Prescripción inducida en atención primaria de la Comarca Bilbao

ObjetivosPrincipales: conocer la proporción de prescripción inducida (PI) en Comarca Bilbao y su procedencia, la proporción de gasto correspondiente a la PI, la proporción de PI en los principales grupos terapéuticos, la actitud del médico de atención primaria ante la prescripción solicitada y su influencia en el gasto, la proporción de desacuerdo con dicha prescripción y los motivos de desacuerdo, y la proporción con informe del especialista. Secundarios: conocer la proporción de PI en los demás grupos terapéuticos, en fármacos VINE, EFG y en los de nula o baja mejora terapéutica.Diseño.Estudio transversal, descriptivoEmplazamientoAtención primariaParticipantesFármacos financiables prescritos por y/o solicitados a los médicos de familia de EAP.Resultados principalesSe estudiaron 7.922 fármacos. Tipo de prescripción: PI, 48,3% (IC del 95%, 47,2–49,4); del médico de atención primaria (PRO), 50,6% (IC del 95%, 49,5–51,7); desconocida, 1,1% (IC del 95%, 0,9–1,3). Procedencia principal: especialista público (72,2%), especialista privado (16,6%). Un 62,5% del gasto correspondió a la PI. En el grupo terapéutico más prescrito, sistema nervioso central (24,2%), PI, 39,8%; PRO, 58,9%; en aparato cardiovascular (19,1%), PI, 56,2%, PRO, 43,1%. Se prescribió el fármaco solicitado en un 98,4% de los casos, se cambio en el 1,2% y se suprimió en un 0,4%. Proporción de desacuerdo, 11%; motivos de desacuerdo, no hay necesidad de tratar (23,9%), grupo terapéutico (34,4%), principio activo (13,2%), marca comercial (28,5%). Hubo informe de especialista en un 62,4% de los casos.ConclusionesSe detecta una proporción considerable de prescripción no atribuible a atención primaria y una proporción importante de fármacos que el médico de primaria prescribe sin estar de acuerdo. Sería necesario un sistema que permitiera separar el gasto por niveles, así como mejorar la comunicación entre éstos.ObjectivesMain objetives: to know the proportion of induced prescription (IP) in Area Bilbao and its source, the proportion of cost IP accounts for, the proportion of IP in the main therapeutic groups, the attitude of GP when requested for prescription and its influence on cost, the proportion of disagreement with requested prescription, the reasons for disagreement, and the proportion with letter from specialist. Secondary objectives: to know the proportion of IP in the remaining therapeutic groups, in drugs of low clinical value, in generic drugs and in new drugs with low or no therapeutic improvement.DesignA descriptive cross-sectional study.SettingPrimary health care.ParticipantsDrugs prescribable under National Health Service prescribed by and/or requested to GPs.Main results7.922 drugs were analysed. Type of prescription: IP, 48.3% (95% CI, 47.2–49.4); GP prescription (GPP), 50.6% (95% CI, 49.5–51.7); unknown source, 1,1% (95% CI, 0.9–1.3). Main source, public specialist (72.2%), private specialist (16.6%). IP accounted for 62.5% of cost. In the most prescribed therapeutic group, central nervous system (24.2%), IP, 39.8%; GPP, 58.9%; in cardiovascular system (19.1%), IP, 56.2%; GPP, 43.1%. 98.4% of requested prescription was actually prescribed, 1.2% was changed and 0.4%, suppressed. Proportion of disagreement, 11%; reasons for disagreement, no need for medical treatment (23.9%), therapeutic group (34.4%), active ingredient (13.2%), brand name (28.5%). There was a 62.4% with letter from specialist.ConclusionsPrimary care is not accountable for a substantial proportion of prescription. GP prescribes a considerable proportion of drugs without agreement. It would be necessary a system that allows to separate the cost by care levels and also improve their communication

Proposal of a water-quality index for high andean basins: application to the Chumbao river, Andahuaylas, Peru

Thewater fromthe high Andean rivers is peculiar due to its composition and the geomorphology of its sources, and naturally or anthropogenically contamination is not discarded along its course. This water is used for agriculture and human consumption, therefore knowing its quality is important. This research aimed to proposing and formulate a water-quality index for high Andean basins through the Delphimethod, and its application in the Chumbao River located in Andahuaylas-Peru. Forty-three water-quality parameters were evaluated through the Delphi method, and the water-quality index (WQIHA) was formulated with a weighted average of the weights of the selected parameters, it was compared with the WQI Dinius. For this purpose, ten sampling points were considered along the Chumbao River located between 4274 and 2572 m of altitude and theWQIHA was applied. In addition, field and laboratory analyses were carried out in 2018, 2019, and 2021, in dry and rainy seasons. Twenty parameters were grouped in the physicochemical sub-index (SIPC), heavy metals sub-index (SIHM), and organic matter sub-index (SIOM). Each group contributed with weights of 0.30, 0.30, and 0.40, respectively, for theWQIHA formulation. The SIPC and SIOM showed that the areas near the head of the basin presented excellent and good quality, while the urbanized areas were qualified as marginal to poor; SIHM reported good quality in all points and seasons. Regarding the WQIHA, the index shows good quality in the zones above 3184 m of altitude, contrasting with poor quality downstream, decreasing notably in both seasons, suggesting continuous degradation of the water body

Insights from Water Quality of High Andean Springs for Human Consumption in Perú

The headwaters of the high Andean basin in Peru accumulate water from the mist, rain, snow, and hail, and it is transported superficially and underground to low-lying areas, mostly used for drinkable purposes. The natural water in these areas might be altered due to legal and illegal mining extraction. The aim of the study was to evaluate the water quality for human consumption. Seventeen water samples were examined from Andahuaylas (A), San Jerónimo (S), Talavera (T), and Chiara (CH) districts located between 2813 and 4004 m altitude in the Andes. We used physic ochemical, microbiological, and metal parameters, and the results were compared to permissible levels established by the WHO and ECA-Peru to examine samples collected in the dry and rainy seasons in 2019. Application of principal component analysis (PCA) identified areas and conditioning parameters. Extractive mining activity influences the quality of springs due to the presence of metals, especially antimony (Sb), arsenic (As), cadmium (Cd), and lead (Pb), values of which are higher than values permissible for human consumption, being higher in the dry season (p < 0.05). In addition, the presence of cations and particulate matter affects physico-chemical parameters, for example turbidity. PCA showed that parameters for water characterization are season-independent, and water quality in the springs would be conditioned by the presence of metals, especially in Andahuaylas and Talavera zones, as well as the parameters that are associated with dissolved solids in the water (turbidity and fluorides). A frequent monitoring program of springs and groundwater is recommended, with the purpose to protect water from contamination and guarantee safe water availability in low-lying and urbanized areas

A common allele in RPGRIP1L is a modifier of retinal degeneration in ciliopathies

Despite rapid advances in the identification of genes involved in disease, the predictive power of the genotype remains limited, in part owing to poorly understood effects of second-site modifiers. Here we demonstrate that a polymorphic coding variant of RPGRIP1L (retinitis pigmentosa GTPase regulator-interacting protein-1 like), a ciliary gene mutated in Meckel-Gruber (MKS) and Joubert (JBTS) syndromes, is associated with the development of retinal degeneration in individuals with ciliopathies caused by mutations in other genes. As part of our resequencing efforts of the ciliary proteome, we identified several putative loss-of-function RPGRIP1L mutations, including one common variant, A229T. Multiple genetic lines of evidence showed this allele to be associated with photoreceptor loss in ciliopathies. Moreover, we show that RPGRIP1L interacts biochemically with RPGR, loss of which causes retinal degeneration, and that the Thr229-encoded protein significantly compromises this interaction. Our data represent an example of modification of a discrete phenotype of syndromic disease and highlight the importance of a multifaceted approach for the discovery of modifier alleles of intermediate frequency and effect.This work was supported by grants R01EY007961 from the National Eye Institute (H.K. and A.S.), R01HD04260 from the National Institute of Child Health and Development (N.K.), R01DK072301, R01DK075972 (N.K.), R01DK068306, R01DK064614, R01DK069274 (F.H.), NRSA fellowship F32 DK079541 (E.E.D.) from the National Institute of Diabetes, Digestive and Kidney disorders, Intramural program of NEI (A.S.), the Macular Vision Research Foundation (N.K.), the Foundation for Fighting Blindness (H.K., S.S.B., A.S. and N.K.), the Foundation for Fighting Blindness Canada (R.K.K.), Le Fonds de la recherche en sante du Québec (FRSQ) (R.K.K.), Research to Prevent Blindness (A.S.), Harold Falls Collegiate Professorship (A.S.), the Midwest Eye Banks and Transplantation Center (H.K.), the Searle Scholars Program (M.A.B.), the Deutsche Forschungsgemeinschaft (DFG grant BE 3910/4-1; C.B.) the UK Medical Research Council (grant number G0700073; C.A.J.), NIHR Biomedical Research Centre for Ophthalmology (S.S.B.) and EU-GENORET Grant LSHG-CT-2005-512036 (S.S.B.). F.H. is an investigator of the Howard Hughes Medical Institute (HHMI) and a Doris Duke Distinguished Clinical Scientist (DDCF)

Gelsolin dysfunction causes photoreceptor loss in induced pluripotent cell and animal retinitis pigmentosa models

Mutations in the Retinitis Pigmentosa GTPase Regulator (RPGR) cause X-linked RP (XLRP), an untreatable, inherited retinal dystrophy that leads to premature blindness. RPGR localises to the photoreceptor connecting cilium where its function remains unknown. Here we show, using murine and human induced pluripotent stem cell models, that RPGR interacts with and activates the actin-severing protein gelsolin, and that gelsolin regulates actin disassembly in the connecting cilium, thus facilitating rhodopsin transport to photoreceptor outer segments. Disease-causing RPGR mutations perturb this RPGR-gelsolin interaction, compromising gelsolin activation. Both RPGR and Gelsolin knockout mice show abnormalities of actin polymerisation and mislocalisation of rhodopsin in photoreceptors. These findings reveal a clinically-significant role for RPGR in the activation of gelsolin, without which abnormalities in actin polymerisation in the photoreceptor connecting cilia cause rhodopsin mislocalisation and eventual retinal degeneration in XLRP.Mutations in the Retinitis Pigmentosa GTPase Regulator (RPGR) cause retinal dystrophy, but how this arises at a molecular level is unclear. Here, the authors show in induced pluripotent stem cells and mouse knockouts that RPGR mediates actin dynamics in photoreceptors via the actin-severing protein, gelsolin

Ciliopathies: an expanding disease spectrum

Ciliopathies comprise a group of disorders associated with genetic mutations encoding defective proteins, which result in either abnormal formation or function of cilia. As cilia are a component of almost all vertebrate cells, cilia dysfunction can manifest as a constellation of features that include characteristically, retinal degeneration, renal disease and cerebral anomalies. Additional manifestations include congenital fibrocystic diseases of the liver, diabetes, obesity and skeletal dysplasias. Ciliopathic features have been associated with mutations in over 40 genes to date. However, with over 1,000 polypeptides currently identified within the ciliary proteome, several other disorders associated with this constellation of clinical features will likely be ascribed to mutations in other ciliary genes. The mechanisms underlying many of the disease phenotypes associated with ciliary dysfunction have yet to be fully elucidated. Several elegant studies have crucially demonstrated the dynamic ciliary localisation of components of the Hedgehog and Wnt signalling pathways during signal transduction. Given the critical role of the cilium in transducing “outside-in” signals, it is not surprising therefore, that the disease phenotypes consequent to ciliary dysfunction are a manifestation of aberrant signal transduction. Further investigation is now needed to explore the developmental and physiological roles of aberrant signal transduction in the manifestation of ciliopathy phenotypes. Utilisation of conditional and inducible murine models to delete or overexpress individual ciliary genes in a spatiotemporal and organ/cell-specific manner should help clarify some of the functional roles of ciliary proteins in the manifestation of phenotypic features

Síndromes muy poco frecuentes

Dismorfología, Citogenética y Clínica: Resultados de estudios sobre los datos del ECEMCSince the year 2002, this Section of the Boletín del ECEMC: Revista de Dismorfología y Epidemiología, is dedicated to dysmorphology, cytogenetics and clinical analysis of congenital anomalies, and includes a chapter on syndromes with very low frequency. The aim of this chapter is to summarize the most important characteristics, the etiology, and the mechanisms involved in the selected syndromes. The low frequency of these syndromes, together with their probable decreasing birth prevalence due to the impact of prenatal diagnosis, imply that pediatricians and other health professionals would have less opportunity to know their clinical characteristics. This circumstance together with the overlapping of the clinical features among some of the syndromes, make difficult to perform an early diagnosis, which is important for genetic counselling, and to provide the most suitable treatment to each pacient. The syndromes included are: Aarskog, Freeman-Sheldon, Cleidocranial dysplasia, Noonan, Cardio-Facio-Cutaneous and Costello. In addition, a short summary about the differential diagnosis among Noonan, Cardio-Facio-Cutaneous and Costello syndromes is also included.N

Rd9 Is a Naturally Occurring Mouse Model of a Common Form of Retinitis Pigmentosa Caused by Mutations in RPGR-ORF15

Animal models of human disease are an invaluable component of studies aimed at understanding disease pathogenesis and therapeutic possibilities. Mutations in the gene encoding retinitis pigmentosa GTPase regulator (RPGR) are the most common cause of X-linked retinitis pigmentosa (XLRP) and are estimated to cause 20% of all retinal dystrophy cases. A majority of RPGR mutations are present in ORF15, the purine-rich terminal exon of the predominant splice-variant expressed in retina. Here we describe the genetic and phenotypic characterization of the retinal degeneration 9 (Rd9) strain of mice, a naturally occurring animal model of XLRP. Rd9 mice were found to carry a 32-base-pair duplication within ORF15 that causes a shift in the reading frame that introduces a premature-stop codon. Rpgr ORF15 transcripts, but not protein, were detected in retinas from Rd9/Y male mice that exhibited retinal pathology, including pigment loss and slowly progressing decrease in outer nuclear layer thickness. The levels of rhodopsin and transducin in rod outer segments were also decreased, and M-cone opsin appeared mislocalized within cone photoreceptors. In addition, electroretinogram (ERG) a- and b-wave amplitudes of both Rd9/Y male and Rd9/Rd9 female mice showed moderate gradual reduction that continued to 24 months of age. The presence of multiple retinal features that correlate with findings in individuals with XLRP identifies Rd9 as a valuable model for use in gaining insight into ORF15-associated disease progression and pathogenesis, as well as accelerating the development and testing of therapeutic strategies for this common form of retinal dystrophy