Radiopharmaceuticals Adverse Events Management.

BACKGROUND AND PURPOSE: Radiopharmaceuticals are radioactive compounds used for diagnostic or therapeutic purposes which are most often administered intravenously. Adverse events that may induce both adverse reactions and drug-to-drug interactions with changes in expected biodistribution, potentially affecting patient safety and diagnostic accuracy. Adverse reactions are relatively rare due to the small doses and under-reporting is the norm. The aim of this study is to increase awareness of the need to report in order to create protocols for the management of such adverse events among professionals in a Nuclear Medicine Department. METHODS: A reporting system was established a decade ago through an electronic form to enhance adverse event registration. The radiopharmacist collects data for further communication with National Health authorities and develops an annual report with recommendations on the management of these adverse events. RESULTS: A total of 128 reports were collected, including 65 cases of extravasations, 18 adverse reactions, and 45 drug interactions. Over the years, reporting has been increasing, adverse reactions occurred at a higher incidence than reported in the literature, and each anomalous biodistribution was analysed for possible drug interaction. The annual reports have been used to develop a local guideline for the management of adverse reactions and recommendations for discontinuation of treatment to avoid interactions with radiopharmaceuticals. CONCLUSION: The recognition of adverse events associated with radiopharmaceuticals is increasing, underlining the need for vigilant reporting and improved management strategies. An efficient reporting system promotes awareness of possible interactions between radiopharmaceuticals and other medicines and their potential adverse reactions to enhance patient safety.

Diagnostic Validation of Anti-TOX Antibody for Early-Stage Mycosis Fungoides Through Digital Analysis of Tissue Samples.

ABSTRACT: Mycosis fungoides (MF) has become one of the most difficult diagnostic challenges for both dermatologists and dermatopathologists because its clinical presentation and microscopic findings may mimic benign reactive processes, specifically those displaying histopathological features of interface dermatitis. The goal of our study was to prove with digital scanning and automated sample methodology through algorithmic analysis, combined with the utility of TOX marker a more precise, faster, and objective evaluation of each sample. Moreover, this would offer high levels of reproducibility with the possibility of establishing cut-off points, allowing us to distinguish between inflammatory dermatoses (ID) and MF. A retrospective longitudinal-descriptive and observational study was conducted to compare the diagnostic criteria (immunohistochemical studies of anti-TOX stain) in patients with clinical suspicion of MF by dividing them into 2 groups: samples with a positive biopsy for MF (MF group) and those with a negative biopsy, therefore diagnosed as an ID (control group). The algorithm assessed 5 selected areas with lymphocytic representative cellularity, and based on the intensity, nuclear staining was classified as 0 (negative), 1+ (weak/yellow), 2+ (moderate/orange), and 3+ (strong/scarlet red) nuclei. The results showed statistically significant differences ( P = 0.040) between the mean number of (2+) nuclei in the positive final diagnosis group (MF group) and the negative final diagnosis group (ID group).

Evaluating Person-Centred Integrated Care to People with Complex Chronic Conditions: Early Implementation Results of the ProPCC Programme.

Introduction: The evaluation of integrated care programmes for high-need high-cost older people is a challenge. We aim to share the early implementation results of the ProPCC programme in the North-Barcelona metropolitan area, in Catalonia, Spain. Methods: We analysed the intervention with retrospective data from May 2018 to December 2021 by describing the cohort complexity and by showing its 6-months pre-post impact on time spent at home and resources used: primary care visits, emergency department visits, hospital admissions and hospital stay. Findings: 264 cases were included (91% at home; 9% in nursing homes). 6-month pre vs. 6-months post results were (mean, p-value): primary care visits 8.2 vs. 11.5 (p < 0.05); emergency department visits 1.4 vs. 0.9 (p < 0.05); hospital admissions 0.7 vs. 0.5 (p < 0.05); hospital stay 12.8 vs. 7.9 days (p < 0.05). Time spent at home was 169.2 vs.174.2 days (p < 0.05). Conclusion: Early implementation of the ProPCC programme results in an increase in time spent at home (up to 3%) and significant reductions in emergency department attendance (-37.2%) and hospital stays (-38.3%). The increased use of primary care resources is compensated by the hospital resources savings, with a result in the average total cost of -46.3%.

Is there interest of Mexican adults in being prepared should they develop Alzheimer's or other dementia? / ¿Existe interés en adultos mexicanos de preparase en caso de llegar a padecer Alzheimer u otra demencia?

Abstract Introduction Alzheimer's disease, as well as other dementias, cause a progressive deterioration of cognitive functions, preventing patients from making decisions and having control over themselves in an advanced stage of the disease. Objective To explore some expectations, wishes and preferences in a sample of mature adults should they develop Alzheimer or other dementia. Method We surveyed 368 mature Mexican adults without dementia using a large survey created by the authors and used in a previous study; data were collected in some public places where mature people were invited to participate. The survey was completed from July 2019 to August 2020. Results Although most participants had considered they might suffer from dementia in the future, less than half had communicated their wishes to their relatives about future medical treatments in case they could no longer decide for themselves; very few had prepared a written advance directive. Most participants agreed that patients should know their initial diagnosis, mainly to be able to prepare themselves. The main reason given by those who would prefer to hide the diagnosis was to avoid suffering. Discussion and conclusion Our results highlight the need for health professionals to promote discussion with people about the possibility of suffering from dementia, as well as the importance of making decisions in advance, and letting their relatives know about them.

Resumen Introducción La enfermedad de Alzheimer, así como las otras demencias, causan un deterioro progresivo de las funciones cognitivas, evitando que en una etapa avanzada de la enfermedad los pacientes puedan tomar decisiones y tener control sobre sí mismos. Objetivo Explorar algunas expectativas, deseos y preferencias en una muestra de adultos maduros en caso de que llegaran a desarrollar Alzheimer u otra demencia. Método Encuestamos a 368 adultos mexicanos maduros sin demencia usando una encuesta creada por los autores y utilizada en un estudio anterior; los datos se recopilaron en algunos lugares públicos donde se invitó a las personas a participar. La encuesta se aplicó de julio de 2019 a agosto de 2020. Resultados Aunque la mayoría de los participantes había considerado que podría sufrir demencia en el futuro, menos de la mitad había comunicado sus deseos a sus familiares sobre futuros tratamientos médicos en caso de que ya no pudieran decidir por sí mismos; muy pocos habían preparado una voluntad anticipada por escrito. La mayoría de los participantes estuvo de acuerdo en que los pacientes deben conocer su diagnóstico inicial, principalmente para poder prepararse. La principal razón aducida por quienes preferirían ocultar el diagnóstico fue el deseo de evitar sufrimiento. Discusión y conclusión Nuestros resultados destacan la necesidad de que el personal de salud promueva la discusión con las personas sobre la posibilidad de padecer demencia, así como la importancia de tomar decisiones por anticipado e informar de ellas a sus familiares.

TACkling Cancer by Targeting Selective Protein Degradation.

Targeted protein degradation has emerged as an alternative therapy against cancer, offering several advantages over traditional inhibitors. The new degrader drugs provide different therapeutic strategies: they could cross the phospholipid bilayer membrane by the addition of specific moieties to extracellular proteins. On the other hand, they could efficiently improve the degradation process by the generation of a ternary complex structure of an E3 ligase. Herein, we review the current trends in the use of TAC-based technologies (TACnologies), such as PROteolysis TArgeting Chimeras (PROTAC), PHOtochemically TArgeting Chimeras (PHOTAC), CLIck-formed Proteolysis TArgeting Chimeras (CLIPTAC), AUtophagy TArgeting Chimeras (AUTAC), AuTophagosome TEthering Compounds (ATTEC), LYsosome-TArgeting Chimeras (LYTAC), and DeUBiquitinase TArgeting Chimeras (DUBTAC), in experimental development and their progress towards clinical applications.

Screening of atrial fibrillation in dental practices: a qualitative feasibility study.

OBJECTIVES: To increase the detection of unknown atrial fibrillation (AF), general practitioners have started screening their patients using small hand-held devices. It is thought that dental settings could be utilized for screening as they have regular access to patients. The aim of this study was to explore the perceptions of dental staff of screening for AF using a hand-held electronic device in primary dental care. METHODS: The research took place in one large mixed NHS and private general dental practice. Views from staff including dentists, dental therapists, dental nurses, and managers were elicited via semi-structured interviews conducted face-to-face, audio recorded, and transcribed verbatim. Interviews continued until there were no new themes or patterns emerging from the data, and thematic saturation had been achieved. RESULTS: Eleven participants were interviewed. The main themes generated were methodology for screening, acceptability for screening within the practice, attitudes to screening, and implementation of screening. Overall, participants were positive about implementing AF screening in a dental practice but expressed concerns about time and remuneration. Staff also gave encouraging feedback regarding the simplicity of the portable screening device. CONCLUSIONS: Participants felt that AF screening in primary care dental practices was a good concept but may be challenging to implement in NHS Dentistry, especially due to the pandemic.

Eficacia y tolerabilidad Resultados del tratamiento para la fibrosis pulmonar idiopática. Experiencia de la vida real / Efficacy and Tolerability Outcomes of Treatment for Idiopathic Pulmonary Fibrosis. Real-life Experience

Introducción: la fibrosis pulmonar idiopática (FPI) es una enfermedad progresiva y cró-nica con muy mal pronóstico. Actualmente, existen dos fármacos para esta patología. El propósito de nuestro estudio es evaluar los efectos del tratamiento en los pacientes de una consulta en vida real.

Introduction: idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with a very poor prognosis. Two drugs are currently available for this disease. The purpo-se of our study is to evaluate the effects of treatment in patients in a real-life practice.

Clinicopathological Profiles Associated with Discordant RAS Mutational Status between Liquid and Tissue Biopsies in a Real-World Cohort of Metastatic Colorectal Cancer.

We aimed to identify common mCRC profiles associated with a discordant mutational status of RAS between the standard of care (SoC) tumour tissue tests and ctDNA tests to understand ctDNA detection and improve treatment responses. This was a multicentre, retrospective and prospective study. A total of 366 Spanish mCRC patients were independently recruited. BEAMing ddPCR technology was employed to detect ctDNA RAS mutations, and logistic regression analyses were performed to investigate clinicopathological factors associated with discordance. The highest concordance ratios were observed in profiles with multiple metastatic sites when the liver was present (89.7%; 95% CI 84.8-93.2), profiles with synchronous disease without primary tumour resection (90.2%; 95% CI 83.6-94.3) and profiles with mCRC originating in the left colon (91.3%; 95% CI 85.0-95.0). Metachronous disease originating in the right colon (OR = 6.1; 95% CI 1.7-26.5; p-value = 0.006) or rectum (OR = 5.0; 95% CI 1.5-17.8; p-value = 0.009) showed the highest probability of discrepancies. Primary tumour resection and a higher frequency of single metastases in the peritoneum or lungs in these patients were associated with reduced plasmatic mutation allele fractions (MAFs) and an increased probability of showing false-negative genotypes. Additional testing of patients with mCRC originating in the right colon or rectum with a single non-mutated ctDNA test is advised before the choice of therapy.

Integrative species delimitation in the common ophiuroid Ophiothrix angulata (Echinodermata: Ophiuroidea): insights from COI, ITS2, arm coloration, and geometric morphometrics.

Ophiothrix angulata (Say, 1825) is one of the most common and well-known ophiuroids in the Western Atlantic, with a wide geographic and bathymetric range. The taxonomy of this species has been controversial for a century because of its high morphological variability. Here we integrate information from DNA sequence data, color patterns, and geometric morphometrics to assess species delimitation and geographic differentiation in O. angulata. We found three deeply divergent mtDNA-COI clades (K2P 17.0-27.9%). ITS2 nuclear gene and geometric morphometrics of dorsal and ventral arm plates differentiate one of these lineages, as do integrative species delineation analyses, making this a confirmed candidate species.

3D Information-Theoretic Analysis of the Simplest Hydrogen Abstraction Reaction.

We investigate the course of an elementary chemical reaction from the perspective of information theory in 3D space through the hypersurface of several information-theoretic (IT) functionals such as disequilibrium (D), Shannon entropy (S), Fisher information (I), and the complexity measures of Fisher-Shannon (FS) and López-Mancini-Calbet (LMC). The probe for the study is the hydrogenic identity abstraction reaction. In order to perform the analysis, the reactivity pattern of the reaction is examined by use of the aforementioned functionals of the single-particle density, which is analyzed in position (r) and momentum (p) spaces. The 3D analyses revealed interesting reactivity patterns in the neighborhood of the intrinsic reaction coordinate (IRC) path, which allow to interpret the reaction mechanism for this reaction in a novel manner. In addition, the chemically interesting regions that have been characterized through the information functionals and their complexity measures are depicted and analyzed in the framework of the three-dimensional structure of the information-theoretical data of a chemical reaction, that is, the reactant/product (R/P) complexes, the transition state (TS), and the ones that are only revealed through IT measures such as the bond-cleavage energy region (BCER), the bond-breaking/forming (B-B/F) region, and the spin-coupling (SC) process. Furthermore, focus has been placed on the diagonal part of the hypersurface of the IT functionals, aside from the IRC path itself, with the purpose of analyzing the dissociation process of the triatomic transition-state complex that has revealed other interesting features of the bond-breaking (B-B) process. In other respects, it is shown throughout the combined analyses of the 3D structure of the IT functionals in conjugated spaces that the chemically significant regions occurring at the onset of the TS are completely characterized by information-theoretic aspects of localizability (S), uniformity (D), and disorder. Further, novel regions of low complexity seem to indicate new boundaries for chemically stable complex molecules. Finally, the study reveals that the chemical reaction occurs at low-complexity regions, where the concurrent phenomena take place: bond-breaking/forming (B-B/F), bond-cleavage energy reservoirs (BCER), spin-coupling (SC), and transition state (TS).

Carbonic maceration vinification: A tool for wine alcohol reduction.

The increase in alcohol content in wine due to climate change is one of the main challenges that winemakers face today. Previous studies have indicated that carbonic maceration processing can be used to obtain a wine fraction with lower alcoholic strength. The aim of this study was to determine the effectiveness of this technique in obtaining wines with lower alcohol content. For this purpose, seven trials were carried out, studying a total of 63 wines. The physico-chemical, phenolic and aromatic composition of the wines was analysed using official methods and gas chromatography. The results showed that it is possible to obtain a fraction of carbonic maceration wine (25-35% of the total) with a reduction in alcohol content of up to almost 4% depending on the vinification conditions and the grape variety used. Therefore, this CM fraction, marketed on its own, could be a low-alcohol alternative to red wines.

A Versatile Urea Type Linker for Functionalizing Natural Glycans and Its Validation in Glycan Arrays.

The isolation from organisms and readily available glycoproteins has become an increasingly convenient source of N-glycans for multiple applications including glycan microarrays, as reference standards in glycan analysis or as reagents that improve bioavailability of protein and peptide therapeutics through conjugation. A problematic step in the isolation process on a preparative scale can be the attachment of a linker for the improved purification, separation, immobilization and quantification of the glycan structures. Addressing this issue, we firstly aimed for the development of an UV active linker for a fast and reliable attachment to anomeric glycosylamines via urea bond formation. Secondly, we validated the new linker on glycan arrays in a comparative study with a collection of N-glycans which were screened against various lectins. In total, we coupled four structurally varied N-glycans to four different linkers, immobilized all constructs on a microarray and compared their binding affinities to four plant and fungal lectins of widely described specificity. Our study shows that the urea type linker showed an overall superior performance for lectin binding and once more, highlights the often neglected influence of the choice of linker on lectin recognition.

Dental student readiness to treat special care patients upon graduation.

INTRODUCTION: There has been a global increase in patients with special needs. Undergraduate dental curricula need to adjust to meet the needs of these patients. This study aimed to identify how confident final year dental students felt about treating patients with special needs upon graduation and evaluate the influence that the curriculum had on their preparedness based on competencies outlined by the International Association for Disability and Oral Health (iADH). METHODS: A questionnaire was administered to final year dental students at two different Universities in Scotland and in Spain to: (1) evaluate how prepared students felt when treating patients with special needs and (2) assess the competencies outlined by iADH. RESULTS: The response rate was 18.4% (30/163 students). Overall, 83.3% of the students (n = 25) perceived they would benefit from more practical sessions with patients with learning and physical disabilities to improve their clinical management of these patients. 53.3% (n = 16) didn't feel that had the knowledge to properly treat all special care dentistry (SCD) patients upon graduation (scored 5 or 6 on the IADH competency framework). 83.3% of the students (n = 25) felt that the mode of teaching should be problem-based complemented with small group seminars. CONCLUSION: Students from both Universities agreed that more clinical practice might be required for them to further their skills to treat special needs patients upon graduation, which correlates with the need to have more practical sessions to consolidate competency 4 (communication skills with SCD) and competency 6 (clinical management of patients requiring SCD).

Synthesis of 1,2-diaminotruxinic δ-cyclobutanes by BF3-controlled [2 + 2]-photocycloaddition of 5(4H)-oxazolones and stereoselective expansion of δ-cyclobutanes to give highly substituted pyrrolidine-2,5-dicarboxylates.

The irradiation of (Z)-4-arylidene-5(4H)-oxazolones 1a-1u with blue light (465 nm) in the presence of the photosensitizer [Ru(bpy)3](BF4)2 (2.5 mol%) and the Lewis acid BF3·OEt2 (2 equiv.) in deoxygenated methanol at room temperature affords the corresponding 1,2-diaminotruxinic cyclobutane bis-amino esters 2a-2u stereoselectively as the δ-isomer. Characterization of cyclobutanes 2 shows that the photocycloaddition takes place by the coupling of two Z-oxazolones in a head-to-head 1,2-anti way. This change in the orientation of the coupling is promoted by O- or/and N-bonding of the BF3 additive. The δ-cyclobutanes 2 undergo a ring expansion when heated in methanol in the presence of NaOMe (1/1 molar ratio) to give densely substituted pyrrolidine-2,5-dicarboxylates 3 in a regio- and stereoselective way. The mechanism of the cyclobutane-to-pyrrolidine ring expansion has been elucidated using DFT methods.

Entropic and Complexity Measures in Atomic and Molecular Systems.

Both entropy and complexity are central concepts for the understanding and development of Information Theory, playing an essential role in the increasingly numerous applications in a huge diversity of fields [...].

Accessing Chiral Pyrrolodiketopiperazines under Organocatalytic Conditions.

The production of chiral pyrrolodiketopiperazines under organocatalytic conditions demonstrates the capacity of bicyclic acylpyrrol lactims to perform as pronucleophiles in direct carbon-carbon bond forming reactions. The good performance of ureidoaminal-derived Brønsted bases in the Michael addition to nitroolefins affords these heterocyclic scaffolds with high skeleton diversity.

Psychometric properties of the Clarke questionnaire for hypoglycemia awareness in the Spanish population with type 2 diabetes.

OBJECTIVES: The Clarke questionnaire, validated in Spanish language, assesses hypoglycemia awareness in patients with type 1 diabetes. This study aimed to analyze its psychometric properties in patients with type 2 diabetes (T2DM). METHODS: This was a questionnaire validation study. Patients with T2DM and treated with insulin, sulfonylureas or glinides were consecutively recruited from six endocrinology consultations and six primary care centers. The internal structure of the 8-item Clarke questionnaire was analyzed by exploratory (training sample) and confirmatory (testing sample) factor analysis; the internal consistency using Omega's McDonald coefficient; and goodness of fit with comparative fit index (CFI, cutoff >0.9), Goodness of Fit Index (GFI, cutoff >0.9), and root mean-square error of approximation (RMSEA, cutoff <0.09), as well as unidimensionality indicators. RESULTS: The 265 participants (56.8% men) had a mean age of 67.8 years. Confirmatory factor analysis for one dimension obtained poor indicators: fit test (p < 0.001); CFI = 0.748; RMSEA = 0.122 and SRMR = 0.134. Exploratory factor analysis showed 2 or 3 dimensions with poor adjustment indicators. Omega's McDonald was 0.739. CONCLUSIONS: The Spanish version of the Clarke questionnaire was not valid or reliable for assessing hypoglycemia awareness in people with T2DM in Spanish population.

Procedural pain in patients with cancer: a Delphi expert management consensus.

OBJECTIVES: Diagnosis, treatment and care of cancer often involve procedures that may be distressing and potentially painful for patients. The PROCEDIO Study aimed to generate expert-based recommendations on the management of moderate to severe procedural pain in inpatients and outpatients with cancer. METHODS: Using a two-round Delphi method, experts from pain and palliative care units, medical and radiation oncology and haematology departments expressed their agreement on 24 statements using a 9-point Likert scale, which were classified as appropriate (median 7-9), uncertain (4-6) or inappropriate (1-3). Consensus was achieved if at least two-thirds of the panel scored within the range containing the median. RESULTS: With an overall agreement on the current definition of procedural pain, participants suggested a wider description based on evidence and their clinical experience. A strong consensus was achieved regarding the need for a comprehensive pre-procedural pain assessment and experts emphasised that healthcare professionals involved in procedural pain management should be adequately trained. Most panellists (98.2%) agreed that pharmacological treatment should be chosen considering the duration of the procedure. Transmucosal fentanyl (96.5%) and morphine (71.7%) were recommended as the most appropriate drugs. Oral and nasal transmucosal fentanyl were agreed as the most suitable for both outpatients and inpatients, while consensus was reached for intravenous and subcutaneous morphine for inpatients. CONCLUSIONS: These results provide updated expert-based recommendations on the definition, prevention and treatment of moderate to severe procedural pain, which could inform specialists involved in pain management of patients with cancer.