Missed opportunities to screen for Barrett's esophagus in the primary care setting of a large health system.

BACKGROUND AND AIMS: The rate of esophageal adenocarcinoma (EAC) is rising. This is partly due to the lack of identification of Barrett's esophagus (BE), the main risk factor for EAC. Identifying neoplastic BE can allow for endoscopic therapy to prevent EAC. Our aim was to determine how many patients eligible for screening are actually being screened for BE in the primary care setting of a large health system. METHODS: A digital search algorithm was constructed using the established gastroenterology guidelines and the Kunzmann model for screening for BE. The algorithm was then applied to the electronic medical record of all patients seen in the primary care setting of the health system. A manual review of charts of the identified patients was performed to confirm the high-risk status and determine if screening occurred. RESULTS: Of 936,371 primary care charts analyzed by the algorithm, 3535 patients (.4%) were determined to be high-risk for BE. Of these 3535 patients, only 1077 (30%) were screened for BE in clinical practice with endoscopy. The algorithm identified 2458 (70%) additional high-risk patients. Of the patients screened in clinical practice, 105 (10%) were found to have BE (10% with neoplasia). CONCLUSIONS: Numerous screening opportunities for BE are missed in the primary care setting of a large health system. Collaboration between gastroenterology and primary care services is needed to improve the screening rate.

Discriminating Acute Respiratory Distress Syndrome from other forms of respiratory failure via iterative machine learning.

Acute Respiratory Distress Syndrome (ARDS) is associated with high morbidity and mortality. Identification of ARDS enables lung protective strategies, quality improvement interventions, and clinical trial enrolment, but remains challenging particularly in the first 24 hours of mechanical ventilation. To address this we built an algorithm capable of discriminating ARDS from other similarly presenting disorders immediately following mechanical ventilation. Specifically, a clinical team examined medical records from 1263 ICU-admitted, mechanically ventilated patients, retrospectively assigning each patient a diagnosis of "ARDS" or "non-ARDS" (e.g., pulmonary edema). Exploiting data readily available in the clinical setting, including patient demographics, laboratory test results from before the initiation of mechanical ventilation, and features extracted by natural language processing of radiology reports, we applied an iterative pre-processing and machine learning framework. The resulting model successfully discriminated ARDS from non-ARDS causes of respiratory failure (AUC = 0.85) among patients meeting Berlin criteria for severe hypoxia. This analysis also highlighted novel patient variables that were informative for identifying ARDS in ICU settings.

Artificial intelligence-enhanced volumetric laser endomicroscopy improves dysplasia detection in Barrett's esophagus in a randomized cross-over study.

Volumetric laser endomicroscopy (VLE) is an advanced endoscopic imaging tool that can improve dysplasia detection in Barrett's esophagus (BE). However, VLE scans generate 1200 cross-sectional images that can make interpretation difficult. The impact of a new VLE artificial intelligence algorithm called Intelligent Real-time Image Segmentation (IRIS) is not well-characterized. This is a randomized prospective cross-over study of BE patients undergoing endoscopy who were randomized to IRIS-enhanced or unenhanced VLE first followed by the other (IRIS-VLE vs. VLE-IRIS, respectively) at expert BE centers. The primary outcome was image interpretation time, which served as a surrogate measure for ease of interpretation. The secondary outcome was diagnostic yield of dysplasia for each imaging modality. 133 patients were enrolled. 67 patients were randomized to VLE-IRIS and 66 to IRIS-VLE. Total interpretation time did not differ significantly between groups (7.8 min VLE-IRIS vs. 7 min IRIS-VLE, P = 0.1), however unenhanced VLE interpretation time was significantly shorter in the IRIS-VLE group (2.4 min vs. 3.8 min, P < 0.01). When IRIS was used first, 100% of dysplastic areas were identified, compared with 76.9% when VLE was the first interpretation modality (P = 0.06). IRIS-enhanced VLE reduced the time of subsequent unenhanced VLE interpretation, suggesting heightened efficiency and improved dysplasia detection. It was also able to identify all endoscopically non-visible dysplastic areas.

Refining the risk of HTLV-1-associated myelopathy in people living with HTLV-1: identification of a HAM-like phenotype in a proportion of asymptomatic carriers.

Up to 3.8% of human T-lymphotropic virus type-1 (HTLV-1)-infected asymptomatic carriers (AC) eventually develop HTLV-1-associated myelopathy (HAM). HAM occurs in patients with high (> 1%) HTLV proviral load (PVL). However, this cut-off includes more than 50% of ACs and therefore the risk needs to be refined. As HAM is additionally characterised by an inflammatory response to HTLV-1, markers of T cell activation (TCA), ß2-microglobulin (ß2M) and neuronal damage were accessed for the identification of ACs at high risk of HAM. Retrospective analysis of cross-sectional and longitudinal routine clinical data examining differences in TCA (CD4/CD25, CD4/HLA-DR, CD8/CD25 & CD8/HLA-DR), ß2M and neurofilament light (NfL) in plasma in ACs with high or low PVL and patients with HAM. Comparison between 74 low PVL ACs, 84 high PVL ACs and 58 patients with HAM revealed a significant, stepwise, increase in TCA and ß2M. Construction of receiver operating characteristic (ROC) curves for each of these blood tests generated a profile that correctly identifies 88% of patients with HAM along with 6% of ACs. The 10 ACs with this 'HAM-like' profile had increased levels of NfL in plasma and two developed myelopathy during follow-up, compared to none of the 148 without this viral-immune-phenotype. A viral-immuno-phenotype resembling that seen in patients with HAM identifies asymptomatic carriers who are at increased risk of developing HAM and have markers of subclinical neuronal damage.

Female Athletes Exhibit Greater Trial-to-Trial Coordination Variability When Provided with Instructions Promoting an External Focus.

The purpose of this study was to examine how instructions promoting different attentional foci influence joint coordination patterns and trial-to-trial coordination variability during landing. Sixteen females performed drop landings with their typical technique (baseline) and after receiving instructions promoting an internal focus and an external focus. The coordination patterns, and trial-to-trial coordination variability, of the sagittal plane hip-knee, hip-ankle, and knee-ankle angle pairings were compared across conditions. While there was no difference in the joint coordination patterns among the conditions, subjects exhibited greater hip-ankle and knee-ankle trial-to-trial coordination variability for the external focus condition, vs. the baseline and internal focus conditions, which may help to explain the improved motor learning outcomes for athletes who train with an external focus.

Trajectories of hypoxemia and pulmonary mechanics of COVID-19 ARDS in the NorthCARDS dataset.

BACKGROUND: Understanding heterogeneity seen in patients with COVIDARDS and comparing to non-COVIDARDS may inform tailored treatments. METHODS: A multidisciplinary team of frontline clinicians and data scientists worked to create the Northwell COVIDARDS dataset (NorthCARDS) leveraging over 11,542 COVID-19 hospital admissions. The data was then summarized to examine descriptive differences based on clinically meaningful categories of lung compliance, and to examine trends in oxygenation. FINDINGS: Of the 1536 COVIDARDS patients in the NorthCARDS dataset, there were 531 (34.6%) who had very low lung compliance (< 20 ml/cmH2O), 970 (63.2%) with low-normal compliance (20-50 ml/cmH2O), and 35 (2.2%) with high lung compliance (> 50 ml/cmH2O). The very low compliance group had double the median time to intubation compared to the low-normal group (107.3 h (IQR 25.8, 239.2) vs. 39.5 h (IQR 5.4, 91.6)). Overall, 68.8% (n = 1057) of the patients died during hospitalization. In comparison to non-COVIDARDS reports, there were less patients in the high compliance category (2.2% vs. 12%, compliance ≥ 50 mL/cmH20), and more patients with P/F ≤ 150 (59.8% vs. 45.6%). There is a statistically significant correlation between compliance and P/F ratio. The Oxygenation Index is the highest in the very low compliance group (12.51, SD(6.15)), and lowest in high compliance group (8.78, SD(4.93)). CONCLUSIONS: The respiratory system compliance distribution of COVIDARDS is similar to non-COVIDARDS. In some patients, there may be a relation between time to intubation and duration of high levels of supplemental oxygen treatment on trajectory of lung compliance.

Neuromuscular training programs predominantly include instructions that promote an internal focus.

Neuromuscular training programs that include movement pattern retraining and strengthening, plyometric, and balance exercises are recommended for anterior cruciate ligament injury prevention. Recent evidence suggests that the effectiveness of these programs may be enhanced when athletes train with an external focus; however, clinicians typically rely predominantly on instructions encouraging an internal focus. The aim of this study was to examine the types of instructions provided as part of popular neuromuscular training programs used for anterior cruciate ligament injury prevention. The technique-related instructions provided as part of the FIFA 11+, HarmoKnee, Knakontroll, and Prevent Injury and Enhance Performance programs were categorized as either promoting an internal focus or an external focus. Instructions provided during movement pattern retraining tasks and strengthening, plyometric, and balance training exercises were specifically examined. Next, the percentage of technique-related instructions that promoted an internal focus, versus the percentage that promoted an external focus, were compared for the various program components. Across all programs examined, the vast majority of technique-related instructions for the movement pattern re-training tasks (≥83.3%) and the strengthening, balance, and plyometric exercises (≥75.0%) appeared to promote an internal focus. Despite evidence suggesting that the effectiveness of neuromuscular training programs may be enhanced by encouraging an external focus, most technique-related instructions provided as part of popular neuromuscular training programs appear to promote an internal focus. Modifying neuromuscular training programs to promote a more external focus could help to improve the effectiveness of these programs for anterior cruciate ligament injury prevention.

Investigating blunt force trauma to the larynx: The role of inferior-superior vocal fold displacement on phonation.

Blunt force trauma to the larynx, which may result from motor vehicle collisions, sports activities, etc., can cause significant damage, often leading to displaced fractures of the laryngeal cartilages, thereby disrupting vocal function. Current surgical interventions primarily focus on airway restoration to stabilize the patient, with restoration of vocal function usually being a secondary consideration. Due to laryngeal fracture, asymmetric vertical misalignment of the left or right vocal fold (VF) in the inferior-superior direction often occurs. This affects VF closure and can lead to a weak, breathy voice requiring increased vocal effort. It is unclear, however, how much vertical VF misalignment can be tolerated before voice quality degrades significantly. To address this need, the influence of inferior-superior VF displacement on phonation is investigated in 1.0mm increments using synthetic, self-oscillating VF models in a physiologically-representative facility. Acoustic (SPL, frequency, H1-H2, jitter, and shimmer), kinematic (amplitude and phase differences), and aerodynamic parameters (flow rate and subglottal pressure) are investigated as a function of inferior-superior vertical displacement. Significant findings include that once the inferior-superior medial length of the VF is surpassed, sustained phonation degrades precipitously, becoming severely pathological. If laryngeal reconstruction approaches can ensure VF contact is maintained during phonation (i.e., vertical displacement doesn't surpass VF medial length), improved vocal outcomes are expected.

Adjunctive Yield of Wide-Area Transepithelial Sampling for Dysplasia Detection After Advanced Imaging and Random Biopsies in Barrett's Esophagus.

INTRODUCTION: Little is known about the additive yield of wide-area transepithelial sampling with computer-assisted three-dimensional analysis (WATS-3D) after a thorough examination with advanced imaging. The aim was to evaluate the adjunctive yield of WATS-3D after advanced imaging. METHODS: This is an observational cohort study from January 2017 to December 2018 for consecutive patients who underwent an examination that consists of high-definition white light endoscopy (HDWLE), narrow-band imaging (NBI), volumetric laser endomicroscopy (VLE), and Seattle protocol (SP) biopsies (collectively termed HDWLE-NBI-VLE-SP examination). Raised lesions were removed by endoscopic resection. Areas suspicious for dysplasia on NBI and VLE were biopsied. This was followed by random biopsies and WATS-3D brush biopsies. RESULTS: One hundred thirty-eight cases were included in this study. Thirty-five cases (25% of the total) were identified as some degree of dysplasia on the HDWLE-NBI-VLE-SP examination. Adjunctive use of WATS-3D yielded an additional 12 new cases of dysplasia (9 with crypt dysplasia and 3 with low-grade dysplasia [LGD]), for added yield of 34.3% (=12/35, 95% confidence interval 14.6%-62.2%). When restricting the analysis to LGD and higher, 21 dysplastic cases (15% of the total cases) were identified by HDWLE-NBI-VLE-SP, while WATS-3D found 4 additional new cases (3 with LGD and 1 with high-grade dysplasia) for an added yield of 19% (=4/21, 95% confidence interval 0.6%-45.7%). DISCUSSION: The addition of WATS-3D to an already thorough examination with HDWLE-NBI-VLE-SP may increase the yield of dysplasia detection.

Volumetric laser endomicroscopy features of dysplasia at the gastric cardia in Barrett's oesophagus: results from an observational cohort study.

OBJECTIVE: Volumetric laser endomicroscopy (VLE) is an advanced imaging modality used in Barrett's oesophagus (BE) to help identify dysplasia in the oesophagus. VLE criteria exist for oesophageal dysplasia but not for dysplasia in the gastric cardia. The aim of this study was to determine if there are in vivo VLE features that can predict gastric cardia dysplasia in BE. DESIGN: This was a single-centre observational cohort study from August 2016 to August 2018. Patients were included if they had BE, were undergoing a VLE exam as standard of care, and had a suspicious target laser marked at the gastric cardia. The following VLE features were correlated to histology to determine if an association existed between histology subtype and VLE feature: wide crypts, irregular surface, one large isolated gland, multiple glands, and complex glands. RESULTS: A total of 110 in vivo gastric cardia targets in 77 patients with BE were analysed. The following abnormalities were identified: 61 wide crypts, 34 isolated glands, 16 irregular surfaces, 15 multiple glands, and 11 complex glands. Complex glands were the only VLE feature that correlated to any histology subtype. They were present in 71% of targets with high-grade dysplasia (HGD), T1a cancer or T1b cancer and had a sensitivity, specificity, and accuracy of 71%, 99%, and 85%, respectively. Of the 10 patients with complex glands on VLE and HGD/cancer on histology, 4 had a normal-appearing mucosa (40%) on endoscopy. CONCLUSION: Identification of complex glands on VLE may aid in detection of HGD or early cancer in the gastric cardia in BE. This is particularly important, as dysplasia at the gastric cardia can be difficult to see endoscopically.

Digital cholangioscopy can detect residual biliary stones missed by occlusion cholangiogram in ERCP: a prospective tandem study.

Background and study aims After stone removal in endoscopic retrograde cholangiopancreatography (ERCP), an occlusion cholangiogram (OC) is performed to confirm bile duct clearance. OC can miss residual stones that can lead to recurrent biliary symptoms. The aim of this study was to assess if digital peroral cholangioscopy (POC) increased the diagnostic yield of residual biliary stones that are missed with OC. Patients and methods Patients having ERCP performed for choledocholithiasis were enrolled into the study only if they had one of the following criteria: dilated bile duct ≥ 12 mm and/or if lithotripsy was being performed. An OC was performed to confirm duct clearance after removal of stones followed by POC, based on inclusion criteria. The incremental yield of biliary stones missed by OC but confirmed by POC was then measured. A total of 96 POC procedures were performed on 93 patients in two tertiary care centers. Results Residual biliary stones were found in 34 % of cases. The average bile duct size in cases with residual stones was 15.1 mm ±â€Š0.7 mm. One- to three-mm stones were found in 41 % of cases, 4- to 7-mm stones in 45 % of cases, and ≥ 8-mm stones in 14 % of cases. Lithotripsy was performed in 13 % of cases and was significantly associated with residual stones (30 % vs. 3 %, P  < 0.001). Conclusions Occlusion cholangiogram can miss residual stones in patients with dilated bile ducts and those receiving lithotripsy. Digital POC can increase the yield of residual stone detection in these patients and should be considered to confirm clearance of stones. (ClinicalTrials.gov-NCT03482375).

Mutational load may predict risk of progression in patients with Barrett's oesophagus and indefinite for dysplasia: a pilot study.

BACKGROUND AND AIMS: Mutational load (ML) has been shown to help risk-stratify those that may progress from non-dysplastic Barrett's oesophagus (BE) to dysplastic disease. Management of patients with BE and indefinite for dysplasia (BE-IND) is challenging and risk stratification tools are lacking. The aim of this pilot study is to evaluate the utility of ML for risk stratification in patients with BE-IND. METHODS: This is a single-centre, retrospective pilot study evaluating ML quantification in patients with BE-IND. Histology at follow-up endoscopy at least 1 year after the baseline endoscopy was used to determine if a patient progressed to low or high dysplasia. The ML levels were then compared among patients who progressed to dysplasia versus those who did not. RESULTS: Thirty-five patients who met the inclusion criteria were identified, and seven met the exclusion criteria. Twenty-eight patients were analysed, of whom eight progressed to low-grade dysplasia (6) and high-grade dysplasia (2). Seven of these eight patients had some level of genomic instability detected in their IND biopsy (ML ≥0.5). Ten of the 20 (50%) who did not progress had no ML level. At an ML cut-off above 1.5, the risk of progression to high-grade dysplasia was 33% vs 0% (p=0.005), with a sensitivity of 100% and a specificity of 85%. CONCLUSION: These results indicate that ML may be able to risk-stratify progression to high-grade dysplasia in BE-IND. Larger studies are needed to confirm these findings.

Incremental yield of dysplasia detection in Barrett's esophagus using volumetric laser endomicroscopy with and without laser marking compared with a standardized random biopsy protocol.

BACKGROUND AND AIMS: Volumetric laser endomicroscopy (VLE) is a new wide-field advanced imaging technology for Barrett's esophagus (BE). No data exist on incremental yield of dysplasia detection. Our aim is to report the incremental yield of dysplasia detection in BE using VLE. METHODS: This is a retrospective study from a prospectively maintained database from 2011 to 2017 comparing the dysplasia yield of 4 different surveillance strategies in an academic BE tertiary care referral center. The groups were (1) random biopsies (RB), (2) Seattle protocol random biopsies (SP), (3) VLE without laser marking (VLE), and (4) VLE with laser marking (VLEL). RESULTS: A total of 448 consecutive patients (79 RB, 95 SP, 168 VLE, and 106 VLEL) met the inclusion criteria. After adjusting for visible lesions, the total dysplasia yield was 5.7%, 19.6%, 24.8%, and 33.7%, respectively. When compared with just the SP group, the VLEL group had statistically higher rates of overall dysplasia yield (19.6% vs 33.7%, P = .03; odds ratio, 2.1, P = .03). Both the VLEL and VLE groups had statistically significant differences in neoplasia (high-grade dysplasia and intramucosal cancer) detection compared with the SP group (14% vs 1%, P = .001 and 11% vs 1%, P = .003). CONCLUSION: A surveillance strategy involving VLEL led to a statistically significant higher yield of dysplasia and neoplasia detection compared with a standard random biopsy protocol. These results support the use of VLEL for surveillance in BE in academic centers.

Domestic violence in the Solomon Islands.

The Solomon Islands has one of the highest rates of family and sexual violence (FSV) in the world with 64% of women aged 15-49 have reported physical and/or sexual abuse by a partner. The National Referral Hospital (NRH) in the capital, Honiara, is the only tertiary hospital for the country. Our 4-week medical elective at the NRH was spent reflecting on healthcare challenges including FSV, with the aim of identifying cases of FSV and assessing on the current strategies to improve care for victims. Throughout our placement, we encountered many cases of probable FSV, particularly in the Emergency Department and Obstetrics and Gynecology. These patients were often not managed effectively, largely due to time pressures and overcrowding in the hospital. However, we identified a number of strategies, which have recently been implemented in order to help FSV victims in the Solomon Islands. These include strategies within the healthcare setting, in particular, the commencement of FSV reporting within the hospital, and the production of a manual to enable healthcare worker education on the issue. Strategies within the criminal justice system are also in place. These include recent changes in legislation and the work of the volunteer police force, Royal Assist Mission to the Solomon Islands, to improve attitudes toward FSV. These approaches to tackle the problem of FSV are currently in their early stages and have largely stemmed from Western policies and ideals. This report concludes that more time is needed to accurately assess the impact of the current changes before further recommendations are made.

Dopaminergic toxicity of the herbicide atrazine in rat striatal slices.

A possible link between Parkinson's disease and pesticide exposure has been suggested, and recently it was shown that the herbicide atrazine (ATR) modulates catecholamine metabolism in PC12 cells and affects basal ganglia function in vivo. Hence, the objectives of this study were to: (i) determine if ATR is capable of modulating dopamine (DA) metabolism in striatal tissue slices in vitro and (ii) explore possible mechanisms of its effects. Striatal tissues from adult male Sprague-Dawley rats were incubated with up to 500 microM ATR in a metabolic shaker bath at 37 degrees C and an atmosphere of 95% O(2) and 5% CO(2) for 4h. At the end of incubation, samples were collected for both tissue and media levels of DA and its metabolites (3,4-dihydroxyphenylacetic acid, DOPAC and homovanillic acid, HVA), which were determined by high-performance liquid chromatography with electrochemical detection (HPLC-ECD). To gain some mechanistic insight in to the way ATR affects DA metabolism, several pharmacological manipulations were performed. Striata exposed to ATR at concentrations of 100 microM and greater had a dose-dependent decrease of tissue levels of DA. At doses of ATR 50 microM and greater, the DOPAC+HVA/DA ratio was dose-dependently increased. Tyrosine hydroxylase (TH, the rate-limiting enzyme in DA synthesis) protein levels and activity were not affected by ATR treatment. However, high potassium-induced DA release into the medium was decreased, whereas the increase in media DA observed in the presence of the DA uptake inhibitor nomifensine was increased even further by ATR in a dose-dependent manner. All of these effects of ATR were observed at levels that were not toxic to the tissue, as LDH release into the medium (lactate dehydrogenase, an index of non-specific cytotoxicity) was not affected by ATR. Taken together, results from this study suggest that ATR decreases tissue DA levels not by affecting TH activity, but possibly by interfering with the vesicular storage and/or cellular uptake of DA.