Ingresos hospitalarios y errores de medicación. Magnitud y dimensión

El medicamento es uno de los recursos sanitarios más utilizados y constituye en la actualidad una potente herramienta terapéutica para la resolución de procesos patológicos. Se considera el principal recurso para el incremento de la esperanza y de la calidad de vida de la población. Sin embargo, no siempre se consigue el resultado esperado con la prescripción del medicamento, ya que son múltiples las causas y factores que pueden hacer que por una parte no se alcance el objetivo esperado y por otra puede producir efectos no deseados o acontecimientos adversos, afectando directamente a la seguridad del paciente. La morbilidad y mortalidad producidas por errores relacionados con los medicamentos es elevada y en gran medida tiene que ver con fallos o errores en el sistema de utilización de éstos. Según la Organización Mundial de la Salud (OMS), en el mundo más del 50% de los medicamentos se prescriben, dispensan y comercializan inadecuadamente. Un gran número de estos problemas o errores derivados del uso de los medicamentos son prevenibles. El error de medicación (EM) engloba todos los incidentes o problemas que puedan estar relacionados con la práctica profesional, con los productos, con los usuarios y con los procedimientos empleados y se define como "cualquier incidente prevenible que pueda causar daño al paciente o dé lugar a una utilización inapropiada de los medicamentos, cuando éstos están bajo el control de los profesionales sanitarios o del paciente o consumidor. Estos incidentes pueden estar relacionados con la práctica profesional, con los procedimientos o con los sistemas, incluyendo fallos en la prescripción, comunicación, etiquetado, envasado, denominación, preparación, dispensación, distribución, administración, educación, seguimiento y utilización". Un acontecimiento adverso por medicamentos (AAM) es cualquier daño, grave o leve, causado por la falta o por el uso terapéutico de un medicamento. Los AAM prevenibles son los causados por errores de medicación, estos implican daño y error. Los AAM no prevenibles se producen a pesar de un uso adecuado de los fármacos, implican un daño pero sin error y son las conocidas Reacciones Adversas a Medicamentos (RAM). Los errores de medicación se pueden producir en cada una de las fases del complejo proceso de utilización de los medicamentos en el que intervienen diferentes profesionales y colectivos (fase de prescripción, fase de dispensación y fase de administración) y también pueden influir otros factores humanos, ambientales y del sistema. En el proceso de utilización de los medicamentos, el 30% de los errores se cometen durante la prescripción de los mismos. Seguida de la fase de administración con un 20% y la de dispensación con un 17% de errores, 48% de los cuales se producen por dispensar un medicamento diferente al prescrito. Aunque la mayoría de los estudios sobre errores de medicación se han venido realizando en el ámbito hospitalario, los acontecimientos adversos se pueden deber tanto a errores ocurridos en la atención hospitalaria, en la atención primaria o por una descoordinación entre ambos niveles. Por ello, tanto el personal médico, de enfermería como el personal farmacéutico son imprescindibles en la detección y prevención de los errores de medicación, ya que algunos de estos acontecimientos pueden llevar a la prescripción de más medicamentos incrementándose, así el riesgo de eventos adversos de mayor gravedad. Aproximadamente el 7,1% de los ingresos hospitalarios están relacionados con problemas de medicación pudiéndose evitar en el 59% de los casos. La mayoría de estos ingresos corresponden a pacientes mayores de 65 años. Los grupos de medicamentos o fármacos implicados más comúnmente en este tipo de acontecimientos son los AINEs, el ácido acetil salicílico, la digoxina y los anticoagulantes. Las manifestaciones clínicas mas usuales son de tipo digestivo y más concretamente la hemorragia digestiva alta. El punto de partida para poder minimizar en lo posible la incidencia de eventos adversos, es la implementación de una cultura institucional que promocione la seguridad y mejore el proceso de utilización de los medicamentos, por ello y para reducir el riesgo de que se produzca un AAM, se deben implementar estrategias de prevención específicas, partiendo de la base de que errar es humano y creando una cultura de seguridad que permita aprender de los errores. Algunas medidas de prevención recomendadas son: Estandarización de la prescripción médica, Registros electrónicos de la actividad asistencial, Estandarización del envasado, etiquetado, almacén, límite de dosis, dispensación… de los medicamentos. Incorporación de un farmacéutico al equipo asistencial, Informar y formar a los pacientes sobre sus tratamientos, pautas y procedimientos, Mejora de la comunicación entre los profesionales sanitarios, Promoción de la notificación de los errores de medicación

Delving into the Causes and Effects of Entomopathogenic Endophytic Metarhizium brunneum Foliar Application-Related Mortality in Spodoptera littoralis Larvae

The aim of the current study was to delve into the causes of mortality of Spodoptera littoralis larvae feeding on Metarhizium-colonized plants in the absence of fungal outgrowth on the cadavers as previous studies reported and to elucidate the possible indirect effects of this fungus-colonized diet. The effect was evaluated in experiments conducted using leaf discs of colonized plants and in planta using fungus-colonized whole plants. The mortality rates of larvae fed on Metarhiziumcolonized melon leaves were 45.0% and 87.5%, and the average survival times were 6.6 and 3.1 days in experiments performed with discs and in planta, respectively. Notably, these mortality levels were not associated with observed apoptosis mediated by caspases 1, 3-7 and 8; thus, further investigation into the possible immune system reaction of the insect after the ingestion of colonized plants is required. The leaf consumption of S. littoralis larvae fed on melon-colonized leaves was lower than that on control plants in the disc experiments but not in experiments conducted in planta. In this regard, in experiments performed in planta, plant damage increased larval mortality in both fungally challenged and control larvae. There was also a meaningful effect of exposure to Metarhiziumcolonized melon leaf discs on S. littoralis fitness, with significant reductions in 39.0% and 22.0% in female fecundity and egg fertility, respectively, detected in females emerging from pupae developing from larvae surviving exposure to colonized plant discs; all larvae died in the in planta experiments. Hence, the present work presents new findings revealing the high potential of endophytic entomopathogenic fungi to improve the outcome of foliar applications against chewing insects in the short, mid- and long term, by the reduction of the reproductive potential of surviving adults and reveals new insights into the development of bioassays with whole plants for more detailed evaluation of the impact of these fungi as endophytes used for plant protection

Production of Microsclerotia by Metarhizium sp., and Factors Affecting Their Survival, Germination, and Conidial Yield

Microsclerotia (MS) produced by some species of Metarhizium can be used as active ingredients in mycoinsecticides for the control of soil-dwelling stages of geophilic pests. In this study, the MS production potential of two Metarhizium brunneum strains and one M. robertsii strain was evaluated. The three strains were able to produce MS in liquid fermentation, yielding between 4.0 × 106 (M. robertsii EAMa 01/158-Su strain) and 1.0 × 107 (M. brunneum EAMa 01/58-Su strain) infective propagules (CFU) per gram of MS. The EAMa 01/58-Su strain was selected for further investigation into the effects of key abiotic factors on their survival and conidial yield. The MS were demonstrated to be stable at different storage temperatures (−80, −18, and 4 °C), with a shelf-life up to one year. The best temperature for MS storage was −80 °C, ensuring good viability of MS for up to one year (4.9 × 1010 CFU/g MS). Moreover, soil texture significantly affected CFU production by MS; sandy soils were the best driver of infective propagule production. Finally, the best combination of soil temperature and humidity for MS germination was 22.7 °C and 7.3% (wt./wt.), with no significant effect of UV-B exposure time on MS viability. These results provide key insights into the handling and storage of MS, and for decision making on MS dosage and timing of application

Survey of Natural Enemies of the Invasive Boxwood Moth Cydalima perspectalis in Southwestern Mediterranean Europe and Biocontrol Potential of a Native Beauveria bassiana (Bals.-Criv.) Vuill. Strain

Cydalima perspectalis (Lepidoptera: Crambidae), a species native to East Asia, has been especially devastating in the Mediterranean region and Catalonia, northeast Spain, where Buxus sempervirens is an essential component of the natural forest. As an invasive species, the lack of biotic mortality factors in the arrival region has been one of the main factors allowing its expansion. Therefore, this study aimed to collect and identify possible indigenous natural enemies adapting to the new species in the boxwood of the southwest Mediterranean region. Later, the efficacy of some of the collected species for controlling C. perspectalis larvae was tested in laboratory conditions. The larval collection was carried out in successive years in the boxwood of the region. Several collected larvae were infected with an entomopathogen, Beauveria bassiana, or parasitized by Compsilura concinnata, both common in native Lepidoptera caterpillars. The B. bassiana strain was found to be highly virulent against the developed larvae of C. perspectalis, which suggests that B. bassiana may be an effective treatment in parks and gardens when the first overwintering larvae are detected. The biology of the parasitoid identified is not very well known in Europe, which suggests the necessity of studying its biology and alternative hosts in the region in order to improve its population

Mycoviral Population Dynamics in Spanish Isolates of the Entomopathogenic Fungus Beauveria bassiana

The use of mycoviruses to manipulate the virulence of entomopathogenic fungi employed as biocontrol agents may lead to the development of novel methods to control attacks by insect pests. Such approaches are urgently required, as existing agrochemicals are being withdrawn from the market due to environmental and health concerns. The aim of this work is to investigate the presence and diversity of mycoviruses in large panels of entomopathogenic fungi, mostly from Spain and Denmark. In total, 151 isolates belonging to the genera Beauveria, Metarhizium, Lecanicillium, Purpureocillium, Isaria, and Paecilomyces were screened for the presence of dsRNA elements and 12 Spanish B. bassiana isolates were found to harbor mycoviruses. All identified mycoviruses belong to three previously characterised species, the officially recognised Beauveria bassiana victorivirus 1 (BbVV-1) and the proposed Beauveria bassiana partitivirus 2 (BbPV-2) and Beauveria bassiana polymycovirus 1 (BbPmV-1); individual B. bassiana isolates may harbor up to three of these mycoviruses. Notably, these mycovirus species are under distinct selection pressures, while recombination of viral genomes increases population diversity. Phylogenetic analysis of the RNA-dependent RNA polymerase gene sequences revealed that the current population structure in Spain is potentially a result of both vertical and horizontal mycovirus transmission. Finally, pathogenicity experiments using the Mediterranean fruit fly Ceratitis capitata showed no direct correlation between the presence of any particular mycovirus and the virulence of the B. bassiana isolates, but illustrated potentially interesting isolates that exhibit relatively high virulence, which will be used in more detailed virulence experimentation in the futur

Soil drenching with entomopathogenic fungi for control of the soil-dwelling life stages and adults of the same generation of Spodoptera littoralis (Boisd.) (Lepidoptera: Noctuidae)

Four Beauveria bassiana and three Metarhizium brunneum isolates were evaluated, as soil drenches, against Spodoptera littoralis prepupae. Treatment efficacy was determined by assessing total mortality during development from prepupae through to pupae and adults; mortality and sub-lethal effects on reproduction were also quantified for adults emerging from surviving prepupae/pupae. All isolates were pathogenic but overall mortality varied between 31.7 and 83.3% (0% for control); average survival time was 7.5–10.5 days (14.0 days for control). From 1.7–15.0% of adults emerging from surviving prepupae/pupae were deformed (0% in control). Contact with fungal suspensions as prepupae/pupae caused a significant reduction in fecundity of emerging adult females (15–58.9%), and a significant reduction in egg viability (6.8–28.4%) compared with controls. Two isolates were selected for virulence evaluation against S. littoralis prepupae. The LC50s were 1.7 × 107 and 1.8 × 107 conidia ml−1 and the median survival times were 7 and 6 days for isolates EAMa 01/58-Su and EAMb 09/01-Su, respectively. Destruxin A was present in pupae developing from prepupae treated with isolates EAMa 01/58-Su (0.010 ± 0.002 µg pupae−1) and EAMb 09/01-Su (0.015 ± 0.003 µg pupae−1). The use of entomopathogenic fungi as soil drenches could be a key component of S. littoralis IPM strategies due to direct reductions in the number of soil-dwelling life stages and, also, the significant reduction in reproductive potential of surviving adults

Genetic and molecular basis of botrydial biosynthesis: connecting cytochrome P450-encoding genes to biosynthetic intermediates

Over two hundred species of plants can be infected by the phytopathogenic fungus Botrytis cinerea under a range of different environmental conditions. In response to these, the fungus produces unique terpenoid and polyketide metabolites. Parts of the plants may be killed by the phytotoxin botrydial, enabling the fungus to feed on the dead cells. In this paper, we describe the genetic and molecular basis of botrydial biosynthesis and the function of the five genes of the genome of B. cinerea that together constitute the botrydial biosynthetic gene cluster. Genes BcBOT3 and BcBOT4, encoding two cytochrome P450 monooxygenases, were inactivated by homologous recombination and were shown to catalyze regio- and stereospecific hydroxylations at the carbons C-10 and C-4, respectively, of the presilphiperfolan-8β-ol skeleton. The null mutants, bcbot3Δ and bcbot4Δ, accumulated key intermediates in the botrydial biosynthesis enabling the complete genetic and molecular basis of the botrydial biosynthetic pathway to be established. Furthermore, the bcbot4Δ mutant overproduced a significant number of polyketides, which included, in addition to known botcinins, botrylactones and cinbotolide A, two new botrylactones and two new cinbotolides, cinbotolides B and C

Antigenotoxicity and Tumor Growing Inhibition by Leafy Brassica carinata and Sinigrin

Cruciferous vegetables are well known and worldwide consumed due to their health benefits and cancer prevention properties. As a desirable cruciferous plant, Ethiopian mustard (Brassica carinata A. Braun) and its glucosinolate sinigrin were tested in the in vivo Drosophila melanogaster (SMART) and the in vitro HL60 (human promyelocytic leukaemia cell line) systems. High performance liquid chromatography (HPLC) analysis of plant samples confirmed the presence of sinigrin as principal B. carinata glucosinolate. SMART was performed by feeding D. melanogaster larvae either with different concentrations of plant/compound samples or combining them with hydrogen peroxide (a potent oxidative mutagen) being both antimutagenics. HL60 assays showed the tumoricidal activity of plant samples (IC50 = 0.28 mg·mL−1) and the breakdown products of sinigrin hydrolysis (IC50 = 2.71 μM). Our results enhance the potential of B. carinata as health promoter and chemopreventive in both systems and the leading role of sinigrin in these effects

Genetic analyses place most Spanish isolates of Beauveria bassiana in a molecular group with word-wide distribution

<p>Abstract</p> <p>Background</p> <p>The entomopathogenic anamorphic fungus <it>Beauveria bassiana </it>is currently used as a biocontrol agent (BCA) of insects. Fifty-seven <it>Beauveria bassiana </it>isolates -53 from Spain- were characterized, integrating group I intron insertion patterns at the 3'-end of the nuclear large subunit ribosomal gene (LSU rDNA) and elongation factor 1-alpha (EF1-α) phylogenetic information, in order to assess the genetic structure and diversity of this Spanish collection of <it>B. bassiana</it>.</p> <p>Results</p> <p>Group I intron genotype analysis was based on the four highly conserved insertion sites of the LSU (Ec2653, Ec2449, Ec2066, Ec1921). Of the 16 possible combinations/genotypes, only four were detected, two of which were predominant, containing 44 and 9 members out of 57 isolates, respectively. Interestingly, the members of the latter two genotypes showed unique differences in their growth temperatures. In follow, EF1-α phylogeny served to classify most of the strains in the <it>B. bassiana s.s</it>. (<it>sensu stricto</it>) group and separate them into 5 molecular subgroups, all of which contained a group I intron belonging to the IC1 subtype at the Ec1921 position. A number of parameters such as thermal growth or origin (host, geographic location and climatic conditions) were also examined but in general no association could be found.</p> <p>Conclusion</p> <p>Most Spanish <it>B. bassiana </it>isolates (77.2%) are grouped into a major phylogenetic subgroup with word-wide distribution. However, high phylogenetic diversity was also detected among Spanish isolates from close geographic zones with low climatic variation. In general, no correlation was observed between the molecular distribution and geographic origin or climatic characteristics where the Spanish <it>B. bassiana </it>isolates were sampled.</p

Hiperparatiroidismo primario secundario a quiste paratiroideo funcionante

Functioning parathyroid cyst is a very rare entity that can lead to misled diagnosis and treatment. We present one case with a literature review on the pathogenesis and diagnosis of this condition. Our patient was referred with hypercalcemia and after primary hyperparathyroidism was established, Localization tests revealed a cystic lesion with a high intact-parathormone (i-PTH) concentration in the cytology establishing the diagnosis. After a right inferior parathyroidectomy the patient achieved biochemical and clinical cure.El quiste paratiroideo es una enfermedad muy rara que puede llevar a un diagnóstico y tratamiento inadecuado. Se presenta un caso clínico junto a una revisión de la literatura disponible sobre patogénesis y proceso diagnóstico terapéutico de esta entidad. Nuestro paciente fue remitido por hipercalcemia siendo diagnosticado de hiperparatiroidismo primario. Las pruebas de localización mostraron una lesión quística con niveles elevados de PTHi (Paratohormona intacta) en la citología, lo que permitió el correcto diagnóstico y tratamiento con paratiroidectomía inferior derecha con resolución del cuadro bioquímico