List of Medicines to Avoid in Primary Care Health and Their Application In Polymedicated Patients

[Resumen] Introduction: La alta prevalencia del uso de medicación inadecuada y sus importantes consecuencias para la salud requieren herramientas específicas y ágiles que ayuden a detectarla y evitarla. Objetivo de este trabajo fue elaborar un listado de medicamentos a evitar en AP y aplicarlo en pacientes polimedicados de un servicio asistencial de Atención Primaria (AP). Métodos: En la Base de datos del Consejo General de Colegios Oficiales de Farmacéuticos español (BOT-Plus) se comprobó el estado y disponibilidad de cada uno de los 93 medicamentos del Listado Prescrire 2019. Se elaboró el Listado de medicamentos a evitar en AP con aquellos que estaban comercializados en España y se excluyeron los que no estaban financiados y los de uso exclusivo hospitalario. 2 2 Con el listado de medicamentos a evitar en AP se hizo un análisis retrospectivo de todos (N=262) los informes de prescripción de polimedicados >10 medicamentos del año 2017 en un servicio asistencial de AP (5 centros de salud). Se realizó análisis de frecuencias, medidas de tendencia central y dispersión; se estimaron (IC 95%) y se utilizó X o exacta de Fisher para determinar la asociación entre variables y análisis de regresión logística. Resultados: Se observó una prevalencia de polimedicados de 1,2%, con una media de edad de 71,7 ± 12,4 años y una media de prescripciones de 12 ±1,7 medicamentos. El listado de medicamentos a evitar en AP incluyó 45 principios activos. Los fármacos a evitar más usados han sido: duloxetina, sitagliptina y olmesartán. El 50,4% de los polimedicados tenían al menos un medicamento a evitar y una edad media de 68,5±11,8 años. El sexo fue un factor de riesgo de prescripción inadecuada, el hecho de ser mujer incrementa con un OR=1,8 (IC 95%=1,3-3,0) la probabilidad de medicamentos a evitar. Conclusiones: Un alto porcentaje de pacientes polimedicados tienen prescripto al menos un medicamento a evitar. El listado de medicamentos a evitar en AP es una herramienta útil para identificar la medicación inadecuada y para uso de los profesionales de AP.[Abstract] Introduction: The high prevalence of inappropriate medication use and its important health consequences for health require specific and agile tools to detect and avoid it. The objective of this work was to elaborate a list of medications to avoid in Primary Care and to apply it on the polymedicated patients of a Primary Care assistance service. Methods: In the Database of the Spanish General Council of Official Associations of Pharmacists (BOT-Plus) the status and availability of each of the 93 MAE of the Prescrire 2019 List was checked. The list of medications to be avoided in Primary Care was drawn up with those that were marketed in Spain and excluded those that were not financed and those for exclusive hospital use. With the list of medicines to avoid in Primary Care, a retrospective analysis was made of all the prescription reports of polimedicated >10 medications for 2017 in a Primary Care services (N=262) in 5 health centers. Frequency analysis, central tendency measures and dispersion were carried out; they were estimated [CI: 95%] and X or Fisher’s exact was used to determine the association between variables and logistic regression analysis. Results: A prevalence of polymedicated drugs of 1.2% was observed, with a mean age of 71.7 years (DT± 12.4) and a mean prescription of 12 drugs (DT±1.7). The list of medications to be avoided in PC included 45 active ingredients. The 50.4% of the polymedicated had at least one drug to avoid and an average age of 68.5 years (DT±11.8). Sex was a risk factor for inappropriate prescription, the fact of being a woman increases with an OR=1.8 (IC95%=1, 3-3.0) the probability of having some medicines to avoid. The most commonly used drugs to avoid were: duloxetine, sitagliptin and olmesartan. Conclusions: A high percentage of polymedicated patients are prescribed at least one drug to avoid. The Primary Care medication avoidance list is a useful tool for identifying inappropriate medication and for the use by Primary Care professionals

Biologic Therapy for Moderate to Severe Psoriasis. Real-World Follow-up of Patients Who Initiated Biologic Therapy at Least 10 Years Ago

[Abstract] Introduction: The aim of this study was to evaluate response and drug survival of biologic therapy in patients with moderate to severe plaque-type psoriasis who initiated biologic therapy at least 10 years ago, in a real-world setting. Methods: This was an observational retrospective follow-up study that included patients with moderate to severe plaque-type psoriasis who initiated biologic therapy between October 2006 and December 2009. Efficacy was expressed as the percentage of patients achieving a 50, 75 and 90% reduction from baseline in the Psoriasis Area and Severity Index (PASI 50, PASI 75, PASI 90, respectively) every 3 months during the first year of therapy and then every 12 months up to the end of follow-up or withdrawal from the study. Results: A total of 56 patients were included in the study, representing 140 treatment lines (median 2, range 1-8); of these patients, 53 were still receiving biologic therapy at the end of the study. The mean duration of biologic therapy was 140.4 (range 47.6-175.4) months. Etanercept was used in 98.2% of patients, followed by efalizumab (42.9%), adalimumab (41.1%), ustekinumab (33.9%) and infliximab (16.1%). Treatment lines were switched in 62.1% of treatments: 24.3% due to secondary failure, 20.7% due to primary failure and 3.6% due to side effects. No patient treated with anti-interleukins had to discontinue treatment due to side effects. Ustekinumab had the highest drug survival. Conclusions: This study in the real-world-setting shows maintenance of long-term efficacy and safety of biologic therapy in patients with moderate to severe plaque psoriasis in daily practice who initiated biologic therapy 10 years ago.The journal’s Rapid Service Fee was paid for by Fundación Profesor Novoa Santos (A Coruña. Spain

Morphometric characterization of the upper watershed of the Sauce Grande river, Buenos Aires, Argentina

La cuenca alta del río Sauce Grande abastece el complejo hidráulico Embalse Paso de las Piedras, comportándose como servicio ambiental primordial para el consumo hídrico de Bahía Blanca. El análisis de las características morfométricas y funcionales de una cuenca hidrográfica a través de parámetros de forma, relieve y red de drenaje, es básico en la modelación hidrológica para determinar el movimiento y captación del agua de lluvia. Estos indicadores pueden apoyar una formulación de un Sistema de Pago por Servicios Ambientales, como estrategia básica de ordenamiento territorial y desarrollo local, centrado en la oferta de agua generada por la cuenca. El objetivo fue caracterizar morfométricamente la cuenca alta del río Sauce Grande. La metodología aplicada se basó en establecer y analizar los parámetros morfométricos mediante el uso de Sistemas de Información Geográfica y planillas de cálculo, a partir de un modelo digital del terreno e imágenes satelitales. Los resultados alcanzados definieron que la cuenca posee un área de 1502.6 km2. La longitud axial es de 41.6 km con un ancho promedio de 36.1 km. El Factor de forma (0.87) indica que posee forma alargada, siendo rectangular oblonga según el coeficiente de compacidad de Gravelius (2.8). La longitud del cauce principal es 58.34 km con pendiente media de 0.48 %. La densidad de drenaje es 0.27 km.km-2 y su coeficiente de sinuosidad 1.42. El tiempo de concentración es 11.8 hs. La curva hipsométrica adimensional corresponde a una cuenca con un avanzado grado de desarrollo. Todos estos parámetros facilitan la cuantificación del caudal líquido en la cuenca.The upper watershed of the Sauce Grande river supplies water to the hydraulic complex of the dike Paso de las Piedras, which is a precious environmental service for water consumption in Bahía Blanca city. A system of payment for environmental services as a basic strategy for territorial management and local development should be based on the water supply generated by the watershed. Analyzing morphometric and functional characteristics of a watershed through parameters of shape, relief, and drainage is basic for hydrologic modeling in order to establish the movement and capture of rainwater. The aim of this work was to make a morphometric characterization of the upper watershed of Sauce Grande river. The methodology was based on the establishment and analysis of morphometric parameters obtained from digital terrain model and satellite imageries, using a Geographic Information System and spreadsheets. The area of the watershed is of 1502.6 km2, the axial longitude of 41.6 km, with a mean width of 36.1 km. The shape factor of 0.87 indicates an elongated shape. The Gravellius coefficient of 2.8 indicates an oblong rectangular shape. The river length is 58.34 km with a mean slope of 0.48 %. The drainage density is 0.27 km.km-2 with a sinuosity coefficient of 1.42. The concentration time is 11.8 hs. The adimensional hypsometric curve corresponds to a watershed with a high level of development. All these parameters contribute to water flow quantification in the watershed.Comité de Medio Ambient

Psychological morbidity as a moderator of intention to quit smoking : a study of smokers and former smokers

Objective: To analyze psychological morbidity as a moderator of the relationship between smoking representations and quality of life in smokers and former smokers, as well as to determine which psychological variables discriminate between smokers with and without the intention to quit smoking. Methods: This was a quantitative, correlational cross-sectional study involving a convenience sample of 224 smokers and 169 former smokers. Results: In smokers and former smokers, psychological morbidity had a moderating effect on the relationship between mental/physical quality of life and smoking representations (cognitive representations, emotional representations, and comprehensibility). Smokers with the intention to quit smoking more often presented with low comprehensibility, threatening emotional representations, behavioral beliefs, and perceived behavioral control, as well as with normative/control beliefs, than did those without the intention to quit. Conclusions: The results of this study underscore the importance of the moderating effect exerted by psychological morbidity, as well as that of sociocognitive variables, among smokers who have the intention to quit smoking.ResumoObjetivo: Analisar a morbidade psicológica como um moderador na relação entre as representações do tabaco e a qualidade de vida em fumantes e ex-fumantes, assim como conhecer as variáveis psicológicas que discriminam os fumantes com e sem intenção para deixar de fumar. Métodos: Estudo quantitativo, correlacional e transversal com uma amostra de conveniência constituída por 224 fumantes e 169 ex-fumantes. Resultados: Verificou-se um efeito moderador da morbidade psicológica na relação entre a qualidade de vida (física e mental) e as representações do tabaco (representações cognitivas e emocionais e compreensão) nos fumantes e nos ex-fumantes. Os fumantes com intenção para deixar de fumar apresentavam menor compreensão, representações emocionais mais ameaçadoras, mais crenças de comportamento, maior controle comportamental percebido e mais crenças normativas/controle do que aqueles sem essa intenção. Conclusões: Os resultados deste estudo enfatizam a importância da morbidade psicológica como moderadora, bem como das variáveis sociocognitivas, junto dos fumantes que querem deixar de fumar

The Trypanosoma cruzi Sylvio X10 strain maxicircle sequence: the third musketeer

<p>Abstract</p> <p>Background</p> <p>Chagas disease has a diverse pathology caused by the parasite <it>Trypanosoma cruzi</it>, and is indigenous to Central and South America. A pronounced feature of the trypanosomes is the kinetoplast, which is comprised of catenated maxicircles and minicircles that provide the transcripts involved in uridine insertion/deletion RNA editing. <it>T. cruzi </it>exchange genetic material through a hybridization event. Extant strains are grouped into six discrete typing units by nuclear markers, and three clades, A, B, and C, based on maxicircle gene analysis. Clades A and B are the more closely related. Representative clade B and C maxicircles are known in their entirety, and portions of A, B, and C clades from multiple strains show intra-strain heterogeneity with the potential for maxicircle taxonomic markers that may correlate with clinical presentation.</p> <p>Results</p> <p>To perform a genome-wide analysis of the three maxicircle clades, the coding region of clade A representative strain Sylvio X10 (a.k.a. Silvio X10) was sequenced by PCR amplification of specific fragments followed by assembly and comparison with the known CL Brener and Esmeraldo maxicircle sequences. The clade A rRNA and protein coding region maintained synteny with clades B and C. Amino acid analysis of non-edited and 5'-edited genes for Sylvio X10 showed the anticipated gene sequences, with notable frameshifts in the non-edited regions of Cyb and ND4. Comparisons of genes that undergo extensive uridine insertion and deletion display a high number of insertion/deletion mutations that are likely permissible due to the post-transcriptional activity of RNA editing.</p> <p>Conclusion</p> <p>Phylogenetic analysis of the entire maxicircle coding region supports the closer evolutionary relationship of clade B to A, consistent with uniparental mitochondrial inheritance from a discrete typing unit TcI parental strain and studies on smaller fragments of the mitochondrial genome. Gene variance that can be corrected by RNA editing hints at an unusual depth for maxicircle taxonomic markers, which will aid in the ability to distinguish strains, their corresponding symptoms, and further our understanding of the <it>T. cruzi </it>population structure. The prevalence of apparently compromised coding regions outside of normally edited regions hints at undescribed but active mechanisms of genetic exchange.</p

Severe manifestations of SARS-CoV-2 in children and adolescents: from COVID-19 pneumonia to multisystem inflammatory syndrome: a multicentre study in pediatric intensive care units in Spain

Background Multisystem inflammatory syndrome temporally associated with COVID-19 (MIS-C) has been described as a novel and often severe presentation of SARS-CoV-2 infection in children. We aimed to describe the characteristics of children admitted to Pediatric Intensive Care Units (PICUs) presenting with MIS-C in comparison with those admitted with SARS-CoV-2 infection with other features such as COVID-19 pneumonia. Methods A multicentric prospective national registry including 47 PICUs was carried out. Data from children admitted with confirmed SARS-CoV-2 infection or fulfilling MIS-C criteria (with or without SARS-CoV-2 PCR confirmation) were collected. Clinical, laboratory and therapeutic features between MIS-C and non-MIS-C patients were compared. Results Seventy-four children were recruited. Sixty-one percent met MIS-C definition. MIS-C patients were older than non-MIS-C patients (p = 0.002): 9.4 years (IQR 5.5–11.8) vs 3.4 years (IQR 0.4–9.4). A higher proportion of them had no previous medical history of interest (88.2% vs 51.7%, p = 0.005). Non-MIS-C patients presented more frequently with respiratory distress (60.7% vs 13.3%, p < 0.001). MIS-C patients showed higher prevalence of fever (95.6% vs 64.3%, p < 0.001), diarrhea (66.7% vs 11.5%, p < 0.001), vomits (71.1% vs 23.1%, p = 0.001), fatigue (65.9% vs 36%, p = 0.016), shock (84.4% vs 13.8%, p < 0.001) and cardiac dysfunction (53.3% vs 10.3%, p = 0.001). MIS-C group had a lower lymphocyte count (p < 0.001) and LDH (p = 0.001) but higher neutrophil count (p = 0.045), neutrophil/lymphocyte ratio (p < 0.001), C-reactive protein (p < 0.001) and procalcitonin (p < 0.001). Patients in the MIS-C group were less likely to receive invasive ventilation (13.3% vs 41.4%, p = 0.005) but were more often treated with vasoactive drugs (66.7% vs 24.1%, p < 0.001), corticosteroids (80% vs 44.8%, p = 0.003) and immunoglobulins (51.1% vs 6.9%, p < 0.001). Most patients were discharged from PICU by the end of data collection with a median length of stay of 5 days (IQR 2.5–8 days) in the MIS-C group. Three patients died, none of them belonged to the MIS-C group. Conclusions MIS-C seems to be the most frequent presentation among critically ill children with SARS-CoV-2 infection. MIS-C patients are older and usually healthy. They show a higher prevalence of gastrointestinal symptoms and shock and are more likely to receive vasoactive drugs and immunomodulators and less likely to need mechanical ventilation than non-MIS-C patients

The C-Terminus of Toxoplasma RON2 Provides the Crucial Link between AMA1 and the Host-Associated Invasion Complex

Host cell invasion by apicomplexan parasites requires formation of the moving junction (MJ), a ring-like apposition between the parasite and host plasma membranes that the parasite migrates through during entry. The Toxoplasma MJ is a secreted complex including TgAMA1, a transmembrane protein on the parasite surface, and a complex of rhoptry neck proteins (TgRON2/4/5/8) described as host cell-associated. How these proteins connect the parasite and host cell has not previously been described. Here we show that TgRON2 localizes to the MJ and that two short segments flanking a hydrophobic stretch near its C-terminus (D3 and D4) independently associate with the ectodomain of TgAMA1. Pre-incubation of parasites with D3 (fused to glutathione S-transferase) dramatically reduces invasion but does not prevent injection of rhoptry bulb proteins. Hence, the entire C-terminal region of TgRON2 forms the crucial bridge between TgAMA1 and the rest of the MJ complex but this association is not required for rhoptry protein injection

The F0F1-ATP Synthase Complex Contains Novel Subunits and Is Essential for Procyclic Trypanosoma brucei

The mitochondrial F0F1 ATP synthase is an essential multi-subunit protein complex in the vast majority of eukaryotes but little is known about its composition and role in Trypanosoma brucei, an early diverged eukaryotic pathogen. We purified the F0F1 ATP synthase by a combination of affinity purification, immunoprecipitation and blue-native gel electrophoresis and characterized its composition and function. We identified 22 proteins of which five are related to F1 subunits, three to F0 subunits, and 14 which have no obvious homology to proteins outside the kinetoplastids. RNAi silencing of expression of the F1 α subunit or either of the two novel proteins showed that they are each essential for the viability of procyclic (insect stage) cells and are important for the structural integrity of the F0F1-ATP synthase complex. We also observed a dramatic decrease in ATP production by oxidative phosphorylation after silencing expression of each of these proteins while substrate phosphorylation was not severely affected. Our procyclic T. brucei cells were sensitive to the ATP synthase inhibitor oligomycin even in the presence of glucose contrary to earlier reports. Hence, the two novel proteins appear essential for the structural organization of the functional complex and regulation of mitochondrial energy generation in these organisms is more complicated than previously thought

ATG5 is essential for ATG8-dependent autophagy and mitochondrial homeostasis in Leishmania major

Macroautophagy has been shown to be important for the cellular remodelling required for Leishmania differentiation. We now demonstrate that L. major contains a functional ATG12-ATG5 conjugation system, which is required for ATG8-dependent autophagosome formation. Nascent autophagosomes were found commonly associated with the mitochondrion. L. major mutants lacking ATG5 (Δatg5) were viable as promastigotes but were unable to form autophagosomes, had morphological abnormalities including a much reduced flagellum, were less able to differentiate and had greatly reduced virulence to macrophages and mice. Analyses of the lipid metabolome of Δatg5 revealed marked elevation of phosphatidylethanolamines (PE) in comparison to wild type parasites. The Δatg5 mutants also had increased mitochondrial mass but reduced mitochondrial membrane potential and higher levels of reactive oxygen species. These findings indicate that the lack of ATG5 and autophagy leads to perturbation of the phospholipid balance in the mitochondrion, possibly through ablation of membrane use and conjugation of mitochondrial PE to ATG8 for autophagosome biogenesis, resulting in a dysfunctional mitochondrion with impaired oxidative ability and energy generation. The overall result of this is reduced virulence