Category: Statistics

BMC Ophthalmol. 2026 Jul 29;26(1):448. doi: 10.1186/s12886-026-05095-y.

ABSTRACT

BACKGROUND: Bipolar disorder and depression are associated with structural and functional changes in the retina, including a thinner retinal nerve fibre layer (RNFL). Lithium is widely considered the most effective treatment for bipolar disorder, but its mechanism of action is not fully understood. We assessed research looking at the effect of lithium on structural or functional retinal outcomes in humans.

METHODS: Searches using the terms ‘Lithium’ AND ‘retina’ were carried out to identify peer reviewed studies assessing the impact of lithium on retinal structure or function. These included those with or without a control group comparison, pre- and post- lithium comparisons and observational studies. There were no exclusions based on the quantity or preparation of lithium administered, or the length of administration. Risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal tool for Analytical Cross Sectional Studies, and a narrative synthesis and tabulated summary of the included studies was completed.

RESULTS: Seven studies assessing structural outcomes and 10 reporting functional ones were identified, all highly heterogenous and with multiple limitations. Structural outcomes were derived exclusively from optical coherence tomography (OCT) with retinal nerve fibre layer (RNFL) being the most common measurement. There was no evidence of differences in the RNFL between participants with bipolar disorder taking lithium and healthy controls in two larger studies. In six studies looking at differences in those with bipolar disorder taking lithium and those taking valproate, two showed no signs of difference and four showed evidence of thicker RNFL in the lithium group. Studies reporting functional outcomes reported a statistically significant effect of lithium on at least one functional measure, derived from electrooculography, electroretinography, and dark adaptation thresholds.

CONCLUSIONS: Current evidence suggests that lithium is likely to have an effect on the retina but limitations in all studies mean better designed and adequately powered prospective studies are required.

REGISTRATION: PROSPERO database (Number-CRD42024516635).

PMID:42527898 | DOI:10.1186/s12886-026-05095-y

Pediatr Blood Cancer. 2026 Jul 29:e70449. doi: 10.1002/1545-5017.70449. Online ahead of print.

ABSTRACT

BACKGROUND: Cerebellar ataxia after pediatric brain tumor treatment can cause persistent gait, balance, and speech impairment, yet no established rehabilitation strategy exists. Somato-cognitive coordination therapy (SCCT) is a virtual reality-guided intervention designed to promote sensorimotor integration through visually constrained reaching tasks. We evaluated the safety, feasibility, and preliminary functional observations of SCCT in this population.

METHODS: This single-center retrospective pilot study included 12 consecutive pediatric patients with cerebellar ataxia following brain tumor treatment who underwent outpatient SCCT between August 2023 and April 2025. SCCT sessions comprised approximately 10 min of alternating reaching tasks with limited visual feedback. Safety, acceptability, and changes in routinely documented selected scale for the assessment and rating of ataxia (SARA) subscale scores (gait, stance, and speech) were reviewed.

RESULTS: Patients received a median of 1 SCCT session (range, 1-7). No serious adverse events occurred. Although two patients reported transient fatigue, all respondents expressed willingness to continue, and 11 patients (92%) spontaneously described the intervention as enjoyable. Preliminary functional changes were observed even after a single 10-min session. The median pooled SARA subscale score showed a statistically significant reduction from 3.0 [interquartile range, 1.0-4.0] to 1.0 [1.0-2.0] (p < 0.001). One patient with cerebellar mutism showed speech-score reduction accompanied by longitudinal diffusion tractography changes.

CONCLUSIONS: SCCT appeared feasible and was not associated with serious adverse events in this retrospective pilot cohort. Exploratory functional observations warrant further evaluation in prospective randomized controlled trials to evaluate therapeutic efficacy and long-term durability.

PMID:42527885 | DOI:10.1002/1545-5017.70449

Pediatr Blood Cancer. 2026 Jul 29:e70477. doi: 10.1002/1545-5017.70477. Online ahead of print.

ABSTRACT

Selumetinib, a mitogen-activated protein kinase kinase inhibitor, was the first Food and Drug Administration-approved treatment for children with neurofibromatosis type 1-associated inoperable plexiform neurofibromas. We evaluated hematologic effects in 98 pediatric participants from the SPRINT Phase 1/2 trial (NCT01362803) with a median follow-up of 5.1 years (range: 0.2-11 years). Over 90% of values for white blood cell count, platelet count, absolute neutrophil count, and absolute lymphocyte count remained within normal limits across timepoints. There was a statistically significant, but unlikely clinically significant, decrease in absolute lymphocyte count and an increase in mean corpuscular volume. Selumetinib was not associated with apparent clinically significant hematologic changes.

PMID:42527881 | DOI:10.1002/1545-5017.70477

J Child Psychol Psychiatry. 2026 Jul 29. doi: 10.1111/jcpp.70208. Online ahead of print.

ABSTRACT

Valstad et al. (2026) presented important methodological advances in the study of indirect genetic effects in developmental psychology and psychiatry. By combining genetically informative family designs with measured genetic data, they addressed how sibling interaction and genetic nurture may contribute to developmental outcomes such as attention-deficit/hyperactivity disorder (ADHD) and educational performance. Their work highlights the importance of disentangling direct genetic effects from indirect genetic effects that arise through family relationships and shared environments. We discuss the conceptual implications of these processes for developmental psychology and psychopathology, and emphasize the interpretational challenges associated with correlated genetic and environmental influences. We note that heterogeneity in developmental processes may complicate statistical modeling approaches designed to estimate indirect genetic effects.

PMID:42527854 | DOI:10.1111/jcpp.70208

J Foot Ankle Res. 2026 Sep;19(3):e70194. doi: 10.1002/jfa2.70194.

ABSTRACT

INTRODUCTION: Diabetes-related distress (DRD) is exacerbated in people at risk of Diabetes-related Foot Disease (DFD); however, knowledge on this topic is still limited, especially in Primary Health Care (PHC), which focuses on prevention and monitoring. This study evaluated DRD and its associated factors in PHC individuals at risk of developing DFD, aiming to support management strategies to reduce complications.

METHOD: Cross-sectional study with 1563 individuals with diabetes mellitus (DM) registered in PHC services in Brazil. Participants were stratified according to their risk of DFD, based on the criteria from the International Working Group on the Diabetic Foot. The DRD was measured using the Problem Areas in Diabetes (B-PAID) scale, considering a score ≥ 40 as indicative of high distress. Sociodemographic, clinical, and behavioral variables were collected and analyzed using Gamma regression on the software Statistical Package for the Social Sciences (SPSS 26.0).

RESULTS: Among 1563 people with DM, 39.8% were at risk for DFD. In the multiple regression model, there is notable increase in DRD associated with greater difficulty in caring for the feet (β = 1.129; 1.014-1.257), loss of protective sensation (β = 1.311; 1.110-1.549), and poor glycemic control (β = 0.850; 0.761-0.951).

CONCLUSION: Sociodemographic and clinical factors, particularly loss of protective sensation in the feet, difficulty in foot care, and inadequate control of glycated hemoglobin, are associated with greater DRD in people at risk for DFD. Primary health care stands out as a strategic space for integrating psychosocial support and clinical management, ensuring that preventive measures are implemented and resulting complications are avoided or detected early.

PMID:42527853 | DOI:10.1002/jfa2.70194

Drugs. 2026 Jul 29. doi: 10.1007/s40265-026-02355-5. Online ahead of print.

ABSTRACT

Inhibition of androgen receptor (AR) signaling remains the cornerstone of systemic therapy for advanced prostate cancer (PC). However, a subset of aggressive tumors either arises de novo with neuroendocrine features or emerges under treatment pressure through lineage plasticity and AR independence. These lethal states are encompassed within the spectrum of aggressive-variant prostate cancer (AVPC), an umbrella term that includes both histologically confirmed neuroendocrine prostate cancer (NEPC)-comprising de novo NEPC and treatment-emergent NEPC (t-NEPC)-and clinically or molecularly defined AVPC lacking histologic confirmation but sharing neuroendocrine-like, AR-indifferent, or small-cell features. These phenotypes are characterized by rapid progression, visceral dissemination, low or discordant prostate-specific antigen (PSA) levels relative to tumor burden, and poor prognosis. Treatment options for NEPC/AVPC remain limited and largely rely on platinum-based chemotherapy, which usually provides only modest and transient benefit. This unmet need has intensified interest in lineage-associated vulnerabilities. Delta-like ligand 3 (DLL3), an inhibitory Notch ligand with restricted expression in normal adult tissues, is aberrantly upregulated in several neuroendocrine malignancies and has emerged as a clinically actionable target. In prostate cancer, DLL3 expression is enriched in neuroendocrine tumor cells, being detected in approximately 76.6% of castration-resistant NEPC compared with only 12.5% of castration-resistant adenocarcinoma, supporting its development as both a biomarker and therapeutic vulnerability. Clinical success of DLL3-targeted therapies in small-cell lung cancer further supports evaluation of DLL3-directed strategies in NEPC and related AVPC states. This review summarizes the biological rationale, translational evidence, and emerging clinical data supporting DLL3-targeted therapies in prostate cancer. Investigational platforms include antibody-drug conjugates, bispecific and trispecific T-cell engagers, and DLL3-directed radiopharmaceuticals. Early clinical studies suggest that activity is largely confined to DLL3-expressing neuroendocrine tumors, highlighting the importance of biomarker-guided patient selection. Delta-like ligand 3-directed therapies may reshape the management of DLL3-expressing prostate cancer if ongoing efforts to refine biomarkers improve patient enrichment and optimize trial design are successfully translated into clinical practice.

PMID:42527846 | DOI:10.1007/s40265-026-02355-5

Arthroscopy. 2026 Jul 29. doi: 10.1002/arj.70409. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the abnormal knee hyperextension and coupled external rotation, varus, and anterior translation that occurs using sequential ligament and capsular sectioning in multiligamentous injuries.

METHODS: A six-degree-of-freedom robotic system measured knee hyperextension and coupled external rotation, varus, and anterior-posterior translation with selective tissue cutting in 23 cadaveric knees. Tests were performed up to 25 Nm hyperextension load before and after cutting 6 structures: oblique popliteal ligament (OPL), posterolateral capsule with the fabellofibular ligament (PLC+FFL), posteromedial capsule with posterior oblique ligament (PMC+POL), lateral collateral ligament and popliteus tendon (LCL+POP), and the anterior cruciate ligament (ACL). Sequence 1 sectioned the posterior capsular structures (OPL, PLC+FFL, and PMC+POL) followed by the LCL+POP and ACL. Sequence 2 simulated a posterolateral injury (LCL+POP) and ACL injury followed by the posterior capsular injuries (OPL, PLC+FFL, and PMC+POL).

RESULTS: In sequence 1, sectioning the posterior capsule caused statistically significant increases to hyperextension (2.5° ± 0.9°; P = .02). Additional injury of the LCL+POP and ACL significantly increased hyperextension to 7.6°± 4.4° (P < .01), external rotation to 2.7° ± 2.8° (P < .01), and varus rotation to 3.2°± 3.9° (P < .01). In sequence 2, sectioning the LCL+POP significantly increased hyperextension (1.4° ± 0.6°; P < .01) and additional ACL sectioning significantly increased hyperextension (2.1° ± 1.0°; P < .01). Further sectioning the posterior capsule significantly increased hyperextension to 6.9° ± 1.7° (P < .01), external rotation to 2.9° ± 2.3° (P < .01), and varus rotation to 2.5° ± 1.4° (P < .01).

CONCLUSIONS: Posterolateral injuries (LCL+POP and PLC+FFL) resulted in small increases in knee hyperextension, external tibial rotation, and varus rotation. Sectioning the entire posterior capsular structures (PLC+FFL, PMC+POL, and OPL) is necessary for major increases in knee hyperextension.

CLINICAL RELEVANCE: Posterolateral ligament injuries may not result in a positive external rotation recurvatum test as only modest increases in external rotation and varus occur with knee hyperextension. Other ligament tests including the dial test for external tibial rotation and varus loading for lateral joint opening in knee flexion are recommended.

PMID:42527843 | DOI:10.1002/arj.70409

J Gen Intern Med. 2026 Jul 29. doi: 10.1007/s11606-026-10556-7. Online ahead of print.

NO ABSTRACT

PMID:42527841 | DOI:10.1007/s11606-026-10556-7

J Gen Intern Med. 2026 Jul 29. doi: 10.1007/s11606-026-10625-x. Online ahead of print.

ABSTRACT

BACKGROUND: Emergency departments (ED) provide timely care for acute conditions and serve as a vital safety net. Longer ED wait times are associated with worse health outcomes, but differences in ED wait times by patient language remain understudied.

OBJECTIVE: Examine differences in ED wait times between English and non-English language patients and its association with ED crowding.

DESIGN: Retrospective cohort study of ED visits at an academic medical center in 2023 and 2024.

PARTICIPANTS: 73,420 ED visits among adult patients not triaged to the highest acuity categories.

MAIN MEASURES: Wait times from triage to provider assignment by patient primary language were assessed via unadjusted analyses and generalized linear models adjusting for demographic, temporal, and system factors as well as patient comorbidities and chief complaint. Language was then interacted with ED census to assess for effect modification from ED crowding. Secondary outcomes were time from provider assignment to ED disposition and rates of left without being seen (LWBS).

KEY RESULTS: Patients with a primary non-English language waited on average 6.5 min (p < 0.001) or 8.4% longer than English-primary patients for an ED provider-a difference that persisted after statistical adjustment (6.6 min, p < 0.001). Cantonese, Spanish, Russian, and Toishanese language patients experienced statistically longer wait times than English language patients. With ED census, each 10 additional patients in the ED were associated with an adjusted 2.3 min (p = 0.02) longer differential wait time for non-English language patients. Despite these differences, rates of LWBS were significantly lower for non-English language patients in both unadjusted and adjusted analyses (p < 0.001).

CONCLUSIONS: Longer ED wait times for patients with a primary non-English language reflect a health inequity affecting a disadvantaged population. The degree of disparity widened as ED census increased. Health system and policy attention is needed to address ED crowding and other factors that could contribute to this disparity.

PMID:42527840 | DOI:10.1007/s11606-026-10625-x

Pediatr Blood Cancer. 2026 Jul 29:e70438. doi: 10.1002/1545-5017.70438. Online ahead of print.

ABSTRACT

Pediatric low-grade gliomas (pLGG) are the predominant childhood central nervous system tumors. While BRAF alterations are known to drive the majority of pLGGs, a subgroup contains activating mutations or fusions involving FGFR1/2/3. FGFR is a receptor tyrosine kinase that plays a crucial role in cell growth, differentiation, and survival through interactions with fibroblast growth factors. Furthermore, FGFR has been shown to interact with the RAS/MAPK, PI3K/AKT, and JAK/STAT pathways. The current understanding of the biological behavior, clinical trajectory, and effectiveness of targeted inhibition in FGFR-altered gliomas is notably limited. We sought to define the epidemiologic characteristics, molecular features, radiographic and histologic characteristics, and clinical course of patients with FGFR-altered pLGGs. We also explored the therapeutic implications of these abnormalities in pediatric cases and highlight both current and emerging treatment strategies for pediatric patients with FGFR-altered cancers.

PMID:42527824 | DOI:10.1002/1545-5017.70438