Efficacy and safety of the pharmacotherapy used in the management of hyperkalemia: a systematic review

Background: Although the management of hyperkalemia follows expert guidelines, treatment approaches are based on traditionally accepted practice standards. New drugs have been assessed such as sodium zirconium cyclosilicate and patiromer; however, their safety and efficacy or effectiveness have not yet been compared to traditional pharmacotherapy. Objective: The present systematic review had the purpose to evaluate the efficacy, effectiveness, and safety of hyperkalemia pharmacotherapies. Methods: PubMed, LILACS, Cochrane Library, and ClinicalTrials were searched through November 2018. Clinical trial, cohort and case-control were searched. The risk of bias (RoB v2.0 and ROBINS-I) and quality of evidence (GRADE) at the level of outcomes were assessed. Results: Sixteen clinical trials and one retrospective cohort were identified regarding efficacy and safety of 24 different alternatives. The management of hyperkalemia remains empirical and off-label, since sodium zirconium cyclosilicate and patiromer are not available in several countries and further studies are required to assess efficacy, effectiveness and safety. Sodium or calcium polystyrene sulfonate (moderate confidence), sodium zirconium cyclosilicate (moderate confidence), and insulin plus dextrose (moderate confidence) showed superior efficacy to, respectively, placebo, no treatment, placebo, and dextrose. Other therapies (low confidence) showed similar efficacy compared to active or inactive alternatives. Most of the adverse events reported were nonspecific, so it was not possible to assign the cause and to classify as defined or probable. Conclusions: Comparative cohort and case-control studies are need to evaluate the safety and effectiveness of new and traditional pharmacotherapies to support the development of guidelines about acute and chronic hyperkalemia, with high-quality evidence

Evaluación de un programa de Atención Farmacéutica en pacientes con Diabetes Mellitus Tipo 2

Introducción: La Atención Farmacéutica es la provisión responsable de la farmacoterapia con el propósito de alcanzar resultados concretos que mejoren la calidad de vida de los pacientes. Objetivo: Evaluar el impacto de las intervenciones farmacéuticas en pacientes con Diabetes Mellitus Tipo 2.  Metodología: Ensayo Clínico Aleatorizado, con medición de variables antes y después. No probabilístico. De conveniencia. Participaron  30  pacientes del grupo  intervenido y 31 en grupo control. Se realizaron entrevistas mensuales en un periodo de intervención farmacéutica de 6 meses (desde octubre 2011 hasta junio 2012). Resultados: La edad de los pacientes fue 55,6±10,6 años. Los pacientes del grupo intervenido mejoraron la glicemia en 34% donde 24 pacientes tenían el valor (≤ 130 mg/dL); la hemoglobina glicosilada mejoró 1,9% donde 15 pacientes lograron los parámetros deseados (≤ 6,5%). La calidad de vida del grupo intervenido fue de (56,3 a 71,3 %) y en el grupo control disminuyó de (57,4 a 46,1 %). En el grupo intervenido se encontraron 80 PRM, en 27 pacientes, se resolvieron 59; al final del estudio 12 pacientes resolvieron todos los PRM; se realizaron 254 intervenciones farmacéuticas, el nivel de conocimiento de los pacientes sobre la enfermedad mejoro en  41%, y el conocimiento sobre sus medicamentos mejoro en  53%.      Conclusión: Se comprobó que las intervenciones farmacéuticas mejoraron la calidad de vida, los parámetros clínicos de glicemia, hemoglobina glicosilada, optimizaron el uso de medicamentos, disminuyeron los PRM, mejoraron la satisfacción de los pacientes

Evaluación de un programa de Atención Farmacéutica en pacientes con Diabetes Mellitus Tipo 2

Introducción: La Atención Farmacéutica es la provisión responsable de la farmacoterapia con el propósito de alcanzar resultados concretos que mejoren la calidad de vida de los pacientes. Objetivo: Evaluar el impacto de las intervenciones farmacéuticas en pacientes con Diabetes Mellitus Tipo 2.  Metodología: Ensayo Clínico Aleatorizado, con medición de variables antes y después. No probabilístico. De conveniencia. Participaron  30  pacientes del grupo  intervenido y 31 en grupo control. Se realizaron entrevistas mensuales en un periodo de intervención farmacéutica de 6 meses (desde octubre 2011 hasta junio 2012). Resultados: La edad de los pacientes fue 55,6±10,6 años. Los pacientes del grupo intervenido mejoraron la glicemia en 34% donde 24 pacientes tenían el valor (≤ 130 mg/dL); la hemoglobina glicosilada mejoró 1,9% donde 15 pacientes lograron los parámetros deseados (≤ 6,5%). La calidad de vida del grupo intervenido fue de (56,3 a 71,3 %) y en el grupo control disminuyó de (57,4 a 46,1 %). En el grupo intervenido se encontraron 80 PRM, en 27 pacientes, se resolvieron 59; al final del estudio 12 pacientes resolvieron todos los PRM; se realizaron 254 intervenciones farmacéuticas, el nivel de conocimiento de los pacientes sobre la enfermedad mejoro en  41%, y el conocimiento sobre sus medicamentos mejoro en  53%.      Conclusión: Se comprobó que las intervenciones farmacéuticas mejoraron la calidad de vida, los parámetros clínicos de glicemia, hemoglobina glicosilada, optimizaron el uso de medicamentos, disminuyeron los PRM, mejoraron la satisfacción de los pacientes

In Vivo and In Vitro Effects of Antituberculosis Treatment on Mycobacterial Interferon-γ T Cell Response

Background: In recent years, the impact of antituberculous treatment on interferon (IFN)-c response to Mycobacterium tuberculosis antigens has been widely investigated, but the results have been controversial. The objective of the present study was: i) to evaluate longitudinal changes of IFN-c response to M. tuberculosis-specific antigens in TB patients during antituberculous treatment by using the QuantiFERON-TB Gold (QFT-G) assay; ii) to compare the differences in T-cell response after a short or prolonged period of stimulation with mycobacterial antigens; iii) to assess the CD4+ and CD8+ T cells with effector/memory and central/memory phenotype; iv) to investigate the direct in vitro effects of antituberculous drugs on the secretion of IFN-c. Principal Findings: 38 TB patients was evaluated at baseline and at month 2 and 4 of treatment and at month 6 (treatment completion). 27 (71%) patients had a QFT-G reversion (positive to negative) at the end of therapy, while 11 (29%) TB patients remained QFT-G positive at the end of therapy. Among the 11 patients with persistent positive QFT-G results, six had a complete response to the treatment, while the remaining 5 patients did not have a resolution of the disease. All 27 patients who became QFT-G negative had a complete clinical and microbiological recovery of the TB disease. In these patients the release of IFN-c is absent even after a prolonged 6-day incubation with both ESAT-6 and CFP-10 antigens and the percentage of effector/memory T-cells phenotype was markedly lower than subjects with persistent positive QFT-G results. The in vitro study showed that antituberculous drugs did not exert any inhibitory effect on IFN-c production within the range of therapeutically achievable concentrations. Conclusions: The present study suggests that the decrease in the M. tuberculosis-specific T cells responses following successful anti-TB therapy may have a clinical value as a supplemental tool for the monitoring of the efficacy of pharmacologic intervention for active TB. In addition, the antituberculous drugs do not have any direct down-regulatory effect on the specific IFN-c response

VEGF, FGF1, FGF2 and EGF gene polymorphisms and psoriatic arthritis

BACKGROUND: Angiogenesis appears to be a first-order event in psoriatic arthritis (PsA). Among angiogenic factors, the cytokines vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and fibroblast growth factors 1 and 2 (FGF1 and FGF2) play a central role in the initiation of angiogenesis. Most of these cytokines have been shown to be upregulated in or associated with psoriasis, rheumatoid arthritis (RA) or ankylosing spondylitis (AS). As these diseases share common susceptibility associations with PsA, investigation of these angiogenic factors is warranted. METHODS: Two hundred and fifty-eight patients with PsA and 154 ethnically matched controls were genotyped using a Sequenom chip-based MALDI-TOF mass spectrometry platform. Four SNPs in the VEGF gene, three SNPs in the EGF gene and one SNP each in FGF1 and FGF2 genes were evaluated. Statistical analysis was performed using Fisher's exact test, and the Cochrane-Armitage trend test. Associations with haplotypes were estimated by using weighted logistic models, where the individual haplotype estimates were obtained using Phase v2.1. RESULTS: We have observed an increased frequency in the T allele of VEGF +936 (rs3025039) in control subjects when compared to our PsA patients [Fisher's exact p-value = 0.042; OR 0.653 (95% CI: 0.434, 0.982)]. Haplotyping of markers revealed no significant associations. CONCLUSION: The T allele of VEGF in +936 may act as a protective allele in the development of PsA. Further studies regarding the role of pro-angiogenic markers in PsA are warranted

Kaposi's Sarcoma Associated Herpes Virus (KSHV) Induced COX-2: A Key Factor in Latency, Inflammation, Angiogenesis, Cell Survival and Invasion

Kaposi's sarcoma (KS), an enigmatic endothelial cell vascular neoplasm, is characterized by the proliferation of spindle shaped endothelial cells, inflammatory cytokines (ICs), growth factors (GFs) and angiogenic factors. KSHV is etiologically linked to KS and expresses its latent genes in KS lesion endothelial cells. Primary infection of human micro vascular endothelial cells (HMVEC-d) results in the establishment of latent infection and reprogramming of host genes, and cyclooxygenase-2 (COX-2) is one of the highly up-regulated genes. Our previous study suggested a role for COX-2 in the establishment and maintenance of KSHV latency. Here, we examined the role of COX-2 in the induction of ICs, GFs, angiogenesis and invasive events occurring during KSHV de novo infection of endothelial cells. A significant amount of COX-2 was detected in KS tissue sections. Telomerase-immortalized human umbilical vein endothelial cells supporting KSHV stable latency (TIVE-LTC) expressed elevated levels of functional COX-2 and microsomal PGE2 synthase (m-PGES), and secreted the predominant eicosanoid inflammatory metabolite PGE2. Infected HMVEC-d and TIVE-LTC cells secreted a variety of ICs, GFs, angiogenic factors and matrix metalloproteinases (MMPs), which were significantly abrogated by COX-2 inhibition either by chemical inhibitors or by siRNA. The ability of these factors to induce tube formation of uninfected endothelial cells was also inhibited. PGE2, secreted early during KSHV infection, profoundly increased the adhesion of uninfected endothelial cells to fibronectin by activating the small G protein Rac1. COX-2 inhibition considerably reduced KSHV latent ORF73 gene expression and survival of TIVE-LTC cells. Collectively, these studies underscore the pivotal role of KSHV induced COX-2/PGE2 in creating KS lesion like microenvironment during de novo infection. Since COX-2 plays multiple roles in KSHV latent gene expression, which themselves are powerful mediators of cytokine induction, anti-apoptosis, cell survival and viral genome maintainence, effective inhibition of COX-2 via well-characterized clinically approved COX-2 inhibitors could potentially be used in treatment to control latent KSHV infection and ameliorate KS

Self-perception of knowledge and adherence reflecting the effectiveness of antiretroviral therapy

Carolina Dagli-Hernandez,1 Rosa Camila Lucchetta,1 Tales Rubens de Nadai,2 José Carlos Fernandez Galduróz,3 Patricia de Carvalho Mastroianni1 1Department of Drugs and Medications, School of Pharmaceutical Sciences of the UNESP – Univ Estadual Paulista, Araraquara, 2Department of Surgery and Anatomy, Americo Brasiliense State Hospital, 3Department of Psychobiology, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil Objectives: To evaluate which indirect method for assessing adherence best reflects highly active antiretroviral therapy (HAART) effectiveness and the factors related to adherence. Method: This descriptive, cross-sectional study was performed in 2012 at a reference center of the state of São Paulo. Self-report (simplified medication adherence questionnaire [SMAQ]) and drug refill parameters were compared to the viral load (clinical parameter of the effectiveness of pharmacotherapy [EP]) to evaluate the EP. The “Cuestionario para la Evaluación de la Adhesión al Tratamiento Antiretroviral” (CEAT-VIH) was used to evaluate factors related to adherence and the EP and, complementarily, patient self-perception of adherence was compared to the clinical parameter of the EP. Results: Seventy-five patients were interviewed, 60 of whom were considered as adherent from the clinical parameter of the EP and ten were considered as adherent from all parameters. Patient self-perception about adherence was the instrument that best reflected the EP when compared to the standardized self-report questionnaire (SMAQ) and drug refill parameter. The level of education and the level of knowledge on HAART were positively correlated to the EP. Forgetfulness, alcohol use, and lack of knowledge about the medications were the factors most frequently reported as a cause of nonadherence. Conclusion: A new parameter of patient self-perception of adherence, which is a noninvasive, inexpensive instrument, could be applied and assessed as easily as self-report (SMAQ) during monthly drug refill, since it allows monitoring adherence through pharmaceutical assistance. Therefore, patient adherence to HAART could be evaluated using self-perception (CEAT-VIH) and the viral load test. Keywords: health literacy, anti-HIV agents, patient compliance, antiretroviral therapy, highly active, acquired immunodeficiency syndrom