Category: Statistics

Eur J Pediatr. 2026 Apr 10;185(5):252. doi: 10.1007/s00431-026-06917-3.

ABSTRACT

Alagille syndrome (ALGS) is a rare multisystem disorder most commonly resulting from pathogenic variants in JAG1 and, less frequently, NOTCH2. We evaluated long-term native liver survival (NLS) and overall survival (OS) in a Korean ALGS cohort and compared the genetic characteristics of this cohort with those of the Global ALagille Alliance (GALA) study cohort. We retrospectively reviewed 60 patients with clinically diagnosed ALGS at Seoul National University Hospital. Forty-three patients with genetically confirmed disease were analyzed. Eight patients (18.6%) underwent liver transplantation (median age: 3.9 years), revealing a lower rate than that in the comparator cohort. The estimated NLS percentages at 5, 10, and 18 years were 86.9%, 86.9%, and 76.6%, respectively, exceeding those in previous reports. The corresponding OS rates were 90.2%, 86.9%, and 86.9%, respectively. The following types of JAG1 variants were identified in 41 patients (95.3%): frameshift (34.1%), nonsense (26.8%), missense (24.4%), and splice-site (9.8%) variants and in-frame deletions (4.9%). Compared with the reference group, our cohort exhibited a greater frequency of non-protein-truncating variants (missense variants and in-frame deletions; p = 0.023) and no structural variants (p = 0.043). Two patients (4.7%) carried NOTCH2 nonsense variants. Mortality was significantly higher among patients with frameshift variants compared with patients with non-frameshift variants (4 of 5 deaths; p = 0.035).

CONCLUSION: Compared with the GALA cohort, Korean patients with ALGS exhibited more favorable long-term NLS and a higher proportion of non-protein-truncating JAG1 variants, alongside the absence of structural variants. These findings suggest potential genetic influences and highlight the need for multicenter validation.

WHAT IS KNOWN: • The Global ALagille Alliance (GALA) study reports native liver survival (NLS) rates of 66.8%, 54.4%, and 40.3% at 5, 10, and 18 years, respectively, in patients with Alagille syndrome. • NLS rates are higher among Asians, with unclear genotype-phenotype correlations.

WHAT IS NEW: • Compared to the GALA study cohort, the Korean cohort demonstrates superior NLS rates of 86.9%, 86.9%, and 76.6% at 5, 10, and 18 years and a higher frequency of non-truncating JAG1 variants, along with the absence of structural variants. • Protein-truncating variants are associated with higher initial gamma-glutamyl transferase levels, while frameshift variants are associated with reduced overall survival.

PMID:41961327 | DOI:10.1007/s00431-026-06917-3

Eur J Pediatr. 2026 Apr 10;185(5):250. doi: 10.1007/s00431-026-06914-6.

ABSTRACT

HyperCKemia is a frequent laboratory finding in pediatric practice and may reflect a wide spectrum of conditions, ranging from benign transient states to rare primary neuromuscular disorders. The lack of pediatric-specific diagnostic algorithms complicates risk stratification and clinical decision-making. A retrospective cohort study was conducted, including patients under 18 years of age with hyperCKemia referred to a tertiary reference center between January 2017 and December 2024. Clinical, laboratory, genetic, and histological data were collected. Statistical analyses included univariate testing and logistic regression to identify predictors of primary disease. A total of 119 patients were included (median age 10 years; 76.5% male). Most were symptomatic at presentation (87.4%), and 80.3% met criteria for rhabdomyolysis. A primary disorder was identified in 25.2% of patients, while 52.1% had secondary causes, predominantly viral myositis, and 22.7% remained undiagnosed. Metabolic myopathies accounted for the majority of primary diagnoses (60.0%), followed by muscular dystrophies (23.3%) and inflammatory myopathies (13.3%). Persistent hyperCKemia and male sex emerged as strong independent predictors of primary disease (OR 8.5 and 5.1, respectively). Muscle weakness and exercise intolerance were exclusive to primary disorders. Genetic testing yielded a diagnosis in 26.8% of tested patients, with targeted next-generation sequencing proving particularly valuable.

CONCLUSIONS: In pediatric hyperCKemia, persistent CK elevation and male sex are key predictors of underlying primary neuromuscular disease. A phenotype-driven, stepwise diagnostic approach incorporating early genetic testing may improve diagnostic yield and optimize resource utilization.

WHAT IS KNOWN: • HyperCKemia in children is most frequently secondary to benign conditions such as viral myositis, while primary neuromuscular disorders are less common but clinically significant. • Creatine kinase levels lack specificity, and the diagnostic approach increasingly relies on genetic testing.

WHAT IS NEW: • Persistent hyperCKemia and male sex were identified as independent predictors of primary disease. • Most primary disorders occurred in patients with CK over 1000 UI/L, and higher inter-crisis CK levels were associated with an increased likelihood of underlying disease.

PMID:41961319 | DOI:10.1007/s00431-026-06914-6

Abdom Radiol (NY). 2026 Apr 10. doi: 10.1007/s00261-026-05420-5. Online ahead of print.

ABSTRACT

BACKGROUND: Response evaluation of pancreatic ductal adenocarcinoma (PDAC) with routine contrast-enhanced CT (CECT) using RECIST is currently inadequate for identification of patients benefiting from chemotherapy treatment, as the majority of patients show stable disease. This might lead to inappropriate treatment and potentially diminishes patients’ quality of life. Recent developments in CT perfusion (CTP) show its potential as a biomarker to evaluate therapy response in PDAC.

PURPOSE: To investigate quantitative CT Perfusion as a prognostic biomarker during chemotherapy treatment in patients with PDAC.

MATERIALS AND METHODS: This prospective cohort trial included patients between January 2018 and December 2022 with biopsy-proven PDAC of all stages who underwent CT Perfusion before (i.e. baseline) and after three months of chemotherapy treatment. A previously developed AI-assisted CTP analysis method provided automatic segmentations of tumor and pancreas parenchyma. A trilinear non-parametric CTP contrast-enhancement model described the upslope and the peak of the time intensity curve for both tumor and parenchyma. Perfusion features of baseline and follow-up scans were compared to calculate the percentual difference. The primary endpoint was the association between quantitative CTP parameters and overall survival (OS). Secondary endpoints included comparison with RECIST 1.1 and CA 19-9 response criteria for prognostic stratification. Statistical analysis included Kaplan-Meier curves and log-rank test.

RESULTS: A total of 25 patients were included. Treatment response based on RECIST 1.1 criteria showed two cases with progressive and 23 with stable disease. Patients with increased peak enhancement after chemotherapy demonstrated significantly longer survival compared to those with decreased enhancement (p = 0.02). In contrast, CA19-9 response (≥ 30% decrease) did not significantly differentiate survival (758 days vs 371 days, p = 0.27). Furthermore, CTP found more patients with a higher chance of long survival compared to RECIST (60% vs 25% survival in 24 months). In the subgroup with RECIST stable disease CTP still finds patients with a significantly longer survival (p = 0.02). Combined analysis showed that patients with both CTP increase and CA19-9 response had the best median survival at 758 days (IQR: 561-895).

CONCLUSION: Our study demonstrates that quantitative CTP is associated with better identification of long-term survivors than RECIST, based on increased peak enhancement after chemotherapy. Quantitative CTP may serve as a valuable complement to current treatment assessment methods in patients with PDAC.

PMID:41961316 | DOI:10.1007/s00261-026-05420-5

Drug Saf. 2026 Apr 10. doi: 10.1007/s40264-026-01650-0. Online ahead of print.

ABSTRACT

INTRODUCTION: Giant cell arteritis (GCA) is an immune-mediated vasculitis of large and medium arteries, mainly affecting older adults. Prompted by a consumer concern, a few spontaneous reports after coronavirus disease 2019 (COVID-19) vaccination and Australian regulator signal, we investigated a possible association between GCA and vaccination.

METHODS: This study analysed multiple data sources from January 2021 to September 2024. We reviewed spontaneous GCA reports submitted to the statewide vaccine safety service, Surveillance of Adverse Events following Vaccination in the Community (SAEFVIC), and applied self-controlled case series (SCCS) to two large Australian healthcare datasets [general practice (GP) and linked hospital data]. SCCS used a 1-42-day risk window, stratified by vaccine type, age, and sex. Incident GCA cases were identified via keyword matching and diagnostic codes [Systematized Nomenclature of Medicine Clinical Terms (SNOMED-CT)/International Classification of Diseases Tenth Revision, Australian Modification (ICD-10-AM)].

RESULTS: Six cases of GCA were spontaneously reported, four with onset within 42 days postvaccination, all following the adenoviral vectored Vaxzevria® {reporting rate 0.10 [95% confidence interval (CI) 0.03-0.27]}. The proportional reporting ratio signal detection method did not indicate a safety signal. Of 2700 incident cases of GCA identified across primary and hospital care datasets, 293 occurred within 42 days of COVID-19 vaccination. There was no increased risk of GCA following COVID-19 vaccination in either dataset [GP relative incidence (RI): 0.96 (95% CI 0.76, 1.21); hospital RI: 0.79 (95% CI 0.68, 0.91)], including by vaccine type, age, or sex.

CONCLUSIONS: Using three Australian data sources, this study found no increase in GCA presentations within 6 weeks of COVID-19 vaccination. These consumer-stimulated findings support informed decisions, strengthen vaccine safety evidence, and help clinicians counsel patients.

PMID:41961244 | DOI:10.1007/s40264-026-01650-0

Jpn J Ophthalmol. 2026 Apr 10. doi: 10.1007/s10384-026-01340-5. Online ahead of print.

ABSTRACT

PURPOSE: To assess the 6-month efficacy and safety of oxymetazoline hydrochloride ophthalmic solution 0.1% (OMZ 0.1%) versus placebo for acquired blepharoptosis.

STUDY DESIGN: A phase 3, randomized, double-masked, parallel-group, multicenter study conducted in Japan.

METHODS: Patients were randomized 1:1:1 to OMZ 0.1%, once daily (QD) or twice daily (BID), or placebo. Patients received OMZ 0.1% for 6 months. Patients in the placebo group were randomized after 3 months (Treatment Period 1) to OMZ 0.1%, either QD or BID, for the remaining 3 months (Treatment Period 2). The primary efficacy endpoint was the marginal reflex distance-1 (MRD-1) change from baseline to Day 14 (2 hours after the morning drop) with OMZ 0.1% QD or BID versus placebo. Adverse events and adverse drug reactions (ADRs) were recorded.

RESULTS: Overall, baseline MRD-1 (standard deviation) of 336 patients analyzed (n=112 per group) was 1.31 (0.83) mm (Day 0). MRD-1 change from baseline to Day 14 (2 hours after the morning drop) was 1.09 (0.07), 0.93 (0.07), and 0.50 (0.07) mm, with OMZ 0.1% QD, BID, and placebo, respectively. There was a statistically significant difference in the least squares mean (standard error) MRD-1 change versus placebo with OMZ 0.1% QD (0.59 [0.10] mm; 95% CI 0.38, 0.79) and OMZ 0.1% BID (0.43 [0.10] mm; 95% CI 0.23, 0.64) (both p<0.05). All ADRs related to the study drug were mild.

CONCLUSION: Fourteen days of OMZ 0.1% treatment significantly increased MRD-1 versus placebo. There was no loss of effect after 6 months of treatment and no significant safety concerns.

PMID:41961227 | DOI:10.1007/s10384-026-01340-5

Clin Exp Nephrol. 2026 Apr 10. doi: 10.1007/s10157-026-02848-3. Online ahead of print.

ABSTRACT

BACKGROUND: Zinc deficiency is highly prevalent in patients undergoing hemodialysis, and may contribute to cognitive impairment, given its essential role in neurotransmission and neurogenesis. This study aimed to examine the association between serum zinc and cognitive function in this population.

METHODS: This was a cross-sectional study (N = 1207). Cognitive function was assessed by using the Modified Mini-Mental State examination (3MS). The association between serum zinc and 3MS score and its domains were examined by using a linear regression model and ordinal logistic regression model, respectively.

RESULTS: In total patients, 3MS score and serum zins levels were 91 (82-97) points and 68 (61-76) μg/dL, respectively. Serum zinc level was not associated with 3MS score in adjusted model with 16 potential confounders. However, there was a significant interaction between serum zinc and albumin levels (p = 0.019). Therefore, participants were categorized into 2 subgroups by the median serum albumin level (3.7 g/dL) in further analyses. In the lower serum albumin group, the positive association between serum zinc and 3MS was significant after adjustment for 15 potential confounders (p = 0.022). After additional adjustment for both magnesium and phosphate, the association showed a similar positive trend but did not reach statistical significance (p = 0.072). Among the cognitive domains of the 3MS, attention was significantly associated with serum zinc level in participants with lower serum albumin (p = 0.016).

CONCLUSIONS: Lower serum zinc was a novel factor associated with cognitive function, particularly in attention in patients undergoing maintenance hemodialysis with low serum albumin.

PMID:41961222 | DOI:10.1007/s10157-026-02848-3

Thorac Cancer. 2026 Apr;17(7):e70280. doi: 10.1111/1759-7714.70280.

ABSTRACT

OBJECTIVES: To evaluate the prognosis of patients with nonsmall cell lung cancer (NSCLC) who did not undergo surgery after neoadjuvant chemotherapy combined with immunotherapy (NACI). Patients were grouped according to subsequent treatment: radiotherapy (RT) or nonradiotherapy (non-RT), and the prognostic importance of positron emission tomography/computed tomography (PET/CT) was further assessed.

MATERIALS AND METHODS: This retrospective study included NSCLC patients who received NACI between November 2020 and September 2024 at the Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College. Not all patients underwent surgery and subsequently received either RT or non-RT treatment. Patients were stratified by whether PET/CT was performed and by their SUV-max values before RT or non-RT. Progression-free survival (PFS) and overall survival (OS) were calculated from the start of neoadjuvant therapy using the Kaplan-Meier method.

RESULTS: A total of 73 eligible patients were enrolled: 21 (28.8%) in the non-RT group (nRTG) and 52 (71.2%) in the RT group (RTG). The median follow-up time for all patients in the group was 18 months. The results show no significant difference in PFS (p = 0.653) or OS (p = 0.742) between RTG and nRTG. Among the patients who did not undergo PET/CT examination, the results showed a significant difference in PFS (p = 0.022), but no difference in OS (p = 0.320). Among the patients undergoing PET/CT examinations, in terms of PFS, compared to nRTG + SUV-max ≤ 4 g/mL, there is no significant difference in RTG + SUV-max ≤ 4 g/mL (p = 0.584), and RTG + SUV-max > 4, < 8 g/mL (p = 0.156). However, RTG + SUV-max ≥ 8 shows a statistical difference (p = 0.005).

CONCLUSION: Among NSCLC patients who did not undergo surgery following NACI, no significant differences in OS or PFS were observed between the RTG and nRTG groups. For patients who did not receive PET/CT evaluation, radiotherapy remains a key therapeutic option. In patients with a PET/CT SUVmax ≤ 4, radiotherapy may be safely omitted. In comparison, patients with a PET/CT SUVmax > 4 should be managed with a comprehensive treatment strategy that includes radiotherapy as the main component. PET/CT plays a critical role in guiding subsequent treatment selection.

PMID:41960615 | DOI:10.1111/1759-7714.70280

Pharmacoepidemiol Drug Saf. 2026 Apr;35(4):e70368. doi: 10.1002/pds.70368.

ABSTRACT

PURPOSE: Concurrent use of benzodiazepines and opioids is discouraged due to synergistic adverse effects. However, patients undergoing total hip or knee arthroplasty (THA/TKA) often receive them, particularly in the first 3 postoperative months. We identified factors associated with new outpatient concurrent benzodiazepine-opioid dispensation following THA/TKA.

METHODS: In this nationwide cohort study, we linked the Dutch Arthroplasty Register with the Dutch Foundation for Pharmaceutical Statistics, which provided medication dispensation data. We included all patients undergoing primary elective THA/TKA (2013-2022) who had no preoperative concurrent use in the 6 months pre-procedure. The primary outcome was ≥ 7 days of a new concurrent benzodiazepine-opioid dispensation within 90-day postoperative. Determinants included patient and implant characteristics, and preoperative medication use. Multivariable logistic regression analyses were performed, adjusted for age, sex, and comorbidity.

RESULTS: Among 89 139 THA and 76 710 TKA patients, 3756 (4%) and 5571 (7%), respectively, received new postoperative concurrent benzodiazepine-opioid dispensation within 90-days postoperative. The main factor associated with such dispensation was preoperative benzodiazepine use (THA: OR 23.5 [95% CI: 21.8-25.3], TKA: OR 22.8 [95% CI: 21.3-24.3]), followed by preoperative antidepressant/anxiolytic use (THA: OR 2.9 [95% CI: 2.6-3.1], TKA: OR 2.5 [95% CI: 2.3-2.7]). Other factors included female sex, current smoking, and American Society of Anesthesiologists (ASA) scale III-IV. Preoperative pain scores, preoperative opioid use, and implant characteristics showed little to no association with the outcome.

CONCLUSIONS: Preoperative benzodiazepine use was the main factor associated with new outpatient concurrent benzodiazepine-opioid dispensation after THA/TKA, followed by preoperative antidepressant/anxiolytic use. These results highlighted that careful review of the patient’s medication history when planning postoperative pain management could help prevent unsafe co-prescription.

PMID:41960602 | DOI:10.1002/pds.70368

Health SA. 2026 Mar 13;31:3233. doi: 10.4102/hsag.v31i0.3233. eCollection 2026.

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic disrupted healthcare systems, posing risks for adolescents living with HIV (ALHIV) in resource-limited, high HIV-prevalence settings. These disruptions threatened antiretroviral therapy (ART) adherence, viral load suppression (VLS) and retention in care (RiC).

AIM: This study aimed to compare treatment outcomes of ALHIV on ART in the Khayelitsha and Eastern Substructure (KESS) before and during the COVID-19 pandemic.

SETTING: The study was performed in KESS, Cape Town, South Africa.

METHODS: A retrospective cohort analysis was conducted among ALHIV aged 10-19 years receiving ART at public health facilities, pre-COVID-19 (before 01 March 2020) and during COVID-19 (01 March 2020-31 December 2021). Sociodemographic, clinical, and treatment data were analysed. Descriptive and inferential statistics compared outcomes and determined factors associated with VLS (< 1000 copies/mL) using SPSS v.30.

RESULTS: Data from 1702 ALHIV (pre-COVID-19) and 2733 ALHIV (during COVID-19) were analysed. Viral load suppression declined from 82.1% to 64.8%, while full VLS (< 50 copies/mL) from 70.8% to 53.7% (p = 0.065). Antiretroviral therapy adherence fell from 96.4% to 70.0% (p < 0.001), and RiC 80.3% to 76.3% (p < 0.001). In multivariate analysis, higher CD4 count, and consistent ART adherence predicted VLS.

CONCLUSION: Antiretroviral therapy adherence and VLS rates among ALHIV declined during COVID-19. Adolescent-centred healthcare delivery models are needed to ensure continuity of HIV treatment during public health emergencies.

CONTRIBUTION: This study provides local evidence on the pandemic’s impact in a high-burden South African context. By quantifying declines in ART adherence, RiC, and VLS, it highlights ALHIV vulnerabilities and the need to strengthen adolescent-responsive, resilient healthcare systems.

PMID:41960585 | PMC:PMC13058524 | DOI:10.4102/hsag.v31i0.3233

Bioinformation. 2026 Jan 31;22(1):385-387. doi: 10.6026/973206300220385. eCollection 2026.

ABSTRACT

Orthodontic appliances influence patients’ oral functions, especially speech and mastication. Therefore, it is of interest to compare speech and mastication difficulties among patients treated with clear aligners and conventional braces. One hundred participants were assessed through a validated questionnaire and performance tests. Clear aligners showed fewer articulation and chewing problems than fixed braces. The differences were statistically significant. Thus, we show clear aligners may provide improved comfort and oral function during orthodontic treatment.

PMID:41960548 | PMC:PMC13058382 | DOI:10.6026/973206300220385