Tag: pubmed

JAMA Intern Med. 2026 Jun 1. doi: 10.1001/jamainternmed.2026.1637. Online ahead of print.

ABSTRACT

IMPORTANCE: Quality metrics with financial incentives are widely used, but their impact on clinical care and patient health remains challenging to isolate.

OBJECTIVE: To evaluate the association of a physician-facing quality metric and financial incentive for hypertension control (blood pressure <140/90 mm Hg) with clinical decisions and health outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This quasi-experimental difference-in-differences study in a large US health system compared changes in outcomes at practices that did vs those that did not adopt the financial incentive before (2021) vs after (2022-2023) adoption. Participants included patients with previously diagnosed hypertension, aged 18 to 85 years, with encounters at eligible primary care practices. Data were analyzed from January 2024 to September 2025.

EXPOSURES: Patient exposure to the financial incentive was determined by which practice delivered their care.

MAIN OUTCOMES AND MEASURES: Initial and final systolic blood pressure at the primary care encounter and number of measurements, antihypertensive prescriptions and dose adjustments, and hospitalizations for incident stroke or acute coronary syndrome (ACS).

RESULTS: The study included 334 364 patients with hypertension (mean [SD] age, 64.9 [12.6] years; 53.3% female) and their 770 907 encounters at 103 primary care practices. In January 2022, the hypertension control financial incentive was introduced in physician contracts for 63 of these practices. In the overall population of patients with hypertension, the financial incentive was associated with an increased probability of blood pressure remeasurement (by 1.9 [95% CI, 0.7-3.1] percentage points [pp]; P = .002) with no statistically significant change in hypertension control, medication outcomes, or cardiovascular hospitalizations. For the subgroup of patients with marginally high blood pressure (defined as initial systolic blood pressure of 140-145 mm Hg), the financial incentive was associated with an increased probability (by 4.1 [95% CI, 2.1-6.0] pp; P < .001) that blood pressure was documented as controlled, subsequent to an increased probability of blood pressure remeasurement (by 5.6 [95% CI, 2.9-8.3] pp; P < .001). The probability of an existing antihypertensive medication dose being increased was reduced (-1.1 [95% CI, -2.0 to -3.0] pp; P = .01), and the 3-month risk of hospitalization for stroke or ACS increased (by 0.25 [95% CI, 0.07-0.44] pp; P = .005), with excess risk growing to 0.52 pp (95% CI, 0.17-0.87 pp; P = .008) pp at 1 year.

CONCLUSIONS AND RELEVANCE: This study’s findings suggest that the addition a quality metric and financial incentive to physicians’ contracts in a large health system had little impact on measured outcomes in the overall population of patients with hypertension. For patients with marginally high blood pressure, the incentive was associated with increased documented hypertension control because of selective remeasurement of blood pressure, decreased medication adjustments, and increased cardiovascular hospitalizations.

PMID:42223964 | DOI:10.1001/jamainternmed.2026.1637

JAMA. 2026 Jun 1. doi: 10.1001/jama.2026.6908. Online ahead of print.

ABSTRACT

IMPORTANCE: Helicobacter pylori infection is the leading cause of gastric cancer, yet the economic value of population-based screening and eradication remains uncertain.

OBJECTIVE: To project the lifetime health benefits and costs of invitation to 1-time H pylori stool antigen testing added to biennial fecal immunochemical test (FIT) screening compared with FIT alone.

DESIGN, SETTING, AND PARTICIPANTS: Lifetime cost-effectiveness analysis conducted using a Markov decision-analytic model to simulate a cohort informed by a pragmatic randomized clinical trial in Changhua County, Taiwan. The model adopted a 30-year time horizon and projected long-term outcomes, including gastric and colorectal cancer mortality, quality-adjusted life-years (QALYs; incorporating both life expectancy and health-related quality of life), and health care expenditures. Costs were evaluated from a societal perspective. One-way and probabilistic sensitivity analyses were performed. Future costs and QALYs were discounted at an annual rate of 3%.

EXPOSURES: Helicobacter pylori stool antigen testing plus FIT or FIT alone.

MAIN OUTCOMES AND MEASURES: Incremental cost-effectiveness ratio of invitation for H pylori stool antigen testing plus FIT vs FIT alone, measured as the additional cost required to gain 1 QALY per person. Secondary outcomes included net monetary benefit and benefit-cost ratio.

RESULTS: Compared with FIT alone, invitation to co-testing was more effective and less expensive (dominant), with a base-case cost-saving incremental cost-effectiveness ratio of $2094 per QALY gained (95% CI, $12 359 saved to $7291 additional cost). This resulted in a positive net monetary benefit, indicating that health benefits exceeded costs, and a benefit-cost ratio of 5.08, indicating an approximately 5-fold return on investment in the Taiwanese population. At a willingness-to-pay threshold of 1 × the Taiwan gross domestic product per QALY ($33 365), invitation to co-testing remained cost-saving in 65.7% of simulations. From a US cost perspective, invitation to co-testing was not cost-saving but remained cost-effective at the trial base-case H pylori prevalence. Sensitivity analyses identified H pylori prevalence as the dominant driver; co-testing exceeded a $100 000-per-QALY threshold when prevalence fell below 21.9%.

CONCLUSIONS AND RELEVANCE: In a pragmatic real-world setting with incomplete adherence, invitation to combined H pylori stool antigen testing and FIT was more cost-effective than FIT alone, improving lifetime outcomes and yielding cost savings in Taiwan while remaining cost-effective in higher-cost settings under moderate H pylori prevalence.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01741363.

PMID:42223961 | DOI:10.1001/jama.2026.6908

JAMA Netw Open. 2026 Jun 1;9(6):e2614764. doi: 10.1001/jamanetworkopen.2026.14764.

ABSTRACT

IMPORTANCE: Antibody-drug conjugates (ADCs), including enfortumab vedotin, disitamab vedotin, and sacituzumab govitecan, are altering the therapeutic landscape for locally advanced or metastatic urothelial carcinoma (la/mUC). Comprehensive comparative evidence evaluating their translation in the clinical setting and modifying clinical covariates is required.

OBJECTIVE: To synthesize multidimensional evidence from interventional and observational settings to evaluate clinical outcomes, define the evolving therapeutic positioning of enfortumab vedotin, disitamab vedotin, and sacituzumab govitecan, and identify drivers of heterogeneity through meta-regression.

DATA SOURCES: PubMed, Embase, Cochrane Library, Web of Science, and Google Scholar were searched from database inception to October 23, 2025.

STUDY SELECTION: Interventional and observational studies of adults with la/mUC treated with enfortumab vedotin, disitamab vedotin, or sacituzumab govitecan.

DATA EXTRACTION AND SYNTHESIS: Independent reviewers extracted data following PRISMA guidelines. A rigorous metadata deduplication algorithm prevented patient double-counting. Random-effects models pooled data. Bayesian network meta-analysis (NMA) used reconstructed individual patient data. Inverse-variance weighted meta-regression assessed clinical covariates.

MAIN OUTCOMES AND MEASURES: Primary outcomes were disease control rate, objective response rate (ORR), and clinical complete response.

RESULTS: Forty independent studies involving 6085 patients were included. For enfortumab vedotin monotherapy, the pooled ORR was 43.9% (95% CI, 40.4%-47.5%) in interventional studies and 44.6% (95% CI, 41.0%-48.2%) in observational cohorts. For enfortumab vedotin plus pembrolizumab, interventional cohorts were associated with a pooled ORR of 67.5% (95% CI, 63.5%-71.3%) overall and 65.4% (95% CI, 60.0%-70.5%) in cisplatin-ineligible patients. Furthermore, disitamab vedotin plus programmed cell death protein 1 (PD-1) inhibitors was associated with an ORR of 74.7% (95% CI, 69.4%-79.4%) in interventional trials and 61.7% (95% CI, 52.6%-70.1%) observationally. Meta-regression identified prior PD-1/L1 exposure (β = -0.071; P = .003) and treatment regimen (β = -0.890; P < .001) as factors associated with primary response. Notably, the pure randomized clinical trial network meta-analysis of first-line treatments for cisplatin-ineligible patients revealed that enfortumab vedotin monotherapy was associated with a statistically significant overall survival advantage over chemotherapy (HR, 0.50; 95% CI, 0.29-0.86; posterior probability >99%).

CONCLUSIONS AND RELEVANCE: In this meta-analysis of ADCs for la/mUC, enfortumab vedotin-based regimens were associated with robust outcomes across clinical settings, and disitamab vedotin combined with immunotherapy was associated with potent clinical activity. Meta-regression indicated that prior immunotherapy exposure and hepatic tumor burden were associated with attenuated treatment responses.

PMID:42223943 | DOI:10.1001/jamanetworkopen.2026.14764

JAMA Netw Open. 2026 Jun 1;9(6):e2615894. doi: 10.1001/jamanetworkopen.2026.15894.

ABSTRACT

IMPORTANCE: Current lung cancer guidelines recommend lymph node sampling (LNS) with the 3 + 1 rule, which recommends station-based sampling with at least 3 N2 (mediastinal) and 1 N1 (hilar) nodal stations. Although there is oncologic benefit to rigorous LNS, potential negative impacts on surgical outcomes have not been well investigated. As adoption of the 3 + 1 rule increases given its formalization as guideline-concordant care, associations with adverse outcomes are crucial to characterize.

OBJECTIVE: To evaluate whether satisfying the 3 + 1 rule is associated with increased postoperative complications.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used the Society of Thoracic Surgeons General Thoracic Database, which was queried for patients with clinical stage T1 to T3, N0, M0 non-small cell lung cancer (NSCLC) who underwent surgical resection with known LNS between July 1, 2021, and January 1, 2023. Statistical analysis was performed from March 2024 to March 2025.

EXPOSURE: A propensity match was conducted to compare the postoperative complication rate by 3 + 1 LNS status.

MAIN OUTCOMES AND MEASURES: Data on demographic characteristics were collected and analyzed. Primary outcomes included postoperative complications, such as arrhythmias, pleural effusion requiring drainage, blood transfusion, prolonged air leak, therapeutic bronchoscopy, pneumonia, respiratory failure, bronchopleural fistula, pulmonary embolism, pneumothorax, prolonged ventilatory support, myocardial infarction, and sepsis. Thirty-day mortality and readmission rates were also evaluated.

RESULTS: The cohort included 28 439 patients (median [IQR] age, 69 [66-75] years; 4791 [59.5%] female). There were 18 939 patients (66.6%) who satisfied the 3 + 1 rule. In the unadjusted group, the 3 + 1 cohort had longer median (IQR) operating room duration (224 [178-281] vs 210 [161-273] minutes, P < .001) and rates of pathologic upstaging (2520 [13.3%] vs 922 [9.7%], P < .001). In the postmatch analysis, there were no other significant differences in postoperative complication rates, and the aforementioned associations in the 3 + 1 group were no longer observed.

CONCLUSIONS AND RELEVANCE: In this cohort study of patients with NSCLC, the 3 + 1 rule was not associated with increased postoperative complications. This study’s findings suggest support for the continued use of this strategy in terms of overall safety profile.

PMID:42223938 | DOI:10.1001/jamanetworkopen.2026.15894

JAMA Intern Med. 2026 Jun 1. doi: 10.1001/jamainternmed.2026.1893. Online ahead of print.

ABSTRACT

IMPORTANCE: Acute and subacute low back pain (LBP) often progresses to a chronic impactful back problem in patients with elevated risk. The most effective way to prevent this progression is unknown.

OBJECTIVE: To determine the effectiveness of spinal manipulation and clinician-supported biopsychosocial self-management vs medical care for preventing chronic impactful LBP.

DESIGN, SETTING, AND PARTICIPANTS: This 2 × 2 factorial randomized clinical trial was conducted in research clinics at the University of Minnesota and the University of Pittsburgh, Pennsylvania, from November 2018 to May 2023, with follow-up concluding in June 2024. Adults with acute or subacute LBP with a moderate to high risk of chronicity were included.

INTERVENTIONS: Four interventions were applied for 8 weeks: spinal manipulation therapy; supported self-management; combined spinal manipulation therapy and supported self-management; and guideline-based medical care. Spinal manipulation and supported self-management were provided by physical therapists and chiropractors.

MAIN OUTCOMES AND MEASURES: Mean LBP impact score per the US National Institutes of Health Task Force on Chronic LBP scale (8 [best] to 50 [worst]) during 10 to 12 months, responder analyses of group differences in the proportion of participants with at least 50% reductions. A reduction of 30% was considered the minimal clinically important within-patient difference. Secondary outcomes included measures of chronicity and LBP burden (ie, health care and medication use, productivity), important patient-reported outcomes (eg, improvement, satisfaction), biopsychosocial measures (eg, Patient-Reported Outcomes Measurement Information System), and potential mediating psychosocial measures (eg, self-efficacy, kinesiophobia, pain catastrophizing).

RESULTS: Of the 1000 participants (mean [SD] age, 47 [16] years; 577 females [58%]) randomized, 928 (93%) completed the trial. An omnibus test of the primary outcome was statistically significant (P = .006). Group differences in mean LBP impact scores were small but statistically significant: supported self-management vs medical care, -1.7 (95% CI, -2.7 to -0.6); combined self-management and spinal manipulation vs medical care, -1.3 (95% CI, -2.5 to 0). Spinal manipulation therapy and medical care did not differ: -0.3 (95% CI, -1.5 to 1.0). Adding spinal manipulation to supported self-management did not provide additional benefit. The supported self-management group had a significantly higher proportion with at least 50% reduction in LBP impact vs medical care (64% vs 55%). Supported self-management also performed better on most secondary outcomes compared to medical care, including 12% fewer reporting chronic pain that frequently interfered with regular activities. Mediation analyses showed changes in psychosocial factors at 6 months and explained 76% of supported self-management effects at 1 year.

CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that for patients with acute or subacute LBP at increased risk of chronic impactful LBP, clinician-supported biopsychosocial self-management resulted in a lower mean LBP impact score at 10 to 12 months vs medical care; spinal manipulation and medical care did not differ. While the LBP impact difference was small, the consistent results of the responder analyses and most secondary outcomes suggest differences between clinician-supported self-management and medical care are clinically relevant.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03581123.

PMID:42223934 | DOI:10.1001/jamainternmed.2026.1893

JACC Cardiovasc Interv. 2026 May 21:S1936-8798(26)01448-2. doi: 10.1016/j.jcin.2026.05.007. Online ahead of print.

ABSTRACT

(350/350) BACKGROUND: Standardized implant protocols have shown promise in improving outcomes in transcatheter aortic valve replacement (TAVR). However, the impact of implant depth on clinical outcomes remains unclear.

OBJECTIVES: To evaluate clinical and hemodynamic outcomes across varying TAVR implantation depths using data from the Optimize PRO study.

METHODS: This prospective, multicenter Optimize PRO study included patients with symptomatic severe aortic stenosis undergoing TAVR with Evolut PRO/PRO+ systems. Patients were stratified by core laboratory-adjudicated non-coronary cusp implant depth. The echocardiographic outcome composite included none/trace paravalvular regurgitation, aortic mean gradient ≤10mmHg and no prosthesis-patient-mismatch at discharge.

RESULTS: Patients (N=603) were stratified by implant depth: <1mm (N=88), 1 to ≤3mm (N=196), >3 to ≤5mm (N=170), and >5mm (N=149). Baseline characteristics were similar across implant depth groups, except for a higher proportion of females in higher implant depths. Higher implant depths were associated with less resheathing and recapture (27.3% [24/88], 33.7% [66/196], 48.8% [83/170], 51.7% [77/149]; P<.001), and shorter median [Q1, Q3] hospital stay (days: 1[1,1], 1[1,2], 2 [1,3], 2 [1,4]; P<.001). Rates of valve migration (0% [95% CI:NA], 0.5% [95% CI:0.1-3.6], 0.6% [95% CI:0.1-4.1], 1.3% [95% CI:0.3-5.3]; P=.63) were low across implant depth groups. The 1-year all-cause mortality or all-stroke rate was comparable across implant depth groups (8.1% [95% CI:3.9-16.2], 7.2% [95% CI:4.3-11.8], 10.7% [95% CI:6.9-16.5], 12.5% [95% CI:8.1-19.2]; P=.40). After 1 year, higher implant depths were associated with lower rates of permanent pacemaker implantation (PPI, 2.3% [95% CI:0.6-8.8], 9.2% [95% CI:5.9-14.3], 15.9% [95% CI:11.2-22.4], 20.3% [95% CI:14.6-27.7]; P<.001). Rates of New York Heart Association functional class I were numerically different across implant depth groups but did not reach statistical significance (NYHA, 77.8% [56/72], 71.8% [130/181], 65.2% [101/155], 67.7% [84/124], P=.09 across all classes). In males, echo outcome composite rates were not statistically different across depth groups (58.6%[17/29], 50.6% [39/77], 43.8% [35/80], 36.1% [26/72]; P=.14), although the exploratory trend test reached statistical significance (P=.02).

CONCLUSIONS: Higher TAVR device implantation was associated with improved clinical outcomes with similar safety events, including valve migration, across depths. The long-term effect of this approach including the ability to perform redo-TAVR safely, will be further studied in the future.

PMID:42223923 | DOI:10.1016/j.jcin.2026.05.007

Acta Crystallogr D Struct Biol. 2026 Jul 1. doi: 10.1107/S2059798326003943. Online ahead of print.

ABSTRACT

Radiation damage to macromolecular structures remains a significant challenge for accurate structure solution by X-ray crystallography, leading to incorrect structural and chemical interpretation of the data. Site-specific radiation damage is insidious, typically unidentifiable solely from summary statistics, and is primarily discussed with reference to the predominant forms: disulfide-bond cleavage, metal-centre reduction and decarboxylation of acidic residues. A method is presented for identifying potentially oxidatively damaged cysteines by interrogating the accuracy of the built model within the electron density and the geometry of the difference density peaks surrounding a cysteine. We also highlight that cysteines located within protein active sites or that are in hydrolases are predisposed to this damage.

PMID:42223917 | DOI:10.1107/S2059798326003943

J Racial Ethn Health Disparities. 2026 Jun 1. doi: 10.1007/s40615-026-02952-w. Online ahead of print.

ABSTRACT

The term “Hispanic Paradox” refers to research findings that Hispanic immigrants often exhibit better health than more socioeconomically advantaged U.S.-born populations. However, much of this research attributes this epidemiological phenomenon to immigration selectivity and rarely examines (1) whether a Hispanic-specific health advantage persists within immigrant-only populations and (2) how any such advantage is structured by race and sex inequalities across highly heterogeneous immigrant groups. Using data from the IPUMS National Health Interview Survey (NHIS), 2006-2018 (N = 166,700), this study applies an intersectional approach to evaluate a Hispanic health effect in health-related functional limitations – a measure strongly linked to mortality and health care needs – across race-sex immigrant groups. Logistic regression and post-estimation results show that a health advantage associated with Hispanic identity appears only among female and male immigrants who identify as White, with no comparable benefit for other race-sex intersections. These findings indicate that a Hispanic health advantage among immigrants is not universal but shaped by structural inequality, underscoring the need for intersectionality-informed research that uncovers masked vulnerabilities across ethnoracially diverse immigrant populations.

PMID:42223888 | DOI:10.1007/s40615-026-02952-w

Ann Nucl Med. 2026 Jun 1. doi: 10.1007/s12149-026-02221-0. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the value of ¹⁸F-FDG PET/CT in assessing the local aggressiveness of desmoid-type fibromatosis (DF) and in predicting prognosis of DF.

METHODS: We retrospectively analyzed ¹⁸F-FDG PET/CT of DF lesions in participants. Clinical data and ¹⁸F-FDG PET/CT imaging features were collected and analyzed. The diagnostic performance of ¹⁸F-FDG PET/CT versus contrast-enhanced MRI (CE-MRI) for assessing peritumoral invasion was compared using reference of pathology. Lesions were followed up to record progressive disease (PD) and postoperative recurrence (POR), and event-free survival (EFS) was determined. Univariate and multivariate Cox regression analyses were performed to identify independent predictors of PD or POR.

RESULTS: Fifty-five lesions from 44 participants were included. ¹⁸F-FDG PET/CT showed higher accuracy and sensitivity than CE-MRI for assessing peritumoral invasion, with no statistically significant differences in paired comparisons. Notably, pathology in one case demonstrated tumor invasion of the lymph node capsules. Furthermore, DF lesions with PD or POR had significantly higher maximum standardized uptake value (SUV_max) and target-to-background ratio (TBR). SUV_max, TBR and irregular lesion morphology were identified as independent predictors of PD or POR. The AUC for SUV_max was 0.79 (95% CI: 0.64-0.95), with sensitivity, specificity, and overall accuracy of 78.6% (11/14), 82.9% (34/41), and 81.8% (45/55), respectively. Kaplan-Meier survival analysis revealed that SUV_max> 5.0 was associated with significantly shorter EFS (692.4 [427.5-957.3] days vs. 2419.9 [1989.5-2850.3] days).

CONCLUSION: ¹⁸F-FDG PET/CT showed numerically higher sensitivity and accuracy than CE-MRI for assessing peritumoral invasion of DF lesions, though with lower specificity. SUV_max, TBR, and lesion morphology were independent predictors of PD or POR.

PMID:42223872 | DOI:10.1007/s12149-026-02221-0

Ann Nucl Med. 2026 Jun 1. doi: 10.1007/s12149-026-02242-9. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the clinical utility of preoperative [¹⁸F]FDG PET/CT for CT-guided biopsy planning of large tumors, including predictors of PET/CT-informed target adjustment and malignant yield with FDG hotspot targeting in very large tumors.

METHODS: In this retrospective single-center study (January 2015-December 2025), we analyzed 82 patients who underwent pre-biopsy [¹⁸F]FDG PET/CT at our institution within 90 days. Target adjustment was retrospectively adjudicated as the presence of a spatial difference between the contrast-enhanced CT-based target and the PET/CT-informed target selected after considering intratumoral FDG uptake. ROC analysis was used to evaluate whether tumor size predicted target adjustment and to determine the optimal cutoff. Multivariable logistic regression included age, sex, tumor size, PET system (analog vs. digital), ΔSUV, lesion location (chest vs. other), and lymphoma (vs. other). In tumors ≥ 52 mm, malignant yield was compared between hotspot (highest uptake) and non-hotspot targeting.

RESULTS: Target adjustment was performed in 28/82 cases (34.1%). Interobserver agreement was 89% with Cohen’s κ = 0.74 (95% CI, 0.58-0.89). Tumor size predicted target adjustment (AUC 0.847; 95% CI 0.761-0.934), and the Youden-optimal cutoff was 52 mm (sensitivity 0.82, specificity 0.81). Target adjustment rates were 5/49 (10.2%) for < 52 mm and 23/33 (69.7%) for ≥ 52 mm (p < 0.001). In multivariable analysis, tumor size (per 10 mm) was independently associated with target adjustment (OR 2.33; 95% CI 1.56-3.50; p < 0.001), while female sex was inversely associated (OR 0.20; 95% CI 0.04-0.96; p = 0.045). Lymphoma showed a trend toward an inverse association that did not reach statistical significance (OR 0.11; 95% CI 0.01-1.11; p = 0.062). The multivariable model showed good discrimination (AUC 0.90; 95% CI 0.82-0.98; DeLong). Among tumors ≥ 52 mm, malignant pathology was obtained in 14/14 cases (100%) with hotspot targeting versus 5/9 (55.6%) with non-hotspot targeting (p = 0.014).

CONCLUSIONS: Preoperative [¹⁸F]FDG PET/CT supports CT-guided biopsy planning of large tumors by identifying cases likely to require target adjustment and was associated with higher malignant yield when the FDG hotspot was targeted in tumors ≥ 52 mm.

PMID:42223871 | DOI:10.1007/s12149-026-02242-9