Therapeutic drug monitoring of infliximab in spondyloarthritis. A review of the literature.

Available evidence indicates that a therapeutic drug monitoring strategy leads to major cost savings related to the anti-tumour necrosis factor-α therapy in both inflammatory bowel disease and rheumatoid arthritis (RA) patients, with no negative impact on efficacy. However, although the systematic use of therapeutic drug monitoring could potentially be beneficial and economically acceptable to drug dose optimization, it is not justifiable for all drugs. Infliximab (IFX) is a chimeric monoclonal immunoglobulin G1 targeting tumour necrosis factor. It has been approved for the treatment of immuno-inflammatory diseases, including RA, ankylosing spondylitis, psoriatic arthritis, Crohn's disease and ulcerative colitis. IFX's pharmacokinetics is highly variable and influences clinical response in chronic inflammatory diseases. Clinical response increases with IFX trough concentrations in RA, ankylosing spondylitis, inflammatory bowel disease and psoriatic patients. Target concentrations predictive of good clinical response were proposed in RA, Crohn's disease and ulcerative colitis. The purpose of this article is to review the current literature surrounding IFX serum concentrations and their related parameters with disease activity in patients with spondyloarthritis. Gathering information about the efficacy of IFX in patients with spondyloarthritis and relating IFX serum concentrations to disease activity were the main goals of this study.

Optical Genome Mapping as a New Tool to Overcome Conventional Cytogenetics Limitations in Patients with Bone Marrow Failure.

Cytogenetic studies are essential in the diagnosis and follow up of patients with bone marrow failure syndromes (BMFSs), but obtaining good quality results is often challenging due to hypocellularity. Optical Genome Mapping (OGM), a novel technology capable of detecting most types chromosomal structural variants (SVs) at high resolution, is being increasingly used in many settings, including hematologic malignancies. Herein, we compared conventional cytogenetic techniques to OGM in 20 patients with diverse BMFSs. Twenty metaphases for the karyotype were only obtained in three subjects (15%), and no SVs were found in any of the samples. One patient with culture failure showed a gain in chromosome 1q by fluorescence in situ hybridization, which was confirmed by OGM. In contrast, OGM provided good quality results in all subjects, and SVs were detected in 14 of them (70%), mostly corresponding to cryptic submicroscopic alterations not observed by standard techniques. Therefore, OGM emerges as a powerful tool that provides complete and evaluable results in hypocellular BMFSs, reducing multiple tests into a single assay and overcoming some of the main limitations of conventional techniques. Furthermore, in addition to confirming the abnormalities detected by conventional techniques, OGM found new alterations beyond their detection limits.

A study of complexation and biological fate of polyethyleneimine-siRNA polyplexes in vitro and in vivo by fluorescence correlation spectroscopy and positron emission tomography imaging.

A deeper knowledge on the formation and biological fate of polymer based gene vectors is needed for their translation into therapy. Here, polyplexes of polyethyleneimine (PEI) and silencing RNA (siRNA) are formed with theoretical N/P ratios of 2, 4 and 12. Fluorescence correlation spectroscopy (FCS) is used to study the formation of polyplexes from fluorescently labelled PEI and siRNA. FCS proves the presence of free PEI. From the analysis of the autocorrelation functions it was possible to determine the actual stoichiometry of polyplexes. FCS and fluorescence cross correlation spectroscopy (FCCS) are used to follow the fate of the polyplexes intracellularly. Polyplexes disassemble after 1 day inside cells. Positron emission tomography (PET) studies are conducted with radiolabelled polyplexes prepared with siRNA or PEI labelled with 2,3,5,6-tetrafluorophenyl 6-[18F]-fluoronicotinate ([18F]F-PyTFP). PET studies in healthy mice show that [18F]siRNA/PEI and siRNA/[18F]PEI polyplexes show similar biodistribution patterns with limited circulation in the bloodstream and accumulation in the liver. Higher activity for [18F]PEI in the kidney and bladder suggests the presence of free PEI.

Insulin eye drops for treating corneal ulcer in a non-diabetic patient: regarding a case.

Corneal ulcers are included in a heterogeneous group of eye injuries. When  patients do not respond to treatment, including even corneal transplant, other  alternatives need to be explored.We present a case of a patient who suffered an accidental spillage from the  contents of a car battery. This corneal lesion was refractory to both surgical and  pharmacological treatment. After four years of a persistent ulcer, insulin topical  treatment 50 IU/mL was started. Improvement began to be observed and  currently the patient has completely recovered the corneal epithelium.Nowadays, evidence of the topical insulin use for the treatment of corneal ulcers  is higher in diabetic patients. In non-diabetic patients, evidence is restricted to a series of cases of neurotrophic corneal ulcers and a case report of a patient who  presented a persistent epithelial defect after resection of a neurinoma. This case  presents the experience of using an insulin drop formulation with effectiveness  and absence of toxicity in a patient nondiabetic with a post-caustic corneal ulcer.

Las úlceras corneales se incluyen dentro de un grupo heterogéneo de lesiones  oculares, las cuales pueden ser de gravedad variable. Cuando los pacientes no  responden al tratamiento, incluyendo incluso el trasplante corneal, se crea la  necesidad de explorar otras alternativas.Presentamos el caso de un paciente que sufrió una salpicadura ocular del  contenido de una batería de automóvil por accidente. Esta lesión corneal, fue  refractaria al tratamiento farmacológico e incluso quirúrgico. Tras cuatro años de persistencia de la úlcera corneal, se inició un tratamiento tópico con insulina 50  UI/ml. Se observó mejoría de forma evidente y actualmente el paciente ha  recuperado completamente el epitelio corneal.Hoy en día, las evidencias disponibles del uso tópico de la insulina para el  tratamiento de las úlceras corneales se centran en pacientes diabéticos. En los  pacientes no diabéticos, la evidencia se limita a una serie de casos de úlceras  neurotróficas corneales y al caso de un paciente que presentó un defecto  epitelial persistente después de la resección de un neurinoma. Este caso,  presenta la experiencia de uso de una formulación magistral de insulina  oftálmica con eficacia y ausencia de toxicidad en un paciente no diabético con  una úlcera corneal post-cáustica resistente al resto de tratamientos.

Concordance between pharmacotherapeutic complexity calculated and perceived by HIV+ patients with antiretroviral treatment.

OBJECTIVE: To determine the difference between the pharmacotherapeutic complexity index by Medication Regimen Complexity Index  and it's perceived by patients through a visual analogue scale in patients  HIV+ with antiretroviral treatment. METHOD: Prospective, observational study of patients HIV+ > 18 years of age  with stable antiretroviral treatment in the last three months, followed up by  external consultations of pharmaceutical care between October´17 and February ´18. The main variable of the study was the concordance between the median of  the score obtained in the pharmacotherapeutic complexity perceived  by the patients using the visual analog scale whose range of values oscillates between 0-10, categorized in low complexity (0-1) and high  complexity (2-10), and the median of the score obtained for the theoretical  pharmacotherapeutic complexity using the Medication Regimen Complexity  Index tool whose ranges of values oscillate between 1 and infinity, categorized  in low complexity (0-11) and high complexity > 11. The overall complexity was calculated: antiretroviral treatment and concomitant treatment. RESULTS: We included 236 patients in the study. There was a discrete concordance between the pharmacotherapeutic complexity perceived by the patients and that calculated according to the Medication Regimen  Complexity Index tool (Cohen's Kappa index 0.203). The median of the Medica tion Regimen Complexity Index of the total medication was 6 (interquartile range: 4-10) versus the median of the Complexity Index measured by visual analog scale of 2 (interquartile range: 0-4). CONCLUSIONS: Patients perceive a pharmacotherapeutic complexity lower than  that calculated. Therefore, we must include the two scales in pharmaceutical care for a better understanding of the patient's perception.

Objetivo: Determinar la diferencia entre el índice de complejidad  farmacoterapéutica calculado mediante la herramienta Medication Regimen  Complexity Index y el percibido por los pacientes a través de la escala visual analógica en pacientes VIH+ en tratamiento antirretroviral.Método: Estudio prospectivo, observacional de pacientes VIH+ > 18 años con  tratamiento antirretroviral estable desde los últimos tres meses, en seguimiento por las consultas de atención farmacéutica entre octubre de 2017 y febrero de 2018. La variable principal fue la concordancia entre la mediana  obtenida de la complejidad farmacoterapéutica percibida por los pacientes  mediante la escala visual analógica, cuyos valores oscilan entre 0-10,  permitiendo categorizar la complejidad en baja (0-1) y alta complejidad (2-10),  y la mediana del cálculo del índice de complejidad farmacoterapéutica medido  mediante la herramienta Medication Regimen Complexity Index, cuyos rangos  oscilan entre 1 e infinito, categorizada en complejidad baja (0-11) y complejidad alta (mayor de 11). La complejidad farmacoterapéutica fue  calculada teniendo en cuenta el tratamiento global del paciente: tratamiento  antirretroviral y tratamiento concomitante.Resultados: Se incluyeron 236 pacientes en el estudio. Hubo una discreta concordancia entre la complejidad farmacoterapéutica percibida por el  paciente y la calculada mediante la herramienta Medication Regimen Complexity  Index (índice de Kappa de Cohen 0,203). La mediana del  índice Medication  Regimen Complexity global fue de 6 (rango intercuartil: 4-10) frente a la  mediana del índice de complejidad farmacoterapéutica percibida por los  pacientes 2 (rango intercuartil: 0-4).Conclusiones: Los pacientes perciben una complejidad farmacoterapéutica menor que la calculada. Por lo tanto, debemos incluir las dos  escalas farmacoterapéuticas para conseguir un mejor entendimiento de la  percepción de los pacientes.

Emergence of Inflammatory Bowel Disease During Treatment With Secukinumab.

Secukinumab is an anti-IL 17A monoclonal antibody currently licensed for the treatment of plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. However, although inflammatory bowel disease is a disorder with related immune characteristics, secukinumab has not proved to be effective in these diseases. In fact, negative results in a clinical trial designed to assess the efficacy of secukinumab in patients with Crohn's disease have been published. On the other hand, the drug fact sheet states that secukinumab should be used with caution in patients with inflammatory bowel disease. Although the drug has shown to worsen these pathologies, there are no published data of cases in which the patient is first diagnosed with inflammatory bowel disease during secukinumab treatment. We present two cases of emergence of inflammatory bowel disease in patients with plaque psoriasis and ankylosing spondylitis, treated with secukinumab.

Concordance between pharmacotherapeutic complexity calculated and perceived by HIV+ patients with antiretroviral treatment / Concordancia entre la complejidad farmacoterapéutica calculada y la percibida por los pacientes VIH+ en tratamiento antirretroviral

Objective: To determine the difference between the pharmacotherapeutic complexity index by Medication Regimen Complexity Index and it's perceived by patients through a visual analogue scale in patients HIV+ with antiretroviral treatment. Method: Prospective, observational study of patients HIV+ > 18 years of age with stable antiretroviral treatment in the last three months, followed up by external consultations of pharmaceutical care between October'17 and February'18. The main variable of the study was the concordance between the median of the score obtained in the pharmacotherapeutic complexity perceived by the patients using the visual analog scale whose range of values oscillates between 0-10, categorized in low complexity (0-1) and high complexity (2-10), and the median of the score obtained for the theoretical pharmacotherapeutic complexity using the Medication Regimen Complexity Index tool whose ranges of values oscillate between 1 and infinity, categorized in low complexity (0-11) and high complexity > 11. The overall complexity was calculated: antiretroviral treatment and concomitant treatment. Results: We included 236 patients in the study. There was a discrete concordance between the pharmacotherapeutic complexity perceived by the patients and that calculated according to the Medication Regimen Complexity Index tool (Cohen's Kappa index 0.203). The median of the Medication Regimen Complexity Index of the total medication was 6 (interquartile range: 4-10) versus the median of the Complexity Index measured by visual analog scale of 2 (interquartile range: 0-4). Conclusions: Patients perceive a pharmacotherapeutic complexity lower than that calculated. Therefore, we must include the two scales in pharmaceutical care for a better understanding of the patient's perception

Objetivo: Determinar la diferencia entre el índice de complejidad farmaco- terapéutica calculado mediante la herramienta Medication Regimen Complexity Index y el percibido por los pacientes a través de la escala visual analógica en pacientes VIH+ en tratamiento antirretroviral. Método: Estudio prospectivo, observacional de pacientes VIH+ > 18 años con tratamiento antirretroviral estable desde los últimos tres meses, en seguimiento por las consultas de atención farmacéutica entre octubre de 2017 y febrero de 2018. La variable principal fue la concordancia entre la mediana obtenida de la complejidad farmacoterapéutica percibida por los pacientes mediante la escala visual analógica, cuyos valores oscilan entre 0-10, permitiendo categorizar la complejidad en baja (0-1) y alta complejidad (2-10), y la mediana del cálculo del índice de complejidad farmacoterapéutica medido mediante la herramienta Medication Regimen Complexity Index, cuyos rangos oscilan entre 1 e infinito, categorizada en complejidad baja (0-11) y complejidad alta (mayor de 11). La complejidad farmacoterapéutica fue calculada teniendo en cuenta el tratamiento global del paciente: tratamiento antirretroviral y tratamiento concomitante. Resultados: Se incluyeron 236 pacientes en el estudio. Hubo una discreta concordancia entre la complejidad farmacoterapéutica percibida por el paciente y la calculada mediante la herramienta Medication Regimen Complexity Index (índice de Kappa de Cohen 0,203). La mediana del índice Medication Regimen Complexity global fue de 6 (rango intercuartil: 4-10) frente a la mediana del índice de complejidad farmacoterapéutica percibida por los pacientes 2 (rango intercuartil: 0-4). Conclusiones: Los pacientes perciben una complejidad farmacoterapéutica menor que la calculada. Por lo tanto, debemos incluir las dos escalas farmacoterapéuticas para conseguir un mejor entendimiento de la percepción de los pacientes

Insulina tópica en el tratamiento de úlcera corneal refractaria en un paciente no diabético: a propósito de un caso / Insulin eye drops for treating corneal ulcer in a non-diabetic patient: regarding a case

Las úlceras corneales se incluyen dentro de un grupo heterogéneo de lesiones oculares, las cuales pueden ser de gravedad variable. Cuando los pacientes no responden al tratamiento, incluyendo incluso el trasplante corneal, se crea la necesidad de explorar otras alternativas. Presentamos el caso de un paciente que sufrió una salpicadura ocular del contenido de una batería de automóvil por accidente. Esta lesión corneal, fue refractaria al tratamiento farmacológico e incluso quirúrgico. Tras cuatro años de persistencia de la úlcera corneal, se inició un tratamiento tópico con insulina 50 UI/ml. Se observó mejoría de forma evidente y actualmente el paciente ha recuperado completamente el epitelio corneal. Hoy en día, las evidencias disponibles del uso tópico de la insulina para el tratamiento de las úlceras corneales se centran en pacientes diabéticos. En los pacientes no diabéticos, la evidencia se limita a una serie de casos de úlceras neurotróficas corneales y al caso de un paciente que presentó un defecto epitelial persistente después de la resección de un neurinoma. Este caso, presenta la experiencia de uso de una formulación magistral de insulina oftálmica con eficacia y ausencia de toxicidad en un paciente no diabético con una úlcera corneal post-cáustica resistente al resto de tratamientos

Corneal ulcers are included in a heterogeneous group of eye injuries. When patients do not respond to treatment, including even corneal transplant, other alternatives need to be explored.We present a case of a patient who suffered an accidental spillage from the contents of a car battery. This corneal lesion was refractory to both surgical and pharmacological treatment. After four years of a persistent ulcer, insulin topical treatment 50 IU/mL was started. Improvement began to be observed and currently the patient has completely recovered the corneal epithelium. Nowadays, evidence of the topical insulin use for the treatment of corneal ulcers is higher in diabetic patients. In non-diabetic patients, evidence is restricted to a series of cases of neurotrophic corneal ulcers and a case report of a patient who presented a persistent epithelial defect after resection of a neurinoma. This case presents the experience of using an insulin drop formulation with effectiveness and absence of toxicity in a patient non-diabetic with a post-caustic corneal ulcer