Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 175
Filtrar
1.
Eur J Cancer Care (Engl) ; 28(4): e13034, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30968997

RESUMO

OBJECTIVE: Real-world evidence data on the use of granulocyte colony-stimulating factor (G-CSF) in patients with non-small cell lung cancer (NSCLC) are limited. MONITOR-GCSF is a pan-European, multicentre, prospective, non-interventional study designed to describe patient characteristics, treatment patterns and clinical outcomes in patients receiving biosimilar filgrastim in the prophylaxis of chemotherapy-induced neutropaenia (CIN) and febrile neutropaenia (FN). METHODS: In this subanalysis, patient characteristics, treatment patterns, and outcomes are described for 345 patients with stage 3 or 4 NSCLC, receiving up to six chemotherapy cycles. Patients were treated with biosimilar filgrastim as per their treating physician's best judgement. RESULTS: CIN (any grade) occurred in 13.6% of patients in Cycle 1 and in 36.5% of patients in all cycles. FN occurred in 1.4% of patients in Cycle 1 and in 5.2% of patients in all cycles. Grade 3-4 FN occurred in 1.2% of patients in Cycle 1 and in 3.8% of patients in all cycles. CONCLUSION: Results show that in real-life practice in patients with NSCLC, biosimilar filgrastim has similar effectiveness and safety to the known effectiveness and safety profile of reference filgrastim, supporting the use of biosimilar filgrastim for the real-world treatment of neutropaenia in patients with NSCLC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neutropenia Febril Induzida por Quimioterapia/prevenção & controle , Filgrastim/uso terapêutico , Fármacos Hematológicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Artralgia/induzido quimicamente , Carcinoma Pulmonar de Células não Pequenas/patologia , Tosse/induzido quimicamente , Substituição de Medicamentos , Feminino , Gastroenterite/induzido quimicamente , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mialgia/induzido quimicamente , Dor/induzido quimicamente , Resultado do Tratamento
2.
Mol Nutr Food Res ; 63(8): e1800720, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30656830

RESUMO

SCOPE: Intestinal dysfunction consists of a defective barrier function, which allows the influx of luminal endotoxins, thus causing intestinal inflammation. Proanthocyanidins are natural bioactive compounds that could modulate intestinal dysfunction. This study analyzes the protective effects of proanthocyanidins in a rat model of intestinal dysfunction. METHODS AND RESULTS: To investigate the preventive effects of both high dietary (75 mg kg-1 body weight) and pharmacological (375 mg kg-1 body weight) oral doses of proanthocyanidins (GSPE), rat intestinal dysfunction is induced with LPS (i.p.). In vivo intestinal permeability (ovalbumin [OVA] assay) and systemic inflammation and endotoxemia (TNF-α and LPS plasma levels) are assessed. Intestinal inflammation and oxidative stress are determined using myeloperoxidase (MPO), cyclooxygenase-2 (COX-2) activities, and reactive oxygen species (ROS) levels, respectively. Ileal gene expression of permeability/inflammatory genes is analyzed. LPS administration induces intestinal permeability, inflammation, and oxidative stress. GSPE normalizes in vivo OVA levels. In the small intestine, the GSPE treatment decreases MPO and COX-2 activities; modulates the ileum inflammatory and permeability proteins gene expression; and in the large intestine, prevents increase of ROS levels. CONCLUSIONS: Proanthocyanidins, at nutritional and pharmacological doses, prevents endotoxin-induced-intestinal inflammation, permeability, and oxidative stress in rats differentially in each intestinal section. Proanthocyanidins are nutritional-therapeutic novel candidates for preventing intestinal dysfunction.


Assuntos
Gastroenterite/prevenção & controle , Extrato de Sementes de Uva/farmacologia , Intestinos/efeitos dos fármacos , Proantocianidinas/farmacologia , Administração Oral , Animais , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Gastroenterite/induzido quimicamente , Gastroenterite/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Extrato de Sementes de Uva/administração & dosagem , Lipopolissacarídeos/toxicidade , Masculino , Ovalbumina/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Permeabilidade , Proantocianidinas/administração & dosagem , Substâncias Protetoras/farmacologia , Ratos Wistar
5.
Adv Healthc Mater ; 7(13): e1701313, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29388390

RESUMO

With the increasing production and widespread potential applications of single-walled carbon nanotubes (SWCNTs), the possible impacts of oral administration of SWCNTs on gastrointestinal tract at currently occupational exposure limits and potential biomedical applications should be concerned. To address the concerns, mice are orally administrated of SWCNTs at doses of 0.05, 0.5, and 2.5 mg kg-1 body weight per day for 7 d. The investigation shows that SWCNT treatment had promoted intestinal injuries at the acute dose of 2.5 mg kg-1 per day, including increase of histological lesion scores, intestinal permeability, and proinflammatory cytokine (IL-1ß, IL-6, and TNF-α) secretion. Analysis of gut microbiota composition using 16S rRNA gene sequencing approach reveals that acute oral administration of SWCNTs induces significant shifts of the predominant microbe phyla from Firmicutes to Bacteroidetes and increases abundance of proinflammatory bacteria Alitipes_uncultured_bacterium and Lachnospiraceae bacterium A4. These notable findings suggest that SWCNT-induced intestinal injury is linked to SWCNT interaction with intestinal tract and gut bacteria and the consequent triggering of "metabolic inflammation" responses. Furthermore, the study has shown that oral administration of carbon nanomaterials, including SWCNTs, multiwalled CNTs, and graphene oxide, can lead to different inflammatory responses and specific alteration in gut microbiota in mice.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Nanotubos de Carbono , Administração Oral , Animais , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Gastroenterite/induzido quimicamente , Gastroenterite/metabolismo , Gastroenterite/patologia , Microbioma Gastrointestinal/fisiologia , Grafite/administração & dosagem , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Masculino , Camundongos Endogâmicos ICR , Microscopia de Força Atômica , Nanotubos de Carbono/efeitos adversos , Nanotubos de Carbono/química , Permeabilidade , RNA Ribossômico 16S
6.
Environ Pollut ; 235: 322-329, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29304465

RESUMO

Microplastic (MP) are environmental pollutants and have the potential to cause varying degrees of aquatic toxicity. In this study, the effects on gut microbiota of adult male zebrafish exposed for 14 days to 100 and 1000 µg/L of two sizes of polystyrene MP were evaluated. Both 0.5 and 50 µm-diameter spherical polystyrene MP increased the volume of mucus in the gut at a concentration of 1000 µg/L (about 1.456 × 1010 particles/L for 0.5 µm and 1.456 × 104 particles/L for 50 µm). At the phylum level, the abundance of Bacteroidetes and Proteobacteria decreased significantly and the abundance of Firmicutes increased significantly in the gut after 14-day exposure to 1000 µg/L of both sizes of polystyrene MP. In addition, high throughput sequencing of the 16S rRNA gene V3-V4 region revealed a significant change in the richness and diversity of microbiota in the gut of polystyrene MP-exposed zebrafish. A more in depth analysis, at the genus level, revealed that a total of 29 gut microbes identified by operational taxonomic unit (OTU) analysis were significantly changed in both 0.5 and 50 µm-diameter polystyrene MP-treated groups. Moreover, it was observed that 0.5 µm polystyrene MP not only increased mRNA levels of IL1α, IL1ß and IFN but also their protein levels in the gut, indicating that inflammation occurred after polystyrene MP exposure. Our findings suggest that polystyrene MP could induce microbiota dysbiosis and inflammation in the gut of adult zebrafish.


Assuntos
Disbiose/veterinária , Doenças dos Peixes/induzido quimicamente , Poliestirenos/toxicidade , Peixe-Zebra , Animais , Bacteroidetes/efeitos dos fármacos , Disbiose/induzido quimicamente , Gastroenterite/induzido quimicamente , Gastroenterite/veterinária , Masculino , Tamanho da Partícula , Poliestirenos/química , Proteobactérias/efeitos dos fármacos , RNA Ribossômico 16S/genética , Peixe-Zebra/genética
7.
Ter Arkh ; 90(8): 95-100, 2018 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-30701943

RESUMO

The review analyzes the main etiological and pathogenetic mechanisms of the development of NSAID-enteropathy. Particular attention is paid to the role of intestinal microbiota in the manifestation and progression of NSAID-enteropathy. The special role of probiotics in the prevention and treatment of NSAIDs enteropathy is considered.


Assuntos
Anti-Inflamatórios não Esteroides/toxicidade , Gastroenterite/induzido quimicamente , Úlcera Péptica/induzido quimicamente , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/microbiologia , Gastroenterite/microbiologia , Gastroenterite/prevenção & controle , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Microbiota/efeitos dos fármacos , Úlcera Péptica/microbiologia , Úlcera Péptica/prevenção & controle , Probióticos/uso terapêutico
8.
Support Care Cancer ; 25(10): 3075-3083, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28447222

RESUMO

INTRODUCTION: Currently, there is no adequate prevention or treatment for both oral and gastrointestinal mucositis induced by chemotherapy and/or radiotherapy. Supportive care of symptoms plays a primary role during mucositis in the pediatric clinical setting. We aimed to get insight in the currently used feeding strategies in clinical practice in pediatric cancer patients with chemotherapy-induced mucositis. METHODS: A prospective observational study was performed to identify feeding strategies after chemotherapy courses causing mucositis in almost all patients at the University Medical Center Groningen (UMCG), the Academic Medical Center Amsterdam (AMC), and the Princess Maxima Center Utrecht (PMC). Consecutive patients, aged 0-18 years, either diagnosed with B cell non-Hodgkin lymphoma (B-NHL) or scheduled for autologous stem cell transplantation (SCT) between April 2015 and September 2016 were included in this study. In addition to the observational study in the Netherlands, an international online questionnaire was conducted for pediatric oncology centers. RESULTS: A total of 13 patients were included, after 21 chemotherapy courses. No nutritional support was administered after 23.8% courses, tube feeding after 19.0% of the courses, TPN in 19.0% of courses, and 38.1% received a combination of tube feeding and TPN. The international survey revealed that 63.2% of the centers administered tube feeding as first choice, 31.6% administered only TPN as first choice, and one center administered a combination as first choice. CONCLUSIONS: There is a variability in feeding strategies in the clinical practice both in the Netherlands as well as worldwide. This study is a basis for future studies in this important clinical field to develop clinical trials comparing tube feeding and TPN both in adult and pediatric patients.


Assuntos
Antineoplásicos/efeitos adversos , Gastroenterite/induzido quimicamente , Gastroenterite/dietoterapia , Mucosite/induzido quimicamente , Mucosite/dietoterapia , Neoplasias/dietoterapia , Terapia Nutricional/métodos , Adolescente , Idade de Início , Criança , Pré-Escolar , Feminino , Humanos , Quimioterapia de Indução/efeitos adversos , Lactente , Recém-Nascido , Internacionalidade , Masculino , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Países Baixos/epidemiologia
9.
Eur J Endocrinol ; 176(6): 715-725, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28292927

RESUMO

OBJECTIVE: To investigate the long-term safety and tolerability of a once-daily, dual-release hydrocortisone (DR-HC) tablet as oral glucocorticoid replacement therapy in patients with primary adrenal insufficiency (AI). DESIGN: Prospective, open-label, multicenter, 5-year extension study of DR-HC conducted at five university clinics in Sweden. METHODS: Seventy-one adult patients diagnosed with primary AI who were receiving stable glucocorticoid replacement therapy were recruited. Safety and tolerability outcomes included adverse events (AEs), intercurrent illness episodes, laboratory parameters and vital signs. Quality of life (QoL) was evaluated using generic questionnaires. RESULTS: Total DR-HC exposure was 328 patient-treatment years. Seventy patients reported 1060 AEs (323 per 100 patient-years); 85% were considered unrelated to DR-HC by the investigator. The most common AEs were nasopharyngitis (70%), fatigue (52%) and gastroenteritis (48%). Of 65 serious AEs reported by 32 patients (20 per 100 patient-years), four were considered to be possibly related to DR-HC: acute AI (n = 2), gastritis (n = 1) and syncope (n = 1). Two deaths were reported (fall from height and subarachnoid hemorrhage), both considered to be unrelated to DR-HC. From baseline to 5 years, intercurrent illness episodes remained relatively stable (mean 2.6-5.4 episodes per patient per year), fasting plasma glucose (0.7 mmol/L; P < 0.0001) and HDL cholesterol (0.2 mmol/L; P < 0.0001) increased and patient-/investigator-assessed tolerability improved. QoL total scores were unchanged but worsening physical functioning was recorded (P = 0.008). CONCLUSIONS: In the first prospective study evaluating the long-term safety of glucocorticoid replacement therapy in patients with primary AI, DR-HC was well tolerated with no safety concerns observed during 5-year treatment.


Assuntos
Doença de Addison/tratamento farmacológico , Glucocorticoides/uso terapêutico , Terapia de Reposição Hormonal/métodos , Hidrocortisona/uso terapêutico , Adulto , Idoso , Preparações de Ação Retardada , Fadiga/induzido quimicamente , Feminino , Gastroenterite/induzido quimicamente , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Nasofaringite/induzido quimicamente , Qualidade de Vida , Suécia , Resultado do Tratamento
10.
Exp Biol Med (Maywood) ; 242(1): 102-112, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27590499

RESUMO

The pulmonary and intestinal systems have several characteristics in common. It is believed that these similarities somehow function to cause pulmonary-intestinal crosstalk during inflammation. Many studies have shown that pulmonary disease occurs in association with inflammatory bowel disease more often than is commonly recognized. Bambusae Caulis in Taeniam, a medicinal herb originated from the inner bark of Phyllostachys nigra var. henosis (Milford) Rendle (Poaceae), has been used to cure fever, diarrhea, and chest inflammation in Korea as well as in China. Cigarette smoke is a well-known risk factor for several inflammatory disorders. In this study, we induced pulmonary and bowel inflammation in mice using cigarette smoke and investigated whether Bambusae Caulis in Taeniam extract modulates the inflammatory response in both the lung and the bowel. C57BL/6 mice were exposed to cigarette smoke for 90 min per day for three weeks, and Bambusae Caulis in Taeniam extract was administered via oral injection 2 h before cigarette smoke exposure. The bronchoalveolar lavage cells were counted and hematoxylin and eosin staining were performed. Levels of inflammatory mediators in lung and large intestine were determined by enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and Western blotting. Our results showed that Bambusae Caulis in Taeniam attenuated cigarette smoke-induced inflammatory response in both the lung and the bowel of mice by inhibiting the production of pro-inflammatory cytokines, chemokines, and protease as well as NF-κB signaling factor. Therefore, we suggest that Bambusae Caulis in Taeniam extract might be a candidate therapeutic agent for inhibiting pulmonary and intestinal inflammation.


Assuntos
Bambusa/química , Gastroenterite/tratamento farmacológico , Extratos Vegetais/farmacologia , Pneumonia/tratamento farmacológico , Fumar/efeitos adversos , Animais , Peso Corporal/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar/química , Quimiocinas/metabolismo , Cromatografia Líquida de Alta Pressão , Colo/efeitos dos fármacos , Colo/patologia , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Gastroenterite/induzido quimicamente , Gastroenterite/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Camundongos Endogâmicos C57BL , Extratos Vegetais/análise , Pneumonia/induzido quimicamente , Pneumonia/patologia
11.
Benef Microbes ; 8(2): 179-192, 2017 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-28008784

RESUMO

Ageing and physiological functions of the human body are inversely proportional to each other. The gut microbiota and host immune system co-evolve from infants to the elderly. Ageing is accompanied by a decline in gut microbial diversity, immunity and metabolism, which increases susceptibility to infections. Any compositional change in the gut is directly linked to gastrointestinal disorders, obesity and metabolic diseases. Increase in opportunistic pathogen invasion in the gut like Clostridium difficile leading to C. difficile infection is more common in the elderly population. Frequent hospitalisation and high prevalence of nosocomial infections with the ageing is also well documented. Long-term utilisation of broad-spectrum antibiotic therapy is being followed in order to control these infections. Nosocomial infections and antibiotic therapy in combination or alone is leading to gastroenteritis followed by Clostridium associated diarrhoea or antibiotic associated diarrhoea. Above all, use of broad-spectrum antibiotics is highly debated all over the world due to growing antimicrobial resistance. The use of narrow spectrum antibiotics could be helpful to some extent. Dietary supplementation of probiotics with prebiotics (synbiotics) or without prebiotics has improved gut commensal diversity and regulated the immune system. The recent emergence of faecal microbiota transplantation has played an important role in treating recurrent Clostridium associated diarrhoea. This review focuses on various therapeutic interventions for gut dysbiosis and gastrointestinal diseases in the elderly. The possible mechanism for antimicrobial resistance and mechanism of action of probiotics are also discussed in detail.


Assuntos
Disbiose/terapia , Enterocolite Pseudomembranosa/terapia , Transplante de Microbiota Fecal , Gastroenterite/terapia , Prebióticos/administração & dosagem , Probióticos/uso terapêutico , Idoso , Envelhecimento , Antibacterianos/uso terapêutico , Clostridium difficile/efeitos dos fármacos , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Suplementos Nutricionais/microbiologia , Enterocolite Pseudomembranosa/microbiologia , Gastroenterite/induzido quimicamente , Gastroenterite/microbiologia , Microbioma Gastrointestinal , Humanos
12.
PLoS One ; 11(12): e0168618, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27997598

RESUMO

INTRODUCTION: To quantify the association between PPI use, type and dose and infectious gastroenteritis hospitalization in a population-based cohort of middle-aged and older adults. METHODS: Prospective study of 38,019 concession card holders followed up over 6 years in the Sax Institute's 45 and Up Study. Data from the baseline questionnaire were linked to prescription medication, hospitalization, notifiable disease, cancer registry and death datasets from 2006-2012. Associations between PPI use and gastroenteritis hospitalization were examined using Cox regressions with age as the underlying time variable. RESULTS: Among 38,019 participants, the median age was 69.7 years, and 57.3% were women. Compared to non-users, current PPI users were more likely to be older, and have a higher BMI. During follow-up there were 1,982 incident gastroenteritis hospitalizations (crude rate: 12.9 per 1000 person-years, 95% CI: 12.3-13.5). PPI use was significantly associated with infectious gastroenteritis hospitalization (aHR 1.4, 95% CI: 1.2-1.5). Among current users, a dose-response relationship was observed between the average daily dose (DDD) dispensed per day and infectious gastroenteritis hospitalization (Ptrend<0.001). We also observed higher rates of infectious gastroenteritis hospitalization and greater PPI use among participants with a history of chronic bowel problems (aHR 2.2, 95% CI: 1.9-2.5). There was no difference in risk by type of PPI. Recent use of H2 receptors was not associated with gastroenteritis hospitalization. CONCLUSION: PPI use is associated with an increased risk of infectious gastroenteritis hospitalization. Clinicians should be aware of this risk when considering PPI therapy.


Assuntos
Infecções Bacterianas , Gastroenterite , Hospitalização , Inibidores da Bomba de Prótons/efeitos adversos , Adulto , Idoso , Austrália/epidemiologia , Infecções Bacterianas/induzido quimicamente , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/terapia , Feminino , Seguimentos , Gastroenterite/induzido quimicamente , Gastroenterite/epidemiologia , Gastroenterite/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/administração & dosagem , Fatores de Risco
13.
Ned Tijdschr Geneeskd ; 160: D487, 2016.
Artigo em Holandês | MEDLINE | ID: mdl-27438396

RESUMO

- Proton pump inhibitors (PPIs) are among the most widely used drugs worldwide. However, some patients use them without a good indication.- Although PPIs are generally safe, there is an increasing number of signals of potentially serious side effects.- This article gives an overview of the incidence and prevalence of the following side effects: gastroenteritis, respiratory tract infections, hypomagnesaemia, renal function disorders, vitamin B12 and iron deficiency, dementia, osteoporosis and fractures.- It is important to prescribe a PPI only when there is a good indication for use. Patients with chronic PPI use should be checked periodically to see whether there is still an indication.- If any of the listed side effects should occur, it is advisable to consider PPI as a possible cause.


Assuntos
Antiulcerosos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Inibidores da Bomba de Prótons/efeitos adversos , Antiulcerosos/administração & dosagem , Esquema de Medicação , Fraturas Ósseas/induzido quimicamente , Gastroenterite/induzido quimicamente , Humanos , Inibidores da Bomba de Prótons/administração & dosagem , Medição de Risco , Fatores de Risco , Deficiência de Vitamina B 12/induzido quimicamente
15.
Rheumatology (Oxford) ; 55(8): 1499-506, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27143789

RESUMO

OBJECTIVE: Anakinra is approved for the treatment of RA and cryopyrin-associated periodic syndromes (CAPS). While the anakinra safety profile is well established in RA, the long-term safety profile in severe CAPS is less well documented and will therefore be discussed in this report. METHODS: A prospective, open-label, single centre, clinical cohort study was conducted at the National Institutes of Health in the USA, from 2003 to 2010, investigating the efficacy and safety of anakinra treatment for up to 5 years in 43 patients with CAPS. Safety was evaluated using adverse event (AE) reports, laboratory assessments, vital signs and diary reports. RESULTS: In total, 1233 AEs were reported during the study, with a yearly rate of 7.7 AEs per patient. The event rate decreased over time, and dose escalation during the study did not affect AE frequency. Anakinra had similar safety profiles in adults and children. The most frequently reported AEs were typical CAPS disease symptoms such as headache and arthralgia. Injection site reactions occurred mainly during the first month of anakinra treatment. In total, 14 patients experienced 24 serious AEs (SAEs), all of which resolved during the study period. The most common types of SAEs were infections such as pneumonia and gastroenteritis. There were no permanent discontinuations of treatment due to AEs. CONCLUSION: In this study anakinra treatment of patients with severe CAPS for up to 5 years was safe and well tolerated both in paediatric and adult patients, with most AEs emerging during the first months after treatment initiation. TRIAL REGISTRATION: ClincialTrials.gov, clinicaltrials.gov, NCT00069329.


Assuntos
Antirreumáticos/efeitos adversos , Síndromes Periódicas Associadas à Criopirina/tratamento farmacológico , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Adolescente , Adulto , Antirreumáticos/administração & dosagem , Artralgia/induzido quimicamente , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Gastroenterite/induzido quimicamente , Transtornos da Cefaleia/induzido quimicamente , Humanos , Injeções Subcutâneas , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Pneumonia/induzido quimicamente , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
16.
Eur J Epidemiol ; 31(10): 1057-1063, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26960438

RESUMO

An association between proton pump inhibitor (PPI) therapy and bacterial gastroenteritis has been suggested as well as contradicted. The aim of this study was to examine the association between the use of PPIs and occurrence of bacterial gastroenteritis in the prospective Rotterdam Study. The Rotterdam Study is a population-based cohort study among 14,926 subjects aged 45 years and older with up to 24 years of follow-up. Analyses were performed with a generalized estimating equations method in participants who handed-in a diagnostic stool sample. Furthermore, a nested case-control analysis was performed using the total cohort as a reference group. A bacterial microorganism was isolated in 125 samples, whereas 1174 samples were culture negative. In the generalized estimating equations analysis, we found that participants with a bacterial gastroenteritis were more likely than controls to be current users of PPIs (adjusted OR 1.94; 95 % CI 1.15-3.25). Different sensitivity analyses did not change this result. A considerably higher effect was observed (adjusted OR 6.14; 95 % CI 3.81-9.91), using the total cohort as a reference in a nested case-control analysis. Current PPI therapy is associated with an increased risk of bacterial gastroenteritis. However, by reducing the risk of selection and information bias in our study design, we demonstrated that the effect is lower than previously assumed.


Assuntos
Gastroenterite/induzido quimicamente , Inibidores da Bomba de Prótons/efeitos adversos , Idoso , Infecções por Campylobacter/induzido quimicamente , Estudos de Casos e Controles , Disenteria Bacilar/induzido quimicamente , Fezes/microbiologia , Feminino , Gastroenterite/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções por Salmonella/induzido quimicamente , Yersiniose/induzido quimicamente
17.
Diabet Med ; 33(4): 511-4, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26605869

RESUMO

AIMS: Metformin is the most widely used oral anti-diabetes agent and has considerable benefits over other therapies, yet 20-30% of people develop gastrointestinal side effects, and 5% are unable to tolerate metformin due to the severity of these side effects. The mechanism for gastrointestinal side effects and their considerable inter-individual variability is unclear. We have recently shown the association between organic cation transporter 1 (OCT1) variants and severe intolerance to metformin in people with Type 2 diabetes. The aim of this study was to explore the association of OCT1 reduced-function polymorphisms with common metformin-induced gastrointestinal side effects in Type 2 diabetes. METHODS: This prospective observational cohort study included 92 patients with newly diagnosed Type 2 diabetes, incident users of metformin. Patients were genotyped for two common loss-of-function variants in the OCT1 gene (SLC22A1): R61C (rs12208357) and M420del (rs72552763). The association of OCT1 reduced-function alleles with gastrointestinal side effects was analysed using logistic regression. RESULTS: Forty-three patients (47%) experienced gastrointestinal adverse effects in the first 6 months of metformin treatment. Interestingly, the number of OCT1 reduced-function alleles was significantly associated with over two-fold higher odds of the common metformin-induced gastrointestinal side effects (odds ratio = 2.31, 95% confidence interval 1.07-5.01, P = 0.034). CONCLUSIONS: In conclusion, we showed for the first time the association between OCT1 variants and common metformin-induced gastrointestinal side effects. These results confirm recent findings related to the role of OCT1 in severe metformin intolerance, and suggest that high inter-individual variability in mild/moderate and severe gastrointestinal intolerance share a common underlying mechanism. These data could contribute to more personalized and safer metformin treatment.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Gastroenterite/induzido quimicamente , Predisposição Genética para Doença , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Transportador 1 de Cátions Orgânicos/genética , Polimorfismo Genético , Idoso , Alelos , Substituição de Aminoácidos , Bósnia e Herzegóvina , Estudos de Coortes , Feminino , Gastroenterite/genética , Gastroenterite/metabolismo , Gastroenterite/fisiopatologia , Deleção de Genes , Estudos de Associação Genética , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Transportador 1 de Cátions Orgânicos/metabolismo , Estudos Prospectivos , Índice de Gravidade de Doença , Caracteres Sexuais
18.
Rev Med Suisse ; 11(485): 1665-71, 2015 Sep 09.
Artigo em Francês | MEDLINE | ID: mdl-26540997

RESUMO

Proton pump inhibitors (PPIs) are among the most widely prescribed medications worldwide and their use is increasing. Their efficiency has been proven and the short term tolerance is good with few reversible side effects. However concerns about possible long term side effects continue to arise. This article reviews proven and potential side effects associated with PPI especially on the long term use.


Assuntos
Antiulcerosos/efeitos adversos , Refluxo Gastroesofágico/tratamento farmacológico , Inibidores da Bomba de Prótons/efeitos adversos , Antiulcerosos/administração & dosagem , Interações de Medicamentos , Medicina Baseada em Evidências , Fraturas Ósseas/induzido quimicamente , Gastroenterite/induzido quimicamente , Humanos , Infarto do Miocárdio/induzido quimicamente , Nefrite Intersticial/induzido quimicamente , Lesões Pré-Cancerosas/induzido quimicamente , Inibidores da Bomba de Prótons/administração & dosagem , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
20.
JAMA Intern Med ; 175(8): 1331-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26121537

RESUMO

IMPORTANCE: Antibiotics are frequently and often inappropriately prescribed to patients in nursing homes. These antibiotics pose direct risks to recipients and indirect risks to others residing in the home. OBJECTIVE: To examine whether living in a nursing home with high antibiotic use is associated with an increased risk of antibiotic-related adverse outcomes for individual residents. DESIGN, SETTING, AND PARTICIPANTS: In this longitudinal open-cohort study performed from January 1, 2010, through December 31, 2011, we studied 110,656 older adults residing in 607 nursing homes in Ontario, Canada. EXPOSURES: Nursing home-level antibiotic use was defined as use-days per 1000 resident-days, and facilities were classified as high, medium, and low use according to tertile of use. Multivariable logistic regression modeling was performed to assess the effect of nursing home-level antibiotic use on the individual risk of antibiotic-related adverse outcomes. MAIN OUTCOMES AND MEASURES: Antibiotic-related harms included Clostridium difficile, diarrhea or gastroenteritis, antibiotic-resistant organisms (which can directly affect recipients and indirectly affect nonrecipients), allergic reactions, and general medication adverse events (which can affect only recipients). RESULTS: Antibiotics were provided on 2,783,000 of 50,953,000 resident-days in nursing homes (55 antibiotic-days per 1000 resident-days). Antibiotic use was highly variable across homes, ranging from 20.4 to 192.9 antibiotic-days per 1000 resident-days. Antibiotic-related adverse events were more common (13.3%) in residents of high-use homes than among residents of medium-use (12.4%) or low-use homes (11.4%) (P < .001); this trend persisted even among the residents who did not receive antibiotic treatments. The primary analysis indicated that residence in a high-use nursing home was associated with an increased risk of a resident experiencing an antibiotic-related adverse event (adjusted odds ratio, 1.24; 95% CI, 1.07-1.42; P = .003). A sensitivity analysis examining nursing home-level antibiotic use as a continuous variable confirmed an increased risk of resident-level antibiotic-related harms (adjusted odds ratio, 1.004 per additional day of nursing home antibiotic use; 95% CI, 1.001-1.006; P = .01). CONCLUSIONS AND RELEVANCE: Antibiotic use is highly variable across nursing homes; residents of high-use homes are exposed to an increased risk of antibiotic-related harms even if they have not directly received these agents. Antibiotic stewardship is needed to improve the safety of all nursing home residents.


Assuntos
Antibacterianos/uso terapêutico , Hipersensibilidade a Drogas/epidemiologia , Enterocolite Pseudomembranosa/epidemiologia , Instituição de Longa Permanência para Idosos , Casas de Saúde , Padrões de Prática Médica/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Diarreia/induzido quimicamente , Diarreia/epidemiologia , Hipersensibilidade a Drogas/etiologia , Farmacorresistência Bacteriana , Enterocolite Pseudomembranosa/induzido quimicamente , Feminino , Gastroenterite/induzido quimicamente , Gastroenterite/epidemiologia , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Análise Multivariada , Ontário/epidemiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA