Safety Analysis Research Articles

Effectiveness and safety analysis of ketogenic diet therapy for drug-resistant epilepsy caused by structural pathology.

To explore the effectiveness and safety of the ketogenic diet (KD) in children with drug resistant epilepsy (DRE) caused by structural etiology. The children were categorized into acquired brain injury group and malformations of cortical development (MCD) group based on the etiology. Follow-up assessments were performed at 1, 3, and 6 months after KD treatment to observe seizure reduction, behavioral and cognitive improvements, adverse reactions events, and reasons for discontinuation withdrawal. Statistical analysis was conducted on the results. We found the seizure-free rates at 1, 3, and 6 months were 4.8% (2/42), 19% (8/42), and 21.4% (9/42), respectively. The seizure control effective rates were 42.9% (18/42), 52.4% (22/42), and 54.8% (23/42) at the corresponding time points. Compared to the acquired brain injury group, the MCD group showed a higher seizure control effective rate. Further analysis within the MCD group revealed the highest efficacy in focal cortical dysplasia (FCD). At the 3-month follow-up, cognitive and behavioral improvements were observed in 69% (29/42) of children. The main reasons for discontinuation were lack of efficacy and poor compliance. Finally, we get that KD is a safe and effective treatment for drug resistant epilepsy caused by structural etiology, with the added benefit of improving behavioral and cognitive abilities in children. The efficacy is higher in children with MCD, particularly in cases of FCD. Early intervention with KD is recommended for this population.

Oral 5-aminolevulinic Acid for Patients With Localized Prostate Cancer Undergoing Low-dose-rate Brachytherapy: AMBER Trial.

Radiotherapy is one of the most frequently used options for prostate cancer (PCa). However, adverse effects related to irradiation of surrounding normal organs are significant clinical concerns. Specifically, genitourinary toxicity can dramatically reduce the quality of life. This clinical trial investigated the efficacy of oral 5-aminolevulinic acid phosphate combined with sodium ferrous citrate (ALA-SFC) in patients treated with low-dose-rate brachytherapy (LDR-BT) using an iodine-125 seed source. The AMBER study was a prospective single-center trial involving patients with localized PCa who underwent LDR-BT without external-beam radiotherapy (jRCTs051190077). Fifty patients were included and instructed to take capsules of ALA-SFC twice a day (200 mg phosphate salt and 229.42 mg per day) for six months from the day of seed implantation (prescribed radiation dose of 160 Gy). Patient data were collected before implantation, during ALA-SFC treatment, and at 1, 3, 6, 9, and 12 months post-LDR-BT. The primary endpoint of this trial was urinary frequency at three months. Other patient-reported outcomes, investigator-reported adverse events, and oncological outcomes were secondary endpoints. Of 50 enrolled cases (45 in the per-protocol analysis, 49 in the safety analysis), urinary frequency and its increase from baseline did not differ from 141 historical controls at any time point, including at three months post-LDR-BT. Propensity score matched analysis confirmed no time-course differences in frequency, volume, or urinary symptom scores between groups. Biochemical failure-free and metastasis-free survival also remained similar. Oral supplementation of ALA-SFC to LDR-BT did not alleviate radiation-induced toxicity or improve oncological outcomes.

Comparative Analysis of Safety and Efficacy Between Anterior and Posterior Calyceal Entry in Supine Percutaneous Nephrolithotomy.

Introduction: One advantage of supine percutaneous nephrolithotomy (sPCNL) is the ability to access anterior as well as posterior calyces, but the safety and efficacy of anterior calyceal entry has never been investigated to our knowledge. We prospectively evaluated patients scheduled for sPCNL comparing anterior and posterior calyceal access. Materials and Methods: After Institutional Review Board approval, we prospectively enrolled 100 consecutive patients undergoing sPCNL from February to September 2023. Primary outcomes included intraoperative complications, blood transfusions, 30-day complication rates, and emergency department (ED) visits or readmissions. Secondary outcomes included stone-free rates (SFR). Results: Seventy-six patients had anterior calyceal entry and 24 had posterior. No significant differences were found in terms of baseline demographics (age, body mass index), stone characteristics (location, density, complexity), or intraoperative features (operative time, location of access). Safety outcomes, including intraoperative complications (1% vs 4%), blood transfusions (3% vs 8%), 30-day complication rates (17% vs 21%), and ED visits (1% vs 0) or readmissions (11% vs 21%) were comparable between groups. Overall SFRs were equivalent (86% vs 90%). Conclusion: We found that anterior and posterior accesses in sPCNL offer similar safety and efficacy, with no significant differences in complications or SFRs. Surgeons can select either approach based on patient anatomy and surgical needs without concern for increased complications. Further research is necessary to confirm these findings and guide best practices for calyx selection in sPCNL.

Aviation-BERT-NER: Named Entity Recognition for Aviation Safety Reports

This work introduces Aviation-BERT-NER, a Named Entity Recognition (NER) system tailored for aviation safety reports, building on the Aviation-BERT base model developed at the Georgia Institute of Technology’s Aerospace Systems Design Laboratory. This system integrates aviation domain-specific data, including aircraft types, manufacturers, quantities, and aviation terminology, to identify named entities critical for aviation safety analysis. A key innovation of Aviation-BERT-NER is its template-based approach to fine-tuning, which utilizes structured datasets to generate synthetic training data that mirror the complexity of real-world aviation safety reports. This method significantly improves the model’s generalizability and adaptability, enabling rapid updates and customization to meet evolving domain-specific requirements. The development process involved careful data preparation, including the synthesis of entity types and the generation of labeled datasets through template filling. Testing on real-world narratives from the National Transportation Safety Board (NTSB) database highlighted Aviation-BERT-NER’s robustness, with a precision of 95.34%, recall of 94.62%, and F1 score of 94.78% when evaluated over 50 manually annotated (BIO tagged) paragraphs. This work addresses a critical gap in English language NER models for aviation safety, promising substantial improvements in the analysis and understanding of aviation safety reports.

B-TBM: A Novel Deep Learning Model with Enhanced Loss Function for HAZOP Risk Classification Using Natural Language Statistical Laws

HAZOP is a paradigm of industrial safety, and the introduction of deep learning-based HAZOP text categorization marks the arrival of an intelligent era of safety analysis. However, existing risk analysis methods have limitations in processing complex texts and extracting deep risk features. To solve this problem, this paper proposes a novel HAZOP risk event classification model based on BERT, BiLSTM, and TextCNN. The complexity of HAZOP text is revealed by introducing statistical laws of natural language, such as Zipf’s law and Heaps’ law, and the outputs of different levels of BERT are further combined linearly to collaborate with BiLSTM and TextCNN to capture long-term dependency and local contextual information for a more accurate classification task. Meanwhile, an improved loss function is proposed to effectively solve the deficiencies of the traditional cross-entropy loss function in the mislabeling process and improve the generalization ability of the model. It is experimentally demonstrated that the accuracy of the model is improved by 3% to 4% compared to the traditional BERT model in the task of severity and possibility classification of HAZOP reports. This study not only improves the accuracy and efficiency of HAZOP risk analysis, but also provides new ideas and methods for the application of natural language processing in industrial safety.

Analysis of safety and outcome of use of NOAC in intracardiac thrombi over warfarin

Abstract Introduction Intracardiac clots occur in 15- 25% of patients post myocardial infarction and in patient with atrial fibrillation. It holds poor outcome if not treated with anticoagulation. Warfarin remains the drug of choice in such patients, however recently according to the newly published data, the European Society of Cardiology (ESC) has recommended non-vitamin K antagonist anticoagulant (NOAC) for intracardiac clots as a class 2A recommendation. There is no documented data in the region of the gulf regarding the use of NOAC in intracardiac clots. Aim We aim in this study to evaluate the use of NOAC in the treatment of intracardiac clots over warfarin, by studying the effectiveness, safety and associated complications. Methodology A retrospective cohort study from April 2017 to December 2023 was conducted of patient’s above 18 years old who have a documented intracardiac clot on echocardiography. The patient were grouped into patients discharged on NOAC and those discharged on warfarin. The participants were studied for resolution of clot and development of complication; death, bleeding and thrombosis. Results A total of 253 patients fulfilled the inclusion criteria. Out of which 45 ( 18%) patients were discharged on NOAC and 208 (82%) on warfarin. The two groups had similar demographics with equally mean age of 71 years old , 89% being males, 38% hypertensive and most common clot in the left ventricle in both groups. From those patients with documented follow up ( NOAC 45% average of 8 months, Warfarin 62% average of 7 months); 48% in the NOAC group had a documented resolution of the clot while 44% in the warfarin group had a documented resolution of the intracardiac clot.(p value of 0.7) The median resolution time in the NOAC group was 4 months while in the warfarin group 3.5 months. Bleeding occurred in 19% and mortality rate was 5% in NOAC group, while in the warfarin group 10% developed bleeding and mortality rate was 6%. Conclusion Our data pointed out the safety of NOAC as a reasonable alternative to warfarin inpatient with intracardiac clots emphasizing the ESC recommendation in this regards. We recommend a randomized studies to prove the superiority of NOAC as anticoagulation of choice in intracardiac thrombi.

Model‐based systems engineering and safety assessment: A workflow for mechatronic systems design

AbstractMechatronic systems become ever more complex because of their increasing number of interconnected safety critical components and sophistication. MBSE (Model‐based Systems Engineering) and MBSA (Model‐Based Safety Assessment) are the most commonly adopted approaches to deal with the design and safety analysis of mechatronic systems. Unfortunately, both approaches are normally adopted separately, especially in the earlier phases of system design, thus leading to a lack of communication between system engineers and the safety team. This work aims to fill that gap at a high level, that is, through process interaction. This paper proposes an enhanced V‐model for the design of safety‐critical mechatronic systems. It relates a system development process with specific safety assessment methods. Specifically, the proposed workflow details exchange flows between the RFLP (Requirements, Functional, Logical, Physical) method, the FHA (Functional Hazard Analysis), the FMEA (Failure Mode and Effects Analysis), the MBSA and simulation, and the FTA (Fault Tree Analysis). These analyses are complemented with multiphysics modeling and simulation to observe system behavior in functional and failure scenarios, with the aim of requirements verification. The design workflow has been applied to a winged Unmanned Aerial Vehicle to apply the parallel process and the necessary interaction of MBSE and MBSA approaches. The information flows between the individual activities proved effective for designing a safe system before the verification phase. The main benefit of the proposed workflow is providing both the design and safety team with some interaction points, thus avoiding a lack of safety‐critical analysis in the early phases of system design.

Efficacy and safety of stem cell therapy for fistula management: An overview of existing systematic reviews.

Fistulas, abnormal connections between two anatomical structures, significantly impact the quality of life and can result from a variety of causes, including congenital defects, inflammatory conditions, and surgical complications. Stem cell therapy has emerged as a promising alternative due to its potential for regenerative and immunomodulatory effects. This overview of systematic reviews aimed to assess the safety and efficacy of stem cell therapy in managing fistulas, drawing on the evidence available. This umbrella review was conducted following the Joanna Briggs Institute (JBI) methodology to assess the efficacy and safety of stem cell therapy for treating various types of fistulas. A comprehensive search was performed across multiple electronic databases including PubMed, Embase, Cochrane Register, and Web of Science up to May 5th, 2024. Systematic reviews focusing on stem cell therapy for fistulas were included, with data extracted on study design, stem cell types, administration methods, and outcomes. The quality of the reviews was assessed using the AMSTAR 2 tool, and meta-analyses were conducted using R software version 4.3. Nineteen systematic reviews were included in our umbrella review. The stem cell therapy demonstrated by significant improvements in clinical remission rates, with a relative risk (RR) of 1.299 (95% CI: 1.192 to 1.420). Stem cell therapy enhanced fistula closure rates, both short-term (RR=1.481; 95% CI: 1.036 to 2.116) and long-term (RR=1.422; 95% CI: 1.091 to 1.854). The safety analysis revealed no significant increase in the risk of adverse events with stem cell therapy, showing a pooled RR of 0.972 (95% CI: 0.739 to 1.278) for general adverse events and 1.136 (95% CI: 0.821 to 1.572) for serious adverse events, both of which indicate a safety profile comparable to control treatments. Re-epithelialization rates also improved (RR=1.44; 95% CI: 1.322 to 1.572). Stem cell therapy shows promise as an effective and safe treatment for fistulas, particularly in inducing remission and promoting closure of complex fistulas. The findings advocate for further high-quality research to confirm these benefits and potentially incorporate stem cell therapy into standard clinical practice for fistula management. Future studies should focus on long-term outcomes and refining stem cell treatment protocols to optimize therapeutic efficacy.

Thermal Fluid Modeling Approaches in SAM for High Temperature Gas-Cooled Reactor Applications

This paper provides an overview of the unique modeling and simulation challenges and needs in the system and safety analysis of two common types of High Temperature Gas-cooled Reactor (HTGR) designs. The challenges are associated with the complex core geometry configurations and the change of the dominant heat removal mechanisms between normal operating conditions and decay heat removal transients. This requires that simulation tools utilize models with reasonable length scales and capture both the localized heat transfer and the core-scale heat transfer at the same time. To meet such analysis needs, different methodologies were developed. This includes adopting existing methods and further developing/improving them, as well as proposing innovative methods that leverage advanced computational frameworks such as the Multiphysics Object Oriented Simulation Environment (MOOSE).

Comparison of 600 mg VS 300 mg clopidogrel loading dose for patients with ischemic heart disease: a meta-analysis of randomized controlled trials

Abstract Background While a 600-mg loading dose (LD) of clopidogrel has demonstrated superior inhibition of platelet function compared to 300-mg LD, the clinical evidence supporting this superiority is limited. The debate centers on whether a higher clopidogrel LD regimen in primary percutaneous coronary intervention outperforms the standard 300 mg LD, with potential benefits being more pronounced in higher-risk patients. Balancing enhanced platelet inhibition to reduce ischemic events against the associated risk of increased bleeding remains a critical consideration in determining the optimal loading dose of clopidogrel for patients with ischemic heart disease. Purpose The objective of this meta-analysis is to validate current randomized trials that investigate the efficacy and safety of two clopidogrel loading regimens (600 mg vs 300 mg) in patients with ischemic heart disease treated with primary percutaneous coronary intervention. Method A systematic literature search for randomized controlled trials was performed comparing 600 mg with 300 mg LD of clopidogrel using PubMed, MEDLINE, Embase, Cochrane, Clinicaltrials.gov. and Herdin PH. Studies included those between 2010 - 2023 involving human subjects. The primary efficacy endpoint was a 1-month rate of major adverse cardiac event (MACE) and the primary safety outcome was bleeding adverse effects. Result Nine randomized control studies involving 29,827 patients were included in the efficacy analysis. Mean duration of follow-up was 30 days. Only 8 studies were eligible for safety analysis. Compared with standard LD clopidogrel, high LD significantly reduced incidence of overall MACE (OR:0.82, 95% CI:0.74-0.91, p=0.0002), nonfatal myocardial infarction (OR:0.56; 95% CI:0.32-0.99, p = 0.15) and target vessel revascularization (OR 0.63; 95% CI 0.41 to 0.95, p = 0.03 ), without significant difference in terms of cardiac death (OR:0.89; 95% CI:0.76-1.04, p=0.15) and stroke (OR 0.92; 95% CI 0.67 to 1.26, p = 0.61). However, major bleeding risk was higher in the 600 mg LD (1.9%; 261/13288) compared with 300 mg LD (2.4%; 328/13242) [OR:1.27; 95% CI:1.08-1.49, p=0.005] without significant difference in minor bleeding (OR:1.05; 95% CI:0.94-1.17, p=0.35). Conclusion The administration of 600 mg of clopidogrel LD reduces the overall risk of MACE with an associated increased risk of major bleeding in patients with ischemic heart disease undergoing primary percutaneous coronary intervention.MACE OUTCOMES

Aficamten in patients with obstructive hypertrophic cardiomyopathy: an integrated safety analysis

Abstract Background Aficamten is a next-in-class, oral, selective cardiac myosin inhibitor targeting the hypercontractility underlying hypertrophic cardiomyopathy (HCM). It relieves left ventricular outflow tract obstruction, improves exercise capacity, symptoms, quality of life, and cardiac biomarkers with a modest effect on left ventricular ejection fraction (LVEF). Purpose To present an integrated safety analysis from all aficamten trials to date. Methods Patients with obstructive HCM (oHCM) who received ≥1 dose of aficamten or placebo [PBO] in the phase 2 REDWOOD-HCM trial, phase 3 SEQUOIA-HCM trial, or the open-label extension FOREST-HCM were included. Results In the PBO-controlled pool of REDWOOD-HCM and SEQUOIA-HCM, 170 patients received aficamten and 153 PBO. In the cumulative (parent+extension) aficamten treated pool, 283 patients were analyzed from initial dose of aficamten or after enrollment in FOREST-HCM (100 PBO-to-aficamten). Overall, mean age was 59 years, 42% were female. In the PBO-controlled pool the mean cumulative follow up was 70.8 patient-years (py) on aficamten, and 66.3 py on PBO, and the total cumulative exposure period to aficamten was 205.2 py. The mean dose of aficamten in the cumulative pool was 12.6 mg/day. Treatment emergent serious adverse events (TESAE) occurred in 10 (5.9%) aficamten patients vs 14 (9.2%) PBO patients in the PBO-controlled pool, and in 24 (8.5%) aficamten patients in the cumulative pool. In the blinded phase, reported AEs were dizziness in 11 (6.5%) aficamten vs 3 (2%) PBO patients, syncope in 3 (1.8%) vs 4 (2.6%), dyspnea in 11 (6.5%) vs 8 (5.2%) and hypertension in 11 (6.5%) vs 4 (2.6%). Site-read LVEF <50%, all resulting in down-titration occurred in 9 (5.3%) aficamten patients [exposure adjusted incidence rate (EAIR) 11.2 per 100 py] and 1 (0.7%) PBO patient (EAIR: 1.3 per 100 py), and in 11 (3.9%) aficamten patients in the cumulative pool (EAIR: 5.3 per 100 py). None of the LVEF <50% events in aficamten patients were associated with heart failure symptoms; 1 PBO patient with a low LVEF had an AE of peripheral edema. During the maintenance phase of the cumulative exposure pool, 1588 echocardiograms were performed, of which 11 (0.7%) led to dose reduction due to LVEF <50%, none resulted in discontinuation or treatment interruption. In the cumulative pool, 6 (2.1%) patients terminated treatment early, none due to aficamten-related AEs. New onset atrial fibrillation occurred in 4 (2.4%) aficamten (EAIR: 4.9 per 100 py) and 5 (3.3%) PBO patients (EAIR: 6.5 per 100 py). There were no deaths during the study period. Conclusions In this integrated safety analysis, aficamten had a safety profile similar to PBO and was consistent over an extended treatment period. There was a low incidence of LVEF <50%, none of which were associated with clinical sequalae, and all were successfully managed by dose reduction. Monitoring echocardiography in the maintenance phase yielded very few actionable results.

Long-term safety of mepolizumab for up to ∼10 years in patients with severe asthma: open-label extension study

Objectives Long-term safety monitoring of mepolizumab is necessary to support real-world use for the treatment of severe asthma. This Long-Term Access Program assessed the safety and benefit:risk of mepolizumab in pediatric, adolescent, and adult patients with severe asthma. Materials and methods This was a multicenter, Phase IIIb safety, open-label extension study of multiple prior studies assessing mepolizumab in addition to standard of care (Aug 2015 − Aug 2022). Adults/adolescents (≥12 years of age) received mepolizumab 100 mg subcutaneously (SC) every 4 weeks until mepolizumab was commercialized. Pediatric patients (6–11 years of age) received mepolizumab 40 mg or 100 mg SC (bodyweight <40 or ≥40 kg, respectively) every 4 weeks. Safety was assessed every 4 weeks and benefit:risk every 12 weeks. Results Of the 514 patients enrolled, 57% were female and the mean age was 51.1 (standard deviation: 14.9) years; 24 (5%) patients were 6–17 years of age. Total cumulative mepolizumab exposure across all mepolizumab studies included in this analysis was 1500.59 patient-years; median exposure was 2.03 (range, 0.08 to 9.97) years. Overall, 37 (7%) patients experienced on-treatment serious adverse events (SAEs): 34/502 (7%) in the 100 mg SC group and 3/7 (43%) in the 40 mg SC pediatric group. Two patients experienced SAEs considered to be treatment-related by the investigator. Infections were the most common SAEs of special interest (9 [2%] patients). Physician-assessed benefit:risk of mepolizumab supported continued treatment over the study period. Conclusions This long-term safety analysis of mepolizumab was consistent with previous reports, with no emerging safety concerns; most patients had a favorable benefit:risk up to ∼10 years. Clinical trial identifier NCT00244686 (GSK ID 201956)

Transoesophageal echocardiography-guided cardioversion and thromboembolism

Abstract Background To perform electrical cardioversion of atrial fibrillation or atrial flutter with a duration of more than 48 hours, it is recommended to initiate anticoagulation therapy for at least three weeks beforehand. In cases where cardioversion is necessary earlier, it is suggested to precede the procedure with a transoesophageal echocardiography to rule out the presence of a thrombus in the left atrium (referred to as TOE-guided cardioversion). This strategy is outlined in current ESC guidelines for atrial fibrillation. However due to limited evidence, no specific level of recommendation for its use is provided. Purpose This study aimed to characterize patients treated by TOE-guided cardioversion in two hospitals and to conduct a safety analysis of the procedure. The 30-day incidence of thromboembolic events was chosen as the main safety objective, the 30-day mortality as the secondary. Method This was a retrospective, two center, cohort register study where information was obtained from patients medical records. All patients who underwent TOE-guided cardioversion between 2012-2020 in the first institute, and between 2015-2020 in the second were included. From the medical records all the patient characteristics and the clinical outcomes were identified. Result A total of 259 patients, with TOE-guided cardioversions, arrhythmia duration over 48 hours and without adequate anticoagulation therapy were included. Patient characteristics are shown in table 1. It was equal incidence of a 30-day thromboembolic event (n=6) and the 30-day mortality (n=6), 2,3% respectively. Three of the six patients died of non-cardiovascular cause. One of the 30-day thromboembolic event resulted in mortality at day 31. Table 2 summarize the data related to the thromboembolic events. There was no statistically significant predictor of any of the two endpoints when comparing the patients with event and patients without. Conclusion This study shows that the risk of thromboembolic events after TOE-guided cardioversion is not negligible, 2,3% within a 30-day follow up. The 30-day mortality was 2,3%, half of which were non-cardiovascular. To analyse potential clinical predictors for any events, larger studies specifically powered for such a question is needed.

The effect of tranexamic acid on postpartum bleeding in women with moderate and severe anaemia (WOMAN-2): an international, randomised, double-blind, placebo-controlled trial

Tranexamic acid, given within 3 h of birth, reduces bleeding deaths in women with postpartum haemorrhage. We examined whether giving tranexamic acid shortly after birth can prevent postpartum haemorrhage in women with moderate or severe anaemia. This international, randomised, double-blind, placebo-controlled trial was done in 34 hospitals across four countries (Nigeria, Pakistan, Tanzania, and Zambia). We recruited women of any age in active labour with moderate or severe anaemia (haemoglobin <100 g/L). We randomly assigned women (1:1) who had given birth vaginally to receive 1 g of tranexamic acid or matching placebo by slow intravenous injection (over 10 min) within 15 min of the umbilical cord being cut or clamped. Women were randomly assigned by selection of the lowest numbered treatment pack from a box containing 20 packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to group assignment. The primary outcome was a clinical diagnosis of primary postpartum haemorrhage, which might be an estimated blood loss of more than 500 mL or any blood loss sufficient to compromise haemodynamic stability within 24 h of randomisation, analysed on an intention-to-treat basis. Safety analyses were performed in all participants included in the intention-to-treat population. This trial was registered on ISRCTN (ISRCTN62396133), ClinicalTrials.gov (NCT03475342), and the Pan African Clinical Trial Registry (PACTR201909735842379) and is closed to recruitment. From Aug 24, 2019, to Sept 19, 2023, 16 586 women aged 14-50 years were invited to take part and 1518 were excluded. 7580 women were randomly assigned to receive tranexamic acid and 7488 to receive placebo. Primary outcome data were unavailable for one woman in each group. The median time interval from the start of the administration of the trial treatment to the diagnosis of postpartum haemorrhage was 18·5 min (IQR 5-58); 20 min (8-64) in women with moderate anaemia and 13 min (7-44) in women with severe anaemia. 358 (35%) of 1024 with postpartum haemorrhage for whom time data were available were diagnosed before the trial treatment had been fully administered. Clinically diagnosed postpartum haemorrhage occurred in 530 (7·0%) of 7579 in the tranexamic acid group and in 497 (6·6%) of 7487 in the placebo group (risk ratio [RR] 1·05, 95% CI 0·94-1·19). There was no strong evidence against the null hypothesis of homogeneity of effects for any of the prespecified subgroup analyses: severity of anaemia (p=0·44), antepartum haemorrhage (p=0·044), birth canal trauma (p=0·37), use of pain control (p=0·37), and baseline risk of postpartum haemorrhage (p=0·31). There were no vascular occlusive events (pulmonary embolism, deep vein thrombosis, stroke, and myocardial infarction) reported in either group. There were no adverse events related to the treatment and no treatment-related deaths. In women with moderate and severe anaemia, giving tranexamic acid within 15 min of the umbilical cord being clamped did not reduce the risk of clinically diagnosed postpartum haemorrhage. The Bill & Melinda Gates Foundation and the Wellcome Trust.

A phase II study of ME2136 (Asenapine Maleate) plus standard antiemetic therapy for patients, including diabetic patients, receiving cisplatin-based chemotherapy.

Olanzapine combined with the neurokinin-1 receptor antagonist, palonosetron and dexamethasone is the standard treatment for chemotherapy-induced nausea and vomiting (CINV) due to highly emetogenic chemotherapy (HEC). However, the use of olanzapine poses challenges in patients with diabetes mellitus (DM) due to the potential risk of hyperglycemia. ME2136, antipsychotic similar to olanzapine, is associated with a lower risk of hyperglycemia. This study investigated the antiemetic efficacy and safety of ME2136 for HEC. This single-arm phase 2 study examined the safety and efficacy of ME2136 5mg for 4days in combination with triplet-combination antiemetic therapy. Two cohorts were established for the safety assessment: DM and non-DM. Eligible patients had malignant tumors and were receiving cisplatin-based chemotherapy for the first time. The primary endpoint was the complete response (CR) rate, defined as the percentage of patients without vomiting and not requiring rescue medications in the delayed phase (24-120h). Between December 2020 and January 2022, 40 patients were enrolled, with 20 in each cohort. All patients were included in the safety analysis and 35 in the efficacy analysis. The CR rate in the delayed phase was 71.4% [60% CI 63.1-78.6%] for all patients, 66.7% in the DM cohort, and 76.5% in the non-DM cohort. No treatment-related adverse events ≥ grade 3, including hyperglycemia, were reported. ME2136, when combined with standard triplet-combination antiemetic therapy, is expected to exert similar antiemetic effects to the standard treatment for CINV due to HEC. Currently, ME2136-02 trial is underway to examine the safety and efficacy of triplet-combination antiemetic therapy and a 5-day treatment with ME2136. This study was registered with the Japan Registry of Clinical Trials (jRCT2041200071) on 10 December 2020. Clinical trial registration: This study was registered with the Japan Registry of Clinical Trials (jRCT2041200071) on 10 December 2020.

Patient safety and quality improvement education in dermatology residency programs: a nationwide survey of program directors.

Patient Safety and Quality Improvement (PSQI) are key components of graduate medical training, as detailed by the Accreditation Council for Graduate Medical Education (ACGME), with specific requirements that residents participate in experiential learning in PSQI during residency training. This study aimed to analyze the breadth of available and required PSQI educational experiences across dermatology residency programs in the United States. The objective of this study was to characterize the scope of PSQI educational experiences across dermatology residency programs. We electronically surveyed program directors of all ACGME-accredited dermatology residency programs from September 2023 to March 2024. Responses to the survey were anonymously collected with Research Electronic Data Capture (REDCap). Of the 145 dermatology programs surveyed, 37 program directors responded (25.5%). 89.2% of programs reported requiring residents to participate in PSQI educational experiences, with the most common being participation in a resident-led QI project (70.3%), which was also the most commonly available experience (91.2%). The least common required experience was observed simulated patient safety events and analyses. 83.8% of programs reported formal mechanisms to assess residents' competency in QI. This study highlights variation in PSQI experiences within dermatology residency programs across the United States. More than 10% of surveyed programs reported no required QI experiences during residency training despite ACGME program requirements. Additional gaps include variation in assessment of resident PSQI competencies. This study provides insight on the current landscape of PSQI education across dermatology residency programs and identifies opportunities to strengthen dermatology programs' PSQI educational offerings.

Assessment of the Choked Flow Model of RELAP5 for Application of Inverse Quantification Methods

In the framework of deterministic safety analysis, best estimate plus uncertainty methodologies can provide a more informative detailed analysis of transients than conservative approaches. However, one important step in the application of such methodologies is derivation of uncertainty of the physical models. Probability density functions of the physical model parameters are obtained by applying inverse uncertainty quantification (IUQ) methods to experimental data. The present work deals with evaluation of the experimental database and assessment of the simulation model, which are required steps prior to the application of IUQ methods. The U.S. Nuclear Regulatory Commission system code RELAP5 has been applied for simulation of three experimental databases on choked/critical flow: Sozzi-Sutherland, Super MobyDick, and Marviken Critical Flow Tests. First, the adequacy of the experimental data to the specific target domain is carried out, to then proceed to calibration of the input model parameters by combining the use of Gaussian Process metamodels and optimization schemes. The assessment of the simulation models is performed by evaluating independently accuracy, precision, and consistency through four statistical indicators, including a novel indicator to evaluate the consistency of the results. The final results indicate that the model is capable of reproducing the selected experimental database and overall average accuracy, precision, and consistency below the 10% threshold and can be used for application of IUQ methods.

Systematic Literature Review on Knowledge-Driven Approaches for Construction Safety Analysis and Accident Prevention

Due to its inherent complexities in the process and the dynamic interactions with external environmental factors, the construction industry is widely considered one of the most hazardous industries worldwide. With advancements in artificial intelligence (AI), construction safety management practices have increasingly used knowledge-driven approaches. Such incorporation of knowledge-based methods has led to significant improvements in various elements of construction safety management systems, including hazard identification and risk assessment, selection of risk mitigation strategies, analysis of accident information, sharing of health and safety knowledge, access to regulations, and identification of applicable safety requirements. Against this background, this paper presents a systematic literature review to provide an overview of the current state of the art in the use of knowledge-driven approaches in construction safety management. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) procedure, this study reviews how the knowledge-driven approach is utilized in the construction safety management field to automate different activities that come under it. Journal papers published from 2000 were considered for this review, and the analysis focused on the contributions of research, the evolution of knowledge-driven approaches, sources of incorporated knowledge, methods of system development, yearly publications, and publication by journals. The results provide a comparison of related studies over two decades and offer insights into trends and gaps in this research field. Notably, the trend analysis shows a dramatic increase in the number, as well as the depth, of research efforts utilizing AI techniques for analyzing unstructured data, such as construction images and texts from construction documents, and drawing data-based decisions for accident prevention.

Non-steroid anti-inflammatory drugs: recommendations and precautions for safe use in a multidisciplinary surgical department

Aim of the study. Conducting a safety analysis of the use of non-steroidal anti-inflammatory drugs in order to develop informed recommendations and precautions for medical practice.Materials and methods. A retrospective analysis of inpatient medical records of 250 patients in the multidisciplinary surgery department was conducted for the period from December 2023 to February 2024.Results and discussion. Based on the results of the analysis of inpatient medical records, such criteria as the presence of indications for the prescription of non-steroidal anti-inflammatory drugs (according to the diagnosis, clinical pain syndrome and according to pain assessment scales), compliance of the choice of non-steroidal anti-inflammatory drugs with national protocols/international recommendations, compliance with age, the patient's physiological/ pathological condition and allergy history for the prescription of non-steroidal anti-inflammatory drugs were 100%. The indicator for compliance of a single therapeutic dose, route of administration, frequency, duration and an appropriate diluent of non-steroidal anti-inflammatory drugs with instructions for use was 86%, where medication errors were mainly made in the frequency of use of drugs. The percentage of polypharmacy was 20%. The criterion for assessing drug-drug interactions between drugs taken by patients showed that interactions of high clinical significance (major) were 8%, while those of moderate clinical significance (moderate) were 40%.Conclusions. Nonsteroidal anti-inflammatory drugs are convenient and affordable drugs that are widely used in the treatment of diseases of various organs and systems. Therefore, to ensure the rational and safe use of drugs in this group, it is necessary to introduce effective recommendations and precautions:1. Timely completion of pain assessment scales and diary records in the Damumed medical information system;2. Development in the Damumed medical information system of divisions of appointments into planned and pro re nata (as necessary), introduction into the system of accurately recording the time of execution of doctors’ prescriptions by nursing staff for strict compliance with the intervals between doses of non-steroidal anti-inflammatory drugs allowed by the instructions.3. Introduction into the practice of doctors the use of tools to combat polypharmacy in patients ≥65 years old: Beers criteria;4. Conducting educational activities, covering both medical personnel and patients, in order to increase the level of registration of unwanted adverse reactions.

A multivalent RSV vaccine based on the modified vaccinia Ankara vector shows moderate protection against disease caused by RSV in older adults in a phase 3 clinical study

Respiratory syncytial virus (RSV) causes a significant disease burden in older adults. The live recombinant vaccine based on a nonreplicating modified vaccinia Ankara (MVA-BN) poxvirus, MVA-BN-RSV, encoding for multiple proteins of RSV subtypes A and B, was assessed for efficacy against respiratory disease caused by RSV.Adults aged ≥60 years, with or without underlying chronic conditions, were enrolled and randomized in a 1:1 ratio to receive a single dose of vaccine or placebo and were followed for disease caused by RSV infection during the 2022–2023 season. The 2 primary endpoints were RSV-associated lower respiratory tract disease (LRTD) with ≥3 and ≥ 2 symptoms; acute respiratory disease (ARD) was a key secondary endpoint. The humoral RSV-specific immune response was assessed at baseline and 14 days post-vaccination. Safety was evaluated by collection of solicited adverse events (AEs) and unsolicited AEs for 7 and 28 days post-vaccination respectively, and SAEs for the entire study period.In total, 18,348 participants were included in the final efficacy and safety analyses. Vaccine efficacy was 42.9 % (95 % CI: −16.1; 71.9) against RSV-associated LRTD with ≥3 symptoms, 59.0 % (95 % CI: 34.7; 74.3) against LRTD with ≥2 symptoms, and 48.8 % (95 % CI: 25.8; 64.7) against ARD. The primary objective was not met for LRTD with ≥3 symptoms since the lower bound of the 95 % CI was below 20 %, the prespecified success criterion. The vaccine-elicited immune response showed mean fold-increases of 1.7 for RSV A and B neutralizing antibodies and 2.9 and 4.3 for RSV-specific IgG and IgA, respectively. The vaccine displayed mild to moderate reactogenicity, and no safety concerns were identified.MVA-BN-RSV induced suboptimal protection against RSV-associated LRTD, likely due to suboptimal neutralizing antibody response. The vaccine had an acceptable safety profile and confirmed immunogenicity, overall showing promise for MVA-BN-vectored constructs targeting other diseases.Trial Registration:Clinicaltrials.gov Identifier NCT05238025 (Registered February 14, 2022).