Biomarkers of disease activity and other factors as predictors of adalimumab pharmacokinetics in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is commonly treated with adalimumab. The main objective of the study was to develop a population pharmacokinetic model of adalimumab in IBD patients evaluating the potential biomarkers of disease activity and other factors and its implications in adalimumab dosing. A prospective observational study was performed in adult patients diagnosed with Crohn's disease and ulcerative colitis treated with adalimumab and following a proactive therapeutic drug monitoring of serum concentrations. Adalimumab serum concentrations (ASC) were quantified mainly prior the administration using an enzyme-linked immunosorbent assay (ELISA). A population pharmacokinetic model was developed based on 303 ASC data of 104 IBD patients using non-linear mixed effect modelling approach. Sixty-five ASC from 20 additional patients were randomly selected as an external validation group. A one-compartment model with first order absorption and elimination best describe the ASC time course. Body mass index (BMI), faecal calprotectin (FCP), unexplained decline in ASC and the specific administration pen device exhibited significant influence on apparent clearance (p-value < 0.001). FCP was the inflammatory activity biomarker showing the most relevant impact on adalimumab exposure, higher than C-reactive protein and albumin, and may be useful for adalimumab dosing adjustment. The population-based pharmacokinetic model developed adequately characterized adalimumab exposure in IBD patients. The unexplained decline in ASC, FCP, BMI and the specific administration pen device were identified as meaningful variables significantly influencing adalimumab pharmacokinetics.

Clinical Characteristics, Associated Malignancies and Management of Primary Sclerosing Cholangitis in Inflammatory Bowel Disease Patients: A Multicentre Retrospective Cohort Study.

BACKGROUND AND AIMS: Primary sclerosing cholangitis [PSC] is usually associated with inflammatory bowel disease [IBD]. An increased risk of malignancies, mainly colorectal cancer [CRC] and cholangiocarcinoma [CCA], has been reported in PSC-IBD patients. Our aim was to determine the clinical characteristics and management of PSC in IBD patients, and the factors associated with malignancies. METHODS: PSC-IBD patients were identified from the Spanish ENEIDA registry of GETECCU. Additional data were collected using the AEG-REDCap electronic data capture tool. RESULTS: In total, 277 PSC-IBD patients were included, with an incidence rate of 61 PSC cases per 100 000 IBD patient-years, 69.7% men, 67.5% ulcerative colitis and mean age at PSC diagnosis of 40 ± 16 years. Most patients [85.2%] were treated with ursodeoxycholic acid. Liver transplantation was required in 35 patients [12.6%] after 79 months (interquartile range [IQR] 50-139). It was more common in intra- and extrahepatic PSC compared with small-duct PSC (16.3% vs 3.3%; odds ratio [OR] 5.7: 95% confidence interval [CI] = 1.7-19.3). The incidence rate of CRC since PSC diagnosis was 3.3 cases per 1000 patient-years [95% CI = 1.9-5.6]. Having symptoms of PSC at PSC diagnosis was the only factor related to an increased risk of CRC after IBD diagnosis [hazard ratio= 3.3: 95% CI = 1.1-9.9]. CCA was detected in seven patients [2.5%] with intra- and extrahepatic PSC, with median age of 42 years [IQR 39-53], and presented a lower life expectancy compared with patients without CCA and patients with or without CRC. CONCLUSIONS: PSC-IBD patients with symptoms of PSC at PSC diagnosis have an increased risk of CRC. CCA was only diagnosed in patients with intra- and extrahepatic PSC and was associated with poor survival.

Comportamiento y actitud frente a la sexualidad de la mujer embarazada durante el último trimestre. Estudio fenomenológico / Behaviour and attitudes towards the sexuality of the pregnant woman during the last trimester. Phenomenological study

Objetivo: Explorar las vivencias y experiencias sobre las relaciones sexuales en el tercer trimestre de gestación en primíparas. Diseño: Estudio cualitativo fenomenológico. Emplazamiento: Cáceres (Extremadura). Participantes: Mujeres embarazadas primíparas en el tercer trimestre de embarazo. Método: Se realizó un muestreo teórico en embarazadas primíparas. Se incluyeron 15 participantes. Los datos se recopilaron mediante entrevistas en profundidad, grabadas en audio y posteriormente transcritas. El análisis se llevó a cabo mediante la propuesta de Giorgi. Resultados: Los resultados muestran 3 temas principales. Temor a hacer daño, mediado por los antecedentes obstétricos y el deseo de tener el hijo tan esperado. Explorando nuevas rutas: las formas de expresión sexual son modificadas por los cambios físicos, los temores y la movilidad, resaltando la importancia de otras muestras de afecto y amor (besos y las caricias). El tabú del sexo: la falta de información frente a la sexualidad durante el embarazo sigue siendo frecuente. Conclusiones: La mujer en el tercer trimestre de embarazo deja al margen su deseo sexual y el de su pareja y se centra en el bienestar del bebé. Destaca el rol incipiente de madre frente al de pareja. Cuando el embarazo es muy deseado y "costoso", más se reduce la vida sexual. Los profesionales sanitarios debemos aconsejar e informar a las parejas con una actitud abierta y amplia, para mantener la calidad y la salud sexual de la pareja

Objective: To explore the life experiences on sexual relationships in the third trimester of pregnancy in primiparous women. Design: Phenomenological qualitative study, Site: Cáceres (Extremadura). Participants: Primiparous women in the third trimester of their pregnancy. Methods: We use theoretical sampling, was conducted on pregnant primiparous. The study included 15 participants. The data was collected using in-depth interviews, that were voiced recorded and later transcribed. The analysis was made using Giorgi's proposal. Results: The results show three main points. Fear of doing damage, mediated by the obstetric history and the desire to have the long-awaited child. Exploring new routes: forms of sexual expression are modified by the physical changes, the fears, and the mobility. Highlighting the importance of other displays of affection and love (kisses and caresses). The Sex Taboo: lack of information against sexuality during pregnancy is still common. Conclusions: Women in the third trimester of their pregnancy put aside their sexual appetite and that of their partners, and concentrate in the wellbeing of their new born baby. It highlights the role of the mother before the couple. The more desired and difficult the pregnancy has been, the more the sexual life is reduced. The Health Professionals must advise and inform the couples with an open-minded attitude

[Behaviour and attitudes towards the sexuality of the pregnant woman during the last trimester. Phenomenological study]. / Comportamiento y actitud frente a la sexualidad de la mujer embarazada durante el último trimestre. Estudio fenomenológico.

OBJECTIVE: To explore the life experiences on sexual relationships in the third trimester of pregnancy in primiparous women. DESIGN: Phenomenological qualitative study, SITE: Cáceres (Extremadura). PARTICIPANTS: Primiparous women in the third trimester of their pregnancy. METHODS: We use theoretical sampling, was conducted on pregnant primiparous. The study included 15 participants. The data was collected using in-depth interviews, that were voiced recorded and later transcribed. The analysis was made using Giorgi's proposal. RESULTS: The results show three main points. Fear of doing damage, mediated by the obstetric history and the desire to have the long-awaited child. Exploring new routes: forms of sexual expression are modified by the physical changes, the fears, and the mobility. Highlighting the importance of other displays of affection and love (kisses and caresses). The Sex Taboo: lack of information against sexuality during pregnancy is still common. CONCLUSIONS: Women in the third trimester of their pregnancy put aside their sexual appetite and that of their partners, and concentrate in the wellbeing of their new born baby. It highlights the role of the mother before the couple. The more desired and difficult the pregnancy has been, the more the sexual life is reduced. The Health Professionals must advise and inform the couples with an open-minded attitude.

Natural gum-type biopolymers as potential modified nonpolar drug release systems.

In this work, the relationship between surface properties and drug release mechanism from binary composition tablets formed by quetiapine fumarate and biopolymer materials was studied. The biopolymers correspond to xanthan and tragacanth gums, which are projected as modified drug release systems. The surface studies were carried out by the sessile drop method, while the surface free energy (SFE) was determinate through Young-Dupree and OWRK semi-empirical models. On the other hand, the drug release studies were performed by in vitro dissolution tests, where the data were analyzed through kinetic models of zero order, first order, Higuchi, and Korsmeyer-Peppas. The results showed that depending on the type and the proportion of biopolymer, surface properties, and the drug release processes are significantly affected, wherein tragacanth gum present a usual erosion mechanism, while xanthan gum describes a swelling mechanism that controls the release of the drug.

Incidence, Clinical Characteristics, and Management of Psoriasis Induced by Anti-TNF Therapy in Patients with Inflammatory Bowel Disease: A Nationwide Cohort Study.

BACKGROUND: Psoriasis induced by anti-tumor necrosis factor-α (TNF) therapy has been described as a paradoxical side effect. AIM: To determine the incidence, clinical characteristics, and management of psoriasis induced by anti-TNF therapy in a large nationwide cohort of inflammatory bowel disease patients. METHODS: Patients with inflammatory bowel disease were identified from the Spanish prospectively maintained Estudio Nacional en Enfermedad Inflamatoria Intestinal sobre Determinantes genéticos y Ambientales registry of Grupo Español de Trabajo en Enfermedad de Croh y Colitis Ulcerosa. Patients who developed psoriasis by anti-TNF drugs were the cases, whereas patients treated with anti-TNFs without psoriasis were controls. Cox regression analysis was performed to identify predictive factors. RESULTS: Anti-TNF-induced psoriasis was reported in 125 of 7415 patients treated with anti-TNFs (1.7%; 95% CI, 1.4-2). The incidence rate of psoriasis is 0.5% (95% CI, 0.4-0.6) per patient-year. In the multivariate analysis, the female sex (HR 1.9; 95% CI, 1.3-2.9) and being a smoker/former smoker (HR 2.1; 95% CI, 1.4-3.3) were associated with an increased risk of psoriasis. The age at start of anti-TNF therapy, type of inflammatory bowel disease, Montreal Classification, and first anti-TNF drug used were not associated with the risk of psoriasis. Topical steroids were the most frequent treatment (70%), achieving clinical response in 78% of patients. Patients switching to another anti-TNF agent resulted in 60% presenting recurrence of psoriasis. In 45 patients (37%), the anti-TNF therapy had to be definitely withdrawn. CONCLUSIONS: The incidence rate of psoriasis induced by anti-TNF therapy is higher in women and in smokers/former smokers. In most patients, skin lesions were controlled with topical steroids. More than half of patients switching to another anti-TNF agent had recurrence of psoriasis. In most patients, the anti-TNF therapy could be maintained.

Infliximab in ulcerative colitis: real-life analysis of factors predicting treatment discontinuation due to lack of response or colectomy: ECIA (ACAD Colitis and Infliximab Study).

OBJECTIVE: To describe clinical practice with infliximab (IFX) in ulcerative colitis (UC); identification of predictive factors for IFX treatment discontinuation due to insufficient response and for colectomy. MATERIAL AND METHODS: Retrospective, multicentric and observational study including every UC IFX-treated patient in 10 Spanish hospitals. Variables analyzed: epidemiological data; variables for poor prognosis; IFX prior treatments; characteristics of the IFX treatment; time from the UC diagnosis to induction with IFX; time from induction to colectomy or until data collection. Predictive and protective factors for IFX discontinuation due to lack of response and for colectomy were analyzed with binary logistic regression and Cox analysis. RESULTS: Follow-up time from induction with IFX to the collection of data or colectomy: 36.7 ± 25.7 months. Prior treatment with immunomodulator medications (IMM): 79%; IFX + immunosuppressant therapy: 77%; discontinuation of IFX: 26%, colectomy 16%. Independent predictive or protective factors for IFX discontinuation: IMM resistance (OR: 2.9, p = 0.022, 95% CI: 1.2-7.2), prior use of leukocytapheresis (OR: 3.3, p = 0.024, 95% CI: 1.1-9.4), IFX + IMM therapy (OR: 0.3, p = 0.022, 95% CI: 0.1-0.9, and HR: 0.4, p = 0.006, 95% CI: 0.2-0.8) and corticosteroid use in induction (HR: 1.9, p = 0.049, 95% CI: 1.0-3.8). Independent predictive or protective factors for colectomy: Use of leukocytapheresis (OR: 3.0, p = 0.036, 95% CI: 1.1-8.4), IFX + IMM therapy (OR: 0.3, p = 0.022, 95% CI: 0.1-0.8, and HR: 0.3, p = 0.011, 95% CI: 0.1-0.8) and severe cortico-resistant flare-up (HR: 2.5, p = 0.032, 95% CI: 1.1-5.9). CONCLUSIONS: Prior use of IMM and leukocytapheresis, the use of corticosteroids in induction and a severe cortico-resistant flare predict a worse response to IFX and the need for colectomy. Combination therapy is a protective factor for both.