Joint WHO/EDQM Collaborative study for the establishment of WHO 3rd International Standard and Ph. Eur. Biological Reference Preparation for Prekallikrein activator in albumin batch 7.

An international collaborative study was jointly organised by the World Health Organization (WHO) and the European Directorate for the Quality of Medicines & HealthCare (EDQM) to establish the WHO 3rd International Standard (IS) for Prekallikrein activator (PKA) and European Pharmacopoeia (Ph. Eur.) PKA in albumin Biological Reference Preparation (BRP) batch 7. Twenty-six laboratories took part in the study to calibrate these replacement batches, as well as an additional reserve batch for the WHO IS, against the current WHO 2nd IS for PKA (02/168). Ph. Eur. PKA in albumin BRP batch 6 was also included to evaluate the continuity of the consecutive batches of BRP. The centrally calculated overall Huber's means based on the results from laboratories with at least two valid assays were 29.6 and 29.6 IU/ampoule for the candidate WHO 3rd IS (Sample A) and reserve batch (Sample B), and were 38.4 and 37.0 IU/vial for the current BRP batch 6 (Sample C) and the candidate BRP batch 7 (Sample D). The intra-laboratory variation expressed as coefficient of variation (CV) ranged between 1.4 and 16.6 %. The inter-laboratory variation expressed as CV based on Huber's means ranged between 4.4 and 5.4 %. The Huber's mean activity of Sample D against Sample C was 36.6 IU/vial with a CV of 1.7 %. These results confirm the good continuity of the consecutive batches of BRP. Based on the results of this study, it is recommended to establish Sample A as the WHO 3rd IS for PKA with an assigned potency of 30 IU/ampoule and Sample D as the Ph. Eur. PKA in albumin BRP batch 7 with an assigned potency of 37 IU/vial. Sample B is intended to be kept as a future reserve replacement WHO IS.

Diagnostic value of high-resolution vessel wall imaging technique in intracranial arterial stenosis and occlusion: a comparative analysis with digital subtraction angiography.

OBJECTIVE: To analyze the diagnostic value of HR-VWI in intracranial arterial stenosis and occlusion and compare it with DSA. METHODS: A retrospective analysis of clinical data of 59 patients with intracranial arterial stenosis in our hospital was conducted to compare the diagnostic results of the two methods for different degrees of intracranial stenosis and various morphological plaques. RESULTS: The diagnosis of stenosis and occlusion by both methods showed no significant difference (p > 0.05). Comparison of plaque morphology detected by HR-VWI with pathological examination results showed no significant difference (p > 0.05); however, there was a significant difference between plaque morphology detected by DSA and pathological examination results (p < 0.05). Additionally, there was a significant difference between plaque morphology detected by HR-VWI and DSA (p < 0.05). CONCLUSION: HR-VWI technique is comparable to DSA technique in diagnosing intracranial arterial stenosis and occlusion, but it is superior to DSA in plaque morphology diagnosis.

Mohs Micrographic Surgery for Cutaneous Squamous Cell Carcinoma.

BACKGROUND: The first-line treatment of the localized form of cutaneous squamous cell carcinoma (cSCC) remains surgical excision. Either conventional excision (CE) with margins or Mohs micrographic surgery (MMS) may be preferred, depending on the risk factors of cSCC, the characteristics of the tumor, and the available technical facilities. METHODS: This article presents a systematic review of the current literature spanning from 1974 to 2023, comparing outcomes of cSCC treated with MMS versus cSCC treated with conventional excision. RESULTS: Out of the 6821 records identified through the database search, a total of 156 studies were screened, of which 10 were included in the review. The majority of the included studies showed that treatment of cSCC with MMS consistently exhibits a significantly lower risk of recurrence compared to treatment with CE. In addition, MMS is emerging as the preferred technique for the resection of cSCC located in aesthetically or functionally challenging anatomical areas. CONCLUSION: The studies generally demonstrate that MMS is a safer and more effective treatment of cSCC than CE. Nevertheless, outcomes such as recurrence rates and cost-effectiveness should be assessed more precisely, in order to allow for a more tailored approach in determining the appropriate indication for the use of MMS.

A high-accuracy measurement procedure for salbutamol, ractopamine, and clenbuterol in pork by isotope dilution-liquid chromatography/tandem mass spectrometry.

In-depth research into the precise evaluation of enzymatic digestion efficiency and the selection of a suitable deuterium-labelled internal standard remains a gap in the accurate determination of ß2-agonists in animal-derived food by isotope dilution-liquid chromatography/tandem mass spectrometry (ID-LC-MS/MS). In this study, the enzymatic digestion conditions were optimized by monitoring the presence of ß2-agonist conjugates in positive samples, which proved to be reliable for ensuring complete enzymatic digestion. Comparative analysis of deuterium-labelled internal standards for salbutamol (SAL), ractopamine (RAC), and clenbuterol (CLB) revealed that CLB-D6 and SAL-D9 were less effective in compensating for matrix effects due to hydrogen­deuterium exchange during MS fragment formation. Consequently, SAL-D3, RAC-D3 and CLB-D9 were chosen for the implementation of ID-LC-MS/MS. The developed method demonstrates high accuracy and precision, with the average recoveries ranging from 93.8% to 107.3% with RSD <6.1%, which can provide higher-order measurement results for ß2-agonists in pork.

Uncovering the Shuixian tea grades hierarchy in Chinese national standard: From sensory evaluation to microstructure and volatile compounds analysis.

Basic standard samples are integral for ensuring consistency and quality control of tea. Understanding the real reasons behind the hierarchical system of Shuixian tea grades in the Chinese national standard is crucial to the scientific development of tea standardization. In this investigation, different grade samples of Shuixian tea strictly conformed to the Chinese national standard, serving as the research objects. Sensory evaluation, SEM and HS-SPME-GC-MS were employed to comprehensively analyze the aroma characteristics. The odor profiles of special grade samples predominantly featured floral and fruity aromas, which attributed to compounds such as geraniol, indole, phenylethyl alcohol. Additionally, hexanal, (E)-3-hexen-1-ol and other compounds contributed to fruity and sweet aroma in first grade. Notably, the predominant roasted and sweet aromas of second grade were attributed to compounds including pyridine, 2,5-dimethyl-pyrazine. This study lays a solid foundation for the scientific development of Chinese national standards and international standard system.

A dataset of Vietnamese university lecturers' teaching skills: A TPACK model.

The dataset described Vietnamese university lecturers' teaching and was constructed using elements of the TPACK model. According to the model of Mishra and Koehler [1], the questionnaire was developed. It was delivered through online platforms. The data collection period was three weeks, from February 6 to February 24, 2024. The survey was conducted using the snowball sampling method, with 503 participants. The article analyzed the remaining 461 records after excluding 41 invalid ones. The dataset was referenced in the Mendeley Data repository [10]. University lecturers could use the data set to enhance their personal professional development. In addition, the dataset could assist higher education institutions in formulating plans and training programs, instruct teaching staff, and assist educational managers and policymakers in formulating policies that encourage technology integration in teaching, thereby enhancing the quality of education.

Evaluating the Commutability of Reference Materials for α-Fetoprotein: Accurate Value Assignment With Multiple Systems and Trueness Verification.

Background: The accurate measurement of α-fetoprotein (AFP) is critical for clinical diagnosis. However, different AFP immunoassays may yield different results. Appropriate AFP reference materials (RMs) were selected and assigned accurate values for applications with external quality assessment (EQA) programs to standardize AFP measurements. Methods: Forty individual clinical samples and six different concentrations of candidate RMs (Can-RMs, L1-L6) were prepared by the Beijing Center for Clinical Laboratories. The Can-RMs were assigned target values by performing five immunoassays, using WHO International Standard 72/225 as a calibrator, and sent to 45 clinical laboratories in Beijing for AFP measurements. The commutability of all RMs was assessed based on CLSI and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) approaches. Analytical performance was assessed for compliance based on accuracy (total error, TE), trueness (bias), and precision (CV). Results: The Can-RMs were commutable for all immunoassays using the CLSI approach and for 6 of 10 assay combinations using the IFCC approach. RMs diluted in WHO RM 72/225 were commutable among all assays with the CLSI approach, except for serum matrix (Autolumo vs. Roche analyzer) and diluted water matrix (Abbott vs. Roche/Mindray analyzer), whereas some inconclusive and non-commutable results were found using the IFCC approach. The average pass rates based on the TE, bias, and CV were 91%, 81%, and 95%, respectively. Conclusions: The commutability of the RMs differed between both evaluation approaches. The Can-RMs exhibited good commutability with the CLSI approach, suggesting their suitability for use with that approach as commutable EQA materials with assigned values and for monitoring the performance of AFP measurements.

Predicting liver function after hemihepatectomy in patients with hepatocellular carcinoma using different modalities.

In response to Dr. Yue et al's study on prognostic factors for post-hemihepatectomy outcomes in hepatocellular carcinoma (HCC) patients, this critical review identifies methodological limitations and proposes enhancements for future research. While the study identifies liver stiffness measure and standard residual liver volume as potential predictors, concerns regarding small sample size, reliance on biochemical markers for safety assessment, and inadequate adjustment for confounding variables are raised. Recommendations for rigorous methodology, including robust statistical analysis, consideration of confounding factors, and selection of outcome measures with clinical components, are proposed to strengthen prognostic assessments. Furthermore, validation of novel evaluation models is crucial for enhancing clinical applicability and advancing understanding of postoperative outcomes in patients with HCC undergoing hemihepatectomy.

Comparison between head rotation and standard techniques for i-gel™ insertion: a randomized controlled trial.

BACKGROUND: This study evaluated the effect of head rotation on the first-attempt success rate of i-gel insertion, aiming to alleviate the effect of gravity on the tongue and reduce resistance between the device and the tongue. METHODS: Adult surgical patients were randomized to standard and head rotation technique groups. In the head rotation technique group, patients' heads were maximally rotated to the left before i-gel insertion. The primary endpoint was the first-attempt success rate. Secondary endpoints included the success rate within two attempts (using the allocated technique), time required for successful i-gel placement within two attempts, and success rate at the third attempt (using the opposite technique). RESULTS: Among 158 patients, the head rotation technique group showed a significantly higher first-attempt success rate (60/80, 75.0%) compared to the standard technique group (45/78, 57.7%; P = 0.021). The success rate within two attempts was similar between the groups (95.0% vs. 91.0%, P = 0.326). The time required for successful i-gel placement was significantly shorter in the head rotation technique (mean [SD], 13.4 [3.7] s vs. 16.3 [7.8] s; P = 0.030). When the head rotation technique failed, the standard technique also failed in all cases (n = 4), whereas the head rotation technique succeeded in five out of the seven patients where the standard technique failed. CONCLUSIONS: The head rotation technique significantly improved the first-attempt success rate and reduced the time required for successful i-gel insertion. It was effective when the standard technique failed. The head rotation technique may be an effective primary or alternative method for i-gel insertion. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT05201339).

Simulated patient methodology as a "gold standard" in community pharmacy practice: Response to criticism.

The simulated patient methodology (SPM) is considered the "gold standard" as covert participatory observation. SPM is attracting increasing interest for the investigation of community pharmacy practice; however, there is criticism that SPM can only show a small picture of everyday pharmacy practice and therefore has limited external validity. On the one hand, a certain design and application of the SPM goes hand in hand with an increase in external validity. Even if, on the other hand, this occurs at the expense of internal validity due to the trade-off situation, the justified criticism of the SPM for investigating community pharmacy practice can be countered.

Nonparametric receiver operating characteristic curve analysis with an imperfect gold standard.

This article addresses the challenge of estimating receiver operating characteristic (ROC) curves and the areas under these curves (AUC) in the context of an imperfect gold standard, a common issue in diagnostic accuracy studies. We delve into the nonparametric identification and estimation of ROC curves and AUCs when the reference standard for disease status is prone to error. Our approach hinges on the known or estimable accuracy of this imperfect reference standard and the conditional independent assumption, under which we demonstrate the identifiability of ROC curves and propose a nonparametric estimation method. In cases where the accuracy of the imperfect reference standard remains unknown, we establish that while ROC curves are unidentifiable, the sign of the difference between two AUCs is identifiable. This insight leads us to develop a hypothesis-testing method for assessing the relative superiority of AUCs. Compared to the existing methods, the proposed methods are nonparametric so that they do not rely on the parametric model assumptions. In addition, they are applicable to both the ROC/AUC analysis of continuous biomarkers and the AUC analysis of ordinal biomarkers. Our theoretical results and simulation studies validate the proposed methods, which we further illustrate through application in two real-world diagnostic studies.

A promising approach utilising photothermal energy to disinfect the root canal system: An in vitro investigation.

This study aimed to assess root canal disinfection through various irrigation protocols, including a novel photothermal system called 'LEAP'. Mandibular premolars were infected with Enterococcus faecalis and divided into five groups for different treatments: Group 1: standard needle irrigation; Group 2: passive ultrasonic irrigation; Group 3: GentleWave; Group 4: LEAP; and Group 5: Group 1 + Group 4. Microbial counts were measured before (S1) and after disinfection (S2) using colony-forming units (CFU) and confocal laser scanning microscopy (CLSM). Results revealed a significant reduction in bacterial counts for all groups (p < 0.05). While the percentage of dead bacteria near the canal wall (0-50 µm) did not differ significantly, at 50-150 µm, LEAP and SNI + LEAP exhibited significantly higher bacterial reduction than other groups (p < 0.05). The findings indicate that LEAP is comparable to existing irrigation devices in the main root canal and notably superior in tubular disinfection.

Coexistence of Standard Modifiable, Other Classical, and Novel and Classical Atherosclerotic Cardiovascular Disease Risk Factors in Middle Eastern Young Women.

Background: The coexistence of multiple standard modifiable risk factors (SMuRFs),classical and novel risk factors (RFs) for atherosclerotic cardiovascular disease (ASCVD) is common in the Middle East (ME). There is a paucity of data on the coexistence of these RFs in ME young women. Aim: Comparing the prevalence and the statistical patterns of the SMuRFs, classical and novel RFs in target population. Methods: In this case-control (1:2) study, consecutive young women aged 18-50 years were enrolled in 12 centers (July 2021 to October 2023). Prevalence and coexistence of 19 RFs were compared between cases with ASCVD and their controls. The RFs included SMuRFs (hypertension, type 2 diabetes, dyslipidemia, and cigarette smoking), other classical RF (obesity, family history of premature ASCVD, and physical inactivity), novel RFs and social determinants of health (health insurance, place of residence, depression, and level of education). Results: The study included 627 subjects; 209 had ASCVD (median age 46 years, IQR 49-42 years) and 418 controls (median age 45 years, IQR 48-41 years). The presence of 1-2 RFs; (ASCVD: 63.2%, Control: 54.1%, p=0.037) and 3-4 RFs; (ASCVD: 27.8%, Control: 3.3%, p < 0.001) SMuRFs was more prevalent in women with ASCVD. Similarly, the presence of 4-5 RFs; (ASCVD: 40.7%, Control: 14.6%, p<0.001), and 6-7 (ASCVD: 10.5%, Control: 1%, p < 0.001). The classical RF were also significantly common in these women. The distribution of multiple novel RF was not statistically significant across both groups. Finally, regarding the socioeconomic RFs in women with ASCVDs, the presence of 1-2 RFs (ASCVD: 59.8%, Control: 76.1%, p < 0.001) was significantly less common while the presence of 3-4 RFs (ASCVD: 39.2%, Control: 21.8%, p < 0.001) was vastly more common. Conclusion: An elevated rate of coexistence of classical RF in the case group, mainly socioeconomic and SMuRFs. By managing them primary and secondary ASCVDs prevention attained.

Effect of the degree of follicular diameter ≥18mm differentiation on the day of hCG administration to the outcome of controlled ovarian hyperstimulation (COH).

Objective: To explore the impact of the level of differentiation in a minimum of two follicles with a diameter of ≥18 mm on the outcome of controlled ovarian hyperstimulation on the day of human chorionic gonadotropin (hCG) administration. Methods: Single-center data from January 2018 to December 2021 was retrospectively analyzed for 1,199 patients with fresh embryo transfer for assisted reproduction. The absolute value of the standard deviation of the follicle size of at least 2 follicles ≥18 mm in diameter in both ovaries on the day of hCG was taken as the degree of differentiation of the dominant follicle after ovulation induction, based on the standard deviation response to the degree of dispersion of the data. The degree of follicular differentiation was divided into 3 groups according to the size of the value, and the general clinical conditions, laboratory indexes, and clinical outcomes of the patients in the 3 groups were compared. Results: Among the three groups, the body mass index (BMI) of the ≤1s group was lower than that of the other two groups (P< 0.05), while the follicle-stimulating hormone (FSH) and Anti-Mullerian hormone (AMH) were higher (P< 0.05), and the implantation rate and clinical pregnancy rate were significantly higher than those of the other two groups (P< 0.01). After multifactorial logistic regression to correct for confounding factors, with the ≤1s group as the reference, the implantation rate, hCG-positive rate, clinical pregnancy rate and live birth rate of embryo transfer in the ≥2S group were significantly lower (P< 0.01). The results of curve fitting analysis showed that the live birth rate decreased gradually with the increase of the absolute standard deviation (P=0.0079). Conclusion: Differences in follicle diameters ≥18 mm on the day of hCG injection did not have an impact on embryo quality, but had an impact on pregnancy outcomes. The less the variation in follicle size, the more homogeneous the follicle development and the higher the likelihood of live births.

Enhancing Treatment Outcomes in Atrial Fibrillation: A Contemporary Literature Review of the Impact of Optimizing Patient Well-Being in Treatment Management.

Atrial fibrillation (AF) is the most common heart rhythm disorder, defined by an irregular and rapid heartbeat. It is the most prevalent cardiac arrhythmia in the United States, characterized by irregular heartbeats due to asynchrony between atrial and ventricular contractions. AF can be categorized as paroxysmal or persistent and, as such, poses significant health risks, including heart failure and stroke. Factors like age, sex, lifestyle, and existing health conditions elevate AF risk. There have been a lot of debates around AF risk management and its impact on prognosis. This literature review aims to explore the influence of addressing modifiable risk factors in AF patients on its morbidity and mortality, exploring various treatment options and their effectiveness. Current guidelines suggest rate control and anticoagulation for persistent AF with medications like beta blockers and non-vitamin K oral anticoagulants. Catheter ablation for rhythm control is contentious. Studies on supplemental treatments, lifestyle changes, and managing comorbidities show mixed results, necessitating further research for comprehensive treatment effectiveness in AF patients, which this literature review will discuss.

Originalbeiträge (Originals). Network meta-analysis: science or alchemy? ­What works best in generalized anxiety disorder?

Recently Papola et al. (2023) published a network meta-analysis (NMA) on psychotherapy of generalized anxiety disorder (GAD) and concluded that cognitive-behavioral therapy (CBT) should be considered the first-line treatment for GAD. However, there are several concerns with regard to the procedures and the conclusions of this NMA and of NMA in general. We show that these concerns question the conclusions by Papola et al. Furthermore, we place concerns about thisNMAin a broader context and question whether existing evidence is consistent with the notion that one form of psychotherapy can be regarded as the gold standard for mental disorders and for all patients and therapists.

Freezing Diluted Bovine Serum Albumin Standards Does Not Significantly Affect Standard Curves.

Total protein isolation followed by quantitation is a common protocol in many laboratories. Quantitation is often done using a colorimetric assay such as the bicinchoninic acid (BCA) assay in which a change in the color of the BCA reagent is related to protein concentration. Extracted protein samples are compared to a standard curve made with dilutions of a protein standard such as bovine serum albumin (BSA) to determine their concentrations. A series of experiments was designed to determine the most reproducible and accurate method for quantifying protein concentrations of samples in an experimental series over time. The effect of freezing on diluted standards was investigated. Standards were frozen at -20°C or -80°C and serially thawed and refrozen up to three times prior to their use in a BCA assay. Thawing and refreezing the standards had no significant effect on protein concentration and the resulting standard curves. Inter-person and intra-person variability in the preparation of standards was also investigated. Protein concentration differences due to inter-person and intra-person variability were greater than protein concentration variability resulting from freezing and thawing, regardless of the freezing temperature. The most reproducible and accurate method for determining the protein concentration of extracted samples in an experimental series over time is diluting a large batch of BSA standards and freezing them at either -20°C or -80°C. Reproducibility was maintained with up to three freeze-thaws.

Investigating spatial patterns and determinants of tourist attractions utilizing POI data: A case study of Hubei Province, China.

Exploring the spatial distribution characteristics of tourist attractions and the influencing factors is of significant importance for destination development, yet little relevant research has been conducted. This study explores the spatial patterns and determinants of tourist attractions using Hubei Province of China as a case based on the POI (Points of Interest) data, combined with standard deviation ellipse, GeoDetector method and so on. The results show that: (1) The distribution of tourist attractions in Hubei Province is concentrated in Wuhan and Huanggang. (2) The overall spatial patterns of tourist attractions in Hubei Province show a trend of "overall dispersion, partial concentration", with the direction of northwest-southeast. (3) The permanent population, passenger traffic volume, per capita GDP, and the added value of the tertiary industry are the primary factors influencing the spatial distribution of tourist attractions in Hubei Province. Additionally, topography and river systems factors also impact their distribution. This study provides critical information for theory and practice in terms of tourism resources optimization.

Explicit inference: A meta-replication of SEER cancer registry research evaluating the Affordable Care Act's Medicaid expansion.

OBJECTIVES: Among the provisions within the Affordable Care Act (ACA), expanding Medicaid was arguably the greatest contributor to increasing access to care. For over a decade, researchers have investigated how Medicaid expansion impacted cancer outcomes. Over this same decade, statistical theory illuminated how state-based policy research could be compromised by invalid inference. After reviewing the literature to identify the inference strategies of state-based cancer registry Medicaid expansion research, this study aimed to assess how inference decisions could change the interpretation of Medicaid expansion's impact on staging, treatment, and mortality in cancer patients. DATA SOURCES: Cancer case data (2000-2019) was obtained from the Surveillance, Epidemiology, End Results (SEER) programme. Cases included all cancer sites combined, top 10 cancer sites combined, and three screening amenable cancers (colorectal, female breast, female cervical). STUDY DESIGN: A Difference-in-Differences design estimated the association between Medicaid expansion and four binary outcomes: distant stage, initiating treatment >1 month after diagnosis, no surgery recommendation, and death. Three inference techniques were compared: (1) traditional, (2) cluster, and (3) Wild Cluster Bootstrap. DATA COLLECTION: Data was accessed via SEER*Stat. PRINCIPAL FINDINGS: Estimating standard errors via traditional inference would suggest that Medicaid expansion was associated with delayed treatment initiation and surgery recommendations. Traditional and clustered inference also suggested that Medicaid expansion reduced mortality. Inference using Wild Cluster Bootstrap techniques never rejected the null hypotheses. CONCLUSIONS: This study reiterates the importance of explicit inference. Future state-based, cancer policy research can be improved by incorporating emerging techniques. These findings warrant caution when interpreting prior SEER research reporting significant effects of Medicaid expansion on cancer outcomes, especially studies that did not explicitly define their inference strategy.