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1.
Clin Rheumatol ; 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39008222

RESUMEN

This study aimed to examine psychometric properties of the Adherence to Refills and Medications Scale (ARMS) in people with gout. We conducted exploratory factor analysis (EFA) and tested internal consistency (ordinal and Cronbach's alpha coefficients) and agreement (intraclass correlation coefficient (2,1)) in ARMS scores across three timepoints (baseline, 6, and 12 months) in 487 people with gout. The Kruskal-Wallis test, Spearman's rank, Kendall's tau-b correlations, and logistic regression were used to examine the criterion-related validity of the ARMS and factors associated with the ARMS. EFA suggested a one-factor structure, explaining 43.2% of total variance. High internal consistency (ordinal alpha = 0.902 at baseline) and moderate agreement in ARMS scores over time (ICCs > 0.5; p < 0.001) were observed. Lower ARMS scores (indicating better adherence) predicted achieving target serum urate (OR, 0.89; 95% CI, 0.83-0.95; p < 0.001), but not urate-lowering therapy (ULT) adherence (Proportion of Days Covered (PDC) ≥ 80%) (OR, 0.93; 95% CI, 0.81-1.05; p = 0.261). Negative correlations between ARMS and PDC were not statistically significant (Kendall's tau-b, r = - 0.126, p = 0.078; Spearman's rho = - 0.173, p < 0.073). Differences in median ARMS scores (IQR) of 16 (14-20), 13 (12-15), and 17.5 (15-21) in three groups of participants who reported (1) not taking ULT, (2) taking ULT and adherent, and (3) taking ULT but not adherent, respectively, were statistically significant (p < 0.001). Age was the only patient factor independently associated with optimal adherence (ARMS score = 12) (OR, 1.91; 95% CI, 1.50-2.43; p < 0.001). The ARMS is a reliable and valid measure of medication adherence behaviours in people with gout, justifying its use in gout medication adherence research.

2.
Br J Clin Pharmacol ; 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38984480

RESUMEN

AIMS: Therapeutic drug monitoring (TDM) aims to optimize drug therapy. As demand on health resources increases, and the technology underpinning TDM becomes more sophisticated, the economic benefits of TDM in hospitals is unclear. The aim of this systematic review was to summarize the economic evidence that could be used to support investment in TDM in hospital settings. In so doing, we sought to provide guidance for future economic evaluations. METHODS: Medline, Embase, CENTRAL, Econlit and NHS Economic Evaluation databases were searched (inception to December 2022) for economic evaluations of hospital-based TDM. Two authors reviewed the studies and extracted data. Overall quality of economic analysis reporting was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. RESULTS: Ten prospective studies (including six randomized studies) and nine retrospective studies were eligible. Overall study reporting was poor, publications meeting a median (range) of 61% (46-82%) of CHEERS checklist criteria. An antimicrobial TDM intervention for adult patients was the focus of most studies (n = 18). Variable clinical outcomes were reported, and length of stay was the primary economic outcome for most studies (n = 13). The majority of studies determined that TDM was economically and clinically favourable (n = 14), four studies reporting a cost-reduction in patient sub-populations. CONCLUSIONS: Significant improvements in both economic and clinical outcomes may be realized with TDM interventions, particularly when targeted to complex patient populations. Attainment of therapeutic target could serve as a feasible surrogate measure of benefit for hospital-based TDM interventions. However, systematic reporting of economic outcomes is needed to inform investment decisions.

3.
Nat Commun ; 15(1): 5763, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38982051

RESUMEN

While high circulating tumor DNA (ctDNA) levels are associated with poor survival for multiple cancers, variant-specific differences in the association of ctDNA levels and survival have not been examined. Here we investigate KRAS ctDNA (ctKRAS) variant-specific associations with overall and progression-free survival (OS/PFS) in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) for patients receiving chemoimmunotherapy ("PRINCE", NCT03214250), and an independent cohort receiving standard of care (SOC) chemotherapy. For PRINCE, higher baseline plasma levels are associated with worse OS for ctKRAS G12D (log-rank p = 0.0010) but not G12V (p = 0.7101), even with adjustment for clinical covariates. Early, on-therapy clearance of G12D (p = 0.0002), but not G12V (p = 0.4058), strongly associates with OS for PRINCE. Similar results are obtained for the SOC cohort, and for PFS in both cohorts. These results suggest ctKRAS G12D but not G12V as a promising prognostic biomarker for mPDAC and that G12D clearance could also serve as an early biomarker of response.


Asunto(s)
Biomarcadores de Tumor , Carcinoma Ductal Pancreático , ADN Tumoral Circulante , Neoplasias Pancreáticas , Proteínas Proto-Oncogénicas p21(ras) , Humanos , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/sangre , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/tratamiento farmacológico , Proteínas Proto-Oncogénicas p21(ras)/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/tratamiento farmacológico , Femenino , Masculino , ADN Tumoral Circulante/sangre , ADN Tumoral Circulante/genética , Persona de Mediana Edad , Anciano , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Pronóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mutación , Supervivencia sin Progresión , Metástasis de la Neoplasia
4.
Neurocrit Care ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38955933

RESUMEN

BACKGROUND: Viscoelastic hemostatic assays (VHAs) provide more comprehensive assessments of coagulation compared with conventional coagulation assays. Although VHAs have enabled guided hemorrhage control therapies, improving clinical outcomes in life-threatening hemorrhage, the role of VHAs in intracerebral hemorrhage (ICH) is unclear. If VHAs can identify coagulation abnormalities relevant for ICH outcomes, this would support the need to investigate the role of VHAs in ICH treatment paradigms. Thus, we investigated whether VHA assessments of coagulation relate to long-term ICH outcomes. METHODS: Patients with spontaneous ICH enrolled into a single-center cohort study receiving admission Rotational Thromboelastometry (ROTEM) VHA testing between 2013 and 2020 were assessed. Patients with previous anticoagulant use or coagulopathy on conventional coagulation assays were excluded. Primary ROTEM exposure variables were coagulation kinetics and clot strength assessments. Poor long-term outcome was defined as modified Rankin Scale ≥ 4 at 6 months. Logistic regression analyses assessed associations of ROTEM parameters with clinical outcomes after adjusting for ICH severity and hemoglobin concentration. RESULTS: Of 44 patients analyzed, the mean age was 64 years, 57% were female, and the median ICH volume was 23 mL. Poor 6-month outcome was seen in 64% of patients. In our multivariable regression models, slower, prolonged coagulation kinetics (adjusted odds ratio for every second increase in clot formation time 1.04, 95% confidence interval 1.00-1.09, p = 0.04) and weaker clot strength (adjusted odds ratio for every millimeter increase of maximum clot firmness 0.84, 95% confidence interval 0.71-0.99, p = 0.03) were separately associated with poor long-term outcomes. CONCLUSIONS: Slower, prolonged coagulation kinetics and weaker clot strength on admission VHA ROTEM testing, not attributable to anticoagulant use, were associated with poor long-term outcomes after ICH. Further work is needed to clarify the generalizability and the underlying mechanisms of these VHA findings to assess whether VHA-guided treatments should be incorporated into ICH care.

5.
Antioxidants (Basel) ; 13(6)2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38929156

RESUMEN

Oxidative stress can damage tissues and cells, and their resilience or susceptibility depends on the robustness of their antioxidant mechanisms. The latter include small molecules, proteins, and enzymes, which are linked together in metabolic pathways. Red blood cells are particularly susceptible to oxidative stress due to their large number of hemoglobin molecules, which can undergo auto-oxidation. This yields reactive oxygen species that participate in Fenton chemistry, ultimately damaging their membranes and cytosolic constituents. Fortunately, red blood cells contain robust antioxidant systems to enable them to circulate and perform their physiological functions, particularly delivering oxygen and removing carbon dioxide. Nonetheless, if red blood cells have insufficient antioxidant reserves (e.g., due to genetics, diet, disease, or toxin exposure), this can induce hemolysis in vivo or enhance susceptibility to a "storage lesion" in vitro, when blood donations are refrigerator-stored for transfusion purposes. Ergothioneine, a small molecule not synthesized by mammals, is obtained only through the diet. It is absorbed from the gut and enters cells using a highly specific transporter (i.e., SLC22A4). Certain cells and tissues, particularly red blood cells, contain high ergothioneine levels. Although no deficiency-related disease has been identified, evidence suggests ergothioneine may be a beneficial "nutraceutical." Given the requirements of red blood cells to resist oxidative stress and their high ergothioneine content, this review discusses ergothioneine's potential importance in protecting these cells and identifies knowledge gaps regarding its relevance in enhancing red blood cell circulatory, storage, and transfusion quality.

7.
Front Immunol ; 15: 1393213, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38938571

RESUMEN

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy in humans. G6PD is an essential enzyme in the pentose phosphate pathway (PPP), generating NADPH needed for cellular biosynthesis and reactive oxygen species (ROS) homeostasis, the latter especially key in red blood cells (RBCs). Beyond the RBC, there is emerging evidence that G6PD exerts an immunologic role by virtue of its functions in leukocyte oxidative metabolism and anabolic synthesis necessary for immune effector function. We review these here, and consider the global immunometabolic role of G6PD activity and G6PD deficiency in modulating inflammation and immunopathology.


Asunto(s)
Deficiencia de Glucosafosfato Deshidrogenasa , Glucosafosfato Deshidrogenasa , Humanos , Glucosafosfato Deshidrogenasa/metabolismo , Deficiencia de Glucosafosfato Deshidrogenasa/inmunología , Deficiencia de Glucosafosfato Deshidrogenasa/metabolismo , Animales , Especies Reactivas de Oxígeno/metabolismo , Vía de Pentosa Fosfato , Inmunidad , Infecciones/inmunología , Inflamación/inmunología , Inflamación/metabolismo
9.
J Eval Clin Pract ; 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38923095

RESUMEN

BACKGROUND: The birthweight of a newborn is critical to their health, development, and well-being. Previous studies that used maternal characteristics to predict birthweight did not employ a harmonised scale to assess the risk of low birthweight (LBW). OBJECTIVE: The goal of this study was to develop a new instrument that uses items on a uniform scale to assess the risk of an LBW in a pregnant woman. METHODS: Item response theory was employed to evaluate a similar existing scale, and some weaknesses were identified. RESULTS: Based on the observed weaknesses of the existing scale, a new uniform scale was developed, which is a 3-point Likert scale consisting of seven items. CONCLUSION: The scale, termed birthweight questionnaire, is a valuable tool for collecting data that could assist in assessing the risk of an LBW at every stage of pregnancy.

10.
Patient Educ Couns ; 127: 108336, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38924978

RESUMEN

OBJECTIVES: How to best care for larger-bodied patients is a complicated issue in modern medicine. The present study seeks to inform current medical practices to ensure the delivery of high-quality and evidence-based care through the examination of higher-weight patients' experiences with weight-related care. METHODS: Higher-weight patients (N = 34) completed semi-structured interviews about their experiences and recommendations for weight-related care. Interviews were coded by two independent coders and harmonized. Findings were organized into broad domains of 1) negative care experiences and 2) positive care experiences and recommendations. RESULTS: Patients described a range of negative care experiences, including stigmatization from providers (e.g., rude, attacking, or insulting communication about weight), while concurrently expressing insufficient weight management support from providers. Positive care experiences and recommendations included patient-centered care (e.g., physician humility and empathy) and attending to the patient's weight, which conveyed concern for the patient. CONCLUSIONS: Our findings reflect patients' ambivalent attitudes toward weight-related care: while weight-focused provider communication can be highly stigmatizing, patients simultaneously desire more weight-management support from providers. PRACTICE IMPLICATIONS: Providers who wish to move their practices from a weight-loss focus to one targeting healthy living should provide a rationale for these shifts to inform patients' perceptions of high-quality care.

11.
Behav Res Methods ; 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38914788

RESUMEN

Traditionally, behavioral, social, and health science researchers have relied on global/retrospective survey methods administered cross-sectionally (i.e., on a single occasion) or longitudinally (i.e., on several occasions separated by weeks, months, or years). More recently, social and health scientists have added daily life survey methods (also known as intensive longitudinal methods or ambulatory assessment) to their toolkit. These methods (e.g., daily diaries, experience sampling, ecological momentary assessment) involve dense repeated assessments in everyday settings. To facilitate research using daily life survey methods, we present SEMA3 ( http://www.SEMA3.com ), a platform for designing and administering intensive longitudinal daily life surveys via Android and iOS smartphones. SEMA3 fills an important gap by providing researchers with a free, intuitive, and flexible platform with basic and advanced functionality. In this article, we describe SEMA3's development history and system architecture, provide an overview of how to design a study using SEMA3 and outline its key features, and discuss the platform's limitations and propose directions for future development of SEMA3.

12.
Glob Health Promot ; : 17579759241245858, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38716708

RESUMEN

This study explored the extent to which health promotion techniques and activities are incorporated into public health and clinical care at a District Hospital in the Greater Accra Region of Ghana, as well as the challenges that this process faces. Information was obtained at the hospital facility through direct observation, interviews and open-ended questionnaires. Findings showed that the process of incorporating health promotion activities into public health and clinical care at the hospital was underdeveloped. The challenges this process faces based on the research findings include structural challenges, inadequate logistics, increased workload, insufficient human resource capacity, lack of motivation for staff, lack of cooperation, teamwork and consultation, inadequate management and enforcement support, prolonged hospital hours for healthcare workers and patients, and inadequate knowledge of health promotion and training. To address these challenges, suggested measures include promoting teamwork and collaboration among healthcare professionals, training and continuous education, government involvement and enforcement of health promotion integration at the hospital, hospital management involvement, media sensitization and advocacy, provision of financial, material and human resources, motivation and encouragement of the process of health promotion integration, and patient involvement. Further research is also recommended to broaden the scope of this study by involving other health practitioner categories and health promotion stakeholders.

13.
PLoS One ; 19(5): e0292978, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38728307

RESUMEN

Endosalpingiosis (ES) and endometriosis (EM) refer to the growth of tubal and endometrial epithelium respectively, outside of their site of origin. We hypothesize that uterine secretome factors drive ectopic growth. To test this, we developed a mouse model of ES and EM using tdTomato (tdT) transgenic fluorescent mice as donors. To block implantation factors, progesterone knockout (PKO) tdT mice were created. Fluorescent lesions were present after oviduct implantation with and without WT endometrium. Implantation was increased (p<0.05) when tdt oviductal tissue was implanted with endometrium compared to oviductal tissue alone. Implantation was reduced (p<0.0005) in animals implanted with minced tdT oviductal tissue with PKO tdT endometrium compared to WT endometrium. Finally, oviductal tissues was incubated with and without a known implantation factor, leukemia inhibitory factor (LIF) prior to and during implantation. LIF promoted lesion implantation. In conclusion, endometrial derived implantation factors, such as LIF, are necessary to initiate ectopic tissue growth. We have developed an animal model of ectopic growth of gynecologic tissues in a WT mouse which will potentially allow for development of new prevention and treatment modalities.


Asunto(s)
Endometriosis , Endometrio , Útero , Animales , Femenino , Ratones , Endometriosis/metabolismo , Endometriosis/patología , Endometriosis/genética , Útero/metabolismo , Endometrio/metabolismo , Factor Inhibidor de Leucemia/metabolismo , Factor Inhibidor de Leucemia/genética , Secretoma/metabolismo , Ratones Transgénicos , Modelos Animales de Enfermedad , Trompas Uterinas/metabolismo , Progesterona/metabolismo , Ratones Noqueados , Implantación del Embrión/fisiología
14.
Ther Drug Monit ; 46(4): 434-445, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38723160

RESUMEN

BACKGROUND: The applicability of currently available tacrolimus population pharmacokinetic models in guiding dosing for lung transplant recipients is unclear. In this study, the predictive performance of relevant tacrolimus population pharmacokinetic models was evaluated for adult lung transplant recipients. METHODS: Data from 43 lung transplant recipients (1021 tacrolimus concentrations) administered an immediate-release oral formulation of tacrolimus were used to evaluate the predictive performance of 17 published population pharmacokinetic models for tacrolimus. Data were collected from immediately after transplantation up to 90 days after transplantation. Model performance was evaluated using (1) prediction-based assessments (bias and imprecision) of individual predicted tacrolimus concentrations at the fourth dosing based on 1 to 3 previous dosings and (2) simulation-based assessment (prediction-corrected visual predictive check; pcVPC). Both assessments were stratified based on concomitant azole antifungal use. Model performance was clinically acceptable if the bias was within ±20%, imprecision was ≤20%, and the 95% confidence interval of bias crossed zero. RESULTS: In the presence of concomitant antifungal therapy, no model showed acceptable performance in predicting tacrolimus concentrations at the fourth dosing (n = 33), and pcVPC plots displayed poor model fit to the data set. However, this fit slightly improved in the absence of azole antifungal use, where 4 models showed acceptable performance in predicting tacrolimus concentrations at the fourth dosing (n = 33). CONCLUSIONS: Although none of the evaluated models were appropriate in guiding tacrolimus dosing in lung transplant recipients receiving concomitant azole antifungal therapy, 4 of these models displayed potential applicability in guiding dosing in recipients not receiving concomitant azole antifungal therapy. However, further model refinement is required before the widespread implementation of such models in clinical practice.


Asunto(s)
Inmunosupresores , Trasplante de Pulmón , Modelos Biológicos , Tacrolimus , Humanos , Tacrolimus/farmacocinética , Tacrolimus/uso terapéutico , Inmunosupresores/farmacocinética , Inmunosupresores/uso terapéutico , Inmunosupresores/administración & dosificación , Persona de Mediana Edad , Femenino , Masculino , Adulto , Antifúngicos/farmacocinética , Antifúngicos/uso terapéutico , Receptores de Trasplantes , Anciano
15.
Health Expect ; 27(3): e14071, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38742836

RESUMEN

INTRODUCTION: Gout management remains suboptimal despite safe and effective urate-lowering therapy. Self-monitoring of urate may improve gout management, however, the acceptability of urate self-monitoring by people with gout is unknown. The aim of this study was to explore the experiences of urate self-monitoring in people with gout. METHODS: Semistructured interviews were conducted with people taking urate-lowering therapy (N = 30) in a 12-month trial of urate self-monitoring in rural and urban Australia. Interviews covered the experience of monitoring and its effect on gout self-management. Deidentified transcripts were analysed thematically. RESULTS: Participants valued the ability to self-monitor and gain more understanding of urate control compared with the annual monitoring ordered by their doctors. Participants indicated that self-monitoring at home was easy, convenient and informed gout self-management behaviours such as dietary modifications, hydration, exercise and medication routines. Many participants self-monitored to understand urate concentration changes in response to feeling a gout flare was imminent or whether their behaviours, for example, alcohol intake, increased the risk of a gout flare. Urate concentrations were shared with doctors mainly when they were above target to seek management support, and this led to allopurinol dose increases in some cases. CONCLUSION: Urate self-monitoring was viewed by people with gout as convenient and useful for independent management of gout. They believed self-monitoring achieved better gout control with a less restricted lifestyle. Urate data was shared with doctors at the patient's discretion and helped inform clinical decisions, such as allopurinol dose changes. Further research on implementing urate self-monitoring in routine care would enable an evaluation of its impact on medication adherence and clinical outcomes, as well as inform gout management guidelines. PATIENT OR PUBLIC CONTRIBUTION: One person with gout, who was not a participant, was involved in the study design by providing feedback and pilot testing the semistructured interview guide. In response to their feedback, subsequent modifications to the interview guide were made to improve the understandability of the questions from a patient perspective. No additional questions were suggested.


Asunto(s)
Gota , Entrevistas como Asunto , Ácido Úrico , Humanos , Gota/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Ácido Úrico/sangre , Anciano , Australia , Supresores de la Gota/uso terapéutico , Automanejo , Autocuidado , Adulto , Investigación Cualitativa
16.
Transfusion ; 64(6): 1109-1115, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38693059

RESUMEN

BACKGROUND: Post-transfusion survival of donor red blood cells (RBCs) is important for effective chronic transfusion therapy in conditions including sickle cell disease (SCD). Biotin labeling RBCs allows direct in vivo measurement of multiple donor RBC units simultaneously post-transfusion. STUDY DESIGN AND METHODS: In an observational trial of patients with SCD receiving monthly chronic transfusion therapy, aliquots of RBCs from one transfusion episode were biotin-labeled and infused along with the unlabeled RBC units. Serial blood samples were obtained to measure RBC survival. Donor units were tested for RBC indices, hemoglobin fractionation, and glucose-6-phosphate dehydrogenase (G6PD) enzyme activity. For microcytic donor RBCs (MCV < 70 fL), HBA1 and HBA2 genetic testing was performed on whole blood. RESULTS: We present one recipient, a pediatric patient with SCD and splenectomy who received two RBC units with aliquots from each unit labeled at distinct biotin densities (2 and 18 µg/mL biotin). One donor unit was identified to have microcytosis (MCV 68.5 fL after biotinylation); whole blood sample obtained at a subsequent donation showed 2-gene deletion alpha-thalassemia trait (ɑ-3.7kb/ɑ-3.7kb) and normal serum ferritin. G6PD activity was >60% of normal mean for both. The RBCs with alpha-thalassemia RBC had accelerated clearance and increased surface phosphatidylserine post-transfusion, as compared with the normocytic RBC (half life 65 vs. 86 days, respectively). DISCUSSION: Post-transfusion RBC survival may be lower for units from donors with alpha-thalassemia trait, although the impact of thalassemia trait donors on transfusion efficacy requires further study.


Asunto(s)
Anemia de Células Falciformes , Donantes de Sangre , Transfusión de Eritrocitos , Eritrocitos , Talasemia alfa , Humanos , Anemia de Células Falciformes/terapia , Anemia de Células Falciformes/sangre , Talasemia alfa/terapia , Talasemia alfa/sangre , Eritrocitos/metabolismo , Masculino , Supervivencia Celular , Biotinilación , Femenino , Niño
17.
Vaccines (Basel) ; 12(5)2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38793703

RESUMEN

BCG vaccination affects other diseases beyond tuberculosis by unknown-potentially immunomodulatory-mechanisms. Recent studies have shown that BCG vaccination administered during overt type 1 diabetes (T1D) improved glycemic control and affected immune and metabolic parameters. Here, we comprehensively characterized Ghanaian T1D patients with or without routine neonatal BCG vaccination to identify vaccine-associated alterations. Ghanaian long-term T1D patients (n = 108) and matched healthy controls (n = 214) were evaluated for disease-related clinical, metabolic, and immunophenotypic parameters and compared based on their neonatal BCG vaccination status. The majority of study participants were BCG-vaccinated at birth and no differences in vaccination rates were detected between the study groups. Notably, glycemic control metrics, i.e., HbA1c and IDAA1c, showed significantly lower levels in BCG-vaccinated as compared to unvaccinated patients. Immunophenotype comparisons identified higher expression of the T cell activation marker CD25 on CD8+ T cells from BCG-vaccinated T1D patients. Correlation analysis identified a negative correlation between HbA1c levels and CD25 expression on CD8+ T cells. In addition, we observed fractional increases in glycolysis metabolites (phosphoenolpyruvate and 2/3-phosphoglycerate) in BCG-vaccinated T1D patients. These results suggest that neonatal BCG vaccination is associated with better glycemic control and increased activation of CD8+ T cells in T1D patients.

18.
Chem Sci ; 15(15): 5496-5506, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38638216

RESUMEN

Tetrapyridyl-functionalized phosphinines were prepared and structurally characterized. The donor-functionalized aromatic phosphorus heterocycles react highly selectively and even reversibly with water. Calculations reveal P,N-cooperativity for this process, with the flanking pyridyl groups serving to kinetically enhance the formal oxidative addition process of H2O to the low-coordinate phosphorus atom via H-bonding. Subsequent tautomerization forms 1,2-dihydrophosphinine derivatives, which can be quantitatively converted back to the phosphinine by applying vacuum, even at room temperature. This process can be repeated numerous times, without any sign of decomposition of the phosphinine. In the presence of CuI·SMe2, dimeric species of the type ([Cu2I2(phosphinine)]2) are formed, in which each phosphorus atom shows the less common µ2-bridging 2e--lone-pair-donation to two Cu(i)-centres. Our results demonstrate that fully unsaturated phosphorus heterocycles, containing reactive P[double bond, length as m-dash]C double bonds, are interesting candidates for the activation of E-H bonds, while the aromaticity of such compounds plays an appreciable role in the reversibility of the reaction, supported by NICS calculations.

19.
Diabetes Obes Metab ; 26(7): 2787-2795, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38618983

RESUMEN

AIM: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycaemic control and cardio-renal outcomes for people with type 2 diabetes (T2D). However, geographic and socio-economic variation in use is not well understood. METHODS: We identified 367 829 New South Wales residents aged ≥40 years who dispensed metformin in 2020 as a proxy for T2D. We estimated the prevalence of use of other glucose-lowering medicines among people with T2D and the prevalence of SGLT2i and GLP-1RA use among people using concomitant T2D therapy (i.e. metformin + another glucose-lowering medicine). We measured the prevalence by small-level geography, stratified by age group, and characterized by remoteness and socio-economic status. RESULTS: The prevalence of SGLT2i (29.7%) and GLP-1RA (8.3%) use in people with T2D aged 40-64 increased with geographic remoteness and in areas of greater socio-economic disadvantage, similar to other glucose-lowering medicines. The prevalence of SGLT2i (55.4%) and GLP-1RA (15.4%) among people using concomitant T2D therapy varied across geographic areas, with lower SGLT2i use in more disadvantaged areas and localized areas of high GLP-1RA use (2.5 times the median). Compared with people aged 40-64 years, the prevalence of SGLT2i and GLP-1RA use was lower in older age groups, but with similar patterns of variation across geographic areas. CONCLUSIONS: The prevalence of SGLT2i and GLP-1RA use varied by geography, probably reflecting a combination of system- and prescriber-level factors. Socio-economic variation in GLP-1RA use was overshadowed by localized patterns of prescribing. Continued monitoring of variation can help shape interventions to optimize use among people who would benefit the most.


Asunto(s)
Diabetes Mellitus Tipo 2 , Receptor del Péptido 1 Similar al Glucagón , Hipoglucemiantes , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Persona de Mediana Edad , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Masculino , Femenino , Nueva Gales del Sur/epidemiología , Adulto , Anciano , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico
20.
Res Sq ; 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38585893

RESUMEN

Background: Viscoelastic hemostatic assays (VHA) provide more comprehensive assessments of coagulation compared to conventional coagulation assays. While VHAs have enabled guided hemorrhage control therapies, improving clinical outcomes in life-threatening hemorrhage, the role of VHAs in intracerebral hemorrhage (ICH) is unclear. If VHAs can identify coagulation abnormalities relevant for ICH outcomes, this would support the need to investigate the role of VHAs in ICH treatment paradigms. Thus, we investigated whether VHA assessments of coagulation relate to long-term ICH outcomes. Methods: Spontaneous ICH patients enrolled into a single-center cohort study receiving admission Rotational Thromboelastometry (ROTEM) VHA testing between 2013 and 2020 were assessed. Patients with prior anticoagulant use or coagulopathy on conventional coagulation assays were excluded. Primary ROTEM exposure variables were coagulation kinetics and clot strength assessments. Poor long-term outcome was defined as modified Rankin Scale ≥ 4 at 6 months. Logistic regression analyses assessed associations of ROTEM parameters with clinical outcomes after adjusting for ICH severity and hemoglobin concentration. Results: Of 44 patients analyzed, mean age was 64, 57% were female, and the median ICH volume was 23 mL. Poor 6-month outcome was seen in 64%. In our multivariable regression models, slower, prolonged coagulation kinetics (adjusted OR for every second increase in clot formation time: 1.04, 95% CI: 1.00-1.09, p = 0.04) and weaker clot strength (adjusted OR for every millimeter increase of maximum clot firmness: 0.84, 95% CI: 0.71-0.99, p = 0.03) were separately associated with poor long-term outcomes. Conclusions: Slower, prolonged coagulation kinetics and weaker clot strength on admission VHA ROTEM testing, not attributable to anticoagulant use, were associated with poor long-term outcomes after ICH. Further work is needed to clarify the generalizability and the underlying mechanisms of these VHA findings to assess whether VHA guided treatments should be incorporated into ICH care.

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