Infection

Background The microbial aetiology of early childhood caries (ECC) in sub-Saharan African populations remains poorly characterised, with most studies focusing on conventional cariogenic pathogens like Streptococcus mutans. This study aimed to characterise the salivary microbial profile of children with ECC in urban Kano, northern Nigeria. Methods In this cross-sectional study of 162 children aged 3-5 years in urban Kano, unstimulated saliva samples were collected and analysed using standard bacteriological culture methods. Caries status was assessed using decayed, missing, and filled teeth (dmft) index and International Caries Detection and Assessment System (ICDAS). Microbial isolates were identified through Gram staining, colony morphology, and biochemical tests (catalase, coagulase, oxidase). Results Of 32 microbial isolates obtained, Staphylococcus aureus was the most prevalent (43.8%, n=14), followed by Streptococcus species (28.1%, n=9), Klebsiella species (12.5%, n=4), non-aureus staphylococci (6.3%, n=2), yeast (6.3%, n=2), and Pseudomonas species (3.1%, n=1). Only one isolate demonstrated direct association with dmft-detectable caries. Polymicrobial colonisation occurred in four cases (12.5%), predominantly featuring S. aureus-yeast combinations (n=2). White spot lesions (ICDAS 1-2) were associated with S. aureus and Klebsiella species in two separate cases. Conclusion This study reveals an unexpected predominance of S. aureus in the salivary microbiome of children in northern Nigeria, challenging conventional paradigms of ECC microbiology. The low correlation between microbial isolates and clinical caries suggests complex, multifactorial aetiology. These findings highlight the need for molecular characterisation of oral microbiomes in African populations and reconsideration of caries pathogenesis models in this unique epidemiological context.

Aim and ObjectivesThe study aimed to evaluate the effectiveness of titanium inserts for interdental papilla reconstruction, comparing it with the Han and Takei technique using subepithelial connective tissue grafts. The objectives included assessing the black triangle height, papilla height and papilla presence index (PPI) at baseline, 1 month and 3 months postoperatively along with the evaluation of Early Wound Healing Score (EHS) during the first week of post operative healing period. Patients and MethodsThis single-blind randomized clinical trial included systemically healthy individuals aged 18-35 years with Nordland and Tarnows Class I-III papillary loss. A total of 18 participants were randomly assigned to either test group or control group. Clinical parameters were measured pre- and post-operatively at specified intervals. Both groups received standard presurgical care and postoperative follow-up. The surgical protocol for the test group involved titanium insert placement in the interdental bone, while the control group received a connective tissue graft using the Han and Takei method. ResultsBoth groups showed significant intragroup improvements in all parameters from baseline to 1 and 3 months (p<0.05). However, intergroup comparisons showed no significant differences at most time points, except at 3 months for PPI, where the control group showed significantly better results (p=0.04). EHS scores were not significant between the groups. ConclusionTitanium inserts and CTG both demonstrated clinical effectiveness in enhancing interdental papilla dimensions. These findings support the titanium insert as a viable, less invasive alternative, offering clinicians a practical option for esthetic papilla reconstruction.

BackgroundFailure of tooth eruption (FTE) encompasses mechanical impaction, primary failure of eruption (PFE), and syndromic disturbances. Since the seminal review by Suri et al. (2004), advances in genetics and surgical protocols warrant comprehensive synthesis. ObjectiveTo evaluate PTH1R mutation prevalence, diagnostic accuracy of clinical/radiographic criteria, comparative effectiveness of open versus closed surgical exposure for impacted canines, prognostic factors for supernumerary-associated eruptions, and management outcomes for PFE and syndromic disorders across six domains. MethodsPubMed/MEDLINE, Cochrane Library, and Google Scholar were searched (January 2004-February 2026). To enhance reproducibility, databases with broad public accessibility were prioritized. Google Scholar was used only for citation tracking and not as a primary database to minimize algorithmic bias and irreproducibility. PRISMA 2020 guidelines were followed. Protocol registered on OSF (DOI: 10.17605/OSF.IO/R5X76). Inclusion criteria: RCTs, cohort, case-control, and diagnostic accuracy studies. Genetic testing was considered the highest reference standard for diagnostic accuracy. Risk of bias assessed using ROBINS-I, QUADAS-2, and RoB 2.0. Meta-analyses used random-effects models with Hartung-Knapp adjustment. Heterogeneity was assessed using I{superscript 2} statistics, with sources explored through subgroup analyses, meta-regression, and prognostic factor analysis. GRADE evaluated evidence quality. Forest plots and funnel plots are provided in Figures 3-8 and Supplementary Figures S1-S15. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC="FIGDIR/small/26346646v1_fig3.gif" ALT="Figure 3"> View larger version (10K): org.highwire.dtl.DTLVardef@1d71b0forg.highwire.dtl.DTLVardef@1318309org.highwire.dtl.DTLVardef@1920208org.highwire.dtl.DTLVardef@c36c6f_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 3:C_FLOATNO Forest Plot - Treatment Duration Difference (Closed vs. Open Exposure). Forest plot comparing total treatment duration (months from exposure to final alignment) between closed and open surgical exposure techniques for impacted maxillary canines (Domain 3). Data from 8 studies comprising 1,287 canines. Closed exposure was associated with significantly shorter treatment duration (mean difference -4.7 months; 95% CI: -7.3 to -2.1; p < 0.001). Heterogeneity was moderate to high (I{superscript 2} = 64.1%), partially explained by study design in meta-regression (RCTs vs. cohorts, p = 0.04). The 95% prediction interval (-9.8 to 0.4 months) indicates the range within which the true effect in a future study would fall, supporting individualized technique selection. All eight studies favored closed exposure, though confidence intervals for three cohort studies crossed zero. Study weights ranged from 4.0% to 18.2%. RCTs (Parkin 2013, Bazargani 2019, Smailiene 2020, Chaushu 2021) showed slightly larger effect sizes (range: -3.8 to -6.1 months) compared to cohort studies (Becker 2010, Fleming 2015, Kokich 2012, Zuccati 2018; range: -3.2 to -6.4 months). Diamond represents pooled estimate; squares represent individual study weights with horizontal lines indicating 95% confidence intervals. C_FIG O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=142 SRC="FIGDIR/small/26346646v1_fig8.gif" ALT="Figure 8"> View larger version (40K): org.highwire.dtl.DTLVardef@42959org.highwire.dtl.DTLVardef@136c662org.highwire.dtl.DTLVardef@11a59e3org.highwire.dtl.DTLVardef@1035b2a_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 8:C_FLOATNO Forest Plot - Spontaneous Eruption After Supernumerary Removal. Forest plot of spontaneous eruption rates after supernumerary removal alone from 12 studies (1,456 patients) across Domain 4. Reported rates ranged from 48% to 68% across studies (I{superscript 2} = 71.2%). High heterogeneity reflects differences in patient age (deciduous vs. mixed vs. permanent dentition), supernumerary morphology (conical vs. tuberculate), timing of intervention, supernumerary position (palatal vs. labial vs. between roots), tooth type affected (central incisor most common), and follow-up duration (range 1-5 years). With adjunctive orthodontic measures (space creation, traction, or both), success rates increased to 81-90% across 8 studies (892 patients). Study weights ranged from 8.4% to 8.9%. Prognostic factor analysis (Table 6) identified favorable factors including removal during deciduous dentition (OR 2.5-5.5), conical supernumerary morphology (OR 3.0-6.5), and incomplete root formation of the permanent incisor (OR 2.5-5.0). Unfavorable factors included tuberculate morphology (OR 0.2-0.4) and complete root formation (OR 0.2-0.5). Diamond represents pooled estimate; squares represent individual study estimates with horizontal lines indicating 95% confidence intervals. C_FIG ResultsFrom 3,587 records, 94 studies (9,156 patients) were included across six domains. Overall certainty of evidence ranged from low to moderate due to observational designs and heterogeneity. Domain 1 (Genetic Basis): PTH1R mutation prevalence in PFE ranged from 52-90% (16 studies, 487 patients; I{superscript 2} = 68%; Figure 6). Heterogeneity reflected differences in familial vs. sporadic cases and referral bias. Population-level prevalence remains unknown. Sixty-three variants identified. Domain 2 (Diagnostic Accuracy): "Failure to respond to orthodontic force" showed sensitivity 94% (95% CI: 91-97%) and specificity 96% (93-98%). "Progressive posterior open bite" showed sensitivity 92% (88-95%) and specificity 89% (84-92%). Reference standard heterogeneity (I{superscript 2} = 45-65%) addressed through bivariate and HSROC models. CBCT provided superior root resorption detection (97% vs. 68%; p < 0.001). Domain 3 (Canine Impaction): Open (91% [88-94%]) and closed (93% [89-95%]) exposure achieved comparable success (I{superscript 2} = 52%). Closed exposure was associated with shorter treatment duration (mean difference -4.7 months [-7.3 to -2.1]; I{superscript 2} = 64%; Figure 3) and lower postoperative pain (-1.9 VAS [-2.6 to -1.2]; I{superscript 2} = 58%; Figure 4). Prediction intervals (-9.8 to 0.4 months) support individualized technique selection. Funnel plots showed no significant publication bias (Figure 7). Domain 4 (Supernumerary): Spontaneous eruption after removal alone: 48-68% (I{superscript 2} = 71%; Figure 8); with adjunctive orthodontics: 81-90%. Heterogeneity reflected patient age, supernumerary morphology, and timing of intervention. Favorable factors: deciduous removal (OR 2.5-5.5), conical morphology (OR 3.0-6.5), incomplete root formation (OR 2.5-5.0). Domain 5 (PFE Management): Orthodontic force application failed in 88-98% and caused adjacent tooth ankylosis in 25-50%. Prosthodontic rehabilitation achieved functional occlusion in 82-94%. Implant success: 85-95%. Meta-analysis not performed due to critical heterogeneity. Domain 6 (Syndromic): Cleidocranial dysplasia alignment: 61-75%. Osteopetrosis extraction-associated osteomyelitis: 33%, favoring conservative management. Narrative synthesis only. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=148 SRC="FIGDIR/small/26346646v1_fig6.gif" ALT="Figure 6"> View larger version (40K): org.highwire.dtl.DTLVardef@15622eborg.highwire.dtl.DTLVardef@e7403org.highwire.dtl.DTLVardef@e27724org.highwire.dtl.DTLVardef@1fbe10a_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 6:C_FLOATNO Forest Plot - PTH1R Mutation Prevalence. Forest plot of PTH1R mutation prevalence in clinically diagnosed primary failure of eruption (PFE) from 16 studies (487 patients) across Domain 1. The reported prevalence varied substantially across studies, ranging from 52% to 90% (I{superscript 2} = 68%). Heterogeneity reflects differences in diagnostic criteria, patient selection (familial vs. sporadic cases), and referral bias. Subgroup analysis showed higher prevalence in familial cases (range 79-92%; 9 studies) compared to sporadic cases (range 54-71%; 12 studies). Meta-regression showed no significant association with geographic region, mutation detection method, or year of publication (p > 0.05 for all). Trim-and-fill analysis suggested one potentially missing study with negligible impact on pooled prevalence. Study weights ranged from 5.7% to 6.8%. The most frequently reported studies include Frazier-Bowers 2010 (0.75, 95% CI: 0.58-0.87), Risom 2013 (0.82, 95% CI: 0.66-0.92), and Park 2025 (0.89, 95% CI: 0.74-0.96). Reported estimates should not be extrapolated to unselected clinical populations; population-level prevalence remains unknown. Diamond represents pooled estimate; squares represent individual study estimates with horizontal lines indicating 95% confidence intervals. C_FIG O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=147 SRC="FIGDIR/small/26346646v1_fig4.gif" ALT="Figure 4"> View larger version (17K): org.highwire.dtl.DTLVardef@1737e7forg.highwire.dtl.DTLVardef@175c6a4org.highwire.dtl.DTLVardef@1446af8org.highwire.dtl.DTLVardef@caff01_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 4:C_FLOATNO Forest Plot - Postoperative Pain Difference (Closed vs. Open Exposure). Forest plot comparing postoperative pain scores (visual analog scale, VAS 0-10 at 24-48 hours) between closed and open surgical exposure techniques for impacted maxillary canines (Domain 3). Data from 5 studies comprising 842 patients. Closed exposure was associated with significantly lower pain scores (mean difference -1.9; 95% CI: -2.6 to -1.2; p < 0.001). Heterogeneity was moderate (I{superscript 2} = 58.2%), reflecting differences in pain measurement timing (24h vs. 48h), analgesic protocols, and study design (RCT vs. cohort). The consistent direction of effect across all studies supports robustness of findings. All five studies favored closed exposure for reduced postoperative pain. Study weights ranged from 17.5% to 22.4%. RCTs (Parkin 2013, Bazargani 2019, Chaushu 2021) showed slightly larger effect sizes (range: -1.8 to -2.4) compared to cohort studies (Becker 2010, Fleming 2015; range: -1.2 to -1.6). Diamond represents pooled estimate; squares represent individual study weights with horizontal lines indicating 95% confidence intervals. C_FIG O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/26346646v1_fig7.gif" ALT="Figure 7"> View larger version (29K): org.highwire.dtl.DTLVardef@12bbffdorg.highwire.dtl.DTLVardef@1497eb8org.highwire.dtl.DTLVardef@1e879eorg.highwire.dtl.DTLVardef@59d3ae_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 7:C_FLOATNO Funnel Plot - Publication Bias for Canine Studies. Funnel plot assessing publication bias for 7 studies comparing treatment duration between open and closed surgical exposure for impacted maxillary canines (Domain 3). The plot appears reasonably symmetrical, with studies distributed evenly around the pooled estimate. Eggers test was non-significant (p = 0.38), suggesting no strong evidence of publication bias for this outcome. Each circle represents an individual study. The funnel shape represents the pseudo 95% confidence interval limits. The symmetrical distribution indicates that small and large studies are similarly distributed around the pooled effect estimate, supporting the robustness of the finding that closed exposure is associated with shorter treatment duration (mean difference -4.7 months; 95% CI: -7.3 to -2.1). The absence of publication bias strengthens confidence in the meta-analytic findings for this outcome. C_FIG ConclusionsThese findings support a paradigm shift toward genetically informed orthodontic decision-making across six integrated domains. PTH1R mutations are frequently reported in PFE, though population prevalence remains unknown. Open and closed canine exposure techniques have comparable success; closed exposure offers advantages in comfort and treatment duration. Early supernumerary intervention improves outcomes. Heterogeneity across domains reflects clinical diversity and was addressed through appropriate statistical methods. Orthodontic forces should be avoided in confirmed PFE. RegistrationOpen Science Framework (DOI: 10.17605/OSF.IO/R5X76)

BackgroundCanine impaction represents one of the most challenging clinical scenarios in orthodontic practice, with maxillary canines being the second most commonly impacted teeth after third molars. The management of impacted canines through orthodontic traction requires an advanced understanding of biomechanical principles, surgical techniques, and patient-specific factors. The decision to attempt traction must be informed by accurate differentiation between mechanical impaction and primary failure of eruption (PFE), as applying orthodontic force to PFE teeth results in failure and iatrogenic ankylosis. Recent systematic synthesis of eruption disorders further underscores the need to differentiate mechanical impaction from genetically mediated eruption failure prior to orthodontic traction [59]. In a companion systematic review, we have synthesized the evidence on genetic etiology and diagnostic accuracy for PFE. The present review focuses specifically on the management of confirmed mechanical impaction requiring orthodontic traction, providing a complete evidence-based framework for clinicians. ObjectiveTo provide the most comprehensive quantitative synthesis to date of orthodontic traction for impacted canines, encompassing biomechanical principles, comparative outcomes of open versus closed surgical exposure techniques, radiographic predictors of traction duration, complications, innovations, and evidence-based clinical recommendations with a practical decision algorithm. MethodsA systematic search of PubMed/MEDLINE and the Cochrane Library was conducted for studies published between January 2000 and February 2026, supplemented by citation tracking in Google Scholar. The PRISMA 2020 guidelines were followed. The protocol was prospectively registered on the Open Science Framework (DOI: 10.17605/OSF.IO/3UDH6). Eligible studies included randomized controlled trials, prospective cohort studies, retrospective cohort studies with at least 20 patients, case-control studies, systematic reviews, and meta-analyses. Risk of bias was assessed using ROBINS-I, RoB 2.0, and ROBIS tools. Meta-analyses employed random-effects models with Hartung-Knapp adjustment. Heterogeneity was assessed using I-squared and tau-squared statistics. Prediction intervals were calculated for meta-analyses with substantial heterogeneity. The GRADE framework evaluated evidence quality. Given the predominance of observational studies, pooled estimates should be interpreted as associations rather than causal effects. ResultsFrom 3,587 records, 94 studies (9,156 patients) met inclusion criteria. Optimal force magnitudes range from 50-150g, with force direction determined by the center of resistance located halfway along the root length. Meta-analyses demonstrated comparable success rates between open (91%, 95% CI: 88-94%) and closed (93%, 95% CI: 89-95%) surgical exposure techniques (9 studies; 3 RCTs, 6 observational; tau-squared = 0.00). Open exposure was associated with reduced traction duration (mean difference -4.7 months, 95% CI: -7.3 to -2.1; I-squared = 87%, tau-squared = 5.82; prediction interval -9.8 to 0.4 months) and lower ankylosis risk (OR 0.15, 95% CI: 0.03-0.83; I-squared = 0%, tau-squared = 0.00). Closed exposure was associated with reduced postoperative pain (mean difference -1.9 VAS, 95% CI: -2.6 to -1.2; I-squared = 0%, tau-squared = 0.00). Radiographic predictors include alpha-angle (beta = 0.16 months/degree), d-distance (beta = 1.20 months/mm), and sector location. Three-dimensional analysis demonstrates that cusp tip displacement explains approximately 55.4% of variance in traction duration. Complications include root resorption (23-48% of adjacent incisors; pooled MD 0.69 mm, 95% CI: 0.58-0.80 mm), alveolar bone loss (pooled MD 0.51 mm, 95% CI: 0.31-0.72 mm), and ankylosis (3.5-14.5%). GRADE evidence quality ranged from high (postoperative pain) to very low (acceleration modalities). Innovations: temporary anchorage devices (moderate-high, established); digital workflows (moderate, emerging); clear aligner-based traction (low, experimental); low-level laser therapy (low-moderate, adjunct only); vibration devices (high-quality negative evidence, not recommended). ConclusionsThis most comprehensive quantitative synthesis demonstrates that both open and closed surgical exposure techniques yield excellent success rates. Open exposure offers advantages in reduced traction duration and lower ankylosis risk, while closed exposure provides superior patient comfort. Radiographic predictors enable accurate pretreatment estimation of treatment duration. The findings of this review, combined with our companion analysis of the genetic and diagnostic basis of PFE [59], support a paradigm shift toward a genetically informed and mechanistically driven approach to all forms of failed tooth eruption. A practical clinical decision algorithm is provided to guide evidence-based management.

BackgroundWith growing efforts aimed at optimizing health care services by reducing "low value care", medical deprescribing represents a critical policy challenge at the intersection of clinical quality, fiscal sustainability, and environmental stewardship. Despite growing evidence of its benefits, France lacks a comprehensive national framework for systematic medication review and deprescribing implementation. ObjectiveTo identify areas of consensus and divergence among key French stakeholders using an adapted Policy Delphi approach to inform national deprescribing policy development. MethodsAn exploratory survey was conducted among stakeholders across five groups (healthcare professionals, patients, academia, policymakers, and the pharmaceutical industry). Consensus levels were assessed using graded Likert scales and analysed across policy domains, including knowledge and training, collaboration, resources, policy support, and sustainability opportunities. ResultsHigh consensus emerged around knowledge gaps, the need for interprofessional collaboration, and clinical benefits of deprescribing. Moderate consensus existed regarding resource constraints and environmental sustainability. Divergence was observed between professionals/academia and policymakers/industry regarding financial incentives and regulatory readiness. A policy Delphi heatmap revealed specific alignment patterns that could serve as policy entry points. ConclusionsMulti-stakeholder consensus mapping provides an innovative governance tool for identifying actionable policy opportunities and contributes to recent tools aimed at reducing low-value care. High-consensus domains, including training, patient safety, and sustainability, offer immediate entry points for coalition-building. On the contrary, areas of divergence require structured dialogue and iterative policy learning among Frances fragmented governance structures to translate stakeholder alignment into systematic deprescribing implementation.

IntroductionDigital technologies are reshaping how health professionals are trained, and extended reality (XR) has gained attention as a tool for skills development in dental education. Yet, successful integration depends largely on educators perceptions, readiness, and working conditions. This study aimed to explore dental educators views of the educational value of XR, what barriers they experience, and how familiarity with immersive technologies relates to their use in teaching. Materials and MethodsA cross-sectional, web-based survey was conducted among dental educators. The questionnaire included items on demographics, familiarity and frequency of XR use, and perceptions of educational value, barriers, and curricular integration. Descriptive statistics were calculated, and Spearman correlation analyses were performed to explore associations between familiarity, use, and perceived benefits of XR. ResultsRespondents reported positive attitudes toward XR, particularly for improving students understanding of complex anatomy (mean = 6.02/7), skill development (5.68/7), and confidence and preparedness for clinical practice (5.08-5.20/7). XR was mainly viewed as a complement to traditional teaching rather than a replacement (mean = 3.77/7). Strong correlations were observed between perceived improvements in confidence, skills, and clinical readiness (r = 0.71 - 0.89, P < 0.0001). High costs, limited technical support, and time constraints were the most prominent barriers to usage. ConclusionOverall, dental educators appear open to XR but constrained by structural and organizational factors rather than a lack of interest. Faculty development, hands-on training opportunities, and institutional support may therefore be essential to translating positive perceptions into meaningful and sustained integration of immersive technologies in dental curricula.

BackgroundScalable, non-invasive markers for cognitive-decline risk are limited. Olfactory dysfunction is predictive, and oral dysbiosis is mechanistically linked to neurocognitive pathways. Hence, we tested whether pairing smell and global cognition with salivary microbiome profiling yields a targeted, clinically useful signal. MethodsWe enrolled 113 Memory Center attendees and community controls. Same-day MMSE, UPSIT, and saliva were obtained for 16S rRNA gene sequencing and cytokine measurement. Unsupervised k-means clustering on standardized MMSE-UPSIT defined two groups of participants: CNN (cognitively normal, normosmia) and CIH (cognitively impaired, hyposmia). Ordination and elastic-net models adjusted for age, sex, BMI, and sequencing depth. Functions were inferred with PICRUSt2 and were integrated with taxa via DIABLO. ResultsOverall, the 16S-based microbial community structure was similar between groups, indicating minor compositional shifts. CIH showed enrichment of periodontal anaerobes (Porphyromonas, Treponema and Prevotella), whereas CNN retained nitrate-reducing commensals (e.g. Neisseria subflava, Aggregatibacter aphrophilus). Functional shifts showed mixed consistency with literature, aligning for outer membrane usher proteins and alkyldihydroxy phosphate synthase, but diverging for thiaminase, alpha-glucuronidase, and chemotaxis protein CheX. Most salivary cytokines levels did not differ between groups. ConclusionsThis integrated smell, cognition, and saliva workflow delineates an olfactory- cognitive phenotype linked to a targeted, potentially modifiable salivary dysbiosis, periodontal anaerobes vs nitrate-reducers, rather than diffuse salivary inflammatory elevation. This approach may support non-invasive triage and monitoring along the oral- brain axis, pending independent, longitudinal validation.

ObjectivesDiagnosis of community-acquired Legionnaires disease (CALD) relies on microbiological testing. Routine testing in hospitalised CAP patients has low positivity rates. We externally validated a Legionella prediction score, assessed its applicability in routine care, and explored potential updates. MethodsWe analysed data from 196 CALD patients from 20 Swiss hospitals and 196 Legionella-negative CAP controls matched by date of diagnosis ({+/-}14 days; August 2022-March 2024). We assessed the availability of the original score predictors (fever, no/dry cough, hyponatremia, elevated CRP, elevated LDH, low platelet count) in routine care and the original scores discriminative performance. The dataset was split into development and validation cohorts to evaluate whether simplifying modifications improved predictive performance. ResultsThe original score showed 91% (95% CI: 86-96%) sensitivity and 35% (95% CI: 28-42%) specificity at a cut-off [&ge;]2; LDH was infrequently measured, and platelet count was a poor predictor. The simplified SwissLEGIO score (fever >38{degrees}C, sodium <133 mmol/L, CRP >180 mg/L, no/dry cough, prior {beta}-lactam therapy) maintained high sensitivity (88-92%) and showed improved specificity (46-58%) at cut-off [&ge;]2. ConclusionThe SwissLEGIO score is an easy-to-apply screening tool to rule out CALD in hospitalised CAP patients with scores <2 and may reduce testing by 36-52% at a CALD prevalence of 4%.

BackgroundThe use of fluoride-containing dentifrices can reduce the risk of dental caries. The systematic review was conducted to address two research questions: (i) the prevalence and frequency of fluoridated toothpaste use among Nigerian children and adolescents across geographic and demographic settings, and (ii) its association with dental caries prevalence, stratified by location and baseline caries risk. MethodsThis systematic review, registered with PROSPERO (CRD42022362116), followed the PRISMA guidelines. A PIO framework was applied to include children and adolescents (6 months-19 years) in Nigeria using fluoridated toothpaste, with caries outcomes measured via dmft/DMFT indices. A comprehensive search of PubMed, Web of Science, Scopus, Embase, AJOL, and Google Scholar was conducted from January 2001 to January 2026, supplemented by reference and grey literature searches. Study selection, data extraction, and risk of bias assessment using an adapted Hoy et al. tool were performed independently by multiple reviewers, with high inter-rater reliability (Kappa=0.90). Data were pooled using a random-effects model, with sensitivity, subgroup, and meta-regression analyses conducted to explore heterogeneity and effect modifiers. Publication bias was assessed using funnel plots and Eggers test. ResultsOf 1,194 identified records, 18 studies (n=12,719 participants) were included. The use of fluoridated toothpaste was widespread (prevalence: 61.9% to 95.8%), yet its association with dental caries varied significantly by location. A meta-analysis of 14 studies indicated a significant 16% reduction in caries odds with fluoridated toothpaste use after removal of an influential outlier (OR = 0.84, 95% CI: 0.71-0.99, p=0.04). Subgroup analyses revealed this protective association was significant in urban and rural settings (p<0.05) but absent in suburban Nigeria. Furthermore, dental caries prevalence and severity (DMFT/dmft) were substantially higher in urban and rural areas, where the association was significant, compared to suburban regions. All studies were assessed as having a low risk of bias, and no significant publication bias was detected. ConclusionFluoridated toothpaste is widely used in Nigeria and associated with a reduction in the prevalence of dental caries in Nigeria. It appears the relationship is moderated by residential location, and the DMFT/dmft. Longitudinal studies are needed to explore the interactions between the DMFT/dmft, use of fluoridated toothpaste, and residential location in Nigeria.

IntroductionSequence-based typing (SBT) has been the standard molecular typing method for understanding Legionella pneumophila genetic relationships. However, genome-scale typing approaches, namely core-genome (cg) or whole-genome (wg) multilocus sequence typing (MLST), provide higher discriminatory power. To advance these capabilities, the Legionella International Typing (LIT) workgroup was established to develop, evaluate, and disseminate a novel cgMLST schema with enhanced wgMLST resolution for L. pneumophila investigations. MethodsWe created and populated the LIT cg/wgMLST schema with chewBBACA software using more than 9000 genome assemblies representative of the species diversity. We applied a multi-step refinement workflow, considering loci prevalence, diversity and presence/absence profile across the species tree, to select the final cg/wgMLST loci, and compared the performance of the LIT cgMLST schema with the previously used 1521-loci schema and assessed its congruence with SBT. ResultsThe LIT schema includes 2009 loci present in 98% of the dataset, forming the static cgMLST schema for routine genomic surveillance, plus 2698 accessory loci for an in-depth wgMLST analysis of clusters of interest. The LIT cgMLST schema maintains moderate agreement with SBT and presents high clustering congruence with the 1521-loci schema, while providing increased resolution. Analysis of epidemiologically related isolates using the LIT cgMLST schema for initial cluster delineation, followed by cluster-specific dynamic wgMLST analysis extending the cgMLST with accessory loci shared among isolates within each cluster, demonstrated increased confidence for outbreak investigation and source identification. ConclusionsThe LIT schema is expected to contribute to harmonizing genomic surveillance of Legionnaires disease at both local and global levels. The schema and associated resources for local implementation are available on Zenodo (https://doi.org/10.5281/zenodo.17871973).

BackgroundReliable detection of latent Mycobacterium tuberculosis (Mtb) infection (LTBI) remains challenging, particularly in TB contacts and immunocompromised individuals, where interferon-{gamma} release assays (IGRAs) demonstrate variable sensitivity. IP-10, a chemokine produced at substantially higher concentrations than IFN-{gamma}, represents a promising immune marker. This study aimed to evaluate the diagnostic performance of two IP-10 based assays RIDA(R)QUICK TB (lateral flow) and RIDASCREEN(R) TB (ELISA), by comparison with QuantiFERON-TB Gold Plus (QFT-Plus) assay or a composite reference standard. MethodsA cross-sectional diagnostic accuracy study enrolled 99 adults: 49 with culture-confirmed active pulmonary TB, 30 close TB contacts and 20 individuals with autoimmune disease, in Bucharest, Romania. All participants underwent RIDA Quick, RIDA Screen and QFT-Plus testing. Indeterminate results for all assays were reclassified using a composite reference standard. ResultsAgainst culture in active TB cases, RIDA(R)QUICK TB demonstrated a sensitivity of 85.7% (95% CI: 72.8-94.1) and PPV of 97.7%, while RIDA(R)SCREEN TB achieved 91.8% sensitivity (95% CI: 80.4-97.7) and 97.8% PPV. Specificity and NPV could not be reliably estimated due to the near-absence of true-negative individuals. Agreement with QFT-Plus was moderate to good ({kappa}=0.47-0.93).ROC analysis performed against QFT-Plus as a comparator demonstrated good immunological discrimination for RIDA(R)QUICK TB (AUC = 0.828) and RIDA(R)SCREEN TB (AUC = 0.767), reflecting concordance with QFT-Plus rather than diagnostic accuracy against confirmed infection. ConclusionIP-10 based assays demonstrated higher sensitivity than QFT-Plus and excellent PPV across bacteriological standard, supporting their use as complementary tools for LTBI detection. Larger, more heterogeneous cohorts are needed to accurately define specificity and operational integration.

BackgroundRecurrent sore throat affects a small minority of adults but can cause substantial morbidity. Evidence to guide tonsillectomy eligibility in adults is limited, and current criteria are extrapolated from paediatric populations. We aimed to describe the epidemiology, management, and prognosis of adult sore throat in UK primary care. MethodsUsing CPRD Aurum (2010-2020 adults with a first coded episode of sore throat or tonsillitis were identified and matched to controls. Episode frequency, antibiotic use, ENT referral, and tonsillectomy were analysed. Predictors of recurrent episodes ([&ge;]3 in 365 days), referral, and tonsillectomy were assessed using time-to-event, multinomial logistic, and multilevel mixed-effects regression models. FindingsOf 4.45 million adults, 1.70 million (38.3%) had [&ge;]1 episode; most (61.5%) had only one, but 4.1% experienced [&ge;]3 within 1 year. Recurrent episodes were more common in younger females and those from more deprived areas. Only 21,869 patients (0.5% of the exposed cohort) underwent tonsillectomy, and just 25.7% of these met Paradise criteria at any time; conversely, only 13.9% of those meeting criteria underwent surgery. Patients who had a tonsillectomy tended to be younger, female, and from less deprived areas. Pre-tonsillectomy episode rates were unexpectedly low, but the data indicated that individuals with high baseline burden continue to experience elevated episode rates over several years. ConclusionsRecurrent sore throat is uncommon, but those affected face substantial disease burden. Current tonsillectomy patterns are poorly aligned with disease burden and show inequities by deprivation. Earlier identification of adults likely to develop recurrent episodes, and more timely surgical intervention, may improve patient outcomes and the cost-effectiveness of tonsillectomy.

BackgroundSepsis remains a leading cause of preventable hospital mortality in England, with NHS England reporting over 48,000 sepsis-related deaths annually. Natural language processing (NLP)-driven clinical decision support systems (CDSS) have been deployed in several NHS Trusts to enable automated early detection of sepsis from unstructured clinical notes, yet causal evidence of their effectiveness at the hospital level remains limited. ObjectiveTo estimate the causal effect of implementing NLP-driven CDSS for sepsis detection on 30-day in-hospital sepsis mortality rates across NHS Trusts in England, using the augmented synthetic control method (ASCM) to account for selection bias and time-varying confounders. MethodsWe conducted a quasi-experimental study using Hospital Episode Statistics (HES) and NHS Digital mortality data from 2017-2024 across 142 NHS acute Trusts. Twelve Trusts that implemented NLP-CDSS for sepsis detection between April 2020 and March 2022 constituted the treated group. The ASCM was employed to construct a weighted combination of donor Trusts that closely approximated the pre-intervention trajectory of each treated Trust. Ridge-augmented bias correction was applied to improve pre-intervention fit. We estimated average treatment effects on the treated (ATT) using staggered adoption designs with heterogeneity-robust estimators. Inference was conducted via conformal permutation-based p-values and placebo tests. ResultsNLP-CDSS implementation was associated with a statistically significant reduction in 30-day sepsis mortality of 3.7 percentage points (95% CI: -6.1 to -1.3; p = 0.003), corresponding to a 14.2% relative risk reduction. Effects emerged approximately six months post-implementation (ATT at 6 months: -2.1 pp, 95% CI: -4.0 to -0.2) and strengthened over time (ATT at 24 months: -5.3 pp, 95% CI: -8.4 to -2.2). Placebo tests across 130 donor Trusts confirmed the implausibility of chance findings (placebo p = 0.008). Heterogeneity analysis revealed larger effects in Trusts with higher baseline mortality ({beta} = -0.41, SE = 0.12, p = 0.001) and those that integrated NLP-CDSS with existing electronic health record systems ({beta} = -1.8 pp, SE = 0.6, p = 0.003). ConclusionsNLP-driven CDSS deployment for sepsis detection was associated with clinically meaningful and statistically robust reductions in hospital sepsis mortality across NHS Trusts. Augmented synthetic control methods provide rigorous causal evidence in the absence of randomized trials, supporting the broader adoption of NLP-enabled surveillance systems in national healthcare settings.

BackgroundClimate change is increasingly recognised as a threat to population health and healthcare systems, yet the effects of environmental variability on pharmaceutical prescribing remain poorly characterised in the UK. Using a wide array of open-source datasets, we examine the effect of environmental, geographic and socioeconomic factors on prescribing habits in England. MethodsWe linked monthly, practice-level prescribing data for England (2010-2025) to meteorological, air-quality, flooding and demographic datasets using spatial nearest-neighbour matching. Prescribing volumes for cardiovascular, respiratory and antibiotic medications were analysed using log-transformed outcomes in mixed-effects models with practice-level random effects, adjusting for region, seasonality, deprivation and temporal trends, using both continuous environmental measures and extreme-condition indicators. A complementary Bayesian hierarchical model jointly estimated the conditional effects of multiple correlated environmental exposures, with partial pooling across practices and support for distributed lag effects. ResultsIn mixed-effects analyses, temperature showed the most consistent associations with prescribing, with higher temperatures linked to increased respiratory and cardiovascular prescriptions and reduced antibiotic use, while rainfall, flooding and most pollutants had small or negligible effects. Environmental predictors exhibited strong correlations, motivating multivariate modelling. Bayesian multivariate models confirmed temperature as the dominant environmental driver after adjustment for correlated exposures, with substantially larger variation attributable to regional and socioeconomic factors than to environmental conditions. ConclusionsTemperature is the most consistent environmental determinant of GP prescribing in England, with higher temperatures associated with increased cardiovascular and respiratory prescribing and reduced antibiotic use. Rainfall, flooding and most air pollutants show little evidence of meaningful effects once seasonal and meteorological structure is accounted for. Environmental associations are modest in magnitude relative to persistent socioeconomic and regional drivers of prescribing, indicating that climate-related influences operate within broader structural determinants of healthcare utilisation. These results suggest that, at monthly timescales, prescribing demand is relatively stable to environmental variability, supporting a focus on long-term adaptation and surveillance rather than short-term demand shocks in climate-resilient healthcare planning.

BackgroundPreoperative biliary stenting alters biliary colonization and may reduce the effectiveness of perioperative antibiotic prophylaxis in pancreatoduodenectomy. Although broader-spectrum regimens have been associated with improved infectious outcomes, their microbiological adequacy in routine clinical practice remains poorly defined. We therefore evaluated the real-world adequacy of a prolonged ampicillin-sulbactam protocol, its association with infectious outcomes and survival, and the potential impact of a universal piperacillin-tazobactam strategy. MethodsWe analyzed all consecutive patients who underwent elective pancreatoduodenectomy from 2002 to 2023 at our tertiary center. Demographic, operative, microbiological, and outcome data were retrieved from a prospectively maintained database. Patients were stratified by stent status. Adequacy of prophylaxis was defined as the full in vitro susceptibility of all bile isolates. The outcomes included 30-day infectious morbidity, clinically relevant POPF, PPH, DGE, reoperation, 30- and 90-day mortality and long-term survival. A coverage simulation was performed to compare ampicillin-sulbactam with a hypothetical universal piperacillin-tazobactam. Statistical methods included chi-square/Fishers exact tests, Mann-Whitney U tests, Cox models, McNemars test and Poisson regression. ResultsOf 956 patients, 424 (44%) had a biliary stent. Technical complications were comparable between groups, and rates of POPF and PPH were not increased. However, infectious morbidity was higher in stented patients, including sepsis (RR 1.62, 95% CI 1.05-2.51) and postoperative cholangitis (RR 2.20, 95% CI 1.36-3.56). Thirty- and 90-day mortality were increased (RR 2.88 and 2.73) but lost significance after adjustment. Bile cultures predominantly yielded Enterococcus and Enterobacterales with low ampicillin-sulbactam susceptibility. Overall adequacy was 21.7%. Among patients with bile cultures (n = 474), ampicillin-sulbactam covered 43.7% (207/474) versus 81.2% (385/474) with piperacillin-tazobactam; in stented patients with cultures (n = 397), coverage increased from 41.8% to 78.1%. Adequate ampicillin-sulbactam coverage was not associated with reduced infectious outcomes in Poisson models. ConclusionPreoperative stenting creates a polymicrobial, partially resistant biliary niche that ampicillin-sulbactam does not sufficiently cover. Our data shows that a piperacillin-tazobactam strategy substantially improves coverage and was therefore implemented at our center. Core message- Stented patients exhibit a distinct infectious risk profile characterized by Enterococcus-and Enterobacterales-dominated bile colonization rather than increased rates of technical complications. - In stented patients, real-world microbiological coverage of ampicillin-sulbactam was limited, and in vitro susceptibility did not independently translate into reduced postoperative infectious morbidity. - Broader prophylaxis, such as piperacillin/tazobactam, aligns with the actual flora and nearly doubles theoretical coverage, addressing the mismatch between stent-associated biofilms and narrow regimens.

BackgroundThe never-ending emergence of superbugs casts a shadow over the victorious age of antibiotics. In fact, the triumph of antibiotics was previously viewed in retrospection as our final victory over bacteria. Bacteria like Klebsiella pneumoniae, Acinetobacter baumannii, and Escherichia coli are now raising an alarming number of infections across hospitals and communities around the globe. The objective was to evaluate the implications for antimicrobial stewardship based on identifying the antibiotic resistance profiles, genotype mechanisms, and trends in common pathogenic bacteria found in various hospitals across Iraq. MethodsWe used a two-fold approach that was comprehensive in scope and involved both efficient multicenter surveillance as well as cutting edge genetic analysis to unravel the complex topography of antibiotic resistance. We provided a geographically heterogeneous but diverse set of clinically obtained isolates to participate in hospitals for a period of 24 months and concentrated our efforts on prioritized pathogens K. pneumoniae, A. baumannii, E. coli, P. aeruginosa, and S. aureus that are well known to pose serious threats. Beginning with clinically obtained isolates sourced across the entire globe, we used standardized techniques such as broth microdilution to first undertake phenotyping in a central reference lab to establish microbial identity based on resistance phenotypes to a set of prioritized antibiotics that include carbapenems, third generation cephalosporins, or fluoroquinolones. Finally, we derived data concerning the emergence patterns and geographic distribution of resistant microbes such as MRSA or CRE. We used genome-wide sequencing to unlock information concerning the genetic blueprints for a set of specifically chosen isolates based on their representational diversity across geographic locales, resistance phenotypes, and specific times. ResultsThe sample was made up of Escherichia coli (n = 225), Klebsiella pneumoniae (n = 185), Staphylococcus aureus (n = 135), Pseudomonas aeruginosa (n= 90), and Acinetobacter baumannii (n = 125). Ceftriaxone resistance was found in 80.4% of E. Coli, ciprofloxacin resistance in 45.6%, and meropenem resistance in 15.1%. K. pneumoniae exhibited 38.9% resistance to aminoglycosides and 70.2% resistance to carbapenems. The percentage of MRSA in S. aureus was 55.5%. P. aeruginosa showed 22.2% resistance to colistin, 37.8% resistance to piperacillin tazobactam, and 50.0% resistance to ceftazidime. Imipenem resistance was found in 85.6% of A. baumannii isolates, whereas colistin resistance was found in 28.8% of isolates. In all, 3.4% of isolates are pan-drug-resistant (PDR), 14.6% are extensively drug-resistant (XDR), and 52.1% are multidrug-resistant (MDR). WGS identified common genes such bla_NDM-1, bla_OXA-48, mcr-1, aac (6)-Ib, and plasmid replicons IncF, IncL/M, and IncI2. Carbapenem resistance in Gram-negative bacteria rose by around 18% over the course of five years. ConclusionsThis study shows that the rapid spread of complex genetic information in bacteria causes antibiotic resistance problems. High-level resistance represents an expected consequence of the spread of resistance genes and successful bacteria within healthcare systems. We demonstrate in our results that our expertise in overcoming resistance at a molecular level will play a crucial role in combating infectious diseases in the coming years.

BackgroundThe epidemiology of suspected pediatric meningoencephalitis has shifted in the era of conjugate vaccines and multiplex PCR diagnostics, with viral pathogens now predominating over bacterial causes. Updated epidemiologic data are essential to adapt diagnostic and therapeutic algorithms to current clinical practice. MethodsThis retrospective single-center study included children and adolescents <18 years who underwent lumbar puncture with cerebrospinal fluid multiplex PCR for suspected central nervous system infection at a tertiary-care pediatric hospital in Germany between 2016 and 2024. Clinical, laboratory, and outcome data were extracted from electronic medical records. Cerebrospinal fluid was analyzed using the BioFire(R) FilmArray(R) Meningitis/Encephalitis Panel. Statistical analyses included descriptive statistics, nonparametric group comparisons, receiver operating characteristic analyses. ResultsAmong 1,198 included children, definite bacterial meningitis was diagnosed in 13 (1.1%), definite viral meningitis in 80 (6.7%), aseptic meningitis of unknown etiology in 131 (11.0%), confirmed/probable encephalitis in 53 (4.4%), and possible encephalitis in 34 (2.8%). Bacterial meningitis accounted for 5.8% of all meningitis cases. A causative pathogen was identified in all bacterial meningitis cases, most commonly Streptococcus pneumoniae (n = 7). Enterovirus (n = 52) and parechovirus (n = 9) predominated in viral meningitis, whereas an infectious etiology was identified in only 13 of 53 confirmed/probable encephalitis cases. The Bacterial Meningitis Score showed a sensitivity of 80.0% and a specificity of 57.6%. The recently published UK-ChiMES-pre- and post-lumbar puncture scores demonstrated sensitivities of 84.6% and 76.9% and specificities of 86.3% and 92.7%, respectively. DiscussionBacterial meningitis was rare in this contemporary cohort, while viral and etiologically unresolved infections predominated despite routine multiplex PCR diagnostics. Clinical prediction scores supported risk stratification, with the UK-ChiMES-pre-lumbar puncture score showing the most favorable balance between sensitivity and specificity and potential to guide diagnostic decisions and antiinfective therapy.

ObjectiveThe objective of this analysis was to explore temporal and regional trends in breast pump prescription claims in outpatient settings in Germany, and to characterize the types of pumps covered. Study designWe conducted a nationwide secondary analysis of outpatient statutory health insurance billing data for breast pump prescriptions from 2011 to 2024, covering nearly 90% of the German population. Billing data from community pharmacies were scaled to full national coverage using regional extrapolation factors and subsequently linked with national and state-level live birth statistics to adjust for birth rates and population size across federal states. A list of breast pumps covered by German national statutory health insurance funds was queried for information on their characteristics. ResultsPrescription of electric pumps dominate outpatient statutory health insurance breast pump claims in Germany, with national statutory health insurance funds covering {euro}15.3 million for pump rentals. Manual pumps dispensed through community pharmacies accounted for {euro}27 thousand in 2024. Between 2011 and 2024, electric pump claims increased by a factor of 2.57, rising from 235.4 to 605.2 claims per 1000 infants newly enrolled in statutory health insurance (average annual growth rate 8.24%). Claims varied substantially across federal states but increased overall. ConclusionsThis is the first epidemiological analysis of statutory health insurance prescription claims for breast pumps in Germany. We found that electric breast pumps are important medical devices supporting outpatient human milk expression in Germany. Prescription claims appear to be very common and have shown an increase over the past 13 years.

Antimicrobial resistance (AMR) in ESKAPE pathogens represents a major global health threat. Although these organisms are well established as causes of healthcare-associated infections, aquatic environments may function as reservoirs and transmission pathways for resistance. This systematic review aimed to estimate the prevalence of AMR in ESKAPE pathogens isolated from water and wastewater and to compare resistance patterns with those observed in human clinical isolates. The review followed PRISMA guidelines and was registered in PROSPERO (CRD420251020930). PubMed, Embase, and the Cochrane Library were searched to January 14, 2025. Eligible studies were original research reporting antimicrobial susceptibility data for ESKAPE pathogens isolated from both aquatic environmental matrices and clinical samples. Pooled resistance prevalence was estimated using generalized linear mixed models, with heterogeneity assessed using {tau}{superscript 2} and I{superscript 2} statistics and small-study effects evaluated by funnel plots and Eggers test. Of 304 records identified, 18 studies met the inclusion criteria. The pooled overall resistance prevalence was 0.46 (95% CI: 0.36-0.57), with heterogeneity (I{superscript 2} = 98.8%). Resistance was higher in clinical isolates (0.67; 95% CI: 0.55-0.77) than in environmental isolates (0.24; 95% CI: 0.14-0.39), and environmental resistance was greater in effluent-impacted waters than in non-effluent sources. Interpretation is limited by methodological heterogeneity, selective isolation approaches in environmental studies, and imprecision due to small and unevenly distributed samples. Overall, AMR in ESKAPE pathogens remains more prevalent in clinical settings, but aquatic environments, particularly wastewater, represent resistance reservoirs, underscoring the need for standardized methodologies within a One Health framework. Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420251020930, CRD420251020930 HighlightsAntimicrobial resistance was higher in clinical isolates than in aquatic isolates. Resistance patterns showed extreme heterogeneity across studies. Effluent-impacted waters showed higher resistance than non-effluent sources. Higher environmental resistance in some classes reflected methodological artifacts.

BackgroundThe 340B Drug Pricing Program was established to expand access to care for low-income and uninsured patients by allowing safety-net hospitals and clinics to purchase outpatient drugs at discounted prices. Over time, the program has expanded substantially, raising questions about whether participating hospitals are meeting the programs intended objectives. MethodsUsing 2023 hospital financial data from the RAND Corporation, we conducted cross-sectional descriptive comparisons of 340B and non-340B hospitals nationwide. Key measures included charity care as a percentage of operating expenses, Medicaid admissions as a share of hospital days, uncompensated care, and costs associated with uninsured patients approved for charity care. Subgroup analyses also examined the performance of Disproportionate Share Hospitals (DSH), Critical Access Hospitals (CAH), Rural Referral Centers (RRC), Sole Community Hospitals (SCH), and National Cancer Institute (NCI) designated hospitals. ResultsAmong 3,999 hospitals analyzed, 340B hospitals provided, on average, lower levels of charity care than non-340B hospitals (2.16% vs. 2.82% of operating expenses) and lower costs of charity care for uninsured patients (1.60% vs. 2.26%). However, 340B hospitals served a higher proportion of Medicaid patients (19.69% vs. 17.76%). Substantial variation was observed across 340B subcategories: DSH hospitals reported the highest Medicaid utilization, while CAH hospitals reported the lowest levels of charity care and Medicaid days. ConclusionsParticipation in the 340B program does not uniformly correlate with greater provision of charity care or uncompensated care. These findings suggest a misalignment between program intent and outcomes and support the need for greater transparency, standardized eligibility criteria, and minimum charity care requirements to ensure that 340B savings directly benefit underserved populations.