMARDs) after adjusting for disease activity. However, TNF antagonists, compared to oral DMARDs, decreased CRP levels more than SAA levels. Our aim was to compare the effect of etanercept (ETN) and/or oral DMARD therapy on serum SAA versus CRP levels, and to determine whether SAA levels model RA disease activity better than CRP levels, especially during treatment with a TNF antagonist. Methods: Samples were analyzed from RA subjects (n = 755) in the Treatment of Early RA (TEAR) study, a randomized, double-blind, comparative effectiveness trial. In the TEAR trial, early RA subjects with less than 2 years of disease duration were randomized to receive either combination ETN/methotrexate (MTX) therapy (n = 244), MTX/hydrochloroquine/sulfasalazine (triple oral) therapy (n = 132) or MTX monotherapy (n = 379). MTX monotherapy subjects with a DAS28-ESR > 3.2 after 6 months were stepped up to either ETN/MTX (n = 205) or triple oral therapy (n = 93). Serum samples and clinical data were collected when treatment was initiated and at 24, 48 and 102 week follow up visits. We used Spearman correlation coefficients (rho) to determine the overall relationship between SAA and CRP levels, and mixed effects models to determine the fit between 1) SAA levels and DAS28-ESR and 2) CRP levels and DAS28-ESR, for subjects treated with ETN/MTX and subjects treated with oral DMARDs, while correcting for baseline SAA and CRP levels, respectively. Akaike information criterion (AIC) and parameter estimates were used to determine model fit, with ΔAIC > 10 used as strong evidence for one model fitting better than another. Results: At the baseline visit, SAA levels were only moderately correlated with CRP levels (rho = 0.42), and the SAA and CRP correlation was similar regardless of treatment or study visit (rho range 0.35 to 0.62). Across all subjects and time points, models of the DAS28-ESR using SAA levels were better than models using CRP; the ΔAIC between the models was 305. The model of DAS28-ESR using SAA was associated with a ~6 fold better fit vs. the CRP model for subjects treated with ETN/MTX, and a ~5 fold better fit vs. the CRP model for subjects treated with oral DMARDs (ΔAIC = 159 vs. ΔAIC = 137, respectively). Conclusion: The lack of a strong correlation between SAA and CRP levels coupled with their different modeling of RA disease activity suggests that SAA levels may be a better biomarker for RA disease activity than CRP, especially during treatment with TNF antagonists.
    American College of Rheumatology conference, San Diego, CA; 10/2013
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    ABSTRACT: Objective Obesity and major depressive disorder often co-occur. However, differences between obese and normal-weight depressed patients and the moderating effect of obesity on antidepressant treatment outcome have not been well studied.Methods Adults (n = 662) with chronic or recurrent major depressive disorder in the Combining Medications to Enhance Depression Outcomes study were randomized to treatment with escitalopram plus placebo, bupropion plus escitalopram, or venlafaxine plus mirtazapine for a 12-week primary treatment phase and 16-week follow-up. Body mass index (BMI) was calculated at baseline and categorized in accordance with World Health Organization criteria: normal (and low) weight (NW), overweight, Obese I and Obese II+. Outcomes were assessed using a repeated-effects model, unadjusted and adjusted for baseline variables.ResultsObesity was common (46.2%), and 25.5% were NW. Higher BMI was associated with greater medical illness (p < .001), social phobia (p = .003), and bulimia (p = .026). Lower BMI was associated with a higher frequency of posttraumatic stress disorder (p = .002) and drug abuse (p < .001). Treatment outcomes did not differ across BMI classes, including Week 12 remission rates (NW 36%, overweight 40%, Obese I 43%, and Obese II+ 37%; p = .69). However, lower BMI was associated with more frequent (p = .024 [unadjusted] and .053 [adjusted]) and more severe (p = .008 [unadjusted] and .053 [adjusted]) adverse effects.ConclusionsBMI was related to the clinical presentation of depression and prevalence of comorbidities, but not medication use and antidepressant outcomes. Lower BMI classes had higher frequencies of psychiatric comorbidities, which may have obscured the relationship between body weight and antidepressive medication effects.Trial RegistrationClinicalTrials.gov identifier: NCT00590863.
    Psychosomatic Medicine 10/2013; · 4.08 Impact Factor
  • ACR/ARHP Annual Meeting, San Diego, CA; 10/2013
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    ABSTRACT: Gestational diabetes mellitus (GDM) affects 7% of pregnant mothers, and those with GDM have increased rates of perinatal complications. Major depressive disorder (MDD) and its pharmacologic treatments are associated with obesity and adverse pregnancy outcomes. In this prospective study, we investigated the relationship between abnormal GDM screens, maternal mood disorders, and adverse outcomes. We examined mothers with MDD, those with bipolar disorder (BD), and healthy controls (HC) at 20, 30, and 36 weeks of gestation and delivery. We obtained demographic data and pre-pregnancy body mass index (BMI), and confirmed diagnoses with the Structured Clinical Interview for DSM-IV. We evaluated smoking, alcohol use, substance use, and medication treatments with the Longitudinal Interval Follow-up Evaluation interview. Mothers received the one-hour 50-g glucose challenge test (GCT) at 26-28 weeks of gestation. Outcome variables were preterm birth, birth weight (BW) and peripartum events. We enrolled 62 HC, 50 BD, 41 past MDD, and 39 current MDD mother-infant pairs. Mean GCT levels and the frequency of abnormal GCT (>140 mg/dL) did not differ across groups. Rates of smoking (χ(2) = 20.68, df = 3, p < 0.001), substance use (χ(2) = 21.76, df = 3, p < 0.001), and pre-pregnancy obesity [BMI ≥ 30 (χ(2) = 9.97, df = 3, p = 0.019)] differed significantly across groups. Mothers with BD received medications associated with weight gain significantly more often than others [13/45 (29%), p < 0.001). After adjusting for group differences, GCT levels were associated significantly with increased odds for preterm birth (odds ratio = 1.29, 95% confidence interval: 1.0-1.7, p = 0.05) and increased perinatal events (beta = 0.11, p = 0.04) but were not associated with BW. In mothers with or without mood disorders, having increased GCT levels contributes to a higher likelihood for adverse pregnancy outcomes. Mothers with BD or current MDD can have additional risks for adverse outcomes and may benefit from early referral for high-risk services and supportive management in pregnancy.
    Bipolar Disorders 10/2013; · 4.62 Impact Factor
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    ABSTRACT: Abstract Background: Respiratory tract infections are a major cause of medical care seeking among people of all ages, yet only a portion are tested to determine the causative organism. The primary purposes of this study were to compare singleplex and multiplex reverse transcriptase polymerase chain reaction (RT-PCR) assays for influenza and examine the distribution and characteristics of viruses responsible for outpatient visits during influenza season. Methods: Individuals presenting for outpatient visits with acute respiratory illness were swabbed for presence of influenza virus using a singleplex RT-PCR assay. A subset of samples (n=662) were assayed for 18 using a multiplex RT-PCR method. Survey data provided demographic characteristics and symptoms. Results: The most commonly found viruses were human rhinovirus (HRV, 15.4%), respiratory syncytial virus (8.4%), human metapneumovirus (8.3%), and influenza (6%). No virus was isolated in 40.3% of cases. Age, self-rated health status, body mass index (BMI), and self-report of cough, fever, sore throat and nasal congestion at enrollment were all significantly more frequent among those with multiplex detected viral infections than those with no virus detected. In regression analyses adjusted for age and self-rated health, type of virus infection was significantly related to age group, BMI, and presence of fever and nasal congestion. Concordance between singleplex and multiplex assays for detection of influenza was high with Kappa =0.81 to 0.87. Co-infections were infrequent (45 of 662, 6.8%) and most common for HRV (19), influenza (12) and coronavirus (8). Conclusions: In this study of outpatient medically attended acute respiratory illnesses, using RT-PCR assays, we found a high correspondence between singleplex and multiplex methods for detection of influenza. Viruses differed in distribution across age groups, self-reported health status, BMI presence of fever and nasal congestion. Co-infections were infrequent.
    The Infectious Diseases Society of America, San Francisco, CA; 10/2013
  • Pediatric Critical Care Medicine 10/2013; 14(8):811-818. · 2.35 Impact Factor
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    ABSTRACT: To determine the prevalence, course, and risk factors for nighttime hot flashes during the pregnancy and postpartum periods. Clinical interview, physical measurements, and questionnaires administered at weeks 20, 30, and 36 of pregnancy and weeks 2, 12, 26, and 52 after delivery. Academic medical setting. 429 women. None. Nighttime hot flashes. Thirty-five percent of women reported nighttime hot flashes during pregnancy and 29% after delivery. In multivariable binomial mixed effects models, women who were younger (per year: odds ratio [OR] 0.94; 95% confidence interval [CI], 0.88-0.99), had a higher prepregnancy body mass index (per unit increase: OR 1.05; 95% CI, 1.01-1.10), and had less than a college education (OR 2.58; 95% CI, 1.19-5.60; vs. ≥college) were more likely to report nighttime hot flashes during pregnancy. Higher depressive symptoms were associated with nighttime hot flashes during pregnancy (per unit increase: OR 1.08; 95% CI, 1.04-1.13) and the postpartum period (OR 1.19; 95% CI, 1.14-1.25, multivariable models). Hot flashes, typically considered a menopausal symptom, were reported by over a third of women during pregnancy and/or the postpartum period. The predictors of these hot flashes, including depressive symptoms, low education, and higher body mass index are similar to those experienced during menopause. Future work should investigate the role of hormonal and affective factors in hot flashes during pregnancy and postpartum.
    Fertility and sterility 09/2013; · 3.97 Impact Factor
  • P David Adelson, Michael J Bell, Stephen R Wisniewski
    The Lancet Neurology 09/2013; 12(9):849-50. · 23.92 Impact Factor
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    ABSTRACT: Approximately 50% of patients with major depressive disorder (MDD) do not respond optimally to antidepressant treatments. Given this is a large proportion of the patient population, pretreatment tests that predict which patients will respond to which types of treatment could save time, money and patient burden. Brain imaging offers a means to identify treatment predictors that are grounded in the neurobiology of the treatment and the pathophysiology of MDD. The international Study to Predict Optimized Treatment in Depression is a multi-center, parallel model, randomized clinical trial with an embedded imaging sub-study to identify such predictors. We focus on brain circuits implicated in major depressive disorder and its treatment. In the full trial, depressed participants are randomized to receive escitalopram, sertraline or venlafaxine-XR (open-label). They are assessed using standardized multiple clinical, cognitive-emotional behavioral, electroencephalographic and genetic measures at baseline and at eight weeks post-treatment. Overall, 2,016 depressed participants (18 to 65 years old) will enter the study, of whom a target of 10% will be recruited into the brain imaging sub-study (approximately 67 participants in each treatment arm) and 67 controls. The imaging sub-study is conducted at the University of Sydney and at Stanford University. Structural studies include high-resolution three-dimensional T1-weighted, diffusion tensor and T2/Proton Density scans. Functional studies include standardized functional magnetic resonance imaging (MRI) with three cognitive tasks (auditory oddball, a continuous performance task, and Go-NoGo) and two emotion tasks (unmasked conscious and masked non-conscious emotion processing tasks). After eight weeks of treatment, the functional MRI is repeated with the above tasks. We will establish the methods in the first 30 patients. Then we will identify predictors in the first half (n = 102), test the findings in the second half, and then extend the analyses to the total sample.Trial registration: International Study to Predict Optimized Treatment - in Depression (iSPOT-D). ClinicalTrials.gov, NCT00693849.
    Trials 07/2013; 14(1):224. · 2.21 Impact Factor
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    ABSTRACT: Objective Disturbed sleep and depression are potential risk factors for pregnancy complications. Both conditions are known to dysregulate biological pathways responsible for maintaining homeostatic balance and pregnancy health. Depression during pregnancy is associated with poor sleep. Thus, we explored whether disturbed sleep was associated with inflammatory cytokines and risk for adverse pregnancy outcomes, as well as whether depression augmented the sleep-cytokine relationship, thereby additively contributing to risk for adverse outcomes.Methods Interview-assessed sleep and plasma cytokine concentrations were evaluated in a cohort of depressed and nondepressed pregnant women (n = 168) at 20 and 30 weeks' gestation. Outcomes evaluated included preterm birth, birth weight, and peripartum events.ResultsAmong depressed women, short sleep duration (<7 hours) was associated with higher interleukin (IL)-8 across time (β = 0.506, p = .001), poor sleep efficiency (<85%) was associated with higher IL-6 (β = 0.205, p = .006), and daytime naps were associated with higher tumor necrosis factor α (β = 0.105, p = .024). Aspects of poor sleep were associated with having a lower weight baby (p values <.053). Among depressed women, interferon-γ increased risk for preterm birth (odds ratio = 1.175, p = .032). Trends for IL-6 and higher birth weight (β = 105.2, p = .085), interferon-γ and lower birth weight (β = -19.92, p < .069), and increased IL-8 and babies weighing less than 4000 grams (odds ratio = 0.72, p < .083) were observed.Conclusions Although speculative, disturbed sleep may disrupt normal immune processes and contribute to adverse pregnancy outcomes. Exploratory analyses indicate that depression modifies these relationships.
    Psychosomatic Medicine 07/2013; · 4.08 Impact Factor
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    ABSTRACT: Background On the basis of mixed results from previous trials, we assessed whether therapeutic hypothermia for 48–72 h with slow rewarming improved mortality in children after brain injury. Methods In this phase 3, multicenter, multinational, randomised controlled trial, we included patients with severe traumatic brain injury who were younger than 18 years and could be enrolled within 6 h of injury. We used a computer-generated randomisation sequence to randomly allocate patients (1:1; stratified by site and age [<6 years, 6–15 years, 16–17 years]) to either hypothermia (rapidly cooled to 32–33°C for 48–72 h, then rewarmed by 0·5–1·0°C every 12–24 h) or normothermia (maintained at 36·5–37·5°C). The primary outcome was mortality at 3 months, assessed by intention-to-treat analysis; secondary outcomes were global function at 3 months after injury using the Glasgow outcome scale (GOS) and the GOS-extended pediatrics, and the occurrence of serious adverse events. Investigators assessing outcomes were masked to treatment. This trial is registered with ClinicalTrials.gov, number NCT00222742. Findings The study was terminated early for futility after an interim data analysis on data for 77 patients (enrolled between Nov 1, 2007, and Feb 28, 2011): 39 in the hypothermia group and 38 in the normothermia group. We detected no between-group difference in mortality 3 months after injury (6 [15%] of 39 patients in the hypothermia group vs two [5%] of 38 patients in the normothermia group; p=0·15). Poor outcomes did not differ between groups (in the hypothermia group, 16 [42%] patients had a poor outcome by GOS and 18 [47%] had a poor outcome by GOS-extended paediatrics; in the normothermia group, 16 [42%] patients had a poor outcome by GOS and 19 [51%] of 37 patients had a poor outcome by GOS-extended paediatrics). We recorded no between-group differences in the occurrence of adverse events or serious adverse events. Interpretation Hypothermia for 48 h with slow rewarming does not reduce mortality of improve global functional outcome after paediatric severe traumatic brain injury. Funding National Institute of Neurological Disorders and Stroke and National Institutes of Health.
    The Lancet Neurology 06/2013; 12(6):546–553. · 23.92 Impact Factor
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    ABSTRACT: OBJECTIVE The authors sought to identify baseline clinical and sociodemographic characteristics associated with work productivity in depressed outpatients and to assess the effect of treatment on work productivity. METHOD Employed depressed outpatients 18-75 years old who completed the Work Productivity and Activity Impairment scale (N=1,928) were treated with citalopram (20-40 mg/day) in the Sequenced Treatment Alternatives to Relieve Depression study. For patients who did not remit after an initial adequate antidepressant trial (level 1), either a switch to sertraline, sustained-release bupropion, or extended-release venlafaxine or an augmentation with sustained-release bupropion or buspirone was provided (level 2). Participants' clinical and demographic characteristics and treatment outcomes were analyzed for associations with baseline work productivity and change in productivity over time. RESULTS Education, baseline depression severity, and melancholic, atypical, and recurrent depression subtypes were all independently associated with lower benefit to work productivity domains. During level 1 treatment, work productivity in several domains improved with reductions in depressive symptom severity. However, these findings did not hold true for level 2 outcomes; there was no significant association between treatment response and reduction in work impairment. Results were largely confirmed when multiple imputations were employed to address missing data. During this additional analysis, an association was also observed between greater impairment in work productivity and higher levels of anxious depression. CONCLUSIONS Patients with clinically significant reductions in symptom severity during initial treatment were more likely than nonresponders to experience significant improvements in work productivity. In contrast, patients who achieved symptom remission in second-step treatment continued to have impairment at work. Patients who have demonstrated some degree of treatment resistance are more prone to persistent impairment in occupational productivity, implying a need for additional, possibly novel, treatments.
    American Journal of Psychiatry 04/2013; · 14.72 Impact Factor

Publication Stats

14k Citations
1,938.40 Total Impact Points

Institutions

  • 1996–2014
    • University of Pittsburgh
      • • Department of Epidemiology
      • • Department of Critical Care Medicine
      • • School of Health and Rehabilitation Sciences
      • • Safar Center for Resuscitation Research
      • • Graduate School of Public Health
      • • Department of Pediatrics
      • • Department of Neurology
      • • Department of Pediatric Neurosurgery
      • • Department of Anesthesiology
      Pittsburgh, Pennsylvania, United States
  • 2013
    • Barrow Neurological Institute
      Phoenix, Arizona, United States
  • 2010–2013
    • Virginia Commonwealth University
      • Institute for Women's Health
      Richmond, VA, United States
  • 2006–2013
    • University of Texas Southwestern Medical Center
      • • Department of Psychiatry
      • • Medical School
      Dallas, TX, United States
    • Via Christi Health
      Wichita, Kansas, United States
    • Baylor College of Medicine
      Houston, Texas, United States
    • Emory University
      • Department of Psychiatry and Behavioral Sciences
      Atlanta, GA, United States
    • Brown University
      • Department of Psychiatry and Human Behavior
      Providence, Rhode Island, United States
    • Vanderbilt University
      • Department of Psychology
      Nashville, MI, United States
  • 2004–2013
    • Childrens Hospital of Pittsburgh
      • Department of Pediatrics
      Pittsburgh, Pennsylvania, United States
  • 2012
    • New York City Department of Health and Mental Hygiene
      New York, United States
    • Carnegie Mellon University
      • Pittsburgh NMR Center for Biomedical Research
      Pittsburgh, PA, United States
    • Boston University
      • Department of Psychology
      Boston, MA, United States
  • 2011–2012
    • Duke-NUS Graduate Medical School Singapore
      Tumasik, Singapore
    • Purdue University
      • Department of Psychological Sciences
      West Lafayette, IN, United States
    • IT University of Copenhagen
      København, Capital Region, Denmark
    • Singapore General Hospital
      • Department of Psychiatry
      Singapore, Singapore
    • VA San Diego Healthcare System
      San Diego, California, United States
    • Northwestern University
      • Department of Psychiatry and Behavioral Sciences
      Evanston, IL, United States
  • 2009–2012
    • VHA National Center for Organization Development (NCOD)
      Cincinnati, Ohio, United States
    • Stony Brook University
      • Department of Psychology
      Stony Brook, NY, United States
  • 2004–2012
    • Massachusetts General Hospital
      • Department of Psychiatry
      Boston, MA, United States
  • 2001–2012
    • Western Psychiatric Institute and Clinic
      Pittsburgh, Pennsylvania, United States
  • 1997–2012
    • University of Michigan
      • Department of Psychiatry
      Ann Arbor, MI, United States
  • 2010–2011
    • West Virginia University
      • Department of Ophthalmology, Eye
      Morgantown, WV, United States
  • 2008–2011
    • University of Louisville
      • Department of Psychiatry and Behavioral Sciences
      Louisville, Kentucky, United States
    • University of Colorado
      • Department of Psychiatry
      Denver, CO, United States
    • Eli Lilly
      Indianapolis, Indiana, United States
    • Mount Sinai School of Medicine
      • Department of Psychiatry
      Manhattan, NY, United States
  • 2006–2011
    • Columbia University
      • Department of Psychiatry
      New York City, NY, United States
  • 2008–2010
    • University of Pennsylvania
      • • Department of Biobehavioral Health Sciences
      • • School of Nursing
      Philadelphia, PA, United States
  • 2007–2009
    • University of North Carolina at Chapel Hill
      • Department of Psychiatry
      Chapel Hill, NC, United States
    • University of California, Los Angeles
      • Department of Psychiatry and Biobehavioural Sciences
      Los Angeles, CA, United States
    • Yale University
      • Department of Psychiatry
      New Haven, CT, United States
    • U.S. Department of Veterans Affairs
      Washington, Washington, D.C., United States
    • Psychotherapy Associates
      Nebraska City, Nebraska, United States
    • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
      Torrance, California, United States
    • University of California, San Diego
      • Department of Psychiatry
      San Diego, CA, United States
  • 2005–2009
    • CSU Mentor
      Long Beach, California, United States
  • 2005–2007
    • University of Colorado at Boulder
      Boulder, Colorado, United States
  • 2004–2007
    • Harvard Medical School
      • Department of Psychiatry
      Cambridge, MA, United States