RESUMO
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.
Assuntos
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: Over the last decades important risk factors for gastrointestinal symptoms have shifted, which may have changed its population prevalence. The aim of this study was to assess the current prevalence of gastrointestinal symptoms, appraise associated factors and assess health-related quality of life in the general population. METHODS: A total of 51,869 questionnaires were sent to a representative sample of the Dutch adult general population in December 2008. Demographic characteristics, gastrointestinal symptoms, health-related quality of life, medication use and co-morbidity were reported. We used multivariable logistic regression analysis to determine factors associated with gastrointestinal symptoms. RESULTS: A total of 18,317 questionnaires were returned, and 16,758 were eligible for analysis. Prevalence of gastrointestinal symptoms was 26%. Most frequent symptoms were bloating (63%), borborygmi (60%) and flatulence (71%). Female gender (adjusted OR (aOR) 1.59, 95% CI 1.43-1.77), asthma/COPD (aOR 1.47, 95% CI 1.21-1.79), use of paracetamol (aOR 1.33, 95% CI 1.20-1.47), antidepressants (aOR 1.56, 95% CI 1.22-2.00) and acid-suppressive medication were independently associated with presence of gastrointestinal symptoms. Age over 65 years (aOR 0.75, 95% CI 0.65-0.87), and use of statins (aOR 0.75, 95% CI 0.61-0.93) were associated with a lower prevalence of gastrointestinal symptoms. Respondents with gastrointestinal symptoms had a lower mean health-related quality of life of 0.81 (SDâ=â0.21) compared to 0.92 (SDâ=â0.14) for persons without gastrointestinal symptoms (P<0.01). CONCLUSIONS: Prevalence of gastrointestinal symptoms in the Dutch community is high and associated with decreased health-related quality of life.
Assuntos
Gastroenteropatias/epidemiologia , Adolescente , Adulto , Idoso , Criança , Estudos Transversais , Feminino , Gastroenteropatias/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Qualidade de Vida , Inquéritos e Questionários , Adulto JovemRESUMO
The Dutch Ministry of Health has instructed the National Institute for Public Health and the Environment (RIVM) to prepare a national screening programme for colorectal cancer. The RIVM put the immunochemical faecal occult blood test (iFOBT) for the programme out to public tender, after which a panel of experts recommended the FOB Gold test. This is surprising since previous studies favoured the OC Sensor test and the FOB Gold test has never been used in the Netherlands. Before starting the national programme in September 2013, the RIVM wants to ascertain which FOB Gold test cut-off value is comparable with the 75 ng/ml of the OC Sensor test recommended by the Health Council of the Netherlands. This cut-off level is crucial for capacity planning of colonoscopies. We advocate starting the national screening programme with the OC Sensor test and subsequent careful comparison with the FOB Gold test during the screening programme.
Assuntos
Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Sangue Oculto , Colonoscopia , Humanos , Programas de Rastreamento , Países BaixosRESUMO
AIM: To improve the interpretation of fecal immunochemical test (FIT) results in colorectal cancer (CRC) cases from screening and referral cohorts. METHODS: In this comparative observational study, two prospective cohorts of CRC cases were compared. The first cohort was obtained from 10 322 average risk subjects invited for CRC screening with FIT, of which, only subjects with a positive FIT were referred for colonoscopy. The second cohort was obtained from 3637 subjects scheduled for elective colonoscopy with a positive FIT result. The same FIT and positivity threshold (OC sensor; ≥ 50 ng/mL) was used in both cohorts. Colonoscopy was performed in all referral subjects and in FIT positive screening subjects. All CRC cases were selected from both cohorts. Outcome measurements were mean FIT results and FIT scores per tissue tumor stage (T stage). RESULTS: One hundred and eighteen patients with CRC were included in the present study: 28 cases obtained from the screening cohort (64% male; mean age 65 years, SD 6.5) and 90 cases obtained from the referral cohort (58% male; mean age 69 years, SD 9.8). The mean FIT results found were higher in the referral cohort (829 ± 302 ng/mL vs 613 ± 368 ng/mL, P = 0.02). Tissue tumor stage (T stage) distribution was different between both populations [screening population: 13 (46%) T1, eight (29%) T2, six (21%) T3, one (4%) T4 carcinoma; referral population: 12 (13%) T1, 22 (24%) T2, 52 (58%) T3, four (4%) T4 carcinoma], and higher T stage was significantly associated with higher FIT results (P < 0.001). Per tumor stage, no significant difference in mean FIT results was observed (screening vs referral: T1 498 ± 382 ng/mL vs 725 ± 374 ng/mL, P = 0.22; T2 787 ± 303 ng/mL vs 794 ± 341 ng/mL, P = 0.79; T3 563 ± 368 ng/mL vs 870 ± 258 ng/mL, P = 0.13; T4 not available). After correction for T stage in logistic regression analysis, no significant differences in mean FIT results were observed between both types of cohorts (P = 0.10). CONCLUSION: Differences in T stage distribution largely explain differences in FIT results between screening and referral cohorts. Therefore, FIT results should be reported according to T stage.
Assuntos
Neoplasias Colorretais/diagnóstico , Programas de Rastreamento , Sangue Oculto , Encaminhamento e Consulta , Idoso , Colonoscopia , Neoplasias Colorretais/patologia , Feminino , Humanos , Imuno-Histoquímica , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Método Simples-CegoRESUMO
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
Lipomas are benign tumours that are sometimes found in the colon, where they may cause symptoms through constriction and blood loss. Until recently, surgical removal of large lipomas was the therapy of choice, because of the danger of bleeding and perforation during endoscopy. The endoloop (PolyLoop, Olympus Medical Systems Corp., Tokyo, Japan), by use of which the base of the lipoma is constricted by a nylon loop, has changed this approach. We describe the successful removal of a large lipoma located in the ascending colon in 2 patients who were referred shortly after one another to the endoscopy department of our hospital. This endoscopic technique should be considered for removal of large pedunculated polyps in the intestine.
Assuntos
Neoplasias do Colo/cirurgia , Colonoscopia/métodos , Lipoma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Colonoscopia/efeitos adversos , Feminino , Humanos , Masculino , Resultado do TratamentoRESUMO
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.
Assuntos
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
NSAIDs are among the most often used drugs worldwide. Numerous NSAID users are at risk for developing gastrointestinal complications. The purpose of this review was to identify and stratify risk factors for gastrointestinal complications in NSAID users documented in guidelines and consensus agreements, and to collect recommendations regarding over-the-counter (OTC) NSAID use. To facilitate this, a PubMed search from 1 January 1999 until 1 March 2009 was performed, resulting in the inclusion of nine English-language guidelines in our analysis. Risk factors were defined as 'definite' if mentioned in all guidelines; otherwise they were defined as 'controversial' risk factors. 'Definite' risk factors were a history of (complicated) peptic ulcer disease, older age (cut-off range 60-75 years), concomitant anticoagulant or corticosteroid use and multiple NSAID use, including low-dose aspirin (acetylsalicylic acid). 'Controversial' risk factors were high-dose NSAID use, concomitant clopidogrel or selective serotonin reuptake inhibitor use, a history of gastrointestinal symptoms, rheumatoid arthritis disability and cardiovascular disease. Infection with Helicobacter pylori was identified as an additive risk factor. Risk factors in OTC NSAID users were difficult to identify in the current literature. Risk factors were not all uniformly present in analysed guidelines and consensus agreements. We identified a history of (complicated) peptic ulcer disease, older age, concomitant anticoagulant or corticosteroid use and multiple NSAID use, including low-dose aspirin, as definite gastrointestinal risk factors in NSAID users.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Gastroenteropatias/induzido quimicamente , Protocolos Clínicos , Consenso , Guias como Assunto , Humanos , Medicamentos sem Prescrição/efeitos adversos , Fatores de RiscoRESUMO
OBJECTIVES: Premature activation of pancreatic digestive enzymes is considered as a major factor in the pathogenesis of pancreatitis. Genetic alterations of different pancreatic zymogens or their inhibitors have been associated with chronic pancreatitis (CP). METHODS: We sequenced all 12 GP2 exons in 380 German CP patients and in 182 German control subjects. In addition, we analyzed exon 3 of GP2 in 803 further CP patients and 1780 controls originating from Germany, the Netherlands, and India by targeted DNA sequencing. RESULTS: We detected 12 nonsynonymous and 6 synonymous exonic variants. All nonsynonymous changes with exception of c.220C>T (p.R74X) and c.502_503delG (p.G168fsX174) in exon 3 and c.541C>T (p.R181X) in exon 4 were missense mutations and predominantly located in exon 3. All nonsynonymous variants were found in single cases only, with exception of 2 alterations, c.355A>G (p.M119V) and c.409G>A (p. A137T), both located in exon 3. To elucidate the role of these 2 exon 3 variants, we investigated additional patients and controls. The frequency of these variants was similar between patients and controls regardless of ethnic background or cause of CP. CONCLUSIONS: Our data suggest that GP2 alterations do not alter the risk for the development of CP.
Assuntos
Glicoproteínas de Membrana/genética , Mutação de Sentido Incorreto , Pancreatite Crônica/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Análise Mutacional de DNA , Éxons , Feminino , Proteínas Ligadas por GPI , Predisposição Genética para Doença , Alemanha , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Países Baixos , Medição de Risco , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: The major clinical feature in chronic pancreatitis is pain, but the genetic basis of pancreatic pain in chronic pancreatitis is poorly understood. The transient receptor potential vanilloid receptor 1 (TRPV1) gene has been associated with pain perception, and genetic variations in TRPV1 may modify the presence and phenotype of chronic pancreatitis. The aim of our study was to investigate the genetic variation of TRPV1 in Dutch patients with chronic pancreatitis and healthy controls. METHODS: We genotyped 4 SNPs (rs222749, rs222747, rs224534 and rs8065080) in 228 chronic pancreatitis-patients and 207 healthy controls by PCR, followed by restriction-fragment-length-polymorphism analysis and DNA sequencing. We generated 27 diplotypes and compared prevalence between patients and controls. RESULTS: There was no significant difference in allele frequency of the 4 TRPV1 gene SNPs in patients with chronic pancreatitis and healthy controls. Distribution of diplotypes was not statistically significantly different between patients and controls. CONCLUSION: TRPV1 diplotypes are not associated with chronic pancreatitis.
Assuntos
Dor/genética , Pancreatite Crônica/genética , Polimorfismo de Nucleotídeo Único/genética , Canais de Cátion TRPV/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Fenótipo , Adulto JovemRESUMO
OBJECTIVE: To assess genetic, clinical and morphological characteristics of hereditary pancreatitis, a rare type of chronic pancreatitis with an early onset of symptoms, which is, among others, caused by mutations in the PRSS1 gene. DESIGN: Observational cohort study. METHOD: The study population consisted of 496 patients (27,375 person-years) who were referred to Radboud University Nijmegen Medical Centre for molecular diagnosis of hereditary pancreatitis during period 2000 to 2007. 61 patients with a positive family history of hereditary pancreatitis were selected. Analysis for PRSS1 gene mutations was performed by complete sequence analysis of the exons. All patients received a structured questionnaire. RESULTS: From 25 families 61 patients were included (2,047 person-years). PRSS1 mutations were detected in 52 patients (85.2%): p.R122H (67.2%), p.N29I (14.8%), p.E79K (1.6%), p.N29T (1.6%). In the 40 patients whose clinical data were known the median age at diagnosis was 10.5 years (range: 0-42 years). Pain was reported in 28 (70% of 40 patients in whom all information was complete). 27 patients (67.5%) were admitted to the hospital once or more due to the attacks of pancreatitis. Exocrine and endocrine dysfunction was seen in 6 patients (15%). 24 patients (60%) had undergone a surgical intervention, 10 of whom had undergone a pancreaticojejunostomy. A family history of pancreatic carcinoma was found in 5 patients (12.5%). CONCLUSION: The percentage of PRSS1 mutation was high (85.2%) among this Dutch population that was selected on basis of a positive family history of hereditary pancreatitis. Most patients had no chronic pain.
Assuntos
Mutação , Dor/epidemiologia , Pancreatite Crônica/genética , Pancreatite Crônica/patologia , Tripsina/genética , Idade de Início , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Países Baixos/epidemiologia , Dor/etiologia , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/genética , Pancreatite Crônica/complicações , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
UDP-glucuronosyltransferase 1A6 (UGT1A6) is involved in metabolizing non-steroidal anti-inflammatory drugs (NSAIDs). Genotype variation in UGT1A6 may influence the metabolism of NSAIDs and we studied whether this might modulate the gastrointestinal toxicity of NSAIDs. UGT1A6 genotypes of 114 patients with peptic ulcer haemorrhage were compared with those of two subsets of controls: 158 cardiology patients using similar amounts of NSAIDs and 140 healthy controls, hardly using NSAIDs. Risk factors for peptic ulcer bleeding were male gender (Odds ratio (OR) 2.66, 95% confidence interval (CI) 1.7-4.2), age above 60 years (OR 2.15, 95% CI 1.4-3.4) and use of NSAIDs/aspirin (OR 4.50, 95% CI 2.8-7.3). UGT1A6 genotype frequencies did not differ between patients with peptic ulcer and the two control groups (p=0.76). We conclude that polymorphic UGT1A6 is not implicated in the pathogenesis of NSAIDs-related peptic ulcer disease.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Glucuronosiltransferase/genética , Úlcera Péptica Hemorrágica/genética , Polimorfismo Genético , Fatores Etários , Idoso , Anti-Inflamatórios não Esteroides/farmacocinética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Glucuronosiltransferase/metabolismo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Úlcera Péptica Hemorrágica/induzido quimicamente , Úlcera Péptica Hemorrágica/enzimologia , Medição de Risco , Fatores de Risco , Fatores SexuaisRESUMO
In 2003, the European Commission advised the Member States to start colorectal cancer screening. More than 12 million Europeans have been tested to date, not only by means of faecal occult blood testing but often also by opportunistic endoscopy. Nearly all of the screening programmes concerned were opportunistic in nature. The Dutch government is currently considering the implementation of an organised screening programme for the detection of colorectal cancer. The question no longer seems to be whether a screening programme should be started but rather which screening test should be used. We argue that an immunological faecal occult blood test is to be preferred over other screening tests, such as endoscopy.
Assuntos
Colonoscopia , Neoplasias Colorretais/diagnóstico , Programas de Rastreamento/métodos , Programas de Rastreamento/organização & administração , Sangue Oculto , HumanosRESUMO
AIM: To determine whether -1195 A-->G and/or -765 G-->C polymorphisms in Cyclooxygenase-2 (COX-2) may have a risk modifying effect on the development of esophageal carcinoma in a Dutch Caucasian population. METHODS: Two study groups were recruited, 252 patients with esophageal carcinoma and 240 healthy controls, matched for race, age, gender and recruiting area. DNA was isolated from whole blood and used for genotyping. PCR products were digested with restriction enzymes and products were analyzed by agarose gel electrophoresis. Odds ratios (OR) and 95% confidence intervals (CI) were estimated. RESULTS: The distribution of the -1195 A-->G polymorphism was significantly different in esophageal cancer patients compared to controls. The -1195 GG genotype resulted in a higher risk of developing esophageal adenocarcinoma (OR = 3.85, 95% CI: 1.45-10.3) compared with the -1195 AA genotype as a reference. The -765 G-->C genotype distribution was not different between the two groups. The GG/GG haplotype was present more often in esophageal adenocarcinoma patients than in controls (OR = 3.45, 95% CI: 1.24-9.58; with AG/AG as a reference). The same trends were observed in patients with squamous cell carcinomas, however, the results did not reach statistical significance. CONCLUSION: Presence of the COX-2 -1195 GG genotype and of the GG/GG haplotype may result in a higher risk of developing esophageal carcinoma.
Assuntos
Adenocarcinoma/genética , Carcinoma de Células Escamosas/genética , Ciclo-Oxigenase 2/genética , Neoplasias Esofágicas/genética , Polimorfismo de Nucleotídeo Único , Idoso , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Razão de ChancesRESUMO
BACKGROUND & AIMS: The success of home parenteral nutrition (HPN) programs is compromised by complications of central venous catheters (CVCs), such as occlusions and bloodstream infections. We performed a retrospective analysis of complication rates of arteriovenous fistulae versus CVCs in patients on long-term HPN. METHODS: Data were collected from 127 consecutive patients who received HPN between January 2000 and October 2006, comprising 344 access years of CVCs and 194 access years of arteriovenous fistulae. We evaluated access-related bloodstream infection and occlusion incidence rates (number of complications per access year) using Poisson-normal regression analysis. Complication incidence rate ratios were calculated by dividing complication incidence rates of CVCs by those of arteriovenous fistulae, adjusting for HPN frequency, medication use, infusion fluid composition, and underlying diseases. RESULTS: Bloodstream infection incidence rates were 0.03/year for arteriovenous fistulae, 1.37/year for long-term CVCs (Port-a-Caths and tunneled catheters), and 3.12/year for short-term CVCs (nontunneled catheters). Occlusion incidence rates were 0.60/year for arteriovenous fistulae, 0.35/year for long-term CVCs, and 0.93/year for shortterm CVCs. Adjusted incidence rate ratios of long-term CVCs over arteriovenous fistulae were 47 (95% confidence interval, 19-117) for bloodstream infections and 0.53 (95% confidence interval, 0.31-0.89) for occlusions. CONCLUSIONS: The occlusion incidence rate was higher for arteriovenous fistulae than for certain types of CVCs. The incidence rate of the most serious access-related complication (bloodstream infections) was much lower for arteriovenous fistulae than for all types of CVCs. Thus, arteriovenous fistulae are safe and valuable alternatives to CVCs for patients requiring long-term HPN.
Assuntos
Derivação Arteriovenosa Cirúrgica/efeitos adversos , Cateterismo Periférico , Nutrição Parenteral no Domicílio , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/etiologia , Bacteriemia/microbiologia , Cateterismo Venoso Central , Cateterismo Periférico/efeitos adversos , Cateteres de Demora , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Nutrição Parenteral no Domicílio/métodos , Adulto JovemRESUMO
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
OBJECTIVES: Chronic pancreatitis (CP) and pancreatic adenocarcinoma (pCA) are associated with risk factors such as alcohol intake and tobacco smoking. Microsomal epoxide hydrolase (EPHX1) is a phase II detoxifying enzyme capable of tobacco-borne toxicant inactivation. We studied the role of the EPHX1 c.337T>C (p.Y113H) variant, whichleads to altered enzyme activity, in pancreatic diseases. METHODS: We genotyped 2391 patients by melting curve analysis. We enrolled 367 patients with pCA, 341 patients with alcoholic CP (aCP), 431 patients with idiopathic CP or hereditary pancreatitis, 192 patients with acute pancreatitis, and 679 controls of German descent. We replicated data in 77 patients with aCP and 304 controls from The Netherlands. RESULTS: In German patients with aCP, Y113 was more common than in controls (allele frequencies, 0.73 vs 0.68; risk ratio, 1.21 [95% confidence interval, 1.05-1.39]). However, we could not confirm this association in the Dutch population (allele frequencies, 0.62 vs 0.68, P=not significant). In total, Y113 frequency was 0.71 in aCP and 0.68 in controls (P = not significant). Allele frequencies did not differ in the other disease groups (acute pancreatitis, 0.69; idiopathic CP or hereditary pancreatitis, 0.68; pCA, 0.68; and control, 0.68). CONCLUSIONS: The EPHX1 Y113H variant is not associated with pancreatic diseases indicating that EPHX1 does not play a significant role in the initiation of pancreatic inflammation or cancer.
Assuntos
Epóxido Hidrolases/genética , Mutação de Sentido Incorreto , Pancreatopatias/genética , Doença Aguda , Adenocarcinoma/enzimologia , Adenocarcinoma/genética , Adolescente , Adulto , Idoso , Criança , Feminino , Frequência do Gene , Variação Genética , Genótipo , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Pancreatopatias/enzimologia , Neoplasias Pancreáticas/enzimologia , Neoplasias Pancreáticas/genética , Pancreatite Alcoólica/enzimologia , Pancreatite Alcoólica/genética , Pancreatite Crônica/enzimologia , Pancreatite Crônica/genética , Fatores de Risco , Adulto JovemRESUMO
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: 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.