Faculty Bibliography

BACKGROUND:Psychiatric comorbidity is highly prevalent in general medicine inpatient settings and is associated with increased duration and cost of hospitalization. OBJECTIVE:To evaluate the impact of integrated, proactive psychiatric care on hospital medicine length of stay (LOS), expanding upon methods from earlier studies. METHODS:A full-time psychiatrist was dedicated to a single hospital medicine unit to focus on early case finding and intensified treatment, interdisciplinary communication, and discharge planning. To a pre-post intervention design, we added a simultaneous usual care comparison. We also added adjustments for age, sex, insurance type, and whether the patient was discharged home or to a facility. We included a sensitivity analysis to remove outliers for whom LOS was ≤30 days. RESULTS:Statistically significant differences in LOS occurred on the pilot unit in the pre-post analysis (-1.66 d, P = 0.04) and on the pilot versus control units in the intervention year (-1.91 d, P = 0.003). The differential pre-post change in LOS on the pilot versus control units revealed a positive trend but was not statistically significant (-1.59 d, P = 0.14). This more rigorous test approached statistical significance when patients with LOS >30 days were excluded (-1.15 d, P = 0.07). CONCLUSION/CONCLUSIONS:This analysis strengthens existing evidence that dedicated, proactive psychiatric services integrated into hospital medicine units lower LOS more than does usual psychiatric consultation upon request, particularly in patients with an LOS ≤30 days.

BACKGROUND: There is a lack of treatment options for HGG and LGG patients. BRAFV600E mutations are uncommon in glioma, with a poor long-term prognosis. Combined BRAF/MEK inhibition extends progression-free survival (PFS) and overall survival (OS) in BRAF V600E- mutated melanoma, non small-cell lung cancer, and anaplastic thyroid cancer.
METHOD(S): This phase 2, open-label trial (NCT02034110) evaluated dabrafenib (BRAF inhibitor, 150mg BID) plus trametinib (MEK inhibitor, 2mg QD) in patients with BRAF V600E mutations in 9 rare tumor types, including HGG and LGG. Eligible patients had histologicallyconfirmed recurrent or progressive glioma (LGG:WHO grade 1 or 2; HGG:WHO grade 3 or 4), with HGG patients required to have received radiotherapy and first-line chemotherapy, or concurrent chemoradiation. Treatment continued until unacceptable toxicity, disease progression, or death. Primary endpoint was investigator-assessed objective response rate (ORR) using RANO criteria. Secondary endpoints included duration of response (DOR), PFS, OS, and safety.
RESULT(S): Interim analysis (IA) #14 (data cutoff: April 2, 2018) reported additional 3 months follow-up, with 49 patients enrolled (HGG, n=39; LGG, n=10) and 3 patients not evaluable for response. In HGG patients, ORR was 27% (10/37; 95%CI: 13.8%-44.1%), including CR (n=1), PR (n=9), and SD (n=11), with 16 patients currently ongoing treatment. In LGG patients, ORR was 56% (5/9; 95%CI: 26.8%-79.3%), including PR (n=5) and SD (n=4), with 6 patients currently ongoing treatment. OS, PFS, and DOR will be presented (IA#15). In HGG patients, adverse events (AEs) included fatigue (33%), headache (31%), rash (28%), and pyrexia (23%); grade 3/4 AEs included neutropenia (8%) and fatigue (5%). In LGG patients, AEs included headache (70%), fatigue, pyrexia (60% each), nausea, and arthralgia (50% each); grade 3/4 AEs included fatigue (20%).
CONCLUSION(S): Dabrafenib plus trametinib demonstrated promising efficacy in patients with recurrent or refractory BRAF V600E-mutated HGG or LGG, with manageable AEs and no new safety signals

BACKGROUND:Recent studies estimate nearly half of the US population can access mobile medical applications (apps) on their smartphones. The are no systematic data available on apps focused on stroke survivors/caregivers. OBJECTIVE:To identify apps (a) designed for stroke survivors/caregivers, (b) dealing with a modifiable stroke risk factor (SRF), or (c) were developed for other purposes but could potentially be used by stroke survivors/caregivers. METHODS:A systematic review of the medical apps in the US Apple iTunes store was conducted between August 2013 and January 2016 using 18 predefined inclusion/exclusion criteria. SRFs considered were: diabetes, hypertension, smoking, obesity, atrial fibrillation, and dyslipidemia. RESULTS:Out of 30,132 medical apps available, 843 (2.7%) eligible apps were identified. Of these apps, (n = 74, 8.7%) apps were specifically designed for stroke survivors/caregivers use and provided the following services: language/speech therapy (n = 28, 37%), communication with aphasic patients (n = 19, 25%), stroke risk calculation (n = 11, 14%), assistance in spotting an acute stroke (n = 8, 10%), detection of atrial fibrillation (n = 3, 4%), direction to nearby emergency room (n = 3, 4%), physical rehabilitation (n = 3, 4%), direction to the nearest certified stroke center (n = 1, < 2%), and visual attention therapy (n = 1, <2%). 769 apps identified that were developed for purposes other than stroke. Of these, the majority (n = 526, 68%) addressed SRFs. CONCLUSIONS:Over 70 medical apps exist to specifically support stroke survivors/caregivers and primarily targeted language and communication difficulties. Apps encompassing most stroke survivor/caregiver needs could be developed and tested to ensure the issues faced by these populations are being adequately addressed.

Myelin has traditionally been considered a static structure that is produced and assembled during early developmental stages. While this characterization is accurate in some contexts, recent studies have revealed that oligodendrocyte generation and patterns of myelination are dynamic and potentially modifiable throughout life. Unique structural and biochemical properties of the myelin sheath provide opportunities for the development and implementation of multimodal label-free and fluorescence optical imaging approaches. When combined with genetically encoded fluorescent tags targeted to distinct cells and subcellular structures, these techniques offer a powerful methodological toolbox for uncovering mechanisms of myelin generation and plasticity in the live brain. Here, we discuss recent advances in these approaches that have allowed the discovery of several forms of myelin plasticity in developing and adult nervous systems. Using these techniques, long-standing questions related to myelin generation, remodeling, and degeneration can now be addressed.

Cerebellar abnormalities are commonly reported in autism spectrum disorder (ASD). Dentate nuclei (DNs) are key structures in the anatomical circuits linking the cerebellum to the extracerebellum. Previous resting-state functional connectivity (RsFc) analyses reported DN abnormalities in high-functioning ASD (HF-ASD). This study examined the RsFc of the DN in young adults with HF-ASD compared with healthy controls (HCs) with the aim to expand upon previous findings of DNs in a dataset using advanced, imaging acquisition methods that optimize spatiotemporal resolution and statistical power. Additional seed-to-voxel analyses were carried out using motor and nonmotor DN coordinates reported in previous studies as seeds. We report abnormal dentato-cerebral and dentato-cerebellar functional connectivity in ASD. Our results expand and, in part, replicate previous descriptions of DN RsFc abnormalities in this disorder and reveal correlations between DN-cerebral RsFc and ASD symptom severity.

BACKGROUND:We aim to describe and psychometrically validate the Rett Syndrome Motor Evaluation Scale, a 25-item ordinal scale examining (loco-)motor function across six sections: standing, sitting, transitions, walking, running, and walking up or downstairs. METHODS:We illustrate the process of item construction and validation, report findings and normative data obtained on a standardization sample of 60 patients with Rett syndrome. We investigate the validity and reliability of the scale and illustrate its psychometric properties using modern multivariate techniques of data analysis. RESULTS:Sixty patients with Rett syndrome were included (all female; mean age 12.45 (S.D. 8.75) years). The multidimensional latent structure of the scale was supported by the results of the confirmatory factor analysis. Rett Syndrome Motor Evaluation Scale showed strong internal consistency reliability as well as excellent inter-rater agreement. The Rett Syndrome Motor Evaluation Scale scores were not predicted by age, but were associated with disease severity, degree of spasticity, and hand dysfunction. We also identified three latent classes with different degrees of impairment. CONCLUSIONS:Rett Syndrome Motor Evaluation Scale is a new, valid, and reliable scale that can be introduced in clinical practice when assessing (loco-)motor function in Rett syndrome.

Case Description: 32-year-old male with history of unintentional heroin overdose complicated by cardiac arrest and anoxic brain injury presenting with functional decline, mutism, catalepsy, rigidity and negativism consistent with catatonia. Marked improvement with lorazepam titration to 4 mg QID but symptoms were subsequently refractory. Eventual lysis of catatonia was achieved with electroconvulsive therapy (ECT) with improvement of Bush Francis Catatonia Rating Scale (BFCRS) from 17 to 0. 65-year-old male with cardiac arrest and anoxic brain injury presenting with mutism, rigidity, negativism, ambitendency, catalepsy. Treatment with lorazepam for 19 days produced significant functional gains and improved BFCRS from 26 to 9.
Setting(s): Acute Inpatient Rehabilitation Facility; Acute Inpatient Psychiatry Unit Patient: 32- and 65-year-old males with catatonia Assessment/Results: Two patients with catatonia following anoxic brain injury. One patient responded to lorazepam and later ECT. A second patient improved with lorazepam alone. Improvement was demonstrated by significant decrease in BFCRS scores.
Discussion(s): Catatonia, a psychomotor dysregulation disorder characterized by difficulty initiating/inhibiting behavior, can occur in the context of psychiatric or medical/neurologic illness and can be difficult to distinguish from static brain injury. Features include stupor, catalepsy, waxy flexibility, mutism, negativism, posturing, mannerisms, stereotypy, agitation, grimacing, echolalia and echopraxia. Standard treatment includes lorazepam, ECT, glutamate antagonists, and anticonvulsants but data is limited on best treatment approaches in the brain injury. While benzodiazepines are typically avoided in patients with brain injury due to their effects on neuroplasticity and sedating properties, and ECT has shown generally poor outcomes after anoxic injury, both can be safe and effective for select patients.
Conclusion(s): Catatonia is a potentially treatable mimic of static cognitive deficits after brain injury. Successful treatment of catatonia after anoxic brain injury can be achieved with lorazepam or ECT. Further research is needed to differentiate catatonia from brain injury-related cognitive and motor deficits for appropriate diagnosis and treatment

Rituximab is a chimeric anti-CD20 monoclonal antibody that is an effective therapy for multiple sclerosis. Rituximab has been associated with the development of serum sickness (type III hypersensitivity) characterized by arthralgia, fever, and rash during the treatment of other conditions, such as rheumatoid arthritis. Here we describe serum sickness associated with rituximab in multiple sclerosis patients and discuss both the management of serum sickness itself and implications for utilizing alternative anti-CD20 monoclonal antibodies for disease management in this patient population.

OBJECTIVES/OBJECTIVE:The objective of this study was to compare safety and efficacy of patent foramen ovale (PFO) closure compared with medical therapy in patients with cryptogenic stroke (CS). BACKGROUND:The role of PFO closure in preventing recurrent stroke in patients with prior CS has been controversial. METHODS:We searched PubMed, EMBASE, the Cochrane Central Register of Controlled trials, and the clinical trial registry maintained at clinicaltrials.gov for randomized control trials that compared device closure with medical management and reported on subsequent stroke and adverse events. Event rates were compared using a forest plot of relative risk using a random-effects model assuming interstudy heterogeneity. RESULTS: = 27%, P = 0.002). The presence/absence of atrial septal aneurysm (P = 0.52) had no effect on the outcome. CONCLUSION/CONCLUSIONS:PFO closure is associated with a significant reduction in the risk of stroke compared to medical management. However, it causes an increased risk of atrial fibrillation.