Faculty Bibliography

Many studies have reported that heavy substance use is associated with impaired response inhibition. Studies typically focused on associations with a single substance, while polysubstance use is common. Further, most studies compared heavy users with light/non-users, though substance use occurs along a continuum. The current mega-analysis accounted for these issues by aggregating individual data from 43 studies (3610 adult participants) that used the Go/No-Go (GNG) or Stop-signal task (SST) to assess inhibition among mostly "recreational" substance users (i.e., the rate of substance use disorders was low). Main and interaction effects of substance use, demographics, and task-characteristics were entered in a linear mixed model. Contrary to many studies and reviews in the field, we found that only lifetime cannabis use was associated with impaired response inhibition in the SST. An interaction effect was also observed: the relationship between tobacco use and response inhibition (in the SST) differed between cannabis users and non-users, with a negative association between tobacco use and inhibition in the cannabis non-users. In addition, participants' age, education level, and some task characteristics influenced inhibition outcomes. Overall, we found limited support for impaired inhibition among substance users when controlling for demographics and task-characteristics.

OBJECTIVE:The current Phase 2b study aimed to evaluate the efficacy of mindfulness-based cognitive therapy for migraine (MBCT-M) to reduce migraine-related disability in people with migraine. BACKGROUND:Mindfulness-based interventions represent a promising avenue to investigate effects in people with migraine. MBCT teaches mindfulness meditation and cognitive-behavioral skills and directly applies these skills to address disease-related cognitions. METHODS:Participants with migraine (6-30 headache days/month) were recruited from neurology office referrals and local and online advertisements in the broader New York City area. During the 30-day baseline period, all participants completed a daily headache diary. Participants who met inclusion and exclusion criteria were randomized in a parallel design, stratified by chronic migraine status, to receive either 8 weekly individual MBCT-M sessions or 8 weeks of waitlist/treatment as usual (WL/TAU). All participants completed surveys including primary outcome evaluations at Months 0, 1, 2, and 4. All participants completed a headache diary during the 30-day posttreatment evaluation period. Primary outcomes were the change from Month 0 to Month 4 in the headache disability inventory (HDI) and the Migraine Disability Assessment (MIDAS) (total score ≥ 21 indicating severe disability); secondary outcomes (headache days/30 days, average headache attack pain intensity, and attack-level migraine-related disability [Migraine Disability Index (MIDI)]) were derived from the daily headache diary. RESULTS:Sixty participants were randomized to receive MBCT-M (n = 31) or WL/TAU (n = 29). Participants (M age = 40.1, SD = 11.7) were predominantly White (n = 49/60; 81.7%) and Non-Hispanic (N = 50/60; 83.3%) women (n = 55/60; 91.7%) with a graduate degree (n = 35/60; 55.0%) who were working full-time (n = 38/60; 63.3%). At baseline, the average HDI score (51.4, SD = 19.0) indicated a moderate level of disability and the majority of participants (50/60, 83.3%) fell in the "Severe Disability" range in the MIDAS. Participants recorded an average of 16.0 (SD = 5.9) headache days/30 days, with an average headache attack pain intensity of 1.7 on a 4-point scale (SD = 0.3), indicating moderate intensity. Average levels of daily disability reported on the MIDI were 3.1/10 (SD = 1.8). For the HDI, mean scores decreased more from Month 0 to Month 4 in the MBCT-M group (-14.3) than the waitlist/treatment as an usual group (-0.2; P < .001). For the MIDAS, the group*month interaction was not significant when accounting for the divided alpha, P = .027; across all participants in both groups, the estimated proportion of participants falling in the "Severe Disability" category fell significantly from 88.3% at Month 0 to 66.7% at Month 4, P < .001. For diary-reported headache days/30 days an average headache attack pain intensity, neither the group*month interaction (Ps = .773 and .888, respectively) nor the time effect (Ps = .059 and .428, respectively) was significant. Mean MIDI scores decreased in the MBCT-M group (-0.6/10), whereas they increased in the waitlist/treatment as an usual group (+0.3/10), P = .007. CONCLUSIONS:MBCT-M demonstrated efficacy to reduce headache-related disability and attack-level migraine-related disability. MBCT-M is a promising emerging treatment for addressing migraine-related disability.

Background. CRAb is a major cause of healthcare-associated infections and is associated with high mortality due to the lack of reliable treatment options. We aimed to elucidate the contemporary population structure of CRAb isolates circulating in US hospitals using whole-genome sequencing (WGS). Methods. A total of 131 CRAb isolates were identified at four tertiary care medical centers located in Ohio, Pennsylvania, Texas and North Carolina between 2017 and 2018. The genomes were sequenced with Illumina NextSeq and De novo assembled. Sequence types (STs) were identified using the Pasteur Institute MLST scheme. beta-Lactamase genes were identified by ResFinder and manually curated. Results. The 131 isolates belonged to 10 different ST types, including 8 known and 2 novel ones. In this collection, 101 isolates (77.1%) belonged to ST2, the dominant drug-resistant clone in the United States and Europe; 20 isolates belonged to ST499, a less common, but also globally distributed clone. Two isolates each belonged to ST46 and ST79, both common in South America. For the chromosomally encoded blaOXA-51-group genes, 11 variants were identified with blaOXA-66, blaOXA-82, and blaOXA-95 being predominant. For the chromosomally encoded blaADC-group genes, 26 variants were identified, with blaADC-161, blaADC-181, and blaADC-30 being the most common. The most frequent acquired carbapenemase gene was blaOXA-23, which was present in 89 isolates (67.9%). Other acquired blaOXA carbapenemase genes were identified much less frequently and included blaOXA-24, blaOXA-72, blaOXA-207, and blaOXA-237. 17 isolates (13.0%) did not contain any known acquired carbapenemase genes despite resistance to carbapenems. Conclusion. ST2 is the most prevalent ST type among contemporary CRAb isolates identified in US hospitals, however, new STs are emerging, most notably ST499. Significant diversity was seen among chromosomal blaOXA-51-group carbapenemase, intrinsic blaADC-group cephalosporinase and plasmid-mediated blaOXA-group carbapenemase genes, which likely represented diversification within the STs. Correlations between clinical presentation and outcomes and the genomic features of the infecting isolates are being investigated

Aneurysm size correlates with rupture risk and is important for treatment planning. User annotation of aneurysm size is slow and tedious, particularly for large data sets. Geometric shortcuts to compute size have been shown to be inaccurate, particularly for nonstandard aneurysm geometries. To develop and train a convolutional neural network (CNN) to detect and measure cerebral aneurysms from magnetic resonance angiography (MRA) automatically and without geometric shortcuts. In step 1, a CNN based on the U-net architecture was trained on 250 MRA maximum intensity projection (MIP) images, then applied to a testing set. In step 2, the trained CNN was applied to a separate set of 14 basilar tip aneurysms for size prediction. Step 1-the CNN successfully identified aneurysms in 85/86 (98.8% of) testing set cases, with a receiver operating characteristic (ROC) area-under-the-curve of 0.87. Step 2-automated basilar tip aneurysm linear size differed from radiologist-traced aneurysm size on average by 2.01 mm, or 30%. The CNN aneurysm area differed from radiologist-derived area on average by 8.1 mm² or 27%. CNN correctly predicted the area trend for the set of aneurysms. This approach is to our knowledge the first using CNNs to derive aneurysm size. In particular, we demonstrate the clinically pertinent application of computing maximal aneurysm one-dimensional size and two-dimensional area. We propose that future work can apply this to facilitate pre-treatment planning and possibly identify previously missed aneurysms in retrospective assessment.

INTRODUCTION: Familial dysautonomia (FD) is a progressive neurogenetic disease with carrier rate as high as 1 in 18 persons in European Jews of Polish origin. Clinical hallmarks include cardiovascular instability, spinal deformities, renal dysfunction, alacrima, ataxia, and impaired nociception. Physical or emotional stress may elicit autonomic crises characterized by hypertension and vomiting. Despite profound sensory deficits, GI perturbations are frequently reported by FD patients. While the incidence of inflammatory bowel disease (IBD) and FD is unknown, concurrence is underreported given increased frequency of both diseases in Ashkenazi Jews. CASE DESCRIPTION/METHODS: We report a 33-year-old female with FD and ulcerative colitis who presented with one week of abdominal pain and bloody diarrhea. She had been maintained on balsalazide. Colonoscopy one year prior revealed endoscopic and histologic remission. On physical examination, her abdomen was tender in the lower quadrants. A CT scan revealed pancolitis. Stool studies resulted negative. Her CRP was 58.4 mg/L and albumin was 2.4 g/dL. A flexible sigmoidoscopy noted Mayo endoscopic score 3 in the rectum and CMV staining was negative. The patient was started on IV steroids. Her hospital course was complicated by ileus, parainfluenza infection, and MSSA bacteremia with a pacemaker lead vegetation, requiring extraction. Lack of optimal clinical response to treatment on hospital day five led to consideration of alternative treatments with careful attention to her underlying FD. A subtotal colectomy with end ileostomy was unfavorable due to concern for volume loss. Infliximab and cyclosporine were opposed due to infection risk and later exhibiting possible nephrotoxicity. During this discussion the patient improved enough to be transitioned to oral steroids with a plan to initiate vedolizumab as an outpatient. On recent colonoscopy she had achieved mucosal healing. DISCUSSION: This is the first case of UC in a FD patient reported. Given myriad GI symptoms in the later diagnosis it can be hard to distinguish disease-related from treatment-related events. Due to the gut-specificity of vedolizumab, infection risk is considerably reduced compared to that of other biologics and is the most favorable option in the setting of underlying FD. This case highlights the difficulty encountered when treating IBD in the setting of systemic illness and underscores the need to carefully consider management options to enhance patient outcomes. (Figure Presented)

Background: Midline catheters (MCs) have arisen as alternatives to peripherally inserted central catheters (PICCs) for both general intravenous therapy and extended outpatient parenteral therapy. However, there is a lack of data concerning the safety of medication therapy through midline for extended durations. Objective: The purpose of this study is to evaluate the safety of MCs for extended intravenous use. Methods: This was a retrospective cohort study evaluating patients who received intravenous therapy through an MC at a tertiary care academic medical center. The primary end point was the incidence of composite catheter-related adverse events that included local events, catheter dislodgment, infiltration, catheter occlusion, catheter-related venous thromboembolism, extravasation, and line-associated infection. Results: A total of 82 MC placements and 50 PICC placements were included; 50 MCs were for outpatient parenteral antimicrobial therapy, and 32 were for inpatient intravenous use. There were 21 complications per 1000 catheter-days in the outpatient group and 7 complications per 1000 catheter-days in the PICC group (P = 0.91). The median time to complication in both groups was 8 days. The antimicrobial classes commonly associated with complications were cephalosporins, carbapenems, and penicillins. Conclusion and Relevance: Our results suggest that intravenous therapy with MCs is generally safe for prolonged courses that do not exceed 14 days as compared with PICC lines, which can be placed for months. There is still limited evidence for the use of MCs between 14 and 28 days of therapy. This study can help guide our selection of intravenous catheters for the purpose of outpatient antimicrobial therapy.

OBJECTIVE:We recently detected a significant racial difference in our population with temporal lobe epilepsy (TLE) at the University of Alabama at Birmingham (UAB) seizure monitoring unit. We found that Black patients were more likely than their White counterparts to carry a TLE diagnosis. Using this same patient population, we focus on the patients with TLE to better describe the relationship between race and epidemiology in this population. METHODS:We analyzed the data from patients diagnosed with TLE admitted to the UAB seizure monitoring unit between January 2000 and December 2011. For patients with a video electroencephalography (EEG) confirmed diagnosis of TLE (n = 385), basic demographic information including race and magnetic resonance imaging (MRI) findings were collected. Descriptive statistics and multivariate logistic regression were used to explore the relationship between MRI findings, demographic data, and race. RESULTS:For Black patients with TLE, we found that they were more likely to be female (odds ratio [OR] = 1.91, 95% confidence interval [CI]: 1.14-3.19), have seizure onset in adulthood (OR = 2.39, 95% CI: 1.43-3.19), and have normal MRIs (OR = 1.69, 95% CI: 1.04-2.77) compared to White counterparts with TLE after adjusting for covariates. CONCLUSIONS:These data suggest that Black race (compared to White) is associated with higher expression of adult-onset MRI-negative TLE, an important subtype of epilepsy with unique implications for evaluation, treatment, and prognosis. If validated in other cohorts, the findings may explain the lower reported rates of epilepsy surgery utilization among Blacks. The racial differences in surgical utilization could be due to a greater prevalence of an epilepsy that is less amenable to surgical resection rather than to cultural differences or access to care.