Category: Statistics

J Neurosurg. 2025 Oct 3:1-10. doi: 10.3171/2025.5.JNS25596. Online ahead of print.

ABSTRACT

OBJECTIVE: Since 2021, there has been a revolution in the understanding of the mutational landscape of sporadic cerebral cavernous malformations (CCMs), with the key discovery of somatic mutations in the PIK3CA and MAP3K3 genes. These genetic alterations have provided new insights into the pathophysiology of CCMs and opened potential venues for personalized treatments. However, establishing robust clinicoradiological and molecular correlations is essential to guide targeted therapeutic approaches and optimize patient outcomes.

METHODS: This study included a cohort of 89 patients diagnosed with sporadic CCMs. The mutational status of each patient was determined using next-generation sequencing (NGS) targeting known mutations including the PIK3CA, MAP3K3, and CCM genes. NGS findings were confirmed by droplet digital polymerase chain reaction for PIK3CA and MAP3K3 mutations. Clinical and radiological data, including Zabramski classification data, were systematically recorded. Statistical analysis was performed to identify significant clinicoradiological and molecular correlations.

RESULTS: In the cohort, PIK3CA somatic mutations were identified in 43 patients (48%), while MAP3K3 somatic mutations were found in 29 (33%). Clinically, PIK3CA-mutated lesions were less frequently revealed by intracranial hypertension (9.3% vs 19.6%; adjusted OR 0.09, p = 0.006), while for MAP3K3-mutated lesions, seizure as a mode of onset was significantly more frequent (85.7% vs 51.7%, p = 0.002). Radiologically, midline lesions were significantly more frequent in the PIK3CA-mutated group (19.0% vs 2.2%, p = 0.01). Importantly, in univariate analysis, the presence of a brainstem lesion was a significant independent predictor of PIK3CA somatic mutation (14.3% vs 2.2%; unadjusted OR 7.33, p = 0.03).

CONCLUSIONS: This study presents new findings linking genetic mutations with clinicoradiological features in sporadic CCMs. The significant association of PIK3CA somatic mutations with brainstem location highlights a potential avenue for personalized therapeutic strategies targeting this mutation, considering the significantly increased morbidity and surgical challenge associated with brainstem lesions. These findings reinforce the importance of integrating genetic data into clinical practice to improve patient outcomes and develop new therapies for CCMs.

PMID:41043184 | DOI:10.3171/2025.5.JNS25596

J Neurosurg Pediatr. 2025 Oct 3:1-5. doi: 10.3171/2025.5.PEDS24551. Online ahead of print.

ABSTRACT

OBJECTIVE: The relationship between Chiari malformation type I (CMI) and tethered cord syndrome (TCS) is not well understood. The aim of this study was to examine conus position and rates of TCS and tethered cord release (TCR) in pediatric patients with CMI at a tertiary hospital.

METHODS: The medical records of children with a diagnosis of CMI based on MRI of the lumbar spine from 2010 to 2023 were retrospectively reviewed. Conus position on MRI, tonsil position below the foramen magnum, presence of fatty filum or filum terminale lipoma, and rates of CMI decompression and TCR were recorded. Age- and sex-matched controls were randomly selected from a cohort of patients who obtained an MRI of the spine for any reason. Conus position was coded and then compared using the Student t-test. Categorical variables were compared using the chi-square test.

RESULTS: A total of 657 pediatric patients with CMI were included. The mean ± SD tonsil position was 11.7 ± 5.6 mm below the foramen magnum, and 44.7% of patients underwent CMI decompression. The conus terminated at or above the L2-3 disc space in 97% of CMI patients. There was no statistical difference in conus position between CMI patients and controls (p = 0.09). Nine patients (1.4%) in the CMI cohort had symptomatic TCS and underwent TCR. This proportion was not statistically different compared to the control group: 11 patients (1.7%) had symptomatic TCS and underwent TCR (p = 0.1).

CONCLUSIONS: Most patients with CMI had a normal conus position (97%), and conus position was not different between CMI and control patients. The number of patients with symptomatic TCS was not statistically different between CMI and control patients.

PMID:41043181 | DOI:10.3171/2025.5.PEDS24551

Compend Contin Educ Dent. 2025 Jul-Aug;46(7):327-334.

ABSTRACT

PURPOSE: The aim of this retrospective pilot study was to use digital implant planning to assess radiographic outcomes of maxillary sinus augmentation bone grafting procedures (ideal, excess, or insufficient) in reference to the planned implant.

MATERIALS AND METHODS: After ethical approval was received, deidentified data for subjects treated for a maxillary sinus elevation procedure was extracted. Patient-specific variables (age group, gender, race, smoking, diabetes, and cardiovascular disease) and site-specific variables (type of bone graft, type of membrane, membrane perforation, and other complications) were collected, as recorded in the electronic health records. For the records that satisfied the inclusion criteria, preoperative and postoperative cone-beam computed tomography scans for lateral sinus augmentation procedures were retrieved, superimposed, and imported into the implant planning software. An ideal implant was planned digitally in a cross-sectional view by an expert in prosthodontics (KV). The implant measurements in apicocoronal (AC) and buccopalatal (BP) dimensions were kept standard for all cases and were confirmed by two previously calibrated co-investigators (GS, ID). Statistical analysis involved descriptive and bivariate analysis.

RESULTS: A total of 350 electronic health records were reviewed and 26 were included. Descriptive analysis revealed that in the AC dimension, 40.63% of procedures resulted in insufficient amount of bone graft and 37.50% of procedures resulted in excess bone graft; 21.88% of procedures had ideal amount of bone graft in the AC dimension. For the BP dimension, 81.25% of procedures resulted in ideal and 18.75% in insufficient amounts of bone graft.

CONCLUSION: This study revealed that a limited number of maxillary sinus procedures resulted in ideal bone grafting in both the AC and BP dimensions when considering predetermined restorative guidelines for the final implant position. An excess and/or insufficient amount of bone grafting in at least one dimension resulted most of the times. With the use of technology and an interdisciplinary team of experts, future studies should aim to quantify the amount of bone graft needed for an ideal maxillary sinus elevation for upcoming implant placement.

PMID:41043157

J Med Internet Res. 2025 Oct 3;27:e77157. doi: 10.2196/77157.

ABSTRACT

BACKGROUND: Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition, the prevalence of which is increasing in China and worldwide. Digital health technologies offer promising solutions for improving screening, diagnosis, and rehabilitation of children with ASD, particularly in resource-limited settings. However, digital health technologies for ASD have not been adopted in China. Understanding utilization patterns, influencing factors, and user needs is essential to inform equitable, effective digital health strategies.

OBJECTIVE: This study aimed to assess the current use, influencing factors, and perceived needs of digital health services among parents of children with ASD and rehabilitation therapists in 2 distinct provinces in China.

METHODS: A cross-sectional survey was carried out between November 2023 and February 2024 in Heilongjiang and Fujian provinces. Purposive sampling recruited a total of 780 parents and 745 rehabilitation therapists to complete a structured questionnaire. Data were analyzed using descriptive statistics, stepwise multivariable logistic regression, and multiple response analysis.

RESULTS: The use of digital health services was low among parents (46/780, 5.9%) and rehabilitation therapists (161/745, 21.6%), although the demand was substantially higher (621/780, 79.6% and 671/745, 90.0%, respectively). Among parents, higher use was positively associated with younger age (20-29 years), employment, lower income (≤CNY 3000/month [US $421.247/month]), and delayed ASD diagnosis (7-12 years old). Among rehabilitation therapists, male, special education background, and autism-specific training experience predicted higher use (all P<.05). Demand was significantly greater in Fujian than in Heilongjiang and was positively associated with higher education levels in parents and rehabilitation therapists (P<.05). Parents and rehabilitation therapists valued a greater understanding of ASD behaviors and development and easier access to resources as primary benefits. Common barriers to the use of digital health services included high cost, need for additional equipment, and usability challenges. The smartphone-WeChat mini-program was the preferred device and platform, respectively. Parents prioritized access to rehabilitation courses, remote guidance, and policy information, while rehabilitation therapists favored personalized plans and professional skills training.

CONCLUSIONS: Despite a strong demand, digital health services are underused in ASD care across China, with adoption of digital health services influenced by regional disparities and sociodemographic factors. This study, as the first comparative analysis of parents and rehabilitation therapists in 2 Chinese provinces, provides stakeholder-specific insights to guide targeted, locally relevant interventions. Bridging the digital divide through inclusive policies, training, and cross-sector collaboration will be essential for equitable integration into ASD care pathways.

PMID:41043146 | DOI:10.2196/77157

JMIR Form Res. 2025 Oct 3;9:e81753. doi: 10.2196/81753.

ABSTRACT

BACKGROUND: Substance use and HIV epidemics have disproportionately affected sexual and gender minoritized (SGM) communities, with heightened risks among men who have sex with men (MSM) and transgender women of color due to intersecting challenges like poverty, mental health issues, and discrimination. Despite overall declines in substance use and sexual risk behaviors in the general population, these issues persist within SGM communities, exacerbated by stigma and systemic barriers to care. Digital health interventions have emerged as promising tools to address these disparities, offering accessible and stigma-reducing alternatives to traditional care, particularly effective among younger individuals and in underserved areas.

OBJECTIVE: This study seeks to examine the social correlates of substance use and sexual risk perception among an online sample of help-seeking MSM and transgender women in San Francisco, California.

METHODS: We recruited 409 help-seeking MSM and transgender women by using social media advertisements on Facebook, Instagram, and Grindr in 2022-2024. Participants provided informed consent and completed a baseline assessment.

RESULTS: Utilization of testing resources for HIV and hepatitis was high among the participants (401/409, 98.04% and 360/409, 88.02%, respectively). Knowledge of HIV or other sexually transmitted infection health services was also high (379/409, 92.67%). Fewer participants (264/409, 64.55%) were knowledgeable about substance use-related services. Although many participants reported that using substances posed a high risk of harm, some perceived engaging in condomless sex, using prescription opioid drugs without a prescription, and using substances during sex as low risk (122/409, 29.83%, 41/409, 10.02%, and 60/409, 14.67%, respectively). Participants who reported experiencing unstable housing were more likely to report perceiving sharing needles (adjusted odds ratio [aOR] 7.20, 95% CI 1.99-27.80) and nonprescription opioid use (aOR 4.02, 95% CI 1.08-14.90) as low risk. Participants who reported an income below the federal poverty level were more likely to report perceiving sharing needles (aOR 6.35, 95% CI 1.84-23.40), prescription opioid use (aOR 2.89, 95% CI 1.32-6.18), and substance use during sex (aOR 2.29, 95% CI 1.14-4.48) as low risk. Participants who have not been tested for hepatitis in the past have 3.31 times the odds of perceiving prescription opioid use as low risk compared to counterparts who have been tested for hepatitis before (95% CI 1.36-7.68).

CONCLUSIONS: This study underscores the importance of social determinants in shaping low risk perception of the harm associated with substance use behaviors among online help-seeking SGM people in San Francisco. These systemic inequities structure participants’ perceptions, access, and utilization of preventive and public health services. Our findings identify critical opportunities for outreach and preventative efforts needed to serve vulnerable populations.

PMID:41043143 | DOI:10.2196/81753

JMIR Form Res. 2025 Oct 3;9:e70602. doi: 10.2196/70602.

ABSTRACT

BACKGROUND: Syndrome differentiation is crucial in traditional Chinese medicine (TCM) diagnosis and treatment, but it heavily relies on expert experience, limiting systematic standardization.

OBJECTIVE: This study developed and validated a BERT (bidirectional encoder representations from transformers)-based model, the traditional Chinese medicine pancreatic cancer syndrome differentiation bidirectional encoder representations from transformers (TCMPCSD-BERT), using in-house pancreatic cancer medical records, to digitalize expert knowledge and support standardized syndrome differentiation in TCM.

METHODS: A retrospective dataset of pancreatic cancer cases (2011-2024) from Fudan University Shanghai Cancer Center was annotated into 4 TCM syndrome types by 2 experts (Cohen κ=0.913). The proposed TCMPCSD-BERT model was compared with conventional models (long short-term memory and text convolutional neural network) embedded in TCM diagnostic tools and with large language models (LLMs; ChatGPT-4o, Kimi, Ernie Bot 4.0 Turbo, and Zhipu Qingyan) under a prompt engineering framework. Performance evaluation on in-house data was supplemented with attention visualizations and integrated gradients analyses for interpretability. The McNemar test assessed classification accuracy differences, while bootstrap 95% CIs quantified statistical uncertainty and stability. The Welch t test (2-tailed) was used to evaluate mean differences between TCMPCSD-BERT and the comparator models.

RESULTS: Among 6830 records, case counts were damp-heat syndrome (n=1694), spleen-deficiency syndrome (n=1185), damp-heat with spleen-deficiency syndrome (n=1178), and others (n=2773). On the test set, McNemar test showed significantly higher accuracy for TCMPCSD-BERT than the 3 baseline models and generally better performance than LLMs. In all comparisons, TCMPCSD-BERT achieved higher mean macroprecision, macrorecall, macro-F₁-score, and accuracy, with nonoverlapping 95% bootstrap CIs and significant Welch t test results (P<.01). The model achieved a macroprecision of 0.935 (95% CI 0.918-0.951), macrorecall of 0.921 (95% CI 0.900-0.942), macro-F₁-score of 0.927 (95% CI 0.908-0.945), and accuracy of 0.919 (95% CI 0.899-0.939). Attention visualizations suggested the model could capture less common TCM term associations, while integrated gradients highlighted high-attribution diagnostic features (eg, “gray-white stool” 0.933 in damp-heat syndrome; “indigestion” 1.204 in spleen-deficiency syndrome). Misclassification analyses indicated challenges in handling overlapping or atypical symptom presentations. Compared with LLMs, web-based platforms, and diagnostic instruments, TCMPCSD-BERT appeared to provide relatively higher accuracy, interpretability, and efficiency in processing long unstructured texts for syndrome differentiation.

CONCLUSIONS: The TCMPCSD-BERT model shows potential for automated syndrome differentiation from unstructured clinical texts and broader application in TCM. Based on this study, it appears to improve operability over 4-diagnostic instruments and web-based platforms, and offers greater stability and accuracy than LLMs in specific tasks. However, these findings should be interpreted cautiously, given the subjectivity of syndrome definitions, data imbalance, and reliance on preprocessed, expert-annotated data. Further studies involving larger and more diverse populations are needed to validate its generalizability and support its broader application in real-world settings.

PMID:41043140 | DOI:10.2196/70602

JMIR Mhealth Uhealth. 2025 Oct 3;13:e59144. doi: 10.2196/59144.

ABSTRACT

BACKGROUND: Adolescent pregnancy is of public health concern due to high rates of pregnancy-related complications and lower antenatal attendance among adolescent girls and young women. Mobile health (mHealth) interventions have the potential to improve pregnancy health behaviors and thereby birth outcomes.

OBJECTIVE: This pilot randomized controlled trial with pre-post design evaluated user acceptability and preliminary efficacy of an mHealth intervention to improve antenatal appointment attendance and its determinants among pregnant adolescent girls and young women in South Africa.

METHODS: The “Teen MomConnect” intervention entailed both fixed and 2-way tailored SMS text messages about antenatal appointment keeping and pregnancy health behaviors. The intervention content and functionality were adapted from MomConnect, a national mHealth program that sends fixed SMS text messages to pregnant women in South Africa. Pregnant adolescent girls and young women aged 13-20 years were recruited from health facilities and community networks in Cape Town during May-December 2018. Simple 1:1 randomization was used to allocate participants into the control group that received the standard MomConnect maternal health messages or the experimental group that received the Teen MomConnect intervention. A subset of experimental group participants received an in-person motivational interviewing session. Questionnaires were administered at baseline and after the end of the participants’ pregnancies. Appointment attendance data were obtained from clinic records. ANOVA, ANCOVA, and logistic regression models assessed the differences in appointments attended, awareness of HIV status, and the psychosocial determinants of antenatal attendance between the control and experimental groups.

RESULTS: Overall, 412 adolescent girls and young women were enrolled, of which 254 (62%) completed the posttest survey (64% control, 59% intervention). Patient record data were obtained for 222 of the 412 (54%; in both control and intervention) participants. A total of 84% (63/75) and 72% (54/75) rated the intervention messages highly regarding their content value and their motivational nature for behavior change, respectively. Participants responded to an average of 20% of the 2-way messages they received. Mean appointment attendance did not differ significantly between the experimental (4.86, SD 1.76) and control (4.79, SD 1.74; P=.79) groups. Appointment attendance was higher among intervention participants who responded to ≥50% of messages (“high-responders”; 5.08, SD 1.66) than intervention participants who responded to fewer messages (4.82, SD 1.79) and control participants (4.79, SD 1.74; P=.86). The mean increase in knowledge scores was significantly higher among experimental group high-responders (2.1, SD 3.17) than the control group (0.7, SD 2.73; β=1.50; P=.045).

CONCLUSIONS: Engagement with the intervention’s 2-way messaging was low, which could have impacted the outcomes. However, the intervention content was deemed acceptable. Appointment attendance did not vary significantly between the intervention and control groups. More intensive intervention may be needed to impact appointment adherence.

TRIAL REGISTRATION: Pan African Clinical Trial Registry (PACTR) PACTR201912734889796; https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=9565.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/43654.

PMID:41043139 | DOI:10.2196/59144

J Med Internet Res. 2025 Oct 3;27:e71212. doi: 10.2196/71212.

ABSTRACT

BACKGROUND: Pacific Island countries and territories (PICTs) face unique challenges in delivering health care and sustaining digital health systems. These challenges include geographically dispersed populations and service delivery points, workforce shortages, and poor infrastructure. National electronic health records (EHRs) can strengthen health systems by facilitating continuity of care but are only available in 47% of countries worldwide. The status of national EHRs in PICTs has not been previously described in the published literature.

OBJECTIVE: This study aimed to map national EHR coverage in 14 PICTs of the World Health Organization (WHO) Western Pacific Region classified as Small Island Developing States (SIDS). This included the presence or absence of a national EHR; identification of EHR software used; coverage nationally and across primary, secondary, and tertiary facilities; presence or absence of supporting digital health or health information system strategies and policies; comparison of national EHR coverage in PICTs with national EHR coverage globally; and exploration of a relationship between EHR coverage and country income in PICTs.

METHODS: Given the absence of peer-reviewed literature on EHRs in PICTs, an environmental scan methodology was selected to review gray literature sources. We conducted a 3-stage environmental scan to systematically search publicly available websites across government, bilateral, multilateral, and philanthropic organizations for documents describing the status of national EHR implementations in the aforementioned 14 PICTs.

RESULTS: Of the 14 PICTs assessed, 12 countries (86%) have an EHR implemented at some level of the public health system, and 8 (57%) have a single national system implemented at more than one facility. Although this is higher than national EHR coverage rates globally (57/122, 47%), average coverage across the 12 PICTs using EHRs was only 39% (median 16%). We also identified a positive relationship between EHR coverage and country income status and generally medium to high EHR coverage across tertiary hospitals (19/41, 46%) and secondary care facilities (29/77, 38%) but low implementation at primary care facilities (61/4158, 1.5%). EHR coverage across all facilities in the 14 countries assessed was 2.5% (108/4267). EHR software used includes Tamanu (Nauru, Palau, Samoa, Kiribati, Fiji [Aspen Medical public-private partnership hospitals]), Medtech (Cook Islands, Niue), Vesalius (Tonga), PATIS Plus (Fiji), and custom systems.

CONCLUSIONS: Our findings demonstrate, for the first time, that EHRs are being implemented in PICTs, including at scale in some settings. Despite high apparent coverage in some PICTs, the success of implementation and health worker usage remains unclear. Gray literature indicates that some EHRs currently available are failing or incapable of scaling nationally. To support sustainability of national EHRs in PICTs, governments should prioritize the implementation of fit-for-purpose, open-source, and scalable EHRs, and future studies should assess the success of EHR adoption and impact in the region.

PMID:41043138 | DOI:10.2196/71212

JMIR Aging. 2025 Oct 3;8:e73254. doi: 10.2196/73254.

ABSTRACT

BACKGROUND: Disability is a global public health challenge, with its prevalence increasing, particularly among older adults, and it exerts a profound impact on both health outcomes and mortality rates.

OBJECTIVE: This study investigates the associations between age at disability onset, severity at disability onset, and all-cause mortality in community-dwelling adults.

METHODS: We analyzed data from waves 10 to 16 (2010-2023) of the Health and Retirement Study, a nationally representative longitudinal survey of US adults aged ≥51 years. Participants without disabilities in activities of daily living (ADLs) or instrumental activities of daily living (IADLs) from the Health and Retirement Study were followed biennially until December 31, 2023. During the follow-up period, 4500 participants developed ADL disability and 4260 developed IADL disability. For each case participant, a control participant matched for age (+1 to -1 y) and sex was randomly selected. Multivariable Cox proportional hazards models were used to assess hazard ratios (HRs) for all-cause mortality among participants with new-onset disabilities, stratified by age groups and severity at disability onset.

RESULTS: Over a median follow-up duration of 8.58 years, 1709 (37.98%) deaths occurred in the ADL group and 1832 (43%) deaths occurred in the IADL group. Individuals who developed ADL disability before the age of 55 years exhibited the highest all-cause mortality risk compared to matched controls (HR 3.12, 95% CI 1.85-5.26), which further increased with severe disability (HR 4.07, 95% CI 2.03-8.19). The mortality risk was inversely associated with age at onset. A parallel trend was identified in the IADL cohort. Notably, men demonstrated a significantly elevated mortality risk compared to women, emphasizing the need for gender-specific interventions.

CONCLUSIONS: Early and severe disability onset significantly increases mortality risk, with men experiencing a disproportionately higher risk. Preventive strategies aimed at addressing early-onset and severe disability, with consideration of gender differences, are essential for improving long-term outcomes in affected populations.

PMID:41043133 | DOI:10.2196/73254

Neurology. 2025 Nov 11;105(9):e213904. doi: 10.1212/WNL.0000000000213904. Epub 2025 Oct 3.

ABSTRACT

BACKGROUND AND OBJECTIVES: Elevated levels of total tau (t-tau) are a key biomarker of neurodegeneration, often seen in Alzheimer disease (AD). Identifying individuals at increased risk of AD using minimally invasive biomarkers can enable early intervention. We developed a polygenic risk score (PRS) for plasma t-tau and examined its association with the risk for developing clinical endophenotypes of AD pathology.

METHODS: This longitudinal cohort study used data from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) study, involving individuals aged 65 years or older, free of AD, or amnestic mild cognitive impairment (aMCI-an AD prodrome) at baseline. Our primary exposure was PRStau, a PRS based on common genetic variants linked to plasma tau levels. The primary outcome was aMCI or AD incidence. We assessed the association between PRStau levels and aMCI/AD risk using Cox regression models adjusted for age, sex, education, APOE ε4 allele carriership, and population structure. We sought replication in a sample of UK Biobank (UKB) participants aged 60 years or older without prevalent dementia.

RESULTS: In the HELIAD sample, among 618 cognitively healthy participants (mean age 73.37 years, 58.4% female), followed for 2.92 ± 0.80 years, 73 developed AD/aMCI. A 1 SD increase in PRStau was linked to a 29% higher AD/aMCI risk (hazard ratio [HR] 1.290, 95% CI 1.006-1.654). Stratified analyses revealed greater effect estimates in women (HR 1.451, 95% CI 1.023-2.058) and younger participants (HR 1.866, 95% CI 1.175-2.962), whereas results in men and older participants did not reach statistical significance. In the UKB sample (n = 142,637, mean age 64.2 years, 52% female), 2,737 participants developed AD over 12.9 ± 2.4 years of follow-up. Higher PRStau was also linked to increased AD risk (HR 1.046, 95% CI 1.007-1.086).

DISCUSSION: These results support the potential utility of PRS for plasma t-tau in predicting AD/aMCI incidence. The relationship between genetic predisposition for elevated plasma t-tau levels and AD pathology might be influenced by sex and age, suggesting that these factors should be considered in AD genetic risk modeling. PRS could serve as an early indicator of genetic propensity for tau pathology, enhancing existing AD diagnostic and risk stratification algorithms.

PMID:41043097 | DOI:10.1212/WNL.0000000000213904