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BACKGROUND & AIMS: Gastrointestinal angiodysplasias are vascular anomalies that may result in transfusion-dependent anemia despite endoscopic therapy. An individual patient data meta-analysis of cohort studies suggests that octreotide decreases rebleeding rates, but component studies possessed a high risk of bias. We investigated the efficacy of octreotide in reducing the transfusion requirements of patients with angiodysplasia-related anemia in a clinical trial setting. METHODS: The study was designed as a multicenter, open-label, randomized controlled trial. Patients with angiodysplasia bleeding were required to have had at least 4 red blood cell (RBC) units or parental iron infusions, or both, in the year preceding randomization. Patients were allocated (1:1) to 40-mg octreotide long-acting release intramuscular every 28 days or standard of care, including endoscopic therapy. The treatment duration was 1 year. The primary outcome was the mean difference in the number of transfusion units (RBC + parental iron) between the octreotide and standard of care groups. Patients who received at least 1 octreotide injection or followed standard of care for at least 1 month were included in the intention-to-treat analyses. Analyses of covariance were used to adjust for baseline transfusion requirements and incomplete follow-up. RESULTS: We enrolled 62 patients (mean age, 72 years; 32 men) from 17 Dutch hospitals in the octreotide (n = 31) and standard of care (n = 31) groups. Patients required a mean number of 20.3 (standard deviation, 15.6) transfusion units and 2.4 (standard deviation, 2.0) endoscopic procedures in the year before enrollment. The total number of transfusions was lower with octreotide (11.0; 95% confidence interval [CI], 5.5-16.5) compared with standard of care (21.2; 95% CI, 15.7-26.7). Octreotide reduced the mean number of transfusion units by 10.2 (95% CI, 2.4-18.1; P = .012). Octreotide reduced the annual volume of endoscopic procedures by 0.9 (95% CI, 0.3-1.5). CONCLUSIONS: Octreotide effectively reduces transfusion requirements and the need for endoscopic therapy in patients with angiodysplasia-related anemia. CLINICALTRIALS: gov, NCT02384122.
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Anemia , Angiodisplasia , Doenças do Colo , Idoso , Humanos , Masculino , Anemia/tratamento farmacológico , Anemia/etiologia , Angiodisplasia/complicações , Angiodisplasia/diagnóstico , Angiodisplasia/terapia , Doenças do Colo/tratamento farmacológico , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/tratamento farmacológico , Hemorragia Gastrointestinal/etiologia , Ferro , Estudos Multicêntricos como Assunto , Octreotida/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Padrão de Cuidado , FemininoRESUMO
BACKGROUND: It remains unclear whether urgent endoscopic retrograde cholangiopancreatography (ERCP) with biliary sphincterotomy improves the outcome of patients with gallstone pancreatitis without concomitant cholangitis. We did a randomised trial to compare urgent ERCP with sphincterotomy versus conservative treatment in patients with predicted severe acute gallstone pancreatitis. METHODS: In this multicentre, parallel-group, assessor-masked, randomised controlled superiority trial, patients with predicted severe (Acute Physiology and Chronic Health Evaluation II score ≥8, Imrie score ≥3, or C-reactive protein concentration >150 mg/L) gallstone pancreatitis without cholangitis were assessed for eligibility in 26 hospitals in the Netherlands. Patients were randomly assigned (1:1) by a web-based randomisation module with randomly varying block sizes to urgent ERCP with sphincterotomy (within 24 h after hospital presentation) or conservative treatment. The primary endpoint was a composite of mortality or major complications (new-onset persistent organ failure, cholangitis, bacteraemia, pneumonia, pancreatic necrosis, or pancreatic insufficiency) within 6 months of randomisation. Analysis was by intention to treat. This trial is registered with the ISRCTN registry, ISRCTN97372133. FINDINGS: Between Feb 28, 2013, and March 1, 2017, 232 patients were randomly assigned to urgent ERCP with sphincterotomy (n=118) or conservative treatment (n=114). One patient from each group was excluded from the final analysis because of cholangitis (urgent ERCP group) and chronic pancreatitis (conservative treatment group) at admission. The primary endpoint occurred in 45 (38%) of 117 patients in the urgent ERCP group and in 50 (44%) of 113 patients in the conservative treatment group (risk ratio [RR] 0·87, 95% CI 0·64-1·18; p=0·37). No relevant differences in the individual components of the primary endpoint were recorded between groups, apart from the occurrence of cholangitis (two [2%] of 117 in the urgent ERCP group vs 11 [10%] of 113 in the conservative treatment group; RR 0·18, 95% CI 0·04-0·78; p=0·010). Adverse events were reported in 87 (74%) of 118 patients in the urgent ERCP group versus 91 (80%) of 114 patients in the conservative treatment group. INTERPRETATION: In patients with predicted severe gallstone pancreatitis but without cholangitis, urgent ERCP with sphincterotomy did not reduce the composite endpoint of major complications or mortality, compared with conservative treatment. Our findings support a conservative strategy in patients with predicted severe acute gallstone pancreatitis with an ERCP indicated only in patients with cholangitis or persistent cholestasis. FUNDING: The Netherlands Organization for Health Research and Development, Fonds NutsOhra, and the Dutch Patient Organization for Pancreatic Diseases.
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Colangiopancreatografia Retrógrada Endoscópica/métodos , Tratamento Conservador/métodos , Cálculos Biliares/terapia , Pancreatite/terapia , Esfinterotomia Endoscópica/métodos , Doença Aguda , Idoso , Terapia Combinada , Feminino , Cálculos Biliares/complicações , Cálculos Biliares/etiologia , Humanos , Masculino , Resultado do TratamentoRESUMO
BACKGROUND: Gastrointestinal symptoms are frequently reported adverse effects of antidepressants, but antidepressants are also a treatment modality in functional gastrointestinal disorders. We aimed to assess the association between antidepressant use and gastrointestinal symptoms in the general adult population. METHODS: We assessed gastrointestinal symptoms, medication use, and comorbidity through structured questionnaires in randomly selected individuals. We compared presence of gastrointestinal symptoms in respondents who reported antidepressant use with those who did not. We used multivariable regression analysis to verify the association between antidepressant use and gastrointestinal symptoms. RESULTS: In total, 16,758 questionnaires were returned and eligible for analysis. Antidepressant use was reported by 701 respondents (4.2%). Gastrointestinal symptoms were more frequently reported by antidepressant users compared with nonusers (40% vs 25%, P < 0.01). This apparent association between antidepressant use and gastrointestinal symptoms did not remain after adjusting for demographic factors, comorbidity, and use of other medications (adjusted odds ratio, 0.94; 95% confidence interval, 0.74-1.18). CONCLUSIONS: In our cross-sectional population-based study, we did not find an association between antidepressant use and gastrointestinal symptoms.
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Antidepressivos/uso terapêutico , Gastroenteropatias/epidemiologia , Adulto , Idoso , Antidepressivos/efeitos adversos , Distribuição de Qui-Quadrado , Comorbidade , Estudos Transversais , Feminino , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/diagnóstico , Inquéritos Epidemiológicos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Países Baixos/epidemiologia , Razão de Chances , Medição de Risco , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Computed tomography-colonography is a diagnostic modality that can be used when the colon is not completely intubated during colonoscopy. It may have the additional advantage that information on extracolonic lesions can be obtained. OBJECTIVE: The aim of this study was to investigate the yield of CT-colonography of relevant intra- and extracolonic findings in patients after incomplete colonoscopy. DESIGN: This was an observational, retrospective study. DATA SOURCES: Data were be obtained from standardized radiology and endoscopy reports and electronic medical records. STUDY SELECTION: In total, 136 consecutive CT-colonographies performed after incomplete colonoscopy were evaluated. MAIN OUTCOME MEASURES: All intra- and extracolonic findings on CT-colonography were recorded and interpreted for clinical relevance, and it was determined whether further diagnostic and/or therapeutic workup was indicated. RESULTS: Major indications for colonoscopy included iron-deficiency anemia (25.7%), hematochezia (20.6%), change in bowel habits (18.4%), and colorectal cancer screening or surveillance (11.0%). Major reasons for incomplete colonoscopy were a fixed colon (34.6%) and strong angulation of the sigmoid colon (17.6%). Introduction of the colonoscope was limited to the left-sided colon in 53.7% of cases. Incomplete colonoscopy detected colorectal cancer in 12 (8.8%) patients and adenomatous polyps in 27 (19.9%) patients. CT-colonography after incomplete colonoscopy additionally revealed 19 polyps in 15 (11.0%) and a nonsynchronous colorectal cancer in 4 (2.9%) patients. CT-colonography also detected extracolonic findings with clinical consequences in 8 (5.9%) patients, including fistulizing diverticulitis (n = 3), gastric tumor (n = 2), liver abscess (n = 1), osteomyelitis (n = 1), and an infected embolus in both renal arteries (n = 1). LIMITATIONS: This study was limited by the lack of confirmation of intraluminal CT-colonography findings in a subset of patients. CONCLUSIONS: Computed tomography-colonography can be of added value in patients with incomplete colonoscopy, because it revealed 27 relevant additional (both intra- and extracolonic) lesions in 19.1% of patients. In cases where CT-colonography detected colorectal cancer after incomplete colonoscopy, it can also be used for staging purposes.
Assuntos
Anemia/etiologia , Pólipos do Colo/diagnóstico por imagem , Colonografia Tomográfica Computadorizada , Neoplasias Colorretais/diagnóstico por imagem , Hemorragia Gastrointestinal/etiologia , Idoso , Colonoscopia , Feminino , Hemorragia Gastrointestinal/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Patients with inflammatory bowel disease (IBD) treated with immunomodulators or biologic therapy are at increased risk of infections. Malnutrition and vitamin or mineral deficiencies are common among patients with IBD. The results of various studies have indicate that vitamin deficiencies might increase the risk of infections. To evaluate the efficacy of a multivitamin and mineral supplement on the incidence of infections in patients with IBD treated with immunomodulators, biologic therapy, or combination therapy. METHODS: This was a single-center, randomized, double-blind, placebo-controlled clinical trial to compare a multivitamin and mineral supplement (supplemented group) vs identical-in-appearance placebo (placebo group) in a total of 320 non-vitamin-deficient patients with IBD (Crohn's disease or ulcerative colitis) in remission with immunomodulators, biologic therapy, or combination therapy. Participants were asked to take a daily multivitamin and mineral supplement or placebo and report the occurrence of infections during a 24-week period of follow-up. RESULTS: Treatment arms consisted of 162 and 158 patients for the supplement and placebo, respectively. In both treatment groups, 107 patients reported an infection during the 24-week follow-up period (unadjusted odds ratio, 0.93; 95% confidence interval, 0.56-1.48). In the supplemented group, 32 patients received antibiotics for an infection compared with 21 patients in the placebo group (unadjusted odds ratio, 1.61; 95% confidence interval, 0.88-2.93). CONCLUSIONS: An over-the-counter multivitamin and mineral supplement did not reduce the risk of infection for patients with IBD in remission with immunomodulators, biologic therapy, or combination therapy.
Patients with inflammatory bowel disease are at increased risk of infections due to vitamin or mineral deficiencies. An over-the-counter supplement did not reduce the risk of infection for patients with inflammatory bowel disease in remission with immunomodulators and/or biologic therapy.
RESUMO
In this letter, an experimental therapy in four patients with therapy-resistant Clostridioides difficile infection is described. These four patients were treated with Manuka honey via colon lavage. First, the patients received a three-day fidaxomicin treatment. The colon lavage was performed on the third day. During a subsequent ileocolonoscopy, 300â mL 15% Manuka honey was applied via a spray catheter. Patients remained in bed for two hours after the procedure and did not defecate. The patient's microbiomes were tested before treatment, after the fidaxomicin treatment, and after honey lavage. A decrease in C. difficile load was found in their microbiomes. Additionally, restoration of microbiota diversity after the honey lavage was also noted. The four patients experienced complete cessation of watery stools and remain symptom free. These results indicate the need for more clinical research into this matter.
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Comparability of cost-effectiveness of colorectal cancer (CRC) screening strategies is limited if heterogeneous study data are combined. We analyzed prospective empirical data from a randomized-controlled trial to compare cost-effectiveness of screening with either one round of immunochemical fecal occult blood testing (I-FOBT; OC-Sensor®), one round of guaiac FOBT (G-FOBT; Hemoccult-II®) or no screening in Dutch aged 50 to 75 years, completed with cancer registry and literature data, from a third-party payer perspective in a Markov model with first- and second-order Monte Carlo simulation. Costs were measured in Euros (), effects in life-years gained, and both were discounted with 3%. Uncertainty surrounding important parameters was analyzed. I-FOBT dominated the alternatives: after one round of I-FOBT screening, a hypothetical person would on average gain 0.003 life-years and save the health care system 27 compared with G-FOBT and 0.003 life years and 72 compared with no screening. Overall, in 4,460,265 Dutch aged 50-75 years, after one round I-FOBT screening, 13,400 life-years and 320 million would have been saved compared with no screening. I-FOBT also dominated in sensitivity analyses, varying uncertainty surrounding important effect and cost parameters. CRC screening with I-FOBT dominated G-FOBT and no screening with or without accounting for uncertainty.
Assuntos
Neoplasias Colorretais/economia , Testes Diagnósticos de Rotina/normas , Detecção Precoce de Câncer/economia , Guaiaco/economia , Sangue Oculto , Idoso , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/prevenção & controle , Análise Custo-Benefício , Feminino , Humanos , Técnicas Imunoenzimáticas , Indicadores e Reagentes/economia , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Sensibilidade e Especificidade , Sigmoidoscopia , Taxa de SobrevidaRESUMO
BACKGROUND: Substantial physician workload and high costs are associated with the treatment of dyspepsia in primary health care. Despite the availability of consensus statements and guidelines, the most cost-effective empirical strategy for initial management of the condition remains to be determined. We compared step-up and step-down treatment strategies for initial management of patients with new onset dyspepsia in primary care. METHODS: Patients aged 18 years and older who consulted with their family doctor for new onset dyspepsia in the Netherlands were eligible for enrolment in this double-blind, randomised controlled trial. Between October, 2003, and January, 2006, 664 patients were randomly assigned to receive stepwise treatment with antacid, H(2)-receptor antagonist, and proton pump inhibitor (step-up; n=341), or these drugs in the reverse order (step-down; n=323), by use of a computer-generated sequence with blocks of six. Each step lasted 4 weeks and treatment only continued with the next step if symptoms persisted or relapsed within 4 weeks. Primary outcomes were symptom relief and cost-effectiveness of initial management at 6 months. Analysis was by intention to treat (ITT); the ITT population consisted of all patients with data for the primary outcome at 6 months. This trial is registered with ClinicalTrials.gov, number NCT00247715. FINDINGS: 332 patients in the step-up, and 313 in the step-down group reached an endpoint with sufficient data for evaluation; the main reason for dropout was loss to follow-up. Treatment success after 6 months was achieved in 238 (72%) patients in the step-up group and 219 (70%) patients in the step-down group (odds ratio 0.92, 95% CI 0.7-1.3). The average medical costs were lower for patients in the step-up group than for those in the step-down group (euro228 vs euro245; p=0.0008), which was mainly because of costs of medication. One or more adverse drug events were reported by 94 (28%) patients in the step-up and 93 (29%) patients in the step-down group. All were minor events, including (other) dyspeptic symptoms, diarrhoea, constipation, and bad/dry taste. INTERPRETATION: Although treatment success with either step-up or step-down treatment is similar, the step-up strategy is more cost effective at 6 months for initial treatment of patients with new onset dyspeptic symptoms in primary care.
Assuntos
Antiácidos/uso terapêutico , Dispepsia/tratamento farmacológico , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Adulto , Antiácidos/economia , Análise Custo-Benefício , Método Duplo-Cego , Dispepsia/classificação , Dispepsia/fisiopatologia , Feminino , Antagonistas dos Receptores H2 da Histamina/economia , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Medição da Dor , Pacientes Desistentes do Tratamento , Inibidores da Bomba de Prótons/economia , Índice de Gravidade de DoençaRESUMO
Glutathione S-transferases (GSTs) are a family of enzymes involved in the detoxification of noxious agents. Genes encoding for GSTA1, GSTP1, GSTT1, and GSTM1 proteins are polymorphic in humans, which can result in (partial) loss of enzyme activity. Previous epidemiologic studies have associated dysfunction of these GST genes with a higher risk of cancer, but this is still controversial. The aim of this study was to investigate the susceptibility to gastric cancer in relation to the above-mentioned GST polymorphisms. Patients visiting the Can Tho General Hospital in Vietnam between January 2004 and August 2004 for upper gastrointestinal endoscopy, who were diagnosed with gastric cancer, were compared with a control group of endoscoped dyspepsia patients with no history of malignancy. Genotypes of the GSTs mentioned above were assessed by multiplex PCR. Fifty-nine patients with gastric cancer (mean age: 63 years, 80% males), and 109 dyspeptic controls (mean age: 46 years, 69% males) were included in this study. The frequencies of the combined heterozygote and homozygote mutant GSTA1 and GSTP1 genotypes were 10% and 48% in patients with gastric cancer versus 28% and 40% in dyspeptic controls, respectively. GSTT1 and GSTM1 were deleted in 42% and 73% of patients with gastric cancer and in 35% and 69% of the controls, respectively. The GSTA1 homozygous wild-type genotype was significantly more often present in patients with gastric cancer compared with controls (odds ratio 4.3, 95% CI 1.2-17), which was even more apparent after adjustment for age, gender, current smoking, current alcohol consumption, and polymorphisms in GSTP1, GSTT1, or GSTM1 (odds ratio 5.0, 95% CI 1.2-25). The present work shows that the homozygous wild-type GSTA1 genotype is associated with gastric cancer in a Vietnamese population, whereas there was no relationship with polymorphisms in GSTP1, GSTT1, or GSTM1.
Assuntos
Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Polimorfismo Genético/genética , Neoplasias Gástricas/genética , Consumo de Bebidas Alcoólicas/genética , DNA de Neoplasias/genética , Feminino , Predisposição Genética para Doença , Genótipo , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Prognóstico , Fatores de Risco , Fumar/genética , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , Vietnã/epidemiologiaRESUMO
OBJECTIVE: Colorectal cancer (CRC) screening programs can decide upon the type of fecal occult blood test (FOBT): the guaiac FOBT (g-FOBT) or the immunological FOBT (i-FOBT). The effectiveness of any screening program depends not only on the diagnostic performance of the screening test but also on the compliance and general acceptance of the test by the public. Any decision on the type of FOBT for CRC screening should also take acceptation and perception into account. The aim of the present study was to study differences in patient perception between i-FOBT and g-FOBT and differences in perception and participation rates among relevant subgroups in a population based study. MATERIAL AND METHODS: Differences in patient perception of i-FOBT and g-FOBT and differences in perception and participation rates among relevant subgroups were investigated (n = 20,623) by sending a short questionnaire to all invited to the first Dutch CRC screening trial. RESULTS: i-FOBT was perceived significantly more favorable than g-FOBT. About 1275 (32%) participants reported the g-FOBT not easy to use, not easy to perform, disgusting or shameful compared to 742 (16%) for the i-FOBT (p < 0.001). The participation rate was significantly higher in those who received i-FOBT compared to the g-FOBT group: 6159 of 10,322 (60%) versus 4839 of 10,301 (47%) (p < 0.001). CONCLUSIONS: These findings support the selection of i-FOBT as the more appropriate test for population screening programs.
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Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Guaiaco/análise , Sangue Oculto , Cooperação do Paciente , Idoso , Biomarcadores Tumorais , Colonoscopia , Neoplasias Colorretais/epidemiologia , Feminino , Seguimentos , Humanos , Testes Imunológicos , Incidência , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Prognóstico , Estudos Prospectivos , Distribuição por Sexo , Inquéritos e QuestionáriosRESUMO
Familial atypical multiple mole melanoma (FAMMM) syndrome is a hereditary syndrome characterized by multiple dysplastic nevi and melanoma. Patients with FAMMM may have a heterozygous, inactivating, pathogenic germline variant in the CDKN2A gene, especially the NM_000077.4: c.225_243del19 (p.p75fs) variant, also known as p16-Leiden variant. Patients with this variant are at high risk for developing melanomas and pancreatic cancer due to somatic inactivation of the wild-type CDKN2A allele. The combination of an inactivating germline CDKN2A mutation and somatic inactivation of the wild-type CDKN2A allele in the same cell results in tumor formation. It has been suggested that carriers of a germline CDKN2A mutation are also at increased risk for several other cancer types, including esophageal cancer. Here, we describe two unrelated patients with the p16-Leiden variant who developed esophageal squamous cell cancer. Evidence of loss of the wild-type CDKN2A allele was obtained in the tumor tissue of both patients indicating biallelic inactivation of p16 in the tumor cells. These results suggest that these patients developed esophageal squamous cell cancer in the context of FAMMM syndrome.
Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/genética , Síndrome do Nevo Displásico/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Neoplasias Cutâneas/genética , Alelos , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Mutação em Linhagem Germinativa , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , LinhagemRESUMO
Delayed return of immunochemical fecal occult blood test (iFOBT) samples to a laboratory might cause false negatives because of hemoglobin degradation. Quantitative iFOBT's became increasingly more accepted in colorectal cancer screening. Therefore, we studied the effects of delay between sampling and laboratory delivery on iFOBT performance. IFOBT positivity (>or=50 ng/ml hemoglobin) in colorectal cancer screening participants without delay between sampling and laboratory delivery (<5 days), was compared with positivity in participants with >or=5 and >or=7 days delay. Additionally, positive tests were stored at room temperature and retested 5 times within 10-14 days. The sampling date was reported by 61% (n = 3,767) of the participants: in 19% delay was >or=5 days and in 5% >or=7 days. Compared with no-delay, the adenoma detection rate was already significantly decreased after >or=5 days delay (OR 0.6; 95%CI 0.4-0.9). We retested iFOBT samples of 170 positives of which 139 (82%) had a colonoscopy: 45 (32%) had advanced adenomas (not colorectal cancer) and 8 (6%) had colorectal cancer. Mean daily fecal hemoglobin decrease was 29 ng/ml (S.D. 38 and median 11 ng/ml). In patients with advanced adenomas, hemoglobin in the sample was <50 ng/ml in 5 (11%) 2-3 days after the initial test and in 16 (36%) after 10-14 days. Seven days after the initial test, 2 (25%) colorectal cancer patients became false negative. Both had stage I colorectal cancer and initial values below 100 ng/ml, where the average for stage I is 532 ng/ml. Delay in sample return increased false negative immunochemical FOBT's. Mainly precursor lesions, but also colorectal cancer, will be missed due to delayed sample return.
Assuntos
Adenoma/diagnóstico , Neoplasias Colorretais/diagnóstico , Hemoglobinas/análise , Sangue Oculto , Adenoma/epidemiologia , Adenoma/prevenção & controle , Pólipos do Colo , Colonoscopia/métodos , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controle , Simulação por Computador , Detecção Precoce de Câncer , Reações Falso-Negativas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Valor Preditivo dos Testes , Estudos Prospectivos , Manejo de EspécimesRESUMO
BACKGROUND: The Rome criteria have been introduced to create order in the heterogeneity of functional dyspepsia. The applicability of these symptom-based classification systems remains controversial. GOAL: To evaluate the successive Rome criteria for functional dyspepsia in a large pool of patients with endoscopically verified functional dyspepsia. STUDY: Patients referred to a secondary care district hospital were asked to fill out a questionnaire on gastrointestinal symptoms 2 weeks before upper gastrointestinal endoscopy. Patients were classified according to the Rome I, II, and III criteria for functional dyspepsia. RESULTS: Nine hundred and twelve (70%) patients had no organic disorder explaining their symptoms. According to the Rome I, II, and III criteria, 371 (41%), 735 (81%), and 551 (60%) of these patients had functional dyspepsia, respectively. Twenty-five percent of patients had functional dyspepsia according to all 3 Rome criteria, whereas 15% was not classifiable at all. Forty-four percent and 42% of the patients, respectively, had epigastric pain syndrome and postprandial distress syndrome according to the Rome III criteria; however, 26% of all patients met both criteria and 40% was not classified at all. CONCLUSIONS: The symptom-based Rome classification of functional dyspepsia does not lead to an easily applicable and consistent system that is useful in clinical practice or scientific research.
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Dispepsia/classificação , Dispepsia/fisiopatologia , Gastroenteropatias/complicações , Trato Gastrointestinal/patologia , Índice de Gravidade de Doença , Adulto , Idoso , Dispepsia/diagnóstico , Dispepsia/epidemiologia , Endoscopia Gastrointestinal , Feminino , Gastroenteropatias/classificação , Gastroenteropatias/diagnóstico , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To compare plasma concentrations of acetylsalicylic acid (ASA) and its metabolites between genetic polymorphisms in the gene encoding for UDP-glucuronosyltransferase 1A6 (UGT1A6), an enzyme involved in ASA metabolism. METHODS: Five UGT1A6*1 and 4 UGT1A6*2 homozygote females were given 320 mg ASA once daily for 8 days. During the first and last day of treatment, several blood samples were taken over a 10-hour time period and analyzed for plasma levels of ASA and its main metabolites salicylic acid (SA) and salicyluric acid (SUA), using a validated HPLC method. The pharmacokinetic data were assessed with the Time Constant Approach and both genotypes were compared using the Mann-Whitney U test. RESULTS: ASA and SUA showed similar pharmacokinetic parameters in the two UGT1A6 genotypes. However, pharmacokinetic parameters for SA differed significantly: the mean area under the pharmacokinetic curve for the UGT1A6*1 and UGT1A6*2 homozygotes was 136 and 94 microg/ml.h (p = 0.04), and median C(max) was 23 and 17 microg/ml (p = 0.01), respectively. CONCLUSION: In females receiving ASA, the presence of the UGT1A6*2 compared to the UGT1A6*1 homozygote genotype is associated with lower plasma levels of SA, indicating faster pharmacokinetics.
Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Aspirina/sangue , Glucuronosiltransferase/genética , Polimorfismo Genético , Feminino , Hipuratos/sangue , Homozigoto , Humanos , Ácido Salicílico/sangue , Adulto JovemRESUMO
BACKGROUND & AIMS: Effervescent calcium carbasalate is a calcium-salt of acetylsalicylic acid causing less local gastric damage than acetylsalicylic acid at high doses in healthy controls. The aim of the study was to investigate the incidence of peptic ulcers in a population-based cohort using bioequivalent low-dose acetylsalicylic acid (80 mg) or effervescent calcium carbasalate (100 mg). METHODS: Incident acetylsalicylic acid or effervescent calcium carbasalate users were identified from the Integrated Primary Care Information database. The study cohort comprised 19,819 subjects: 11,891 on acetylsalicylic acid and 7928 on effervescent calcium carbasalate. Incidence rates for documented peptic ulcer disease confirmed by endoscopy were calculated and time-dependent adjusted Cox regression analysis was used to compare the risk of peptic ulcers for patients using acetylsalicylic acid or effervescent calcium carbasalate. RESULTS: During an average 1.85 years of follow-up evaluation, 115 ulcers were found. The risk for developing a peptic ulcer during drug use was: 3.07 per 1000 person-years for acetylsalicylic acid and 4.31 for effervescent calcium carbasalate. The risk of peptic ulcers was not statistically significantly higher in patients using effervescent calcium carbasalate than in acetylsalicylic acid users (adjusted hazard ratio, 1.39; 95% confidence interval, 0.92-2.12). CONCLUSIONS: The incidence rate of peptic ulcer disease is similar in patients using low-dose effervescent calcium carbasalate compared with regular low-dose acetylsalicylic acid. This implicates that peptic ulcers seem to be related to systemic rather than to local effects of low-dose acetylsalicylic acid.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Úlcera Péptica/induzido quimicamente , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Aspirina/administração & dosagem , Aspirina/análogos & derivados , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Incidência , Masculino , Países Baixos/epidemiologia , Úlcera Péptica/epidemiologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Ureia/administração & dosagem , Ureia/efeitos adversos , Ureia/análogos & derivadosRESUMO
BACKGROUND & AIMS: Antidepressants could be effective in the treatment of functional gastrointestinal disorders through their anticholinergic and pain-modulating effects. Previous studies with these drugs lacked sufficient power and were predominantly conducted in patients with irritable bowel syndrome. This study aimed to assess the effectiveness of the serotonin and norepinephrine reuptake inhibitor venlafaxine in patients with functional dyspepsia. METHODS: This was a multi-center, randomized, double-blind, placebo-controlled trial. Participants had persistent dyspeptic symptoms and underwent upper gastrointestinal endoscopy in a secondary care hospital to exclude organic abnormalities. They were randomly assigned to receive 8 weeks of treatment with either venlafaxine XR (2 weeks 75 mg once daily, 4 weeks 150 mg once daily, and 2 weeks 75 mg once daily) or placebo. Symptoms, health-related quality of life, anxiety, and depression were assessed before and at 4, 8, 12, and 20 weeks after inclusion. RESULTS: One hundred sixty patients were randomized; 56% and 73% of participants completed treatment with venlafaxine or placebo, respectively, according to protocol. There was no difference in proportions of symptom-free patients after 8 weeks of treatment or at 20 weeks after inclusion, with venlafaxine in comparison to placebo (37% and 39%, respectively; odds ratio [OR], 0.8; 95% confidence interval [CI], 0.3-2.1; and 42% and 41%, respectively; OR, 3.1; 95% CI, 0.9-12.6). Per-protocol analysis did not reveal any differences between venlafaxine and placebo either (38% and 39% symptom-free, respectively; OR, 1.0; 95% CI, 0.4-2.4 at 8 weeks). CONCLUSIONS: Treatment with the selective serotonin and norepinephrine reuptake inhibitor venlafaxine is not more effective than placebo in patients with functional dyspepsia.
Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Cicloexanóis/uso terapêutico , Dispepsia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antidepressivos de Segunda Geração/administração & dosagem , Ansiedade , Cicloexanóis/administração & dosagem , Depressão , Método Duplo-Cego , Dispepsia/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Qualidade de Vida , Cloridrato de VenlafaxinaRESUMO
Elevated total plasma homocysteine is an established risk factor for cardiovascular disease. Experimental evidence suggests that non-protein-bound free homocysteine is particularly hazardous to the vascular endothelium. This study evaluates the predictive role of free plasma homocysteine levels on cardiovascular endpoints in patients with acute coronary syndrome (ACS). In a cohort of 379 hospitalized patients with a diagnosis of myocardial infarction or unstable angina pectoris, total and free plasma homocysteine levels were measured by high performance liquid chromatography. The patients were followed for a median 2.7 years. The primary endpoint was a composite of cardiovascular death, myocardial infarction and stroke during follow-up. Stepwise Cox regression was used for multivariate analysis. Primary outcome events occurred in 82 patients (22%) with a median time to event of 6 months. The unadjusted hazard ratio for a free homocysteine level >4.11 micromol/L was 2.16 (95% confidence intervals [CI] 1.36 to 3.42) compared with the 4 lower quintiles. After adjusting for the covariates the hazard ratio was 2.25 (95% CI 1.41 to 3.58, p = 0.01). Compared with the lower 4 quintiles, patients with a total homocysteine level >22.4 micromol/L had a 2.09-fold higher risk (95% CI 1.31 to 3.35) for an event during follow-up. Adjusted for age, discharge diagnosis, serum creatinine, history of atherothrombotic events, and diabetes mellitus, the adjusted hazard ratio was 1.37 (95% CI 0.83 to 2.25, p = 0.22). In conclusion, plasma free homocysteine levels >4.11 micromol/L are a significant and independent risk factor for recurrent cardiovascular events in patients hospitalized for ACS, although total plasma homocysteine levels have no predictive value.
Assuntos
Síndrome Coronariana Aguda/sangue , Homocisteína/sangue , Idoso , Cromatografia Líquida de Alta Pressão , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/sangue , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/sangueRESUMO
HYPOTHESIS: Little information about the long-term results of endovascular abdominal aortic aneurysm repair is available. This study was performed to evaluate the long-term data of patients treated with the first generation of commercially available stent grafts. DESIGN: Multicenter registry. SETTING: Sixty-two European centers that participated in the EUROSTAR (EUROpean collaborators on Stent-graft Techniques for abdominal aortic Aneurysm Repair) registry. PATIENTS: A total of 1190 patients with a follow-up of up to 8 years, who underwent endovascular abdominal aortic aneurysm repair with a stent graft (Stentor or Vanguard). INTERVENTION: Elective endovascular abdominal aortic aneurysm repair. MAIN OUTCOME MEASURES: The morbidity and mortality data of patients treated with the first-generation stent graft who enrolled in the EUROSTAR registry were analyzed. Incidence rates of complications were calculated to quantify annual risks. Life-table analyses and multivariate Cox proportional hazards models were used for the survival analysis. RESULTS: Conversion to open repair, aneurysm rupture, all-cause death, and aneurysm-related death occurred in 7.1%, 2.4%, 19.9%, and 3.0% of the patients, respectively. The cumulative percentage of the combined outcome event, conversion-free and rupture-free survival, after 8 years was 48.0%. Procedure-related complications that frequently occurred were endoleak (13.0 cases per 100 patient-years), stenosis/thrombosis (4.6 cases per 100 patient-years), and stent migration (4.3 cases per 100 patient-years). CONCLUSIONS: Patients treated with the first generation of stent grafts will need lifelong surveillance because of a considerable risk of late complications. How these findings translate to the outcome of newer-generation stent grafts is unknown. For this reason, vigilant surveillance remains indicated in all patients who undergo endovascular abdominal aortic aneurysm repair.
Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular , Stents , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/mortalidade , Implante de Prótese Vascular/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Pragmatic randomised controlled trials are often used in primary care to evaluate the effect of a treatment strategy. In these trials it is difficult to achieve both high internal validity and high generalisability. This article will discuss several methodological challenges in designing and conducting a pragmatic primary care based randomised controlled trial, based on our experiences in the DIAMOND-study and will discuss the rationale behind the choices we made. From the successes as well as the problems we experienced the quality of future pragmatic trials may benefit. DISCUSSION: The first challenge concerned choosing the clinically most relevant interventions to compare and enable blinded comparison, since two interventions had very different appearances. By adding treatment steps to one treatment arm and adding placebo to both treatment arms both internal and external validity were optimized. Nevertheless, although blinding is essential for a high internal validity, it should be warily considered in a pragmatic trial because it decreases external validity. Choosing and recruiting a representative selection of participants was the second challenge. We succeeded in retrieving a representative relatively large patient sample by carefully choosing (few) inclusion and exclusion criteria, by random selection, by paying much attention to participant recruitment and taking the participant's reasons to participate into account. Good and regular contact with the GPs and patients was to our opinion essential. The third challenge was to choose the primary outcome, which needed to reflect effectiveness of the treatment in every day practice. We also designed our protocol to follow every day practice as much as possible, although standardized treatment is usually preferred in trials. The aim of this was our fourth challenge: to limit the number of protocol deviations and increase external validity. SUMMARY: It is challenging to design and conduct a pragmatic trial. Thanks to thorough preparation, we were able to collect highly valid data. To our opinion, a critical deliberation of where on the pragmatic--explanatory spectrum you want your trial to be on forehand, in combination with consulting publications especially on patient recruitment procedures, has been helpful in conducting a successful trial.
Assuntos
Dispepsia/tratamento farmacológico , Antagonistas dos Receptores H2 da Histamina/administração & dosagem , Atenção Primária à Saúde/métodos , Inibidores da Bomba de Prótons , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Adulto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Dispepsia/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Países Baixos , Seleção de Pacientes , Projetos de Pesquisa , Resultado do TratamentoRESUMO
BACKGROUND/AIM: Over the past 15 years, there were considerable changes in factors associated with the development and treatment of upper gastrointestinal symptoms, of which the introduction of proton pump inhibitors and Helicobacter pylori eradication in guidelines for treatment of patients with dyspepsia are the most prominent: findings at open-access upper gastrointestinal endoscopy have not been evaluated properly ever since. This study aims to compare the current prevalence of upper gastrointestinal endoscopic findings to the prevalence 15 years ago. METHODS: Data about endoscopic findings of consecutive patients for the first time referred for open-access upper gastrointestinal endoscopy between January 2002 and December 2004 was collected from medical files. The prevalence of each specific finding was compared with data described in three historical populations about 15 years ago. RESULTS: The current and historical study population consisted of 1,286 and 3,062 subjects, respectively. The prevalence of peptic ulcer disease and duodenitis significantly decreased by 12.6% (95% CI: 14.5-10.7) and 2.9% (95% CI: 4.5-1.3), respectively. On the other hand, the prevalence of reflux esophagitis and Barrett's esophagus both significantly increased by 6.9% (95% CI: 4.2-9.6) and 2.1% (95% CI: 0.8-4.4), respectively. CONCLUSIONS: Compared to 15 years ago, the prevalence of specific findings at open-access upper gastrointestinal endoscopy has changed considerably.