Severe Acute Respiratory Syndrome Coronavirus 2 Delta Variant Genomic Variation Associated With Breakthrough Infection in Northern California: A Retrospective Cohort Study.

BACKGROUND: The association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic variation and breakthrough infection is not well defined among persons with Delta variant SARS-CoV-2 infection. METHODS: In a retrospective cohort, we assessed whether individual nonlineage defining mutations and overall genomic variation (including low-frequency alleles) were associated with breakthrough infection, defined as SARS-CoV-2 infection after coronavirus disease 2019 primary vaccine series. We identified all nonsynonymous single-nucleotide polymorphisms, insertions, and deletions in SARS-CoV-2 genomes with ≥5% allelic frequency and population frequency of ≥5% and ≤95%. Using Poisson regression, we assessed the association with breakthrough infection for each individual mutation and a viral genomic risk score. RESULTS: Thirty-six mutations met our inclusion criteria. Among 12 744 persons infected with Delta variant SARS-CoV-2, 5949 (47%) were vaccinated and 6795 (53%) were unvaccinated. Viruses with a viral genomic risk score in the highest quintile were 9% more likely to be associated with breakthrough infection than viruses in the lowest quintile, but including the risk score improved overall predictive model performance (measured by C statistic) by only +0.0006. CONCLUSIONS: Genomic variation within SARS-CoV-2 Delta variant was weakly associated with breakthrough infection, but several potential nonlineage defining mutations were identified that might contribute to immune evasion by SARS-CoV-2.

Identification of visible lesions during surveillance endoscopy for Barrett's esophagus: a video-based survey study.

BACKGROUND AND AIMS: Visible lesion (VL) detection is essential in patients with Barrett's esophagus (BE). We sought to assess the rate of VL detection by academic and community endoscopists using high-definition white-light endoscopy (HD-WLE) and narrow-band imaging (NBI) during surveillance endoscopy. METHODS: Fifty endoscopists were invited to participate in a prospective video survey study. Participants viewed 25 standardized clips of patients referred for endoscopic therapy. Participants noted identification of anatomic landmarks and VLs using HD-WLE and NBI and reported practice-level data. The criterion standard of VL identification was established by consensus of 5 BE experts. Our primary outcome was the rate of VL identification using HD-WLE and NBI. RESULTS: Forty-four of 50 participants completed the study (22 academic and 22 community). Compared with the criterion standard, participants did not identify 28% (HD-WLE) and 31% (NBI) of VLs. Community endoscopists had more experience (>5 years in practice: community 85% vs academic 54.5%, P = .041; >5 surveillance endoscopies a month: community 85% vs academic 31.8%, P = .046). Across all participants, VL detection using NBI improved significantly with a minimum of 5 surveillance endoscopies per month (area under the curve = .72; 95% confidence interval, .56-.85; P = .006). CONCLUSIONS: Despite improved endoscope resolution and availability of virtual chromoendoscopy, the overall rate of VL detection remains low. Identification of VLs using NBI may be volume dependent. Further education and training efforts focused on VL detection during BE surveillance endoscopy are needed.

Recurrence Is Rare Following Complete Eradication of Intestinal Metaplasia in Patients With Barrett's Esophagus and Peaks at 18 Months.

BACKGROUND & AIMS: There have been few studies describing the long-term durability of complete eradication of intestinal metaplasia (CE-IM) in patients with Barrett's esophagus (BE)-related neoplasia who received endoscopic eradication therapy (EET). Data are needed to guide surveillance interval protocols and identify patients at risk for recurrence. We assessed the rate of recurrence of intestinal metaplasia and dysplasia, histologic features, and outcomes after recurrence of CE-IM, and identified factors associated with recurrence. METHODS: We performed a prospective study of 807 patients with BE who underwent EET, which produced CE-IM, at 4 tertiary-care referral centers, from January 2013 to October 2018. Kaplan-Meier estimates of cumulative incidence rates (IR) of recurrence were calculated for up to 5 years following CE-IM and were stratified by baseline level of histology. Density estimates of recurrence were used to determine the change in the rate of recurrence over time. We conducted logistic regression analysis to identify factors associated with recurrence. RESULTS: Intestinal metaplasia recurred in 121 patients (15%; IR, 5.2/100 person-years), and dysplasia recurred in 41 patients (5.1%; IR, 1.8/100 person-years), after a median follow-up time of 2317 person-years. The rate of recurrence was not constant and the time to any recurrence converged to a normal distribution; recurrences peaked at 1.6 y after patients had CE-IM. Baseline high-grade dysplasia or intramucosal cancer (adjusted odds ratio [aOR], 4.19), presence of reflux symptoms (aOR, 12.1) or hiatal hernia (aOR, 13.8), and number of sessions required to achieve CE-IM (aOR, 1.8) were associated with recurrence. CONCLUSIONS: In a prospective study of a large cohort of patients with BE undergoing EET, we found a low rate of recurrence after CE-IM. The rate of recurrence peaked at 1-2 y after CE-IM. These findings indicate that aggressive surveillance might not be necessary more than 1 y after CE-IM and should be considered in surveillance guidelines. Clinicaltrials.gov no: NCT02634645.

Colon polypectomy report card improves polypectomy competency: results of a prospective quality improvement study (with video).

BACKGROUND AND AIMS: Polypectomy competency varies significantly among providers. Poor polypectomy technique may lead to interval cancer and/or adverse events. Our aim was to determine the effect of a polypectomy skills report card on subsequent polypectomy performance. METHODS: We conducted a 3-phase, prospective, single-blinded study. In phase 1 ("baseline"), we graded 10 polypectomies per endoscopist using the Direct Observation of Polypectomy Skills (DOPyS) tool (scores 1-4); mean overall scores ≥3 are competent. In phase 2 ("pre-report card"), we selected 10 additional polypectomies per endoscopist. We subsequently gave endoscopists a report card with baseline scores and instructional videos demonstrating optimal polypectomy technique. In phase 3 ("post-report card"), 10 additional polypectomies per endoscopist were selected. Raters, blinded to study phase, graded 10 pre- and 10 post-report card polypectomies per endoscopist. We compared mean DOPyS scores and rate of competent polypectomy in the pre- and post-report card phases. RESULTS: We graded 110 pre- and 110 post-report card polypectomies performed by 11 endoscopists. The mean DOPyS score increased between the pre- and post-report card phases (2.7 ± .9 vs 3.0 ± .8, P = .01); this improvement was seen for diminutive (P < .0001) but not for small-to-large polyps. Rate of competent polypectomy significantly improved from the pre- to post-report card phase (56% vs 69%, P = .04); this improvement was seen for diminutive (57% vs 81%, P = .001) but not for small-to-large polyps (55% vs 36%, P = .2). CONCLUSIONS: Report cards with educational videos effectively improved polypectomy technique, primarily because of improvements in resecting diminutive polyps. The improved competency and decreased piecemeal resection may reduce the risk of polyp recurrence. Further education is needed to improve larger polyp resection.

Anatomic location of Barrett's esophagus recurrence after endoscopic eradication therapy: development of a simplified surveillance biopsy strategy.

BACKGROUND AND AIMS: Surveillance endoscopy is recommended after endoscopic eradication therapy (EET) for Barrett's esophagus (BE) because of the risk of recurrence. Currently recommended biopsy protocols are based on expert opinion and consist of sampling visible lesions followed by random 4-quadrant biopsy sampling throughout the length of the original BE segment. Despite this protocol, some recurrences are not visibly identified. We aimed to identify the anatomic location and histology of recurrences after successful EET with the goal of developing a more efficient and evidence-based surveillance biopsy protocol. METHODS: We performed an analysis of a large multicenter database of 443 patients who underwent EET and achieved complete eradication of intestinal metaplasia (CE-IM) from 2005 to 2015. The endoscopic location of recurrence relative to the squamocolumnar junction (SCJ), visible recurrence identified during surveillance endoscopy, and time to recurrence after CE-IM were assessed. RESULTS: Fifty patients with BE recurrence were studied in the final analysis. Seventeen patients (34%) had nonvisible recurrences. In this group, biopsy specimens demonstrating recurrence were taken from within 2 cm of the SCJ in 16 of these 17 patients (94%). Overall, 49 of 50 recurrences (98%) occurred either within 2 cm of the SCJ or at the site of a visible lesion. Late recurrences (>1 year) were more likely to be visible than early (<1 year) recurrences (P = .006). CONCLUSIONS: Recurrence after EET detected by random biopsy sampling is identified predominately in the distal esophagus and occurs earlier than visible recurrences. As such, we suggest a modified biopsy protocol with targeted sampling of visible lesions followed by random biopsy sampling within 2 cm of the SCJ to optimize detection of recurrence after EET. (Clinical trial registration number: NCT02634645.).

Individualized feedback on colonoscopy skills improves group colonoscopy quality in providers with lower adenoma detection rates.

Background and study aims Colonoscopy inspection quality (CIQ) assesses skills (fold examination, cleaning, and luminal distension) during inspection for polyps and correlates with adenoma detection rate (ADR) and serrated detection rate (SDR). We aimed to determine whether providing individualized CIQ feedback with instructional videos improves quality metrics performance. Methods We prospectively studied 16 colonoscopists who already received semiannual benchmarked reports of quality metrics (ADR, SDR, and withdrawal time [WT]). We randomly selected seven colonoscopies/colonoscopist for evaluation. Six gastroenterologists graded CIQ using an established scale. We created instructional videos demonstrating optimal and poor inspection techniques. Colonoscopists received the instructional videos and benchmarked CIQ performance. We compared ADR, SDR, and WT in the 12 months preceding ("baseline") and following CIQ feedback. Colonoscopists were stratified by baseline ADR into lower (≤ 34 %) and higher-performing (> 34 %) groups. Results Baseline ADR was 38.5 % (range 26.8 %-53.8 %) and SDR was 11.2 % (2.8 %-24.3 %). The proportion of colonoscopies performed by lower-performing colonoscopists was unchanged from baseline to post-CIQ feedback. All colonoscopists reviewed their CIQ report cards. Post-feedback, ADR (40.1 % vs 38.5 %, P  = 0.1) and SDR (12.2 % vs. 11.2 %, P  = 0.1) did not significantly improve; WT significantly increased (11.4 vs 12.4 min, P  < 0.01). Among the eight lower-performing colonoscopists, group ADR (31.1 % vs 34.3 %, P  = 0.02) and SDR (7.2 % vs 9.1 %, P  = 0.02) significantly increased post-feedback. In higher-performing colonoscopists, ADR and SDR did not change. Conclusions CIQ feedback modestly improves ADR and SDR among colonoscopists with lower baseline ADR but has no effect on higher-performing colonoscopists. Individualized feedback on colonoscopy skills could be used to improve polyp detection by lower-performing colonoscopists.

Risk of severe clinical outcomes among persons with SARS-CoV-2 infection with differing levels of vaccination during widespread Omicron (B.1.1.529) and Delta (B.1.617.2) variant circulation in Northern California: A retrospective cohort study.

Background: The incidence of and risk factors for severe clinical outcomes with the Omicron (B.1.1.529) SARS-CoV-2 variant have not been well-defined. Methods: We conducted a retrospective cohort study to assess risks of severe clinical outcomes within 21 days after SARS-CoV-2 diagnosis in a large, diverse, integrated health system. Findings: Among 118,078 persons with incident SARS-CoV-2 infection, 48,101 (41%) were during the Omicron period and 69,977 (59%) during the Delta (B.1.617.2) period. Cumulative incidence of any hospitalization (2.4% versus 7.8%; adjusted hazard ratio [aHR] 0.55; 95% confidence interval [CI] (0.51-0.59), with low-flow oxygen support (1.6% versus 6.4%; aHR 0.46; CI 0.43-0.50), with high-flow oxygen support (0.6% versus 2.8%; aHR 0.47; CI 0.41-0.54), with invasive mechanical ventilation (0.1% versus 0.7%; aHR 0.43; CI 0.33-0.56), and death (0.2% versus 0.7%; aHR 0.54; CI 0.42-0.70) were lower in the Omicron than the Delta period. The risk of hospitalization was higher among unvaccinated persons (aHR 8.34; CI 7.25-9.60) and those who completed a primary COVID-19 vaccination series (aHR 1.72; CI 1.49-1.97) compared with those who completed a primary vaccination series and an additional dose. The strongest risk factors for all severe clinical outcomes were older age, higher body mass index and select comorbidities. Interpretation: Persons with SARS-CoV-2 infection were significantly less likely to develop severe clinical outcomes during the Omicron period compared with the Delta period. COVID-19 primary vaccination and additional doses were associated with reduced risk of severe clinical outcomes among those with SARS-CoV-2 infection. Funding: National Cancer Institute and The Permanente Medical Group.

Development and validation of a prediction algorithm to identify birth in countries with high tuberculosis incidence in two large California health systems.

OBJECTIVE: Though targeted testing for latent tuberculosis infection ("LTBI") for persons born in countries with high tuberculosis incidence ("HTBIC") is recommended in health care settings, this information is not routinely recorded in the electronic health record ("EHR"). We develop and validate a prediction model for birth in a HTBIC using EHR data. MATERIALS AND METHODS: In a cohort of patients within Kaiser Permanente Southern California ("KPSC") and Kaiser Permanent Northern California ("KPNC") between January 1, 2008 and December 31, 2019, KPSC was used as the development dataset and KPNC was used for external validation using logistic regression. Model performance was evaluated using area under the receiver operator curve ("AUCROC") and area under the precision and recall curve ("AUPRC"). We explored various cut-points to improve screening for LTBI. RESULTS: KPSC had 73% and KPNC had 54% of patients missing country-of-birth information in the EHR, leaving 2,036,400 and 2,880,570 patients with EHR-documented country-of-birth at KPSC and KPNC, respectively. The final model had an AUCROC of 0.85 and 0.87 on internal and external validation datasets, respectively. It had an AUPRC of 0.69 and 0.64 (compared to a baseline HTBIC-birth prevalence of 0.24 at KPSC and 0.19 at KPNC) on internal and external validation datasets, respectively. The cut-points explored resulted in a number needed to screen from 7.1-8.5 persons/positive LTBI diagnosis, compared to 4.2 and 16.8 persons/positive LTBI diagnosis from EHR-documented birth in a HTBIC and current screening criteria, respectively. DISCUSSION: Using logistic regression with EHR data, we developed a simple yet useful model to predict birth in a HTBIC which decreased the number needed to screen compared to current LTBI screening criteria. CONCLUSION: Our model improves the ability to screen for LTBI in health care settings based on birth in a HTBIC.

Colonoscopy education delivered via the patient portal does not improve adherence to scheduled first-time screening colonoscopy.

Background and study aims Non-adherence to scheduled colonoscopy burdens endoscopic practices and innovative approaches to improve adherence are needed. We aimed to assess the effect of an educational video emphasizing colonoscopy importance delivered through the electronic health record patient portal upon "no-show" and late cancellation rates (non-adherence) in patients scheduled for first-time screening colonoscopy. Patients and methods We conducted a single center randomized controlled trial among patients scheduled for their first screening colonoscopy. Patients were randomized to routine care ("control") or video education ("video"). Control patients received a portal message 14 days prior to colonoscopy date; video patients additionally received a link to the educational video. Results In total, 830 patients (59 % female, median age 55 years) were randomized ("control": 406; "video": 424). Nearly all (88 %) opened the message; in the video arm, most (72 %) watched a majority of the video. Overall, 80 % attended their scheduled colonoscopy appointment (late cancel: 18 %, "no show": 1 %) and 90 % underwent colonoscopy within 3 months of appointment. Adherence rates did not differ between video and control arms for the scheduled appointment (OR 1.2, CI 0.9-1.8) or for colonoscopy within 3 months of scheduled appointment (OR 1.3, CI 0.8-2.1). Bowel preparation quality did not differ between the groups. Conclusion Most patients scheduled for colonoscopy will open a patient portal message and, when delivered, watch an educational video. However, delivery of an educational video two weeks prior to screening colonoscopy appointment did not improve adherence.

Athletic equipment microbiota are shaped by interactions with human skin.

BACKGROUND: Americans spend the vast majority of their lives in built environments. Even traditionally outdoor pursuits, such as exercising, are often now performed indoors. Bacteria that colonize these indoor ecosystems are primarily derived from the human microbiome. The modes of human interaction with indoor surfaces and the physical conditions associated with each surface type determine the steady-state ecology of the microbial community. RESULTS: Bacterial assemblages associated with different surfaces in three athletic facilities, including floors, mats, benches, free weights, and elliptical handles, were sampled every other hour (8 am to 6 pm) for 2 days. Surface and equipment type had a stronger influence on bacterial community composition than the facility in which they were housed. Surfaces that were primarily in contact with human skin exhibited highly dynamic bacterial community composition and non-random co-occurrence patterns, suggesting that different host microbiomes-shaped by selective forces-were being deposited on these surfaces through time. However, bacterial assemblages found on the floors and mats changed less over time, and species co-occurrence patterns appeared random, suggesting more neutral community assembly. CONCLUSIONS: These longitudinal patterns highlight the dramatic turnover of microbial communities on surfaces in regular contact with human skin. By uncovering these longitudinal patterns, this study promotes a better understanding of microbe-human interactions within the built environment.