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The goals of the present study were to examine the associations between depressive symptoms, sleep problems and the risk of developing heart disease in a Canadian community sample.
Baseline data were from the CARTaGENE study, a community health survey of adults aged 40–69 years in Quebec, Canada. Incidence of heart disease was examined in N = 33 455 participants by linking survey data with administrative health insurance data. Incident heart disease was identified using the World Health Organization's International Classification of Diseases, 9th or 10th edition (ICD-9 and ICD-10) diagnostic codes for heart disease. Sleep problems were assessed with diagnostic codes for sleep disorders within the 2 years preceding the baseline assessment. Average sleep duration was assessed by self-report. Depressive symptoms were assessed with the nine-item Patient Health Questionnaire.
In total, 2448 (7.3%) participants developed heart disease over an average follow-up period of 4.6 years. Compared to those without depressive symptoms and with no sleep disorders, those with elevated depressive symptoms and a sleep disorder (HR = 2.60, 95% CI 1.83–3.69), those with depressive symptoms alone (HR = 1.40, 95% CI 1.25–1.57) and those with sleep disorders alone (HR = 1.33, 95% CI 1.03–1.73) were more likely to develop heart disease. Test of additive interaction suggested a synergistic interaction between depressive symptoms and sleep disorders (synergy index = 2.17 [95% CI 1.01–4.64]). When sleep duration was considered, those with long sleep duration and elevated depressive symptoms were more likely to develop heart disease than those with long sleep alone (HR = 1.77, 95% CI 1.37–2.28; and HR = 1.16, 95% CI 0.99–1.36, respectively).
Depression and diagnosed sleep disorders or long sleep duration are independent risk factors for heart disease and are associated with a stronger risk of heart disease when occurring together.
Major depressive disorder (MDD) is a leading cause of disease burden worldwide, with lifetime prevalence in the United States of 17%. Here we present the results of the first prospective, large-scale, patient- and rater-blind, randomized controlled trial evaluating the clinical importance of achieving congruence between combinatorial pharmacogenomic (PGx) testing and medication selection for MDD.
1,167 outpatients diagnosed with MDD and an inadequate response to ≥1 psychotropic medications were enrolled and randomized 1:1 to a Treatment as Usual (TAU) arm or PGx-guided care arm. Combinatorial PGx testing categorized medications in three groups based on the level of gene-drug interactions: use as directed, use with caution, or use with increased caution and more frequent monitoring. Patient assessments were performed at weeks 0 (baseline), 4, 8, 12 and 24. Patients, site raters, and central raters were blinded in both arms until after week 8. In the guided-care arm, physicians had access to the combinatorial PGx test result to guide medication selection. Primary outcomes utilized the Hamilton Depression Rating Scale (HAM-D17) and included symptom improvement (percent change in HAM-D17 from baseline), response (50% decrease in HAM-D17 from baseline), and remission (HAM-D17<7) at the fully blinded week 8 time point. The durability of patient outcomes was assessed at week 24. Medications were considered congruent with PGx test results if they were in the ‘use as directed’ or ‘use with caution’ report categories while medications in the ‘use with increased caution and more frequent monitoring’ were considered incongruent. Patients who started on incongruent medications were analyzed separately according to whether they changed to congruent medications by week8.
At week 8, symptom improvement for individuals in the guided-care arm was not significantly different than TAU (27.2% versus 24.4%, p=0.11). However, individuals in the guided-care arm were more likely than those in TAU to achieve remission (15% versus 10%; p<0.01) and response (26% versus 20%; p=0.01). Remission rates, response rates, and symptom reductions continued to improve in the guided-treatment arm until the 24week time point. Congruent prescribing increased to 91% in the guided-care arm by week 8. Among patients who were taking one or more incongruent medication at baseline, those who changed to congruent medications by week 8 demonstrated significantly greater symptom improvement (p<0.01), response (p=0.04), and remission rates (p<0.01) compared to those who persisted on incongruent medications.
Combinatorial PGx testing improves short- and long-term response and remission rates for MDD compared to standard of care. In addition, prescribing congruency with PGx-guided medication recommendations is important for achieving symptom improvement, response, and remission for MDD patients.
Funding Acknowledgements: This study was supported by Assurex Health, Inc.
I. De Pater, University of California, Berkeley Berkeley, California, USA,
D. P. Hamilton, University of Maryland College Park, Maryland, USA,
M. R. Showalter, SETI Institute Mountain View, California, USA,
H. B. Throop, Planetary Science Institute Tucson, Arizona, USA,
J. A. Burns, Cornell University Ithaca, New York, USA
Previous studies have examined associations of cardiometabolic factors with depression and cognition separately.
To determine if depressive symptoms mediate the association between cardiometabolic factors and cognitive decline in two community studies.
Data for the analyses were drawn from the Rotterdam Study, the Netherlands (n = 2940) and the Whitehall II study, UK (n = 4469).
Mediation analyses suggested a direct association between cardiometabolic factors and cognitive decline and an indirect association through depression: poorer cardiometabolic status at time 1 was associated with a higher level of depressive symptoms at time 2 (standardised regression coefficient 0.07 and 0.06, respectively), which, in turn, was associated with greater cognitive decline between time 2 and time 3 (standardised regression coefficient of −0.15 and −0.41, respectively).
Evidence from two independent cohort studies suggest an association between cardiometabolic dysregulation and cognitive decline and that depressive symptoms tend to precede this decline.
There is growing interest in linking vitamin D deficiency with autism spectrum disorders (ASDs). The association between vitamin D deficiency during gestation, a critical period in neurodevelopment, and ASD is not well understood.
To determine the association between gestational vitamin D status and ASD.
Based on a birth cohort (n=4334), we examined the association between 25-hydroxyvitamin D (25OHD), assessed from both maternal mid-gestation sera and neonatal sera, and ASD (defined by clinical records; n=68 cases).
Individuals in the 25OHD-deficient group at mid-gestation had more than twofold increased risk of ASD (odds ratio (OR)=2.42, 95% confidence interval (CI) 1.09 to 5.07, P=0.03) compared with the sufficient group. The findings persisted in analyses including children of European ethnicity only.
Mid-gestational vitamin D deficiency was associated with an increased risk of ASD. Because gestational vitamin D deficiency is readily preventable with safe, inexpensive and readily available supplementation, this risk factor warrants closer scrutiny.
Written in the shadow of the approaching millennium, American literature in the 1990s was beset by bleak announcements of the end of books, the end of postmodernism, and even the end of literature. Yet, as conservative critics marked the century's twilight hours by launching elegies for the conventional canon, American writers proved the continuing vitality of their literature by reinvigorating inherited forms, by adopting and adapting emerging technologies to narrative ends, and by finding new voices that had remained outside that canon for too long. By reading 1990s literature in a sequence of shifting contexts - from independent presses to the AIDS crisis, and from angelology to virtual reality - American Literature in Transition, 1990–2000 provides the fullest map yet of the changing shape of a rich and diverse decade's literary production. It offers new perspectives on the period's well-known landmarks, Toni Morrison, Thomas Pynchon, David Foster Wallace, but also overdue recognition to writers such as Ana Castillo, Evan Dara, Steve Erickson, and Carole Maso.
Infections caused by multidrug-resistant gram-negative organisms (MDRGNOs) have been increasing every year. The objective of this study was to describe the prevalence of MDRGNOs and factors associated with MDRGNOs in patients with spinal cord injury or disorder (SCI/D).
Retrospective cohort study.
Department of Veterans Affairs (VA) electronic health record data from 142 VA facilities were evaluated for 19,642 patients with SCI/D. Multivariable cluster-adjusted models were fit to identify factors associated with MDRGNO.
Gram-negative (GN) cultures occurred in 44% of patients with SCI/D receiving care at VA facilities, and 11,527 (41.3%) GN cultures had an MDRGNO. The most frequent GN organisms (GNOs) were Escherichia coli (28.5%), Klebsiella pneumoniae (17.0%), and Pseudomonas aeruginosa (16.0%). Two-thirds of GN cultures were from the outpatient setting, where MDRGNO prevalence was 37.6%. Significant geographic variation in the prevalence of MDRGNOs was identified (South, 44.7%; Northeast, 44.3%; West, 36.8%; Midwest, 34.4%). Other factors associated with an MDRGNO were older age, injury characteristics, comorbidities, specimen type, healthcare setting, and healthcare exposure. Black (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.39–1.78) and Hispanic race (OR, 1.58; 95% CI, 1.28–1.95), polymicrobial culture (OR, 2.67; 95% CI, 2.46–2.90), and antibiotic use in the previous 90 days (OR, 1.62; 95% CI, 1.50–1.76) were also associated with having an MDRGNO.
MDRGNOs were common in community and healthcare settings among veterans with SCI/D, with significant geographic variation. Health care and antibiotic exposures were significant factors associated with MDRGNOs. Priority should be given to controlling the spread of MDRGNOs in this special population, including a focus on judicious use of antibiotics.