Infection

Importance: Clinicians often look for a dental source in Staphylococcus aureus bacteremia (SAB), but how often dental disease is found, compared with other bacteremias, is unclear. Objective: To compare documented dental disease in adults with SAB, Escherichia coli bacteremia, and a general population cohort. Design, Setting, and Participants: Retrospective cohort study in the Protege database of 48 975 adults with bacteremia from January 1, 2015, through December 31, 2023, assigned by earliest in-window organism, and 81 945 general population adults. Exposures: SAB, with E coli bacteremia as the primary comparator and the general population as the secondary comparator. Main Outcomes and Measures: Documented dental disease from 7 days before through 30 days after index, defined by a qualifying dental procedure or disease-specific note text and adjusted for age, sex, race, and documentation intensity. Results: Dental disease occurred in 528 of 16 435 patients with SAB (3.21%) and 179 of 24 942 patients with E coli bacteremia (0.72%). The adjusted odds ratio was 3.86 (95% CI, 3.23 to 4.63). By the pathology-only definition, disease occurred in 517 patients with SAB (3.15%) and 399 general population patients (0.49%). The adjusted odds ratio was 3.71 (95% CI, 3.08 to 4.46). Within SAB, rates were highest with prior infective endocarditis (9.8%), opioid use disorder (6.2%), injection drug use (5.3%), and prosthetic valve (5.0%). Prevalence ranged from 0.49% in the general population to 7.98% in other streptococcal bacteremia. Of 437 patients with SAB and an assignable first finding date, 333 (76.2%) had the finding after the index date. Conclusions and Relevance: Dental disease was documented more often in SAB than in E coli bacteremia after adjustment. Most findings were first recorded after bacteremia was recognized, during SAB evaluation. These data do not show that dental disease caused the bacteremia.

Background: Common variable immunodeficiency is frequently underrecognized due to its heterogeneous clinical presentation, resulting in diagnostic delays that increase disease-related complications, with each year of delay increasing mortality risk by 4% for the most common inborn error of immunity. Objective: In individuals with established common variable immunodeficiency, we sought to recognize patterns in patient diagnostic trajectories to identify opportunities for interventions to reduce time to diagnosis. Methods: We analyzed retrospective electronic health records data from 139 individuals with physician-confirmed common variable immunodeficiency across five academic health systems representing >10million patients. We evaluated diagnosing specialties and international classification of disease code trajectories in the two years prior to and at common variable immunodeficiency confirmation. Additionally, we construct specialty-specific prediction on a 1:50 case: control cohort using a gradient boosting algorithm. Results: The leading diagnoses at common variable immunodeficiency determination were respiratory (35% of individuals), and individuals with respiratory symptoms were more likely to be diagnosed by Allergy / Immunology than by other specialties (odds ratio 2.9, standard error 0.35, p-value 1.9x10-3) and had a higher frequency of visits to pulmonary disease in the two years prior to diagnosis. Individuals with neoplasms were 50% more likely than other patients (OR 2.0, SE 0.29, p-value 0.02) to receive a diagnosis at each visit, reducing their diagnostic delay by up to a year. We find that a larger ratio of number of specialties visited to the total number of visits is significantly correlated with an increased time to diagnosis. A trajectory-informed specialty-specific prediction improved detection with an area under the precision-recall curve of fifty times the value expected under the null. Conclusions: Individuals referred to Allergy / Immunology have shorter time to diagnosis, and a specialty-specific prediction could improve detection of common variable immunodeficiency. Clinical Implications: Overall, we find that phenotype-specialty interactions may inform targeted interventions to improve common variable immunodeficiency recognition across specialties, reducing diagnostic odyssey and disease-related complications.

BackgroundCOVID-19 pandemic modified trends of infant bronchiolitis, leading cause of emergency room (ER) attendance in infants in high income countries, primarily due to Respiratory Syncytial Virus. Understanding recent pandemic-related epidemiological shifts could inform affordable prevention efforts to improve sustainability and coverage of prophylactic treatments beyond maternal vaccines and infant monoclonal antibodies. MethodsWe estimated incidence rates (IR) of bronchiolitis ER presentations in 0-6month olds in 2012-2023 in a region-wide cohort of almost 1 million births using administrative health data from Lombardy, Italy. To assess potential contributors, we investigated direct and indirect COVID-19-related factors, including disease severity, shape of the epidemic peak, parental health seeking behaviour and vaccine coverage. We estimated COVID-19 maternal vaccination associations using mothers-infants data linkages and multivariable-adjusted logistic regression. FindingsCompared to pre-pandemic levels, IRs doubled in 2021-2023 (from 2 to [≥] 4/100 person-time). The surge could not be explained by changes in infant age at ER visit, clinical severity or in the shape of the epidemic peak. Adjusted models showed little support for a role of infant routine or maternal COVID-19 vaccination on bronchiolitis episodes (respectively hazard ratio 1.09, 95%CI: 0.98-1.22 and odds ratio 0.91, 95%CI: 0.76-1.09). InterpretationThe post-pandemic increase in infant bronchiolitis is likely driven by multiple epidemiological changes rather than a single factor. As maternal RSV vaccination and infant RSV monoclonal antibodies are introduced and scale up, identifying these mechanisms will be critical to maximise their public health impact, inform complementary prevention strategies, and improve preparedness for future RSV epidemics.

Background: Nicotine pouches (NPs) are increasingly popular tobacco-free nicotine products, particularly among young people. Despite growing use, evidence regarding their oral health effects remains limited. Methods: We employed a mixed-methods approach comprising: (1) a national cross-sectional survey of NP users, (2) a survey of UK dental professionals, and (3) in-person clinical assessments of NP users. Survey data explored patterns of NP use, oral and dental side effects, and perceptions of risk. Clinical assessments included comprehensive oral examinations, periodontal assessments, and histopathological investigation of lesions where indicated. Results: A total of 3,659 NP users completed the public survey. Participants were predominantly male (89%) and aged 16-22 years (78%). Overall, 45% reported at least one oral or dental side effect. The most commonly reported effects were gingival recession (60%), burning sensations (41%), white patches (30%), and dry mouth (29%). Higher nicotine exposure was associated with increasing numbers of reported side effects. Among 126 dental professionals, oral lesions associated with NP use were commonly observed clinically, while only 17% reported seeing no oral or dental effects. Thirty-three NP users underwent in-person assessment. Ten lesions were biopsied; six demonstrated hyperkeratosis and four showed oral epithelial dysplasia (three mild, one moderate). All dysplastic lesions occurred at pouch placement sites. In two cases, clinical follow-up demonstrated partial or complete resolution of lesions following cessation of NP use. Periodontal assessments demonstrated generally low levels of periodontal disease and gingival recession across the cohort. Conclusions: Oral and dental side effects associated with NP use were commonly reported by users and observed by dental professionals. Histopathological assessment identified biopsy-confirmed oral epithelial dysplasia in lesions occurring at pouch placement sites, representing, to our knowledge, the first such report associated with NP use. Evidence of lesion improvement following discontinuation of use suggests that at least some NP-associated oral changes may be reversible. Although causality cannot be established, these findings highlight the need for vigilance among dental professionals and urgent longitudinal research to determine the incidence, progression, and reversibility of NP-associated oral lesions.

Importance: Nirsevimab, a monoclonal antibody against RSV, was implemented in France in September 2023. Recently, rare resistance-associated substitutions were described in RSV but the effectiveness according to lineages remains unclear. Objective: We aimed to estimate the effectiveness of nirsevimab against hospitalization for RSV bronchiolitis according to RSV lineages. Design: We conducted a multicenter test-negative case-control study from October 15, 2023 to March 15, 2025. Setting: This study was based on data from three national multicentric prospective studies. The 12 participating centers were secondary or tertiary hospital with a pediatric department located in France. Participants: We included all children younger than 12 months who were hospitalized for RSV bronchiolitis in one of the participating centers in France during the two first RSV epidemic seasons following the implementation of nirsevimab (from October 15, 2023 to February 29, 2024, and from October 10, 2024 to March 15, 2025). Main outcomes and measures: The main outcome of the study was the RSV test result of bronchiolitis cases. RSV whole-genome sequencing was performed using a tiled amplicon approach covering the complete viral genome, as previously described in the POLYRES studies. We estimated the effectiveness of nirsevimab by a multivariable logistic regression model adjusted for potential confounders. We estimated the adjusted risk of immunization failure for each lineage by calculating relative odds ratio to a reference lineage. A range of sensitivity analyses were conducted. Results: We included 3019 infants with bronchiolitis among which 2273 had a positive RSV test (case patients) and 746 had a negative RSV test (control patients). Overall, 373/2273 (16.4%) case patients were immunized by nirsevimab versus 423/746 (56.7%) control patients. The adjusted effectiveness of nirsevimab against hospitalization for bronchiolitis was 88.4% (95% CI, 84.5-91.4) with RSV-B and 79.4% (95% CI, 73.7-83.8) with RSV-A. The risk of immunization failure was 3.2-fold (95% CI 1.8-5.7) higher for lineages derived from A.D.3 than for lineages derived from B.D.4.1. Conclusion and relevance: In this multicentric case-control study, we observed that nirsevimab effectiveness was variable across RSV lineages, with a lower effectiveness against A.D.3 lineages compare to others. Further surveillance is needed to confirm these findings and assess their implication on RSV lineages epidemiology as nirsevimab use expands.

Objectives: A previously published conceptual mapping review integrated fragmented evidence on dental anxiety (DA) into a broader conceptual model of potential causes and consequences. This study focused on consequences, extending from oral health-related behaviours through oral disease to systemic health, and empirically evaluated these hypothesized relationships on the population level. Methods: Cross-sectional data from the 46-year follow-up of the Northern Finland Birth Cohort 1966 (n = 1,859) were analysed using structural equation modelling. DA was modelled as a latent construct; delayed/problem-oriented dental attendance and home oral care as behavioural proxies; periodontal disease burden as the percentage of sites with probing pocket depth >=4 mm; and cardiovascular risk as a Framingham-based risk score. Generalized anxiety, sex, and education were covariates. Smoking-stratified multigroup analyses assessed model robustness. Results: The prespecified associations were observed across behavioural, periodontal, and systemic-risk domains. Higher DA was associated with more delayed/problem-oriented attendance and poorer home care; both were associated with greater periodontal disease burden, which in turn was associated with higher cardiovascular risk. Model fit was good (chi-square(119) = 529.98, CFI = 0.962, TLI = 0.951, RMSEA = 0.043, SRMR = 0.051). The overall association between DA and cardiovascular risk was small (beta = 0.066, p = .004), with a small decomposed indirect association (beta = 0.013, p = .006) and a remaining direct association (beta = 0.053, p = .022). Smoking-stratified multigroup comparisons found no differences in the structural associations by smoking status. Conclusions: This population-based evaluation provides preliminary empirical support for the conceptual model. Findings extend the relevance of DA beyond dental attendance and oral health outcomes to a broader oral-systemic public-health context. Cross-sectional data cannot establish temporal or causal ordering; longitudinal replication is needed.

Objective Describe the profile of consumers utilising Emergency Departments (ED) across Victorian hospitals for dental conditions between financial year 2018-19 to 2022-23. Methods Dental conditions were grouped according to the diagnosis categories using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification (ICD-10-AM). Presentations for non-dental conditions were classified as 'Other'. Dependent variables included age, sex, Aboriginal and Torres Strait Islander (Aboriginal) background, language other than English, interpreter required, remoteness, and socio-economic disadvantage according to the Index of Relative Socio-economic Disadvantage (IRSD). The primary outcome evaluated is the relative risk ratio (RRR) of having a hospital ED presentation for a dental condition compared to a non-dental condition and age-specific rates per 100,000 population. Multinomial logistic regression was performed following the backwards elimination method. Results Over the years 2018-19 to 2022-23, 0.55% (n=44,382) of ED presentations across Victorian hospitals by Victorian residents were due to dental conditions. Patients aged 20-44 years have the highest RRR compared to other age groups for dental-related ED presentations. Patients experiencing social inequity in terms of demographic factors such as Aboriginal background, requiring an interpreter, not living in a major city and living in areas of greater disadvantage (IRSD) have statistically significant increased RRR for dental-related ED presentations. Conclusion Patient characteristics were useful for identifying the relative risk of dental-related ED presentations between socio-economic and demographic groups to inform relevant public policy design focus on preventing dental-related ED.

Purpose: To compare the performance of three large language models (LLMs), ChatGPT-o1, Grok 3, and Gemini 2.0 Pro, on the American College of Prosthodontists' National Prosthodontic Resident Examination (NPRE). Materials and Methods: Official NPRE examinations from years 2015-2024 were retrieved from the American College of Prosthodontists website and used to prompt each LLM. Paid access tiers and advanced reasoning were enabled. Responses from LLMs were recorded and compared against the official answer keys for accuracy, variability across years, and consistency of responses. Duplicate questions were retained for the primary analysis and removed in a sensitivity analysis. Accuracy (percent correct) was compared using generalized estimating equations binary logistic regression (primary); Cochran's Q with Bonferroni-adjusted McNemar tests (sensitivity). Year-to-year variability (SD of annual accuracy) was compared using weighted Levene tests. Consistency across duplicate items was quantified as the percentage of perfect matches and compared using Cochran's Q with Bonferroni-adjusted McNemar tests. Results: Across 1,487 questions, overall accuracy differed among models (global P < 0.001). ChatGPT-o1 achieved 78.4% correct, Grok 3 76.4%, and Gemini 2.0 Pro 73.2%; ChatGPT-o1 and Grok 3's accuracy significantly exceeded Gemini 2.0 Pro (both P [&le;] 0.016), with no significant difference between ChatGPT-o1 and Grok 3 (P = 0.099). After removing duplicates (n = 1,200), results were similar: ChatGPT-o1, Grok 3, and Gemini 2.0 Pro were 77.1%, 76.6%, and 71.5% correct, respectively; ChatGPT-o1 and Grok 3's accuracy was significantly higher than Gemini 2.0 Pro (both P < 0.001). Variability across years did not differ significantly (P [&ge;] 0.097). Grok 3 showed significantly higher perfect-match consistency (79.2%) than ChatGPT-o1 (69.4%) and Gemini 2.0 Pro (64.5%) (P [&le;] 0.010). Conclusions: Contemporary LLMs showed 70-80% accuracy on postgraduate prosthodontic multiple-choice content. While promising for educational support, residual error and inconsistency warrant human oversight and transparent methods reporting before curricular adoption.

Background: Pharmacogenomic point-of-care testing (PGx POCT) enables genotype-informed prescribing at the bedside, but implementation is limited by the lack of suitable reference materials and standardised external quality assessment (EQA). Methods: Fixed lymphoblastoid cell lines were formulated as swab-based materials at defined cellular inputs for MTRNR1 POCT. Materials were evaluated using Genedrive MTRNR1 assays, quantitative PCR, acceptance quality limit batch release, workflow perturbation testing and stability studies, then deployed in an international EQA programme. Results: Materials were homogeneous, workflow-compatible and reproducible, with 100% correct genotype calls at the lowest intended manufacturing cell load. Seven EQA surveys yielded 253 participant results, with full-mark rates between 87.5 and 100%, and six test failures. Most failures occurred with low cell-input materials near the assay limit of detection. The materials supported genotype concordance, performance monitoring and identification of workflow and sample-related variability. Conclusions: Workflow-compatible cell-based reference materials combined with EQA provide a scalable framework for quality-assured PGx POCT beyond specialist laboratories. International MT-RNR1 PGx POCT EQA programme deployment demonstrated feasibility in decentralised settings. The framework may provide a model for the implementation, verification and ongoing quality assessment of PGx POCT. Further evaluation across platforms, analytes, settings and participant groups is required to establish broader applicability.

ObjectivesRespiratory Syncytial Virus (RSV) vaccine policies have varied globally since their approval in 2023. In the UK, policy has adapted in line with National evidence generation such that from Autumn 2026 at-risk persons [&ge;]65 years old will become eligible for vaccination. Immunosuppressed persons <65 years will still not be offered protection. The objective of this study is to investigate the relative burden of RSV infection by age and immunosuppressed status (IC). DesignRetrospective observational cohort study using routine healthcare data from North West London Integrated Care System. ParticipantsPatients with a confirmed diagnosis of a respiratory viral infection (RSV, Influenza A and B, SARS-CoV2) between October 2021 and July 2025. Main outcomes measuresPrevalence and severity of RSV infection in immunosuppressed persons <65 years old, and to provide a comparative analysis with Influenza and SARS-CoV2 in a sub-cohort tested using a 4-in-1 combined rapid PCR test. ResultsDuring the study period, 1226 patients were diagnosed with RSV of whom 596 (48.6%) were <65 years old. In 1091 patients with clinical data, 341 (31.3%) were IC. Fifty (9.9%) patients <65 years old had severe infection (ICU admission or death within 28 days of diagnosis), of whom 14 (28.0%) were IC. Proportionally, 16.7% of all RSV-associated deaths and 55.1% of all ICU RSV-admissions occurred in adult patients <65 years old. RSV accounted for 665 (10.1%) infections confirmed by 4-in-1 viral PCR testing. Eight-nine (13.4%), 172 (9.3%) and 448 (12.0%) patients with RSV, Influenza A and SARS-COV2 experienced severe infection, of whom 32 (36.0%), 82 (47.7%) and 156 (34.8%) were <65 years old respectively. Eight (25.0%), 20 (24.4%) and 52 (33.3%) of patients <65 years old with severe infection were IC. On adjusted analysis, having an immunosuppressive condition increased the odds of a severe SARS-CoV2 infection, OR (95% CI) 1.36 (1.08-1.71) but not a severe RSV or Influenza infection. ConclusionsSevere RSV infections occur in persons <65 years old, with a significant proportion of patients having an immunosuppressive condition. Urgent research is needed to investigate the potential benefit of extending the current UK RSV vaccine policy to protect younger immunosuppressed adults.

Objectives: To investigate whether the PneumoRator wearable sensor could accurately assess Respiratory Rate (RR) and signs of air hunger (SAH) compared with clinician-observed assessment in adults with and without breathing pattern disorder (BrPD). Design: A pilot cross-sectional observational study. Setting: A research laboratory on a university campus. Participants: Healthy adults aged 18-40, who were not pregnant, no smokers or history of cardiovascular, respiratory or neurological illness. Thirty consented to the study, Twenty-nine had full data for analysis. Interventions: Participants wore the PneumoRator chest-worn sensor continuously for 10 minutes while seated at rest. Main outcome measures: Respiratory Rate was compared between PneumoRator-derived measurements and randomised 1-minute observer manual counts. Clinician-observed SAH and BrPD were assessed using the Breathing Pattern Assessment Tool (BPAT). Participants also completed the Nijmegen Questionnaire. PneumoRator signals were analysed to identify large-volume breaths as potential SAH events. Results: Thirty participants were recruited. Twelve participants met BPAT criteria for BrPD and four met Nijmegen Questionnaire criteria. There was no significant difference between manual and PneumoRator RR measurements (p=0.89). No significant difference was observed between methods for SAH detection (p=0.17). Participants with clinician-observed SAH demonstrated significantly higher PneumoRator signal amplitudes than those without SAH (p=0.035). Conclusion: The PneumoRator produced RR measurements comparable to clinician assessment and demonstrated potential for identifying signs of air hunger. Findings from this pilot study indicate that the PneumoRator device shows promise as a tool for continuous RR monitoring and as an adjunct to BrPD assessment. Larger clinical validation studies are now warranted.

Background: Both over- and under-antibiotic use pose major global health challenges, yet there is no consensus on how to quantify deviations from optimal prescribing or set evidence-based targets. We developed a benchmarking tool for inpatient antibiotic use and evaluated its application in 10 countries. Methods: We developed decision-tree models to estimate expected empiric antibiotic use for 11 indications, based on the WHO AWaRe book for two age groups: 28 days to 12 years and >12 years. We parameterised the models using country-specific antimicrobial resistance estimates in the 10 countries and cross-sectional Global Point Prevalence Survey (Global-PPS) case-mix data from 2021 for 10 countries and from 2015-2022 in a subset of five countries. We then compared estimated expected antibiotic use with observed empiric use (from Global-PPS) in defined daily doses for adults and days of therapy for children, across indications and AWaRe categories. Findings: In 2021, among patients aged >12 years, in all countries but one, observed empiric Access antibiotic use, as a proportion of total antibiotic use, was lower than expected and empiric Watch antibiotic use was higher than expected. Similar patterns were observed in all countries but one in patients aged 28 days to 12 years. The magnitude of discrepancies between expected and observed Access and Watch antibiotic use varied across indications and countries. The median observed-to-expected ratios of usage across countries ranged from 0.3-0.8 for Access antibiotics, and 0.7-5.3 for Watch antibiotics in patients aged >12 years in 2021. Temporal trends from repeated surveys from 2015 to 2022 showed little change in observed-to-expected ratios for Access and Watch antibiotics. Interpretation: This benchmarking tool uses Global-PPS data to quantify differences between observed antibiotic use and WHO AWaRe recommendations. Our tool can be adaptable to local guidelines, provides policy-relevant estimates of expected antibiotic use to support monitoring, procurement planning, and targeted stewardship intervention.

Introduction Reliable, well-maintained laboratory equipment is essential for timely, accurate and reliable laboratory results for patient care, surveillance, and health system resilience. Tanzania implemented the Standard Medical Laboratory Equipment Guideline (SMLEG-2018) to harmonise procurement and improve efficiency across a tiered laboratory system and network. However, equipment functionality gaps remain a critical challenge for healthcare delivery. This study determined the functionality status of standardised laboratory analysers in Tanzania mainland and identified the drivers of non-functionality. Methods We conducted a facility-based cross-sectional study to identify the causes of non-functionality of standardised chemistry, haematology, and urine analysers across mainland Tanzania. We assessed 3,044 analysers and used Pareto analysis to identify the primary drivers of non-functionality. Results Of the 3,044 standardised analysers assessed, 987 (32.4%) chemistry 1,308 (43.0%) haematology, and 749 (24.6%) urine) assessed; 397 (13.0%) were non-functional. Proportionally, urine analysers were the most non-functional (n=176/749, 23.5%), followed by chemistry (n=135/987, 13.7%), and haematology (n=86/1308, 6.6%) analysers, p<0.001. Urine analysers had significantly higher non-functional equipment (23.5%), followed by Chemistry analysers (13.7%), than Haematology analysers (6.6%), p<0.001. Equipment breakdown was the leading cause of non-functionality, accounting for 70.9% (61/86), 70.5% (124/176) and 60.0% (81/135) of the non-functional haematology, urine and chemistry analysers, respectively, among all causes identified for each analyser type. Conclusion Although the SMLEG 2018 implementation identified broad coverage of functional standardised laboratory equipment, persistent equipment breakdowns of more than 10% highlight a systemic, concerning gap that requires immediate corrective action to sustain high performance. Strengthening preventive maintenance, timely repair services and sustainable equipment lifecycle planning is critical to sustaining quality laboratory services for robust preventive and curative care.

Background Medicine shortages are monitored within national borders, but complementarity across national markets is poorly characterised. Objective To characterise medicines supplied through South Korea's national access programme and to quantify this complementarity between South Korea and Italy. Methods In this cross-sectional study, we linked shortage records from the Italian Medicines Agency and Korean Ministry of Food and Drug Safety, Korea Orphan and Essential Drug Center supply notices, and national reimbursement lists. The primary outcome was the proportion of shortage configurations with a reimbursed counterpart in the partner country, identified by normalised ingredient, pharmaceutical form, and route, and not recorded as withdrawn or in shortage. The primary analysis covered Jan 1 to June 30, 2026, and the secondary analysis covered 2023-26. Results Among 341 formulations supplied through the Korean national access programme, 242 (71.0%) lacked domestic marketing authorisation at first observed supply or were supplied after market withdrawal. Of 338 Italian shortage configurations in the first half of 2026, 228 (67.5%) had an available reimbursed Korean counterpart; over 2023-26, 332 of 549 (60.5%) did. Conversely, 27 of 47 Korean configurations (57.4%) had such an Italian counterpart; over 2023-26, 93 of 184 (50.5%) did. In both directions, ingredients on EU critical or Korean essential medicine lists more often had a cross-border match than unlisted ingredients. Conclusions About half of shortage or access-gap medicines had a potentially available reimbursed counterpart in the other country. Cross-national linkage of medicine data may help identify potential counterparts, although these require regulatory, clinical, and procurement review.

Objectives To characterise COVID-19 inpatients with and without bacterial/fungal preceding, co- and secondary infections, and describe the distribution of organisms associated with COVID-19 and antibiotic use. Methods We linked ISARIC/WHO CCP-UK data from hospitals in England (admissions 01/01/2020-18/10/2021) with UK Health Security Agency infections datasets of COVID-19, and bacterial- and fungal-positive specimens using a multi-step hierarchical algorithm. We retained those aged >18 years and categorised COVID-19-associated infection as preceding (2-28 days prior to SARS-CoV-2 PCR positive date), co-infection ({+/-}1 day) or secondary (2-28 days after). Results During the study period, there were 173,947 hospitalised episodes of COVID-19; 5.8% (n=10,017) with a bacterial or fungal preceding, co- or secondary infection. Preceding and co-infections were rare (preceding: 0.7%; co-infection: 1.5%) while secondary infections were more common (3.5%). Escherichia coli (29.6%) and Staphylococcus aureus (15.2%) were the most identified organisms in blood specimens, while S. aureus (22.9%) and Pseudomonas aeruginosa (20.4%) were most common in lower respiratory tract specimens. The 28-day case fatality rate (CFR) remained static (36%) in those with secondary infection, whereas it decreased between early 2020 and mid-2021 in the other infection groups (37% to 27%). Of those with no positive microbiology, 72.8% received antibiotics, though this decreased between January-June 2020 (77.6%) and April-October 2021 (62.6%). Conclusion Bacterial and fungal infections complicated approximately 1-in-17 hospitalised episodes of COVID-19, with CFR of >25%. Antibiotic prescribing was common in those without firm evidence of bacterial infection. We recommend adhering to NICE guidance which discourages empirical antibiotic use for hospitalised COVID-19 patients.

Objective: To critically evaluate the influence of extracellular matrix stiffness on tumor progression, prognosis, and clinical implications in patients with oral squamous cell carcinoma. Design: This systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, and the protocol was registered in PROSPERO (CRD420251156429). Five databases (PubMed, Scopus, Embase, Web of Science, and OATD) were searched without restrictions on publication year or language. Human studies that evaluated extracellular matrix stiffness in oral squamous cell carcinoma, either as an assessment method or as a prognostic factor, were included; in vitro and animal studies were excluded. Results: Eight human studies involving 436 patients were included. Elastography was the most frequent measurement method, employed in four studies. Mean tumor thickness was reported in three studies and ranged from 3.0 to 4.4 mm. Extracellular matrix stiffness was expressed in various units (e.g., 37.7 gf, 23.5 kPa) and was consistently higher in tumor tissue than in normal mucosa in all studies. Three studies demonstrated a significant positive correlation between stiffness and tumor thickness. One study identified predictive cut-off values for lymph node metastasis and reported that high matrix stiffness was an independent predictor of worse overall survival (HR = 4.022; 95% CI: 1.294-12.495; p = 0.016) and recurrence-free survival (HR = 5.680; 95% CI: 1.146-28.143; p = 0.033). A meta-analysis of five studies (307 patients) showed a significantly higher standardized stiffness in oral squamous cell carcinoma compared with normal oral mucosa (standardized mean difference = 5.28; 95% CI: 2.61-7.94; p < 0.001), with substantial heterogeneity (I2= 98.6%). Conclusions: Extracellular matrix stiffness is elevated in oral squamous cell carcinoma and is associated with greater tumor thickness, lymph node metastasis and, in one study, worse survival. These findings support extracellular matrix stiffness as a potential biomechanical marker, pending further validation in standardized prospective studies.

Introduction Within the Tobacco and Vapes Act 2026, the UK Government is considering restricting retail displays of vaping and other nicotine products to discourage youth uptake. We explored how adult nicotine users and adolescents responded to conventional and restricted displays. Methods Two UK-wide cross-sectional online surveys were conducted April-June 2026, with current and former adult nicotine users (n=2,851), and adolescents (11-17 years; n=2,123). Participants rated images of vape and nicotine pouch point-of-sale (POS) displays (two conventional, two restricted) across 10 items. Other measures included demographics, smoking/vaping/nicotine pouch use, vaping susceptibility, and product choice. Results Ratings of two conventional POS images were consistently favourable. Two restricted POS images were almost exclusively rated unfavourably. GEE analyses, controlling for demographics and behaviour, indicated that a display with standardised white packs (versus a conventional display) consistently had lower odds of favourable ratings (adults range:0.13-0.31; adolescents range:0.11-0.32). A fully covered display had even lower odds of favourable ratings on all items (adults range:0.06-0.19; adolescents range:0.05-0.10). Presented with hypothetical restricted displays, most adults using nicotine remained consistent with their product choice. Favourable ratings of conventional displays were positively associated with adolescents' vaping susceptibility. Those favourably rating a large, branded display were more likely to be susceptible than those giving unfavourable/neutral ratings (AOR=2.73, 95%CI [2.16-3.45] p<0.001). No association was found between favourable ratings of restricted displays and susceptibility. Conclusion Restricting POS displays could reduce positive messaging around vaping and adolescent susceptibility. The potential impact of restrictions on adult users' perceptions of harm and accessibility should be considered.

Background: Indwelling urinary catheters can cause pain, urethral irritation and trauma and provide surfaces for microbial colonisation and biofilm formation. The LubriShield(R) Foley catheter incorporates a covalently bonded, superhydrophilic antifouling hydrogel designed to reduce surface friction and limit biofilm accumulation without releasing an antimicrobial agent. This study evaluated its safety and clinical performance compared with an uncoated silicone Foley catheter, including usability and patient comfort, and explored catheter-associated microbial colonisation and biofilm formation. Methods: This prospective, randomised, single-blind, single-centre controlled clinical investigation enrolled 33 adults requiring indwelling urinary catheterisation for 72 hours to 14 days. Participants received either the LubriShield(R) Foley catheter (n = 16) or an uncoated Sterimed all-silicone Foley catheter (n = 17). The primary endpoint was safety based on adverse-event reporting; the prespecified safety criterion was the absence of a serious adverse device effect in the LubriShield(R) group. Secondary endpoints included investigator-rated ease and functionality of catheter insertion and removal and participant-reported pain and irritation/discomfort assessed using 0-10 numerical rating scales. Urine microbiology, catheter colonisation and catheter-level biofilm measurements were exploratory endpoints. Analyses were performed in the as-treated population. Numerical rating scale outcomes were compared using two-sided Mann-Whitney U tests; exploratory biofilm analyses used permutation tests with bootstrap confidence intervals. Results: No serious adverse events or serious adverse device effects occurred. Nine non-serious adverse events were reported and resolved completely. At least one adverse event occurred in 4/16 (25.0%) participants in the LubriShield(R) group and 4/17 (23.5%) participants in the control group. The prespecified safety criterion, defined as the absence of a SADE in the LubriShield(R) group, was met. LubriShield(R) was rated more favourably for ease of insertion (p = 0.0096), functionality during insertion (p = 0.0051), ease of removal (p = 0.0037) and functionality during removal (p = 0.0085). Participants reported significantly less pain and irritation/discomfort during insertion, while the catheter was indwelling and during removal (all p < 0.05). Outcomes 7 {+/-} 1 days after catheter removal were similar between groups. Absolute biofilm biomass and bacterial and fungal loads did not differ significantly. In a post hoc exploratory normalised analysis, the biofilm-to-bacterial-load ratio was lower with LubriShield(R) (median 0.052 vs 0.080; permutation p = 0.043), although the bootstrap 95% confidence interval for the between-group difference included zero. Conclusions: The LubriShield(R) Foley catheter demonstrated a favourable short-term safety profile and was associated with improved investigator-rated usability and participant-reported comfort compared with an uncoated silicone Foley catheter. A post hoc exploratory analysis was compatible with reduced biofilm accumulation relative to bacterial load, but this finding is hypothesis-generating only and requires confirmation in larger, adequately powered studies with prespecified biofilm endpoints.

Increasing evidence highlights the important role the oral ecosystem plays in systemic health. Despite the fact that oral diseases affect nearly 3.5 billion people globally, our understanding of the precise drivers of these diseases remains limited. To bridge this gap and provide broader understanding of oral public health, a clinical study involving 595 participants 20-78 years of age was conducted over 8 weeks. Characterization of the oral ecosystem using metabolomics, metagenomics, and targeted immune markers were analyzed in conjunction with demographic, lifestyle, and medical history metadata. This comprehensive approach allowed for the identification of specific links between microbial and metabolic signatures and overall wellness, providing a contemporary baseline to enable the development of personalized prevention and treatment strategies to help safeguard oral and systemic public health.

Consumer-grade wearables can continuously and longitudinally measure health signals such as heart rate (HR), activity, and sleep. While changes in these signals have been implicated in the early detection of infection (e.g., influenza, SARS-CoV-2) and real-time alerting systems have been developed, evidence from prospective deployment in pediatric transplant households remains limited. Here, we study the application of a resting heart rate (RHR)-based real-time alerting algorithm to detect respiratory virus infection in a cohort of solid organ transplant recipients and their household members (n=146) in a Phase IV clinical trial (NCT06161454). Reliable and efficient alerting for infection events may be particularly relevant for this population, enabling isolation, clinical management, and/or treatment. Of 31 antigen-test outcomes, nearly all (29/31, 93.5%) correspond to either influenza, COVID, or other patient-reported symptoms. We describe RHR, HR, activity, and sleep/circadian rhythm features around clinical alarm events, identifying candidate features for further investigation and algorithm improvement.