Tag: statistics

Acta Neurochir (Wien). 2026 Jul 1. doi: 10.1007/s00701-026-06971-8. Online ahead of print.

ABSTRACT

PURPOSE: The efficacy and safety of various dural sealants for dural closure have been evaluated in randomized controlled trials (RCTs). However, their associations with postcraniotomy complications remain to be compared.

METHODS: A Bayesian network meta-analysis (BNMA) was designed on the basis of studies published in PubMed, Embase, the Cochrane Library, Scopus, and Web of Science through July 9, 2025. Quality assessment was conducted using the National Institutes of Health (NIH) scale. BNMA was performed in R 4.5.1 with the “GeMTC” package, with SUCRA values and league tables generated to display comprehensive pairwise comparisons among different sealants. The certainty of evidence for each network estimate was assessed using the Confidence in Network Meta-Analysis (CINeMA) framework.

RESULTS: Eleven studies (3094 patients who underwent craniotomy) were included. TissuePatchDural (RR = 0.03, 95% CrI (0.0007, 0.42), SUCRA = 90.52%), autologous materials (RR = 0.09, 95% CrI (0.003, 0.69), SUCRA = 73.07%) and synthetic hydrogels (RR = 0.16, 95% CrI (0.04, 0.48), SUCRA = 59.68%) had 95% CrIs excluding 1, suggesting a lower risk of postcraniotomy cerebrospinal fluid leakage than for conventional closure alone. Autologous materials showed a favorable probability for meningitis prevention (RR = 0.13, 95% CrI (0.02, 0.74), SUCRA = 82.70%). The SUCRA values indicated favorable probabilities for TissuePatchDural to prevent surgical site infection and pseudomeningocele and for autologous materials to reduce the risk of unplanned interventions, although these secondary outcomes lacked statistical significance.

CONCLUSION: The results of this BNMA suggest that compared with conventional closure alone, TissuePatchDural has a greater probability of reducing cerebrospinal fluid leakage, whereas autologous materials showed favorable efficacy signals for postoperative meningitis.

PMID:42387243 | DOI:10.1007/s00701-026-06971-8

Nat Med. 2026 Jul 1. doi: 10.1038/s41591-026-04514-3. Online ahead of print.

ABSTRACT

Blood pressure (BP)-lowering therapy reduces cardiovascular risk, but whether its proportional benefits increase with longer treatment duration remains unclear. We conducted an individual participant-level data meta-analysis of 51 randomized trials from the Blood Pressure Lowering Treatment Trialists’ Collaboration (358,642 participants; median follow-up: 4.2 years). Using Cox proportional hazards models, we estimated time-stratified hazard ratios (HRs) for major cardiovascular events (MACE; fatal or non-fatal stroke, ischemic heart disease or heart failure) across annual follow-up intervals up to more than 5 years, standardized to a 5-mmHg systolic BP reduction. Network meta-analysis examined whether temporal patterns differed across antihypertensive drug classes. Annual MACE incidence was highest during year 1 (3.0% treatment versus 3.6% control), declined during years 1-5 and then rose at more than 5 years (3.1% versus 3.4%). BP lowering reduced MACE risk, with benefits established early and not progressively increasing over time. A 5-mmHg systolic BP reduction was associated with a 12% lower MACE risk in year 1 (HR = 0.88, 95% confidence interval (CI): 0.84-0.91), with modest attenuation thereafter: HRs were 0.88 (0.85-0.92) in years 1-2, 0.94 (0.90-0.98) in years 2-3, 0.87 (0.83-0.92) in years 3-4, 0.97 (0.91-1.03) in years 4-5 and 0.94 (0.87-1.01) at more than 5 years (P for trend = 0.006). Similar patterns occurred across five drug classes. These findings indicate that the relative cardiovascular benefits of BP lowering emerge within months and do not increase over time, suggesting that prioritizing higher-risk individuals for treatment yields greater clinical utility than prolonged treatment in low-risk individuals.

PMID:42387214 | DOI:10.1038/s41591-026-04514-3

Br J Cancer. 2026 Jul 1. doi: 10.1038/s41416-026-03529-4. Online ahead of print.

ABSTRACT

BACKGROUND: Cancer is a major cause of mortality after solid organ transplantation (SOT). Quantifying this risk is difficult due to heterogeneous reports and methodological limitations.

METHODS: We conducted a population-based cohort study linking data between the UK Transplant Registry, National Cancer Registry, Civil Registration of Deaths, and Hospital Episode Statistics for all SOT recipients in England between 1st June 1992 and 31st December 2015.

FINDINGS: Among 50,762 SOT recipients, 22,361 deaths were recorded, of which 3550 (15.9%) were due to cancer, making it the second leading cause of mortality. Overall cancer (excluding non-melanomatous skin cancer) standardised mortality ratio (SMR) was 2.12 (95% CI: 2.05-2.19). Cancer mortality was highest among lung recipients (SMR 3.49; 95% CI: 2.96-4.06), and lowest in kidney recipients (SMR 2.00; 95% CI: 1.92-2.08). Non-Hodgkin’s Lymphoma had highest mortality after SOT (SMR 9.86; 95% CI: 9.01-10.75) and was elevated across all transplant types. However, liver and kidney cancer mortality was disproportionately elevated among liver (SMR: 9.30; 95% CI: 7.53-11.24) and kidney transplant recipients (SMR: 5.11; 95% CI: 4.34-5.93), respectively. Several cancers showed no increased mortality.

INTERPRETATION: De novo cancer remains a major cause of long-term mortality after SOT in England, with risk stratified by cancer and/or allograft.

PMID:42387207 | DOI:10.1038/s41416-026-03529-4

EJNMMI Res. 2026 Jul 1. doi: 10.1186/s13550-026-01468-y. Online ahead of print.

ABSTRACT

BACKGROUND: Manual segmentation of prostate cancer metastases on PSMA PET/CT and SPECT/CT is time-consuming and poorly scalable, particularly in highly metastatic patients. This study evaluated nnU-Net-based automatic segmentation models trained on PET and SPECT either separately or jointly and assessed whether PET-derived information can improve SPECT lesion segmentation. Seventy-three patients with metastatic castration-resistant prostate cancer treated with ¹⁷⁷Lu-PSMA were retrospectively included: 48 from the Henri Becquerel Cancer Center (HBCC) and 25 from Nantes University Hospital (NUH). For each patient, ⁶⁸Ga-PSMA PET/CT and ¹⁷⁷Lu-PSMA SPECT/CT were acquired before and during the first treatment cycle respectively. All images were manually segmented by four nuclear medicine physicians in consensus. Four nnU-Net models were trained: M1 (PET/CT only), M2 (SPECT/CT only), M3 (joint PET/CT+SPECT/CT, unimodal input at inference), and M4 (SPECT/CT with PET/CT segmentation as a priori input). Models were first trained and internally validated on HBCC data, then retrained on the full HBCC cohort and externally validated on NUH data.

RESULTS: For PET/CT segmentation, M1 and M3 achieved comparable performance. M1 reached DSCs of 0.83 ± 0.19 (internal) and 0.76 ± 0.22 (external), while M3 achieved 0.83 ± 0.16 (internal) and 0.77 ± 0.21 (external). For SPECT/CT, the PET-guided model M4 (DSC: 0.63 ± 0.24 internal; 0.78 ± 0.14 external; PPV: 0.65 ± 0.26 internal; 0.75 ± 0.23 external) provided the best results. Compared with the SPECT-only model M2 (DSC: 0.61 ± 0.26 internal; 0.70 ± 0.25 external; PPV: 0.63 ± 0.25 internal; 0.71 ± 0.24 external), M4 showed no statistically significant difference in internal validation (DSC p = 0.35), while being statistically significant in external validation (DSC p = 0.014).

CONCLUSION: The nnU-Net framework enables accurate lesion segmentation on both ⁶⁸Ga-PSMA PET/CT and ¹⁷⁷Lu-PSMA SPECT/CT. While PET-only and joint PET+SPECT models perform similarly on PET images, incorporating PET-derived segmentations as prior information tends to improve SPECT/CT lesion segmentation. This PET-guided SPECT segmentation strategy leverages the higher spatial resolution of PET and represents a key step towards fully automated extraction of volumetric and dosimetric biomarkers for personalized prostate cancer treatment.

PMID:42387196 | DOI:10.1186/s13550-026-01468-y

Dermatol Ther (Heidelb). 2026 Jul 1. doi: 10.1007/s13555-026-01840-9. Online ahead of print.

ABSTRACT

INTRODUCTION: Topical therapy plays an essential role in psoriasis management. However, lack of rapid improvement may negatively impact adherence. The calcipotriol and betamethasone dipropionate (CAL/BDP) cream based on polyaphron dispersion (PAD) technology has demonstrated high efficacy, favorable safety, and convenience compared with CAL/BDP gel in phase III trials. This post-hoc analysis aims to assess early treatment response to CAL/BDP PAD-cream at Week (W) 4.

METHODS: This was a post-hoc pooled analysis of adults with mild-to-moderate psoriasis from two multicenter, investigator-blind, phase III trials (MC2-01-C2 and MC2-01-C7). Patients were randomized 3:1:3 to CAL/BDP PAD-cream (N = 551), PAD-cream vehicle (N = 178), or CAL/BDP gel (N = 542) once daily for 8 weeks. Physician’s Global Assessment (PGA) and Subject’s Global Assessment (SGA) were assessed at W1 and W4. At W4, early responders were defined as patients achieving PGA controlled disease (i.e., any improvement from baseline to a PGA score of 0-1), while PGA success was defined as a PGA score of 0-1 combined with a minimum 2-point improvement from baseline. SGA controlled disease and SGA success were also assessed. Comparisons between groups were performed by logistic regression models using multiple imputation. Rates of PGA/SGA concordance were assessed by simple percent agreement.

RESULTS: At W4, CAL/BDP PAD-cream was associated with a significantly higher proportion of patients achieving early response compared with CAL/BDP gel (32.1% vs 21.4%, P < 0.0001). Differences were already significant at W1 (7.8% vs 4.8%, P = 0.0410). PGA success at W4 was also higher with CAL/BDP PAD-cream than with CAL/BDP gel (23.6% vs 14.8%, P < 0.0001). Rates of SGA controlled disease and success were also statistically significantly higher for CAL/BDP PAD-cream at W4. Concordance between PGA/SGA assessments at W4 was observed in 65.5% (controlled disease) and 69.5% (success) of patients treated with CAL/BDP PAD-cream.

CONCLUSION: CAL/BDP PAD-cream was associated with significantly higher early response rates at W4 than CAL/BDP gel, suggesting earlier clinical improvements.

PMID:42387164 | DOI:10.1007/s13555-026-01840-9

Sci Rep. 2026 Jul 1. doi: 10.1038/s41598-026-60239-w. Online ahead of print.

ABSTRACT

Physical inactivity is prevalent among university students, and psychosocial factors shape participation patterns. This study examined the concurrent and independent associations between fatigue, appetite-related eating behaviours, and perceived barriers to physical activity. A total of 666 students aged 18-24 participated in this cross-sectional study. Data were collected using the Chalder Fatigue Scale, the University Students’ Eating Behaviour Scale, and the Barriers to Physical Activity Participation Scale. Analyses included Pearson correlations, multiple linear regression, and bootstrapped indirect association analyses. Fatigue was positively associated with perceived barriers (r = .336, p < .01). Both physical and mental fatigue were positively associated with personal and social barriers (β = 0.136-0.227), while mental fatigue was associated with environmental barriers (β = 0.195). Eating behaviours, particularly satiety responsiveness (β = 0.142-0.235) and hunger (β = 0.110-0.157), showed independent positive associations with barrier domains; slowness in eating was associated only with personal barriers (β = 0.087). Bootstrapped analyses indicated small but statistically significant indirect association patterns. Fatigue and appetite-related eating behaviours are modest but consistent correlates of perceived physical activity barriers. These findings should be interpreted as cross-sectional associations rather than causal or directional mechanisms.

PMID:42387156 | DOI:10.1038/s41598-026-60239-w

Clin Transl Oncol. 2026 Jul 1. doi: 10.1007/s12094-026-04471-w. Online ahead of print.

ABSTRACT

BACKGROUND: Pembrolizumab, a PD-1 immune checkpoint inhibitor, has become a standard first-line treatment for metastatic non-small cell lung cancer (mNSCLC), administered either as monotherapy or combined with platinum-based chemotherapy. Although current guidelines endorse a fixed dose of 200 mg every three weeks, initial clinical studies supported a weight-based dosing strategy (2 mg/Kg). The comparative effectiveness of these dosing strategies in real-world settings remains unclear.

METHODS: A multicenter, retrospective cohort study was conducted across three universitary hospitals to compare the effectiveness of two pembrolizumab dosing regimens as first line treatment in patients with mNSCLC. Patients were divided into two groups: the standard-dose group (STD, ≤ 2 mg/Kg) and high-dose group (HD, > 2 mg/Kg), both administered every 3 weeks. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Kaplan-Meier and Cox regression analyses were used to compare outcomes between dosing groups.

RESULTS: Among 198 patients analyzed, baseline characteristics were similar between groups, except for a higher proportion of ECOG 0 in the HD group. Median PFS was 14.9 months in the STD group versus 8.3 months in the HD group, without statistical significance (HR 1.27, 95% CI 0.87-1.86, p = 0.215). Similarly, median OS was numerically longer in the STD group (27.7 months) compared to the HD group (17.3 months) (HR 1.39, 95% CI 0.97-2.03, p = 0.072). Rates of treatment discontinuation due to adverse events were similar between groups.

CONCLUSIONS: In this real-world cohort of mNSCLC patients, pembrolizumab administered at 2 mg/Kg every three weeks appears to provide similar progression free survival and overall survival outcomes compared to higher doses. These findings support the clinical effectiveness of lower pembrolizumab doses, aligning with prior pharmacokinetic and clinical studies indicating a lack of dose-response relationship for PD-1 inhibitors in mNSCLS, potentially optimizing treatment cost without compromising survival outcomes.

PMID:42387154 | DOI:10.1007/s12094-026-04471-w

Aesthetic Plast Surg. 2026 Jul 1. doi: 10.1007/s00266-026-06044-2. Online ahead of print.

ABSTRACT

BACKGROUND: Patient complaints can provide valuable feedback on objective deficiencies in medical services. At present, there are few studies on patient complaints regarding autologous fat transfer procedures. Our findings suggest that, in real-world clinical practice, the complaint rate may exceed 5% (7.18% in the present study), underscoring the importance of further research in this area. Therefore, this study aims to analyze the complaints of patients who have undergone autologous fat transfer procedures to understand their expectations and requirements.

METHODS: Our study conducted a statistical analysis of the chief complaints of patients who have undergone autologous fat transfer procedures. The research focused on various aspects, including the treatment items, content of complaints, types of complaints, economic compensation, and the temporal trends in the number of complaints.

RESULTS: Between 2016 and 2022, a total of 571 autologous fat transfer procedures were performed, among which 41 cases involved complaints, resulting in a complaint rate of 7.18%. According to the standardized coding classification of complaints by Reader et al., the numbers of complaints in the Clinical, Management, and Relationships categories were 33 (80.49%), 6 (14.63%), and 2 (4.88%), respectively. Specifically, the subcategories included Treatment (48.78%), Safety incidents (31.71%), Bureaucracy (9.76%), Finance and billing (2.44%), Referrals (2.44%), Patient-staff dialogue (2.44%), and Staff attitudes (2.44%). The most common subcategories were Treatment (48.78%) and Safety incidents (31.71%). There were 15 cases (36.59%) where patients demanded compensation for losses and 1 case (2.44%) where patients requested free repairs or consultations. Ultimately, three patients received financial compensation. At the significance level of P = 0.05, although the number of annual complaints increased over time, the growth trend was not significant.

CONCLUSIONS: The complaints from patients regarding autologous fat transfer procedures are primarily of a clinical nature. Combined with the survey findings, it can be seen that quality and safety issues are the main content of complaints.

LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID:42387137 | DOI:10.1007/s00266-026-06044-2

Pharm Res. 2026 Jul 1. doi: 10.1007/s11095-026-04130-3. Online ahead of print.

ABSTRACT

PURPOSE: Glioblastoma(GBM) is highly aggressive and therapeutically refractory brain malignancy. Despite maximal intervention, patient prognosis remains dismal. A major obstacle in its management is the limited permeation of therapeutic agents across the blood-brain barrier(BBB), further intensified by resistance to standard chemotherapy such as temozolomide(TMZ). Proteolysis-targeting chimeras(PROTACs), offer new opportunities by enabling selective degradation of oncogenic proteins. A1874, a heterobifunctional molecule, has demonstrated potent, selective degradation of oncogenic driver-BRD4 in pancreatic, breast, and colon cancer. BRD4 drives GBM cell proliferation, survival, and resistance to therapy; therefore, we investigated the therapeutic potential of A1874 in brain cancer.

METHODS: Herein, we developed brain-targeted self-nanoemulsifying drug delivery system, termed PRONano, designed to enhance the targeted delivery of A1874. The system is functionalized with Palmitoyl-DL-carnitine chloride(PC) to facilitate transport across the BBB. Physicochemical characterization was performed to assess particle size. In-vitro cytotoxicity, qualitative and quantitative cellular uptake was analyzed. Mechanistic validation was conducted using western blot and qPCR, while 3D spheroid assay was employed to assess efficacy in tumor-mimicking microenvironment.

RESULTS: PRONano exhibited nanoscale particle size and significantly enhanced intracellular uptake of A1874. Formulation exhibited enhanced cytotoxicity in temozolomide-sensitive and resistant GBM cells. Effective BRD4 protein degradation was identified in the Western blot. PRONano significantly inhibited 3-D spheroid tumor growth suggesting better penetration and efficacy in tumor-like microenvironment.

CONCLUSIONS: PRONano is brain-targeted, rationally designed nanoformulation which can overcome major A1874 delivery constraints. This strategy augmented PROTAC delivery and therapeutic potential in GBM, supporting future preclinical development.

PMID:42387117 | DOI:10.1007/s11095-026-04130-3

Sci Rep. 2026 Jul 1. doi: 10.1038/s41598-026-59706-1. Online ahead of print.

ABSTRACT

Accurate day-ahead cooling load forecasting is a time series forecasting problem that is essential for optimizing the scheduling and energy efficiency of chilled water plants (CWPs). While previous studies have explored different forecasting models and input features, the combined effects of key factors such as historical context length (including regressor lags), sampling resolution, and exogenous inputs remain insufficiently examined for real industrial data. This study examines, under varying regressors and data granularity, the amount of historical context that provides stable and reliable forecasts with low computational cost. The experimental results show that (i) weekly scale look-back windows (LBW) provide an optimal balance between accuracy and computational cost for day-ahead horizons, (ii) hourly inputs often match or exceed finer-resolution accuracy and reveal distinct compute scaling: deep-learning (DL) models remain comparatively efficient as resolution increases, whereas the machine learning (ML) model, XGBoost, grows steeply, (iii) incorporating weather and calendar features enhances prediction accuracy around weekends and holidays. The DL model NHiTS, when integrating exogenous features and a 7-day LBW, improves forecasting accuracy by 50.8%, outperforming all other deep learning, machine learning, and statistical forecasting models by achieving a MASE of 1.88, compared to 3.82 for the baseline. These findings provide practical insights for smart-building and industrial applications, guiding practitioners such as building-energy engineers and facility managers in selecting optimal historical data lengths and parameter combinations to improve forecasting accuracy.

PMID:42387106 | DOI:10.1038/s41598-026-59706-1