Understanding the factors that influence veterans’ functional outcome after deployment is critical to provide appropriately targeted care. Mild traumatic brain injury (mTBI) and posttraumatic stress ...disorder (PTSD) have been related to disability, but other psychiatric and behavioral conditions are not as well examined. We investigated the impact of deployment‐related psychiatric and behavioral conditions on disability among 255 OEF/OIF/OND service members and veterans. Structured clinical interviews assessed TBI and the psychiatric conditions of depression, PTSD, anxiety, and substance use. Self‐report questionnaires assessed disability and the behavioral conditions of sleep disturbance and pain. Over 90% of participants had a psychiatric and/or behavioral condition, with approximately half presenting with ≥ 3 conditions. Exploratory factor analysis revealed 4 clinically relevant psychiatric and behavioral factors which accounted for 76.9% of the variance: (a) depression, PTSD, and military mTBI (deployment trauma factor); (b) pain and sleep (somatic factor); (c) anxiety disorders, other than PTSD (anxiety factor); and (d) substance abuse or dependence (substance use factor). Individuals with the conditions comprising the deployment trauma factor were more likely to be substantially disabled than individuals with depression and PTSD, but no military mTBI, OR = 3.52; 95% CI 1.09, 11.37. Depression, PTSD, and a history of military mTBI may comprise an especially harmful combination associated with high risk for substantial disability.
Resumen
Entender los factores que influyen en el funcionamiento de los veteranos después de los despliegues militares es clave para proporcionar cuidados específicos apropiados. La lesión cerebral traumática leve (mTBI) y el Trastorno de Estrés Postraumático (TEPT) han sido vinculados a discapacidad, pero otras alteraciones psiquiátricas y conductuales no han sido tan evaluadas. Investigamos el impacto de Alteraciones Psiquiátricas y Conductuales relacionadas a Despliegues militares en la discapacidad de 225 veteranos y miembros de servicio OEF/OIF/OND. Entrevistas clínicas estructuradas evaluaron TBI y alteraciones psiquiátricas como Depresión, TEPT, Ansiedad y Uso de sustancias. Cuestionarios de autoreporte evaluaron discapacidad y las alteraciones conductuales trastornos del sueño y dolor. Sobre el 90% de los participantes tenían una alteración psiquiátrica y/o conductual, con aproximadamente la mitad presentando ≥3 alteraciones. El análisis factorial exploratorio mostró 4 factores clínicamente relevantes psiquiátricos y conductuales (varianza explicada: 76,9%): (a) Depresión, TEPT, y mTBI militar (factor trauma en despliegue militar); (b) dolor y sueño (factor somático); (c) Otros Trastornos Ansiosos, aparte de TEPT (factor ansiedad); (d) Abuso de sustancias o dependencia (factor uso de sustancias). Los individuos con las alteraciones relacionadas al factor trauma en despliegue militar presentaron considerable mayor probabilidad de discapacidad que los individuos con Depresión y TEPT sin mTBI militar (OR: 3,52; 95%CI:{1.09, 11.37}). Depresión, TEPT, y una historia de mTBI podrían constituir una combinación especialmente dañina asociado con un alto riesgo para discapacidad considerable.
抽象
Traditional and Simplified Chinese s by AsianSTSS
標題 : 與退役有關的精神和行為狀況以及它們跟OEF/OIF/OND退役軍人功能障礙的關聯
撮要: 了解軍人退役後影響其功能結果的因素，是合適地提供針對性治療的關鍵。輕微創傷性腦損傷(mTBI)和創傷後壓力症(PTSD) 一直被視為與失能有關，但其他精神和行為狀況則缺乏深入研究。本研究探討255個OEF/OIF/OND的服務成員和退役軍人中，與退役相關的精神和行為狀況對失能構成的影響。結構式診斷晤談量表用以評估TBI以及抑鬱症、PTSD、焦慮症和藥物使用致使的精神狀況。自評測量表用以評估失能以及睡眠障礙和痛楚構成的行為狀況。超過九成的參與者有一種精神和/或行為狀況，大概半數呈現出≥3的狀況。探索因素分析顯示四個臨床有關的精神和行為因素（已解釋的方差為76.9%）：（一）抑鬱症、PTSD和軍事mTBI（退役創傷因素）；（二）痛楚和睡眠（軀體因素）；（三）PTSD以外的焦慮症 （焦慮因素）；（四）濫用或倚賴藥物（藥物使用因素）。有退役創傷因素的參與者，比有抑鬱症和PTSD但無軍事mTBI(OR = 3.52; 95% CI = 1.09,11.37)的參與者，更大可能有嚴重殘疾。患有抑鬱症、PTSD及曾有軍事mTBI經歷有可能構成一個特別危險的組合，與有高危患上嚴重殘疾有關。
标题 : 与退役有关的精神和行为状况以及它们跟OEF/OIF/OND退役军人功能障碍的关联
撮要: 了解军人退役后影响其功能结果的因素，是合适地提供针对性治疗的关键。轻微创伤性脑损伤(mTBI)和创伤后压力症(PTSD) 一直被视为与失能有关，但其他精神和行为状况则缺乏深入研究。本研究探讨255个OEF/OIF/OND的服务成员和退役军人中，与退役相关的精神和行为状况对失能构成的影响。结构式诊断晤谈量表用以评估TBI以及抑郁症、PTSD、焦虑症和药物使用致使的精神状况。自评测量表用以评估失能以及睡眠障碍和痛楚构成的行为状况。超过九成的参与者有一种精神和/或行为状况，大概半数呈现出≥3的状况。探索因素分析显示四个临床有关的精神和行为因素（已解释的方差为76.9%）：（一）抑郁症、PTSD和军事mTBI（退役创伤因素）；（二）痛楚和睡眠（躯体因素）；（三）PTSD以外的焦虑症 （焦虑因素）；（四）滥用或倚赖药物（药物使用因素）。有退役创伤因素的参与者，比有抑郁症和PTSD但无军事mTBI(OR = 3.52; 95% CI = 1.09,11.37)的参与者，更大可能有严重残疾。患有抑郁症、PTSD及曾有军事mTBI经历有可能构成一个特别危险的组合，与有高危患上严重残疾有关。
Purpose/Objective: To examine factors related to perceived caregiving burden in a sample of caregivers assisting service members and veterans (SMVs) across four areas: SMV injury and health status; ...caregiver life circumstances; caregiver duty and responsibilities; and caregiver needs. Research Method/Design: Participants were 214 caregivers (95.8% female; 86.0% spouse/partner; Age: M = 38.6 years SD = 10.4) of SMVs who sustained a mild, moderate, severe, or penetrating traumatic brain injury (TBI). Caregivers were recruited from Walter Reed National Military Medical Center and via community outreach. Participants completed the Caregiver Appraisal Scale, Mayo-Portland Adaptability Inventory-4, and Caregiver Questionnaire. The sample was divided into 2 Caregiver Burden groups: High (n = 138) and Low Burden (n = 76). Results: Factors significantly related to higher levels of perceived burden were (a) experiencing a greater caregiving time commitment now and over time, (b) caring for activities of daily living/instrumental activities of daily living, (c) experiencing an impact of caregiving on employment, income, and out of pocket expenses, (d) parenting more than 1 child, (e) having less time to devote to one's self now and over time, (f) having caregiver needs, and/or (g) assisting a SMV who had incurred a mild TBI; was experiencing greater functional disability; had a posttraumatic stress disorder (PTSD) diagnosis; received mental health and rehabilitation treatment; and/or used an assistive device (all p < .05; odds ratios ORs = 1.13 to 14.57; ds = .02 to 1.30). Conclusions/Implications: Providing care for a SMV after a TBI can impose a heavy burden, particularly for caregivers who provide support to SMVs with comorbid mental health problems, such as PTSD.
Impact and Implications
Caregivers play an important role in the long-term care of service members and veterans (SMV), saving the U.S. government and society millions of dollars in health care and social service costs. Providing care to SMVs can require a sizable time commitment and a high intensity of care, which can be burdensome for the caregiver. If the burden of care exceeds the caregiver's capacity (e.g., health, well-being, and finances), and they are no longer able to care for the SMV, the responsibility and cost for care of both the SMV and caregiver falls to government and society. This study highlights that many factors relating to the SMV's injury and health status, and the caregiver's life circumstances, responsibilities, and needs can impose a heavy burden of care. This is particularly true for caregivers assisting SMVs who incurred a mild TBI and have a diagnosis of posttraumatic stress disorder. It is critical that the caregiver's own health care and social service needs are acknowledged and attended to, and that they have access to adequate education, training, and resources. It is also critical that the long-term impact of providing care to SMVs, as well as their children and families, is monitored longitudinally in future research.
The purpose of this study was to extend previous research by examining the relationship between lifetime blast exposure and neurobehavioral functioning after mild TBI (MTBI) by (a) using a ...comprehensive measure of lifetime blast exposure, and (b) controlling for the influence of post-traumatic stress disorder (PTSD). Participants were 103 United States service members and veterans (SMVs) with a medically documented diagnosis of MTBI, recruited from three military treatment facilities (74.8%) and community-based recruitment initiatives (25.2%, e.g., social media, flyers). Participants completed a battery of neurobehavioral measures 12 or more months post-injury (Neurobehavioral Symptom Inventory, PTSD-Checklist PCLC, TBI-Quality of Life), including the Blast Exposure Threshold Survey (BETS). The sample was classified into two lifetime blast exposure (LBE) groups: High (
= 57) and Low (
= 46) LBE. In addition, the sample was classified into four LBE/PTSD subgroups: High PTSD/High LBE (n = 38); High PTSD/Low LBE (
= 19); Low PTSD/High LBE (
= 19); and Low PTSD/Low LBE (
= 27). The High LBE group had consistently worse scores on all neurobehavioral measures compared with the Low LBE group. When controlling for the influence of PTSD (using ANCOVA), however, only a handful of group differences remained. When comparing measures across the four LBE/PTSD subgroups, in the absence of clinically meaningful PTSD symptoms (i.e., Low PTSD), participants with High LBE had worse scores on the majority of neurobehavioral measures (e.g., post-concussion symptoms, sleep, fatigue). When examining the total number of clinically elevated measures, the High LBE subgroup consistently had a greater number of clinically elevated scores compared with the Low LBE subgroup for the majority of comparisons (i.e., four to 15 or more elevated symptoms). In contrast, in the presence of clinically meaningful PTSD symptoms (i.e., High PTSD), there were no differences between High versus Low LBE subgroups for all measures. When examining the total number of clinically elevated measures, however, there were meaningful differences between High versus Low LBE subgroups for those comparisons that included a high number of clinically elevated scores (i.e., six to 10 or more), but not for a low number of clinically elevated scores (i.e., one to five or more). High LBE, as quantified using a more comprehensive measure than utilized in past research (i.e., BETS), was associated with worse overall neurobehavioral functioning after MTBI. This study extends existing literature showing that lifetime blast exposure, that is largely subconcussive, may negatively impact warfighter brain health and readiness beyond diagnosable brain injury.
Causal Genetic Variants in Stillbirth Stanley, Kate E; Giordano, Jessica; Thorsten, Vanessa ...
The New England journal of medicine,
09/2020, Letnik:
383, Številka:
12
Journal Article
Recenzirano
Odprti dostop
In the majority of cases, the cause of stillbirth remains unknown despite detailed clinical and laboratory evaluation. Approximately 10 to 20% of stillbirths are attributed to chromosomal ...abnormalities. However, the causal nature of single-nucleotide variants and small insertions and deletions in exomes has been understudied.
We generated exome sequencing data for 246 stillborn cases and followed established guidelines to identify causal variants in disease-associated genes. These genes included those that have been associated with stillbirth and strong candidate genes. We also evaluated the contribution of 18,653 genes in case-control analyses stratified according to the degree of depletion of functional variation (described here as "intolerance" to variation).
We identified molecular diagnoses in 15 of 246 cases of stillbirth (6.1%) involving seven genes that have been implicated in stillbirth and six disease genes that are good candidates for phenotypic expansion. Among the cases we evaluated, we also found an enrichment of loss-of-function variants in genes that are intolerant to such variation in the human population (odds ratio, 2.15; 95% confidence interval CI, 1.46 to 3.06). Loss-of-function variants in intolerant genes were concentrated in genes that have not been associated with human disease (odds ratio, 2.22; 95% CI, 1.41 to 3.34), findings that differ from those in two postnatal clinical populations that were also evaluated in this study.
Our findings establish the diagnostic utility of clinical exome sequencing to evaluate the role of small genomic changes in stillbirth. The strength of the novel risk signal (as generated through the stratified analysis) was similar to that in known disease genes, which indicates that the genetic cause of stillbirth remains largely unknown. (Funded by the Institute for Genomic Medicine.).
Females are often excluded from military-related mild traumatic brain injury (mTBI) research because of its relatively low prevalence in this population. The purpose of this study was to focus on ...outcome from mTBI in female service members, compared with males. Participants were 172 United States military service members selected from a larger sample that had sustained an mTBI, and were evaluated within 24 months of injury (Age: mean = 28.9, SD = 8.1) at one of six military medical centers. Eighty-six women were matched to 86 men on nine key variables: TBI severity, mechanism of injury, bodily injury severity, days post-injury, age, number of deployments, theater where wounded, branch of service, and rank. Participants completed the Neurobehavioral Symptom Inventory (NSI) and the Posttraumatic Stress Disorder Checklist (PCL-C). There were no meaningful gender differences across all demographic and injury-related variables (p > 0.05). There were significant group differences and medium effect sizes for the NSI total score and all four NSI cluster scores. Symptoms most affected related to nausea, sensitivity to light, change in taste/smell, change in appetite, fatigue, and poor sleep. There were significant group differences and small-medium effect sizes for the PCL-C total score and two of the three PCL-C cluster scores. Symptoms most affected related to poor concentration, trouble remembering a stressful event, and disturbing memories/thoughts/images. Females consistently experienced more symptoms than males. As females become more active in combat-related deployments, it is critical that future studies place more emphasis on this important military population.
Lewy body dementia (LBD), including dementia with Lewy bodies and Parkinson's disease dementia, affects over a million people in the USA and has a substantial impact on patients, caregivers, and ...society. Symptomatic treatments for LBD, which can include cognitive, neuropsychiatric, autonomic, sleep, and motor features, are limited with only two drugs (cholinesterase inhibitors) currently approved by regulatory agencies for dementia in LBD. Clinical trials represent a top research priority, but there are many challenges in the development and implementation of trials in LBD. To address these issues and advance the field of clinical trials in the LBDs, the Lewy Body Dementia Association formed an Industry Advisory Council (LBDA IAC), in addition to its Research Center of Excellence program. The LBDA IAC comprises a diverse and collaborative group of experts from academic medical centers, pharmaceutical industries, and the patient advocacy foundation. The inaugural LBDA IAC meeting, held in June 2019, aimed to bring together this group, along with representatives from regulatory agencies, to address the topic of optimizing the landscape of LBD clinical trials. This review highlights the formation of the LBDA IAC, current state of LBD clinical trials, and challenges and opportunities in the field regarding trial design, study populations, diagnostic criteria, and biomarker utilization. Current gaps include a lack of standardized clinical assessment tools and evidence-based management strategies for LBD as well as difficulty and controversy in diagnosing LBD. Challenges in LBD clinical trials include the heterogeneity of LBD pathology and symptomatology, limited understanding of the trajectory of LBD cognitive and core features, absence of LBD-specific outcome measures, and lack of established standardized biologic, imaging, or genetic biomarkers that may inform study design. Demands of study participation (e.g., travel, duration, and frequency of study visits) may also pose challenges and impact trial enrollment, retention, and outcomes. There are opportunities to improve the landscape of LBD clinical trials by harmonizing clinical assessments and biomarkers across cohorts and research studies, developing and validating outcome measures in LBD, engaging the patient community to assess research needs and priorities, and incorporating biomarker and genotype profiling in study design.
The purpose of this cross-sectional study was to examine the influence of subthreshold posttraumatic stress disorder (PTSD) and full PTSD on quality of life following mild traumatic brain injury ...(mTBI).
Participants were 734 service members and veterans (SMV) classified into two injury groups: uncomplicated mild TBI (MTBI; n = 596) and injured controls (IC, n = 139). Participants completed a battery of neurobehavioral measures, 12-or-more months post-injury, that included the PTSD Checklist Civilian version, Neurobehavioral Symptom Inventory, and select scales from the TBI-QOL and MPAI. The MTBI group was divided into three PTSD subgroups: No-PTSD (n = 266), Subthreshold PTSD (n = 139), and Full-PTSD (n = 190).
There was a linear relationship between PTSD severity and neurobehavioral functioning/quality of life in the MTBI sample. As PTSD severity increased, significantly worse scores were found on 11 of the 12 measures (i.e., MTBI: Full-PTSD > Sub-PTSD > No-PTSD). When considering the number of clinically elevated scores, a linear relationship between PTSD severity and neurobehavioral functioning/quality of life was again observed in the MTBI sample (e.g., 3-or-more elevated scores: Full-PTSD = 92.1 %, Sub-PTSD = 61.9 %, No-PTSD = 19.9 %).
Limitations included the use of a self-report measure to determine diagnostic status that may under/overcount or mischaracterize individuals.
PTSD symptoms, whether at the level of diagnosable PTSD, or falling short of that because of the intensity or characterization of symptoms, have a significant negative impact on one's quality of life following MTBI. Clinicians' treatment targets should focus on the symptoms that are most troubling for an individual and the individual's perception of quality of life, regardless of the diagnosis itself.
RNA plays a central role in all organisms and can fold into complex structures to orchestrate function. Visualization of such structures often requires crystallization, which can be a bottleneck in ...the structure-determination process. To promote crystallization, an RNA-recognition motif (RRM) of the U1A spliceosomal protein has been co-opted as a crystallization module. Specifically, the U1-snRNA hairpin II (hpII) single-stranded loop recognized by U1A can be transplanted into an RNA target to promote crystal contacts and to attain phase information via molecular replacement or anomalous diffraction methods using selenomethionine. Herein, we produced the F37M/F77M mutant of U1A to augment the phasing capability of this powerful crystallization module. Selenomethionine-substituted U1A(F37M/F77M) retains high affinity for hpII (
of 59.7 ± 11.4 nM). The 2.20 Å resolution crystal structure reveals that the mutated sidechains make new S-π interactions in the hydrophobic core and are useful for single-wavelength anomalous diffraction. Crystals were also attained of U1A(F37M/F77M) in complex with a bacterial preQ
-II riboswitch. The F34M/F37M/F77M mutant was introduced similarly into a lab-evolved U1A variant (TBP6.9) that recognizes the internal bulged loop of HIV-1 TAR RNA. We envision that this short RNA sequence can be placed into non-essential duplex regions to promote crystallization and phasing of target RNAs. We show that selenomethionine-substituted TBP6.9(F34M/F37M/F77M) binds a TAR variant wherein the apical loop was replaced with a GNRA tetraloop (
of 69.8 ± 2.9 nM), laying the groundwork for use of TBP6.9(F34M/F37M/F77M) as a crystallization module. These new tools are available to the research community.
Self-report measures are commonly relied upon in military healthcare environments to assess service members following a mild traumatic brain injury (mTBI). However, such instruments are susceptible ...to over-reporting and rarely include validity scales. This study evaluated the utility of the mild Brain Injury Atypical Symptoms scale (mBIAS) and the Neurobehavioral Symptom Inventory Validity-10 scale to detect symptom over-reporting. A total of 359 service members with a reported history of mTBI were separated into two symptom reporting groups based on MMPI-2-RF validity scales (i.e., non-over-reporting versus symptom over-reporting). The clinical utility of the mBIAS and Validity-10 as diagnostic indicators and screens of symptom over-reporting were evaluated by calculating sensitivity, specificity, positive test rate, positive predictive power (PPP), and negative predictive power (NPP) values. An mBIAS cut score of ≥10 was optimal as a diagnostic indicator, which resulted in high specificity and PPP; however, sensitivity was low. The utility of the mBIAS as a screening instrument was limited. A Validity-10 cut score of ≥33 was optimal as a diagnostic indicator. This resulted in very high specificity and PPP, but low sensitivity. A Validity-10 cut score of ≥7 was considered optimal as a screener, which resulted in moderate sensitivity, specificity, NPP, but relatively low PPP. Owing to low sensitivity, the current data suggests that both the mBIAS and Validity-10 are insufficient as stand-alone measures of symptom over-reporting. However, Validity-10 scores above the identified cut-off of ≥7should be taken as an indication that further evaluation to rule out symptom over-reporting is necessary.
Traumatic brain injury (TBI) can be associated with long-term neurobehavioral symptoms. Here, we examined levels of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in ...extracellular vesicles isolated from blood, and their relationship with TBI severity and neurobehavioral symptom reporting. Participants were 218 service members and veterans who sustained uncomplicated mild TBIs (mTBI, n = 107); complicated mild, moderate, or severe TBIs (smcTBI, n = 66); or Injured controls (IC, orthopedic injury without TBI, n = 45). Within one year after injury, but not after, NfL was higher in the smcTBI group than mTBI (p = 0.001, d = 0.66) and IC (p = 0.001, d = 0.35) groups, which remained after controlling for demographics and injury characteristics. NfL also discriminated the smcTBI group from IC (AUC:77.5%, p < 0.001) and mTBI (AUC:76.1%, p < 0.001) groups. No other group differences were observed for NfL or GFAP at either timepoint. NfL correlated with post-concussion symptoms (r
= - 0.38, p = 0.04) in the mTBI group, and with PTSD symptoms in mTBI (r
= - 0.43, p = 0.021) and smcTBI groups (r
= - 0.40, p = 0.024) within one year after injury, which was not confirmed in regression models. Our results suggest the potential of NfL, a protein previously linked to axonal damage, as a diagnostic biomarker that distinguishes TBI severity within the first year after injury.
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