Interreader Variability of Dynamic Contrast-enhanced MRI of Recurrent Glioblastoma: The Multicenter ACRIN 6677/RTOG 0625 Study.

Purpose To evaluate factors contributing to interreader variation (IRV) in parameters measured at dynamic contrast material-enhanced (DCE) MRI in patients with glioblastoma who were participating in a multicenter trial. Materials and Methods A total of 18 patients (mean age, 57 years ± 13 [standard deviation]; 10 men) who volunteered for the advanced imaging arm of ACRIN 6677, a substudy of the RTOG 0625 clinical trial for recurrent glioblastoma treatment, underwent analyzable DCE MRI at one of four centers. The 78 imaging studies were analyzed centrally to derive the volume transfer constant (Ktrans) for gadolinium between blood plasma and tissue extravascular extracellular space, fractional volume of the extracellular extravascular space (ve), and initial area under the gadolinium concentration curve (IAUGC). Two independently trained teams consisting of a neuroradiologist and a technologist segmented the enhancing tumor on three-dimensional spoiled gradient-recalled acquisition in the steady-state images. Mean and median parameter values in the enhancing tumor were extracted after registering segmentations to parameter maps. The effect of imaging time relative to treatment, map quality, imager magnet and sequence, average tumor volume, and reader variability in tumor volume on IRV was studied by using intraclass correlation coefficients (ICCs) and linear mixed models. Results Mean interreader variations (± standard deviation) (difference as a percentage of the mean) for mean and median IAUGC, mean and median Ktrans, and median ve were 18% ± 24, 17% ± 23, 27% ± 34, 16% ± 27, and 27% ± 34, respectively. ICCs for these metrics ranged from 0.90 to 1.0 for baseline and from 0.48 to 0.76 for posttreatment examinations. Variability in reader-derived tumor volume was significantly related to IRV for all parameters. Conclusion Differences in reader tumor segmentations are a significant source of interreader variation for all dynamic contrast-enhanced MRI parameters. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Wolf in this issue.

Exploratory study of ultraviolet B (UVB) radiation and age of onset of bipolar disorder.

BACKGROUND: Sunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about > 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample. METHODS: Data for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P ≤ 0.001. RESULTS: The 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset of 25.6 years. Of the onset locations, 34.0% had at least 1 month below the threshold for UVB sufficient for vitamin D production. The age of onset at locations with 1 or more months of less than or equal to the threshold for UVB was 1.66 years younger. CONCLUSION: UVB and vitamin D may have an important influence on the development of bipolar disorder. Study limitations included a lack of data on patient vitamin D levels, lifestyles, or supplement use. More study of the impacts of UVB and vitamin D in bipolar disorder is needed to evaluate this supposition.

Association between polarity of first episode and solar insolation in bipolar I disorder.

OBJECTIVE: Circadian rhythm disruption is commonly observed in bipolar disorder (BD). Daylight is the most powerful signal to entrain the human circadian clock system. This exploratory study investigated if solar insolation at the onset location was associated with the polarity of the first episode of BD I. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area of the Earth. METHODS: Data from 7488 patients with BD I were collected at 75 sites in 42 countries. The first episode occurred at 591 onset locations in 67 countries at a wide range of latitudes in both hemispheres. Solar insolation values were obtained for every onset location, and the ratio of the minimum mean monthly insolation to the maximum mean monthly insolation was calculated. This ratio is largest near the equator (with little change in solar insolation over the year), and smallest near the poles (where winter insolation is very small compared to summer insolation). This ratio also applies to tropical locations which may have a cloudy wet and clear dry season, rather than winter and summer. RESULTS: The larger the change in solar insolation throughout the year (smaller the ratio between the minimum monthly and maximum monthly values), the greater the likelihood the first episode polarity was depression. Other associated variables were being female and increasing percentage of gross domestic product spent on country health expenditures. (All coefficients: P ≤ 0.001). CONCLUSION: Increased awareness and research into circadian dysfunction throughout the course of BD is warranted.

Variations in seasonal solar insolation are associated with a history of suicide attempts in bipolar I disorder.

BACKGROUND: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. METHODS: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun's electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). RESULTS: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. CONCLUSION: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed.

Hospital Stay in Synthetic Cannabinoid Users With Bipolar Disorder, Schizophrenia, or Other Psychotic Disorders Compared With Cannabis Users.

OBJECTIVE: The use of synthetic cannabinoid (SC) products has become popular in recent years, but data regarding their impact on hospital stays are limited. The impact of SC and cannabis use on hospital length of stay and doses of antipsychotics at discharge was assessed in this study. METHOD: The sample consisted of inpatients with discharge diagnoses of bipolar disorder, schizophrenia, or other psychotic disorders. Medical records of patients with self-reported SC use and negative urine drug screens (SC group, n = 77), with cannabis use confirmed by urine drug screen (cannabis group, n = 248), and with no drug use confirmed by urine drug screen (no-drug group, n = 1,336) were examined retrospectively. RESULTS: Length of stay (mean [SD] days) significantly differed (p < .001) among the SC (8.29 [4.29]), cannabis (8.02 [5.21]), and no-drug groups (10.19 [9.08]). Antipsychotic doses (chlorpromazine milligram equivalent doses) also significantly differed (p = .002) among the SC (254.64 [253.63]), cannabis (219.16 [216.71]), and no-drug groups (294.79 [287.85]). Unadjusted and adjusted pairwise comparisons showed that the cannabis group had a shorter length of stay (p < .001) and received lower doses of antipsychotics (p = .003) than the no-drug group. SC users did not differ significantly from the other two groups in either length of stay or doses of antipsychotics. CONCLUSIONS: Our findings suggest that acute SC exposure is not predictive of a more prolonged time for response to antipsychotic medications or of a need for larger doses of these medications compared with cannabis users.

Religious Activity, Psychotic Features, and Suicidality in 688 Acute Psychiatric Inpatients.

BACKGROUND: Religiosity has been linked to mental health outcomes for decades. This study examined the potential relationship between religiosity and demographic and clinical variables in a sample of psychiatric inpatients. METHODS: In total, 688 adults admitted to an acute psychiatric facility with a primary mood or psychotic disorder completed the Duke University Religion Index (DUREL). The DUREL measures religious activity in 3 domains: organizational religious activity (ORA), nonorganizational religious activity (NORA), and intrinsic (or subjective) religiosity (IR). We categorized scores into high and low religiosity. Bivariate analyses with χ and independent sample t tests were used to examine the association between the DUREL subscales and demographic, clinical, and outcome measures. A generalized linear model was used to identify predictors of suicidality, psychosis, and 30-day rehospitalization. RESULTS: Elevated religious activity was common in the inpatient sample, with 58% categorized as high IR, 43% as high NORA, and 36% as high ORA. For all 3 DUREL subscales, high religiosity scores were associated with significantly more psychosis (P<0.05) and significantly less suicidal ideation (P<0.001). High ORA (P=0.001) and high IR (P=0.01) were associated with significantly fewer suicide attempts. High ORA scores were also associated with an increased length of stay (P<0.05) and more frequent 30-day readmission rates (P=0.01). In the generalized linear model, predictors of lower levels of suicidality were high ORA, high IR, and a diagnosis of schizophrenia, schizoaffective disorder, or other psychotic disorder, whereas a diagnosis of depressive disorder was associated with greater suicidality. Predictors of psychosis were high IR and Hispanic ethnicity, whereas a diagnosis of depressive disorder was associated with lower rates of psychosis. Female inpatients were more likely than male inpatients to score high on the ORA (P<0.05), NORA (P<0.05), and IR (P<0.0001) subscales. In addition, a significant relationship was detected between age and high IR scores (P<0.005), with increasing age associated with higher IR scores. CONCLUSIONS: Although preliminary, these results suggest that a brief measure of religiosity may provide important information concerning clinical features and acute outcomes in patients hospitalized with serious mental illness.

Ethnic differences in the diagnosis of schizophrenia and mood disorders during admission to an academic safety-net psychiatric hospital.

U.S. Hispanics, now the single largest minority group in the country, face unique mental health disparities. The current study utilizes Andersen's Behavioral Model of Health Service Use to examine ethnic disparities in receiving a schizophrenia or mood disorder diagnosis at psychiatric hospital admission. Our retrospective cohort study examined electronic health record data at an academic safety-net psychiatric hospital for adult patients (n = 5571) admitted between 2010 and 2013. Logistic regression with block-wise entry of predisposing, enabling and need variables was used to examine ethnic disparities in receiving a schizophrenia diagnosis at admission. The block of need factors was the strongest predictor of receiving a schizophrenia diagnosis compared to predisposing and enabling factors. Compared to non-Hispanic whites, Hispanics and African Americans had a greater likelihood of receiving a schizophrenia diagnosis at admission. Additionally, patients diagnosed with schizophrenia had elevated positive and negative symptoms and were more likely to be male, single/unmarried, homeless, high inpatient service utilizers, involuntarily hospitalized, and to exhibit functional impairment at psychiatric hospital admission. To address elevated positive and negative symptoms of schizophrenia, functional impairment, social withdrawal, and high inpatient service utilization, promising psychosocial interventions should be adapted for racial and ethnic minority populations and utilized as an adjuvant to antipsychotic medication.

Factors Associated With the Likelihood of Hospitalization Following Emergency Department Visits for Behavioral Health Conditions.

OBJECTIVES: Behavioral health-related emergency department (ED) visits have been linked with ED overcrowding, an increased demand on limited resources, and a longer length of stay (LOS) due in part to patients being admitted to the hospital but waiting for an inpatient bed. This study examines factors associated with the likelihood of hospital admission for ED patients with behavioral health conditions at 16 hospital-based EDs in a large urban area in the southern United States. METHODS: Using Andersen's Behavioral Model of Health Service Use for guidance, the study examined the relationship between predisposing (characteristics of the individual, i.e., age, sex, race/ethnicity), enabling (system or structural factors affecting healthcare access), and need (clinical) factors and the likelihood of hospitalization following ED visits for behavioral health conditions (n = 28,716 ED visits). In the adjusted analysis, a logistic fixed-effects model with blockwise entry was used to estimate the relative importance of predisposing, enabling, and need variables added separately as blocks while controlling for variation in unobserved hospital-specific practices across hospitals and time in years. RESULTS: Significant predisposing factors associated with an increased likelihood of hospitalization following an ED visit included increasing age, while African American race was associated with a lower likelihood of hospitalization. Among enabling factors, arrival by emergency transport and a longer ED LOS were associated with a greater likelihood of hospitalization while being uninsured and the availability of community-based behavioral health services within 5 miles of the ED were associated with lower odds. Among need factors, having a discharge diagnosis of schizophrenia/psychotic spectrum disorder, an affective disorder, a personality disorder, dementia, or an impulse control disorder as well as secondary diagnoses of suicidal ideation and/or suicidal behavior increased the likelihood of hospitalization following an ED visit. CONCLUSION: The block of enabling factors was the strongest predictor of hospitalization following an ED visit compared to predisposing and need factors. Our findings also provide evidence of disparities in hospitalization of the uninsured and racial and ethnic minority patients with ED visits for behavioral health conditions. Thus, improved access to community-based behavioral health services and an increased capacity for inpatient psychiatric hospitals for treating indigent patients may be needed to improve the efficiency of ED services in our region for patients with behavioral health conditions. Among need factors, a discharge diagnosis of schizophrenia/psychotic spectrum disorder, an affective disorder, a personality disorder, an impulse control disorder, or dementia as well as secondary diagnoses of suicidal ideation and/or suicidal behavior increased the likelihood of hospitalization following an ED visit, also suggesting an opportunity for improving the efficiency of ED care through the provision of psychiatric services to stabilize and treat patients with serious mental illness.

Lymph flow in instrumented dogs varies with exercise intensity.

BACKGROUND: Although it is generally accepted that exercise accelerates lymph flow, no study has directly measured lymph flow as a function of exercise intensity. In this study, we have measured flow in the thoracic lymph duct of five instrumented dogs while they ran on a treadmill. METHODS AND RESULTS: Dogs were surgically instrumented with an ultrasonic flow transducer on the thoracic lymph duct and a catheter in the descending thoracic aorta. After recovery from surgery, the dogs ran on a treadmill at speeds which varied stepwise from 0 to 10 mph and from 10 to 0 mph. Dogs ran for 1 min at each speed with 15 min rest between each exercise. Heart rate increased significantly during exercise, whereas mean aortic pressure did not change. Resting lymph flow was 1.7+/-0.2 ml/min. Exercise at 1.5 mph significantly increased lymph flow to 3.9 +/- 0.6 ml/min (P < 0.01), 121% higher than resting flow. Lymph flow was further elevated at higher treadmill speeds, reaching 9.0 +/-1.6 ml/min (P < 0.01) at 10 mph, 419% higher than resting flow. Regression analysis demonstrated a linear relationship between treadmill speed and the percent increase in lymph flow. Lymph flow returned to the resting rate 1-2 min post-exercise. CONCLUSION: Lymph flow in the thoracic duct is positively correlated with exercise intensity.

Lymphatic pump treatment increases thoracic duct lymph flow in conscious dogs with edema due to constriction of the inferior vena cava.

BACKGROUND: Osteopathic lymphatic pump treatments (LPT) are used to treat edema, but their direct effects on lymph flow have not been studied. In the current study, we examined the effects of LPT on lymph flow in the thoracic duct of instrumented conscious dogs in the presence of edema produced by constriction of the inferior vena cava (IVC). METHODS AND RESULTS: Six dogs were surgically instrumented with an ultrasonic flow transducer on the thoracic lymph duct and catheters in the descending thoracic aorta and in IVC. After postoperative recovery, lymph flow and hemodynamic variables were measured 1) pre-LPT, 2) during 4 min LPT, 3) post-LPT, in the absence and presence of edema produced by IVC constriction. This constriction increased abdominal girth from 60 +/-2.6 to 75 +/- 2.9 cm. Before IVC constriction, LPT increased lymph flow (P < 0.05) from 1.9 +/- 0.2 ml/min to a maximum of 4.7 +/-1.2 ml/min, whereas after IVC constriction, LPT increased lymph flow (P < 0.05) from 7.9 +/-2.2 to a maximum of 11.7 +/-2.2 ml/min. The incremental lymph flow mobilized by 4 min of LPT (ie, the flow that exceeded 4 min of baseline flow), was 10.6 ml after IVC constriction. This incremental flow was not significantly greater than that measured before IVC constriction. CONCLUSIONS: Edema caused by IVC constriction markedly increased lymph flow in the thoracic duct. LPT increased thoracic duct lymph flow before and after IVC constriction. The lymph flow mobilized by 4 min of LPT in presence of edema was not significantly greater than that mobilized prior to edema.