Nevin Manimala

JAMA Netw Open. 2026 Mar 2;9(3):e260762. doi: 10.1001/jamanetworkopen.2026.0762.

ABSTRACT

IMPORTANCE: Current guidance from the American Diabetes Association recommends liver stiffness measurement (LSM) only when the Fibrosis-4 (FIB-4) index is elevated. However, LSM may provide additional valuable information compared with FIB-4, which is known to underperform in certain populations, such as individuals with type 2 diabetes.

OBJECTIVE: To assess whether liver fibrosis evaluated by LSM is associated with increased mortality in individuals with and without diabetes.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included adult patients with complete vibration-controlled transient elastography (VCTE) and controlled attenuation parameter (CAP) data. Baseline data, including demographics and routine laboratory tests, were obtained from the 2017 to 2018 National Health and Nutrition Examination Survey and linked to data from the National Center for Health Statistics and National Death Index up to December 31, 2019. Patients with a history of liver disease other than metabolic dysfunction-associated steatotic liver disease were excluded. Data were analyzed from December 2024 to December 2025, accounting for the complex survey design using examination weights.

EXPOSURES: Liver disease based on CAP results and LSM by VCTE. CAP results 274 dB/m or higher indicate a diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD) and LSM results 9.7 kPa or higher indicate advanced liver fibrosis.

MAIN OUTCOMES AND MEASURES: All-cause mortality. Mortality risk was expressed as hazard ratios (HRs) with 95% CIs calculated using Cox proportional hazards regression models.

RESULTS: A total of 4102 adult patients (mean [SEM] age, 47 [1] years; 50.7% female), were included in the study. The mean (SEM) body mass index (BMI), calculated as weight in kilograms divided by height in meters squared, was 29.5 (0.3). Diabetes was present in 14.5% of participants. After a mean (SEM) follow-up of 24 (2) months, 59 patients (1.4%) had died. Patients who died during follow-up vs those who did not were older (mean [SEM] age, 62 [3] years vs 47 [1] years; P < .001), had a higher prevalence of diabetes (35.7% vs 14.2%; P = .01), and were more likely to be of non-Hispanic White race (85.1% vs 62.7%, P = .002). Increased risk of all-cause mortality was associated with the coexistence of diabetes with MASLD (adjusted hazard ratio [AHR], 2.77; 95% CI, 1.16-6.65; P = .03) and diabetes with advanced liver fibrosis (AHR 6.41; 95% CI, 1.03-39.85; P = .047). In patients with diabetes, LSM (AHR, 1.06; 95% CI, 1.04-1.09; P < .001) but not FIB-4 index remained associated with all-cause mortality even after adjusting for other clinical variables, such as age, sex, BMI, and hemoglobin A1c.

CONCLUSIONS AND RELEVANCE: In this cohort study, LSM was an independent risk factor for all-cause mortality in individuals with diabetes, even after a relatively short follow-up. Implementing LSM to screen for liver fibrosis as part of routine diabetes management could aid in early identification of patients with high mortality risk.

PMID:41848734 | DOI:10.1001/jamanetworkopen.2026.0762

JAMA Netw Open. 2026 Mar 2;9(3):e260908. doi: 10.1001/jamanetworkopen.2026.0908.

ABSTRACT

IMPORTANCE: Distinguishing primary lung squamous cell carcinoma (SCC) from squamous metastases to the lung is a clinical challenge due to histopathologic similarities. Accurate diagnosis is essential to guide treatment decisions.

OBJECTIVE: To assess the utility of an artificial intelligence (AI) approach that includes evaluation of key orthogonal evidence in distinguishing primary lung SCCs from metastatic tumors of other tissue origins.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used GPSai, a tissue-of-origin AI model run automatically on each sample submitted for molecular profiling, to flag potential misdiagnoses among research-eligible cases submitted as lung SCC. Molecularly profiled cases within the Caris Life Sciences clinicogenomic database from January 1, 2024, to January 31, 2025, were queried. All cases were reviewed by board-certified pathologists.

MAIN OUTCOMES AND MEASURES: The primary outcome was the rate of misdiagnosis among presumed lung SCCs confirmed by pathologist review and orthogonal evidence, which included clinical history and clinical findings, GATA3 and uroplakin II immunohistochemistry for urothelial carcinoma, UV variant signature for cutaneous SCC, CD5 and CD117 (c-KIT) immunohistochemistry for thymic carcinoma, and human papillomavirus positivity for orogenital SCC (eg, head and neck, cervical).

RESULTS: Through a combination of AI and orthogonal evidence, 123 (3.1%) misdiagnoses were confirmed among 3958 cases submitted as presumed lung SCC (patients misdiagnosed: median [range] age, 71 [39 to >89]; 76.4% male). The cohort included 50 cutaneous SCCs (40.7%), 33 orogenital SCCs (26.8%) (including 25 head and neck [75.8%]), 20 urothelial carcinomas (16.3%), 15 thymic carcinomas (12.2%), 4 NUT carcinomas (3.3%), and 1 prostate SCC (0.8%). Ninety-two of the 123 patients (74.8%) had clinical history or findings consistent with the new diagnosis. Eighty-eight cases (71.5%) had differences in guideline-preferred first-line systemic therapies following the diagnosis change.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of patients diagnosed with lung SCC, a meaningful number of patients experienced misdiagnosis, which was identified using a multipronged AI-assisted approach. Diagnosis changes prompted by AI and orthogonal evidence may assist clinicians in prognostication and therapy selection.

PMID:41848733 | DOI:10.1001/jamanetworkopen.2026.0908

JAMA Netw Open. 2026 Mar 2;9(3):e262201. doi: 10.1001/jamanetworkopen.2026.2201.

ABSTRACT

IMPORTANCE: Biologic manufacturer copay coupon programs reduce patient out-of-pocket spending but may undermine biosimilar competition. Whether biologic manufacturers deploy coupons strategically to facilitate shifting patients to reformulated drugs to extend market exclusivity (ie, product hopping), remains unclear.

OBJECTIVE: To examine coupon use and coupon value for biologics line extensions whose originators are at risk of biosimilar competition.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from national prescription drug claims from the IQVIA Formulary Impact Analyzer, October 1, 2017, through September 30, 2019, including 43 088 commercially insured patients with 382 550 claims across 47 biologic products. Analyses were conducted February to September 2025.

EXPOSURES: Candidate product hop status interacted with the time since originator approval (≥12 vs <12 years). Candidate product hops were defined as biologic line extensions approved between 2017 and 2019; comparators were biologics with earlier approval.

MAIN OUTCOME AND MEASURES: The primary outcome was manufacturer coupon use. Secondary outcomes included coupon amount, share of patient costs covered by coupons, and postbuydown out-of-pocket spending. Linear probability models with product line random effects estimated associations among candidate hop status, time since originator approval (≥12 vs <12 years), and coupon outcomes.

RESULTS: Among 43 088 patients (22 113 [51.3%] female; mean [SD] age, 47.6 [15.2] years), coupon use for candidate hops increased relative to comparators as originators approached 12 years since approval (change, 19.0 [95% CI, 1.7-36.4] percentage points; P = .03). For products with older originators, coupons for candidate hops offset 38.8 (95% CI, 28.0 to 49.7) percentage points more of patient cost-sharing than comparators (P < .001), and postbuydown costs were $124 (95% CI, -$183 to -$65) lower (P < .001). Candidate hops accounted for 11 122 of 382 550 claims (2.9%).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, manufacturer coupon use for candidate hop biologics diverged from comparators as originators neared exclusivity loss, suggesting coupons may facilitate product hopping. Regulators should consider monitoring coupon programs during biologic exclusivity transitions.

PMID:41848732 | DOI:10.1001/jamanetworkopen.2026.2201

JAMA Netw Open. 2026 Mar 2;9(3):e262279. doi: 10.1001/jamanetworkopen.2026.2279.

ABSTRACT

IMPORTANCE: A greater understanding of the factors associated with occupational distress for female physicians will allow organizations to more effectively realize the benefits of improving physician occupational well-being.

OBJECTIVE: To identify factors associated with occupational distress among female physicians.

DESIGN, SETTING, AND PARTICIPANTS: This survey study was conducted at 15 US academic medical institutions who participate in the Healthcare Professional Well-Being Academic Consortium. A cross-sectional, voluntary survey was administered to attending physicians from October 2019 to July 2021 to assess occupational well-being. Data were analyzed from April to September 2023.

EXPOSURE: Physician gender was used as the exposure variable.

MAIN OUTCOMES AND MEASURES: Burnout and professional fulfillment were measured using the Professional Fulfillment Index, which included subscales to assess leadership support, personal-organizational values alignment, control over schedule, electronic health record helpfulness, and self-valuation. A secondary data analysis was performed to describe markers of occupational well-being by gender. Mediation models were used to assess the degree to which contributing factors mediated the difference in occupational distress between female and male physicians.

RESULTS: The survey was completed by 19 088 of 37 511 attending physicians (response rate of 50.8%), among whom 16 731 self-identified as male or female and were included in the analysis (8197 female [43%] and 8534 male [45%]), and 2357 (12%) either did not report their gender or reported a gender other than male or female. Respondents’ ages ranged from younger than 29 to older than 60 years, with 40 to 49 years being the most common age bracket for both female (2788 participants [34%]) and male (2448 participants [29%]) physicians. Compared with male physicians, female physicians experienced more burnout (3338 of 8052 participants [42%] vs 2769 of 8404 participants [33%]; P < .001) and less professional fulfillment (2786 of 8133 participants [34%] vs 3852 of 8463 participants [46%]; P < .001). In mediation models including 5 factors associated with occupational well-being, the direct association between burnout and gender was no longer significant (B = 0.04; 95% CI, -0.01 to 0.08; P = .14), while the gender difference in professional fulfillment remained significant (B = -0.09; 95% CI, -0.14 to -0.04; P = .001). The indirect association of gender with burnout through self-valuation (B = 0.27; 95% CI, 0.24 to 0.29; P < .001) accounted for the majority (63%) of the total difference in burnout between female and male physicians.

CONCLUSIONS AND RELEVANCE: In this survey study of attending physicians, the gender difference in burnout was fully mediated by 5 factors associated with occupational well-being, with self-valuation being the largest mediator. These same factors did not fully explain the difference in professional fulfillment, suggesting that further research is needed.

PMID:41848730 | DOI:10.1001/jamanetworkopen.2026.2279

JAMA Netw Open. 2026 Mar 2;9(3):e262284. doi: 10.1001/jamanetworkopen.2026.2284.

ABSTRACT

IMPORTANCE: Social media is a dominant source of health information, including vaccine information, but little is known about which message characteristics audiences prefer when deciding what social media content to engage with and about how to measure these preferences.

OBJECTIVE: To quantify the attributes of existing social media vaccination posts that are associated with the preference for and confidence in vaccination-related content.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used a combination of the discrete choice experiment (DCE) and the Swiss tournament approaches to evaluate preferences, which were collected in an online survey between March and May 2024. Participants (aged ≥18 years) from a previous California-based COVID-19 study were recontacted through social media between January and August 2024. Participants completed the DCE and Swiss tournament test.

EXPOSURES: Participants viewed pairs of vaccination-related social media posts that varied systematically by attributes, such as messenger, source, tone, artwork type, age group of messenger, and topic.

MAIN OUTCOMES AND MEASURES: Participants selected which post they were most likely to engage with (like, share, or comment). Preferences were analyzed using a conditional logit model to estimate relative importance of post attributes.

RESULTS: Among 243 participants (mean [SD] age, 36.4 [12.4] years; 127 males [52.5%]), 153 (63.0%) reported favorable attitudes toward vaccines in general, 167 (68.7%) toward influenza vaccines, and 117 (48.2%) toward COVID-19 vaccines. Daily social media use was common (228 [93.8%]), and most participants preferred visual content, such as pictures (206 [84.8%]) or short videos (184 [75.7%]). In the DCE, social media vaccination posts from public health agencies such as California Department of Public Health (adjusted odds ratio [AOR], 1.80; 95% CI, 1.57-2.07) and University of California San Francisco (AOR, 1.67; 95% CI, 1.21-2.29) and posts depicting health care workers (AOR, 1.28; 95% CI, 1.12-1.47) or older adults (AOR, 1.48; 95% CI, 1.22-1.80) were more likely to be preferred. Humorous tone was associated with reduced preference (AOR, 0.45; 95% CI, 0.36-0.57), whereas COVID-19 (AOR, 2.35; 95% CI, 1.95-2.87) and influenza (AOR, 1.78; 95% CI, 1.54-2.06) topics were associated with increased likelihood for preference. Artwork type showed no significant association with preference.

CONCLUSIONS AND RELEVANCE: This cross-sectional study found that participants preferred social media-based vaccination posts that were factual, featured health care professionals, and were sourced from public health organizations. Understanding communication preferences through innovative experimental methods can inform the design of digital public health communications.

PMID:41848729 | DOI:10.1001/jamanetworkopen.2026.2284

JAMA Cardiol. 2026 Mar 18. doi: 10.1001/jamacardio.2026.0212. Online ahead of print.

ABSTRACT

IMPORTANCE: Premature onset of menopause is associated with increased short-term risk of coronary heart disease (CHD), but the associated long-term CHD risk and whether this differs by self-identified race are not known.

OBJECTIVE: To calculate lifetime risk estimates of incident CHD and to estimate years lived free of and with CHD by premature menopause status stratified by self-identified race.

DESIGN, SETTING, AND PARTICIPANTS: This prospective population-based cohort study was conducted with 163 600 person-years of follow-up, from 1964 to 2018. Individual-level data from postmenopausal women (aged 55-69 years) who self-identified their race as Black or White across 6 US cohorts were included. All participants were free of CHD at baseline and had data on menopausal status and CHD outcomes. Individuals who self-reported surgically induced menopause were excluded.

EXPOSURE: Premature onset of natural menopause (age <40 years).

MAIN OUTCOME AND MEASURES: The primary outcome was CHD (fatal and nonfatal myocardial infarction). The following analyses were performed: (1) modified Kaplan-Meier analysis to estimate lifetime risks, (2) adjusted competing Cox models to estimate joint cumulative risks for CHD or non-CHD death, and (3) Irwin restricted mean survival time to estimate mean years lived free of CHD and with CHD.

RESULTS: Of the 3522 Black women and 6514 White women included, mean (SD) age at baseline was 61.2 (4.3) years and 60.0 (4.4) years, respectively. Premature natural menopause occurred more frequently in Black women (545 [15.5%]) compared with White women (313 [4.8%]). Premature menopause was associated with a higher lifetime risk of incident CHD, with hazard ratios of 1.41 (95% CI, 1.04-1.90) for Black women and 1.39 (95% CI, 1.03-1.87) for White women. Mean years lived free of CHD were 18.2 years (95% CI, 17.5-18.9) for Black women with premature menopause compared to 19.1 years (95% CI, 18.8-19.4) for Black women without premature menopause; a similar pattern was seen in White women with and without premature menopause, but neither met statistical significance.

CONCLUSIONS AND RELEVANCE: In this cohort study, premature menopause was associated with 40% higher lifetime risk of CHD in Black and White women. This suggests that premature onset of menopause is an important risk-enhancing factor for lifetime risk and should be routinely assessed in clinical practice to consider intensification of preventive efforts.

PMID:41848694 | DOI:10.1001/jamacardio.2026.0212

Photobiomodul Photomed Laser Surg. 2026 Mar 18:25785478261425318. doi: 10.1177/25785478261425318. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the effects of beyond cold light whitening and desensitization on shear bond strength of orthodontic metal brackets.

MATERIALS AND METHODS: Ninety-eight extracted human premolars were randomly divided into seven groups (n = 14). Group 1 was the control (no treatment). Group 2 underwent bleaching, followed by bonding after 24 h. Group 3 received desensitization, then bonding after 24 h. Group 4 combined bleaching and desensitization, with bonding after 24 h. Groups 5, 6, and 7 followed the same procedure as Group 4, but bonding occurred 1, 2, and 3 weeks later, respectively. All samples were stored in 37°C artificial saliva after treatment and bonded with 3 M light-cure composite resin using halogen light. Shear bond strength was tested with a universal testing machine (INSTRON 5848). Adhesive remnant index (ARI) scores were assessed post-debonding. Statistical analysis was conducted using Analysis of Variance (ANOVA), Tukey’s test, and chi-square tests, with significance set at p < 0.05.

RESULT: The shear bond strength 24 h after bleaching (7.5 ± 1.77 MPa) was significantly lower than the control (12.24 ± 3.71 MPa, p < 0.05). Desensitization alone (11.68 ± 3.49 MPa) showed no significant difference compared with the control (p > 0.05). Shear bond strength significantly decreased 24 h after bleaching and desensitization (p < 0.05) but recovered to control levels after 1 week (p > 0.05). ARI scores showed no significant differences.

CONCLUSIONS: (1) Brackets bonded 24 h after bleaching or combined treatment showed reduced shear bond strength but were clinically acceptable; (2) The use of nano-biomaterial desensitizers slightly reduces the shear strength of brackets, but it will repair the damage of teeth caused by bleaching; (3) The impacts of bleaching and desensitization gradually reduce and return to normal levels after 1 week.

PMID:41848671 | DOI:10.1177/25785478261425318

Clin Transplant. 2026 Mar;40(3):e70506. doi: 10.1111/ctr.70506.

ABSTRACT

BACKGROUND: A minority of liver transplant (LT) recipients are not diagnosed with HCC (u-HCC) until their explanted liver is examined. The primary aim of this study was to examine HCC screening before LT in patients with u-HCC compared to those with known HCC (k-HCC). Secondary aims included assessment of inter-reader variability of diagnostic imaging used for HCC screening; predictors of u-HCC; and post-LT outcomes in u-HCC.

METHODS: A single center retrospective review of patients with HCC on explant from 2012-2023 was performed. A randomized subset of imaging studies from patients with k-HCC and u-HCC was reevaluated by two independent, blinded radiologists and inter-reader concordance was measured.

RESULTS: Thirty-seven (7.8%) patients had u-HCC, of whom 26 (70.3%) underwent contrast-enhanced magnetic resonance imaging (MRI) and 11 (29.7%) underwent computed tomography with delayed contrast phase (73% within 6 months of LT). Patients with metabolic liver disease and steatohepatitic HCC were more likely to have u-HCC (32% vs 16%, p = 0.01; 19% vs 7%, p = 0.01, respectively). Thirty-two patients with u-HCC had no suspicious lesions noted on imaging. 60% of all studies with second evaluation by blinded radiologists had concordant findings compared to 44% in metabolic liver disease.

CONCLUSIONS: Patients with metabolic liver disease may be at higher risk of u-HCC compared to other etiologies of liver disease despite regular, contrast-enhanced, cross-sectional imaging. One possible explanation for this is the difficulty of HCC detection in metabolic liver disease, as demonstrated by greater likelihood of inter-reader discordance in imaging assessment in these patients. KEYWORDS (INDEX MEDICUS).

PMID:41848630 | DOI:10.1111/ctr.70506

Clin Transplant. 2026 Mar;40(3):e70508. doi: 10.1111/ctr.70508.

ABSTRACT

INTRODUCTION: Liver transplantation (LT) significantly improves survival and quality of life for patients with end-stage liver disease. Whilst it is believed that need for LT vastly exceeds organ supply, quantifying the demand accurately is challenging. The performance metrics of the transplant system, such as waitlist mortality, may be misleading as they capture only patients who are referred, evaluated and listed for LT. Although means of increasing organ availability are available, they have financial costs and may be technically and ethically challenging (such as live donation and normothermic regional perfusion). The imperative to embrace these techniques can be obscured if the waitlist is assumed to be representative of the actual demand for transplantation.

METHODS: An international comparative analysis of transplantation, donation and waitlist outcomes versus measures of demand for LT was performed using publicly available data.

RESULTS: The comparative analysis revealed no correlation between disease prevalence and waitlist metrics across jurisdictions internationally, suggesting that waitlisting practices are largely independent of actual LT demand and are constrained by other factors.

CONCLUSION: Adult LT systems globally are supply driven and uncorrelated to demand, implying that all jurisdictions are unable to meet the demand of their community and are limited by the supply of viable organs. The study underscores the inadequacy of waitlist data in representing true demand and highlights the need for improved data to inform LT policy and practice to improve access to this life-enhancing and life-saving treatment.

PMID:41848624 | DOI:10.1111/ctr.70508

Clin Transplant. 2026 Mar;40(3):e70503. doi: 10.1111/ctr.70503.

ABSTRACT

INTRODUCTION: In Mexico, more than 15,000 patients are waiting for a kidney transplant, and there are not enough kidneys from deceased donors to transplant them. A kidney exchange program could increase kidney transplants from living donors by matching altruistic living donors and biologically incompatible donor-recipient pairs. Several countries have implemented successful kidney exchange programs. We evaluated the impact of implementing a kidney exchange program in Mexico.

METHODS: We simulated kidney exchange in Mexico using data from Mexican population distributions. We used an optimization model to maximize the number of compatible patient-donor matchings. Three different scenarios were evaluated.

RESULTS: We estimated that almost 45% of patients on the waiting list have an incompatible donor, and 995 transplant candidates who have a living donor available are added to the waiting list annually. If a kidney exchange program were established in Mexico, the number of living-donor transplants could increase by up to 20%.

CONCLUSIONS: Implementing kidney exchange in the country may reduce the increase in the number of recipients on the waiting list and reduce costs in the long term. To succeed, the program must not only draw sufficient participation from incompatible pairs, but also ensure that these pairs remain in the program even if they have to wait to be matched.

PMID:41848616 | DOI:10.1111/ctr.70503