Nevin Manimala

Head Neck. 2025 Aug 26. doi: 10.1002/hed.70018. Online ahead of print.

ABSTRACT

BACKGROUND: Podoplanin is a mucin-like transmembrane glycoprotein expressed in oral epithelium with a documented role in cell motility, tumorigenesis, tumor invasion, and metastasis. Podoplanin is a potentially valuable biomarker for determining malignant transformation of oral premalignant disease (OPMD).

METHODS: A systematic search was done in accordance with PRISMA guidelines for articles reporting podoplanin expression in OPMD. The outcomes compared were the presence of podoplanin expression, the grade of podoplanin expression, and the incidence of malignant transformation. Statistical analysis of these outcomes included proportions (%), sensitivity, negative predictive value, and hazard ratio (HR) with 95% confidence intervals (CI).

RESULTS: There were 14 included studies (N = 971) with 78.7% OPMD, 13.9% OSCC, and 7.4% healthy controls. Positive expression of podoplanin had a sensitivity and negative predictive value for malignant transformation of 78.9% [95% CI: 69.7%-86.2%] and 88.8% [84.4%-92.1%], respectively. The hazard ratio was 4.4 for the malignant transformation of podoplanin expressing OPMDs [95% CI: 2.6-7.4].

CONCLUSIONS: Podoplanin expression levels increased in a gradient from normal tissue to OPMD to OSCC, respectively. Furthermore, OPMD with podoplanin expression has higher rates of malignant transformation than OPMDs not expressing podoplanin.

PMID:40857023 | DOI:10.1002/hed.70018

Stat Med. 2025 Aug;44(18-19):e70168. doi: 10.1002/sim.70168.

ABSTRACT

The incorporation of real-world data to supplement the analysis of trials and improve decision-making has spurred the development of statistical techniques to account for introduced confounding. Recently, “hybrid” methods have been developed through which measured confounding is first attenuated via propensity scores and unmeasured confounding is addressed through (Bayesian) dynamic borrowing. Most efforts to date have focused on augmenting control arms with historical controls. Here we consider augmenting treatment arms through “expanded access”, which is a pathway of nontrial access to investigational medicine for patients with seriously debilitating or life-threatening illnesses. Motivated by a case study on expanded access, we developed a novel method (the ProPP) that provides a conceptually simple and easy-to-use combination of propensity score weighting and the modified power prior. Our weighting scheme is based on the estimation of the average treatment effect of the patients in the trial, with the constraint that external patients cannot receive higher weights than trial patients. The causal implications of the weighting scheme and propensity-score integrated approaches in general are discussed. In a simulation study, our method compares favorably with existing (hybrid) borrowing methods in terms of precision and type I error rate. We illustrate our method by jointly analyzing individual patient data from the trial and expanded access program for vemurafenib to treat metastatic melanoma. Our method provides a double safeguard against prior-data conflict and forms a straightforward addition to evidence synthesis methods of trial and real-world (expanded access) data.

PMID:40857021 | DOI:10.1002/sim.70168

Oral Health Prev Dent. 2025 Aug 26;23:499-506. doi: 10.3290/j.ohpd.c_2226.

ABSTRACT

PURPOSE: This study aimed to assess factors that impact midazolam dose for intravenous sedation (IVS) in dental patients with anxiety.

MATERIALS AND METHODS: This was a retrospective, observational study for adult, anxious patients (moderate to severe dental anxiety) who had different types of dental procedures under IVS with midazolam and local anaesthesia. A logbook of dental patients who had dental procedures was used to collect data on an Excel sheet (Microsoft Excel Workbook 2024).

RESULTS: Data of 233 patients were recorded. The average dose of IVS with midazolam delivered was 6.62 mg (SD = 3.24). Multivariable logistic regression found that two variables were statistically significant predictors for the IVS with midazolam dose, which are age (B = 1.30, S.E = 0.47, Exp(B) = 3.68, 95% CI = 1.45-9.33, P = 0.006) and non-surgical periodontal therapy with root planing (B = 0.85, SE = 0.39, Exp(B) = 2.35, 95% CI = 1.08-5.12, P = 0.031).

CONCLUSIONS: Younger patients and non-surgical periodontal therapy with root planing appear to be predictors for higher doses of IVS with midazolam. Other variables that were not predictors to affect IVS with midazolam dose, such as medical history, American Society of Anesthesiologists (ASA) classification, medications, and others, are crucial, and they should not be neglected when designing the treatment plan to deliver dental treatment under IVS with midazolam.

PMID:40857015 | DOI:10.3290/j.ohpd.c_2226

Oral Health Prev Dent. 2025 Aug 26;23:489-498. doi: 10.3290/j.ohpd.c_2231.

ABSTRACT

PURPOSE: This study aimed to assess the utilisation of Instagram primarily as a marketing tool among dentists in Saudi Arabia and its perceived impact on patient engagement.

MATERIALS AND METHODS: A cross-sectional survey was conducted among 385 dentists using a convenience sampling method. The questionnaire collected data on demographics, Instagram usage patterns, perception of marketing strategies on the platform, and factors influencing the selection of a dentist or dental clinic. Data were analysed using IBM SPSS Statistics and presented as descriptive statistics and bivariate analyses.

RESULTS: A total of 385 responses were received, yielding a response rate of 64.2%. Approximately 77.1% of participants reported regular Instagram use, with nearly half accessing the platform more than three times per day. Most respondents indicated using Instagram for personal purposes (42.9%) and marketing (39%). The most effective marketing strategies identified were paid promotional advertisements (75%), Instagram searches (55%), and patient recommendations (50.1%). Key content-related factors enhancing account appeal included clinical case photos (84.9%) and high-quality images (99%). Dentists working in the private sector were more likely to utilise Instagram for marketing and reported a significant increase in patient flow (60%) as a result.

CONCLUSION: Instagram serves as a valuable marketing platform for Saudi dental professionals, particularly in the private sector. The platform enhances patient outreach, practice visibility, and brand building. Further research is recommended to explore ethical guidelines, content strategies, and potential applications in professional and patient education.

PMID:40857014 | DOI:10.3290/j.ohpd.c_2231

Oral Health Prev Dent. 2025 Aug 26;23:479-487. doi: 10.3290/j.ohpd.c_2234.

ABSTRACT

PURPOSE: The aim of the present study was to evaluate the association between periodontitis and SARS-CoV-2 infection severity in a Turkish population.

METHODS: Adult patients attending hospital consultation and testing positive for SARS-CoV-2 infection were consecutively enrolled in this study. Demographic variables, smoking status, COVID-19 symptoms, SpO2 levels, and markers of inflammation (D-Dimer, lymphocytes and white blood cells count, CRP) were recorded. Patients suspected of periodontal disease were evaluated using self-reported questionnaires (OHIP-14, modified CDC/AAP questionnaire). Periodontal screening score (PESS) was calculated from the questionnaire. Univariate and multivariate logistic regression analyses were performed to evaluate the association between COVID-19-associated parameters and periodontitis.

RESULTS: The study included 134 patients diagnosed with COVID-19. Nearly half of the participants were female (n = 68, 50.7%), and the mean age of the patients was 48.7 ± 18.2 years. A statistically significant majority of individuals (69.2%) were asymptomatic, while 22.3% experienced mild symptoms, and 8.5% reported moderate or severe symptoms. Oxygen saturation was found to be higher in asymptomatic patients (96.4 ± 2.8) compared to mild (90.4 ± 5.1) and moderate/severe patients (86.6 ± 8.9) (P 0.001). There was no statistically significant difference concerning OHIP-14 score (P = 0.316), periodontitis (PESS ≥ 5) (P = 0.130), brushing habits (P = 0.901), and frequency of dental visits (P = 0.975) when considering SARS-CoV-2 infection severity. In multivariate logistic regression analysis, it was concluded that male gender (OR = 2.90, 95% CI: 1.04-8.04, P = 0.040), age 55 and above (OR = 5.94, 95% CI: 1.22-28.76, P = 0.026), and smoking (OR = 0.14, 95% CI: 0.02-0.75, P = 0.022) were statistically significant predictors of SARS-CoV-2 infection severity.

CONCLUSIONS: Even the association between SARS-CoV-2 infection severity and periodontitis, evaluated through self-reported outcome measures, were weak: male gender, age, and smoking were independent risk factors for SARS-CoV-2 infection severity in this patient cohort. Further research is warranted to explore these associations comprehensively.

PMID:40857013 | DOI:10.3290/j.ohpd.c_2234

JAMA Netw Open. 2025 Aug 1;8(8):e2528875. doi: 10.1001/jamanetworkopen.2025.28875.

ABSTRACT

IMPORTANCE: High body mass index (BMI) has been associated with increased postoperative complications including mortality in the general population, leading many perioperative clinicians to recommend preoperative lifestyle modifications aimed at achieving normal body weight. However, aging introduces physiological changes associated with frailty, such as altered body composition, fat redistribution, and stature reduction due to height loss, all of which may modify the association between BMI and surgical outcomes in older adults.

OBJECTIVE: To determine if a higher BMI in older adults who are undergoing major elective surgery is associated with rates of all-cause mortality.

DESIGN, SETTING, AND PARTICIPANTS: Cohort study of adults aged 65 years or older presenting for surgery from February 2019 to January 2022 at a preoperative clinic before planned major elective surgery at a large academic Center in Southern California.

EXPOSURE: Body mass index.

MAIN OUTCOMES AND MEASURES: Postoperative outcomes included all-cause 30-day and 1-year mortality, postoperative delirium, discharge disposition, and complications classified using the Clavien-Dindo system.

RESULTS: The study included 414 older adults undergoing major elective surgery with a mean (SD) age of 75.9 (7.2) years; 54.8% (95% CI, 50.2%-60.4%) of the cohort were female. The prevalence of frailty was 24.2% (95% CI, 20.3%-28.5%), and 37.0% (95% CI, 32.6%-41.8%) of the cohort was prefrail. The overall 30-day all-cause mortality rate was 11.0% (95% CI, 8.5%-14.5%). Patients categorized as overweight (BMI, 25.0-29.9; calculated as weight in kilograms divided by height in meters squared) had the lowest 30-day all-cause mortality rate, with a significant risk reduction compared with patients with a normal BMI (18.5-24.9) (1 of 128 patients [0.8%] vs 25 of 133 patients [18.8%]; odds ratio [OR], 0.03; 95% CI, 0.01-0.26; P = .001). This association remained significant in the multivariable logistic regression model after adjusting for potential confounders (OR, 0.14; 95% CI, 0.06-0.34; P < .001). Patients categorized as underweight (BMI <18.5) had the highest 30-day all-cause mortality rate (15 of 20 patients [75.0%]; 95% CI, 55.0%-90.0%).

CONCLUSIONS AND RELEVANCE: In this observational cohort study of older adults undergoing major elective surgery, being overweight was associated with lower odds of 30-day all-cause mortality. These findings suggest that traditional weight loss recommendations based on achieving normal BMI may need to be reevaluated for this population.

PMID:40857003 | DOI:10.1001/jamanetworkopen.2025.28875

JAMA Netw Open. 2025 Aug 1;8(8):e2528924. doi: 10.1001/jamanetworkopen.2025.28924.

ABSTRACT

IMPORTANCE: Owing to a high prevalence of obesity, Pacific Islander individuals in the US are at higher risk for preterm birth (PTB), but outcomes after PTB remain understudied. Existing literature suggests that associations between prepregnancy obesity and neonatal mortality stratified by gestational age (GA) are modest or null, which may be a result of overlooked stratification bias.

OBJECTIVE: To estimate the association between prepregnancy body mass index (BMI) and neonatal death (NND) following PTB by different degrees of prematurity in US Pacific Islander neonates using birth-based and fetuses-at-risk (FAR) approaches.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study used 2014 to 2018 data files from the National Center for Health Statistics for Pacific Islander singletons born at 22 to 41 weeks’ GA without congenital anomalies. The 2 at-risk populations were PTBs (for the birth-based approach) and all identified pregnancies resulting in live birth (for the FAR approach). Analyses were finished in March 2023.

MAIN OUTCOMES AND MEASURES: The primary outcome was NND following PTB stratified by GA intervals (22-27 weeks, 22-31 weeks, and 22-36 weeks). Cox proportional hazards models were used and stratified by GA at birth.

RESULTS: Among 55 975 mother-neonate dyads (27 320 [48.8%] female neonates), the mean (SD) maternal age was 27.8 (5.8) years, and the mean (SD) gestational age of all neonates was 38.5 (1.9) weeks. The PTB prevalence was 9.3% (5192 neonates), and the neonatal mortality rate was 20.4 deaths per 1000 PTBs by the birth-based approach and 1.9 deaths per 1000 live-born pregnancies by the FAR approach. Among extreme PTBs (22-27 weeks), using the FAR approach, associations between prepregnancy obesity and NND following PTB were evident for obesity class I (adjusted hazard ratio [aHR], 2.31; 95% CI, 1.12-4.79) and class II (aHR, 2.82; 95% CI, 1.24-6.41). These associations were attenuated using the birth-based approach (obesity class I aHR, 1.33; 95% CI, 0.61-2.87; class II aHR, 1.73; 95% CI, 0.71-4.28).

CONCLUSIONS AND RELEVANCE: In this cohort study of US Pacific Islander individuals, according to the FAR approach, prepregnancy obesity class I and II were associated with an increased rate of NND following PTB, yet these associations may be overlooked when analyses use the birth-based approach. This is likely because prepregnancy BMI affects GA at birth, which, in turn, may have its own confounded association with NND, leading to stratification bias and attenuated associations between prepregnancy BMI and NND using the birth-based approach. The FAR approach offers an alternative that may highlight important risk factors for key perinatal outcomes.

PMID:40856998 | DOI:10.1001/jamanetworkopen.2025.28924

Int J Cancer. 2025 Aug 26. doi: 10.1002/ijc.70108. Online ahead of print.

ABSTRACT

Men have a higher risk than women for most cancers affecting both sexes. Since taller stature is associated with increased cancer risk and men are, on average, taller than women, we investigated to what extent adult body height, as a proxy for stem cell number, explains the elevated cancer risk in men. This population-based cohort study linked adult height information from Swedish conscripts, mothers, and passports to the National Cancer and Cause of Death Registers (1960-2011). We used mediation survival analysis to estimate the proportion of the association between male sex and site-specific cancer risk mediated by adult height, our main outcome. Statistical significance was assessed using two-sided tests with a .05 significance level. Among 6,156,659 adults, we observed 285,778 non-sex-specific cancer cases. Male sex was significantly associated with cancer risk at 33 of 39 sites, and greater height with increased risk at 27 of 39 sites. Height mediated 0.5%-100% of the excess male cancer risk, with the highest proportions for salivary gland cancer, colon cancer, melanoma, and acute myeloid leukemia. The effects of height and its mediated effect were most consistent for malignancies with weak or no established environmental risk factors. These findings indicate that a substantial proportion of the excess cancer risk in men may be explained by height. This highlights the role of stochastic biological processes linked to height, as well as genetic and early-life determinants of height, in contributing to sex differences in cancer risk, beyond influences of adult lifestyle and environmental exposures.

PMID:40856995 | DOI:10.1002/ijc.70108

Environ Sci Process Impacts. 2025 Aug 26. doi: 10.1039/d5em00511f. Online ahead of print.

ABSTRACT

The Mongolian Plateau grasslands constitute a vital ecological barrier in inland Asia. Within these ecosystems, the mineral-associated soil fraction (<53 μm, MASF) is the dominant component, and its iron (Fe) oxides play a pivotal role in mediating carbon (C), nitrogen (N), and phosphorus (P) cycling. Using sequential chemical extraction, we quantified seven Fe fractions (Fe_ex, Fe_carb, Fe_ox1, Fe_ox2, Fe_mag, Fe_prs, and Fe_U) within the MASF across the plateau. The relative abundance of these fractions followed the sequence: Fe_U > Fe_prs > Fe_ox2 > Fe_ox1 > Fe_mag > Fe_carb > Fe_ex. The combined Fe_ox1 and Fe_ox2 fractions, representing highly reactive Fe (Fe_HR), constituted 6.82-55.77% of total iron (FeT), identifying them as the dominant Fe_HR components. Both Fe fraction abundance and inorganic phosphorus extracted by sequential extraction (IP_SE) decreased significantly along the grassland gradient: meadow steppe > typical steppe > desert steppe. This parallel decline underscores the key regulatory role of Fe (hydr)oxides in governing P fractionation and bioavailability within the MASF. Multivariate statistical analyses revealed soil physicochemical properties as the primary drivers of Fe_HR variability, explaining 64.52% of the variance, followed by climatic factors (18.6%) and vegetation factors (11.7%). IP_SE drivers exhibited a similar hierarchy, suggesting a coupled geochemical cycling mechanism between Fe_HR and IP_SE. This study provides fundamental geochemical insights into Fe fractionation within the MASF, advancing analytical approaches for understanding elemental cycling and ecological processes in Mongolian Plateau grasslands.

PMID:40856992 | DOI:10.1039/d5em00511f

J Endocrinol Invest. 2025 Aug 26. doi: 10.1007/s40618-025-02582-9. Online ahead of print.

ABSTRACT

PURPOSE: A sharp increase in diabetes-related mortality has been registered during the pandemic. Although immigrants are known to suffer from a higher prevalence of diabetes than host populations, data on diabetes-related mortality in pandemic years among immigrants are lacking.

METHODS: All deaths with any mention of diabetes (multiple causes of death-MCOD) among subjects aged 20-64 years were extracted from the Italian National Cause of Death Register in the years 2019-2021. Directly age-standardized mortality rates (2013 European standard population) were computed. Standardized mortality ratios (SMR) for different immigrant groups were estimated with expected numbers based on rates registered among Italian citizens.

RESULTS: Overall age-standardized mortality rates related to diabetes increased by 30% in 2020 compared to 2019, remaining high in 2021. Before the pandemic, large differences were observed across different immigrant groups; during the pandemic, the mortality disadvantage versus the native population widened among those already at increased risk. Among female immigrants, SMR in 2021 were 1.9 (95% Confidence Interval 1.1-2.8) in North Africans, 4.4 (2.5-6.3) in Sub-Saharan Africans and 2.8 (1.6-4.1) in South Asians.

CONCLUSION: Surveillance based on MCOD is warranted to assess if the large differences in diabetes-related mortality observed across different populations living in Italy will reduce in the next years.

PMID:40856980 | DOI:10.1007/s40618-025-02582-9