Eficacia de una estrategia combinada para mejorar el control del colesterol unido a lipoproteínas de baja densidad en pacientes con hipercolesterolemia. Ensayo clínico aleatorizado

Introducción y objetivos: Intervenciones diferentes pueden mejorar el control del colesterol unido a lipoproteínas de baja densidad (cLDL). El objetivo principal era evaluar la eficacia de una intervención combinada para mejorar el control del cLDL de pacientes con hipercolesterolemia. También se evaluó su eficacia para mejorar el cumplimiento (farmacológico, dieta y ejercicio). Métodos: Ensayo clínico aleatorizado, de grupos paralelos y multicéntrico (atención primaria) que incluyó a 358 adultos diagnosticados de hipercolesterolemia con tratamiento previo farmacológico o no. Se comparó a 178 sujetos que recibieron intervención combinada (material escrito, tarjetas autocumplimentadas y mensajes al móvil) frente a 178 controles. La variable principal de resultado fue la proporción de sujetos con adecuado control del cLDL (valores recomendados en las guías europeas de dislipemias y riesgo cardiovascular) a los 24 meses. Resultados: El grupo de intervención mostró una reducción media del cLDL significativamente superior a los 24 meses respecto al control, 23, 8 mg/dl (IC95%, 17, 5-30, 1) y 14, 6 mg/dl (IC95%, 8, 9-20, 4), respectivamente (p = 0, 034). El promedio de la reducción del cLDL fue del 13, 1 ± 28, 6%. La proporción de sujetos con adecuado control al año fue significativamente superior en el grupo de intervención (43, 7 frente a 30, 1%; p = 0, 011; RR = 1, 46). En el grupo de intervención, el cumplimiento farmacológico fue significativamente superior (77, 2 frente a 64, 1%; p = 0, 029) y de la práctica de ejercicio (64, 9 frente a 35, 8%; p < 0, 001), aunque no de la dieta. Conclusiones: La intervención combinada consigue una reducción significativa de las cifras de cLDL (superior al 13% al cabo de 2 años) y mejora el grado de control de pacientes con hipercolesterolemia al año. Introduction and objectives: Several interventions can improve low-density lipoprotein cholesterol (LDL-C) control. Our main objective was to evaluate the efficacy of a combined intervention to improve LDL-C control in patients with hypercholesterolemia. The study also assessed the efficacy of the intervention in improving adherence (pharmacological, diet, and exercise). Methods: A multicenter, parallel group, randomized clinical trial (primary care) was conducted in 358 adults diagnosed with hypercholesterolemia, whether receiving prior drug therapy or not. We compared 178 participants who received the combined intervention (written material, self-completed registration cards, and messages to mobile telephones) with 178 controls. The main outcome variable was the proportion of participants with adequate LDL-C control (target levels of the European guidelines on dyslipidemia and cardiovascular risk) at 24 months. Results: At 24 months, the mean reduction in LDL-C was significantly higher in the intervention group (23.8 mg/dL [95%CI, 17.5-30.1]) than in the control group (14.6 mg/dL [95%CI, 8.9-20.4]; P = .034). The mean LDL-C decrease was 13.1% +/- 28.6%. At 1 year, the proportion of participants with adequate control was significantly higher in the intervention group than in the control group (43.7% vs 30.1%; P = .011; RR, 1.46). Adherence was significantly higher in the intervention group, both to drug therapy (77.2% vs 64.1%; P = .029) and exercise (64.9% vs 35.8; P < .001), but not to diet. Conclusions: The combined intervention significantly reduced LDL-C (by more than 13% at 2 years) and improved the degree of LDL-C control in patients with hypercholesterolemia at 1 year

High prognostic value of measurable residual disease detection by flow cytometry in chronic lymphocytic leukemia patients treated with front-line fludarabine, cyclophosphamide, and rituximab, followed by three years of rituximab maintenance

It has been postulated that monitoring measurable residual disease (MRD) could be used as a surrogate marker of progression-free survival (PFS) in chronic lymphocytic leukemia (CLL) patients after treatment with immunochemotherapy regimens. In this study, we analyzed the outcome of 84 patients at 3 years of follow-up after first-line treatment with fludarabine, cyclophosphamide and rituximab (FCR) induction followed by 36 months of rituximab maintenance thearpy. MRD was assessed by a quantitative four-color flow cytometry panel with a sensitivity level of 10-4. Eighty out of 84 evaluable patients (95.2%) achieved at least a partial response or better at the end of induction. After clinical evaluation, 74 patients went into rituximab maintenance and the primary endpoint was assessed in the final analysis at 3 years of follow-up. Bone marrow (BM) MRD analysis was performed after the last planned induction course and every 6 months in cases with detectable residual disease during the 36 months of maintenance therapy. Thirty-seven patients (44%) did not have detectable residual disease in the BM prior to maintenance therapy. Interestingly, 29 patients with detectable residual disease in the BM after induction no longer had detectable disease in the BM following maintenance therapy. After a median followup of 6.30 years, the median overall survival (OS) and PFS had not been reached in patients with either undetectable or detectable residual disease in the BM, who had achieved a complete response at the time of starting maintenance therapy. Interestingly, univariate analysis showed that after rituximab maintenance OS was not affected by IGHV status (mutated vs. unmutated OS: 85.7% alive at 7.2 years vs. 79.6% alive at 7.3 years, respectively). As per protocol, 15 patients (17.8%), who achieved a complete response and undetectable peripheral blood and BM residual disease after four courses of induction, were allowed to stop fludarabine and cyclophosphamide and complete two additional courses of rituximab and continue with maintenance therapy for 18 cycles. Surprisingly, the outcome in this population was similar to that observed in patients who received the full six cycles of the induction regimen. These data show that, compared to historic controls, patients treated with FCR followed by rituximab maintenance have high-quality responses with fewer relapses and improved OS. The tolerability of this regime is favorable. Furthermore, attaining an early undetectable residual disease status could shorten the duration of chemoimmunotherapy, reducing toxicities and preventing long-term side effects. The analysis of BM MRD after fludarabine-based induction could be a powerful predictor of post-maintenance outcomes in patients with CLL undergoing rituximab maintenance and could be a valuable tool to identify patients at high risk of relapse, influencing further treatment strategies

The Association Between Benzodiazepine Use and Depression Outcomes in Older Veterans

Benzodiazepines (BZDs) are commonly prescribed to older adults with depression, but it is unknown whether they improve antidepressant (AD) adherence or depressive symptoms. We followed 297 older veterans diagnosed with depression and provided a new AD medication prospectively for four months. Data includes validated self-report measures and VA pharmacy records. At initial assessment, 20.5% of participants were prescribed a BZD. Those with a BZD prescription at baseline were significantly more likely than those without to have a personality disorder, schizophrenia spectrum disorder, or other anxiety disorder, and higher depressive symptom and anxiety symptom scale scores on average. In adjusted regressions, BZD use was not significantly associated with AD adherence, any improvement in depressive symptoms, or a 50% reduction in depressive symptoms. Our results suggest BZD use concurrent with AD treatment does not significantly improve depressive outcomes in older veterans

Immunogenomic identification and characterization of granulocytic myeloid-derived suppressor cells in multiple myeloma

Granulocytic myeloid-derived suppressor cells (G-MDSCs) promote tumor growth and immunosuppression in multiple myeloma (MM). However, their phenotype is not well established for accurate monitoring or clinical translation. We aimed to provide the phenotypic profile of G-MDSCs based on their prognostic significance in MM, immunosuppressive potential, and molecular program. The preestablished phenotype of G-MDSCs was evaluated in bone marrow samples from controls and MM patients using multidimensional flow cytometry; surprisingly, we found that CD11b1CD142CD151CD331HLADR2 cells overlapped with common eosinophils and neutrophils, which were not expanded in MM patients. Therefore, we relied on automated clustering to unbiasedly identify all granulocytic subsets in the tumor microenvironment: basophils, eosinophils, and immature, intermediate, and mature neutrophils. In a series of 267 newly diagnosed MM patients (GEM2012MENOS65 trial), only the frequency of mature neutrophils at diagnosis was significantly associated with patient outcome, and a high mature neutrophil/T-cell ratio resulted in inferior progression-free survival (P &lt;.001). Upon fluorescence-activated cell sorting of each neutrophil subset, T-cell proliferation decreased in the presence of mature neutrophils (0.5-fold; P 5.016), and the cytotoxic potential of T cells engaged by a BCMA3CD3-bispecific antibody increased notably with the depletion of mature neutrophils (fourfold; P 5.0007). Most interestingly, RNA sequencing of the 3 subsets revealed that G-MDSC-related genes were specifically upregulated in mature neutrophils from MM patients vs controls because of differential chromatin accessibility. Taken together, our results establish a correlation between the clinical significance, immunosuppressive potential, and transcriptional network of well-defined neutrophil subsets, providing for the first time a set of optimal markers (CD11b/CD13/CD16) for accurate monitoring of G-MDSCs in MM

A contribuição dos estudos transculturais dos países latino-americanos e caribenhos para a revisão da CID-10: resultados preliminares The contribution of Latin American and Caribbean countries on culture bound syndromes studies for the ICD-10 revision: key findings from a working in progress

OBJETIVO: Esta revisão visa identificar as evidências dos estudos de países da América Latina e do Caribe para a inclusão das síndromes transculturais na versão da Classificação Internacional de Doenças para sua 11ª Edição. MÉTODO: Os estudos foram identificados nas bases do Medline, LILACS e EMBASE, no período de 1992 a 2008, e classificados segundo o tipo de estudo, tipo de transtorno, país e número de publicações por ano. RESULTADOS: Foram selecionadas e classificadas 163 publicações: 33 no Medline, 90 no EMBASE e 40 no LILACS. A percentagem das síndromes transculturais ("culture bound-syndrome") correspondeu a 9% no Medline, 12% no EMBASE e 2,5% no LILACS. Dos 15 estudos sobre síndromes transculturais, dois eram sobre "nervios e ataque de nervios", dois sobre "susto", quatro sobre a relação entre crenças religiosas, "feitiçaria", transe e apresentação dos transtornos mentais, um sobre proposta de uma nova categoria diagnóstica, três artigos teóricos e três sobre psicopatoplastia dos transtornos mentais. CONCLUSÃO: A escassez de estudos sobre síndromes transculturais pode ter ocorrido pela dificuldade em rastrear os estudos por problema de indexação das publicações, falta de interesse em publicar tais estudos em periódicos indexados e a dificuldade de acesso às publicações. Dentre os estudos identificados, não há uma evidência clara que aponte quais modificações são necessárias nas classificações diagnósticas atuais.<br>OBJECTIVE: This review aims to verify the scientific evidences for the inclusion of culture bound syndromes in the International Classification of Diseases towards its 11th edition based on studies from Latin American and Caribbean countries. METHOD: Studies were identified in Medline, LILACS and EMBASE databases for the period between 1992 and 2008, and then classified according to the type of study, to the mental disorder, country and number of publications per year. RESULTS: 163 studies were selected and classified: 33 in MedlLne, 90 in EMBASE e 40 in LILACS. The percentage of culture bound-syndrome corresponded to 9% in Medline, 12% in EMBASE e 2.5% in LILACS. Among fifteen studies on cultural bound syndromes, two were about "nervios and ataque de nervios", two about "susto", four about the relationship between religion beliefs, witchery, trance and mental disorders, one with a proposal for new diagnostic category, three about theoretic issues and three about the pathoplasty of mental disorders. CONCLUSION: The scarcity of studies on culture bound syndromes might be due to the indexation problems hindering the screening of studies; lack of interest on publishing such studies in indexed journals (publication bias) and due to difficulty to access them. There is no robust evidence identified among cross-cultural studies to recommend changes for International Classification of Diseases-11th edition