The molecular architecture of Lactobacillus S-layer: Assembly and attachment to teichoic acids.

S-layers are crystalline arrays found on bacterial and archaeal cells. Lactobacillus is a diverse family of bacteria known especially for potential gut health benefits. This study focuses on the S-layer proteins from Lactobacillus acidophilus and Lactobacillus amylovorus common in the mammalian gut. Atomic resolution structures of Lactobacillus S-layer proteins SlpA and SlpX exhibit domain swapping, and the obtained assembly model of the main S-layer protein SlpA aligns well with prior electron microscopy and mutagenesis data. The S-layer's pore size suggests a protective role, with charged areas aiding adhesion. A highly similar domain organization and interaction network are observed across the Lactobacillus genus. Interaction studies revealed conserved binding areas specific for attachment to teichoic acids. The structure of the SlpA S-layer and the suggested incorporation of SlpX as well as its interaction with teichoic acids lay the foundation for deciphering its role in immune responses and for developing effective treatments for a variety of infectious and bacteria-mediated inflammation processes, opening opportunities for targeted engineering of the S-layer or lactobacilli bacteria in general.

HbA1c overestimates the glucose management indicator: a pilot study in patients with diabetes, chronic kidney disease not on dialysis, and anemia using isCGM.

Introduction: There are multiple mechanisms by which HbA1c values can be altered in chronic kidney disease (CKD), which limits its usefulness as a strategy to assess glycemic control in this population. Methods: Concordance and agreement study between two diagnostic tests: HbA1c and glucose management indicator (GMI) measured by intermittently scanned continuous glucose monitoring (isCGM), based in a prospective cohort of patients with diabetes, CKD (glomerular filtration rate between 15 and 60 ml/min/1.73 m²), and anemia. The isCGM was performed for 3 months, and the GMI was compared with the HbA1c levels taken at the end of isCGM. Agreement was evaluated using Bland-Altman graph analysis and Lin's concordance correlation coefficient (CCC). The concordance of the measures with good glycemic control (<7%) was also evaluated. Results: A total of 74 patients were enrolled (median age 68.5 years, 51.3% female, 64.9% with CKD stage 3, hemoglobin 11.1 ± 1.2 g/l). The Bland-Altman analysis shows a mean difference between GMI and HbA1c of 0.757 ± 0.687% (95% limits of agreement: -0.590 and 2.105). Difference was greater as the values of GMI and HbA1c increased. The agreement was poor [CCC 0.477; 95% confidence interval (CI): 0.360-0.594], as well as the concordance of values with good glycemic control according to GMI versus HbA1c (67.5% versus 29.7%, p < 0.001) (Kappa 0.2430; 95% CI: 0.16-0.32). Conclusion: The HbA1c overestimates the GMI values with highly variable ranges of difference, which prevents a precise correction factor. isCGM probably is a safer option for monitoring and decision-making in this population, especially in patients treated with insulin where the risk of hypoglycemia is greater.

Molecular and structural basis of oligopeptide recognition by the Ami transporter system in pneumococci.

ATP-binding cassette (ABC) transport systems are crucial for bacteria to ensure sufficient uptake of nutrients that are not produced de novo or improve the energy balance. The cell surface of the pathobiont Streptococcus pneumoniae (pneumococcus) is decorated with a substantial array of ABC transporters, critically influencing nasopharyngeal colonization and invasive infections. Given the auxotrophic nature of pneumococci for certain amino acids, the Ami ABC transporter system, orchestrating oligopeptide uptake, becomes indispensable in host compartments lacking amino acids. The system comprises five exposed Oligopeptide Binding Proteins (OBPs) and four proteins building the ABC transporter channel. Here, we present a structural analysis of all the OBPs in this system. Multiple crystallographic structures, capturing both open and closed conformations along with complexes involving chemically synthesized peptides, have been solved at high resolution providing insights into the molecular basis of their diverse peptide specificities. Mass spectrometry analysis of oligopeptides demonstrates the unexpected remarkable promiscuity of some of these proteins when expressed in Escherichia coli, displaying affinity for a wide range of peptides. Finally, a model is proposed for the complete Ami transport system in complex with its various OBPs. We further disclosed, through in silico modelling, some essential structural changes facilitating oligopeptide transport into the cellular cytoplasm. Thus, the structural analysis of the Ami system provides valuable insights into the mechanism and specificity of oligopeptide binding by the different OBPs, shedding light on the intricacies of the uptake mechanism and the in vivo implications for this human pathogen.

Impact of Risk Stratification in Patients With Diabetes Mellitus in a Health System Specialty Pharmacy Setting.

Background: Integrated pharmacist care into health systems results in significant A1c reduction and improved outcomes in patients with diabetes. However, little is known about the adoption of Health System Specialty Pharmacy (HSSP) chronic disease management (CDM) services within diabetes clinics. Risk stratification is proven to enhance care in various patient populations. Objective: The objective of this study is to describe how the implementation of risk stratification in the HSSP setting results in optimized patient outcomes in diabetes. Method: This is a retrospective descriptive study reporting the results of expanding the HSSP care model to implement risk stratified CDM services for patients with diabetes. A total of 285 patients were enrolled in the HSSP CDM pharmacy services and were stratified into high- or low-risk groups. Results: Eighty-eight patients were stratified as high-risk with an average baseline A1c of 11.47% and a most recent average of 8.84%. The remaining 285 patients were stratified into the low-risk group. Their average baseline A1c was 7.48% and the last recorded average A1c was 7.15%. Patients not enrolled in HSSP CDM services (N = 100) had a lower reduction in average A1c compared to patients enrolled in the program. Conclusion: Patients stratified into high- and low-risk groups had greater reductions in A1c compared to patients who did not use HSSP CDM services. These results showcase the success of risk stratification and demonstrate the impact HSSP has on patients needing CDM services and outlines a strategy to provide the greatest impact in a high-volume patient population.

Cross-cultural adaptation, reliability and validity of the Spanish version of the long-term quality of life questionnaire.

Purpose: The aim of this study was to translate, culturally adapt, and evaluate the psychometric properties of the Spanish Long-Term Quality of Life (LTQL) questionnaire. Methods: The LTQL was initially translated into Spanish and cross-culturally adapted based on established guidelines. The Spanish LTQL was administered to patients with breast cancer who had completed their initial treatment 5 years earlier, along with other self-report measures: Quality of Life in Adult Cancer Survivors (QLACS), Hospital Anxiety and Depression Scale (HADS) and EORT-QLQ-BR23. Reliability was evaluated using internal consistency and test-retest. Convergent and known-groups validity were examined. Structural validity as determined by confirmatory factor analysis (CFA) and Rasch analyses was used to assess the unidimensionality and item-functioning of the LTQL domains. Results: Cronbach's alpha were above 0.7 in all domains. Test-retest coefficients were between 0.72 to 0.96 for LTQL domains. LTQL total score was correlated with others total scores of other measures: QLACS (r=-0.39), HADS depression (r=-0.57), HADS anxiety (-0.45) and EORTC-QLQ-BR23 (r=-0.50). CFA provided satisfactory fit indices, with RMSEA value of 0.077 and TLI and CFI values of 0.901 and 0.909, respectively. All factor loadings were higher than 0.40 and statistically significant (P<0.001). Rasch analysis showed that Somatic Concerns domain had 4 misfitting items, and Philosophical/Spiritual View of Life and social Support domains only 1 misfit item. However, unidimensionality was supported for the four domains. Conclusion: The findings support the validity and reliability of the Spanish version of LTQL questionnaire to be used in long-term cancer female survivors.

Comprehension and usefulness of Spanish language health information about depression treatment.

US Latine adults who prefer the Spanish language for healthcare encounter communication have high risk of health disparitiesm in part from low organizational health literacy, mental health stigma and discrimination. Organizational health literacy includes the provision of culturally responsive, language concordant health information, which supports good comprehension and usefulness and could mitigate some health disparities. We conducted a pilot study to assess commonly provided patient health information handouts about depression treatment and antidepressant consumer medication information sheets. Thirty Latine adults with a Spanish language preference and a history of depression and antidepressant use participated in one phone interview. Descriptive statistics and thematic analysis were used to assess comprehension and usefulness of selected sections extracted verbatim from these documents. Overall, 83% (n = 25) participants reported that all sections were easy to understand, and 97% (n = 29) said that they were useful. Yet, responses to open-ended questions for 53% (n = 16) of participants revealed 'confusing' terminology in at least one section, and 10% (n = 3) expressed concerns about or misunderstood an idiomatic phrase as reinforcing mental health stigma. The seriousness of the organizational health literacy-based issues identified in this and previous studies require that government and health service organizations make necessary and timely revisions to address them.

Characteristics Associated With Elevated Time Below Range in Elderly Patients With Type 1 Diabetes Using an Automated Insulin Delivery System.

BACKGROUND: This study investigated the characteristics associated with an increased risk of hypoglycemia, in elderly patients with type 1 diabetes mellitus (T1D) using automated insulin delivery (AID) systems. METHODS: Cross-sectional observational study including patients >60 years, using sensor-augmented insulin pump therapy with predictive low-glucose management (SAPT-PLGM), hybrid closed-loop (HCL), and advanced hybrid closed-loop (AHCL), for more than three months. A geriatric assessment was performed, and body composition was determined to investigate its association with achieving time below range (TBR) <70 mg/dL goals. RESULTS: The study included 59 patients (47.5% of men, mean age of 67.6 years, glycated hemoglobin [HbA1c] of 7.5 ± 0.6%, time in range (TIR) 77.8 ± 9.9%). Time below range <70 and <54 mg/dL were 2.2 ± 2.3% and 0.4 ± 0.81%, respectively. Patients with elevated TBR <70 mg/dL (>1%) had higher HbA1c levels, lower TIR, elevated time above range (TAR), and high glycemic variability. Regarding body composition, greater muscle mass, grip strength, and visceral fat were associated with a lower TBR <70 mg/dL. These factors were independent of the type of technology used, but TIR was higher when using AHCL systems compared with SAPT-PLGM and HCL systems. CONCLUSIONS: In elderly patients treated with AID systems with good functional status, lower lean mass, lower grip strength, and lower visceral fat percentage were associated with TBR greater than 1%, regardless of the device used. A similar finding along was found with CGM indicators such as higher HbA1c levels, lower TIR, higher TAR, and higher CV. Geriatric assessment is crucial for personalizing patient management.

Genetic risk factors for drug-induced long QT syndrome: findings from a large real-world case-control study.

Aim: Drug-induced long QT syndrome (diLQTS), an adverse effect of many drugs, can lead to sudden cardiac death. Candidate genetic variants in cardiac ion channels have been associated with diLQTS, but several limitations of previous studies hamper clinical utility. Materials & methods: Thus, the purpose of this study was to assess the associations of KCNE1-D85N, KCNE2-I57T and SCN5A-G615E with diLQTS in a large observational case-control study (6,083 self-reported white patients treated with 27 different high-risk QT-prolonging medications; 12.0% with diLQTS). Results: KCNE1-D85N significantly associated with diLQTS (adjusted odds ratio: 2.24 [95% CI: 1.35-3.58]; p = 0.001). Given low minor allele frequencies, the study had insufficient power to analyze KCNE2-I57T and SCN5A-G615E. Conclusion: KCNE1-D85N is a risk factor for diLQTS that should be considered in future clinical practice guidelines.

Some medications can lead to a condition called drug-induced long QT syndrome (diLQTS), which can be a serious abnormal heart rhythm in some patients. In our research, we explored three specific changes in DNA related to the electrical function of the heart (KCNE1-D85N, KCNE2-I57T, SCN5A-G615E) and their link to diLQTS. Our study revealed a connection between KCNE1-D85N and diLQTS. This study emphasized the importance of including KCNE1-D85N in the medical guidelines to help identify patients at risk of diLQTS. We were unable to identify the connection of KCNE2-I57T and SCN5A-G615E with diLQTS, due to a low number of carriers in the study.

Health-system specialty pharmacist intervention types, acceptance, and associated actions for patients with multiple sclerosis.

PURPOSE: Health-system specialty pharmacy (HSSP) pharmacists play an integral role in the care of patients with multiple sclerosis (PwMS) by facilitating medication access, providing counseling, improving adherence, and decreasing provider workload. However, current literature detailing pharmacist interventions and their acceptance rates in this population is limited. The purpose of this study was to identify the types and acceptance rate of clinical interventions completed by pharmacists for PwMS. METHODS: To evaluate the acceptance rate of HSSP pharmacist interventions, we conducted a retrospective, multicenter, observational, descriptive study for the period from October 2019 to August 2022. Intervention types were categorized into reasons for intervention, recommendations from the pharmacists, and their acceptance rates. RESULTS: For 225 patients enrolled in HSSP services, 449 interventions were completed, with an average of 2.0 interventions per patient. Most interventions identified were associated with medication adherence (28.7%), medication regimen (27.6%), adverse drug reaction (ADR) (20.7%), and laboratory values (15.1%). The average adherence, defined by the proportion of days covered, was 94%. The most common recommendations were to continue therapy (14.9%), schedule laboratory tests (12.7%), and follow up with providers (11.8%). Recommendations had an acceptance rate of 85.3%, with 3.8% of recommendations declined and 10.9% requiring follow-up with providers. CONCLUSION: Pharmacists impact patient outcomes through the completion of clinical interventions that improve adherence, identify medication regimen problems, manage ADRs, and coordinate proper laboratory testing. Pharmacist recommendations were most often accepted for interventions related to medication regimen and ADRs. Proper identification and management of medication regimen concerns, as well as tolerability of medications, can positively impact adherence and improve overall patient outcomes.

Clinical dashboard development and implementation to standardize data capture and reporting across health-system specialty pharmacies.

PURPOSE: To describe the development and implementation of clinical dashboards to standardize data capturing and reporting across multiple partner health systems. SUMMARY: Between July and September 2020, clinical dashboards were developed and implemented across multiple partner health-system specialty pharmacies (HSSPs) located throughout the United States. The dashboards were developed via collaboration between personnel involved in clinical subcommittees, clinical outcomes, data analytics, information technology, and clinical and central operations. Utilizing a cloud-scale business intelligence service, patient clinical data documented in a shared patient management system was utilized to create customizable dashboards that displayed patient-reported outcome measures, collected laboratory or test results, and completed pharmacist interventions. Separate dashboards were developed for several disease states and/or medication classes. Based on specialty pharmacy recommendations, medical literature, and clinical guidelines, internally developed disease-specific protocols defined data included in the dashboards and ensured consistent data collection amongst partner health systems. Having access to real-time clinical information allows health systems to closely monitor performance metrics, track patient outcomes, and identify operational gaps. CONCLUSION: Accurately capturing and reporting clinical metrics using clinical dashboards can assist HSSPs in delivering high-quality care. Having access to clinical outcome measures allows HSSPs to better understand the impact of their services on patients' health and quality of life. Health systems can utilize this data to analyze trends and recognize areas of opportunity so that measures can be taken to improve patient care.

Biosimilar perceptions among autoimmune prescribers and pharmacists in health system specialty pharmacy.

BACKGROUND: By the end of 2023, 10 self-administered biosimilars indicated for autoimmune conditions are expected to launch in the United States, resulting in alternative treatment options for patients and a potential for cost savings. However, studies about perception and knowledge of self-administered biosimilars among health system prescribers and health system specialty pharmacists are limited. OBJECTIVE: To assesses knowledge and perceptions of biosimilars among autoimmune prescribers and health system specialty pharmacists across the United States. METHODS: An anonymous, cross-sectional self-administered online questionnaire was conducted among prescribers and health system specialty pharmacists practicing in the specialties of rheumatology, dermatology, and gastroenterology across the United States. The survey was available from January 2023 to February 2023. RESULTS: 31 prescribers and 44 pharmacists completed the questionnaire. Only 16.0% of prescribers and 13.4% of pharmacists reported being "very prepared" to have conversations with patients about biosimilar options. 43% of prescribers indicated they would prescribe a biosimilar to biologic naive patients. However, 13.3% of prescribers would be willing to prescribe a biosimilar to patients successfully established on biologic therapy. Among pharmacists, 68.1% were comfortable recommending a biosimilar substitution to a biologic naive patient, but only 18.1% would recommend a biosimilar substitution to an existing patient successfully established on a biologic therapy. Less than half of prescribers (48.0%) and pharmacists (42.0%) understood regulations of interchangeability and substitution. CONCLUSIONS: Our study highlights several knowledge gaps and hesitancies that exist among health system specialty prescribers and pharmacists regarding biosimilar products. Education efforts are needed to overcome the lack of biosimilar adoption, which will increase affordability of therapy for patients and health care savings.

Defining criteria for disease activity states in juvenile dermatomyositis based on the Juvenile Dermatomyositis Activity Index.

OBJECTIVES: To develop and validate the cut-offs in the Juvenile DermatoMyositis Activity Index (JDMAI) to distinguish the states of inactive disease (ID), low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA) in children with juvenile dermatomyositis (JDM). METHODS: For cut-off definition, data from 139 patients included in a randomised clinical trial were used. Among the six versions of the JDMAI, JDMA1 (score range 0-40) and JDMAI2 (score range 0-39) were selected. Optimal cut-offs were determined against external criteria by calculating different percentiles of score distribution and through receiver operating characteristic curve analysis. External criteria included the modified Pediatric Rheumatology International Trials Organization (PRINTO) criteria for clinically ID in JDM (for ID) and PRINTO levels of improvement in the clinical trial (for LDA and HDA). MDA cut-offs were set at the score interval between LDA and HDA cut-offs. Cut-off validation was conducted by assessing construct and discriminative ability in two cohorts including a total of 488 JDM patients. RESULTS: The calculated JDMAI1 cut-offs were ≤2.4 for ID, ≤6.6 for LDA, 6.7-11 for MDA and >11 for HDA. The calculated JDMAI2 cut-offs were ≤5.2 for ID, ≤8.5 for LDA, 8.6-11.3 for MDA and >11.3 for HDA. The cut-offs discriminated strongly among disease activity states defined subjectively by caring physicians and parents, parents' satisfaction or non-satisfaction with illness outcome, levels of pain, fatigue, physical functional impairment and physical well-being. CONCLUSIONS: Both JDMAI1 and JDMAI2 cut-offs revealed good metrologic properties in validation analyses and are, therefore, suited for application in clinical practice and research.

Structural characterization of PaaX, the main repressor of the phenylacetate degradation pathway in Escherichia coli W: A novel fold of transcription regulator proteins.

PaaX is a transcriptional repressor of the phenylacetic acid (PAA) catabolic pathway, a central route for bacterial aerobic degradation of aromatic compounds. Induction of the route is achieved through the release of PaaX from its promoter sequences by the first compound of the pathway, phenylacetyl-coenzyme A (PA-CoA). We report the crystal structure of PaaX from Escherichia coli W. PaaX displays a novel type of fold for transcription regulators, showing a dimeric conformation where the monomers present a three-domain structure: an N-terminal winged helix-turn-helix domain, a dimerization domain similar to the Cas2 protein and a C-terminal domain without structural homologs. The domains are separated by a crevice amenable to harbour a PA-CoA molecule. The biophysical characterization of the protein in solution confirmed several hints predicted from the structure, i.e. its dimeric conformation, a modest importance of cysteines and a high dependence of solubility and thermostability on ionic strength. At a moderately acidic pH, the protein formed a stable folding intermediate with remaining α-helical structure, a disrupted tertiary structure and exposed hydrophobic patches. Our results provide valuable information to understand the stability and mechanism of PaaX and pave the way for further analysis of other regulators with similar structural configurations.

Adherencia al automonitoreo en diabetes tipo 2: plataforma "ClouDi" vs. Educación presencial. / Adherence to self-monitoring in type 2 diabetes: "ClouDi" platform vs. Face-to-face follow-up / Adesão à automonitorização na diabetes tipo 2: plataforma "ClouDi" vs. acompanha-mento presencial

Introducción: El uso de mHealth puede mejorar la adherencia a el automonitoreo con glucometría capilar (GC) en la transición del ámbito hospitalario al ambulatorio. Objetivo: evaluar la adherencia al automonitoreo con GC de los pacientes con Diabetes Tipo 2 (DM2) vinculados a un programa de educación usuarios de mHealth (ClouDi) comparado con el programa de educación y seguimiento presencial usual. Materiales y métodos: Estudio longitudinal prospectivo. Se analizaron pacientes con DM2 valorados por consulta de educación de diabetes con indicación de tratamiento con insulina al egreso hospitalario. Se analizaron dos grupos: uno con seguimiento presencial y otro vinculado a un programa educativo y uso de ClouDi. Resultados: De los 86 pacientes (44% de sexo femenino, 41 usuarios ClouDi, edad promedio 58.8 ± 11.2 años, con una media de duración de la diabetes de 7.8 ± 7.4 años), 53.6% se encontraban en estrato 2, el 92.9% pertenecían al régimen contributivo, el 42.9% con educación básica primaria y 51.2% empleados. Fue considerada la adherencia a la GC al realizar y registrar 3 o más mediciones por día en los pacientes de ClouDi fue mayor comparado con los pacientes en cuidado usual (64.4% vs 28.2%, p <0.001), independiente de las variables sociodemográficas. Conclusión: El uso de ClouDi se asoció a mayor adherencia a automonitoreo con GC comparado con seguimiento presencial independiente de variables sociodemográficas. El uso de esta tecnología podría ser útil en el seguimiento de pacientes usuarios de insulina al egreso hospitalario

Introduction: The use of mHealth can improve adherence to self-monitoring blood Glucose (SMBG) in the transition from hospital to outpatient setting. Objective: To evaluate adherence to self-monitoring with GC in patients with type 2 diabetes (T2DM) linked to an mHealth user education program (ClouDi) compared with the usual face-to-face education and follow-up program. Materials and Methods: Prospective longitudinal study. Patients with T2D assessed by diabetes education counseling with an indication for insulin treatment at hospital discharge were analyzed. Two groups were analyzed: one with face-to-face follow-up and another linked to an educational program and use of ClouDi. Results: Of the 86 patients (44% female, 41 ClouDi users, mean age 58.8 ± 11.2 years, with a mean duration of diabetes of 7.8 ± 7.4 years), 53.6% were in stratum 2, 92.9% belonged to the contributory system, 42.9% with basic pri-mary education and 51.2% were employed. Compliance with the SMBG was considered if 3 or more measurements per day were taken and recorded, was higher in ClouDi patients com-pared to usual care patients (64.4% vs. 28.2%, p <0.001), independent of sociodemographic variables.Conclusions: The use of ClouDi was associated with greater adherence to SMBG compared to in-person follow-up, independent of sociodemographic variables. The use of this technology may be useful in monitoring insulin-using patients after hospital discharge

Introdução: A utilização do mHealth pode melhorar a adesão à automonitorização com glico-metria capilar (GC) na transição do hospital para o ambulatório. Objetivo: avaliar a adesão ao automonitoramento com GC de pacientes com Diabetes Tipo 2 (DM2) vinculados a um progra-ma de educação de usuários de mHealth (ClouDi) em comparação com o programa habitual de educação e acompanhamento presencial. Materiais e métodos: Estudo prospectivo longitudi-nal. Foram analisados pacientes com DM2 avaliados por consulta de educação em diabetes com indicação de tratamento insulínico na alta hospitalar. Foram analisados dois grupos: um com acompanhamento presencial e outro vinculado a um programa educativo e uso do ClouDi. Re-sultados: Dos 86 doentes (44% do sexo feminino, 41 utilizadores do ClouDi, idade média 58,8 ± 11,2 anos, com duração média da diabetes de 7,8 ± 7,4 anos), 53,6% encontravam-se no estra-to 2, 92,9% pertenciam ao regime contributivo, 42,9% com ensino fundamental básico e 51,2% empregados. A adesão ao GC foi considerada quando realizada e registrada 3 ou mais medidas por dia em pacientes ClouDi foi maior em comparação aos pacientes em cuidados habituais (64,4% vs 28,2%, p <0,001), independente das variáveis sociodemográficas. Conclusão: O uso do ClouDi esteve associado à maior adesão ao automonitoramento com GC em comparação ao acompanhamento presencial independente das variáveis sociodemográficas. O uso dessa tecnologia pode ser útil no monitoramento de pacientes usuários de insulina na alta hospitalar

Results From a Virtual Clinic for the Follow-up of Patients Using the Advanced Hybrid Closed-Loop System.

BACKGROUND: Evidence regarding the implementation of medium-term strategies in advanced hybrid closed-loop (AHCL) system users is limited. Therefore, this study aimed to describe the efficacy and safety of the AHCL system in patients with type 1 diabetes (T1D) on a six-month follow-up in a virtual diabetes clinic (VDC). METHOD: A prospective cohort of adult patients with T1D treated using the AHCL system (Mini Med 780G; Medtronic, Northridge, California) in a VDC follow-up. Standardized training and follow-up were conducted virtually. Clinical data and metabolic control outcomes were reported at baseline, and at three and six months. RESULTS: Sixty-four patients (mean age = 42 ± 14.6 years, 65% men, 54% with graduate education) were included. Percentage time in range (%TIR) increased significantly regardless of prior therapy with intermittently scanned continuous glucose monitoring + multiple daily injections and sensor-augmented pump therapy with predictive low-glucose management after starting AHCL and persisted during the follow-up period with no hypoglycemic events. The %TIR 70 to 180 mg/dL according to socioeconomic strata was 73.4% ± 5.3%, 78.1% ± 8.1%, and 84.2% ± 7.5% for the lower, middle, and upper strata, respectively. The sensor was used more frequently in the population with a higher education level. Adherence to sensor use and SmartGuard retention were higher in patients who underwent the VDC follow-up. CONCLUSIONS: Medium-term follow-up of users of AHCL systems in a VDC contributes to safely achieving %TIR goals. Virtual diabetes clinic follow-up favored adherence to sensor use and continuous SmartGuard use. Socioeconomic strata were associated with a better glycemic profile and education level was associated with better adherence to sensor use.

Impact of hospitalization on nutritional status in persons aged 65 years and over (NUTRIFRAG Study): Protocol for a prospective observational study.

BACKGROUND: Malnutrition is a recurring problem that has become more relevant in recent years. The aim of this study is to assess the risk of malnutrition and nutritional status on admission and its evolution until discharge in patients aged 65 and over admitted to medical and surgical hospitalization units in hospitals of the Spanish National Health System. METHODS: Prospective observational study to be carried out in the medical-surgical hospitalization units of 9 public hospitals between 01/09/2022 and 31/12/2024. Using consecutive sampling, a total of 4077 patients will be included (453 in each hospital). Variables included are related to the care process, functionality, cognition and comorbidity, risk profile, nutritional status and dysphagia; as well as frailty, dietary quality and contextual variables. The incidence of risk of malnutrition, undernutrition and dysphagia during the care process and at discharge will be calculated. The association with risk factors will be studied with logistic regression models and multivariate Cox regression models. In addition, an analysis of participants' satisfaction with food services will be carried out. The study was approved by the Ethics and Research Committee on 30/09/2020, approved for funding on 02/12/2021 and with registration number RBR-5jnbyhk in the Brazilian clinical trials database (ReBEC) for observational studies. DISCUSSION: Some studies address nutritional status or dysphagia in older people in various care settings. However, there is a lack of large sample studies including both processes of the impact of hospitalization. The results of the project will provide information on the incidence and prevalence of both pathologies in the study subjects, their associated factors and their relationship with the average length of stay, mortality and early readmission. In addition, early detection of a problem such as malnutrition related to the disease and/or dysphagia during a hospital stay will favor the action of professionals to resolve both pathologies and improve the health status of patients.

Prospective Assessment of Bone Metabolism Biomarkers and Survival in Metastatic Castration-resistant Prostate Cancer Patients Treated with Radium-223: The PRORADIUM Study.

BACKGROUND: Radium-223 is an active therapy option for bone metastatic castration-resistant prostate cancer (mCRPC). The lack of adequate biomarkers for patient selection and response assessment are major drawbacks for its use. OBJECTIVE: To assess the prognostic value of bone metabolism biomarkers (BMBs) in ra-223-treated mCRPC patients. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of mCRPC patients treated with Ra-223 (PRORADIUM study: NCT02925702) was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The main objective of the study was to evaluate the association between high (≥median) baseline values in at least three bone formation (bone alkaline phosphatase [BAP] and C-terminal type-I collagen propeptide) and bone resorption (N-terminal telopeptide and pyridinoline) biomarkers, and survival. The independent prognostic value of each BMB was also assessed. The association with time to radiographic, clinical, and prostate-specific antigen (PSA) progression; time to skeletal-related events; and PSA response were secondary objectives. Multivariable (MV) Cox-regression models were evaluated. RESULTS AND LIMITATIONS: A total of 169 patients were included. Of the patients, 70.4% received Ra-223 in second/third line; 144 (85.2%) were Eastern Cooperative Oncology Group 0-1, 126 (74.6%) were in pain, and 80 (47.5%) had more than ten bone metastases. Sixty-seven (39.6%) patients had elevation in at least three BMBs. The median overall survival was 12.1 mo (95% confidence interval [CI]: 10-14.7). No association was observed with other treatment-related secondary outcome parameters. Patients with high values in three or more BMBs had significantly worse survival (9.9 vs 15.2 mo; hazard ratio [HR]: 1.8 [95% CI: 1.3-2.5]; p < 0.001) in the univariate analysis, but not independent in the MV analysis (HR: 1.33; 95% CI: 0.89-2; p = 0.181). High baseline BAP was the only biomarker associated with survival in the MV model (HR: 1.89; 95% CI: 1.28-2.79; p = 0.001). Addition of BAP to the MV clinical model increased the area under the receiver operating characteristic curve 2-yr value from 0.667 to 0.755 (p = 0.003). CONCLUSIONS: Biomarkers of bone formation, especially BAP, have prognostic value in mCRPC patients treated with radium-223. Its predictive value remains to be assessed, ideally in prospective, adequately powered, randomised clinical trials. PATIENT SUMMARY: In this study, we evaluate the role of bone metabolism biomarkers to help improve the use of radium-223 as therapy for advanced prostate cancer. We found that bone alkaline phosphatase may be a suitable tool.

Glycemic control metrics in a cohort of hospitalized patients with type 1 diabetes using hybrid closed-loop and advanced hybrid closed-loop systems.

AIMS: To describe Hybrid closed-loop (HCL) and advanced hybrid closed-loop (AHCL) performance in the hospital setting based on the continuous glucose monitoring (CGM) metrics description. METHODS: This was an observational study from a cohort of patients with T1D using HCL/AHCL with history of hospitalization. CGM metrics were analyzed during the hospital stay. CGM metrics sub-analysis of the population with active Automated Mode (AM) and SmartGuard (SG) during hospitalization and/or surgical procedure was performed. RESULTS: Twenty-four patients were included (50 % women; mean age, 49 years [inter-quartile range (IQR), 39-62 years]). During hospitalization 70.8 % patients achieved %Time in Range (TIR) between 70 and 180 mg/dL ≥ 70 %. The overall %TIR was 75.5 % (IQR, 67.3-81.5 %), % time below range (TBR) < 70 mg/dL was 2.1 % (IQR, 0.7-5.4 %) and %TBR < 54 mg/dL was 0 % (IQR, 0-5.4 %). Users of the AHCL with active SG achieved a non-significant higher %TIR during hospitalization (79 % [73.8.88 %] vs. 76 % [72.81 %], p = 0.312) and had a shorter stay (3[IQR, 2.4] vs. 6 days[IQR, 5.7], p = 0.045) compared to the users of the HCL with AM active. No device-related serious adverse events occurred for users of either system. CONCLUSIONS: HCL/AHCL systems with active AM/SG in patients with T1D in the hospital environment leads to %TIR > 70 % in ranges of 70-180 mg/dL in patients without increasing hypoglycemia.

Internalizing and externalizing behaviors in high school adolescents in a northern border city of Mexico and their type of family.

OBJECTIVE: Identify externalizing and internalizing behaviors in high school adolescents in three schools in a northern border city in Mexico and their type of family. DESIGN: Cross-sectional survey. LOCATION: Three schools in the city of Tijuana, Mexico: two public and one private. PARTICIPANTS: 454 baccalaureate students 14-19 years old. MAIN MEASUREMENTS: We utilized Youth Self Report Scale, adapted and validated in Spanish, that measure internalization behaviors (anxiety, depression, isolation or somatic complaints), and externalization behaviors (verbal aggressiveness, delinquent behavior and attention-seeking). For dichotomous discrimination between deviant and nondeviant scores, we use the borderline clinical range by classifying YSR scale's T scores≥60, and to analyze the relationship between behavior problems or competencies and living or not in a nuclear family we utilized multiple logistic regression. RESULTS: 55% were female, mean age 16.4 years±0.98, and 62.3% came from a nuclear family. Prevalence of internalizing behaviors was 15.6%, and externalizing behaviors 14.8%. Women had statistically higher mean scores in depressive, anxious and verbally aggressive behavior, somatic complaints, and thought problems. The prevalence of internalizing behaviors in adolescents with nuclear family was 11.7% (n=33), and for adolescents with another type of family was 22.2% (n=38), OR 2.17 (CI 95% 1.30-3.61, p=0.003), but no differences was observed for externalizing behaviors and family type. When adjusted for sex, age, and public or private school, internalizing behaviors and specifically depressive behavior remained significant. CONCLUSIONS: We detected a moderate prevalence of internalizing behaviors in Mexican adolescents, predominantly among women, and also observed that not living with a nuclear family increases the odds of presenting internalizing behaviors. It is important that parents, teachers, and healthcare workers remain vigilant to detect these problems in a timely manner and develop interventions to improve the mental health and well-being of adolescents.