Outcomes After Pseudomonas Prosthetic Joint Infections.

BACKGROUND: Pseudomonas species are a less common but devastating pathogen family in prosthetic joint infections (PJIs). Despite advancements in management, Pseudomonas PJIs remain particularly difficult to treat because of limited antibiotic options and robust biofilm formation. This study aimed to evaluate Pseudomonas PJI outcomes at a single institution and review outcomes reported in the current literature. METHODS: All hip or knee PJIs at a single institution with positive Pseudomonas culture were evaluated. Forty-two patients (24 hips, 18 knees) meeting inclusion criteria were identified. The primary outcome of interest was infection clearance at 1 year after surgical treatment, defined as reassuring aspirate without ongoing antibiotic treatment. Monomicrobial and polymicrobial infections were analyzed separately. A focused literature review of infection clearance after Pseudomonas PJIs was performed. RESULTS: One-year infection clearance was 58% (n = 11/19) for monomicrobial PJIs and 35% (n = 8/23) for polymicrobial PJIs. Among monomicrobial infections, the treatment success was 63% for patients treated with DAIR and 55% for patients treated with two-stage exchange. Monotherapy with an oral or intravenous antipseudomonal agent (minimum 6 weeks) displayed the lowest 1-year clearance of 50% (n = 6/12). Resistance to antipseudomonal agents was present in 16% (n = 3/19), and two of eight patients with monomicrobial and polymicrobial PJIs developed resistance to antipseudomonal therapy in a subsequent Pseudomonas PJI. Polymicrobial infections (55%) were more common with a mortality rate of 44% (n = 10/23) at a median follow-up of 3.6 years. CONCLUSION: Pseudomonas infections often present as polymicrobial PJIs but are difficult to eradicate in either polymicrobial or monomicrobial setting. A review of the current literature on Pseudomonas PJI reveals favorable infection clearance rates (63 to 80%) after DAIR while infection clearance rates (33 to 83%) vary widely after two-stage revision.

Impact of proactive of infliximab monitoring using the Bayesian approach in the maintenance phase in patients with inflammatory bowel disease / Impacto de la monitorización proactiva de infliximab en fase de mantenimiento mediante estimación bayesiana en pacientes con enfermedad inflamatoria intestinal

Background and objectives: There is increasing evidence that proactive monitoring is useful in improving the control of inflammatory bowel disease, although it remains controversial. The aim of this study was to evaluate the efficacy of proactive TDM based on the Bayesian approach to optimise the IFX dose compared with the standard of care dosing in patients with IBD. Methods: Retrospective observational cohort of inflammatory bowel disease patients>18 years. Patients were classified into two groups according to the strategy used to optimise the dose of IFX: a standard therapy group (ST-group) with clinically based dose adjustment and therapeutic drug monitoring group (TDM-group), with estimation of pharmacokinetic parameters calculated by Bayesian prediction. Results: A total of 153 patients were included. Of these, 75 were in the TDM-group. Clinical response at week 52 was evaluated in 114 patients. The proportion of patients who achieved clinical remission was higher in the TDM than in the ST-group (80.7% vs 61.4%, respectively, p=0.023). A total of 28 patients (24.6%) met the parameters for the composite variable ‘poor clinical outcome’ at week 52. The proportion of patients who reached this outcome was lower in the TDM-group than in the ST-group (12.3% vs 36.8%, respectively, p=0.002). Conclusions: Proactive therapeutic drug monitoring using Bayesian approach is associated with higher secondary response and fewer long-term complications.(AU)

Antecedentes y objetivos: Cada vez hay más evidencia de que la monitorización proactiva es útil para mejorar el control de la enfermedad inflamatoria intestinal (EII), aunque sigue siendo controvertida. El objetivo de este estudio fue evaluar la eficacia de la monitorización de fármacos terapéuticos (TDM) proactiva basada en el enfoque bayesiano en comparación con el manejo estándar en pacientes con EII. Métodos: Cohorte observacional retrospectiva de pacientes con EEI > 18 años. Los pacientes se clasificaron en dos grupos de acuerdo con la estrategia utilizada para optimizar la dosis de infliximab (IFX): un grupo de terapia estándar (grupo-ST) con ajuste de dosis basado en la clínica y un grupo de monitorización terapéutica del fármaco (grupo-TDM), con estimación de parámetros farmacocinéticos calculados mediante estimación bayesiana. Resultados: Se incluyeron un total de 153 pacientes. De estos, 75 estaban en el grupo-TDM. La respuesta clínica en la semana 52 se evaluó en 114 pacientes. La proporción de pacientes que alcanzaron la remisión clínica fue mayor en el grupo-TDM que en el grupo-ST (80,7 vs. 61,4%, respectivamente, p = 0,023). Un total de 28 pacientes (24,6%) cumplieron los parámetros de la variable compuesta «resultado clínico deficiente» en la semana 52. La proporción de pacientes que alcanzaron este resultado fue menor en el grupo-TDM que en el grupo-ST (12,3 vs. 36,8%, respectivamente, p = 0,002). Conclusiones: La TDM proactiva mediante el enfoque bayesiano se asocia con una mayor respuesta secundaria y menos complicaciones a largo plazo.(AU)

Comparative effectiveness and drug survival of biosimilar infliximab CPT-13 vs. reference infliximab in inflammatory bowel disease: A retrospective cohort study.

BACKGROUND: Studies have investigated the efficacy and safety of switching to the biosimilar infliximab (CT-P13) in patients with inflammatory bowel disease (IBD). However, there is limited research directly comparing the effectiveness, drug survival, and pharmacokinetic profiles of the reference infliximab (IFX) and CT-P13 in real clinical settings. OBJECTIVE: To compare the effectiveness and drug survival of CPT-13 and reference IFX at weeks 26 and 52, and to determine the pharmacokinetic profiles and safety profile in real-world settings. METHODS: A retrospective observational cohort analysis was conducted at a single center. The study compared the proportion of patients achieving clinical remission and experiencing poor clinical outcomes at weeks 26 and 52. The drug survival rate of CT-P13 and reference infliximab was also assessed during the follow-up period. RESULTS: A total of 153 patients were included in the study, 39.2% receiving CPT-13 and 60.8% reference IFX. At week 26, clinical remission rates were 66.7% (CPT-13: 74.4% vs. reference IFX: 62.3%, p=0.178), and at week 52, they were 64% (CPT-13: 85.4% vs. reference IFX: 63.0%, p=0.012). Subgroup analysis with therapeutic drug monitoring (TDM) found no significant differences at week 26 (CPT-13: 74.4% vs. reference IFX: 58.8%, p=0.235) or at week 52 (CPT-13: 85.4% vs. reference IFX: 68.8%, p=0.153). CONCLUSION: Our study demonstrates comparable efficacy, drug survival, pharmacokinetic profiles, and incidence of immunogenicity between both drugs in a real clinical setting. Further studies with greater statistical power are needed to validate these findings.

A New Trend in Social Media and Medicine: The Poor Quality of Videos Related to Ankle Sprain Exercises on TikTok.

Background: Social media platforms, like TikTok, have become popular options for the distribution of health care information. Because of the lack of scientific oversight, the quality of health care-related videos has become a focus of the current literature. However, orthopaedic surgery has lagged behind other fields in acknowledging the widespread utilization of TikTok videos for medical information consumption. This study aims to assess the quality and educational benefits of ankle sprain-related TikTok videos. Methods: TikTok was queried using the hashtag "#anklesprainexercises." One hundred videos were included after applying the exclusion criteria. The number of views, likes, shares, comments, and favorites was recorded. The content was graded using DISCERN (a well-validated informational analysis tool) and ASEES (a self-designed tool for exercise evaluation). We hypothesized that information on TikTok related to ankle sprain exercises would be poor in quality. Results: The total number of views of the 100 videos was 6 483 412, with a median of 5377.5 (IQR = 1074-20 275). The videos collectively received 385 847 likes, 3642 comments, 55 574 favorites, and 14 918 shares with a median of 267.5 (IQR = 41.5-1678.0), 4.0 (IQR = 0.0-23.0), 42.0 (IQR = 4.8-264.5), and 13.0 (IQR = 1.8-67.8), respectively. General users had a higher percentage of their videos graded as "very poor" (61.8%) in comparison to the number of videos uploaded by health care professionals deemed "very poor" (34.4%). Neither general user nor health care professionals had videos graded as "good" or "excellent." There were significant differences between the 2 groups for DISCERN 1, 3, and ASSES scores. Conclusion: Although TikTok is a powerful tool for information distribution, the educational value of the videos related to ankle sprain injury exercises was poor. With only 2% of videos receiving a grade of "fair," and no videos reaching a score of "good" or "excellent," health care professionals should be aware of the low-quality content easily accessible on TikTok. Level of Evidence: Level III, cross-sectional study.

Impact of proactive therapeutic drug monitoring of infliximab during the induction phase in IBD patients. A Bayesian approach.

BACKGROUND AND OBJECTIVES: there is increasing evidence that proactive therapeutic drug monitoring in induction is useful to improve the control of inflammatory bowel disease (IBD), although it remains controversial. The primary objective of the study was to assess the short-term outcomes of proactive Bayesian therapeutic drug monitoring (TDM) during induction, to optimize infliximab (IFX) maintenance dose. METHODS: retrospective observational cohort of IBD patients > 18 years. They were divided into two cohorts, standard therapy group (ST-group), with clinically based dose adjustment, and monitoring group (iTDM-group), with pharmacokinetic parameters calculated by Bayesian prediction at week 6 and individualized dosage regimens thereafter. In patients with an infliximab trough level (ITL) at week 6 below the optimal therapeutic range, the dose adjustment was performed at the first maintenance dose. RESULTS: a total of 153 patients were included, 40 in the iTDM-group. Median ITL at week 6 during the induction period was 12.8 µg/ml (IRQ: 12.7) in this group. Only 16 patients (40.0 %) had ITL ≥ 15 µg/ml. Half of the patients (50.3 %) received intensified maintenance therapy during the study period (57.5 % iTDM vs 47.8 % ST, p = 0.291). The proportion of patients achieving primary response at week 14 was 51.8 %. When comparing the two groups, this proportion was higher in the iTDM group (74.3 % vs 44.2 %, p = 0.002). With regards to the variable "poor clinical outcomes" at week 26, this proportion was lower in the iTDM group (3.3 % iTDM vs 21.1 % ST, p = 0.024). CONCLUSIONS: proactive therapeutic drug monitoring using Bayesian approach is associated with higher primary response rates and fewer short-term complications.

Impact of proactive of infliximab monitoring using the Bayesian approach in the maintenance phase in patients with inflammatory bowel disease.

BACKGROUND AND OBJECTIVES: There is increasing evidence that proactive monitoring is useful in improving the control of inflammatory bowel disease, although it remains controversial. The aim of this study was to evaluate the efficacy of proactive TDM based on the Bayesian approach to optimise the IFX dose compared with the standard of care dosing in patients with IBD. METHODS: Retrospective observational cohort of inflammatory bowel disease patients>18 years. Patients were classified into two groups according to the strategy used to optimise the dose of IFX: a standard therapy group (ST-group) with clinically based dose adjustment and therapeutic drug monitoring group (TDM-group), with estimation of pharmacokinetic parameters calculated by Bayesian prediction. RESULTS: A total of 153 patients were included. Of these, 75 were in the TDM-group. Clinical response at week 52 was evaluated in 114 patients. The proportion of patients who achieved clinical remission was higher in the TDM than in the ST-group (80.7% vs 61.4%, respectively, p=0.023). A total of 28 patients (24.6%) met the parameters for the composite variable 'poor clinical outcome' at week 52. The proportion of patients who reached this outcome was lower in the TDM-group than in the ST-group (12.3% vs 36.8%, respectively, p=0.002). CONCLUSIONS: Proactive therapeutic drug monitoring using Bayesian approach is associated with higher secondary response and fewer long-term complications.

Impact of proactive therapeutic drug monitoring of infliximab during the induction phase in IBD patients. A Bayesian approach

Background and objectives: there is increasing evidence that proactive therapeutic drug monitoring in induction is useful to improve the control of inflammatory bowel disease (IBD), although it remains controversial. The primary objective of the study was to assess the short-term outcomes of proactive Bayesian therapeutic drug monitoring (TDM) during induction, to optimize infliximab (IFX) maintenance dose. Methods: retrospective observational cohort of IBD patients > 18 years. They were divided into two cohorts, standard therapy group (ST-group), with clinically based dose adjustment, and monitoring group (iTDM-group), with pharmacokinetic parameters calculated by Bayesian prediction at week 6 and individualized dosage regimens thereafter. In patients with an infliximab trough level (ITL) at week 6 below the optimal therapeutic range, the dose adjustment was performed at the first maintenance dose. Results: a total of 153 patients were included, 40 in the iTDM-group. Median ITL at week 6 during the induction period was 12.8 µg/ml (IRQ: 12.7) in this group. Only 16 patients (40.0 %) had ITL ≥ 15 µg/ml. Half of the patients (50.3 %) received intensified maintenance therapy during the study period (57.5 % iTDM vs 47.8 % ST, p = 0.291). The proportion of patients achieving primary response at week 14 was 51.8 %. When comparing the two groups, this proportion was higher in the iTDM group (74.3 % vs 44.2 %, p = 0.002). With regards to the variable “poor clinical outcomes” at week 26, this proportion was lower in the iTDM group (3.3 % iTDM vs 21.1 % ST, p = 0.024). Conclusions: proactive therapeutic drug monitoring using Bayesian approach is associated with higher primary response rates and fewer short-term complications (AU)

3D printed architected conducting polymer hydrogels.

Conducting polymer hydrogels combine electrical conductivity and tunable water content, rendering them strong candidates for a range of applications including biosensors, cell culture platforms, and energy storage devices. However, these hydrogels are mechanically brittle and prone to damage, prohibiting their use in emerging applications involving dynamic movement and large mechanical deformation. Here, we demonstrate that applying the concept of architecture to conducting polymer hydrogels can circumvent these impediments. A stereolithography 3D printing method is developed to successfully fabricate such hydrogels in complex lattice structures. The resulting hydrogels exhibit elastic compressibility, high fracture strain, enhanced cycling stability, and damage-tolerant properties despite their chemical composition being identical to their brittle, solid counterparts. Furthermore, concentrating the deformation to the 3D geometry, rather than polymer microstructure, effectively decouples the mechanical and electrical properties of the hydrogel lattices from their intrinsic properties associated with their chemical composition. The confluence of these new physical properties for conducting polymer hydrogels opens broad opportunities for a myriad of dynamic applications.

Biosimilar infliximab CPT-13 for inflammatory bowel disease in a real clinical setting: pharmacokinetic outcomes, immunogenicity, and drug survival.

BACKGROUND: efficacy and safety were evaluated after switching to a biosimilar infliximab (CPT-13) in patients with inflammatory bowel disease (IBD). However, few cohort studies compare the pharmacokinetic profiles, immunogenicity, and safety of the reference infliximab (IFX) and CPT-13 in a real clinical setting. OBJECTIVE: to compare the pharmacokinetic profiles and drug survival on the long term of reference IFX and CPT-13 at weeks 54 and 104. A secondary objective was to determine the long-term immunogenicity and safety profile of CPT-13 in patients with IBD in a real clinical setting. METHODS: a retrospective, observational cohort analysis was performed in a single center, including patients with IBD under treatment with reference IFX or CPT-13. Serum drug concentrations were compared to determine if there were any significant differences in pharmacokinetic outcomes between reference IFX and CPT-13 at 26, 54, 78, and 104 weeks. The drug survival of reference IFX and CPT-13 was determined at weeks 54 and 104. RESULTS: one hundred and six patients were included during the study period. Forty-five (42.5 %) patients received CPT-13 and 61 (57.5 %) received reference IFX. A total of 347 serum samples were analyzed and no significant differences were observed between reference IFX and CPT-13. The percentage of patients who achieved serum concentrations within the target therapeutic range was similar in both groups (74.1 % for reference IFX and 72.5 % for CPT-13, p = 0.741). At week 54, withdrawal rates for reference IFX and CPT-13 were 11.5 % and 20.0 %, respectively (p = 0.226), whereas at week 104 they were 26.2 % and 28.9 %, respectively (p = 0.761). CONCLUSION: the pharmacokinetic characteristics and incidence of immunogenicity of CPT-13 in a real clinical setting are comparable to those of the infliximab originator. The two products also have similar long-term drug survival and the same safety profile.

Association between ustekinumab trough concentrations and biochemical outcomes in patients with Crohn's disease. A real life study.

INTRODUCTION: numerous studies have shown a positive correlation between serum biologic drug concentrations and favorable therapeutic outcomes during the induction and maintenance period in patients with Crohn's disease (CD). To our knowledge, only a few and contradictory studies have determined the association between ustekinumab (UST) trough concentrations and biological outcomes. This study aimed to investigate the relationship between ustekinumab trough concentrations and biological outcomes in a real-world setting. METHODS: a cross-sectional cohort study was performed. All adult patients with CD who received maintenance therapy (≥ 24 weeks) with ustekinumab were included in the study. Clinical response was determined using the Harvey-Bradshaw Index. Biochemical remission was defined as a fecal calprotectin level < 150 µg/g in feces and a biochemical response as > 50 % reduction of fecal calprotectin. RESULTS: a total of 58 CD patients were included in the study and the median UST trough concentration was 1.78 µg/ml (IQR: 2.56). Differences in ustekinumab trough concentrations were observed for clinical (2.25 µg/ml vs 0.65 µg/ml; p = 0.006) and biochemical remission (2.33 µg/ml vs 1.03 µg/ml; p = 0.047). According to ROC analysis, a cut-off of 1.4 µg/ml (AUC: 077) and 2.0 µg/ml (AUC: 0.65) were identified for predicting clinical and biochemical remission, respectively. Likewise, ustekinumab trough levels were also higher in "composite clinical/biochemical remission" (2.38 µg/ml vs 1.08 µg/ml; p = 0.042). The trough level that was best associated with composite clinical/biochemical remission was 2.2 µg/ml (AUC: 0.69). CONCLUSION: this real-life study shows the association between ustekinumab trough concentration and clinical and biochemical remission and we suggest an optimal cut-off point higher than 2.2 µg/ml. Further studies are needed to confirm the findings and to identify the optimal cut-off in different disease outcomes and disease phenotypes.

Socioeconomic status and childhood central nervous system tumors in California.

PURPOSE: Childhood central nervous system (CNS) tumors are the leading cause of cancer mortality in children. Previous studies have suggested that some childhood cancers, including primary CNS tumors, may be associated with higher socioeconomic status (SES). METHODS: We linked data from the California Cancer Registry to California birth records for children (age 0-19 years) diagnosed with primary CNS tumors during 1988-2011 and analyzed multiple measures of parental SES around the birth of their children and subsequent risk for childhood CNS tumors. Our SES measures included birth record-derived parental education and insurance utilization. For a subset of subjects born between 1997 and 2007, we geocoded addresses and examined census-derived median household income and educational level. RESULTS: We analyzed data for 3,022 children with primary CNS tumors and 10,791 matched controls. We found consistent evidence across multiple measures that lower estimates of SES are associated with a reduced risk of CNS tumors. In tumor subgroup analyses, this relationship was most consistent in astrocytomas and ependymomas, with varying findings for embryonal tumors. CONCLUSION: Higher parental SES appears to be a risk factor for childhood CNS tumors in California. Further research is needed to determine specific exposures that may explain this increased risk.

Encuesta nacional on-line sobre el consentimiento informado para la realización de paracentesis. ¿Lo tenemos? ¿Lo utilizamos? / No disponible

INTRODUCCIÓN: el uso del consentimiento informado es necesario en los procedimientos invasivos como documento garantizador de la relación sanitaria ética y de la seguridad del paciente. OBJETIVO: analizar si se poseen y utilizan los documentos de consentimiento informado para paracentesis en los centros sanitarios, así como obtener algunos datos de interés sobre la técnica. MATERIAL Y MÉTODO: realizamos un estudio observacional descriptivo mediante una encuesta transversal on-line difundida por redes sociales, destinada a los especialistas y residentes de aparato digestivo durante diciembre de 2019. RESULTADOS: incluimos 203 encuestas anónimas (55,2 % adjuntos y 44,8 % residentes) de 74 centros sanitarios de 34 provincias españolas. Noventa encuestados (44,3 %) tenían dicho documento en sus centros; de estos, 29 (32,2 %) lo entregaban siempre; 31 (34,4 %), algunas veces; y 21 (23,3 %), nunca. Setenta y dos profesionales (35,5 %) contestaron no tenerlo y 41 (20,5 %), ser desconocedores; de entre ellos, 77 (68,1 %) consideraban necesaria su creación, 31 (27,4 %) no lo creían así y cinco (4,4 %) no contestaron. En cuanto a la técnica, 173 facultativos (85,2 %) realizan la punción bajo visión directa y 30 (14,8 %), ecoguiada en la mayoría de las ocasiones. Ciento nueve (53,7 %) aplican siempre anestésico local, 80 (39,4 %) lo aplican en algunas ocasiones y 14 (6,9 %) no lo utilizan. Ciento sesenta y siete encuestados (82,3 %) consideraron que es una técnica sencilla, frente a 36 (17,7 %) que la consideran de complejidad intermedia. En cuanto al riesgo, 150 (73,5 %) lo consideran bajo y 52 (25,6 %), medio. Noventa y nueve de ellos (48,8 %) refieren haber tenido complicaciones menores y 37 (18,2 %), mayores. CONCLUSIONES: la paracentesis es una técnica habitual en los servicios de digestivo y, a pesar de ser considerada sencilla y segura, entraña complicaciones. Por ello consideramos necesaria la formación reglada en esta técnica, así como la creación, difusión y utilización de los consentimientos informados dada la importante variabilidad intra e interhospitalaria que presenta

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Spanish online survey on informed consent for the performance of paracentesis. Do we have it? Do we use it?

INTRODUCTION: informed consent is necessary for invasive procedures as a document that guarantees the ethical health relationship and patient safety. AIMS: to analyze whether we have and use informed consent documents for paracentesis in our hospitals and to obtain data on the technique. METHODS: a descriptive observational study was performed during December 2019, via a cross-sectional survey disseminated through social networks, aimed at specialists and residents of gastroenterology. RESULTS: two hundred and three anonymous surveys were included (55.2 % gastroenterologist and 44.8 % residents) from 74 hospitals in 34 Spanish provinces. Ninety respondents (44.3 %) stated that they had the document in their centers. Of these, 29 (32.2 %) always provided it, 31 (34.4 %) provided it sometimes and 21 (23.3 %) never. Seventy-two professionals (35.5 %) answered that they did not have it and 41 (20.5 %) selected "unknown". Of these, 77 (68.1 %) considered it was necessary to create this document, 31 (27.4 %) did not think it was necessary and five (4.4 %) did not answer. With regards to the technique, 173 (85.2 %) performed paracentesis under direct visualization and 30 (14.8 %) were eco-guided on most occasions. One hundred and nine (53.7 %) always applied local anesthetic, 80 (39.4 %) sometimes and 14 (6.9 %) did not. One hundred and sixty-seven respondents (82.3 %) considered it to be a simple technique versus 36 (17.7 %) who thought that it was of intermediate complexity. In terms of risk, 150 (73.5 %) considered it was low and 52 (25.6 %), medium. Ninety-nine (48.8 %) experienced minor complications and 37 (18.2 %) experienced major complications. CONCLUSIONS: paracentesis is a common technique in digestive services and could be associated with complications, even though it is considered to be simple and safe. Due to the important intra- and inter-hospital variability that this technique presents, we consider standardized training in this technique is necessary, as well as the creation, spread and use of informed consents.

Usefulness of population pharmacokinetics to optimize the dosage regimen of infliximab in inflammatory bowel disease patients

INTRODUCTION: infliximab is used in inflammatory bowel disease, which has a great inter-individual pharmacokinetic variability. Thus, it is necessary to individualize the therapy in many cases. The main objective of our study was to compare two methods of a dose adjustment strategy using therapeutic drug monitoring: a) based on an algorithm and b) based on Bayesian prediction, to achieve an optimal infliximab trough level in patients with inflammatory bowel diseases. The secondary objective was to evaluate the predictive performance of a population pharmacokinetic model of infliximab in patients with inflammatory bowel diseases and therefore, its clinical utility. Furthermore, the factors associated with a suboptimal adjustment of the model were analyzed. METHODS: a retrospective observational cohort analysis was performed of patients with inflammatory bowel disease and available serum levels of infliximab. The relationship between trough concentration and dosing strategy was compared in both groups. The external validation of a previously published population pharmacokinetic model was performed using the NONMEM software. The mean prediction error and mean absolute prediction error were calculated to evaluate the predictive performance of the model. RESULTS: a total of 94 infliximab serum samples were obtained from 47 patients. After the adjustment, a total of 30 patients (63.8 %) achieved optimal infliximab trough levels. A dosing strategy based on Bayesian was associated with optimal infliximab trough levels that were higher than the strategy based on an algorithm (OR: 8.94 [95 % CI: 2.24 - 35.6], p = 0.001). For the individual predictions, the mean prediction error was 0.118 Mug/ml (95 % CI: -0.149-0.384) and the mean absolute prediction error was 0.935 Mug/ml (95 % CI: 0.569-1.075). CONCLUSIONS: the application of a population pharmacokinetic model based on Bayesian prediction is an important advance in the optimization of infliximab dosage in the treatment of inflammatory bowel disease

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Usefulness of population pharmacokinetics to optimize the dosage regimen of infliximab in inflammatory bowel disease patients.

INTRODUCTION: infliximab is used in inflammatory bowel disease, which has a great inter-individual pharmacokinetic variability. Thus, it is necessary to individualize the therapy in many cases. The main objective of our study was to compare two methods of a dose adjustment strategy using therapeutic drug monitoring: a) based on an algorithm and b) based on Bayesian prediction, to achieve an optimal infliximab trough level in patients with inflammatory bowel diseases. The secondary objective was to evaluate the predictive performance of a population pharmacokinetic model of infliximab in patients with inflammatory bowel diseases and therefore, its clinical utility. Furthermore, the factors associated with a suboptimal adjustment of the model were analyzed. METHODS: a retrospective observational cohort analysis was performed of patients with inflammatory bowel disease and available serum levels of infliximab. The relationship between trough concentration and dosing strategy was compared in both groups. The external validation of a previously published population pharmacokinetic model was performed using the NONMEM software. The mean prediction error and mean absolute prediction error were calculated to evaluate the predictive performance of the model. RESULTS: a total of 94 infliximab serum samples were obtained from 47 patients. After the adjustment, a total of 30 patients (63.8 %) achieved optimal infliximab trough levels. A dosing strategy based on Bayesian was associated with optimal infliximab trough levels that were higher than the strategy based on an algorithm (OR: 8.94 [95 % CI: 2.24 - 35.6], p = 0.001). For the individual predictions, the mean prediction error was 0.118 µg/ml (95 % CI: -0.149-0.384) and the mean absolute prediction error was 0.935 µg/ml (95 % CI: 0.569-1.075). CONCLUSIONS: the application of a population pharmacokinetic model based on Bayesian prediction is an important advance in the optimization of infliximab dosage in the treatment of inflammatory bowel disease.

Usefulness of therapeutic drug monitoring of infliximab during the induction period in patients with inflammatory bowel disease

INTRODUCTION: previous studies have shown that higher infliximab trough levels are associated with favorable shortterm and long-term therapeutic outcomes in inflammatory bowel disease. There is a need to determine which patients could benefit from proactive therapeutic drug monitoring in the induction phase. The aim of this study was to evaluate the pharmacokinetic variability of infliximab, determine the factors associated with achieving target infliximab trough levels in the induction phase and analyze the clinical and biochemical response at week 26 of treatment. PATIENTS AND METHODS: a retrospective observational study was performed of patients with inflammatory bowel disease and data available on serum levels of infliximab during the induction period. The percentage of patients that achieved target infliximab trough levels at week 6 was determined. Clinical remission and response and biochemical remission were evaluated at week 26. RESULTS: thirty patients were included and only 13 (43.3 %) had infliximab trough levels > 15 μg/mL at week 6. A clinical response was observed during the maintenance period in 71.4 % of patients, their infliximab levels were significantly higher than in non-responders (6.3 μg/mL [IQR: 6.7] vs 1.0 μg/mL [IQR: 5.0], respectively; p = 0.016). Likewise, 53.6 % of patients achieved biochemical remission (responders 6.2 μg/mL [IQR: 5.2] vs non-responders 3.2 μg/mL [IQR: 5.0]; p = 0.031). CONCLUSION: less than half of patients had target infliximab levels during the induction period. Therapeutic drug monitoring during this period is related to the achievement of therapeutic levels of infliximab and may lead to a better clinical response in these patients

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Usefulness of therapeutic drug monitoring of infliximab during the induction period in patients with inflammatory bowel disease.

INTRODUCTION: previous studies have shown that higher infliximab trough levels are associated with favorable short-term and long-term therapeutic outcomes in inflammatory bowel disease. There is a need to determine which patients could benefit from proactive therapeutic drug monitoring in the induction phase. The aim of this study was to evaluate the pharmacokinetic variability of infliximab, determine the factors associated with achieving target infliximab trough levels in the induction phase and analyze the clinical and biochemical response at week 26 of treatment. PATIENTS AND METHODS: a retrospective observational study was performed of patients with inflammatory bowel disease and data available on serum levels of infliximab during the induction period. The percentage of patients that achieved target infliximab trough levels at week 6 was determined. Clinical remission and response and biochemical remission were evaluated at week 26. RESULTS: thirty patients were included and only 13 (43.3 %) had infliximab trough levels > 15 µg/mL at week 6. A clinical response was observed during the maintenance period in 71.4 % of patients, their infliximab levels were significantly higher than in non-responders (6.3 µg/mL [IQR: 6.7] vs 1.0 µg/mL [IQR: 5.0], respectively; p = 0.016). Likewise, 53.6 % of patients achieved biochemical remission (responders 6.2 µg/mL [IQR: 5.2] vs non-responders 3.2 µg/mL [IQR: 5.0]; p = 0.031). CONCLUSION: less than half of patients had target infliximab levels during the induction period. Therapeutic drug monitoring during this period is related to the achievement of therapeutic levels of infliximab and may lead to a better clinical response in these patients.

EXP1 is critical for nutrient uptake across the parasitophorous vacuole membrane of malaria parasites.

Intracellular malaria parasites grow in a vacuole delimited by the parasitophorous vacuolar membrane (PVM). This membrane fulfils critical roles for survival of the parasite in its intracellular niche such as in protein export and nutrient acquisition. Using a conditional knockout (KO), we here demonstrate that the abundant integral PVM protein exported protein 1 (EXP1) is essential for parasite survival but that this is independent of its previously postulated function as a glutathione S-transferase (GST). Patch-clamp experiments indicated that EXP1 is critical for the nutrient-permeable channel activity at the PVM. Loss of EXP1 abolished the correct localisation of EXP2, a pore-forming protein required for the nutrient-permeable channel activity and protein export at the PVM. Unexpectedly, loss of EXP1 affected only the nutrient-permeable channel activity of the PVM but not protein export. Parasites with low levels of EXP1 became hypersensitive to low nutrient conditions, indicating that EXP1 indeed is needed for nutrient uptake and experimentally confirming the long-standing hypothesis that the channel activity measured at the PVM is required for parasite nutrient acquisition. Hence, EXP1 is specifically required for the functional expression of EXP2 as the nutrient-permeable channel and is critical for the metabolite supply of malaria parasites.

Qualidade de vida: o desafio do trabalho noturno para a equipe de enfermagem / Life quality: the night shift work challenge to nursing team / Calidad de vida: el reto de trabajar en la noche para el equipo de enfermería

Objective: Our goal herein has been to gain further insights regarding the life quality and its association with sociodemographic characteristics of nursing professionals working at night shift. Methods: It is an analytical research type with quantitative approach. The research was performed in a hospital of Montes Claros city, Minas Gerais State, Brazil, over the year of 2014 and had 145 workers participants. The survey has been done by applying a sociodemographic questionnaire and the Abbreviated Instrument for the Assessment of the Life Quality (WHOQOL-bref) in August 2014. The descriptive analysis and student's t-test was used in order to check for possible associations. Results: The majority of the workers were female, aged up to 35 years old, having intimate partner and children. The following dimensions had shown the worst scores: environment and physical. The comparison of average scores within the four dimensions has revealed that the most significant covariates were as follows: sex, physical activity, additional job, civil status and working time. Conclusion: In the present study was observed that the workers require greater attention to the environmental and physical dimensions, and also in the sociodemographic characteristics that interfered in their life quality

Objetivo: Avaliar a qualidade de vida e sua associação com as características sociodemográficas dos trabalhadores da enfermagem do período noturno. Métodos: Pesquisa do tipo analítico, com abordagem quantitativa, com 145 trabalhadores, realizada em 2014 em uma instituição hospitalar de Montes Claros, Minas Gerais-Brasil. Foram aplicados um questionário sociodemográfico e o Instrumento Abreviado de Avaliação da Qualidade de Vida, em agosto de 2014. Realizou-se a análise descritiva e o teste t student para verificação de associações. Resultados: Predominaram trabalhadores do sexo feminino, com idade de até 35 anos, com companheiro(a) e filhos. Os domínios meio ambiente e físico apresentaram piores escores. Na comparação dos escores médios nos quatro domínios, as covariáveis mais significativas foram: sexo, atividade física, outro vínculo, estado civil e tempo de trabalho. Conclusão: Os trabalhadores demandam maior atenção nas dimensões ambientais e físicas, e nas características sociodemográficas que interferiram na qualidade de vida

Objetivo: Evaluar la calidad de vida y su asociación con características sociodemográficas de los trabajadores de la enfermería durante la noche. Método: Un estudio de tipo analítico, con un enfoque cuantitativo, con 145 trabajadores, que se celebró en 2014 en un hospital de Montes Claros, Minas Gerais Gerais-Brasil. Se les aplicó un cuestionario sociodemográfico y el abreviado Instrumento de Evaluación de la Calidad de Vida (WHOQOLbref), en 2014 agosto. El análisis descriptivo y la prueba t de student para comprobar para las asociaciones. Resultados: La mayoría de los trabajadores era una mujer, a la edad de 35 años, con compañero(a) y los niños. Las esferas física y medio ambiente tuvo las peores puntuaciones. La comparación de puntuaciones medias en cuatro zonas, las covariables fueron: El sexo, la actividad física, otro bono, el estado civil y el tiempo de trabajo. Conclusión: Los trabajadores requieren una mayor atención en las zonas con menor puntuación y las características que interfieren con la calidad de vida

Violacein Treatment Modulates Acute and Chronic Inflammation through the Suppression of Cytokine Production and Induction of Regulatory T Cells.

Inflammation is a necessary process to control infection. However, exacerbated inflammation, acute or chronic, promotes deleterious effects in the organism. Violacein (viola), a quorum sensing metabolite from the Gram-negative bacterium Chromobacterium violaceum, has been shown to protect mice from malaria and to have beneficial effects on tumors. However, it is not known whether this drug possesses anti-inflammatory activity. In this study, we investigated whether viola administration is able to reduce acute and chronic autoimmune inflammation. For that purpose, C57BL/6 mice were intraperitoneally injected with 1 µg of LPS and were treated with viola (3.5mg/kg) via i.p. at the same time-point. Three hours later, the levels of inflammatory cytokines in the sera and phenotypical characterization of leukocytes were determined. Mice treated with viola presented a significant reduction in the production of inflammatory cytokines compared with untreated mice. Interestingly, although viola is a compound derived from bacteria, it did not induce inflammation upon administration to naïve mice. To test whether viola would protect mice from an autoimmune inflammation, Experimental Autoimmune Encephalomyelitis (EAE)-inflicted mice were given viola i.p. at disease onset, at the 10th day from immunization. Viola-treated mice developed mild EAE disease in contrast with placebo-treated mice. The frequencies of dendritic cells and macrophages were unaltered in EAE mice treated with viola. However, the sole administration of viola augmented the levels of splenic regulatory T cells (CD4+Foxp3+). We also found that adoptive transfer of viola-elicited regulatory T cells significantly reduced EAE. Our study shows, for the first time, that violacein is able to modulate acute and chronic inflammation. Amelioration relied in suppression of cytokine production (in acute inflammation) and stimulation of regulatory T cells (in chronic inflammation). New studies must be conducted in order to assess the possible use of viola in therapeutic approaches in human autoimmune diseases.