Sex Differences in Delirium after Coronary Artery Bypass Graft Surgery and Perioperative Neuropsychiatric Conditions: A Secondary Analysis of a Cohort Study.

BACKGROUND: Biological sex influences the risk of depression and cognitive impairment, but its role in relation to postoperative delirium is unclear. This analysis investigates sex differences in delirium risk after coronary artery bypass graft (CABG) surgery and sex-related differences in relation to affective and cognitive symptoms. METHODS: This is a secondary analysis of the Neuropsychiatric Outcomes After Heart Surgery (NOAHS) study, a single-site, observational study of a CABG surgery cohort (n = 149). Preoperative characteristics are stratified by sex, and baseline variables that differ by sex are evaluated to understand whether sex modifies their relationships with delirium. We also evaluate sex differences in one-month depression and cognition. RESULTS: Female sex is associated with several delirium risk factors, including higher risk of preoperative depression and middle cerebral artery (MCA) stenosis. MCA stenosis was statistically associated with delirium only among women (OR 15.6, 95% CI 1.5, 164.4); mild cognitive impairment (MCI) was associated with delirium only in men (OR 4.6, 95% CI 1.2, 17.9). Other sex-based differences failed to reach statistical significance. Depression remained commoner among women 1 month post-CABG. CONCLUSIONS: Women in this CABG cohort were more likely to have depression at baseline and 1 month postoperatively, as well as MCA stenosis and postoperative delirium. Sex might modify the relationship between post-CABG delirium and its risk factors including MCA stenosis and MCI. Cerebrovascular disease deserves study as a potential explanation linking female sex and a range of poor outcomes among women with coronary heart disease.

The Delphi Delirium Management Algorithms. A practical tool for clinicians, the result of a modified Delphi expert consensus approach.

Delirium is common in hospitalised patients, and there is currently no specific treatment. Identifying and treating underlying somatic causes of delirium is the first priority once delirium is diagnosed. Several international guidelines provide clinicians with an evidence-based approach to screening, diagnosis and symptomatic treatment. However, current guidelines do not offer a structured approach to identification of underlying causes. A panel of 37 internationally recognised delirium experts from diverse medical backgrounds worked together in a modified Delphi approach via an online platform. Consensus was reached after five voting rounds. The final product of this project is a set of three delirium management algorithms (the Delirium Delphi Algorithms), one for ward patients, one for patients after cardiac surgery and one for patients in the intensive care unit.

Validation of complex radiotherapy techniques using polymer gel dosimetry.

Modern radiotherapy delivers highly conformal dose distributions to irregularly shaped target volumes while sparing the surrounding normal tissue. Due to the complex planning and delivery techniques, dose verification and validation of the whole treatment workflow by end-to-end tests became much more important and polymer gel dosimeters are one of the few possibilities to capture the delivered dose distribution in 3D. The basic principles and formulations of gel dosimetry and its evaluation methods are described and the available studies validating device-specific geometrical parameters as well as the dose delivery by advanced radiotherapy techniques, such as 3D-CRT/IMRT and stereotactic radiosurgery treatments, the treatment of moving targets, online-adaptive magnetic resonance-guided radiotherapy as well as proton and ion beam treatments, are reviewed. The present status and limitations as well as future challenges of polymer gel dosimetry for the validation of complex radiotherapy techniques are discussed.

Single-fraction Radiation Treatment Dose Response in a Genetically Engineered Mouse Model of Medulloblastoma.

Medulloblastoma is the most common malignant brain tumor of children. Although standard of care radiotherapy for pediatric medulloblastoma (PM) can lead to long-term remission or cure in many patients, it can also cause life-long cognitive impairment and other adverse effects. The pathophysiological mechanisms involved in radiation-induced cerebral damage are incompletely understood, and their elucidation may lead to interventions that mitigate radiation toxicity. To explore the mechanisms of radiation-induced cerebral damage, transgenic mouse models of PM and non-tumor-bearing controls were exposed to radiation doses that ranged from 0 to 30 Gy. Between 0-20 Gy, a significant dose-dependent reduction in tumor-associated hydrocephalus and increase in overall survival were observed. However, at 30 Gy, hydrocephalus incidence increased and median overall survival fell to near-untreated levels. Immunohistochemistry revealed that both tumor-bearing and non-tumor-bearing mice treated with 30 Gy of radiation had significantly more reactive astrocytes and microvascular damage compared to untreated controls. This effect was persistent across mice that were given 1 and 2 weeks of recovery time after irradiation. Our data suggest that radiation therapy promotes neural death by inducing long-term neuroinflammation in PM, suggesting radiation delivery methods that limit inflammation may be effective at widening the therapeutic window of radiation therapy in PM patients.

Functional, cognitive, and cerebrovascular aspects of depression before coronary artery bypass graft surgery: Testing the vascular depression hypothesis.

OBJECTIVE: Depression in patients undergoing coronary artery graft bypass (CABG) surgery is associated with morbidity and mortality, making its early identification and clinical management crucial. Vasculopathy and older age, hallmarks of patients requiring CABG, are also features of vascular depression. In this study, we assess for features of vascular depression in patients undergoing CABG surgery. METHODS: This is a cross-sectional analysis of a single-site prospective observational cohort study of patients undergoing CABG surgery. Subjects were assessed preoperatively using the Depression Interview and Structured Hamilton (DISH), depression scales, transcranial Doppler, neuropsychological testing, and clinical dementia rating (CDR). RESULTS: Of 161 subjects (mean age 66.2 ± 9.3, female 25%) who completed DISH, 18 had major or minor depression, 17 of whom had a past history of major or minor depression (mean age of onset 35.8 years-old). Pre-CABG depression was associated with greater functional impairment on CDR Sum of Boxes (OR = 3.7, 95% CI: 1.4, 9.7) and worse performance on letter fluency test (OR = 0.90, 95% CI: 0.81, 0.99) and trail-making tests (A: OR = 1.06, 95% CI: 1.01, 1.12; B: OR 1.02, 95% CI: 1.01, 1.04). Pre-CABG depression was not associated with middle cerebral artery (MCA) stenosis. CONCLUSIONS: Pre-CABG depression is associated with cognitive and functional impairment similar to vascular depression, but we did not find evidence of an association with older age of onset and MCA stenosis. Further studies on white matter disease in this population are needed to examine the vascular depression hypothesis for pre-CABG depression.

Investigation of a 3D dosimetry system utilizing radio-chromic gel and telecentric optical-CT readout.

BACKGROUND: Sophisticated modern radiation therapy treatments require comprehensive validation in 3D. PURPOSE: Investigation and characterization of a novel 3D dosimetry system consisting of ClearView radiochromic gel dosimeters (commercially available from Modus Inc) and an in-house telecentric optical CT scanner DLOS (the Duke Large Field of View Optical-CT Scanner). METHODS: Spectrophotometry measurements were made on small volumes of ClearView gel irradiated with 6X photon doses up to 40 Gy to determine linearity and temporal stability of dose response. Clinical evaluation of Clearview/DLOS system was conducted in two phases. Phase one involved simple photon and electron benchmark irradiations, delivered to 15 and 10 cm diameter dosimeters, at various energies and doses. Phase 2 investigated application to the verification of two single isocenter multi-target (SIMT) stereotactic radiosurgery (SRS) deliveries. These were patient treatments for two and five brain lesions, respectively, and delivered to 15 cm diameter dosimeters. SIMT treatments were delivered by Varian TrueBeam 6X with doses of 40 Gy. For dose read-out, dosimeters were optically scanned in the DLOS both pre- and post- irradiation (within 24 h). 3D reconstructions (1 mm3 resolution) of the change in linear-optical- attenuation (proportional to dose) was obtained using in-house software and 3D Slicer. Measured and predicted (Eclipse TPS) doses were compared through percent depth-dose (PDD), cross plane and in-plane profiles, and relative 3D gamma analysis (performed at a range of 7%/4 mm down to 2%/2 mm). Regions of known artifacts were excluded from analysis (jar base, neck, and wall). The SIMT SRS deliveries were additionally compared to SciMoca, an independent Monte Carlo second check software. RESULTS: Linearity of dose response was confirmed with R2 ≥ 0.9986 at both 520 and 630 nm wavelengths and at three post-irradiation time points: 21 h, 6 and 10 days. Dose profiles of all benchmark irradiations, in both 15 and 10 cm dosimeters, show good agreement in useable areas of the gel compared to Eclipse dose calculations, with root mean square errors (RMSE) ≤ 0.0054, and R2 ≥ 0.9808. Gamma pass rates for the 15 cm dosimeter benchmark irradiations were ≥ 94% at 2%/2 mm (central axis), ≥ 90% at 3%/3 mm (left lateral), ≥ 90% at 2%/2 mm (electron), and ≥ 94% at 3%/2 mm (stacking field). Similar high passing rates were observed for benchmark irradiations to the smaller 10 cm diameter dosimeters. Very high Gamma pass rates were found for SIMT SRS deliveries, with 99.82% and 97.80% at 3%/2 mm, for the two and five target plans, respectively. CONCLUSION: This work presents the first investigation of ClearView dosimeters in combination with a telecentric optical-CT scanner (DLOS). Simple benchmark irradiations demonstrate ClearView/DLOS can accurately recreate and measure relative 3D dose within non-artifact regions (i.e., > 1 cm away from walls). Application to SIMT SRS deliveries demonstrated the viability of the system as a means for comprehensive 3D verification of complex treatment deliveries as well as confirming the treatment planning system dose distribution. The results indicate that DLOS/ClearView system is a highly effective 3D verification tool for SIMT irradiations and can be applied with 3%/2 mm gamma criteria where passing rates of > 95% are to be expected.

Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.

The British Association for Psychopharmacology developed an evidence-based consensus guideline on the management of catatonia. A group of international experts from a wide range of disciplines was assembled. Evidence was gathered from existing systematic reviews and the primary literature. Recommendations were made on the basis of this evidence and were graded in terms of their strength. The guideline initially covers the diagnosis, aetiology, clinical features and descriptive epidemiology of catatonia. Clinical assessments, including history, physical examination and investigations are then considered. Treatment with benzodiazepines, electroconvulsive therapy and other pharmacological and neuromodulatory therapies is covered. Special regard is given to periodic catatonia, malignant catatonia, neuroleptic malignant syndrome and antipsychotic-induced catatonia. There is attention to the needs of particular groups, namely children and adolescents, older adults, women in the perinatal period, people with autism spectrum disorder and those with certain medical conditions. Clinical trials were uncommon, and the recommendations in this guideline are mainly informed by small observational studies, case series and case reports, which highlights the need for randomised controlled trials and prospective cohort studies in this area.

Malignant Catatonia: A Review for the Intensivist.

Catatonia is a clinical syndrome characterized by psychomotor, neurological and behavioral changes. The clinical picture of catatonia ranges from akinetic stupor to severe motoric excitement. Catatonia can occur in the setting of a primary psychiatric condition such as bipolar disorder or secondary to a general medical illness like autoimmune encephalitis. Importantly, it can co-occur with delirium or coma. Malignant catatonia describes catatonia that presents with clinically significant autonomic abnormalities including change in temperature, blood pressure, heart rate, and respiratory rate. It is a life-threatening form of acute brain dysfunction that has several motoric manifestations and occurs secondary to a primary psychiatric condition or a medical cause. Many of the established predisposing and precipitating factors for catatonia such as exposure to neuroleptic medications or withdrawal states are common in the setting of critical illness. Catatonia typically improves with benzodiazepines and treatment of its underlying psychiatric or medical conditions, with electroconvulsive therapy reserved for catatonia refractory to benzodiazepines or for malignant catatonia. However, some forms of catatonia, such as catatonia secondary to a general medical condition or catatonia comorbid with delirium, may be less responsive to traditional treatments. Prompt recognition and treatment of catatonia are crucial because malignant catatonia may be fatal without treatment. Given the high morbidity and mortality associated with malignant catatonia, intensivists should familiarize themselves with this important and under-recognized condition.

The Effect of Atm Loss on Radiosensitivity of a Primary Mouse Model of Pten-Deleted Brainstem Glioma.

Diffuse midline gliomas arise in the brainstem and other midline brain structures and cause a large proportion of childhood brain tumor deaths. Radiation therapy is the most effective treatment option, but these tumors ultimately progress. Inhibition of the phosphoinositide-3-kinase (PI3K)-like kinase, ataxia-telangiectasia mutated (ATM), which orchestrates the cellular response to radiation-induced DNA damage, may enhance the efficacy of radiation therapy. Diffuse midline gliomas in the brainstem contain loss-of-function mutations in the tumor suppressor PTEN, or functionally similar alterations in the phosphoinositide-3-kinase (PI3K) pathway, at moderate frequency. Here, we sought to determine if ATM inactivation could radiosensitize a primary mouse model of brainstem glioma driven by Pten loss. Using Cre/loxP recombinase technology and the RCAS/TVA retroviral gene delivery system, we established a mouse model of brainstem glioma driven by Pten deletion. We find that Pten-null brainstem gliomas are relatively radiosensitive at baseline. In addition, we show that deletion of Atm in the tumor cells does not extend survival of mice bearing Pten-null brainstem gliomas after focal brain irradiation. These results characterize a novel primary mouse model of PTEN-mutated brainstem glioma and provide insights into the mechanism of radiosensitization by ATM deletion, which may guide the design of future clinical trials.

Evaluating the Effectiveness of an Educational Module for the Bush-Francis Catatonia Rating Scale.

OBJECTIVE: Catatonia is widely underdiagnosed, in large part due to inaccurate recognition of its specific features. This study aimed to evaluate the effectiveness of an online educational module to improve theoretical and practical knowledge of the Bush-Francis Catatonia Rating Scale (BFCRS) across a broad range of clinicians and medical students. METHOD: A 1-h online module, including a training manual and videos, was disseminated to medical students, psychiatry residents and fellows, and psychiatrists through national Listservs and through the Academy of Consultation-Liaison Psychiatry. Participants completed pre- and post-module testing consisting of a 50-question multiple-choice test and a 3-min standardized patient video scored using the 23-item BFCRS. Participants accessed the module from October 1, 2020, to April 4, 2021. Immediate improvement and 3-month knowledge retention were assessed using quantitative and qualitative analyses. RESULTS: Study enrollment was high with moderate dropout (pre-testing: n = 482; post-testing: n = 236; 3-month testing: n = 105). Adjusting for demographics, large pre-post improvements were found in performance (multiple-choice: 11.3 points; standardized patient scoring: 4.2 points; both p < 0.001) and for nearly all individual BFCRS items. Knowledge attrition was modest, and improvements persisted at 3 months. CONCLUSIONS: This educational resource provides descriptive and demonstrative reference standards of the items on the BFCRS. This curriculum improved identification of catatonia's features on both multiple choice and standardized patient scoring across all ages and training levels with good overall knowledge retention.

An investigation of kV mini-GRID spatially fractionated radiation therapy: dosimetry and preclinical trial.

Objective. To develop and characterize novel methods of extreme spatially fractionated kV radiation therapy (including mini-GRID therapy) and to evaluate efficacy in the context of a pre-clinical mouse study.Approach. Spatially fractionated GRIDs were precision-milled from 3 mm thick lead sheets compatible with mounting on a 225 kVp small animal irradiator (X-Rad). Three pencil-beam GRIDs created arrays of 1 mm diameter beams, and three 'bar' GRIDs created 1 × 20 mm rectangular fields. GRIDs projected 20 × 20 mm2fields at isocenter, and beamlets were spaced at 1, 1.25, and 1.5 mm, respectively. Peak-to-valley ratios and dose distributions were evaluated with Gafchromic film. Syngeneic transplant tumors were induced by intramuscular injection of a soft tissue sarcoma cell line into the gastrocnemius muscle of C57BL/6 mice. Tumor-bearing mice were randomized to four groups: unirradiated control, conventional irradiation of entire tumor, GRID therapy, and hemi-irradiation (half-beam block, 50% tumor volume treated). All irradiated mice received a single fraction of 15 Gy.Results. High peak-to-valley ratios were achieved (bar GRIDs: 11.9 ± 0.9, 13.6 ± 0.4, 13.8 ± 0.5; pencil-beam GRIDs: 18.7 ± 0.6, 26.3 ± 1.5, 31.0 ± 3.3). Pencil-beam GRIDs could theoretically spare more intra-tumor immune cells than bar GRIDs, but they treat less tumor tissue (3%-4% versus 19%-23% area receiving 90% prescription, respectively). Bar GRID and hemi-irradiation treatments significantly delayed tumor growth (P < 0.05), but not as much as a conventional treatment (P < 0.001). No significant difference was found in tumor growth delay between GRID and hemi-irradiation.Significance. High peak-to-valley ratios were achieved with kV grids: two-to-five times higher than values reported in literature for MV grids. GRID irradiation and hemi-irradiation delayed tumor growth, but neither was as effective as conventional whole tumor uniform dose treatment. Single fraction GRID therapy could not initiate an anti-cancer immune response strong enough to match conventional RT outcomes, but follow-up studies will evaluate the combination of mini-GRID with immune checkpoint blockade.

Sensitization of Endothelial Cells to Ionizing Radiation Exacerbates Delayed Radiation Myelopathy in Mice.

Delayed radiation myelopathy is a rare, but significant late side effect from radiation therapy that can lead to paralysis. The cellular and molecular mechanisms leading to delayed radiation myelopathy are not completely understood but may be a consequence of damage to oligodendrocyte progenitor cells and vascular endothelial cells. Here, we aimed to determine the contribution of endothelial cell damage to the development of radiation-induced spinal cord injury using a genetically defined mouse model in which endothelial cells are sensitized to radiation due to loss of the tumor suppressor p53. Tie2Cre; p53FL/+ and Tie2Cre; p53FL/- mice, which lack one and both alleles of p53 in endothelial cells, respectively, were treated with focal irradiation that specifically targeted the lumbosacral region of the spinal cord. The development of hindlimb paralysis was followed for up to 18 weeks after either a 26.7 Gy or 28.4 Gy dose of radiation. During 18 weeks of follow-up, 83% and 100% of Tie2Cre; p53FL/- mice developed hindlimb paralysis after 26.7 and 28.4 Gy, respectively. In contrast, during this period only 8% of Tie2Cre; p53FL/+ mice exhibited paralysis after 28.4 Gy. In addition, 8 weeks after 28.4 Gy the irradiated spinal cord from Tie2Cre; p53FL/- mice showed a significantly higher fractional area positive for the neurological injury marker glial fibrillary acidic protein (GFAP) compared with the irradiated spinal cord from Tie2Cre; p53FL/+ mice. Together, our findings show that deletion of p53 in endothelial cells sensitizes mice to the development of delayed radiation myelopathy indicating that endothelial cells are a critical cellular target of radiation that regulates myelopathy.

Pseudodelirium: Psychiatric Conditions to Consider on the Differential for Delirium.

OBJECTIVE: The phenotypes of several psychiatric conditions can very closely resemble delirium; the authors describe such presentations as pseudodelirium. However, because the clinical management of these conditions differs markedly from that of delirium, prompt differentiation is essential. The authors provide an educational review to assist clinicians in identifying and managing psychiatric conditions that may be especially challenging to differentiate from delirium. METHODS: Based on clinical experience, the authors identified four psychiatric conditions as among the most difficult to differentiate from delirium: disorganized psychosis, Ganser syndrome, delirious mania, and catatonia. An overview of each condition, description of clinical features, differentiation of specific phenotypes from delirium, and review of clinical management are also provided. RESULTS: The thought and behavioral disorganization in disorganized psychosis can be mistaken for the clouded sensorium and behavioral dysregulation encountered in delirium. The fluctuating alertness and apparent confusion in Ganser syndrome resemble delirium's altered arousal and cognitive features. As its name suggests, delirious mania presents as a mixture of hyperactive delirium and mania; additional features may include psychosis, autonomic activation, and catatonia. Both delirium and catatonia have hypokinetic and hyperkinetic variants, and the two syndromes can also co-occur. CONCLUSIONS: The clinical presentations of several psychiatric conditions can blend with the phenotype of delirium, at times even co-occurring with it. Detailed evaluation is often required to differentiate such instances of pseudodelirium from delirium proper.

Prevalent Gaps in Understanding the Features of Catatonia Among Psychiatrists, Psychiatry Trainees, and Medical Students.

Background: Catatonia is often overlooked, and a key factor for underdiagnosis may be an inadequate understanding of catatonia's heterogeneous phenotypes. The aim of this study was to identify the current state of theoretical and applied knowledge of catatonic features among psychiatry trainees and practitioners using the Bush-Francis Catatonia Rating Scale (BFCRS), the most commonly used instrument to identify and score catatonia.Methods: We created an online 50-item multiple-choice test and 3-minute standardized patient video to be scored using the BFCRS. Email invitations were sent to medical students and psychiatry residents and fellows through listservs of psychiatry clerkship and residency directors and to consultation-liaison psychiatrists through the Academy of Consultation-Liaison Psychiatry. Participants could access the exam from October 1 to December 31, 2020.Results: In our sample (n = 482), participants correctly answered an average of 55% of test questions and identified 69% of BFCRS items on the standardized patient exam. Multivariable regression adjusting for demographics revealed that, compared to medical students, psychiatrists scored 7 points higher on the multiple-choice test and identified only 2 more items correctly on the BFCRS. Older participants performed worse than younger participants. No meaningful performance differences were identified by region or gender. Several items were consistently misidentified.Conclusions: We found significant inaccuracies in clinicians' understanding of catatonic features irrespective of their stage of training and years of experience. These data suggest prevalent gaps in catatonia recognition among psychiatrists, psychiatry trainees, and medical students utilizing the BFCRS. This has important implications for clinical research and patient care.

Report of AAPM Task Group 155: Megavoltage photon beam dosimetry in small fields and non-equilibrium conditions.

Small-field dosimetry used in advance treatment technologies poses challenges due to loss of lateral charged particle equilibrium (LCPE), occlusion of the primary photon source, and the limited choice of suitable radiation detectors. These challenges greatly influence dosimetric accuracy. Many high-profile radiation incidents have demonstrated a poor understanding of appropriate methodology for small-field dosimetry. These incidents are a cause for concern because the use of small fields in various specialized radiation treatment techniques continues to grow rapidly. Reference and relative dosimetry in small and composite fields are the subject of the International Atomic Energy Agency (IAEA) dosimetry code of practice that has been published as TRS-483 and an AAPM summary publication (IAEA TRS 483; Dosimetry of small static fields used in external beam radiotherapy: An IAEA/AAPM International Code of Practice for reference and relative dose determination, Technical Report Series No. 483; Palmans et al., Med Phys 45(11):e1123, 2018). The charge of AAPM task group 155 (TG-155) is to summarize current knowledge on small-field dosimetry and to provide recommendations of best practices for relative dose determination in small megavoltage photon beams. An overview of the issue of LCPE and the changes in photon beam perturbations with decreasing field size is provided. Recommendations are included on appropriate detector systems and measurement methodologies. Existing published data on dosimetric parameters in small photon fields (e.g., percentage depth dose, tissue phantom ratio/tissue maximum ratio, off-axis ratios, and field output factors) together with the necessary perturbation corrections for various detectors are reviewed. A discussion on errors and an uncertainty analysis in measurements is provided. The design of beam models in treatment planning systems to simulate small fields necessitates special attention on the influence of the primary beam source and collimating devices in the computation of energy fluence and dose. The general requirements for fluence and dose calculation engines suitable for modeling dose in small fields are reviewed. Implementations in commercial treatment planning systems vary widely, and the aims of this report are to provide insight for the medical physicist and guidance to developers of beams models for radiotherapy treatment planning systems.

Proactive Consultation-Liaison Psychiatry: American Psychiatric Association Resource Document.

In 2019, the American Psychiatric Association Council on Consultation-Liaison (C-L) Psychiatry convened a work group to develop a resource document on proactive C-L psychiatry. A draft of this document was reviewed by the Council in July 2020, and a revised version was approved by this Council in September 2020. The accepted version was subsequently reviewed by the American Psychiatric Association Council on Health Care Systems and Financing in November 2020. The final version was approved by the Joint Reference Committee on November 24, 2020, and received approval for publication by the Board of Trustees on December 12, 2020. This resource document describes the historical context and modern trends that have given rise to the model of proactive C-L psychiatry. Styled as an inpatient corollary to outpatient collaborative care models, proactive C-L provides a framework of mental health care delivery in the general hospital designed to enhance mental health services to a broad range of patients. Its 4 elements include systematic screening for active mental health concerns, proactive interventions tailored to individual patients, team-based care delivery, and care integration with primary teams and services. Studies have found that proactive C-L psychiatry is associated with reduced hospital length of stay, enhanced psychiatric service utilization, reduced time to psychiatric consultation, and improved provider and nurse satisfaction. These favorable results encourage further studies that replicate and build upon these findings. Additional outcomes such as patient experience, health outcomes, and readmission rates deserve investigation. Further studies are also needed to examine a broader array of team compositions and the potential value of proactive C-L psychiatry to different hospital settings such as community hospitals, surgery, and critical care.

Depression predicts cognitive and functional decline one month after coronary artery bypass graft surgery (Neuropsychiatric Outcomes After Heart Surgery study).

BACKGROUND: Prior research on cognitive and functional outcomes after coronary artery bypass graft (CABG) surgery has largely explored these two domains in isolation. In this study, we assess baseline depression and cognition as risk factors for decline in the Clinical Dementia Rating Sum-of-Boxes (CDR-SB) 1 month post-CABG surgery, which a combined measure of cognition and function. DESIGN: The Neuropsychiatric Outcomes After Heart Surgery study is a prospective observational cohort study. SETTING: A tertiary care, academic center. PARTICIPANTS: Of a total study sample of 148 patients undergoing CABG surgery, 124 (83.8%) completed 1-month follow-up assessment. Mean age was 66.3, 32 (25.8%) female and 112 (90.3%) White. MEASUREMENTS: Cognition, function, and depression were assessed on semi-structured clinical interviews. Cognitive and functional status were defined using CDR-SB; mild or major depression was defined by the Hamilton Depression Rating Scale. Additionally, neuropsychological battery was performed at baseline. RESULTS: CDR-SB decline occurred in 18 (14.5%) subjects. Older age, depression, baseline CDR-SB, and postoperative delirium were associated with 1-month decline on univariate analysis. Older age (OR 1.1 [1.0-1.2]) and depression (OR 6.2 [1.1-35.0]) remained significant on multivariate regression. In separate models, baseline performance on visual Wechsler memory scale (delayed), Hopkins verbal learning test (immediate and delayed), controlled oral word fluency test, and Trails B predicted CDR-SB decline. CONCLUSION: Roughly one in seven patients experienced CDR-SB decline 1 month after CABG surgery. Also, preoperative depression deserves recognition for being a predictor of CDR-SB decline one month post-CABG.

Clinical Approach to Personality Change Due to Another Medical Condition.

BACKGROUND: Medical personality change (MPC) is a codable diagnosis (i.e., F07.0) that deserves consideration when a patient is inexplicably no longer "acting like him/herself." Its presentation ranges from subtle to severe and is often characterized by bafflingly poor judgment and impairment in several aspects of a person's life. Despite the global impact that MPC can have on a patient's functioning, occupation, and relationships, this condition receives far less clinical consideration than better known syndromes such as depression or anxiety and is often likely incorrectly formulated as such. OBJECTIVE/METHODS: This article provides a clinically focused review of MPC. We review its clinical assessment followed by a review of its subtypes, which we have categorized to reflect the behavioral correlates of known frontotemporal-subcortical circuits. These include the apathetic type (ventromedial prefrontal cortex), the labile and disinhibited types (orbitofrontal cortex), and the aggressive and paranoid types (medial temporal lobes). RESULTS: For each of these 3 categories, we describe the clinical presentation and review management strategies. For each category, we focus on 3 common causes for MPC-traumatic brain injury, Huntington disease, and brain tumors-which we have selected because clinical features of MPC due to these conditions generalize to many other etiologies of MPC. CONCLUSIONS: MPC warrants clinical attention for the range of dysfunction and distress it can cause. It also deserves further scientific study to better characterize its phenotypes, to tailor instruments for its clinical assessment, and to identify effective treatments.

A method for generating intensity-modulated radiation therapy fields for small animal irradiators utilizing 3D-printed compensator molds.

PURPOSE: The purpose of this study was to investigate the feasibility of using fused deposition modeling (FDM) three-dimensional (3D) printer to generate radiation compensators for high-resolution (~1 mm) intensity-modulated radiation therapy (IMRT) for small animal radiation treatment. We propose a novel method incorporating 3D-printed compensator molds filled with NaI powder. METHODS: The inverse planning module of the computational environment for radiotherapy research (CERR) software was adapted to simulate the XRAD-225Cx irradiator, both geometry and kV beam quality (the latter using a phase space file provided for XRAD-225Cx). A nine-field IMRT treatment was created for a scaled-down version of the imaging and radiation oncology core (IROC) Head and Neck IMRT credentialing test, recreated on a 2.2-cm-diameter cylindrical phantom. Optimized fluence maps comprising nine fields and a total of 2564 beamlets were calculated at resolution of 1.25 × 1.25 mm2 . A hollow compensator mold was created (using in-house software and algorithm) for each field using 3D printing with polylactic acid (PLA) filaments. The molds were then packed with sodium iodide powder (NaI, measured density ρNaI  = 2.062 g/cm3 ). The mounted compensator mold thickness was limited to 13.8 mm due to clearance issues with couch collision. At treatment delivery, each compensator was manually mounted to a customized block tray attached to the reference 40 × 40 mm2 collimator. Compensator reproducibility among three repeated 3D-printed molds was measured with Radiochromic EBT2 film. The two-dimensional (2D) dose distributions of the nine fields were compared to calculated 2D doses from CERR using gamma comparisons with distance-to-agreement criteria of 0.5-0.25 mm and dose difference criteria of 3-5%. RESULTS: Good reproducibility of 3D-printed compensator manufacture was observed with mean error of ±0.024 Gy and relative dose error of ±4.2% within the modulated part of the beam. Within the limit of 13.8 mm compensator height, a maximum radiation blocking efficiency of 91.5% was achieved. Per field, about 45.5 g of NaI powder was used. Gamma analysis on each of the nine delivered IMRT fields using radiochromic films resulted in eight of nine treatment fields with >90% pass rate with 5%/0.5 mm tolerances. However, low gamma passing rate of 49-66% (3%/0.25 mm to 5%/0.5 mm) was noted in one field, attributed to fabrication errors resulting in over-filling the mold. The nine-field treatment plan was delivered in under 30 min with no mechanical or collisional issues. CONCLUSIONS: We show the feasibility of high spatial resolution IMRT treatment on a small animal irradiator utilizing 3D-printed compensator shells packed with NaI powder. Using the PLA mold with NaI powder was attractive due to the ease of 3D printing a PLA mold at high geometric resolution and the well-balanced attenuation properties of NaI powders that prevented the mold from becoming too bulky. IMRT fields with 1.25-mm resolution are capable with significant fluence modulation with relative dose accuracy of ±4.2%.

Comprehensive radiation and imaging isocenter verification using NIPAM kV-CBCT dosimetry.

PURPOSE: To develop and demonstrate a comprehensive method to directly measure radiation isocenter uncertainty and coincidence with the cone-beam computed tomography (kV-CBCT) imaging coordinate system that can be carried out within a typical quality assurance (QA) time slot. METHODS: An N-isopropylacrylamide (NIPAM) three-dimensional (3D) dosimeter for which dose is observed as increased electron density in kV-CBCT is irradiated at eight couch/gantry combinations which enter the dosimeter at unique orientations. One to three CBCTs are immediately acquired, radiation profile is detected per beam, and displacement from imaging isocenter is quantified. We performed this test using a 5 mm diameter MLC field, and 7.5 and 4 mm diameter cones, delivering approximately 16 Gy per beam. CBCT settings were 1035-4050 mAs, 80-125 kVs, smooth filter, 1 mm slice thickness. The two-dimensional (2D) displacement of each beam from the imaging isocenter was measured within the planning system, and Matlab code developed in house was used to quantify relevant parameters based on the actual beam geometry. Detectability of the dose profile in the CBCT was quantified as the contrast-to-noise ratio (CNR) of the irradiated high-dose regions relative to the surrounding background signal. Our results were compared to results determined by the traditional Winston-Lutz test, film-based "star shots," and the vendor provided machine performance check (MPC). The ability to detect alignment errors was demonstrated by repeating the test after applying a 0.5 mm shift to the MLCs in the direction of leaf travel. In addition to radiation isocenter and coincidence with CBCT origin, the analysis also calculated the actual gantry and couch angles per beam. RESULTS: Setup, MV irradiation, and CBCT readout were carried out within 38 min. After subtracting the background signal from the pre-CBCT, the CNR of the dosimeter signal from the irradiation with the MLCs (125 kVp, 1035 mAs, n = 3), 7.5 mm cone (125 kVp, 1035 mAs, n = 3), and 4 mm cone (80 kVp, 4050 mAs, n = 1) was 5.4, 5.9, and 2.9, respectively. The minimum radius that encompassed all beams calculated using the automated analysis was 0.38, 0.48, and 0.44 mm for the MLCs, 7.5 mm cone, and 4 mm cone, respectively. When determined manually, these values were slightly decreased at 0.28, 0.41, and 0.40 mm. For comparison, traditional Winston-Lutz test with MLCs and MPC measured the 3D isocenter radius to be 0.24 mm. Lastly, when a 0.5 mm shift to the MLCs was applied, the smallest radius that intersected all beams increased from 0.38 to 0.90 mm. The mean difference from expected value for gantry angle was 0.19 ± 0.29°, 0.17 ± 0.23°, and 0.12 ± 0.14° for the MLCs, 7.5 mm cone, and 4 mm cone, respectively. The mean difference from expected for couch angle was -0.07 ± 0.28°, -0.08 ± 0.66°, and 0.04 ± 0.25°. CONCLUSIONS: This work demonstrated the feasibility of a comprehensive isocenter verification using a NIPAM dosimeter with sub-mm accuracy which incorporates evaluation of coincidence with imaging coordinate system, and may be applicable to all SRS cones as well as MLCs.