Category: Statistics

Neurology. 2025 Oct 21;105(8):e214140. doi: 10.1212/WNL.0000000000214140. Epub 2025 Sep 15.

ABSTRACT

BACKGROUND AND OBJECTIVES: Patients with brain tumors face an increased risk of arterial and venous thromboembolic events. However, owing to risk of intracranial hemorrhage (ICH), clinician practice patterns vary on preference for anticoagulation treatment. This meta-analysis evaluates the safety of direct oral anticoagulants (DOACs) vs low-molecular-weight heparin (LMWH) on the development of ICH in patients with brain tumor.

METHODS: We searched MEDLINE, Embase, Web of Science, and Cochrane Central Register of Controlled Trials (January 2010-June 2025) for randomized-controlled trials or cohort studies enrolling adults (age ≥18 years) with primary or metastatic brain tumors receiving therapeutic DOACs (apixaban, rivaroxaban, edoxaban, betrixaban, and dabigatran) vs LMWH (enoxaparin, dalteparin, nadroparin, and tinzaparin). Studies limited to prophylactic dosing or non-brain tumor patients were excluded. Pooled risk ratios (RRs) with 95% CIs were calculated using a restricted random-effects model. Heterogeneity (I²) and bias were evaluated, with prespecified subgroups (tumor type, follow-up duration, and study quality) and sensitivity analyses. The study protocol was registered on PROSPERO (CRD42025635334).

RESULTS: Among 762 publications identified, 10 retrospective cohort studies (1,572 patients: 645 DOAC, 895 LMWH) were included. Patients’ mean or median age ranged 60.4-67 years (DOAC) vs 53-64 years (LMWH), with follow-up durations ranging from 3 to 12 months. Patients with primary or metastatic brain tumors receiving DOACs had a statistically significantly lower risk of any ICH compared with LMWH (RR = 0.50, 95% CI 0.29-0.87; p = 0.01, I² = 49.50%). Reduction was more pronounced in 3 studies with three-month follow-up (RR = 0.23, 95% CI 0.09-0.57; p < 0.01, I² < 0.01%). Stratified analyses showed reduced ICH risk with DOACs in primary brain tumors (5 studies, RR = 0.20, 95% CI 0.08-0.54; p < 0.01, I² < 0.01%) but not in metastatic brain tumors (5 studies, RR = 0.86, 95% CI 0.44-1.68; p = 0.66, I² = 36.04%). Leave-one-out analyses confirmed robustness, and cumulative meta-analysis demonstrated stable estimates with narrowing CIs. Egger (p = 0.19) and Begg (p = 0.59) tests showed no statistical evidence of publication bias.

DISCUSSION: In the current meta-analysis, DOACs were associated with significantly lower ICH risk than LMWH in patients with anticoagulated brain tumor, particularly those with primary brain tumors. Findings support DOACs as a safe anticoagulant in arterial and venous thromboembolism. Given observational designs with inherent confounding, findings warrant cautious interpretation.

PMID:40953341 | DOI:10.1212/WNL.0000000000214140

JCO Clin Cancer Inform. 2025 Sep;9:e2500182. doi: 10.1200/CCI-25-00182. Epub 2025 Sep 15.

ABSTRACT

PURPOSE: Ipsilateral breast tumor recurrence (IBTR) remains a critical concern for patients undergoing breast-conserving surgery (BCS). Reliable risk estimation tools for IBTR risk can support personalized surgical and adjuvant treatment decisions, especially in the era of evolving systemic therapies. We aimed to develop and validate models to estimate IBTR risk.

PATIENTS AND METHODS: This multicenter retrospective cohort study included 8,938 women who underwent partial mastectomy for invasive breast cancer between 2008 and 2017. Prediction models were developed using Cox proportional hazards regression and validated via bootstrap resampling. Model performance was assessed using Harrell’s C-index, Brier scores, calibration plots, and goodness-of-fit tests.

RESULTS: During a median follow-up of 9.0 years (IQR, 6.6-10.9), IBTR occurred in 320 patients (3.6%). The initial model, based on variables from Sanghani et al, achieved a Harrell’s C-index of 0.74. Incorporating hormonal receptor status, human epidermal growth factor receptor 2 status, radiotherapy, and targeted therapy as predictors reduced the C-index to 0.65, despite their clinical relevance. Importantly, the inclusion of these factors improved calibration, demonstrating better alignment between predicted and observed IBTR probabilities. Although the hazard ratios (HRs) for radiotherapy aligned with the Early Breast Cancer Trialists’ Collaborative Group meta-analyses (MA), those for chemotherapy and endocrine therapy showed slight differences. Therefore, HRs from the MA were used to represent treatment effects in our model.

CONCLUSION: We have developed and internally validated a new risk estimation model for IBTR using Cox regression and bootstrap methods. A Web-based risk estimation tool is now available to facilitate individualized risk assessment and treatment planning.

PMID:40953336 | DOI:10.1200/CCI-25-00182

J Am Acad Orthop Surg Glob Res Rev. 2025 Sep 9;9(9). doi: 10.5435/JAAOSGlobal-D-25-00062. eCollection 2025 Sep 1.

ABSTRACT

BACKGROUND: Femoral neck fractures (FNFs) pose a notable challenge in the elderly population, given the high associated mortality rates and costs. The choice between internal fixation (IF) and hip arthroplasty (HA) has long been debated, yet existing guidelines often overlooked the crucial influence of comorbidities. With the increasing number of hip fracture cases globally and the complexity of patient conditions, it is essential to identify the key factors that truly affect surgical outcomes.

METHODS: We conducted a large-scale retrospective study across 152 Beijing hospitals, including 25,764 patients aged 60+ years with FNF. After excluding those with severe preexisting conditions, we collected data on patient characteristics and used advanced statistical methods for analysis.

RESULTS: Among the patients, 4568 received IF and 21,196 received HA. IF decreased 1-year mortality in patients with fewer than four comorbidities, whereas HA was more beneficial for those with four or more comorbidities. Mortality predicted by comorbidities was notably lower than that by age and sex (2.379% versus 2.790%, P < 0.001), and age had no marked influence on outcomes.

CONCLUSION: In summary, for elderly patients with FNF, comorbidity profile, rather than age or sex, should be the key determinant in surgical choices to reduce all-cause mortality. These findings support the refinement of surgical guidelines and have implications for geriatric care. Future research should focus on enhancing comorbidity assessment in surgical planning.

PMID:40953329 | DOI:10.5435/JAAOSGlobal-D-25-00062

Adv Sci (Weinh). 2025 Sep 15:e09090. doi: 10.1002/advs.202509090. Online ahead of print.

ABSTRACT

With the rapid accumulation of spatial transcriptomics (ST) data across diverse tissues, individuals, and technological platforms, there is an urgent need for a robust and reliable multi-slice integration framework to enable 3D spatial domain identification. However, existing methods largely focus on 2D spatial domain identification within individual slices and fail to adequately account for inter-slice spatial correlations and batch effect correction, thereby limiting the accuracy of cross-slice 3D spatial domain identification. In this study, SpaBatch is presented, a novel framework for integrating and analyzing multi-slice ST data, which effectively corrects batch effects and enables cross-slice 3D spatial domain identification. To demonstrate the power of SpaBatch, SpaBatch is applied to eight real ST datasets, including human cortical slices from different individuals, mouse brain slices generated using two different techniques, mouse embryo slices, human embryonic heart slices, HER2+ breast cancer tissues and mouse hypothalamic slices profiled using the MERFISH platforms. Comprehensive validation demonstrates that SpaBatch consistently outperforms state-of-the-art methods in 3D spatial domain identification while effectively correcting batch effects. Moreover, SpaBatch efficiently captures conserved tissue architectures and cancer-associated substructures across slices, and leverages limited annotations to predict spatial domain in unannotated sections, highlighting its potential for tissue-structure interpretation and developmental biology studies. All code and public datasets used in this study are available at: https://github.com/wenwenmin/SpaBatch.

PMID:40953305 | DOI:10.1002/advs.202509090

J Am Acad Orthop Surg. 2025 Sep 10. doi: 10.5435/JAAOS-D-25-00395. Online ahead of print.

ABSTRACT

BACKGROUND: There is no consensus on whether the benefits of participating in formal hand therapy outweigh the investment required for patients following basal joint arthroplasty. The purpose of this study was to compare patient-reported and functional outcome measures between patients who did and did not participate in formal hand therapy following basal joint arthroplasty. Furthermore, we evaluated the distance patients traveled and the financial burden associated with participating in formal hand therapy.

METHODS: Using a retrospective cohort study design, patients who underwent primary basal joint arthroplasty by the fellowship-trained orthopaedic hand surgeons at our institution between 2021 and 2023 were included in this study. Patients who did not have complete data or had revision surgery were excluded. Patient-Reported Outcomes Measurement Information System Upper Extremity (PROMIS UE) scores, Kapandji scores, therapy data, and therapy costs were collected. Mann-Whitney U-tests, chi square tests, and Z-tests were used for statistical analysis. The cutoff for statistical significance was set at P < 0.05.

RESULTS: A total of 73 surgeries in 70 patients were included in this study; 33 out of 73 surgical encounters participated in formal therapy after surgery. The median max Kapandji score and mean increase in PROMIS UE score were higher in the therapy users compared with nontherapy users. Although these differences in PROMIS UE scores were not statistically significant, they were greater than the proposed minimal clinically important difference. Formal hand therapy users did attend more postoperative clinic appointments than nontherapy users. Both the patient-reported and standardized estimated cost of therapy and postoperative clinic appointment cost were higher for therapy groups compared with nontherapy groups.

CONCLUSION: The results of this study suggest that although there is no statistically significant difference in PROMIS UE improvement between groups, formal hand therapy may provide a clinically meaningful benefit.

PMID:40953295 | DOI:10.5435/JAAOS-D-25-00395

J Spinal Cord Med. 2025 Sep 15:1-4. doi: 10.1080/10790268.2025.2554011. Online ahead of print.

ABSTRACT

Context: Frailty has emerged as a key determinant of surgical outcomes, surpassing chronological age and comorbidity indices in prognostic value. The Risk Analysis Index (RAI), a multidomain frailty assessment tool, has shown strong predictive utility in spine surgery. Recent analyses specifically evaluated RAI in urgent surgical intervention for acute traumatic spinal cord injury (SCI), where timely outcome prediction is critical.Findings: In 10,000 SCI patients, frailty demonstrated a graded association with adverse 30-day outcomes. Mortality increased from 1.5% in robust individuals (RAI 0-20) to 11.8% in very frail patients (RAI >41), paralleled by increased non-home discharge and complications. The RAI consistently outperformed the modified frailty index (mFI-5), achieving c-statistics >0.72 for mortality and discharge outcomes. These results align with broader spine surgery literature, where the RAI has demonstrated superior discrimination compared to mFI-5 across elective cases, degenerative conditions, spinal deformity, and tumor surgery. Predictive strength reflects incorporation of functional and nutritional domains, which comorbidity-based indices miss. Importantly, RAI-based analyses have identified high-risk subsets even in lower-risk cohorts, such as anterior cervical discectomy, underscoring its generalizability.Conclusion/Clinical Relevance: The RAI reliably predicts short-term outcomes after SCI and across diverse spine surgery populations, outperforming simpler frailty measures. Its integration into neurosurgical assessment enables more accurate risk stratification, informs perioperative management, and supports shared decision-making. Routine use of the RAI may guide multidisciplinary optimization and resource allocation, and future interventions targeting frail patients may leverage its predictive capacity to improve outcomes.

PMID:40952757 | DOI:10.1080/10790268.2025.2554011

JAMA. 2025 Sep 15. doi: 10.1001/jama.2025.14194. Online ahead of print.

ABSTRACT

IMPORTANCE: Preterm infants with severe thrombocytopenia (platelet count <50 × 109/L) frequently receive platelet transfusions. However, it is unclear in what cases prophylactic transfusion truly reduces bleeding risk or whether it does more harm than good.

OBJECTIVE: To develop and validate a dynamic prediction model for major bleeding or mortality if prophylactic platelet transfusion were or were not to be given to infants with severe thrombocytopenia.

DESIGN, SETTING, AND PARTICIPANTS: The dynamic prediction model was developed in an international multicenter cohort (2017-2021) comprising 14 neonatal intensive care units in the Netherlands, Sweden, and Germany. Model evaluation was performed in a national multicenter cohort (2010-2014) including 7 Dutch neonatal intensive care units. The study population consisted of infants with severe thrombocytopenia less than 34 weeks’ gestation.

EXPOSURE: Two transfusion strategies were contrasted at each prediction point: receiving a platelet transfusion within 6 hours (prophylaxis) vs no platelet transfusion for 3 days (no prophylaxis).

MAIN OUTCOMES AND MEASURES: The primary outcome was the 3-day risk of major bleeding or mortality, reestimated every 2 hours during the first week after severe thrombocytopenia onset. Predictors included gestational and postnatal age, small-for-gestational-age infant, necrotizing enterocolitis, sepsis, mechanical ventilation, vasoactive agents, platelet count, and prior platelet transfusion(s). Landmarking combined with the clone-censor-weight approach enabled dynamic prediction under the 2 transfusion strategies, accounting for time-varying confounding. Model performance was evaluated in the external validation cohort.

RESULTS: In both the development (n = 1042) and validation (n = 637) cohorts, the median gestational age was 28 weeks and median birth weight was 900 g; there were 613 (59%) and 370 (58%) males, respectively. Major bleeding or death occurred in 235 infants (23%) in the development cohort and 135 (21%) in the validation cohort. In the validation cohort, the time-dependent area under the receiver operating characteristic curve was 0.69 (95% CI, 0.60-0.76) for the prophylaxis strategy and 0.85 (95% CI, 0.76-0.92) for the no prophylaxis strategy, with calibration plots showing good calibration. Estimated risks under both strategies varied considerably depending on the infant’s clinical condition at the time of prediction.

CONCLUSIONS AND RELEVANCE: Among preterm infants with severe thrombocytopenia, this modeling study found substantial variation among individuals in predicted benefits and harms of prophylactic platelet transfusion based on their current clinical characteristics. The dynamic prediction model performed well in a validation cohort, and its value to support individualized decisions warrants evaluation in future studies.

PMID:40952748 | DOI:10.1001/jama.2025.14194

JAMA Netw Open. 2025 Sep 2;8(9):e2531568. doi: 10.1001/jamanetworkopen.2025.31568.

ABSTRACT

IMPORTANCE: Some shift work arrangements allow for less than 11 hours off between shifts. The consequences of short daily rest periods are currently not well understood.

OBJECTIVE: To determine the effect and cost-benefit of reducing the number of short daily rest periods on sickness-related absence among health care workers.

DESIGN, SETTING, AND PARTICIPANTS: This 2-arm cluster-randomized clinical trial was conducted between January 11, 2021, and May 22, 2022, in hospital care units at Haukeland University Hospital in Bergen, Norway. Statistical analysis was performed from April to May 2025.

INTERVENTION: The intervention group followed a 6-month shift schedule with reduced instances of short daily rest periods, whereas the control group adhered to a 6-month shift schedule maintaining the usual number of short daily rest periods.

MAIN OUTCOMES AND MEASURES: Primary analyses followed intention-to-treat principles. The outcome was change in sickness-related absence days and absence spells (ie, each uninterrupted period of ≥1 consecutive sickness-related absence days) over the final 5 months of the intervention (allowing a 1-month stabilization period), compared with the same period in the preceding year and against a control group. The economic returns, measured as the increase in net present value of production from reduced sickness-related absence days due to the intervention, was estimated using a standard cost-benefit formula.

RESULTS: Of 66 hospital units with 811 health care workers (mean [SD] age, 39.8 [12.8] years; 626 of 808 women [77.5%]) in 80% or more full-time positions, 31 units (344 workers) were randomized to the intervention group and 35 units (467 workers) to the control group. The mean (SD) number of short daily rest periods among the intervention group was halved from 18.0 (8.4) during the reference period to 9.1 (6.2) in the intervention period, while the frequency remained unchanged among the control group (reference period, 18.3 [8.3] days; and intervention period, 17.5 [8.4] days). The intervention group showed a significantly smaller increase in sickness-related absence days (incidence rate ratio [IRR], 0.56; 95% CI, 0.41-0.79; P < .001) and spells (IRR, 0.73; 95% CI, 0.61-0.86; P < .001) compared with the control group. The effect on sickness-related absence days in the intervention units resulted in a positive estimated net economic return of approximately NOK 2 174 620 (USD $213 600) over 5 months.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of health care workers, reducing the frequency of short daily rest periods had positive effects on sickness-related absences and reduced expenses. These findings should guide organizational practices and inform legislative policies to enhance the health of workers by increasing daily rest periods to 11 hours or more between shifts.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04693182.

PMID:40952742 | DOI:10.1001/jamanetworkopen.2025.31568

J Spinal Cord Med. 2025 Sep 15:1-7. doi: 10.1080/10790268.2024.2414146. Online ahead of print.

ABSTRACT

OBJECTIVES: In all patients, LFAS To explore the effect of low frequency antidromic stimulation (LFAS) of the pelvic somatic serves on intestinal peristalsis and heart rate in individuals with chronic spinal cord ird injury and spasticity.

SETTING: Hospital in Zürich, Switzerland.

METHODS: Ten consecutive patients underwent laparoscopic implantation of neuroprosthesis to sciatic/femoral nerves – the LION procedure: 5 patients with Thoracic (T) SCI AIS A, 1 patient T4 AIS C, 1 patient C3 AIS A, and 3 patients with cervical injury (AIS B/C). At the end of the implantation, intestinal peristalsis observed laparoscopically was recorded before and after starting with LFAS at 10 Hz. On the first postoperative day, heart rates before and after the beginning of the same LFAS were checked. Statistical analyses were performed using a paired Student’s t-test.

RESULTS: LFAS Of the pelvic somatic nerves induced strong peristalsis in the small bowel and ascending/transverse colon without affecting the urinary bladder or descending colon/rectum, and a significant slowing of the heart rate in 8 patients with an overall reduction from 96.3 bpm (bpm) (P < 0.01).

CONCLUSIONS: This case series study reports on the effect of continuous antidromic pelvic neuromodulation (CAPN) on extraspinal somatic and autonomic pathways in chronic SCI. The discussion poses a novel hypothesis about the effect of CAPN on spinal pathways and activation of corticospinal pathways and neuroplasticity via the Renshaw cells. A rationale is provided for CAPN-induced activation of the vagus nerve (VN) and the existence of anastomotic pathways between the lumbosacral somatic nerves and the VN, and the capability of an activation of the motor functions of the VN. A second hypothesis is posed for the activation of cortico-vagal plasticity that may improve recovery after complete SCI by combining CAPN with neuromodulation of the VN.Trial registration NCT03441256.

PMID:40952735 | DOI:10.1080/10790268.2024.2414146

JAMA. 2025 Sep 15. doi: 10.1001/jama.2025.14389. Online ahead of print.

NO ABSTRACT

PMID:40952725 | DOI:10.1001/jama.2025.14389