Impact of the endoscopic surgical skill qualification system on the oncological safety of laparoscopic gastrectomy for gastric cancer: A single-center retrospective cohort study.

BACKGROUND: This study aimed to investigate the laparoscopic gastrectomy (LG) performance of non-Endoscopic Surgical Skill Qualification System (ESSQS)-qualified surgeons under the ESSQS-qualified surgeon guidance and compare oncological outcomes of gastric cancer to LG performed by the ESSQS-qualified surgeons. METHODS: This study enrolled 1,030 patients diagnosed with both clinical and pathological stage ≤ III gastric cancer and undergoing LG from January 2009 to June 2019. ESSQS-qualified surgeons served as the operator or the instructive assistant in all LG procedures involving them. A propensity score-matched analysis was used to retrospectively compare the long-term outcomes between the ESSQS-qualified and non-ESSQS-qualified surgeons. RESULTS: Each group included 315 pairs after propensity score matching. The 3-year recurrence-free survival rates were 84.4% and 81.7% in the non-ESSQS and ESSQS groups, respectively. The difference was 2.7% (95% confidence interval: - 3.20%-8.44%, P < 0.001), and the non-ESSQS group statistically demonstrated noninferiority as the lower 95% confidence limit was greater than the prespecified margin of -10%, indicating the achieved primary endpoint. No significant differences in 5-year recurrence-free survival (non-ESSQS: 78.5% vs. ESSQS: 77.4%, P = 0.627) and 5-year overall survival (non-ESSQS: 80.9% vs. ESSQS: 79.3%, P = 0.475) were found between the two groups. The oncological outcomes stratified according to the presence of pathological stage I, II, and III disease did not significantly differ between the two groups. CONCLUSIONS: LG performed by non-ESSQS-qualified surgeons achieved comparable oncological outcomes to the ESSQS-qualified surgeons, as long as ESSQS-qualified surgeons provided intraoperative instructions, in a high-volume center.

[The impact of public organizations on development of professional qualification of medical workers].

The professional development of personnel is one of highest priority task of development of both medicine as science and health system as mechanism protecting health of citizens. The public organizations are professional communities of medical specialists specializing in particular sectors of medicine that actively participate in implementation of educational measures and other initiatives targeted to support opportunities for professional growth and improving competence level of participants of these communities. The article considers examples of such initiatives as exemplified by foreign and Russian public organizations of pulmonologists and dentists.

Predictor Selection for Case Complexity Based on Routine Data for Needs-Based and Competence-Based Staff Planning.

Due to nursing staff shortage and growing nursing care demand, resource allocation and optimal task distribution have become primary concerns of nursing management. Grade mix analysis based on nursing interventions and nurse qualifications from routine patient documentation can support this. Case complexity is a key linking factor of nursing interventions, workload, and grade mix. This study determined case complexity predictors based on one year of routine patient documentation (n = 3,373 cases) from a Swiss hospital and predicted the patient clinical complexity level via weighted cumulative logistic regression models. Significant predictors were sex, age, pre-admission residence, admission type, self- care index, pneumonia risk, and number of nursing interventions. The models' accuracy is limited yet appropriate for applications such as needs- and competence- based staff-planning. After calibration via in-hospital data it could support nursing management in these tasks. The next step is now to test the model in a clinical setting.

Development of a Cell-Based Reporter Potency Assay for Live Virus Vaccines.

The rapid development of potency assays is critical in the development of life-saving vaccines. The traditional plaque assay or fifty percent tissue culture infectious dose (TCID50) assay used to measure the potency of live virus vaccines is time consuming, labor intensive, low throughput and with high variability. Described here is the development and qualification of a cell-based reporter potency assay for two vaccines for respiratory viral infection, one based on the recombinant vesicular stomatitis virus (rVSV) backbone, termed Vaccine 1 in this paper, and the other based on the measles virus vector, termed Vaccine 2. The reporter potency assay used a Vero E6 cell line engineered to constitutively express NanuLuc® luciferase, termed the VeroE6-NLuc or JM-1 cell line. Infection of JM-1 cells by a live virus, such as rVSV or measles virus, causes a cytopathic effect (CPE) and release of NanuLuc® from the cytoplasm into the supernatant, the amount of which reflects the intensity of the viral infection. The relative potency was calculated by comparison to a reference standard using parallel line analysis (PLA) in a log-log linear model. The reporter assay demonstrated good linearity, accuracy, and precision, and is therefore suitable for a vaccine potency assay. Further evaluation of the Vaccine 1 reporter assay demonstrated the robustness to a range of deliberate variation of the selected assay parameters and correlation with the plaque assay. In conclusion, we have demonstrated that the reporter assay using the JM-1 cell line could be used as a potency assay to support the manufacturing and release of multiple live virus vaccines.

Research on the Influence of HMFI and PWHT Treatments on the Properties and Stress States of MAG-Welded S690QL Steel Joints.

The aim of this study was to analyze the effect of the HFMI (high-frequency mechanical impact) treatment of each weld bead on the properties of a butt joint with a ceramic backing welded by robotic method 135 (MAG-metal active gas welding method) and to determine the effect of HMFI on the stress level. This analysis was based on a comparison of three butt joints made of a S690QL plate, in the as-welded condition, with the HFMI of each bead and with the heat treatment carried out with PWHT stress relief annealing. The high-frequency (90 Hz) peening of each weld bead was linked with a stress reduction in the weld via the implementation of compressive stresses into the joint. The HFMI pneumatic hammer was used for this. The correctness of treatment was achieved when 100% of the surface of each bead including the face was treated. As part of the post-welding tests, basic tests were carried out based on the standards for the qualification of welding technology, and as a supplementary test, a stress state analysis using the Barkhausen effect was carried out. The tests carried out showed that the use of high-frequency peening after each pass did not affect the negative results of all the required tests when qualifying the welding technology of S690QL sheet metal compared to the test plates in the as-welded condition and after heat treatment-stress relief annealing. Inter-pass peening of the welded face and HAZ (heat-affected zone) resulted in a reduction in post-weld residual stresses at a distance of 12 mm from the joint axis compared to the stress measurement result for the sample in the as-welded condition. This allowed for a positive assessment of peening in the context of reducing the notch, which is the concentration of tensile stresses in the area of the fusion line and HAZ. The tests carried out showed that the peening process does not reduce the strength properties of welded joints, and the results obtained allow the technology to be qualified based on applicable standards.

Community interpreting in Germany: results of a nationwide cross-sectional study among interpreters.

BACKGROUND: Community interpreters (CIPs) play a crucial role in various community services, including healthcare, when service providers and users do not share a common language. However, there is a lack of evidence-based data on this population globally. This explorative cross-sectional study aims to gain a better understanding of CIPs and their work in Germany. METHODS: A nationwide online survey was conducted among CIPs in Germany to collect data on their qualification background, working conditions, mental health, interpreting-related psychosocial distress and sociodemographics. Participants were recruited through interpreting pools, training institutions and migrant organizations. Data were analyzed descriptively, dependent t-test, multiple logistic and hierarchical stepwise regression analyses were performed to predict participation in interpreting-specific training, interpreting competence and interpreting-related psychosocial distress. RESULTS: Across all 16 federal states, N = 873 responses were used for analysis. Most participants are female (74%), born abroad (77%) and have a high level of education (69%). The vast majority interpret occasionally in their leisure time (44%) and are self-employed/freelance (51%). 34% interpret solely or additional on a voluntary basis (unpaid). The median hours of interpreting per month are 10 h, 75% do not exceed 30 h. On average interpreters work in four different settings. 69% attended any kind of interpreting training with a median of 25 h in total. Interpreting in more settings emerged as an associated factor with participation in training. Of those who have never attended any training, 69% consider themselves as rather/very competent in interpreting. Interpreting more frequently, having less severe anxiety symptoms, getting higher and more often paid and being less satisfied with the payment is associated with self-reported interpreting competence. In total, 36% reported moderate or severe psychosocial distress regarding interpreting. Higher general psychosocial distress and depressive symptoms, higher interpreting frequency and lower payment satisfaction were found to be associated with higher distress regarding interpreting. Additionally, factors such as precarious work conditions, lack of recognition and discrimination (e.g. racism and sexism) were reported as distressing. CONCLUSION: This study provides a first comprehensive evidence-based national database on CIPs in Germany. The findings can be valuable for the development of qualifications, guidelines, policies and the process of professionalizing the field of CIPs.

How to Accelerate Early Stage of Malaria Vaccine Development by Optimizing Functional Assays.

While two Plasmodium falciparum circumsporozoite protein-based pre-erythrocytic vaccines (PEV), RTS,S and R21, have been approved by the WHO, no blood-stage vaccine (BSV) or transmission-blocking vaccine (TBV) has reached a phase 3 trial. One of the major obstacles that slows down malaria vaccine development is the shortage (or lack) of in vitro assays or animal models by which investigators can reasonably select the best vaccine formulation (e.g., antigen, adjuvant, or platform) and/or immunization strategy (e.g., interval of inoculation or route of immunization) before a human phase 2 trial. In the case of PEV, RTS,S and R21 have set a benchmark, and a new vaccine can be compared with (one of) the approved PEV directly in preclinical or early clinical studies. However, such an approach cannot be utilized for BSV or TBV development at this moment. The focus of this review is in vitro assays or in vivo models that can be used for P. falciparum BSV or TBV development, and I discuss important considerations during assay selection, standardization, qualification, validation, and interpretation of the assay results. Establishment of a robust assay/model with proper interpretation of the results is the one of key elements to accelerate future vaccine development.

O perfil dos egressos de um mestrado profissional: uma contribuição para o entendimento da relação formação-trabalho no SUS / Profile of graduates of a Professional Master's Degree: a contribution to understanding the training-work relationship in the SUS

RESUMO Este artigo apresenta perfil dos egressos, efeitos da formação e trajetória profissional dos concluintes do Curso de Mestrado Profissional em Saúde Pública, do Instituto Aggeu Magalhães, parte de pesquisa avaliativa em desenvolvimento. Dos 99 egressos convidados que concluíram seus cursos entre 2013-2020, 54 responderam a um questionário aplicado por meio do software Lime Survey. O estudo descritivo e transversal utilizou frequência absoluta e relativa e cruzamento de variáveis na análise, cujo instrumento constou dos temas: identificação do egresso e do programa/curso; atividade profissional antes e ao término do curso e expectativas; condição empregatícia atual e efeitos da formação; avaliação da trajetória formativa. Entre os respondentes, a maioria é do sexo feminino, com idade entre 31-40 anos, enfermeiros de formação, autodeclarados pretos ou pardos, não ser pessoa com deficiência, predominantemente residentes em Pernambuco e não ingressaram mediante cota. Como efeito na vida profissional, encontrou-se que o curso aumentou o prestígio/reconhecimento dos colegas, qualificou para atividades que já exerciam e para atividades diferentes, e trouxe ganhos de remuneração, proporcionando mudanças na vida pessoal e profissional. Os resultados estão em conformidade com achados científicos desse mesmo contexto, e a ferramenta desenvolvida pela Fiocruz permitiu conhecer a relação entre formação e trabalho.

ABSTRACT This article presents the profile of graduates, the effects of training, and the professional trajectory of the Professional Master's Course in Public Health graduates at the Aggeu Magalhaes Institute. Of the 99 invited graduates who completed the program between 2013-2020, 54 responded to a questionnaire applied through the Lime Survey software. The descriptive and cross-sectional study used absolute and relative frequency cross-tabulation variables in the analysis, with the instrument covering the following themes: identification of the graduate and program/course; professional activity before and at the end of the program and expectations; current employment status and formation effects; evaluation of the formative trajectory. Among the respondents, most are female, aged between 31-40 years, trained as nurses, self-declared as black or brown-skinned, not having a disability, predominantly residing in Pernambuco, and did not enter through a quota system. As an effect on their professional life, it was found that the program increased prestige/recognition among colleagues, qualified them for activities they were already performing and also different activities, and brought salary increases leading to changes in personal and professional lives. The results are consistent with scientific findings in the same context, and the tool developed by FIOCRUZ made it possible to understand the relationship between education and work.

Influence of Physical Attractiveness and Gender on Patient Preferences in Digital Doctor Consultations: Experimental Study.

BACKGROUND: The rise of digital health services, particularly digital doctor consultations, has created a new paradigm in health care choice. While patients traditionally rely on digital reviews or referrals to select health care providers, the digital context often lacks such information, leading to reliance on visual cues such as profile pictures. Previous research has explored the impact of physical attractiveness in general service settings but is scant in the context of digital health care. OBJECTIVE: This study aims to fill the research gap by investigating how a health care provider's physical attractiveness influences patient preferences in a digital consultation setting. We also examine the moderating effects of disease severity and the availability of information on health care providers' qualifications. The study uses signal theory and the sexual attribution bias framework to understand these dynamics. METHODS: Three experimental studies were conducted to examine the influence of health care providers' physical attractiveness and gender on patient preferences in digital consultations. Study 1 (n=282) used a 2×2 between-subjects factorial design, manipulating doctor attractiveness and gender. Study 2 (n=158) focused on women doctors and manipulated disease severity and participant gender. Study 3 (n=150) replicated study 2 but added information about the providers' abilities. RESULTS: This research found that patients tend to choose attractive doctors of the opposite gender but are less likely to choose attractive doctors of the same gender. In addition, our studies revealed that such an effect is more prominent when the disease severity is high. Furthermore, the influence of gender stereotypes is mitigated in both the high and low disease severity conditions when service providers' qualification information is present. CONCLUSIONS: This research contributes to the literature on medical information systems research and sheds light on what information should be displayed on digital doctor consultation platforms. To counteract stereotype-based attractiveness biases, health care platforms should consider providing comprehensive qualification information alongside profile pictures.

Analysis of non-mutagenic substances in the context of drug impurity assessment - Few are potent toxicants.

ICH Q3A/B guidelines provide qualification thresholds for impurities or degradation products in new drug substances and products. However, the guidelines note that certain impurities/degradation products may warrant further safety evaluation for being unusually potent or toxic. The purpose of this study was to confirm that especially toxic non-mutagenic compounds are rare and to identify classes of compounds that could warrant lower qualification thresholds. A total of 2815 compounds were evaluated, of which 2213 were assessed as non-mutagenic. For the purpose of this analysis, compounds were considered potent when the point of departure was ≤0.2 mg/kg/day based on the qualification threshold (1 mg/day or 0.02 mg/kg/day for a 50 kg human) in a new drug substance, with an additional 10-fold margin. Only 54 of the entire set (2.4%) would be considered potent based on this conservative potency analysis, confirming that the existing ICH Q3A/B qualification thresholds are appropriate for the majority of impurities. If the Q3A/B threshold, without the additional 10-fold margin is used, 14 compounds (0.6%) are considered "highly potent". Very few non-mutagenic structural classes were identified, including organothiophosphates and derivatives, polychlorinated benzenes and polychlorinated polycyclic aliphatics, that correlate with potential high potency, consistent with prior publications.

Deriving acceptable limits for non-mutagenic impurities in medicinal products - Durational adjustments.

ICH Q3A/B guidelines are not intended for application during the clinical research phase of development and durationally adjusted qualification thresholds are not included. A central tenet of ICH Q3A is that lifetime exposure to 1 mg/day of an unqualified non-mutagenic impurity (NMI) is not a safety concern. An analysis of in vivo toxicology data from 4878 unique chemicals with established NO(A)ELs was conducted to determine whether durationally adjusted qualification limits can be supported. Although not recommended in ICH Q3A/B, a conservative approach was taken by using allometric scaling in the analysis. Following allometric scaling of the 5th percentile of the distribution of NO(A)ELs from available chronic toxicology studies, it was reconfirmed that there is a safety basis for the 1 mg/day qualification threshold in ICH Q3A. Additionally, allometric scaling of the 5th percentile of the distribution of NO(A)ELs from sub-acute and sub-chronic toxicology studies could support acceptable limits of 20 and 5 mg/day for an unqualified NMI for dosing durations of less than or greater than one month, respectively. This analysis supports durationally adjusted NMI qualification thresholds for pharmaceuticals that protect patient safety and contribute to 3Rs efforts for qualifying impurities using new approach methods.

Evaluation of the advantage of surgeons certified by the endoscopic surgical skill qualification system participating in laparoscopic low anterior rectal resection.

Background: A technical qualification system was developed in 2004 by the Japan Society for Endoscopic Surgery. An analysis of the EnSSURE study on 3188 stage II-III rectal cancer patients, which was performed by including the participation of qualified surgeons as assistants and advisers without restricting their participation as operators, revealed that the participation of technically qualified surgeons in surgery improved the technical and oncological safety of laparoscopic rectal resection. Aim: This secondary retrospective analysis of the EnSSURE study examined the advantage of qualified surgeons participating in laparoscopic low anterior resection (LAR). Methods: The outcomes of low anterior resection were compared between groups with and without the participation of surgeons qualified by the Endoscopic Surgical Skill Qualification System (Q and non-Q groups, respectively). We used propensity score matching to generate paired cohorts at a one-to-one ratio. The postoperative complication rate, short-term results (hemorrhage volume, operative time, number of dissected lymph nodes, open conversion rate, intraoperative complication rate, and R0 resection rate), and long-term results (disease-free survival rate, local recurrence rate, and overall survival rate) were evaluated. Results: The frequencies of postoperative complications, anastomotic bleeding, and intraperitoneal abscess were significantly lower, the operative time was significantly shorter, the postoperative hospital stay was significantly shorter, and the number of dissected lymph nodes was higher in the Q group. No significant differences were observed in disease-free survival, local recurrence, or overall survival rate rates between the groups. Conclusion: The participation of qualified surgeons in LAR is technically advantageous.

New limits proposed for the management of non-mutagenic impurities.

Multiple international guidelines exist that describe both quality and safety considerations for the control of the broad spectrum of impurities inherent to drug substance and product manufacturing processes. However, regarding non-mutagenic impurities (NMI) the most relevant ICH Q3A/B guidelines are not applicable during early phases of drug development leading to confusion about acceptable limits at this stage. Thus, there is need for more flexible approaches that ensure that patient safety remains paramount, while taking into consideration the limited duration of exposure. An EFPIA survey, which collected quantitative data from different types of studies applied to qualify impurities in accordance with ICH Q3A, shows that no toxicities could be attributed to any of the 467 impurities at any tested level in vivo. This data combined with earlier published toxicological datasets encompassing drug substances and intermediates, food related substances and chemicals provide convincing evidence that for NMIs, the application of a generic 5 mg/day limit for an exposure duration <6 months, and a 1 mg/day generic limit for life-long exposure, provides sufficient margins to ensure patient safety. Hence, application of these absolute limits to trigger qualification studies (instead of the relative limits described in Q3A/B), is considered warranted. This approach will prevent conduct of unnecessary dedicated impurity qualification studies and the resulting use of animals.

Critical View on the Qualification of Electronic Tongues Regarding Their Performance in the Development of Peroral Drug Formulations with Bitter Ingredients.

In this review, we aim to highlight the advantages, challenges, and limitations of electronic tongues (e-tongues) in pharmaceutical drug development. The authors, therefore, critically evaluated the performance of e-tongues regarding their qualification to assess peroral formulations containing bitter active pharmaceutical ingredients. A literature search using the keywords 'electronic', 'tongue', 'bitter', and 'drug' in a Web of Science search was therefore initially conducted. Reviewing the publications of the past decade, and further literature where necessary, allowed the authors to discuss whether and how e-tongues perform as expected and whether they have the potential to become a standard tool in drug development. Specifically highlighted are the expectations an e-tongue should meet. Further, a brief insight into the technologies of the utilized e-tongues is given. Reliable protocols were found that enable (i) the qualified performance of e-tongue instruments from an analytical perspective, (ii) proper taste-masking assessments, and (iii) under certain circumstances, the evaluation of bitterness.

[Prehospital chest tube placement: Which factors are associated with feeling confident to perform the procedure?] / Prähospitale Anlage von Thoraxdrainagen: Welche Faktoren sind mit einem subjektivem Sicherheitsgefühl assoziiert?

BACKGROUND: The prehospital placement of chest tubes is a rare but potentially life-saving procedure. A high level of subjective confidence with the procedure is essential for emergency medical doctors. This study aims to identify if there is a statistically significant difference in the subjective sense of confidence in prehospital chest tube placement regarding medical experience and qualification, clinical routine, and attendance at simulation courses. METHODS: Prehospital emergency physicians of three emergency medical services in Southwest Saxony, Greifswald, and Vechta, Germany, were invited to participate in an online survey from January to March 2022 using the online survey service limesurvey. The question "Do you feel confident in chest tube placement?" was used to measure the subjective level of confidence. Answers were compared with data concerning medical qualification, experience in prehospital emergency medicine, clinical routine, and attendance at simulation courses. Statistical analysis was performed using chi-squared test and Fisher's exact test. RESULTS: Three out of four participants felt confident in chest tube placement (53/71; 74.6%). More than half of the participants reported that they did not perform this procedure regularly (35/53, 66%). Subjective confidence was highest in physicians who regularly place chest tubes during their non-prehospital work (34/37; 91,9%; p<0.001), and more often when participants had clinical routine and attended simulation courses than when none of this applied (p=0.012). Attendance at simulation courses alone was not associated with a higher level of confidence (p=0.002). Specialists showed significantly more often subjective confidence in chest tube placement (p=0.0401). CONCLUSION: Prehospital chest tube placement is rare, but potentially lifesaving. An adequately high level of subjective confidence in the placement of chest tubes is a key condition for prehospital emergency doctors. Inhospital clinical routine and attendance at simulation courses are significantly associated with high levels of confidence. Our data indicate that working only in prehospital emergency settings without further clinical routine or medical specialization is not sufficient for achieving and ensuring subjective confidence in chest tube placement.

Correlation between 146S Antigen Content in Foot-and-Mouth Disease Inactivated Vaccines and Immunogenicity Level and Vaccine Potency Alternative Test Methods.

To investigate the association between 146S antigen contents in FMD inactivated vaccines and levels of antiviral immunity, this study vaccinated 30 kg pigs with three batches of FMD types O and A bivalent inactivated vaccines. Antibody titers and interferon-gamma (IFN-γ) secretion levels were measured on days 7, 14, 21, and 28 after primary immunization and on days 14 and 28 following booster immunization to assess associations between 146S contents and both antibody titers and IFN-γ secretion levels. Furthermore, 30 kg pigs were vaccinated with 46 batches of FMD type O inactivated vaccines and challenged on day 28, after which PD50 values were determined to evaluate the association between 146S content and PD50. The findings suggested that antibody titers and IFN-γ secretion levels at specific time points after immunization were positively associated with 146S contents. Additionally, 146S content showed a positive correlation with PD50, with greater PD50 values recorded for 146S contents ranging from 4.72 to 16.55 µg/dose. This investigation established a significant association between the 146S content in FMD inactivated vaccines and induced immune response against FMDV, thereby emphasizing its critical role in vaccine quality control. The determination of 146S content could serve as a new method for potency testing, offering an alternative to animal challenge tests.

Comparing the prognostic performance of iBOX and biopsy-proven acute rejection for long-term kidney graft survival.

Biopsy-proven acute rejection (BPAR) occurs in approximately 10% of kidney transplant recipients in the first year, making superiority trials unfeasible. iBOX, a quantitative composite of estimated glomerular filtration rate, proteinuria, antihuman leukocyte antigen donor-specific antibody, and + full/- abbreviated kidney histopathology, is a new proposed surrogate endpoint. BPAR's prognostic ability was compared with iBOX in a pooled cohort of 1534 kidney transplant recipients from 4 data sets, including 2 prospective randomized controlled trials. Discrimination analyses showed mean c-statistic differences between both iBOX compared with BPAR of 0.25 (95% confidence interval: 0.17-0.32) for full iBOX and 0.24 (95% confidence interval: 0.16-0.32) for abbreviated iBOX, indicating statistically significantly higher c-statistic values for the iBOX prognosis of death-censored graft survival. Mean (± standard error) c-statistics were 0.81 ± 0.03 for full iBOX, 0.80 ± 0.03 for abbreviated iBOX, and 0.57 ± 0.03 for BPAR. In calibration analyses, predicted graft loss events from both iBOX models were not significantly different from those observed. However, for BPAR, the predicted events were significantly (P < .01) different (observed: 64; predicted: 70; full iBOX: 76; abbreviated iBOX: 173 BPAR). IBOX at 1-year posttransplant is superior to BPAR in the first year posttransplant in graft loss prognostic performance, providing valuable additional information and facilitating the demonstration of superiority of novel immunosuppressive regimens.

Pt/NiFe-LDH hybrids for quantification and qualification of polyphenols.

Polyphenols with antioxidant properties are of significant interest in medical and pharmaceutical applications. Given the diverse range of activities of polyphenols in vivo, accurate detection of these compounds plays a crucial role in nutritional surveillance and pharmaceutical development. Yet, the efficient quantitation of polyphenol contents and qualification of monomer compositions present a notable challenge when studying polyphenol bioavailability. In this study, platinum-modified nickel-iron layered double hydroxide (Pt/NiFe-LDH hybrids) were designed to mimic peroxidases for colorimetric analysis and act as enhanced matrices for laser desorption/ionization mass spectrometry (LDI MS) to quantify and qualify polyphenols. The hybrids exhibited an enzymatic activity of 33.472 U/mg for colorimetric assays, facilitating the rapid and direct quantitation of total tea polyphenols within approximately 1 min. Additionally, the heterogeneous structure and exposed hydroxyl groups on the hybrid surface contributed to photoelectric enhancement and in-situ enrichment of polyphenols in LDI MS. This study introduces an innovative approach to detect polyphenols using advanced materials, potentially inspiring the future development and applications of other photoactive nanomaterials.

Innovative research methodologies in the EU regulatory framework: an analysis of EMA qualification procedures from a pediatric perspective.

Introduction: The European Medicines Agency (EMA) offers scientific advice to support the qualification procedure of novel methodologies, such as preclinical and in vitro models, biomarkers, and pharmacometric methods, thereby endorsing their acceptability in medicine research and development (R&D). This aspect is particularly relevant to overcome the scarcity of data and the lack of validated endpoints and biomarkers in research fields characterized by small samples, such as pediatrics. Aim: This study aimed to analyze the potential pediatric interest in methodologies qualified as "novel methodologies for medicine development" by the EMA. Methods: The positive qualification opinions of novel methodologies for medicine development published on the EMA website between 2008 and 2023 were identified. Multi-level analyses were conducted to investigate data with a hierarchical structure and the effects of cluster-level variables and cluster-level variances and to evaluate their potential pediatric interest, defined as the possibility of using the novel methodology in pediatric R&D and the availability of pediatric data. The duration of the procedure, the type of methodology, the specific disease or disease area addressed, the type of applicant, and the availability of pediatric data at the time of the opinion release were also investigated. Results: Most of the 27 qualifications for novel methodologies issued by the EMA (70%) were potentially of interest to pediatric patients, but only six of them reported pediatric data. The overall duration of qualification procedures with pediatric interest was longer than that of procedures without any pediatric interest (median time: 7 months vs. 3.5 months, respectively; p = 0.082). In parallel, qualification procedures that included pediatric data lasted for a longer period (median time: 8 months vs. 6 months, respectively; p = 0.150). Nephrology and neurology represented the main disease areas (21% and 16%, respectively), while endpoints, biomarkers, and registries represented the main types of innovative methodologies (32%, 26%, and 16%, respectively). Discussion: Our results underscore the importance of implementing innovative methodologies in regulatory-compliant pediatric research activities. Pediatric-dedicated research infrastructures providing regulatory support and strategic advice during research activities could be crucial to the design of ad hoc pediatric methodologies or to extend and validate them for pediatrics.