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Ligula intestinalis infection as a potential source of bias in the bioindication of endocrine disruption in the European chub Leuciscus cephalus
- M. Schabuss, M. Gemeiner, A. Gleiß, J.W. Lewis, I Miller, E. Möstl, U. Schober, W. Tschulenk, I. Walter, B. Grillitsch
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- Journal:
- Journal of Helminthology / Volume 79 / Issue 1 / March 2005
- Published online by Cambridge University Press:
- 12 April 2024, pp. 91-94
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European chub Leuciscus cephalus collected from five localities in the lowland and subalpine regions of Austria were analysed for oestrogenic effects of endocrine-disrupting chemicals and the presence of the plerocercoid of the tapeworm Ligula intestinalis. Of 1494 chub analysed, only seven (six males, one female) were found to be infected with single, but large plerocercoids up to 15 cm in length. Ligula-infected fish showed comparatively immature gonads, as demonstrated by the gonadosomatic index and gamete developmental stages. Plasma levels of the egg precursor protein vitellogenin also showed concentrations ranging below the detection limit. The present results indicate that chub infected with L. intestinalis and exposed to exogenous oestrogenic compounds can result in reduced gonadal maturation and produce false oestrogen-positive diagnoses in male fish. For plasma vitellogenin levels, L. intestinalis infections can result in false oestrogen-negative diagnoses in male and female fish.
Establishing Disorder-Specific and Transdiagnostic Neural Features of Psychiatric Disorders Through Large-Scale Functional Magnetic Resonance Imaging Meta-Analyses
- C. H. Miller, E. Pritchard, S. Saravia, M. Duran, S. L. Santos, J. P. Hamilton, D. W. Hedges, I. H. Gotlib, M. D. Sacchet
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S547-S548
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Introduction
Meta-analyses of functional magnetic resonance imaging (fMRI) studies have been used to elucidate the most reliable neural features associated with various psychiatric disorders. However, it has not been well-established whether each of these neural features is linked to a specific disorder or is transdiagnostic across multiple disorders and disorder categories, including mood, anxiety, and anxiety-related disorders.
ObjectivesThis project aims to advance our understanding of the disorder-specific and transdiagnostic neural features associated with mood, anxiety, and anxiety-related disorders as well as to refine the methodology used to compare multiple disorders.
MethodsWe conducted an exhaustive PubMed literature search followed by double-screening, double-extraction, and cross-checking to identify all whole-brain, case-control fMRI activation studies of mood, anxiety, and anxiety-related disorders in order to construct a large-scale meta-analytic database of primary studies of these disorders. We then employed multilevel kernel density analysis (MKDA) with Monte-Carlo simulations to correct for multiple comparisons as well as ensemble thresholding to reduce cluster size bias to analyze primary fMRI studies of mood, anxiety, and anxiety-related disorders followed by application of triple subtraction techniques and a second-order analysis to elucidate the disorder-specificity of the previously identified neural features.
ResultsWe found that participants diagnosed with mood, anxiety, and anxiety-related disorders exhibited statistically significant (p < .05 – 0.0001; FWE-corrected) differences in neural activation relative to healthy controls throughout the cerebral cortex, limbic system, and basal ganglia. In addition, each of these psychiatric disorders exhibited a particular profile of neural features that ranged from disorder-specific, to category-specific, to transdiagnostic.
ConclusionsThese findings indicate that psychiatric disorders exhibit a complex profile of neural features that vary in their disorder-specificity and can be detected with large-scale fMRI meta-analytic techniques. This approach has potential to fundamentally transform neuroimaging investigations of clinical disorders by providing a novel procedure for establishing disorder-specificity of observed results, which can be then used to advance our understanding of individual disorders as well as broader nosological issues related to diagnosis and classification of psychiatric disorders.
Disclosure of InterestNone Declared
Major Depressive Disorder Across Development and Course of Illness: A Functional Neuroimaging Meta-Analysis
- C. Baten, A. M. Klassen, J. H. Shepherd, G. Zamora, E. Pritchard, S. Saravia, Z. Ali, J. Jordan, S. K. Kahlon, G. Maly, M. Duran, S. Santos, A. F. Nimarko, D. W. Hedges, P. Hamilton, I. H. Gotlib, M. D. Sacchet, C. H. Miller
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- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S345-S346
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Introduction
Functional magnetic resonance imaging (fMRI) has been used to identify the neural activity of both youth and adults diagnosed with major depressive disorder (MDD) in comparison to healthy age-matched controls. Previously reported abnormalities in depressed youth appear to mostly align with those found in depressed adults; however, some of the reported aberrant brain activity in youth has not been consistent with what is observed in adults, and to our knowledge there has not yet been a formal, quantitative comparison of these two groups. In addition, it is not known whether these observed differences between youth and adults with depression are attributable to developmental age or length-of-illness.
ObjectivesThe aim of this study is to elucidate the similarities and differences in patterns of abnormal neural activity between adults and youth diagnosed with MDD and to then determine whether these observed differences are due to either developmental age or length-of-illness.
MethodsWe used multilevel kernel density analysis (MKDA) with ensemble thresholding and triple subtraction to separately determine neural abnormalities throughout the whole brain in primary studies of depressed youth and depressed adults and then directly compare the observed abnormalities between each of those age groups. We then conducted further comparisons between multiple subgroups to control for age and length-of-illness and thereby determine the source of the observed differences between youth and adults with depression.
ResultsAdults and youth diagnosed with MDD demonstrated reliable, differential patterns of abnormal activation in various brain regions throughout the cerebral cortex that are statistically significant (p < .05; FWE-corrected). In addition, several of these brain regions that exhibited differential patterns of neural activation between the two age groups can be reliably attributed to either developmental age or length-of-illness.
ConclusionsThese findings indicate that there are common and disparate patterns of brain activity between youth and adults with MDD, several of which can be reliably attributed to developmental age or length-of-illness. These results expand our understanding of the neural basis of depression across development and course of illness and may be used to inform the development of new, age-specific clinical treatments as well as prevention strategies for this disorder.
Disclosure of InterestNone Declared
Major Depressive Disorder in Youth: A Meta-Analysis of Functional Magnetic Resonance Imaging Studies
- G. Zamora, C. Baten, A. M. Klassen, J. H. Shepherd, E. Pritchard, S. Saravia, Z. Ali, J. Jordan, S. K. Kahlon, G. Maly, M. Duran, S. L. Santos, A. F. Nimarko, D. W. Hedges, J. P. Hamilton, I. H. Gotlib, M. D. Sacchet, C. H. Miller
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S219-S220
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Introduction
Major depressive disorder (MDD) is a highly prevalent mental illness that frequently originates in early development and is pervasive during adolescence. Despite its high prevalence and early age of onset, our understanding of the potentially unique neural basis of MDD in this age group is still not well understood, and the existing primary literature on the topic includes many new and divergent results. This limited understanding of MDD in youth presents a critical need to further investigate its neural basis in youth and presents an opportunity to also improve clinical treatments that target its neural abnormalities.
ObjectivesThe present study aims to advance our understanding of the neural basis of MDD in youth by identifying abnormal functional activation in various brain regions compared with healthy controls.
MethodsWe conducted a meta-analysis of functional magnetic resonance imaging (fMRI) studies of MDD by using a well-established method, multilevel kernel density analysis (MKDA) with ensemble thresholding, to quantitatively combine all existing whole-brain fMRI studies of MDD in youth compared with healthy controls. This method involves a voxel-wise, whole-brain approach, that compares neural activation of patients with MDD to age-matched healthy controls across variations of task-based conditions, which we subcategorize into affective processing, executive functioning, positive valence, negative valence, and symptom provocation tasks.
ResultsYouth with MDD exhibited statistically significant (p<0.05; FWE-corrected) hyperactivation and hypoactivation in multiple brain regions compared with age-matched healthy controls. These results include significant effects that are stable across various tasks as well as some that appear to depend on task conditions.
ConclusionsThis study strengthens our understanding of the neural basis of MDD in youth and may also be used to help identify possible similarities and differences between youth and adults with depression. It may also help inform the development of new treatment interventions and tools for predicting unique treatment responses in youth with depression.
Disclosure of InterestNone Declared
The Neural Basis of Major Depressive Disorder in Adults: A Meta-Analysis of Functional Magnetic Resonance Imaging Activation Studies
- A. M. Klassen, C. Baten, J. H. Shepherd, G. Zamora, S. Saravia, E. Pritchard, Z. Ali, J. Jordan, S. K. Kahlon, G. Maly, M. Duran, S. L. Santos, A. F. Nimarko, D. W. Hedges, J. P. Hamilton, I. H. Gotlib, M. D. Sacchet, C. H. Miller
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S158
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Introduction
Major depressive disorder (MDD) is a highly prevalent mental illness that often first occurs or persists into adulthood and is considered the leading cause of disability and disease burden worldwide. Unfortunately, individuals diagnosed with MDD who seek treatment often experience limited symptom relief and may not achieve long-term remission, which is due in part to our limited understanding of its underlying pathophysiology. Many studies that use task-based functional magnetic resonance imaging (fMRI) have found abnormal activation in brain regions in adults diagnosed with MDD, but those findings are often inconsistent; in addition, previous meta-analyses that quantitatively integrate this large body literature have found conflicting results.
ObjectivesThis meta-analysis aims to advance our understanding of the neural basis of MDD in adults, as measured by fMRI activation studies, and address inconsistencies and discrepancies in the empirical literature.
MethodsWe employed multilevel kernel density analysis (MKDA) with ensemble thresholding, a well-established method for voxel-wise, whole-brain meta-analyses, to conduct a quantitative comparison of all relevant primary fMRI activation studies of adult patients with MDD compared to age-matched healthy controls.
ResultsWe found that adults with MDD exhibited a reliable pattern of statistically significant (p<0.05; FWE-corrected) hyperactivation and hypoactivation in several brain regions compared to age-matched healthy controls across a variety of experimental tasks.
ConclusionsThis study supports previous findings that there is reliable neural basis of MDD that can be detected across heterogenous fMRI studies. These results can be used to inform development of promising treatments for MDD, including protocols for personalized interventions. They also provide the opportunity for additional studies to examine the specificity of these effects among various populations-of-interest, including youth vs. adults with depression as well as other related mood and anxiety disorders.
Disclosure of InterestNone Declared
Associations of alcohol and cannabis use with change in posttraumatic stress disorder and depression symptoms over time in recently trauma-exposed individuals
- Cecilia A. Hinojosa, Amanda Liew, Xinming An, Jennifer S. Stevens, Archana Basu, Sanne J. H. van Rooij, Stacey L. House, Francesca L. Beaudoin, Donglin Zeng, Thomas C. Neylan, Gari D. Clifford, Tanja Jovanovic, Sarah D. Linnstaedt, Laura T. Germine, Scott L. Rauch, John P. Haran, Alan B. Storrow, Christopher Lewandowski, Paul I. Musey, Phyllis L. Hendry, Sophia Sheikh, Christopher W. Jones, Brittany E. Punches, Michael C. Kurz, Robert A. Swor, Lauren A. Hudak, Jose L. Pascual, Mark J. Seamon, Elizabeth M. Datner, Anna M. Chang, Claire Pearson, David A. Peak, Roland C. Merchant, Robert M. Domeier, Niels K. Rathlev, Paulina Sergot, Leon D. Sanchez, Steven E. Bruce, Mark W. Miller, Robert H. Pietrzak, Jutta Joormann, Diego A. Pizzagalli, John F. Sheridan, Steven E. Harte, James M. Elliott, Ronald C. Kessler, Karestan C. Koenen, Samuel A. McLean, Kerry J. Ressler, Negar Fani
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- Journal:
- Psychological Medicine / Volume 54 / Issue 2 / January 2024
- Published online by Cambridge University Press:
- 13 June 2023, pp. 338-349
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Background
Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians.
MethodsIn total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance.
ResultsThree trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12.
ConclusionsOur findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.
Childhood adversities and risk of posttraumatic stress disorder and major depression following a motor vehicle collision in adulthood
- H. N. Ziobrowski, B. Holt-Gosselin, M. V. Petukhova, A. J. King, S. Lee, S. L. House, F. L. Beaudoin, X. An, J. S. Stevens, D. Zeng, T. C. Neylan, G. D. Clifford, S. D. Linnstaedt, L. T. Germine, K. A. Bollen, S. L. Rauch, J. P. Haran, A. B. Storrow, C. Lewandowski, P. I. Musey, P. L. Hendry, S. Sheikh, C. W. Jones, B. E. Punches, M. C. Kurz, R. A. Swor, L. A. Hudak, J. L. Pascual, M. J. Seamon, E. Harris, C. Pearson, R. C. Merchant, R. M. Domeier, N. K. Rathlev, B. J. O'Neil, P. Sergot, L. D. Sanchez, S. E. Bruce, M. W. Miller, R. H. Pietrzak, J. Joormann, D. M. Barch, D. A. Pizzagalli, S. E. Harte, J. M. Elliott, K. J. Ressler, S. A. McLean, K. C. Koenen, R. C. Kessler
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- Journal:
- Epidemiology and Psychiatric Sciences / Volume 32 / 2023
- Published online by Cambridge University Press:
- 10 January 2023, e1
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Aims
Childhood adversities (CAs) predict heightened risks of posttraumatic stress disorder (PTSD) and major depressive episode (MDE) among people exposed to adult traumatic events. Identifying which CAs put individuals at greatest risk for these adverse posttraumatic neuropsychiatric sequelae (APNS) is important for targeting prevention interventions.
MethodsData came from n = 999 patients ages 18–75 presenting to 29 U.S. emergency departments after a motor vehicle collision (MVC) and followed for 3 months, the amount of time traditionally used to define chronic PTSD, in the Advancing Understanding of Recovery After Trauma (AURORA) study. Six CA types were self-reported at baseline: physical abuse, sexual abuse, emotional abuse, physical neglect, emotional neglect and bullying. Both dichotomous measures of ever experiencing each CA type and numeric measures of exposure frequency were included in the analysis. Risk ratios (RRs) of these CA measures as well as complex interactions among these measures were examined as predictors of APNS 3 months post-MVC. APNS was defined as meeting self-reported criteria for either PTSD based on the PTSD Checklist for DSM-5 and/or MDE based on the PROMIS Depression Short-Form 8b. We controlled for pre-MVC lifetime histories of PTSD and MDE. We also examined mediating effects through peritraumatic symptoms assessed in the emergency department and PTSD and MDE assessed in 2-week and 8-week follow-up surveys. Analyses were carried out with robust Poisson regression models.
ResultsMost participants (90.9%) reported at least rarely having experienced some CA. Ever experiencing each CA other than emotional neglect was univariably associated with 3-month APNS (RRs = 1.31–1.60). Each CA frequency was also univariably associated with 3-month APNS (RRs = 1.65–2.45). In multivariable models, joint associations of CAs with 3-month APNS were additive, with frequency of emotional abuse (RR = 2.03; 95% CI = 1.43–2.87) and bullying (RR = 1.44; 95% CI = 0.99–2.10) being the strongest predictors. Control variable analyses found that these associations were largely explained by pre-MVC histories of PTSD and MDE.
ConclusionsAlthough individuals who experience frequent emotional abuse and bullying in childhood have a heightened risk of experiencing APNS after an adult MVC, these associations are largely mediated by prior histories of PTSD and MDE.
Prior differences in previous trauma exposure primarily drive the observed racial/ethnic differences in posttrauma depression and anxiety following a recent trauma
- N. G. Harnett, N. M. Dumornay, M. Delity, L. D. Sanchez, K. Mohiuddin, P. I. Musey, Jr., M. J. Seamon, S. A. McLean, R. C. Kessler, K. C. Koenen, F. L. Beaudoin, L. A. M. Lebois, S. J. H. van Rooij, N. A. Sampson, V. Michopoulos, J. L. Maples-Keller, J. P. Haran, A. B. Storrow, C. Lewandowski, P. L. Hendry, S. Sheikh, C. W. Jones, B. E. Punches, M. C. Kurz, R. A. Swor, M. E. McGrath, L. A. Hudak, J. L. Pascual, S. L. House, X. An, J. S. Stevens, T. C. Neylan, T. Jovanovic, S. D. Linnstaedt, L. T. Germine, E. M. Datner, A. M. Chang, C. Pearson, D. A. Peak, R. C. Merchant, R. M. Domeier, N. K. Rathlev, B. J. O'Neil, P. Sergot, S. E. Bruce, M. W. Miller, R. H. Pietrzak, J. Joormann, D. M. Barch, D. A. Pizzagalli, J. F. Sheridan, J. W. Smoller, B. Luna, S. E. Harte, J. M. Elliott, K. J. Ressler
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- Psychological Medicine / Volume 53 / Issue 6 / April 2023
- Published online by Cambridge University Press:
- 31 January 2022, pp. 2553-2562
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Background
Racial and ethnic groups in the USA differ in the prevalence of posttraumatic stress disorder (PTSD). Recent research however has not observed consistent racial/ethnic differences in posttraumatic stress in the early aftermath of trauma, suggesting that such differences in chronic PTSD rates may be related to differences in recovery over time.
MethodsAs part of the multisite, longitudinal AURORA study, we investigated racial/ethnic differences in PTSD and related outcomes within 3 months after trauma. Participants (n = 930) were recruited from emergency departments across the USA and provided periodic (2 weeks, 8 weeks, and 3 months after trauma) self-report assessments of PTSD, depression, dissociation, anxiety, and resilience. Linear models were completed to investigate racial/ethnic differences in posttraumatic dysfunction with subsequent follow-up models assessing potential effects of prior life stressors.
ResultsRacial/ethnic groups did not differ in symptoms over time; however, Black participants showed reduced posttraumatic depression and anxiety symptoms overall compared to Hispanic participants and White participants. Racial/ethnic differences were not attenuated after accounting for differences in sociodemographic factors. However, racial/ethnic differences in depression and anxiety were no longer significant after accounting for greater prior trauma exposure and childhood emotional abuse in White participants.
ConclusionsThe present findings suggest prior differences in previous trauma exposure partially mediate the observed racial/ethnic differences in posttraumatic depression and anxiety symptoms following a recent trauma. Our findings further demonstrate that racial/ethnic groups show similar rates of symptom recovery over time. Future work utilizing longer time-scale data is needed to elucidate potential racial/ethnic differences in long-term symptom trajectories.
Science with the Murchison Widefield Array: Phase I results and Phase II opportunities – Corrigendum
- A. P. Beardsley, M. Johnston-Hollitt, C. M. Trott, J. C. Pober, J. Morgan, D. Oberoi, D. L. Kaplan, C. R. Lynch, G. E. Anderson, P. I. McCauley, S. Croft, C. W. James, O. I. Wong, C. D. Tremblay, R. P. Norris, I. H. Cairns, C. J. Lonsdale, P. J. Hancock, B. M. Gaensler, N. D. R. Bhat, W. Li, N. Hurley-Walker, J. R. Callingham, N. Seymour, S. Yoshiura, R. C. Joseph, K. Takahashi, M. Sokolowski, J. C. A. Miller-Jones, J. V. Chauhan, I. Bojičić, M. D. Filipović, D. Leahy, H. Su, W. W. Tian, S. J. McSweeney, B. W. Meyers, S. Kitaeff, T. Vernstrom, G. Gürkan, G. Heald, M. Xue, C. J. Riseley, S. W. Duchesne, J. D. Bowman, D. C. Jacobs, B. Crosse, D. Emrich, T. M. O. Franzen, L. Horsley, D. Kenney, M. F. Morales, D. Pallot, K. Steele, S. J. Tingay, M. Walker, R. B. Wayth, A. Williams, C. Wu
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- Publications of the Astronomical Society of Australia / Volume 37 / 2020
- Published online by Cambridge University Press:
- 23 March 2020, e014
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Science with the Murchison Widefield Array: Phase I results and Phase II opportunities
- A. P. Beardsley, M. Johnston-Hollitt, C. M. Trott, J. C. Pober, J. Morgan, D. Oberoi, D. L. Kaplan, C. R. Lynch, G. E. Anderson, P. I. McCauley, S. Croft, C. W. James, O. I. Wong, C. D. Tremblay, R. P. Norris, I. H. Cairns, C. J. Lonsdale, P. J. Hancock, B. M. Gaensler, N. D. R. Bhat, W. Li, N. Hurley-Walker, J. R. Callingham, N. Seymour, S. Yoshiura, R. C. Joseph, K. Takahashi, M. Sokolowski, J. C. A. Miller-Jones, J. V. Chauhan, I. Bojičić, M. D. Filipović, D. Leahy, H. Su, W. W. Tian, S. J. McSweeney, B. W. Meyers, S. Kitaeff, T. Vernstrom, G. Gürkan, G. Heald, M. Xue, C. J. Riseley, S. W. Duchesne, J. D. Bowman, D. C. Jacobs, B. Crosse, D. Emrich, T. M. O. Franzen, L. Horsley, D. Kenney, M. F. Morales, D. Pallot, K. Steele, S. J. Tingay, M. Walker, R. B. Wayth, A. Williams, C. Wu
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- Publications of the Astronomical Society of Australia / Volume 36 / 2019
- Published online by Cambridge University Press:
- 13 December 2019, e050
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The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together $60+$ programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.
Automated data mining of the electronic health record for investigation of healthcare-associated outbreaks
- Alexander J. Sundermann, James K. Miller, Jane W. Marsh, Melissa I. Saul, Kathleen A. Shutt, Marissa Pacey, Mustapha M. Mustapha, Ashley Ayres, A. William Pasculle, Jieshi Chen, Graham M. Snyder, Artur W. Dubrawski, Lee H. Harrison
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- Journal:
- Infection Control & Hospital Epidemiology / Volume 40 / Issue 3 / March 2019
- Published online by Cambridge University Press:
- 18 February 2019, pp. 314-319
- Print publication:
- March 2019
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Background:
Identifying routes of transmission among hospitalized patients during a healthcare-associated outbreak can be tedious, particularly among patients with complex hospital stays and multiple exposures. Data mining of the electronic health record (EHR) has the potential to rapidly identify common exposures among patients suspected of being part of an outbreak.
Methods:We retrospectively analyzed 9 hospital outbreaks that occurred during 2011–2016 and that had previously been characterized both according to transmission route and by molecular characterization of the bacterial isolates. We determined (1) the ability of data mining of the EHR to identify the correct route of transmission, (2) how early the correct route was identified during the timeline of the outbreak, and (3) how many cases in the outbreaks could have been prevented had the system been running in real time.
Results:Correct routes were identified for all outbreaks at the second patient, except for one outbreak involving >1 transmission route that was detected at the eighth patient. Up to 40 or 34 infections (78% or 66% of possible preventable infections, respectively) could have been prevented if data mining had been implemented in real time, assuming the initiation of an effective intervention within 7 or 14 days of identification of the transmission route, respectively.
Conclusions:Data mining of the EHR was accurate for identifying routes of transmission among patients who were part of the outbreak. Prospective validation of this approach using routine whole-genome sequencing and data mining of the EHR for both outbreak detection and route attribution is ongoing.
Description of a method for inducing fetal growth restriction in the spiny mouse
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- H. Dickinson, S. Ellery, M. Davies-Tuck, M. Tolcos, I. Nitsos, D. W. Walker, S. L. Miller
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- Journal of Developmental Origins of Health and Disease / Volume 8 / Issue 5 / October 2017
- Published online by Cambridge University Press:
- 29 June 2017, pp. 550-555
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Intrauterine or fetal growth restriction (IUGR) is a major complication of pregnancy and leads to significant perinatal morbidities and mortality. Typically, induction of IUGR in animals involves the complete occlusion or ablation of vessels to the uterus or placenta, acutely impairing blood flow and fetal growth, usually with high fetal loss. We aimed to produce a model of reduced fetal growth in the spiny mouse with minimal fetal loss. At 27 days gestational age (term is 38–39 days), a piece of silastic tubing was placed around the left uterine artery to prevent the further increase of uterine blood flow with advancing gestation to induce IUGR (occluded). Controls were generated from sham surgeries without placement of the tubing. Dams were humanely euthanized at 37 days gestational age and all fetuses and placentas were weighed and collected. Of the 17 dams that underwent surgery, 15 carried their pregnancies to 37 days gestational age and 95% of fetuses survived to this time. The difference in fetal body weight between occluded and control was ~21% for fetuses in the left uterus side: there were no differences for fetuses in the right uterus side. Offspring from the occluded group had significantly lower brain, liver, lung, kidney and carcass weights compared with shams. Preventing the gestation-related increase of uterine blood flow induced significant growth restriction in the fetal spiny mouse, with minimal fetal loss. This technique could be readily adapted for other small animal.
Farmers’ Adoption Path of Precision Agriculture Technology
- N. J. Miller, T. W. Griffin, J. Bergtold, I. A. Ciampitti, A. Sharda
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- Advances in Animal Biosciences / Volume 8 / Issue 2 / July 2017
- Published online by Cambridge University Press:
- 01 June 2017, pp. 708-712
- Print publication:
- July 2017
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Precision agriculture technologies have been adopted individually and in bundles. A sample of 348 Kansas Farm Management Association farm-level observations provides insight into technology adoption patterns of precision agriculture technologies. Estimated transition probabilities shed light on how adoption paths lead to bundling of technologies. Three information intensive technologies were assigned to one of eight possible bundles, and the sequence of adoption was examined using Markov transition processes. The probability that farms remain with the same bundle or transition to a different bundle by the next time period are reported. Farms with the complete bundle of all three technologies were likely to persist with their current technology.
Adjunctive yoga v. health education for persistent major depression: a randomized controlled trial
- L. A. Uebelacker, G. Tremont, L. T. Gillette, G. Epstein-Lubow, D. R. Strong, A. M. Abrantes, A. R. Tyrka, T. Tran, B. A. Gaudiano, I. W. Miller
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- Journal:
- Psychological Medicine / Volume 47 / Issue 12 / September 2017
- Published online by Cambridge University Press:
- 06 April 2017, pp. 2130-2142
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Background
The objective of this study was to determine whether hatha yoga is an efficacious adjunctive intervention for individuals with continued depressive symptoms despite antidepressant treatment.
MethodWe conducted a randomized controlled trial of weekly yoga classes (n = 63) v. health education classes (Healthy Living Workshop; HLW; n = 59) in individuals with elevated depression symptoms and antidepressant medication use. HLW served as an attention-control group. The intervention period was 10 weeks, with follow-up assessments 3 and 6 months afterwards. The primary outcome was depression symptom severity assessed by blind rater at 10 weeks. Secondary outcomes included depression symptoms over the entire intervention and follow-up periods, social and role functioning, general health perceptions, pain, and physical functioning.
ResultsAt 10 weeks, we did not find a statistically significant difference between groups in depression symptoms (b = −0.82, s.e. = 0.88, p = 0.36). However, over the entire intervention and follow-up period, when controlling for baseline, yoga participants showed lower levels of depression than HLW participants (b = −1.38, s.e. = 0.57, p = 0.02). At 6-month follow-up, 51% of yoga participants demonstrated a response (⩾50% reduction in depression symptoms) compared with 31% of HLW participants (odds ratio = 2.31; p = 0.04). Yoga participants showed significantly better social and role functioning and general health perceptions over time.
ConclusionsAlthough we did not see a difference in depression symptoms at the end of the intervention period, yoga participants showed fewer depression symptoms over the entire follow-up period. Benefits of yoga may accumulate over time.
DESAlert: Enabling Real-Time Transient Follow-Up with Dark Energy Survey Data
- A. Poci, K. Kuehn, T. Abbott, F. B. Abdalla, S. Allam, A.H. Bauer, A. Benoit-Lévy, E. Bertin, D. Brooks, P. J. Brown, E. Buckley-Geer, D. L. Burke, A. Carnero Rosell, M. Carrasco Kind, R. Covarrubias, L. N. da Costa, C. B. D’Andrea, D. L. DePoy, S. Desai, J. P. Dietrich, C. E Cunha, T. F. Eifler, J. Estrada, A. E. Evrard, A. Fausti Neto, D. A. Finley, B. Flaugher, P. Fosalba, J. Frieman, D. Gerdes, D. Gruen, R. A. Gruendl, K. Honscheid, D. James, N. Kuropatkin, O. Lahav, T. S. Li, M. March, J. Marshall, K. W. Merritt, C.J. Miller, R. C. Nichol, B. Nord, R. Ogando, A. A. Plazas, A. K. Romer, A. Roodman, E. S. Rykoff, M. Sako, E. Sanchez, V. Scarpine, M. Schubnell, I. Sevilla, C. Smith, M. Soares-Santos, F. Sobreira, E. Suchyta, M. E. C. Swanson, G. Tarle, J. Thaler, R. C. Thomas, D. Tucker, A. R. Walker, W. Wester, (The DES Collaboration)
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- Journal:
- Publications of the Astronomical Society of Australia / Volume 33 / 2016
- Published online by Cambridge University Press:
- 30 September 2016, e049
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The Dark Energy Survey is undertaking an observational programme imaging 1/4 of the southern hemisphere sky with unprecedented photometric accuracy. In the process of observing millions of faint stars and galaxies to constrain the parameters of the dark energy equation of state, the Dark Energy Survey will obtain pre-discovery images of the regions surrounding an estimated 100 gamma-ray bursts over 5 yr. Once gamma-ray bursts are detected by, e.g., the Swift satellite, the DES data will be extremely useful for follow-up observations by the transient astronomy community. We describe a recently-commissioned suite of software that listens continuously for automated notices of gamma-ray burst activity, collates information from archival DES data, and disseminates relevant data products back to the community in near-real-time. Of particular importance are the opportunities that non-public DES data provide for relative photometry of the optical counterparts of gamma-ray bursts, as well as for identifying key characteristics (e.g., photometric redshifts) of potential gamma-ray burst host galaxies. We provide the functional details of the DESAlert software, and its data products, and we show sample results from the application of DESAlert to numerous previously detected gamma-ray bursts, including the possible identification of several heretofore unknown gamma-ray burst hosts.
Phanerozoic trends in the global geographic disparity of marine biotas
- Arnold I. Miller, Devin P. Buick, Katherine V. Bulinski, Chad A. Ferguson, Austin J. W. Hendy, Martin Aberhan, Wolfgang Kiessling
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- Paleobiology / Volume 35 / Issue 4 / Fall 2009
- Published online by Cambridge University Press:
- 08 April 2016, pp. 612-630
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Previous analyses of the history of Phanerozoic marine biodiversity suggested that the post-Paleozoic increase observed at the family level and below was caused, in part, by an increase in global provinciality associated with the breakup of Pangea. Efforts to characterize the Phanerozoic history of provinciality, however, have been compromised by interval-to-interval variations in the methods and standards used by researchers to calibrate the number of provinces. With the development of comprehensive, occurrence-based data repositories such as the Paleobiology Database (PaleoDB), it is now possible to analyze directly the degree of global compositional disparity as a function of geographic distance (geo-disparity) and changes thereof throughout the history of marine animal life. Here, we present a protocol for assessing the Phanerozoic history of geo-disparity, and we apply it to stratigraphic bins arrayed throughout the Phanerozoic for which data were accessed from the PaleoDB. Our analyses provide no indication of a secular Phanerozoic increase in geo-disparity. Furthermore, fundamental characteristics of geo-disparity may have changed from era to era in concert with changes to marine venues, although these patterns will require further scrutiny in future investigations.
Sample preparation artifacts in nuclear materials and mitigation strategies
- A. Aitkaliyeva, J. W. Madden, B. D. Miller, J. I. Cole, J. Gan
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- Journal:
- Microscopy and Microanalysis / Volume 21 / Issue S3 / August 2015
- Published online by Cambridge University Press:
- 23 September 2015, pp. 999-1000
- Print publication:
- August 2015
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Microstractural characterization of alnico 9 alloy
- Lin Zhou, M. Miller, D. A. Cullen, Ping Lu, R. W. McCallum, I. E. Anderson, S. Constantinides, M. J. Kramer
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- Microscopy and Microanalysis / Volume 21 / Issue S3 / August 2015
- Published online by Cambridge University Press:
- 23 September 2015, pp. 1343-1344
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- August 2015
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Contributors
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- By Mitchell Aboulafia, Frederick Adams, Marilyn McCord Adams, Robert M. Adams, Laird Addis, James W. Allard, David Allison, William P. Alston, Karl Ameriks, C. Anthony Anderson, David Leech Anderson, Lanier Anderson, Roger Ariew, David Armstrong, Denis G. Arnold, E. J. Ashworth, Margaret Atherton, Robin Attfield, Bruce Aune, Edward Wilson Averill, Jody Azzouni, Kent Bach, Andrew Bailey, Lynne Rudder Baker, Thomas R. Baldwin, Jon Barwise, George Bealer, William Bechtel, Lawrence C. Becker, Mark A. Bedau, Ernst Behler, José A. Benardete, Ermanno Bencivenga, Jan Berg, Michael Bergmann, Robert L. Bernasconi, Sven Bernecker, Bernard Berofsky, Rod Bertolet, Charles J. Beyer, Christian Beyer, Joseph Bien, Joseph Bien, Peg Birmingham, Ivan Boh, James Bohman, Daniel Bonevac, Laurence BonJour, William J. Bouwsma, Raymond D. Bradley, Myles Brand, Richard B. Brandt, Michael E. Bratman, Stephen E. Braude, Daniel Breazeale, Angela Breitenbach, Jason Bridges, David O. Brink, Gordon G. Brittan, Justin Broackes, Dan W. Brock, Aaron Bronfman, Jeffrey E. Brower, Bartosz Brozek, Anthony Brueckner, Jeffrey Bub, Lara Buchak, Otavio Bueno, Ann E. Bumpus, Robert W. Burch, John Burgess, Arthur W. Burks, Panayot Butchvarov, Robert E. Butts, Marina Bykova, Patrick Byrne, David Carr, Noël Carroll, Edward S. Casey, Victor Caston, Victor Caston, Albert Casullo, Robert L. Causey, Alan K. L. Chan, Ruth Chang, Deen K. Chatterjee, Andrew Chignell, Roderick M. Chisholm, Kelly J. Clark, E. J. Coffman, Robin Collins, Brian P. Copenhaver, John Corcoran, John Cottingham, Roger Crisp, Frederick J. Crosson, Antonio S. Cua, Phillip D. Cummins, Martin Curd, Adam Cureton, Andrew Cutrofello, Stephen Darwall, Paul Sheldon Davies, Wayne A. Davis, Timothy Joseph Day, Claudio de Almeida, Mario De Caro, Mario De Caro, John Deigh, C. F. Delaney, Daniel C. Dennett, Michael R. DePaul, Michael Detlefsen, Daniel Trent Devereux, Philip E. Devine, John M. Dillon, Martin C. Dillon, Robert DiSalle, Mary Domski, Alan Donagan, Paul Draper, Fred Dretske, Mircea Dumitru, Wilhelm Dupré, Gerald Dworkin, John Earman, Ellery Eells, Catherine Z. Elgin, Berent Enç, Ronald P. Endicott, Edward Erwin, John Etchemendy, C. Stephen Evans, Susan L. Feagin, Solomon Feferman, Richard Feldman, Arthur Fine, Maurice A. Finocchiaro, William FitzPatrick, Richard E. Flathman, Gvozden Flego, Richard Foley, Graeme Forbes, Rainer Forst, Malcolm R. Forster, Daniel Fouke, Patrick Francken, Samuel Freeman, Elizabeth Fricker, Miranda Fricker, Michael Friedman, Michael Fuerstein, Richard A. Fumerton, Alan Gabbey, Pieranna Garavaso, Daniel Garber, Jorge L. A. Garcia, Robert K. Garcia, Don Garrett, Philip Gasper, Gerald Gaus, Berys Gaut, Bernard Gert, Roger F. Gibson, Cody Gilmore, Carl Ginet, Alan H. Goldman, Alvin I. Goldman, Alfonso Gömez-Lobo, Lenn E. Goodman, Robert M. Gordon, Stefan Gosepath, Jorge J. E. Gracia, Daniel W. Graham, George A. Graham, Peter J. Graham, Richard E. Grandy, I. Grattan-Guinness, John Greco, Philip T. Grier, Nicholas Griffin, Nicholas Griffin, David A. Griffiths, Paul J. Griffiths, Stephen R. Grimm, Charles L. Griswold, Charles B. Guignon, Pete A. Y. Gunter, Dimitri Gutas, Gary Gutting, Paul Guyer, Kwame Gyekye, Oscar A. Haac, Raul Hakli, Raul Hakli, Michael Hallett, Edward C. Halper, Jean Hampton, R. James Hankinson, K. R. Hanley, Russell Hardin, Robert M. Harnish, William Harper, David Harrah, Kevin Hart, Ali Hasan, William Hasker, John Haugeland, Roger Hausheer, William Heald, Peter Heath, Richard Heck, John F. Heil, Vincent F. Hendricks, Stephen Hetherington, Francis Heylighen, Kathleen Marie Higgins, Risto Hilpinen, Harold T. Hodes, Joshua Hoffman, Alan Holland, Robert L. Holmes, Richard Holton, Brad W. Hooker, Terence E. Horgan, Tamara Horowitz, Paul Horwich, Vittorio Hösle, Paul Hoβfeld, Daniel Howard-Snyder, Frances Howard-Snyder, Anne Hudson, Deal W. Hudson, Carl A. Huffman, David L. Hull, Patricia Huntington, Thomas Hurka, Paul Hurley, Rosalind Hursthouse, Guillermo Hurtado, Ronald E. Hustwit, Sarah Hutton, Jonathan Jenkins Ichikawa, Harry A. Ide, David Ingram, Philip J. Ivanhoe, Alfred L. Ivry, Frank Jackson, Dale Jacquette, Joseph Jedwab, Richard Jeffrey, David Alan Johnson, Edward Johnson, Mark D. Jordan, Richard Joyce, Hwa Yol Jung, Robert Hillary Kane, Tomis Kapitan, Jacquelyn Ann K. Kegley, James A. Keller, Ralph Kennedy, Sergei Khoruzhii, Jaegwon Kim, Yersu Kim, Nathan L. King, Patricia Kitcher, Peter D. Klein, E. D. Klemke, Virginia Klenk, George L. Kline, Christian Klotz, Simo Knuuttila, Joseph J. Kockelmans, Konstantin Kolenda, Sebastian Tomasz Kołodziejczyk, Isaac Kramnick, Richard Kraut, Fred Kroon, Manfred Kuehn, Steven T. Kuhn, Henry E. Kyburg, John Lachs, Jennifer Lackey, Stephen E. Lahey, Andrea Lavazza, Thomas H. Leahey, Joo Heung Lee, Keith Lehrer, Dorothy Leland, Noah M. Lemos, Ernest LePore, Sarah-Jane Leslie, Isaac Levi, Andrew Levine, Alan E. Lewis, Daniel E. Little, Shu-hsien Liu, Shu-hsien Liu, Alan K. L. Chan, Brian Loar, Lawrence B. Lombard, John Longeway, Dominic McIver Lopes, Michael J. Loux, E. J. Lowe, Steven Luper, Eugene C. Luschei, William G. Lycan, David Lyons, David Macarthur, Danielle Macbeth, Scott MacDonald, Jacob L. Mackey, Louis H. Mackey, Penelope Mackie, Edward H. Madden, Penelope Maddy, G. B. Madison, Bernd Magnus, Pekka Mäkelä, Rudolf A. Makkreel, David Manley, William E. Mann (W.E.M.), Vladimir Marchenkov, Peter Markie, Jean-Pierre Marquis, Ausonio Marras, Mike W. Martin, A. P. Martinich, William L. McBride, David McCabe, Storrs McCall, Hugh J. McCann, Robert N. McCauley, John J. McDermott, Sarah McGrath, Ralph McInerny, Daniel J. McKaughan, Thomas McKay, Michael McKinsey, Brian P. McLaughlin, Ernan McMullin, Anthonie Meijers, Jack W. Meiland, William Jason Melanson, Alfred R. Mele, Joseph R. Mendola, Christopher Menzel, Michael J. Meyer, Christian B. Miller, David W. Miller, Peter Millican, Robert N. Minor, Phillip Mitsis, James A. Montmarquet, Michael S. Moore, Tim Moore, Benjamin Morison, Donald R. Morrison, Stephen J. Morse, Paul K. Moser, Alexander P. D. Mourelatos, Ian Mueller, James Bernard Murphy, Mark C. Murphy, Steven Nadler, Jan Narveson, Alan Nelson, Jerome Neu, Samuel Newlands, Kai Nielsen, Ilkka Niiniluoto, Carlos G. Noreña, Calvin G. Normore, David Fate Norton, Nikolaj Nottelmann, Donald Nute, David S. Oderberg, Steve Odin, Michael O’Rourke, Willard G. Oxtoby, Heinz Paetzold, George S. Pappas, Anthony J. Parel, Lydia Patton, R. P. Peerenboom, Francis Jeffry Pelletier, Adriaan T. Peperzak, Derk Pereboom, Jaroslav Peregrin, Glen Pettigrove, Philip Pettit, Edmund L. Pincoffs, Andrew Pinsent, Robert B. Pippin, Alvin Plantinga, Louis P. Pojman, Richard H. Popkin, John F. Post, Carl J. Posy, William J. Prior, Richard Purtill, Michael Quante, Philip L. Quinn, Philip L. Quinn, Elizabeth S. Radcliffe, Diana Raffman, Gerard Raulet, Stephen L. Read, Andrews Reath, Andrew Reisner, Nicholas Rescher, Henry S. Richardson, Robert C. Richardson, Thomas Ricketts, Wayne D. Riggs, Mark Roberts, Robert C. Roberts, Luke Robinson, Alexander Rosenberg, Gary Rosenkranz, Bernice Glatzer Rosenthal, Adina L. Roskies, William L. Rowe, T. M. Rudavsky, Michael Ruse, Bruce Russell, Lilly-Marlene Russow, Dan Ryder, R. M. Sainsbury, Joseph Salerno, Nathan Salmon, Wesley C. Salmon, Constantine Sandis, David H. Sanford, Marco Santambrogio, David Sapire, Ruth A. Saunders, Geoffrey Sayre-McCord, Charles Sayward, James P. Scanlan, Richard Schacht, Tamar Schapiro, Frederick F. Schmitt, Jerome B. Schneewind, Calvin O. Schrag, Alan D. Schrift, George F. Schumm, Jean-Loup Seban, David N. Sedley, Kenneth Seeskin, Krister Segerberg, Charlene Haddock Seigfried, Dennis M. Senchuk, James F. Sennett, William Lad Sessions, Stewart Shapiro, Tommie Shelby, Donald W. Sherburne, Christopher Shields, Roger A. Shiner, Sydney Shoemaker, Robert K. Shope, Kwong-loi Shun, Wilfried Sieg, A. John Simmons, Robert L. Simon, Marcus G. Singer, Georgette Sinkler, Walter Sinnott-Armstrong, Matti T. Sintonen, Lawrence Sklar, Brian Skyrms, Robert C. Sleigh, Michael Anthony Slote, Hans Sluga, Barry Smith, Michael Smith, Robin Smith, Robert Sokolowski, Robert C. Solomon, Marta Soniewicka, Philip Soper, Ernest Sosa, Nicholas Southwood, Paul Vincent Spade, T. L. S. Sprigge, Eric O. Springsted, George J. Stack, Rebecca Stangl, Jason Stanley, Florian Steinberger, Sören Stenlund, Christopher Stephens, James P. Sterba, Josef Stern, Matthias Steup, M. A. Stewart, Leopold Stubenberg, Edith Dudley Sulla, Frederick Suppe, Jere Paul Surber, David George Sussman, Sigrún Svavarsdóttir, Zeno G. Swijtink, Richard Swinburne, Charles C. Taliaferro, Robert B. Talisse, John Tasioulas, Paul Teller, Larry S. Temkin, Mark Textor, H. S. Thayer, Peter Thielke, Alan Thomas, Amie L. Thomasson, Katherine Thomson-Jones, Joshua C. Thurow, Vzalerie Tiberius, Terrence N. Tice, Paul Tidman, Mark C. Timmons, William Tolhurst, James E. Tomberlin, Rosemarie Tong, Lawrence Torcello, Kelly Trogdon, J. D. Trout, Robert E. Tully, Raimo Tuomela, John Turri, Martin M. Tweedale, Thomas Uebel, Jennifer Uleman, James Van Cleve, Harry van der Linden, Peter van Inwagen, Bryan W. Van Norden, René van Woudenberg, Donald Phillip Verene, Samantha Vice, Thomas Vinci, Donald Wayne Viney, Barbara Von Eckardt, Peter B. M. Vranas, Steven J. Wagner, William J. Wainwright, Paul E. Walker, Robert E. Wall, Craig Walton, Douglas Walton, Eric Watkins, Richard A. Watson, Michael V. Wedin, Rudolph H. Weingartner, Paul Weirich, Paul J. Weithman, Carl Wellman, Howard Wettstein, Samuel C. Wheeler, Stephen A. White, Jennifer Whiting, Edward R. Wierenga, Michael Williams, Fred Wilson, W. Kent Wilson, Kenneth P. Winkler, John F. Wippel, Jan Woleński, Allan B. Wolter, Nicholas P. Wolterstorff, Rega Wood, W. Jay Wood, Paul Woodruff, Alison Wylie, Gideon Yaffe, Takashi Yagisawa, Yutaka Yamamoto, Keith E. Yandell, Xiaomei Yang, Dean Zimmerman, Günter Zoller, Catherine Zuckert, Michael Zuckert, Jack A. Zupko (J.A.Z.)
- Edited by Robert Audi, University of Notre Dame, Indiana
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- The Cambridge Dictionary of Philosophy
- Published online:
- 05 August 2015
- Print publication:
- 27 April 2015, pp ix-xxx
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Lithium Plus Valproate as Maintenance Polypharmacy for Patients With Bipolar I Disorder: A Review
- David A. Solomon, Gabor I. Keitner, Christine E. Ryan, Ivan W. Miller
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- CNS Spectrums / Volume 5 / Issue S1 / February 2000
- Published online by Cambridge University Press:
- 07 November 2014, pp. 19-31
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Standard pharmacotherapy for the maintenance of treatment of patients with bipolar I disorder consists of lithium, valproate, or carbamazepine. However, many patients fail to respond to monotherapy with any of these agents, and as a result, psychiatrists often resort to polypharmacy. Findings from some open-label trials and retrospective chart reviews suggest this approach may be useful, but in the few controlled trials that have been conducted, the results have been negative. One drug combination that warrants further study as maintenance therapy is lithium plus valproate. Each is approved by the U.S. Food and Drug Administration for treatment of acute mania, and lithium has demonstrated efficacy for maintenance treatment as well. Some preliminary evidence suggests that the combination can be effective for patients who do not respond to monotherapy, and it seems to be no more dangerous than monotherapy. Concomitant administration of lithium plus valproate does not significantly alter lithium pharmacokinetics, and statistically significant changes that arise in valproate pharmacokinetics are not clinically significant. Although it is not known whether the drugs interact to augment response, many of their effects in the central nervous system do differ, and there is no indication of pharmacodynamic interactions that oppose each other. Finally, some evidence suggests that lithium and valproate may differ with regard to clinical variables that predict response to treatment. (J Clin Psychopharmacol 1998;18:38–49)
Bipolar I disorder afflicts approximately 1% of the U.S. adult population, with a median age at onset of 19 years. In many respects, it is a disabling disease. Acute episodes of mania and depression are often protracted with 24% of patients still acutely ill after 1 year has elapsed, 16% after 2 years, and 9% after 5 years. Subsyndromal symptoms, which impose significant morbidity that falls short of meeting full criteria for a mood episode, may occur frequently. Patients with bipolar I disorder are more likely than not to be unemployed or underemployed, less likely to marry and more likely to divorce than matched control subjects, and almost every family perceives the illness as a burden. Even remitted patients manifest poor psychosocial functioning, Ultimately, nearly 19% of patients die from suicide.