Prostaglandin-Induced Resorption of the Adult Rat Calvarium

Prostaglandin E1-containing solutions injected under the skin overlying the calvarium of adult rats produced a visible resorptive lesion within the bone in seven days. The resorptive process was characterized by fibrous replacement of bone matrix and by increased vascularity. Inflammatory cells were not apparent.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67319/2/10.1177_00220345740530032601.pd

Daily longitudinal self-monitoring of mood variability in bipolar disorder and borderline personality disorder

Background Traditionally, assessment of psychiatric symptoms has been relying on their retrospective report to a trained interviewer. The emergence of smartphones facilitates passive sensor-based monitoring and active real-time monitoring through time-stamped prompts; however there are few validated self-report measures designed for this purpose. Methods We introduce a novel, compact questionnaire, Mood Zoom (MZ), embedded in a customized smartphone application. MZ asks participants to rate anxiety, elation, sadness, anger, irritability and energy on a 7-point Likert scale. For comparison, we used four standard clinical questionnaires administered to participants weekly to quantify mania (ASRM), depression (QIDS), anxiety (GAD-7), and quality of life (EQ-5D). We monitored 48 Bipolar Disorder (BD), 31 Borderline Personality Disorder (BPD) and 51 Healthy Control (HC) participants to study longitudinal (median±iqr: 313±194 days) variation and differences of mood traits by exploring the data using diverse time-series tools. Results MZ correlated well (|R| &gt; 0.5, p &lt; 0.0001) with QIDS, GAD-7, and EQ-5D. We found statistically strong (|R| &gt; 0.3, p &lt; 0.0001) differences in variability in all questionnaires for the three cohorts. Compared to HC, BD and BPD participants exhibit different trends and variability, and on average had higher self-reported scores in mania, depression, and anxiety, and lower quality of life. In particular, analysis of MZ variability can differentiate BD and BPD which was not hitherto possible using the weekly questionnaires. Limitations All reported scores rely on self-assessment; there is a lack of ongoing clinical assessment by experts to validate the findings. Conclusions MZ could be used for efficient, long-term, effective daily monitoring of mood instability in clinical psychiatric practice.</p

Post-traumatic stress and future substance use outcomes: leveraging antecedent factors to stratify risk

Background: Post-traumatic stress disorder (PTSD) and substance use (tobacco, alcohol, and cannabis) are highly comorbid. Many factors affect this relationship, including sociodemographic and psychosocial characteristics, other prior traumas, and physical health. However, few prior studies have investigated this prospectively, examining new substance use and the extent to which a wide range of factors may modify the relationship to PTSD. Methods: The Advancing Understanding of RecOvery afteR traumA (AURORA) study is a prospective cohort of adults presenting at emergency departments (N = 2,943). Participants self-reported PTSD symptoms and the frequency and quantity of tobacco, alcohol, and cannabis use at six total timepoints. We assessed the associations of PTSD and future substance use, lagged by one timepoint, using the Poisson generalized estimating equations. We also stratified by incident and prevalent substance use and generated causal forests to identify the most important effect modifiers of this relationship out of 128 potential variables. Results: At baseline, 37.3% (N = 1,099) of participants reported likely PTSD. PTSD was associated with tobacco frequency (incidence rate ratio (IRR): 1.003, 95% CI: 1.00, 1.01, p = 0.02) and quantity (IRR: 1.01, 95% CI: 1.001, 1.01, p = 0.01), and alcohol frequency (IRR: 1.002, 95% CI: 1.00, 1.004, p = 0.03) and quantity (IRR: 1.003, 95% CI: 1.001, 1.01, p = 0.001), but not with cannabis use. There were slight differences in incident compared to prevalent tobacco frequency and quantity of use; prevalent tobacco frequency and quantity were associated with PTSD symptoms, while incident tobacco frequency and quantity were not. Using causal forests, lifetime worst use of cigarettes, overall self-rated physical health, and prior childhood trauma were major moderators of the relationship between PTSD symptoms and the three substances investigated. Conclusion: PTSD symptoms were highly associated with tobacco and alcohol use, while the association with prospective cannabis use is not clear. Findings suggest that understanding the different risk stratification that occurs can aid in tailoring interventions to populations at greatest risk to best mitigate the comorbidity between PTSD symptoms and future substance use outcomes. We demonstrate that this is particularly salient for tobacco use and, to some extent, alcohol use, while cannabis is less likely to be impacted by PTSD symptoms across the strata

Predicting at-risk opioid use three months after ed visit for trauma: Results from the AURORA study

OBJECTIVE: Whether short-term, low-potency opioid prescriptions for acute pain lead to future at-risk opioid use remains controversial and inadequately characterized. Our objective was to measure the association between emergency department (ED) opioid analgesic exposure after a physical, trauma-related event and subsequent opioid use. We hypothesized ED opioid analgesic exposure is associated with subsequent at-risk opioid use. METHODS: Participants were enrolled in AURORA, a prospective cohort study of adult patients in 29 U.S., urban EDs receiving care for a traumatic event. Exclusion criteria were hospital admission, persons reporting any non-medical opioid use (e.g., opioids without prescription or taking more than prescribed for euphoria) in the 30 days before enrollment, and missing or incomplete data regarding opioid exposure or pain. We used multivariable logistic regression to assess the relationship between ED opioid exposure and at-risk opioid use, defined as any self-reported non-medical opioid use after initial ED encounter or prescription opioid use at 3-months. RESULTS: Of 1441 subjects completing 3-month follow-up, 872 participants were included for analysis. At-risk opioid use occurred within 3 months in 33/620 (5.3%, CI: 3.7,7.4) participants without ED opioid analgesic exposure; 4/16 (25.0%, CI: 8.3, 52.6) with ED opioid prescription only; 17/146 (11.6%, CI: 7.1, 18.3) with ED opioid administration only; 12/90 (13.3%, CI: 7.4, 22.5) with both. Controlling for clinical factors, adjusted odds ratios (aORs) for at-risk opioid use after ED opioid exposure were: ED prescription only: 4.9 (95% CI 1.4, 17.4); ED administration for analgesia only: 2.0 (CI 1.0, 3.8); both: 2.8 (CI 1.2, 6.5). CONCLUSIONS: ED opioids were associated with subsequent at-risk opioid use within three months in a geographically diverse cohort of adult trauma patients. This supports need for prospective studies focused on the long-term consequences of ED opioid analgesic exposure to estimate individual risk and guide therapeutic decision-making

The AURORA Study: a longitudinal, multimodal library of brain biology and function after traumatic stress exposure

Adverse posttraumatic neuropsychiatric sequelae (APNS) are common among civilian trauma survivors and military veterans. These APNS, as traditionally classified, include posttraumatic stress, postconcussion syndrome, depression, and regional or widespread pain. Traditional classifications have come to hamper scientific progress because they artificially fragment APNS into siloed, syndromic diagnoses unmoored to discrete components of brain functioning and studied in isolation. These limitations in classification and ontology slow the discovery of pathophysiologic mechanisms, biobehavioral markers, risk prediction tools, and preventive/treatment interventions. Progress in overcoming these limitations has been challenging because such progress would require studies that both evaluate a broad spectrum of posttraumatic sequelae (to overcome fragmentation) and also perform in-depth biobehavioral evaluation (to index sequelae to domains of brain function). This article summarizes the methods of the Advancing Understanding of RecOvery afteR traumA (AURORA) Study. AURORA conducts a large-scale (n = 5000 target sample) in-depth assessment of APNS development using a state-of-the-art battery of self-report, neurocognitive, physiologic, digital phenotyping, psychophysical, neuroimaging, and genomic assessments, beginning in the early aftermath of trauma and continuing for 1 year. The goals of AURORA are to achieve improved phenotypes, prediction tools, and understanding of molecular mechanisms to inform the future development and testing of preventive and treatment interventions

Robust parameter extraction for decision support using multimodal intensive care data

Digital information flow within the intensive care unit (ICU) continues to grow, with advances in technology and computational biology. Recent developments in the integration and archiving of these data have resulted in new opportunities for data analysis and clinical feedback. New problems associated with ICU databases have also arisen. ICU data are high-dimensional, often sparse, asynchronous and irregularly sampled, as well as being non-stationary, noisy and subject to frequent exogenous perturbations by clinical staff. Relationships between different physiological parameters are usually nonlinear (except within restricted ranges), and the equipment used to measure the observables is often inherently error-prone and biased. The prior probabilities associated with an individual's genetics, pre-existing conditions, lifestyle and ongoing medical treatment all affect prediction and classification accuracy. In this paper, we describe some of the key problems and associated methods that hold promise for robust parameter extraction and data fusion for use in clinical decision support in the ICU.National Library of Medicine (U.S.)National Institute of Biomedical Imaging and Bioengineering (U.S.)National Institutes of Health (NIH) (grant no. R01 EB001659)National Center for Research Resources (U.S.) (grant no. U01EB008577)Philips Medical SystemsInformation and Communication University (ICU), Kore