Efficacy and safety of uncovered self-expandable metal stents for distal malignant biliary obstruction in unresectable non-pancreatic cancer.

Objectives: The efficacy of uncovered self-expandable metal stents (UCSEMS) versus fully covered self-expandable metal stents for distal malignant biliary obstruction remains controversial. Additionally, the heterogeneity of the disease conditions has been indicated in previous studies because pancreatic and non-pancreatic cancers have different characteristics in clinical course. Therefore, the etiology of biliary obstruction necessitates investigations stratified by primary disease. This study aimed to evaluate the outcomes of UCSEMS, specifically for non-pancreatic cancer-induced distal malignant biliary obstruction. Methods: We conducted a single-center retrospective review to evaluate the time to recurrent biliary obstruction and frequency of adverse events (AEs) in patients receiving UCSEMS for unresectable non-pancreatic cancer-induced malignant biliary obstruction. Results: Overall, 32 patients were enrolled in the study between January 2016 and December 2023. The median time to recurrent biliary obstruction was 140 days. AE rates were low at 3.1% for both pancreatitis and cholecystitis, suggesting a potential benefit of UCSEMS in reducing post-procedural AEs. Conclusion: UCSEMS may reduce the risk of post-procedural AEs and should be considered in patients at high risk of post-endoscopic retrograde cholangiopancreatography pancreatitis. However, the patency period may be shorter, necessitating future comparative research with fully covered self-expandable metal stents to determine the optimal stent choice.

Ethnobotanical knowledge on non-conventional food plants and medicinal plants in Extractivist Reserve in the Brazilian Amazon / Conocimiento etnobotánico sobre plantas alimenticias no convencionales y plantas medicinales en una Reserva Extractivista en la Amazonía Brasileña

Information on the knowledge and ways of using food and medicinal plants by traditional populations, family farmers and Brazilian native population in the Amazon is essential to guarantee the food sovereignty of these groups. This study was conducted using semi-structured interviews applied to local respondents. A total of 269 species of both non-conventional food plants and medicinal plants were identified, distributed in 83 botanical families and 198 genera. The Arecaceae and Lamiaceae families had the highest species richness (11 and 7, respectively). The Shannon-Wiener (H') and Pielou (J') diversity indices were considered high (5.02 and 0.9, respectively) when compared to other ethnobotanical works. In the environment in which these families are found, these species become the only food and medicinal resources available.

La información sobre los saberes y formas de uso de las plantas alimenticias y medicinales por parte de las poblaciones tradicionales, agricultores familiares e indígenas brasileños en la Amazonía es fundamental para garantizar la soberanía alimentaria de estos grupos. Este estudio se realizó utilizando entrevistas semiestructuradas aplicadas a encuestados locales. Se identificaron un total de 269 especies tanto de plantas alimenticiasno convencionales como de plantas medicinales, distribuidas en 83 familias botánicas y 198 géneros. Las familias Arecaceae y Lamiaceae tuvieron la mayor riqueza de especies (11 y 7, respectivamente). Los índices de diversidad de Shannon-Wiener (H') y Pielou (J') fueron considerados altos (5,02 y 0,9, respectivamente) en comparación con otros trabajos etnobotánicos. En el ambiente en que se encuentran estas familias, estas especies se convierten en los únicos recursos alimenticios y medicinales disponibles.

Cultura de segurança em unidades de terapia intensiva na perspectiva da equipe multiprofissional: Estudo multicêntrico / Cultura de seguridad en unidades de terapia intensiva en la perspectiva del equipo multiprofesional: Estudio multicéntrico / Safety Culture in intensive care units from multiprofessional team perspective: A multicenter study

Resumo Introdução: A Cultura de Segurança do Paciente é considerada um importante componente estrutural dos serviços, que favorece a implantação de práticas seguras e a diminuição da ocorrência de eventos adversos. Objetivo: Identificar os fatores associados à cultura de segurança do paciente nas unidades de terapia intensiva adulto em hospitais de grande porte da região Sudeste do Brasil. Método: Estudo transversal do tipo survey e multicêntrico. Participaram 168 profissionais de saúde de quatro unidades (A, B, C e D) de terapia intensiva adulto. Foi utilizado o questionário "Hospital Survey on Patient Safety Culture". Considerou-se como variável dependente o nível de cultura de segurança do paciente e variáveis independentes aspectos sociodemográficos e laborais. Foram usadas estatísticas descritivas e para a análise dos fatores associados foi elaborado um modelo de regressão logística múltipla. Resultados: Identificou-se associação entre tipo de hospital com onze dimensões da cultura de segurança, quanto à função a categoria profissional médico, técnico de enfermagem e enfermeiro foram relacionadas com três dimensões; o gênero com duas dimensões e tempo de atuação no setor com uma dimensão. Conclusão: Evidenciou-se que o tipo de hospital, categoria profissional, tempo de atuação no setor e gênero foram associados às dimensões de cultura de segurança do paciente.

Resumen Introducción: La cultura de seguridad del paciente se considera un componente estructural importante de los servicios, que favorece la aplicación de prácticas seguras y la reducción de la aparición de acontecimientos adversos. Objetivo: Identificar los factores asociados a la cultura de seguridad del paciente en unidades de terapia intensiva adulto en hospitales de la región Sudeste del Brasil. Metodología: Estudio transversal de tipo encuesta y multicéntrico. Participaron 168 profesionales de salud de cuatro unidades (A, B, C y D) de terapia intensiva adulto. Se utilizó el cuestionario "Hospital Survey on Patient Safety Culture". Se consideró como variable dependiente el nivel de cultura de seguridad del paciente y variables independientes los aspectos sociodemográficos y laborales. Fueron usadas estadísticas descriptivas y, para analizar los factores asociados, fue elaborado un modelo de regresión logística múltiple. Resultados: Se identificó asociación entre tipo de hospital con once dimensiones de cultura de seguridad del paciente. En relación a la función, personal médico, técnicos de enfermería y personal de enfermería fueron asociados con tres dimensiones, el género con dos dimensiones y tiempo de actuación con una dimensión en el modelo de regresión. Conclusión: Se evidenció que el tipo de hospital, función, tiempo de actuación en el sector y género fueron asociados a las dimensiones de la cultura de seguridad del paciente.

Abstract Introduction: Patient safety culture is considered an important structural component of the services, which promotes the implementation of safe practices and the reduction of adverse events. Objective: To identify the factors associated with patient safety culture in adult intensive care units in large hospitals in Belo Horizonte. Method: Cross-sectional survey and multicenter study. A total of 168 health professionals from four units (A, B, C and D) of adult intensive care participated. The questionnaire "Hospital Survey on Patient Safety Culture" was used. The patient's level of safety culture was considered as a dependent variable, and sociodemographic and labor aspects were the independent variables. Descriptive statistics were used and a multiple logistic regression model was developed to analyze the associated factors. Results: An association was identified between the type of hospital and eleven dimensions of the safety culture. In terms of function, the doctors, nursing technicians, and nurse were related to three dimensions; gender with two dimensions, and time working in the sector with one dimension. Conclusion: It was evidenced that the type of hospital, function, time working in the sector, and gender were associated with the dimensions of patient safety culture.

Prevalence and Correlates of Poor Safety Awareness and Accidental Injury in AASD, ADHD, ASD + ADHD, and Neurotypical Youth Samples.

The purpose of the present study is to compare risk and predictors of poor safety awareness and accidental injuries in ASD, ADHD, and neurotypical samples. Neurodivergent groups (ADHD-I n = 309; ADHD-C n = 747; ASD-only n = 328; ASD + ADHD n = 1,108) were 2-17 years old. The neurotypical group (n = 186) was 6-12 years of age. Maternal ratings on the Pediatric Behavior Scale examined safety awareness, accidental injury, and psychological problems. Children with ASD + ADHD had significantly poorer safety awareness and accidental injury ratings than all other groups. Predictors of poor safety awareness in the total ASD and/or ADHD sample were: impulsivity, younger age, lower IQ, and hyperactivity. Predictors of accidental injuries were: incoordination, hyperactivity, and conduct problems. Clinicians working with children who have ASD and ADHD are encouraged to screen for poor safety awareness, discuss child safety measures, and provide evidence-based intervention to improve safety awareness and mitigate the risk of injury.

The effect of mailed outreach on FIT completion among patients aged 45-50 in a safety net healthcare system.

PURPOSE: Colorectal cancer screening is recommended starting at age 45, but there has been little research on strategies to promote screening in patients younger than 50. METHODS: An outreach program quasi-randomly assigned patients aged 45-50 without recent fecal immunochemical test (FIT), colonoscopy or contraindications to screening to two intervention arms: electronic outreach with email and text (electronic outreach only) versus electronic outreach plus mailed outreach with FIT, an instructional letter and a prepaid return envelope (mailed + electronic outreach). In response to known disparities in screening uptake, all Black patients were assigned to receive mailed + electronic outreach. RESULTS: Among patients quasi-randomly assigned to an intervention (non-Black patients), the 180-day FIT completion rate was 18.8% in the electronic outreach only group (n = 1,318) and 25.0% in the mailed + electronic outreach group (n = 1,364) (difference 6.2% [95% CI 3.0, 9.4]). FIT completion was 16.6% among Black patients (n = 469), 8.4% (95% CI 4.1, 12.6) lower than among non-Black patients also assigned to mailed + electronic outreach. CONCLUSION: Among patients aged 45-50, mailed + electronic outreach had a greater effect on FIT completion than electronic outreach alone. Crossover between intervention groups likely lead to an underestimation of the effect of mailed outreach.

[How to generate recommendations for venous thromboprophylaxis in health institutions?] / Cómo generar recomendaciones de tromboprofilaxis venosa en instituciones de salud.

Venous thromboembolism disease (VTE) prevention strategy has to be constantly updated based on new evidence that is generated every year. Each institution must have a formal and active prevention policy against VTE and must develop guidelines or standards for thromboprophylaxis (TP) according to the local reality. During this process of adapting a guideline to the region and the generation of hospital recommendations, we must always consider the available local resources, the thromboembolic and hemorrhagic risk of the patients, even after discharge, and also their considerations and preferences. Adherence to local TP recommendations is one of the most important items evaluated by organizations that measure institutional quality. Individualized prophylaxis should consider personal and family history of VTE, the use of validated risk assessment models or RAMs for thrombosis and bleeding events, as well as the special characteristics of each patient. Ideally, each center's own statistics should be available for decision-making. Extrapolating guidelines from developed countries could have a negative impact, if we ignore our hospital's reality. In this document we will find practical tools for health institutions that will allow them to prepare recommendations or guidelines for adequate VTE prophylaxis.

La prevención de la enfermedad tromboembólica venosa (ETV) es motivo de continua actualización en función de nueva evidencia que se genera permanentemente. Cada institución debe contar con una estrategia activa de prevención contra la ETV y debe generar normas de tromboprofilaxis (TP) de acuerdo con la realidad local. Durante este proceso de adaptación de una guía a la región debemos siempre tener en cuenta los recursos locales disponibles, el riesgo tromboembólico y hemorrágico propio del paciente, de la enfermedad por la que se encuentra internado (ya sea clínica o quirúrgica) y las consideraciones o preferencias del paciente. La tasa de adherencia a recomendaciones locales de TP es uno de los indicadores de excelencia más importantes evaluados en organismos que califican la calidad de una institución de salud. Las medidas de profilaxis que propongamos para los centros de salud, deben ser individualizadas para cada paciente, tienen que considerar antecedentes personales y familiares del enfermo y utilizar modelos de evaluación de riesgo validados de trombosis y de sangrado. También deben incluir a la población con riesgo de trombosis persistente luego del alta. Lo ideal es tener estadísticas propias de cada nosocomio para la toma de decisiones de cómo implementar una correcta TP. Extrapolar guías de los países desarrollados a nuestro ámbito podría tener un impacto negativo, si no se conoce la propia realidad. En este documento encontraremos herramientas prácticas para las instituciones de salud de la región, que les permita orientarse al momento de confeccionar recomendaciones para una adecuada TP.

Immunogenicity and safety evaluation of a newly manufactured recombinant Baculovirus-Expressed quadrivalent influenza vaccine in adults 18 years old and Above: An Open-Label, phase III extension study.

In the face of global health threats, there is a growing demand for vaccines that can be manufactured on a large scale within compressed timeline. This study responds to this imperative by delving into the evaluation of FluGuard, a novel recombinant influenza vaccine developed by Nivad Pharmed Salamat Company in Iran. Positioned as a phase 3 extension, the research aimed to evaluate the safety and immunogenicity of FluGuard in volunteers aged 18 and above. The study was conducted as a single-center, open-label clinical trial. All eligible volunteers received FluGuard (2021-2022 Formula) on day 0. Safety assessments occurred at days 1, 4, 7, 14, 28 and 42 post-vaccination. Immunogenicity was measured through seroconversion, seroprotection, and geometric mean titer fold increase in subgroups of 250 volunteers. Among the 4,260 volunteers were screened and assessed for eligibility, 1000 were enrolled. At day 28 post-vaccination, seroconversion rates for A/H1N1, A/H3N2, B/Yamagata, B/Victoria were 53.4 % [95 %CI: 46.7-60], 57.7 % [95 %CI: 51.1-64.3], 54.3 % [95 %CI: 47.7-60.9], and 36.2 % [95 %CI: 29.8-42.6], respectively in volunteers 18 years and above. The most common solicited adverse events were pain at the injection site, malaise, and headache. No suspected unexpected adverse events and adverse events of special interest occurred during the study period. Our findings suggested that FluGuard® exhibits a desirable safety profile and provides sufficient immunogenicity against influenza virus types A and B. However, extended studies are warranted to assess the long-term protective efficacy. Trial Registration: The study protocol was accepted by Iranian registry of clinical trial; https://www.irct.ir; IRCT20201104049265N2.

Safe and efficient practice of parenteral nutrition in neonates and children aged 0-18 years - The role of licensed multi-chamber bags.

Parenteral nutrition (PN) is recognized as a complex high-risk therapy. Its practice is highly variable and frequently suboptimal in pediatric patients. Optimizing care requires evidence, consensus-based guidelines, audits of practice, and standardized strategies. Several pediatric scientific organizations, expert panels, and authorities have recently recommended that standardized PN should generally be used over individualized PN in the majority of pediatric patients including very low birth weight premature infants. In addition, PN admixtures produced and validated by a suitably qualified institution are recommended over locally produced PN. Licensed multi chamber bags are standardized PN bags that comply with Good Manufacturing Practice and high-quality standards for the finished product in the frame of their full manufacturing license. The purpose of this article is to review the practical aspects of PN and the evidence for using such multi-chamber bags in pediatric patients. It highlights the safety characteristics and the limitations of the different PN practices and provides some guidance for ensuring safe and efficient therapy in pediatric patients.

Machine learning to predict the relationship between Vibrio spp. concentrations in seawater and oysters and prevalent environmental conditions.

Vibrio parahaemolyticus and Vibrio vulnificus are bacteria with a significant public health impact. Identifying factors impacting their presence and concentrations in food sources could enable the identification of significant risk factors and prevent incidences of foodborne illness. In recent years, machine learning has shown promise in modeling microbial presence based on prevalent external and internal variables, such as environmental variables and gene presence/absence, respectively, particularly with the generation and availability of large amounts and diverse sources of data. Such analyses can prove useful in predicting microbial behavior in food systems, particularly under the influence of the constant changes in environmental variables. In this study, we tested the efficacy of six machine learning regression models (random forest, support vector machine, elastic net, neural network, k-nearest neighbors, and extreme gradient boosting) in predicting the relationship between environmental variables and total and pathogenic V. parahaemolyticus and V. vulnificus concentrations in seawater and oysters. In general, environmental variables were found to be reliable predictors of total and pathogenic V. parahaemolyticus and V. vulnificus concentrations in seawater, and pathogenic V. parahaemolyticus in oysters (Acceptable Prediction Zone >70 %) when analyzed using our machine learning models. SHapley Additive exPlanations, which was used to identify variables influencing Vibrio concentrations, identified chlorophyll a content, seawater salinity, seawater temperature, and turbidity as influential variables. It is important to note that different strains were differentially impacted by the same environmental variable, indicating the need for further research to study the causes and potential mechanisms of these variations. In conclusion, environmental variables could be important predictors of Vibrio growth and behavior in seafood. Moreover, the models developed in this study could prove invaluable in assessing and managing the risks associated with V. parahaemolyticus and V. vulnificus, particularly in the face of a changing environment.

[The population perspective in assessing the performance of Germany's health care system: Results of a cross-sectional survey among members of a statutory health insurance]. / Die Bevölkerungsperspektive in der Bewertung der Leistungsfähigkeit des deutschen Gesundheitssystems: Ergebnisse einer Querschnittsbefragung GKV-Versicherter.

INTRODUCTION: Since the World Health Report in 2000, Health System Performance Assessment (HSPA) has been established as a tool for the evaluation and evidence-informed governance of health systems. So far, the population perspective has not been integrated into HSPA in a systematic manner, although people's experiences and expectations are of great importance to improve health systems and especially to strengthen patient-centered care. Therefore, this study aims to conduct an HSPA of Germany's health system from the population's perspective covering all eight goals of WHO's Health Systems Framework, and to identify strengths and needs for improvement. METHODS: In 2018, 32,000 people insured with the German sickness fund 'AOK Nordost' were invited by mail to participate in the survey. The questionnaire contained a total of 43 items covering the eight goals of WHO's Health Systems Framework (e.g., access, quality, safety) plus socioeconomics and other characteristics of the insured persons. The data on the health system goals were analyzed descriptively and by subgroups (age, sex, income, chronic conditions, health literacy). RESULTS: The sample (n=1,481; response rate 4.6%) was 54.8% female and had a mean age of 59.1 years (±18.5). Altogether, the participants saw several needs for improvement within the German health system. For instance, 60.0% found quality differences between hospitals to be big, and between 3.9% and 8.5% reported mistakes related to their treatment or prescription medication in the previous two years. A big need for reform was especially seen regarding out-of-pocket payments (51.5%) and the coordination of ambulatory care physicians among each other (44.2%) and with hospitals (41.9%). In addition, big subgroup differences were seen, especially for income and health literacy. Of the participants in the lower income group, 37.2% reported a (very) strong financial burden due to out-of-pocket payments (vs. 20.7%). People with limited health literacy (52.1%) assessed the access to care generally as not being good, and they perceived greater quality differences and needs for reform, compared to their counterparts. For instance, 36.6% had experienced discrimination in the previous year (vs. 19.9%). DISCUSSION: The survey results provide a comprehensive picture of Germany's health system from the population perspective. In some areas, previous findings were confirmed (e.g., a lack of coordination between providers). Other results expand existing knowledge (e.g., the role of health literacy in health care provision) or raise new questions (e.g., the difference between the subjectively assessed burden from out-of-pocket payments and the objective measures currently used). The great differences between subgroups are a call to action on the level of both politics and practice to better consider the individual's needs in order to make health better for everyone. Further research could provide deeper insights in this regard. CONCLUSION: Strengthening the population perspective in HSPA allows for a better understanding and evaluation of health systems and, in particular, helps to identify areas for improvement in patient-centered care.

Survival analysis for AdVerse events with VarYing follow-up times (SAVVY): summary of findings and assessment of existing guidelines.

BACKGROUND: The SAVVY project aims to improve the analyses of adverse events (AEs) in clinical trials through the use of survival techniques appropriately dealing with varying follow-up times and competing events (CEs). This paper summarizes key features and conclusions from the various SAVVY papers. METHODS: Summarizing several papers reporting theoretical investigations using simulations and an empirical study including randomized clinical trials from several sponsor organizations, biases from ignoring varying follow-up times or CEs are investigated. The bias of commonly used estimators of the absolute (incidence proportion and one minus Kaplan-Meier) and relative (risk and hazard ratio) AE risk is quantified. Furthermore, we provide a cursory assessment of how pertinent guidelines for the analysis of safety data deal with the features of varying follow-up time and CEs. RESULTS: SAVVY finds that for both, avoiding bias and categorization of evidence with respect to treatment effect on AE risk into categories, the choice of the estimator is key and more important than features of the underlying data such as percentage of censoring, CEs, amount of follow-up, or value of the gold-standard. CONCLUSIONS: The choice of the estimator of the cumulative AE probability and the definition of CEs are crucial. Whenever varying follow-up times and/or CEs are present in the assessment of AEs, SAVVY recommends using the Aalen-Johansen estimator (AJE) with an appropriate definition of CEs to quantify AE risk. There is an urgent need to improve pertinent clinical trial reporting guidelines for reporting AEs so that incidence proportions or one minus Kaplan-Meier estimators are finally replaced by the AJE with appropriate definition of CEs.

Beyond 1D and oversimplified kinematics: A generic analytical framework for surrogate safety measures.

This paper presents a generic analytical framework tailored for surrogate safety measures (SSMs) that is versatile across various highway geometries, capable of encompassing vehicle dynamics of differing dimensionality and fidelity, and suitable for dynamic, real-world environments. The framework incorporates a generic vehicle movement model, accommodating a spectrum of scenarios with varying degrees of complexity and dimensionality, facilitating the estimation of future vehicle trajectory evolution. It establishes a generic mathematical criterion to denote potential collisions, characterized by the spatial overlap between a vehicle and any other entity. A collision risk is present if the collision criterion is met at any non-negative estimated future time point, with the minimum threshold representing the remaining time to collision. The framework's proficiency spans from conventional one-dimensional (1D) SSMs to extended multi-dimensional, high-fidelity SSMs. Its validity is corroborated through simulation experiments that assess the precision of the framework when linearization is performed on the vehicle movement model. The outcomes showcase remarkable accuracy in estimating vehicle trajectory evolution and the time remaining before potential collisions occur, comparing to high-accuracy numerical integration solutions. The necessity of higher-dimensional and higher-fidelity SSMs is highlighted through a comparison of conventional 1D SSMs and extended three-dimensional (3D) SSMs. The results showed that using 1D SSMs over 3D SSMs could be off by 300% for Time-to-Collision (TTC) values larger than 1.5 s and about 20% for TTC values below 1.5 s. In other words, conventional 1D SSMs can yield highly inaccurate and unreliable results when assessing collision proximity and substantially misjudge the count of conflicts with predefined threshold (e.g., below 1.5s). Furthermore, the framework's practical application is demonstrated through a case study that actively evaluates all potential conflicts, underscoring its effectiveness in dynamic, real-world traffic situations.

The generalization of threat beliefs to novel safety stimuli induced by safety behaviors.

Safety behaviors are responses that can reduce or even prevent an expected threat. Moreover, empirical studies have shown that using safety behaviors to a learnt safety stimulus can induce threat beliefs to it. No research so far has examined whether threat beliefs induced this way generalize to other novel stimuli related to the safety stimulus. Using a fear and avoidance conditioning model, the current study (n=116) examined whether threat beliefs induced by safety behaviors generalize to other novel generalization stimuli (GSs). Participants first acquired safety behaviors to a threat predicting conditioned stimulus (CSthreat). Safety behaviors could then be performed in response to one safe stimulus (CSsafeShift) but not to another (CSsafe). In a following generalization test, participants showed a significant but small increase in threat expectancies to GSs related to CSsafeShift compared to GSs related to CSsafe. Interestingly, the degree of safety behaviors used to the CSsafeShift predicted the subsequent increase in threat expectancies, and this link was elevated in trait anxious individuals. The findings suggest that threat beliefs induced by unnecessary safety behaviors generalize to other related stimuli. This study provides a potential explanation for the root of threat belief acquisition to a wide range of stimuli or situations.

Quality of reporting and concordance between sources of adverse events in the treatment of moderate-to-severe psoriasis: a cross-sectional study of RCTs from a Cochrane systematic review.

OBJECTIVES: Incomplete reporting of safety outcomes in quality and availability of safety reporting in published articles of randomized clinical trials (RCTs) were described in different medical areas. The number of RCTs assessing systemic treatments for psoriasis has increased considerably. Complete and precise reporting of safety is mandatory for the efficacy/harms balance evaluation. We aimed to assess the quality and availability of safety reporting in published RCTs assessing systemic treatments for psoriasis, as well as the concordance of data between published trials and clinicaltrials.gov (CT). STUDY DESIGN AND SETTING: We included all RCTs in adults initiated after September 2009, assessing systemic psoriasis treatments compared with placebo or with an active comparator. All trials were selected in duplicate by two independent authors from the latest search of the dedicated Cochrane review. We described quality of safety reporting for all published RCTs, using a modified CONSORT harms scale by using descriptive analysis, and a composite score of 3 key items of safety report. For each RCT, data on adverse events (AEs)/serious AEs (SAEs) were extracted from the publication and CT: total number of AEs/SAEs, patients with AEs/SAEs, SAEs by system organ class classification and deaths. These data were compared between sources for each RCT. RESULTS: In total, 128 trials were included in the analysis of reporting quality, and 76 in the analysis of data concordance between sources. The median number of reported CONSORT harms items per article was 9 out of 18 (IQR 7-10), and mean number was 8.39 (sd = 3.02). Items in the methods section were the least frequently reported. The proportion of RCTs reporting the number of SAEs and death were significantly higher on ClinicalTrials.gov than in the published article ((100% (76/76) vs 88.2%, McNemar test, p <0.0016). At least one discrepancy between sources for SAE safety data was found in 30/76 (39.5%) RCTs. DISCUSSION: Shortcomings and gaps in the quality of safety reporting in publications of RCTs of systemic psoriasis treatments have been identified. A lack of data in published articles and discrepancies between published articles and CT data complete this finding.

Longitudinal patient-reported outcomes on genotype-guided irinotecan dosing: feasibility and clinical relevance.

INTRODUCTION: Standard investigator-based adverse events (AE) assessment is via CTCAE for clinical trials. However, including the patient perspective through PRO (patient-reported outcomes) enhances clinicians' understanding of patient toxicity and fosters early detection of AEs. We assessed longitudinal integration of PRO-CTCAE within clinical workflow in a phase II trial. MATERIALS AND METHODS: As a sub-study in a phase II trial of genotype-directed irinotecan dosing evaluating efficacy in patients with metastatic colorectal cancer receiving FOLFIRI and bevacizumab, patients reported on 13 AEs generating a PRO-CTCAE form. The primary objective was to estimate forms completed by patients and clinicians at least 80% of time. Secondary objectives were estimating concordance and time to first score of specific symptoms between patient and clinician pairs. RESULTS: Feasibility of longitudinal PRO-CTCAE integration was met as 96% of patients and clinician-patient pairs completed at least 80% of PRO-CTCAE forms available to them with 79% achieving 100% completion. Concordance between patient and clinician reporting a severe symptom was 73% with 24 disconcordant pairs, 21 involved patients who reported a severe symptom that the clinician did not. Although protocol-mandated dose reductions were guided by CTCAE not PRO-CTCAE responses, the median time to dose reduction of 2.53 months, and the time-to-event curve closely approximated time to patient-reported toxicity. CONCLUSION: Longitudinal integration of PRO-CTCAE paired CTCAE proved feasible. Compared to clinicians, patients reported severe symptoms more frequently and earlier. Patient-reported toxicity more closely aligned with dose decreases indicating incorporation into routine clinical practice may enhance early detection of toxicity improving patient safety and quality of life.

Bridging the gap from medical to psychological safety assessment: consensus study in a digital mental health context.

BACKGROUND: Digital Mental Health Interventions (DMHIs) that meet the definition of a medical device are regulated by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. The MHRA uses procedures that were originally developed for pharmaceuticals to assess the safety of DMHIs. There is recognition that this may not be ideal, as is evident by an ongoing consultation for reform led by the MHRA and the National Institute for Health and Care Excellence. AIMS: The aim of this study was to generate an experts' consensus on how the medical regulatory method used for assessing safety could best be adapted for DMHIs. METHOD: An online Delphi study containing three rounds was conducted with an international panel of 20 experts with experience/knowledge in the field of UK digital mental health. RESULTS: Sixty-four items were generated, of which 41 achieved consensus (64%). Consensus emerged around ten recommendations, falling into five main themes: Enhancing the quality of adverse events data in DMHIs; Re-defining serious adverse events for DMHIs; Reassessing short-term symptom deterioration in psychological interventions as a therapeutic risk; Maximising the benefit of the Yellow Card Scheme; and Developing a harmonised approach for assessing the safety of psychological interventions in general. CONCLUSION: The implementation of the recommendations provided by this consensus could improve the assessment of safety of DMHIs, making them more effective in detecting and mitigating risk.

How and why do doctors communicate diagnostic uncertainty: An experimental vignette study.

BACKGROUND: Diagnostic uncertainty is common, but its communication to patients is under-explored. This study aimed to (1) characterise variation in doctors' communication of diagnostic uncertainty and (2) explore why variation occurred. METHODS: Four written vignettes of clinical scenarios involving diagnostic uncertainty were developed. Doctors were recruited from five hospitals until theoretical saturation was reached (n = 36). Participants read vignettes in a randomised order, and were asked to discuss the diagnosis/plan with an online interviewer, as they would with a 'typical patient'. Semi-structured interviews explored reasons for communication choices. Interview transcripts were coded; quantitative and qualitative (thematic) analyses were undertaken. RESULTS: There was marked variation in doctors' communication: in their discussion about differential diagnoses, their reference to the level of uncertainty in diagnoses/investigations and their acknowledgement of diagnostic uncertainty when safety-netting. Implicit expressions of uncertainty were more common than explicit. Participants expressed both different communication goals (including reducing patient anxiety, building trust, empowering patients and protecting against diagnostic errors) and different perspectives on how to achieve these goals. Training in diagnostic uncertainty communication is rare, but many felt it would be useful. CONCLUSIONS: Significant variation in diagnostic uncertainty communication exists, even in a controlled setting. Differing communication goals-often grounded in conflicting ethical principles, for example, respect for autonomy versus nonmaleficence-and differing ideas on how to prioritise and achieve them may underlie this. The variation in communication behaviours observed has important implications for patient safety and health inequalities. Patient-focused research is required to guide practice. PATIENT OR PUBLIC CONTRIBUTION: In the design stage of the study, two patient and public involvement groups (consisting of members of the public of a range of ages and backgrounds) were consulted to gain an understanding of patient perspectives on the concept of communicating diagnostic uncertainty. Their feedback informed the formulations of the research questions and the choice of vignettes used.

The OsZIP2 transporter is involved in root-to-shoot translocation and intervascular transfer of cadmium in rice.

Cadmium (Cd) is a toxic metal that poses serious threats to human health. Rice is a major source of dietary Cd but how rice plants transport Cd to the grain is not fully understood. Here, we characterize the function of the ZIP (ZRT, IRT-like protein) family protein, OsZIP2, in the root-to-shoot translocation of Cd and intervascular transfer of Cd in nodes. OsZIP2 is localized at the plasma membrane and exhibited Cd2+ transport activity when heterologously expressed in yeast. OsZIP2 is strongly expressed in xylem parenchyma cells in roots and in enlarged vascular bundles in nodes. Knockout of OsZIP2 significantly enhanced root-to-shoot translocation of Cd and alleviated the inhibition of root elongation by excess Cd stress; whereas overexpression of OsZIP2 decreased Cd translocation to shoots and resulted in Cd sensitivity. Knockout of OsZIP2 increased Cd allocation to the flag leaf but decreased Cd allocation to the panicle and grain. We further reveal that the variation of OsZIP2 expression level contributes to grain Cd concentration among rice germplasms. Our results demonstrate that OsZIP2 functions in root-to-shoot translocation of Cd in roots and intervascular transfer of Cd in nodes, which can be used for breeding low Cd rice varieties.

A Minimal Approach to Demonstrate Concordance of Digital and Conventional Microscopy in Toxicologic Pathology.

Digitalization of pathology workflows has undergone a rapid evolution and has been widely established in the diagnostic field but remains a challenge in the nonclinical safety context due to lack of regulatory guidance and validation experience for good laboratory practice (GLP) use. One means to demonstrate that digital slides are fit for purpose, that is, provide sufficient quality for pathologists to reach a diagnosis, is conduction of comparison studies, which have been published both, for veterinary and human diagnostic pathology, but not for toxicologic pathology. Here, we present an approach that uses study material from nonclinical safety studies and that allows for the statistical comparison of concordance rates for glass and digital slide evaluation while minimizing time and effort for the involved personnel. Using a benchmark study design, we demonstrate that evaluation of digital slides fits the purpose of nonclinical safety evaluation. These results add to reports of successful workflow validations and support the full adaptation of digital pathology in the regulatory field.