Drinkable in situ-forming tough hydrogels for gastrointestinal therapeutics.

Pills are a cornerstone of medicine but can be challenging to swallow. While liquid formulations are easier to ingest, they lack the capacity to localize therapeutics with excipients nor act as controlled release devices. Here we describe drug formulations based on liquid in situ-forming tough (LIFT) hydrogels that bridge the advantages of solid and liquid dosage forms. LIFT hydrogels form directly in the stomach through sequential ingestion of a crosslinker solution of calcium and dithiol crosslinkers, followed by a drug-containing polymer solution of alginate and four-arm poly(ethylene glycol)-maleimide. We show that LIFT hydrogels robustly form in the stomachs of live rats and pigs, and are mechanically tough, biocompatible and safely cleared after 24 h. LIFT hydrogels deliver a total drug dose comparable to unencapsulated drug in a controlled manner, and protect encapsulated therapeutic enzymes and bacteria from gastric acid-mediated deactivation. Overall, LIFT hydrogels may expand access to advanced therapeutics for patients with difficulty swallowing.

Synthetic extremophiles via species-specific formulations improve microbial therapeutics.

Microorganisms typically used to produce food and pharmaceuticals are now being explored as medicines and agricultural supplements. However, maintaining high viability from manufacturing until use remains an important challenge, requiring sophisticated cold chains and packaging. Here we report synthetic extremophiles of industrially relevant gram-negative bacteria (Escherichia coli Nissle 1917, Ensifer meliloti), gram-positive bacteria (Lactobacillus plantarum) and yeast (Saccharomyces boulardii). We develop a high-throughput pipeline to define species-specific materials that enable survival through drying, elevated temperatures, organic solvents and ionizing radiation. Using this pipeline, we enhance the stability of E. coli Nissle 1917 by more than four orders of magnitude over commercial formulations and demonstrate its capacity to remain viable while undergoing tableting and pharmaceutical processing. We further show, in live animals and plants, that synthetic extremophiles remain functional against enteric pathogens and as nitrogen-fixing plant supplements even after exposure to elevated temperatures. This synthetic, material-based stabilization enhances our capacity to apply microorganisms in extreme environments on Earth and potentially during exploratory space travel.

Quality of life in chordoma survivors: results from the Chordoma Foundation Survivorship Survey.

OBJECTIVE: Chordomas are rare malignant bone tumors whose location in the skull base or spine, invasive surgical treatment, and accompanying adjuvant radiotherapy may all lead patients to experience poor quality of life (QOL). Limited research has been conducted on specific demographic and clinical factors associated with decreased QOL in chordoma survivors. Thus, the aim of the present study was to investigate several potential variables and their impact on specific QOL domains in these patients as well the frequencies of specific QOL challenges within these domains. METHODS: The Chordoma Foundation (CF) Survivorship Survey was electronically distributed to chordoma survivors subscribed to the CF Chordoma Connections forum. Survey questions assessed QOL in three domains: physical, emotional/cognitive, and social. The degree of impairment was assessed by grouping the participants into high- and low-challenge groups designated by having ≥ 5 or < 5 symptoms or challenges within a given QOL domain. Bivariate analysis of demographic and clinical characteristics between these groups was conducted using Fisher's exact test and the Mann-Whitney U-test. RESULTS: A total of 665 chordoma survivors at least partially completed the survey. On bivariate analysis, female sex was significantly associated with increased odds of significant emotional (p = 0.001) and social (p = 0.019) QOL burden. Younger survivors (age < 65 years) were significantly more likely to experience significant physical (p < 0.0001), emotional (p < 0.0001), and social (p < 0.0001) QOL burden. Skull base chordoma survivors had significantly higher emotional/cognitive QOL burden than spinal chordoma survivors (p = 0.022), while the converse was true for social QOL challenges (p = 0.0048). Survivors currently in treatment were significantly more likely to experience significant physical QOL challenges compared with survivors who completed their treatment > 10 years ago (p = 0.0074). Fear of cancer recurrence (FCR) was the most commonly reported emotional/cognitive QOL challenge (49.6%). Only 41% of the participants reported having their needs met for their physical QOL challenges as well as 25% for emotional/cognitive and 18% for social. CONCLUSIONS: The authors' findings suggest that younger survivors, female survivors, and survivors currently undergoing treatment for chordoma are at high risk for adverse QOL outcomes. Additionally, although nearly half of the participants reported a FCR, very few reported having adequate emotional/cognitive care. These findings may be useful in identifying specific groups of chordoma survivors vulnerable to QOL challenges and bring to light the need to expand care to meet the QOL needs for these patients.

COVID-19 vaccines reduce mortality in hospitalized patients with oxygen requirements: Differences between vaccine subtypes. A multicontinental cohort study.

The aim of this study was to analyze whether the coronavirus disease 2019 (COVID-19) vaccine reduces mortality in patients with moderate or severe COVID-19 disease requiring oxygen therapy. A retrospective cohort study, with data from 148 hospitals in both Spain (111 hospitals) and Argentina (37 hospitals), was conducted. We evaluated hospitalized patients for COVID-19 older than 18 years with oxygen requirements. Vaccine protection against death was assessed through a multivariable logistic regression and propensity score matching. We also performed a subgroup analysis according to vaccine type. The adjusted model was used to determine the population attributable risk. Between January 2020 and May 2022, we evaluated 21,479 COVID-19 hospitalized patients with oxygen requirements. Of these, 338 (1.5%) patients received a single dose of the COVID-19 vaccine and 379 (1.8%) were fully vaccinated. In vaccinated patients, mortality was 20.9% (95% confidence interval [CI]: 17.9-24), compared to 19.5% (95% CI: 19-20) in unvaccinated patients, resulting in a crude odds ratio (OR) of 1.07 (95% CI: 0.89-1.29; p = 0.41). However, after considering the multiple comorbidities in the vaccinated group, the adjusted OR was 0.73 (95% CI: 0.56-0.95; p = 0.02) with a population attributable risk reduction of 4.3% (95% CI: 1-5). The higher risk reduction for mortality was with messenger RNA (mRNA) BNT162b2 (Pfizer) (OR 0.37; 95% CI: 0.23-0.59; p < 0.01), ChAdOx1 nCoV-19 (AstraZeneca) (OR 0.42; 95% CI: 0.20-0.86; p = 0.02), and mRNA-1273 (Moderna) (OR 0.68; 95% CI: 0.41-1.12; p = 0.13), and lower with Gam-COVID-Vac (Sputnik) (OR 0.93; 95% CI: 0.6-1.45; p = 0.76). COVID-19 vaccines significantly reduce the probability of death in patients suffering from a moderate or severe disease (oxygen therapy).

Can OpenEHR, ISO 13606, and HL7 FHIR Work Together? An Agnostic Approach for the Selection and Application of Electronic Health Record Standards to the Next-Generation Health Data Spaces.

In order to maximize the value of electronic health records (EHRs) for both health care and secondary use, it is necessary for the data to be interoperable and reusable without loss of the original meaning and context, in accordance with the findable, accessible, interoperable, and reusable (FAIR) principles. To achieve this, it is essential for health data platforms to incorporate standards that facilitate addressing needs such as formal modeling of clinical knowledge (health domain concepts) as well as the harmonized persistence, query, and exchange of data across different information systems and organizations. However, the selection of these specifications has not been consistent across the different health data initiatives, often applying standards to address needs for which they were not originally designed. This issue is essential in the current scenario of implementing the European Health Data Space, which advocates harmonization, interoperability, and reuse of data without regulating the specific standards to be applied for this purpose. Therefore, this viewpoint aims to establish a coherent, agnostic, and homogeneous framework for the use of the most impactful EHR standards in the new-generation health data spaces: OpenEHR, International Organization for Standardization (ISO) 13606, and Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR). Thus, a panel of EHR standards experts has discussed several critical points to reach a consensus that will serve decision-making teams in health data platform projects who may not be experts in these EHR standards. It was concluded that these specifications possess different capabilities related to modeling, flexibility, and implementation resources. Because of this, in the design of future data platforms, these standards must be applied based on the specific needs they were designed for, being likewise fully compatible with their combined functional and technical implementation.

Healthcare outcomes in patients with HIV infection at a tertiary hospital during the COVID-19 pandemic.

Background: The COVID-19 pandemic has affected the care of patients with other diseases. Difficulty in access to healthcare during these months has been especially relevant for persons with HIV infection (PWH). This study therefore sought to ascertain the clinical outcomes and effectiveness of the measures implemented among PWH in a region with one of the highest incidence rates in Europe. Methods: Retrospective, observational, pre-post intervention study to compare the outcomes of PWH attended at a high-complexity healthcare hospital from March to October 2020 and during the same months across the period 2016-2019. The intervention consisted of home drug deliveries and preferential use of non face-to-face consultations. The effectiveness of the measures implemented was determined by reference to the number of emergency visits, hospitalisations, mortality rate, and percentage of PWH with viral load >50 copies, before and after the two pandemic waves. Results: A total of 2760 PWH were attended from January 2016 to October 2020. During the pandemic, there was a monthly mean of 106.87 telephone consultations and 2075 home deliveries of medical drugs dispensed to ambulatory patients. No statistically significant differences were found between the rate of admission of patients with COVID-HIV co-infection and that of the remaining patients (1172.76 admissions/100,000 population vs. 1424.29, p = 0.401) or in mortality (11.54% vs. 12.96%, p = 0.939). The percentage of PWH with viral load >50 copies was similar before and after the pandemic (1.20% pre-pandemic vs. 0.51% in 2020, p = 0.078). Conclusion: Our results show that the strategies implemented during the first 8 months of the pandemic prevented any deterioration in the control and follow-up parameters routinely used on PWH. Furthermore, they contribute to the debate about how telemedicine and telepharmacy can fit into future healthcare models.

Introducción: La pandemia causada por el SARS-CoV-2 ha afectado a la atención de pacientes con otras enfermedades. La dificultad en el acceso a la asistencia sanitaria durante estos meses es especialmente relevante en las personas con infección por VIH (PCV). El objetivo del estudio fue conocer los resultados clínicos y la efectividad de las medidas implementadas en PCV en una de las regiones con mayor incidencia de Europa. Métodos: Estudio observacional retrospectivo, pre-postintervención, comparando los resultados de PCV atendidos en un hospital de alta complejidad entre marzo-octubre de 2020 y el mismo periodo de 2016 a 2019. La intervención consistió en el envío a domicilio de medicamentos y la realización preferente de consultas no presenciales. La efectividad de las medidas implementadas se determinó por el número de visitas a urgencias, hospitalizaciones, mortalidad y porcentaje de PCV con carga viral > 50 copias antes y después de 2 olas pandémicas. Resultados: Se atendieron 2.760 PCV entre enero de 2016 y octubre de 2020. Durante la pandemia se realizaron una media mensual de 106,87 consultas telefónicas y 2.075 envíos a domicilio de medicamentos de dispensación ambulatoria. No se encontraron diferencias estadísticamente significativas en la frecuentación de pacientes con coinfección COVID-VIH respecto al resto (1.172,76 ingresos/100.000 habitantes vs. 1.424,29, p = 0,401), ni en su mortalidad (11,54 vs. 12,96%, p = 0,939). El porcentaje de PCV con carga viral > 50 copias fue similar antes y después de la pandemia (1,20% prepandemia vs. 0,51% en 2020, p = 0,078). Conclusión: Nuestros resultados revelan que las estrategias implementadas durante los 8 primeros meses de pandemia han evitado el deterioro en parámetros de control y seguimiento empleados habitualmente en PCV. Además, contribuyen a la reflexión sobre el encaje de la telemedicina y telefarmacia en modelos asistenciales futuros.

Integrase inhibitors in children and adolescents: clinical use and resistance.

BACKGROUND: Although integrase inhibitor (INI)-based regimens are now the first-line choice for all people living with HIV, experience among children and adolescents is still scarce. We describe the characteristics and outcomes of a paediatric/adolescent cohort on INI-based ART. METHODS: Retrospective analysis of HIV-infected patients below 18 years of age who started an INI-based regimen from 2007 to 2019, enrolled in the Spanish National Adult (CoRIS) and Paediatric (CoRISpe) cohorts. Resistance mutations were identified by the Stanford HIV Drug Resistance Database. RESULTS: Overall, 318 INI-based regimens were implemented in 288 patients [53.8% female; median age at start of 14.3 years (IQR 12.0-16.3)]. Most were born in Spain (69.1%), vertically infected (87.7%) and treatment-experienced (92.7%). The most frequently prescribed INI was dolutegravir (134; 42.1%), followed by raltegravir (110; 34.6%) and elvitegravir (73; 23.0%). The median exposure was 2.0 years (IQR 1.1-3.0). The main reasons to start an INI-based therapy were treatment simplification (54.4%) and virological failure (34.3%). In total, 103 (32.4%) patients interrupted their regimen: 14.5% for simplification and 8.5% due to virological failure. Most subjects who received dolutegravir (85.8%) and elvitegravir (83.6%) did not interrupt their regimen and maintained undetectable viral load. There were only five virological failures with dolutegravir and three with elvitegravir. There were no interruptions related to adverse events. Seven patients with virological failure presented major resistance mutations to INIs; none of them were on dolutegravir. CONCLUSIONS: INI-based regimens were effective and safe for HIV treatment in children and adolescents. Dolutegravir and elvitegravir presented an excellent profile, and most patients achieved and maintained viral suppression.

Integrating data types to estimate spatial patterns of avian migration across the Western Hemisphere.

For many avian species, spatial migration patterns remain largely undescribed, especially across hemispheric extents. Recent advancements in tracking technologies and high-resolution species distribution models (i.e., eBird Status and Trends products) provide new insights into migratory bird movements and offer a promising opportunity for integrating independent data sources to describe avian migration. Here, we present a three-stage modeling framework for estimating spatial patterns of avian migration. First, we integrate tracking and band re-encounter data to quantify migratory connectivity, defined as the relative proportions of individuals migrating between breeding and nonbreeding regions. Next, we use estimated connectivity proportions along with eBird occurrence probabilities to produce probabilistic least-cost path (LCP) indices. In a final step, we use generalized additive mixed models (GAMMs) both to evaluate the ability of LCP indices to accurately predict (i.e., as a covariate) observed locations derived from tracking and band re-encounter data sets versus pseudo-absence locations during migratory periods and to create a fully integrated (i.e., eBird occurrence, LCP, and tracking/band re-encounter data) spatial prediction index for mapping species-specific seasonal migrations. To illustrate this approach, we apply this framework to describe seasonal migrations of 12 bird species across the Western Hemisphere during pre- and postbreeding migratory periods (i.e., spring and fall, respectively). We found that including LCP indices with eBird occurrence in GAMMs generally improved the ability to accurately predict observed migratory locations compared to models with eBird occurrence alone. Using three performance metrics, the eBird + LCP model demonstrated equivalent or superior fit relative to the eBird-only model for 22 of 24 species-season GAMMs. In particular, the integrated index filled in spatial gaps for species with over-water movements and those that migrated over land where there were few eBird sightings and, thus, low predictive ability of eBird occurrence probabilities (e.g., Amazonian rainforest in South America). This methodology of combining individual-based seasonal movement data with temporally dynamic species distribution models provides a comprehensive approach to integrating multiple data types to describe broad-scale spatial patterns of animal movement. Further development and customization of this approach will continue to advance knowledge about the full annual cycle and conservation of migratory birds.

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study.

BACKGROUND: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). METHODS: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. RESULTS: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83-7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97-2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14-1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25-1.30]). CONCLUSIONS: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.

SurvMaximin: Robust federated approach to transporting survival risk prediction models.

OBJECTIVE: For multi-center heterogeneous Real-World Data (RWD) with time-to-event outcomes and high-dimensional features, we propose the SurvMaximin algorithm to estimate Cox model feature coefficients for a target population by borrowing summary information from a set of health care centers without sharing patient-level information. MATERIALS AND METHODS: For each of the centers from which we want to borrow information to improve the prediction performance for the target population, a penalized Cox model is fitted to estimate feature coefficients for the center. Using estimated feature coefficients and the covariance matrix of the target population, we then obtain a SurvMaximin estimated set of feature coefficients for the target population. The target population can be an entire cohort comprised of all centers, corresponding to federated learning, or a single center, corresponding to transfer learning. RESULTS: Simulation studies and a real-world international electronic health records application study, with 15 participating health care centers across three countries (France, Germany, and the U.S.), show that the proposed SurvMaximin algorithm achieves comparable or higher accuracy compared with the estimator using only the information of the target site and other existing methods. The SurvMaximin estimator is robust to variations in sample sizes and estimated feature coefficients between centers, which amounts to significantly improved estimates for target sites with fewer observations. CONCLUSIONS: The SurvMaximin method is well suited for both federated and transfer learning in the high-dimensional survival analysis setting. SurvMaximin only requires a one-time summary information exchange from participating centers. Estimated regression vectors can be very heterogeneous. SurvMaximin provides robust Cox feature coefficient estimates without outcome information in the target population and is privacy-preserving.

COVID-19-associated mucormycosis, diabetes and steroid therapy: Experience in a single centre in Western Mexico.

BACKGROUND: COVID-19-associated mucormycosis (CAM) has emerged as a challenging complication as the current pandemic has increased the population requiring treatment with corticosteroids. CAM has caused a massive outbreak in India, reported to be causing cases in Iran, Egypt and The Netherlands. OBJECTIVES: To describe CAM cases occurring in a single centre in Western Mexico. METHODS: Our group carried out a retrospective study from May 2020 to May 2021 to identify CAM cases in patients with previous COVID-19 diagnosis. RESULTS: Six CAM cases occurred in a single centre in Western Mexico during the study period, most of them with diabetes (n = 5/6) and all received corticosteroid therapy even when only three had severe COVID-19. After analysing local COVID-19 burden, it was estimated that in this region, CAM was 300 times more frequent among COVID individuals than the estimates for general population. CONCLUSION: Similar to large reports in India and other countries, CAM cases reported in this study were diagnosed in individuals with diabetes, hyperglycaemic status and with history of previous use of corticosteroids. Identifying these individuals at risk can help the early identification of CAM. In addition, strict glycaemic control and avoidance of unnecessary corticosteroid in non-severe COVID-19 cases could help in preventing this complicated fungal infection.

An open-source low-cost wireless sensor system for acquisition of human movement data.

Several fields of research such as medicine, robotics, sports, informatics, etc., require the analysis of human movement. Traditional systems for acquisition and analysis of human movement data are based on video cameras or active sensors. However, those systems are limited to high-resource settings. Wearable devices allow monitoring subjects outside typical clinical or research environments. Here, we present an open source low-cost wireless sensor system for acquisition of human movement data. Our system consists of two main parts: a server that stores data and, one or more wearable sensor modules that collect movement data through Inertial Measurement Units (IMUs) and transmit them wirelessly to the server. As a proof of concept, we measured human gait activity. Our results show that our system with IMUs can acquire quantifiable movement data. Characteristics such as open source code and its low-cost, make our system a viable alternative for clinical or research.

Endurance Exercise Training reduces Blood Pressure according to the Wilder's Principle.

The effect of antihypertensive medicine (AHM) is larger the higher the pre-treatment blood pressure level. It is unknown whether this Wilder's principle, also applies for the exercise-training blood pressure (BP) lowering effect. One hundred seventy-eight (n=178) middle-aged individuals (55±8 y) with metabolic syndrome (MetS), underwent high intensity interval training (3 days·week-1) for 16 weeks. Participants were divided into medicated (Med; n=103) or not medicated (No Med; n=75) with AHM. Office BP was evaluated before and after the exercise-training. Correlations and stepwise regression analysis were used to determine which variable better predicted the reductions in systolic BP (SBP) with training. After training, participants with hypertension lowered SBP by a similar magnitude regardless of if they were in the Med (-15 mmHg, 95% CI-12,-19; P<0.001) or No Med group (-13 mmHg, 95% CI-9,-16; P<0.001). However, SBP did not decrease among normotensive groups (P=0.847 for Med and P=0.937 for No Med). Pre-treatment SBP levels was the best predictor of exercise-training lowering effect (r=-0.650; ß=-0.642; P<0.001). For each 10 mmHg higher pre-training SBP there were a 5 mmHg deeper SBP reduction (Wilder principle). Furthermore, AHM does not interfere with exercise-training BP-lowering effect.

Design, Fabrication, and Characterisation of a Label-Free Nanosensor for Bioapplications.

In this paper, we present a hybrid semiconductor structure for biosensing applications that features the co-integration of nanoelectromechanical systems with the well-known metal oxide semiconductor technology. The proposed structure features an MOSFET as a readout element, and a doubly clamped beam that is isolated from the substrate by a thin air gap, as well as by a tunnel oxide layer. The beam structure is functionalised by a thin layer of biotargets, and the main aim is to detect a particular set of biomolecules, such as enzymes, bacteria, viruses, and DNA/RNA chains, among others. In here, a three-dimensional finite element analysis is performed in order to study the behaviour of the functionalised, doubly clamped beam. Preliminary results for the fabrication and characterisation processes show good agreement between the simulated and measured characteristics.

Effects of statins and exercise on postprandial lipoproteins in metabolic syndrome vs metabolically healthy individuals.

AIMS: To determine if the combination of exercise and statin could normalize postprandial triglyceridaemia (PPTG) in hypercholesteraemic individuals. METHODS: Eight hypercholesteraemic (blood cholesterol 182 ± 38 mg dL-1 ; low-density lipoprotein-cholesterol [LDL-c] 102 ± 32 mg dL-1 ) overweight (body mass index 30 ± 4 kg m-2 ) individuals with metabolic syndrome (MetS) were compared to a group of 8 metabolically healthy (MetH) controls (blood cholesterol 149 ± 23 mg dL-1 ; LDL-c 77 ± 23 mg dL-1 , and body mass index 23 ± 2 kg m-2 ). Each group underwent 2 PPTG tests, either 14 hours after a bout of intense exercise or without previous exercise. Additionally, MetS individuals were tested 96 hours after withdrawal of their habitual statin medication to study medication effects. RESULTS: A bout of exercise before the test meal did not reduce PPTG in MetS (P = .347), but reduced PPTG by 46% in MetH (413 ± 267 to 224 ± 142 mg dL-1 for 5 h incremental area under the curve; P = .02). In both trials (i.e., either after a bout of intense exercise or without previous exercise), statin withdrawal in MetS greatly increased PPTG (average 65%; P < .01), mean LDL-c (average 25%; P < .01), total cholesterol (average 16%; P < .01) and apolipoprotein (Apo) B48 (24%; P < .01), without interference from exercise. However, Apo B100 was not affected by statin withdrawal. CONCLUSION: Hypercholesteraemic MetS individuals (compared to MetH controls) fail to show an effect of exercise on reducing PPTG. However, chronic statin medication blunts the elevations in triglyceride after a fat meal (i.e., incremental area under the curve of PPTG) reducing their cardiovascular risk associated with their atherogenic dyslipidaemia. Statin decreases PPTG by reducing the secretion or accelerating the catabolism of intestinal Apo B48.

Obtaining EHR-derived datasets for COVID-19 research within a short time: a flexible methodology based on Detailed Clinical Models.

BACKGROUND: COVID-19 ranks as the single largest health incident worldwide in decades. In such a scenario, electronic health records (EHRs) should provide a timely response to healthcare needs and to data uses that go beyond direct medical care and are known as secondary uses, which include biomedical research. However, it is usual for each data analysis initiative to define its own information model in line with its requirements. These specifications share clinical concepts, but differ in format and recording criteria, something that creates data entry redundancy in multiple electronic data capture systems (EDCs) with the consequent investment of effort and time by the organization. OBJECTIVE: This study sought to design and implement a flexible methodology based on detailed clinical models (DCM), which would enable EHRs generated in a tertiary hospital to be effectively reused without loss of meaning and within a short time. MATERIAL AND METHODS: The proposed methodology comprises four stages: (1) specification of an initial set of relevant variables for COVID-19; (2) modeling and formalization of clinical concepts using ISO 13606 standard and SNOMED CT and LOINC terminologies; (3) definition of transformation rules to generate secondary use models from standardized EHRs and development of them using R language; and (4) implementation and validation of the methodology through the generation of the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC-WHO) COVID-19 case report form. This process has been implemented into a 1300-bed tertiary Hospital for a cohort of 4489 patients hospitalized from 25 February 2020 to 10 September 2020. RESULTS: An initial and expandable set of relevant concepts for COVID-19 was identified, modeled and formalized using ISO-13606 standard and SNOMED CT and LOINC terminologies. Similarly, an algorithm was designed and implemented with R and then applied to process EHRs in accordance with standardized concepts, transforming them into secondary use models. Lastly, these resources were applied to obtain a data extract conforming to the ISARIC-WHO COVID-19 case report form, without requiring manual data collection. The methodology allowed obtaining the observation domain of this model with a coverage of over 85% of patients in the majority of concepts. CONCLUSION: This study has furnished a solution to the difficulty of rapidly and efficiently obtaining EHR-derived data for secondary use in COVID-19, capable of adapting to changes in data specifications and applicable to other organizations and other health conditions. The conclusion to be drawn from this initial validation is that this DCM-based methodology allows the effective reuse of EHRs generated in a tertiary Hospital during COVID-19 pandemic, with no additional effort or time for the organization and with a greater data scope than that yielded by conventional manual data collection process in ad-hoc EDCs.

Concurrent endurance and resistance training enhances muscular adaptations in individuals with metabolic syndrome.

The purpose of the study was to determine if concurrent training (endurance and resistance in a single session) elicits leg muscular adaptations beyond the ones obtained by endurance training alone in sedentary individuals with metabolic syndrome (MetS). Sixty-six MetS individuals (37% women, age 56 ± 7 years, BMI 32 ± 5 kg m-2 and 3.8 ± 0.8 MetS factors) were randomized to undergo one of the following 16-week isocaloric exercise programs: (i) 4 + 1 bouts of 4 min at 90% of HRMAX of intense aerobic cycling (IAC + IAC group; n = 33), (ii) 4 IAC bouts followed by 3 sets of 12 repetitions of 3 lower-limb free-weight exercises (IAC + RT group; n = 33). We measured the effects of training on maximal cycling power, leg press maximum strength (1RM), countermovement jump height (CMJ), and mean propulsive velocity (MPV) at workloads ranging from 10% to 100% of baseline 1RM leg press. After intervention, MetS components (Z-score) improved similarly in both groups (p = 0.002). Likewise, maximal cycling power during a ramp test improved similarly in both groups (time effect p < 0.001). However, leg press 1RM improved more in IAC + RT than in IAC + IAC (47 ± 5 vs 13 ± 5 kg, respectively, interaction p < 0.001). CMJ only improved with IAC + RT (0.8 ± 0.2 cm, p = 0.001). Leg press MPV at heavy loads (ie, 80%-100% 1RM) improved more with concurrent training (0.12 ± 0.01 vs 0.06 ± 0.02 m s-1 , interaction p = 0.013). In conclusion, in unconditioned MetS individuals, intense aerobic cycling alone improves leg muscle performance. However, substituting 20% of intense aerobic cycling by resistance training further improves 1RM leg press, MPV at high loads, and jumping ability while providing similar improvement in MetS components.

Effects of antihypertensive medication and high-intensity interval training in hypertensive metabolic syndrome individuals.

Pharmacological and non-pharmacological therapies are simultaneously prescribed when treating hypertensive individuals with elevated cardiovascular risk (ie, metabolic syndrome individuals). However, it is unknown if the interactions between antihypertensive medication (AHM) and lifestyle interventions (ie, exercise training) may result in a better ambulatory blood pressure (ABP) control. To test this hypothesis, 36 hypertensive individuals with metabolic syndrome (MetS) under long-term prescription with AHM targeting the renin-angiotensin-aldosterone system (RAAS) were recruited. Before and after 4 months of high-intensity interval training (HIIT), participants completed two trials in a double-blind, randomized order: (a) placebo trial consisting of AHM withdrawal for 3 days and (b) AHM trial where individuals held their habitual dose of AHM. In each trial, 24-h mean arterial pressure (MAP) was monitored and considered the primary study outcome. Secondary outcomes included plasma renin activity (PRA) and aldosterone concentration to confirm withdrawal effects on RAAS, along with the analysis of urine albumin-to-creatinine ratio (UACR) to assess kidney function. The results showed main effects from AHM and HIIT reducing 24-h MAP (-5.7 mmHg, p < 0.001 and -2.3 mmHg, p = 0.007, respectively). However, there was not interaction between AHM and HIIT on 24-h MAP (p = 0.240). There was a main effect of AHM increasing PRA (p < 0.001) but no effect on plasma aldosterone concentration (p = 0.368). HIIT did not significantly improve RAAS hormones or the UACR. In conclusion, AHM and HIIT have independent and additive effects in lowering ABP. These findings support the combination of habitual AHM with exercise training with the goal to reduce ABP in hypertensive MetS individuals.

What Every Reader Should Know About Studies Using Electronic Health Record Data but May Be Afraid to Ask.

Coincident with the tsunami of COVID-19-related publications, there has been a surge of studies using real-world data, including those obtained from the electronic health record (EHR). Unfortunately, several of these high-profile publications were retracted because of concerns regarding the soundness and quality of the studies and the EHR data they purported to analyze. These retractions highlight that although a small community of EHR informatics experts can readily identify strengths and flaws in EHR-derived studies, many medical editorial teams and otherwise sophisticated medical readers lack the framework to fully critically appraise these studies. In addition, conventional statistical analyses cannot overcome the need for an understanding of the opportunities and limitations of EHR-derived studies. We distill here from the broader informatics literature six key considerations that are crucial for appraising studies utilizing EHR data: data completeness, data collection and handling (eg, transformation), data type (ie, codified, textual), robustness of methods against EHR variability (within and across institutions, countries, and time), transparency of data and analytic code, and the multidisciplinary approach. These considerations will inform researchers, clinicians, and other stakeholders as to the recommended best practices in reviewing manuscripts, grants, and other outputs from EHR-data derived studies, and thereby promote and foster rigor, quality, and reliability of this rapidly growing field.

[Family Medicine in the face of the law on medical aid in dying responsibility and guarantees]. / La Medicina de Familia ante la ley sobre la ayuda médica para morir: responsabilidad y garantías.

The approval of the euthanasia law represents a challenge for medicine and culminates a process of civic maturation of society in the face of death. There are challenges that the application of the law will have to meet. Seeking an objective and irreversible medical solution to subjective suffering - where there may be conditioning social determinants - implies a serious risk of inequity that requires policies that establish a pre-decisional guaranteeing framework. Euthanasia should be an exception thanks to the existence of strong clinical, informational and relational safeguards that can only be guaranteed in the context of a solvent primary care that accompanies people throughout their lives. In this primarist and community context, euthanasia can be the last resort of a professional committed to not abandoning a patient with severe and irreversible suffering who requests it.