Citations

AbstractINTRODUCTIONThe Rey Auditory Verbal Learning Test (RAVLT) is a useful neuropsychological test for describing episodic memory impairment in dementia. However, there is limited research on its utility in early‐onset Alzheimer's disease (EOAD). We assess the influence of amyloid and diagnostic syndrome on several memory scores in EOAD.METHODSWe transcribed RAVLT recordings from 303 subjects in the Longitudinal Early‐Onset Alzheimer's Disease Study. Subjects were grouped by amyloid status and syndrome. Primacy, recency, J‐curve, duration, stopping time, and speed score were calculated and entered into linear mixed effects models as dependent variables.RESULTSCompared with amyloid negative subjects, positive subjects exhibited effects on raw score, primacy, recency, and stopping time. Inter‐syndromic differences were noted with raw score, primacy, recency, J‐curve, and stopping time.DISCUSSIONRAVLT measures are sensitive to the effects of amyloid and syndrome in EOAD. Future work is needed to quantify the predictive value of these scores.Highlights RAVLT patterns characterize various presentations of EOAD and EOnonAD Amyloid impacts raw score, primacy, recency, and stopping time Timing‐based scores add value over traditional count‐based scores

Abstract Objectives To describe and assess the feasibility of an ultrasound-guided technique for intra-articular injection of the costovertebral joints, in an unembalmed cadaveric specimen, utilizing fluoroscopy and cone beam computerized tomography for confirmation of contrast spread and needle tip position, respectively. Methodology A single unembalmed cadaveric specimen was obtained. A single interventionist performed the placement of the needles under ultrasound guidance. Contrast dye was then injected through each of the needles under real-time fluoroscopy. Finally, the specimen was submitted to a cone beam computerized tomography with 3-dimensional acquisition and multiplanar reformatting to assess final needle tip position relative to the costovertebral joints. Results In total, 18 spinal needles were placed under ultrasound guidance. Fluoroscopy showed 4 distinct patterns of contrast spread: intra-articular in the costovertebral joint (13 levels in total), epidural (1 level), intra-articular in the facet joint of the target level (3 levels), and undetermined (1 level). Cone-beam computerized tomography confirmed 13 out of 18 needles to be adequately placed in the costovertebral joints (72% of the total) and 5 out of the 18 needles to be misplaced: 3 needles were placed in the facet joint of the target level, and 2 needles were placed in the epidural space. Conclusions This study suggests that, when performed by experienced interventionists, this technique has an accuracy rate of 72%. Further studies are warranted before these results can be extrapolated to daily clinical practice.

Background Matters of workplace harassment are an important issue. This issue needs to be recognized and studied to prevent occurrences. These important sensitive areas of effective workplace management are increasingly gaining more interest. We aimed to identify the prevalence of workplace sexual, verbal and physical harassment among headache professionals. Methods We adopted a cross‑sectional exploratory survey approach with quantitative design. The survey was distributed electronically among headache healthcare and research professionals globally through the International Headache Society (IHS). Results Data were obtained from 579 respondents (55.3%; 320/579 women). A large percentage of respondents (46.6%; 270/579) had experienced harassment; specifically, 16.1% (93/578) reported sexual harassment, 40.4% (234/579) verbal harassment and 5.5% (32/579) physical harassment. Women were almost seven times more likely to experience sexual harassment compared to men (odds ratio = 6.8; 95% confidence interval = 3.5–13.2). Although women did also more frequently report other types of harassment, this was not statistically significant (odds ratio = 1.4; 95% confidence interval = 1.0–2.0). Conclusions Lifetime exposure to workplace harassment is prevalent among headache professionals, especially in women. The present study uncovers a widespread issue and calls for strategies to be implemented for building a healthy and safe workplace environment.

AbstractBackgroundCoronary calcification is a strong indicator of coronary artery disease, and patients with a “zero” coronary calcification score have a much lower risk of future cardiac events than those with even small amounts of calcium. However, false‐negative (incorrect zero scores) may occur if small calcifications are missed at CT due to limited spatial resolution.PurposeTo demonstrate lower limits of detection for coronary calcification using an ultra‐high‐resolution (UHR) mode on a clinical photon‐counting‐detector CT (PCD‐CT), compared to a conventional energy‐integrating‐detector CT (EID‐CT).MethodsChicken eggshell fragments (0.4–0.8 mm) mimicking coronary calcifications were scanned on a clinical PCD‐CT (NAEOTOM Alpha) in UHR mode and a conventional EID‐CT (SOMATOM Force) with matched tube potential and radiation dose levels to the PCD‐CT. PCD‐CT images were reconstructed with a sharp kernel (Qr68) and a quantum iterative algorithm (QIR‐3). Two sets of EID‐CT images were reconstructed: routine clinical kernel (Qr36, ADMIRE‐3) and a sharper kernel (Qr54) with similar noise to PCD‐CT images. With institutional review board approval, in vivo exams performed with the PCD‐CT in UHR mode were compared against patients’ clinical EID‐CT exams. The visibility of calcifications on PCD‐CT and EID‐CT images was assessed and compared qualitatively.ResultsPCD‐CT images visualized all calcified fragments, while EID‐CT failed to detect those below 0.6 mm using a routine protocol. EID‐CT with Qr54 improved visibility but distorted boundaries. Calcifications were less visible on EID‐CT than PCD‐CT as phantom sizes increased. 0.6‐ and 0.7‐mm calcified fragments were barely visible on 35‐ and 40‐cm phantom EID‐CT images. Patient cases showed small calcifications missed on EID‐CT but detected on PCD‐CT.ConclusionAt matched radiation dose, PCD‐CT in UHR mode provided higher spatial resolution and improved the detectability of small calcified fragments for different phantom/patient sizes in comparison to EID‐CT.

To investigate downstream molecular changes caused by mitogen-activated protein kinase (MEK) inhibitor treatment and further explore the impact of direct knockdown of early growth response-1 (EGR1) in melanoma cell culture. RNA-sequencing (RNA-Seq) was performed to determine gene expression changes with MEK inhibitor treatment. Treatment with MEK inhibitor (trametinib) was then assessed in two cutaneous (MEL888, MEL624) and one conjunctival (YUARGE 13-3064) melanoma cell line. Direct knockdown of EGR1 was accomplished using lentiviral vectors containing shRNA. Cell viability was measured using PrestoBlueHS Cell Viability Reagent. Total RNA and protein were assessed by qPCR and SimpleWestern. RNA-Seq demonstrated a profound reduction in EGR1 with MEK inhibitor treatment, prompting further study of melanoma cell lines. Following trametinib treatment of melanoma cells, viability was reduced in both cutaneous (MEL888 26%, P < 0.01; MEL624 27%, P < 0.001) and conjunctival (YUARGE 13-3064 33%, P < 0.01) melanoma compared with DMSO control, with confirmed EGR1 knockdown to 0.04-, 0.01-, and 0.16-fold DMSO-treated levels (all P < 0.05) in MEL888, MEL624, and YUARGE 13-3064, respectively. Targeted EGR1 knockdown using shRNA reduced viability in both cutaneous (MEL624 78%, P = 0.05) and conjunctival melanoma (YUARGE-13-3064 67%, P = 0.02). RNA-Sequencing in MEK inhibitor-treated cells identified EGR1 as a candidate effector molecule of interest. In a malignant melanoma cell population, MEK inhibition reduced viability in both cutaneous and conjunctival melanoma with a profound downstream reduction in EGR1 expression. Targeted knockdown of EGR1 reduced both cutaneous and conjunctival melanoma cell viability independent of MEK inhibition, suggesting a key role for EGR1 in melanoma pathobiology.

Abstract Background Given the complexity of inflammatory bowel disease (IBD) care, utilization of multidisciplinary teams is recommended to optimize outcomes. There is a growing recognition that clinical pharmacists should be an integral part of this care model. We sought to define the roles of IBD clinical pharmacists in the United States. Methods A national multidisciplinary expert panel of 12 gastroenterologists and clinical pharmacists practicing in IBD clinics was assembled. We used the RAND/University of California, Los Angeles appropriateness method, with a total of 281 statements generated based on a systematic literature review and expert opinion. Each statement was anonymously rated as appropriate, uncertain, or inappropriate in 2 rounds of voting. Results The number of publications evaluating the clinical pharmacists’ roles in IBD is limited, primarily focusing on thiopurine initiation and monitoring, medication adherence, and switching to biosimilars. Medication education; medication initiation and monitoring; therapeutic drug monitoring; biosimilar management; health maintenance review; and transitions of care were deemed by the panel to be appropriate roles for IBD clinical pharmacists. In considering real-world settings, IBD clinical pharmacists should practice clinically under a predefined scope and primarily focus on complex treatments (eg, immunomodulators, biologics, and small molecules). Clinical pharmacists should also be included in practice settings with IBD specialized physicians. Additionally, clinical pharmacists caring for patients with IBD should be residency trained and board certified. Conclusions This consensus defines IBD clinical pharmacists’ roles and provides a framework for embedded clinical pharmacists in IBD care.