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Nevin Manimala Statistics

Applying polygenic risk score methods to pharmacogenomics GWAS: challenges and opportunities

Brief Bioinform. 2023 Nov 22;25(1):bbad470. doi: 10.1093/bib/bbad470.

ABSTRACT

Polygenic risk scores (PRSs) have emerged as promising tools for the prediction of human diseases and complex traits in disease genome-wide association studies (GWAS). Applying PRSs to pharmacogenomics (PGx) studies has begun to show great potential for improving patient stratification and drug response prediction. However, there are unique challenges that arise when applying PRSs to PGx GWAS beyond those typically encountered in disease GWAS (e.g. Eurocentric or trans-ethnic bias). These challenges include: (i) the lack of knowledge about whether PGx or disease GWAS/variants should be used in the base cohort (BC); (ii) the small sample sizes in PGx GWAS with corresponding low power and (iii) the more complex PRS statistical modeling required for handling both prognostic and predictive effects simultaneously. To gain insights in this landscape about the general trends, challenges and possible solutions, we first conduct a systematic review of both PRS applications and PRS method development in PGx GWAS. To further address the challenges, we propose (i) a novel PRS application strategy by leveraging both PGx and disease GWAS summary statistics in the BC for PRS construction and (ii) a new Bayesian method (PRS-PGx-Bayesx) to reduce Eurocentric or cross-population PRS prediction bias. Extensive simulations are conducted to demonstrate their advantages over existing PRS methods applied in PGx GWAS. Our systematic review and methodology research work not only highlights current gaps and key considerations while applying PRS methods to PGx GWAS, but also provides possible solutions for better PGx PRS applications and future research.

PMID:38152980 | DOI:10.1093/bib/bbad470

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Nevin Manimala Statistics

Bayesian random-effects meta-analysis with empirical heterogeneity priors for application in health technology assessment with very few studies

Res Synth Methods. 2023 Dec 28. doi: 10.1002/jrsm.1685. Online ahead of print.

ABSTRACT

In Bayesian random-effects meta-analysis, the use of weakly informative prior distributions is of particular benefit in cases where only a few studies are included, a situation often encountered in health technology assessment (HTA). Suggestions for empirical prior distributions are available in the literature but it is unknown whether these are adequate in the context of HTA. Therefore, a database of all relevant meta-analyses conducted by the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) was constructed to derive empirical prior distributions for the heterogeneity parameter suitable for HTA. Previously, an extension to the normal-normal hierarchical model had been suggested for this purpose. For different effect measures, this extended model was applied on the database to conservatively derive a prior distribution for the heterogeneity parameter. Comparison of a Bayesian approach using the derived priors with IQWiG’s current standard approach for evidence synthesis shows favorable properties. Therefore, these prior distributions are recommended for future meta-analyses in HTA settings and could be embedded into the IQWiG evidence synthesis approach in the case of very few studies.

PMID:38152969 | DOI:10.1002/jrsm.1685

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Nevin Manimala Statistics

Comparing the EdgeFile X3, GenEndo, HeroGold, and ProTaper Gold Rotary Instruments Regarding the Effect of Different Concentrations and Temperature of NaOCl on Cyclic Fatigue Resistance

J Contemp Dent Pract. 2023 Sep 1;24(9):715-721. doi: 10.5005/jp-journals-10024-3515.

ABSTRACT

AIM: This research was carried out with the objective of comparison between GenEndo, Protaper Gold, Hero Gold and EdgeFile X3 regarding the effect of different concentrations of NaOCl.

MATERIALS AND METHODS: About 720 study specimens were included in the study. They were divided into four groups. Each group consisted of 180 files. Group A: GenEndo, Group B: Protaper Gold, Group C: Hero Gold, Group D: EdgeFile X3. Each group of instruments were further subdivided into nine subgroups (n = 20 for each subgroup). Testing of the cyclic fatigue was carried out in artificial canals which were prepared inside the blocks of stainless steel. The stainless steel blocks with artificial canals were established in a receiver that was packed with experimental solutions like distilled water, 5.25% NaOCl and 2.5% NaOCl. The adjustment of temperature was done at 25, 37, and 60°C. The rotation of the instrument was carried out inside the artificial canal as per the instructions of the manufacturer. The instrument was rotated until it got fractured. The time taken by the instrument to fracture was recorded in seconds. The number of cycles to fracture (NCF) was analyzed with the help of the equation (NCF = time to fracture × rpm/60). Surfaces at the site of fracture were examined with the help of a scanning electron microscope (EVOLS10, ZEISS) at magnification (300x and 2000x).

RESULTS: It was noticed that there was a statistically significant increase in cyclic fatigue when sodium chloride was used as an endodontic irrigant instead of distilled water. The increase in cyclic fatigue was also observed when 5.25% sodium chloride was used instead of 2.5% sodium hypochlorite. Cyclic fatigue increased on change in temperature from 25 to 37°C and from 37 to 60°C. The difference was statistically significant (p < 0.05). It was observed that resistance against cyclic fatigue on treatment with different irrigation solutions at different temperatures was in the order of GenEndo > Protaper Gold > Hero Gold > EdgeFile X3.

CONCLUSION: The resistance against cyclic fatigue in new NiTi rotary files can be affected significantly by different concentrations of sodium hypochlorite irrigant solution and the GenEndo rotary endodontic instrument has the maximum resistance against cyclic fatigue.

CLINICAL SIGNIFICANCE: Irrigation of the root canal with irrigants, such as sodium hypochlorite (NaOCl) has been recommended strongly. NaOCl is used in the range of 0.5 and 6.5% concentration owing to its antimicrobial activity and tissue dissolution activities, particularly at higher temperatures. It has been postulated that fatigue of rotary endodontic instruments can be influenced by adjoining medium and their concentration.

PMID:38152947 | DOI:10.5005/jp-journals-10024-3515

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Nevin Manimala Statistics

Antimicrobial Activity of Five Calcium Silicate Based Root Canal Sealers against a Multispecies Engineered Biofilm: An In Vitro Study

J Contemp Dent Pract. 2023 Sep 1;24(9):707-714. doi: 10.5005/jp-journals-10024-3556.

ABSTRACT

AIM: The present study’s objective was to compare the impact of CerasealR, total fill BC SealerR, Bio-C SealerR, AH Plus BioceramicR, and K-BiocerR on the elimination of a multispecies’ endodontic biofilm at 3, 7 and 14 days.

MATERIALS AND METHODS: A total of 20 freshly extracted, caries-free premolars were prepared for the study to create dentinal disks. For the multispecies biofilm formation, Enterococcus faecalis, Proteus mirabilis, Pseudomonas aeruginosa, and Candida albicans were cultured and used to inoculate hydroxyapatite discs. After incubation, the biofilms were placed on blotting papers in petri dishes with an orthodontic bend. Different root canal sealers, including CeraSeal, total Fill BC Sealer, Bio-C Sealer, AH Plus Bioceramic, K-Biocer, and Sealite, were injected into the bend, facilitating contact with the biofilms. The samples were divided into seven groups, including a negative control. At specific intervals, 3, 7, and 14 days, 3 biofilm samples from each group were collected, diluted, and plated on Agar media for colony counting and analysis.

RESULTS: In all tested groups, the total bacterial count significantly decreased between day 3 and 14 (p < 0.05) with no statistically significant differences among the different sealers’ groups at all-time points for the total bacterial count, E. faecalis count, and P. mirabilis count. However, Sealite demonstrated the most consistent effectiveness in reducing bacterial counts across multiple categories. The sealite group was capable of decreasing the C. albicans count significantly between day 3 and day 14 (p < 0.05) in comparison with the bioceramic groups.

CONCLUSION: All sealers had antibacterial activity against the multispecies biofilm between day 3 and day 14. The ascending order of sealers in terms of their effectiveness in killing bacteria, based on the provided results, is as follows: Sealite, Bio-C Sealer, AH Plus, CeraSeal, TotalFill, and K-Biocer. However, there were no statistically significant differences in the bacterial counts among the different sealer groups at any time point.

CLINICAL SIGNIFICANCE: The role of sealers in combating biofilm-associated infections highlights their potential clinical utility in preserving root canal health. Understanding the antimicrobial properties of these sealers is vital for informed decision-making in selecting the most effective materials for improved treatment outcomes and long-term success in endodontic procedures.

PMID:38152946 | DOI:10.5005/jp-journals-10024-3556

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Nevin Manimala Statistics

Gender Dimorphism of Skeletal Measurements and Dental Angle Classification in Orthodontic Patients

J Contemp Dent Pract. 2023 Sep 1;24(9):700-706. doi: 10.5005/jp-journals-10024-3524.

ABSTRACT

AIM: The present study aimed to evaluate gender dimorphism of the skeletal and dental angles and measurements among different types of malocclusions in the Population of Jizan, Kingdom of Saudi Arabia (KSA).

MATERIALS AND METHODS: Cephalometric data were retrieved from the archived records of 272 dental patients, comprising 134 males and 138 females. Skeletal and dental malocclusions in both the sub-groups were digitally studied.

STATISTICAL ANALYSIS: The measurement reliability was assessed using the intra-class correlation coefficient (ICC). Non-parametric Mann-Whitney U tests were performed to evaluate the difference in skeletal and dental parameters between genders. The Chi-square test was done to determine the difference in malocclusion patterns amongst the gender.

RESULTS: Statistical significance was noted in dental malocclusion (p-value = 0.003) and facial height, with females having a steeper mandible plan than males. The Sella-nasion-Nasion-Vertical line angles were reported high in females with no statistical significance. Linear cephalometric values were measured higher in males than females, whereas angular values and facial height parameters were lower in females than male.

CONCLUSION: Within the limitation of this study, it could be concluded that there is a prominent difference measured in facial profiles of males and females with higher facial height in males. Clinical significance and limitations: These clinical outcomes will help orthodontists to analyze the accurate base angles and points to draft proper treatment plans considering the variation in the profile of males and females.

PMID:38152945 | DOI:10.5005/jp-journals-10024-3524

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Nevin Manimala Statistics

Effect of Novel Low-intensity Pulsed Ultrasound Stimulation on Accelerated Implant Osteointegration in Canine

J Contemp Dent Pract. 2023 Sep 1;24(9):679-687. doi: 10.5005/jp-journals-10024-3565.

ABSTRACT

AIM: To evaluate the effect of low-intensity pulsed ultrasound (LIPU) application on dental implant accelerated osseointegration in the two-stage implant protocol.

MATERIALS AND METHODS: A total of 20 implants were placed in 10 mature mongrel dogs, two implants for each dog replacing the lower 3rd premolars bilaterally. After 3 months of extraction, implants were placed. After 24 hours of implantation, the right sides received LIPU for 20 mins/day, continuously for 20 days. The left sides didn’t receive LIPU (control). Standardized radiographs were taken before LIPU and after 10 and 20 days for both sides. After 20 days of LIPU application, second-stage surgery was performed and provisional crowns were placed on each implant. Implants were subjected to functional occlusal loading for 4 weeks. Standardized radiographs were taken after 2 and 4 weeks of loading and analyzed to assess the peri-implant bone density changes. All data were collected, tabulated, and statistically analyzed.

RESULTS: All tissues appeared clinically normal, with the absence of inflammation and peri-implant radiolucency. The survival rate was 100%. The LIPU group showed a statistically significantly higher percentage increase in mean bone density after 10 LIPU sessions, 20 LIPU sessions, and 2 and 4 weeks of loading, than a control group.

CONCLUSION: The LIPU stimulation radiographically increased the bone density around implant area and accelerated osseointegration in the two-stage implant protocol.

CLINICAL SIGNIFICANCE: Low-intensity pulsed ultrasound stimulation could be beneficial in accelerating osseointegration and thus shortening the waiting period for final prosthetic delivery.

PMID:38152942 | DOI:10.5005/jp-journals-10024-3565

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Nevin Manimala Statistics

Tracing of Microbes in Prepared Cavity Following Different Minimally Invasive Caries Removal Protocols

J Contemp Dent Pract. 2023 Sep 1;24(9):674-678. doi: 10.5005/jp-journals-10024-3569.

ABSTRACT

AIMS: The conventional caries removal technique has been replaced with minimally invasive (MI) techniques to preserve healthy natural teeth and to provide durable dental restorations. Each of these MI caries removal protocols is reported to be favorable in dealing with different caries conditions. The current study aimed to trace the residual bacteria that may remain in a prepared cavity following a visual-tactile (VT), caries detection dye (CDD), and chemo-mechanical caries removal (CMCR) protocol.

MATERIALS AND METHODS: A total of 29 extracted human molar teeth with visible caries lesions were randomly divided into three groups. The cavity preparation and caries removal of each group was accomplished following one of the MI caries removal protocols. Swab samples (one from each specimen) were taken and inoculated onto a blood agar plate and incubated for 48 hours. The growth of the bacterial colony was observed under a microscope and the specific genome of the bacteria was identified by polymerase chain reaction (PCR) test.

RESULTS: The maximum number of traceable bacteria was observed following the chemo-mechanical caries removal group followed by the caries detection dye group and the least in the visual-tactile group. The PCR test revealed the presence of Streptococcus mutans in all the observed colonies; however, Streptococcus sobrinus was absent completely. The Chi-square test reveals a statistically insignificant (p = 0.646) difference among the tested groups.

CONCLUSION: All of the MI caries removal protocols used in this study showed a trace of microbes in certain teeth. The cavity prepared following a visual tactile protocol showed the least amount of traceable bacteria in the prepared cavity.

CLINICAL SIGNIFICANCE: Cavity that is prepared following individual MI protocol has a risk of leaving microbes in it.

PMID:38152941 | DOI:10.5005/jp-journals-10024-3569

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Nevin Manimala Statistics

Comparison of Fracture Resistance between Different Treatment Modalities of Mutilated Endodontically Treated Teeth Using Polyether Ether Ketone

J Contemp Dent Pract. 2023 Sep 1;24(9):668-673. doi: 10.5005/jp-journals-10024-3558.

ABSTRACT

AIM: To compare fracture resistance of multiple treatment modalities intended for mutilated teeth using polyether ether ketone (PEEK) and zirconia materials.

MATERIALS AND METHODS: The study was divided into four groups according to treatment modality adopted (n = 14): fiber post (F), Nayyar core (N), endocrown (E), and Richmond crown (R). Each group was further subdivided into two groups (n = 7) according to the type of material used: zirconia (Z) and PEEK (P). Using computer-aided design/computer-aided manufacturing, restorations were constructed from both materials following tested treatment options and manufacturer direction. Finished restorations were then tried, seated, and cemented to their corresponding acrylic teeth. All specimens were tested for fracture resistance in universal testing machine with cross head speed of 0.5 mm/min speed until failure, which was confirmed by a sudden drop in the measurements of the testing machine. Results were recorded, tabulated, and statistically analyzed. Shapiro-Wilk normality tests were considered to evaluate the normality of the data distributions. One-way analysis of variance (ANOVA) followed by Tukey’s post hoc analysis was conducted to analyze the fracture resistance significant differences.

RESULTS: Descriptive statistics of the restoration material revealed statistically a higher mean value for PEEK material (3609 ± 188.1) than zirconia (2404 ± 425.6). One-way ANOVA revealed statistically significant differences between zirconia group (p < 0.0001). Regarding zirconia group statistical significance was detected between fiber post vs endocrown (p = 0.0299), fiber post vs Richmond crown (p < 0.0001), and Nayyar core vs Richmond crown (p = 0.0004). However, there was no statistically significant difference between PEEK group (P = 0.1614).

CONCLUSION: Polyether ether ketone could present a reliable treatment option in endodontically treated teeth.

CLINICAL SIGNIFICANCE: Using one-piece Richmond crowns constructed of PEEK could present a viable treatment option against conventional treatment options of root canal treatment (RCT) single-rooted teeth.

PMID:38152940 | DOI:10.5005/jp-journals-10024-3558

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Nevin Manimala Statistics

Morphometric Evaluation of Morphological Variations of the Nasopalatine Canal: A Retrospective Study Using Cone-beam Computed Tomography

J Contemp Dent Pract. 2023 Sep 1;24(9):660-667. doi: 10.5005/jp-journals-10024-3561.

ABSTRACT

AIM: The study aimed to analyze the morphological and anatomical variations of the nasopalatine canal (NPC) using cone-beam computed tomography (CBCT) images and their association with age and gender among the subpopulation of the Qassim region of Saudi Arabia.

MATERIALS AND METHODS: The CBCT records of 401 patients referred to the Department of Radiology between January 2020 and July 2023 were randomly selected in the retrospective cross-sectional study. The anatomical characteristics such as the length of the NPC, and the superior and inferior width of the canal, were analyzed. In the sagittal and axial planes, the morphological variants of the shape of the NPC were also investigated. The Statistical Package for the Social Sciences (SPSS) software was used for statistical analyses at a 5% significance level.

RESULTS: The study examined the CBCT images of 219 females (54.6%) and 182 males (45.4%) with an overall mean age of 40.17 ± 2.31 years. The overall length of the NPC and superior and inferior canal width were 13.86 ± 2.68 mm, 3.4 ± 1.42 mm, and 4.07 ± 2.06 mm, respectively. Independent t-test revealed that the males had a statistically significant larger superior (3.62 ± 1.78 mm) and inferior canal width (4.33 ± 1.79 mm). In terms of gender, the Chi-square test revealed a statistically significant association (p < 0.01) between the morphological shape of the NPC in the axial and sagittal planes. The heart-shaped (51.4%) and cone-shaped canals (34.2%) were the most frequently recorded NPC in the axial and sagittal planes, respectively. Pearson’s correlation found a statistically significant positive relationship (p < 0.05) between the superior and inferior canal width and the canal length. Spearman’s correlation revealed a statistically highly significant correlation between the NPC shape in the sagittal plane and gender (p < 0.001).

CONCLUSION: The study findings revealed a statistically significant difference in the anatomical and morphological traits of the NPC in the axial and sagittal planes based on gender. The effect of age and gender was found to exhibit significant differences with the NPC parameters. The heart-shaped canal in the axial plane and the cone-shaped canal in the sagittal plane were more prevalent in the study sample. A three-dimensional (3D) examination of the NPC will be crucial to avert challenging circumstances prior to surgical treatments in the anterior maxilla.

CLINICAL SIGNIFICANCE: The NPC is a long, narrow canal that can take up to 58% of the buccal bone plate width, and an accurate 3D anatomic illustration of the NPC allows for reliable surgical planning and dental implant placement.

PMID:38152939 | DOI:10.5005/jp-journals-10024-3561

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Nevin Manimala Statistics

Impact of Orofacial Clefts on Oral Health Quality of Life: A Cross-sectional Survey Study in Saudi Arabia

J Contemp Dent Pract. 2023 Sep 1;24(9):655-659. doi: 10.5005/jp-journals-10024-3531.

ABSTRACT

AIM: To evaluate the effect of facial clefts on the dental health quality of life of affected individuals, and to determine whether age and gender affect the oral health quality of life differently.

MATERIALS AND METHODS: The cross-sectional survey included 50 participants (32 females and 18 males) from the northern region of Saudi Arabia, using a reliable and validated questionnaire, the Child Oral Health Impact Profile (COHIP), which measured self-reported oral health-related quality of life (OHRQoL) in children and adults using a five-point Likert scale. Statistical analysis was performed, and results were considered significant if the p-value was less than 0.05.

RESULTS: The highest scores in the oral health domain were related to bad breath and reluctance in speaking or reading aloud in class within the school environment domain, with mean scores of 3.44 ± 1.3 and 3.52 ± 1.2, respectively. Most patients showed apprehension regarding necessary dental treatments (mean = 1.44 ± 0.07). The study found a non-statistically significant difference in tooth discomfort between age groups (p = 0.092), with individuals aged from 20 to 29 experiencing higher levels of discomfort than other age groups surveyed.

CONCLUSION: The two topics with the highest mean scores in the oral health domain and the school environment domain were bad breath and not wanting to speak or read aloud in class. Females reported more discomfort, and there was a substantial association between gender and tooth pain/sensitivity.

CLINICAL SIGNIFICANCE: Understanding the difficulties cleft patients face is crucial, as doing so will enable dentists to encourage and handle these issues more effectively.

PMID:38152938 | DOI:10.5005/jp-journals-10024-3531