Effectiveness of the 2023-to-2024 XBB.1.5 COVID-19 Vaccines Over Long-Term Follow-up: A Target Trial Emulation: Annals of Internal Medicine: Vol 178, No 3

Background: Monovalent COVID-19 vaccines targeting the XBB.1.5 Omicron variant were introduced in September 2023. In the absence of randomized controlled trials demonstrating their efficacy, information on real-world vaccine effectiveness (VE) is needed. Objective: To determine XBB.1.5 COVID-19 VE and the extent to which it declines over time. Design: Target trial emulation. Setting: U.S. Veterans Health Administration. Participants: Eligible XBB.1.5 vaccine recipients were matched 1:1 to unvaccinated persons in 7 sequential biweekly trials with enrollment from 2 October 2023 through 3 January 2024. Intervention: XBB.1.5 COVID-19 vaccination versus no XBB.1.5 vaccination. Measurements: Outcomes were ascertained through 10 May 2024 and included any positive result on a SARS-CoV-2 test from day 10 after the matched index date, subsequent hospitalization within 1 day before or 10 days after the positive result, or death within 30 days after the positive result. Vaccine effectiveness was estimated as 100 × (1 − risk ratio). Results: Participants (91.3% male; mean age, 69.9 years) included 587 137 pairs of vaccinated and matched unvaccinated persons. Over a mean follow-up of 176 days (range, 118 to 211 days), VE was −3.26% (95% CI, −6.78% to −0.22%) against documented SARS-CoV-2 infection, 16.64% (CI, 6.47% to 25.77%) against SARS-CoV-2–associated hospitalization, and 26.61% (CI, 5.53% to 42.32%) against SARS-CoV-2–associated death. When estimated at 60, 90, and 120 days, respectively, VE against documented infection (14.21%, 7.29%, and 3.15%), hospitalization (37.57%, 30.84%, and 25.25%), or death (54.24%, 44.33%, and 30.25%) showed substantial waning. Limitation: Potential for residual confounding and incomplete capture of COVID-19 vaccination and SARS-CoV-2–related outcomes. Conclusion: COVID-19 vaccines targeting the XBB.1.5 variant of Omicron were not effective in preventing infection and had relatively low VE against hospitalization and death, which declined rapidly over time. Primary Funding Source: U.S. Department of Veterans Affairs.

Artificial Intelligence–Assisted Colonoscopy for Polyp Detection: A Systematic Review and Meta-analysis: Annals of Internal Medicine: Vol 177, No 12

Background: Randomized clinical trials (RCTs) of computer-aided detection (CADe) system–enhanced colonoscopy compared with conventional colonoscopy suggest increased adenoma detection rate (ADR) and decreased adenoma miss rate (AMR), but the effect on detection of advanced colorectal neoplasia (ACN) is unclear. Purpose: To conduct a systematic review to compare performance of CADe-enhanced and conventional colonoscopy. Data Sources: Cochrane Library, Google Scholar, Ovid EMBASE, Ovid MEDLINE, PubMed, Scopus, and Web of Science Core Collection databases were searched through February 2024. Study Selection: Published RCTs comparing CADe-enhanced and conventional colonoscopy. Data Extraction: Average adenoma per colonoscopy (APC) and ACN per colonoscopy were primary outcomes. Adenoma detection rate, AMR, and ACN detection rate (ACN DR) were secondary outcomes. Balancing outcomes included withdrawal time and resection of nonneoplastic polyps (NNPs). Subgroup analyses were done by neural network architecture. Data Synthesis: Forty-three RCTs with 34 896 cases were included. Computer-aided detection–enhanced colonoscopies have higher average APC (12 090 of 12 279 [0.98] vs. 9690 of 12 292 [0.78], incidence rate difference [IRD] = 0.22 [95% CI, 0.16 to 0.28]) and higher ADR (6951 of 15 523 [44.8%] vs. 5669 of 15 151 [37.4%], rate ratio [RR] = 1.22 [CI, 1.16 to 1.29]). Average ACN per colonoscopy was similar (1512 of 9296 [0.16] vs. 1392 of 9121 [0.15], IRD = 0.01 [CI, −0.01 to 0.02]), but ACN DR was higher with CADe system use (1260 of 9899 [12.7%] vs. 1119 of 9746 [11.5%], RR = 1.16 [CI, 1.02 to 1.32]). Using CADe systems resulted in resection of almost 2 extra NNPs per 10 colonoscopies and longer total withdrawal time (0.57 minutes [CI, 0.34 to 0.81]). Limitation: Statistically significant heterogeneity in quality and sample size and inability to blind endoscopists to the intervention in included studies may affect the performance estimates. Conclusion: Computer-aided detection–enhanced colonoscopies have increased APC and adenoma detection rate but no difference in ACN per colonoscopy and a small increase in ACN DR. There is minimal increase in procedure time and no difference in performance across neural network architectures. Primary Funding Source: None. (PROSPERO: CRD42023422835)

Projected Impact and Cost-Effectiveness of Novel Molecular Blood-Based or Stool-Based Screening Tests for Colorectal Cancer

Background: Cell-free DNA blood tests (cf-bDNA) and next-generation stool tests could change colorectal cancer (CRC) screening. Objective: To estimate the clinical and economic impacts of novel CRC screening tests. Design: Cost-effectiveness analysis using MOSAIC (Model of Screening and Surveillance for Colorectal Cancer). Data sources: Published data. Target Population: Average-risk persons. Time Horizon: Ages 45 to 100 years. Perspective: Health sector. Intervention: Novel versus established CRC screening tests. Outcome Measures: Incidence and mortality of CRC, quality-adjusted life-years (QALYs), costs. Results of Base-Case Analysis: For colonoscopy every 10 years, annual fecal immunochemical test (FIT), and triennial next-generation multitarget stool DNA, FIT-RNA, cf-bDNA (Guardant Shield), or cf-bDNA (Freenome), the relative rates (RRs) and 95% uncertainty intervals (UIs) versus no screening for CRC incidence were 0.21 (0.19 to 0.22), 0.29 (0.27 to 0.31), 0.33 (0.32 to 0.36), 0.32 (0.30 to 0.34), 0.58 (0.55 to 0.61) and 0.58 (0.55 to 0.60), respectively; the RRs for CRC death were 0.19 (0.17 to 0.20), 0.25 (0.23 to 0.27), 0.28 (0.27 to 0.30), 0.28 (0.26 to 0.30), 0.44 (0.42 to 0.47), and 0.46 (0.44 to 0.49), respectively. The cf-bDNA test (Shield; list price $1495) cost $89 600 ($74 800 to $102 300) per QALY gained versus no screening; alternatives were less costly and more effective. Results of Sensitivity Analysis: Incremental costs exceeded incremental benefits when novel test intervals were shortened to 2 or 1 years. The cf-bDNA test matched FIT’s impact on CRC mortality at 1.35 (1.30 to 1.40)-fold FIT’s uptake rate, assuming equal colonoscopy follow-up. If persons who accept colonoscopy or stool tests shifted to cf-bDNA, CRC deaths increased. This adverse effect was overcome if every 3 such substitutions were counterbalanced by cf-bDNA uptake by 2 or more persons refusing alternatives, assuming equal colonoscopy follow-up. Limitation: Longitudinal test-specific participation patterns are unknown. Conclusion: First-generation cf-bDNA tests may deliver net benefit or harm, depending on the balance between achieving screening in persons who decline alternatives versus substituting cf-bDNA for more effective alternatives. Primary Funding Source: The Gorrindo Family Fund.

Association of Work Control With Burnout and Career Intentions Among U.S. Physicians: A Multi-institution Study: Annals of Internal Medicine: Vol 178, No 1

Background: Physician control over their clinical work is hypothesized to be associated with both burnout and career intentions. Objective: To assess the association of perceived work control with burnout and career intentions. Design: A multi-institution study. Setting: Cross-sectional survey. Participants: A sample of U.S. physicians between November 2022 and December 2023. Measurements: A novel multicomponent measure of work control, Mini-Z single-item burnout measure, intent to reduce clinical hours (ITR), and intent to leave the current practice. Results: Among respondents, 61.4% (1318 of 2144) reported adequate control over patient load, 60.6% (1301 of 2144) adequate control over membership of their clinical team, and 61.3% (1434 of 2339) adequate control over workload. Adequate control over hiring of staff and clinical schedule were reported by 49.0% (772 of 1574) and 74.6% (1175 of 1574), respectively. Most respondents (58.3% [692 of 1186]) reported that they had sufficient authority/autonomy over that for which they are accountable. On multivariable analyses adjusting for personal and professional characteristics, poor control over patient load, team composition, clinical schedule, domains for which the physician is accountable, and workload were independently associated with burnout. Poor control over patient load and workload were each independently associated with ITR. Limitation: This is a cross-sectional study, so causation cannot be determined, and it is a convenience sample of practices with more than 100 physicians, so it may not be representative of all U.S. physicians. Conclusion: In this large, cross-sectional study, poor control over specific aspects of work was associated with burnout and intentions to reduce clinical effort or leave one’s organization. Efforts to reduce burnout and improve retention should consider how to provide physician control over appropriate aspects of their clinical work environment. Primary Funding Source: American Medical Association.

In grade C/D erosive esophagitis, vonoprazan ranks highest among PPIs and P-CABs for healing and maintaining remission

Source Citation Zhuang Q, Chen S, Zhou X, et al. Comparative efficacy of P-CAB vs proton pump inhibitors for grade C/D esophagitis: a systematic review and network meta-analysis. Am J Gastroenterol. 2024;119:803-813. 38345252

Increasing Incidence and Stable Mortality of Pancreatic Cancer in Young Americans

In transfusion-dependent, angiodysplasia-related anemia, adding octreotide to usual care reduced transfusions at 1 y

Source Citation Goltstein LC, Grooteman KV, Bernts LH, et al. Standard of care versus octreotide in angiodysplasia-related bleeding (the OCEAN study): a multicenter randomized controlled trial. Gastroenterology. 2024;166:690-703. 38158089

In NASH with liver fibrosis, resmetirom improved NASH resolution and reduced fibrosis at 1 y

Source Citation Harrison SA, Bedossa P, Guy CD, et al. MAESTRO-NASH Investigators. A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis. N Engl J Med. 2024;390:497-509. 38324483

Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) is a condition that occurs when reflux of gastric contents into the esophagus causes symptoms and/or complications. The prevalence of GERD in Western societies has been estimated at 30%, making it one of the most commonly encountered disorders in primary care. The spectrum of GERD includes typical symptoms of esophageal reflux (heartburn and/or regurgitation); esophageal injury (erosive esophagitis; stricture; Barrett esophagus; and, rarely, adenocarcinoma); and extraesophageal symptoms, such as hoarseness and chronic cough. Proper diagnosis and treatment of GERD includes symptom control, exclusion of other disorders, avoiding overuse of medications and invasive testing, and minimizing complications.

Screening for Colorectal Cancer

Colorectal cancer (CRC) is the second leading cause of cancer death. Screening has been proven to reduce both cancer incidence and cancer-related mortality. Various screening tests are available, each with their own advantages and disadvantages and varying levels of evidence to support their use. Clinicians should offer CRC screening to average-risk persons aged 50 to 75 years; starting screening at age 45 years remains controversial. Screening may be beneficial in select persons aged 76 to 85 years, based on their overall health and screening history. Offering a choice of screening tests or sequentially offering an alternate test for those who do not complete screening can significantly increase participation.