Experiencia clínica en hipertensión arterial pulmonar en un hospital general de tercer nivel / Clinical experience in pulmonary arterial hypertension in a general tertiary hospital

Introducción: La hipertensión arterial pulmonar es una enfermedad rara. Cursa con aumento progresivo de la resistencia vascular pulmonar e insuficiencia ventricular derecha y muerte precoz. Los tratamientos específicos han mejorado la esperanza de vida aunque el pronóstico a largo plazo sigue siendo desfavorable con una mortalidad del 40% a los tres años.Materiales y métodos: El estudio es descriptivo observacional trasversal y retrospectivo realizado en un hospital general de tercer nivel entre mayo de 2004 y agosto de 2020. Se midió la capacidad funcional (CF), la presión arterial pulmonar media, el test de la marcha de los 6 minutos (PM6M) entre otras variables. Se recogieron variables de tratamiento farmacológico específico y efectos adversos, así como la adherencia farmacológica.Resultados: La población fue de 27 pacientes, la mayoría mujeres con edad media de 62 años. Más del 80% de los pacientes presentaban CF II-III y PM6M de riesgo intermedio. Los tratamientos en primera línea y monoterapia mayoritarios fueron el sildenafilo y bosentán con un grado de recomendación de Ia, seguidos de ambrisentán. Los otros grupos de fármacos fueron minoritarios en los pacientes. No se encontraron diferencias estadísticamente significativas en la variación del PM6M, sí hubo variación de PAPm de forma positiva. Conclusiones: Todos los pacientes llevaban en tratamiento específico más de tres años, aunque sería necesario ampliar el tamaño muestral. En cuanto a la seguridad los efectos adversos fueron de grado leve y la adherencia al tratamiento elevada. (AU)

Introduction: Pulmonary arterial hypertension is a rare disease. It results a progressive increase in pulmonary vascular resistance and in right ventricular failure and early death. Specific treatments have improved the life expectancy of patients but the long-term prognosis remains poor, resulting in a high mortality of 40% at 3 years. Materials and methods: The research conducted is descriptive, cross-sectional and retrospective. It was carried out in a third level general hospital between May 2004 and August 2020. The measured variables were functional capacity (CF), PAPm, 6-minute walk test (PM6M) and other clinical parameters. Variables related to specific pharmacological treatment and adverse effects, as well as pharmacological adherence were also collected. Results: The study population was 27 patients, most of them women, with an average age of 62 years. More than 80% of patients presented CF II-III and PM6M of moderate risk. First-line and monotherapy treatments were mainly sildenafil and bosentan, with an Ia recommendation level. Ambrisentan was also a first-line treatment. The other drug groups were in the minority among patients. On the other hand, no statistically significant differences in PM6M variation were found, although there was positive variation in PAPm. Conclusions: The patients had been on specific treatment for more than three years. In terms of safety, adverse effects were minor and adherence to treatment high. (AU)

[Effectiveness on adherence to biological drugs and experience of a pharmaceutical intervention based on CMO model in patients with rheumatic disease (AdhER-2 study)].

BACKGROUND: We aimed to assess the effectiveness on adherence to treatment with biologic disease modifying anti-rheumatic drugs (b-DMARD) and experience with providers of healthcare of a CMO pharmaceutical intervention care model in subjects with rheu-matoid arthritis, psoriatic arthritis, and ankylosing spondylitis stratified according to their needs. METHOD: Prospective, single-centre randomized controlled study. The study period was eleven months. Non-compliant patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondy-litis treated with b-DMARD were included. Patients were randomized to a control (CG) or intervention group (IG) who received regular or the CMO pharmaceutical intervention model treatment, respec-tively. Baseline and final adherence were determined using medication possession ratio, the Compliance Questionnaire on Rheu-matology, and Morisky Medication Adherence Scale. To assess baseline and final patient experience with providers of healthcare we applied the Chronic Patient Experience Assessment Instrument (IEXPAC). RESULTS: For the IG, one patient (5.6%) was categorized as priority 1, nine (50.0%) as priority 2, and eight (44.4%) as priority 3. Ninety pharmaceutical interventions were carried out (5.1±1.8 interventions / patient). At the end of the study, the IG showed higher fre-quency of patients who adhered to the pharmaceutical intervention (77.8 vs 18.8%; p=0.002) and higher mean IEXPAC score (7.6±1.3 vs 5.8±1.1; p <0.001) in comparison to the CG. Conclusion The CMO pharmaceutical intervention model significantly improves patient adherence to b-DMARD and their experience with the providers of healthcare.

Eficacia de una intervención farmacéutica basada en el modelo CMO sobre la adherencia a fármacos biológicos y la experiencia del pacientecon enfermedad reumática (Estudio ADhER-2) / Effectiveness on adherence to biological drugs and experience of a pharmaceutical intervention based on CMO model in patients with rheumatic disease (AdhER-2 study)

Fundamento: Analizar la eficacia de una intervención farmacéutica basada en el modelo CMO sobre la adherencia a fármacos biológicos modificadores de la enfermedad (FAME-b) y sobre la experiencia con los profesionales y servicios sanitarios de pacientescon artritis reumatoide, artritis psoriásica y espondilitis anquilosante estratificados según sus necesidades de atención. Material y métodos: Estudio experimental prospectivo, unicéntrico y controlado de once meses de duración. Se incluyeron pacientes con artritis reumatoide, artritis psoriásica y espondilitis anquilosante no adherentes a FAME-b. Se aleatorizaron en grupo control (GC) e intervención (GI), que recibieron atención farmacéutica habitual o basada en CMO, respectivamente. La adherencia basaly final se calculó mediante la ratio media de posesión de medicamentos y las puntuaciones obtenidas en Compliance Questionnaire on Rheumatology y en Morisky Medication Adherence Scale. Para valorar la experiencia basal y final de los pacientes con los profesionales y servicios sanitarios se utilizó el instrumento de Evaluaciónde la Experiencia del Paciente Crónico (IEXPAC). Resultados: En el GI (n=18), solo un paciente fue estratificado como prioridad 1 (5,6%), nueve se estratificaron como prioridad2 (50,0%) y ocho como prioridad 3 (44,4%). Se realizaron 90 intervenciones farmacéuticas (5,1±1,8 intervenciones por paciente). Al finalizar el estudio, el GI mostró respecto del GC más pacientes adherentes (77,8 vs 18,8%; p=0,002) y mayor puntuación IEXPAC (7,6±1,3 vs 5,8±1,1; p <0,001). Conclusiones: La intervención farmacéutica basada en el modelo CMO mejoró significativamente la adherencia a FAME-b y la experiencia de los pacientes con los profesionales y el sistema sanitario.(AU)

Background: We aimed to assess the effectiveness on adherence to treatment with biologic disease modifying antirheumatic drugs (b-DMARD) and experience with providers of healthcare of a CMO pharmaceutical intervention care model in subjects with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis stratified according to their needs. Method: Prospective, single centre randomized controlled study. The study period was eleven months. Non compliant patients withrheumatoid arthritis, psoriatic arthritis, and ankylosing spondy litis treated with b-DMARD were included. Patients were randomized to a control (CG) or intervention group (IG) who receivedregular or the CMO pharmaceutical intervention model treatment, respectively. Baseline and final adherence were determined using medication possession ratio, the Compliance Questionnaire onRheumatology, and Morisky Medication Adherence Scale. To assess baseline and final patient experience with providers of healthcare we applied the Chronic Patient Experience Assessment Instrument (IEXPAC). Results: For the IG, one patient (5.6%) was categorized as priority1, nine (50.0%) as priority 2, and eight (44.4%) as priority 3. Ninety pharmaceutical interventions were carried out (5.1±1.8 interventions / patient). At the end of the study, the IG showed higherfrequency of patients who adhered to the pharmaceutical intervention (77.8 vs 18.8%; p=0.002) and higher mean IEXPAC score (7.6±1.3 vs 5.8±1.1; p <0.001) in comparison to the CG. Conclusion: The CMO pharmaceutical intervention model significantly improves patient adherence to b-DMARD and their experience with the providers of healthcare.(AU)

[Adherence to biological therapies in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. (Study ADhER-1)]. / Adherencia terapéutica a fármacos biológicos en pacientes con artritis reumatoide, artritis psoriásica y espondilitis anquilosante. (Estudio ADhER-1).

BACKGROUND: To quantify adherence to biological disease-modifying anti-rheumatic drugs (DMARD) and to determine the factors that can predict adherence in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis in daily clinical practice. METHODS: An observational, descriptive, cross-sectional and single-center study was carried out. Patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis who were in treatment with subcutaneous biological DMARD were included. Variables related to socioeconomic status, disease, biological therapy and safety were recorded. Adherence was calculated by using medication possession ratio, Compliance Questionnaire on Rheumatology and Morisky Medication Adherence Scale Questionnaire. RESULTS: One hundred twelve patients and 6 different biological DMARDs were included. Mean age was 56.8±13.2 years and 52.7% were women. The percentage of adherent patients was 59.3% in rheumatoid arthritis, 62.5% in psoriatic arthritis and 76.2% in ankylosing spondylitis. Lesser adherence was associated with the administration of the drug by a family member and/or caregiver (odds ratio: 9.6; 95% confidence interval: 1.5-61.8 (p <.05)). There were no differences between adherent and non-adherent patients in terms of the biological DMARD used. CONCLUSIONS: There are no differences in adherence to biological therapies among patients with chronic inflammatory arthropathies. Adherence correlates negatively with administration of biological DMARD by a family member and / or caregiver.

Plasma vitellogenin levels during the annual reproductive cycle of the female rainbow trout (Oncorhynchus mykiss): establishment and validation of an ELISA.

Rainbow trout, Oncorhynchus mykiss, vitellogenin (Vtg) was purified from plasma of E2-treated male by direct anion exchange chromatography and some of its biochemical characteristics were studied. Our results demonstrated that, under SDS-PAGE conditions, rainbow trout Vtg was composed of two molecular forms of 390 and 176 kDa representing, respectively, the dimeric form and the monomeric from of the molecule. The purified Vtg was used to raise a polyclonal antibody for Vtg (anti-Vtg). Using this anti-Vtg, a competitive enzyme-linked immunosorbent assay (ELISA) was developed for the quantification of rainbow trout Vtg. The practical sensitivity range of this ELISA was 20-320 ng/ml (80-20% of binding) and the detection limit was 9 ng/ml. The intra- and the inter-assay coefficients of variation (at 50% of binding) were estimated at 1.8% (n = 10) and 3.9% (n = 13), respectively. This ELISA was validated by detecting changes in Vtg levels in rainbow trout at different physiological stages, as well as in 2-year-old female rainbow trout throughout the reproductive cycle.

Identification of vitellogenin receptors in the ovary of a teleost fish, the Mediterranean sea bass (Dicentrarchus labrax).

The characterization of vitellogenin (VTG) receptors in ovarian membranes from vitellogenic female sea bass (Dicentrarchus labrax) is described. Incubation of membrane proteins with radiolabeled VTG (125I-VTG) after SDS-electrophoresis showed specific binding of 125I-VTG to a protein band of 100 kDa. Filter binding assays showed that binding of 125I-VTG to membrane receptors was saturable with increasing amounts of 125I-VTG. Scatchard analysis of the saturation data revealed a single class of binding sites with an apparent KD of 1.04 x 10(-8) M. The specificity of the VTG receptors was tested in competition assays; binding of 125I-VTG to ovarian membranes was completely abolished with an excess of purified sea bass VTG (cold VTG, VTG degree) or plasma from estradiol (E2)-treated fish, while the addition of control male plasma (without VTG) caused negligible effect.

Vitellogenin receptors during vitellogenesis in the rainbow trout Oncorhynchus mykiss.

Rainbow trout vitellogenin receptors have been characterized by ligand blotting and Scatchard analysis. Their evolution has been studied over a reproductive cycle in a broodstock of 2-year-old females. The receptors were prepared from ovarian membrane homogenates and were solubilized using n-octyl-beta-D-glucopyranoside. The visualization of the receptor by ligand blotting using 125iodine-vitellogenin after sodium dodecyl sulfate electrophoresis revealed the existence of one major binding component corresponding to a protein of 113 kDa. The Scatchard transformation of the binding data revealed a single class of binding sites with an apparent Kd of 1.8 x 10(-8) M/L. The variations of the binding characteristics (Kd and maximum binding) were investigated during vitellogenesis. This study revealed that the Kd was not affected by oocyte growth during vitellogenesis, but was highly decreased in ovulated eggs. The receptor number increased during the same period from 35 to 860 fM per oocyte, while the receptor number per mm2 of oocyte membrane surface was doubled during the same period.

Development of an enzyme-linked immunosorbent assay for goldfish gonadotropin.

An enzyme-linked immunosorbent assay (ELISA) for goldfish gonadotropin (GTH) was developed with the intent of devising a simple, reliable and nonradioisotopic assay for the measurement of GTH in goldfish biological samples. In this assay, soluble GTH of the standards or samples competes with carp GTH (cGTH) immobilized on a solid support (96-well microplate) for the fixation on antibodies to the beta-subunit of carp gonadotropin. The immobilized antigen-antibody complexes are then revealed by the peroxidase-antiperoxidase (PAP) technique. After revelation of the peroxidase activity, the absorbance value of each well is measured with a microplate reader. The cGTH concentration used for coating the wells is 2 ng/ml and the final dilution of the specific antibody is 1:80,000. The assay can be performed within 24 h and can be used over a range of 0.125-4 ng/ml. At about 50% binding, the intra- and interassay coefficients of variation are 5% and 9% respectively. The displacement curves generated by goldfish plasma or pituitary perifusion fractions were strictly parallel to the standard cGTH. In addition, the stimulation by salmon gonadotropin-releasing hormone of pituitary fractions perifused in vitro caused an immediate increase in the GTH measured in the collected fractions, strongly reinforcing the assumption that this assay indeed measures GTH.

Immunohistochemical investigation of the pituitary of the sturgeon (Acipenser baeri, Chondrostei).

An immunohistochemical study of the sturgeon (Acipenser baeri) pituitary was undertaken using antisera directed against hormones from various classes of vertebrates, including the only pituitary hormone available from sturgeon, gonadotrophin. A positive reaction was obtained after application of antisera towards the following hormones 1-24 synthetic ACTH (1-24 ACTH), melanophore stimulating hormone (MSH), ovine prolactin (oPRL), ovine growth hormone (oGH), salmon growth hormone (sGH), carp gonadotrophin (cGTH) and its beta subunit (ßcGTH), sturgeon gonadotrophin (aciGTH), carp thyrotrophin (cTSH) and ß subunit of the human thyrotrophin (ßhTSH). The results demonstrate that, in general, the sturgeon pituitary resembles that of teleosts as regards the distribution of the different cell types: ACTH and PRL cells in the rostral pars distalis, GTH, TSH and GH cells in the proximal pars distalis and MSH and PAS-cells in pars intermedia. In addition to the topographical organization of the sturgeon pituitary, this study provides data on the immunological relationships between sturgeon pituitary hormones and those of other vertebrates.

A reinvestigation of the Gn-RH (gonadotrophin-releasing hormone) systems in the goldfish brain using antibodies to salmon Gn-RH.

The organization of Gn-RH systems in the brain of teleosts has been investigated previously by immunohistochemistry using antibodies against the mammalian decapeptide which differs from the teleostean factor. Here, we report the distribution of immunoreactive Gn-RH in the brain of goldfish using antibodies against synthetic teleost peptide. Immunoreactive structures are found along a column extending from the rostral olfactory bulbs to the pituitary stalk. Cell bodies are observed within the olfactory nerves and bulbs, along the ventromedial telencephalon, the ventrolateral preoptic area and the latero-basal hypothalamus. Large perikarya are detected in the dorsal midbrain tegmentum, immediately caudal to the posterior commissure. A prominent pathway was traced from the cells located in the olfactory nerves through the medial olfactory tract and along all the perikarya described above to the pituitary stalk. In the pituitary, projections are restricted to the proximal pars distalis. A second immunoreactive pathway ascends more dorsally in the telencephalon and arches to the periventricular regions of the diencephalon. Part of this pathway forms a periventricular network in the dorsal and posterior hypothalamus, whereas other projections continue caudally to the medulla oblongata and the spinal cord. Lesions of the ventral preoptic area demonstrate that most of the fibers detected in the pituitary originate from the preoptic region.