Implementation of Billing for Patient Portal Messages as E-visits in a Large Integrated Health System

Background: Patient–provider communication through the patient portal has markedly increased in recent years. Some health care facilities implemented programs to enable providers to bill for responding to patient-initiated messages that require substantive medical decision making through an e-visit. Objective: To evaluate the effect of billing eligible patient-initiated portal messages as e-visits using a mixed-methods approach. Design: Retrospective observational pre–post comparison and prospective survey. Setting: Large integrated health system with sites in 4 U.S. states. Participants: Patients initiating portal message threads and health system providers completing an online survey. Intervention: E-visit billing was implemented 18 August 2023. Measurements: The volume of patient-initiated medical advice message threads pre- versus postimplementation of e-visit billing was compared. Health system provider perceptions of e-visit billing were assessed using an online survey. Results: In the 6 months after e-visit billing implementation (18 August 2023 through 18 February 2024), the volume of patient-initiated medical advice message threads decreased by 8.8% (from 1 813 818 to 1 653 708) compared with the same dates the year prior (P = 0.002). A total of 5183 (0.3%) medical advice messages were billed. There was no difference in 7-day use of emergency services (emergency department visits or hospitalizations) in patients who proceeded with sending a message versus those that did not send a message after viewing the billing disclaimer on the patient portal. Providers reported overall acceptance of e-visit billing but expressed concerns about increased workload with the current process. Limitation: Cannot assess changes in other forms of contact, including telephone calls. Conclusion: These findings suggest that implementation of e-visit billing was associated with a modest decrease in patient-initiated portal message volume and was overall acceptable to providers in a large integrated health system. Primary Funding Source: None.

Thyroid Function Reference Intervals by Age, Sex, and Race: A Cross-Sectional Study: Annals of Internal Medicine: Vol 178, No 7

Background: Current clinical practice uses a one-size-fits-all approach to define reference intervals for the results of diagnostic tests about thyroid function. This approach does not recognize subgroup differences according to age, sex, or race. Objective: To identify age-, sex-, and race-specific reference intervals for the common diagnostic tests that measure thyroid function and to examine how these new reference intervals reclassify persons into disease categories when compared with current reference intervals. Design: Cross-sectional analysis. Setting: Data from the U.S. NHANES (National Health and Nutrition Examination Survey) supplemented with data from a multicenter Chinese study. Participants: A nationally representative sample from NHANES aged 20 years or older (n = 8308) supplemented with a Chinese database of routine health checkups from 49 hospitals in 10 provinces aged 18 years or older (n = 314 302). Measurements: The thyroid function reference interval was defined as the interval of diagnostic indicator levels from the 2.5th (lower limit) to the 97.5th (upper limit) percentile by age, sex, and race subgroups. Results: In 8308 NHANES participants, the 97.5th percentile levels of thyroid-stimulating hormone (TSH) increased with age, whereas total triiodothyronine (TT3) levels declined with age and total thyroxine (TT4) levels were stable across different ages. Women had higher TT4 levels, and White participants had higher TSH levels. Using current reference intervals, the prevalence of subclinical hypothyroidism increased from 2.4% for ages 20 to 29 years to 5.9% for ages 70 years and older. In contrast, using age-, sex-, and race-specific reference intervals reclassified 48.5% of persons with subclinical hypothyroidism as normal, especially women and White participants, and reclassified 31.2% of persons with subclinical hyperthyroidism as normal, especially women, Black participants, and Hispanic participants. When compared with the findings from U.S. participants, many of the findings from 314 302 Chinese participants were similar. Limitation: Cross-sectional data; sample size limitations for subgroup. Conclusion: These findings should help establish more accurate reference intervals for thyroid diseases and facilitate development of a consensus about how to define and manage those diseases. Primary Funding Source: National Key Research and Development Program of China and National Natural Science Foundation.

Impaired Wnt/Planar Cell Polarity Signaling in Yellow Nail Syndrome

Background: Yellow nail syndrome (YNS) is a rare disorder characterized by a triad of yellow dystrophic nails, lymphedema, and chronic lung disease. Most patients present in adulthood, with only a few congenital or familial cases described. The cause of YNS remains largely unknown, although defects in lymphatic vessel development are suggested to play a significant role. Objective: To elucidate the genetic mechanisms underlying YNS. Design: Analysis of genetic sequencing data and gene and protein expression studies. Setting: A tertiary care academic medical center. Patients: 6 patients with congenital YNS (cYNS) and 5 with sporadic YNS (sYNS). Measurements: Exome and genome sequencing were used to detect disease-causing variants, complemented by RNA analyses for intronic variants. Protein and gene expressions were studied by immunofluorescence staining and real-time reverse transcriptase quantitative polymerase chain reaction analyses. Results: Biallelic variants in CELSR1 (n = 5) or likely FZD6 (n = 1), both core molecules in the Wnt/planar cell polarity (PCP) pathway, were identified in all patients with cYNS; none of the patients with sYNS had candidate genetic variants. Immunofluorescence staining showed that CELSR1 colocalizes with lymphatic vessels in the skin but not in the lungs or the intestine. Moreover, levels of CELSR1 and FZD6 proteins were negligible to zero in patient tissues (n = 2) compared with control tissues. Gene expression of Wnt/PCP–related genes was reduced in patients with cYNS (n = 3), and patients with sYNS (n = 4) showed milder gene expression impairments. Limitation: Small cohort size and limited sample availability. Conclusion: Defects in PCP organization may play a major role in the pathogenesis of YNS. To the authors’ knowledge, this is the first demonstration of a mechanism explaining YNS development, mainly in its congenital form but also in patients with sporadic disease. Primary Funding Source: The Prof. Baum Research Fund of Israel Lung Association.

Patterns in Mental Health– and Substance Use–Related Visits From 2003 to 2022 Among Registered Ontario Physicians

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