The CNIC-polypill (acetylsalicylic acid, atorvastatin, and ramipril), an effective and cost-saving secondary prevention strategy compared with other therapeutic options in patients with ischaemic heart disease.

Aims: The retrospective NEPTUNO study evaluated the effectiveness of the Centro Nacional de Investigaciones Cardiovasculares (CNIC)-polypill (including acetylsalicylic acid, ramipril, and atorvastatin) vs. other therapeutic approaches in secondary prevention for cardiovascular (CV) disease. In this substudy, the focus was on the subgroup of patients with ischaemic heart disease (IHD). Methods and results: Patients on four strategies: CNIC-polypill, its monocomponents as loose medications, equipotent medications, and other therapies. The primary endpoint was the incidence of recurrent major adverse CV events (MACEs) after 2 years. After matching, 1080 patients were included in each cohort. The CNIC-polypill cohort had a significantly lower incidence of recurrent MACE compared with monocomponents, equipotent drugs, and other therapies cohorts (16.1 vs. 24, 24.4, and 24.3%, respectively; P < 0.001). The hazard ratios (HRs) for recurrent MACE were higher in monocomponents (HR = 1.12; P = 0.042), equipotent drugs (HR = 1.14; P = 0.031), and other therapies cohorts (HR = 1.17; P = 0.016) compared with the CNIC-polypill, with a number needed to treat of 12 patients to prevent a MACE. The CNIC-polypill demonstrated a greater reduction in LDL cholesterol (LDL-c; -56.1 vs. -43.6, -33.3, and -33.2% in the monocomponents, equipotent drugs, and other therapies, respectively; P < 0.001) and systolic blood pressure (-13.7 vs. -11.5, -10.6, and -9.1% in the CNIC-polypill, monocomponents, equipotent drugs, and other therapies, respectively; P < 0.001) compared with other cohorts. The CNIC-polypill intervention was less costly and more effective than any other therapeutic option, with €2317-€2407 cost savings per event prevented. Conclusion: In IHD, the CNIC-polypill exemplifies a guideline-recommended secondary prevention treatment linked to better outcomes and cost saving compared with other therapeutic options.

Caring to care: Nurturing ICU healthcare professionals' wellbeing for enhanced patient safety.

Healthcare professionals working in the Intensive Care Unit (ICU) care for patients suffering from a critical illness and their relatives. Working within a team of people with different personalities, competencies, and specialties, with constraints and demands might contribute to a working environment that is prone to conflicts and disagreements. This highlights that the ICU is a stressful place that can threaten healthcare professionals' wellbeing. This article aims to address the concept of wellbeing by describing how the stressful ICU work-environment threatens the wellbeing of health professionals and discussing how this situation jeopardizes patient safety. To promote wellbeing, it is imperative to explore actionable interventions such as improve communication skills, educational sessions on stress management, or mindfulness. Promoting ICU healthcare professionals' wellbeing through evidence-based strategies will not only increase their personal resilience but might contribute to a safer and more efficient patient care.

Seroprevalence of SARS-CoV-2 in Patients with Multiple Sclerosis under Disease-Modifying Therapies: A Multi-Centre Study.

BACKGROUND: The EMCOVID project conducted a multi-centre cohort study to investigate the impact of COVID-19 on patients with Multiple Sclerosis (pwMS) receiving disease-modifying therapies (DMTs). The study aimed to evaluate the seroprevalence and persistence of SARS-CoV-2 antibodies in MS patients enrolled in the EMCOVID database. The DMTs were used to manage MS by reducing relapses, lesion accumulation, and disability progression. However, concerns arose regarding the susceptibility of pwMS to COVID-19 due to potential interactions between SARS-CoV-2 and the immune system, as well as the immunomodulatory effects of DMTs. METHODS: This prospective observational study utilized data from a Multiple Sclerosis and COVID-19 (EMCOVID-19) study. Demographic characteristics, MS history, laboratory data, SARS-CoV-2 serology, and symptoms of COVID-19 were extracted for pwMS receiving any type of DMT. The relationship between demographics, MS phenotype, DMTs, and COVID-19 was evaluated. The evolution of SARS-CoV-2 antibodies over a 6-month period was also assessed. RESULTS: The study included 709 pwMS, with 376 patients providing samples at the 6-month follow-up visit. The seroprevalence of SARS-CoV-2 antibodies was higher among pwMS than the general population, with Interferon treatment being significantly associated with greater seroprevalence (16.9% vs. 8.4%; p 0.003). However, no other specific DMT showed a significant association with antibody presence. A total of 32 patients (8.5%) tested positive for IgG, IgM, or IgA antibodies against SARS-CoV-2 at baseline, but then tested negative at 6 months. Most of the pwMS in the cohort were asymptomatic for COVID-19 and, even among symptomatic cases, the prognosis was generally favourable. CONCLUSION: pwMS undergoing DMTs exhibited a higher seroprevalence of COVID-19 than the general population. Interferon treatment was associated with a higher seroprevalence, suggesting a more robust humoral response. This study provides valuable insights into the seroprevalence and persistence of SARS-CoV-2 antibodies in pwMS and contributes to our understanding of the impact of COVID-19 amongst this population.

Key steps and suggestions for a promising approach to a critical care mentoring program.

In critical care medicine, where there is a demanding career with a problematic work-life balance, mentoring is an important support tool to grow professionally, creating a network of support throughout the career. The mentoring process consists of evidence-based steps to guide critical care mentors and mentees and pair them with each other according to the correct selection and matching of participants.In order to focus on the active role of a young intensivist selected as a mentee at any level and to support their success in a mentoring relationship, the NEXT Committee of the European Society of Intensive Care Medicine (ESICM) developed 2012 a mentoring program.The critical steps of the mentoring program start from establishing a policy and program objectives, passing through the selection of participants, and matching with mentors up to the definition of the personal development plan supported by checklists, worksheets, and evaluation forms. The present manuscript provides key steps and tips for a good, essential based on our experience in the ESICM NEXT-Mentoring Program so that they guide for future mentoring programs conducted by other scientific societies. In addition, we discuss common challenges and how to avoid them.

Would anti-choking devices be correctly and quickly managed by health science students? A manikin crossover trial.

BACKGROUND: The brand-new anti-choking devices (LifeVac® and DeCHOKER®) have been recently developed to treat Foreign Body Airway Obstruction (FBAO). However, the scientific evidence around these devices that are available to the public is limited. Therefore, this study aimed to assess the ability to use the LifeVac® and DeCHOKER® devices in an adult FBAO simulated scenario, by untrained health science students. METHODS: Forty-three health science students were asked to solve an FBAO event in three simulated scenarios: 1) using the LifeVac®, 2) using the DeCHOKER®, and 3) following the recommendations of the current FBAO protocol. A simulation-based assessment was used to analyze the correct compliance rate in the three scenarios based on the correct execution of the required steps, and the time it took to complete each one. RESULTS: Participants achieved correct compliance rates between 80-100%, similar in both devices (p = 0.192). Overall test times were significantly shorter with LifeVac® than DeCHOKER® device (36.6 sec. [31.9-44.4] vs. 50.4 s [36.7-66.9], p < 0.001). Regarding the recommended protocol, a 50% correct compliance rate was obtained in those with prior training vs. 31.3% without training, (p = 0.002). CONCLUSIONS: Untrained health science students are able to quickly and adequately use the brand-new anti-choking devices but have more difficulties in applying the current recommended FBAO protocol.

Cell-Based Fluorescent Screen Amenable to HTS to Identify Inhibitors of Bacterial Translation Initiation.

A strategy that can be applied to the research of new molecules with antibacterial activity is to look for inhibitors of essential bacterial processes within large collections of chemically heterogeneous compounds. The implementation of this approach requires the development of assays aimed at the identification of molecules interfering with specific cell pathways that can also be used in high-throughput analysis of large chemical libraries. Here, we describe a fluorescence-based whole-cell assay in Escherichia coli devised to find inhibitors of the translation initiation pathway. Translation is a complex and essential mechanism. It involves numerous sub-steps performed by factors that are in many cases sufficiently dissimilar in bacterial and eukaryotic cells to be targetable with domain-specific drugs. As a matter of fact, translation has been proven as one of the few bacterial mechanisms pharmacologically tractable with specific antibiotics. The assay described in this updated chapter is tailored to the identification of molecules affecting the first stage of translation initiation, which is the most dissimilar step in bacteria versus mammals. The effect of the compounds under analysis is measured in living cells, thus allowing evaluation of their in vivo performance as inhibitors of translation initiation. Compared with other assays for antibacterials, the major advantages of this screen are its simplicity, high mechanism specificity, and amenability to scaling up to high-throughput analyses.

Safety and efficacy of a cardiovascular polypill in people at high and very high risk without a previous cardiovascular event: the international VULCANO randomised clinical trial.

BACKGROUND: Cardiovascular (CV) polypills are a useful baseline treatment to prevent CV diseases by combining different drug classes in a single pill to simultaneously target more than one risk factor. The aim of the present trial was to determine whether the treatment with the CNIC-polypill was at least non-inferior to usual care in terms of low-density lipoprotein cholesterol (LDL-c) and systolic BP (SBP) values in subjects at high or very high risk without a previous CV event. METHODS: The VULCANO was an international, multicentre open-label trial involving 492 participants recruited from hospital clinics or primary care centres. Patients were randomised to the CNIC-polypill -containing aspirin, atorvastatin, and ramipril- or usual care. The primary outcome was the comparison of the mean change in LDL-c and SBP values after 16 weeks of treatment between treatment groups. RESULTS: The upper confidence limit of the mean change in LDL-c between treatments was below the prespecified margin (10 mg/dL) and above zero, and non-inferiority and superiority of the CNIC-polypill (p = 0.0001) was reached. There were no significant differences in SBP between groups. However, the upper confidence limit crossed the prespecified non-inferiority margin of 3 mm Hg. Significant differences favoured the CNIC-polypill in reducing total cholesterol (p = 0.0004) and non-high-density lipoprotein cholesterol levels (p = 0.0017). There were no reports of major bleeding episodes. The frequency of non-serious gastrointestinal disorders was more frequent in the CNIC-polypill arm. CONCLUSION: The switch from conventional treatment to the CNIC-polypill approach was safe and appears a reasonable strategy to control risk factors and prevent CVD. Trial registration This trial was registered in the EU Clinical Trials Register (EudraCT) the 20th February 2017 (register number 2016-004015-13; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2016-004015-13 ).

Solar Energy Harvesting to Improve Capabilities of Wearable Devices.

The market of wearable devices has been growing over the past decades. Smart wearables are usually part of IoT (Internet of things) systems and include many functionalities such as physiological sensors, processing units and wireless communications, that are useful in fields like healthcare, activity tracking and sports, among others. The number of functions that wearables have are increasing all the time. This result in an increase in power consumption and more frequent recharges of the battery. A good option to solve this problem is using energy harvesting so that the energy available in the environment is used as a backup power source. In this paper, an energy harvesting system for solar energy with a flexible battery, a semi-flexible solar harvester module and a BLE (Bluetooth® Low Energy) microprocessor module is presented as a proof-of-concept for the future integration of solar energy harvesting in a real wearable smart device. The designed device was tested under different circumstances to estimate the increase in battery lifetime during common daily routines. For this purpose, a procedure for testing energy harvesting solutions, based on solar energy, in wearable devices has been proposed. The main result obtained is that the device could permanently work if the solar cells received a significant amount of direct sunlight for 6 h every day. Moreover, in real-life scenarios, the device was able to generate a minimum and a maximum power of 27.8 mW and 159.1 mW, respectively. For the wearable system selected, Bindi, the dynamic tests emulating daily routines has provided increases in the state of charge from 19% (winter cloudy days, 4 solar cells) to 53% (spring sunny days, 2 solar cells).

The CNIC-Polypill reduces recurrent major cardiovascular events in real-life secondary prevention patients in Spain: The NEPTUNO study.

BACKGROUND: To evaluate the effectiveness of a cardiovascular polypill including aspirin, ramipril and atorvastatin (CNIC-Polypill), on the incidence of recurrent major cardiovascular events (MACE) and risk factor control in patients with established atherosclerotic cardiovascular disease (ASCVD) vs different pharmacological therapeutic strategies. METHODS: Retrospective, observational study using data from electronic-health records. Patients were distributed into 4 different cohorts: CNIC-Polypill (case cohort) vs 3 control cohorts: same monocomponents taken separately (Monocomponents), equipotent drugs (Equipotent) and other drugs not included in the previous cohorts (Other therapies). Patients were followed for 2 years or until MACE or death. RESULTS: After propensity score matching, a total of 6456 patients (1614 patients per cohort) were analysed. After 2 years, the risk of recurrent MACE was lower in the CNIC-Polypill cohort compared to the control groups (22%; p = 0.017, 25%; p = 0.002, 27%; p = 0.001, higher in the Monocomponents, Equipotent and Other therapies cohorts, respectively). The incremental proportion of patients who achieved blood pressure (BP) and low-density lipoprotein cholesterol (LDLc) control from baseline was higher in the CNIC-Polypill cohort vs control cohorts (BP controlled patients: +12.5% vs + 6.3%; p < 0.05, +2.2%; p < 0.01, +2.4%; p < 0.01, LDLc controlled patients: +10.3% vs + 4.9%; p < 0.001, +5.7%; p < 0.001, +4.9%; p < 0.001, respectively). Medication persistence was higher in patients treated with the CNIC-Polypill (72.1% vs 62.2%, 60.0% and 54.2%, respectively; p < 0.001) at study end. CONCLUSIONS: In secondary prevention patients, compared with control groups, treatment with the CNIC-Polypill was associated with significant reductions in the accumulated incidence of recurrent MACE, improved BP and LDLc control rates, and increased medication persistence.

Measuring family-centred care practices in adult intensive care units: The EMPATHIC-F questionnaire.

BACKGROUND: Engaging relatives in the care of critically ill patients is associated with better outcomes. It is crucial to empower relatives to provide feedback. Valid satisfaction instruments are essential to identify best practices and areas for improvement. AIM: The aim of the study was to adapt the Spanish version of the EMpowerment of PArents in The Intensive Care-30 (EMPATHIC-30) questionnaire in adult intensive care units (ICUs) and psychometrically test the EMpowerment of PAtients in The Intensive Care-Family (EMPATHIC-F) questionnaire to measure family satisfaction. DESIGN: This is a cross-sectional, prospective study conducted in two adult ICUs. Participants were relatives of patients who were discharged alive from the ICUs with an ICU length-of-stay >24 hours. The EMPATHIC-F questionnaire is divided into five domains that are related to the family-centred care principles. Responses are provided on a 6-point ordinal Likert scale, a score of >5 is considered acceptable. RESULTS: Patients' relatives confirmed the adaptation of the instrument. A total of 262 relatives responded to the EMPATHIC-F questionnaire (97% response rate). The empirical structure of the instrument was established by confirmatory factor analysis confirming 30 statements within five theoretically conceptualized domains: information, care and treatment, family participation, organization, and professional attitude. On item level, two statements scored a mean below 5.0. Cronbach's α at the domain level was between .64 and .75. Congruent validity was adequate between the five domains and four general satisfaction items (r's .26-.54). The non-differential validity was confirmed with no significant effect size between three patients' demographic characteristics and the domains. CONCLUSIONS: The EMPATHIC-F questionnaire is a reliable and valid quality performance indicator to measure the perceptions of family members in adult ICU settings. RELEVANCE TO CLINICAL PRACTICE: The EMPATHIC-F questionnaire can be used to benchmark and provides a framework for standardized quality improvement towards the development of a family-centred care philosophy within adult ICUs.

Minimal invasive fluorescence methods to quantify advanced glycation end products (AGEs) in skin and plasma of humans.

Advanced glycation end products (AGEs) are non-enzymatic modifications of proteins and lipids, which are spontaneously produced in the body in relation with several human diseases. Their relevance on protein functions alteration, either structural or enzymatic is under study, but their value as biomarkers or predictors of disease progression and clinical outcomes is unquestionable. The heterogeneity and amplitude of these modifications make their analysis difficult, although, different methods have been developed for specific AGEs based on colorimetric reactions, immunoassays or chromatography. However, for a massive application on human population, methods based on the autofluorescence of some AGEs stand out. Several qualities of these methods such as label-free measurement, rapidity, cost-effectiveness, and minimal invasiveness make them very useful for periodic measurements in critically ill patients and for the analysis of large populations. Here we explain the rationale of these methods, and we present a step-by-step protocol and the equipment requirements to carry out the estimation of AGE content in skin and plasma. AGE plasma content and skin accumulation are temporally related, so AGE plasmatic levels are a possible predictor of skin AGE content. On the other hand, AGE skin accumulation is a surrogate or an indicator of past AGE levels in plasma and in the rest of the body. AGE levels or their variations have shown to be related with prognosis of several diseases, so they can be used as predictor biomarkers for clinicians.

Impact of the Coronavirus Disease 2019 Pandemic on Moral Distress Among Nurses and Physicians in Spanish ICUs.

OBJECTIVES: To assess the impact of COVID-19 pandemic on moral distress (MD) among healthcare professionals (HCPs) (physicians and nurses) in Spanish ICUs. DESIGN: Cross-sectional, prospective study. SETTING: ICUs in Spain. PARTICIPANTS: HCPs currently working in Spanish ICUs. INTERVENTIONS: Data were collected via electronic survey with the use of a 50-item questionnaire in two different periods: prepandemic (October-December 2019) and during the second wave of COVID-19 (September-November 2020). MEASUREMENTS AND MAIN RESULTS: During the prepandemic and pandemic periods, 1,065 (57.1% nurses) and 1,115 (58.5% nurses) HCPs completed the questionnaire, respectively. Higher MD levels were reported during COVID-19 pandemic, particularly among ICU nurses, when compared with the prepandemic period. Before COVID-19, physicians reported significantly higher levels of MD than ICU nurses (80.0 [interquartile range {IQR}, 40.0-135.0] vs 61.0 [IQR, 35.0-133.0]; p = 0.026). These differences disappeared during the pandemic period (81.0 [IQR, 39.0-138.5] vs 74.0 [IQR, 41.0-143.0]; p = 0.837). During the pandemic, younger and less experienced HCPs working in hospital areas that were converted in ICU or in ICUs with multiple occupancy rooms reported higher MD levels. In addition, HCPs who were off work for psychologic burden reported higher MD levels (108.0 [IQR, 66.0-139.0] vs 76.0 [IQR, 40.0-141.0]; p < 0.05). In the prepandemic period, patient-level root causes were the most morally distressing for nurses, whereas physicians reported higher MD on system-level root causes. During the pandemic, both groups reported higher MD on system-level root causes. During COVID-19, significantly more HCPs considered leaving their job due to MD. CONCLUSIONS: MD has increased among ICU HCPs in Spain during COVID-19 pandemic. Physicians reported higher MD levels than nurses in the prepandemic period, whereas both HCPs groups reported similar MD levels in the pandemic period. Strategies are needed and should be implemented to mitigate MD among HCPs.

A new Oligocene-Miocene tree from Panama and historical Anacardium migration patterns.

Migration of Boreotropical megathermal taxa during the Oligocene and Miocene played a key role in assembling diversity in tropical regions. Despite scattered fossil reports, the cashew genus Anacardium offers an excellent example of such migration. The fossil woods described here come from localities in Veraguas, Panama mapped as Oligocene-Miocene. We studied, described, and identified two well-preserved specimens using wood anatomical characteristics and completed extensive comparisons between fossil and extant material. The studied fossil woods share several diagnostic features with the modern Anacardium genus, including large solitary vessels, large intervessel-pitting, a simple vessel-ray pitting pattern, and mostly 1-3 seriate rays with large rhomboidal solitary crystals. We propose a new fossil species named Anacardium gassonii sp. nov., that adds an essential piece to the understanding of the historical biogeography of the genus. In addition, our findings confirm previous interpretations of this species' migration from Europe to North America and its crossing through Panama, leading to subsequent diversification in South America. This discovery provides an important link to the historical migration patterns of the genus, supporting the notion of an Eocene migration to the Neotropics via Boreotropical bridges, as well as an Oligocene-Miocene crossing of Central America followed by diversification in South America.

Considerations and Guidance for the Structure, Organisation, and Operation of Cardiometabolic Prevention Units: A Consensus Statement of the Inter-American Society of Cardiology.

Cardiovascular diseases (CVDs) remain the leading cause of death worldwide, particularly in low- and middle-income regions such as Latin America. This is because of the combination and interaction in different proportions of a high prevalence of cardiometabolic risk factors and socio-economic and cultural characteristics. This reality brings about the need to change paradigms to consistently and systematically boost cardiovascular prevention as the most cost-effective medium- to long-term strategy to reduce their prevalence in medium- and low-resource countries, not only in Latin America but also in other global regions. To achieve the therapeutic goals in various diseases, including CVD, the current literature demonstrates that the most effective way is to carry out the patient's diagnosis and treatment in multidisciplinary units. For this reason, the Inter American Society of Cardiology (IASC) proposes the creation of cardiometabolic prevention units (CMPUs) as a regional initiative exportable throughout the world to standardise cardiovascular prevention based on the best available evidence. This ensures homogeneity in the global management of cardiometabolic risk factors and access to quality medicine independently of the population's social situation. These guidelines, written by a panel of experts in cardiovascular prevention, defines what a CMPU is, its objectives and the minimum requirements for it, as well as proposing three categories and suggesting an operational scheme. It must be used as a guide for all individuals or centres that, aware of the need for multidisciplinary and standardised work, want to create a unit for the comprehensive management of cardiometabolic risk established as an international research network. Lastly, the document makes meaningful points on the determination of cardiovascular risk and its importance. These guidelines do not cover specific targets and therapeutic schemes, as these topics will be extensively discussed in another SIAC publication, namely a statement on residual cardiometabolic risk.