Management of hyponatremia associated with acute porphyria-proposal for the use of tolvaptan

Hyponatremia is a common feature during the neurovisceral acute attacks which characterize hepatic porphyrias, as well as a sign of its severity. Therapeutic options for first-line acute attacks are intravenous administration of glucose and/or exogenous heme. The former treatment can aggravate hyponatremia by dilution and cause seizures; thus, the correction of hyponatremia must be carried out with extreme caution. This review summarizes recommendations for the management of hyponatremia during acute episodes of porphyria. Hyponatremia should be corrected slowly and seizures treated with medications in order to not exacerbate motor and sensory axonal neuropathy. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is considered a frequent cause of hyponatremia in acute porphyrias and must be identified as a symptom of an acute porphyria attack. Tolvaptan produces aquaresis and is considered a safe drug in porphyria. However, its use has only been reported in isolated cases during a porphyria attack. The convenience and usefulness of this drug in acute porphyria are discussed

A personalized intervention to prevent depression in primary care based on risk predictive algorithms and decision support systems: protocol of the e-predictD study

The predictD is an intervention implemented by general practitioners (GPs) to prevent depression, which reduced the incidence of depression-anxiety and was cost-effective. The e-predictD study aims to design, develop, and evaluate an evolved predictD intervention to prevent the onset of major depression in primary care based on Information and Communication Technologies, predictive risk algorithms, decision support systems (DSSs), and personalized prevention plans (PPPs). A multicenter cluster randomized trial with GPs randomly assigned to the e-predictD intervention + care-as-usual (CAU) group or the active-control + CAU group and 1-year follow-up is being conducted. The required sample size is 720 non-depressed patients (aged 18–55 years), with moderate-to-high depression risk, under the care of 72 GPs in six Spanish cities. The GPs assigned to the e-predictD-intervention group receive brief training, and those assigned to the control group do not. Recruited patients of the GPs allocated to the e-predictD group download the e-predictD app, which incorporates validated risk algorithms to predict depression, monitoring systems, and DSSs. Integrating all inputs, the DSS automatically proposes to the patients a PPP for depression based on eight intervention modules: physical exercise, social relationships, improving sleep, problem-solving, communication skills, decision-making, assertiveness, and working with thoughts. This PPP is discussed in a 15-min semi-structured GP-patient interview. Patients then choose one or more of the intervention modules proposed by the DSS to be self-implemented over the next 3 months. This process will be reformulated at 3, 6, and 9 months but without the GP–patient interview. Recruited patients of the GPs allocated to the control-group+CAU download another version of the e-predictD app, but the only intervention that they receive via the app is weekly brief psychoeducational messages (active-control group). The primary outcome is the cumulative incidence of major depression measured by the Composite International Diagnostic Interview at 6 and 12 months. Other outcomes include depressive symptoms (PHQ-9) and anxiety symptoms (GAD-7), depression risk (predictD risk algorithm), mental and physical quality of life (SF-12), and acceptability and satisfaction (‘e-Health Impact' questionnaire) with the intervention. Patients are evaluated at baseline and 3, 6, 9, and 12 months. An economic evaluation will also be performed (cost-effectiveness and cost-utility analysis) from two perspectives, societal and health systems.Trial registrationClinicalTrials.gov, identifier: NCT03990792

Clinical features and health-related quality of life in adult patients with mucopolysaccharidosis IVA: the Spanish experience

Background: Mucopolysaccharidosis (MPS) IVA or Morquio A syndrome is a progressive and disabling disease characterized by a deficiency of the enzyme N-acetylgalactosamine-6-sulphate sulphatase. Its clinical presentation is very heterogeneous and poorly understood in adults. The aim of this study was to describe the clinical manifestations of MPS IVA in adult patients in Spain and to assess their health-related quality of life (HRQoL). Results: Thirty-three patients from nine reference centres participated in the study. The median age was 32 (interquartile range [IQR]: 20.5–40.5) years. The phenotype was classical in 54.5% of patients, intermediate in 33.3% of patients, and non-classical in 12.1% of patients. The most common clinical manifestation was bone dysplasia, with a median height of 118 (IQR: 106–136) cm. Other frequent clinical manifestations were hearing loss (75.7%), ligamentous laxity (72.7%), odontoid dysplasia (69.7%), limb deformities that required orthopaedic aids (mainly hip dysplasia and genu valgus) (63.6%), and corneal clouding (60.6%). In addition, 36.0% of patients had obstructive sleep apnoea/hypopnoea syndrome and 33.3% needed non-invasive ventilation. Cervical surgery and varisation osteotomy were the most common surgical interventions (36.4% each). Almost 80% of patients had mobility problems and 36.4% used a wheelchair at all times. Furthermore, 87.9% needed help with self-care, 33.3% were fully dependent, and 78.8% had some degree of pain. HRQoL according to the health assessment questionnaire was 1.43 (IQR: 1.03–2.00) in patients with the non-classical phenotype, but 2.5 (IQR: 1.68–3.00) in those with the classical phenotype. Seven patients were initiated on enzyme replacement therapy (ERT), but two of them were lost to follow-up. Lung function improved in four patients and slightly worsened in one patient. The distance achieved in the six-minute walk test increased in the four patients who could perform it. HRQoL was better in patients treated with elosulfase alfa, with a median (IQR) of 1.75 (1.25–2.34) versus 2.25 (1.62–3.00) in patients not treated with ERT. Conclusions: The study provides real-world data on patients with MPS IVA. Limited mobility, difficulties with self-care, dependence, and pain were common, together with poor HRQoL. The severity and heterogeneity of clinical manifestations require the combined efforts of multidisciplinary teams

A personalized intervention to prevent depression in primary care based on risk predictive algorithms and decision support systems: protocol of the e-predictD study

The predictD is an intervention implemented by general practitioners (GPs) to prevent depression, which reduced the incidence of depression-anxiety and was cost-effective. The e-predictD study aims to design, develop, and evaluate an evolved predictD intervention to prevent the onset of major depression in primary care based on Information and Communication Technologies, predictive risk algorithms, decision support systems (DSSs), and personalized prevention plans (PPPs). A multicenter cluster randomized trial with GPs randomly assigned to the e-predictD intervention + care-as-usual (CAU) group or the active-control + CAU group and 1-year follow-up is being conducted. The required sample size is 720 non-depressed patients (aged 18–55 years), with moderate-to-high depression risk, under the care of 72 GPs in six Spanish cities. The GPs assigned to the e-predictD-intervention group receive brief training, and those assigned to the control group do not. Recruited patients of the GPs allocated to the e-predictD group download the e-predictD app, which incorporates validated risk algorithms to predict depression, monitoring systems, and DSSs. Integrating all inputs, the DSS automatically proposes to the patients a PPP for depression based on eight intervention modules: physical exercise, social relationships, improving sleep, problem-solving, communication skills, decision-making, assertiveness, and working with thoughts. This PPP is discussed in a 15-min semi-structured GP-patient interview. Patients then choose one or more of the intervention modules proposed by the DSS to be self-implemented over the next 3 months. This process will be reformulated at 3, 6, and 9 months but without the GP–patient interview. Recruited patients of the GPs allocated to the control-group+CAU download another version of the e-predictD app, but the only intervention that they receive via the app is weekly brief psychoeducational messages (active-control group). The primary outcome is the cumulative incidence of major depression measured by the Composite International Diagnostic Interview at 6 and 12 months. Other outcomes include depressive symptoms (PHQ-9) and anxiety symptoms (GAD-7), depression risk (predictD risk algorithm), mental and physical quality of life (SF-12), and acceptability and satisfaction (‘e-Health Impact' questionnaire) with the intervention. Patients are evaluated at baseline and 3, 6, 9, and 12 months. An economic evaluation will also be performed (cost-effectiveness and cost-utility analysis) from two perspectives, societal and health systems.Trial registrationClinicalTrials.gov, identifier: NCT03990792

Large-scale unit commitment under uncertainty: an updated literature survey

The Unit Commitment problem in energy management aims at finding the optimal production schedule of a set of generation units, while meeting various system-wide constraints. It has always been a large-scale, non-convex, difficult problem, especially in view of the fact that, due to operational requirements, it has to be solved in an unreasonably small time for its size. Recently, growing renewable energy shares have strongly increased the level of uncertainty in the system, making the (ideal) Unit Commitment model a large-scale, non-convex and uncertain (stochastic, robust, chance-constrained) program. We provide a survey of the literature on methods for the Uncertain Unit Commitment problem, in all its variants. We start with a review of the main contributions on solution methods for the deterministic versions of the problem, focussing on those based on mathematical programming techniques that are more relevant for the uncertain versions of the problem. We then present and categorize the approaches to the latter, while providing entry points to the relevant literature on optimization under uncertainty. This is an updated version of the paper "Large-scale Unit Commitment under uncertainty: a literature survey" that appeared in 4OR 13(2), 115--171 (2015); this version has over 170 more citations, most of which appeared in the last three years, proving how fast the literature on uncertain Unit Commitment evolves, and therefore the interest in this subject

Seguimiento de las guías españolas para el manejo del asma por el médico de atención primaria: un estudio observacional ambispectivo

Objetivo Evaluar el grado de seguimiento de las recomendaciones de las versiones de la Guía española para el manejo del asma (GEMA 2009 y 2015) y su repercusión en el control de la enfermedad. Material y métodos Estudio observacional y ambispectivo realizado entre septiembre del 2015 y abril del 2016, en el que participaron 314 médicos de atención primaria y 2.864 pacientes. Resultados Utilizando datos retrospectivos, 81 de los 314 médicos (25, 8% [IC del 95%, 21, 3 a 30, 9]) comunicaron seguir las recomendaciones de la GEMA 2009. Al inicio del estudio, 88 de los 314 médicos (28, 0% [IC del 95%, 23, 4 a 33, 2]) seguían las recomendaciones de la GEMA 2015. El tener un asma mal controlada (OR 0, 19, IC del 95%, 0, 13 a 0, 28) y presentar un asma persistente grave al inicio del estudio (OR 0, 20, IC del 95%, 0, 12 a 0, 34) se asociaron negativamente con tener un asma bien controlada al final del seguimiento. Por el contrario, el seguimiento de las recomendaciones de la GEMA 2015 se asoció de manera positiva con una mayor posibilidad de que el paciente tuviera un asma bien controlada al final del periodo de seguimiento (OR 1, 70, IC del 95%, 1, 40 a 2, 06). Conclusiones El escaso seguimiento de las guías clínicas para el manejo del asma constituye un problema común entre los médicos de atención primaria. Un seguimiento de estas guías se asocia con un control mejor del asma. Existe la necesidad de actuaciones que puedan mejorar el seguimiento por parte de los médicos de atención primaria de las guías para el manejo del asma. Objective: To assess the degree of compliance with the recommendations of the 2009 and 2015 versions of the Spanish guidelines for managing asthma (Guía Española para el Manejo del Asma [GEMA]) and the effect of this compliance on controlling the disease. Material and methods: We conducted an observational ambispective study between September 2015 and April 2016 in which 314 primary care physicians and 2864 patients participated. Results: Using retrospective data, we found that 81 of the 314 physicians (25.8%; 95% CI 21.3–30.9) stated that they complied with the GEMA2009 recommendations. At the start of the study, 88 of the 314 physicians (28.0%; 95% CI 23.4–33.2) complied with the GEMA2015 recommendations. Poorly controlled asthma (OR, 0.19; 95% CI 0.13–0.28) and persistent severe asthma at the start of the study (OR, 0.20; 95% CI 0.12–0.34) were negatively associated with having well-controlled asthma by the end of the follow-up. In contrast, compliance with the GEMA2015 recommendations was positively associated with a greater likelihood that the patient would have well-controlled asthma by the end of the follow-up (OR, 1.70; 95% CI 1.40–2.06). Conclusions: Low compliance with the clinical guidelines for managing asthma is a common problem among primary care physicians. Compliance with these guidelines is associated with better asthma control. Actions need to be taken to improve primary care physician compliance with the asthma management guidelines

Novel molecular targeted therapies for patients with neurofibromatosis type 1 with inoperable plexiform neurofibromas: a comprehensive review

Neurofibromatosis type 1 (NF1) is a genetic disorder that carries a higher risk of tumor development. Plexiform neurofibromas (PNs) are present in 50% of NF1 and cause significant morbidity when surgery is not feasible. Systemic therapies had not succeeded to reduce PN tumor volume until 2016 when the first trial with an MAPK/extracellular-signal-regulated kinase (MEK) inhibitor was published. We performed a systematic research on novel targeted therapies for patients with NF1 and PNs in PubMed, EMBASE, and conference abstracts with the last update in February 2021. Since 2016, seven trials have reported positive results with MEK inhibitors and other molecular targeted therapies (cabozantinib). Selumetinib has shown an overall response rate of 68% in children with NF1 and symptomatic inoperable PNs, and was associated with pain improvement and a manageable adverse events profile. This led to Food and Drug Administration (FDA) approval of selumetinib in May 2020. Recently, cabozantinib and mirdametinib have also proven their efficacy in adult population. Other MEK inhibitors such as trametinib and binimetinib have also communicated promising preliminary results. Ongoing trials in different populations and with intermittent dosing strategies are underwa

First record of Beauveria bassiana (Ascomycota: Clavicipitaceae) infecting Cerambyx welensii (Coleoptera: Cerambycidae) and pathogenicity tests using a new bioassay method

The pathogenicity of Beauveria bassiana on Cerambyx welensii is first reported. Three native fungal isolates from Badajoz (Spain) were bioassayed on neonates using cork oak disks and LC50s were 1.16–1.76 × 105 and 0.30–0.61 × 105 spores/ml on the 7th and 14th day post-inoculation. The fungus is potentially a biocontrol agent of C. welensii