Optimising the Therapeutic Interval for Biologics in Patients with Psoriasis.

In our clinical experience, more than half of patients do not present a complete response to biologic drugs, or drug loses its efficacy over time. Plasma determinations of drug and anti-drug antibodies levels are an objective tool for optimisation in these patients; however, established therapeutic ranges are not suitable, so the objective of this study was to study these patients and optimise their healthcare. We have made a retrospective, observational study, using data of plasma levels of drugs and anti-drugs antibodies of infliximab, adalimumab or Etanercept, we summarise all data and make a study of sensitivity, specificity, positive and negative predictive value on current therapeutic ranges. We have found a statistically significant association between subtherapeutic levels and therapeutic failure in psoriasis treated with infliximab and adalimumab. New ranges were found with higher sensitivity than the established ones, we propose 2-10 µg/mL therapeutic range for infliximab, 3-11 µg/mL for adalimumab, and 1-7 µg/mL for etanercept. In conclusion, levels of drug and anti-drug antibodies are a decisive tool for predicting therapeutic response. The current therapeutic ranges may have minimum values that are excessively high, owing to which lowering them significantly increases the sensitivity of the test in all cases, and negative predictive value in the case of etanercept. Further prospective studies are needed to prove the usefulness of these new ranges.

Uso de ustekinumab tras otras terapias biológicas en psoriasis moderada-grave: Resultados en salud en vida real a largo plazo / Use of ustekinumab after other biological therapies in moderate-severe psoriasis: Real long-term data

OBJETIVO: Ustekinumab se usa en psoriasis en placas moderada-grave con respuesta inadecuada a fármacos antifactor de necrosis tumoral α. Recientes estudios sostienen la escasez de resultados en vida real a largo plazo. El objetivo es evaluar la efectividad y seguridad de larga duración de ustekinumab en psoriasis en placas moderada-severa refractaria a dos fármacos antifactor de necrosis tumoral α. MÉTODO: Estudio descriptivo retrospectivo entre enero de 2010 y marzo de 2019. Se incluyeron pacientes con psoriasis en placas moderada-grave tratados previamente con al menos dos agentes biológicos antifactor de ne-crosis tumoral α. Las variables de efectividad fueron respuestas Psoriasis Area and Severity Index 90 y 75 a las 24, 48, 72 y 96 semanas. La seguridad fue valorada mediante reacciones adversas y suspensiones de tratamiento. RESULTADOS: Se incluyeron 36 pacientes. El 61% fueron varones. Ustekinumab fue usado tras dos fármacos antifactor de necrosis tumoral α en el 88,9% de los pacientes. Los agentes biológicos previos más frecuentes fueron infliximab (94,4%) y etanercept (91,7%). Se observó que, al menos, el 66,7% de los pacientes alcanzaron Psoriasis Area and Severity Index90 en las semanas 24, 48, 72 y 96. Se registraron reacciones adversas asociadas a ustekinumab en 6 pacientes. No hubo suspensiones. CONCLUSIONES: Ustekinumab ha demostrado ser efectivo y seguro a largo plazo según resultados de vida real en psoriasis en placas moderada-severa tras respuesta inadecuada a dos fármacos antifactor de necrosis tumoral alfa

OBJECTIVE: Ustekinumab is used in moderate-severe plaque psoriasis with inadequate response to anti-tumour necrosis factor α drugs. Recent studies support the need to assess real long-term data. The aim of this study was to evaluate the real long-term effectiveness and safety of ustekinumab in moderate-severe plaque psoriasis refractory to 2 anti-tumour necrosis factor α drugs. METHOD: Retrospective descriptive study from January 2010 to March 2019. The study included patients with moderate-severe plaque psoriasis previously treated with at least 2 anti-tumour necrosis factor α biologic drugs. The effectiveness endpoints were Psoriasis Area and Severity Index 90 and 75 response rates at weeks 24, 48, 72, and 96. Safety was assessed using adverse effects and treatment withdrawal. RESULTS: A total of 36 patients were included (men, 61%). Ustekinumab was used after treatment with 2 anti-tumour necrosis factor α drugs in 88.9% of patients. The biologic drugs most frequently administered prior to ustekinumab were infliximab (94.4%) and etanercept (91.7%). It was observed that at least 66.7% of patients reached Psoriasis Area and Severity Index 90 at weeks 24, 48, 72, and 96. Adverse effects were recorded in 6 patients. There were no treatment withdrawals. CONCLUSIONS: Ustekinumab showed real long-term effectiveness and safety in moderate-severe plaque psoriasis with inadequate response to 2 previous anti-tumour necrosis factor Alpha drugs

Use of ustekinumab after other biological therapies in moderate-severe psoriasis: Real long-term data.

OBJECTIVE: Ustekinumab is used in moderate-severe plaque psoriasis with  inadequate response to anti-tumour necrosis factor α drugs. Recent studies  support the need to assess real long-term data. The aim of this study was to  evaluate the real long-term effectiveness and safety of ustekinumab in  moderate-severe plaque psoriasis refractory to 2 anti-tumour necrosis factor α  drugs. METHOD: Retrospective descriptive study from January 2010 to March 2019. The study included patients with moderate-severe plaque psoriasis previously treated with at least 2 anti-tumour necrosis factor α biologic drugs. The effectiveness  endpoints were Psoriasis Area and Severity Index 90 and 75 response rates at  weeks 24, 48, 72, and 96. Safety was assessed using adverse effects and  treatment withdrawal. RESULTS: A total of 36 patients were included (men, 61%). Ustekinumab was  used after treatment with 2 anti-tumour necrosis factor α drugs in 88.9% of  patients. The biologic drugs most frequently administered prior to ustekinumab  were infliximab (94.4%) and etanercept (91.7%). It was observed that at least  66.7% of patients reached Psoriasis Area and Severity Index 90 at weeks 24,  48, 72, and 96. Adverse effects were recorded in 6 patients. There were no  treatment withdrawals. CONCLUSIONS: Ustekinumab showed real long-term effectiveness and safety in  moderate-severe plaque psoriasis with inadequate response to 2 previous anti- tumour necrosis factor α drugs.

Objetivo: Ustekinumab se usa en psoriasis en placas moderada-grave con  respuesta inadecuada a fármacos antifactor de necrosis tumoral α. Recientes  estudios sostienen la escasez de resultados en vida real a largo plazo. El objetivo es evaluar la efectividad y seguridad de larga duración de ustekinumab en  psoriasis en placas moderada-severa refractaria a dos fármacos antifactor de  necrosis tumoral α.Método: Estudio descriptivo retrospectivo entre enero de 2010 y marzo de  2019. Se incluyeron pacientes con psoriasis en placas moderada-grave tratados  previamente con al menos dos agentes biológicos antifactor de necrosis tumoral  α. Las variables de efectividad fueron respuestas Psoriasis Area and Severity  Index 90 y 75 a las 24, 48, 72 y 96 semanas. La seguridad fue valorada  mediante reacciones adversas y suspensiones de tratamiento.Resultados: Se incluyeron 36 pacientes. El 61% fueron varones. Ustekinumab fue usado tras dos fármacos antifactor de necrosis tumoral α en el  88,9% de los pacientes. Los agentes biológicos previos más frecuentes fueron  infliximab (94,4%) y etanercept (91,7%). Se observó que, al menos, el 66,7%  de los pacientes alcanzaron Psoriasis Area and Severity Index 90 en las semanas 24, 48, 72 y 96. Se registraron reacciones adversas asociadas a ustekinumab en  6 pacientes. No hubo suspensiones. Conclusiones: Ustekinumab ha demostrado ser efectivo y seguro a largo plazo  según resultados de vida real en psoriasis en placas moderada-severa tras  respuesta inadecuada a dos fármacos antifactor de necrosis tumoral α.

Prevalencia y niveles de exposición a factores y riesgos psicosociales a través del ISTAS-21 / Prevalence and exposure levels to psychosocial factors and risks through ISTAS-21

El presente trabajo tiene como finalidad la evaluación y descripción de los riesgos psicosociales en una muestra de profesionales de Extremadura que prestan servicios de atención a personas con discapacidad intelectual o del desarrollo. Para ello, se ha utilizado el cuestionario Istas-21 (ISTAS, 2010). La muestra está formada por 518 trabajadores y trabajadoras, 169 son hombres (30,11 %) y 349 son mujeres (67,37 %) de diferentes entidades. Se han analizado tres constructos psicosociales: exigencias psicológicas, doble presencia y control del trabajo, en función de la edad, sexo, departamento, antigüedad, puesto de trabajo y tipo de contrato. Estos constructos engloban 10 dimensiones del cuestionario que se han analizado pormenorizadamente. Los resultados indican que los participantes están más afectados por las dimensiones de las exigencias de esconder emociones, doble presencia y control de los tiempos en el trabajo

The main purpose of the present study is to evaluate and to explain the presence of psychosocial risks in a cross-section of staff working with people with in¬tellectual disabilities from Extremadura (Spain). With this aim, Istas-21 instrument has been used. The cross-section was composed of 518 workers of different entities, 169 are men (30,11 %) and 349 are women (67,37 %). Three psychosocial constructs of Istas-21 have been analyzed: psychosocial demands, double presence and time manage¬ment, considering different variables (age, sex, department, numbers of years spent on the work, job position and type of contract). These constructs include ten dimensions of the questionnaire which have been deeply evaluated. The results indicate that partici¬pants are more affected by the dimensions of the demands of hiding emotions, double presence and time management at work

Cost-effectiveness of lenalidomide maintenance in patients with multiple myeloma who have undergone autologous transplant of hematopoietic progenitor cells.

The objective of this article is to analyze the ratio of cost-effectiveness and budgetary impact of lenalidomide treatment in patients with multiple myeloma who have undergone autologous transplant in Spain. The analyses were based on clinical trials CALGB 100104 and IFM 2005-02, from the perspective of the National Health System. The alternatives compared were the treatment with lenalidomide against maintenance without treatment (MwT). Efficiency measures used were years of life gained (YGs) and quality-adjusted life years (QALYs). According to the CALGB 100104 trial data, the average health costs of patients who were treated with lenalidomide for 120 months was €836,534.31 and without treatment was €528,963.63. The effectiveness of the lenalidomide group was 7.59YGs (5.72 QALY) against 6.58 of MwT (4.61 QALY). The incremental cost-utility ratio (ICUR) was €277,456.72/QALY and the incremental cost-effectiveness ratio was €303,191.05/YGs. From the analysis, the IFM2005-02 trial obtained 5.13 QALY in the lenalidomide group against the 4.98 QALY in the MwT group, with an ICUR of €1,502,780.55/QALY. In terms of budgetary impact, a range between 799 and 1452 patients susceptible to receive treatment with lenalidomide was assumed in Spain. In conclusion, the results show a high ICUR and budgetary impact, which adds uncertainty about the maximum prudent duration of the treatment.

Network meta-analysis of tofacitinib versus biologic treatments in moderate-to-severe rheumatoid arthritis patients.

WHAT IS KNOWN AND OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune disease characterized primarily by inflammation and pain in the joints. Tofacitinib is an oral drug recently approved for RA treatment; it inhibits Janus protein kinases (JAK) that reduces RA symptoms when conventional DMARDs do not trigger a response. This study aimed to compare the efficacy of biological DMARDs in monotherapy or combined with methotrexate in RA patients and compare the treatments. METHODS: We reviewed the literature for articles published up to June 2017, evaluating the efficacy and safety of the biological DMARDs indicated for RA in patients with inadequate responses to conventional DMARDs and naïve to biological DMARDs, in similar populations, considering ACR50 as the efficacy variable. The odds ratio (OR) and 95% confidence interval (CI) were calculated for each drug combination, and these parameters were transformed into differences in responses to assess the effectiveness of the alternative medicines. Equivalence therapeutic alternatives (ETA) were ensured to assess the possibility of considering these medications with equivalent efficacy. A network meta-analysis (NMA) was performed using Bayesian approaches and the fixed-effects model. RESULTS AND DISCUSSION: Twenty-seven randomized clinical trials (RCTs) that met the pre-established criteria were identified. The 95% CI of biological DMARDs was higher than that of placebo without methotrexate, except for certolizumab, golimumab-m, anakinra-m and adalimumab monotherapy. These DMARDs performed significantly better than the placebo, except for etanercept, certolizumab, tofacitinib and golimumab. Certolizumab-m was better than anakinra-m and adalimumab, and tocilizumab alone or combined with methotrexate was superior to adalimumab. Etanercept-m yielded a higher difference in responses compared with the other biological DMARDs, which presented more homogeneous responses, except for adalimumab and anakinra-m, which yielded worse results. None of the biological DMARDs displayed ETA to etanercept-m; however, they displayed ETA with certolizumab-m, except for adalimumab and anakinra-m. WHAT IS NEW AND CONCLUSION: All biological DMARDs used in combination with methotrexate, except for etanercept, anakinra, certolizumab and tocilizumab without methotrexate, were displayed ETA on using ACR50 at week 24 in patients naïve to biological DMARDs. Etanercept displayed a greater difference in responses, although the high uncertainty of the comparative results prevented the confirmation of the increased efficacy of this drug.

Dificultades en el abordaje terapéutico: a propósito de un caso clínico en un paciente adolescente / Difficulties in the therapeutic approach: Clinical case of a teen patient

La complejidad del trabajo psicoterapéutico con adolescentes, edad conflictiva por antonomasia, supone no pocos desafíos para el equipo de Salud Mental Infanto Juvenil. En este artículo presentaremos un caso clínico, sobre el recorrido de una paciente adolescente atendida en un Centro de Salud Mental, diagnosticada de trastorno limite de la personalidad. Explicaremos su evolución psicopatológica, a la vez que las dificultades que encontramos a lo largo del tratamiento. Pretendemos ilustrar cómo la paciente encuentra una estabilidad sintomatológica al establecer relaciones objetales de tipo anaclíticas, primero con su pareja, y luego más tarde, en la búsqueda incesante de tener un hijo

The complexity of the psychotherapeutic work with adolescents, conflicting age by antonomasia, involves few challenges for the team of Mental Health Infanto Juvenil. In this article we will present a clinical case, about the course of a teenage patient attended at a Mental Health Center, diagnosed with borderline personality disorder. We will explain its psychopathological evolution, as well as the difficulties that we find throughout the treatment. We intend to illustrate how the patient finds a symptomatic stability in establishing anaclitic object relations, first with her partner, and later, in the incessant search for having a child

Efecto reductor del colesterol de una combinación de levadura roja de arroz y policosanol / Efeito de reduçao do colesterol de uma combinaçao de arroz vermelho fermentado e policosanol / Cholesterol lowering effect of a combination of red yeast rice and polycosanol

Es ampliamente conocido que los niveles altos de colesterol están relacionados con el riesgo cardiovascular. La levadura de arroz rojo o levadura roja de arroz es un producto obtenido a partir de una levadura (Monascus purpureus Went.), que crece sobre este cereal. Entre sus componentes destaca la monacolina K, también conocida como lovastatina, sustancia relacionada con la disminución del colesterol mediante la inhibición de la HMG-CoA reductasa. El policosanol, mezcla de alcoholes alifáticos, obtenido de la caña de azúcar (Saccharum officinarum L.), además de modular dicha enzima, aumenta la actividad de los receptores LDL y tiene un efecto antioxidante y antiagregante. Mediante este trabajo se aportan los resultados de 65 pacientes en los cuales se ha observado una disminución media, estadísticamente significativa, de los niveles de colesterol (22% del colesterol total y 29% del LDL) y una disminución del 22% de los triglicéridos, tras tomar durante 2 meses un producto compuesto por: levadura roja de arroz con un contenido diario de 10 mg monacolina K y 14 mg de policosanol extraído de la caña de azúcar. La combinación de la monacolina K y el policosanol se plantean como una opción en pacientes con riesgo cardiovascular bajo o moderado (AU)

É amplamente conhecido que os níveis elevados de colesterol estão associados a um risco acrescido de doença cardiovascular. O arroz vermelho fermentado (ou levedura de arroz vermelho) é um produto obtido a partir de uma levedura (Monascus purpureus Went.), que cresce no arroz. Entre os seus componentes destaca-se a monacolina K, também conhecida como lovastatina, substância relacionada com a redução do colesterol através da inibição da HMG-CoA redutase. O policosanol, que consiste numa mistura de álcoois alifáticos de cadeia longa obtida a partir da cana-de-açúcar (Saccharum officinarum L.), além de modular a mesma enzima (HMG-CoA redutase), aumenta a actividade de receptores de LDL e tem efeitos antioxidantes e antiagregantes plaquetários. Este trabalho reporta os resultados de 65 participantes nos quais se observou uma diminuição média estatisticamente significativa do valor de colesterol (22% do colesterol total e 29% do LDL), assim como uma diminuição de 22% do valor dos triglicéridos, após a toma, durante dois meses, de um produto composto por arroz vermelho fermentado e policosanol, correspondendo a uma toma diária de 10 mg de monacolina K e 14 mg de policosanol. Assim, a associação de monacolina K, e policosanol apresenta-se como uma opção para doentes com risco cardiovascular baixo ou moderado (AU)

It is widely known that high cholesterol levels are associated with cardiovascular risk. Red yeast rice or red rice yeast is a product obtained from a yeast (Monascus purpureus Went.), which grows on rice. Among its constituents, it stand out monacolin K, also known as lovastatin, compound related to the cholesterol lowering effect through the inhibition of the HMG-CoA reductase. Polycosanol is a mixture of long chain aliphatic alcohols obtained from sugar cane (Saccharum officinarum L.). In addition of modulating that enzyme, it increases the activity of LDL receptors and has antioxidant and antiplatelet effect. In the present work, results in 65 patients treated for 2 mounts with a product combining red yeast rice (providing 10 mg/day of monacolin K) and policosanol from sugar cane (14 mg/day). An average decrease, statistically significant, of blood cholesterol (22% of total cholesterol and 29% of LDL) and triglycerides (22% ) has been observed. The combination of monacolin K and polycosanol is considered an option for patients with low or moderate cardiovascular risk (AU)

Pilot of a diabetes primary prevention program in a hard-to-reach, low-income, immigrant Hispanic population.

An immigrant Hispanic population in the Texas-Mexico border region urgently requested assistance with diabetes. The project team implemented an exploratory pilot intervention to prevent type 2 diabetes in the general population through enhanced nutrition and physical activity. Social networks in low-income rural areas(colonias) participated in an adaptation of the Diabetes Empowerment Education Program. The program had a pre-post-test design with a comparison group. The intervention had a small but significant effect in lowering body mass index, the biological outcome variable. The process evaluation shows that the participants valued the pilot project and found it culturally and economically appropriate. This program was the first primary prevention program in diabetes to address a general population successfully. The study shows that low-income, rural Mexican American families will take ownership of a program that is participatory and tailored to their culture and economic situation.

[Open splenectomy: ten-year experience in an oncological referral center]. / Esplenectomía a cielo abierto. Experiencia de 10 años en un centro oncológico.

BACKGROUND: Open splenectomy is a useful procedure for some diseases with splenomegaly >1500 g. We undertook this study to evaluate open splenectomy morbidity and mortality at the Instituto Nacional de Cancerologia in Mexico City. METHODS: We reviewed the clinical files of patients with benign and malignant hematological diseases, as well as other diseases, who underwent splenectomy from 1994 to 2005. RESULTS: Twenty five patients with a mean age of 38.5 years were submitted for open splenectomy. Splenomegaly was found in 12 patients (48%). The most frequent abdominal wall incision was transverse left subcostal (64%). Average surgical time was 125 min, bleeding 485 ml, spleen weight 1553.6 g and mean size 15 x 11 x 12 cm. Mean hospital stay was 7.5 days. Eighteen patients (72%) did not have immediate complications. One patient (4%) developed surgical wound infection, two patients (8%) had significant pain, three patients (12%) had bleeding and one patient (4%) developed intraabdominal fluid collection. Twenty one patients (84%) did not have further complications. One patient (4%) developed multiple organ failure, another patient (4%) developed thrombocytopenia and another (4%) developed severe pain. During an average 81-month follow-up we found 14 patients (56%) asymptomatic, two patients (8%) with documented tumoral activity (angiosarcoma and non-Hodgkin's lymphoma) and one patient (4%) developed a second neoplasm. Six patients (24%) died due to underlying disease (chronic myeloid leukemia and lymphoma), one patient (4%) with active disease (Hodgkin's disease) and one patient (4%) died due to other causes. CONCLUSIONS: With a spleen >1500 g, open surgery offers better visibility and, in fact, less morbidity and mortality.