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Infection

Springer Science and Business Media LLC

Preprints posted in the last 90 days, ranked by how well they match Infection's content profile, based on 14 papers previously published here. The average preprint has a 0.05% match score for this journal, so anything above that is already an above-average fit.

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Unusual predominance of Staphylococcus aureus in the salivary microbiome of children with Early Childhood Caries in Kano, Nigeria

Okolo, C. C.; Amole, T. G.

2026-03-06 dentistry and oral medicine 10.64898/2026.03.05.26347684
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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.

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Comparison of anxiety and satisfaction levels in patients undergoing digital versus conventional dental impressions

Farfan, M. E.; Pinzon, A. P.; Armijos Briones, M.

2026-02-06 dentistry and oral medicine 10.64898/2026.02.05.26345703
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Dental impressions are a routine component of prosthodontic care, yet the patient experience may vary depending on the technique used. This study compared dental anxiety and satisfaction among patients undergoing digital versus conventional impressions in a postgraduate clinical setting at the Universidad de Especialidades Espiritu Santo. A total of 85 adult patients were included: 44 received conventional impressions and 41 received digital impressions. Dental anxiety was assessed using the Modified Dental Anxiety Scale (MDAS) before the procedure, and satisfaction was evaluated using a Visual Analog Scale (VAS) immediately after the procedure. Anxiety scores did not differ significantly between groups (p = 0.232). However, patients in the digital group reported significantly greater satisfaction than those in the conventional group (p < 0.001). These findings suggest an association between the use of digital impression techniques and higher levels of patient satisfaction, while no significant association was observed between impression technique and dental anxiety.

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Efficacy Of Connective Tissue Graft Versus Titanium Papillary Inserts in the Surgical Reconstruction of Interdental Papilla: A Randomized Controlled Clinical Trial

Nagar, S. S.; Chandra, R. V.; Aileni, A. R.; Goud, V. S.

2026-03-04 dentistry and oral medicine 10.64898/2026.02.26.26345466
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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.

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Oral Hygiene Practices and Dental Caries Experience in Nigeria: A Systematic Review and Meta-Analysis

Aborisade, A.; Mohammed Ali, A.; Okolo, C.; Gbaja-Biamila, T. A.; Akinsolu, F. T.; Salako, A. O.; Adewole, I. E.; Olagunju, M. T.; Abodurin, O. R.; Eleje, G. U.; Nwaozuru, U. C.; Ehizele, A. O.; Lusher, J. M.; El Tantawi, M.; Folayan, M. O.

2026-01-30 dentistry and oral medicine 10.64898/2026.01.30.26345076
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BackgroundOral hygiene is linked with dental caries experience. This systematic review and meta-analysis assessed the associations between oral hygiene status, the frequency of tooth brushing, and the prevalence of dental caries in Nigeria. Tools used for maintaining oral hygiene were also identified. MethodsRegistered with PROSPERO (CRD42022367763), this review searched PubMed, Web of Science, Scopus, African Journals Online, African Index Medicus, and Google Scholar in January 2026. Observational studies and clinical trials reporting baseline caries prevalence were included. There was no language restriction. Studies were excluded if they did not provide information on the sample size, had no study outcome data, or featured duplicate samples, and if they were review articles, systematic reviews and meta-analyses, case reports, case series, in vitro studies, commentaries/letters (editorials, opinion pieces) devoid of primary data. Pooled odds ratios (ORs) were estimated using random-effects models. Subgroup analyses were conducted by dentition type, geopolitical zone, study design, publication year, mean age, and sample size. ResultsTwenty-three cross-sectional studies were included, of which 20 (86.9%) were conducted in Southern Nigeria. After removing an influential outlier, poor oral hygiene was associated with a 38% reduction in caries odds (OR 0.62, 95% CI 0.46-0.84). Brushing at least twice daily was strongly associated with reduced caries (OR 0.01, 95% CI 0.00-0.01). No significant association was found between the type of cleaning device and caries prevalence. Subgroup analyses identified dentition type and publication year as significant moderators. Heterogeneity ranged from low to moderate, and no publication bias was detected for primary associations. The most common cleaning tool was a toothbrush with toothpaste, though chewing sticks, cotton wool, and other traditional tools were also reported. ConclusionTwice-daily tooth brushing is strongly associated with lower caries prevalence in Nigeria. Poor oral hygiene was linked to reduced caries odds in pooled analysis, a finding that may reflect socio-economic and dietary confounding. The type of cleaning tool was not significantly associated with caries risk, highlighting the importance of brushing frequency and technique over tool type. Future research should prioritize Northern Nigeria to address the geographic skewness of the data and improve national representativeness.

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Serum Vitamin D Status and Risk of Early and Late Dental Implant Failure: A Systematic Review of Multivariate-Adjusted Primary Studies with Explicit Vitamin D Cut-off Classification

Pardal-Pelaez, B.; Pardal-Refoyo, J. L.

2026-01-06 dentistry and oral medicine 10.64898/2026.01.05.26343458
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Statement of problemDental implant failure remains a significant clinical concern, with early loss often attributed to impaired osseointegration. Recent research has considered the role of serum vitamin D in implant integration, yet the precise relationship between vitamin D status and implant loss, particularly when distinguishing early and late failures, is not fully established. PurposeThe objective of this analysis was to evaluate the association between explicit serum vitamin D cut-off values and clinically confirmed dental implant failure, with a particular focus on differentiating early (pre-loading) from late (post-loading) failures. The review also sought to determine whether primary studies used multivariate adjustment for potential confounders. Material and methodsThe draft of this revision was registered in PROSPERO (CRD420251049631, https://www.crd.york.ac.uk/PROSPERO/view/CRD420251049631). A comprehensive literature search was conducted using AI-assisted tools to identify primary research studies, including randomized controlled trials and cohort studies, published in English, Spanish, French, German, or Italian. Eligible studies required explicit vitamin D threshold categorization, clinically verified implant loss, and clear differentiation of early and late failures. Data extraction included study design, vitamin D categorization, analytical methods, and outcomes. ResultsIdentified studies predominantly consisted of retrospective and prospective cohorts examining early implant failures, frequently using cut-offs such as >30 ng/mL, 10-30 ng/mL, and <10 ng/mL for serum vitamin D. Results suggested a higher frequency of early failures in individuals with severe vitamin D deficiency; however, all studies relied on univariate analyses without multivariate adjustment for confounders. Late implant failures were rarely addressed. ConclusionsCurrent evidence indicates a possible association between low serum vitamin D and early dental implant failure, but the lack of robust statistical adjustment prevents definitive conclusions. High-quality studies with rigorous confounder control and explicit early versus late failure analysis are needed.

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Establishment of a large-scale oral disease registry (NDCS-ODR) in a national specialty center

Tay, J.; Nasimento, G. G.; Ho, J. S. H.; Ragavendran, N.; Yeo, B. W. R.; Lim, S. S. W.; Kallam, H. R.; Peres, M. A.

2026-01-16 dentistry and oral medicine 10.64898/2026.01.13.26344086
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This study describes the establishment of the National Dental Center Singapore Oral Disease Registry (NDCS-ODR), a large-scale, electronic health records registry designed to capture real-world data on oral diseases. The NDCS-ODR was developed to standardize and integrate oral health data within Singapore Health Services, the countrys largest healthcare cluster. Its development, governance, and data architecture are described, with an overview of individuals with oral diseases recorded in the registry. Data collection from 2013 to June 2025 has been completed. As of June 2025, the NDCS-ODR comprises 229,249 unique patients, with a mean (SD) age of 49.1 (19.5) years and an approximately equal sex distribution. Most were of Chinese ethnicity (77.6%), and Singapore citizens (92.5%). Clinical variables indicated substantial disease and treatment burden, with a mean of 7.9 (7.7) missing teeth, 4.8 (6.2) restored surfaces, and 2.8 (3.4) restored teeth per patient. Among 108,517 recorded periodontal diagnoses, Stage III periodontitis (2018 EFP/AAP Classification) and severe chronic periodontitis (1999 Classification of Periodontal Diseases and Conditions) were most common. The NDCS-ODR represents Singapores first large-scale, real-world oral disease registry embedded within a national specialty center, demonstrating the feasibility of leveraging electronic health record data for research and service evaluation.

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Failure of Tooth Eruption: A Systematic Review and Meta-Analysis Integrating Genetic Etiology, Diagnostic Accuracy, and Clinical Management Outcomes

Mahfouz, M.; Alzaben, E.

2026-02-23 dentistry and oral medicine 10.64898/2026.02.21.26346646
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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)

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Awareness and Acceptance of Deep Margin Elevation amongst Dental Practitioners- A cross-sectional multicentric study

Jethwani, J.; Sundari, G.; Mnnamma, L. M.; Tashkandi, E.; Carrico, C. K.

2026-01-18 dentistry and oral medicine 10.64898/2026.01.16.26344250
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BackgroundDeep margin elevation (DME) is a restorative technique that facilitates the placement of restorations in cases of subgingival margins. Although clinically reported, very few data are available on dental practitioners awareness and use of DME. ObjectivesTo evaluate awareness and clinical acceptance toward deep margin elevation (DME) use in subgingival restorative cases among dental practitioners worldwide. MethodologyA cross-sectional questionnaire-based study was conducted among practicing dentists at various dental educational institutions, private dental practices, and a combination of academic and private dental practices across multiple centers globally. The self-administered questionnaire consisted of 20 closed-ended questions to evaluate awareness and clinical acceptance. The data were entered into and analyzed using a Chi-square test and descriptive statistics in the Statistical Package for the Social Sciences (SPSS) software. ResultsOut of 450 invited participants, 349 general dental practitioners completed the survey (77.6%). The purely educational institutions response rate was 79 (23%), the strictly private dental practice response rate was 134 (39%), and the combined academic and private practice response rate was 131 (38%). Sixty-six percent of respondents agreed that predictable adhesive bonding to cervical/root dentin can be achieved in restorations with deep margins. Although a majority of respondents had heard of DME (77%), the majority reported a preference for surgical crown lengthening (75%) when favorable conditions were present. ConclusionThe study highlights moderate DME awareness among the study participants. The findings of this study revealed that the number of dentists who use the technique to restore large subgingival defects in posterior teeth with proximal caries is very small. Thus, it is recommended that dental practitioners introduce this technique in their dental clinics as an alternative to surgical crown lengthening. Although years of experience and a dentists rank may influence clinical decisions, an in-depth factorial analysis with a larger sample size is necessary.

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Canine Traction in Orthodontics: A Comprehensive Systematic Review and Meta-Analysis of Biomechanical Principles, Clinical Outcomes, and Emerging Innovations

Mahfouz, M.; Alzaben, E.

2026-03-04 dentistry and oral medicine 10.64898/2026.03.03.26347399
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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.

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Mapping Stakeholder Alignment for Deprescribing Policy in France: Insights from a Policy Delphi Approach

Oliveira, S.; Dariel, O.; Brunn, M.

2026-02-12 health policy 10.64898/2026.02.11.26346080
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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.

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Senior dental students reflective activities involving community-service learning

Brondani, M.; Elias, R.; Pereira, R. P. L.

2025-12-22 dentistry and oral medicine 10.64898/2025.12.21.25342789
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ObjectiveCommunity service-learning (CSL) placements engage with equity-deserving groups. They receive oral health care and students can critically reflect on their experiences. This study aimed to thematically explore the reflections of senior dental students providing oral health services to equity-deserving communities in British Columbia, Canada. MethodsSemi-structured written reflections were collected cross-sectionally from three consecutive graduating cohorts of fourth-year dental students (2022-23, 2023-24, and 2024-25). Reflections were a mandatory component of a community placement course, were approximately 500 words in length, and were prompted as follows: "Describe your personal experience at the assigned community clinic, noting moments of revelation, valuable learning, and/or disappointment for you." An exploratory thematic analysis was conducted using an iterative coding process to identify and interpret categories and themes. ResultsFrom all the three years, 764 reflections were collected (191-625 words each) from 171 students. Of these, 124 reflections were excluded because they consisted solely of descriptions of procedures. Data saturation was reached after in-depth analysis of 205 reflections, yielding four overarching themes, including learning across differences; and pause-breathe-refine. These themes were informed by categories highlighting that detrimental impact of overly controlling mentorship styles and observation-only experiences on students learning. ConclusionTransformative experiences were observed, while students also reflected on less positive practices. Students emphasized the importance of CSL placements for their education, professional growth, and understanding of underserved populations, while also highlighting implementation challenges. Future research should examine the long-term impact of CSL activities once these challenges are addressed.

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Assessing causal relationships between oral microbiota and Periodontitis: evidence from Mendelian randomization analysis

Wei, Z.-f.; Wuzhang, J.-p.; Huang, Y.-t.

2026-02-03 dentistry and oral medicine 10.64898/2026.02.01.26345317
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ObjectiveThis study utilizes small-sample periodontitis data to exploratively investigate causal relationships between the oral microbiome and periodontitis in East Asian populations. We aimed to identify specific oral microbial taxa that may drive disease pathogenesis. Given the exploratory nature of the dataset, findings should be interpreted as hypothesis-generating. MethodsWe performed a two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary statistics for tongue dorsum and salivary microbiomes alongside periodontitis data in East Asian populations. Primary causal estimates were derived using the inverse-variance weighted (IVW) method, supplemented by MR-Egger, weighted median, weighted mode, and simple mode methods. To ensure robustness, we assessed heterogeneity using Cochrans Q test, evaluated horizontal pleiotropy via the MR-Egger intercept and MR-PRESSO tests, and applied Steiger filtering to rule out reverse causality. ResultsWe identified 60 species-level microbial taxa causally associated with periodontitis, comprising 29 negative and 31 positive associations. These taxa were predominantly enriched within the genera Campylobacter, Pauljensenia, Solobacterium, and Streptococcus. ConclusionThis study provides tentative evidence for causal links between specific species-level oral microbial taxa and periodontitis, highlighting potential targets for prevention and therapeutic intervention.

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Dental teachers perspectives on Extended Reality in dental education: an international survey

Bjelovucic, R.; de Freitas, B. N.; Norholt, S. E.; Taneja, P.; Terp Hoybye, M.; Pauwels, R.

2026-03-05 dentistry and oral medicine 10.64898/2026.03.05.26347677
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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.

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Burden of oral disorders in the U.S. from 1990 to 2023: Findings from GBD study

tavazozadeh, e.; shakour, n.; veysi, g.; nasiri, k.; jamilian, a.

2026-01-19 public and global health 10.64898/2026.01.18.26344340
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ObjectivesThere is no comprehensive study comparing the burden of different oral diseases across states, years, and different demographics in the United States (US). Therefore, to address this gap, we aimed to evaluate the burden of oral disorders in the US and its states from 1990 to 2023. MethodsWe used the Global Burden of Disease (GBD) 2023 data to evaluate the burden of oral disorders in the USA from 1990 to 2023 in different age groups, sexes, states, and years. We aim to report the incidence, prevalence, and Disability-Adjusted Life Year (DALY) rates of caries of deciduous teeth, caries of permanent teeth, periodontal diseases, edentulism, and other oral disorders, accompanied by 95% uncertainty intervals (UIs). ResultsFrom 1990 to 2023, age-standardized prevalence, incidence, and DALY rates of total oral disorders in the USA declined slightly by 2.3%, 0.14%, and 4.82%, respectively. Among all oral disorders, caries of permanent teeth had the highest age-standardized prevalence and incidence rates, while edentulism accounted for the highest DALY burden in both 1990 and 2023. Males had higher incidence and prevalence, whereas females had higher DALY rates across all these 34 years. The burden of oral disorders varied by age and state, with older adults and states such as West Virginia showing the highest DALY rates. ConclusionsAlthough the decline in the burden of oral disorders in the US over the past decades was a promising trend, the recent increases are concerning and warrant attention from policymakers.

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A Canadian Perspective on Family Medicine Residents' Attitudes and Practices Toward Infants' Oral Health

Abushanan, A.; Doan, Q.; Aleksejuniene, J.; Brondani, M.

2026-02-04 dentistry and oral medicine 10.64898/2026.01.31.26345294
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ObjectivesTo explore the extent to which infant oral health is addressed within the family medicine residencies in Canada, and the attitudes and practices of Canadian family medicine residents towards infant oral health. MethodsTwo brief self-administered online surveys, one to 17 Canadian family medicine training program directors and another to current residents within these programs, were conducted using Research Electronic Data Capture (REDCap). Questions focused around respondents attitudes and practices towards infants oral health and infant oral health content within family medicine curricula. Results11 family medicine directors and 155 family medicine residents responded to the survey. 90% of the directors indicated that clinical oral screening was not incorporated in the curriculum. 53% of the residents reported that they did not feel their training was adequate to identify dental caries. 41% described the quality of their oral health training to be poor. While 72% reported lack of knowledge and training as the major barrier to performing oral health-related practices. ConclusionMost of the family medicine training programs in Canada do not include infant oral health screening in their curriculum. The family medicine residents reported lack of knowledge and training is preventing them from performing various oral health-related practices.

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Salivary Dysbiosis Aligns with an Olfactory-Cognitive Phenotype in Aging

de Coning, E.; Barve, A.; Alberti, L.; Bertelli, C.; Richetin, K.

2026-02-16 dentistry and oral medicine 10.64898/2026.02.12.26346193
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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.

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Viral metagenomic sentinel surveillance of acute respiratory infections in primary care as a public health strategy: a prospective national pilot study

Mourik, K.; Sidorov, I.; Meijers, E.; van den Brink, S.; Bos, S.; Aarts, L.; Kuttiyarthu Veetil, N.; Boers, S. A.; Eggink, D.; Meijer, A.; de Vries, J. J. C.

2025-12-19 public and global health 10.64898/2025.12.18.25342553
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BackgroundWith the introduction of metagenomics in clinical diagnostics unfolding and the expanding role of pathogen genomics in national surveillance, the stage is set for its launch into public health surveillance. This report pilots the use of metagenomics for nationwide sentinel general practitioner (GP) monitoring and genomic characterisation of both anticipated and emerging respiratory viruses in primary care. MethodsThis prospective pilot study included a selection of 93 patients with acute respiratory illness in GP practices participating in nationwide sentinel virological surveillance during winter 2024-2025. Specimens underwent parallel metagenomic testing using probes targeting human and animal viruses. The primary outcome was detection and in-depth genomic characterisation of viruses covered by standard screening and those outside the scope of standard methods. FindingsMetagenomic surveillance detected viruses in 95% of the specimens, including latent ones. Overall, 83% of specimens were positive by standard PCR-based screening. For viruses targeted by routine PCR, metagenomics showed a sensitivity of 94% (95%CI 86-97), specificity of 100% (95%CI 99-100), positive predictive value of 96% (95%CI 89-99), and negative predictive value of 100% (95%CI 99-100), with median genome coverage of more than 99% (95%CI 23-100%). Metagenomic data enabled instant full genomic characterisation of circulating viruses targeted by current amplicon-based surveillance, including influenza viruses, SARS-CoV-2, and respiratory syncytial viruses (RSV), as well as less frequently targeted viruses such as human metapneumoviruses (hMPV), betacoronaviruses OC43 and HKU1, and non-targeted viruses such as adenoviruses. The data facilitated characterisation of a reassortant H3N2 influenza virus, potential vaccine escape mutants, markers of susceptibility to influenza antiviral drugs and RSV monoclonal antibodies, and a human H1N2 swine influenza virus infection, demonstrating comprehensive and robust performance regardless of the circulating viruses. InterpretationIn this pilot study, metagenomic data enhanced standard typing through its broad scope and simultaneous detection and genome characterisation, enabling drug and vaccine resistance monitoring. These capabilities support the potential of metagenomics to expand current diagnostic approaches and gradual integration into public health surveillance. FundingThe Netherlands Organisation for Health Research and Development (ZonMw), and Ministry of Health, Welfare and Sport (VWS). Research in contextO_ST_ABSEvidence before this studyC_ST_ABSTo identify studies using metagenomics for screening of patients with infectious diseases, we searched PubMed using the following search terms in the title/abstract: (metagenomic OR metagenomics OR mNGS) AND (prospective OR trial OR RCT). The results were filtered for prospective studies involving humans and written in English. The search was performed on December 10, 2025. The search results showed an exponential growth of prospective clinical studies on metagenomics, from only a few publications in 2021 to over 90 reports up to end-2025. The typical setting was diagnostic testing in hospitalised patients, and the primary focus of clinical performance assessment was detection as a dichotomous outcome rather than full genome characterisation. Around 80% of all prospective studies were observational: while sampling was prospective, metagenomic results were not reported in real-time as part of the study. One prospective study focused on respiratory metagenomic testing of outpatients in a public health setting. The study explored the use of untargeted metagenomics in Swiss outpatients, comparing COVID-19 pre-pandemic and pandemic periods, with retrospective reporting. This comparative study was limited to detection while the untargeted metagenomic approach did not demonstrate full genome characterisation. A recent News report in this journal announced the launch of the UK metagenomic Surveillance Collaboration and Analyses Programme (mSCAPE) for winter 2025-26, leveraging clinical metagenomic data from diagnostic laboratories in hospitalised patients for surveillance purposes. To our knowledge, no pilot results from this initiative have been reported to date. Added value of this studyThese data represent the first on the performance and feasibility of metagenomic surveillance integrated within the existing nationwide primary care sentinel GP infrastructure for genomic virological surveillance of acute respiratory infections. By performing viral detection and providing simultaneous full genome consensus sequences, typing of all circulating respiratory pathogens, as well as antiviral reduced susceptibility and antibody escape mutation analyses, could be performed directly. Prospective inclusion and metagenomic analyses were conducted in parallel with standard analyses and reporting to GPs and national and international stake holders. Although the metagenomic data delayed virus detection reporting compared to the standard approach, it outperformed standard surveillance sequencing by enabling full genome characterisation of all circulating viral pathogens, highlighting its potential in sentinel GP surveillance of acute respiratory infections. Implications of all the available evidenceEvidence is emerging that metagenomic approaches are effective and feasible for implementation not only in the clinical diagnostic setting but also for genomic characterisation in outpatient public health settings.

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Multicentre validation and update of a Legionella prediction score to guide testing and treatment in community-acquired pneumonia

Bigler, M.; Draeger, S.; Zacher, F.; Hattendorf, J.; Maeusezahl, D.; Albrich, W. C.; SwissLEGIO Hospital Network,

2026-02-27 infectious diseases 10.64898/2026.02.25.26347092
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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%.

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Association between fluoridated toothpaste use and dental caries in Nigeria: A systematic review and meta-analysis

Aborisade, A.; Ali, A. M.; Amedari, M.; Salako, A. O.; Akinsolu, F. T.; Abodunrin, O. R.; Ola, O. M.; Olagunju, M. T.; Eleje, G. U.; Lusher, J.; Ezechi, O. C.; Folayan, M. O.

2026-02-28 dentistry and oral medicine 10.64898/2026.02.27.26346208
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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.

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Evidence Supporting EMA Drug Approvals (2020-2023): A Cross-Sectional Study of Trial Design and Outcomes

Siebert, M.; Caquelin, L.; Naudet, F.; Ross, J. S.; Ramachandran, R.

2026-02-05 health policy 10.64898/2026.02.04.26345500
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BackgroundThe strength and transparency of clinical trial evidence supporting drug approvals has become increasingly scrutinized, particularly considering the increased use of regulatory flexibility and expedited pathways. While U.S. Food and Drug Administration (FDA) standards have been extensively analyzed, evidence standards at the European Medicines Agency (EMA) remain less well-characterized. Thus, this study aims to systematically assess the design, quality, and outcomes of pivotal efficacy trials supporting EMA drug approvals between 2020 and 2023. MethodsWe conducted a cross-sectional analysis of new medicines and biosimilars receiving positive opinions from the EMAs Committee for Medicinal Products for Human Use (CHMP) and subsequent approval by the European Commission between January 2020 and December 2023. Data were extracted from European Public Assessment Reports (EPARs) and EMA medicine databases. Key variables included trial design features, primary endpoint type and achievement status, and justification for approval in cases of failed efficacy endpoints. ResultsBetween 2020 and 2023, 232 drugs were approved by the EMA for 281 indications. Of these, 205 (88.4%) were new active substances and 65 (28.0%) were granted orphan designation. Forty-six products (19.8%) were approved via a special regulatory program, most commonly Conditional Approval (26 products; 11.2%). Cancer was the leading therapeutic area, accounting for 61 approvals (26.3%). Approvals were supported by 393 pivotal clinical trials. Of these, 327 (83.2%) were randomized controlled trials (RCTs) and 218 (66.6% of RCTs) had a superiority design. A total of 232/393 trials (59.0%) relied on surrogate endpoints. Overall, 22 approvals (9.5%) were supported by at least one pivotal trial in which at least one primary endpoint was not met; in seven of these cases (31.8%), the failed trial was the sole pivotal trial. The most common rationale for approval despite null primary results was reliance on the totality of evidence, secondary endpoints, or clinical judgment (9 products; 40.9%). ConclusionsOur findings reveal substantial variability in the design and evidentiary strength of pivotal trials supporting EMA approvals between 2020 and 2023. While the majority of studies were RCTs, reliance on surrogate endpoints was common. That 10% of approvals were based on pivotal trials with null primary endpoints highlights the nuanced role of regulatory judgment in therapeutic evaluation. These findings prompt reflection on evolving evidence standards in drug regulation and underscore the need for transparency and consistent justifications.