Commissioning and clinical evaluation of the IDENTIFYTM surface imaging system for frameless stereotactic radiosurgery.

PURPOSE: To commission and assess the clinical performance of a new commercial surface imaging (SI) system by analyzing intra-fraction motion from the initial cohort of patients treated with frameless stereotactic radiosurgery (fSRS). METHODS: The IDENTIFYTM SI system was commissioned for clinical use on an Edge (Varian Medical Systems, Palo Alto, CA) linear accelerator. All patients who received intracranial radiotherapy with HyperArcTM (Varian Medical Systems, Palo Alto, CA) were immobilized with the EncompassTM (Qfix, Avondale, PA) thermoplastic mask and monitored for intra-fraction motion with SI. IDENTIFYTM log files were correlated with trajectory log files to correlate treatment parameters with SI-reported offsets. IDENTIFYTM reported offsets were correlated with gantry and couch angles to assess system performance for obstructed and clear camera field of view. Data were stratified by race to evaluate performance differences due to skin tone. RESULTS: All commissioning data were found to meet recommended tolerances. IDENTIFYTM was used to monitor intra-fraction motion on 1164 fractions from 386 patients. The median magnitude of translational SI reported offsets at the end of treatment was 0.27 mm. SI reported offsets were shown to increase when camera pods are blocked by the gantry with larger increases seen at non-zero couch angles. With camera obstruction, the median magnitude of the SI reported offset was 0.50 and 0.80 mm for White and Black patients, respectively. CONCLUSIONS: IDENTIFYTM performance during fSRS is comparable to other commercially available SI systems where offsets are shown to increase at non-zero couch angles and during camera pod blockage.

Forecasting seizure clusters from chronic ambulatory electrocorticography.

Seizure clusters are seizures that occur in rapid succession during periods of heightened seizure risk and are associated with substantial morbidity and sudden unexpected death in epilepsy. The objective of this feasibility study was to evaluate the performance of a novel seizure cluster forecasting algorithm. Chronic ambulatory electrocorticography recorded over an average of 38 months in 10 subjects with drug-resistant epilepsies was analyzed pseudoprospectively by dividing data into training (first 85%) and validation periods. For each subject, the probability of seizure clustering, derived from the Kolmogorov-Smirnov statistic using a novel algorithm, was forecasted in the validation period using individualized autoregressive models that were optimized from training data. The primary outcome of this study was the mean absolute scaled error (MASE) of 1-day horizon forecasts. From 10 subjects, 394 ± 142 (mean ± SD) electrocorticography-based seizure events were extracted for analysis, representing a span of 38 ± 27 months of recording. MASE across all subjects was .74 ± .09, .78 ± .09, and .83 ± .07 at .5-, 1-, and 2-day horizons. The feasibility study demonstrates that seizure clusters are quasiperiodic and can be forecasted to clinically meaningful horizons. Pending validation in larger cohorts, the forecasting approach described herein may herald chronotherapy during imminent heightened seizure vulnerability.

Healthy days at home: A population-based quality measure for cancer patients at the end of life.

BACKGROUND: Healthy Days at Home (HDAH) is a novel population-based outcome measure. In this study, its use as a potential measure for cancer patients at the end of life (EOL) was explored. METHODS: Patient demographics and health care use among Medicare beneficiaries with cancer who died over the years 2014 to 2017 were identified. The HDAH was calculated by subtracting the following components from 180 days: number of days spent in inpatient and outpatient hospital observation, the emergency room, skilled nursing facilities (SNF), inpatient psychiatry, inpatient rehabilitation, long-term hospitals, and inpatient hospice. How HDAH and its components varied by beneficiary demographics and health care market were evaluated. A patient-level linear regression model with HDAH as the outcome, hospital referral region (HRR) random effects, and market fixed effects were specified, as well as beneficiary age, sex, and comorbidities as covariates. RESULTS: The 294,751 beneficiaries at the EOL showed a mean number of 154.0 HDAH (out of 180 days). Inpatient (10.7 days) and SNF (9.7 days) resulted in the most substantial reductions in HDAH. Males had fewer adjusted HDAH (153.1 vs 155.7, P < .001) than females; Medicaid-eligible patients had fewer HDAH compared with non-Medicaid-eligible patients (152.0 vs 154.9; P < .001). Those with hematologic malignancies had the fewest number of HDAH (148.9). Across HRRs, HDAH ranged from 10.8 fewer to 10.9 more days than the national mean. At the HRR-level, home hospice was associated with greater HDAH, whereas home health was associated with fewer HDAH. CONCLUSIONS: HDAH may be a useful measure to understand, quantify, and improve patient-centered outcomes for cancer patients at EOL.

Hyperarousal and Insomnia in Survivors of Cancer.

BACKGROUND: Cancer survivors are prone to insomnia due to the physical and psychological sequelae of cancer and treatment. Individuals with insomnia may present symptoms of hyperarousal. Cancer survivors with insomnia and trait hyperarousal may require different clinical treatments than patients with insomnia without trait hyperarousal. To our knowledge, no study has examined these factors previously. This study examined the relation between insomnia and trait hyperarousal in cancer survivors. METHODS: The sample included 160 individuals with previous cancer diagnoses who met DSM-5 criteria for insomnia disorder. Measures were collected with cross-sectional batteries of questionnaires, including the Insomnia Severity Index (ISI) and Hyperarousal Scale (HAS). This study is based on baseline data collected in a randomized clinical trial comparing CBT-I to acupuncture for cancer survivors with insomnia (Garland, Gehrman, Barg, Xie, & Mao, 2016). RESULTS: Hyperarousal was positively associated with insomnia (ISI total score) in bivariate correlations (r = .350, p < .01) and linear regressions (F = 22.06, p < .001). In bivariate correlations, hyperarousal was related to perceptions about the consequences of disturbed sleep rather than reported sleep patterns. For example, hyperarousal was positively related to reported satisfaction (r = .159, p < .05) and worry about sleep (r = .415, p < .01), but not to falling asleep, staying asleep, or awakening too early. In regressions, younger age, insomnia duration, and worry about sleep were uniquely associated with hyperarousal when adjusting for insomnia (B = 0.200, B = 0.177, B = -0.182, p < .05). CONCLUSIONS: Hyperarousal is associated with psychological appraisal of insomnia rather than reported sleep pattern. Younger age and longer duration of insomnia are associated with trait hyperarousal. These findings suggest targeting trait hyperarousal with amplified psychological treatment may lead to more personalized, effective treatment for insomnia.

Lung Cancer Stigma: Does Smoking History Matter?

BACKGROUND: Lung cancer patients commonly report stigma, often attributing it to the well-established association of smoking as the leading preventable cause. Theory and research suggest that patients' smoking history may differentiate patients' experience of lung cancer stigma. However, there is inconsistent evidence whether lung cancer stigma varies by patients' smoking history, owing to limitations in the literature. PURPOSE: This study examined differences in lung cancer patients' reported experience of lung cancer stigma by smoking history. METHOD: Participants (N = 266, 63.9% female) were men and women with lung cancer who completed a validated, multidimensional questionnaire measuring lung cancer stigma. Multivariable regression models characterized relationships between smoking history (currently, formerly, and never smoked) and lung cancer stigma, controlling for psychological and sociodemographic covariates. RESULTS: Participants who currently smoked reported significantly higher total, internalized, and perceived lung cancer stigma compared to those who formerly or never smoked (all p < .05). Participants who formerly smoked reported significantly higher total and internalized stigma compared to those who never smoked (p < .001). Participants reported similar levels of constrained disclosure, regardless of smoking history (p = .630). CONCLUSIONS: Total, internalized, and perceived stigma vary meaningfully by lung cancer patients' smoking history. Patients who smoke at diagnosis are at risk for experiencing high levels of stigma and could benefit from psychosocial support. Regardless of smoking history, patients reported similar levels of discomfort in sharing information about their lung cancer diagnosis with others. Future studies should test relationships between health-related stigma and associated health behaviors in other stigmatized groups.

Optimizing therapies for neurobehavioral comorbidities of epilepsy using chronic ambulatory electrocorticography.

There is an unmet need to improve therapy for neuropsychiatric comorbidities that are highly prevalent in persons with epilepsy (PWE). However, diagnosing and monitoring the neurobehavioral symptoms is challenging as their presentation can overlap with seizures. In this retrospective study, we report the advantage of chronic ambulatory electrocorticography (ECoG) from implanted Responsive Neurostimulator System (RNS®) in characterizing these psychosomatic paroxysms as a possible ictal, postictal, or interictal phenomenon and how the diagnosis guided the therapy choices. Five out of 21 patients with RNS had neuropsychiatric symptoms (panic attack, psychosis, conversion, and somatization disorders) that overlapped with their seizure semiology and were found to benefit from the use of RNS ECoG data by timely diagnosing and titrating targeted therapies. The cases illustrate the use of RNS ECoG data in diagnosing and improving the management of comorbidities in PWE. The ability to access RNS ECoG data and correlate it with patient symptoms is unique among available therapeutic options for PWE.

Robot-assisted stereoelectroencephalography exploration of the limbic thalamus in human focal epilepsy: implantation technique and complications in the first 24 patients.

OBJECTIVE: Despite numerous imaging studies highlighting the importance of the thalamus in a patient's surgical prognosis, human electrophysiological studies involving the limbic thalamic nuclei are limited. The objective of this study was to evaluate the safety and accuracy of robot-assisted stereotactic electrode placement in the limbic thalamic nuclei of patients with suspected temporal lobe epilepsy (TLE). METHODS: After providing informed consent, 24 adults with drug-resistant, suspected TLE undergoing evaluation with stereoelectroencephalography (SEEG) were enrolled in the prospective study. The trajectory of one electrode planned for clinical sampling of the operculoinsular cortex was modified to extend it to the thalamus, thereby preventing the need for additional electrode placement for research. The anterior nucleus of the thalamus (ANT) (n = 13) and the medial group of thalamic nuclei (MED) (n = 11), including the mediodorsal and centromedian nuclei, were targeted. The postimplantation CT scan was coregistered to the preoperative MR image, and Morel's thalamic atlas was used to confirm the accuracy of implantation. RESULTS: Ten (77%) of 13 patients in the ANT group and 10 (91%) of 11 patients in the MED group had electrodes accurately placed in the thalamic nuclei. None of the patients had a thalamic hemorrhage. However, trace asymptomatic hemorrhages at the cortical-level entry site were noted in 20.8% of patients, who did not require additional surgical intervention. SEEG data from all the patients were interpretable and analyzable. The trajectories for the ANT implant differed slightly from those of the MED group at the entry point-i.e., the precentral gyrus in the former and the postcentral gyrus in the latter. CONCLUSIONS: Using judiciously planned robot-assisted SEEG, the authors demonstrate the safety of electrophysiological sampling from various thalamic nuclei for research recordings, presenting a technique that avoids implanting additional depth electrodes or compromising clinical care. With these results, we propose that if patients are fully informed of the risks involved, there are potential benefits of gaining mechanistic insights to seizure genesis, which may help to develop neuromodulation therapies.

Surface guided imaging during stereotactic radiosurgery with automated delivery.

PURPOSE: To report on the use of surface guided imaging during frameless intracranial stereotactic radiotherapy with automated delivery via HyperArcTM (Varian Medical Systems, Palo Alto, CA). METHODS: All patients received intracranial radiotherapy with HyperArcTM and were monitored for intrafraction motion by the AlignRT® (VisionRT, London, UK) surface imaging (SI) system. Immobilization was with the EncompassTM (Qfix, Avondale, PA) aquaplast mask device. AlignRT® log files were correlated with trajectory log files to correlate treatment parameters with SI reported offsets. SI reported offsets were correlated with gantry angle and analyzed for performance issues at non-zero couch angles and during camera-pod blockage during gantry motion. Demographics in the treatment management system were used to identify race and determine if differences in SI reported offsets are due to skin tone settings. RESULTS: A total of 981 fractions were monitored over 14 months and 819 were analyzed. The median AlignRT® reported motion from beginning to the end of treatment was 0.24 mm. The median offset before beam on at non-zero couch angles was 0.55 mm. During gantry motion when camera pods are blocked, the median magnitude was below 1 mm. Median magnitude of offsets at non-zero couch angles was not found to be significantly different for patients stratified by race. CONCLUSIONS: Surface image guidance is a viable alternative to scheduled mid-treatment imaging for monitoring intrafraction motion during stereotactic radiosurgery with automated delivery.

The Relationship Between Physical Activity and Executive Functions Among Youth in Low-Income Urban Schools in the Northeast and Southwest United States.

The purpose of this study was to examine if physical activity is related to greater executive functions among youth in poverty. Executive functions (cognitive flexibility, inhibition, and working memory) and physical activity were measured in participants (N = 149) in the fifth to eighth grade from three schools located in high-poverty districts. Pearson correlations revealed a statistically significant correlation between physical activity and cognitive flexibility (r = .18, p < .05). Hierarchical multiple regressions revealed that physical activity significantly improved prediction for cognitive flexibility, R2 = .09, F(6, 142) = 2.26, p = .041, adjusted R2 = .05, above sex, maturity, and school district. A two-way multivariate analysis of covariance revealed statistically significant differences in working memory in more active youth compared with less active but no statistically significant differences in cognitive flexibility or inhibition (p < .05). Greater physical activity is associated with greater working memory among youth in poverty.

Human and rodent temporal lobe epilepsy is characterized by changes in O-GlcNAc homeostasis that can be reversed to dampen epileptiform activity.

Temporal Lobe Epilepsy (TLE) is frequently associated with changes in protein composition and post-translational modifications (PTM) that exacerbate the disorder. O-linked-ß-N-acetyl glucosamine (O-GlcNAc) is a PTM occurring at serine/threonine residues that is derived from and closely associated with metabolic substrates. The enzymes O-GlcNActransferase (OGT) and O-GlcNAcase (OGA) mediate the addition and removal, respectively, of the O-GlcNAc modification. The goal of this study was to characterize OGT/OGA and protein O-GlcNAcylation in the epileptic hippocampus and to determine and whether direct manipulation of these proteins and PTM's alter epileptiform activity. We observed reduced global and protein specific O-GlcNAcylation and OGT expression in the kainate rat model of TLE and in human TLE hippocampal tissue. Inhibiting OGA with Thiamet-G elevated protein O-GlcNAcylation, and decreased both seizure duration and epileptic spike events, suggesting that OGA may be a therapeutic target for seizure control. These findings suggest that loss of O-GlcNAc homeostasis in the kainate model and in human TLE can be reversed via targeting of O-GlcNAc related pathways.

Lung cancer stigma and depression: Validation of the Lung Cancer Stigma Inventory.

OBJECTIVE: In an effort to provide further evidence for the validity of the Lung Cancer Stigma Inventory (LCSI), this paper examined group differences in lung cancer stigma for patients who report clinically significant depressive symptoms and established a suggested scoring benchmark to identify patients with clinically meaningful levels of lung cancer stigma. METHODS: Patients (N = 231) who were diagnosed with lung cancer and treated within the past 12 months at one of two National Cancer Institute (NCI)-designated Cancer Centers located in the northeast and southern parts of the United States completed a single battery of questionnaires examining lung cancer stigma and depressed mood. Group differences, bivariate correlations, and receiver operating characteristic (ROC) analyses were conducted. RESULTS: Slightly more than a third of patients (35.9%) reported an elevated level of depression. There was a significant correlation (r = 0.44) between lung cancer stigma and depressive mood. The ROC curve analysis indicated an area under curve (AUC) of 0.71. A LCSI cutoff score of 37.5 yielded the optimal ratio of sensitivity (0.93) to specificity (0.70) for identifying patients with clinically meaningful lung cancer stigma. CONCLUSIONS: Consistent with prior work, lung cancer stigma, as measured by the LCSI, was found to be moderately associated with depressed mood. Clinical investigators may use an LCSI total score above 37.5 (ie, greater than or equal to 38 on the LCSI scale of integer scores) as a clinical threshold for identifying patients who may be experiencing clinically meaningful stigma and may benefit from stigma-reducing interventions.

A Daily Diary Study of Rumination and Health Behaviors: Modeling Moderators and Mediators.

OBJECTIVE: Rumination, thinking about a negative mood repetitively, is a common cognitive process that may affect health behavior engagement or avoidance. Little research has examined relations between rumination and health behaviors. PURPOSE: We aimed to test links between rumination and health behaviors as well as possible moderators and mediators of those links. METHODS: We used an 11-day online daily diary design. Health behavior outcomes included fruit intake, vegetable intake, exercise, alcohol intake, sexual risk taking behavior, and cigarette smoking. RESULTS: Rumination was related to alcohol intake at the within-person level. Using multivariate modeling, we found that significant within-person mediators for rumination to health behaviors included impulsivity, amotivation, self control, and using health behaviors as coping, with each of these mediating relationships for one to four out of the five health behavior outcomes. A significant between-person moderator includes perceived behavioral control for alcohol intake only, and intention was not a significant moderator of the rumination to health behavior relationships. CONCLUSIONS: Rumination affects various maladaptive health behaviors differentially, through a number of mechanisms and under a moderating condition whereby those who feel more control are better able to buffer rumination's deleterious effects. Future interventions can apply the results to individual and multiple behavior change interventions for chronic disease prevention, especially for those who are particularly suffering from ruminative thoughts.

Ecdysone- and NO-mediated gene regulation by competing EcR/Usp and E75A nuclear receptors during Drosophila development.

The Drosophila ecdysone receptor (EcR/Usp) is thought to activate or repress gene transcription depending on the presence or absence, respectively, of the hormone ecdysone. Unexpectedly, we found an alternative mechanism at work in salivary glands during the ecdysone-dependent transition from larvae to pupae. In the absense of ecdysone, both ecdysone receptor subunits localize to the cytoplasm, and the heme-binding nuclear receptor E75A replaces EcR/Usp at common target sequences in several genes. During the larval-pupal transition, a switch from gene activation by EcR/Usp to gene repression by E75A is triggered by a decrease in ecdysone concentration and by direct repression of the EcR gene by E75A. Additional control is provided by developmentally timed modulation of E75A activity by NO, which inhibits recruitment of the corepressor SMRTER. These results suggest a mechanism for sequential modulation of gene expression during development by competing nuclear receptors and their effector molecules, ecdysone and NO.

Lay beliefs about risk: relation to risk behaviors and to probabilistic risk perceptions.

Lay illness risk beliefs are commonly held philosophies about how risk works. These include beliefs that one's personal illness risk is unknowable and beliefs that thinking about one's risk can actually increase that risk. Beliefs about risk may impact risk behaviors and thereby subsequent health status. However, limited research examines the relation between lay risk beliefs and health behavior. This paper explores this possible relation. A nationally representative sample of adults (N = 1005) recruited from an internet panel were surveyed about lay risk beliefs and risk perceptions regarding diabetes and colorectal cancer, psychosocial factors (i.e., health literacy, need for cognition, locus of control), demographics, and current health behaviors (i.e., cigarette smoking, red meat intake, physical activity). In separate sets of regressions controlling for either demographics, psychosocial factors, or risk perceptions, lay risk beliefs remained significantly related to health behaviors. It may be important to consider how to address lay risk beliefs in intervention content and targeting in order to increase adaptive health behaviors and thereby prevent chronic disease.

Optical surface guidance for submillimeter monitoring of patient position during frameless stereotactic radiotherapy.

PURPOSE: To evaluate the accuracy of monitoring intrafraction motion during stereotactic radiotherapy with the optical surface monitoring system. Prior studies showing a false increase in the magnitude of translational offsets at non-coplanar couch positions prompted the vendor to implement software changes. This study evaluated two software improvements intended to address false offsets. METHODS: The vendor implemented two software improvements: a volumetric (ACO) rather than planar calibration and, approximately 6 months later, an improved calibration workflow (CIB) designed to better compensate for thermal drift. Offsets relative to the reference position, obtained at table angle 0 following image-guided setup, were recorded before beam-on at each table position and at the end of treatment the table returned to 0° for patients receiving SRT. RESULTS: Prior to ACO, between ACO and CIB, and after CIB, 223, 155, and 436 fractions were observed respectively. The median magnitude of translational offsets at the end of treatment was similar for all three intervals: 0.29, 0.33, and 0.27 mm. Prior to ACO, the offset magnitude for non-zero table positions had a median of 0.79 mm and was found to increase with increasing distance from isocenter to the anterior patient surface. After ACO, the median magnitude was 0.74 mm, but the dependence on surface-to-isocenter distance was eliminated. After CIB, the median magnitude for non-zero table positions was reduced to 0.57 mm. CONCLUSION: Ongoing improvements in software and calibration procedures have decreased reporting of false offsets at non-zero table angles. However, the median magnitude for non-zero table angles is larger than that observed at the end of treatment, indicating that accuracy remains better when the table is not rotated.

Associations of parents' self, child, and other "fat talk" with child eating behaviors and weight.

OBJECTIVE: Fat talk, negative communication about weight, is common in the media, peer groups, and families. Little is known about parental fat talk directed at oneself or others. This study examined associations between different forms of parental fat talk and child disordered eating behaviors and weight, and differences by child sex and age. METHOD: Parents of preadolescents or adolescents (n = 581) reported fat talk about themselves (self-fat talk), others (obesity-fat talk), and their child (child-fat talk). RESULTS: 76.0% of parents reported regular self-fat talk in front of children, 51.5% reported obesity-fat talk, and 43.6% reported child-fat talk. Fat talk did not differ significantly between parents of preadolescents and adolescents but was more common with sons than daughters. Of the three forms of fat talk, only child-fat talk was associated with all child eating and weight variables (binge eating, overeating, secretive eating, and overweight/obesity); associations were strongest for adolescent girls. Child sex was associated with secretive eating and overweight/obesity. CONCLUSIONS: Parents reported using different forms of fat talk frequently. Parent self- and obesity-fat talk were reported more frequently, but child-fat talk was the most strongly associated with children's eating and weight. Because of associations with disordered eating behaviors, intervening to reduce fat talk might contribute to improving pediatric disordered eating and weight-related interventions.

Assessment of driving outcomes after epilepsy surgery.

INTRODUCTION: Driving is an important factor contributing to good quality of life in patients with epilepsy. Little work has been undertaken to explore the details of driving experience alone in this patient population. We assessed the driving status of our patients prior to and following surgery for epilepsy. We also sought to determine what associations exist between patient characteristics and postoperative driving status. METHODS: The participants were selected from those adult patients with epilepsy who have required surgical treatment at our home institution between 2006 and 2010. Each participant received a questionnaire asking about driving and seizure status before and after surgery. The surveys were distributed using a modified Dillman approach. Perioperative patient data were obtained from the electronic medical record system in addition to a previously assembled epilepsy database from the Neurology Department at our institution. Independent variables were analyzed to look for significant associations with driving outcomes. RESULTS: One hundred forty eligible patients were included in the survey population; 78 patients returned a questionnaire for a response rate of 55.7%. Eighty percent of patients experienced driving as a regular part of life at some point prior to surgery. At the time of the questionnaire distribution, 68% of patients had returned to regular driving. Demographic characteristics did not play a significant role in whether or not the patient had a favorable driving outcome after surgery. However, patients who had a history of driving on a regular basis prior to surgery and those who had an Engel Class I outcome after surgery had significantly higher rates of good driving outcomes. Also, patients with an unfavorable preoperative driving status were more likely to have a favorable driving outcome after surgery if they had an Engel Class I outcome. Patients in whom intracranial electroencephalography (EEG) was utilized prior to resection had worse driving outcomes. CONCLUSIONS: A surprisingly high percentage of patients with epilepsy have experienced driving on a regular basis prior to surgery. We can assume that most patients were not driving immediately prior to surgery, given the fact that they had progressed to requiring surgery for treatment of their epilepsy. Thus, a driving rate of 68% after surgery can be considered good. We found that a patient's preoperative driving history, the use of intracranial EEG before surgical resection, and Engel classification were significant predictors of postoperative driving outcomes. These data provide patients with assistance in preoperative counseling. More investigation needs to be completed in other patient variables - such as seizure types, magnetic resonance imaging (MRI) findings, and patient motivators for driving - as possible predictors of driving outcomes.