Abstract
Objectives
To assess efficacy and safety of biologic therapy (BT) in neurobehçet’s disease (NBD) refractory to glucocorticoids and at least one conventional immunosuppressive drug.
Methods
...Open-label, national, multicentre study. NBD diagnosis was based on the International Consensus Recommendation criteria. Outcome variables were efficacy and safety. Main efficacy outcome was clinical remission. Other outcome variables analysed were glucocorticoid-sparing effect and improvement in laboratory parameters.
Results
We studied 41 patients 21 women; age 40.6 (10.8) years. Neurological damage was parenchymal (n = 33, 80.5%) and non-parenchymal (n = 17, 41.5%). First BTs used were infliximab (n = 19), adalimumab (n = 14), golimumab (n = 3), tocilizumab (n = 3) and etanercept (n = 2). After 6 months of BT, neurological remission was complete (n = 23, 56.1%), partial (n = 15, 37.6%) and no response (n = 3, 7.3%). In addition, median (IQR) dose of oral prednisone decreased from 60 (30–60) mg/day at the initial visit to 5 (3.8–10) mg/day after 6 months (P < 0.001). It was also the case for mean erythrocyte sedimentation rate 31.5 (25.6)–15.3 (11.9) mm/1st h, P = 0.011 and median (IQR) C-reactive protein 1.4 (0.2–12.8) to 0.3 (0.1–3) mg/dl, P = 0.001. After a mean follow-up of 57.5 months, partial or complete neurological remission persisted in 37 patients (90.2%). BT was switched in 22 cases (53.6%) due to inefficacy (n = 16) or adverse events (AEs) (n = 6) and discontinued due to complete prolonged remission (n = 3) or severe AE (n = 1). Serious AEs were observed in two patients under infliximab treatment.
Conclusions
BT appears to be effective and relatively safe in refractory NBD.
The differential impact of solution‐focused brief therapy questions was tested. A total of 246 subjects described a personal problem they wanted to solve and were randomly assigned to one of four ...interventions that involved answering problem‐focused versus solution‐focused questions: a problem‐focused condition, a miracle condition, a scaling condition or an exception condition. Before and after answering the questions, participants completed measures of positive and negative affect, self‐efficacy, goal attainment, action steps and solution‐focused thinking. The miracle and exception conditions were more effective than the problem‐focused condition in reducing negative affect. The scaling condition generated more action steps than the miracle question or the exception question. These findings support solution‐focused ideas on the different effects of solution‐focused questions, but also suggest that solution‐focused and problem‐focused questions might be more similar than different in their immediate impact on clients.
Practitioner points
Solution‐focused and problem‐focused questions are more similar than different in their immediate impact on clients.
Among solution‐focused questions, the miracle question and the exception question are more effective in reducing negative affect, and scaling questions in generating specific action steps.
Integrative therapists could use solution‐focused questions not only with clients who seem more optimistic but also with less solution‐minded ones.
摘要
本研究测试了聚焦解决的短期治疗问题的差异影响。共有246名受试者描述了他们想要解决的个人问题，并被随机分配到四种干预措施中的一种，这些干预措施涉及回答聚焦问题的问题和聚焦解决的问题：一个问题聚焦情境，一个奇迹情境、一个量表情境，或者一个例外情境。在回答问题前后，参与者完成了积极和消极情绪、自我效能、目标达成、行动步骤和聚焦解决式思维的量表。奇迹情境和例外情境在减少负面情绪方面比问题聚焦情境更有效。量表情境比奇迹问题或例外问题生成了更多的行动步骤。这些发现支持聚焦解决的观点，即聚焦解决的提问会产生不同效果，但也表明聚焦解决的提问和聚焦问题的提问在对来访者的直接影响方面可能相似性大于差异性。
给从业者的启示
聚焦解决的提问和聚焦问题的提问在对来访者的直接影响方面可能相似性大于差异性。
在聚焦解决的问题中，奇迹问题和例外问题在减少负面影响方面更为有效，在制定具体行动步骤方面，量表问题更为有效。
整合型的治疗师不仅可以对看似更为乐观的来访者使用聚焦解决的问题，也可以对不太具有问题解决思维的来访者使用这类问题。
Resumen
Se examinó el impacto diferencial de las preguntas esenciales de terapia breve centrada en soluciones. Un total de 246 sujetos describieron un problema personal que querían resolver y fueron asignados al azar a una de las cuatro intervenciones que implicaban responder preguntas centradas en el problema versus centradas en la solución: una condición centrada en el problema, una condición de pregunta milagro, una condición de pregunta de escala o una condición de pregunta sobre excepción. Antes y después de responder las preguntas, los participantes completaron medidas de afecto positivo y negativo, autoeficacia, logro de metas, pasos de acción y pensamiento centrado en soluciones. Las condiciones de pregunta milagro y excepción fueron más efectivas que la condición centrada en el problema para reducir el afecto negativo. La condición de pregunta de escala generó más pasos de acción que la pregunta del milagro o la pregunta de excepción. Estos hallazgos respaldan las ideas centradas en soluciones sobre los diferentes efectos de las preguntas centradas en soluciones, pero también sugieren que las preguntas centradas en soluciones y centradas en problemas pueden ser más similares que diferentes en su impacto inmediato en los clientes.
Puntos del practicante
Las preguntas centradas en soluciones y centradas en problemas son más similares que diferentes en su impacto inmediato en los clientes.
Entre las preguntas centradas en la solución, la pregunta del milagro y la pregunta de la excepción son más efectivas para reducir el afecto negativo y escalar las preguntas para generar pasos de acción específicos.
Los terapeutas integradores podrían utilizar preguntas centradas en la solución no sólo con los clientes que parecen más optimistas, sino también con los menos orientados a las soluciones.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Generation of new reagents that can be used to screen or monitor HIV-1-specific responses constituted an interesting field in the development of HIV vaccines to improve their efficacy.
We have ...evaluated the specific T cell response against different types of NL4-3 virions (including NL4-3 aldrithiol-2 treated, NL4-3/ΔRT and R5 envelopes: NL4-3/ΔRT/ΔEnvAC10 and NL4-3/ΔRT/ΔEnvBal) and against pools of overlapping peptides (15 mer) encompassing the HIV-1 Gag and Nef regions. Cryopreserved PBMC from a subset of 69 chronic asymptomatic HIV positive individuals have been employed using different techniques including IFN-γ ELISPOT assay, surface activation markers and intracellular cytokine staining (ICS) by flow cytometry.
The differential response obtained against NL4-3 aldrithiol-2 treated and NL4-3/ΔRT virions (25% vs 55%, respectively) allow us to divide the population in three groups: "full-responders" (positive response against both viral particles), "partial-responders" (positive response only against NL4-3/ΔRT virions) and "non-responders" (negative responses). There was no difference between X4 and R5 envelopes. The magnitude of the total responses was higher against NL4-3/ΔRT and was positively correlated with gender and inverse correlated with viral load. On the contrary CD4+ T cell count was not associated with this response. In any case responses to the viruses tended to be lower in magnitude than those detected by the overlapping peptides tested. Finally we have found an increased frequency of HLA-B27 allele (23% vs 9%) and a significant reduction in some activation markers (CD69 and CD38) on T cells surface in responders vs non-responders individuals.
In summary these virions could be considered as alternative and useful reagents for screening HIV-1-specific T cell responses in HIV exposed uninfected people, HIV infected patients and to assess immunogenicity of new prototypes both in vitro and in vaccine trials, by a feasible, simply, effective and low cost assay.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Two antigenically distinct influenza B lineages have co-circulated since the 1980s, yet inactivated trivalent influenza vaccines (TIVs) include strains of influenza A/H1N1, A/H3N2, and only one ...influenza B from either the Victoria or Yamagata lineage. This means that exposure to B-lineage viruses mismatched to the TIV is frequent, reducing vaccine protection. Formulations including both influenza B lineages could improve protection against circulating influenza B viruses. We assessed a candidate inactivated quadrivalent influenza vaccine (QIV) containing both B lineages versus TIV in adults in stable health.
A total of 4659 adults were randomized 5:5:5:5:3 to receive one dose of QIV (one of three lots) or a TIV containing either a B/Victoria or B/Yamagata strain. Hemagglutination-inhibition assays were performed pre-vaccination and 21-days after vaccination. Lot-to-lot consistency of QIV was assessed based on geometric mean titers (GMT). For QIV versus TIV, non-inferiority against the three shared strains was demonstrated if the 95% confidence interval (CI) upper limit for the GMT ratio was ≤1.5 and for the seroconversion difference was ≤10.0%; superiority of QIV versus TIV for the alternate B lineage was demonstrated if the 95% CI lower limit for the GMT ratio was > 1.0 and for the seroconversion difference was > 0%. Reactogenicity and safety profile of each vaccine were assessed. Clinicaltrials.gov: NCT01204671.
Consistent immunogenicity was demonstrated for the three QIV lots. QIV was non-inferior to TIV for the shared vaccine strains, and was superior for the added alternate-lineage B strains. QIV elicited robust immune responses against all four vaccine strains; the seroconversion rates were 77.5% (A/H1N1), 71.5% (A/H3N2), 58.1% (B/Victoria), and 61.7% (B/Yamagata). The reactogenicity and safety profile of QIV was consistent with TIV.
QIV provided superior immunogenicity for the additional B strain compared with TIV, without interfering with antibody responses to the three shared antigens. The additional antigen did not appear to alter the safety profile of QIV compared with TIV. This suggests that the candidate QIV is a viable alternative to TIV for use in adults, and could potentially improve protection against influenza B.
Clinical Trials.gov: NCT01204671/114269.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Las microempresas poseen una singular importancia, debido a la capacidad de generación de empleo e ingresos, útiles para que el aparato productivo sea capaz de dinamizar la actividad económica, en ...Ecuador y en particular en Jipijapa. El impacto de la COVID-19, ha sido devastador en el desarrollo económico de los micro empresarios. La COVID-19, es una enfermedad que ha generado un impacto económico desfavorable. Los sistemas económicos están afectados por esta pandemia y la región latinoamericana, es considerada las más golpeada de todas. En la presente investigación se propone realizar una actualización de los conocimientos, para percibir cuál es la situación que presentan los micro empresarios de la ciudad de Jipijapa, Ecuador, respecto al impacto de la COVID-19, en cuanto a sus planeaciones estratégicas. Para tal fin se desarrolla una investigación a nivel exploratorio, descriptivo y documental, apoyada en una análisis bibliométrico, orientado al análisis de artículos científicos, se presentan resultados de la investigación de campo a 250 microempresarios del cantón Jipijapa, de la provincia de Manabí, en aras de tener una visión real de la problemática que enfrentan los micro empresarios, útil en la concientización de la necesidad de plantear estrategias para su fortalecimiento, innovación y alcance de las principales características que son necesarias para crear ventajas competitivas y posicionarse en el mercado.
Recent decades have seen a growing acknowledgement of violence against women (VAW) as a serious social and public health problem of epidemic proportions. The prevention of VAW and intimate partner ...violence against women (IPVAW) has become a priority within this context, and includes various prevention strategies such as social participation and helping behaviors. In different countries, conducting research on help-seeking behavior and bystander intervention in cases of VAW is a common practice, but addressing these issues is much less common in Spain. In this context, the objective of this study is to provide a preliminary estimation of the volume of bystanders in cases of IPVAW in Spain between 2005 and 2020 (since the entry into force of Organic Law 1/2004), their willingness to intervene and, in the case of intervention, the type of helping behavior (real or hypothetical) preferred, using the sources (secondary data) available (specifically, survey data, as the surveys of social perception of gender violence and the 2014 and 2019 macro-surveys, and also administrative data, as the database of reports filed). The data analyzed allow us to determine that, in fact, in the cases of IPVAW there are usually persons within the victim’s inner circle who are firsthand witnesses or have been informed by the victim of the existence of this type of violence, but, although the bystanders generally claim they would engage in an active and supportive response, this is in fact not always the case. These results underscore the need to develop intervention programs aimed at IPVAW bystanders to improve their reaction and contribute to the development of helpful and efficient active responses.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The aim of this work was to develop niosomes for the ocular delivery of epalrestat, a drug that inhibits the polyol pathway and protects diabetic eyes from damage linked to sorbitol production and ...accumulation. Cationic niosomes were made using polysorbate 60, cholesterol, and 1,2-di-O-octadecenyl-3-trimethylammonium propane. The niosomes were characterized using dynamic light scattering, zeta-potential, and transmission electron microscopy to determine their size (80 nm; polydispersity index 0.3 to 0.5), charge (-23 to +40 mV), and shape (spherical). The encapsulation efficiency (99.76%) and the release (75% drug release over 20 days) were measured with dialysis. The ocular irritability potential (non-irritating) was measured using the Hen's Egg Test on the Chorioallantoic Membrane model, and the blood glucose levels (on par with positive control) were measured using the gluc-HET model. The toxicity of the niosomes (non-toxic) was monitored using a zebrafish embryo model. Finally, corneal and scleral permeation was assessed with the help of Franz diffusion cells and confirmed with Raman spectroscopy. Niosomal permeation was higher than an unencapsulated drug in the sclera, and accumulation in tissues was confirmed with Raman. The prepared niosomes show promise to encapsulate and carry epalrestat through the eye to meet the need for controlled drug systems to treat the diabetic eye.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
To evaluate if the two-layer bandage is more effective than the crepe bandage in the healing of venous ulcers after 12 weeks of follow-up.
Randomized multicentre controlled clinical trial.
22 Primary ...Health Centers of Madrid.
Over 18 years old, with diagnosis of venous ulcers. 93 patients were randomized, 56 in the double layer group and 37 in the crepe group. Withdrawals: 16 in double layer group, 7 in crepe group.
Control group: usual clinical practice: treatment of the wound and bandage with crepe. Experimental group: same usual clinical practice for wound treatment and bandage with double layer.
Primary outcome: complete healing at 12 weeks.
severity of ulceration, health-related quality of life, adverse events. Blind evaluation of the response variable.
Complete healing: in crepe group, 25, 67.5% (95% CI 50.2-81.9) and in double layer group, 32, 57.1% (95% CI 43.2-70.3). No evidence of a difference in both groups, RR=1.10 (95% CI 0.864-1.424). The basal severity of the ulcers is associated with the healing time. HR=0.86 (95% CI 0.78-0.94). Our data showed a significant improvement in health-related quality of life, total and in the of cosmesis and emotional dimensions. No evidence of a difference in both groups. We didn't find serious adverse events in any of the groups.
We didn't find significant differences in the healing between the two bandages evaluated. Both are appropriate for ulcer healing and to improve the health-related quality of life.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The reactions of PbR2(OAc)2 (R = Me, Ph) with 3-(2-thienyl)-2-sulfanylpropenoic acid (H2tspa) in methanol or ethanol afforded complexes PbR2(tspa) that electrospray ionization-mass spectrometry ...(ESI-MS) and IR data suggest are polymeric. X-ray studies showed that PbPh2(tspa)(dmso)·dmso, crystallized from a solution of PbPh2(tspa) in dmso, is dimeric, and that HQ2PbPh2(tspa)2 (Q = diisopropylamine), obtained after removal of PbPh2(tspa) from a reaction including Q, contains the monomeric anion PbPh2(tspa)22−. In the solid state the lead atoms are O,S-chelated by the tspa2− ligands in all these products, and in the latter two have distorted octahedral coordination environments. NMR data suggest that tspa2− remains coordinated to PbR2 2+ in solution in dmso. Neither thiamine nor thiamine diphosphate reacted with PbMe2(NO3)2 in D2O. Prior addition of H2tspa protected LLC-PK1 renal proximal tubule cells against PbMe2(NO3)2; thiamine had no statistically significant effect by itself, but greatly potentiated the action of H2tspa. Administration of either H2tspa or thiamine to male albino Sprague−Dawley rats dosed 30 min previously with PbMe2(NO3)2 was associated with reduced inhibition of δ-ALAD by the organolead compound, and with lower lead levels in kidney and brain, but joint administration of both H2tspa and thiamine only lowered lead concentration in the kidney.
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IJS, KILJ, NUK, PNG, UL, UM
OBJECTIVE To compare the incidence of enteral nutrition-related gastrointestinal complications, the efficacy of diet administration, and the incidence of nosocomial pneumonia in patients fed in the ...stomach or in the jejunum.
DESIGN Prospective, randomized multicenter study.
SETTING Intensive care units (ICUs) in 11 teaching hospitals.
PATIENTS Critically ill patients who could receive early enteral nutrition more than 5 days.
INTERVENTIONS Enteral nutrition was started in the first 36 hrs after admission. One group was fed with a nasogastric tube (GEN group) and the other in the jejunum through a dual-lumen nasogastrojejunal tube (JEN group).
MEASUREMENTS AND MAIN RESULTS Gastrointestinal complications were previously defined. The efficacy of diet administration was calculated using the volume ratio (expressed as the ratio between administered and prescribed volumes). Nosocomial pneumonia was defined according the Centers for Disease Control and Prevention’s definitions. One hundred ten patients were included (GEN51, JEN50). Both groups were comparable in age, gender, Acute Physiology and Chronic Health Evaluation II, and Multiple Organ Dysfunction Score. There were no differences in feeding duration, ICU length of stay, or mortality (43% vs. 38%). The JEN group had lesser gastrointestinal complications (57% vs. 24%, p < .001), mainly because of a lesser incidence of increased gastric residuals (49% vs. 2%, p < .001). Volume ratio was similar in both groups. A post hoc analysis showed that the JEN group had a higher volume ratio at day 7 than the GEN group (68% vs. 82%, p < .03) in patients from ICUs with previous experience in jejunal feeding. Both groups had a similar incidence of nosocomial pneumonia (40% vs. 32%).
CONCLUSIONS Gastrointestinal complications are less frequent in ICU patients fed in the jejunum. Nevertheless, it seems to be a necessary learning curve to achieve better results with a postpyloric access. Early enteral nutrition using a nasojejunal route seems not to be an efficacious measure to decrease nosocomial pneumonia in critically ill patients.
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