Clinical performance of the novel full-genotyping OncoPredict HPV Quantitative Typing assay using the VALGENT framework.

Clinical validation of human papillomavirus (HPV) assays according to international criteria is prerequisite for their implementation in cervical cancer screening. OncoPredict HPV Quantitative Typing (QT) assay (Hiantis Srl, Milan, Italy) is a novel full-genotyping multiplex real-time PCR quantitative assay targeting E6/E7 genes, allowing individual viral load determination of 12 high-risk (HR) HPV types. Quality controls for sample adequacy, efficiency of nucleic acid extraction and PCR inhibition are included in the assay. Clinical performance of OncoPredict HPV QT test was assessed as part of the "Validation of HPV Genotyping Tests" (VALGENT-2) framework, consisting of 1300 cervical liquid-based cytology (LBC) samples of women aged between 20 and 60 years who had originally attended for routine cervical screening in Scotland. The clinical accuracy of the OncoPredict HPV QT (index test) for the detection of CIN2+ was assessed relative to the GP5+/6+ Enzyme ImmunoAssay (GP5+/6+ EIA) (comparator test), using noninferiority criteria. Intra- and interlaboratory reproducibility of the assay was assessed on a subpopulation, comprising 526 samples. The relative sensitivity and specificity for OncoPredict HPV QT vs GP5+/6+-PCR-EIA were 1.01 (95% CI: 0.99-1.03) and 1.03 (95% CI: 1.0-1.06) respectively. The P-values for noninferiority were ≤0.001. The intra- and inter-laboratory reproducibility demonstrated a high concordance (>98.7%) with kappas for individual types ranging from 0.66 to 1.00. OncoPredict HPV QT fulfills the international validation criteria for the use of HPV tests in cervical cancer screening.

Gender-Based Differences in Medical Student Self-Ratings of Clinical Performance.

INTRODUCTION: While prior literature demonstrates gender-based differences in surgical residents' self-assessments, limited data exist examining these effects at the medical student level. This study aimed to understand how self-ratings of clinical performance differ across genders for clerkship students. METHODS: This was a retrospective study examining the results of an institutional Clinical Performance Examination administered at the end of the clerkship year. Students were tasked with obtaining a history and physical examination and developing an assessment and plan based on standardized patient cases. After the examination, students were asked to estimate the percentile rating of their performance. Female and male students' true scores, self-rated percentiles, and differences between true and self-rated percentiles were compared. RESULTS: One hundred twenty three male and 113 female medical students were included in the analysis. Female medical students performed statistically significantly better overall (79.65% versus 78.23%, P = 0.0039), in history skills (76.90% versus 75.19%, P = 0.012), and in communication skills (94.05% versus 92.58%, P = 0.0085). No statistically significant differences were seen between self-rated percentiles between male and female students. However, when comparing the difference between self-rated and true percentile scores (Δ = self-rated - true percentile), male students were more likely to rate themselves higher than their true percentile on history (male students Δ = 12.26 versus female students Δ = -1.24, P = 0.00076) and communication metrics (male students Δ = 14.12 versus female students Δ = 6.05, P = 0.037). CONCLUSIONS: Despite higher performance, female students rate themselves similarly to male medical students, suggesting a pattern of underestimation. Faculty must recognize that gender-based differences in self-evaluations begin at the medical student level, potentially impacting future trainee development.

Outcome-based analytical performance specifications: current status and future challenges.

Analytical performance specifications (APS) based on outcomes refer to how 'good' the analytical performance of a test needs to be to do more good than harm to the patient. Analytical performance of a measurand affects its clinical performance. Without first setting clinical performance requirements, it is difficult to define how good analytically the test needs to be to meet medical needs. As testing is indirectly linked to health outcomes through clinical decisions on patient management, often simulation-based studies are used to assess the impact of analytical performance on the probability of clinical outcomes which is then translated to Model 1b APS according to the Milan consensus. This paper discusses the related key definitions, concepts and considerations that should assist in finding the most appropriate methods for deriving Model 1b APS. We review the advantages and limitations of published methods and discuss the criteria for transferability of Model 1b APS to different settings. We consider that the definition of the clinically acceptable misclassification rate is central to Model 1b APS. We provide some examples and guidance on a more systematic approach for first defining the clinical performance requirements for tests and we also highlight a few ideas to tackle the future challenges associated with providing outcome-based APS for laboratory testing.

Should we screen aging physicians for cognitive decline?

OBJECTIVES: To synthesize evidence relevant for informed decisions concerning cognitive testing of older physicians. METHODS: Relevant literature was systematically searched in Medline, EMBASE, PsycInfo, and ERIC, with key findings abstracted and synthesized. RESULTS: Cognitive abilities of physicians may decline in an age range where they are still practicing. Physician competence and clinical performance may also decline with age. Cognitive scores are lower in physicians referred for assessment because of competency or performance concerns. Many physicians do not accurately self-assess and continue to practice despite declining quality of care; however, perceived cognitive decline, although not an accurate indicator of ability, may accelerate physicians' decision to retire. Physicians are reluctant to report colleagues' cognitive problems. Several issues should be considered in implementing cognitive screening. Most cognitive assessment tools lack normative data for physicians. Scientific evidence linking cognitive test results with physician performance is limited. There is no known level of cognitive decline at which a doctor is no longer fit to practice. Finally, relevant domains of cognitive ability vary across medical specialties. CONCLUSION: Physician cognitive decline may impact clinical performance. If cognitive assessment of older physicians is to be implemented, it should consider challenges of cognitive test result interpretation.

Understanding the performance-related psychological characteristics and skills of doctors: A sport psychology perspective.

INTRODUCTION: Doctors need to consistently maintain their clinical performance across a range of different situations by managing the stress response provoked by these situations. Six performance-related adaptive and maladaptive psychological characteristics and psychological skills can distinguish between how athletes manage their stress response and consistently maintain an optimal level of performance across a variety of situations. The aim of the study was to understand how the performance-related psychological characteristics and skills identified in athletes are applied by doctors. METHODS: An exploratory qualitative study was conducted with semi-structured interviews. A purposive sample of 10 doctors were interviewed and the data were analysed by template analysis. RESULTS: Doctors have similar performance-related psychological characteristics and skills as identified in athletes for managing their stress response to consistently maintain optimal clinical performance. The importance of maladaptive characteristics was also identified, especially in junior doctors. CONCLUSIONS: The findings of this pilot study can be used for informing the design of performance-related educational interventions for doctors to manage their stress response for consistently maintaining optimal clinical performance. An important consideration will need to be a focus on specific groups in their career journey and the development of a multi-dimensional, reflective, and problem-solving approach.

Two-year clinical performance of dual- and light-cure bulk-fill resin composites in Class ӀӀ restorations: a randomized clinical trial.

OBJECTIVE: This study aimed to compare the clinical performance of dual- and light-cure bulk-fill resin composites (BFRCs) in Class ӀӀ restorations after 2 years. MATERIALS AND METHODS: A double-blinded, prospective, randomized clinical trial (RCT) was conducted following the CONSORT (Consolidated Standard of Reporting Trials) guidelines. Forty patients were enrolled in the study. Each patient received three compound Class ӀӀ restorations. One dual-cure (Fill-Up; Coltene Waledent AG) and two light-cure (QuiXfil; Dentsply, and Tetric N-Ceram Bulk Fill; Ivoclar Vivadent) BFRCs were used for 120 Class ӀӀ restorations. A universal adhesive (ONE COAT 7 UNIVERSAL; Coltene Waledent AG) was used with all restorations. Restorations were clinically evaluated after 1 week (baseline), 6 months, 12 months, 18 months, and finally after 24 months using the FDI World Dental Federation (FDI) criteria. The Kruskal-Wallis test was used for comparison between BFRCs groups at baseline and at each recall period, and the Wilcoxon signed-rank test was used for comparing different follow-up times of each BFRC to baseline. The level of significance was set at p < 0.05. RESULTS: All BFRCs restorations showed only minor changes and revealed no statistically significant differences between their clinical performance for all evaluated parameters at all recall periods; also, there was no statistically significant difference between all recall periods and baseline for all evaluated parameters. CONCLUSION: The two-year clinical performance of dual-cure BFRC was comparable to light-cure BFRCs in Class ӀӀ restorations. CLINICAL RELEVANCE: Dual- and light-cure BFRCs showed excellent clinical performance in Class ӀӀ restorations after a 2-year clinical follow-up.

Linking Patient-Reported Outcome Measure Scores to Adverse Event Data to Gain Insight into Overestimation of Postoperative Patient-Reported Outcome Measure Improvement After Total Hip Arthroplasty and Total Knee Arthroplasty Due to Selective Nonresponse.

BACKGROUND: The purpose of the study was to gain insight into how clinically relevant improvement in patient-reported outcome measure scores after total hip arthroplasty (THA) and total knee arthroplasty (TKA) may be underestimated or overestimated, we compared patient-reported outcome measure respondents and nonrespondents on their adverse event rates and assessed whether adverse event occurrence was associated with clinically relevant patient-reported outcome measure improvement from those without adverse events. METHODS: All primary THAs and TKAs performed in 19 Dutch hospitals between January 2017 and December 2019 were included. The hip disability and osteoarthritis outcome score-physical function short form (HOOS-PS) and knee injury and osteoarthritis outcome score-physical function short form (KOOS-PS) were used to assess the physical function after THA and TKA, respectively. Adverse events included 1-year revision, 30-day readmission, 30-day complications, and long (ie, >75th percentile) length of stay. A clinically relevant improvement was defined as at least a 10-point decrease in HOOS-PS and 9 points in KOOS-PS scores. Associations between adverse events and clinically relevant HOOS-PS and KOOS-PS improvement were assessed using binary logistic regression models adjusted for patient characteristics and clustering of patients within hospitals. RESULTS: There were 20,338 THA and 18,082 TKA procedures included. Adverse events occurred more frequently in HOOS-PS and KOOS-PS nonrespondents than in respondents. The THA patients experiencing revision, complications, or long length of stay were less likely to experience clinically relevant HOOS-PS improvements (odds ratios of 0.11 [0.06 to 0.20], 0.44 [0.30 to 0.63], and 0.66 [0.50 to 0.88], respectively). The TKA patients experiencing revision or long length of stay were less likely to experience clinically relevant KOOS-PS improvements (odds ratios of 0.26 [0.12 to 0.55] and 0.63 [0.50 to 0.80], respectively). CONCLUSIONS: Clinically relevant HOOS-PS and KOOS-PS improvements are likely overestimated, as nonrespondents had higher adverse event rates which were associated with lower likelihood to achieve clinically relevant HOOS-PS and KOOS-PS improvements.

CAD/CAM versus traditional complete dentures: A systematic review and meta-analysis of patient- and clinician-reported outcomes and costs.

STATEMENT OF PROBLEM: Computer-aided design and manufacturing (CAD/CAM) have been increasingly used to enhance the patient and clinician experiences with removable complete dentures (CDs). Yet, evidence from systematic reviews is lacking to validate the clinical significance of these digital prostheses. PURPOSE: The purpose of this systematic review was to compare CAD/CAM CDs with the traditional ones in terms of patient and clinician-reported outcomes, post-insertion adjustment visits and costs. MATERIALS AND METHODS: An electronic search of four databases [Medline (Ovid), Embase, Scopus and Cochrane CENTRAL; last update: May 2022] was performed to retrieve clinical studies comparing CAD/CAM and traditional CDs. Two independent reviewers screened the articles, extracted data (methods and outcomes) and assessed risk of bias of the included studies. The following outcomes underwent meta-analysis (random-effects model): overall patient and clinician satisfaction, oral health-related quality of life (OHRQoL), number of post-insertion adjustment visits, as well as laboratory and total costs. RESULTS: This review included 11 studies. Meta-analysis revealed that CAD/CAM CDs are comparable to the traditional CDs in terms of overall patient satisfaction and OHRQoL. Clinician-reported data depended on the manufacturing technique: whereas milled CDs performed better than traditional CDs in terms of clinician satisfaction and number of adjustments, 3D printed and traditional CDs were similar. Fabrication of CAD/CAM CDs required significantly less laboratory and overall costs than the traditional CDs. CONCLUSIONS: There is some evidence showing that CAD/CAM CDs are at least comparable to traditional CDs. Further well-designed randomized clinical trials are needed to evaluate the performance of specific CAD/CAM approaches for manufacturing CDs, however.

Clinical performance of different bulk-fill composite resin systems in class II cavities: A 2-year randomized clinical trial.

OBJECTIVES: This study evaluated the clinical performance of bulk-fill resin composite systems with different viscosities in class II cavities. MATERIALS AND METHODS: A total of 80 class II restorations were performed with a single operator in 50 patients using four different bulk-fill resin composite materials: Filtek™ Bulk Fill, Heated Filtek™ Bulk Fill, G-ænial™ BULK Injectable, and SonicFill3. A double-blinded randomized clinical trial was designed to evaluate the two-year clinical performance of the four bulk-fill composite resins using modified FDI criteria. Data were analyzed descriptively. Level of significance was set at 0.05. Differences between groups were tested using Wilcoxon-signed-rank and Mann-Whitney-U test as nonparametric tests. RESULTS: Data were analyzed using Kruskal-Wallis, Mann-Whitney U, and Wilcoxon signed rank tests (p < 0.05). Eighty restorations were available for evaluation, with a survival function of 100%. No statistically significant differences were observed between the four groups regarding assessing esthetic, functional, and biological properties during different follow-up periods. CONCLUSIONS: After 2 years of clinical follow-up, the bulk-fill composite systems with different viscosities seem to be esthetically, functionally, and biologically acceptable, with a promising clinical performance in class II cavities.

Laboratory validation and clinical performance of a saliva-based test for monkeypox virus.

Improved diagnostic tests and accessibility are essential for controlling the outbreak of monkeypox. We describe a saliva-based polymerase chain reaction (PCR) assay for monkeypox virus, in vitro test performance, and clinical implementation of that assay in Los Angeles, San Francisco, and Palm Springs, CA. Finally, using prespecified search terms, we conducted a systematic rapid review of PubMed and Web of Science online databases of studies reporting the performance of oral pharyngeal or saliva-based tests for the monkeypox virus. The assay showed in silico inclusivity of 100% for 97 strains of monkeypox virus, with an analytic sensitivity of 250 copies/ml, and 100% agreement compared to known positive and negative specimens. Clinical testing identified 22 cases of monkeypox among 132 individuals (16.7%), of which 16 (72.7%) reported symptoms, 4 (18.2%) without a rash at the time of testing. Of an additional 18 patients with positive lesion tests, 16 (88.9%) had positive saliva tests. Our systematic review identified six studies; 100% of tests on oropharyngeal specimens from 23 patients agreed with the PCR test result of a lesion. Saliva-based PCR tests are potential tools for case identification, and further evaluation of the performance of such tests is warranted.

The Impact of Cancer Relapse and Poor Patient Outcomes on Health Care Providers Practicing in the Oncology Field.

INTRODUCTION: Devastating cancer-related events are not uncommon, and these events have weakened communication performance and induced stress among health care providers (HCPs), particularly physicians. This study aimed to investigate the perspective of HCPs emotionally affected by poor clinical outcomes due to the failure of cancer therapy. METHODS: A cross-sectional, online survey was conducted over 3 months among HCPs practicing in the field of oncology in Saudi Arabia, comprising physicians, pharmacists, and nurses. Data were analyzed using Statistical Package for Social Sciences version 26.0. A P-value <.05 was considered statistically significant. RESULTS: This study demonstrated a positive correlation between HCPs' length of experience and emotional impact of treatment failure, albeit this was not statistically significant (P = .071). Analysis of their perspective toward failure of cancer therapies revealed a significant impact of occupation and sex (P = .014 and P = .047, respectively). Moreover, occupation played a significant role in shaping the viewpoint of HCPs toward the need for conducing further research to test the appropriateness of treatment protocols on local patients (P = .022). Despite the emotional responses of HCPs to suboptimal clinical outcomes, factors such as work burnout, lack of concentration and patience, work or personal problems, and under appreciation were frequently identified as triggers of such outcomes. CONCLUSION: Our results revealed that poor clinical outcomes observed among cancer patients are emotional triggers for HCPs practicing in the oncology field. The emotional response is often perceived negatively, and can potentially lead to a decline in the quality of care provided to these patients.

Clinical evidence requirements according to the IVDR 2017/746: practical tools and references for underpinning clinical evidence of IVD-MDs.

In May 2022, the European Regulation 2017/746 (IVDR) came into force. It changes the approach of in vitro medical devices (IVD-MDs) for industry and institutions. It reinforces the clinical evidence requirements to improve performance, safety and transparency. Despite extended transition periods and existing guides, IVDR remains difficult to interpret and bringing devices into compliance requires efforts. The generation of clinical evidence is essential to demonstrate compliance with IVDR, and encompasses scientific validity, analytical performance and clinical performance. It is required to demonstrate, per intended use in the target population and clinical care pathway, IVD-MDs clinical performance (compared to a predefined clinical performance). Thus, there is a need for IVD-manufacturers and end-users in health care institutions, to obtain guidance on how to generate this clinical evidence. This article aims industrials and clinicians to identify key steps imposed by the IVDR for bringing IVD-MDs to the EU-market. We propose a general view of performance evaluation requirements for IVD-MDs and provide key references, including how to establish study design that will enable to document clinical performance of existing, refined or emerging medical tests. Finally, we propose a roadmap to address the relevant questions and studies in relation to the documents requested in the IVDR.

Clinical evaluation of the novel Capiox NX19 adult oxygenator-a multicenter study.

INTRODUCTION: The novel Capiox NX19 adult oxygenator is, compared to its predecessors, improved with enhanced air removal technology, a polymer heat exchanger and smaller, innovative hollow fibers resulting in a surface area reduction and a lower priming volume. The aim of this study was to evaluate the NX19 oxygenator performance in a clinical setting. METHODS: A prospective multicenter study was performed involving three large European university hospitals. The Capiox NX19 (n = 150) performance was assessed during adult cardiopulmonary bypass and involved gaseous microemboli handling and gas transfer efficiency. The heat exchanger performance was evaluated separately in vitro. RESULTS: The heat exchanger performance factors were 0.80 ± 0.03 and 0.58 ± 0.04 at pump flow rates of 3 L/min and 6 L/min, respectively. After priming, residual post-oxygenator gaseous microemboli count and volume were decreased by 91% and 93.7%, respectively. The gas compartment pressure was 6.0 ± 2.5 mmHg, while the O2 transfer was 69 ± 30 mL/min/m2 and the CO2 transfer 73 ± 34 mL/min/m2. The O2 gradient was 44 ± 19 mmHg/LPM and the O2 diffusing capacity 0.38 ± 0.14 mL/min/mmHg. The shunt fraction was 0.19 ± 0.13, whereas oxygenator resistance and shear stress were 10.5 ± 3.7 mmHg/LPM and 5.1 ± 3.1 dyn/cm2, respectively. CONCLUSION: This multicenter study displayed good clinical safety and performance of the NX19 oxygenator.

Five-year randomized clinical trial to evaluate the clinical performance of high-viscosity glass ionomer restorative systems in small class II restorations.

OBJECTIVE: Evaluate and compare the 5-year clinical performance of three high-viscosity glass ionomer restorative materials in small class II restorations. MATERIALS AND METHODS: Forty patients, each with four class II restorations, were enrolled in this trial. A total of 160 restorations were placed, 25% for each material, as follows: three high-viscosity conventional glass ionomer restorative systems (Ketac Universal Aplicap, EQUIA Forte and Riva Self Cure HV) and a microhybrid resin composite system (Filtek Z250). Clinical evaluation was performed at baseline and after 1, 3, and 5 years by two independent examiners using FDI criteria. Epoxy resin replicas were observed under scanning electron microscope (SEM) to examine surface characteristics. Data were analyzed with Kruskal-Wallis, Mann-Whitney U, Friedman, and Wilcoxon signed-rank tests (p < 0.05). RESULTS: The success rates were 100% for resin composite, 97.4% for Ketac Universal, and 94.9% for both EQUIA Forte and Riva HV restorations. Statistically significant differences were observed between all groups in terms of surface luster and color match criteria (p < 0.05). Statistically significant changes were found over time for all criteria except for fracture of material, postoperative hypersensitivity, recurrence of caries, tooth integrity, periodontal response, adjacent mucosa, and oral health criteria (p > 0.05). SEM evaluations were in accordance with the clinical findings. CONCLUSIONS: Although drawbacks in surface luster and color match appeared over the 5-year evaluation period, the three high-viscosity glass ionomer restorative materials provided successful clinical performance in small to medium sized class II cavities compared to microhybrid resin composite. CLINICAL SIGNIFICANCE: Glass ionomer restorations exhibited clinical performance similar to that of microhybrid resin composite restorations in small class II cavities subsequent to 5-year evaluation.

Can Modification with Urethane Derivatives or the Addition of an Anti-Hydrolysis Agent Influence the Hydrolytic Stability of Resin Dental Composite?

Due to the questionable durability of dental restorations, there is a need to increase the lifetime of composite restoration. The present study used diethylene glycol monomethacrylate/4,4'-methylenebis(cyclohexyl isocyanate) (DEGMMA/CHMDI), diethylene glycol monomethacrylate/isophorone diisocyanate (DEGMMA/IPDI) monomers, and bis(2,6-diisopropylphenyl)carbodiimide (CHINOX SA-1) as modifiers of a polymer matrix (40 wt% urethane dimethacrylate (UDMA), 40 wt% bisphenol A ethoxylateddimethacrylate (bis-EMA), and 20 wt% triethyleneglycol dimethacrylate (TEGDMA)). Flexural strength (FS), diametral tensile strength (DTS), hardness (HV), sorption, and solubility were determined. To assess hydrolytic stability, the materials were tested before and after two aging methods (I-7500 cycles, 5 °C and 55 °C, water and 7 days, 60 °C, 0.1 M NaOH; II-5 days, 55 °C, water and 7 days, 60 °C, 0.1 M NaOH). The aging protocol resulted in no noticeable change (median values were the same as or higher than the control value) or a decrease in the DTS value from 4 to 28%, and a decrease in the FS value by 2 to 14%. The hardness values after aging were more than 60% lower than those of the controls. The used additives did not improve the initial (control) properties of the composite material. The addition of CHINOX SA-1 improved the hydrolytic stability of composites based on UDMA/bis-EMA/TEGDMA monomers, which could potentially extend the service life of the modified material. Extended studies are needed to confirm the possible use of CHINOX SA-1 as an antihydrolysis agent in dental composites.

Can students develop clinical competency in treatment planning remotely through flipped collaborative case discussion?

INTRODUCTION: Effectiveness of flipped learning in clinical education is unknown. This study evaluates the effectiveness of remote case-based learning for teaching clinical treatment planning compared with traditional in-person clinical experience. MATERIALS AND METHODS: Four cases containing medical and dental charts were discussed through flipped learning with faculty panel during the COVID-19 lockdown. Prior to each session, students worked individually or in groups to complete assignments with leading questions. After the final assignment, students completed a survey to rate the learning experience from each case, compare the remote experience with the previous in-person clinical experience and provide suggestions to improve remote clinical instruction in the future. Students' performance measured by the number of case assessments and competencies completed post-lockdown was compared with pre-lockdown and the previous year using odd ratio (OR), Chi-squared test (χ2) and significant level p < .05. RESULTS: A total of 106 students completed the course, and 99 students completed all survey questions. Students reported positive learning experiences (overall mean = 7.84, SD = 1.11). Post-lockdown, statistically significant increase in the proportions of total passed attempts (χ2 p = .002, OR = 2.23), competencies (χ2 p = .028, OR = 2.05) and case assessments (χ2 p = .004, OR = 2.73) was observed between the current class and the previous pre-COVID-19 class (108 students). Post-lockdown, students also passed significantly more attempts (χ2 p < .0001), competencies (χ2 p < .0001) and case assessments (χ2 p = .008) compared with pre-lockdown. CONCLUSIONS: Although a flipped classroom does not replace in-person clinical experience, teaching clinical treatment planning remotely improved students' readiness and clinical performance through collaborative learning, practice and case exposure.

Patient-reported outcomes and framework fit accuracy of removable partial dentures fabricated using digital techniques: A systematic review and meta-analysis.

PURPOSE: This review aimed to summarize the evidence on patient-reported outcomes and clinical performance of digitally fabricated removable partial dentures (RPDs) compared to traditionally fabricated dentures. METHODS: Three databases were systematically searched (PubMed, CENTRAL, and Wiley online library) for clinical studies comparing digitally and conventionally fabricated RPDs regardless of data acquisition methods used for fabrication. The Cochrane Collaboration risk of bias assessment tool 2 and the Oxford Center for Evidence-based Medicine tool were used to assess risk of bias, and level of evidence, respectively. Descriptive narrative analysis was used to summarize data on patient-reported outcomes, as there were inadequate studies to pool data in a meta-analysis. A random-effects model was used to analyze the data of framework fit accuracy. RESULTS: Ten randomized controlled trials were included in the systematic review, and 4 were included in the meta-analysis. Two studies showed that digitally fabricated RPDs are associated with higher patient satisfaction than conventionally fabricated RPDs (with a mean difference of 12.5 mm on a 100-satisfaction scale, p = .008). The pooled standardized mean difference for framework fit accuracy was 0.49 (p = 0.02) in favor of conventionally fabricated RPDs, which showed that conventionally fabricated RPDs have a quantitatively better fit compared to digitally fabricated RPDs. However, clinical evaluation studies showed that both frameworks have clinically acceptable fit. CONCLUSIONS: Current evidence shows that digitally fabricated RPDs are associated with higher patient satisfaction compared to conventionally fabricated RPDs. However, the scarcity of literature here warrants the generalization of this conclusion. Both digitally and conventionally fabricated metal RPD frameworks showed acceptable fit clinically.

Short-Term Comparison of Clinical Performance of Universal Adhesives with Self-Etch Mode in NCCL Restorations.

OBJECTIVES: To evaluate the clinical performance of universal adhesives with self-etch mode regarding their functional monomer and HEMA contents. METHODS: The study involved 27 patients (108 restorations) aged between 34 and 69 (mean age: 53.8). Each restoration contained one of four different universal adhesives applied in self-etch mode: G-Premio Bond (HEMA-free, MDP and 4-MET containing), Xeno Select (HEMA and MDP-free), Tetric-n-Bond Universal (HEMA and MDP-containing) and Clearfil Universal Bond Quick (HEMA, MDP and amide monomers containing). The restorations were evaluated according to the FDI criteria at baseline, 6, and 12 months. The data were statistically analyzed using Friedman's and Kruskal-Wallis tests for significance in each pair (p⟨0.05). RESULTS: After 12 months, one restoration was lost in each of the G-Premio Bond and Clearfil Bond Quick groups. The success rate was 96.3% for both adhesives and 100% for Xeno Select and Tetric-n-Bond adhesives. There was no statistically significant difference between the four dentin adhesive groups among all the evaluation periods regarding any evaluation criteria. However, four universal adhesives showed clinically acceptable marginal discoloration and marginal deterioration in a few restorations. CONCLUSION: Monomer contents of universal adhesives with self-etch mode had no significant effect on the success of restorations.

Performance of DNA methylation analysis of ASCL1, LHX8, ST6GALNAC5, GHSR, ZIC1 and SST for the triage of HPV-positive women: Results from a Dutch primary HPV-based screening cohort.

Methylation of host-cell deoxyribonucleic acid (DNA) has been proposed as a promising biomarker for triage of high-risk (hr) human papillomavirus (HPV) positive women at screening. Our study aims to validate recently identified host-cell DNA methylation markers for triage in an hrHPV-positive cohort derived from primary HPV-based cervical screening in The Netherlands. Methylation markers ASCL1, LHX8, ST6GALNAC5, GHSR, ZIC1 and SST were evaluated relative to the ACTB reference gene by multiplex quantitative methylation-specific PCR (qMSP) in clinician-collected cervical samples (n = 715) from hrHPV-positive women (age 29-60 years), who were enrolled in the Dutch IMPROVE screening trial (NTR5078). Primary clinical end-point was cervical intraepithelial neoplasia grade 3 (CIN3) or cancer (CIN3+). The single-marker and bi-marker methylation classifiers developed for CIN3 detection in a previous series of hrHPV-positive clinician-collected cervical samples were applied. The diagnostic accuracy was visualised using receiver operating characteristic (ROC) curves and assessed through area under the ROC curve (AUC). The performance of the methylation markers to detect CIN3+ was determined using the predefined threshold calibrated at 70% clinical specificity. Individual methylation makers showed good performance for CIN3+ detection, with highest AUC for ASCL1 (0.844) and LHX8 (0.830). Combined as a bi-marker panel with predefined threshold, ASCL1/LHX8 yielded a CIN3+ sensitivity of 76.9% (70/91; 95% CI 68.3-85.6%) at a specificity of 74.5% (465/624; 95% CI 71.1-77.9%). In conclusion, our study shows that the individual host-cell DNA methylation classifiers and the bi-marker panel ASCL1/LHX8 have clinical utility for the detection of CIN3+ in hrHPV-positive women invited for routine screening.

Clinical validation of full HR-HPV genotyping HPV Selfy assay according to the international guidelines for HPV test requirements for cervical cancer screening on clinician-collected and self-collected samples.

BACKGROUND: According to international guidelines, Human Papillomavirus (HPV) DNA tests represent a valid alternative to Pap Test for primary cervical cancer screening, provided that they guarantee balanced clinical sensitivity and specificity for cervical intraepithelial neoplasia grade 2 or more (CIN2+) lesions. The study aimed to assess whether HPV Selfy (Ulisse BioMed - Trieste, Italy), a full-genotyping HPV DNA test that detects and differentiates 14 high-risk HPV (HR-HPV) types, meets the criteria for primary cervical cancer screening described in the international guidelines, on clinician-collected as well as on self-collected samples. METHODS: For each participant woman, consecutively referring to Azienda Sanitaria Universitaria Giuliano Isontina (Trieste, Italy) and CRO-National Cancer Institute (Aviano, Italy) for the cervical cancer screening program, the following samples were tested: (a) a clinician-collected cervical specimen, analyzed with the reference test (Hybrid Capture®2 test, HC2) and HPV Selfy; and (b) a self-collected vaginal sample, analyzed with HPV Selfy. Enrolled women were also asked to fulfill a questionnaire about self-sampling acceptability. As required by guidelines, a non-inferiority test was conducted to compare the clinical performance of the test under evaluation with its reference test. RESULTS: HPV Selfy clinical sensitivity and specificity resulted non-inferior to those of HC2. By analysis of a total of 889 cervical liquid-based cytology samples from a screening population, of which 98 were from women with CIN2+, HPV Selfy showed relative sensitivity and specificity for CIN2+ of 0.98 and 1.00 respectively (non-inferiority score test: P = 0.01747 and P = 0.00414, respectively); the test reached adequate intra- and inter-laboratory reproducibility. Moreover, we demonstrated that the performance of HPV Selfy on self-collected vaginal samples was non-inferior to the performance obtained on clinician-collected cervical specimen (0.92 relative sensitivity and 0.97 relative specificity). Finally, through HPV Selfy genotyping, we were able to describe HPV types prevalence in the study population. CONCLUSIONS: HPV Selfy fulfills all the requirements of the international Meijer's guidelines and has been clinically validated for primary cervical cancer screening purposes. Moreover, HPV Selfy has also been validated for self-sampling according to VALHUDES guidelines. Therefore, at date, HPV Selfy is the only full-genotyping test validated both for screening purposes and for self-sampling. Trial registration ASUGI Trieste n. 16008/2018; CRO Aviano n.17149/2018.