A value-based healthcare model for initiating and switching psoriasis therapies-Results from the prospective multicentre IMPROVE study.

BACKGROUND: Little is known about the therapeutic benefits of a value-based healthcare model compared to a traditional activity-based incentive model in psoriasis (PsO). OBJECTIVES: This prospective non-interventional study evaluated an outcome-based, patient-centred management model for patients with PsO. METHODS: In total, 49 patients with a Psoriasis Area and Severity Index (PASI) ≥3 who were starting or switching between treatments were included. Patients were assessed at baseline, 3 and 9 months. The patient benefit index (PBI) was calculated using predefined questionnaires. An expected PBI was calculated and adjusted for risk factors known to complicate treatment, that is overweight and smoking. The model remunerated the department on whether the observed PBI exceeded the expected PBI to incentivize over-performance. RESULTS: In total, 40 patients (80%) completed all three visits; 32.7% were smokers and 73.5% were overweight. Mean PASI at baseline was 11.5 (SD 9.1); PASI improved significantly from baseline through 3 months: mean reduction, 8.0 (SD 9.2), p < 0.001 and was maintained until 9 months: mean further reduction, 0.1 (SD 3.3), p = 0.893. The mean PBI was 2.5 (SD 1.3) and 2.8 (SD 1.1) at 3 and 9 months, respectively. A PBI ≥1 was achieved by 87.8% at 3 and 95.1% at 9 months. Overall, the department was remunerated a mean 2721.1 DKK (SD 4472.8) per patient. In subgroup analysis, the department was remunerated a mean of, respectively, 2428.6 (SD 5089.5), 2636.6 (SD 4471.3) and 3196.5 (SD 4497.1) DKK for patients with none, 1 or 2 risk factors, that is smoking or/and overweight. CONCLUSIONS: The model evaluated herein is the first value-based model to calculate remuneration from patient reported outcomes and showed to successfully predict the expected PBI and remunerate treatment based on whether the expected treatment goal was met or exceeded. This can be utilized in the patient-centred management of PsO.

Evaluation of thyroid nodules by shear wave elastography: a review of current knowledge.

PURPOSE: Shear wave elastography (SWE), as a tool for diagnosing thyroid malignancy, has gathered considerable attention during the past decade. Diverging results exist regarding the diagnostic performance of thyroid SWE. METHODS: A comprehensive literature review of thyroid SWE was conducted using the terms "Thyroid" and "shear wave elastography" in PubMed. RESULTS: The majority of studies found SWE promising for differentiating malignant and benign thyroid nodules on a group level, whereas results are less convincing on the individual level due to huge overlap in elasticity indices. Further, there is lack of consensus on the optimum outcome reflecting nodule elasticity and the cut-off point predicting thyroid malignancy. While heterogeneity between studies hinders a clinically meaningful meta-analysis, the results are discussed in a clinical perspective with regard to applicability in clinical practice as well as methodological advantages and pitfalls of this technology. CONCLUSION: Technological as well as biological hindrances seem to exist for SWE to be clinically reliable in assessing benign and malignant thyroid nodules. Structural heterogeneity of thyroid nodules in combination with operator-dependent factors such as pre-compression and selection of scanning plane are likely explanations for these findings. Standardization and consensus on the SWE acquisition process applied in future studies are needed for SWE to be considered a clinically reliable diagnostic tool for detection of thyroid cancer.

Autoagresiones en adolescentes atendidos en un hospital de alta complejidad: Serie de casos clínicos / Self-injurious behavior in adolescents seen at a tertiary-level hospital: A case series

Dentro de los daños intencionales en adolescentes, las autoagresiones se han convertido en los últimos años en un tema de interés clínico, social y público, en constante investigación. Una conducta autolesiva es toda conducta autodeliberada destinada a producir daño físico directo en el cuerpo, sin la intención de provocar la muerte. Objetivos: Describir los casos de pacientes con autoagresiones que fueron atendidos por el equipo de adolescencia (clínica pediátrica y salud mental) en el Hospital Garrahan desde el año 2015 al 2017. Diseño observacional, descriptivo y retrospectivo. Se incluyeron todos los adolescentes que fueron evaluados en conjunto por el servicio de adolescencia y salud mental. Resultados: Se atendieron 17 casos, rango de edad 12 a 16 años, 14 mujeres. Los motivos de consulta fueron variados, el principal mecanismo de autoagresión elegido fue cortes superficiales en antebrazo y piernas. La mayoría presentó como factor de riesgo principal conflictos familiares, coincidiendo con la bibliografía revisada. Un abordaje integral por personal capacitado en un servicio amigable es necesario para no perder la oportunidad de pesquisar estas situaciones. Así, mediante un trabajo interdisciplinario disminuir los riesgos que conllevan estas conductas (AU)

Within intentional harm in adolescents, over the last years selfinjury has become an issue of clinical, social, and public interest in ongoing research. Self-injurious behavior is all deliberate behavior aimed at producing direct physical harm to the body, without the intention to cause death. Objectives: To describe cases of patients with self-injurious behavior seen by the adolescents team (pediatrics and mental health) at Garrahan Hospital between 2015 and 2017. A retrospective, observational, descriptive study was conducted. All adolescents seen together by the Departments of Adolescence and Mental Health were included in the study. Results: 17 patients were evaluated, with ages ranging from 12 to 16 years; 14 were girls. Main complaints were varied. The main mechanism of self-injury were superficial cuts on the forearms and legs. The main risk factor in the majority of patients were family conflicts, as reported in the literature. A comprehensive approach by trained personnel from a friendly team is necessary so as not to lose the opportunity to screen this type of situations. An interdisciplinary approach may reduce the risks associated with these behaviors (AU)

Role of heme modulation in inhibition of Atheris, Atractaspis, Causus, Cerastes, Echis, and Macrovipera hemotoxic venom activity.

Venomous snake bite and subsequent coagulopathy is a significant source of morbidity and mortality worldwide. The gold standard to treat coagulopathy caused by these venoms is the administration of antivenom; however, despite this therapy, coagulopathy still occurs and recurs. Of interest, our laboratory has demonstrated in vitro and in vivo that coagulopathy-inducing venom exposed to carbon monoxide (CO) is inhibited, potentially by an attached heme. The present investigation sought to determine if venoms derived from snakes of the African genera Atheris, Atractaspis, Causus, Cerastes, Echis, and Macrovipera that have no or limited antivenoms available could be inhibited with CO or with the metheme-inducing agent, O-phenylhydroxylamine (PHA). Assessing changes in coagulation kinetics of human plasma with thrombelastography, venoms were exposed in isolation to CO or PHA. Eight species were found to have procoagulant activity consistent with the generation of human thrombin, while one was likely fibrinogenolytic. All venoms were significantly inhibited by CO/PHA with species-specific variation noted. These data demonstrate indirectly that the heme is likely bound to these disparate venoms as an intermediary modulatory molecule. In conclusion, future investigation is warranted to determine if heme could serve as a potential therapeutic target to be modulated during treatment of envenomation by hemotoxic enzymes.

La somatización y conversión en la adolescencia: Un desafío diagnóstico y terapéutico en la consulta / Somatization and conversion in adolescence: A diagnostic and therapeutic challenge in the consultation

El término somatización está muy extendido en el campo de la clínica psicológica y psiquiátrica. Desde el punto de vista nosográfico la somatización y la conversión se encuentran conceptualizadas en el Manual Diagnóstico y Estadístico de las Enfermedades mentales (DSM-IV-TR) dentro de los Trastornos Somatomorfos. Los trastornos Somatomorfos (TS) agrupan diversos cuadros con una característica en común: la presencia de síntomas somáticos vinculados a un malestar psíquico y deterioro significativo, presentándose frecuentemente en niños y adolescentes. Los síntomas se corresponden con dolencias simples hasta cuadros funcionales invalidantes no explicados por una condición médica general, consumo de sustancias, simulación u otra patología mental. La prevalencia de los TS en la adolescencia ha aumentado en las últimas décadas, representando un desafío clínico y terapéutico para el médico por su dificultad clínica y general desconocimiento (AU)

The term somatization is a broad concept in the field of clinical psychology and psychiatry. From the nosographic point of view, somatization and conversion are conceptualized in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IVTR) within the somatoform disorders (SD) characterized by the presence of somatic symptoms associated with psychic pain and significant deterioration, often seen in children and adolescents. The symptoms range from simple discomfort to invalidating functional impairment unexplained by the general medical condition, substance abuse, and simulation or any other mental disorder. Prevalence of SD in adolescence has increased over the past decades, becoming a therapeutic and clinical challenge due to clinical difficulties and lack of unawareness of the disorde (AU)

Adolescentes y niños con ERC estadio V: Adherencia, estrategias de afrontamiento y percepción de relación parental / Adolescents and children with stage V CKD: adherence, coping strategies and perception of parental bond

La presente investigación tuvo como objetivo evaluar las siguientes variables: adherencia al tratamiento, afrontamiento y percepción del vínculo con los padres en pacientes niños y adolescentes de 8 a 18 años con Enfermedad Renal Crónica (ERC) estadio V atendidos en el Hospital Garrahan en el período julio 2014 - junio 2015. Materiales y métodos: Estudio observacional, prospectivo y transversal. Se realizaron entrevistas individuales semiestructuradas con pacientes y padres. Se utilizaron instrumentos validados en nuestro país para evaluar adherencia, afrontamiento y percepción de la relación parental. Resultados: Participaron 58 pacientes (55% de sexo femenino), 47 de estos pacientes son adolescentes, de los cuales el 72% presentó adherencia objetiva (corroborada por el especialista), el 72% presentó adherencia subjetiva al tratamiento y el 70% de los padres perciben a sus hijos como adherentes. Se ha hallado una distorsión entre la percepción que los pacientes tienen de su adherencia al tratamiento y el cumplimiento del mismo en aquellos que no adhieren en forma objetiva al tratamiento. El 84% de los pacientes adolescentes no adherentes, según el especialista, se perciben a sí mismos como adherentes. El 32% de los pacientes adherentes se perciben a sí mismos como no adherentes. En los padres de los adolescentes se han hallado cifras similares respecto del cumplimiento de tratamiento de sus hijos. Las estrategias de afrontamiento más utilizadas por los adolescentes son: ansiedad preocupación, reestructuración cognitiva y apoyo emocional. La mayoría (81%) percibe un control aceptable por parte de sus padres. Los adolescentes que perciben un control patológico por parte de sus padres usan como estrategias de afrontamiento más frecuentes ansiedad y evasión por la diversión. De los 11 niños que participaron en el trabajo, el 82% presenta adherencia objetiva (corroborada por el especialista), el 73% presenta adherencia subjetiva al tratamiento y el 73% de los padres perciben a sus hijos como adherentes. Las estrategias de afrontamiento más utilizadas por los niños son: búsqueda de gratificaciones alternativas y reestructuración cognitiva. La mayoría (91%) percibe un control aceptable por parte de sus padres. Dado que la n de niños es muy pequeña no se han realizado correlaciones entre los datos. Conclusión: Los mayoría de los pacientes incluidos en este trabajo son adherentes al tratamiento prescripto. El análisis de las divergencias encontradas entre adherencia objetiva y subjetiva puede ser de utilidad para la modificación de conductas que tiendan a un mayor cumplimiento del tratamiento (AU)

The aim of this study was to evaluate the following variables: treatment adherence, coping skills and perception of the parental bond in patients ­ children and adolescents ­ between 8 and 18 years of age with stage V chronic kidney disease (CKD) seen at Garrahan Hospital from July 2014 to June 2015. Material and methods: A prospective, observational, cross-sectional study was conducted. Individual semistructured interviews were held with the patients and parents. Locally validated instruments were used to evaluate treatment adherence, coping skills, and perception of the relationship with the parents. Results: 58 patients participated in the study (55% female), 47 of these patients were adolescents, of whom 72% had objective adherence (confirmed by specialist), 72% had subjective adherence to the treatment, and 70% of the parents felt their children adhered to treatment. Inconsistency was found between the patients' perceived adherence to treatment and adherence of those who were not considered to objectively adhere to treatment. Of the adolescent patients who did not adhere to treatment according to the specialist, 84% felt that they did adhere. Of the patients who adhered 32% perceived themselves as non-adherent. Similar figures regarding treatment adherence of their children were found in the parents. The most common coping strategies used by the adolescents were anxiety, worrying, cognitive estructuration, and emotional support. The majority (81%) felt control by the parents to be acceptable. Adolescents who perceived the control of the parents as pathological more commonly use anxiety and fun for denial as coping strategies. Of the 11 children who participated in the study, 82% had objective adherence to treatment (confirmed by the specialist) and 73% subjective adherence to treatment, and 73% of the parents perceived their children as adherent to treatment. The coping strategies most commonly used by the children were search for alternative gratifications and cognitive restructuration. The majority (91%) felt control by the parents to be acceptable. As the sample size of the children was very small no correlations among the data were analyzed. Conclusion: The majority of the patients included in the study adhered to the treatment prescribed. Analysis of the inconsistencies found between objective and subjective adherence may be useful to modify behaviors for better treatment compliance (AU)

Effects of iron and carbon monoxide on Lachesis muta muta venom-mediated degradation of plasmatic coagulation.

Hypofibrinogenemia is an important clinical consequence following envenomation by Lachesis muta muta, usually attenuated or prevented by administration of antivenom. The venom of L. m. muta contains both a metalloproteinase fibrinogenase and a serine protease thrombin-like enzyme, and exposure of fibrinogen to iron (Fe) and carbon monoxide (CO) has been demonstrated to decrease its catalysis by such enzymes. Using thrombelastographic analytical techniques, it was determined that this venom displayed weak procoagulant effects combined with fibrinogenolytic effects, and pretreatment of plasma with Fe and CO markedly attenuated venom-mediated effects. Additional experiments involving heparin exposure and varying calcium concentrations demonstrated that modification of fibrinogen with Fe and CO in human plasma rendered fibrinogen not recognizable to the fibrinogenolytic metalloproteinase but did not prevent polymerization by the thrombin-like serine protease. Lastly, when venom was exposed to CO in isolation and then placed in plasma, the fibrinogenase was inhibited but the thrombin-like enzyme was not inhibited. In sum, utilizing relatively facile modifications, we demonstrated with thrombelastography that Fe and/or CO addition can protect human plasmatic coagulation from fibrinogenase activity but not the effects of the thrombin-like activity of L. m. muta venom.

Microsatellite diversity of the Nordic type of goats in relation to breed conservation: how relevant is pure ancestry?

In the last decades, several endangered breeds of livestock species have been re-established effectively. However, the successful revival of the Dutch and Danish Landrace goats involved crossing with exotic breeds and the ancestry of the current populations is therefore not clear. We have generated genotypes for 27 FAO-recommended microsatellites of these landraces and three phenotypically similar Nordic-type landraces and compared these breeds with central European, Mediterranean and south-west Asian goats. We found decreasing levels of genetic diversity with increasing distance from the south-west Asian domestication site with a south-east-to-north-west cline that is clearly steeper than the Mediterranean east-to-west cline. In terms of genetic diversity, the Dutch Landrace comes next to the isolated Icelandic breed, which has an extremely low diversity. The Norwegian coastal goat and the Finnish and Icelandic landraces are clearly related. It appears that by a combination of mixed origin and a population bottleneck, the Dutch and Danish Land-races are separated from the other breeds. However, the current Dutch and Danish populations with the multicoloured and long-horned appearance effectively substitute for the original breed, illustrating that for conservation of cultural heritage, the phenotype of a breed is more relevant than pure ancestry and the genetic diversity of the original breed. More in general, we propose that for conservation, the retention of genetic diversity of an original breed and of the visual phenotype by which the breed is recognized and defined needs to be considered separately.

15q13.3 homozygous knockout mouse model display epilepsy-, autism- and schizophrenia-related phenotypes.

The 15q13.3 microdeletion syndrome is caused by a 1.5-MB hemizygous microdeletion located on 15q13.3 affecting seven genes: FAN1; MTMR10; TRPM1; miR-211; KLF13; OTUD7A; and CHRNA7. The 15q13.3 microdeletion increases the risk of intellectual disability, epilepsy, autism spectrum disorder and schizophrenia, though the clinical profile varies considerably. Two mouse models of this syndrome, with hemizygous deletion of the orthologous region in the murine genome, have recently been shown to recapitulate a number of the behavioral and physiological deficits that characterize the human condition. Still, little is known of the underlying biological mechanisms. Eleven human cases with homozygous deletion of the 15q13.3 region have been reported, all with severe functional and physiological impairments. We therefore hypothesized that a 15q13.3 homozygous knockout would confer more pronounced behavioral and physiological deficits in mice than the 15q13.3 hemizygous deletion. Here we report the characterization of a 15q13.3 knockout mouse. We observed marked deficits including altered seizure susceptibility, autistic behavior-related phenotypes, and auditory sensory processing. Several of these deficits, albeit less pronounced, were also found in the 15q13.3 hemizygous littermates indicating a gene-dosage dependency. Our findings strongly indicate that studies of the hemi- and homozygous 15q13.3 mouse strains will facilitate understanding of the biological mechanisms of severe mental disorders.

Iron and carbon monoxide prevent degradation of plasmatic coagulation by thrombin-like activity in rattlesnake venom.

Thousands suffer poisonous snake bite, often from defibrinogenating species annually. Three rattlesnake species in particular, the timber rattlesnake, Eastern diamondback rattlesnake, and Southern Pacific rattlesnake, cause clinically relevant hypofibrinogenemia via thrombin-like activity in their venom. It has been demonstrated that iron (Fe) and carbon monoxide (CO) change the ultrastructure of plasma thrombi and improve coagulation kinetics. Thus, the present investigation sought to determine if pretreatment of plasma with Fe and CO could attenuate venom-mediated catalysis of fibrinogen via thrombin-like activity. Human plasma was pretreated with ferric chloride (0-10 µM) and CO-releasing molecule-2 (0-100 µM) prior to exposure to 2.5-10 µg/ml of venom obtained from the aforementioned three species of rattlesnake. Coagulation kinetics were determined with thrombelastography. All three snake venoms degraded plasmatic coagulation kinetics to a significant extent, especially diminishing the speed of clot growth and strength. Pretreatment of plasma with Fe and CO completely abrogated the effects of all three venoms on coagulation kinetics. Further in vitro investigation of other pit viper venoms that possess thrombin-like activity is indicated to see if there is significant conservation of venom enzymatic target recognition of specific amino acid sequences such that Fe and CO can reliably attenuate venom-mediated catalysis of fibrinogen. These data also serve as a rationale for future preclinical investigation.

Longitudinal analysis of residual feed intake and BW in mink using random regression with heterogeneous residual variance.

The aim of this study was to determine the genetic background of longitudinal residual feed intake (RFI) and BW gain in farmed mink using random regression methods considering heterogeneous residual variances. The individual BW was measured every 3 weeks from 63 to 210 days of age for 2139 male+female pairs of juvenile mink during the growing-furring period. Cumulative feed intake was calculated six times with 3-week intervals based on daily feed consumption between weighing's from 105 to 210 days of age. Genetic parameters for RFI and BW gain in males and females were obtained using univariate random regression with Legendre polynomials containing an animal genetic effect and permanent environmental effect of litter along with heterogeneous residual variances. Heritability estimates for RFI increased with age from 0.18 (0.03, posterior standard deviation (PSD)) at 105 days of age to 0.49 (0.03, PSD) and 0.46 (0.03, PSD) at 210 days of age in male and female mink, respectively. The heritability estimates for BW gain increased with age and had moderate to high range for males (0.33 (0.02, PSD) to 0.84 (0.02, PSD)) and females (0.35 (0.03, PSD) to 0.85 (0.02, PSD)). RFI estimates during the growing period (105 to 126 days of age) showed high positive genetic correlations with the pelting RFI (210 days of age) in male (0.86 to 0.97) and female (0.92 to 0.98). However, phenotypic correlations were lower from 0.47 to 0.76 in males and 0.61 to 0.75 in females. Furthermore, BW records in the growing period (63 to 126 days of age) had moderate (male: 0.39, female: 0.53) to high (male: 0.87, female: 0.94) genetic correlations with pelting BW (210 days of age). The result of current study showed that RFI and BW in mink are highly heritable, especially at the late furring period, suggesting potential for large genetic gains for these traits. The genetic correlations suggested that substantial genetic gain can be obtained by only considering the RFI estimate and BW at pelting, however, lower genetic correlations than unity indicate that extra genetic gain can be obtained by including estimates of these traits during the growing period. This study suggests random regression methods are suitable for analysing feed efficiency and BW gain; and genetic selection for RFI in mink is promising.

Identifying QTL and genetic correlations between fur quality traits in mink (Neovison vison).

Mapping of QTL affecting fur quality traits (guard hair length, guard hair thickness, density of wool, surface of the fur and quality) and skin length was performed in a three-generation mink population (F2 design). In the parental generation, Nordic Brown mink were crossed reciprocally with American Black short nap mink. In all, 1082 mink encompassing three generations were used for the analyses. The mink were genotyped for 104 microsatellites covering all 14 autosomes. The QTL analyses were performed by least-square regression implemented in gridqtl software. Genetic and phenotypic correlations and heritabilities were estimated using the average information-restricted maximum-likelihood method. Evidence was found for QTL affecting fur quality traits on nine autosomes. QTL were detected for guard hair thickness on chromosomes 1, 2, 3, 6 and 13; for guard hair length on chromosomes 2, 3 and 6; for wool density on chromosomes 6 and 13; for surface on chromosomes 7, 12 and 13; for quality on chromosomes 6, 7, 11 and 13; and for skin length on chromosomes 7 and 9. Proximity of locations of QTL for guard hair length, guard hair thickness and for wool density and quality suggests that some of the traits are in part under the influence of the same genes. Traits under the influence of QTL at close or identical positions also were traits that were strongly genotypically correlated. Based on the results of correlation analyses, the most important single traits influencing the quality were found to be density of wool, guard hair thickness and appearance of the surface.

Inbreeding affects fecundity of American mink (Neovison vison) in Danish farm mink.

Inbreeding is an increasing problem in farmed mink, because of limited exchange of individuals between farms. In this study, genetic relatedness within seven American mink (Neovison vison) colour strains originating from 13 different mink farms in Denmark was analysed using 21 polymorphic microsatellite loci. We detected large differences in the level of relatedness (range 0.017-0.520) within colour strains. Moreover, a very strong and highly significant negative correlation between the level of relatedness and fecundity was observed (r = 0.536, P < 0.001) [Correction added after online publication on 9 March 2011: r(2) has been changed to r]. To our knowledge, this is the first time that such a correlation has been demonstrated for commercially farmed mink.