RESUMO
BACKGROUND/AIMS: Abexol is a mixture of primary aliphatic alcohols purified from beeswax (Apis mellifera), that produces anti-inflammatory, antioxidant and gastroprotective effects, as well as it is safe and well tolerated. To investigate and compare the efficacy and safety of Abexol (suspension versus tablets) in patients with gastrointestinal symptoms. METHODS: Monocentric study, open-label, randomized design, with two parallel groups receiving Abexol tablets (150 mg/d) or Abexol suspension (75 mg/d) for 8 weeks. Primary efficacy variable (significant improvement in the total score of Gastrointestinal Symptom Rating Scale [GSRS]). Significant reduction in the intensity of the gastrointestinal-symptoms and the reduction in the consumption of antacids are considered secondary efficacy variable. Short form-36 (SF-36) quality of life questiongenonaire was evaluated as collateral variable. Data were analyzed as per intention to treat. RESULTS: A significantly decrease in the overall score of the survey was observed with respect to the baseline level (p < 0.001) of 81.4% in the Abexol suspension group and 77.9% in the Abexol tablets group. At the end of the trial, most gastrointestinal- symptoms disappeared or reduced significantly. The frequency of consumption of neutralizing antacids was low. The significantly improvement in the perception of the state of health obtained in the Abexol is in correspondence with the improvement achieved in some of the components evaluate in the SF-36 questionnaire. Both treatments were safe and well tolerated. CONCLUSION: Abexol suspension showed efficacy and safety similar to Abexol tablets in patients with gastrointestinal symptoms, but using half the dose.
Assuntos
Antiácidos , Qualidade de Vida , Animais , Humanos , Método Duplo-Cego , Comprimidos , Resultado do TratamentoRESUMO
BACKGROUND: Despite the broad adoption of Soleris® technology in the food industry as semiquantitative method, it is almost completely unexplored in the pharmaceutical industry as a quantitative method for quantification of Burkholderia cepacia complex (Bcc). OBJECTIVE: The efficacy of an automated growth-based system for a quantitative determination of the Bcc in an antacid oral suspension was studied. The main purpose of this validation study was to prove that the alternative method's entire performance is not inferior to the conventional method for a quantitative determination of Bcc. METHOD: The antacid oral suspension's preservatives were neutralized, leading to the Burkholderia complex's recovery by means of the alternative method and the reference method. A calibration curve was generated for each strain by plotting DTs relative to the corresponding log CFU values. An equivalence of results was done through the construction of calibration curves that allowed the establishment of numerically equivalent results between the enumeration data from the reference method and the alternative method. RESULTS: Thus following the guidelines of USP, essential validation parameters were shown, such as equivalence of results (CC >0.95), linearity (R2 >0.9025), accuracy (% recovery >70%), operating range, precision and ruggedness (DS <5 and CV <35%), specificity (inclusivity and exclusivity), limit of detection (LOD), and limit of quantification (LOQ). CONCLUSIONS: It was shown that all the test results obtained from the alternative method were in statistical agreement with the standard method. Thus this new technology was found to meet all the validation criteria needed to be considered as an alternative method for the quantification of the Burkholderia complex in the antacid oral suspension tested. HIGHLIGHTS: As outlined in USP chapter <1223> and demonstrated in this research the implementation of alternative methods can offer benefits in execution and automation while improving accuracy, sensitivity, and precision and can reduce the microbiological process time compared to the traditional ones.
Assuntos
Complexo Burkholderia cepacia , Antiácidos , Limite de Detecção , AutomaçãoRESUMO
PURPOSE: Intestinal dysbiosis has emerged as a biomarker of response to immune checkpoint inhibitors (ICIs). It can be caused by antibiotics, although it may also result from the use of other drugs that have been studied to a lesser extent. The objective of our study was to analyze the association between the use of potentially dysbiosis-related drugs and survival in patients treated with ICIs in the clinical practice. MATERIALS AND METHODS: A retrospective, multicenter, cohort study was conducted. Clinicopathological variables were collected and the concomitant use of drugs was analyzed. A descriptive analysis of variables and overall survival, estimated by the Kaplan-Meier method, was performed, and association with various independent variables was assessed using Cox regression. RESULTS: We included 253 patients, mainly with non-small cell lung cancer and melanoma. The most commonly used drugs were acid reducers, prescribed to 55.3% of patients, followed by corticosteroids (37.9%), anxiolytic drugs (35.6%), and antibiotics (20.5%). The use of acid reducers (9 vs. 18 months, P < .0001), antibiotics (7 vs. 15 months, P < .017), anxiolytic drugs (8 vs. 16 months, P < .015), and corticosteroids (6 vs. 19 months, P < .00001) was associated with poorer overall survival. Furthermore, the greater the number of drugs used concomitantly with ICIs, the higher the risk of death (1 drug: hazard ratio, 1.88; CI 95%, 1.07-3.30; 4 drugs: hazard ratio, 4.19; CI9 5%, 1.77-9.92; P < .001). CONCLUSION: Response to ICIs may be influenced by the use of drugs that lead to intestinal dysbiosis. Although a confirmatory prospective controlled study is required, our findings should be taken into account when analyzing ICI efficacy.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Disbiose/induzido quimicamente , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Melanoma/tratamento farmacológico , Corticosteroides/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiácidos/efeitos adversos , Ansiolíticos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Helicobacter pylori (H. pylori) is a gram-negative bacterium that infects approximately 4.4 billion individuals worldwide. However, its prevalence varies among different geographic areas, and is influenced by several factors. The infection can be acquired by means of oral-oral or fecal-oral transmission, and the pathogen possesses various mechanisms that improve its capacity of mobility, adherence and manipulation of the gastric microenvironment, making possible the colonization of an organ with a highly acidic lumen. In addition, H. pylori presents a large variety of virulence factors that improve its pathogenicity, of which we highlight cytotoxin associated antigen A, vacuolating cytotoxin, duodenal ulcer promoting gene A protein, outer inflammatory protein and gamma-glutamyl transpeptidase. The host immune system, mainly by means of a Th1-polarized response, also plays a crucial role in the infection course. Although most H. pylori-positive individuals remain asymptomatic, the infection predisposes the development of various clinical conditions as peptic ulcers, gastric adenocarcinomas and mucosa-associated lymphoid tissue lymphomas. Invasive and non-invasive diagnostic methods, each of them with their related advantages and limitations, have been applied in H. pylori detection. Moreover, bacterial resistance to antimicrobial therapy is a major challenge in the treatment of this infection, and new therapy alternatives are being tested to improve H. pylori eradication. Last but not least, the development of effective vaccines against H. pylori infection have been the aim of several research studies.
Assuntos
Mucosa Gástrica/microbiologia , Infecções por Helicobacter/terapia , Helicobacter pylori/patogenicidade , Gastropatias/terapia , Antiácidos/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Vacinas Bacterianas/uso terapêutico , Farmacorresistência Bacteriana , Quimioterapia Combinada , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/transmissão , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/imunologia , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Probióticos/administração & dosagem , Inibidores da Bomba de Prótons/uso terapêutico , Gastropatias/diagnóstico , Gastropatias/microbiologia , Resultado do Tratamento , Fatores de Virulência/metabolismoRESUMO
BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most prevalent gastrointestinal diseases. GERD generates significant impairment in patients' quality of life and it is associated to relevant medical resources utilization. A better understanding of GERD pathophysiology in the past five decades has favored the evolution of therapeutic strategies from non-drug interventions and antacids to more efficacious and safer alternatives. OBJECTIVE: To summarize data about the historical evolution of GERD management in Brazil, focusing on medical therapy and addressing evidence on efficacy and safety of drug classes currently recommended. METHODS: A narrative review was conducted by systematizing information about discoveries on GERD pathophysiology. We also addressed efficacy and safety of medications currently used to reduce symptoms and improve endoscopic healing of esophageal lesions. A structured search on Pubmed was performed to identify systematic reviews and meta-analysis investigating GERD outcomes positively impacted by proton pump inhibitors (PPIs), the first choice of pharmacotherapy for the disease. RESULTS: The chronological development of therapeutic measures for GERD in Brazil evolved from lifestyle interventions with relative poor effect on symptoms related to esophageal acid exposure, particularly heartburn, to effective and safe pharmacological interventions such as histamine H2-receptor antagonists and PPIs. In the present days, some drug classes play a minor role in disease management, namely prokinetics and antacids, due to their reduced efficacy and relevant safety concerns (particularly with prokinetics). The main challenge for prescribers and researchers seems to be finding long-acting acid suppressants strategies able to ameliorate patients' symptoms and quality of life, thereafter, reducing medical resource consumption. The dual delayed-release PPI dexlansoprazole seems to respond for some of the limitations other PPIs have. CONCLUSION: Recognizing the historical evolution of GERD management can help care providers to better understand therapeutic options for their patients, as well as focus on unmet needs that deserve further attention. PPIs are still the first choice therapy, with good evidence in favor of their efficacy, despite some safety concerns. However, as with any medical intervention, it is recommended to prescribe PPIs for patients with clear indication, using adequate dosing and monitoring for adverse events.
Assuntos
Terapia Comportamental/métodos , Medicina Baseada em Evidências , Refluxo Gastroesofágico/terapia , Estilo de Vida , Antiácidos/uso terapêutico , Antieméticos/uso terapêutico , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Humanos , Inibidores da Bomba de Prótons/uso terapêuticoRESUMO
ABSTRACT BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most prevalent gastrointestinal diseases. GERD generates significant impairment in patients' quality of life and it is associated to relevant medical resources utilization. A better understanding of GERD pathophysiology in the past five decades has favored the evolution of therapeutic strategies from non-drug interventions and antacids to more efficacious and safer alternatives. OBJECTIVE: To summarize data about the historical evolution of GERD management in Brazil, focusing on medical therapy and addressing evidence on efficacy and safety of drug classes currently recommended. METHODS: A narrative review was conducted by systematizing information about discoveries on GERD pathophysiology. We also addressed efficacy and safety of medications currently used to reduce symptoms and improve endoscopic healing of esophageal lesions. A structured search on Pubmed was performed to identify systematic reviews and meta-analysis investigating GERD outcomes positively impacted by proton pump inhibitors (PPIs), the first choice of pharmacotherapy for the disease. RESULTS: The chronological development of therapeutic measures for GERD in Brazil evolved from lifestyle interventions with relative poor effect on symptoms related to esophageal acid exposure, particularly heartburn, to effective and safe pharmacological interventions such as histamine H2-receptor antagonists and PPIs. In the present days, some drug classes play a minor role in disease management, namely prokinetics and antacids, due to their reduced efficacy and relevant safety concerns (particularly with prokinetics). The main challenge for prescribers and researchers seems to be finding long-acting acid suppressants strategies able to ameliorate patients' symptoms and quality of life, thereafter, reducing medical resource consumption. The dual delayed-release PPI dexlansoprazole seems to respond for some of the limitations other PPIs have. CONCLUSION: Recognizing the historical evolution of GERD management can help care providers to better understand therapeutic options for their patients, as well as focus on unmet needs that deserve further attention. PPIs are still the first choice therapy, with good evidence in favor of their efficacy, despite some safety concerns. However, as with any medical intervention, it is recommended to prescribe PPIs for patients with clear indication, using adequate dosing and monitoring for adverse events.
RESUMO CONTEXTO: A doença do refluxo gastroesofágico (DRGE) é uma das doenças gastrointestinais mais prevalentes, resultando em limitações significativas na qualidade de vida dos pacientes e, também, relevante utilização de recursos médicos. Um melhor entendimento da fisiopatologia da doença nas últimas cinco décadas tem favorecido a evolução das estratégias de tratamento, desde intervenções não farmacológicas e antiácidos, a alternativas mais eficazes e seguras. OBJETIVO: Resumir os dados sobre a evolução histórica do manejo da DRGE no Brasil, focando na terapia medicamentosa e abordando evidências sobre a eficácia e segurança de classes medicamentosas atualmente recomendadas. MÉTODOS: Uma revisão narrativa foi conduzida para sistematizar informações sobre descobertas na fisiopatologia da DRGE e, também, sobre a eficácia e segurança de medicamentos utilizados atualmente para reduzir os sintomas e melhorar a cicatrização endoscópica de lesões esofágicas. Uma busca estruturada na base de dados Pubmed foi realizada para identificar revisões sistemáticas e metanálises que investigassem desfechos da doença impactados positivamente pelos inibidores da bomba de prótons (IBPs), a primeira escolha farmacológica para a doença. RESULTADOS: O desenvolvimento cronológico das medidas terapêuticas para a DRGE no Brasil evoluiu de modificações no estilo de vida que demonstraram relativamente pouco efeito sobre os sintomas relacionados à exposição esofágico ao ácido, particularmente a azia, a intervenções farmacológicas eficazes e seguras como os anti-histamínicos H2 e os IBPs. Atualmente, algumas classes de medicamentos exercem um papel menor no manejo da doença, procinéticos e antiácidos por exemplo, devido à sua eficácia reduzida e a preocupações relevantes quanto a segurança (particularmente com os procinéticos). O principal desafio para os prescritores e pesquisadores parece ser encontrar estratégias supressoras de ácidos de longa duração capazes de melhorar os sintomas e a qualidade de vida dos pacientes, reduzindo assim o consumo de recursos médicos. O dexlansoprazol, um IBP de liberação retardada dupla, parece responder a algumas limitações que outros IBPs têm. CONCLUSÃO: O reconhecimento da evolução histórica do manejo da DRGE pode auxiliar aos profissionais assistentes a melhor entender as opções terapêuticas para seus pacientes, assim como focar em necessidades não atendidas que necessitem de maior atenção. IBPs ainda são a terapia de escolha inicial, com boas evidências a favor de sua eficácia, apesar algumas questões acerca da segurança de seu uso. No entanto, assim como para qualquer intervenção medicamentosa, é recomendada a prescrição dos IBPs para pacientes com indicação clara, utilizando doses adequadas e monitorando a ocorrência de eventos adversos.
Assuntos
Humanos , Terapia Comportamental/métodos , Refluxo Gastroesofágico/terapia , Medicina Baseada em Evidências , Estilo de Vida , Inibidores da Bomba de Prótons/uso terapêutico , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Antiácidos/uso terapêutico , Antieméticos/uso terapêuticoRESUMO
INTRODUCTION: The evaluation of expectorant activity has been extensively studied in murine models, involving the secretion of phenol red in the trachea or bronchus to estimate the secretory capacity of lower airway mucosa. However, differences in the experimental protocols of several studies evidenced the need of to standardize the quantification of phenol red in the bronchoalveolar fluid (BALF). METHODS: The analytical methodology for the quantification of phenol red in the BALF was optimized by investigation of pH influence, quantity of the alkali agent added and appropriate wavelength for quantification of phenol red by UV-VIS spectroscopy. Different phenol red suspensions (0.05, 0.5, 1.25, 2.5 and 5%) were prepared and administered intraperitoneally in mice at doses 5, 25, 50, 250 or 500â¯mg/kg. RESULTS: It was shown that phenol red should be used at dose 500â¯mg/kg and intraperitoneal administration should be performed from a suspension at 1.25% (w/v). Furthermore, the alkalinizing agent of choice would be NaOH (0.1â¯M). The pharmacological validation of the analytical method showed that ambroxol (30, 60 or 120â¯mg/kg), guaifenesin (100â¯mg/kg), NH4Cl (2000â¯mg/kg) or salbutamol (4â¯mg/kg) can be used as positive controls. DISCUSSION: The phenol red quantification in the BALF is a rapid and low cost assay for the discovery of new expectorant drugs. Thus, it was proposed a standardization of the analytical and pharmacological methods to ensure the reliability of BALF processing and reproducibility of phenol red quantification for data analysis.
Assuntos
Expectorantes/química , Fenolsulfonaftaleína/química , Animais , Antiácidos/química , Brônquios/química , Líquido da Lavagem Broncoalveolar/química , Masculino , Camundongos , Modelos Animais , Preparações Farmacêuticas/química , Reprodutibilidade dos Testes , Traqueia/químicaRESUMO
Although lifestyle and physiology in obese individuals are accepted to lead to changes in the intestinal microbiota, uncertainty remains about microbiota dysbiosis, and xenobiotics intake, as a source of selective pressure, independent of antimicrobial chemotherapy. The aim of this study was to compare the occurrence of antimicrobial resistance genetic markers (ARG) in faecal specimens of eutrophic, overweight and obese individuals, and their correlation with xenobiotic intake and gut bacteria density. Methods: This was a cross-sectional case-controlled study including 72 adult participants with no record of intestinal or systemic diseases, or recent use of antimicrobials, grouped as eutrophic, overweight, or obese. Anthropometric profile, eating habits and oral xenobiotics intake were recorded. Faecal metagenomic DNA was used to screen for ARG by PCR, and to measure bacterial groups by fluorescence in situ hybridization (FISH). Student's t and Wilcoxon tests were used to compare means and differences in ARG detection (95% confidence intervals). Correlation analyses (odds ratio) and relationships between bacteria density and ARG were determined. Results: Increase in abdominal circumference, waist circumference, hip, waist-hip ratio, BMI, carbohydrate, fibres, and total calorie intakes were different from eutrophic to obese participants. Habitual use of antihypertensive and anti-inflammatory drugs, antacids, and artificial sweeteners were associated mainly with obesity and overweight. Nutritional supplements were associated to the eutrophic group. ARG screening showed differences being more frequent among obese, and positive for 27 genetic markers related to ß-lactams, tetracyclines, the macrolide lincosamide and streptogramin group, quinolones, sulfonamides, aminoglycosides, and efflux pump. Positive correlation between ARG and BMI, caloric intake, and intake of xenobiotics, was observed for obese individuals. Relationships among ARG detection and bacteria densities were also different. Conclusions: This study reinforces the hypothesis that obese individuals may harbour an altered gut microbiota, if compared to eutrophic. The overweight individuals display a transitional gut microbiota which seems to be between eutrophic and obese. Furthermore, the increased xenobiotic intake associated to obesity may play an important role in the antimicrobial resistance phenomenon.
Assuntos
Resistência Microbiana a Medicamentos/genética , Trato Gastrointestinal/microbiologia , Sobrepeso/microbiologia , Adulto , Antiácidos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Suplementos Nutricionais , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Edulcorantes/administração & dosagem , Xenobióticos/administração & dosagem , Adulto JovemRESUMO
A nationwide shortage of intravenous (IV) sodium bicarbonate required institutions to explore alternative options for urinary alkalinization for high-dose methotrexate (HDMTX). Children's Hospital Colorado implemented a protocol utilizing oral alkalinizing agents as alternatives to intravenous sodium bicarbonate during the shortage. The purpose of this study was to determine the safety and efficacy of oral alkalinization strategies for HDMTX administration. This retrospective study was conducted at a pediatric institution and evaluated cycles of HDMTX administered with at least one dose of oral sodium bicarbonate tablets or sodium citrate-citric acid oral solution. The time to achieve urine pH of ≥7 was 3.48 hours from the start of alkalinization. A median dose of 66.4 mEq/m/day of oral sodium bicarbonate was administered to maintain a urine pH of ≥7 until methotrexate was cleared. Gastrointestinal side effects occurred with 43% of HDMTX cycles and patients switched to IV sodium acetate in 25.5% of HDMTX cycles, primarily due to inadequate alkalinization or intolerance. During a shortage of IV sodium bicarbonate, oral alkalinization is an effective strategy for most patients to allow for administration of HDMTX.
Assuntos
Antiácidos/uso terapêutico , Concentração de Íons de Hidrogênio , Metotrexato/administração & dosagem , Bicarbonato de Sódio/provisão & distribuição , Urina/química , Administração Intravenosa , Antiácidos/administração & dosagem , Antiácidos/efeitos adversos , Criança , Feminino , Gastroenteropatias/induzido quimicamente , Humanos , Masculino , Metotrexato/efeitos adversos , Estudos Retrospectivos , Acetato de Sódio/administração & dosagem , Bicarbonato de Sódio/administração & dosagemRESUMO
Objetivo: realizar una revisión sistemática de la literatura para identificar los estudios que reportan la frecuencia del consumo drogas médicas, medicamentos de venta libre y alcohol, así como el consumo combinado de estas sustancias en los adultos mayores. Método: se utilizó como guía la Preferred Reporting Items for Systematic Reviews and Meta-Analyses, se identificaron 4,881 artículos a través de las bases de datos y tres artículos en el buscador google scholar, se eligieron doce estudios ya que cumplieron con los criterios de elegibilidad y por su calidad metodológica. Resultados: la revisión de la literatura permitió identificar que las drogas médicas más utilizadas fueron los benzodiacepinas, los sedantes, los antidepresivos y los psicotrópicos, los medicamentos de venta libre más usados fueron los analgésicos, laxantes, antiácidos y antihistamínicos; la combinación con el alcohol son prácticas observadas entre los adultos mayores. Conclusión: las drogas médicas y medicamentos de venta libre son consumidas para tratar los trastornos del sueño, depresión, ansiedad y estrés; con relación al alcohol entre el 20.3% y el 57.1% de los adultos mayores lo consumen; la combinación de alcohol y drogas médicas se observó entre el 9.3% y el 18.1%.(AU)
Objective: to perform a systematic review of the literature to identify the studies that report the frequency of consumption of medical drugs, over-the-counter medications and alcohol, as well as the combined use of these substances in the elderly. Method: the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes were used as a guide, 4,881 items through the databases and three items in the search google scholar were identified, twelve studies were chosen as they met the eligibility criteria and their methodological quality. Results: the literature review allowed us to identify that the most used medical drugs were benzodiazepines, sedatives, antidepressants and psychotropic drugs, the most used over-the-counter medications were analgesics, laxatives, antacids and antihistamines; the combination with alcohol are practices observed among the elderly. Conclusion: medical drugs and over-the-counter medications are consumed to treat sleep disorders, depression, anxiety and stress; in relation to alcohol between 20.3% and 57.1% of the elderly consume it; the combination of alcohol and medical drugs was observed between 9.3% and 18.1%.(AU)
Objetivo: realizar uma revisão sistemática da literatura para identificar os estudos que revelam a frequência do consumo de drogas médicas, medicamentos de venda livre e álcool, assim como o consumo combinado dessas substâncias em idosos. Método: foi utilizada como guia a Preferred Reporting Items for Systematic Reviews and MetaAnalyses, foram identificados 4,881 artigos através das bases de dados e três artigos no Navegador Google Scholar, foram selecionados doze exames já que cumpriram com os critérios de elegibilidade e pela sua qualidade metodológica. Resultados: a revisão da literatura permitiu identificar que as drogas médicas mais utilizadas foram as benzodiazepínicas, sedativos, antidepressivos e os psicotrópicos. Os medicamentos de venda livre mais usados foram os analgésicos, laxantes, antiácidos e anti-histamínicos. A combinação com o álcool é um comportamento observado nos idosos. Conclusão: as drogas médicas e medicamentos de venda livre são consumidos para o tratamento dos distúrbios do sono, depressão, ansiedade e estresse. Com relação ao álcool, entre 20.3% e 57.1% das pessoas idosas o consomem. A combinação de álcool e drogas médicas foi observada entre 9.3% e 18.1%.(AU)