Mihaela Aslan

Prolonged Grief Disorder: Psychometric Validation of Criteria Proposed for DSM-V and ICD-11

Holly Prigerson and colleagues tested the psychometric validity of criteria for prolonged grief disorder (PGD) to enhance the detection and care of bereaved individuals at heightened risk of persistent distress and dysfunction.

Hyperplastic Cellular Remodeling of the Media in Ascending Thoracic Aortic Aneurysms

Background—Progressive medial degeneration and atrophy is thought to be a cause of ascending thoracic aortic aneurysms in the elderly. Extensive apoptosis of vascular smooth muscle cells (VSMCs) has been demonstrated in the media of abdominal aortic aneurysms. We investigated whether medial atrophy from loss of VSMCs occurs in primary ascending thoracic aortic aneurysms. Methods and Results—Morphometric analysis of 28 nonaneurysmal ascending thoracic aortas and 29 ascending thoracic aortic aneurysms was performed by directly measuring the thickness of their vascular layers and by indirectly calculating the area of their vascular compartments. The cellular and matrix composition of the media was assessed at the structural, protein, and transcript levels. Despite thinning of the media secondary to vascular dilatation, there was an overall increase in the medial area of aneurysms. VSMC density was preserved, implying cellular hyperplasia as a result of the increased medial mass. There was decreased expression of matrix proteins, despite sustained synthesis of these molecules, which was associated with evidence of increased matrix degradation. The remodeling and expansion of the media was most evident in comparisons between nonaneurysmal aortas versus smaller aneurysms and did not evolve further in larger aneurysms. Conclusions—The mechanisms for luminal enlargement in thoracic and abdominal aortic aneurysms differ significantly with regard to the survival of VSMCs and atrophy of the media but share common pathophysiology involving degeneration of the matrix. Hyperplastic cellular remodeling of the media in ascending thoracic aortic aneurysms may be an initial adaptive response to minimize increased wall stress resulting from vascular dilatation.

Million Veteran Program: A mega-biobank to study genetic influences on health and disease.

OBJECTIVE To describe the design and ongoing conduct of the Million Veteran Program (MVP), as an observational cohort study and mega-biobank in the Department of Veterans Affairs (VA) health care system. STUDY DESIGN AND SETTING Data are being collected from participants using questionnaires, the VA electronic health record, and a blood sample for genomic and other testing. Several ongoing projects are linked to MVP, both as peer-reviewed research studies and as activities to help develop an infrastructure for future, broad-based research uses. RESULTS Formal planning for MVP commenced in 2009; the protocol was approved in 2010, and enrollment began in 2011. As of August 3, 2015, and with a steady state of ≈50 recruiting sites nationwide, N = 397,104 veterans have been enrolled. Among N = 199,348 with currently available genotyping data, most participants (as expected) are male (92.0%) between the ages of 50 and 69 years (55.0%). On the basis of self-reported race, white (77.2%) and African American (13.5%) populations are well represented. CONCLUSIONS By helping to promote the future integration of genetic testing in health care delivery, including clinical decision making, the MVP is designed to contribute to the development of precision medicine.

Validity of using an electronic medical record for assessing quality of care in an outpatient setting.

Objective:We sought to evaluate the validity of retrieving data from a commercial, outpatient electronic medical record (EMR) to assess the management of pharyngitis, an important measure of quality of healthcare in pediatrics and a new measure for the Health Plan Employer Data and Information Set (HEDIS). Methods:For children ages 3–18 years, we electronically identified clinical encounters with diagnoses of pharyngitis using 3 different strategies (an EMR-based strategy, an administrative data-based strategy, and a reference strategy which used medical record review). By each strategy, we calculated the proportion of episodes of pharyngitis during 1 year for which management of pharyngitis adhered to published guidelines. Results:Among 479 total episodes of pharyngitis, 434 (91%) were from the EMR-based strategy and 281 (59%) from the administrative data-based strategy. Review of the records (the reference strategy) found that 391 of 479 (82%) were confirmed episodes of pharyngitis. A diagnostic test for group A streptococcus (GAS) was performed at 310 of 434 (71%) of episodes identified by the EMR-based strategy and at 214 of 281 (76%) of episodes by the administrative data-based strategy (P = 0.045). By the reference strategy, a diagnostic test was done in 301 of 391 (77%); more than at episodes found by the EMR-based strategy (71%, P < 0.001). Conclusions:The EMR-based strategy resulted in a statistically different proportion of episodes having diagnostic testing for GAS compared with a reference strategy. Complete evaluations to validate strategies for extracting data from electronic databases are necessary before assuming that measures of quality of care will be the same regardless of the source of data.

‘Race’ and Prostate Cancer Mortality in Equal-access Healthcare Systems

BACKGROUND Reports suggest worse health-related outcomes among black (vs white) men diagnosed with prostate cancer, but appropriate cause-effect inferences are complicated by the relationship of race and other prognostic factors. METHODS We searched the literature to find contemporary articles focusing on mortality among black and white men with prostate cancer in equal-access healthcare systems. We also directly assessed the association of race and prostate cancer mortality by conducting an observational cohort analysis of 1270 veterans diagnosed with prostate cancer and followed for 11 to 16 years at 9 medical centers within the Veterans Health Administration. RESULTS Among 5 reports providing quantitative results for the association of race and mortality among men with prostate cancer in equal-access systems, outcomes were similar for black and white men. Race also was not a prognostic factor in the observational cohort analysis of US veterans, with an adjusted hazard ratio for black (vs white) men and prostate cancer mortality of 0.90 (95% confidence interval, 0.58-1.40; P = .65). CONCLUSIONS Mortality among black and white patients with prostate cancer is similar in equal-access healthcare systems. Studies that find racial differences in mortality (including cause-specific mortality) among men with prostate cancer may not account fully for socioeconomic and clinical factors.

The genetics of functional disability in schizophrenia and bipolar illness: Methods and initial results for VA cooperative study #572

Given the prominence of cognitive impairments and disability associated with schizophrenia and bipolar disorder, substantial interest has arisen in identifying determinants of the diseases and their features. Genetic variation has been linked to skills that underlie disability (“functional capacity” or FC), highlighting need for understanding of these relationships. We describe the design and methods of a large, multisite, observational study focusing on the genetics of functional disability in schizophrenia and bipolar disorder, presenting initial data on recruitment, and characterization of the sample. Known as Veterans Affairs (VA) Cooperative Studies Program (CSP)#572, this study is recruiting, diagnosing, and assessing U.S. Veterans with either schizophrenia or bipolar I disorder. Assessments include neuropsychological (NP) testing, FC, suicidality, and co‐morbid conditions such as posttraumatic stress disorder (PTSD). A sample of “psychiatrically healthy” Veterans from another project serves as a comparison group. An interim total of 8,140 participants (42.1% schizophrenia) have been recruited and assessed as of September 30, 2013, with 9 months of enrollment remaining and with a target sample size of 9,500. Veterans with schizophrenia were more likely to never have married, whereas lifetime PTSD and suicidality were more common in the bipolar veterans. Performance on the FC measures and NP tests was consistent with previous results, with mean t‐scores of 35 (−1.5 SD) for schizophrenia and 41 (−0.9 SD) for the bipolar Veterans. This large population is representative of previous studies in terms of patient performance and co‐morbidities. Subsequent genomic analyses will examine the genomic correlates of performance‐based measures. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Consistency of Recall for Deployment-Related Traumatic Brain Injury.

Objective:To examine the temporal consistency of self-reported deployment-related traumatic brain injury (TBI) and its association with posttraumatic stress disorder (PTSD) symptom severity. Setting:In-person interviews at US Army installations (postdeployment); phone interviews (long-term follow-up). Participants:A total of 378 US Army soldiers and veterans deployed to Iraq; 14.3% (n = 54) reported TBI with loss of consciousness during an index deployment. Design:Participants were evaluated after returning from deployment and again 5 to 9 years later. Main Measures:Temporal consistency of TBI endorsement based on TBI screening interviews; PTSD Checklist, Civilian Version. Results:The concordance of deployment-related TBI endorsement from the postdeployment to long-term follow-up assessment was moderate (&kgr; = 0.53). Of the 54 participants reporting (predominantly mild) TBI occurring during an index deployment, 32 endorsed TBI inconsistently over time. More severe PTSD symptoms at postdeployment assessment were independently associated with discordant reporting (P = .0004); each 10-point increase in PCL scores increasing odds of discordance by 69% (odds ratio = 1.69; 95% confidence interval, 1.26-2.26). Conclusions:Deployment-related TBI may not be reported reliably over time, particularly among war-zone veterans with greater PTSD symptoms. Results of screening evaluations for TBI history should be viewed with caution in the context of PTSD symptom history.

Factor structure of cognition and functional capacity in two studies of schizophrenia and bipolar disorder: Implications for genomic studies

OBJECTIVE Impairments in cognition and everyday functioning are common in schizophrenia and bipolar disorder (BPD). In this article, we present factor analyses of cognitive and functional capacity (FC) measures based on 2 studies of schizophrenia (SCZ) and bipolar I disorder (BPI) using similar methods. The overall goal of these analyses was to determine whether performance-based assessments should be examined individually, or aggregated on the basis of the correlational structure of the tests, as well as to evaluate the similarity of factor structures of SCZ and BPI. METHOD Veterans Affairs Cooperative Studies Program Study #572 (Harvey et al., 2014) evaluated cognitive and FC measures among 5,414 BPI and 3,942 SCZ patients. A 2nd study evaluated similar neuropsychological (NP) and FC measures among 368 BPI and 436 SCZ patients. Principal components analysis, as well as exploratory and CFAs, were used to examine the data. RESULTS Analyses in both datasets suggested that NP and FC measures were explained by a single underlying factor in BPI and SCZ patients, both when analyzed separately or as in a combined sample. The factor structure in both studies was similar, with or without inclusion of FC measures; homogeneous loadings were observed for that single factor across cognitive and FC domains across the samples. CONCLUSION The empirically derived factor model suggests that NP performance and FC are best explained as a single latent trait applicable to people with SCZ and BPD. This single measure may enhance the robustness of the analyses relating genomic data to performance-based phenotypes.

Design of "neuropsychological and mental health outcomes of operation Iraqi freedom: a longitudinal cohort study".

Objective This study aimed to describe methodological challenges encountered in designing a follow-up assessment of US Army Soldiers who served in Operation Iraqi Freedom. Study Design and Setting The Neurocognition Deployment Health Study (NDHS) enrolled 1595 soldiers at 2 military installations, starting in 2003. Prior work compared predeployment and postdeployment assessments among Iraq-deployed and nondeployed soldiers. The current phase, as VA Cooperative Studies Program #566, is collecting follow-up data on participants who were deployed to Iraq or Afghanistan. Specific aims include evaluating the prevalence and course of posttraumatic stress disorder (PTSD), the persistence of previously observed neuropsychological changes, and the relationship of these changes—and traumatic brain injury—to subsequent PTSD. The target sample size is 817 participants, with 200 participants also receiving performance-based neuropsychological assessments. Results We describe 6 methodological challenges and their implications for longitudinal research among a “closed,” young, mobile study population: transitioning from cluster-based (battalion) sampling to individual-level sampling; overcoming practical barriers (such as location searches); selecting exposure and outcome measures that combine previously collected and current study data; accounting for loss of an exposed (deployed) versus (nonexposed) nondeployed comparison; determining timing of assessments; and developing a complex statistical analysis plan. Enrollment is ongoing. Conclusions The study provides unique insights regarding elements of study design and analysis that are relevant to longitudinal research. In particular, the dynamic “real-life” context of military deployment provides a basis for applying observational methodology to characterize mental health disorders associated with exposure to war-zone deployment and other contexts associated with exposure to extreme stress.

Longitudinal Associations among Posttraumatic Stress Disorder Symptoms, Traumatic Brain Injury, and Neurocognitive Functioning in Army Soldiers Deployed to the Iraq War

OBJECTIVES Military deployment is associated with increased risk of adverse emotional and cognitive outcomes. Longitudinal associations involving posttraumatic stress disorder (PTSD), relatively mild traumatic brain injury (TBI), and neurocognitive compromise are poorly understood, especially with regard to long-term outcomes, and rigorous research is necessary to better understand the corresponding relationships. The objective of this study was to examine short-term and long-term (>5 years) longitudinal associations among PTSD, neurocognitive performance, and TBI following military deployment. METHODS In this prospective study, N=315 U.S. Army soldiers were assessed at military installations before (2003-2005) and after (2004-2006) an index deployment to the Iraq War, and again an average of 7.6 years later (2010-2014) as a nationally dispersed cohort of active duty soldiers, reservists, and veterans. Thus, the study design allowed for two measurement intervals over which to examine changes. All assessments included the PTSD Checklist, civilian version, and individually-administered performance-based neurocognitive tests. TBI history was derived from clinical interview. RESULTS Autoregressive analyses indicated that visual reproduction scores were inversely related to subsequent PTSD symptom severity at subsequent assessments. Conversely, increases in PTSD symptom severity over each measurement interval were associated with poorer verbal and/or visual recall at the end of each interval, and less efficient reaction time at post-deployment. TBI, primarily mild in this sample, was associated with adverse PTSD symptom outcomes at both post-deployment and long-term follow-up. CONCLUSIONS These results suggest longitudinal relationships among PTSD symptoms, TBI, and neurocognitive decrements may contribute to sustained emotional and neurocognitive symptoms over time. (JINS, 2018, 24, 311-323).