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PURPOSE: To evaluate the impact of the pandemic on the consumption of antidepressive agents in Central Portugal. METHODS: To estimate the causal effect of the pandemic an interrupted time series analysis was conducted. Data of antidepressant drugs monthly dispensed in community pharmacies between Jan-2010 and Dec-2021 were provided by the regional Health Administration. Anti-Parkinson dopaminergic agents and statins, theoretically not influenced by COVID-19 pandemics, were used as comparator series. The number of packages was converted into defined daily doses and presented as defined daily doses/1000 inhabitants/day. A Bayesian structural time-series model with CausalImpact on R/RStudio was used to predict the counterfactual. Analyses with different geographical granularity (9 sub-regions and 78 municipalities) were performed. RESULTS: When compared to counterfactual, regional consumption non-significantly increased after the pandemic declaration, with a relative effect of + 1.30% [95%CI -1.6%:4.2%]. When increasing the granularity, differences appeared between sub-region with significant increases in Baixo Mondego + 6.5% [1.4%:11.0%], Guarda + 4.4% [1.1%:7.7%] or Cova da Beira + 4.1% [0.17%:8.3%], but non-significant variation in the remaining 6 sub-regions. Differences are more obvious at municipality level, ranging from increases of + 37.00% [32.00%:42.00%] to decreases of -11.00% [-17.00%:-4.20%]. Relative impact positively correlated with percentage of elderly in the municipality (r = 0.301; p = 0.007), and negatively with population density (r=-0.243; p = 0.032). No other predicting variables were found. CONCLUSION: Antidepressant consumption suffered very slight variations at regional level after the COVID-19 pandemic declaration. Analysis with higher granularity allowed identifying municipalities with higher impact (increase or decrease). The absence of clear association patterns suggests other causal hypotheses of the differences.
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This study aimed to synthesize the evidence on the effects of disease-modifying agents for managing sickle cell disease (SCD) in children and adolescents by means of a systematic review with network meta-analyses, surface under the cumulative ranking curve (SUCRA) and stochastic multicriteria acceptability analyses (SMAA) (CRD42022328471). Eightteen randomized controlled trials (hydroxyurea [n = 7], l-arginine [n = 3], antiplatelets [n = 2], immunotherapy/monoclonal antibodies [n = 2], sulfates [n = 2], docosahexaenoic acid [n = 1], niprisan [n = 1]) were analyzed. SUCRA and SMAA demonstrated that hydroxyurea at higher doses (30 mg/kg/day) or at fixed doses (20 mg/kg/day) and immunotherapy/monoclonal antibodies are more effective for preventing vaso-occlusive crisis (i.e., lower probabilities of incidence of this event; 14, 25, and 30%, respectively), acute chest syndrome (probabilities ranging from 8 to 30%), and needing of transfusions (11-31%), while l-arginine (100-200 mg/kg) and placebo were more prone to these events. Therapies were overall considered safe; however, antiplatelets and sulfates may lead to more severe adverse events. Although the evidence was graded as insufficient and weak, hydroxyurea remains the standard of care for this population, especially if a maximum tolerated dose schedule is considered.
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Anemia Falciforme , Hidroxiureia , Criança , Adolescente , Humanos , Hidroxiureia/uso terapêutico , Antidrepanocíticos/uso terapêutico , Metanálise em Rede , Anemia Falciforme/complicações , Anticorpos Monoclonais/uso terapêuticoRESUMO
OBJECTIVE 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 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 that were also evaluated were alkaloid, saponin, quinone, substances found in essential oils, and primary metabolites 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, what contributes as a basis for choosing compounds and directing the further experimental and clinical investigation on the applications these compounds in biotechnological and health processes as in COVID-19 pandemic.
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Inibidores da Enzima Conversora de Angiotensina , Tratamento Farmacológico da COVID-19 , Humanos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Pandemias , Flavonoides , AngiotensinasRESUMO
BACKGROUND: We aimed to synthesize the evidence on the efficacy and safety of different treatment regimens for latent tuberculosis infection (LTBI) in children and adolescents. METHODS: A systematic review with network meta-analysis was performed (CRD142933). Searches were conducted in Pubmed and Scopus (Nov-2021). Randomized controlled trials comparing treatments for LTBI (patients up to 15 years), and reporting data on the incidence of the disease, death or adverse events were included. Networks using the Bayesian framework were built for each outcome of interest. Results were reported as odds ratio (OR) with 95% credibility intervals (CrI). Rank probabilities were calculated via the surface under the cumulative ranking analysis (SUCRA) (Addis-v.1.16.8). GRADE approach was used to rate evidence's certainty. RESULTS: Seven trials (n = 8696 patients) were included. Placebo was significantly associated with a higher incidence of tuberculosis compared to all active therapies. Combinations of isoniazid (15-25 mg/kg/week) plus rifapentine (300-900 mg/week), followed by isoniazid plus rifampicin (10 mg/kg/day) were ranked as best approaches with lower probabilities of disease incidence (10% and 19.5%, respectively in SUCRA) and death (20%). Higher doses of isoniazid monotherapy were significantly associated to more deaths (OR 18.28, 95% ICr [1.02, 48.60] of 4-6 mg/kg/day vs. 10 mg/kg/3x per week). CONCLUSIONS: Combined therapies of isoniazid plus rifapentine or rifampicin for short-term periods should be used as the first-line approach for treating LTBI in children and adolescents. The use of long-term isoniazid as monotherapy and at higher doses should be avoided for this population.
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Tuberculose Latente , Adolescente , Antituberculosos/efeitos adversos , Teorema de Bayes , Criança , Humanos , Isoniazida/efeitos adversos , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/epidemiologia , Metanálise em Rede , Rifampina/uso terapêuticoRESUMO
Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which has a high mortality rate and transmissibility. In this context, medicinal plants have attracted attention due to the wide availability and variety of therapeutic compounds, such as alkaloids, a vast class with several proven pharmacological effects, like the antiviral and anti-inflammatory activities. Therefore, this scoping review aimed to summarize the current knowledge of the potential applicability of alkaloids for treating COVID-19. A systematic search was performed on PubMed and Scopus, from database inception to August 2021. Among the 63 eligible studies, 65.07% were in silico model, 20.63% in vitro and 14.28% clinical trials and observational studies. According to the in silico assessments, the alkaloids 10-hydroxyusambarensine, cryptospirolepine, crambescidin 826, deoxynortryptoquivaline, ergotamine, michellamine B, nigellidine, norboldine and quinadoline B showed higher binding energy with more than two target proteins. The remaining studies showed potential use of berberine, cephaeline, emetine, homoharringtonine, lycorine, narciclasine, quinine, papaverine and colchicine. The possible ability of alkaloids to inhibit protein targets and to reduce inflammatory markers show the potential for development of new treatment strategies against COVID-19. However, more high quality analyses/reviews in this field are necessary to firmly establish the effectiveness/safety of the alkaloids here described.
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Alcaloides , Tratamento Farmacológico da COVID-19 , Alcaloides/química , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Antivirais/química , Antivirais/farmacologia , Antivirais/uso terapêutico , Humanos , SARS-CoV-2RESUMO
Primary hyperhidrosis (HH), the excessive sweating exceeding physiological demand, has been associated to a complex dysfunction of the autonomic nervous system which may explain the disfunction in sweating but may also cause unrevealed alterations in skin blood flow regulation. In fact, HH patients present a sympathetic over-function with less reflex bradycardia in response to the Valsalva maneuver and higher sympathetic skin responses. We aimed to identify response patterns to room thermal stimulus in HH patients compared to a control group in order to investigate putative differences in blood flow assuming that skin temperature in glabrous (non-hairy) areas reflect the sympathetic tone in arteriovenous anastomoses (AVAs). Infrared thermography images were obtained from a cohort of patients diagnosed with HH, followed at a hospital pediatric surgical department and to a sex- and age-matched control group of patients admitted for other surgical procedures. With the participants in Fowler's position, a set of 3 images were captured simultaneously and 44 regions of interest were analyzed, distributed on the palms of the hands, soles of the feet, axilla, and inner canthus. After an acclimatization period at 20 °C, the room temperature was increased to 24, 28 and 32 °C to obtain similar sets of thermograms. A total of 37 patients with HH and 16 participants in the control group were included in the study. At baseline (20 °C), body core temperature (measured in the inner canthus) was significantly higher in the HH patients compared to the controls (p = 0.019 and p = 0.003 in right and left inner canthi, respectively), without any significant differences in the other thermograms. When room temperature was increased, differences in core temperature disappeared, while differences appeared in axilla and palms of the hands with HH patients presenting significantly lower temperature at the three thermal stimulus stages. Patients with HH presented a lower thermoregulatory response when submitted to room temperature increase, which may reflect a vasomotor sympathetic over-function in AVAs.
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Hiperidrose , Temperatura Cutânea , Regulação da Temperatura Corporal/fisiologia , Criança , Humanos , Hiperidrose/diagnóstico , Hiperidrose/cirurgia , Pele/irrigação sanguínea , Sudorese , TemperaturaRESUMO
The use of anticholinergic drugs and other drugs with anticholinergic activity is highly prevalent in older people. Cumulative anticholinergic effects, known as anticholinergic burden, are associated with important peripheral and central adverse effects and outcomes. Several methods have been developed to quantify anticholinergic burden and to estimate the risk of adverse anticholinergic effects. Serum anticholinergic activity (SAA) and anticholinergic burden scoring systems are the most commonly used methods to predict the occurrence of important negative outcomes. These tools could guide clinicians in making more rational prescriptions to enhance patient safety, especially in older people. However, the literature has reported conflicting results about the predictive ability of these tools. The majority of these instruments ignore relevant pharmacologic aspects such as the doses used, differential muscarinic receptor subtype affinities, and blood-brain barrier permeability. To increase the clinical relevance of these tools, mechanistic and clinical pharmacology should collaborate. This narrative review describes the rational and pharmacological basis of anticholinergic burden tools and provides insight about their predictive value for adverse outcomes.
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Antagonistas Colinérgicos/efeitos adversos , Idoso , Uso de Medicamentos/estatística & dados numéricos , HumanosRESUMO
PURPOSE: To quantitatively assess the benefit-risk ratio on the efficacy and safety of all phosphodiesterase type 5 inhibitors (PDE5i) in men with erectile dysfunction. METHODS: A systematic review with network meta-analysis, surface under the cumulative ranking analysis and stochastic multicriteria acceptability analyses were performed. Searches were conducted in Pubmed, Scopus, Web of Science without limits for time-frame or language. Randomized controlled trials evaluating the efficacy or safety of any PDE5i compared to a placebo or to other PDE5i in males with erectile disfunction were included. RESULTS: Overall, 184 articles representing 179 randomized controlled trials (50,620 patients) were included. All PDE5i were significantly more efficient than placebo. Sildenafil 25 mg was statistically superior to all interventions in enhancing IIEF (with a 98% probability of being the most effective treatment), followed by sildenafil 50 mg (80% of probability). Taladafil 10 mg and 20 mg also presented good profiles (73% and 76%, respectively). Avanafil and lodenafil were less effective interventions. Mirodenafil 150 mg was the treatment that caused more adverse events, especially flushing and headaches. Sildenafil 100 mg was more related to visual disorders, while vardenafil and udenafil were more prone to cause nasal congestion. CONCLUSION: Sildenafil at low doses and tadalafil should be the first therapeutic options. Avanafil, lodenafil and mirodenafil use are hardly justified given the lack of expressive efficacy or high rates of adverse events.
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Técnicas de Apoio para a Decisão , Disfunção Erétil/tratamento farmacológico , Inibidores da Fosfodiesterase 5/administração & dosagem , Administração Oral , Humanos , Masculino , Metanálise em Rede , Inibidores da Fosfodiesterase 5/efeitos adversos , Resultado do TratamentoRESUMO
AIMS: Given the discrepancies between PDDs (prescribed daily doses) and DDDs (defined daily doses), we aimed to assess the extent of error in the results of an 18-year population-level study on statin utilization in Portugal. METHODS: The Portuguese regulatory agency provided data for the period 2000-2018 on statin dispensing (C10AA). The DDDs were gathered from the ATC/DDD database. DDDs were calculated by the DDD year-by-year approach (DDDYEAR ) and by the DDD last-year approach (DDDLAST ). PDDs were calculated according to the year-by-year approach (PDDYEAR ). Statin annual utilization rates per 1000 inhabitants per day were also calculated. Percent errors were calculated for PDDYEAR and DDDYEAR units. RESULTS: The DDDYEAR approach revealed decreases in the consumption of atorvastatin, fluvastatin, lovastatin, pravastatin and simvastatin in 2009, when their DDD was modified. Conversely, the results from both DDDLAST and PDDYEAR approaches indicated gradual changes in the actual consumption of all statins in Portugal. Before 2009, atorvastatin, pravastatin and simvastatin utilization was greatly overestimated by DDDYEAR /1000 inhabitants/day. The average dose of lovastatin prescribed in the past 18 years (20 mg) was below the assigned DDDs during the study period, varying from 30 mg to 45 mg. Conversely, the PDD for fluvastatin was above the DDD values (ranging from 40 mg in 2000 to 70 mg in 2016). For atorvastatin, pravastatin and simvastatin, national PDDs were above the assigned DDD until the DDD modification in 2009. CONCLUSIONS: A more dynamic system, based on national and annually updated DDDs, should be able to reduce discrepancies between DDDs and PDDs and the bias in utilization studies.
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Inibidores de Hidroximetilglutaril-CoA Redutases , Atorvastatina , Uso de Medicamentos , Humanos , Portugal/epidemiologia , SinvastatinaRESUMO
AIMS: Despite their overall favourable safety profile, tyrosine kinase inhibitors (TKIs) are related to severe adverse events including haematological toxicities such as anaemia, leucopenia, neutropenia and thrombocytopenia. We designed a systematic review and network meta-analysis of randomised controlled trials to compare safety among TKIs (bosutinib, dasatinib, imatinib, nilotinib, ponatinib and radotinib) used by patients diagnosed with chronic myeloid leukaemia. METHODS: We obtained data from the PubMed, Scopus, Web of Science, and SciELO databases. The Bayesian approach was used for direct and indirect comparisons, and the treatments were ranked by the surface under the cumulative ranking curve (SUCRA). RESULTS: Seventeen studies were included in the network meta-analysis. Our data show that dasatinib was generally considered worse than the other TKIs, with SUCRA values ââfor 140 mg dasatinib of 90.3% for anaemia, 87.4% for leucopenia, 90.6% for neutropenia and 97.2% for thrombocytopenia. In addition, nilotinib was shown to be safer, with SUCRA values ââfor 600 and 800 mg doses of 21.9 and 35.8% for anaemia, 23.8 and 14.6% for leucopenia, 33.0 and 17.7% for neutropenia, and 28.7 and 32.6% for thrombocytopenia, respectively. CONCLUSION: Dasatinib appeared as the least safe drug for chronic myeloid leukaemia, probably because it binds to multiple key kinase targets, being more prone to cause serious haematological adverse events. Nilotinib demonstrated a safer profile, mostly due to its selective binding capacity.
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Antineoplásicos/efeitos adversos , Doenças Hematológicas/induzido quimicamente , Inibidores de Proteínas Quinases/efeitos adversos , Antineoplásicos/administração & dosagem , Teorema de Bayes , Doenças Hematológicas/epidemiologia , Doenças Hematológicas/fisiopatologia , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como AssuntoAssuntos
Hiperidrose , Temperatura Cutânea , Simpatectomia , Termografia , Humanos , Hiperidrose/cirurgia , Hiperidrose/fisiopatologia , Criança , Masculino , Feminino , Temperatura Cutânea/fisiologia , Simpatectomia/métodos , Termografia/métodos , Seguimentos , Adolescente , Vértebras Torácicas/cirurgiaRESUMO
OBJECTIVES: Limited studies have assessed the financial benefit of professional pharmacy services (PPSs) to the community pharmacy as a business. These studies are crucial in developing an insight into the long-term sustainability and broader implementation of services. We reviewed the literature to identify measures and indicators used to assess the financial performance of professional services in community pharmacy. DATA SOURCES: The literature search was undertaken in Pubmed and Scopus, and a gray literature search was performed in Google.com. References of the included papers were reviewed for other relevant studies. STUDY SELECTION: Articles were reviewed against the following exclusion criteria: 1) literature reviews, 2) studies not reporting quantitative financial data from community pharmacy, 3) studies not assessing a PPS, 4) studies lacking a methodology for the measurement and assessment of financial outcomes, and 5) cost-effectiveness analysis, cost-utility analysis, or cost-benefit analysis studies. DATA EXTRACTION: A piloted data extraction form was used. A selection of key data collected is as follows: 1) method of data collection and calculation, 2) currency, limitations for cost and revenue and method of data collection and method of calculation, 3) standardized currency value for the results reported, 4) professional services: number assessed, type of service, name of services, nature of services, implementation stage reported, financial result, the frequency of service, costs, sources of revenue, net total cost, net total revenue, break-even point, break-even price, net profit and loss. RESULTS: The 21 studies included used different methodologies and indicators to financially assess PPSs. This has led to the development of a model for assessing PPSs composed of the key financial elements identified in this systematic review. CONCLUSION: From this review, we propose a model that provides a structured approach for pharmacists to manage the financial performance of services.
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Serviços Comunitários de Farmácia/economia , Modelos Econômicos , HumanosRESUMO
BACKGROUND: Acromegaly results from the hypersecretion of growth hormone. Because of the low incidence rates of this disease worldwide, few clinical trials evaluating drug treatments have been conducted. OBJECTIVES: To conduct the first network meta-analysis simultaneously comparing all available drugs used in acromegaly treatment so as to provide more robust evidence in this field. METHODS: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane Collaboration recommendations (PROSPERO database under the registration number CRD42017059880). The electronic searches were conducted in PubMed (MEDLINE), Scopus, and Web of Science databases. Randomized controlled trials comparing any drug for the treatment of acromegaly head-to-head or versus placebo were included. Outcomes concerning the efficacy and safety of treatments were evaluated. The statistical analyses were performed using Aggregate Data Drug Information System version 1.16.8 (drugis.org, Groningen, The Netherlands). RESULTS: The initial search retrieved 2059 articles. Of these, 10 randomized controlled trials were included in a qualitative analysis and 7 in a quantitative analysis. The network meta-analysis for the efficacy outcome (number of patients achieving insulinlike growth factor 1 control) showed that pegvisomant and lanreotide autogel were statistically superior to placebo (odds ratio [95% credible interval] 0.06 [0.00-0.55] and 0.09 [0.01-0.88]). No further differences were found. The probability rank indicated that pegvisomant and pasireotide have the highest probabilities (33% and 34%, respectively) of being the best therapeutic options. No major side effects were noted. CONCLUSIONS: Pegvisomant is still a good option for acromegaly treatment, but pasireotide seems to be a promising alternative. Nevertheless, other important key factors such as drug costs and effectiveness (real-world results) should be taken into account when selecting acromegaly treatment.
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Acromegalia/tratamento farmacológico , Antagonistas de Hormônios/uso terapêutico , Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/metabolismo , Peptídeos Cíclicos/uso terapêutico , Receptores da Somatotropina/antagonistas & inibidores , Somatostatina/análogos & derivados , Acromegalia/metabolismo , Acromegalia/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Antagonistas de Hormônios/efeitos adversos , Hormônio do Crescimento Humano/efeitos adversos , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos Cíclicos/efeitos adversos , Receptores da Somatotropina/metabolismo , Somatostatina/efeitos adversos , Somatostatina/uso terapêutico , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: Although randomized controlled trials (RCTs) are the gold standard for the assessment of clinical outcomes, long-term extension trials (LTEs) and observational cohorts may help generate evidence. Our goal was to compare the discontinuation rates of abatacept, rituximab, and tocilizumab in rheumatoid arthritis (RA) reported in different study designs. METHODS: A systematic review was conducted with searches in PubMed, Scopus, and the Cochrane Library, plus a manual search, for RCTs, LTEs, and observational cohorts reporting discontinuation rates by any of three causes (all-cause, inefficacy, adverse events). Meta-analyses with sensitivity analyses and meta-regressions were conducted. RESULTS: Of the 111 studies included, 74 were RCTs (n = 55) or LTEs (n = 17) reporting data on abatacept (n = 33), rituximab (n = 10), and tocilizumab (n = 31) and 37 were observational cohort studies (abatacept = 11, rituximab = 8, tocilizumab = 18). The follow-up duration did not differ among the study designs. Discontinuation rates were similar among the drugs but varied among the study designs. Discontinuation rates were significantly higher in cohort studies than those in interventional studies for the three drugs. Sensitivity analyses could not identify patient characteristics associated with these differences. Meta-regression analyses demonstrated no correlation between study follow-up duration and discontinuation rates. CONCLUSIONS: The discontinuation rates reported for non-anti-TNF drugs varied relative to the study design in which they were investigated. Regulatory agencies, price-setting entities, and evidence-gathering researchers should consider the effect of the real-life environment in their decisions and conclusions.
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Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Projetos de Pesquisa , Abatacepte/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Rituximab/administração & dosagemRESUMO
OBJECTIVE: Pharmacists have adopted an active role in asthma management. This review aimed to analyze the intervention dose, understood as the "amount of program delivered," and core components of the intervention provided by pharmacists in asthma management. DATA SOURCES: A literature search was conducted in December 2016 using PubMed. STUDY SELECTION: A 2-stage approach was used. At the first stage, systematic reviews of pharmacists' interventions in asthma management were identified. At the second stage, primary studies included in the systematic reviews were selected. DATA EXTRACTION: The DEPICT-2 (Descriptive Elements of Pharmacist Intervention Characterization Tool) was used for data extraction. In addition GINA (Global Initiative for Asthma) guidelines were used as a reference to classify the interventions' core components. RESULTS: Thirty-one studies were included. In most of the studies, the pharmacist-patient intervention occurred at the community pharmacy setting (n = 22). The most common core components used in pharmacists' interventions were the provision of drug information and patient counseling (n = 27). Pharmacists' interventions frequently were targeted at assessing and improving the use of patient's inhaler technique (n = 27). Educational materials and written action plans were the materials most commonly used in the interventions (n = 20). The duration (n = 13) and the frequency (n = 16) of the intervention were the most frequent information about the intervention dose measure reported. CONCLUSION: Pharmacists' interventions in asthma management are complex. Structured educational programs and patient counseling appear to be the most frequent core components of pharmacists' interventions. Interventions were focused on providing information about the condition and on inhaler technique assessment and training. However, most studies failed to report the intervention dose sufficiently to be reproduced. The reporting of this indicator is crucial to ensure the reproducibility of the interventions assessed and their implementation in practice. (Registration number CRD42016029181.).
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Asma/tratamento farmacológico , Serviços Comunitários de Farmácia/normas , Farmácias/normas , Farmacêuticos/normas , Humanos , Papel ProfissionalRESUMO
PURPOSE: This study aimed to compare the efficacy among direct-acting antiviral agents (first and second-generation direct-acting antiviral agents (DAAs)) with placebo and with standard dual therapy (pegylated interferon + ribavirin (Peg-IFN + RBV)) in terms of rapid virologic response (RVR) and sustained virologic response (SVR) in chronic hepatitis C genotype 1 treatment. METHODS: We performed a systematic review of randomized controlled trials (RCTs) in MEDLINE, International Pharmaceutical Abstracts, Cochrane Library, SCIELO, and Scopus and conducted a network meta-analysis to compare the efficacy of boceprevir (BOC), daclatasvir (DCV), grazoprevir, simeprevir (SMV) and telaprevir (TVR), in treatment-naive and treatment-experienced patients. RESULTS: Sixteen studies encompassing 7171 patients were analysed. Associations between DAAs therapies (IFN-free regimens) could not be addressed since no common comparator was found in the RCTs among these associations and the other agents included in the present analysis. All agents were more efficacious than placebo or Peg-IFN + RBV in terms of RVR, while only BOC and SMV showed statistically significant superiority for the SVR outcome when compared to placebo or standard dual therapy. No significant differences between the DAAs were observed. The analysis prioritized treatment with DCV for both efficacy outcomes. Node-splitting analysis showed that our networks are robust (p > 0.05). CONCLUSIONS: The superiority of DAAs over placebo or standard dual therapy with Peg-IFN + RBV was confirmed, indicating the greater efficacy of DCV. This study is the first network meta-analysis that included RVR as an outcome in the evaluation of these agents via indirect comparison. Further investigation should be carried out addressing safety and tolerability outcomes.
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Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Inibidores de Proteases/uso terapêutico , Genótipo , Humanos , Interferons/uso terapêutico , Metanálise em Rede , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Resposta Viral SustentadaRESUMO
Invasive fungal infections, an important cause of mortality, are primarily treated using amphotericin B, which is available in different formulations, both conventional and lipid-based (liposomal, lipid complex, colloidal dispersion and Intralipid® infusion). The aim of our study was to determine the efficacy and safety of conventional amphotericin B vs its lipid-based formulations. A systematic review followed by pairwise meta-analysis was performed, including randomised controlled trials (RCTs) that evaluated the use of lipid-based amphotericin B in patients with any degree of immunosuppression and susceptibility to invasive fungal infection. An electronic search was conducted using PubMed, Scopus, Web of Science and Scielo databases. Extracted outcomes were related to efficacy (cure) and safety (incidence of adverse events). Results were evaluated and meta-analyses were performed. Twenty-three RCTs were identified (n=2677 participants) for meta-analysis. No significant differences between conventional amphotericin B and any of the five formulations evaluated were observed, with regard to the efficacy analysis. With respect to the adverse events of nephrotoxicity, fever, chills and vomiting, all lipid formulations presented better profiles than the conventional formulation. The present systematic review and meta-analysis showed that conventional amphotericin B presents the same efficacy profile as lipid-based formulations, although the latter were associated with a safer profile.
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Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Infecções Fúngicas Invasivas/tratamento farmacológico , Anfotericina B/efeitos adversos , Anfotericina B/uso terapêutico , Antifúngicos/efeitos adversos , Antifúngicos/uso terapêutico , Ensaios Clínicos como Assunto , Coloides , Composição de Medicamentos , Emulsões , Febre , Humanos , Infecções Fúngicas Invasivas/microbiologia , Infecções Fúngicas Invasivas/mortalidade , Lipídeos , Fosfolipídeos , Óleo de SojaRESUMO
The aim of this study was to create a standard set of essential drug information items as a tool to assess the completeness of any type of drug information source, regardless of its length, using a Delphi consensus panel of European health care professionals. A compilation of drug-related information items was performed by searching several resources for health care professionals and a final list of 162 items was obtained. Fifty-seven experts in drug information from 23 different European countries were invited to participate in a three-round Delphi technique to obtain consensus on items considered essential and non-essential content of information. Consensus for the first, second, and third rounds was defined as ≥90%, ≥80%, and ≥75% agreement, respectively. Of the 57 experts invited, 32 completed the first round, 27 the second, and 29 the third. Consensus was achieved for 28.3% of the items in the first round, 49.3% in the second, and 58.3% in the third. The final cumulative consensus was 67.7% (n = 126) for items considered essential and 16.1% (n = 30) for items considered non-essential. The final tool obtained to assess the completeness of drug information sources was composed by 126 essential items grouped into 11 sections. This tool allows for the comparison of different information sources for the same medicine and the information content for different medicines in the same source.
Assuntos
Técnica Delphi , Disseminação de Informação , Inquéritos e Questionários , Consenso , Europa (Continente) , Pessoal de Saúde , HumanosRESUMO
The objective of this systematic review was to evaluate the impact of pharmacists' interventions on clinical asthma outcomes on adult patients and to identify the outcome indicators used.PubMed, Scopus, Web of Science and Scielo were searched. Studies addressing pharmacists' interventions on adult asthma patients reporting clinical asthma outcomes were incorporated.11 clinical outcomes were identified in 21 studies. 10 studies measured the impact of the intervention on asthma control. Randomised controlled trials (RCT) and non-RCTs found positive results in percentages of controlled patients and Asthma Control Questionnaire (ACQ) scores. Discordant results were found for Asthma Control Test results. Asthma severity was assessed in four studies. One RCT found a significant decrease in the percentage of severe patients; two non-RCTs found significant improvements in severity scores. 11 studies reported pulmonary function indicators, showing inconsistent results. Eight studies measured asthma symptoms; three RCTs and four non-RCTs showed significant improvements.RCTs and non-RCTs generated similar results for most outcomes. Based on the evidence generated by RCTs, pharmacists' have a positive impact on the percentage of controlled patients, ACQ scores, severity and symptoms. Future research should report using the core outcome set of indicators established for asthma (PROSPERO CRD42014007019).