Birth Cohort Effects in Appendiceal Adenocarcinoma Incidence Across the United States

Background: Incidence rates of appendiceal adenocarcinoma (AA) are increasing across all age groups in the United States. Birth cohort patterns of AA can provide new, etiologic clues into increasing rates but have not been examined. Objective: To estimate incidence rates of AA across birth cohorts in the United States. Design: Retrospective cohort study. Setting: The National Institutes of Health and National Cancer Institute SEER (Surveillance, Epidemiology, and End Results) Program of 8 population-based cancer registries. Patients: A total of 4858 persons aged 20 years or older when diagnosed with a pathologically confirmed primary AA (nonmucinous, mucinous, goblet cell, or signet ring cell carcinoma) from 1975 to 2019. Measurements: Five-year age groups and time periods were used to create 21 overlapping birth cohorts (1891–1899 to 1991–1999). The ratio of age-specific incidence rates was estimated in each birth cohort relative to the 1945 birth cohort (birth years 1941 to 1949) and reported as incidence rate ratios (IRRs) with 95% CIs. Results: Incidence rates of AA more than tripled among the 1980 birth cohort (IRR, 3.41 [95% CI, 2.54 to 4.56]) and quadrupled among the 1985 birth cohort (IRR, 4.62 [CI, 3.12 to 6.82]) compared with the 1945 birth cohort. Age-specific incidence rates of AA increased across successive birth cohorts after 1945—although to varying degrees—for all tumor histologic types. Limitation: The rarity of AA precluded investigations specific to signet ring cell carcinomas of the appendix and across population groups (for example, sex and race). Conclusion: There are strong yet distinct birth cohort effects for AAs across histologic subtypes that remain unexplained—particularly among persons born after 1945. Given these patterns, there is a timely need for etiologic research as well as increased AA awareness among providers and the public. Similar trends have been reported for other gastrointestinal cancers, suggestive of potential shared cause contributing to this increasing cancer burden across generations. Primary Funding Source: Appendix Cancer Pseudomyxoma Peritonei Research Foundation, National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and National Cancer Institute.

Trends in Alcohol Use After the COVID-19 Pandemic: A National Cross-Sectional Study

In adults with metabolic dysfunction, the MAF-5 score predicted risk for liver fibrosis (AUC range, 0.73 to 0.81)

Source Citation van Kleef LA, Francque SM, Prieto-Ortiz JE, et al. Metabolic Dysfunction-Associated Fibrosis 5 (MAF-5) score predicts liver fibrosis risk and outcome in the general population with metabolic dysfunction. Gastroenterology. 2024;167:357-367.e9. 38513745

In patients receiving invasive ventilation, PPIs reduce upper GI bleeding but did not affect mortality at 90 d

Source Citation Cook D, Deane A, Lauzier F, et al; REVISE Investigators. Stress ulcer prophylaxis during invasive mechanical ventilation. N Engl J Med. 2024;391:9-20. 38875111

Patient Navigation to Improve Colonoscopy Completion After an Abnormal Stool Test Result: A Randomized Controlled Trial: Annals of Internal Medicine: Vol 178, No 5

Background: Patient navigation is a recommended practice of the Guide to Community Preventive Services; little is known about whether it improves colonoscopy completion for adults who have received an abnormal stool test result. Objective: To determine whether patient navigation delivered to persons with an abnormal stool test result increased follow-up colonoscopy completion (primary) at 1 year. Design: Randomized controlled trial. (ClinicalTrials.gov: NCT03925883) Setting: A federally qualified health center (n = 32 clinics) in Washington state. Patients: Persons aged 50 to 75 years with an abnormal fecal test result in the prior month. Intervention: A 6-topic, telephone-based patient navigation program delivered by bilingual (English and Spanish) clinical staff. Measurements: Receipt of follow-up colonoscopy at 1 year (primary); time to colonoscopy receipt (secondary); and program effectiveness by patient characteristics, including patients’ probability of obtaining a colonoscopy without navigation, derived using health record data (secondary). Results: Of 985 participants enrolled (mean age, 61 years [SD, 6.8]; 170 [18%] had a Spanish-language preference listed in the medical record), 967 were included in the primary intention-to-treat analysis (479 in patient navigation, 488 in usual care). Receipt of follow-up colonoscopy was higher in the patient navigation group than in the usual care group (55.1% vs. 42.1%; risk difference, 13.0 percentage points [95% CI, 6.5 to 19.4 percentage points]). The intervention effect was not moderated by patients’ probability of obtaining a colonoscopy without navigation. Limitation: The study was primarily done during the height of the COVID-19 pandemic, which created additional barriers to colonoscopy at the health system and patient levels. Conclusion: These findings support the effectiveness of patient navigation for follow-up colonoscopy completion. Primary Funding Source: National Cancer Institute.

How Would You Manage This Patient With Obesity? Grand Rounds Discussion From Beth Israel Deaconess Medical Center

In 2022, 1 in 8 people in the world were living with obesity, and lifestyle interventions that include diet, exercise, and behavioral modification have been the foundation for management of obesity. Recently, pharmacologic therapies have been developed for management of obesity, the newest of these being glucagon-like peptide 1 receptor agonists. With the development of new pharmacologic options, the American Gastroenterological Association developed a guideline in 2022 to provide evidence-based recommendations for the pharmacologic management of obesity in adults and recommended, for adults with obesity or overweight with weight-related complications who have had an inadequate response to lifestyle interventions, adding pharmacologic agents to lifestyle interventions over continuing lifestyle interventions alone. In this article, 2 experts review the available evidence to answer the following questions: How effective are lifestyle interventions for the treatment of obesity? How effective are pharmacologic interventions for the treatment of obesity? Given these options, how do you engage in a shared decision-making discussion to develop a mutually agreed-on treatment plan?

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