THE 72-KDA PROTEIN OF NAEGLERIA FOWLERI PLAYS AN IMPORTANT ROLE IN THE ADHESION OF TROPHOZOITES TO BALB/C MICE NASAL EPITHELIUM.

Naegleria fowleri is a protozoan that causes primary amebic meningoencephalitis (PAM). The infection occurs when the trophozoites enter the nasal cavity, adhere to the nasal mucosa, invade the epithelium, and migrate until they reach the olfactory bulb. Like other pathogens, there is evidence that the adhesion of N. fowleri to host cells is an important factor in the process of cytopathogenicity and disease progression. However, the factors involved in the adhesion of the pathogen to the cells of the nasal epithelium have not been characterized. The objective of this study was to identify a protein on the surface of N. fowleri, which could act as adhesin to the mouse nasal epithelium in the PAM model. The interaction between proteins of extracts of N. fowleri and cells of the nasal epithelium of BALB/c mice was analyzed using overlay and Western blot assays. A 72-kDa band of N. fowleri interacted directly with epithelial cell proteins, this polypeptide band was purified and analyzed by mass spectrometry. Analysis revealed that polypeptide bands of 72 kDa contained peptides that matched the membrane protein, actin 1 and 2, and Hsp70. Moreover, the N. fowleri extracts resolved in 2D-SDS-PAGE showed that 72-kDa spot interacted with proteins of mouse epithelial cells, which include characteristics of the theoretical data of molecular weight and pH obtained in the analysis by mass spectrometry. Immunofluorescence tests showed that this protein is located on the surface of trophozoites and plays an important role in the adhesion of amoeba either in vitro or in vivo assays, suggesting that this protein contributes during the N. fowleri invasion and migration to the brain, causing primary amoebic meningoencephalitis.

Pharmacological Inventions for Alzheimer Treatment in the United States of America: A Revision Patent from 2010 - 2020.

Alzheimer's disease (AD) is the most common form of dementia. There is currently no cure, and the available pharmacological treatment focuses on treating the symptoms. This study aimed to analyze the pharmacological treatments for AD protected in the US Patent Office. The Matheo Patent software was used to search for patents granted in the 2010-2020 period in the USPTO database. The search strategy «Alzheimer¼ was used in title and abstract and the International Patent Classification (IPC) codes A61P* and A61K*. The selected patents were divided into six categories according to therapeutic target. Complementary information from scientific databases was used to determine the stage of investigation and efficacy of the patented molecules. In the analyzed period, 58 patents were granted: 10 directed to Aß peptide metabolism and deposition, three to tau, seven to inflammation, nine to cholinergic, two to glutamatergic and 27 to other targets. More than 80.0% belong to holders from the USA, France, and Japan. The molecules Elenbecestat and LY3202626 decreased the burden of Aß plaques without significant cognitive improvement, Donanemab is in Phase 3 clinical trial, and the FDA has designated it Breakthrough Therapy. CPC-201 and PXT864 demonstrated, in Phase 2, good tolerability and improvement of AD symptoms. Most of the inventions are focused on treating the earliest phase of AD. The most advanced treatments in their research are those focused on treating Aß accumulation. More studies are needed to prove the efficacy of the patented molecules.

Lower uterine segment thickness assessed by transvaginal ultrasound before labor induction: reproducibility analysis and relationship with delivery outcome.

OBJECTIVES: To evaluate the reproducibility of lower uterine segment (LUS) thickness measurement before induction of labor (IOL), and to assess the relationship between LUS thickness and IOL outcomes. METHODS: This was a prospective cohort study of pregnant women undergoing IOL at term, conducted in a single tertiary hospital between July 2014 and February 2017. Women with a singleton pregnancy at ≥ 37 weeks' gestation, with a live fetus in cephalic presentation and a Bishop score of ≤ 6, were eligible for inclusion. Both nulliparous and parous women, and those with a previous Cesarean section (CS), were eligible. All women underwent transvaginal ultrasound assessment before IOL admission, and cervical length and LUS thickness were measured offline after delivery. Maternal and obstetric characteristics and Bishop score were recorded. The main outcome was the overall rate of CS after IOL, and secondary outcomes were CS for either failure to progress in the active phase of labor or failed IOL, and CS for failed IOL only. Interobserver agreement for measurement of LUS thickness between two operators was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis with the ANOVA test to evaluate systematic bias. Univariable and multivariable analysis were employed to evaluate the relationship between clinical and sonographic characteristics and IOL outcomes. RESULTS: Of 265 women included in the analysis, 195 (73.6%) had a vaginal delivery and 70 (26.4%) required a CS after IOL. Reproducibility analysis showed excellent interobserver agreement for the measurement of LUS thickness (ICC, 0.96 (95% CI, 0.93-0.98)). On Bland-Altman analysis, the mean difference in LUS thickness between the two operators was 0.15 mm (95% limits of agreement, -1.84 to 2.14 mm), and there was no evidence of systematic bias (ANOVA test, P = 0.46). Univariable analysis showed that LUS thickness was associated significantly with overall CS (P = 0.002), CS for failure to progress in the active phase of labor or failed IOL (P = 0.03) and CS for failed IOL (P = 0.037). On multivariable logistic regression analysis, LUS thickness was an independent predictive factor for overall CS (odds ratio (OR), 1.149 (95% CI, 1.031-1.281)) and CS for failure to progress in the active phase of labor or failed IOL (OR, 1.226 (95% CI, 1.039-1.445)). CONCLUSIONS: In women undergoing IOL at term, measurement of LUS thickness is feasible and reproducible, and is associated significantly with IOL outcome. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Asociación entre gastritis biliar y gastritis por Helicobacter pylori en pacientes con reflujo duodenogástrico en el Hospital Central Militar / Association between biliary gastritis and gastritis by Helicobacter pylori in patients with duodenogastric reflection in the Military Central Hospital

Resumen Introducción: Esta investigación está orientada a conocer si existe una asociación (directa o indirecta) entre el reflujo duodenogástrico y las gastritis crónicas por Helicobacter pylori. Material y Metodo: Se recolectaron los datos de pacientes a quienes se les realizó panendoscopía diagnóstica en el departamento de endoscopia del Hospital Central Militar desde marzo del 2018 a febrero del 2019, por medio de una entrevista clínica y una hoja de recolección de datos. Resultados: Del grupo evaluado con reflujo duodenogástrico, el 44.1% (202 casos) presentaron gastritis química por reporte histopatológico. En el grupo de pacientes con reflujo duodenogástrico y gastritis química o biliar (n=202), el 22.7% (46 casos) presentó en el reporte histopatológico gastritis por Helicobacter pylori. En los pacientes con reflujo duodenogástrico y sin gastritis biliar (n=256), el 92.57% (237 casos) presentó gastritis por Helicobacter pylori en el reporte histopatológico. Discusión: Existe una asociación alta de tipo indirecto entre la gastritis biliar y gastritis por Helicobacter pylori en pacientes con reflujo duodenogástrico o biliar. Aproximadamente la mitad de los pacientes con reflujo duodenogástrico presentan gastritis biliar con el riesgo de desarrollar metaplasia intestinal. La gastropatía mixta (gastritis biliar y por Helicobacter pylori) es un factor de riesgo para mayor daño a la mucosa gástrica, como es la expresión de metaplasia intestinal.

Abstract Introduction: This research is oriented to know if there is an association (direct or indirect) between duodenogastric reflux and chronic gastritis by Helicobacter pylori. Material and Method: We collected data from patients who underwent diagnostic panendoscopy in the endoscopy department of the Central Military Hospital from March 2018 to February 2019, through a clinical interview and a data collection sheet. Results: Of the group evaluated with duodenogastric reflux, 44.1% (202 cases) presented chemical gastritis due to histopathological report. In the group of patients with duodenogastric reflux and chemical or biliary gastritis (n = 202), 22.7% (46 cases) presented gastritis due to Helicobacter pylori in the histopathological report. In patients with duodenogastric reflux and without biliary gastritis (n = 256), 92.57% (237 cases) presented gastritis due to Helicobacter pylori in the histopathological report. Discussion: There is a high association of indirect type between biliary gastritis and gastritis due to Helicobacter pylori in patients with duodenogastric or biliary reflux. Approximately half of the patients with duodenogastric reflux present biliary gastritis with the risk of developing intestinal metaplasia. Mixed gastropathy (biliary gastritis and Helicobacter pylori) is a risk factor for greater damage to the gastric mucosa, such as the expression of intestinal metaplasia.

Determination of bisphenols, parabens, and benzophenones in placenta by dispersive liquid-liquid microextraction and gas chromatography-tandem mass spectrometry.

Human exposure to endocrine disrupting chemicals (EDCs) is of particular concern during development. Bisphenols, parabens, and benzophenones are EDCs widely used in the manufacture of numerous goods, personal care products, and cosmetics. The aim of this study was to develop a new and practical method for determining three bisphenols, four parabens, and five benzophenones in placenta samples. It uses dispersive liquid-liquid microextraction (DLLME) in combination with gas chromatography-tandem mass spectrometry (GC-MS/MS). Several chemometric approaches were employed to optimize the experimental parameters. Limits of detection ranged from 0.04 to 0.08 ng g-1 and inter-day variabilities (evaluated as relative standard deviation) from 4.2% to 13.4%. The method was validated using matrix-matched standard calibration followed by a recovery assay with spiked samples. Recovery percentages ranged from 87.1% to 113.2%. Finally, the method was used to measure target compounds in 20 placental tissue samples from voluntary donors. This analytical procedure can provide information on the exposure of the fetus to non-persistent EDCs.

Preventing the recurrence of depression with a Mediterranean diet supplemented with extra-virgin olive oil. The PREDI-DEP trial: study protocol.

BACKGROUND: The role of dietary patterns in the prevention of unipolar depression has been analyzed in several epidemiological studies. The primary aims of this study are to determine the effectiveness of an extra-olive oil-enriched Mediterranean diet in reducing the recurrence of depression and improving the symptoms of this condition. METHODS: Multicenter, two-arm, parallel-group clinical trial. Arm 1, extra-virgin olive oil Mediterranean diet; Arm 2, control group without nutritional intervention. Dieticians are in charge of the nutritional intervention and regular contact with the participants. Contacts are made through our web platform ( https://predidep.es/participantes/ ) or by phone. Recurrence of depression is assessed by psychiatrists and clinical psychologists through clinical evaluations (semi-structured clinical interviews: Spanish SCID-I). Depressive symptoms are assessed with the Beck Depression Inventory. Information on quality of life, level of physical activity, dietary habits, and blood, urine and stool samples are collected after the subject has agreed to participate in the study and once a year. DISCUSSION: To the best of our knowledge, the PREDI-DEP trial is the first ongoing randomized clinical trial designed to assess the role of the Mediterranean diet in the prevention of recurrent depression. It could be a cost-effective approach to avoid recurrence and improve the quality of life of these patients. TRIAL REGISTRATION: The study has been prospectively registered in the U.S. National Library of Medicine ( https://clinicaltrials.gov ) with NCT number: NCT03081065.

Diagnóstico y tratamiento de la enfermedad pélvica inflamatoria / Diagnosis and treatment of pelvic inflammatory disease

Objetivo: Estudiar los factores de riesgo y la relación entre los hallazgos clínico-ecográficos y los hallazgos microbiológicos y anatomopatológicos en el contexto de una enfermedad pélvica inflamatoria. Material y métodos: Estudio observacional retrospectivo realizado entre enero de 2010 y noviembre de 2015. Se incluyó a aquellas pacientes con diagnóstico de enfermedad pélvica inflamatoria registradas en la base de datos informatizada del Servicio de Obstetricia y Ginecología del Complejo Hospitalario Universitario Insular Materno-Infantil y con criterios para ser hospitalizadas. Se excluyeron las pacientes tratadas de forma ambulatoria. Resultados: Se obtuvo una muestra de 112 pacientes con una edad media de 35,4 años. Solamente el 11,6% cumplían todos los criterios mínimos de diagnóstico de enfermedad pélvica inflamatoria. Los patógenos aislados en mayor porcentaje fueron clamidia y gonococo. Se hizo biopsia de endometrio en un 55,6% de los casos y la ecografía informó de una imagen sugestiva de EPI en un 56,3%. La pauta antibiótica más empleada fue la asociación de clindamicina y gentamicina. Se instauró tratamiento de la pareja sexual en el 48,2% de los casos. El 82,15% de las pacientes recibieron tratamiento quirúrgico. Conclusión: La población estudiada es atípica en cuanto a edad media y factores de riesgo, aunque la recogida de datos en la anamnesis es mejorable. La incidencia de gonorrea ha disminuido en nuestro medio, coincidiendo con la aparición de nuevos patógenos que adquieren mayor importancia. Se debe insistir en la toma de biopsia de endometrio para aumentar el índice de sospecha y en la realización del tratamiento a la pareja sexual. Aun así, los resultados del tratamiento hospitalario y quirúrgico fueron favorables

Objective: To analyse the risk factors and the relationship between clinical and sonographic findings and microbiological and pathological findings in the context of pelvic inflammatory disease. Materials and methods: Retrospective observational study conducted between January 2010 and November 2015. Patients with a diagnosis of pelvic inflammatory disease, registered in the electronic database of the Department of Obstetrics and Gynaecology of Complejo Hospitalario Universitario Insular Materno-Infantil, who met the hospitalisation criteria for the Gynaecology Department, were selected. Patients treated on an outpatient basis were excluded. Results: A sample of 112 patients was obtained, with a mean age of 35.4 years. Only 11.6% of patients met all minimum diagnosis criteria of pelvic inflammatory disease. Chlamydia and gonorrhoea were the most frequently isolated pathogens. Endometrial biopsy was performed in 55.6% of the cases, while ultrasonography showed images suggestive of pelvic inflammatory disease in 56.3% of the patients. The combination of clindamycin and gentamicin was the most used antibiotic regimen, with 48.2% of sexual partners being treated. A number of 82.15% of patients underwent surgery. Conclusion: The study population is atypical in terms of average age and risk factors, although there is room for improvement in relation to data collected from the patients’ medical history. The incidence of gonorrhoea has declined in our area, which is consistent with the emergence of new pathogens that are more prevalent. Endometrial biopsy should be performed to increase the index of suspicion and the treatment of sexual partners. On the whole, however, the hospital and surgical treatment results were favourable

Smart Release Nano-formulation of Cytochrome C and Hyaluronic Acid Induces Apoptosis in Cancer Cells.

Herein we tested a nanosized cancer-cell targeted delivery system based on cytochrome c (Cyt c) and hyaluronic acid. Cyt c was chosen since it is a per se non-toxic protein but causes apoptosis when delivered to the cytoplasm of target cells. Hyaluronic acid was employed to create the nanosized delivery system with passive targeting capability in order to exploit the enhanced permeation and retention (EPR) effect and active targeting capability of hyaluronic acid. In addition, our goal was to incorporate a smart release strategy to only promote protein release upon reaching its target. Nanoparticles were formed by a simple yet precise nanoprecipitation process based on desolvation. They were physically characterized to select precipitation conditions leading to adequate size, shape, protein bioactivity, and protein loading to produce a feasible targeted cancer treatment. We synthesized nanoparticles of around 500 nm diameter with a 60% protein loading and more than 80% of protein bioactivity. In vitro, cumulative release of 92% of Cyt c was observed after 8 h under conditions mimicking the reductive intracellular environment, while under non-denaturing conditions only 20% was released. The nanoparticles displayed a selective cytotoxic effect on cancer cells. After 6 h of incubation with the nanoparticles, hyaluronic acid receptor over expressing A549 human lung adenocarcinoma cells showed a viability of ca. 20% at 0.16 mg/ml of Cyt c concentration. Only a negligible effect was observed on viability of COS-7 African green monkey kidney fibroblast, a normal cell line notoverexpressing the hyaluronic acid receptor. Confocal microscopy confirmed that the drug delivery system indeed delivered Cyt c to the cytoplasm of the target cells. We conclude that we were able to create a smart stimuli-responsive targeted drug delivery system with significant potential in cancer therapy.

Ecotoxicidad aguda en semillas de Lactuca sativa L. de antibacterianos con riesgo ambiental / Acute ecotoxicity in seeds of Lactuca sativa L. Antibacterial with environmental risk

En los últimos años existe una creciente preocupación por los efectos que los desechos de los medicamentos producen en el medio ambiente. El objetivo de esta investigación fue evaluar la ecotoxicidad aguda de antibacterianos en Lactuca sativa que se vierten a uno de los dos ríos que atraviesan las zonas más urbanizadas de la ciudad de Santa Clara (Cuba). Para esto se realizó un estudio de consumo de los antibacterianos consumidos en el hospital durante un año, se predijo sus concentraciones ambientales mediante un modelo matemático y se determinó su riesgo ecotoxicológico. En el período de estudio se utilizaron 22 antibacterianos, el de mayor consumo fue la ceftriaxona y el de menor la doxiciclina. Todos constituyen un riesgo para el ambiente exceptuando doxiciclina y miconazol. Se observó inhibición de la germinación de Lactuca sativa L. en todos los antibacterianos resaltando el cotrimoxazol con 38.78% (CI50=0.52g/L) y vancomicina la de menor efecto en la inhibición de la germinación con un 8.56% (CI50=44,14g/L). En la mezcla solamente hubo inhibición de la geminación a la mayor concentración evaluada, mientras que en el resto de las concentraciones no se evidenciaron diferencias estadísticamente significativas con respecto al control. El tipo de interacción de la mezcla se clasifica como sinérgica. El vertimiento de residuos de antibacterianos puede ser causa de contaminación ambiental perjudicial

In recent years there is growing concern about the effects that drugs produce waste in the environment. The objective of this research was to evaluate the acute ecotoxicity of antibacterials in Lactuca sativa discharged into one of two rivers that cross the most urbanized areas of the city of Santa Clara (Cuba). For this, a consumer study of antibacterial consumed in the hospital for a year was made, its environmental concentrations predicted by a mathematical model and determined their ecotoxicological risk. In the study period 22 antibacterials were used, the highest consumption was lower ceftriaxone and doxycycline. All pose a risk to the environment except doxycycline and miconazole. inhibition of germination of Lactuca sativa L. was observed in all antibacterial highlighting cotrimoxazole with 38.78% (IC50 = 0.52g / L) and vancomycin the least effect on the inhibition of germination with 8.56% (IC50 = 44,14g / L). In the mixture there was only germination inhibition at the highest concentration tested, while in other concentrations no statistically significant differences were found with respect to control. The type of interaction is classified as synergistic mixture. Shedding of antibiotics residues can cause harmful environmental pollution. while in other concentrations were not statistically significantly different from control is evidenced. The type of interaction is classified as synergistic mixture. Shedding of antibiotics residues can cause harmful environmental pollution. while in other concentrations were not statistically significantly different from control is evidenced. The type of interaction is classified as synergistic mixture. Shedding of antibiotics residues can cause harmful environmental pollution

Caso clínico de seguimiento farmacoterapéutico: paciente hipertensa no controlada / Clinical case of a Pharmacotherapeutical follow up: hypertensive patient uncontrolled

No disponible

Static behavior of a zirconia abutment subjected to artificial aging: finite element method / Comportamiento estático de un pilar de circona sometido a envejecimiento artificial: método de elementos finitos

ABSTRACT. Introduction: some studies on the effect of zirconia aging mention a degree of reduction of zirconia′s fracture strength varying from 20 to 40%, while other authors argue that aging does not affect the material′s strength. The aim of this study was to evaluate the response of a zirconia abutment subjected to static loads and artificial aging using the finite element method (FEM). Methods: modeling of the Tapered Screw- Vent implant and the zirconia Zimmer® abutment (Zimmer Dental1 900 Aston Avenue Carlsbad, CA 92008-7308 USA). Four models were designed: one with an implant of 3.7 mm in diameter and a 3.5 mm diameter abutment, another with an implant of 4.7 mm in diameter and a 4.5 mm diameter abutment, and other two with the same dimensions but changing the final fracture limit to 40%, analyzing the response of different components to specific loads. Results: models subjected to decreases in zirconia abutment fracture strength did not show zirconia differences in terms of von Mises values. A factor of safety allowed observing the working threshold of the zirconia abutment; failure occurred at values lower than 1. Conclusions: by modifying zirconia′s properties in order to simulate aging, the factor of safety decreases at values lower than 1. However, the applied forces under which the safety factor decreases are higher than normal masticatory forces.

RESUMEN. Introducción: estudios sobre el efecto del envejecimiento de la circona refieren una disminución de la resistencia a la fractura de la circona que varía del 20 al 40%, mientras que otros argumentan que no influye en la resistencia del material. El propósito de este estudio fue evaluar la respuesta de un pilar de circona sometido a carga estática y envejecimiento artificial usando el método de elementos finitos (MEF). Métodos: se modelaron el implante Tapered Screw-Vent y el pilar de circona Zimmer® (Zimmer Dental1 900 Aston Avenue Carlsbad, CA 92008- 7308 USA). Se diseñaron cuatro modelos: uno con implante de 3,7 de diámetro y pilar de 3,5 mm de diámetro, otro con un implante de 4,7 de diámetro y un pilar de 4,5 mm de diámetro, y otros dos con las mismas dimensiones pero modificando el limite último de fractura en un 40%. Se observó el comportamiento de los diferentes componentes ante la carga. Resultados: en los modelos donde se aplicó la disminución de la resistencia a la fractura del pilar de circona, no se observaron diferencias en la circona en cuanto a los valores de von Mises. Se generó un coeficiente de seguridad que permitió observar el umbral de trabajo del pilar de circona, a valores inferiores a 1 se presentó la falla. Conclusiones: al modificar las propiedades de la circona, para simular el envejecimiento, el factor de seguridad disminuye a valores inferiores a 1. Sin embargo, las fuerzas aplicadas bajo las cuales disminuye el factor de seguridad son superiores a las fuerzas de la masticación normal.

Biosimilares en dermatología. Situación actual (parte I) / Biosimilars in Dermatology: Current Situation (Part I)

El 16 de febrero de este año se han comercializado en España los primeros biosimilares de un tratamiento biológico para la psoriasis (infliximab), y en los próximos meses y años está prevista la incorporación de otros biosimilares, con un previsible impacto económico y en los hábitos de prescripción dermatológicos. En la presente revisión se abordan los aspectos regulatorios de la aprobación de biosimilares, con especial referencia al entorno de la Unión Europea, prestando especial atención a la caracterización analítica de la biosimilaridad y las consideraciones especiales referidas al diseño de ensayos clínicos con biosimilares. También se abordan aspectos objeto de cierta controversia, como la extrapolación de indicaciones, la intercambiabilidad y sustitución automática, los biosimilares en fase clínica de desarrollo con indicaciones que incluyen la psoriasis y unas consideraciones finales sobre el potencial de estos fármacos para proporcionar unas alternativas terapéuticas de eficacia y seguridad comparables a las de sus productos de referencia, contribuyendo a la sostenibilidad del sistema sanitario público

The first biosimilar version of a biologic agent used to treat psoriasis (infliximab) entered the Spanish market on February 16 of this year, and more biosimilars can be expected to follow in the coming months and years. Logically, this new situation will have economic repercussions and alter prescribing patterns among dermatologists. In this article, we review regulatory issues related to the approval of biosimilars, with a particular focus on the situation in the European Union. We will examine analytical characterization studies and special considerations for clinical trials with biosimilars, and also look at several somewhat contentious issues, such as the extrapolation of indications, interchangeability, and automatic substitution. Finally, we will review the biosimilars with indications for psoriasis currently in the clinical development pipeline and assess their potential to offer comparable efficacy and safety to the reference product while contributing to the sustainability of the public health care system

Biosimilares en dermatología. Situación actual (parte II) / Biosimilars in Dermatology: Current Situation (Part II)

El 16 de febrero de este año se han comercializado en España los primeros biosimilares de un tratamiento biológico para la psoriasis (infliximab), y en los próximos meses y años está prevista la incorporación de otros biosimilares, con un previsible impacto económico y en los hábitos de prescripción dermatológicos. En esta parte de la revisión se abordan aspectos objeto de cierta controversia, como la extrapolación de indicaciones, la intercambiabilidad y sustitución automática, los biosimilares en fase clínica de desarrollo con indicaciones que incluyen la psoriasis, y unas consideraciones finales sobre el potencial de estos fármacos para proporcionar unas alternativas terapéuticas de eficacia y seguridad comparables a las de sus productos de referencia, contribuyendo a la sostenibilidad del sistema sanitario público

The first biosimilar version of a biologic agent used to treat psoriasis (infliximab) entered the Spanish market on February 16 of this year, and more biosimilars can be expected to follow in the coming months and years. Logically, this new situation will have economic repercussions and alter prescribing patterns among dermatologists. In this second part of the review, we will look at several somewhat contentious issues, such as the extrapolation of indications, interchangeability, and automatic substitution. We will also review the biosimilars with indications for psoriasis currently in the clinical development pipeline and assess their potential to offer comparable efficacy and safety to the reference product while contributing to the sustainability of the public health care system

Biosimilars in Dermatology: Current Situation (Part II).

The first biosimilar version of a biologic agent used to treat psoriasis (infliximab) entered the Spanish market on February 16 of this year, and more biosimilars can be expected to follow in the coming months and years. Logically, this new situation will have economic repercussions and alter prescribing patterns among dermatologists. In this second part of the review, we will look at several somewhat contentious issues, such as the extrapolation of indications, interchangeability, and automatic substitution. We will also review the biosimilars with indications for psoriasis currently in the clinical development pipeline and assess their potential to offer comparable efficacy and safety to the reference product while contributing to the sustainability of the public health care system.

Biosimilars in Dermatology: Current Situation (Part I).

The first biosimilar version of a biologic agent used to treat psoriasis (infliximab) entered the Spanish market on February 16 of this year, and more biosimilars can be expected to follow in the coming months and years. Logically, this new situation will have economic repercussions and alter prescribing patterns among dermatologists. In this article, we review regulatory issues related to the approval of biosimilars, with a particular focus on the situation in the European Union. We will examine analytical characterization studies and special considerations for clinical trials with biosimilars, and also look at several somewhat contentious issues, such as the extrapolation of indications, interchangeability, and automatic substitution. Finally, we will review the biosimilars with indications for psoriasis currently in the clinical development pipeline and assess their potential to offer comparable efficacy and safety to the reference product while contributing to the sustainability of the public health care system.

Ascorbic acid PEG-2L is superior for early morning colonoscopies in colorectal cancer screening programs: A prospective non-randomized controlled trial

BACKGROUND: The quality of colon cleansing and the tolerability of anterograde preparation are essential to the success of colorectal cancer screening. AIM: To compare the tolerability and efficacy of low-volume preparations vs the standard regimen in individuals scheduled for an early morning colonoscopy. Study: Participants in a population-based colorectal cancer screening program using the fecal immunochemical test who were scheduled for a colonoscopy from 09:00 a.m. to 10:20 a.m. were prospectively included and assigned to: (1) control group (PEG-ELS 4L): PEG 4L and electrolytes; (2) group AscPEG-2L: a combination of PEG and ascorbic acid 2L; and (3) group PiMg: sodium picosulfate and magnesium citrate 500 mL plus 2 L of clear fluids. Tolerability was evaluated with a questionnaire and the quality of bowel preparation with the Boston Bowel Preparation Scale. RESULTS: A total of 292 participants were included: 98 in the PEG-ELS 4L control group, 96 in the AscPEG-2L study group and 98 in the PiMg study group. Low-volume treatments were better tolerated than the standard solution (AscPEG-2L 94.8% and PiMg 93.9% vs PEG-ELS 4L 75.5%; p < 0.0001). The effectiveness of AscPEG-2L was superior to that of PEG-ELS 4L and PiMg (p = 0.011 and p = 0.032, respectively). Patient acceptance was higher for single-dose than for split-dose administration but efficacy was higher with the split dose than with other doses. CONCLUSIONS: In early morning colonoscopies, ascPEG-2L appears to be the best option, especially when administered in a split-dose

ANTECEDENTES: La calidad de la limpieza del colon y la tolerancia a la preparación anterógrada son claves para el éxito de un programa de cribado de cáncer colorrectal. OBJETIVO: Comparar la tolerancia y eficacia de las preparaciones de volumen reducido frente a la preparación estándar en pacientes programados para colonoscopia a primera hora de la mañana. Estudio: Individuos del programa de cribado poblacional con test de sangre oculta en heces programados para colonoscopia entre las 09:00 y 10:20 a.m fueron prospectivamente asignados a: 1) Grupo Control (PEG-ELS 4L): PEG con electrolitos 4 litros; 2) Grupo AscPEG-2L: PEG más ácido ascórbico 2 litros; y 3) Groupo PiMg: picosulfato sódico más citrato de magnesio 500 ml seguido de 2 litros de líquidos claros. Se evaluó la tolerancia mediante cuestionario y la calidad mediante la Boston Bowel Preparation Scale. RESULTADOS: Se incluyeron 292 sujetos: 98 en el grupo control PEG-ELS 4L, 96 en el grupo a estudio AscPEG-2L y 98 en el grupo a estudio PiMg. Las soluciones de volumen reducido fueron mejor toleradas que la solución estándar (AscPEG-2L 94.8% y PiMg 93.9% vs PEG-ELS 4L 75.5%; p < 0.0001). La calidad de la preparación fue superior en el grupo AscPEG-2L que en el grupo control PEG-ELS 4L y grupo PiMg (p = 0.011 and p = 0.032, respectivamente). Las dosis partidas fueron peor aceptadas por los sujetos pero resultaron en una mayor calidad de la preparación. CONCLUSIONES: AscPEG-2L es la mejor opción para las colonoscopias programadas a primera hora de la mañana, especialmente cuando se administra en dosis partida

Ascorbic acid PEG-2L is superior for early morning colonoscopies in colorectal cancer screening programs: a prospective non-randomized controlled trial.

BACKGROUND: The quality of colon cleansing and the tolerability of anterograde preparation are essential to the success of colorectal cancer screening. AIM: To compare the tolerability and efficacy of low-volume preparations vs the standard regimen in individuals scheduled for an early morning colonoscopy. STUDY: Participants in a population-based colorectal cancer screening program using the fecal immunochemical test who were scheduled for a colonoscopy from 09:00 a.m. to 10:20 a.m. were prospectively included and assigned to: (1) control group (PEG-ELS 4L): PEG 4L and electrolytes; (2) group AscPEG-2L: a combination of PEG and ascorbic acid 2L; and (3) group PiMg: sodium picosulfate and magnesium citrate 500 mL plus 2L of clear fluids. Tolerability was evaluated with a questionnaire and the quality of bowel preparation with the Boston Bowel Preparation Scale. RESULTS: A total of 292 participants were included: 98 in the PEG-ELS 4L control group, 96 in the AscPEG-2L study group and 98 in the PiMg study group. Low-volume treatments were better tolerated than the standard solution (AscPEG-2L 94.8% and PiMg 93.9% vs PEG-ELS 4L 75.5%; p < 0.0001). The effectiveness of AscPEG-2L was superior to that of PEG-ELS 4L and PiMg (p = 0.011 and p = 0.032, respectively). Patient acceptance was higher for single-dose than for split-dose administration but efficacy was higher with the split dose than with other doses. CONCLUSIONS: In early morning colonoscopies, ascPEG-2L appears to be the best option, especially when administered in a split-dose.

Value of endoscopy and MRI for predicting intestinal surgery in patients with Crohn's disease in the era of biologics.

OBJECTIVE: Severe endoscopic lesions (SEL) in patients with colonic Crohn's disease (CD) have been linked to higher risk of colectomy. The aims of this study were to reassess the predictive value of colonoscopy compared against MRI for requirement of resection surgery in patients with CD and determine the influence of current therapeutic options. DESIGN: In this single-centre, observational, prospective, longitudinal study, patients with an established diagnosis of CD and suspected activity were included. After baseline assessment, including colonoscopy and MRI, patients were followed until resection surgery or the end of study. RESULTS: 112 patients were eligible for analysis. Ulcers were present in 94/112 (84%) of patients at colonoscopy (SELs in 51/112 (46%)) and stenosis in 38/112 (34%). MRI identified ulcers in 79/112 (71%) of patients, stenosis in 36/112 (32%) and intra-abdominal fistulae in 20/112 (18%). Surgical resection requirements (29/112 (26%)) were not associated with the presence of SELs at colonoscopy. The presence of stenosis (p<0.001) or intra-abdominal fistulae (p<0.001) at MRI correlated with a higher risk of surgery. In the multivariate analysis, perianal disease (OR 9 (2 to 39), p=0.003), stenosis (OR 3.4 (1 to 11), p=0.04) and fistulae at MRI (OR 10.6 (2 to 46), p=0.002) increased the risk of abdominal resection surgery, while months under immunomodulators (OR 0.94 (0.90 to 0.98), p=0.002) and/or antitumor necrosis factor (anti-TNF) therapy (OR 0.97 (0.94 to 1), p=0.04) during follow-up decreased this risk. CONCLUSIONS: Perianal disease, stenosis and/or intra-abdominal fistulae at MRI independently predict an increased risk of resection surgery in patients with CD, whereas immunosuppressants and/or anti-TNF therapy reduce such risk. Under current therapeutic strategies, the presence of SELs is not a predictor of resection surgery in patients with CD.

Intervención farmacéutica sobre Resultados negativos asociados a la medicación de necesidad, inefectividad e inseguridad del tratamiento en un paciente polimedicado incluido en el del programa conSIGUE-Implantación / conSIGUE-implementation program for Medication Review with Follow-Up (SFT) Case Study: Pharmaceutical intervention of a polymedicated patient with medication-related negative outcomes

No disponible