JAMA Network Open

Introduction: Breast, cervical, and colorectal cancer screening guidelines changed substantially between 2010 and 2019. We examined trends in the annual utilization of these screenings among commercially insured enrollees in the United States from 2010 to 2019 by age group, geographic region, and screening modality. Methods: We conducted a retrospective, serial cross-sectional analysis of the MarketScan Commercial Claims Database from 2010 through 2019, comprising approximately 141.2 million privately insured enrollees. Annual screening rates, defined as the proportion of eligible enrollees receiving a given test within each calendar year, were estimated for cervical, breast, and colorectal cancer using procedure codes, stratified by age group, screening modality, and geographic residence. These reflect annual utilization rather than up-to-date (guideline-concordant) screening. Temporal trends were evaluated using two-sided Poisson regression, and urban-rural disparities in 2019 were assessed using multivariate generalized estimating equations. Results: Cancer screening utilization remained stagnant or declined across all three cancer types over the study period. Among women aged 30-64 years, cervical cytology alone declined substantially from 28.2% in 2010 to 8.8% in 2019, while co-testing increased from 11.4% to 20.3%. Screening mammography among women aged 50-64 showed minimal change, remaining stable at 45.7% in 2010 and 45.8% in 2019. Colorectal cancer screening across enrollees aged <64 decreased modestly from 7.7% in 2010 to 6.5% in 2019, with a more pronounced decline among adults aged 45-49 years. Across all three cancer types, screening utilization was higher among urban residents than rural residents, with incidence rate ratios ranging from 1.02 to 1.05 in 2019. Conclusions: Utilization of cervical, breast, and colorectal cancer screening among commercially insured adults did not improve between 2010 and 2019. Persistent urban-rural disparities highlight ongoing gaps in preventive care delivery. Targeted interventions may help improve screening utilization, particularly in rural and underserved populations.

Despite known carcinogenic properties, indoor tanning remains popular among young adults and may contribute to early-onset melanoma. Our study aims to compare early-onset melanoma incidence by state availability of tanning beds. We analyzed population-based melanoma incidence data (2019-2023) from the National Program of Cancer Registries and calculated Incidence Rate Ratios (IRR) using verified state-level quintiles of tanning bed availability. Overall, in the Midwest/South regions, melanoma incidence increased with greater tanning-bed availability, from 8.7 cases per 100,000 population in Quintile 1 to 14.8 cases per 100,000 population in Quintile 5 (IRR = 1.69; CI = 1.65-1.74). No such relationship was found in the Northeast/West regions. In conclusion, we found that in Southern and Midwest states, increased availability of tanning beds was associated with higher early-onset melanoma in non-Hispanic White males and females, in both metro and non-metro counties. Policies which reduce tanning bed availability in high utilization regions may have potential to reduce early-onset melanoma.

Objective To identify optimal initiation ages and screening intervals for low-dose computed tomography (LDCT) screening among never-smoking Asian women using an integrated polygenic risk score (PRS)-environmental tobacco smoke (ETS) risk model, and to evaluate the cost-effectiveness of alternative screening strategies at these optimized ages. Design Integrated PRS-ETS microsimulation modelling. Setting Japan. Participants Never-smoking women stratified into eight risk groups defined by combinations of PRS levels and ETS exposure. Interventions LDCT screening at intervals of 1 to 10 years, annual chest radiography (CXR), or no screening. Main outcome measures Costs, quality-adjusted life years (QALYs), incremental cost-effectiveness ratios (ICERs), net monetary benefits, lung adenocarcinoma incidence and mortality, and optimal LDCT initiation ages. Sensitivity analyses used a willingness-to-pay threshold of US$50,000 per QALY gained. Results Optimal initiation ages ranged from 40 to 55 years across the eight PRS-ETS risk groups, with higher PRS-ETS risk associated with younger optimal initiation ages. Annual LDCT was the most cost-effective strategy across all PRS-ETS risk strata, yielding an ICER of US$40,471 per QALY in the lowest risk stratum and becoming cost-saving in higher risk strata. Over a lifetime, annual LDCT averted 8,534 lung adenocarcinoma deaths compared with annual CXR and 14,940 deaths compared with no screening. Conclusions Tailoring LDCT initiation age across integrated PRS-ETS risk groups maximizes mortality reduction achievable with cost-effective annual LDCT screening among never-smoking Asian women. These findings highlight an urgent limitation of global lung cancer screening guidelines that rely exclusively on smoking history and provide policy-ready evidence supporting the integration of PRS and ETS into future recommendations for precision LDCT screening for never-smoking populations.

Purpose: Lung cancer screening (LCS) with low-dose computed tomography (LDCT) reduces lung cancer mortality, yet screening participation remains low. We evaluated whether a brief informational video nudge delivered immediately before a scheduled clinical encounter increased LCS ordering and baseline LCS completion. Patients and Methods: We conducted a randomized feasibility trial within Kaiser Permanente Colorado from March through October 2025. LCS-eligible patients with an upcoming primary care or pulmonology appointment were assigned to intervention or usual care based on birth month. Intervention patients were split into two group, a group who received the LCS informational video nudge via text message within 24 hours of an eligible appointment; and second group who received the text plus a QR code video link during appointment rooming. Outcomes included LCS orders, baseline LCS-LDCT completion, and video engagement. Multivariable logistic regression was used to evaluate factors associated with LCS ordering. Results: Among 1,093 patients, 549 were assigned to intervention and 544 to usual care. Intervention patients were more likely to receive an LCS order within 1 day of their appointment (22.6% vs 16.4%; p=.010) and any time during follow-up (32.6% vs 24.1%; p=.002). Baseline LCS-LDCT completion was 51% higher in the intervention group, although the difference was not statistically significant (8.6% vs 5.7%; p=.078). Among the intervention group, 93 individuals (17%) viewed the video, generating 114 total views, and viewers watched an average of 79% of the video. Most views (82.5%) occurred through text-message delivery rather than QR codes. Conclusion: A brief, low-burden LCS informational video delivered immediately before a clinical encounter and integrated into existing workflows significantly increased LCS ordering and was associated with higher screening completion. Timely, scalable digital nudges may provide an effective strategy for improving LCS participation. Based on the observed effectiveness, feasibility, and efficiency of the intervention, KPCO incorporated the behavioral nudge into standard clinical care in February 2026.

Background To characterize Coronavirus disease 2019 (COVID-19) symptom severity, and recovery from pre-infection through one month, overall and by risk groups. Methods Symptomatic adults aged [&ge;]18 years with test-confirmed COVID-19 were enrolled from ambulatory care clinics within a national U.S. retail pharmacy network between 10/24/2024 and 08/29/2025 (NCT05160636). Adjusted mixed models for repeated measures estimated least-squares mean changes (LSE) and standard errors (SE) from pre-infection and on Days 1-7, 10, 14, and Week 4 from enrollment in composite symptom scores (sum of severity ratings (0-3) across 14 symptoms), counts of mild-to-severe, moderate-to-severe, and severe symptoms, overall and by age and clinical risk status. Effect sizes (ES) were defined as small (0.2-<0.5), medium ([&ge;]0.5), and large ([&ge;]0.8). Results The analysis included 608 adults. On Day 1, symptom severity rose sharply from pre-infection for the composite symptom score (LSE 14.2 [SE 0.3]; ES 2.22), mild-to-severe (7.6 [0.1]; 2.72), moderate-to-severe (5.0 [0.2]; 1.77); and severe (1.8 [0.1]; 0.92) (all p<0.001). By Week 4, composite score (0.7 [0.2]; 0.26), mild-to-severe (0.5 [0.1]; 0.23); moderate-to-severe symptoms (0.1 [0.1]; 0.17) and severe symptoms (0.2 [0.1]; 0.5) remained slightly above baseline (all p[&le;]0.025). Elevated severe symptom durations varied: high-risk adults (through Day 3), adults <50 years (through Day 7), and adults [&ge;]50 years (through Day 7). Conclusions COVID-19 was associated with notable acute symptoms in outpatients, followed by gradual improvement over time, although symptoms still persisted at four weeks. Improvement in severe symptoms varied by individual risk profile, reinforcing the importance risk-based follow-up and ongoing monitoring.

BackgroundObservational comparisons of former smokers who use non-combusted nicotine products with former smokers who quit without them require that two quantities be measured precisely: which product is being used, and how long ago cigarette smoking stopped. Neither quantity is recorded by the National Health Insurance Service (NHIS) screening instrument used in a recent Korean cohort study of post-cessation e-cigarette use and lung cancer risk. We characterized both quantities in a contemporaneous, nationally representative survey of the same population. MethodsWe analyzed the public-release microdata of the Korea National Health and Nutrition Examination Survey (KNHANES), 2018 to 2023, restricted to adults aged 19 years and older. Former smokers were identified by smoking status, and cessation duration was taken from the item recording months since the last cigarette. Former smokers currently using a heated tobacco product (HTP) or an e-cigarette (EC) were compared with former smokers using neither. KNHANES 2018 asked a generic e-cigarette question and, separately, a checklist naming HTP brands, allowing the two product classes to be separated. Distributions were compared with rank-based methods, the age-duration relationship with Theil-Sen regression, and residual imbalance by restricting the comparison group to respondents age-matched to within two years. ResultsThe 2018 analytic sample comprised 1,348 former smokers, of whom 43 currently used HTP or EC and 1,305 used neither. Among the product-using former smokers, 58% reported HTP use without e-cigarette use, 21% reported both, and 21% reported e-cigarette use without HTP use; 79% reported any HTP use. Median cessation duration was 0.7 years (IQR 0.25 to 1.5) among product users and 12.0 years (IQR 5.0 to 20.0) among those using neither (Kolmogorov- Smirnov D = 0.76, P < 0.001), with the product user having quit more recently in 92% of cross-group pairs. The separation persisted within the short-term (<5 year) stratum (D = 0.34, P < 0.001; 73% of pairs) and after age matching, where the residual gap was 9.3 years. Cessation duration rose with age among those using no product (Theil-Sen slope +0.30 years per year) but was flat among product users (-0.01). Restricting to the screening-eligible stratum used in the cohorts high-risk analysis did not attenuate the imbalance: among those aged 50 to 80, median cessation among no-product quitters rose to 15.5 years (n = 858), and adding a 20 pack-year criterion left 421 no-product quitters with a median of 11.0 years against three HTP/EC users who had quit 0.25, 1.0 and 2.0 years earlier, despite closely matched cumulative exposure (mean 37.6 vs 37.7 pack-years). The overall contrast reproduced in every wave from 2018 to 2023, with an age-matched residual of 9 to 11 years. ConclusionsIn a nationally representative survey of the same population and the same calendar year as the NHIS screening cohort analyzed by Kim et al., Korean former smokers using non-combusted nicotine products differed from other former smokers in two respects that bear directly on how such comparisons should be read. First, they were predominantly HTP users: 79% reported any HTP use, and only 21% reported e-cigarette use without HTP use. Second, they had stopped smoking approximately a decade more recently, a difference that survived stratification at five years and exact age matching. Neither quantity is recorded in the NHIS screening instrument. Cohort estimates comparing post-cessation product users with other quitters should therefore be interpreted with caution if they do not precisely characterize product composition and to time since cessation, and future studies should measure both directly.

Purpose To estimate the per-protocol effect of red blood cell (RBC) transfusion strategies on ICU-acquired infection in critically ill adults with sepsis using a target trial emulation framework. We evaluated whether restrictive strategy and liberal strategy, defined by hemoglobin (Hgb) thresholds, differ in their effect on ICU-acquired infection during ICU stay. Methods We conducted a target trial emulation using the MIMIC-IV database and included adults who met Sepsis criteria at ICU admission. Clones were assigned to restrictive or liberal transfusion strategies. Under the restrictive strategy, RBC transfusion was permitted only when Hgb was [&le;]7.0 g/dL, whereas under the liberal strategy, transfusion was permitted when Hgb was >7.0 g/dL. The primary outcome was the first ICU-acquired infection occurring at least 72 hours after ICU admission. Per-protocol effects were estimated using a clone-censor-weight approach with a marginal structural model. A parametric g-formula was used as a complementary analysis that jointly modeled ICU discharge and ICU mortality as competing events to derive strategy-specific 28-day cumulative incidences and risk differences. Results 8 Among 4,013 eligible ICU stays, the liberal-versus-restrictive comparison provided little evidence of a difference in the risk of ICU-acquired infection (adjusted conditional OR, 0.954; 95% CI, 0.797 to 1.142). In the complementary g-formula analysis, the 28-day risk difference for the liberal versus restrictive comparison was -0.02 percentage points (95% CI, -0.15 to 0.11), consistent with the primary analysis. Findings were generally robust across prespecified subgroup and sensitivity analyses. Conclusion In this target trial emulation of adults with sepsis, we observed no clinically meaningful difference in ICU-acquired infection between RBC transfusion strategies defined by hemoglobin thresholds.

Background: Cone-beam computed tomography (CBCT) frequently captures the maxillary sinuses incidentally, and reliable automated detection of sinus abnormality is clinically relevant. Unlike most vision-language benchmarks in medical imaging, which pair images with pre-existing, human-authored clinical reports, findings text can also be generated directly by a large language model from the image itself--raising the question of how much diagnostic value such AI-derived text carries, and whether that value depends on independent verification. Multimodal artificial intelligence (AI) benchmarks risk overstating performance if the provenance of each input--image, raw AI-generated text, or radiologist-verified text--is not clearly separated and reported. Methods: We used 300 mid-sagittal CBCT slices from the MMDental dataset. ChatGPT generated findings text and a provisional normal/abnormal label for every slice (majority vote, three independent readings from the image alone); primary classification performance was assessed on this full, unfiltered set (n=300). A radiologist then independently reviewed each case's image together with ChatGPT's description, producing their own diagnosis; three cases were excluded as insufficient, yielding 297 confirmed cases. On this subset, every model was retrained and re-evaluated under identical 10-fold cross-validation on both the provisional ChatGPT-only labels ("pre") and the radiologist-confirmed labels ("post"), isolating the effect of label provenance from image or architecture. Eight vision architectures, seven language classifiers, and five VLMs were evaluated throughout; three generative models performed exploratory note-drafting. Findings: Raw ChatGPT-generated text produced the highest performance of any modality or condition: language models reached near-ceiling AUC (0.992 to 1.000, n=300), exceeding every vision model (AUC 0.799 to 0.880) and every VLM image-only probe (AUC 0.63 to 0.69). On the 297-case pre/post analysis, this advantage depended heavily on label source: language and text-derived VLM performance fell substantially from ChatGPT-only to radiologist-confirmed labels (e.g. BERT-base AUC 0.999 to 0.837), while vision-model performance was stable or modestly improved (e.g. DenseNet-121 0.867 to 0.891). The radiologist reclassified 62 of 297 cases (21%) relative to ChatGPT's provisional read, and a meaningful proportion of raw ChatGPT text was clinically uninterpretable or unsupported by the imaging. Interpretation: As shown here for the first time, raw, image-derived AI-generated text yields the highest apparent classification performance in this benchmark, but this reflects the text's alignment with its own self-generated labels rather than verified diagnostic content, and a substantial share of that text is not clinically explainable. Radiologist-confirmed text and labels give a lower but trustworthy estimate of true performance, on which convolutional neural network (CNN) vision models remain a stable, comparatively inexpensive baseline. Multimodal dental AI should report performance separately by modality and label provenance rather than pooling headline metrics.

The U.S. House's approval of the Sunshine Protection Act has revived the debate over permanent daylight saving time (DST) versus permanent standard time (ST). Health and sleep organizations favor permanent ST because it benefits health, especially for children with rigid school schedules. Further, permanent DST would push school start times to before sunrise in many regions, leading to dark-morning commutes. However, the safety consequences of this shift remain unquantified. Using real school start times for 14 states that have enacted permanent DST legislation, together with local sunrise time, we counted the school days on which students must leave home before sunrise under permanent ST, the current system, and permanent DST. In Washington State, where schools start on average at 08:27, neither permanent ST nor the current system requires any pre-sunrise departure, whereas permanent DST would for most of the winter. Using real school start-time data, permanent DST would add about 35 million child-days of pre-sunrise travel in Washington alone relative to the current system, with similar patterns across the other 13 states. Extrapolated to all U.S. public schools and assuming an 8:00 departure, permanent DST would generate more than 2 billion additional dark-morning commutes each year relative to the current system. Finally, analyzing Seattle traffic collisions, we found that the odds that a crash involved a pedestrian were 143% higher on dark mornings (adjusted odds ratio 2.4). Permanent DST would therefore expose many more children, on many more days, to elevated pedestrian-crash risk, evidence that deserves consideration as the United States chooses a time standard.

Background: Although the acute phase of the COVID-19 pandemic has passed, SARS-CoV-2 continues to cause outpatient morbidity. Antioxidant micronutrients support immune regulation and may offer a low-cost, scalable adjunctive treatment in early infection. Objective: To evaluate a pilot combination antioxidant therapy within CanTreatCOVID. Methods: This pilot sub-protocol enrolled non-hospitalized adults across five Canadian provinces (September 5th, 2024-March 31st, 2025) with mild-to-moderate SARS-CoV-2 infection within five days of symptom onset. Participants were randomized to usual care plus a 10-day antioxidant regimen (selenium 300 g, zinc 40 mg, lycopene 45 mg, vitamin C 1.5 g) or usual care alone. Pilot objectives assessed feasibility, retention, adherence, and safety. The primary outcome was hospitalization or death within 28 days; exploratory outcomes included recovery and symptom measures by day 14. Results: Eighty-one participants were randomized (41 antioxidant; 40 usual care). Retention was high 85.4% antioxidant; 82.5% usual care), and 90.2% of antioxidant participants completed the intervention course. Adverse events were infrequent (9.8% vs 2.5%), with no serious adverse events reported. No deaths occurred in either group; no hospitalizations occurred in the antioxidant arm versus 2/40 (5%) in usual care. By day 14, recovery was reported in 32/40 (80.0%) participants receiving antioxidants versus 23/36 (63.9%) in usual care (OR 2.128; 95% CI 0.7474.871). Sustained alleviation of all symptoms occurred in 38/40 (95.0%) versus 29/36 (80.6%), respectively (OR 3.498; 95% CI 0.872 --10.017). Return to usual activity by day 14 occurred in 38/40 (95.0%) versus 30/36 (83.3%) (OR 3.113; 95% CI 0.762--9.022). Adjusted between-group differences in dietary intake were not statistically significant. Conclusions: Combination antioxidant therapy was feasible to deliver in a decentralized outpatient setting, with high adherence and tolerability. While the trial was not powered for definitive efficacy conclusions, consistent directional improvements across symptom outcomes support evaluation of this host-directed antioxidant strategy in larger trials. Keywords: Adaptive Platform Trial; Antioxidant Therapy; SARS-CoV-2 ; Outpatient Therapeutics; Micronutrient Supplementation Trial registration number: https://clinicaltrials.gov/study/NCT05614349

Importance: Adolescent cannabis use is a growing concern due to its associations with long-term adverse mental health outcomes. However, the distinct, temporal associations of neurodevelopmental factors and childhood adverse life experiences (ALEs) with adolescent substance use in have not yet been fully elucidated. The Adolescent Brain Cognitive Development (ABCD) Study offers an unprecedented opportunity to prospectively examine neurobiological and socioenvironmental predictors of cannabis onset. Objective: To investigate magnetic resonance imaging-derived neurodevelopmental cortical brain Age Gap Estimate (brainAGE) and adverse life events as risk factors of early cannabis initiation. Design, Setting, and Participants: The ABCD Study is a longitudinal study across 22 sites in the United States. Data are collected starting at approximately 10 years old (currently at year-7 follow-up). Our analyses comprised 6688 (48% female) youth after exclusions. Main Outcomes and Measures: Cox proportional hazard models were computed to investigate brainAGE-sex interactions and 10 adversity dimensions at baseline as predictors of time to cannabis initiation up to age 18. Results: Mean age of initiation was 14.8 years (SD=1.43). Global brainAGE was modestly associated with cannabis initiation in females only (Hazard Ratio [HR]=1.05; 95% Confidence Interval [CI]=1.00-1.10, p = .049). Low socioeconomic status, caregiver substance use, family anger and arguments, and caregiver lack of supervision were associated with initiation (HRs = 1.11, 1.56, 1.09, 0.85, respectively; CIs = 1.04-1.19, 1.44-1.69, 1.09-1.19, 0.76-0.91, respectively; p's < .05). Other ALE dimensions and network-specific brainAGEs were not significantly associated with initiation. Conclusions and Relevance: Findings suggest that while cortical brainAGE may be somewhat increase vulnerability to adolescent cannabis use in females, its contributions are modest at best. In contrast, early childhood adversities such as socioeconomic factors and familial characteristics may present more substantive targets for prevention and intervention.

Background YouTube highlights packages are a major and growing route to football consumption, particularly among children and young people, but brand exposure within them has not been quantified. We measured unhealthy commodity brand exposure in English Premier League (EPL) and FIFA World Cup (WC) highlights. Methods We coded brand appearances lasting two or more seconds in 10 Sky Sports EPL highlights (final 10 games of the 2025/26 season) and 19 official FIFA 2026 WC highlights, recording commodity category, placement, and match moment, alongside pre-roll YouTube adverts. Data were collected between 4 June and 27 July 2026. Five highlights were double-coded (Cohen's kappa 0.85). Results Overall brand density was similar across competitions (13.1 vs 13.9 references per minute), but composition differed markedly. Unhealthy commodity branding occupied 38.0% of EPL screen time versus 18.7% at the WC, a difference driven almost entirely by gambling (32.6% vs 1.5%). Gambling appeared in every EPL package, mainly on pitchside boards and LED screens (50.4%), with front-of-shirt accounting for 27.1%. WC exposure was more evenly spread across HFSS food (13%), alcohol (4%) and trading/crypto/prediction markets (3.7%), and appeared almost exclusively pitchside. Gambling brands accounted for ten of twelve pre-roll EPL adverts (123 of 153 seconds); no gambling adverts preceded WC highlights. Conclusions Gambling dominates unhealthy commodity exposure in EPL highlights, both in-video and in pre-roll advertising. Because most appearances occur away from the front of shirt, the voluntary front-of-shirt sponsorship withdrawal will leave the majority of this exposure intact. The WC comparison shows that tighter central control of the advertising environment produces lower and more diffuse exposure, and that governments and governing bodies with such control could restrict unhealthy categories altogether.

Importance: Chronic stress may contribute to adverse health outcomes through cumulative physiologic dysregulation. Allostatic load (AL), a composite measure of multisystem physiologic burden, may capture biologic effects of structural, social, and psychosocial stress not reflected by self-reported measures. Objective: To evaluate racial and ethnic differences in AL among women with familial cancer risk and examine how socioeconomic status, psychosocial factors, clinical characteristics, and health behaviors contribute to variations in AL. Design: Cross-sectional study of underrepresented minority participants enrolled in the HERSTORY cohort from October 2023 through September 2025, with comparison participants from the UCLA ATLAS biobank. Setting: UCLA academic health system. Participants: The study included 303 racially and ethnically diverse female HERSTORY participants aged [&ge;]35 years with a family history of cancer and matched non-Hispanic White female ATLAS participants (n=709). Exposures: Race and ethnicity, age, neighborhood deprivation, cancer history and stage, depression, perceived stress, cancer worry, and physical activity. Main Outcomes and Measures: The primary outcome was AL, calculated from cardiometabolic and organ-function measures. A secondary index incorporated race- and ethnicity-specific neutrophil-to-lymphocyte ratio (NLR) derived from 326,826 women in the UCLA Health population. Multivariable regression models evaluated factors associated with elevated AL. Results: Compared with matched non-Hispanic White participants, Black and Asian/Pacific Islander HERSTORY participants had significantly higher AL after adjustment. Hispanic/Latina participants did not have significantly elevated AL. Older age, greater area-level socioeconomic deprivation, and depression were independently associated with higher AL. Prior cancer diagnosis, cancer worry and perceived stress were not significantly associated with AL, whereas regular physical activity was associated with lower AL. Among cancer patients, advanced stage was associated with greater AL. Conclusions and Relevance: This study demonstrates elevated AL among understudied racial/ethnic minority groups with familial cancer risk and identifies associations with neighborhood deprivation, depression, and physical activity. The association between cancer stage and AL suggests that physiologic stress may reflect variation in cancer burden. The lack of association with perceived stress and cancer worry further indicates that physiologic and self-reported psychosocial measures capture distinct dimensions of stress. The development of race/ethnicity-specific NLR thresholds derived from large population samples provide a benchmark for future studies.

Background: Subepithelial connective tissue grafting remains a reference treatment for predictable root coverage. Although short- and medium-term outcomes of tunnel-based procedures are well documented, evidence regarding stability beyond 10 years remains limited. This study evaluated the long-term clinical performance of a minimally invasive tunnel technique combined with subepithelial connective tissue grafting (SCTG) under routine clinical conditions. Methods: This retrospective longitudinal cohort study included 74 patients (57 women and 17 men) contributing 710 gingival recession sites treated between 2009 and 2025. All sites were treated with a tunnel approach and SCTG, with enamel matrix derivative (EMD) used in selected cases. The mean follow-up was 6.0 for 4.0 years, with a maximum observation period of 16 years. The primary outcome was recession depth reduction. Secondary outcomes included complete root coverage (CRC), mean root coverage, and long-term marginal stability. Clinically relevant relapse was defined as a 1 mm increase in recession after initial healing. Results: Mean recession reduction was 2.72 mm. Complete root coverage was achieved at 83.4% of treated sites. At the final available follow-up, no treated site showed a clinically relevant relapse of 1 mm after initial healing, and no site deteriorated beyond its baseline recession level. Treatment effects were observed across anterior and posterior regions. Conclusions: Within the limitations of a retrospective cohort design, tunnel surgery combined with SCTG was associated with high root-coverage predictability and durable marginal soft-tissue stability for observation periods extending to 16 years. These real-world data support phenotype-enhancing, minimally invasive soft-tissue augmentation as a durable therapeutic strategy for localized and multiple gingival recessions. Keywords: gingival recession; tunnel technique; subepithelial connective tissue graft; root coverage; periodontal plastic surgery; long-term stability

Background and Aims: Anxiety remains prevalent among adolescents while tobacco and nicotine product use, especially the recent increases of novel product use such as e-cigarettes and nicotine pouches, raises further public health concerns. The associations between novel tobacco and nicotine product use and anxiety remains understudied. This study aims to determine whether tobacco and nicotine product use is associated with generalised anxiety and whether this association differs by used product. Design: Cross-sectional survey, School Health Promotion study in 2025. Setting: A school-based nationwide survey conducted in all Finnish lower and upper secondary schools. Participants: Students aged 13-20 years in three school levels: 8.-9. grade students in lower secondary schools (N= 94 743, 73% of the students), 1st and 2nd-year students in general upper secondary schools (n=47 248, 70% of the students) and of vocational institutions (n=24 998, 38% of the students). Measurements: Exclusive (single product) and non-exclusive ([&ge;]1 products) daily or weekly use of tobacco and nicotine products, including nicotine pouches, e-cigarettes, cigarettes, and smokeless tobacco (snus). Generalised anxiety was measured using the Generalised Anxiety Disorder Scale (GAD-7). The cut-off of >10 points indicated participants with moderate to severe self-reported generalised anxiety symptoms. Background variables included sociodemographic variables and heavy drinking. Results: Of the 166,989 participants 51.4% were females, mean age was 15.7 (SD 1.27), 21.2% reported generalised anxiety. Prevalence of generalised anxiety increased gradient-wise in accordance with both non-exclusive and exclusive use frequency of different tobacco and nicotine products, as well as with number of products used. Daily use of nicotine pouches was associated with higher odds of anxiety compared with never use (boys: adjusted odds ratios (aOR) 1.19, 95% CI, 1.05 to 1.34; girls: aOR 1.74, 95% CI, 1.58 to 1.91), yet the association between daily e-cigarette use seemed to be stronger (boys aOR 1.96, 95% CI, 1.54 to 2.49; girls: aOR 2.29, 95% CI, 2.09 to 2.51). Summary: Any use of tobacco and nicotine products, including new products, is associated with generalised anxiety among adolescents, with some differences between products. Measures to prevent the initiation of tobacco and nicotine product use and to promote mental health among adolescents should be enacted.

In February 2021, Oregon became the first US state to decriminalize possession of small amounts of all commonly used illicit drugs (Measure 110); twenty-four days later, Washington's Supreme Court Blake ruling produced a weaker, shorter-lived decriminalization. Evaluations of these policy periods have focused on overdose deaths, with contested results; their association with the mental health of the general population is unknown. Using surveillance data on 6.3 million adult interviews (2011-2024) and synthetic control methods with permutation inference, we find frequent mental distress an estimated 2.15 percentage points higher in Oregon than in its synthetic counterfactual (largest positive gap among 45 jurisdictions; two-sided rank 2/45, p = 0.044, though not significant under the alternative fit-normalized statistic), with directionally consistent estimates in Washington and a joint test on the pair at p = 0.015. The increase concentrates in self-reported distress, among women and young adults, and is not mirrored in diagnoses, police-recorded partner violence or suicide.

Objectives To evaluate whether access to a certified large language model (LLM)-based clinical decision support system improves physician diagnostic performance in rheumatology compared with conventional diagnostic resources alone. Methods In this multicentre, open-label, randomised controlled trial, 82 physicians from seven hospitals in two countries were randomised 1:1 to conventional diagnostic resources plus Prof. Valmed or conventional resources alone. Participants assessed three rheumatology vignettes before and after assistance. The primary outcome was top-1 diagnostic accuracy. Secondary outcomes included top-3 accuracy, diagnostic reasoning, confidence, case-processing time and perceived support quality. Results Top-1 accuracy increased from 22.2% to 33.3% in the intervention group and from 23.3% to 35.0% in the control group, with no between-group difference in improvement (adjusted OR 0.99, 95% CI 0.45 to 2.19; p=0.979). Differences in top-3 accuracy, diagnostic reasoning and confidence were also not significant. Assisted case-processing time was substantially shorter with LLM support (94 vs 206 s; adjusted mean difference -112 s, 95% CI -141 to -83; p<0.001). Information timeliness and perceived diagnostic support quality were rated significantly higher in the intervention group. Exploratory analyses showed persistent overconfidence and substantial AI over-reliance. Conclusions Certified LLM-based diagnostic support did not improve diagnostic accuracy compared with conventional resources, but substantially reduced case-processing time and improved perceived support quality. These findings suggest potential workflow benefits while highlighting overconfidence and over-reliance as important safety considerations.

Introduction Smoking prevalence remains higher in rural than in urban populations in the United States. To examine recent trends, we assessed state-level differences in cigarette smoking between urban and rural areas from 2018 to 2024. Methods Using repeated cross-sectional data from the Behavioral Risk Factor Surveillance System, we estimated state-specific logistic regression models to examine the relationship between urban-rural county residence and cigarette smoking. Unadjusted models (model 1) included urban-rural county status and year. Subsequent models (model 2) added age, sex, and race/ethnicity. A final model (model 3) included education and an interaction term between urban-rural county status and year to examine whether gaps in urban-rural smoking changed over time. In states with significant interactions, simple effects tests compared trends for urban-rural groups separately. Results Compared to urban adults, rural adults had higher unadjusted odds of cigarette smoking (odds ratio [OR] range:1.07-1.88) in 88.4% (38/43) of states. Adjusting for demographic covariates (model 2) increased the proportion of states with significant marginal effects of rurality to 90.7% (ORs:1.09-1.87). A final model that also controlled for education (model 3) decreased the proportion of states with significant marginal effects of rurality to 60.5% (ORs:1.10-1.54). Among the 14 states with significant interaction terms, the odds of smoking declined faster among urban than rural residents. Conclusion Urban-rural differences in smoking persist across most states. No state showed a reduction in urban-rural disparities over time, and the urban-rural gap widened in 14 states. Demographic variation accounted for some, but not the majority, of observed urban-rural differences.

Background The phase 3 ADVOCATE trial evaluated the efficacy and safety of avacopan in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Concerns raised regarding the 2019 primary endpoint adjudication process prompted a blinded, independent readjudication of all participants' primary outcomes, the results of which are described here. Methods Patients with GPA or MPA were randomized 1:1 to receive oral avacopan 30 mg twice daily or oral prednisone on a scheduled taper, each in combination with rituximab- or cyclophosphamide-based standard of care. In 2026, the Duke Clinical Research Institute Clinical Events Classification group conducted an independent, blinded committee re-adjudicated the Birmingham Vasculitis Activity Score (BVAS), relapse, and remission from weeks 26 through 52 using procedures aligned with the original adjudication charter. The primary endpoints were remission at week 26 and sustained remission at week 52. As per the original analysis plan, noninferiority and superiority were declared if the lower bounds of the 95% confidence interval (CI) for the difference in the primary outcome rates between avacopan and a prednisone taper were greater than -20.0 and 0.0 percentage points, respectively. Results Among 330 participants in the intent-to-treat population, remission at week 26 was achieved by 68.1% (113/166) and 67.1% (110/164) of participants in the avacopan and prednisone taper groups, respectively, in the 2026 readjudication (adjusted difference: 2.2%; 95% CI, -7.5, 11.9), compared with 72.3% (120/166) and 70.1% (115/164) in the 2019 primary outcome adjudication (adjusted difference: 3.4%; 95% CI, -6.0, 12.8). Sustained remission at week 52 was achieved by 61.4% (102/166) and 52.4% (86/164) of participants, respectively, in the 2026 readjudication (adjusted difference: 9.8%; 95% CI, -0.3, 19.9), compared with 65.7% (109/166) and 54.9% (90/164) in the 2019 readjudication (adjusted difference: 12.5%; 95% CI, 2.6, 22.3). Concordance between the 2019 and 2026 adjudications was 95.2% for remission and 93.6% for sustained remission. Conclusion The re-analysis of ADVOCATE based on the 2026 readjudication further supports the efficacy of avacopan for GPA/MPA. Non-inferiority of avacopan versus a prednisone taper was confirmed at weeks 26 and 52 despite a median 81% reduction in glucocorticoid exposure observed in the avacopan versus prednisone taper groups. While a consistent numerical difference favoring avacopan at week 52 was observed in the 2019 and 2026 analyses, this difference did not reach statistical superiority.

Importance: While increased physical activity (PA) and decreased sedentary behavior (SB) are associated with favorable health outcomes, evidence regarding their causal effects on healthcare costs remains limited. Objective: To assess the causal effects of PA and SB on healthcare costs. Design: A two-sample Mendelian randomization (MR) study. Setting: Separate, non-overlapping cohorts with genetic instruments for self-reported and device-based PA and SB, and healthcare costs. Participants: The instruments used to assess self-reported PA were derived from a genome-wide meta-analysis of 606,820 individuals across 51 cohorts. Two large genome-wide association studies (GWASs) were used for self-reported SB (leisure screen time N=526,725; television watching N=408,815), while accelerometer-based GWASs (N=89,683-91,105) were used for device-based PA and SB. The instruments used to assess the outcome data were obtained from the FinnGen cohort (N=373,160). Exposures: Genetically predicted PA and SB. Main Outcomes and Measures: Validated genetic instruments for log-transformed annual healthcare costs derived from registers, including primary care, secondary care, and medication costs. Inverse variance weighting was used as the primary MR measure, while the sensitivity analyses included MR-Egger, weighted median, simple mode, weighted mode, F-score, Cochran's Q, and leave-one-out analysis. Results: Higher genetically predicted self-reported PA was associated with lower healthcare costs (causal estimate, {beta} = -0.166; 95% CI, -0.270 to -0.062). In contrast, higher genetically predicted SB (leisure screen time or television watching) was associated with higher healthcare costs across self-reported datasets ({beta} = 0.097; 95% CI, 0.064 to 0.130; {beta} = 0.114; 95% CI, 0.063 to 0.165, respectively). No associations were observed for device-based PA ({beta} = -0.014; 95% CI, -0.040 to 0.014) or SB ({beta} = -0.009; 95% CI, -0.197 to 0.179). Conclusions and Relevance: Findings based on genetically predicted PA and SB support a causal association between these behaviors and healthcare costs, suggesting that increasing population's leisure-time PA and reducing SB may decrease healthcare expenditure. This highlights the importance of promoting PA for both population health and long-term sustainability of healthcare systems. However, causal evidence remains partly limited, particularly for device-based measures of these behaviors.