[Referral Criteria for Asthma: An Updated Consensus]. / Criterios de derivación en asma: Actualización documento de consenso.

Asthma is one of the most prevalent chronic diseases in Spain. In 2019, the Spanish Society of Allergology and Clinical Immunology (SEAIC), the Spanish Society of Primary Care Physicians (SEMERGEN), the Spanish Society of Family and Community Medicine (semFYC), the Spanish Society of General and Family Physicians (SEMG) and the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) drafted a document laying down the criteria for referral and action guidelines in the diagnosis, control and monitoring of the asthmatic patient to facilitate ongoing care and improved attention in every setting. The new circumstances derived from the Covid-19 pandemic have demanded that some of the recommendations of the previous edition be updated and adapted to the new healthcare situation.

Identification of Selective Inhibitors of Plasmodium N-Myristoyltransferase by High-Throughput Screening.

New drugs that target Plasmodium species, the causative agents of malaria, are needed. The enzyme N-myristoyltransferase (NMT) is an essential protein, which catalyzes the myristoylation of protein substrates, often to mediate membrane targeting. We screened ∼1.8 million small molecules for activity against Plasmodium vivax (P. vivax) NMT. Hits were triaged based on potency and physicochemical properties and further tested against P. vivax and Plasmodium falciparum (P. falciparum) NMTs. We assessed the activity of hits against human NMT1 and NMT2 and discarded compounds with low selectivity indices. We identified 23 chemical classes specific for the inhibition of Plasmodium NMTs over human NMTs, including multiple novel scaffolds. Cocrystallization of P. vivax NMT with one compound revealed peptide binding pocket binding. Other compounds show a range of potential modes of action. Our data provide insight into the activity of a collection of selective inhibitors of Plasmodium NMT and serve as a starting point for subsequent medicinal chemistry efforts.

Quantification of inaccurate diagnosis of COPD in primary care medicine: an analysis of the COACH clinical audit.

Background: Inaccurate diagnosis in COPD is a current problem with relevant consequences in terms of inefficient health care, which has not been thoroughly studied in primary care medicine. The aim of the present study was to evaluate the degree of inaccurate diagnosis in Primary Care in Spain and study the determinants associated with it. Methods: The Community Assessment of COPD Health Care (COACH) study is a national, observational, randomized, non-interventional, national clinical audit aimed at evaluating clinical practice for patients with COPD in primary care medicine in Spain. For the present analysis, a correct diagnosis was evaluated based on previous exposure and airway obstruction with and without the presence of symptoms. The association of patient-level and center-level variables with inaccurate diagnosis was studied using multivariate multilevel binomial logistic regression models. Results: During the study 4,307 cases from 63 centers were audited. The rate of inaccurate diagnosis was 82.4% (inter-regional range from 76.8% to 90.2%). Patient-related interventions associated with inaccurate diagnosis were related to active smoking, lung function evaluation, and specific therapeutic interventions. Center-level variables related to the availability of certain complementary tests and different aspects of the resources available were also associated with an inaccurate diagnosis. Conclusions: The prevalence data for the inaccurate diagnosis of COPD in primary care medicine in Spain establishes a point of reference in the clinical management of COPD. The descriptors of the variables associated with this inaccurate diagnosis can be used to identify cases and centers in which inaccurate diagnosis is occurring considerably, thus allowing for improvement.

Community Assessment of COPD Health Care (COACH) study: a clinical audit on primary care performance variability in COPD care.

BACKGROUND: A thorough evaluation of the adequacy of clinical practice in a designated health care setting and temporal context is key for clinical care improvement. This study aimed to perform a clinical audit of primary care to evaluate clinical care delivered to patients with COPD in routine clinical practice. METHODS: The Community Assessment of COPD Health Care (COACH) study was an observational, multicenter, nationwide, non-interventional, retrospective, clinical audit of randomly selected primary care centers in Spain. Two different databases were built: the resources and organization database and the clinical database. From January 1, 2015 to December 31, 2016 consecutive clinical cases of COPD in each participating primary care center (PCC) were audited. For descriptive purposes, we collected data regarding the age at diagnosis of COPD and the age at audit, gender, the setting of the PCC (rural/urban), and comorbidities for each patient. Two guidelines widely and uniformly used in Spain were carefully reviewed to establish a benchmark of adequacy for the audited cases. Clinical performance was analyzed at the patient, center, and regional levels. The degree of adequacy was categorized as excellent (> 80%), good (60-80%), adequate (40-59%), inadequate (20-39%), and highly inadequate (< 20%). RESULTS: During the study 4307 cases from 63 primary care centers in 6 regions of the country were audited. Most evaluated parameters were judged to fall in the inadequate performance category. A correct diagnosis based on previous exposure plus spirometric obstruction was made in an average of 17.6% of cases, ranging from 9.8 to 23.3% depending on the region. During the audited visit, only 67 (1.6%) patients had current post-bronchodilator obstructive spirometry; 184 (4.3%) patients had current post-bronchodilator obstructive spirometry during either the audited or initial diagnostic visit. Evaluation of dyspnea was performed in 11.1% of cases. Regarding treatment, 33.6% received no maintenance inhaled therapies (ranging from 31.3% in GOLD A to 7.0% in GOLD D). The two most frequently registered items were exacerbations in the previous year (81.4%) and influenza vaccination (87.7%). CONCLUSIONS: The results of this audit revealed a large variability in clinical performance across centers, which was not fully attributable to the severity of the disease.

Do not do in COPD: consensus statement on overuse.

Background: To identify practices that do not add value, cause harm, or subject patients with chronic obstructive pulmonary disease (COPD) to a level of risk that outweighs possible benefits (overuse). Methods: A qualitative approach was applied. First, a multidisciplinary group of healthcare professionals used the Metaplan technique to draft and rank a list of overused procedures as well as self-care practices in patients with stable and exacerbated COPD. Second, in successive consensus-building rounds, description files were created for each "do not do" (DND) recommendation, consisting of a definition, description, quality of supporting evidence for the recommendation, and the indicator used to measure the degree of overuse. The consensus group comprised 6 pulmonologists, 2 general practitioners, 1 nurse, and 1 physiotherapist. Results: In total, 16 DND recommendations were made for patients with COPD: 6 for stable COPD, 6 for exacerbated COPD, and 4 concerning self-care. Conclusion: Overuse poses a risk for patients and jeopardizes care quality. These 16 DND recommendations for COPD will lower care risks and improve disease management, facilitate communication between physicians and patients, and bolster patient ability to provide self-care.

Trait-based approaches to analyze links between the drivers of change and ecosystem services: Synthesizing existing evidence and future challenges.

Understanding the responses of biodiversity to drivers of change and the effects of biodiversity on ecosystem properties and ecosystem services is a key challenge in the context of global environmental change. We performed a systematic review and meta-analysis of the scientific literature linking direct drivers of change and ecosystem services via functional traits of three taxonomic groups (vegetation, invertebrates, and vertebrates) to: (1) uncover trends and research biases in this field; and (2) synthesize existing empirical evidence. Our results show the existence of important biases in published studies related to ecosystem types, taxonomic groups, direct drivers of change, ecosystem services, geographical range, and the spatial scale of analysis. We found multiple evidence of links between drivers and services mediated by functional traits, particularly between land-use changes and regulating services in vegetation and invertebrates. Seventy-five functional traits were recorded in our sample. However, few of these functional traits were repeatedly found to be associated with both the species responses to direct drivers of change (response traits) and the species effects on the provision of ecosystem services (effect traits). Our results highlight the existence of potential "key functional traits," understood as those that have the capacity to influence the provision of multiple ecosystem services, while responding to specific drivers of change, across a variety of systems and organisms. Identifying "key functional traits" would help to develop robust indicator systems to monitor changes in biodiversity and their effects on ecosystem functioning and ecosystem services supply.

Hitting the caspofungin salvage pathway of human-pathogenic fungi with the novel lasso peptide humidimycin (MDN-0010).

Fungal infections have increased dramatically in the last 2 decades, and fighting infectious diseases requires innovative approaches such as the combination of two drugs acting on different targets or even targeting a salvage pathway of one of the drugs. The fungal cell wall biosynthesis is inhibited by the clinically used antifungal drug caspofungin. This antifungal activity has been found to be potentiated by humidimycin, a new natural product identified from the screening of a collection of 20,000 microbial extracts, which has no major effect when used alone. An analysis of transcriptomes and selected Aspergillus fumigatus mutants indicated that humidimycin affects the high osmolarity glycerol response pathway. By combining humidimycin and caspofungin, a strong increase in caspofungin efficacy was achieved, demonstrating that targeting different signaling pathways provides an excellent basis to develop novel anti-infective strategies.

Sponge-derived Kocuria and Micrococcus spp. as sources of the new thiazolyl peptide antibiotic kocurin.

Forty four marine actinomycetes of the family Microccocaceae isolated from sponges collected primarily in Florida Keys (USA) were selected from our strain collection to be studied as new sources for the production of bioactive natural products. A 16S rRNA gene based phylogenetic analysis showed that the strains are members of the genera Kocuria and Micrococcus. To assess their biosynthetic potential, the strains were PCR screened for the presence of secondary metabolite genes encoding nonribosomal synthetase (NRPS) and polyketide synthases (PKS). A small extract collection of 528 crude extracts generated from nutritional microfermentation arrays was tested for the production of bioactive secondary metabolites against clinically relevant strains (Bacillus subtilis, methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumannii and Candida albicans). Three independent isolates were shown to produce a new anti-MRSA bioactive compound that was identified as kocurin, a new member of the thiazolyl peptide family of antibiotics emphasizing the role of this family as a prolific resource for novel drugs.

Kocurin, the true structure of PM181104, an anti-methicillin-resistant Staphylococcus aureus (MRSA) thiazolyl peptide from the marine-derived bacterium Kocuria palustris.

A new thiazolyl peptide, kocurin (1), was isolated from culture broths of a marine-derived Kocuria palustris. Its structural elucidation was accomplished using a combination of spectroscopic and chemical methods, including HRMS, extensive 1D and 2D NMR analysis, MS/MS fragmentation, and chemical degradation and Marfey's analysis of the resulting amino acid residues. The structure herein reported corrects that previously assigned to PM181104 (3). Kocurin displayed activity against methicillin-resistant Staphylococcus aureus (MRSA), with MIC values in the submicromolar range.