Epidemiology of herpes simplex virus type 2 in Europe: systematic review, meta-analyses, and meta-regressions.

Background: Herpes simplex virus type 2 (HSV-2) infection is a globally prevalent, life-long, sexually transmitted infection. This study characterized HSV-2 seroprevalence in Europe for various at-risk populations and proportions of HSV-2 detection in genital ulcer disease (GUD) and in genital herpes. Data on neonatal herpes and HSV-2's contribution to HIV transmission were also reviewed. Methods: Cochrane and PRISMA guidelines were followed to systematically review, synthesize, and report HSV-2 related findings. The search was conducted in PubMed and Embase databases up to February 20, 2022. Any publication reporting data on the outcome measures was included. Meta-analyses and meta-regressions were conducted. Findings: 211 relevant reports were identified, including 12 overall incidence measures, 294 overall (813 stratified by factors such as age and sex) seroprevalence measures, 13 overall (15 stratified by sex) proportions of HSV-2 detection in clinically diagnosed GUD, and 70 overall (183 stratified by factors such as age and sex) proportions of HSV-2 detection in laboratory-confirmed genital herpes. Pooled mean seroprevalence was 12.4% (95% CI: 11.5-13.3%) among general populations, 27.8% (95% CI: 17.5-39.4%) among men who have sex with men, 46.0% (95% CI: 40.1-51.8%) among people living with HIV and people in HIV discordant couples, and 63.2% (95% CI: 55.5-70.6%) among female sex workers. Most measures showed heterogeneity in HSV-2 seroprevalence. The pooled mean seroprevalence among general populations increased with age and was 0.65-fold (95% CI: 0.58-0.74) lower in men than women. Seroprevalence decreased by 1% per calendar year. Pooled mean proportions of HSV-2 detection in GUD and in genital herpes were 22.0% (95% CI: 15.3-29.6%) and 66.0% (95% CI: 62.9-69.1%), respectively. HSV-2 detection in genital herpes cases was 1.21-fold (95% CI: 1.10-1.32) higher in men compared to women and decreased by 1% per calendar year. Incidence of neonatal herpes indicated an increasing trend. Interpretation: Although seroprevalence is declining, a significant proportion of Europe's population is infected with HSV-2. HSV-2 accounts for approximately one-fifth of GUD cases and two-thirds of genital herpes cases. Findings support the need to invest in HSV-2 vaccine development, and sexual and reproductive health services. Funding: Qatar National Research Fund [NPRP 9-040-3-008] and pilot funding from the Biomedical Research Program at Weill Cornell Medicine in Qatar supported this study.

Gene-specific machine learning model to predict the pathogenicity of BRCA2 variants.

Background: Existing BRCA2-specific variant pathogenicity prediction algorithms focus on the prediction of the functional impact of a subtype of variants alone. General variant effect predictors are applicable to all subtypes, but are trained on putative benign and pathogenic variants and do not account for gene-specific information, such as hotspots of pathogenic variants. Local, gene-specific information have been shown to aid variant pathogenicity prediction; therefore, our aim was to develop a BRCA2-specific machine learning model to predict pathogenicity of all types of BRCA2 variants. Methods: We developed an XGBoost-based machine learning model to predict pathogenicity of BRCA2 variants. The model utilizes general variant information such as position, frequency, and consequence for the canonical BRCA2 transcript, as well as deleteriousness prediction scores from several tools. We trained the model on 80% of the expert reviewed variants by the Evidence-Based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium and tested its performance on the remaining 20%, as well as on an independent set of variants of uncertain significance with experimentally determined functional scores. Results: The novel gene-specific model predicted the pathogenicity of ENIGMA BRCA2 variants with an accuracy of 99.9%. The model also performed excellently on predicting the functional consequence of the independent set of variants (accuracy was up to 91.3%). Conclusion: This new, gene-specific model is an accurate method for interpreting the pathogenicity of variants in the BRCA2 gene. It is a valuable addition for variant classification and can prioritize unreviewed variants for functional analysis or expert review.

Role of Newly Introduced Teledentistry Service in the Management of Dental Emergencies During COVID-19 Pandemic in Qatar: A Cross-Sectional Analysis.

Introduction: The lockdown imposed by the COVID-19 pandemic rendered teledentistry (TD) necessary to maintain the continuity of oral health services and avoid missing emergency dental conditions, while minimizing face-to-face visits. Our objective was to evaluate the ability of a newly introduced triage-based TD service to deliver its goals, by evaluating its processes and outcomes and assessing the demand for TD. Methods: This cross-sectional report assessed the triage processes and outcomes (triage category, referral to emergency/dental facility undertaken, remote medications prescribed, and procedures performed at the point of referral); and evaluated the demand for the newly introduced TD service during 5 months of the first wave of the pandemic. Results: Of 850 calls, about 70.6% of the samples were managed remotely; 29.4% were categorized as emergency/urgent and referred to the emergency/dental facility. Compared with other complaints, orofacial dental pain was the most common reason for the calls (41.6%, p < 0.0001). About 14.71% of callers received prescription for medications remotely. The most demanded disciplines were general dentistry, orthodontics, and oral surgery, respectively (p < 0.0001). Of those referred to a dental facility, 31.84% required no clinical intervention, 28.7% received orthodontic appliance repair, and 14.3% and 11.2% had urgent dental extractions or root canal treatments. Demand on the service fluctuated through various distinct stages of the lockdown. Conclusions: There has been continuous demand for the newly introduced TD service throughout the period of the current report despite the fluctuations, with most complaints managed remotely. TD was effective and suitable for triage, service delivery, and care during the pandemic.

Evaluation of commonly used occlusal indices in determining orthodontic treatment need.

OBJECTIVE: The main objective of this study was to validate commonly used occlusal indices in measuring treatment need, irrespective of their original objective: Index of Orthodontic Treatment Need (IOTN) that includes a dental health component (DHC) and an aesthetic component (AC), Peer Assessment Rating (PAR) index, Index of Complexity, Outcome, and Need (ICON), Discrepancy Index (DI), and Facial Aesthetic Index (FAI). METHODS: The dental casts, x-rays, and photographs of 101 participants were randomly selected among patients whose orthodontic treatment was completed. The indices were validated against the panel assessments of four experts using the receiver operating characteristic curve analysis. The area under the curve (AUC) helped to determine their optimal cut-off points. RESULTS: The raters exhibited an excellent level of inter-rater reliability in assessing need scores [intra-class correlation coefficients (ICC) = 0.85]. The DHC, AC, ICON, and PAR demonstrated 'good' diagnostic properties (AUC = 0.85, 0.84, 0.83, and 0.82, respectively). Adding the AC and the DHC into a combined index score [our proposed Combined Index of Orthodontic Treatment Need (CIOTN)] yielded the strongest correlation with need (r = 0.79) and the highest AUC value of 88 per cent with 91 per cent sensitivity and 71 per cent specificity. The DI had poor discriminating abilities (AUC = 0.69), however, its dental component was substantially better (AUC = 0.81). The supplemental FAI did not enhance the correlation of indices with need. CONCLUSION: The DHC, AC, ICON, PAR, and only the dental component of the DI reliably captured treatment need. The newly combined CIOTN had superior diagnostic properties than its components and all other indices, probably because of the cumulative values of its components. The FAI could not be validated as a supplemental measure of treatment need.

The adaptation of Demirjian's dental age estimation method on North German children.

The aim of this study was to test the accuracy of Demirjian's method for dental age (DA) estimation on north German children, to adapt the method used in case of inaccuracy in this sample and to construct dental maturity percentile curves for this population. Orthopantomograms (OPGs) of 1260 north German children (566 males and 694 females) aged 5-17 years were used from patients' records of the Department of Orthodontics, Dentofacial Orthopedics and Pedodontics, Charité - Universitätsmedizin Berlin, Germany. Demirjian's dental maturity scale for the seven left mandibular teeth was applied to the first sample (951 OPGs) to estimate the DA and compare it to the chronological age (CA) of each child. For the adaptation of Demirjian's method on this sample of radiographs, new weighted maturity scores were created by the use of linear regression. Polynomial percentile curves of the total dental maturity in comparison to the CA are presented. The second sample (309 OPGs) was used to evaluate the adapted method and compare it to Demirjian's method. Demirjian's method overestimated the mean CA of boys by 0.46±0.86 years (mean difference±standard deviation) and of girls by 0.55±0.95 years. The new adapted weighted scores estimated the CA of boys (0.07±0.82 years) and girls (-0.04±0.82 years) more accurately. The adapted method showed no significant difference between DA and CA. The method by Demirjian et al., when applied to north German children, significantly overestimated most age cohorts for both sexes. The adapted north German weighted scores and percentile curves showed a notable improvement in age estimation and were more reliable for CA estimation and DA assessment.