Unidirectional association of clonal hematopoiesis with atherosclerosis development.

Clonal hematopoiesis, a condition in which acquired somatic mutations in hematopoietic stem cells lead to the outgrowth of a mutant hematopoietic clone, is associated with a higher risk of hematological cancer and a growing list of nonhematological disorders, most notably atherosclerosis and associated cardiovascular disease. However, whether accelerated atherosclerosis is a cause or a consequence of clonal hematopoiesis remains a matter of debate. Some studies support a direct contribution of certain clonal hematopoiesis-related mutations to atherosclerosis via exacerbation of inflammatory responses, whereas others suggest that clonal hematopoiesis is a symptom rather than a cause of atherosclerosis, as atherosclerosis or related traits may accelerate the expansion of mutant hematopoietic clones. Here we combine high-sensitivity DNA sequencing in blood and noninvasive vascular imaging to investigate the interplay between clonal hematopoiesis and atherosclerosis in a longitudinal cohort of healthy middle-aged individuals. We found that the presence of a clonal hematopoiesis-related mutation confers an increased risk of developing de novo femoral atherosclerosis over a 6-year period, whereas neither the presence nor the extent of atherosclerosis affects mutant cell expansion during this timeframe. These findings indicate that clonal hematopoiesis unidirectionally promotes atherosclerosis, which should help translate the growing understanding of this condition into strategies for the prevention of atherosclerotic cardiovascular disease in individuals exhibiting clonal hematopoiesis.

Analysis after posterior chamber phakic intraocular lens implantation: 17- to 19-year follow-up study.

PURPOSE: To evaluate the clinical outcomes of the Visian implantable collamer lens (ICL) in eyes with ≥17 years of follow-up. SETTING: Single-center. DESIGN: Retrospective observational study. METHODS: 70 eyes from 38 patients who underwent surgery between 2002 and 2006 with V4 ICL implantation were analyzed. Preintervention data included corrected distance visual acuity (CDVA), refraction, and intraocular pressure (IOP). At the 19-year mark, CDVA, refraction, IOP, endothelial count, and vault were measured using Tomey Casia 2 anterior pole tomography, along with recording long-term events. RESULTS: The operated patients had a spherical correction between -4 diopters (D) and -21 D and a cylinder up to 7.5 D. The mean CDVA (decimal) at the 17-year check-up was 0.89 ± 0.18, with a spherical equivalent of -1.05 ± 1.36 D. IOP has remained stable because mean measurements before surgery and currently were 15.16 ± 2.54 mm Hg and 16.19 ± 3.29 mm Hg, respectively. The endothelial cell count showed values of 2191 ± 386 cells/mm2, with a maximum of 2804 cells and a minimum of 1125 cells. Finally, the vault obtained was 348.53 ± 234.58 mm. Over the years, 2 eyes developed angle-closure glaucoma and 9 eyes were operated on for the development of anterior subcapsular cataracts. CONCLUSIONS: Visian ICL implantation demonstrated long-term visual and refractive stability, indicating it as a low-risk procedure. The ICL V4 model yielded satisfactory results for myopia and astigmatism correction after 17 years.

Clinical and Patient Reported Outcomes of an Optimized Trifocal Intraocular Lens.

Background/Objectives: To evaluate the clinical and patient-reported outcomes (PROMs) obtained with an optimized version of a previously investigated trifocal IOL. Methods: Prospective non-comparative single-center study enrolling 29 patients (55-71 years) undergoing bilateral cataract surgery with implantation of the trifocal diffractive IOL Liberty 677CMY (Medicontur Medical Engineering Ltd., Zsámbék, Hungary). Visual and refractive outcomes as well as PROMs were evaluated during a 3-month follow-up: measurement of uncorrected and corrected distance (UDVA, CDVA), intermediate (UIVA, DCIVA) and near visual acuities (UNVA, DCNVA), defocus curve, patient satisfaction, photic phenomena perception, spectacle independence, and difficulty in performing some vision-related activities. Results: A total of 100%, 92%, and 80% of patients achieved a postoperative binocular UDVA, UIVA, and UNVA of 20/25 or better, respectively. Likewise, 100%, 80%, and 84% of patients achieved a postoperative binocular CDVA, DCIVA, and DCNVA of 20/25 or better, respectively. In the defocus curve, all mean visual acuity values were better than 0.15 logMAR for all defocus levels. A total of 95.8%, 95.8%, and 91.7% of patients referred to be satisfied with their distance, intermediate, and near visual vision, respectively. Mean overall Catquest Rasch calibrated score was -3.12 ± 0.98. Most of the patients were spectacle independent: far (95.8%), intermediate (95.8%) or near vision (91.7%). No bothersome or minimal to moderately bothersome halo, starburst, and glare was perceived by 83.3%, 83.4%, and 83.3% of patients, respectively. Conclusions: The trifocal IOL evaluated provides a visual acuity improvement, with high levels of spectacle independence, patient satisfaction, and perceived visual quality associated.

National health examination surveys; a source of critical data.

The aim of this paper is to contribute technical arguments to the debate about the importance of health examination surveys and their continued use during the post-pandemic health financing crisis, and in the context of a technological innovation boom that offers new ways of collecting and analysing individual health data (e.g. artificial intelligence). Technical considerations demonstrate that health examination surveys make an irreplaceable contribution to the local availability of primary health data that can be used in a range of further studies (e.g. normative, burden-of-disease, care cascade, cost and policy impact studies) essential for informing several phases of the health planning cycle (e.g. surveillance, prioritization, resource mobilization and policy development). Examples of the use of health examination survey data in the World Health Organization (WHO) European Region (i.e. Finland, Italy, Malta and the United Kingdom of Great Britain and Northern Ireland) and the WHO Region of the Americas (i.e. Chile, Mexico, Peru and the United States of America) are presented, and reasons why health provider-led data cannot replace health examination survey data are discussed (e.g. underestimation of morbidity and susceptibility to bias). In addition, the importance of having nationally representative random samples of the general population is highlighted and we argue that health examination surveys make a critical contribution to external quality control for a country's health system by increasing the transparency and accountability of health spending. Finally, we consider future technological advances that can improve survey fieldwork and suggest ways of ensuring health examination surveys are sustainable in low-resource settings.

Cet article a pour objet d'apporter des arguments techniques au débat sur l'importance des enquêtes de santé par examen et sur leur utilisation continue pendant la crise post-pandémique du financement de la santé et dans le contexte d'un essor de l'innovation technologique qui offre de nouvelles façons de collecter et d'analyser les données individuelles sur la santé (comme l'intelligence artificielle). Les considérations techniques démontrent que les enquêtes de santé par examen apportent une contribution irremplaçable à la disponibilité locale de données de santé primaires qui peuvent servir dans une série d'études complémentaires (telles que des études normatives, sur la charge de morbidité, la cascade des soins, les coûts et l'impact des politiques). Ces études sont essentielles pour renseigner plusieurs phases du cycle de planification sanitaire (par exemple: surveillance, priorisation, mobilisation de ressources et élaboration de politiques). Cet article présente des exemples d'utilisation des données d'enquêtes de santé par examen dans la Région OMS de l'Europe (Finlande, Italie, Malte et Royaume-Uni de Grande-Bretagne et d'Irlande du Nord) et dans la Région OMS des Amériques (Chili, États-Unis d'Amérique, Mexique et Pérou) et aborde les raisons pour lesquelles les données fournies par les prestataires de soins de santé ne peuvent pas remplacer les données d'enquêtes de santé par examen (par exemple la sous-estimation de la morbidité et la vulnérabilité aux biais). En outre, il soulignet l'importance de disposer d'échantillons aléatoires représentatifs de la population générale au niveau national, et nous soutenons que les enquêtes de santé par examen apportent une contribution essentielle au contrôle externe de la qualité du système de santé d'un pays en renforçant la transparence des dépenses de santé et l'obligation de rendre des comptes à leur sujet. Enfin, nous envisageons les futures avancées technologiques susceptibles d'améliorer le travail d'enquête sur le terrain et suggérons des moyens d'assurer la viabilité des enquêtes de santé par examen dans les environnements à faibles ressources.

El objetivo de este artículo es aportar argumentos técnicos al debate sobre la importancia de las encuestas de salud y su uso continuado durante la crisis de financiación sanitaria pospandémica y en el contexto de un auge de la innovación tecnológica que ofrece nuevas formas de recopilar y analizar datos sanitarios individuales (por ejemplo, la inteligencia artificial). Las consideraciones técnicas demuestran que las encuestas de salud contribuyen de manera insustituible a la disponibilidad local de datos sanitarios primarios que pueden utilizarse en toda una serie de estudios posteriores (por ejemplo, estudios normativos, de carga de morbilidad, de cascada asistencial, de costes y de impacto de las políticas) esenciales para fundamentar varias fases del ciclo de planificación sanitaria (por ejemplo, vigilancia, establecimiento de prioridades, movilización de recursos y elaboración de políticas). Se presentan ejemplos del uso de los datos de las encuestas de salud en la Región Europea de la Organización Mundial de la Salud (Finlandia, Italia, Malta y el Reino Unido de Gran Bretaña e Irlanda del Norte) y en la Región de las Américas de la OMS (Chile, Estados Unidos de América, México y Perú) y se analizan las razones por las que los datos obtenidos por los proveedores sanitarios no pueden sustituir a los de las encuestas de salud (por ejemplo, la subestimación de la morbilidad y la posibilidad de sesgo). Además, se destaca la importancia de contar con muestras aleatorias representativas de la población general a escala nacional y se argumenta que las encuestas de salud contribuyen de forma decisiva al control de calidad externo del sistema sanitario de un país, al aumentar la transparencia y la rendición de cuentas del gasto sanitario. Por último, se examinan los futuros avances tecnológicos que pueden mejorar el trabajo de campo de las encuestas y se sugieren métodos para garantizar que las encuestas de salud sean sostenibles en entornos con pocos recursos.

Cryptotanshinone-Induced Permeabilization of Model Phospholipid Membranes: A Biophysical Study.

The Danshen terpenoid cryptotanshinone (CPT) is gaining enormous interest in light of its various outstanding biological activities. Among those, CPT has been shown to interact with cell membranes and, for instance, to have antibacterial activity. Several works have shown that CPT alone, or in combination with other drugs, can effectively act as an antibiotic against various infectious bacteria. Some authors have related the mechanism underlying this action to CPT-membrane interaction. This work shows that CPT readily partitions into phosphatidylcholine membranes, but there is a limiting capacity of accommodation of ca. 1 mol CPT to 3 mol phospholipid. The addition of CPT to unilamellar liposomes composed of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) causes membrane permeabilization, as shown by fluorescent probe leakage. This process has been kinetically studied, as well as its modulation by incorporation of phosphatidylethanolamine or phosphatidylglycerol, as a model for pathogenic cell membranes. The thermotropic behavior of 1,2-dimyristoylphosphatidylcholine (DMPC) model membranes is weakly affected by CPT, but the terpenoid causes significant dehydration of the polar region of the bilayer and weak disordering of the acyl chain palisade, as observed in Fourier-transform infrared spectroscopy (FTIR) results. Small-angle X-ray scattering (SAXS) shows that CPT increases DMPC bilayer thickness, which could be due to localization near the phospholipid/water interface. Molecular dynamics (MD) simulations show that the lateral diffusion coefficient of the phospholipid increases with the presence of CPT. CPT extends from the polar head region to the center of the bilayer, being centered between the carbonyl groups and the unsaturated region of the POPC, where there is greater overlap. Interestingly, the free energy profiles of a water molecule crossing the lipid membrane show that the POPC membrane becomes more permeable in the presence of CPT. In summary, our results show that CPT perturbs the physicochemical properties of the phospholipid membrane and compromises its barrier function, which could be of relevance to explain part of its antimicrobial or anticancer activities.

Superiority of 3D planimetry over pressure half-time method for the assessment of mitral valve area after percutaneous edge-to-edge mitral repair.

INTRODUCTION AND OBJECTIVES: There is limited evidence to identify the most accurate method for measuring the mitral valve area (MVA) after percutaneous edge-to-edge mitral repair. Our objective was to evaluate the optimal method in this context and its correlation with the mean transmitral gradient. METHODS: A registry of patients undergoing percutaneous mitral repair was conducted, analyzing different methods of measuring MVA and their correlation with the mean gradient. RESULTS: We analyzed data from 167 patients. The mean age was 76±10.3 years, 54% were men, and 46% were women. Etiology was degenerative in 45%, functional in 39%, and mixed in 16%. Postclip MVA measurements were 1.89±0.60 cm2 using pressure half-time (PHT), 2.87±0.83 cm2 using 3D planimetry, and the mean gradient was 3±1.19mmHg. MVA using 3D planimetry showed a stronger correlation with the mean gradient (r=0.46, P<.001) than MVA obtained by PHT (r=0.19, P=.048). Interobserver agreement was also higher with 3D planimetry than with PHT (intraclass correlation coefficient of 0.90 vs 0.81 and variation coefficient of 9.6 vs 19.7%, respectively). CONCLUSIONS: Our study demonstrates that the PHT method significantly underestimates MVA after clip implantation compared with direct measurement using transesophageal 3D planimetry. The latter method also correlates better with postimplantation gradients and has less interobserver variability. These results suggest that 3D planimetry is a more appropriate method for assessing postclip mitral stenosis.

Femtosecond-Assisted Mushroom Deep Anterior Lamellar Keratoplasty.

PURPOSE: The aim of this study was to describe our technique for performing femtosecond laser (FSL)-assisted mushroom configuration in deep anterior lamellar keratoplasty (DALK). METHODS: We describe our surgical technique for a mushroom-configuration DALK using a femtosecond laser (FSL) both to prepare the graft and to perform a precut of the recipient cornea, as well as the steps for the dissection of the recipient cornea and for donor cornea implantation. Moreover, we show the parameters of energy and spot separation and the external and internal diameters as well as the thickness of the external and internal keratotomy. RESULTS: We performed a retrospective case series study of 20 patients with a mean follow-up of 4.36 ± 2.54 years. The indication for surgery was leukoma in 15 cases (75%), keratoconus in 4 cases (20%), and stromal corneal dystrophy in 1 case (5%). Four cases had to be converted to penetrating keratoplasty. The overall results were as follows: The mean preoperative corrected distance visual acuity increased from 0.11 ± 0.09 (0.01-0.30) to 0.78 ± 0.22 (0.30-1.0) with spectacles and to 0.92 ± 0.13 (0.5-1.0) with a gas permeable contact lens. The mean final cylinder was 3.90 ± 1.86 (1.25-7.0). The mean endothelial cell count at 6 months was 2033.83 ± 570.53 cells/mm 2 (930-3207), and the mean final spherical equivalent was -4.67 ± 2.91 (-0.25 to -9.00). CONCLUSIONS: FSL-assisted technology is useful to achieve a predictable and safe procedure when using mushroom configuration to perform DALK. Our conversion rate from DALK to penetrating keratoplasty was similar to or even lower than that reported in the literature. In the successful DALK cases, the visual and refractive results were similar to those reported in other studies using FSL-assisted DALK (with a standard or mushroom configuration).

Time-dependent ligand-receptor binding kinetics and functionality in a heterodimeric receptor model.

GPCRs heteromerize both in CNS and non-CNS regions. The cell uses receptor heteromerization to modulate receptor functionality and to provide fine tuning of receptor signaling. In order for pharmacologists to explore these mechanisms for therapeutic purposes, quantitative receptor models are needed. We have developed a time-dependent model of the binding kinetics and functionality of a preformed heterodimeric receptor involving two drugs. Two cases were considered: both or only one of the drugs are in excess with respect to the total concentration of the receptor. The latter case can be applied to those situations in which a drug causes unwanted side effects that need to be reduced by decreasing its concentration. The required efficacy can be maintained by the allosteric effects mutually exerted by the two drugs in the two-drug combination system. We discuss this concept assuming that the drug causing unwanted side effects is an opioid and that analgesia is the therapeutic effect. As additional points, allosteric modulation by endogenous compounds and synthetic bivalent ligands was included in the study. Receptor heteromerization offers a mechanistic understanding and quantification of the pharmacological effects elicited by combinations of two drugs at different doses and with different efficacies and cooperativity effects, thus providing a conceptual framework for drug combination therapy.

Elevated Troponins after COVID-19 Hospitalization and Long-Term COVID-19 Symptoms: Incidence, Prognosis, and Clinical Outcomes-Results from a Multi-Center International Prospective Registry (HOPE-2).

Background: Acute cardiac injury (ACI) after COVID-19 has been linked with unfavorable clinical outcomes, but data on the clinical impact of elevated cardiac troponin on discharge during follow-up are scarce. Our objective is to elucidate the clinical outcome of patients with elevated troponin on discharge after surviving a COVID-19 hospitalization. Methods: We conducted an analysis in the prospective registry HOPE-2 (NCT04778020). Only patients discharged alive were selected for analysis, and all-cause death on follow-up was considered as the primary endpoint. As a secondary endpoint, we established any long-term COVID-19 symptoms. HOPE-2 stopped enrolling patients on 31 December 2021, with 9299 patients hospitalized with COVID-19, of which 1805 were deceased during the acute phase. Finally, 2382 patients alive on discharge underwent propensity score matching by relevant baseline variables in a 1:3 fashion, from 56 centers in 8 countries. Results: Patients with elevated troponin experienced significantly higher all-cause death during follow-up (log-rank = 27.23, p < 0.001), and had a higher chance of experiencing long-term COVID-19 cardiovascular symptoms. Specifically, fatigue and dyspnea (57.7% and 62.8%, with p-values of 0.009 and <0.001, respectively) are among the most common. Conclusions: After surviving the acute phase, patients with elevated troponin on discharge present increased mortality and long-term COVID-19 symptoms over time, which is clinically relevant in follow-up visits.

Multimorbidity and acute infectious diseases in urban and semi-urban settings in Peru: A mixed-methods study.

Background: The co-occurrence of chronic diseases and acute infectious events exacerbates disability and diminishes quality of life, yet research in Low- and Middle-Income countries is scarce. We aimed to investigate the relationship between infectious events and multimorbidity in resource-constrained settings. Methods: We conducted a sequential mixed-method study in Lima and Tumbes, Peru, with participants having multimorbidity from the CRONICAS Cohort Study. They completed a questionnaire on the occurrence, treatment, and health-seeking behaviour related to acute infectious events. Qualitative interviews explored the perceptions and links between multimorbidity and acute infectious events for a subgroup of participants. Findings: Among individuals with multimorbidity, low awareness of chronic conditions and poor medication adherence. The cumulative incidence for respiratory and gastrointestinal infections, the most reported acute conditions, was 2.0 [95%CI: 1.8-2.2] and 1.6 [1.2-1.9] events per person per year, respectively. Individuals with cancer (6.4 [1.6-11.2] events per person per year) or gastrointestinal reflux (7.2 [4.4-10.1] events per person per year) reported higher cumulative incidence of infectious events than others, such as those with cardiovascular and metabolic conditions (5.2 [4.6-5.8] events per person per year). Those with three or more chronic conditions had a slightly higher cumulative incidence compared with individuals with two conditions (5.7 [4.4-7.0] vs 5.0 [4.4-5.6] events per person per year). Around 40% of individuals with multimorbidity sought healthcare assistance, while others chose drugstores or didn't seek help. Our qualitative analysis showed diverse perceptions among participants regarding the connections between chronic and acute conditions. Those who recognized a connection emphasized the challenges in managing these interactions. Interpretation: Our study advances understanding of multimorbidity challenges in resource-limited settings, highlighting the impact of acute infections on patients' existing multimorbidity burden.

A multimodal approach using fundus images and text meta-data in a machine learning classifier with embeddings to predict years with self-reported diabetes - An exploratory analysis.

AIMS: Machine learning models can use image and text data to predict the number of years since diabetes diagnosis; such model can be applied to new patients to predict, approximately, how long the new patient may have lived with diabetes unknowingly. We aimed to develop a model to predict self-reported diabetes duration. METHODS: We used the Brazilian Multilabel Ophthalmological Dataset. Unit of analysis was the fundus image and its meta-data, regardless of the patient. We included people 40 + years and fundus images without diabetic retinopathy. Fundus images and meta-data (sex, age, comorbidities and taking insulin) were passed to the MedCLIP model to extract the embedding representation. The embedding representation was passed to an Extra Tree Classifier to predict: 0-4, 5-9, 10-14 and 15 + years with self-reported diabetes. RESULTS: There were 988 images from 563 people (mean age = 67 years; 64 % were women). Overall, the F1 score was 57 %. The group 15 + years of self-reported diabetes had the highest precision (64 %) and F1 score (63 %), while the highest recall (69 %) was observed in the group 0-4 years. The proportion of correctly classified observations was 55 % for the group 0-4 years, 51 % for 5-9 years, 58 % for 10-14 years, and 64 % for 15 + years with self-reported diabetes. CONCLUSIONS: The machine learning model had acceptable accuracy and F1 score, and correctly classified more than half of the patients according to diabetes duration. Using large foundational models to extract image and text embeddings seems a feasible and efficient approach to predict years living with self-reported diabetes.

Sarcopenia and sarcopenic obesity among community-dwelling Peruvian adults: A cross-sectional study.

INTRODUCTION: Sarcopenia and sarcopenic obesity (SO) have emerged as significant contributors to negative health outcomes in the past decade. We aimed to estimate the prevalence of probable sarcopenia, sarcopenia, and SO in a community-dwelling population of 1151 adults aged ≥55 years in Lima, Peru. METHODS: This cross-sectional study was conducted between 2018 and 2020. Sarcopenia was defined as the presence of low muscle strength (LMS) and low muscle mass (LMM) according to European (EWGSOP2), US (FNIH) and Asian (AWGS2) guidelines. We measured muscle strength by maximum handgrip strength and muscle mass using bioelectrical impedance analyzer. SO was defined as a body mass index ≥ 30 kg/m2 and sarcopenia. RESULTS: The study participants had a mean age of 66.2 years (SD 7.1), age range between 60 to 92 years old, of which 621 (53.9%) were men. Among the sample, 41.7% were classified as obese (BMI ≥30.0 kg/m²). The prevalence of probable sarcopenia was estimated to be 22.7% (95%CI: 20.3-25.1) using the EWGSOP2 criteria and 27.8% (95%CI: 25.2-30.4) using the AWGS2 criteria. Sarcopenia prevalence, assessed using skeletal muscle index (SMI), was 5.7% (95%CI: 4.4-7.1) according to EWGSOP2 and 8.3% (95%CI: 6.7-9.9) using AWGS2 criteria. The prevalence of sarcopenia based on the FNIH criteria was 18.1% (95%CI: 15.8-20.3). The prevalence of SO, considering different sarcopenia definitions, ranged from 0.8% (95%CI: 0.3-1.3) to 5.0% (95%CI: 3.8-6.3). CONCLUSION: Our findings reveal substantial variation in the prevalence of sarcopenia and SO, underscoring the necessity for context-specific cut-off values. Although the prevalence of SO was relatively low, this result may be underestimated. Furthermore, the consistently high proportion of probable sarcopenia and sarcopenia point to a substantial public health burden.

Association between subclinical atherosclerosis burden and unrecognized myocardial infarction detected by cardiac magnetic resonance in middle-aged low-risk adults.

AIMS: Evidence on the association between subclinical atherosclerosis (SA) and cardiovascular (CV) events in low-risk populations is scant. To study the association between SA burden and an ischaemic scar (IS), identified by cardiac magnetic resonance (CMR), as a surrogate of CV endpoint, in a low-risk population. METHODS AND RESULTS: A cohort of 712 asymptomatic middle-aged individuals from the Progression of Early SA (PESA-CNIC-Santander) study (median age 51 years, 84% male, median SCORE2 3.37) were evaluated on enrolment and at 3-year follow-up with 2D/3D vascular ultrasound (VUS) and coronary artery calcification scoring (CACS). A cardiac magnetic study (CMR) was subsequently performed and IS defined as the presence of subendocardial or transmural late gadolinium enhancement (LGE). On CMR, 132 (19.1%) participants had positive LGE, and IS was identified in 20 (2.9%) participants. Individuals with IS had significantly higher SCORE2 at baseline and higher CACS and peripheral SA burden (number of plaques by 2DVUS and plaque volume by 3DVUS) at both SA evaluations. High CACS and peripheral SA (number of plaques) burden were independently associated with the presence of IS, after adjusting for SCORE2 [OR for 3rd tertile, 8.31; 95% confidence interval (CI) 2.85-24.2; P < 0.001; and 2.77; 95% CI, 1.02-7.51; P = 0.045, respectively] and provided significant incremental diagnostic value over SCORE2. CONCLUSION: In a low-risk middle-aged population, SA burden (CAC and peripheral plaques) was independently associated with a higher prevalence of IS identified by CMR. These findings reinforce the value of SA evaluation to early implement preventive measures. CLINICAL TRIAL REGISTRATION: Progression of Early Subclinical Atherosclerosis (PESA) Study Identifier: NCT01410318.

Compliance with eye and foot preventive care in people with self-reported diabetes in Latin America and the Caribbean: Pooled, cross-sectional analysis of nine national surveys.

AIMS: To estimate the proportion of people with self-reported diabetes receiving eye and foot examinations in Latin America and the Caribbean (LAC). METHODS: Cross-sectional analysis of national health surveys in nine countries. Adults aged 25-64 years with self-reported diabetes. We quantified the proportion who reported having an eye examination in the last two years or a foot examination in the last year. We fitted multilevel Poisson regressions to assess socio-demographic (age and sex) and clinical (oral hypoglycemic medication and insulin treatment) variables associated with having had examinations. RESULTS: There were 7435 people with self-reported diabetes included in the analysis. In three countries (Chile [64%; 95% CI: 56%-71%], British Virgin Islands [58%; 95% CI: 51%-65%], and Brazil [54%; 95% CI: 50%-58%]), >50% of people with diabetes reported having had an eye examination in the last two years. Fewer participants (<50% across all countries) reported having had a foot examination in the last year, with Ecuador having the lowest proportion (12%; 95% CI: 8%-17%). Older people, and those taking oral medication or insulin, were more likely to have eye/foot examinations. CONCLUSIONS: The proportion of eye and foot examinations in people with self-reported diabetes across nine countries in LAC is low.

Co-creation process of an intervention to implement a multiparameter point-of-care testing device in a primary healthcare setting for non-communicable diseases in Peru.

BACKGROUND: Point-of-care testing (POCT) devices are diagnostic tools that can provide quick and accurate results within minutes, making them suitable for diagnosing non-communicable diseases (NCDs). However, these devices are not widely implemented in healthcare systems and for this reason is relevant to understand the implementation process. AIM: To describe the process and define a strategy to implement a multiparameter POCT device for diagnosing and managing NCDs in one region of Peru. METHODS: A descriptive and non-experimental study, using the participatory methodologies of co-creation process. It was conducted in one region of Peru (Tumbes) to design an intervention for implementing a multiparameter POCT device. Two co-creation sessions were conducted involving five groups: community members, primary healthcare workers, these groups in both rural and urban settings, and regional decision-makers. These sessions included activities to understand patient journeys in receiving care for NCDs, identify facilitators and barriers to POCT devices usage, and define an implementation strategy for POCT devices in both rural and urban settings of Tumbes. The research team analysed the data and summarized key topics for discussion after each session. RESULTS: A total of 78 participants were enrolled across the five groups. Among community members: 22.2% had only diabetes, 24.1% had only hypertension, and 18.5% had both diagnoses. In the patient journey, community members mentioned that it took at least three days to receive a diagnosis and treatment for an NCD. Most of the participants agreed that the POCT devices would be beneficial for their communities, but they also identified some concerns. The strategy for POCT devices implementation included healthcare workers training, POCT devices must be placed in the laboratory area and must be able to perform tests for glucose, glycated haemoglobin, cholesterol, and creatinine. Advertising about POCT devices should be displayed at the healthcare centres and the municipality using billboards and flyers. CONCLUSIONS: The co-creation process was useful to develop strategies for the implementation of multiparameter POCT devices for NCDs, involving the participation of different groups of stakeholders guided by moderators in both, rural and urban, settings in Peru.

Prevalence, trends, and factors associated with hypertensive crisis among Peruvian adults.

There are few studies focused on the epidemiology of hypertensive crisis at the population level in resource-constrained settings. This study aimed to determine the prevalence and trends over time of hypertensive crisis, as well as the factors associated with this condition among adults. A secondary data analysis was carried out using the Peruvian Demographic and Family Health Survey (ENDES). Hypertensive crisis was defined based on the presence of systolic (≥ 180mmHg) or diastolic (≥ 110mmHg) blood pressure, regardless of previous diagnosis or medication use. The factors associated with our outcome were evaluated using multinomial logistic regression, and the trend of hypertensive crisis was evaluated using the Cochrane-Armitage test. Data from 260,167 participants were analyzed, with a mean age of 44.2 (SD: 16.9) years and 55.5% were women. Hypertension prevalence was 23% (95%CI: 22.7-23.4) and, among them, 5.7% (95%CI: 5.4-5.9) had hypertensive crisis, with an overall prevalence of 1.5% (95%CI: 1.4-1.6). From 2014 to 2022, a significant decrease in the prevalence of hypertensive crisis was observed, from 1.7% in 2014 to 1.4% in 2022 (p = 0.001). In the multivariable model, males, increasing age, living in urban areas, high body mass index, and self-reported type 2 diabetes were positively associated with hypertensive crisis, whereas higher educational level, socioeconomic status, and high altitude were inversely associated. There is a need to improve strategies for the diagnosis, treatment, and control of hypertension, especially hypertensive crisis.

Standard of care plus telmisartan on respiratory failure due to COVID-19 (STAR-COVID trial).

BACKGROUND: The potential influence of renin-angiotensin inhibitors on the severity of SARS-CoV-2 infection has been considered in preclinical and observational studies with contradictory results. Therefore, we investigated the effect of telmisartan in reducing lung injury among hospitalized COVID-19 patients. METHODS: The STAR-COVID trial was conducted as a prospective, parallel-group, randomized, open-label study involving hospitalized adult patients with severe COVID-19 (NCT04510662). Sixty-six patients were enrolled: 33 were assigned to the telmisartan group and 33 to the control group. The mean age of participants was 48.8 years, with 62.5% being male. Participants were randomly assigned in a 1:1 ratio to receive either telmisartan (40 mg daily for 14 days or until discharge) plus standard of care or standard of care alone. The primary outcome assessed was the initiation of mechanical ventilation within 14 days. Secondary outcomes included 30-day mortality, the need for vasopressors, hemodialysis requirements, and length of hospital stay. RESULTS: Comparison between the telmisartan group and the control group revealed no significant difference in the occurrence of mechanical ventilation at 14 days (25% with telmisartan vs. 18.7% with control, P=0.579). Additionally, there were no significant differences observed in terms of mortality (25% vs. 21.9%, P=0.768), the need for vasopressors (18.8% in both groups, P=1.000), hemodialysis requirements (6.3% vs. 3.1%, P=0.500), and length of hospital stay (median of 7 days in both groups, P=0.962). CONCLUSIONS: Compared with the standard of care, telmisartan therapy demonstrated no significant impact on respiratory failure in hospitalized patients with severe COVID-19.

Apolipoprotein E-ε2 and Resistance to Atherosclerosis in Midlife: The PESA Observational Study.

BACKGROUND: APOE is a known genetic contributor to cardiovascular disease, but the differential role APOE alleles play in subclinical atherosclerosis remains unclear. METHODS: The PESA (Progression of Early Subclinical Atherosclerosis) is an observational cohort study that recruited 4184 middle-aged asymptomatic individuals to be screened for cardiovascular risk and multiterritorial subclinical atherosclerosis. Participants were APOE-genotyped, and omics data were additionally evaluated. RESULTS: In the PESA study, the frequencies for APOE -ε2, -ε3, and -ε4 alleles were 0.060, 0.844, and 0.096, respectively. This study included a subcohort of 3887 participants (45.8±4.3 years of age; 62% males). As expected, APOE-ε4 carriers were at the highest risk for cardiovascular disease and had significantly greater odds of having subclinical atherosclerosis compared with ε3/ε3 carriers, which was mainly explained by their higher levels of low-density lipoprotein (LDL)-cholesterol. In turn, APOE-ε2 carriers were at the lowest risk for cardiovascular disease and had significantly lower odds of having subclinical atherosclerosis in several vascular territories (carotids: 0.62 [95% CI, 0.47-0.81]; P=0.00043; femorals: 0.60 [0.47-0.78]; P=9.96×10-5; coronaries: 0.53 [0.39-0.74]; P=0.00013; and increased PESA score: 0.58 [0.48-0.71]; P=3.16×10-8). This APOE-ε2 atheroprotective effect was mostly independent of the associated lower LDL-cholesterol levels and other cardiovascular risk factors. The protection conferred by the ε2 allele was greater with age (50-54 years: 0.49 [95% CI, 0.32-0.73]; P=0.00045), and normal (<150 mg/dL) levels of triglycerides (0.54 [0.44-0.66]; P=4.70×10-9 versus 0.90 [0.57-1.43]; P=0.67 if ≥150 mg/dL). Omics analysis revealed an enrichment of several canonical pathways associated with anti-inflammatory mechanisms together with the modulation of erythrocyte homeostasis, coagulation, and complement activation in ε2 carriers that might play a relevant role in the ε2's atheroprotective effect. CONCLUSIONS: This work sheds light on the role of APOE in cardiovascular disease development with important therapeutic and prevention implications on cardiovascular health, especially in early midlife. REGISTRATION: URL: https://www.clinicaltrials.gov: NCT01410318.

Mean age and body mass index at type 2 diabetes diagnosis: Pooled analysis of 56 health surveys across income groups and world regions.

BACKGROUND: Screening for type 2 diabetes mellitus (T2DM) targets people aged 35+ years and those with overweight/obesity. With mounting evidence on young-onset T2DM and T2DM patients with lean phenotypes, it is worth revising the screening criteria to include younger and leaner adults. We quantified the mean age and body mass index (BMI; kg/m2 ) at T2DM diagnosis in 56 countries. METHODS: Descriptive cross-sectional analysis of WHO STEPS surveys. We analysed adults (25-69 years) with new T2DM diagnosis (not necessarily T2DM onset) as per fasting plasma glucose ≥126 mg/dL measured during the survey. For people with new T2DM diagnosis, we summarized the mean age and the proportion of each five-year age group; also, we summarized the mean BMI and the proportion of mutually exclusive BMI categories. RESULTS: There were 8695 new T2DM patients. Overall, the mean age at T2DM diagnosis was 45.1 years in men and 45.0 years in women; and the mean BMI at T2DM diagnosis was 25.2 in men and 26.9 in women. Overall, in men, 10.3% were 25-29 years and 8.5% were 30-34 years old; in women, 8.6% and 12.5% were 25-29 years and 30-34 years old, respectively. 48.5% of men and 37.3% of women were in the normal BMI category. CONCLUSIONS: A non-negligible proportion of new T2DM patients were younger than 35 years. Many new T2DM patients were in the normal weight range. Guidelines for T2DM screening may consider revising the age and BMI criteria to incorporate young and lean adults.