Category: Statistics

Ther Innov Regul Sci. 2026 Apr 30. doi: 10.1007/s43441-026-00974-4. Online ahead of print.

ABSTRACT

BACKGROUND: The U.S. Food and Drug Administration conducts Good Clinical Practice (GCP) assessments and provides recommendations through Clinical Inspection Summary (CIS) reports to inform marketing application reviews. Despite their integral role in regulatory oversight, the characteristics of GCP assessments and recommendations have not been comprehensively evaluated.

METHODS: This 10-year retrospective descriptive study analyzed CIS reports supporting marketing applications from 2015 to 2024. Data were extracted from FDA internal databases and analyzed. CIS reports were categorized into Tier 1-3, a framework developed by the authors for this study. In Tiers 1 and 2, data were recommended as acceptable to support the marketing application. In Tier 3, specific actions were recommended to address data quality issues.

RESULTS: The analysis included 1,200 CIS reports supporting regulatory review of predominantly New Drug Applications (69.9%) and Biologics License Applications (29.9%), with 68.0% supporting original submissions. The most frequent recommendation tier was Tier 1 (69.5%), followed by Tier 3 (22.5%), and Tier 2 (8.0%). Within Tier 3, most CIS reports contained a single type of recommended action (66.7%), and the most common recommended actions involved requesting additional information (32.8%), conducting additional statistical analyses (28.3%), and incorporating updated data (24.8%).

CONCLUSIONS: GCP oversight largely supported data acceptability for marketing applications, with specific actions recommended to address data quality issues, underscoring its critical role in ensuring reliable clinical data.

PMID:42062756 | DOI:10.1007/s43441-026-00974-4

Odontology. 2026 Apr 30. doi: 10.1007/s10266-026-01397-1. Online ahead of print.

ABSTRACT

The aim of the study was to compare the clinical efficacy of Platelet Lysate (PL) versus Hyaluronic Acid (HA) after arthrocentesis in the management of patients with anterior disc displacement with reduction. This randomized clinical trial was conducted on 60 patients (17 males and 43 females) with anterior disc displacement with reduction confirmed with magnetic resonance imaging (MRI). The patients were split into two equal groups at random based on the type of treatment that was used. Group 1: arthrocentesis plus PL, Group 2 arthrocentesis plus HA. The pain intensity, clicking sound, maximum inter-incisal opening (MIO) and range of lateral mandibular excursions were measured. All the measured parameters were statistically analyzed. After 6 months, both groups demonstrated a significant improvement in all the parameters that were measured. The PL Group showed a statistically better resolution of clicking compared to HA Group with an Absolute Risk Difference of 33.3% (P < 0.05). The MIO between-group difference was 4.867 mm (P < 0.001), so exceeding the Minimum Clinically Important Difference (MCID). On the other hand, although the PL Group demonstrated statistical superiority in pain scores and range of lateral mandibular excursions (P < 0.05), the clinical magnitude of the between-group difference was modest. PL appears to be a safe and effective adjunctive intra-articular therapy after arthrocentesis for the management of patients with anterior disc displacement with reduction. It provides a clinical advantage over HA in resolving joint clicking and improving MIO. For pain reduction and range of lateral mandibular excursions, the therapeutic benefits of PL and HA are clinically comparable. Trial registration: On 4/12/2024, it was registered in Clinical-Trials.gov PRS ( https://register.clinicaltrials.gov ) with identification number NCT06441279.

PMID:42062696 | DOI:10.1007/s10266-026-01397-1

Curr Environ Health Rep. 2026 May 1;13(1):20. doi: 10.1007/s40572-026-00538-6.

ABSTRACT

PURPOSE OF REVIEW: Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) have been linked to environmental exposures, yet the underlying neurobiological mechanisms remain poorly understood. Magnetic resonance imaging (MRI) offers an important in vivo tool for examining how environmental neurotoxicants impact brain development. This scoping review synthesizes current evidence on the associations between air pollution, metals, environmental tobacco smoke, and endocrine-disrupting chemicals (EDCs) assessed from pregnancy through childhood and neuroimaging findings in children diagnosed with NDDs.

RECENT FINDINGS: We identified 14 studies examining associations between environmental exposures and MRI outcomes in children with NDDs. Air pollution exposure was linked to reduced volumes in the caudate nucleus and corpus callosum. Metal exposure was associated with changes in cortical thickness and functional connectivity, varying by metal and diagnosis. Tobacco smoke exposure correlated with reduced volumes in the cerebellum and frontal cortex and disruptions in white matter and neural networks. EDCs were linked to cortical thinning and altered task-related brain activity, with some studies reporting associations with symptom severity among children with ADHD. Overall, the literature suggests that exposure to neurotoxicants may disrupt brain development in children with NDDs. Future research should prioritize longitudinal, transdiagnostic designs with repeated exposure assessments and multimodal imaging, as well as advanced statistical modeling, to better capture the complex relationships between exposure and outcome. These findings underscore the importance of public health interventions to mitigate exposure to neurotoxicants and minimize potential neurodevelopmental risks.

PMID:42062691 | DOI:10.1007/s40572-026-00538-6

Methods Mol Biol. 2026;2995:119-127. doi: 10.1007/978-1-0716-5027-1_8.

ABSTRACT

Understanding complex diseases such as cancer requires insight into both the intrinsic properties of individual cells and their interactions within the tumor microenvironment. Integrating single-cell RNA sequencing (scRNA-seq), which captures transcriptional states, with spatial proteomics, which provides spatially resolved protein expression data, offers a powerful opportunity to unravel disease mechanisms. In this protocol, we describe a framework that unifies scRNA-seq and spatial proteomics into a joint graph-based representation. This approach enables accurate prediction of disease pathologies and reveals critical cell-cell interactions that drive disease progression.

PMID:42062682 | DOI:10.1007/978-1-0716-5027-1_8

Spine Deform. 2026 Apr 30. doi: 10.1007/s43390-026-01383-1. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate pelvic incidence (PI) as a reliable parameter for analysing sagittal profiles in patients with adolescent idiopathic scoliosis (AIS).

METHODS: This retrospective cohort study included 100 patients with AIS (aged 12-17 years) who underwent posterior spinal deformity correction and had a 2-year follow-up. Radiographic parameters-Pelvic Incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), thoracic kyphosis (TK), sagittal vertical axis (SVA), and T1 pelvic angle (TPA)-were evaluated preoperatively, at 6 months, and at 2 years postoperatively. Sagittal profiles were classified using the theoretical Roussouly system. Statistical analysis used repeated-measures ANOVA with Tukey HSD post hoc testing to assess temporal variability and Pearson correlation coefficients to assess associations between pelvic and spinal parameters.

RESULTS: The mean age was 13.3 years, with females comprising 66% of the cohort; Lenke type 5 was the most common curve type. Roussouly type 3 predominated at all time points. Pelvic parameters (PI and SS) remained stable (p > 0.1), whereas spinal parameters showed significant changes in LL (p = 0.000) and TK (p = 0.001). Global alignment shifted in SVA (p = 0.014), while TPA remained unchanged (p > 0.3). PI consistently correlated with PT (r = 0.60), SS (r = 0.64), and LL (r = – 0.55) across intervals.

CONCLUSION: PI showed minimal temporal variability, confirming its reliability as a morphological parameter in AIS. These findings support the role of PI in sagittal alignment assessment and reinforce the applicability of the Roussouly classification in AIS patients.

PMID:42062673 | DOI:10.1007/s43390-026-01383-1

Oncol Ther. 2026 Apr 30. doi: 10.1007/s40487-026-00436-9. Online ahead of print.

ABSTRACT

INTRODUCTION: Laryngeal cancer (LC) constitutes almost one third of the head and neck cancers, and its main risk factors, alcohol use and smoking, are well established. Our aim was to explore the variation in the incidence of LC between different occupations.

METHODS: This study was based on data from the Nordic Occupational Cancer Study (NOCCA), involving 14.9 million individuals from Denmark, Finland, Iceland, Norway, and Sweden. Occupational data from censuses were linked to cancer registry data from a period of up to 45 years (21,166 LC diagnoses) using personal identity codes. Standardized incidence ratios (SIRs) were calculated for different occupations, using the respective national populations as a reference.

RESULTS: Of the 21,166 patients with LC, 18,488 (87%) were men. The highest SIRs in men were noted among waiters (3.31, 95% confidence interval [CI] 2.69-4.02), beverage workers (2.51, 95% CI 1.91-3.24), and cooks and stewards (2.25, 95% CI 1.82-2.74). Among women, the highest SIRs were observed among building hands (7.37, 95% CI 3.53-13.55) and public safety workers (3.60, 95% CI 1.17-8.40). Farming and teaching occupations showed reduced SIRs in both sexes. The SIRs among male farmers, teachers, gardeners, and technical workers were reduced in all countries. The SIRs remained elevated and stable among cooks and stewards, waiters, packers, seamen, sales agents, and economically inactive males across the three 15-year periods from 1961 to 2005.

CONCLUSION: The study confirms a major variation in the incidence of LC between occupations. The findings underscore the importance of considering lifestyle factors typical of each occupation in cancer risk assessments and the potential benefits of targeted prevention efforts.

PMID:42062661 | DOI:10.1007/s40487-026-00436-9

Curr Environ Health Rep. 2026 May 1;13(1):19. doi: 10.1007/s40572-026-00536-8.

ABSTRACT

PURPOSE OF REVIEW: Exposure to endocrine disrupting chemicals (EDC) is linked to numerous adverse health outcomes. However, limiting exposure to EDCs remains a significant challenge due to their widespread uses and persistence in the environment. Adequate micronutrient status supports optimal health and may offer actionable strategies for mitigating the adverse health effects of EDCs. This scoping review aimed to summarize the epidemiologic evidence on micronutrients as potential mitigators of EDC-related health outcomes, with the goal of guiding future research and methodologies.

RECENT FINDINGS: We identified 71 epidemiologic studies assessing micronutrients as mitigators of EDC-outcome relations, focused primarily on exposures during pregnancy (n = 34). Most studies examined phthalates and/or environmental phenols (n = 25), per- and polyfluoroalkyl substances (n = 15), polycyclic aromatic hydrocarbons (n = 10), and self-reported pesticide exposure (n = 6). Most studies suggested higher levels of some micronutrients attenuated adverse associations of EDCs with some health outcomes, particularly iodine (thyroid hormones); folic acid (fertility, birth outcomes, neurodevelopment); vitamin D (lung function, neurodevelopment); and antioxidants (birth outcomes, aging, metabolic health). However, included studies assessed a wide range of micronutrients, EDCs, and outcomes, with limited overlap across studies. This scoping review identified few topics with substantial evidence to warrant focused systematic reviews, suggesting that additional prospective research is needed, especially in at-risk populations and sensitive periods outside of pregnancy. Future epidemiologic research should consider the co-occurrence of EDCs and micronutrients in foods and include multiple methods for assessing micronutrients. Finally, to strengthen causal inference, future research should thoughtfully model potential confounding, mediation, effect measure modification, and/or statistical interaction.

PMID:42062659 | DOI:10.1007/s40572-026-00536-8

CNS Drugs. 2026 Apr 30. doi: 10.1007/s40263-026-01293-w. Online ahead of print.

ABSTRACT

BACKGROUND: Augmentation of collateral circulation is an alternative method to improve cerebral hypoperfusion when revascularization is not suitable. DL-3-n-butylphthalide (NBP) has been shown to enhance cerebral collateral circulation and improve cerebral blood flow (CBF) in previous studies. The objective of this study was to explore the effect of NBP on cerebral hemodynamic impairment due to atherosclerotic stenosis in internal carotid system.

METHODS: This was a double-blind, placebo-controlled, randomized clinical trial conducted in 38 Chinese hospitals between 14 January 2022, and 11 April 2024. Eligible participants were aged 35-85 years with ≥ 70% stenosis in unilateral internal carotid artery or middle cerebral artery, accompanied by cerebral hypoperfusion and no recent cerebral ischemic events. The patients were randomly assigned in a 1:1 ratio to a treatment group receiving 600 mg NBP daily or a placebo group receiving an ineffective dose of NBP daily for 4 weeks. The cerebral perfusion was assessed by computed tomography perfusion. The grades of cerebral perfusion change from baseline to 12 weeks were classified into amelioration, stabilization, and deterioration. The primary efficacy outcome was the percentage of patients achieving CBF amelioration.

RESULTS: Of 485 enrolled patients (median age 63 years, 66.6% men), 244 were assigned to the NBP group and 241 to the placebo group. At the end of follow-up, 204 in the NBP group and 212 in the placebo group completed second cerebral perfusion. NBP group had 113 (55.4%) patients with CBF amelioration in stenotic territory and placebo group had 93 (43.9%) comparable patients at 12 weeks (risk ratio 1.32; 95% confidence interval 1.08-1.61; p = 0.006).

CONCLUSIONS: For cerebral hypoperfusion from atherosclerotic stenosis in internal carotid system, NBP treatment resulted in a higher proportion of patients achieving CBF amelioration than placebo.

TRIAL REGISTRATION: chictr.org.cn: ChiCTR2100053112.

PMID:42062656 | DOI:10.1007/s40263-026-01293-w

Cardiovasc Intervent Radiol. 2026 Apr 30. doi: 10.1007/s00270-026-04452-0. Online ahead of print.

ABSTRACT

BACKGROUND: Endovascular options for infrapopliteal artery disease include plain balloon angioplasty (PTA), drug‑coated balloons (DCB), drug‑eluting and bare‑metal stents (DES), and atherectomy. Retrievable scaffold therapy (RST) has recently emerged as a temporary scaffolding strategy used with DCB, but its comparative effectiveness remains uncertain.

METHODS: A comprehensive literature search identified 21 randomized and 4 single‑arm trials (n = 3184). Eligible studies reported at least one prespecified outcome: 30‑day major adverse events (MAE), 12‑month all‑cause mortality, 6‑month clinically driven target lesion revascularization (CD‑TLR), or 6‑month major amputation. Random‑effects models generated odds ratios (ORs) with 95% credible intervals (CrIs). SUCRA values summarized treatment rankings.

RESULTS: Atherectomy ranked best for 30‑day MAE (SUCRA 77.2%), though no treatment yielded a statistically significant reduction in the Odds Ratio. It was also associated with a significantly reduced 12‑month mortality versus PTA (OR 0.39, 95% CrI 0.15-0.90; SUCRA 97.8%). For 6‑month CD‑TLR, atherectomy (OR 0.26, 95% CrI 0.00-0.62), DCB (OR 0.42, 95% CrI 0.30-0.58), and DES (OR 0.43, 95% CrI 0.19-0.88) showed significant benefit. No treatment significantly reduced major amputation. RST showed favorable but nonsignificant reductions, indicating a smaller number of available studies, consistently ranking mid‑tier across all outcomes. Meta‑regression identified CKD and longer lesion length as predictors of higher CD‑TLR risk.

CONCLUSIONS: Atherectomy showed the most consistent benefits across mortality and reintervention outcomes, while RST demonstrated promising but inconclusive performance. Larger randomized trials are needed to clarify RST’s role in infrapopliteal revascularization.

PMID:42062609 | DOI:10.1007/s00270-026-04452-0

Diabetologia. 2026 Apr 30. doi: 10.1007/s00125-026-06727-0. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: Women with a history of gestational diabetes mellitus (GDM) have an elevated risk of type 2 diabetes in their later life, yet the underlying mechanisms of this remain unclear. We aimed to investigate the long-term impact of GDM on gut microbiota and related metabolites and to explore whether such alterations may contribute to type 2 diabetes risk.

METHODS: Among parous women from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we identified microbial species associated with a history of GDM (visit 2, 2014-2017, n=1525), and serum metabolites associated with both a history of GDM (visit 1, 2008-2011, n=2968) and GDM-related microbiota (visit 2, n=391). We further examined prospective associations of the GDM-related microbiome (visit 2, n=925) with incident type 2 diabetes over 6 years of follow-up, and of microbial-related metabolites (visit 1, n=2341) with incident type 2 diabetes over 12 years.

RESULTS: Among 1525 US Hispanic/Latino parous women (median age: 58 years), seven species differed between women with and without a history of GDM, including higher abundances of four species (e.g. Parabacteroides merdae CAG:48, a proinflammatory taxon) and lower abundances of three species (e.g. Dialister sp. CAG:588, a short-chain fatty acid producer). Fifteen metabolites were associated with both a history of GDM and the GDM-related microbiome in a consistent direction, nine of which (e.g. saturated sphingomyelins and unsaturated fatty acids) were associated with glycaemic traits and incident type 2 diabetes. Using these microbial-related metabolites as proxy measures, proxy analysis suggested a positive relationship between the GDM-related microbiome and type 2 diabetes (r=0.55, p=0.036). A metabolite score derived from the nine microbial-related metabolites mediated an estimated 20% (95% CI 9%, 42%) of the association between a history of GDM and type 2 diabetes.

CONCLUSIONS/INTERPRETATION: A history of GDM is associated with an unfavourable gut microbiota and related metabolites in US Hispanic/Latino women, suggesting a potential role of the gut microbiota in GDM-related type 2 diabetes.

PMID:42062589 | DOI:10.1007/s00125-026-06727-0