Tag: pubmed

Stat Methods Med Res. 2026 Mar 18:9622802261418211. doi: 10.1177/09622802261418211. Online ahead of print.

ABSTRACT

In interventional health studies, causal mediation analysis can be employed to investigate mechanisms through which the intervention affects the targeted health outcome. Identifying direct and indirect effects from empirical data become complicated, however, when a confounder of the mediator-outcome association is itself affected by the treatment. Here, we investigate identification of mediational effects under such post-treatment confounding in a setting with a longitudinal mediator, time-to-event outcome and an ordinal treatment-dependent confounder. If the treatment affects the treatment-dependent confounder only in one direction (monotonicity), we show that the mediational effects are identified up to stratum-specific sensitivity parameters and derive their empirical non-parametric expressions. The feasibility of the monotonicity assumption can be assessed using empirical data, based on restrictions on the marginal distributions of counterfactuals of the treatment-dependent confounder. In an empirical analysis, we use data from the Finnish Diabetes Prevention Study to assess the extent to which the effect of a lifestyle intervention on avoiding type 2 diabetes is mediated through weight reduction in a high-risk population, with other health-related changes acting as treatment-dependent confounders. We avoid pitfalls related to post-treatment conditioning by treating the mediator as a functional entity and defining the time-to-event outcome as a restricted disease-free time.

PMID:41847826 | DOI:10.1177/09622802261418211

Vestn Oftalmol. 2026;142(1):108-111. doi: 10.17116/oftalma2026142011108.

ABSTRACT

Glaucoma remains one of the leading causes of irreversible vision loss, making it one of the most pressing problems in modern public health.

PURPOSE: This study aimed to identify trends in glaucoma morbidity among adults, adolescents, and children in the Republic of Uzbekistan based on a comprehensive analysis of its prevalence.

MATERIAL AND METHODS: The study used statistical data from the Republican Medical Information Center of the Ministry of Health of the Republic of Uzbekistan for the period 2016-2022. Changes in glaucoma morbidity in 2017-2022 years were analyzed using statistical methods to identify trends and patterns.

RESULTS: The analysis of changes in glaucoma prevalence demonstrated increases in 2016, 2018, and 2021, indicating the potential influence of factors affecting the conditions of glaucoma diagnosis and treatment.

CONCLUSION: The findings confirm the growing relevance of glaucoma as a serious medical and social problem, particularly among the adult population. The results may serve as a basis for developing effective preventive measures and optimizing treatment strategies to reduce the rate of irreversible vision loss.

PMID:41847815 | DOI:10.17116/oftalma2026142011108

Vestn Oftalmol. 2026;142(1):79-86. doi: 10.17116/oftalma202614201179.

ABSTRACT

PURPOSE: The secondary objectives of the study were to describe the sociodemographic and clinical characteristics of patients with inherited retinal dystrophy (IRD) phenotypes, including Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP), to characterize the diagnostic and treatment pathways of patients with confirmed biallelic mutations in the RPE65 and/or RLBP1 genes, and to estimate the prevalence of RPE65-associated inherited retinopathy and RLBP1-associated pathology in Russia.

MATERIAL AND METHODS: This noninterventional cohort study was conducted using retrospective data collected from patients with LCA and RP phenotypes in Russia and annual prospective follow-up of patients with IRDs caused by biallelic mutations in the RPE65 or RLBP1 genes. The registry was formed between July 20, 2022 and March 3, 2025. Eligible participants were entered into the database, followed by a two-stage genetic diagnostic algorithm to confirm biallelic mutations in the RPE65 or RLBP1 genes. The data were entered into standardized electronic case report forms, verified, and analyzed using descriptive statistical methods.

RESULTS: The study included 2425 patients from 83 regions of the Russian Federation diagnosed with IRDs. The majority of patients were from Moscow, the Moscow Region, the Republic of Dagestan, the Republic of Tatarstan, Saint Petersburg, and the Republic of Bashkortostan. The mean age was 23.22±16.74 years, pediatric patients accounted for 51.34% of analyzed cases. Females and males comprised 47.01% and 52.99% of the cohort, respectively. In patients with confirmed biallelic mutations in the RPE65 gene, disease onset was characterized by nyctalopia (47.5%), nystagmus (40%), pigment redistribution (40%), non-recordable/extinguished electroretinogram (45.0%), and prolonged dark adaptation (35.0%). Mean best-corrected visual acuity was reduced (OD: 0.14±0.12; OS: 0.15±0.13), while central retinal thickness in the foveal region remained relatively preserved (OD: 178.70±38.43 µm; OS: 179.17±35.97 µm).

CONCLUSION: The study “Registry of patients with inherited retinal dystrophies caused by confirmed biallelic mutations in the RPE65 and RLBP1 genes in Russia (REGINA)” allowed evaluation of a representative IRD cohort, providing a detailed description of key clinical, social, and demographic characteristics.

PMID:41847811 | DOI:10.17116/oftalma202614201179

Vestn Oftalmol. 2026;142(1):70-78. doi: 10.17116/oftalma202614201170.

ABSTRACT

PURPOSE: The primary objective of the study was to investigate and describe the molecular genetic characteristics of patients with inherited retinal dystrophies (IRDs) presenting with phenotypes of Leber congenital amaurosis (LCA) or retinitis pigmentosa (RP), taking into account clinical polymorphism.

MATERIAL AND METHODS: This noninterventional cohort study was conducted in Russia by collecting retrospective data from patients with LCA and RP phenotypes and annual prospective follow-up of patients with IRDs caused by biallelic mutations in the RPE65 or RLBP1 genes, entered into the registry between July 20, 2022 and March 3, 2025. Eligible participants were entered into the IRD database, followed by a two-stage genetic diagnostic algorithm to confirm the presence of biallelic mutations in RPE65 or RLBP1. The data were entered into standardized electronic case report forms, verified, and analyzed using descriptive statistical methods.

RESULTS: The study cohort included 2425 patients with IRDs from 83 regions of the Russian Federation. The mean age was 23.22±16.74 years, with predominance of pediatric patients (51.34%) and males (52.99%).

Genetic testing was performed in two stages. At the first stage, mutations in RPE65 and/or RLBP1 were identified in 84 (3.52%) of 2388 examined patients. The second stage involving direct Sanger sequencing was conducted in 48 (2.01%) patients, it confirmed biallelic mutations in RPE65 in 1.68% and in RLBP1 in 0.04% of cases. In one case, mutations in both genes were verified. Among RPE65 variants, 61 mutations were identified, including frequent pathogenic variants (c.304G>T, c.272G>A, c.370C>T); seven variants were detected in the RLBP1 gene.

The frequency of biallelic RPE65 mutations in the subgroup with LCA/RP phenotype was 1.68%, and 1.65% in the overall IRD cohort, which is consistent with published data from European populations.

CONCLUSION: The study “Registry of patients with inherited retinal dystrophies caused by confirmed biallelic mutations in the RPE65 and RLBP1 genes in Russia” allowed characterization of the key molecular genetic features of a representative sample of patients with IRDs.

PMID:41847810 | DOI:10.17116/oftalma202614201170

Vestn Oftalmol. 2026;142(1):60-69. doi: 10.17116/oftalma202614201160.

ABSTRACT

PURPOSE: This study aimed to investigate the morphological features of the lamina cribrosa (LC) of the scleral in terms of their potential role in optic nerve (ON) axonal injury.

MATERIAL AND METHODS: Longitudinal sections of the prelaminar, laminar, and postlaminar portions of the ON from human corneal donors were examined. Sections were stained with Masson’s trichrome and analyzed using the Bioscan AT+ software. Neurofilament (NF) expression was assessed immunohistochemically using the Neurofilament NE-14 antibody and quantified with ImageJ 1.54i. Statistical analysis included Pearson and Spearman correlation coefficients, as well as the Kruskal-Wallis, Mann-Whitney, and Kendall’s tau tests.

RESULTS: The ratio of connective tissue to neural components in the LC varied and correlated with age (χ²=21.09, p=0.0018). Based on these differences, three LC patterns were identified: mixed, elastic, and collagenous. The mixed LC pattern was most prevalent across all age groups; the elastic pattern predominated in younger individuals (<44 years); the collagenous pattern was most common in individuals older than 60 years. NF expression was lowest in the mixed type LC, increased significantly in the elastic type LC, and was highest in the >60-year age group with the collagenous type LC.

CONCLUSION: Remodelling of the LC of the sclera characterized by a predominance of collagenous tissue, primarily perivascularly, and accompanied by deformation of the anterior LC surface in individuals older than 60 years, together with a tendency toward increased deviation of ON axons passing through the LC, should be considered potential risk factors for ON axonal injury. The observed variability in the NF cytoskeleton, which preceded changes in axonal transport, may be used as an early marker of retinal ganglion cell damage.

PMID:41847809 | DOI:10.17116/oftalma202614201160

Vestn Oftalmol. 2026;142(1):14-20. doi: 10.17116/oftalma202614201114.

ABSTRACT

INTRODUCTION: The ability of the crystalline lens to change its shape is a key component of accommodation. As part of the lenticular theory of presbyopia, involutional changes in the lens substance itself are considered to be of primary importance. At the same time, the role of the capsule, which essentially serves as a structural, shape-modifying “framework” for the lens substance, remains insufficiently studied. Accordingly, one approach to clarification of the pathogenesis of presbyopia may involve investigating the relationship between potential changes in lens shape during accommodation and the biomechanical properties of its capsule.

PURPOSE: This study aimed to assess the potential relationship between accommodative stimulus-induced changes in the curvature of the anterior lens surface and the biomechanical parameters of the anterior capsule based on sequential clinical and experimental analysis.

MATERIAL AND METHODS: The study was conducted in a group of 11 patients (11 eyes, i.e., clinical observations) of presbyopic age scheduled for and undergoing standard phacoemulsification with intraocular lens implantation for uncomplicated cataract. Prior to surgery, the radius of curvature of the anterior lens surface was measured at baseline and under accommodative stimulus using the CASIA2 device (Tomey, Japan). Anterior lens capsule specimens with a diameter of 4.0-5.5 mm were obtained during surgery after continuous curvilinear capsulorhexis. The elastic modulus (Young’s modulus) of the specimens was determined using atomic force microscopy.

RESULTS: Correlation analysis involved the use of an integral parameter – the magnitude of change in the radius of curvature of the anterior lens surface induced by accommodative stimulus. A pronounced moderate positive correlation was identified between changes in the radius of curvature of the anterior lens surface and the elastic moduli of the outer and inner surfaces of the anterior capsule (r=0.560 and r=0.603, respectively). However, this relationship was statistically significant only for the inner surface of the capsule but not for the outer surface (p=0.050 and p=0.073, respectively).

CONCLUSION: This is the first study investigating the potential relationship between changes in the curvature of the anterior lens surface and the biomechanical properties of the anterior capsule using the same study object, which enabled sequential clinical (morphometric) and experimental (biomechanical) analyses. Based on the obtained results, age-related changes in the biomechanical properties of the lens capsule may be considered one of the factors within the lenticular theory of presbyopia development.

PMID:41847803 | DOI:10.17116/oftalma202614201114

Vestn Oftalmol. 2026;142(1):5-13. doi: 10.17116/oftalma20261420115.

ABSTRACT

INTRODUCTION: The structural approach to studying the mechanism of accommodation and its age-related changes focuses on analyzing morphometric parameters (size, shape, and position) of the crystalline lens as the key element responsible for changes in clinical refraction during accommodation. The latest-generation swept-source (SS) anterior segment optical coherence tomography (AS-OCT) device CASIA2 (Tomey, Japan) enables near-screening evaluation of lens shape and position both at baseline and under accommodative stimulus. In the latter case, the integrated optical system provides lens-induced accommodative stress directly in the examined eye.

PURPOSE: This study aimed to evaluate age-related changes in various morphometric parameters of the lens measured by CASIA2 OCT under accommodative stimulus.

MATERIAL AND METHODS: The study cohort comprised 74 healthy volunteers (123 eyes, i.e., clinical observations) aged 20-85 years. The exclusion criteria were clinically significant refractive errors and ocular diseases. Three groups were formed according to age: 20-30 years, 31-50 years, and >51 years (43, 33, and 47 clinical observations, respectively). Scanning was performed under conditions of relative accommodative rest and during accommodative stimulus. In the latter case, a lens-induced method of accommodative stimulus was used, employing a -5.0 D negative spherical lens and a fixation target in the form of a radial figure integrated into the optical system of the CASIA2 OCT device.

RESULTS: Analysis of the entire cohort (n=123) revealed significant changes in morphometric parameters of the lens under accommodative stimulus, including a decrease in the radius of curvature of the anterior (p=0.003) and posterior (p=0.045) lens surfaces, an increase in lens thickness (p=0.011) and nuclear thickness (p=0.007), as well as a reduction in lens diameter (p=0.026) and anterior chamber depth (p=0.033). The radius of curvature of the anterior lens surface under relative accommodative rest in Group 1 (20-30 years) was significantly higher (p=0.00) than in Groups 2 (31-50 years) and 3 (>51 years), with median values of 11.62, 9.47, and 9.25 mm, respectively. The magnitude of changes in lens curvature radius significantly decreased with increasing age for both the anterior and posterior surfaces. Baseline lens thickness and nuclear thickness increased significantly with age and also demonstrated an increase under accommodative stimulus across all age groups. A statistically significant correlation with age was found for the radius of curvature of the anterior surface (r=-0.371; p=0.00) and the posterior surface (r=-0.224; p=0.013), as well as for lens thickness (r=0.268; p=0.003).

CONCLUSION: Anterior segment OCT using the CASIA2 system is a highly informative method for assessing morphometric parameters of the crystalline lens under conditions of relative accommodative rest and lens-induced accommodative stress. Under accommodative stress, statistically significant changes included a decrease in the radius of curvature of the anterior and posterior lens surfaces, an increase in lens thickness and nuclear thickness, and a decrease in lens diameter and anterior chamber depth. Analysis of the magnitude of changes induced by accommodative stimulus and their correlation with age demonstrated statistically significant negative associations between age and the radius of curvature of the anterior and posterior lens surfaces, and a positive association with lens thickness.

PMID:41847802 | DOI:10.17116/oftalma20261420115

Wilderness Environ Med. 2026 Mar 18:10806032261426910. doi: 10.1177/10806032261426910. Online ahead of print.

ABSTRACT

IntroductionPharmaceutical stability is a key concern for space missions, where radiation, microgravity, and prelaunch repackaging may accelerate drug degradation. While prior studies examined medications in environmentally controlled spacecraft, data on vacuum exposure are limited. The Polaris Dawn mission provided an opportunity to evaluate drug content following depressurization of the Dragon spacecraft and exposure to the vacuum of space during extravehicular activity.MethodsNineteen medications (13 repackaged solid, 6 liquid) flew as part of the SpaceX medical kit and were analyzed with lot-matched terrestrial controls. All samples underwent ultra-performance liquid chromatography mass spectrometry analysis upon return. The primary outcome was the percent difference in active pharmaceutical ingredient (API) between vacuum exposure and ground controls. A secondary outcome was the absolute API content expressed as a percentage of labeled dosage.ResultsSeventeen of the 19 flown medications demonstrated a < 5% mean API difference between spaceflight and lot-matched terrestrial controls, remaining within the prespecified threshold for clinical significance. Seven medications showed statistically significant differences (p < 0.05) between the 2 groups, yet all but one medication remained within this 5% range. Against the narrow 95%-105% of labeled dosage criterion, 10 ground controls and 11 spaceflight-exposed medications fell outside this range. Expanding to the broader 80%-120% range, nearly all medications were within acceptable limits.ConclusionsShort-duration spaceflight with vacuum exposure resulted in modest differences in drug content between spaceflight and terrestrial samples. However, high concordance suggests no clinically meaningful degradation, supporting the feasibility of repackaged pharmaceuticals for commercial and exploratory missions.

PMID:41847800 | DOI:10.1177/10806032261426910

Biometrics. 2026 Jan 6;82(1):ujag043. doi: 10.1093/biomtc/ujag043.

ABSTRACT

Motivated by a multi-indication basket trial aiming to assess the efficacy of a novel biomarker-targeted therapy in gastric or gastroesophageal junction (G/GEJ), pancreatic, and other related cancers, we consider a statistical design and decision-making framework for such trials. Typically, the investigational therapy in the trial targets a biomarker that is present in multiple cancer indications, and patients with higher biomarker expression tend to exhibit higher response rates, assuming the targeting biomarkers are over-expressed in tumor cells. To enable information sharing across indications, the proposed SIMBA method introduces a Bayesian hierarchical model that defines positive and negative biomarker subgroups and identifies optimal go/no-go decisions. The operating characteristics of SIMBA are assessed via simulations and compared against existing methods in the literature. Overall, SIMBA is constructed to improve the identification of patient sub-populations who may benefit from biomarker-targeted therapeutics.

PMID:41847799 | DOI:10.1093/biomtc/ujag043

Int Health. 2026 Mar 18:ihag014. doi: 10.1093/inthealth/ihag014. Online ahead of print.

ABSTRACT

BACKGROUND: Implementing three months of once-weekly rifapentine and isoniazid (3HP) for tuberculosis preventive therapy among household contacts (HHCs) of bacteriologically confirmed pulmonary TB patients in India presents programmatic challenges requiring understanding from beneficiary and provider perspectives.

METHODS: From May 2023 to March 2024, nine focus group discussions were conducted across five rural and urban program settings: three with HHCs who received 3HP (n=28) and six with frontline healthcare providers (n=69) delivering the regimen within a multicentric implementation study. Descriptive thematic analysis explored experiences, perceptions, and implementation challenges.

RESULTS: Analysis of FGDs yielded four major themes: (i) perceptions and acceptance of 3HP; (ii) barriers to 3HP; (iii) advocacy and communication and social mobilization; and (iv) suggestions for improving 3HP. Participants appreciated the short, once-weekly regimen and family encouragement supporting adherence. However, reluctance to undergo testing without symptoms, fear of side effects, stigma, and access barriers limited uptake. Suggested solutions included transport support, mobile X-ray services, reminder tools, and family DOTS providers. Providers highlighted workforce shortages and the need for additional staff.

CONCLUSION: Both groups emphasized tailored counselling, strengthened community awareness, and media advocacy to improve uptake, adherence, and program sustainability of 3HP implementation at scale nationwide.

PMID:41847763 | DOI:10.1093/inthealth/ihag014