RESUMO
BACKGROUND: Epidemiologic and preclinical data suggest that higher intake and serum levels of vitamin D and higher intake of calcium reduce the risk of colorectal neoplasia. To further study the chemopreventive potential of these nutrients, we conducted a randomized, double-blind, placebo-controlled trial of supplementation with vitamin D, calcium, or both for the prevention of colorectal adenomas. METHODS: We recruited patients with recently diagnosed adenomas and no known colorectal polyps remaining after complete colonoscopy. We randomly assigned 2259 participants to receive daily vitamin D3 (1000 IU), calcium as carbonate (1200 mg), both, or neither in a partial 2×2 factorial design. Women could elect to receive calcium plus random assignment to vitamin D or placebo. Follow-up colonoscopy was anticipated to be performed 3 or 5 years after the baseline examinations, according to the endoscopist's recommendation. The primary end point was adenomas diagnosed in the interval from randomization through the anticipated surveillance colonoscopy. RESULTS: Participants who were randomly assigned to receive vitamin D had a mean net increase in serum 25-hydroxyvitamin D levels of 7.83 ng per milliliter, relative to participants given placebo. Overall, 43% of participants had one or more adenomas diagnosed during follow-up. The adjusted risk ratios for recurrent adenomas were 0.99 (95% confidence interval [CI], 0.89 to 1.09) with vitamin D versus no vitamin D, 0.95 (95% CI, 0.85 to 1.06) with calcium versus no calcium, and 0.93 (95% CI, 0.80 to 1.08) with both agents versus neither agent. The findings for advanced adenomas were similar. There were few serious adverse events. CONCLUSIONS: Daily supplementation with vitamin D3 (1000 IU), calcium (1200 mg), or both after removal of colorectal adenomas did not significantly reduce the risk of recurrent colorectal adenomas over a period of 3 to 5 years. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00153816.).
Assuntos
Adenoma/prevenção & controle , Cálcio/uso terapêutico , Neoplasias Colorretais/prevenção & controle , Suplementos Nutricionais , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Adenoma/epidemiologia , Idoso , Cálcio/efeitos adversos , Neoplasias Colorretais/epidemiologia , Suplementos Nutricionais/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Falha de Tratamento , Vitamina D/análogos & derivados , Vitamina D/sangueRESUMO
INTRODUCTION: Whether body position affects lower esophageal sphincter (LES) function and detection of hiatal hernia is unknown. Moreover, the yield of high-resolution esophageal pressure topography (HREPT) when compared with endoscopy for detection of hiatal hernia is unclear. AIM: The aims of this study were to examine (a) the effects of body position (standing vs. supine) on LES function, and (b) to determine the diagnostic yield of HREPT and endoscopy for detection of hiatal hernia. METHODS: A total of 50 subjects underwent both HREPT and endoscopy. The manometric/topographic changes of LES were examined in both supine and standing positions. Endoscopy assessed presence and length of hiatal hernia. Diagnostic agreement was compared between HREPT and endoscopy. RESULTS: The resting LES pressure was higher (P=0.0001), its mean length was longer (P=0.0003), and length of high-pressure zone was longer (P=0.0001) in the standing position compared with the supine position. HREPT detected twice as many subjects with hiatal hernia in standing (P=0.0001) compared with supine position or endoscopy with significant new diagnostic information (79%). Endoscopy detection rate (34%) was similar to supine manometry with good diagnostic agreement (77%) between HREPT and endoscopy. Hiatal hernia length was longer (P=0.0001) with HREPT in standing position compared with endoscopy. CONCLUSIONS: Body position significantly affects in the LES function and its measurements. HREPT when performed on standing position offers the best yield for detection of hiatal hernia and is superior to endoscopy or supine manometry.
Assuntos
Esfíncter Esofágico Inferior/fisiopatologia , Hérnia Hiatal/diagnóstico , Posicionamento do Paciente , Adulto , Idoso , Deglutição , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/patologia , Transtornos de Deglutição/fisiopatologia , Endoscopia Gastrointestinal , Esfíncter Esofágico Inferior/patologia , Feminino , Hérnia Hiatal/patologia , Hérnia Hiatal/fisiopatologia , Humanos , Masculino , Manometria , Pessoa de Meia-Idade , Mucosa/patologia , Postura , Valor Preditivo dos Testes , Pressão , Estudos Prospectivos , Decúbito Dorsal , Adulto JovemRESUMO
The Aspirin/Folate Polyp Prevention Study is a randomized, placebo-controlled trial of aspirin use and folic acid supplementation and incidence of colorectal adenomas in individuals with a history of these lesions. The trial showed that folic acid supplementation does not prevent the occurrence of new adenomas and may increase risk. We extend these results by investigating whether the effect of folic acid treatment differed by baseline dietary and circulating folate levels. Diet and supplement use were ascertained at baseline through a food-frequency questionnaire; a blood sample was used to determine plasma and RBC folate levels. Individuals were followed for 3 years (first follow-up) and subsequently for an additional 3 to 5 years (second follow up). We used generalized linear regression to estimate risk ratios and 95% confidence limits as measures of association. There was little evidence that baseline dietary and total folate intake, and plasma and RBC folate modified the association between folic acid treatment and risk of any adenomas or advanced lesions. However, there was a protective association of the highest tertile of dietary and total intake as well as circulating folate with risk of any adenomas among those in the placebo group but no association among individuals in the folic acid group. Our findings support the idea that although moderate doses of folate may be protective compared with deficiency, at some point of sufficiency, supplementation provides no additional benefit.
Assuntos
Adenoma/prevenção & controle , Neoplasias Colorretais/prevenção & controle , Ácido Fólico/administração & dosagem , Ácido Fólico/sangue , Adenoma/epidemiologia , Aspirina/administração & dosagem , Colonoscopia , Neoplasias Colorretais/epidemiologia , Intervalos de Confiança , Dieta , Feminino , Humanos , Incidência , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Placebos , Distribuição de Poisson , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Laboratory and epidemiologic data suggest that aspirin has an antineoplastic effect in the large bowel. METHODS: We performed a randomized, double-blind trial of aspirin as a chemopreventive agent against colorectal adenomas. We randomly assigned 1121 patients with a recent history of histologically documented adenomas to receive placebo (372 patients), 81 mg of aspirin (377 patients), or 325 mg of aspirin (372 patients) daily. According to the protocol, follow-up colonoscopy was to be performed approximately three years after the qualifying endoscopy. We compared the groups with respect to the risk of one or more neoplasms (adenomas or colorectal cancer) at least one year after randomization using generalized linear models to compute risk ratios and 95 percent confidence intervals. RESULTS: Reported adherence to study medications and avoidance of nonsteroidal antiinflammatory drugs were excellent. Follow-up colonoscopy was performed at least one year after randomization in 1084 patients (97 percent). The incidence of one or more adenomas was 47 percent in the placebo group, 38 percent in the group given 81 mg of aspirin per day, and 45 percent in the group given 325 mg of aspirin per day (global P=0.04). Unadjusted relative risks of any adenoma (as compared with the placebo group) were 0.81 in the 81-mg group (95 percent confidence interval, 0.69 to 0.96) and 0.96 in the 325-mg group (95 percent confidence interval, 0.81 to 1.13). For advanced neoplasms (adenomas measuring at least 1 cm in diameter or with tubulovillous or villous features, severe dysplasia, or invasive cancer), the respective relative risks were 0.59 (95 percent confidence interval, 0.38 to 0.92) and 0.83 (95 percent confidence interval, 0.55 to 1.23). CONCLUSIONS: Low-dose aspirin has a moderate chemopreventive effect on adenomas in the large bowel.
Assuntos
Adenoma/prevenção & controle , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Neoplasias Colorretais/prevenção & controle , Adenoma/mortalidade , Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Pólipos do Colo/diagnóstico , Pólipos do Colo/prevenção & controle , Colonoscopia , Neoplasias Colorretais/mortalidade , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Risco , Prevenção SecundáriaRESUMO
Immune-mediated diseases (e.g. inflammatory bowel disease, asthma, multiple sclerosis and autoimmune diabetes) are increasing in prevalence and emerge as populations adopt meticulously hygienic lifestyles. This change in lifestyles precludes exposure to helminths (parasitic worms). Loss of natural helminth exposure removes a previously universal Th2 and regulatory immune biasing imparted by these organisms. Helminths protect animals from developing immune-mediated diseases (colitis, reactive airway disease, encephalitis and diabetes). Clinical trials show that exposure to helminths can reduce disease activity in patients with ulcerative colitis or Crohn's disease. This paper summarises work by multiple groups demonstrating that colonization with helminths alters immune reactivity and protects against disease from dysregulated inflammation.
Assuntos
Helmintos/imunologia , Doenças do Sistema Imunitário/imunologia , Doenças Inflamatórias Intestinais/imunologia , Animais , Asma/imunologia , Asma/parasitologia , Asma/terapia , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/parasitologia , Diabetes Mellitus Tipo 1/terapia , Modelos Animais de Doenças , Helmintíase/imunologia , Helmintíase/parasitologia , Humanos , Doenças do Sistema Imunitário/parasitologia , Doenças do Sistema Imunitário/terapia , Doenças Inflamatórias Intestinais/parasitologia , Doenças Inflamatórias Intestinais/terapia , Esclerose Múltipla/imunologia , Esclerose Múltipla/parasitologia , Esclerose Múltipla/terapiaRESUMO
The treatment of inflammatory bowel disease (IBD) is undergoing rapid and profound change. Entirely new approaches are being developed that reflect a greater understanding of how to control the inflammatory process. These began with inflixumab therapy for Crohn's disease. Additional tumor necrosis antibodies will soon be employed, and other biological agents are being investigated. Probiotics, helminth ova therapy, alternative and complementary treatments, leukocytophoresis, and bone-marrow and stem-cell transplantation are additional exciting regimens that are being explored. Although some of these approaches provide marked improvement in these parameters, others are unproven or fraught with adverse effects and complications. Still, control of ulcerative colitis and Crohn's is improving with more changes likely to come.
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Terapias Complementares , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/terapia , Animais , Anticorpos Monoclonais/uso terapêutico , Transplante de Medula Óssea , Interações Hospedeiro-Parasita , Humanos , Doenças Inflamatórias Intestinais/parasitologia , Leucócitos , Óvulo , Probióticos/uso terapêutico , Transplante de Células-TroncoRESUMO
CONTEXT: Laboratory and epidemiological data suggest that folic acid may have an antineoplastic effect in the large intestine. OBJECTIVE: To assess the safety and efficacy of folic acid supplementation for preventing colorectal adenomas. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, placebo-controlled, 2-factor, phase 3, randomized clinical trial conducted at 9 clinical centers between July 6, 1994, and October 1, 2004. Participants included 1021 men and women with a recent history of colorectal adenomas and no previous invasive large intestine carcinoma. INTERVENTION: Participants were randomly assigned in a 1:1 ratio to receive 1 mg/d of folic acid (n = 516) or placebo (n = 505), and were separately randomized to receive aspirin (81 or 325 mg/d) or placebo. Follow-up consisted of 2 colonoscopic surveillance cycles (the first interval was at 3 years and the second at 3 or 5 years later). MAIN OUTCOME MEASURES: The primary outcome measure was occurrence of at least 1 colorectal adenoma. Secondary outcomes were the occurrence of advanced lesions (> or =25% villous features, high-grade dysplasia, size > or =1 cm, or invasive cancer) and adenoma multiplicity (0, 1-2, or > or =3 adenomas). RESULTS: During the first 3 years, 987 participants (96.7%) underwent colonoscopic follow-up, and the incidence of at least 1 colorectal adenoma was 44.1% for folic acid (n = 221) and 42.4% for placebo (n = 206) (unadjusted risk ratio [RR], 1.04; 95% confidence interval [CI], 0.90-1.20; P = .58). Incidence of at least 1 advanced lesion was 11.4% for folic acid (n = 57) and 8.6% for placebo (n = 42) (unadjusted RR, 1.32; 95% CI, 0.90-1.92; P = .15). A total of 607 participants (59.5%) underwent a second follow-up, and the incidence of at least 1 colorectal adenoma was 41.9% for folic acid (n = 127) and 37.2% for placebo (n = 113) (unadjusted RR, 1.13; 95% CI, 0.93-1.37; P = .23); and incidence of at least 1 advanced lesion was 11.6% for folic acid (n = 35) and 6.9% for placebo (n = 21) (unadjusted RR, 1.67; 95% CI, 1.00-2.80; P = .05). Folic acid was associated with higher risks of having 3 or more adenomas and of noncolorectal cancers. There was no significant effect modification by sex, age, smoking, alcohol use, body mass index, baseline plasma folate, or aspirin allocation. CONCLUSIONS: Folic acid at 1 mg/d does not reduce colorectal adenoma risk. Further research is needed to investigate the possibility that folic acid supplementation might increase the risk of colorectal neoplasia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00272324.
Assuntos
Adenoma/prevenção & controle , Neoplasias Colorretais/prevenção & controle , Ácido Fólico/uso terapêutico , Adenoma/epidemiologia , Adenoma/etiologia , Adulto , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Distribuição de Qui-Quadrado , Neoplasias Colorretais/epidemiologia , Método Duplo-Cego , Feminino , Ácido Fólico/administração & dosagem , Ácido Fólico/efeitos adversos , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/etiologia , Risco , Falha de TratamentoRESUMO
BACKGROUND: Calcium supplements are widely used among older adults for osteoporosis prevention and treatment. However, their effect on creatinine levels and kidney function has not been well studied. METHODS: We investigated the effect of calcium supplementation on blood creatinine concentration in a randomized controlled trial of colorectal adenoma chemoprevention conducted between 2004-2013 at 11 clinical centers in the United States. Healthy participants (Nâ=â1,675) aged 45-75 with a history of colorectal adenoma were assigned to daily supplementation with calcium (1200 mg, as carbonate), vitamin D3 (1000 IU), both, or placebo for three or five years. Changes in blood creatinine and total calcium concentration were measured after one year of treatment and multiple linear regression was used to estimate effects on creatinine concentrations. RESULTS: After one year of treatment, blood creatinine was 0.013±0.006 mg/dL higher on average among participants randomized to calcium compared to placebo after adjustment for other determinants of creatinine (Pâ=â0.03). However, the effect of calcium treatment appeared to be larger among participants who consumed the most alcohol (2-6 drinks/day) or whose estimated glomerular filtration rate (eGFR) was less than 60 ml/min/1.73 m2 at baseline. The effect of calcium treatment on creatinine was only partially mediated by a concomitant increase in blood total calcium concentration and was independent of randomized vitamin D treatment. There did not appear to be further increases in creatinine after the first year of calcium treatment. CONCLUSIONS: Among healthy adults participating in a randomized clinical trial, daily supplementation with 1200 mg of elemental calcium caused a small increase in blood creatinine. If confirmed, this finding may have implications for clinical and public health recommendations for calcium supplementation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00153816.
Assuntos
Cálcio da Dieta/administração & dosagem , Colecalciferol/administração & dosagem , Creatinina/sangue , Osteoporose/dietoterapia , Adulto , Idoso , Suplementos Nutricionais , Feminino , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Osteoporose/patologiaAssuntos
Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/terapia , Tricuríase/imunologia , Trichuris/imunologia , Animais , Ensaios Clínicos como Assunto , Humanos , Imunoterapia/métodos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/parasitologia , Tricuríase/complicações , Tricuríase/parasitologiaRESUMO
BACKGROUND: Frequent use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been shown to reduce the risk of colorectal adenomas in randomized trials. We examined the persistence of the protective effect after the cessation of randomized aspirin treatment and whether it is affected by the duration and frequency of subsequent NSAID use. METHODS: We used data from the Aspirin/Folate Polyp Prevention Study (AFPPS), in which 1121 subjects were randomly assigned to receive placebo or aspirin (81 or 325 mg/d) for 3 years. After the end of treatment and a follow-up colonoscopy, AFPPS participants were invited to remain under follow-up until their next surveillance colonoscopies, scheduled 3-5 years later. Information regarding use of NSAIDs during posttreatment follow-up was gathered periodically via questionnaires. Average weekly NSAID use was classified as sporadic (<2 days per week), moderate (2 to <4 days per week), or frequent (>or=4 days per week). The analysis was stratified according to randomized aspirin groups and posttreatment NSAID use; placebo subjects who later were sporadic NSAID users formed the reference group. The primary outcomes were all adenomas and advanced lesions. Adjusted relative risks and 95% confidence intervals were computed with generalized linear models. All statistical tests were two-sided. RESULTS: A total of 850 subjects underwent a posttreatment colonoscopy, on average 4 years after the end of study treatment. The protective effect of 81 mg of aspirin for colorectal adenomas persisted with continued posttreatment NSAID use. The risk of any adenoma among frequent NSAID users was 26.8% vs 39.9% among placebo subjects who later used NSAIDs sporadically (adjusted relative risk = 0.62, 95% confidence interval [CI] = 0.39 to 0.98; P(trend) with NSAID use frequency = .03). The unadjusted absolute risk reduction was 13.1 percentage points (95% CI = -0.3 to 26.5 percentage points) (P = .07). Results for 325 mg of aspirin were similar, although not statistically significant. For advanced lesions, small numbers of endpoints limited the analysis, but findings among subjects randomly assigned to 81 mg of aspirin suggested a protective association regardless of posttreatment NSAID use. CONCLUSION: Long-term and frequent use of NSAIDs may enhance the chemopreventive effect of aspirin against colorectal neoplasia.
Assuntos
Adenoma/prevenção & controle , Anti-Inflamatórios não Esteroides/administração & dosagem , Anticarcinógenos/administração & dosagem , Aspirina/administração & dosagem , Neoplasias Colorretais/prevenção & controle , Adenoma/diagnóstico , Adenoma/epidemiologia , Idoso , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Intervalos de Confiança , Fatores de Confusão Epidemiológicos , Feminino , Seguimentos , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Razão de Chances , Medição de Risco , Fatores de Risco , Inquéritos e Questionários , Fatores de Tempo , Resultado do TratamentoRESUMO
Data regarding the association between folate status and risk of prostate cancer are sparse and conflicting. We studied prostate cancer occurrence in the Aspirin/Folate Polyp Prevention Study, a placebo-controlled randomized trial of aspirin and folic acid supplementation for the chemoprevention of colorectal adenomas conducted between July 6, 1994, and December 31, 2006. Participants were followed for up to 10.8 (median = 7.0, interquartile range = 6.0-7.8) years and asked periodically to report all illnesses and hospitalizations. Aspirin alone had no statistically significant effect on prostate cancer incidence, but there were marked differences according to folic acid treatment. Among the 643 men who were randomly assigned to placebo or supplementation with folic acid, the estimated probability of being diagnosed with prostate cancer over a 10-year period was 9.7% (95% confidence interval [CI] = 6.5% to 14.5%) in the folic acid group and 3.3% (95% CI = 1.7% to 6.4%) in the placebo group (age-adjusted hazard ratio = 2.63, 95% CI = 1.23 to 5.65, Wald test P = .01). In contrast, baseline dietary folate intake and plasma folate in nonmultivitamin users were inversely associated with risk of prostate cancer, although these associations did not attain statistical significance in adjusted analyses. These findings highlight the potential complex role of folate in prostate cancer and the possibly different effects of folic acid-containing supplements vs natural sources of folate.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Neoplasias Colorretais/prevenção & controle , Suplementos Nutricionais , Ácido Fólico/uso terapêutico , Neoplasias da Próstata/epidemiologia , Complexo Vitamínico B/uso terapêutico , Adenoma/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Inibidores de Ciclo-Oxigenase/uso terapêutico , Método Duplo-Cego , Ácido Fólico/sangue , Seguimentos , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Neoplasias da Próstata/induzido quimicamente , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/prevenção & controle , Projetos de Pesquisa , Inquéritos e Questionários , Estados Unidos/epidemiologia , Complexo Vitamínico B/sangueRESUMO
Some serrated polyps of the colorectum are likely preinvasive lesions, evolving through a newly recognized serrated pathway to colorectal cancer. To assess possible risk and protective factors for serrated polyps and particularly to explore differences in risk factors between polyps in the right and left colorectum, we pooled data from three large multicenter chemoprevention trials. A serrated polyp was defined broadly as any serrated lesion (hyperplastic, sessile serrated adenoma, "traditional" serrated adenoma, mixed adenoma) diagnosed during each trial's main treatment period of approximately 3 to 4 years. Using generalized linear regression, we computed risk ratios and 95% confidence intervals as measures of the association between risk for serrated polyps and demographic, lifestyle, and dietary variables. Of the 2,830 subjects that completed at least one follow-up exam after randomization, 675 (23.9%) had at least one left-sided serrated polyp and 261 (9.2%) had at least one right-sided lesion. In the left colorectum, obesity, cigarette smoking, dietary fat, total energy intake, and red meat intake were associated with an increased risk for serrated polyps. In the right colon, aspirin treatment was associated with a reduced risk and family history of polyps and folate treatment were associated with an increased risk for serrated polyps. Our results suggest that several common lifestyle and dietary variables are associated with risk for serrated polyps, and some of these may differ for the right and left colorectum.
Assuntos
Pólipos do Colo/etiologia , Dieta , Estilo de Vida , Doenças Retais/etiologia , Fatores Etários , Consumo de Bebidas Alcoólicas/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Antioxidantes/uso terapêutico , Aspirina/uso terapêutico , Índice de Massa Corporal , Cálcio/uso terapêutico , Pólipos do Colo/patologia , Pólipos do Colo/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Lesões Pré-Cancerosas/etiologia , Lesões Pré-Cancerosas/patologia , Grupos Raciais , Ensaios Clínicos Controlados Aleatórios como Assunto , Doenças Retais/patologia , Fatores de Risco , Fatores Sexuais , Fumar/efeitos adversosRESUMO
BACKGROUND: Calcium supplementation has been shown to decrease the risk of recurrence of colorectal adenomas in randomized trials. However, the duration of this protective effect after cessation of active supplementation is not known. METHODS: In the Calcium Polyp Prevention Study, 930 subjects with a previous colorectal adenoma were randomly assigned from November 1988 through April 1992 to receive placebo or 1200 mg of elemental calcium daily for 4 years. The Calcium Follow-up Study was an observational phase of the trial that tracked adenoma occurrence for an average of 7 years after the end of randomized treatment and gathered information regarding the use of medications, vitamins, and supplements during that time. We obtained follow-up information for 822 subjects, 597 of whom underwent at least one colonoscopy after the end of study treatment and are included in this analysis. Generalized linear models were used to compute relative risks (RRs) and 95% confidence intervals (CIs) for the effect of randomized calcium treatment on risk of adenoma recurrence during the first 5 years after study treatment ended and during the subsequent 5 years. Statistical tests were two-sided. RESULTS: During the first 5 years after randomized treatment ended, subjects in the calcium group still had a substantially and statistically significantly lower risk of any adenoma than those in the placebo group (31.5% versus 43.2%; adjusted RR = 0.63, 95% CI = 0.46 to 0.87, P = .005) and a smaller and not statistically significant reduction in risk of advanced adenomas (adjusted RR = 0.85, 95% CI = 0.43 to 1.69, P = .65). However, the randomized treatment was not associated with the risk of any type of polyp during the next 5 years. The findings were broadly similar when the analysis was restricted to subjects who did not report use of any calcium supplements after the treatment phase of the trial ended. CONCLUSION: The protective effect of calcium supplementation on risk of colorectal adenoma recurrence extends up to 5 years after cessation of active treatment, even in the absence of continued supplementation.
Assuntos
Adenoma/prevenção & controle , Anticarcinógenos/administração & dosagem , Cálcio da Dieta/administração & dosagem , Neoplasias Colorretais/prevenção & controle , Suplementos Nutricionais , Adenoma/diagnóstico , Adenoma/epidemiologia , Idoso , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Razão de Chances , Projetos de Pesquisa , Medição de Risco , Fatores de TempoRESUMO
The authors describe the University of Iowa Department of Radiology's business planning process to initiate a new service in computed tomographic colonography (CTC). Also known as virtual colonoscopy, CTC is a noninvasive technology that offers less risk, and potentially similar sensitivity and specificity, than conventional optical colonoscopy (OC). Although not currently covered by all insurance payers, about a year ago, the Centers for Medicare and Medicaid Services instituted temporary Current Procedural Terminology codes (Category III) for CTC. In locales where the procedure is not covered by insurers, it is likely to be sought by patients willing to pay out of pocket to undergo noninvasive cancer screening as an alternative to OC. Thus, CTC could become the preferred method of colon cancer surveillance by insurance providers in the near future. In developing the business plan, the authors reviewed pertinent scientific and clinical data to evaluate the need for and efficacy of CTC. Local market data were used to estimate patient and procedure volumes and utilization. The authors modeled financial expectations with respect to return on investment on the basis of recently reported models specific to CTC, resource requirements, and the operational impact of the new service on existing hospital and departmental clinical functions. Because there are few local providers of CTC in the authors' region, the business plan also included a publicity campaign and plan to market the new service, stimulate general public interest early, and differentiate the program as a leader in applying this unique new technology to promote cancer screening. Finally, the planning committee acknowledged and accommodated needs specific to the missions of an academic medical center with respect to research and education in designing the new service.
Assuntos
Centros Médicos Acadêmicos/organização & administração , Colonografia Tomográfica Computadorizada/economia , Planejamento de Instituições de Saúde/organização & administração , Marketing de Serviços de Saúde/organização & administração , Modelos Organizacionais , Objetivos Organizacionais/economia , Serviço Hospitalar de Radiologia/organização & administração , Iowa , Modelos Econômicos , Técnicas de PlanejamentoRESUMO
The rapid rise in prevalence of ulcerative colitis (UC) and Crohn's disease (CD) in highly developed countries suggests that environmental change engenders risk for inflammatory bowel disease (IBD). Eradication of parasitic worms (helminths) through increased hygiene may be one such change that has led to increased prevalence of these diseases. Helminths alter host mucosal and systemic immunity, inhibiting dysregulated inflammatory responses. Animals exposed to helminths are protected from experimental colitis, encephalitis, and diabetes. Patients with CD or UC improve when exposed to whipworm. Lamina propria (LP) mononuclear cells from helminth-colonized mice make less interleukin (IL)-12 p40 and IFN-gamma, but more IL-4, IL-13, IL-10, TGF-beta, and PGE(2) compared to LP mononuclear cells from naive mice. Systemic immune responses show similar skewing toward Th2 and regulatory cytokine production in worm-colonized animal models and humans. Recent reports suggest that helminths induce regulatory T cell activity. These effects by once ubiquitous organisms may have protected individuals from many of the emerging immune-mediated illnesses like IBD, multiple sclerosis, type I diabetes, and asthma.
Assuntos
Citocinas/metabolismo , Helmintos/imunologia , Mediadores da Inflamação/metabolismo , Doenças Inflamatórias Intestinais/imunologia , Mucosite/imunologia , Linfócitos T Reguladores/imunologia , Animais , Citocinas/imunologia , Humanos , Mediadores da Inflamação/imunologia , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/parasitologia , Mucosite/metabolismo , Mucosite/parasitologia , Linfócitos T Reguladores/metabolismoRESUMO
PURPOSE OF REVIEW: Inflammatory bowel disease is an emerging illness associated with socioeconomic development. The current epidemic of immune-mediated diseases may result from our loss of exposure to parasitic worms (helminths). This review summarizes some of the recent findings showing that helminths induce regulatory circuits that could prevent and treat inflammatory bowel disease. RECENT FINDINGS: Inflammatory bowel disease appears to result from a dysregulated immune response. Although genes influence the risk of inflammatory bowel disease, it seems that critical changes in our environment have permitted its expression. One such change is the eradication of helminths. Helminths can impede interleukin-12, interferon gamma, and tumor necrosis factor alpha release and promote interleukin-10, transforming growth factor beta, and regulatory T-cell production. Helminths can prevent and reverse intestinal inflammation in animal models of inflammatory bowel disease. In clinical studies of patients with inflammatory bowel disease, exposure to the helminth Trichuris suis reduces disease activity. SUMMARY: If harboring helminths protects against immune-mediated disease, then these animals must be viewed in a new light. Are there "good" helminths in addition to bad? Instead of being detestable objects marked for eradication, helminths should be viewed as useful animals that may produce important compounds helpful for therapy of human disease.
Assuntos
Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/terapia , Trichuris/imunologia , Animais , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Mucosa Intestinal/imunologiaRESUMO
The purpose of this study was to determine if lowering carbohydrate (CHO) concentration in a sport drink influences gastric emptying, intestinal absorption, or performance during cycle ergometry (85 min, 60% VO(2peak)). Five subjects (25 +/- 1 y, 61.5 +/- 2.1 mL . kg(-1) . min(-1) VO(2peak)) ingested a 3% CHO, 6% CHO, or a water placebo (WP) beverage during exercise. Gastric emptying was determined by repeated double sampling and intestinal absorption by segmental perfusion. Total solute absorption and plasma glucose was greater for 6% CHO; however, neither gastric emptying, intestinal water absorption, or 3-mi time trial performance (7:58 +/- 0:33 min, 8:13 +/- 0:25 min, and 8:25 +/- 0:29 min, respectively, for 6% CHO, 3% CHO, and WP) differed among solutions. These results indicate lowering the CHO concentration of a sport drink from 6% CHO does not enhance gastric emptying, intestinal water absorption, or time trial performance, but reduces CHO and total solute absorption.
Assuntos
Bebidas , Ciclismo/fisiologia , Carboidratos da Dieta/administração & dosagem , Carboidratos da Dieta/farmacocinética , Esvaziamento Gástrico/fisiologia , Absorção Intestinal/fisiologia , Adulto , Estudos Cross-Over , Relação Dose-Resposta a Droga , Ingestão de Líquidos , Feminino , Esvaziamento Gástrico/efeitos dos fármacos , Humanos , Absorção Intestinal/efeitos dos fármacos , Masculino , Consumo de OxigênioRESUMO
BACKGROUND & AIMS: Ulcerative colitis is most common in Western industrialized countries. Inflammatory bowel disease is uncommon in developing countries where helminths are frequent. People with helminths have an altered immunological response to antigens. In animal models, helminths prevent or improve colitis by the induction of regulatory T cells and modulatory cytokines. This study determined the efficacy and safety of the helminth Trichuris suis in therapy of ulcerative colitis. METHODS: This was a randomized, double blind, placebo-controlled trial conducted at the University of Iowa and select private practices. Trichuris suis ova were obtained from the US Department of Agriculture. The trial included 54 patients with active colitis, defined by an Ulcerative Colitis Disease Activity Index of > or =4. Patients were recruited from physician participants and were randomly assigned to receive placebo or ova treatment. Patients received 2500 Trichuris suis ova or placebo orally at 2-week intervals for 12 weeks. RESULTS: The primary efficacy variable was improvement of the Disease Activity Index to > or =4. After 12 weeks of therapy, improvement according to the intent-to-treat principle occurred in 13 of 30 patients (43.3%) with ova treatment compared with 4 of 24 patients (16.7%) given placebo (P = .04). Improvement was also found with the Simple Index that was significant by week 6. The difference in the proportion of patients who achieved an Ulcerative Colitis Disease Activity Index of 0-1 was not significant. Treatment induced no side effects. CONCLUSIONS: Ova therapy seems safe and effective in patients with active colitis.