Category: Statistics

Clin Trials. 2025 Jan 25:17407745241309056. doi: 10.1177/17407745241309056. Online ahead of print.

ABSTRACT

INTRODUCTION: The sequential parallel comparison design has emerged as a valuable tool in clinical trials with high placebo response rates. To further enhance its efficiency and effectiveness, adaptive strategies, such as sample size adjustment and allocation ratio modification can be employed.

METHODS: We compared the performance of Jennison and Turnbull’s method and the Promising Zone approach for sample size adjustment in a two-phase sequential parallel comparison design study. We also evaluated the impact of allocation ratio adjustments using Neyman and Optimal allocation strategies. Various scenarios were simulated to assess the effects of different design parameters, including weight in the test statistic, initial randomization ratio, and interim analysis timing.

RESULTS: The Promising Zone approach demonstrated superior or comparable power to Jennison and Turnbull’s method at equivalent expected sample sizes while maintaining the intuitive property that more promising interim results lead to smaller required follow-up sample sizes. However, the Promising Zone approach may require a larger maximum possible sample size in some cases. The addition of allocation ratio adjustments offered minimal improvements overall, but showed potential benefits when the variance in the treatment group was larger than that in the placebo group. We also applied our findings to a real-world example from the AVP-923 trial in patients with Alzheimer’s disease-related agitation, demonstrating the practical implications of adaptive sequential parallel comparison designs in clinical research.

DISCUSSION: Adaptive strategies can significantly enhance the efficiency of sequential parallel comparison designs. The choice between sample size adjustment methods should consider trade-offs between power, expected sample size, and maximum adjusted sample size. Although allocation ratio adjustments showed limited overall impact, they may be beneficial in specific scenarios. Future research should explore the application of these adaptive strategies to binary and survival outcomes in sequential parallel comparison designs.

PMID:39862109 | DOI:10.1177/17407745241309056

Front Biosci (Landmark Ed). 2025 Jan 20;30(1):26299. doi: 10.31083/FBL26299.

ABSTRACT

BACKGROUND: In this study, we prepared a porous gradient scaffold with hydroxyapatite microtubules (HAMT) and chitosan (CHS) and investigated osteogenesis induced by these scaffolds.

METHODS: The arrangement of wax balls in the mold can control the size and distribution of the pores of the scaffold, and form an interconnected gradient pore structure. The scaffolds were systematically evaluated in vitro and in vivo for biocompatibility, biological activity, and regulatory mechanisms.

RESULTS: The porosity of the four scaffolds was more than 80%. The 50% and 70% HAMT-CHS scaffolds formed an excellent gradient pore structure, with interconnected pores. Furthermore, the 70% HAMT-CHS scaffold showed better anti-compressive deformation ability. In vitro experiments indicated that the scaffolds had good biocompatibility, promoted the expression of osteogenesis-related genes and proteins, and activated the oxidative phosphorylation pathway to promote bone regeneration. Eight weeks after implanting the HAMT-CHS scaffold in rat skull defects, new bone formation was observed in vivo by micro-computed tomographic (CT) staining. The obtained data were statistically analyzed, and the p-value < 0.05 was statistically significant.

CONCLUSION: HAMT-CHS scaffolds can accelerate osteogenesis in bone defects, potentially through the activation of the oxidative phosphorylation pathway. These results highlight the potential therapeutic application of HAMT-CHS scaffolds.

PMID:39862088 | DOI:10.31083/FBL26299

Int J Stroke. 2025 Jan 25:17474930241313301. doi: 10.1177/17474930241313301. Online ahead of print.

ABSTRACT

BACKGROUND: The usual antithrombotic treatment for symptomatic intracranial atherosclerotic stenosis (ICAS) consists of dual treatment with clopidogrel and aspirin for 90 days followed by aspirin alone but the risk of recurrent stroke remains high up to 12 months. The Comparison of Anticoagulation and anti-Platelet Therapies for Intracranial Vascular Atherostenosis (CAPTIVA) trial was designed to determine whether other combinations of dual antithrombotic therapy are superior to clopidogrel and aspirin.

METHODS: CAPTIVA is an ongoing, prospective, double-blinded, three-arm clinical trial at over 100 sites in the United States and Canada that will randomize 1683 high-risk subjects with a symptomatic infarct attributed to 70-99% stenosis of a major intracranial artery to 12 months of treatment with (1) ticagrelor (180 mg loading dose, then 90 mg twice daily), (2) low-dose rivaroxaban (2.5 mg twice daily), or (3) clopidogrel (600 mg loading dose, then 75 mg daily). All subjects receive aspirin (81 mg daily), intensive risk factor management, and will undergo blinded CYP2C19 genotype analysis. The primary goal of the trial is to determine whether rivaroxaban or ticagrelor or both are superior to clopidogrel for lowering the primary endpoint (ischemic stroke, intracerebral hemorrhage (ICH), or vascular death) within 12 months. A prespecified interim safety analysis will be conducted when the first 450 randomized subjects have been followed for 12 months to evaluate the risk of major hemorrhage in the rivaroxaban and ticagrelor arms.

RESULTS: Enrollment began in August 2022 and, as of 26 June 2024, the 450th subject was randomized into the study.

CONCLUSION: CAPTIVA is evaluating two alternative dual antithrombotic therapies to clopidogrel and aspirin to maximize the chance of establishing more effective antithrombotic therapy for symptomatic ICAS, one of the most common and high-risk cerebrovascular diseases worldwide.

PMID:39862061 | DOI:10.1177/17474930241313301

Nurs Leadersh (Tor Ont). 2025 Jun;37(3):8-29. doi: 10.12927/cjnl.2025.27506.

ABSTRACT

INTRODUCTION: Black nurses are under-represented in the Canadian nursing workforce. A legacy of discrimination and systemic barriers reinforce the under-representation of Black nurses in the nursing workforce throughout the health system.

OBJECTIVE: The objective of this study was to identify and describe organizational initiatives for the recruitment, retention and advancement of Black nurses in the healthcare system.

METHODS: We conducted a rapid review of peer-reviewed and grey literature regarding the recruitment, retention and advancement initiatives for Black nurses, in North America and the UK.

RESULTS: Thirty-eight sources were included in this review. Majority of the included sources focused on leadership initiatives that described a multi-pronged approach for recruitment, retention or advancement. Examples of useful initiatives included mentorship, dedicated leadership and advancement programs, as well as supportive institutional policies. In addition, several Black nurse-led organizations/initiatives were identified.

CONCLUSION: These findings highlight the importance of multi-pronged approaches to enhance and support the Black nurse workforce. In addition, implementing and evaluating initiatives is critical to understanding how workforce representation and inclusion is strengthened.

PMID:39862050 | DOI:10.12927/cjnl.2025.27506

Br J Hosp Med (Lond). 2025 Jan 24;86(1):1-12. doi: 10.12968/hmed.2024.0582. Epub 2025 Jan 24.

ABSTRACT

Aims/Background Gestational diabetes mellitus (GDM) is a common complication during pregnancy. This retrospective study investigates the correlation between umbilical blood flow index and maternal-fetal outcomes in pregnant women with GDM, aiming to contribute to evidence-based risk assessment and management strategy in this high-risk obstetric population. Methods This retrospective study recruited 119 pregnant women with GDM who were admitted to the Yichang Central People’s Hospital, between January 2022 and January 2024. Based on the umbilical blood flow index, the study participants were divided into a normal umbilical blood flow (UBF) index group (n = 56) and a high UBF index group (n = 63). Colour Doppler ultrasound was used to assess umbilical blood flow, and relevant data on maternal, fetal, and neonatal outcomes were obtained from the hospital’s electronic medical records. Results We observed that, compared to the normal UBF index group, the high UBF index group exhibited significantly higher rates of adverse pregnancy outcomes, including the cesarean section (p = 0.022), preterm delivery (p = 0.020), gestational hypertension (p = 0.019), neonatal hypoglycemia (p = 0.015), as well as increased incidence of neonatal complications such as respiratory distress syndrome (p = 0.009), neonatal jaundice (p = 0.022), neonatal intensive care unit (NICU) admission (p = 0.015), lower 5-minute Apgar scores (p = 0.013), and neonatal sepsis (p = 0.005). Furthermore, significant differences were observed in fetal biometric parameters and placental morphology between the two groups (fetal weight: p = 0.003; estimated fetal weight percentile: p = 0.017; femur length: p = 0.018; placental weight: p = 0.019; placental volume: p = 0.021). Additionally, correlation analyses indicated significant associations between umbilical blood flow index and maternal and fetal outcomes (p < 0.05). Conclusion We observed a significant correlation between umbilical blood flow indices and maternal and fetal outcomes in pregnant women with gestational diabetes mellitus, implying its utility as a non-invasive parameter for risk stratification and personalized management in this high-risk obstetric population.

PMID:39862042 | DOI:10.12968/hmed.2024.0582

Br J Hosp Med (Lond). 2025 Jan 24;86(1):1-11. doi: 10.12968/hmed.2024.0577.

ABSTRACT

Aims/Background Artificial intelligence (AI), with advantages such as automatic feature extraction and high data processing capacity and being unaffected by fatigue, can accurately analyze images obtained from colonoscopy, assess the quality of bowel preparation, and reduce the subjectivity of the operating physician, which may help to achieve standardization and normalization of colonoscopy. In this study, we aimed to explore the value of using an AI-driven intestinal image recognition model to evaluate intestinal preparation before colonoscopy. Methods In this retrospective analysis, we analyzed the clinical data of 98 patients who underwent colonoscopy in Nantong First People’s Hospital from May 2023 to October 2023. Among them, 47 cases were evaluated based on the intestinal preparation map and the last fecal characteristics (Regular group), and 51 cases were evaluated using an AI-driven intestinal image recognition model (AI group). The duration of colonoscopy examination, intestinal cleanliness, incidence of adverse reactions, and satisfaction with intestinal preparation of the two groups were analyzed. Results The time for colonoscopy in the AI group was shorter than that in the Regular group, and the intestinal cleanliness score in the AI group was higher than that in the Regular group (p < 0.05). The incidence of adverse reactions in the AI group (3.92%) was lower than that in the Regular group (10.64%), but the difference was not statistically significant (p > 0.05). The satisfaction rate of intestinal preparation in the AI group (96.08%) was comparable to that of the Regular group (82.98%) (p > 0.05). Conclusion Compared with the assessment based solely on the intestinal preparation map and the last fecal characteristics, the application of AI intestinal image recognition model in intestinal preparation before colonoscopy can shorten the time of colonoscopy and improve intestinal cleanliness, but with comparable patient satisfaction and safety.

PMID:39862028 | DOI:10.12968/hmed.2024.0577

Br J Hosp Med (Lond). 2025 Jan 24;86(1):1-19. doi: 10.12968/hmed.2024.0575. Epub 2025 Jan 24.

ABSTRACT

Aims/Background Atopic dermatitis (AD) is a common chronic inflammatory skin disorder globally. Crisaborole, a nonsteroidal topical phosphodiesterase 4 inhibitor (PDE4i), has been utilized in treating AD. Crisaborole regulates the production of inflammatory cytokines, which are usually overactive among AD patients. Therefore, this study aimed to explore the efficacy and safety of crisaborole in treating AD in patients aged ≤18 years. Methods A literature search was performed across PubMed, MEDLINE, Embase, Cochrane, and Google Scholar. The inclusion criteria involved primary studies evaluating the effect of crisaborole in treating dermatitis, articles exploring the use of crisaborole in AD patients below 18 years (>two years), and articles published in English between 2000 and 2022. However, the studies evaluating AD in adult patients, those reporting treatments other than crisaborole, those published before 2000, and articles written in languages other than English were excluded from this analysis. Furthermore, secondary data sources such as case reports, newspaper articles, magazines, and other systematic reviews and meta-analyses were excluded. A meta-analysis was conducted using RevMan 5.4. The risk of bias in the manuscripts was assessed using the Cochrane tool. The I-square test statistic was used to determine heterogeneity, and Egger’s test was used to evaluate publication bias. Results Ten studies met the eligibility criteria and were included in the final analysis. Most of the studies exhibited a low risk of bias with no publication bias. Meta-analysis indicated a significant difference in the number of patients attaining Investigator Static Global Assessment (ISGA) success at day 29, with significantly higher patients in the crisaborole group than in the vehicle group (odds ratio (OR) 1.56, 95% CI 1.24 to 1.96; I² = 77%; p = 0.0001). Similarly, pruritus improvement was significant between the two cohorts at day 29, indicating significantly higher heterogeneity (OR 1.70, 95% CI 1.10 to 2.63; I² = 91%; p = 0.02). Furthermore, the safety profiling of the treatments was insignificant, demonstrating no statistical difference in the treatment-emergent adverse events (TEAEs) between the two groups with high heterogeneity (OR 0.53, 95% CI 0.14 to 1.98; I² = 99%; p = 0.35). Conclusion Crisaborole demonstrates substantial efficacy in treating mild to moderate AD compared to vehicle therapies, as it reduces the signs and symptoms of the disease. Furthermore, crisaborole is well tolerated and has an acceptable safety profile in treating mild to moderate AD patients.

PMID:39862023 | DOI:10.12968/hmed.2024.0575

Br J Hosp Med (Lond). 2025 Jan 24;86(1):1-13. doi: 10.12968/hmed.2024.0538. Epub 2025 Jan 14.

ABSTRACT

Aims/Background Deep venous thrombosis (DVT) represents a significant postoperative complication after artificial femoral head replacement, with the incidence increasing proportionally with patient age. This study aimed to evaluate the effect of early postoperative use of intermittent pneumatic compression devices (IPC), followed by the combined use of low molecular weight heparin (LMWH) after 48 hours, for the prevention of postoperative lower limb DVT in elderly patients undergoing hip arthroplasty. Methods The retrospective study included 100 elderly patients who underwent unilateral femoral head replacement. The control group (n = 55) received combined LMWH initiated 12 hours postoperatively, while the observation group (n = 45) started combined LMWH 48 hours postoperatively. Changes in coagulation parameters, perioperative complications, and the incidence of postoperative lower limb DVT were compared between the two groups. Results Coagulation parameters showed significant changes post-intervention in both groups, with no statistically significant inter-group differences observed post-intervention (p > 0.05). The incidence of postoperative lower limb DVT did not differ significantly between the two groups (p > 0.05). However, the observation group demonstrated significantly lower postoperative blood loss, incidence of periwound hematoma, and transfusion rates compared to the control group (p < 0.05). Conclusion The sequential application of IPC in the early postoperative period, followed by combined LMWH administration after 48 hours, demonstrates comparable efficacy in preventing lower limb DVT formation in elderly patients undergoing hip arthroplasty when compared to the initiation of combined LMWH starting 12 hours postoperatively. In addition, this approach significantly reduces the risk of postoperative bleeding and exhibits a high safety profile.

PMID:39862017 | DOI:10.12968/hmed.2024.0538

J Integr Neurosci. 2025 Jan 7;24(1):25731. doi: 10.31083/JIN25731.

ABSTRACT

BACKGROUND: Observation, execution, and imitation of target actions based on mirror neuron network (MNN) have become common physiotherapy strategies. Electrical stimulation (ES) is a common intervention to improve muscle strength and motor control in rehabilitation treatments. It is possible to enhance MNN’s activation by combining motor execution (ME) and motor imitation (MI) with ES simultaneously. This study aims to reveal whether ES could impact cortical activation during ME and MI.

METHODS: We recruited healthy individuals and assigned them randomly to the control group (CG) or experiment group (EG). Participants in EG performed ME and MI tasks with ES, while participants in CG performed the same two tasks with sham ES. We utilized functional near-infrared spectroscopy (fNIRS) to detect brain activation of MNN during ME and MI with and without ES, a randomized block design experiment paradigm was designed. Descriptive analysis of oxy-hemoglobin (HbO) and deoxy-hemoglobin (HbR) were used to show the hemoglobin (Hb) concentration changes after different event onsets in both CG and EG, a linear mixed-effects model (LMM) of HbO data was employed to analyze the effect of ES on the activation of MNN.

RESULTS: A total of 102 healthy adults were recruited and 72 participants’ data were analysed in the final report. The block averaged Hb data showed that HbO concentration increased and HbR concentration decreased in most MNN regions during ME and MI in both groups. The LMM results showed that ES can significantly improve the activation of inferior frontal gyrus, middle frontal gyrus, and precentral gyrus during MI, the supplementary motor area, inferior parietal lobule, and superior temporal gyri showed increased activation, but without statistical significance. Although the results did not reach statistical significance during ME, ES still showed positive effects on increased overall activations.

CONCLUSIONS: In this study, we present potential novel rehabilitation approaches that combines MNN strategies and low-frequency ES to enhance cortical activation. Our results revealed that ES has potential to increase activation of most MNN brain areas, providing evidence for related rehabilitative interventions and device development.

CLINICAL TRIAL REGISTRATION: This study was registered on the China Clinical Trial Registration Center (identifier: ChiCTR2200064082, registered 26, September 2022, https://www.chictr.org.cn/showproj.html?proj=178285).

PMID:39862008 | DOI:10.31083/JIN25731

Artif Organs. 2025 Jan 24. doi: 10.1111/aor.14953. Online ahead of print.

ABSTRACT

BACKGROUND: Kidney transplantation (KT) is the most effective treatment for end-stage renal disease. End-ischemic hypothermic machine perfusion (EI-HMP) has emerged as a promising method for preserving grafts before transplantation. This study aimed to compare graft function recovery in KT recipients of deceased brain-death (DBD) grafts preserved with EI-HMP versus static cold storage (SCS). The primary outcome was the rate of delayed graft function (DGF). Secondary outcomes included urine output, intensive care unit (ICU) stay, hospital stay duration, and survival rates.

METHODS: A retrospective, single-center observational study was conducted at Sapienza University of Rome, analyzing 313 KT patients between January 2014 and September 2021. Patients were stratified into two groups based on graft preservation methods (EI-HMP, n = 95; SCS, n = 218). A stabilized inverse probability treatment weighting (IPTW) method was employed to adjust for potential confounders.

RESULTS: There were no significant differences in DGF rates between the two groups (17.9% vs. 15.6% in SCS and EI-HMP cases, respectively; p = 0.75). EI-HMP group demonstrated a higher urine output on day 2 (p = 0.046), a shorter ICU stay (p < 0.0001), and a trend toward a shorter overall hospital stay (p = 0.07). No statistically significant differences were found between EI-HMP and SCS cases in 1- and 3-year overall survival rates (3.2% and 6.7% vs. 5.6% and 6.6%, respectively; log-rank p = 0.53) or in death-censored graft loss rates (5.4% and 8.9% vs. 5.7% and 7.3%, respectively; log-rank p = 0.88). In a sub-analysis of expanded criteria donors (ECD), EI-HMP demonstrated a protective effect by reducing the risk of DGF (OR = 0.31, 95% CI = 0.09-0.95; p = 0.047).

CONCLUSION: EI-HMP was associated with certain short-term benefits, including increased urine output and reduced ICU stays, but showed no significant impact on long-term survival outcomes. A reduction in DGF rates was observed only in the ECD subgroup. Randomized controlled trials are necessary to further investigate the long-term clinical benefits of EI-HMP.

PMID:39861988 | DOI:10.1111/aor.14953