Angiotensin Receptor-Neprilysin Inhibition in Acute Myocardial Infarction.

BACKGROUND: In patients with symptomatic heart failure, sacubitril-valsartan has been found to reduce the risk of hospitalization and death from cardiovascular causes more effectively than an angiotensin-converting-enzyme inhibitor. Trials comparing the effects of these drugs in patients with acute myocardial infarction have been lacking. METHODS: We randomly assigned patients with myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril-valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to recommended therapy. The primary outcome was death from cardiovascular causes or incident heart failure (outpatient symptomatic heart failure or heart failure leading to hospitalization), whichever occurred first. RESULTS: A total of 5661 patients underwent randomization; 2830 were assigned to receive sacubitril-valsartan and 2831 to receive ramipril. Over a median of 22 months, a primary-outcome event occurred in 338 patients (11.9%) in the sacubitril-valsartan group and in 373 patients (13.2%) in the ramipril group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P = 0.17). Death from cardiovascular causes or hospitalization for heart failure occurred in 308 patients (10.9%) in the sacubitril-valsartan group and in 335 patients (11.8%) in the ramipril group (hazard ratio, 0.91; 95% CI, 0.78 to 1.07); death from cardiovascular causes in 168 (5.9%) and 191 (6.7%), respectively (hazard ratio, 0.87; 95% CI, 0.71 to 1.08); and death from any cause in 213 (7.5%) and 242 (8.5%), respectively (hazard ratio, 0.88; 95% CI, 0.73 to 1.05). Treatment was discontinued because of an adverse event in 357 patients (12.6%) in the sacubitril-valsartan group and 379 patients (13.4%) in the ramipril group. CONCLUSIONS: Sacubitril-valsartan was not associated with a significantly lower incidence of death from cardiovascular causes or incident heart failure than ramipril among patients with acute myocardial infarction. (Funded by Novartis; PARADISE-MI ClinicalTrials.gov number, NCT02924727.).

Interleukin-21 in autoimmune and inflammatory skin diseases.

Studies on the role of interleukins (ILs) in autoimmune and inflammatory diseases allow for the better understanding of pathologic mechanisms of disease and reshaping of treatment modalities. The development of monoclonal antibodies targeting specific ILs or IL signaling pathways (i.e., anti-IL-17/IL-23 in psoriasis or anti-IL-4/IL-13 in atopic dermatitis) is the shining example of therapeutic interventions in research. IL-21, belonging to the group of ɣc-cytokines (IL-2, IL-4, IL-7, IL-9, and IL-15), is gaining attention for its pleiotropic role in several types of immune cells as activator of various inflammatory pathways. In both health and disease, IL-21 sustains T- and B-cell activity. Together with IL-6, IL-21 helps to generate Th17 cells, promotes CXCR5 expression in T cells, and their maturation into follicular T helper cells. In B cells, IL-21 sustains their proliferation and maturation into plasma cells and promotes class switching and antigen-specific antibody production. Due to these characteristics, IL-21 is a main factor in numerous immunologic disorders, such as rheumatoid arthritis and MS. Studies in preclinical skin disease models and on human skin strongly suggest that IL-21 is crucially involved in inflammatory and autoimmune cutaneous disorders. Here, we summarize the current knowledge of IL-21 in well-known skin diseases.

Nonunique UPGMA clusterings of microsatellite markers.

Agglomerative hierarchical clustering has become a common tool for the analysis and visualization of data, thus being present in a large amount of scientific research and predating all areas of bioinformatics and computational biology. In this work, we focus on a critical problem, the nonuniqueness of the clustering when there are tied distances, for which several solutions exist but are not implemented in most hierarchical clustering packages. We analyze the magnitude of this problem in one particular setting: the clustering of microsatellite markers using the Unweighted Pair-Group Method with Arithmetic Mean. To do so, we have calculated the fraction of publications at the Scopus database in which more than one hierarchical clustering is possible, showing that about 46% of the articles are affected. Additionally, to show the problem from a practical point of view, we selected two opposite examples of articles that have multiple solutions: one with two possible dendrograms, and the other with more than 2.5 million different possible hierarchical clusterings.

Pulmonary thrombosis associated with COVID-19 pneumonia: Beyond classical pulmonary thromboembolism.

BACKGROUND: Classical pulmonary thromboembolism (TE) and local pulmonary thrombosis (PT) have been suggested as mechanisms of thrombosis in COVID-19. However, robust evidence is still lacking because this was mainly based on retrospective studies, in which patients were included when TE was suspected. METHODS: All patients with COVID-19 pneumonia underwent computed tomography and pulmonary angiography in a prospective study. The main objective was to determine the number and percentage of thrombi surrounded by lung opacification (TSO) in each patient, as well as their relationship with percentage of lung involvement (TLI), to distinguish classical TE (with a random location of thrombi that should correspond to a percentage of TSO equivalent to the TLI) from PT. We determined TLI by artificial intelligence. Analyses at patient level (TLI and percentage of TSO) and at thrombi level (TLI and TSO) were performed. RESULTS: We diagnosed TE in 70 out of 184 patients. Three (2-8) thrombi/patient were detected. The percentage of TSO was 100% (75-100) per patient, and TLI was 19.9% (4.6-35.2). Sixty-five patients (92.9%) were above the random scenario with higher percentage of TSO than TLI. Most thrombi were TSO (n = 299, 75.1%). When evaluating by TLI (<10%, 10%-20%, 20%-30% and >30%), percentage of TSO was higher in most groups. Thrombi were mainly in subsegmental/segmental arteries, and percentage of TSO was higher in all locations. CONCLUSIONS: Thrombi in COVID-19 were found within lung opacities in a higher percentage than lung involvement, regardless of TLI and clot location, supporting the hypothesis of local PT rather than "classic TE".

TYK2 inhibition with deucravacitinib ameliorates erosive oral lichen planus.

Erosive oral lichen planus (OLP) is a challenging disease. This T cell driven disorder frequently shows a treatment unresponsive course and strongly limits patients' quality of life. The disease lacks FDA or EMA approved drugs for its treatment and the efficacy of the commonly administered treatments (i.e. topical and systemic steroids, steroid sparing agents) is often only partial. Although the etiopathogenesis of the disease still needs to be fully elucidated, recent advances helped to identify interferon-É£ (IFN-É£) as a pivotal cytokine in OLP pathogenesis, thus making the interference with its signalling a therapeutic target. Janus kinase (JAK) inhibitors therefore gained relevance for their inhibitory effect on IFN-É£ signalling. While some drugs such as abrocitinib, upadacitinib, tofacitinib directly interfere with IFN-É£ signalling through blockade of JAK1 and/or JAK2, deucravacitinib, a selective TYK-2 inhibitor indirectly interferes on IFN-É£ activation through interference with interleukin (IL)-12, a potent promotor for Th1/IFN-É£ responses. This mechanism of action makes deucravacitinib a candidate drug for the treatment of OLP. Here we provide initial evidence that deucravacitinib 6 mg daily has a beneficial effect in three patients with oral OLP.

Environmental footprint and material composition comparison of single-use and reusable duodenoscopes.

BACKGROUND: Infection outbreaks associated with contaminated reusable duodenoscopes (RUDs) have induced the development of novel single-use duodenoscopes (SUDs). This study aimed to analyze the material composition and life cycle assessment (LCA) of RUDs and SUDs to assess the sustainability of global and partial SUD implementation. METHODS: A single-center study evaluated material composition analysis and LCA of one RUD and two SUDs from different manufacturers (A/B). Material composition analysis was performed to evaluate the thermochemical properties of the duodenoscope components. The carbon footprint was calculated using environmental software. We compared the sustainability strategies of universal use of RUDs, frequent use of RUDs with occasional SUDs, and universal use of SUDs over the lifetime of one RUD. RESULTS: RUDs were substantially heavier (3489 g) than both SUD-A (943 g) and SUD-B (716 g). RUDs were mainly metal alloys (95%), whereas SUDs were mainly plastic polymers and resins (70%-81%). The LCA demonstrated the sustainability of RUDs, with a life cycle carbon footprint 62-82 times lower than universal use of SUDs (152 vs. 10 512-12 640 kg CO2eq) and 10 times lower than occasional use of SUDs (152 vs. 1417-1677 kg CO2eq). Differences were observed between SUD-A and SUD-B (7.9 vs. 6.6 kg CO2eq per endoscope). End-of-life incineration emissions for SUDs were the greatest environmental contributors. CONCLUSIONS: Widespread adoption of SUDs has greater environmental challenges; it requires a balance between infection control and environmental responsibility. Carbon footprint labelling can help healthcare institutions make sustainable choices and promote environmentally responsible healthcare practices.

Social and clinical predictors of perianal colonisation by multidrug-resistant bacteria for geriatric patients in the internal medicine service.

BACKGROUND: Colonisation by multidrug-resistant (MDR) bacteria is a global health issue. The identification of patients with a higher risk of colonisation is essential. Patients admitted to internal medicine services might represent a vulnerable population with a high risk of colonisation. This study was the first to assess social and clinical variables associated with a higher risk of perianal colonisation by MDR bacteria in a Spanish cohort of patients admitted to internal medicine service. METHODS: Patients admitted to an internal medicine service during 12 months of recruitment (1 March 2022 to 1 March 2023) were included in the study. Perianal swabs were performed at admission to identify the presence of MDR bacteria. Social and clinical variables were collected following a directed acyclic graph. A cluster analysis was performed to identify clinical profiles of higher risk. Bivariate analyses and multivariable logistic regression models were fitted to identify potential predictors of MDR bacteria colonisation. RESULTS: A total of 245 patients, according to the required sample size, were included. Of them, 46 (18.8%) were colonised by MDR bacteria in perianal swabs. Female sex, age > 80 years, dependency on activities of daily living, cognitive deterioration and living in long-term care facilities constituted the highest risk clinical profile. After adjustments, living in long-term care facilities and malnutrition remained the main risk factors identified. CONCLUSION: Patients admitted to internal medicine services presented a high frequency of perianal colonisation by MDR bacteria. Social and clinical variables associated with bio-psycho-social susceptibility were associated with colonisation. Special surveillance is needed in internal medicine services to control the transmission.

Composition dependence of X-ray stability and degradation mechanisms at lead halide perovskite single crystal surfaces.

The multiple applications of lead halide perovskite materials and the extensive use of X-ray based techniques to characterize them highlight a need to understand their stability under X-ray irradiation. Here, we present a study where the X-ray stability of five different lead halide perovskite compositions (MAPbI3, MAPbCl3, MAPbBr3, FAPbBr3, CsPbBr3) was investigated using photoelectron spectroscopy. To exclude effects of thin film formation on the observed degradation behaviors, we studied clean surfaces of single crystals. Different X-ray resistance and degradation mechanisms were observed depending on the crystal composition. Overall, perovskites based on the MA+ cation were found to be less stable than those based on FA+ or Cs+. Metallic lead formed most easily in the chloride perovskite, followed by bromide, and only very little metallic lead formation was observed for MAPbI3. MAPbI3 showed one main degradation process, which was the radiolysis of MAI. Multiple simultaneous degradation processes were identified for the bromide compositions. These processes include ion migration towards the perovskite surface and the formation of volatile and solid products in addition to metallic lead. Lastly, CsBr formed as a solid degradation product on the surface of CsPbBr3.

Continuous Positive Airway Pressure Effect on Albuminuria Progression in Patients with Obstructive Sleep Apnea and Diabetic Kidney Disease: A Randomized Clinical Trial.

Rationale: Obstructive sleep apnea (OSA) is associated with impaired glycemic control and a higher risk of vascular complications, such as diabetic kidney disease (DKD). However, the effect of apnea-hypopnea suppression on DKD progression is unclear. Objectives: To assess the effect of continuous positive airway pressure (CPAP) on the urinary albumin-to-creatinine ratio (UACR) in patients with DKD and OSA. Methods: In a 52-week, multicentric, open-label, parallel, and randomized clinical trial, 185 patients with OSA and DKD were randomized to CPAP and usual care (n = 93) or usual care alone (n = 92). Measurements and Main Results: UACR, estimated glomerular filtration rate, serum concentrations of creatinine and glycated hemoglobin, insulin resistance, lipid concentrations, sleepiness, and quality of life. A 52-week change in UACR from baseline did not differ significantly between the CPAP group and the usual-care group. However, in per-protocol analyses that included 125 participants who met prespecified criteria for adherence, CPAP treatment was associated with a great reduction in UACR (mean difference, -10.56% [95% confidence interval, -19.06 to -2.06]; P = 0.015). CPAP effect on UACR was higher in nonsleepy patients with more severe OSA, worse renal function, and a more recent diagnosis of DKD. CPAP treatment also improved glycemic control and insulin resistance, as well as sleepiness and health-related quality of life. Conclusions: In patients with OSA and DKD, the prescription of CPAP did not result in a statistically significant reduction in albuminuria. However, good adherence to CPAP treatment in addition to usual care may result in long-term albuminuria reduction compared with usual care alone. Clinical trial registered with www.clinicaltrials.gov (NCT02816762).

Design of Wearable Textile Electrodes for the Monitorization of Patients with Heart Failure.

Heart failure is a severe medical condition with an important worldwide incidence that occurs when the heart is unable to efficiently pump the patient's blood throughout the body. The monitoring of edema in the lower limbs is one of the most efficient ways to control the evolution of the condition. Impedance spectroscopy has been proposed as an efficient technique to monitor body volume in patients with heart failure. It is necessary to research new wearable devices for remote patient monitoring, which can be easily worn by patients in a continuous way. In this work, we design and implement new wearable textile electrodes for the monitoring of edema evolution in patients with heart failure. Impedance spectroscopy measurements were carried out in 5 healthy controls and 2 patients with heart failure using our wearable electrodes for 3 days. The results show the appropriateness of impedance spectroscopy and our wearable electrodes to monitor body volume evolution. Impedance spectroscopy is shown to be an efficient marker of the presence of edema in heart failure patients. Initial patient positive feedback was obtained for the use of the wearable device.

Multi-organ clinical ultrasound as a complement to the diagnostic process in an internal medicine consultation.

INTRODUCTION: Evaluating outpatient cases in internal medicine consultations presents a significant diagnostic challenge. Ultrasound can be a highly useful tool in assessment and decision-making. PATIENTS AND METHODS: A prospective observational study was conducted on a cohort of patients attending an internal medicine rapid assessment clinic. Eighty patients were prospectively recruited. A medical consultation was conducted as per usual clinical practice, followed by a POCUS evaluation; collecting pulmonary, cardiac, and abdominal data. All findings were analyzed and recorded, particularly those that were significant or altered the initial diagnosis, subsequent tests, or treatment. RESULTS: Significant ultrasound findings were found in 37.5% of the patients. Of all ultrasound scans, the most clinically relevant were in the heart region (31.9%), followed by the abdomen (26%). These findings led to a change in overall management in 27.5% of patients. Using logistic regression, a model was developed to estimate the presence of clinically relevant findings with an area under the curve (AUC) of 0.78 (95% CI 0.66-0.89; p < 0.001) with 80% Sensitivity and 66% Specificity. CONCLUSION: The systematic and standardized incorporation of clinical ultrasound in internal medicine consultations contributes to decision-making, can provide significant findings that allow for modifications in clinical suspicion and therapeutic management.

Cardiopulmonary Complications after Pulmonary Embolism in COVID-19.

Although pulmonary embolism (PE) is a frequent complication in COVID-19, its consequences remain unknown. We performed pulmonary function tests, echocardiography and computed tomography pulmonary angiography and identified blood biomarkers in a cohort of consecutive hospitalized COVID-19 patients with pneumonia to describe and compare medium-term outcomes according to the presence of PE, as well as to explore their potential predictors. A total of 141 patients (56 with PE) were followed up during a median of 6 months. Post-COVID-19 radiological lung abnormalities (PCRLA) and impaired diffusing capacity for carbon monoxide (DLCOc) were found in 55.2% and 67.6% cases, respectively. A total of 7.3% had PE, and 6.7% presented an intermediate-high probability of pulmonary hypertension. No significant difference was found between PE and non-PE patients. Univariate analysis showed that age > 65, some clinical severity factors, surfactant protein-D, baseline C-reactive protein, and both peak red cell distribution width and Interleukin (IL)-10 were associated with DLCOc < 80%. A score for PCRLA prediction including age > 65, minimum lymphocyte count, and IL-1ß concentration on admission was constructed with excellent overall performance. In conclusion, reduced DLCOc and PCRLA were common in COVID-19 patients after hospital discharge, but PE did not increase the risk. A PCRLA predictive score was developed, which needs further validation.

De novo assembly of sialotranscriptome of Hyalomma anatolicum and insights into expression dynamics in response to Theileria annulata infection.

Hyalomma anatolicum is a tick of significant one-health importance due to its role as a vector for various pathogens affecting humans, animals and the environment, such as Theileria annulata, which causes tropical theileriosis in cattle, leading to severe economic losses. When infected with pathogens like T. annulata, the salivary glands of H. anatolicum undergo gene expression changes, secrete modified proteins and activate immune responses, all of which facilitate pathogen survival and transmission by modulating the host immune response and optimizing conditions for pathogen development. Understanding these responses is crucial for developing control strategies for tick-borne diseases. To understand the interaction between H. anatolicum and T. annulata, we performed a differential gene expression analysis of H. anatolicum salivary glands. An average of approximately 25 million raw sequencing reads were generated in each replicate using Illumina Sequencing. The sequenced reads were de novo assembled and the assembled transcriptome yielded approximately 50,231 non-redundant transcripts after clustering with CD-HIT using a sequence identity of 95% and alignment coverage of 90%. The assembly quality was evaluated with BUSCO analysis and found to be 86% complete using the Arachnida dataset and then blasted against non-redundant protein sequence database from NCBI followed by counting of reads and differential expression analysis. Overall, around 2400 and 400 genes were found differentially expressed with logFC > 1 and logFC > 2 respectively at FDR < 0.05. Top up-regulated genes included Calpain, Papilin, Neprilysin, and Ankyrin repeat-containing protein. Top down-regulated genes included Scoloptoxin, and Selenoprotein S and other uncharacterized proteins. Many other up-regulated proteins with high significance were uncharacterized suggesting room for further H. anatolicum functional and structural characterization studies. To our best knowledge, this is the first study of H. anatolicum sialotranscriptome which greatly contributes to sialotranscriptome information not only as sequence database but also indicates the potential targets for development of vaccine against ticks and transmission-blocking vaccines against T. annulata.

Pathogenic relevance of antibodies against desmoglein 3 in patients with oral lichen planus.

BACKGROUND AND OBJECTIVES: Oral lichen planus (OLP) is a T cell driven disorder that significantly impairs patients' quality of life. Previous reports suggest that both cellular and humoral activities against desmoglein (dsg) 1 and 3 may be involved in OLP pathogenesis. Here, we aim to analyze the frequency of occurrence and pathological significance of anti-dsg antibodies in a large cohort of OLP patients. MATERIALS AND METHODS: OLP patients were screened for anti-dsg antibodies by enzyme-linked immunosorbent assay in three tertiary referral centers. OLP sera with anti-dsg antibodies were further analyzed by Western blot and dispase-based keratinocyte dissociation assay (DDA) to identify the targeted dsg ectodomains and to assess their pathogenicity. RESULTS: Of 151-screened individuals with OLP, only four patients (2.6%) with erosive OLP showed serum IgG against dsg1/3. Western blot analysis with recombinant dsg3 ectodomains revealed preferential recognition of the extracellular domain 5. By DDA with spontaneously immortalized human keratinocytes, none of the sera from these four patients induced acantholysis. CONCLUSIONS: Activation of humoral immunity occurs prevalently in patients with erosive OLP, probably due to epitope spreading. OLP serum antibodies are unable to induce loss of intercellular adhesion in vitro, strongly suggesting that they are not disease causing but rather an epiphenomenon.

The MultiFurcating Neighbor-Joining Algorithm for Reconstructing Polytomic Phylogenetic Trees.

Results from phylogenetic analyses that study the evolution of species according to their biological characteristics are frequently structured as phylogenetic trees. One of the most widely used methods for reconstructing them is the distance-based method known as the neighbor-joining (NJ) algorithm. It is known that the NJ algorithm can produce different phylogenetic trees depending on the order of the taxa in the input matrix of evolutionary distances, because the method only yields bifurcating branches or dichotomies. According to this, results and conclusions published in articles that only calculate one of the possible dichotomic phylogenetic trees are somehow biased. We have generalized the formulas used in the NJ algorithm to cope with Multifurcating branches or polytomies, and we have called this new variant of the method the multifurcating neighbor-joining (MFNJ) algorithm. Instead of the dichotomic phylogenetic trees reconstructed by the NJ algorithm, the MFNJ algorithm produces polytomic phylogenetic trees. The main advantage of using the MFNJ algorithm is that only one phylogenetic tree can be obtained, which makes the experimental section of any study completely reproducible and unbiased to external issues such as the input order of taxa.

DFV890: a new oral NLRP3 inhibitor-tested in an early phase 2a randomised clinical trial in patients with COVID-19 pneumonia and impaired respiratory function.

BACKGROUND: Coronavirus-associated acute respiratory distress syndrome (CARDS) has limited effective therapy to date. NLRP3 inflammasome activation induced by SARS-CoV-2 in COVID-19 contributes to cytokine storm. METHODS: This randomised, multinational study enrolled hospitalised patients (18-80 years) with COVID-19-associated pneumonia and impaired respiratory function. Eligible patients were randomised (1:1) via Interactive Response Technology to DFV890 + standard-of-care (SoC) or SoC alone for 14 days. Primary endpoint was APACHE II score at Day 14 or on day-of-discharge (whichever-came-first) with worst-case imputation for death. Other key assessments included clinical status, CRP levels, SARS-CoV-2 detection, other inflammatory markers, in-hospital outcomes, and safety. FINDINGS: Between May 27, 2020 and December 24, 2020, 143 patients (31 clinical sites, 12 countries) were randomly assigned to DFV890 + SoC (n = 71) or SoC alone (n = 72). Primary endpoint to establish clinical efficacy of DFV890 vs. SoC, based on combined APACHE II score, was not met; LSM (SE), 8·7 (1.06) vs. 8·6 (1.05); p = 0.467. More patients treated with DFV890 vs. SoC showed ≥ 1-level improvement in clinical status (84.3% vs. 73.6% at Day 14), earlier clearance of SARS-CoV-2 (76.4% vs. 57.4% at Day 7), and mechanical ventilation-free survival (85.7% vs. 80.6% through Day 28), and there were fewer fatal events in DFV890 group (8.6% vs. 11.1% through Day 28). DFV890 was well tolerated with no unexpected safety signals. INTERPRETATION: DFV890 did not meet statistical significance for superiority vs. SoC in primary endpoint of combined APACHE II score at Day 14. However, early SARS-CoV-2 clearance, improved clinical status and in-hospital outcomes, and fewer fatal events occurred with DFV890 vs. SoC, and it may be considered as a protective therapy for CARDS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04382053.

Interface Energy Alignment between Lead Halide Perovskite Single Crystals and TIPS-Pentacene.

At present, there is a huge development in optoelectronic applications using lead halide perovskites. Considering that device performance is largely governed by the transport of charges across interfaces and, therefore, the interfacial electronic structure, fundamental investigations of perovskite interfaces are highly necessary. In this study, we use high-resolution soft X-ray photoelectron spectroscopy based on synchrotron radiation to explore the interfacial energetics for the molecular layer of TIPS-pentacene and lead halide perovskite single crystals. We perform ultrahigh vacuum studies on multiple thicknesses of an in situ formed interface of TIPS-pentacene with four different in situ cleaved perovskite single crystals (MAPbI3, MAPbBr3, FAPbBr3, and CsxFA1-xPbBryI3-y). Our findings reveal a substantial shift of the TIPS-pentacene energy levels toward higher binding energies with increasing thickness, while the perovskite energy levels remain largely unaffected regardless of their composition. These shifts can be interpreted as band bending in the TIPS-pentacene, and such effects should be considered when assessing the energy alignment at perovskite/organic transport material interfaces. Furthermore, we were able to follow a reorganization on the MAPbI3 surface with the transformation of the surface C 1s into bulk C 1s.

Do Elderly Patients with Heart Failure and Reduced Ejection Fraction Benefit from Pharmacological Strategies for Prevention of Arrhythmic Events?

BACKGROUND: Heart failure is associated with aging. It is one of the leading causes of morbidity and mortality in Western countries and constitutes the main cause of hospitalization among elderly patients. The pharmacological therapy of patients with heart failure with reduced ejection fraction (HFrEF) has greatly improved during the last years. However, elderly patients less frequently receive recommended medical treatment. SUMMARY: The quadruple therapy (sacubitril/valsartan, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors) is nowadays the cornerstone of medical treatment since it associates lower risk of heart failure hospitalizations and mortality (also of arrhythmic origin). Cardiac arrhythmias, including sudden cardiac death, are common in patients with HFrEF, entailing worse prognosis. Previous studies addressing the role of blocking the renin-angiotensin-aldosterone system and beta-adrenergic receptors in HFrEF have suggested different beneficial effects on arrhythmia mechanisms. Therefore, the lower mortality associated with the use of the four pillars of HFrEF therapy depends, in part, on lower sudden (mostly arrhythmic) cardiac death. KEY MESSAGES: In this review, we highlight and assess the role of the four pharmacological groups that constitute the central axis of the medical treatment of patients with HFrEF in clinical prognosis and prevention of arrhythmic events, with special focus on the elderly patient, since evidence supports that most benefits provided are irrespective of age, but elderly patients receive less often guideline-recommended medical treatment.

An approach for prevention planning based on the prevalence and comorbidity of neurodevelopmental disorders in 6-year-old children receiving primary care consultations on the island of Menorca.

BACKGROUND: Few studies have estimated the real prevalence of neurodevelopmental disorders according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) in Spain and worldwide. However, there are disparate prevalence figures. We consider research in this field essential to improve early detection, secondary prevention, and health planning. METHODS: The Minikid ADHD and TICS-Mini International Neuropsychiatric Interview for Children and Adolescents, the Autism Spectrum Quotient (Children's version, AQ- Child) and a protocol of general medical questions were administered for screening purposes. The PROLEXIA battery for children aged from 4 to 6 years was used for direct assessments. Parents provided information on emotional, medical, and school aspects. The final population evaluated using these tools consisted of 291 6-year-old subjects. RESULTS: The overall risk of presenting with a neurodevelopmental disorder was 55.4%. A 23.4% risk of presenting with attention-deficit/hyperactivity disorder (ADHD) in any modality (inattentive, hyperactive-impulsive and combined), a 2.8% risk of developing autism spectrum disorder (ASD), a 30.6% risk of presenting with a learning disorder with reading difficulties, a 5.5% risk of tics and a 22.5% risk of language problems (incomprehensible language or minor language problems) were detected in the sample. The most common combination of disorders was learning and language difficulties, accounting for 6.9% of the sample. The second most frequent combination was the presence of learning and language difficulties and ADHD, accounting for 4.5% of the sample. CONCLUSIONS: The prevalence of risks detected in our sample seems to be consistent with national and international studies. A significant proportion of our sample had never been previously diagnosed (85%), so early detection programs are recommended.

Quality improvement collaborative to optimize heart failure care in patients from a network of clinics in Argentina during the COVID-19 pandemic.

Heart failure (HF) is a major clinical and public health problem associated with significant mortality, morbidity, and health-care costs. Despite the existence of evidence-based guidelines for the optimal treatment of HF, the quality of care remains suboptimal. Our aim was to increase the use a care bundle in 50% of enrolled subjects during their hospitalization and discharge and to reduce their readmission for HF causes by 10%. We conducted an uncontrolled before-after study in eight hospitals in Argentina to evaluate the effect of a quality improvement intervention on the use of an HF care bundle in patients with HF New York Heart Association (NYHA) Class II-III. The HF bundle of care included medication, continuum of care, lifestyle habits, and predischarge examinations. Training and follow-up of multidisciplinary teams in each center were performed through learning sessions and plan-do-study-act improvement cycles. Data collectors reviewed bundle compliance in the health records of recruited patients after their hospital discharge and verified readmissions through phone calls to patients within 30-40 days after discharge. We recruited 200 patients (83 before and 127 during the intervention phase), and bundle compliance increased from 9.6% to 28.3% [odds ratio 3.71, 95% confidence interval (8.46; 1.63); P = .002]. Despite a slow improvement during the first months, bundle compliance gained momentum near the end of the intervention surpassing 80%. We observed a non-significant decreased readmission rate within 30 days of discharge due to HF in the postintervention period [8.4% vs. 5.5%, odds ratio 0.63, 95% CI (1.88; 0.21); P = .410]. Qualitative analysis showed that members of the intervention teams acknowledged the improvement of work organization and standardization of care, teamwork, shared mental model, and health record completeness as well as the utility of training fellows. Despite the challenges related to the pandemic, better care of patients with HF NYHA Class II-III was possible through simple interventions and collaborative work. Graphical abstract.