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1.
J Med Chem ; 63(4): 1750-1762, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32011136

RESUMO

Ivermectin is a powerful endectocide, which reduces the incidence of vector-borne diseases. Besides its strong insecticidal effect on mosquito vectors of the disease, ivermectin inhibits Plasmodium falciparum sporogonic and blood stage development and impairs Plasmodium berghei development inside hepatocytes, both in vitro and in vivo. Herein, we present the first report on structural modification of ivermectin to produce dual-action molecular hybrids with good structure-dependent in vitro activity against both the hepatic and erythrocytic stages of P. berghei and P. falciparum infection, suggesting inclusion of ivermectin antimalarial hybrids in malaria control strategies. The most active hybrid displayed over threefold and 10-fold higher in vitro activity than ivermectin against hepatic and blood stage infections, respectively. Although an overwhelming insecticidal effect against Anopheles stephensi mosquitoes in laboratory conditions was not noticed, in silico docking analysis supports allosteric binding to glutamate-gated chloride channels similar to ivermectin.

2.
J Hosp Med ; 15(1): 52-59, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30897055

RESUMO

BACKGROUND: Transitions of care can contribute to medication errors and other adverse drug events. PURPOSE: The aim of this study was to evaluate the impact of pharmacist-led discharge counseling on hospital readmission and emergency department visits through a systematic review and meta-analysis. EDATA SOURCES: Lectronic searches were performed in PubMed, Scopus, and DOAJ (Directory of Open Access Journals), along with a manual search (July 2017). PROSPERO registration no. CRD42017068444. STUDY SELECTION: Two independent reviewers performed all the steps of the systematic review process (screening of titles and abstracts, full-text appraisal, data extraction, and quality assessment), with contributions from a third researcher. We included randomized controlled trials (RCTs) reporting data on pharmacist-led discharge counseling. DATA EXTRACTION: Primary extracted outcomes were emergency department visits and hospital readmission rates. DATA SYNTHESIS: Meta-analyses of intervention versus usual care for hospital readmission and emergency department visit rates were performed using the inverse variance method. Results are reported as risk ratios (RRs) with 95% confidence intervals (CIs). Prediction intervals (PIs) were also calculated. Sensitivity and subgroup analyses were performed. A total of 21 RCTs were included in the qualitative synthesis and 18 in the meta-analyses (n = 7,244 patients). The original meta-analysis revealed a significant difference in the impact between pharmacist-led discharge counseling and usual care on overall hospital readmission (RR = 0.864 [95% CI 0.763-0.997], P = .020) and emergency department (RR = 0.697 [95% CI 0.535-0.907], P = .007) visits. However, the small number of included studies, the high heterogeneity among trials (I2 between 40% and 60%), and the wide PIs (hospital readmission: PI 0.542-1.186; emergency department visits: PI 0.027-1.367) prevented drawing further conclusions. CONCLUSIONS: Insufficient evidence exists regarding the effect of pharmacist-led discharge counseling on hospital readmission and emergency department visits. Further well-designed clinical trials with defined core outcome sets are needed.

3.
J Theor Biol ; 484: 110030, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31568789

RESUMO

We introduce an agent-based model describing a susceptible-infectious-susceptible (SIS) system of humans and mosquitoes to predict malaria epidemiological scenarios in realistic biological conditions. Emphasis is given to the transition from endemic behavior to eradication of malaria transmission induced by combined drug therapies acting on both the gametocytemia reduction and on the selective mosquito mortality during parasite development in the mosquito. Our mathematical framework enables to uncover the critical values of the parameters characterizing the effect of each drug therapy. Moreover, our results provide quantitative evidence of what was up to now only partially assumed with empirical support: interventions combining gametocytemia reduction through the use of gametocidal drugs, with the selective action of ivermectin during parasite development in the mosquito, may actively promote disease eradication in the long run. In the agent model, the main properties of human-mosquito interactions are implemented as parameters and the model is validated by comparing simulations with real data of malaria incidence collected in the endemic malaria region of Chimoio in Mozambique. Finally, we discuss our findings in light of current drug administration strategies for malaria prevention, which may interfere with human-to-mosquito transmission process.

4.
PLoS Pathog ; 15(11): e1008145, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31703103

RESUMO

Sleeping sickness and malaria are parasitic diseases with overlapping geographical distributions in sub-Saharan Africa. We hypothesized that the immune response elicited by an infection with Trypanosoma brucei, the etiological agent of sleeping sickness, would inhibit a subsequent infection by Plasmodium, the malaria parasite, decreasing the severity of its associated pathology. To investigate this, we established a new co-infection model in which mice were initially infected with T. brucei, followed by administration of P. berghei sporozoites. We observed that a primary infection by T. brucei significantly attenuates a subsequent infection by the malaria parasite, protecting mice from experimental cerebral malaria and prolonging host survival. We further observed that an ongoing T. brucei infection leads to an accumulation of lymphocyte-derived IFN-γ in the liver, limiting the establishment of a subsequent hepatic infection by P. berghei sporozoites. Thus, we identified a novel host-mediated interaction between two parasitic infections, which may be epidemiologically relevant in regions of Trypanosoma/Plasmodium co-endemicity.

5.
Clinics (Sao Paulo) ; 74: e1091, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31778428

RESUMO

OBJECTIVES: This is a randomized controlled trial that aims to evaluate the impact of pharmacist-led discharge counseling on reducing pharmacotherapy problems in the 30-day postdischarge period of cardiology patients from a tertiary hospital in Brazil. METHODS: At discharge, two cardiovascular pharmacy residents performed a medication counseling session with the intervention group, and the follow-up was performed by telephone (3 and 15 days after discharge). The number of pharmacotherapy problems was evaluated during a pharmacist-led ambulatory consultation 30 days after discharge. RESULTS: A total of 66 and 67 patients were randomized to the intervention and control groups, respectively, but only 51 patients were analyzed in each group, all with similar baseline characteristics. The intervention group had significantly fewer pharmacotherapy problems compared to the control (p<0.001), and 100% of the patients had at least one problem. We observed five problems significantly more frequently in the control group: "incorrect time of taking" (p=0.003), "use higher dose of medication" (p=0.007), "use lower dose of medication" (p=0.014), "restart discontinued medication" (p=0.011), and "underdosing prescription" (p=0.009). Simvastatin, enalapril, carvedilol, and atorvastatin were the medications more associated with pharmacotherapy problems. CONCLUSIONS: We concluded that pharmacist-led discharge counseling should be an indispensable service, as patients exhibited less pharmacotherapy problems in the 30-day postdischarge period, especially related to drug administration and adherence.

6.
Parasit Vectors ; 12(1): 549, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752986

RESUMO

BACKGROUND: The transmissible forms of Plasmodium parasites result from a process of sporogony that takes place inside their obligatory mosquito vector and culminates in the formation of mammalian-infective parasite forms. Ivermectin is a member of the avermectin family of endectocides, which has been proposed to inhibit malaria transmission due its insecticidal effect. However, it remains unclear whether ivermectin also exerts a direct action on the parasite's blood and transmission stages. METHODS: We employed a rodent model of infection to assess the impact of ivermectin treatment on P. berghei asexual and sexual blood forms in vivo. We then made use of a newly established luminescence-based methodology to evaluate the activity of ivermectin and other avermectins against the sporogonic stages of P. berghei parasites in vitro independent of their role on mosquito physiology. RESULTS: Our results show that whereas ivermectin does not affect the parasite's parasitemia, gametocytemia or exflagellation in the mammalian host, several members of the avermectin family of compounds exert a strong inhibitory effect on the generation and development of P. berghei oocysts. CONCLUSIONS: Our results shed light on the action of avermectins against Plasmodium transmission stages and highlight the potential of these compounds to help prevent the spread of malaria.

7.
PLoS One ; 14(2): e0212650, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30785955

RESUMO

BACKGROUND: The conduction and report of network meta-analysis (NMA), including the presentation of the network-plot, should be transparent. We aimed to propose metrics adapted from graph theory and social network-analysis literature to numerically describe NMA geometry. METHODS: A previous systematic review of NMAs of pharmacological interventions was performed. Data on the graph's presentation were collected. Network-plots were reproduced using Gephi 0.9.1. Eleven geometric metrics were tested. The Spearman test for non-parametric correlation analyses and the Bland-Altman and Lin's Concordance tests were performed (IBM SPSS Statistics 24.0). RESULTS: From the 477 identified NMAs only 167 graphs could be reproduced because they provided enough information on the plot characteristics. The median nodes and edges were 8 (IQR 6-11) and 10 (IQR 6-16), respectively, with 22 included studies (IQR 13-35). Metrics such as density (median 0.39, ranged 0.07-1.00), median thickness (2.0, IQR 1.0-3.0), percentages of common comparators (median 68%), and strong edges (median 53%) were found to contribute to the description of NMA geometry. Mean thickness, average weighted degree and average path length produced similar results than other metrics, but they can lead to misleading conclusions. CONCLUSIONS: We suggest the incorporation of seven simple metrics to report NMA geometry. Editors and peer-reviews should ensure that guidelines for NMA report are strictly followed before publication.


Assuntos
Meta-Análise em Rede , Bibliometria , Mineração de Dados , Bases de Dados Bibliográficas , Humanos , Editoração
8.
Res Social Adm Pharm ; 15(12): 1464-1471, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30683600

RESUMO

BACKGROUND: Pharmacy journals constitute a heterogeneous group that can be map to identify Pharmacy scientific subareas. OBJECTIVE: This study aimed to objectively map Pharmacy journals by means of a lexicographic analysis of the titles of published articles. METHODS: Active journals between 2006 and 2016 containing any of the terms 'pharmacy', 'pharmacist*', 'pharmaceut*', 'pharmacol*', or 'pharmacotherap*' in their titles were searched in four databases (01/15/2018): Medline, PubMed Central, Science Citation Index expanded/Social Sciences Citation Index expanded (SCIe/SSCIe), and Scopus CiteScore Metrics. The titles of all the articles (Jan-2006 to Dec-2016) in the identified journals were gathered into a single text corpus. The following analyses were performed (Iramuteq 0.7): lexicographic analysis to determine the number, frequency and distribution of active words; descending hierarchical classification (DHC) to categorize active words and journals into lexical classes; factorial correspondence analyses (FCA) to obtain bi- and tri-dimensional graphs. RESULTS: A total of 285 journals comprising 316,089 articles (median 70.4 articles [IQR 34.0-141.0] per journal per year) were included for the analyses. The journals were indexed in Scopus (90.2%) with a median CiteScore of 1.16 (IQR 0.28-2.55); in SCIe/SSCIe (44.6%) with a median impact factor of 2.410 (IQR 1.629-3.316); and in PubMed (65.7%). The DHC of active words produced three major groups (A, B, C) with two lexical classes each, representing six Pharmacy subareas depicted by the FCA as: Group A comprising 'Cell Pharmacology' (20 journals) and 'Molecular Pharmacology' (46 journals), Group B with 'Clinical Pharmacology' (57 journals) and 'Pharmacy Practice' (67 journals), and Group C with 'Pharmaceutics' (35 journals) and 'Pharmaceutical Analysis' (60 journals). Coverage of the classes in bibliographic databases and impact metrics is unbalanced. CONCLUSIONS: Pharmacy journals that can be objectively classified into six different classes that represent different research subareas with uneven coverage in bibliographic databases.

9.
Int J Epidemiol ; 48(2): 620-632, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30212868

RESUMO

BACKGROUND: We aimed to determine the methodological quality of network meta-analyses (NMAs) and their compliance with reporting guidelines. METHODS: A systematic review of NMAs comparing any pharmacological interventions was performed (searches in Medline and Scopus). The characteristics of NMAs were collected by two independent reviewers. We applied R-AMSTAR to all NMAs, generating a methodological quality score that could range from 11 to 44 points. PRISMA and PRISMA-NMA reporting checklists were converted into quantitative scores (maximum values of 27 and 32 points). To normalize the values between these two checklists, a third score (PRISMA-SCORE) of 0-1 was created. The correlation of the scores with NMA publication year, journal impact factor and most productive countries were calculated using non-parametric tests. RESULTS: We identified 477 NMAs. Only 36.1% of studies reported having followed PRISMA statements. The medians of R-AMSTAR, PRISMA and PRISMA-NMA scores were 28 (IQR 25-31), 21 (IQR 19-23) and 23 (IQR 19-26), respectively. Several problems were noted in NMAs (e.g. lack of study protocol, issues in literature searches, lack of raw data). NMAs from the most productive countries (USA and China) have similar methodological quality. Correlation analyses between R-AMSTAR and normalized PRISMA-SCORE revealed a strong positive correlation (Spearman's ρ = 0.776; P <0.001). A weak but positive correlation was found for PRISMA-SCORE and journal impact factor (0.193; P <0.001). CONCLUSIONS: The important growth of NMA publication rate during the past 5 years is not associated with better methodological and reporting quality. Editors, peer reviewers, researchers and funding agencies should ensure that methodological and reporting standards are met before publication.

10.
NPJ Vaccines ; 3: 54, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30510775

RESUMO

Whole-sporozoite vaccination/immunization induces high levels of protective immunity in both rodent models of malaria and in humans. Recently, we generated a transgenic line of the rodent malaria parasite P. berghei (Pb) that expresses the P. falciparum (Pf) circumsporozoite protein (PfCS), and showed that this parasite line (PbVac) was capable of (1) infecting and developing in human hepatocytes but not in human erythrocytes, and (2) inducing neutralizing antibodies against the human Pf parasite. Here, we analyzed PbVac in detail and developed tools necessary for its use in clinical studies. A microbiological contaminant-free Master Cell Bank of PbVac parasites was generated through a process of cyclic propagation and clonal expansion in mice and mosquitoes and was genetically characterized. A highly sensitive qRT-PCR-based method was established that enables PbVac parasite detection and quantification at low parasite densities in vivo. This method was employed in a biodistribution study in a rabbit model, revealing that the parasite is only present at the site of administration and in the liver up to 48 h post infection and is no longer detectable at any site 10 days after administration. An extensive toxicology investigation carried out in rabbits further showed the absence of PbVac-related toxicity. In vivo drug sensitivity assays employing rodent models of infection showed that both the liver and the blood stage forms of PbVac were completely eliminated by Malarone® treatment. Collectively, our pre-clinical safety assessment demonstrates that PbVac possesses all characteristics necessary to advance into clinical evaluation.

11.
NPJ Vaccines ; 3: 33, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30155278

RESUMO

There is a pressing need for safe and highly effective Plasmodium falciparum (Pf) malaria vaccines. The circumsporozoite protein (CS), expressed on sporozoites and during early hepatic stages, is a leading target vaccine candidate, but clinical efficacy has been modest so far. Conversely, whole-sporozoite (WSp) vaccines have consistently shown high levels of sterilizing immunity and constitute a promising approach to effective immunization against malaria. Here, we describe a novel WSp malaria vaccine that employs transgenic sporozoites of rodent P. berghei (Pb) parasites as cross-species immunizing agents and as platforms for expression and delivery of PfCS (PbVac). We show that both wild-type Pb and PbVac sporozoites unabatedly infect and develop in human hepatocytes while unable to establish an infection in human red blood cells. In a rabbit model, similarly susceptible to Pb hepatic but not blood infection, we show that PbVac elicits cross-species cellular immune responses, as well as PfCS-specific antibodies that efficiently inhibit Pf sporozoite liver invasion in human hepatocytes and in mice with humanized livers. Thus, PbVac is safe and induces functional immune responses in preclinical studies, warranting clinical testing and development.

12.
PLoS One ; 13(4): e0196644, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29709028

RESUMO

BACKGROUND: Network meta-analysis (NMA) is a new tool developed to overcome some limitations of pairwise meta-analyses. NMAs provide evidence on more than two comparators simultaneously. This study aimed to map the characteristics of the published NMAs on drug therapy comparisons. METHODS: A systematic review of NMAs comparing pharmacological interventions was performed. Searches in Medline (PubMed) and Scopus along with manual searches were conducted. The main characteristics of NMAs were systematically collected: publication metadata, criteria for drug inclusion, statistical methods used, and elements reported. A methodological quality score with 25 key elements was created and applied to the included NMAs. To identify potential trends, the median of the publication year distribution was used as a cut-off. RESULTS: The study identified 365 NMAs published from 2003 to 2016 in more than 30 countries. Randomised controlled trials were the primary source of data, with only 5% including observational studies, and 230 NMAs used a placebo as a comparator. Less than 15% of NMAs were registered in PROSPERO or a similar system. One third of studies followed PRISMA and less than 9% Cochrane recommendations. Around 30% presented full-search strategies of the systematic review, and 146 NMAs stated the selection criteria for drug inclusion. Over 75% of NMAs presented network plots, but only half described their geometry. Statistical parameters (model fit, inconsistency, convergence) were properly reported by one third of NMAs. Although 216 studies exhibited supplemental material, no data set of primary studies was available. The methodological quality score (mean 13·9; SD 3·8) presented a slightly positive trend over the years. CONCLUSION: The map of the published NMAs emphasises the potential of this tool to gather evidence in healthcare, but it also identified some weaknesses, especially in the report, which limits its transparency and reproducibility.


Assuntos
Tratamento Farmacológico/métodos , Meta-Análise em Rede , Algoritmos , Teorema de Bayes , Tomada de Decisões , Humanos , Internet , MEDLINE , Metanálise como Assunto , Preparações Farmacêuticas , Reprodutibilidade dos Testes , Projetos de Pesquisa , Software
13.
Clinics (Sao Paulo) ; 73: e325, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29723341

RESUMO

OBJECTIVES: This study aimed to evaluate the impact of pharmacist-provided discharge counseling on mortality rate, hospital readmissions, emergency department visits, and medication adherence at 30 days post discharge. METHODS: This randomized controlled trial was approved by the local ethics committee and included patients aged 18 years or older admitted to the cardiology ward of a Brazilian tertiary hospital. The intervention group received a pharmacist-led medication counseling session at discharge and a telephone follow-up three and 15 days after discharge. The outcomes included the number of deaths, hospital readmissions, emergency department visits, and medication adherence. All outcomes were evaluated during a pharmacist-led ambulatory consultation performed 30 days after discharge. RESULTS: Of 133 patients, 104 were included in the analysis (51 and 53 in the intervention and control groups, respectively). The intervention group had a lower overall readmission rate, number of emergency department visits, and mortality rate, but the differences were not statistically significant (p>0.05). However, the intervention group had a significantly lower readmission rate related to heart disease (0% vs. 11.3%, p=0.027), despite the small sample size. Furthermore, medication counseling contributed significantly to improved medication adherence according to three different tools (p<0.05). CONCLUSIONS: Pharmacist-provided discharge medication counseling resulted in better medication adherence scores and a lower incidence of cardiovascular-associated hospital readmissions, thus representing a useful service for cardiology patients.


Assuntos
Aconselhamento Diretivo , Alta do Paciente/normas , Farmacêuticos/psicologia , Idoso , Brasil , Serviço Hospitalar de Cardiologia/estatística & dados numéricos , Feminino , Cardiopatias/mortalidade , Humanos , Masculino , Adesão à Medicação/psicologia , Pessoa de Meia-Idade , Readmissão do Paciente/estatística & dados numéricos , Farmacêuticos/normas , Papel Profissional/psicologia , Centros de Atenção Terciária/estatística & dados numéricos
14.
J Eval Clin Pract ; 24(3): 570-579, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29691955

RESUMO

RATIONALE, AIMS, AND OBJECTIVES: Discharge medication counselling has produced improved quality of care and health outcomes, especially by reducing medication errors and readmission rates, and improving medication adherence. However, no studies have assembled an evidence-based discharge counselling process for clinical pharmacists. Thus, the present study aims to map the components of the pharmacist-led discharge medication counselling process. METHODS: We performed a scoping review by searching electronic databases (Pubmed, Scopus, and DOAJ) and conducting a manual search to identify studies published up to July 2017. Studies that addressed pharmacist-led discharge medication counselling, regardless of the population, clinical conditions, and outcomes evaluated, were included. RESULTS: A total of 1563 studies were retrieved, with 75 matching the inclusion criteria. Thirty-two different components were identified, and the most prevalent were the indication of the medications and adverse drug reactions, which were reported in more than 50% of the studies. The components were reported similarly by studies from the USA and the rest of the world, and over the years. However, 2 differences were identified: the use of a dosage schedule, which was more frequent in studies published in 2011 or before and in studies outside the USA; and the teach-back technique, which was used more frequently in the USA. Poor quality reporting was also observed, especially regarding the duration of the counselling, the number of patients, and the medical condition. CONCLUSION: Mapping the components of the pharmacist-led discharge counselling studies through a scoping review allowed us to reveal how this service is performed around the world. Wide variability in this process and poor reporting were identified. Future studies are needed to define the core outcome set of this clinical pharmacy service to allow the generation of robust evidence and reproducibility in clinical practice.


Assuntos
Aconselhamento , Reconciliação de Medicamentos , Serviço de Farmácia Hospitalar , Humanos , Farmacêuticos , Papel Profissional
15.
Diabetol Metab Syndr ; 10: 18, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29568330

RESUMO

Background: Vitamins are essential micronutrients with antioxidant potential that may provide a complementary treatment for patients with chronic diseases. Our aim was to assess the effect of vitamin supplementation on the antioxidant status and glycemic index of type 2 diabetes mellitus patients. Methods: We performed a systematic review with meta-analyses. Electronic searches were conducted in PubMed, Scopus, and Web of Science (December 2017). Randomized controlled trials evaluating the effect of any vitamin or vitamin complex supplementation on antioxidant status as primary outcome were included. The outcomes considered were: reduction of malondialdehyde (MDA); augmentation of glutathione peroxidase (GPx); changes in total antioxidant capacity (TAC), enhance in superoxide dismutase enzyme-SOD, and thiobarbituric acid reactive substances (TBARS). Outcomes of glycemic control were also evaluated. Pairwise meta-analyses were performed using software Review Manager 5.3. Results: Thirty trials fulfilled the inclusion criteria, but only 12 could be included in the meta-analyses of antioxidant outcomes. The most commonly studied vitamins were B, C, D and E. Vitamin E was related to significant reduction of blood glucose as well as glycated hemoglobin compared to placebo, while both vitamins C and E were mainly associated with reducing MDA and TBARS and elevating GPx, SOD and TAC, compared to placebo. However, outcome reports in this field are still inconsistent (e.g. because of a lack of standard measures). Conclusions: Supplementation of vitamin E may be a valuable strategy for controlling diabetes complications and enhancing antioxidant capacity. The effects of other micronutrients should be further investigated in larger and well-designed trials to properly place these complementary therapies in clinical practice.

16.
Clinics ; 73: e325, 2018. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-890741

RESUMO

OBJECTIVES: This study aimed to evaluate the impact of pharmacist-provided discharge counseling on mortality rate, hospital readmissions, emergency department visits, and medication adherence at 30 days post discharge. METHODS: This randomized controlled trial was approved by the local ethics committee and included patients aged 18 years or older admitted to the cardiology ward of a Brazilian tertiary hospital. The intervention group received a pharmacist-led medication counseling session at discharge and a telephone follow-up three and 15 days after discharge. The outcomes included the number of deaths, hospital readmissions, emergency department visits, and medication adherence. All outcomes were evaluated during a pharmacist-led ambulatory consultation performed 30 days after discharge. RESULTS: Of 133 patients, 104 were included in the analysis (51 and 53 in the intervention and control groups, respectively). The intervention group had a lower overall readmission rate, number of emergency department visits, and mortality rate, but the differences were not statistically significant (p>0.05). However, the intervention group had a significantly lower readmission rate related to heart disease (0% vs. 11.3%, p=0.027), despite the small sample size. Furthermore, medication counseling contributed significantly to improved medication adherence according to three different tools (p<0.05). CONCLUSIONS: Pharmacist-provided discharge medication counseling resulted in better medication adherence scores and a lower incidence of cardiovascular-associated hospital readmissions, thus representing a useful service for cardiology patients.

17.
Artigo em Inglês | MEDLINE | ID: mdl-28770176

RESUMO

Recent WHO guidelines on control of human immunodeficiency virus (HIV) call for the widespread use of antiretroviral (AR) therapy (ART) for people living with HIV. Given the considerable overlap between infections by HIV and Plasmodium, the causative agent of malaria, it is important to understand the impact of AR compounds and ART regimens on infections by malaria parasites. We undertook a systematic approach to identify AR drugs and ART drug combinations with inhibitory activity against the obligatory hepatic stage of Plasmodium infection. Our in vitro screen of a wide array of AR drugs identified the non-nucleoside reverse transcriptase inhibitors efavirenz and etravirine (ETV), and the protease inhibitor nelfinavir, as compounds that significantly impair the development of the rodent malaria parasite P. berghei in an hepatoma cell line. Furthermore, we show that WHO-recommended ART drug combinations currently employed in the field strongly inhibit Plasmodium liver infection in mice, an effect that may be significantly enhanced by the inclusion of ETV in the treatment. Our observations are the first report of ETV as an anti-Plasmodial drug, paving the way for further evaluation and potential use of ETV-containing ARTs in regions of geographical overlap between HIV and Plasmodium infections.


Assuntos
Antirretrovirais/farmacologia , Antimaláricos/farmacologia , Malária/prevenção & controle , Plasmodium berghei/efeitos dos fármacos , Animais , Benzoxazinas/farmacologia , Linhagem Celular , Modelos Animais de Doenças , Hepatócitos/parasitologia , Humanos , Masculino , Camundongos Endogâmicos C57BL , Nelfinavir/farmacologia , Piridazinas/farmacologia
18.
Sci Rep ; 7(1): 4072, 2017 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-28642498

RESUMO

Prior to infecting erythrocytes and causing malaria symptoms, Plasmodium parasites undergo an obligatory phase of invasion and extensive replication inside their mammalian host's liver cells that depends on the parasite's ability to obtain the nutrients it requires for its intra-hepatic growth and multiplication. Here, we show that L-arginine (Arg) uptake through the host cell's SLC7A2-encoded transporters is essential for the parasite's development and maturation in the liver. Our data suggest that the Arg that is taken up is primarily metabolized by the arginase pathway to produce the polyamines required for Plasmodium growth. Although the parasite may hijack the host's biosynthesis pathway, it relies mainly upon its own arginase-AdoMetDC/ODC pathway to acquire the polyamines it needs to develop. These results identify for the first time a pivotal role for Arg-dependent polyamine production during Plasmodium's hepatic development and pave the way to the exploitation of strategies to impact liver infection by the malaria parasite through the modulation of Arg uptake and polyamine synthesis.


Assuntos
Arginina/metabolismo , Fígado/metabolismo , Fígado/parasitologia , Malária/metabolismo , Malária/parasitologia , Plasmodium , Animais , Transportador 2 de Aminoácidos Catiônicos/genética , Transportador 2 de Aminoácidos Catiônicos/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Regulação da Expressão Gênica , Hepatócitos/metabolismo , Hepatócitos/parasitologia , Interações Hospedeiro-Patógeno , Humanos , Malária/genética , Camundongos , Camundongos Knockout , Plasmodium berghei
19.
Pharm Pract (Granada) ; 15(1): 943, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28503228

RESUMO

Systematic reviews and pairwise meta-analyses of randomized controlled trials, at the intersection of clinical medicine, epidemiology and statistics, are positioned at the top of evidence-based practice hierarchy. These are important tools to base drugs approval, clinical protocols and guidelines formulation and for decision-making. However, this traditional technique only partially yield information that clinicians, patients and policy-makers need to make informed decisions, since it usually compares only two interventions at the time. In the market, regardless the clinical condition under evaluation, usually many interventions are available and few of them have been studied in head-to-head studies. This scenario precludes conclusions to be drawn from comparisons of all interventions profile (e.g. efficacy and safety). The recent development and introduction of a new technique - usually referred as network meta-analysis, indirect meta-analysis, multiple or mixed treatment comparisons - has allowed the estimation of metrics for all possible comparisons in the same model, simultaneously gathering direct and indirect evidence. Over the last years this statistical tool has matured as technique with models available for all types of raw data, producing different pooled effect measures, using both Frequentist and Bayesian frameworks, with different software packages. However, the conduction, report and interpretation of network meta-analysis still poses multiple challenges that should be carefully considered, especially because this technique inherits all assumptions from pairwise meta-analysis but with increased complexity. Thus, we aim to provide a basic explanation of network meta-analysis conduction, highlighting its risks and benefits for evidence-based practice, including information on statistical methods evolution, assumptions and steps for performing the analysis.

20.
Artigo em Inglês | MEDLINE | ID: mdl-28348156

RESUMO

The sporogonic stage of the life cycle of Plasmodium spp., the causative agents of malaria, occurs inside the parasite's mosquito vector, where a process of fertilization, meiosis, and mitotic divisions culminates in the generation of large numbers of mammalian-infective sporozoites. Efforts to cultivate Plasmodium mosquito stages in vitro have proved challenging and yielded only moderate success. Here, we describe a methodology that simplifies the in vitro screening of much-needed transmission-blocking (TB) compounds employing a bioluminescence-based method to monitor the in vitro development of sporogonic stages of the rodent malaria parasite Plasmodium berghei Our proof-of-principle assessment of the in vitro TB activity of several commonly used antimalarial compounds identified cycloheximide, thiostrepton, and atovaquone as the most active compounds against the parasite's sporogonic stages. The TB activity of these compounds was further confirmed by in vivo studies that validated our newly developed in vitro approach to TB compound screening.


Assuntos
Antimaláricos/farmacologia , Malária/transmissão , Plasmodium berghei/efeitos dos fármacos , Animais , Anopheles/efeitos dos fármacos , Antimaláricos/uso terapêutico , Drosophila , Proteínas de Drosophila/metabolismo , Insetos Vetores/efeitos dos fármacos , Malária/tratamento farmacológico , Esporozoítos/efeitos dos fármacos
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