Browsing by Author "Fernandez-Llimos, Fernando"
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- Bioactive compounds as potential angiotensin-converting enzyme II inhibitors against COVID-19: a scoping reviewPublication . Matos, Pedro Henrique de; Silva, Thalita Prates da; Mansano, Amanda Benites; Gancedo, Naiara Cássia; Tonin, Fernanda; Pelloso, Fernando Castilho; Petruco, Marcus Vinicius; Melo, Eduardo Borges de; Fernandez-Llimos, Fernando; Sanches, Andreia Cristina Conegero; Mello, João Carlos Palazzo de; Chierrito, Danielly; Araújo, Daniela Cristina de MedeirosObjective and design: The current study aimed to summarize the evidence of compounds contained in plant species with the ability to block the angiotensin-converting enzyme 2 (ACE-II), through a scoping review. Methods: PubMed and Scopus electronic databases were used for the systematic search and a manual search was performed RESULTS: Studies included were characterized as in silico. Among the 200 studies retrieved, 139 studies were listed after the exclusion of duplicates, and 74 were included for the full read. Among them, 32 studies were considered eligible for the qualitative synthesis. The most evaluated class of secondary metabolites was flavonoids with quercetin and curcumin as most actives substances and terpenes (isothymol, limonin, curcumenol, anabsinthin, and artemisinin). Other classes also evaluated were alkaloid, saponin, quinone, substances found in essential oils, and primary metabolites such as the aminoacid L-tyrosine and the lipidic compound 2-monolinolenin. Conclusion: This review suggests the most active substance from each class of metabolites, which presented the strongest affinity to the ACE-II receptor, which contributes as a basis for choosing compounds and directing further experimental and clinical investigation on the applications these compounds in biotechnological and health processes as in COVID-19 pandemic.
- Chemical constituents, anticancer and anti-proliferative potential of limonium species: a systematic reviewPublication . Gancedo, Naiara Cássia; Isolani, Raquel; Oliveira, Natalia Castelhano de; Nakamura, Celso Vataru; Araújo, Daniela Cristina Medeiros; Sanches, Andreia Cristina Conegero; Tonin, Fernanda; Fernandez-Llimos, Fernando; Chierrito, Danielly; Mello, João Carlos Palazzo deLimonium species represent a source of bioactive compounds that have been widely used in folk medicine. This study aimed to synthesize the anticancer and anti-proliferative potential of Limonium species through a systematic review. Searches were performed in the electronic databases PubMed/MEDLINE, Scopus, and Scielo and via a manual search. In vivo or in vitro studies that evaluated the anticancer or anti-proliferative effect of at least one Limonium species were included. In total, 942 studies were identified, with 33 articles read in full and 17 studies included for qualitative synthesis. Of these, 14 (82.35%) refer to in vitro assays, one (5.88%) was in vivo, and two (11.76%) were designed as in vitro and in vivo assays. Different extracts and isolated compounds from Limonium species were evaluated through cytotoxic analysis against various cancer cell lines (especially hepatocellular carcinoma—HepG2; n = 7, 41.18%). Limonium tetragonum was the most evaluated species. The possible cellular mechanism involved in the anticancer activity of some Limonium species included the inhibition of enzymatic activities and expression of matrix metalloproteinases (MMPs), which suggested anti-metastatic effects, anti-melanogenic activity, cell proliferation inhibition pathways, and antioxidant and immunomodulatory effects. The results reinforce the potential of Limonium species as a source for the discovery and development of new potential cytotoxic and anticancer agents. However, further studies and improvements in experimental designs are needed to better demonstrate the mechanism of action of all of these compounds.
- Comparative efficacy and safety of pharmacological interventions for managing sickle cell disease complications in children and adolescents: a systematic review with network meta-analysesPublication . Tonin, Fernanda; Ginete, Catarina; Ferreira, Joao; Delgadinho, Mariana; Fernandez-Llimos, Fernando; Brito, MiguelObjectives: Sickle cell disease (SCD), an inherited hemoglobinopathy that causes anemia, severe pain, and vaso-occlusive crisis (VOC), is currently recognized as a global public health concern, being the leading cause of pediatric stroke. Our aim was to synthesize the evidence on the efficacy and safety of interventions for managing SCD in this population. Methods: A systematic review with searches in PubMed, Scopus, and Web of Science was performed (April-2022). Randomized controlled trials comparing disease-modifying agents in SCD patients under 18 years old were included. For each outcome of interest, data were pooled by means of Bayesian network meta-analyses with the surface under the cumulative ranking curve analyses (SUCRA). Results were reported as odds ratio (OR) with 95% credibility intervals (CrI). Results: Seventeen trials (1982-2022) mostly from African countries (65%) and North America (53%), assessing the effect of different interventions’ regimens (hydroxyurea [n=6 trials], L-arginine [n=3], antiplatelets [n=2], immunotherapy/monoclonal antibodies [n=2], sulfates [n=2], docosahexaenoic acid [n=1], niprisan [n=1]) and placebo were included. No statistical differences among treatments were found for the main outcomes. SUCRA revealed that immunotherapy/monoclonal antibodies and hydroxyurea 20 mg/kg are potentially more effective against acute chest syndrome (83% and 76% probabilities, respectively), VOC (71% and 80%, respectively) and needing of transfusions (72% and 75%, respectively), while L-arginine (100-200 mg/kg) and placebo were more prone to these events. Although therapies were overall considered safe, antiplatelet and sulfates may lead to more discontinuations and severe adverse events (uncertainty evidence). Results were similar between age subgroups (<10 years vs. 10-19 years). Conclusions: The available evidence on the effect of drugs on managing SCD in children and adolescents is insufficient and weak. No clear definition for some outcomes exists. Hydroxyurea may remain the standard of care for this population, however, long-term well-designed, and well-reported trials comparing new immunotherapy/monoclonal antibodies should be performed.
- Comparative efficacy and safety of pharmacological interventions for sickle cell disease in children and adolescents: a network meta-analysisPublication . Tonin, Fernanda; Ginete, Catarina; Ferreira, J.; Delgadinho, Mariana; Fernandez-Llimos, Fernando; Brito, MiguelBackground: Sickle cell disease (SCD), an inherited hemoglobinopathy characterized by anemia, severe pain, acute chest syndrome (ACS), and vaso-occlusive crisis (VOC), has an important impact on morbidity and mortality worldwide, especially in the pediatric population (over 50% die before age of 5). Although few treatment options are available, new disease-modifying therapies, intended to prevent or reduce SCD-related complications are under development. Previous systematic reviews are limited to adult patients or focused only on gathering data on a few therapies. Aims: Our aim was to synthetize the evidence on the efficacy and safety profiles of pharmacological interventions for managing SCD in children and adolescents. Methods: A systematic review with searches in PubMed, Scopus, and Web of Science was performed (May-2022). The protocol is registered at PROSPERO CRD42022328471. We included randomized controlled trials comparing any disease-modifying agent used to treat SCD complications in patients under 18 years old. The outcomes of interest included: VOC, ACS, transfusions, hospital admission, discontinuation, and serious adverse events. Data were pooled by means of Bayesian network meta-analyses with the surface under the cumulative ranking curve analyses (SUCRA). Results were reported as odds ratio (OR) with 95% credibility intervals (CrI). Additionally, stochastic multicriteria acceptability analyses (SMAA) were performed. The methodological quality of the trials and certainty of evidence were evaluated through RoB 2.0 tool and the GRADE approach, respectively. Results: Overall, 17 randomized controlled trials (n=1,972 patients) published between 1982-2022, conducted mostly in Africa (41%) and North America (35%) were included for analyses. Around one-third of the trials were restricted to homozygous patients for the SCD allele (SS HMZ); yet when reported, patients with heterozygous S-C combination represented less than 30% of the population. Males accounted for 49.0% of the cases, with ages varying from 1 to 19 years old. Almost all trials (n=15, 88.2%) directly compared active drugs with placebo. The evaluated interventions were: hydroxyurea [n=6 trials], L-arginine [n=3], antiplatelets [n=2], immunotherapy/monoclonal antibodies [n=2], sulfates [n=2], docosahexaenoic acid [n=1], niprisan [n=1] (Figure 1). SUCRA and SMAA revealed that immunotherapy/monoclonal antibodies and hydroxyurea 20 mg/kg are potentially more effective against ACS (17% and 24% probabilities, respectively), VOC (around 29% and 20%, respectively) and needing of transfusions (around 25%), while L-arginine (100-200 mg/kg) and placebo were more associated with these events. Although therapies were overall considered safe, antiplatelet and sulfates may lead to more discontinuations and severe adverse events (uncertainty evidence). Results were similar between age subgroups (<10 years vs. 10-19 years). Summary - Conclusion: The available evidence on the effect of drugs on managing SCD in children and adolescents is still insufficient and weak. No clear definition and reporting criteria for some outcomes exist. Hydroxyurea 20 mg/kg/day may remain the standard of care for these patients, however, long-term, well-designed trials comparing new immunotherapy/monoclonal antibodies should be performed. The use of monotherapies with L-arginine, antiplatelets, or sulfates should be avoided given the poor benefit-risk ratio for this population.
- Complexidade do regime terapêutico geriátrico: doentes institucionalizados versus doentes em ambulatórioPublication . Advinha, Ana; Soares, Maria Augusta; Mateus, Vanessa; Graça, Anabela; Pajote, Sara Grou; Lopes, Manuel José; Fernandez-Llimos, Fernando; Cabrita, José; Morais, JoséO envelhecimento populacional representa um fenómeno demográfico crescente e um importante problema social, o que tem despoletado o interesse dos investigadores pela geriatria e pela gerontologia. A falta de suporte doméstico, familiar e social pode muitas vezes conduzir a problemas de adesão e gestão da terapêutica nos idosos. Por vezes, o internamento em lares de terceira idade constitui o único meio de obtenção de cuidados de saúde de que necessitam. O envelhecimento surge também acompanhado por alterações fisiológicas, metabólicas e funcionais que conduzem a alterações farmacocinéticas e farmacodinâmicas. As múltiplas patologias do idoso associam-se inevitavelmente à toma de medicamentos que muitas vezes resulta em polimedicação. Com o aumento de consumo de medicamentos e a diminuição das capacidades do idoso para gerir a sua terapêutica, torna-se fundamental efectuar a determinação da complexidade do regime terapêutico, tanto pelas implicações em termos de adesão à medicação como pelos resultados clínicos. A complexidade do regime terapêutico de um indivíduo caracteriza-se por ser um elemento conciliador de diversos factores da sua farmacoterapia, como sejam, o número de medicamentos tomados, as formas farmacêuticas, as frequências de dose e as indicações adicionais.
- Critical appraisal of dyslipidaemia clinical practice guidelines: a scoping reviewPublication . Deffert, Flávia; Tonin, Fernanda; Pontarolo, Roberto; Fernandez-Llimos, FernandoBackground information: Dyslipidaemia, the unbalanced level of lipoproteins and triglycerides, contributes to or aggravates cardiovascular diseases. In 2019, high LDL-c levels were responsible for 5 million deaths worldwide. Several clinical practice guidelines (CPG) about dyslipidaemia aiming at guiding healthcare professionals towards more assertive decisions exist. However, previous studies reported low quality of the clinical content and evidence supporting recommendations provided by CPGs in different areas, and a lack of involvement of multi-professional experts and stakeholders, such as pharmacists, in their development. This may lead to inconsistencies and risk of bias in decision-making and negatively impact patients’ outcomes. The quality of CPG can be assessed through Appraisal of Guidelines, Research and Evaluation (AGREE) tools as the AGREE II (methodological assessment) and AGREE REX (clinical recommendations). Purpose: We aim to evaluate the quality of available CPG on dyslipidaemia and assess the extent of involvement of stakeholders using AGREE II and AGREE REX appraisal tools.
- Definitions and indexing of 'simulated patient’ studies in health: a classification system proposalPublication . Tonin, Fernanda; Pina, Isabela; Pontarolo, Roberto; Fernandez-Llimos, FernandoBackground information: Several inconsistencies in the definition and indexing of the term ‘simulated patient’ have been reported in the health literature, including in pharmacy practice. Purpose: To propose a classification system for studies on ‘simulated patient’ and to assess the coverage of ‘simulated patient’ in the National Library of Medicine’s (NLM) Medical Subject Headings (MeSH) thesaurus.
- Effectiveness of strategies to delay sexual activity onset to prevent pregnancy in the adolescence: a systematic reviewPublication . Rotta, Inajara; Rodrigues, Alice Teotonio; Fernandes, Brígida Dias; Komoda, Dênis Satoshi; Tonin, Fernanda; Fernandez-Llimos, FernandoAdolescent pregnancy is associated with health, social, and economic burdens. Different strategies have been implemented to prevent this outcome, yet few updated data on their effectiveness exist. We aim to synthetize the available evidence on the impact of interventions to delay sexual activity onset in adolescents by means of a broader systematic review. A literature search to gather interventional and observational analytical studies published since 2010 was conducted in PubMed, Scopus, PsycINFO, CINAHL Plus, ERIC, and LILACS, being complemented by grey literature and manual searches. A total of 57 studies were identified reporting data on 60 comprehensive and 9 abstinence-only interventions. The interventions were predominantly provided in schools (69.6%), in person (82.6%), and in groups (66.7%), by trained facilitators or educators (43.5%). The recipient of the intervention was exclusively the adolescent in 85.5% of the studies. Five out of 9 abstinence-only interventions presented a statistically favorable result towards the use of the intervention for any of the evaluated outcomes (delay/intention to delay sexual intercourse and pregnancy; this rate was 22 from the 60 comprehensive interventions. Most intervention components had similar effects as the comparator group (no statistical differences) or data was limited to reach any conclusion. This review showed a scarcity and low-quality evidence on the effectiveness of abstinence-only interventions, and the absence of robust evidence for comprehensive strategies aiming at delaying sexual practice by adolescents to avoid early pregnancy. Further well-designed and well-reported studies are needed to help stakeholders understand this scenario and enable the decision-making process within public policies for this population.
- Efficacy and safety of daily treatments for drug-susceptible pulmonary tuberculosis: a systematic review and network meta-analysisPublication . Imazu, Priscila; Santos, Josiane M.; Beraldi-Magalhães, Francisco; Fernandez-Llimos, Fernando; Tonin, Fernanda; Pontarolo, RobertoObjectives: To evaluate and update the evidence on the comparative efficacy and safety of antimicrobial drugs regimens for treating pulmonary drug-susceptible tuberculosis (DS-TB). Methods: A systematic review was performed with searches in PubMed and Scopus (PROSPERO-CRD42019141463). We included randomised controlled trials comparing the effect of any antimicrobial regimen lasting at least 2 weeks. The outcomes of interest were culture conversion and incidence of adverse events. Bayesian network meta-analyses and surface under the cumulative ranking curve (SUCRA) analyses were performed. Results were reported as odds ratio with 95% credibility intervals. Key findings: Fifteen studies were included in the meta-analysis (n = 7560 patients). No regimen was statistically more effective than the WHO standard approach (rifampicin, isoniazid, ethambutol, and pyrazinamide). The use of rifapentine 450 mg instead of rifampicin in the standard regimen demonstrated to be statistically safer than all other options for serious adverse events (e.g. hepatotoxicity, arthralgia) (OR ranging from 0.0 [Crl 0.00-0.04] to 0.0 [0.00-0.97]; SUCRA probabilities of 10%). Therapies containing rifapentine (Rp1500HEZ, Rp900HEZ) and moxifloxacin (RMEZ, RHMZ) are effective regarding culture conversion, but statistical uncertainty on their safety profile exists. Conclusion: The WHO standard regimen remains an overall effective and safe alternative for DS-TB. For intensive phase treatments, drugs combinations with rifapentine and moxifloxacin seem to reduce treatment duration while maintaining efficacy.
- Efficacy and safety of pharmacological interventions for managing sickle cell disease in children and adolescents: protocol for a systematic review with network meta-analysisPublication . Tonin, Fernanda; Ginete, Catarina; Fernandez-Llimos, Fernando; Ferreira, Joana; Delgadinho, Mariana; Brito, MiguelIntroduction: Sickle cell disease (SCD), an inherited haemoglobinopathy, has an important impact on morbidity and mortality, especially in paediatrics. Previous systematic reviews are limited to adult patients or focused only on a few therapies. We aim to synthesise the evidence on the efficacy and safety of pharmacological interventions for managing SCD in children and adolescents. Methods and analysis: This systematic review protocol is available at Open Science Framework (doi:10.17605/OSF.IO/CWAE9). We will follow international recommendations on the conduction and report of systematic reviews and meta-analyses. Searches will be conducted in PubMed, Scopus, and Web of Science (no language nor time restrictions) (first pilot searches performed in May 2022). We will include randomised controlled trials comparing the effects of disease-modifying agents in patients with SCD under 18 years old. Outcomes of interest will include: vaso-occlusive crisis, haemoglobin levels, chest syndrome, stroke, overall survival, and adverse events. We will provide a narrative synthesis of the findings, and whenever possible, results will be pooled by means of pairwise or Bayesian network meta-analyses with the surface under the cumulative ranking curve analyses. Different statistical methods and models will be tested. Dichotomous outcomes will be reported as OR, risk ratio, or HR, while continuous data will be reported as standard mean differences, both with 95% CI/credibility interval. The methodological quality of the trials will be evaluated using the Risk of Bias 2.0 tool, and the certainty of the evidence will be assessed with the Grading of Recommendations Assessment, Development, and Evaluation approach. Ethics and dissemination: This study refers to a systematic review, so no ethics approval is necessary. We intend to publish our findings in an international, peer-reviewed journal. Data will also be presented to peers at scientific events. Additionally, the results obtained in this study may contribute towards the update of therapeutic guidelines and the development of health policies for SCD.