Category: Statistics

BMC Med. 2026 Jul 20. doi: 10.1186/s12916-026-05078-2. Online ahead of print.

ABSTRACT

INTRODUCTION: Spinal cord injury (SCI) precipitates a multiphasic secondary injury cascade that establishes a hostile, inhibitory microenvironment, rendering the condition refractory to conventional surgical stabilization and rehabilitation. While cell-based therapies offer promise for neural reconstruction, their clinical translation is impeded by protocol heterogeneity and fragmented safety data. To address this, we mapped clinical trials for SCI to quantify patient demographic parameters, identify lineage-specific adverse-event patterns, evaluate objective motor and sensory efficacy outcomes, and analyze methodological trial designs to formulate concrete structural recommendations for future advanced-phase trials.

METHODS: We analyzed clinical trials from the Web of Science Core Collection (SCIE and ESCI) published since 2005. The dataset comprised 116 eligible studies involving patients with SCI receiving cellular therapies with reported safety outcomes. We employed a dual-method approach combining manual extraction of clinical characteristics (demographics, interventions, adverse events, efficacy outcomes) with quantitative data analysis. Statistical associations between therapeutic variables (cell type, route, dosage) and safety profiles were evaluated using Fisher’s exact test.

RESULTS: The clinical landscape is predominantly defined by early-phase (Phase 1: 59.5%), single-arm investigations (63.8%) utilizing autologous bone marrow-derived cells. Reflecting a cautious paradigm to minimize severe complications, patient selection frequently targeted the hemodynamically stable chronic phase (58.3%) and thoracic SCI (21.6%). Safety analyses revealed lineage-specific profiles: mesenchymal stromal cells were significantly associated with transient fever (P = 0.038), whereas intrathecal administration correlated with procedural symptoms such as headache (P < 0.001). The observation of higher systemic adverse event rates in low-dose cohorts was likely confounded by the mandatory concurrent immunosuppressive regimens required for specific allogeneic lineages, rather than the absolute cell dose. Regarding therapeutic efficacy, outcomes were critically influenced by the chronological phase of injury. Patients treated in the acute or subacute phases exhibited higher rates of neurological improvement, though distinguishing this from spontaneous recovery remains challenging, whereas chronic phase interventions demonstrated more limited primary sensorimotor gains. Additionally, intrathecal administration showed an advantage in preserving sensory pathways due to minimized structural disruption, while dose requirements could not be generalized and varied fundamentally based on specific cellular mechanisms of action.

DISCUSSION: While the baseline safety of cellular transplantation for spinal cord injury is established, clinical translation remains hindered by methodological heterogeneity, imprecise patient stratification, and a reliance on single-arm trial designs. To navigate this translational bottleneck, future investigations should adopt multi-tiered methodological frameworks. First, study designs should transition toward controlled protocols, utilizing crossover designs for chronic cohorts and matched historical or synthetic controls for acute and subacute phases. Concurrently, patient selection must evolve from broad clinical grading to advanced stratification. Integrating biomarkers, electrophysiology, and imaging to objectively quantify tissue sparing can better identify responsive subgroups, thereby improving trial efficiency and accelerating clinical translation. Beyond cohort refinement, intervention parameters, specifically dosage and delivery routes, should be individualized according to cell lineage, as adverse events associate more with intrinsic cellular biology and procedural invasiveness. Furthermore, isolating the true therapeutic effect requires the standardization and reporting of confounding variables, such as immunosuppressive regimens and physical rehabilitation. Finally, by separating shorter-term efficacy measurements from long-term safety registries, the field can facilitate a more reliable and objective clinical translation.

PMID:42477724 | DOI:10.1186/s12916-026-05078-2

BMC Womens Health. 2026 Jul 20. doi: 10.1186/s12905-026-04716-4. Online ahead of print.

ABSTRACT

BACKGROUND: Benign uterine disorders, including uterine leiomyomas and uterine endometriosis/adenomyosis-related conditions, are common causes of gynecologic morbidity and represent an important women’s health issue. Although these conditions are generally non-malignant, a subset of hospitalizations may involve substantial anemia-related clinical burden. Evidence describing severe inpatient anemia, red cell product ordering, intensive care unit (ICU) use, and short-term hospital outcomes in this population remains limited.

METHODS: We conducted a retrospective cohort study using hospital data from the Medical Information Mart for Intensive Care IV (MIMIC-IV). Adult female hospitalizations with diagnostic codes related to benign uterine disorders were identified. Hospitalizations with missing hemoglobin data, pregnancy- or obstetric-related diagnoses, and gynecologic malignancy-related diagnoses were excluded. The unit of analysis was hospitalization. Severe anemia was defined as a minimum inpatient hemoglobin level < 8 g/dL during hospitalization. The main outcome was red cell product ordering identified from Blood Bank provider order entry records, which was interpreted as a transfusion-related resource use indicator rather than confirmed red cell administration. Additional hospital burden outcomes included hospital length of stay, ICU admission during hospitalization, in-hospital mortality, and gynecologic procedure-related outcomes. Multivariable logistic regression was used to evaluate the association of severe anemia with red cell product ordering and ICU admission. Models were adjusted for age, race/ethnicity, insurance status, marital status, admission type, and disease group. Sensitivity analyses used hemoglobin < 10 g/dL as an alternative anemia threshold.

RESULTS: The final cohort included 1,860 non-obstetric, non-malignant hospitalizations with available hemoglobin data. Severe anemia was present in 425 hospitalizations (22.8%). Compared with hospitalizations without severe anemia, those with severe anemia had a higher proportion of red cell product orders (63.29% vs. 5.09%), longer hospital length of stay [3.436 (1.911-6.389) vs. 2.310 (1.335-3.816) days], and more frequent ICU admission during hospitalization (15.06% vs. 6.13%). In-hospital mortality was uncommon overall and was analyzed only exploratorily. After multivariable adjustment, severe anemia was associated with red cell product ordering [adjusted odds ratio (OR) 33.61, 95% confidence interval (CI) 24.23-47.29] and ICU admission during hospitalization (adjusted OR 2.69, 95% CI 1.84-3.91). In the fibroid-only subgroup, the corresponding adjusted ORs were 35.55 (95% CI 24.96-50.64) for red cell product ordering and 2.68 (95% CI 1.83-3.92) for ICU admission. Sensitivity analyses using hemoglobin < 10 g/dL showed directionally consistent findings. Additional sensitivity analyses using earlier hemoglobin definitions showed that early 24-hour Hb < 8 g/dL remained strongly associated with red cell product ordering (adjusted OR 22.57, 95% CI 15.54-32.80), whereas the corresponding ICU admission estimate was attenuated and not statistically significant (adjusted OR 1.09, 95% CI 0.66-1.80).

CONCLUSIONS: Among women hospitalized with benign uterine disorders, severe inpatient anemia was common and was associated with greater red cell product ordering and higher hospital resource use. These findings suggest that severe inpatient anemia may serve as a practical marker of anemia-related hospital burden in this defined hospitalized population, while ICU-related findings and causal interpretation require caution.

PMID:42477721 | DOI:10.1186/s12905-026-04716-4

BMC Womens Health. 2026 Jul 20. doi: 10.1186/s12905-026-04698-3. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: We compared the outcomes of complete pelvic lymph node dissection performed via multiport conventional laparoscopy (MCL) versus vaginal natural orifice transluminal endoscopic surgery (vNOTES) in patients with endometrial cancer in whom sentinel lymph node (SLN) mapping was unsuccessful.

METHODS: This retrospective cohort study included 42 patients with grade I or II endometrioid endometrial cancer who underwent hysterectomy with bilateral salpingo-oophorectomy, followed by comprehensive retroperitoneal pelvic lymphadenectomy after failed bilateral SLN mapping. Patients underwent either vNOTES (n = 21) or MCL (n = 21). Demographic characteristics, operative times, perioperative and postoperative complications, pain scores, and quality of recovery-15 (QoR-15) scores were collected and compared between the two groups.

RESULTS: Demographic and clinical characteristics were comparable between the two groups, with no statistically significant differences. Operative times were significantly longer in the vNOTES group (53.8 ± 7.4 min) compared to the MCL group (46.9 ± 9.2 min; P = 0.01), whereas estimated blood loss (17.7 ± 5.6 mL vs. 18.8 ± 5.0 mL; P = 0.50) and lymph node yield (32.1 ± 6.6 vs. 35.0 ± 8.1; P = 0.21) did not differ significantly. Postoperative pain assessed by visual analogue scale (VAS) was lower in the vNOTES group at 6 h (4.3 ± 1.1 vs. 5.5 ± 1.0; P = 0.01), 12 h (3.5 ± 0.8 vs. 4.8 ± 1.1; P < 0.001), and 24 h (2.1 ± 0.6 vs. 3.1 ± 0.9; P < 0.001). These findings were corroborated by the faces pain scale-revised (FPS-R), which demonstrated significantly lower pain in the vNOTES group at all time points. QoR-15 scores at 48 h were higher in the vNOTES group (109.3 ± 4.7 vs. 104.9 ± 4.1; P = 0.002), indicating improved postoperative recovery. The observed mean difference of approximately 4.4 points remained below the reported minimal clinically important difference of 8.0 points for this instrument, indicating that the statistically significant benefit should be interpreted with caution regarding its clinical magnitude.

CONCLUSION: vNOTES for complete pelvic lymphadenectomy offers reduced postoperative pain, scar-free surgery, and enhanced recovery while maintaining staging adequacy comparable to MCL. Future prospective, multicentre, randomised trials with long-term oncologic follow-up are required to validate these findings.

PMID:42477715 | DOI:10.1186/s12905-026-04698-3

BMC Womens Health. 2026 Jul 20. doi: 10.1186/s12905-026-04714-6. Online ahead of print.

ABSTRACT

BACKGROUND: To investigate whether vaginal dysbiosis is associated with an increased risk of cervical lesions infected with non-16/18 high-risk human papillomavirus (HR-HPV) genotypes and to inform risk-stratified cervical cancer screening strategies.

METHODS: This cross‑sectional study included 2,264 women attending Jiaxing Maternal and Child Health Hospital between June 2023 and October 2024. HPV genotyping, vaginal microecological assessment, and Thinprep cytologic test (TCT) were performed. HR- HR-HPV infections were classified as HPV16/18-positive or non-16/18 HR-HPV infections. Logistic regression models were used to evaluate associations, adjusting for age. Multiplicative interaction was assessed using Wald tests for product terms. Benjamini‑Hochberg FDR correction was applied for multiple comparisons.

RESULTS: The overall HPV prevalence was 49.87%, with HR-HPV detected in 36.13%. HR‑HPV infection was significantly associated with cervical lesions in both normal (OR = 11.45) and dysbiotic (OR = 4.40) vaginal microbiota (both P < 0.001). Stratified analyses showed higher point estimates for HPV58 and HPV59 in the dysbiosis group (OR = 10.98 and 9.51, respectively) than in the normal group (OR = 7.50 and 6.44, respectively). However, formal multiplicative interaction tests did not reach statistical significance (Wald P = 0.526 and 0.559, respectively; FDR‑adjusted q = 0.559 for both). No HPV subtype remained significantly associated with ASC‑US after FDR correction.

CONCLUSIONS: In this cross‑sectional study, vaginal dysbiosis is specifically associated with cervical lesions among women with non‑16/18 HR‑HPV infections, particularly HPV58 and HPV59, which showed elevated point estimates in the presence of dysbiosis. However, formal multiplicative interaction tests did not reach statistical significance. These findings are exploratory and hypothesis‑generating; causality cannot be inferred due to the cross‑sectional design. Prospective studies are needed to validate the observed associations before any clinical application can be considered. Our results should be interpreted with caution and do not support changes to current screening practice.

PMID:42477712 | DOI:10.1186/s12905-026-04714-6

BMC Med. 2026 Jul 20. doi: 10.1186/s12916-026-05018-0. Online ahead of print.

ABSTRACT

BACKGROUND: The development of second primary cancers (SPCs) has become an important late effect in gastric cancer (GC) survivors, yet its incidence, risk factors, and clinical implications remain poorly defined. This study aimed to evaluate the long-term risk of SPCs, identify clinical factors associated with SPC occurrence, and describe detection patterns and stage distribution of SPCs during long-term follow-up.

METHODS: Patients with GC who underwent curative-intent radical gastrectomy between 2007 and 2021 were identified from the Multidisciplinary Alliance of Gastric Integrative Studies (MAGIS) cohort. Clinical factors associated with SPC occurrence were selected using LASSO-penalized Cox regression, and exploratory risk-based stratification was performed. Stage distribution was descriptively compared between SPCs detected during asymptomatic surveillance and those diagnosed after symptom onset.

RESULTS: Among 11,027 GC survivors (8,519 men and 2,508 women), 241 (2.19%) developed SPCs during a follow-up of up to 16 years. The cumulative incidence of SPCs was 1.25% (95% CI, 1.03%-1.46%) at 5 years, 2.97% (95% CI, 2.55%-3.39%) at 10 years, and 4.15% (95% CI, 3.40%-4.91%) at 15 years after gastrectomy. The most frequent SPCs were lung (23.2%), colorectal (21.6%), and esophageal (12.9%) cancers, showing marked sex-specific differences: lung cancer predominated in males, whereas cervical cancer was most common in females. Factors associated with SPC occurrence included older age at time of gastrectomy (HR 1.04, 95% CI 1.02-1.05; p < 0.001), chronic HBV/HCV infection (HR 2.15, 95% CI 1.29-3.58; p = 0.003), family history of cancer (HR 1.57, 95% CI 1.16-2.12; p = 0.003), and elevated preoperative systemic inflammation (Log-SIRI; HR 1.86, 95% CI 1.31-2.65; p < 0.001). The derived model stratified patients into low-, intermediate-, and high-risk groups with corresponding 10-year SPC risks of 2.07%, 3.61%, and 4.33%. SPCs detected during asymptomatic surveillance were more frequently diagnosed at stage I than those identified after symptom onset (47.4% vs 17.6%; p < 0.001).

CONCLUSIONS: SPCs represent an important long-term health burden among GC survivors, with distinct sex-specific disease patterns. The exploratory risk-scoring model showed preliminary risk stratification, and SPCs detected during asymptomatic surveillance were more often diagnosed at an earlier stage. These findings support further evaluation of risk-adapted, organ- and sex-specific surveillance strategies in methodologically rigorous studies.

PMID:42477705 | DOI:10.1186/s12916-026-05018-0

BMC Public Health. 2026 Jul 20. doi: 10.1186/s12889-026-28633-1. Online ahead of print.

ABSTRACT

BACKGROUND: Vaccine-preventable diseases (VPDs) continue to impose a significant health and economic burden globally, despite advances in immunization programs. Narrower to the context of Saudi Arabia, the current literature consistently shows that the high vaccination coverage has had the primary impact of reducing disease incidence. Regardless, the broader economic impact of VPDs and the financial benefits of immunization remain important for policy evaluation within Saudi Arabia.

METHODS: This study employed a model-based economic evaluation using a societal perspective in order to carry out an estimation of the economic burden of measles, influenza, and pneumococcal diseases. We utilized the Cost of Illness (COI) approach for the purpose of quantifying direct medical costs and indirect productivity losses. On the other hand, the Value of Statistical Life (VSL) approach helped in the estimation of the monetary value of mortality reduction. A comparative framework analyzed current vaccination coverage against a counterfactual no-vaccination scenario for the calculation of the return on investment (ROI).

RESULTS: The estimated annual economic burden of the three selected VPDs in the absence of vaccination was USD 385 (95% CI: 315-460) million. Immunization programs generated substantial economic benefits, with total benefits estimated at USD 1085 (95% CI: 815-1360) million annually. The calculated ROI was 9.85 (95% CI: 6.8-11.3), essentially an indication that for each dollar invested in vaccination, there was multiple economic returns yielded. Sensitivity analyses confirmed the robustness of these findings.

CONCLUSION: Immunization programs in Saudi Arabia provide significant economic and public health benefits and for this reason, sustained investment in vaccination is fundamentally essential towards the reduction of disease burden, improve population health, and ultimately support long-term economic productivity.

PMID:42477699 | DOI:10.1186/s12889-026-28633-1

BMC Oral Health. 2026 Jul 21. doi: 10.1186/s12903-026-09361-9. Online ahead of print.

ABSTRACT

BACKGROUND: Endodontic treatment is fundamental to preserving teeth affected by pulpal and periapical diseases. Robust evidence on treatment outcomes and their determinants is essential for optimizing clinical practice, yet data from sub-Saharan Africa remain scarce. This study assessed the prevalence, clinical and radiographic outcomes, and determinants of endodontic treatment success and failure among patients treated at Jimma Medical Center (JMC), Ethiopia.

METHODS: An ambispective single-cohort study was conducted among a sample of 404 patients who received endodontic treatment at JMC from September 1, 2025, to November 30, 2025. Data were collected on socio-demographics, preoperative clinical and radiographic characteristics, procedural details, and patient-reported outcomes. Clinical and radiographic success was assessed using the Periapical Index (PAI) and symptom resolution. Logistic regression analyses were performed to identify determinants of treatment outcomes, with adjusted odds ratios (AORs) and 95% confidence intervals (CIs) estimated, and statistical significance set at p < 0.05.

RESULTS: The majority of participants were aged 25-44 years (49.6%) and female (55.8%), with an overall treatment success rate of 84.2%. Most teeth were non-vital (96.4%) and presented with symptomatic pulpitis or apical periodontitis. Irrigation was primarily performed with saline (85.2%), and optimal obturation quality was achieved in 90.1% of cases. At follow-up, 84.2% of teeth were classified as successful, defined as absence of symptoms and PAI ≤ 2, while 15.8% failed. The most frequent causes of failure were persistent infection (42.6%) and coronal leakage (41.0%). Patient-reported outcomes indicated high satisfaction, with 89.1% of patients reporting satisfaction and 73.0% reporting complete absence of pain post-treatment. Multivariable logistic regression analysis identified several independent determinants of treatment success. Male patients had 2.86 times higher odds of treatment success than female patients (AOR = 2.86, 95% CI: 1.98-3.53; p < 0.04). Conversely, symptomatic periapical lesions or abscesses were associated with 43% lower odds of treatment success (AOR = 0.57, 95% CI: 0.05-0.86; p < 0.03). Similarly, the use of saline as the primary irrigant was associated with 54% lower odds of treatment success than H₂O₂ alone or saline combined with H₂O₂ (AOR = 0.46, 95% CI: 0.21-0.91; p < 0.04). In addition, a temporary or inadequate coronal seal at treatment completion was associated with 62% lower odds of treatment success than a composite restoration or crown (AOR = 0.38, 95% CI: 0.16-0.88; p < 0.02).

CONCLUSION: Endodontic treatment at JMC demonstrates a high success rate, with most teeth showing favorable clinical, radiographic, and patient-reported outcomes. Male gender, preoperative periapical pathology, type of primary irrigant, and coronal restoration quality were significant determinants of treatment outcome. These findings underscore the importance of meticulous procedural protocols and proper coronal sealing to enhance treatment success.

PMID:42477696 | DOI:10.1186/s12903-026-09361-9

BMC Med Educ. 2026 Jul 20. doi: 10.1186/s12909-026-09925-x. Online ahead of print.

ABSTRACT

BACKGROUND: Nursing assistants (NAs) are a key occupational group that provide daily living care and nursing support across medical and integrated healthcare settings. NAs have been introduced to alleviate nursing shortages and better meet patients’ care needs. In many countries, mandatory pre-employment training programs are tailored to the NAs’ role. However, China lacks a standardized pre-service training program, leading to fragmented content and variable training quality. In response to national policy priorities, this study aims to develop a standardized pre-service training program for NAs in China.

METHODS: A modified Delphi method and the Analytic Hierarchy Process (AHP) were used to establish a competency-based pre-service training program, guided by the Competency Iceberg Model, from June to October 2022. An expert panel (n = 12) from nine tertiary hospitals across eight provinces participated in two rounds of Delphi consultations to reach consensus on program content. Expert agreement was evaluated using consensus levels and Kendall’s W coefficient.

RESULTS: The final training program comprises a three-level framework with three first-level indicators, 25 s-level indicators, and 100 third-level indicators, encompassing both practical care competencies and latent professional competencies. Expert consensus was achieved across all hierarchical indicators. Kendall’s W values for the second- and third-level indicators were 0.222 and 0.179, respectively, both of which were statistically significant (p < 0.001). The AHP results assigned the highest priority to skills (0.50), followed by professionalism (0.25) and knowledge (0.25). Within these domains, practical care skills, including mobility care, sputum management, and latent competencies, including emotional management and communication, received the highest priority weightings. These weightings can provide an evidence-informed rationale for prioritising training content, allocating instructional time, and further guiding practical implementation.

CONCLUSION: This study established a structured, competency-based pre-service training program for NAs by integrating expert consensus with quantitative prioritization. The program provides a holistic framework and evidence-informed basis for developing NAs training and standardizing pre-service training in Chinese healthcare settings. Future research should examine its feasibility, effectiveness, and implementation across diverse clinical contexts.

PMID:42477695 | DOI:10.1186/s12909-026-09925-x

BioData Min. 2026 Jul 20. doi: 10.1186/s13040-026-00584-8. Online ahead of print.

ABSTRACT

The advent of high-throughput sequencing technologies has generated increasingly large and complex genomic datasets, necessitating analytical approaches capable of capturing high-dimensional and potentially nonlinear genetic interactions. This situation has significantly impacted the entire field of Genome-Wide Association Study (GWAS), whose primary goal is the identification of genomic traits and variants that are statistically associated with the risk of a disease. However, traditional GWAS methods may show reduced performance when applied to highly polygenic and nonlinear genetic architectures. Computational strategies from Artificial Intelligence (AI) and, in particular, from machine- and deep-learning may provide a powerful tool to overcome such limitations, especially by capturing nonlinear interactions and complex hidden regularities in large-scale data, which traditional GWAS approaches might overlook. To date, only a few approaches have been introduced and systematically assessed. In this review, we describe the main characteristics and limitations of standard statistical approaches for GWAS, the main uses of AI methods in computational genomics, and recent attempts to leverage AI strategies in GWAS. Particular attention will be devoted to key issues, such as the interpretability of methods and results, and the curse of dimensionality. More specifically, the review presents 30 methods designed to leverage AI in GWAS, as well as presenting a comprehensive set of evaluation metrics for their performance, also providing references to the most frequently used databases, and biobanks. Overall, this work may serve as a starting point for both dry- and wet-lab researchers, aiming to extract deeper insights from genomic data by moving beyond traditional linear additive assumptions, and leveraging large-scale datasets through AI-driven approaches.

PMID:42477691 | DOI:10.1186/s13040-026-00584-8

BMC Musculoskelet Disord. 2026 Jul 20. doi: 10.1186/s12891-026-10257-6. Online ahead of print.

ABSTRACT

BACKGROUND: Hip dysplasia (HD) is a known risk factor for early morbidity in the young adult hip. HD causes a variety of pathologic changes to the hip through an asymmetrical distribution of forces. Periacetabular osteotomy (PAO) is becoming increasingly recognized as a treatment. Labral tears occur frequently in the setting of HD and there still remain questions regarding the best treatment practices for labral pathology. We sought to determine whether intraoperative labral tear size was associated with short-term patient-reported outcomes following concomitant hip arthroscopy and PAO.

METHODS: Seventy-one hips that underwent PAO with concomitant hip arthroscopy at our tertiary care hip center from February 2017 to June 2021 who had PROM follow-up time of more than one year were investigated (88.7% women and 11.3% men with mean patient age of 29.5 years). Labral tear sizes were recorded intraoperatively and sorted into three groups: < 5 mm, 5 – 10 mm, and > 10 mm. HOOS scores were collected pre- and postoperatively and were compared across the three labral tear size groups. The association between labral tear size and postoperative HOOS was evaluated while accounting for preoperative HOOS, age, sex, and BMI. The mean follow-up time was 1.57 years ± 250 days.

RESULTS: Across all patients, the mean preoperative HOOS was 66.9 ± 14.5, and the mean postoperative HOOS was 77.8 ± 16.3. Statistically significant improvement was observed in the <5 mm and 5-10 mm groups (p<0.001) but not in the >10 mm group (p=0.310). Mean postoperative HOOS values in the <5 mm, 5-10mm, and >10 mm labral tear groups were 84.3 ± 13.7, 76.9 ± 16.6, and 69.2 ± 16.1, respectively. Larger labral tear size was associated with worse postoperative HOOS (p=0.004).

CONCLUSION: Among patients undergoing concomitant hip arthroscopy and PAO, larger intraoperative labral tear size was associated with worse short-term postoperative HOOS. However, larger labral tears were also associated with older age and worse markers of intra-articular disease, suggesting that tear size may reflect more advanced disease rather than independently determine outcome.

PMID:42477690 | DOI:10.1186/s12891-026-10257-6