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Machine Learning Prediction of Pharmacogenetic Testing Uptake Among Opioid-Prescribed Patients Using Electronic Health Records: Retrospective Cohort Study

JMIR Med Inform. 2026 Jan 21;14:e81048. doi: 10.2196/81048.

ABSTRACT

BACKGROUND: Opioids are a widely prescribed class of medication for pain management. However, they have variable efficacy and adverse effects among patients, due to the complex interplay between biological and clinical factors. Pharmacogenetic testing can be used to match patients’ genetic profiles to individualize opioid therapy, improving pain relief and reducing the risk of adverse effects. Despite its potential, the pharmacogenetic testing uptake (use of pharmacogenetic testing) remains low due to a range of barriers at the patient, health care provider, infrastructure, and financial levels. Since testing typically involves a shared decision between the provider and patient, predicting the likelihood of a patient undergoing pharmacogenetic testing and understanding the factors influencing that decision can help optimize resource use and improve outcomes in pain management.

OBJECTIVE: This study aimed to develop machine learning (ML) models, identifying patients’ likelihood of pharmacogenetic uptake based on their demographics, clinical variables, medication use, and social determinants of health.

METHODS: We used electronic health record data from a single center health care system to identify patients prescribed opioids. We extracted patients’ demographics, clinical variables, medication use, and social determinants of health, and developed and validated ML models, including a neural network, logistic regression, random forest, extreme gradient boosting (XGB), naïve Bayes, and support vector machines for pharmacogenetic testing uptake prediction based on procedure codes. We performed 5-fold cross-validation and created an ensemble probability-based classifier using the best-performing ML models for pharmacogenetic testing uptake prediction. Various performance metrics, uptake stratification analysis, and feature importance analysis were used to evaluate the performance of the models.

RESULTS: The ensemble model using XGB and support vector machine-radial basis function classifiers had the highest C-statistics at 79.61%, followed by XGB (78.94%), and neural network (78.05%). While XGB was the best-performing model, the ensemble model achieved a high accuracy (32,699/48,528, 67.38%), recall (537/702, 76.50%), specificity (32,162/47,826, 67.25%), and negative predictive value (32,162/32,327, 99.49%). The uptake stratification analysis using the ensemble model indicated that it can effectively distinguish across uptake probability deciles, where those in the higher strata are more likely to undergo pharmacogenetic testing in the real world (320/4853, 6.59% in the highest decile compared to 6/4853, 0.12% in the lowest). Furthermore, Shapley Additive Explanations value analysis using the XGB model indicated age, hypertension, and household income as the most influential factors for pharmacogenetic testing uptake prediction.

CONCLUSIONS: The proposed ensemble model demonstrated a high performance in pharmacogenetic testing uptake prediction among patients using opioids for pain. This model can be used as a decision support tool, assisting clinicians in identifying patients’ likelihood of pharmacogenetic testing uptake and guiding appropriate decision-making.

PMID:41564302 | DOI:10.2196/81048

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Implementation and Evaluation of a Cancer Immunotherapy Elective for Medical Students: Mixed Methods Descriptive Study

JMIR Med Educ. 2026 Jan 21;12:e71628. doi: 10.2196/71628.

ABSTRACT

BACKGROUND: Cancer immunotherapy represents a transformative advancement in oncology, offering new avenues for treating malignancies by harnessing the immune system. Despite its growing clinical relevance, immunotherapy remains underrepresented in undergraduate medical education, particularly in curricula integrating foundational immunology with clinical application. To address this gap, we developed and implemented a fully online elective for fourth-year medical students focused on core immunology concepts, immunotherapy mechanisms, Food and Drug Administration-approved treatments, immune-related adverse events, and patient-centered therapeutic decision-making.

OBJECTIVE: This study aimed to evaluate the effectiveness of an asynchronous-synchronous online cancer immunotherapy elective in improving medical student knowledge, engagement, and critical-thinking skills. We hypothesized that participation in the elective would be associated with perceived improvements in knowledge and clinical preparedness and inform future strategies for integrating cancer immunotherapy into medical curricula.

METHODS: We conducted a mixed methods study with fourth-year medical students enrolled in a 2-week elective at a US medical school. The curriculum included a self-paced foundational module, online discussion board, and a capstone oral presentation requiring students to propose a novel immunotherapy approach. Participants completed pre- and postcourse quizzes assessing immunotherapy knowledge and an anonymous postcourse Likert-scale survey. Quantitative data were summarized descriptively, and Likert responses were reported using medians and IQRs. Due to the small sample size, 2-tailed unpaired t tests comparing pre- and postcourse quiz averages were underpowered to detect statistically significant differences. Qualitative data were analyzed using inductive thematic analysis with investigator triangulation.

RESULTS: A total of 35 students completed the elective, and 20 submitted the postcourse survey (response rate: 57%). Across all Likert-scale items, students reported a median response of 5 (Strongly Agree), with IQR values ranging from 0 to 1, indicating uniformly positive perceptions and minimal variability in their evaluation of the course. Descriptively, average postcourse quiz scores were higher than precourse scores, suggesting improved conceptual understanding. Qualitative thematic analysis revealed three major themes: (1) increased confidence engaging with complex immunotherapy mechanisms, (2) appreciation for the flexibility and interactivity afforded by the hybrid asynchronous-synchronous model, and (3) enhanced understanding of the real-world clinical application of immunotherapy across interdisciplinary settings.

CONCLUSIONS: Descriptive quantitative and qualitative findings suggest that a targeted online cancer immunotherapy elective may enhance learners’ perceived knowledge and critical-thinking capacity related to emerging cancer therapies. The course’s hybrid structure offered flexibility, accessibility, and potential scalability. As immunotherapy continues to expand in clinical practice, this model provides a promising framework for integration into medical curricula. Future work should include larger cohorts and longitudinal follow-up into residency to more rigorously assess educational impact.

PMID:41564300 | DOI:10.2196/71628

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Association Between Mandibular Third Molar Position and Recurrent Pericoronitis: Protocol for a Cross-Sectional Study

JMIR Res Protoc. 2026 Jan 21;15:e72682. doi: 10.2196/72682.

ABSTRACT

BACKGROUND: Pericoronitis is a common pathological condition associated with mandibular third molars that may cause pain and discomfort. This condition may be chronic, exhibiting episodic symptoms that last for a few days to weeks and recurring multiple times in less than a year. The operculum covering the erupting mandibular third molars may become obscured by the eruption of maxillary third molars. Such recurrent traumas might exacerbate the symptoms and lead to ulcerations. With clinical monitoring at regular intervals and with the help of radiographic examinations, clinicians can develop the most effective treatment plan.

OBJECTIVE: This study aims to determine the association between mandibular third molar position and recurrent pericoronitis.

METHODS: This cross-sectional study will include 200 patients having partially impacted mandibular third molar with recurrent pericoronitis. Patients aged 18-40 years with occurrence of pericoronitis will be included in this study. The impacted tooth’s side and the symptoms associated with pericoronitis will be recorded during clinical examination. All these patients will be evaluated using panoramic radiographs to assess the position of the unerupted/impacted mandibular third molar.

RESULTS: The duration of this study will be 6 months from October 2025 to April 2026. Approval for this study has been granted by the institutional ethics committee of Datta Meghe Institute of Higher Education and Research (deemed to be university), Sawangi, Wardha (DMIHER (DU)/IEC/2024/53). In panoramic radiographs, the impaction status of the mandibular third molar will be evaluated based on Winter’s and Pell and Gregory classification systems. Patients’ data will be recorded and analyzed for statistical significance.

CONCLUSIONS: The detection of the position and intervention at the early stage for pericoronitis in individuals with impacted third molars is vital.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/72682.

PMID:41563821 | DOI:10.2196/72682

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Retrospective analysis of cutaneous immune-related adverse events following checkpoint inhibitor therapy in melanoma patients reveals increased risk associated with the HLA-B*51:01 allele

Cancer. 2026 Feb 1;132(3):e70262. doi: 10.1002/cncr.70262.

ABSTRACT

BACKGROUND: While immune checkpoint inhibitors (ICIs) have shown significant efficacy, a common side effect is cutaneous immune-related adverse events (irAEs). This study focuses on exploring the association between specific human leukocyte antigen (HLA) alleles and the development of cutaneous irAEs in melanoma patients undergoing ICI monotherapy and combination therapy. As certain HLA types are indicative of susceptibility to autoimmune diseases, it was hypothesized that HLA typing could serve as a potential screening tool for identifying patients at increased risk for developing irAEs.

METHODS: A retrospective chart review was performed of 515 patients with melanoma who underwent ICI therapy, either as monotherapy or in combination, and had HLA typing available. This analysis spans from 2003 to 2023 with a focus on cutaneous irAEs. Statistical analyses were conducted to assess the association between HLA alleles and irAEs.

RESULTS: Our analysis revealed that the HLA-B*51:01 allele was associated with a higher risk of cutaneous irAEs after adjusting for ICI regimen (hazard ratio: 1.71 [95% CI, 1.12-2.61], p = .013.) CONCLUSION: This is the largest study to link an HLA allele with ICI-induced cutaneous irAEs. The findings may support the use of HLA typing as an initial screen for developing irAEs, providing a simple, straightforward metric that can be rapidly performed on patients prior to initiation of ICIs. However, further research is needed across different cancer and toxicity types.

PMID:41563778 | DOI:10.1002/cncr.70262

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Global Burden of Violence Against Transgender and Gender-Diverse Adults: A Systematic Review and Meta-Analysis

JAMA Netw Open. 2026 Jan 2;9(1):e2552953. doi: 10.1001/jamanetworkopen.2025.52953.

ABSTRACT

IMPORTANCE: Interpersonal violence perpetrated against transgender and gender-diverse people is prevalent across many settings and may contribute to substantial health disparities.

OBJECTIVE: To estimate the prevalence of overall, physical, sexual, and psychological violence against transgender and gender-diverse adults globally.

DATA SOURCES: Studies were identified through PubMed, Embase, CINAHL, Cochrane Central, LILACS, PsycINFO, gray literature, and conference abstracts. Secondary searches of article references and relevant systematic reviews for articles published between January 1, 2010, and January 2, 2023, without language or geographical restrictions were performed.

STUDY SELECTION: Articles presenting quantitative data on interpersonal violence prevalence against transgender and gender-diverse adults using any study design and from any geographic region were included. Review articles, editorials, commentaries, studies that included minors and did not disaggregate data by age, studies that did not disaggregate data by gender identity, and studies with fewer than 10 participants were excluded. Full texts of potentially eligible articles were independently assessed for inclusion by 2 independent reviewers, with differences resolved through consensus.

DATA EXTRACTION AND SYNTHESIS: This study followed the PRISMA 2020 and MOOSE reporting guidelines. Prevalence data were extracted independently in duplicate and pooled using random-effects meta-analysis.

MAIN OUTCOMES AND MEASURES: The lifetime and recent pooled prevalences of physical, sexual, and overall physical or sexual interpersonal violence against transgender and gender-diverse populations globally, as formulated prior to data collection, were estimated. Heterogeneity was assessed using I2 values and examination of 95% prediction intervals. For analyses composed of single studies, the unadjusted crude prevalence and 95% CI were presented.

RESULTS: A total of 94 studies published in 137 of the 29 987 identified articles (65 608 participants) were included in this review. Estimates from 98 articles were pooled in meta-analysis. The pooled prevalence of physical or sexual violence was 64.23% (9 studies; 95% CI, 47.38%-78.17%) for lifetime and 59.81% (2 studies; 95% CI, 11.73%-94.34%) for recent. The pooled prevalence of lifetime physical violence was 35.89% (45 studies; 95% CI, 28.97%-43.46%), and that of sexual violence was 32.70% (40 studies; 95% CI, 25.20%-41.20%).

CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis of interpersonal violence experienced globally by transgender and gender-diverse adults, a high prevalence was found, which should be addressed through evidence-based prevention and response strategies.

PMID:41563760 | DOI:10.1001/jamanetworkopen.2025.52953

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Nevin Manimala Statistics

Pregnancy- and Abortion-Related Mortality in the US, 2018-2021

JAMA Netw Open. 2026 Jan 2;9(1):e2554793. doi: 10.1001/jamanetworkopen.2025.54793.

ABSTRACT

IMPORTANCE: The 2022 Supreme Court decision Dobbs v. Jackson Women’s Health Organization and the subsequent legal restrictions to abortion have prompted national discussion about the importance of abortion access for maternal health. A commonly cited statistic in these debates, based on data from 1998 to 2005, is that the risk of death associated with childbirth is approximately 14 times higher than that of abortion.

OBJECTIVE: To estimate the ratio of pregnancy-related to abortion-related mortality using updated data (2018-2021), capturing increased detection of maternal death and increased safety of abortion since the original estimate.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included all births (live and stillbirths) and pregnancy-related deaths from the National Vital Statistics System from 2018 to 2021. The number of abortion related deaths was obtained from the Pregnancy Mortality Surveillance System, and the number of abortions was obtained from the Guttmacher Institute. Data were analyzed between February and October 2025.

MAIN OUTCOMES AND MEASURES: Pregnancy-related deaths were identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes A34, O10 to O95, O96, O98 to O99. Pregnancy- and abortion-related mortality ratios were calculated per 100 000 births and abortions, respectively, per year and overall. To calculate the ratio, the pregnancy-related mortality rate per 100 000 births was divided by the abortion-related mortality rate per 100 000 abortions. Sensitivity analyses excluded ICD-10 codes commonly misclassified as pregnancy related and COVID-19-related deaths.

RESULTS: During the period between 2018 and 2021, there were 14 902 571 births and 3 662 580 abortions. The mean ratio between pregnancy-related and abortion-related mortality was 69.6 (range, 52.9-105.2). Excluding nonspecific causes of pregnancy-related death, the mean pregnancy- to abortion-related mortality ratio was 52.9 (range, 38.2-74.2). Further excluding COVID-19-related mortality, the ratio was 44.3 (range, 34.5 to 74.2).

CONCLUSIONS AND RELEVANCE: This cross-sectional study found that the ratio of pregnancy- to abortion-related mortality from 2018 to 2021 ranged from 44.3 to 69.6, at least 3 times higher than the ratio of 14.7 calculated using data from 1998 to 2005. These findings suggest that by taking away the option to end a pregnancy, abortion bans force pregnant people to take on the increased health risks associated with continued pregnancy.

PMID:41563758 | DOI:10.1001/jamanetworkopen.2025.54793

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Modeled Health and Economic Burden of Frailty and Falls Among Adults With HIV

JAMA Netw Open. 2026 Jan 2;9(1):e2554809. doi: 10.1001/jamanetworkopen.2025.54809.

ABSTRACT

IMPORTANCE: People with HIV experience higher rates of frailty and falls than age-matched people without HIV.

OBJECTIVE: To estimate the life-years lost, quality-adjusted life-years (QALYs) lost, and costs attributable to prefrailty, frailty, and falls among people with HIV and viral suppression in the United States.

DESIGN, SETTING, AND PARTICIPANTS: This decision analytic modeling study used the Frailty Policy Model, a microsimulation model, to project lifetime health and cost outcomes associated with frailty and falls among people with HIV in the United States. The model simulated individuals representing people with HIV and viral suppression in the United States aged 40 years and older in 2022, and results were scaled to the estimated population size of 521 994 individuals. Simulation model parameters were drawn from the Advancing Clinical Therapeutics Globally (ACTG) A5322 Study, the Multicenter AIDS Cohort Study (MACS)/Women’s Interagency HIV Study (WIHS) Combined Cohort Study, and published literature. Data analysis was conducted from November 2023 to October 2025.

EXPOSURES: Prefrailty, frailty, and falls.

MAIN OUTCOMES AND MEASURES: Life-years lost, QALYs lost, and costs attributable to prefrailty, frailty, and falls.

RESULTS: The simulated individuals representing people with HIV and viral suppression had a mean (SD) age of 56 (10) years; 25% were female; 41% had prefrailty, and 7% had frailty. The model projected that the simulated individuals would have a remaining life expectancy of 20.3 (95% uncertainty interval [UI], 19.7-20.8) years, with a mean of 12.0 (95% UI, 11.2-12.8) years with prefrailty or frailty and 10.1 (95% UI, 8.2-12.1) falls per person. Scaled to the population level, the model projected that there would be 31 000 (95% UI, 16 000-57 000) life-years lost, 214 000 (95% UI, 130 000-292 000) QALYs lost, and $5.0 (95% UI, $3.2-$7.2) billion in lifetime costs attributable to prefrailty. There would be 1 352 000 (95% UI, 84 000-3 336 000) life-years lost, 1 091 000 (95% UI, 209 000-2 500 000) QALYs lost, and $8.8 (95% UI, $4.7-$14.2) billion in lifetime costs attributable to frailty. There would be 183 000 (95% UI, 120 000-266 000) life-years lost, 141 000 (95% UI, 94 000-198 000) QALYs lost, and $3.4 (95% UI, $2.2-$4.8) billion attributable to falls.

CONCLUSIONS AND RELEVANCE: In this decision analytic modeling study of frailty and falls among people with HIV and viral suppression, the lifetime QALYs lost and costs attributable to frailty and falls were substantial. These findings highlight the potential clinical and economic benefits that could result from interventions to identify, prevent, and treat frailty and falls among people with HIV.

PMID:41563756 | DOI:10.1001/jamanetworkopen.2025.54809

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Generative AI Use and Depressive Symptoms Among US Adults

JAMA Netw Open. 2026 Jan 2;9(1):e2554820. doi: 10.1001/jamanetworkopen.2025.54820.

ABSTRACT

IMPORTANCE: Generative artificial intelligence (AI) has rapidly entered mainstream use in the US, but its association with mental health has not been characterized.

OBJECTIVE: To examine the associations of the extent and type of generative AI use among US adults with negative affective symptoms in a large, nationally representative sample.

DESIGN, SETTING, AND PARTICIPANTS: This survey study used data from a 50-state US internet nonprobability survey conducted between April and May 2025. Survey respondents were aged 18 years and older. Data were analyzed in August 2025.

EXPOSURE: Participants self-reported generative AI and social media use.

MAIN OUTCOMES AND MEASURES: The outcome of interest, negative affect, was measured using the Patient Health Questionnaire 9-item (PHQ-9).

RESULTS: There were 20 847 unique participants, with mean (SD) age 47.3 (17.1) years and 10 327 (49.5%) female, 10 386 (49.8%) male, and 134 (0.6%) nonbinary participants; 2152 participants (10.3%) reported using AI at least daily, including 1053 participants (5.1%) who reported daily use and 1099 participants (5.3%) who reported use multiple times per day. Among participants who used daily or more frequently, 1033 (48.0%) reported use for work, 246 (11.4%) for school, and 1875 (87.1%) for personal applications. In survey-weighted regression models, daily or more frequent AI use was significantly more common among men, younger adults, those with higher education and income, and those in urban settings. Greater AI use was associated with greater levels of depressive symptoms in sociodemographic-adjusted regression models: (daily use: β = 1.08 [95% CI, 0.55-1.62]; multiple times per day: β = 0.86 [95% CI, 0.35-1.37]) compared with nonuse, and with greater likelihood of reporting at least moderate depressive symptoms (odds ratio [OR], 1.29 [95% CI, 1.15-1.46]); similar patterns were observed for anxiety and irritability. The highest estimates were observed among individuals using AI for personal use (β = 0.31 [95% CI, 0.10-0.52]) and those aged 25 to 44 years (β = 1.22 [95% CI, 0.70-1.74]) or 45 to 64 years (β = 1.38 [95% CI, 0.72-2.05]).

CONCLUSIONS AND RELEVANCE: This survey study found that AI use was significantly associated with greater depressive symptoms, with magnitude of differences varying by age group. Further work is needed to understand whether these associations are causal and explain heterogeneous effects.

PMID:41563755 | DOI:10.1001/jamanetworkopen.2025.54820

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Prior Concussions and Risk of Disability for Patients After a Motor Vehicle Crash

JAMA Netw Open. 2026 Jan 2;9(1):e2554831. doi: 10.1001/jamanetworkopen.2025.54831.

ABSTRACT

IMPORTANCE: Recovery after a motor vehicle crash can be slow, frustrating, and incomplete with lingering neurocognitive complications.

OBJECTIVE: To examine whether a prior concussion is associated with increased risk of long-term disability after a motor vehicle crash.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included adults surviving a motor vehicle crash treated in Ontario, Canada, from April 2003 to March 2023 with analyses to November 2025.

EXPOSURE: Prior concussion.

MAIN OUTCOME AND MEASURES: Long-term disability defined by official social service records, comparing those with a prior concussion and those with no history of a prior concussion.

RESULTS: A total of 907 984 patients injured in a motor vehicle crash were included (mean [SD] age, 37 [14] years; 472 435 male [52.0%]); 19 851 patients had a prior concussion and 888 133 had no prior concussion. A total of 54 678 patients were subsequently diagnosed with long-term disability over 9 543 505 patient-years of follow-up (mean [SD], 10.5 [5.8] years), equal to an absolute risk of 1 in 17 per decade (5.7 per 1000 patient-years). Patients with a prior concussion had a 15% higher adjusted risk of long-term disability (95% CI, 9%-21%; P < .001) compared with those with no prior concussion. The increased risk of long-term disability was independent of other measured risk factors, applied to diverse patient groups, and included those involved as passengers or pedestrians. The increased risk extended across a spectrum of crash severity, was accentuated for single-vehicle events, replicated in analyses with artificial intelligence models adjusting for confounding, and remained distinct from the risks of death, readmission, or short-term health care costs.

CONCLUSIONS AND RELEVANCE: This population-based cohort study suggests a significant increased risk of long-term disability after a motor vehicle crash, particular among patients with a prior concussion. More efforts at concussion prevention and traffic safety counseling may be justified for patients.

PMID:41563754 | DOI:10.1001/jamanetworkopen.2025.54831

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Factors influencing parental acceptance of preventive dental treatments and its impact on children’s oral health-related quality of life: an observational study

Eur Arch Paediatr Dent. 2026 Jan 21. doi: 10.1007/s40368-026-01165-3. Online ahead of print.

ABSTRACT

BACKGROUND: The clinical efficacy of preventive dental treatments (PDTs) is well established. However, limited evidence exists regarding parental acceptance and its impact on children’s oral health-related quality of life (COHRQoL).

OBJECTIVE: To assess factors influencing parental acceptance of PDTs and their impact on COHRQoL.

METHODS: A cross-sectional, observational study was conducted amongst 200 parents of children aged 6-14 years who had been exclusively advised PDTs by a paediatric dentist. Sociodemographic factors, parental knowledge, and attitudes were assessed using a validated questionnaire. Parental acceptance of PDTs was recorded at the time the preventive treatment plan was explained. For those who accepted and underwent PDTs, COHRQoL was measured at baseline and 6 months post-treatment using the short-form parental/caregiver perception questionnaire (P-CPQ-8), family impact scale (FIS-8), and a global oral health rating scale. Data were analysed using appropriate statistical tests.

RESULTS: Only 36.5% of parents accepted PDTs. Non-acceptance was mainly due to perceived non-necessity (21.3%). Acceptance was significantly associated with education, family size, residence, prior dental visits, awareness, and attitudes. Logistic regression identified higher education, urban residence, and frequent dental visits as strong predictors for parental acceptance of PDTs. Following PDTs, COHRQoL improved significantly, with reductions in global oral health scores (1.19 ± 1.22 to 0.81 ± 0.77), P-CPQ-8 scores (9.22 ± 2.84 to 7.86 ± 2.59), and FIS-8 scores (7.58 ± 2.49 to 7.03 ± 2.15).

CONCLUSION: Parental acceptance of PDTs is moderate and influenced by sociodemographic and behavioural factors. PDTs significantly improved COHRQoL, emphasising that parents should recognise their importance whilst dentists must play an active role in motivating and guiding parents towards preventive care.

PMID:41563692 | DOI:10.1007/s40368-026-01165-3