RESUMO
BACKGROUND: Temporary prophylactic pancreatic duct stenting effectively reduces post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk patients, but the optimal stent remains unclear. We compared rate of spontaneous passage, and technical difficulty of placement for 3-Fr and 5-Fr stents. METHODS: A randomized controlled trial at a single academic medical center. Patients deemed high risk for PEP randomly received 5-Fr or 3-Fr pancreatic duct stents. Primary outcome was spontaneous stent passage by 2 weeks. Secondary outcomes were ease and time for stent placement, and number of guide wires required for the entire procedure. RESULTS: Patients (69 female [89 %]; mean age 44.9 years, standard deviation [SD] 16.8) were randomly assigned to receive 5-Fr (n = 38) and 3-Fr (n = 40) stents. Indications for stenting were similar. Seven patients in the 3-Fr group actually received a 5-Fr stent, and two in the 5-Fr group had a 3-Fr stent. Spontaneous passage or non-passage was confirmed in 64 (83 %). No statistically significant difference in spontaneous passage rates was seen (5-Fr group, 68.4 %; 3-Fr group 75.0 %; P = 0.617). Non-passage rates were 10.5 % (5-Fr group) and 10.0 % (3-Fr group) ( P = 1.00). The study was stopped after a futility analysis for the primary end point. Placement of 5-Fr stents was rated easier, at a mean score of 1.8 (5-Fr) vs. 3.4 (3-Fr), P < 0.001, with a trend towards being faster, 9.2 vs. 11.1 minutes ( P = 0.355). Fewer guide wires were required for 5-Fr stent placement, 1.5 vs. 1.9 ( P = 0.002). PEP rates did not differ ( P = 0.519). CONCLUSION: Placement of 5-Fr compared to 3-Fr pancreatic duct stents for PEP prophylaxis is easier, faster, and requires fewer wires. No statistically significant difference in spontaneous passage was found between the two sizes.
Assuntos
Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Ductos Pancreáticos/cirurgia , Pancreatite/etiologia , Pancreatite/prevenção & controle , Stents , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Stents/efeitos adversosRESUMO
Recent international consensus guidelines propose that cystic pancreatic tumors less than 3 cm in size in asymptomatic patients with no radiographic features concerning for malignancy are safe to observe; however, there is little published data to support this recommendation. The purpose of this study was to determine the prevalence of malignancy in this group of patients using pancreatic resection databases from five high-volume pancreatic centers to assess the appropriateness of these guidelines. All pancreatic resections performed for cystic neoplasms < or =3 cm in size were evaluated over the time period of 1998-2006. One hundred sixty-six cases were identified, and the clinical, radiographic, and pathological data were reviewed. The correlation with age, gender, and symptoms (abdominal pain, nausea and vomiting, jaundice, presence of pancreatitis, unexplained weight loss, and anorexia), radiographic features suggestive of malignancy by either computed tomography, magnetic resonance imaging, or endoscopic ultrasound (presence of solid component, lymphadenopathy, or dilated main pancreatic duct or common bile duct), and the presence of malignancy was assessed using univariate and multivariate analysis. Among the 166 pancreatic resections for cystic pancreatic tumors < or =3 cm, 135 cases were benign [38 serous cystadenomas, 35 mucinous cystic neoplasms, 60 intraductal papillary mucinous neoplasms (IPMN), 1 cystic papillary tumor, and 1 cystic islet cell tumor], whereas 31 cases were malignant (14 mucinous cystic adenocarcinomas and 13 invasive carcinomas and 4 in situ carcinomas arising in the setting of IPMN). A greater incidence of cystic neoplasms was seen in female patients (99/166, 60%). Gender was a predictor of malignant pathology, with male patients having a higher incidence of malignancy (19/67, 28%) compared to female patients (12/99, 12%; p < 0.02). Older age was associated with malignancy (mean age 67 years in patients with malignant disease vs 62 years in patients with benign lesions (p < 0.05). A majority of the patients with malignancy were symptomatic (28/31, 90%). Symptoms that correlated with malignancy included jaundice (p < 0.001), weight loss (p < 0.003), and anorexia (p < 0.05). Radiographic features that correlated with malignancy were presence of a solid component (p < 0.0001), main pancreatic duct dilation (p = 0.002), common bile duct dilation (p < 0.001), and lymphadenopathy (p < 0.002). Twenty-seven of 31(87%) patients with malignant lesions had at least one radiographic feature concerning for malignancy. Forty-five patients (27%) were identified as having asymptomatic cystic neoplasms. All but three (6.6%) of the patients in this group had benign disease. Of the patients that had no symptoms and no radiographic features, 1 out of 30 (3.3%) had malignancy (carcinoma in situ arising in a side branch IPMN). Malignancy in cystic neoplasms < or =3 cm in size was associated with older age, male gender, presence of symptoms (jaundice, weight loss, and anorexia), and presence of concerning radiographic features (solid component, main pancreatic duct dilation, common bile duct dilation, and lymphadenopathy). Among asymptomatic patients that displayed no discernable radiographic features suggestive of malignancy who underwent resection, the incidence of occult malignancy was 3.3%. This study suggests that a group of patients with small cystic pancreatic neoplasms who have low risk of malignancy can be identified, and selective resection of these lesions may be appropriate.
Assuntos
Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Idoso , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Cistadenoma Seroso/patologia , Cistadenoma Seroso/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pancreaticoduodenectomia , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: The use of non-steroidal anti-inflammatory drugs (NSAIDs) is often associated with upper gastrointestinal symptoms such as heartburn and acid regurgitation. AIM: To assess the efficacy of esomeprazole 20 and 40 mg for resolution of heartburn and acid regurgitation in continuous NSAIDs. METHODS: A post hoc analysis of five clinical trials was performed. Two identically designed, placebo-controlled, 4-week studies (NASA1, SPACE1) enrolled non-ulcer, NSAIDs-treated patients with upper abdominal pain, discomfort or burning. PLUTO and VENUS were identically designed, placebo-controlled, 6-month studies that enrolled patients at risk of NSAIDs-induced ulcers. Study 285 was an 8-week comparative study with ranitidine (300 mg/day) in patients with NSAIDs-induced gastric ulcers. Resolution of investigator-assessed heartburn and acid regurgitation was defined as symptom severity of 'none' in the last 7 days. RESULTS: In NASA1/SPACE1, heartburn resolved in 61% and 62% of patients taking esomeprazole 20 and 40 mg, respectively (vs. 36% on placebo, P < 0.001), and acid regurgitation resolved in 65% and 67% (vs. 48%, P < 0.001). Resolution of both symptoms was greater with esomeprazole than with placebo in PLUTO/VENUS (P Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos
, Antiulcerosos/uso terapêutico
, Esomeprazol/uso terapêutico
, Refluxo Gastroesofágico/prevenção & controle
, Azia/prevenção & controle
, Adulto
, Feminino
, Refluxo Gastroesofágico/induzido quimicamente
, Azia/induzido quimicamente
, Humanos
, Pessoa de Meia-Idade
, Estudos Multicêntricos como Assunto
, Ensaios Clínicos Controlados Aleatórios como Assunto
, Resultado do Tratamento
RESUMO
Proton pump inhibitors have dramatically improved the management options available for patients with acid-related disorders. In patients with gastro-oesophageal reflux disease, currently available proton pump inhibitors provide an excellent outcome for the majority; however, they do not provide optimal pH control in many. Proton pump inhibitors co-therapy reduces, but does not eliminate, the risk of gastrointestinal ulcers and complications in patients taking non-steroidal anti-inflammatory drugs, while in patients with upper gastrointestinal bleeding, it may be difficult to reach and maintain the current therapeutic target of intragastric pH of 6-7. This article reviews the effectiveness of current antisecretory therapy in these three acid-related diseases and areas of unmet clinical need. The potential role of a proton pump inhibitor with an extended duration of action and enhanced acid control from a single daily dose, particularly improved control at night, is discussed. Finally, therapy that could be administered without regard to time of day and/or food intake would offer dosing flexibility and thus have a positive effect on patients' compliance.
Assuntos
Antiácidos/uso terapêutico , Antiulcerosos/uso terapêutico , Gastroenteropatias/tratamento farmacológico , Inibidores da Bomba de Prótons , Anti-Inflamatórios não Esteroides/efeitos adversos , Refluxo Gastroesofágico/tratamento farmacológico , Gastroenteropatias/induzido quimicamente , Hemorragia Gastrointestinal/tratamento farmacológico , Humanos , Concentração de Íons de Hidrogênio , Úlcera Péptica/tratamento farmacológicoRESUMO
BACKGROUND: Colorectal cancer screening rates among patients with upper gastrointestinal symptoms undergoing oesophagogastroduodenoscopy have not been previously established. We hypothesize that gastroenterologists seize this opportunity more frequently than primary care providers. AIMS: To assess colorectal cancer screening rates at the time of direct access oesophagogastroduodenoscopy and gastrointestinal clinic evaluation for upper gastrointestinal symptoms. To compare rates in the 6 months following the oesophagogastroduodenoscopy in both cohorts of patients. METHODS: Retrospective review. primary care physician group: direct access oesophagogastroduodenoscopy (n = 247) vs. gastrointestinal group (n = 278). Multivariable regression analysis utilized to assess predictors of screening outcome. RESULTS: Colorectal cancer screening at the time of referral was 54%. Among the 243 unscreened patients, an additional 29% in the primary care physician group vs. 59% in the gastrointestinal group completed colorectal cancer screening in 6 months of follow-up. Nearly 60% patients evaluated in gastrointestinal clinic for upper symptoms had documented discussion, and 99% of those patients underwent colonoscopy (P < 0.001). Gastrointestinal consultation increased the probability of colorectal cancer screening completion eightfold (95% CI 3.69-18.96). CONCLUSIONS: At the time of evaluation for upper symptoms, half of patients were not current with colorectal cancer screening recommendations. Referrals for the direct access oesophagogastroduodenoscopy and, more importantly, the gastroenterology consult represent key opportunities for colorectal cancer screening education and improved compliance.
Assuntos
Neoplasias Colorretais/diagnóstico , Endoscopia do Sistema Digestório/métodos , Fatores Etários , Idoso , Estudos de Coortes , Colonoscopia/métodos , Duodenoscopia/métodos , Esofagoscopia/métodos , Feminino , Gastroscopia/métodos , Nível de Saúde , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Relações Médico-Paciente , Atenção Primária à Saúde/métodos , Encaminhamento e Consulta , Estudos Retrospectivos , Fatores SexuaisRESUMO
AIM: To assess primary care physician perceptions of non-steroidal anti-inflammatory drug (NSAID) and aspirin-associated toxicity. METHODS: A group of gastroenterologists and internal medicine physicians created a survey, which was administered via the Internet to a large number of primary care physicians from across the US. RESULTS: One thousand primary care physicians participated. Almost one-third of primary care physicians recommended 325 mg rather than 81 mg of aspirin/day for cardioprotection. Fifty-nine percent thought enteric-coated or buffered aspirin reduced the risk of upper gastrointestinal (GI) bleeding. Seventy-six percent believed that Helicobacter pylori infection increased the risk of NSAID ulcers but fewer than 25% tested NSAID users for this infection. More than two-thirds were aware that aspirin co-therapy decreased the GI safety benefits of the cyclo-oxygenase 2 selective NSAIDs. However, 84% felt that aspirin with a cyclo-oxygenase 2 selective NSAID was safer than aspirin with a non-selective NSAID. When presented a patient at high risk for NSAID-related GI toxicity, almost 50% of primary care physicians recommended a proton pump inhibitor and cyclo-oxygenase 2 selective NSAID. CONCLUSIONS: This survey has identified areas of misinformation regarding the risk-benefit of NSAIDs and aspirin and the utilization of gastroprotective strategies. Further education on NSAIDs for primary care physicians is warranted.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Atenção Primária à Saúde , Adulto , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Atitude do Pessoal de Saúde , Cardiotônicos/efeitos adversos , Cardiotônicos/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Feminino , Hemorragia Gastrointestinal/complicações , Pesquisas sobre Atenção à Saúde , Infecções por Helicobacter/complicações , Helicobacter pylori , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/complicações , Médicos de Família/psicologia , Inibidores da Bomba de Prótons , Fatores de RiscoRESUMO
Sarcoidosis is a granulomatous disease of unknown origin with a variable clinical presentation. The presenting complaint is usually referable to the lung. We describe an unusual presentation of sarcoidosis in a young black man who received medical attention for evaluation of pancytopenia, giant splenomegaly, and marked, refractory hypercalcemia. After extensive evaluation, including exploratory laparotomy, he was found to have sarcoidosis, with extensive involvement of his spleen, liver, and abdominal lymph nodes. Pulmonary involvement was notably absent, with no suggestive findings radiographically on gallium citrate Ga 67 scanning or on bronchoscopy with transbronchial biopsy. This patient underwent splenectomy and, following removal of the massive splenic granuloma burden, the hypercalcemia resolved completely with no other therapy.
Assuntos
Hipercalcemia/etiologia , Sarcoidose/complicações , Esplenectomia , Esplenomegalia/etiologia , Adulto , Humanos , Masculino , Esplenomegalia/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Helicobacter pylori infection has been identified as a risk factor for certain types of gastric cancer. However, the extent to which H. pylori eradication decreases the risk of gastric cancer is unknown, raising the question of whether population-based H. pylori screening should be undertaken. OBJECTIVE: To compare clinical and economic effects of H. pylori screening, with and without confirmatory testing, with no screening to prevent gastric cancer. DESIGN: Decision analysis incorporating a Markov simulation. PATIENTS: Simulated cohorts of men and women with varying risk of gastric cancer. INTERVENTION: Three strategies were evaluated: (1) no screening; (2) H. pylori serologic testing, treat those positive for H. pylori, no follow-up testing; and (3) H. pylori serologic testing, treat those positive for H. pylori, followed by a test to confirm H. pylori eradication, retreat those who test positive. In the principal analysis, the risk of gastric cancer after H. pylori eradication was assumed to be similar to that for those without H. pylori infection. Scenarios with less optimistic assumptions regarding risk reduction of cancer were evaluated. MAIN OUTCOME MEASURES: Gastric cancer rates, discounted cost per life-year saved. RESULTS: If H. pylori eradication reduced the risk of cancer to that of people never infected, both H. pylori intervention strategies reduced gastric cancer rates so that each yielded at least 12 additional life-years per 1000 40-year-old white men screened when compared with no screening. Helicobacter pylori serologic testing without posttreatment confirmatory testing resulted in the lowest cost per additional life-year saved (S6264). The cost-effectiveness of the H. pylori screening strategies varied substantially as the level of risk reduction of cancer was varied, but remained cost-effective even at moderate rates (<30%) of excess risk reduction of cancer in all cohorts evaluated. CONCLUSIONS: Population-based H. pylori screening has the potential to produce important health benefits at a reasonable cost at moderate rates of excess risk reduction of cancer. Controlled studies are necessary to confirm and quantify the impact of H. pylori eradication on the risk of gastric cancer.
Assuntos
Infecções por Helicobacter/complicações , Infecções por Helicobacter/economia , Helicobacter pylori , Programas de Rastreamento , Vigilância da População , Neoplasias Gástricas/economia , Neoplasias Gástricas/prevenção & controle , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Feminino , Infecções por Helicobacter/diagnóstico , Humanos , Masculino , Cadeias de Markov , Programas de Rastreamento/economia , Risco , Sensibilidade e Especificidade , Neoplasias Gástricas/microbiologia , Resultado do Tratamento , Estados UnidosRESUMO
Coprescription of gastroprotective agents is a common practice for patients requiring nonsteroidal anti-inflammatory drug (NSAID) therapy, although there is limited evidence that some of these agents are effective. The prostaglandin analog misoprostol and the proton pump inhibitor omeprazole appear to be efficacious in decreasing NSAID-associated ulcers. Misoprostol has also been shown to decrease NSAID-associated gastrointestinal (GI) complications by 40% compared with placebo. Despite the efficacy of these drugs, their effectiveness in the general population has not yet been adequately determined with respect to reduction of symptoms and improvement in patient quality of life. Sucralfate and bismuth appear to be largely ineffective, and histamine receptor antagonists, when given at traditional ulcer-healing doses, decrease symptoms and duodenal ulcers only. The issue of outcomes research, therefore, needs to be more fully incorporated into any analysis of the effectiveness or cost-effectiveness of the widespread clinical use of such gastroprotective drugs.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Antiulcerosos/uso terapêutico , Úlcera Péptica/tratamento farmacológico , Antiulcerosos/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Humanos , Mucosa Intestinal/efeitos dos fármacos , Misoprostol/uso terapêutico , Omeprazol/uso terapêutico , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/prevenção & controle , Inibidores da Bomba de PrótonsRESUMO
Rheumatoid arthritis and osteoarthritis are prevalent and costly conditions. A large proportion of the direct costs associated with these conditions relates to management of iatrogenic side effects. The cyclooxygenase (COX)-2-specific inhibitors lead to equivalent control of pain and disability compared with traditional NSAIDs. However, the COX-2-specific inhibitors have significant potential to reduce health-care costs, principally through the reduction of side effects. These cost savings are most likely to be realized through reductions in costs associated with dyspepsia and upper gastrointestinal ulcers and bleeding. Reduced indirect costs through improved disability scores and improved health-related quality of life are also predictable with the use of COX-2-specific inhibitors. This is accomplished without the attendant increase in risk to the gastrointestinal tract associated with traditional NSAIDs.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/economia , Inibidores de Ciclo-Oxigenase/efeitos adversos , Inibidores de Ciclo-Oxigenase/economia , Isoenzimas/antagonistas & inibidores , Osteoartrite/tratamento farmacológico , Osteoartrite/economia , Artrite Reumatoide/epidemiologia , Canadá , Redução de Custos , Efeitos Psicossociais da Doença , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Custos de Medicamentos/estatística & dados numéricos , Farmacoeconomia , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Proteínas de Membrana , Osteoartrite/epidemiologia , Prevalência , Prostaglandina-Endoperóxido Sintases , Fatores de RiscoRESUMO
Traditional nonsteroidal anti-inflammatory drugs (NSAIDs) increase the risk of clinically important upper gastrointestinal ulcers and bleeds about fourfold. Other risk factors for these events include advanced age, higher NSAID dose, prior ulcer or bleed, use of anticoagulants, use of corticosteroids, and poor general health. Among NSAID users with more than one risk factor, the incidence of serious ulcer complications may be as high as 4% to 8% per year. NSAIDs may also increase blood pressure and have adverse effects on renal function. NSAID-associated toxicity may be decreased by (1) trying less toxic alternative drugs; (2) using NSAIDs less frequently or at a lower dose; (3) use of cotherapy, such as misoprostol or proton pump inhibitors, to prevent complications; (4) or use of the more selective cyclooxygenase-2 inhibitors. More research is needed to determine which of these strategies or combination of strategies is optimal in terms of patient safety and cost.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Antiulcerosos/uso terapêutico , Hipertensão/induzido quimicamente , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/prevenção & controle , Anti-Inflamatórios não Esteroides/administração & dosagem , Antiulcerosos/economia , Pressão Sanguínea/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase/uso terapêutico , Custos de Medicamentos , Quimioterapia Combinada , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Humanos , Hipertensão/prevenção & controle , Incidência , Misoprostol/uso terapêutico , Medicamentos sem Prescrição/uso terapêutico , Úlcera Péptica/tratamento farmacológico , Úlcera Péptica Hemorrágica/induzido quimicamente , Úlcera Péptica Hemorrágica/prevenção & controle , Fatores de Risco , Estados UnidosRESUMO
Infection with Helicobacter pylori is now recognized as the primary cause of peptic ulcers and their recurrence. Compelling evidence has also been found linking H. pylori infection to gastric cancer, the second most common cancer in the world. Given the high rate of patient morbidity and mortality associated with gastric cancer, any method by which one can reduce the occurrence of the disease or increase its early detection is desirable. The strong correlation with H. pylori infection and the current availability of easily administered tests for the detection of the pathogen argue for screening at least those individuals with a family history of gastric cancer or other risk factors. This article reviews the association between H. pylori and gastric cancer and the pathologic changes that the infection produces in the gastric mucosa, as well as the cost-effectiveness of universal testing and eradication of the infection in H. pylori-positive individuals to reduce gastric cancer.
Assuntos
Gastrite Atrófica/complicações , Infecções por Helicobacter/complicações , Helicobacter pylori , Neoplasias Gástricas/microbiologia , Gastrite Atrófica/microbiologia , Gastrite Atrófica/fisiopatologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/fisiopatologia , Humanos , Neoplasias Gástricas/fisiopatologiaRESUMO
Nonsteroidal antiinflammatory drugs (NSAIDs) initiate gastroduodenal ulceration and promote complications such as bleeding and perforation by interfering with the ability of the proximal gastrointestinal tract to maintain its defensive capabilities. Mucosal defense is composed of three critical components: preepithelial, epithelial, and postepithelial. Preepithelial defense is composed of the mucous gel containing mucin, bicarbonate, and surface-active phospholipids. The epithelial component includes the surface cells, their apical tight junctions, and membrane transporters. Postepithelial defense is maintained by mucosal blood flow, which is essential for both defense and repair. NSAIDs interfere with each component of mucosal defense via direct toxic effects along with cyclooxygenase inhibition and depletion of endogenous prostaglandins. Although NSAID injury is dependent on luminal acid, attempts to prevent NSAID injury by acid suppression using H2-receptor antagonists in humans have had limited success, whereas complete inhibition of acid secretion with proton pump inhibition may have promise. Prostaglandins appear most effective for prevention of NSAID injury, sucralfate appears ineffective, and bismuth compounds have not been studied extensively. Recent evidence suggests that NSAID ulcers heal quickly with proton pump inhibitors compared with H2-receptor antagonists in patients who continue NSAID therapy.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Úlcera Péptica/induzido quimicamente , Humanos , Úlcera Péptica/prevenção & controle , Úlcera Péptica/terapiaRESUMO
Animal models have identified multiple mechanisms of aspirin toxicity. Aspirin inhibits cyclooxygenase in the gastroduodenal mucosa leading to a decrease in endogenous prostaglandins. Prostaglandin mediated mucus and bicarbonate secretion, epithelial hydrophobicity, blood flow, and cellular proliferation are all decreased. Salicylates may cause direct cellular toxicity via inhibition of energy metabolism and membrane transport properties. Salicylate preparations have been designed to decrease gastroduodenal absorption. Endoscopic studies in humans have confirmed that buffering of aspirin does not ameliorate damage, but enteric coating does. Salicylsalicylic acid (salsalate) is an effective antirheumatic drug that bypasses gastric absorption and also avoids cyclooxygenase inhibition. In a randomized, single-blind, endoscopic comparison of salsalate versus enteric-coated aspirin, significantly less gastroduodenal damage was observed in volunteers after salsalate administration compared to enteric-coated aspirin. An endoscopic study in rheumatoid arthritics also confirmed the ability of salsalate to spare gastroduodenal mucosa when compared to naproxen administration. Salsalate may cause less gastroduodenal damage than enteric-coated aspirin based on the results of animal models and endoscopic studies in humans.
Assuntos
Aspirina/efeitos adversos , Duodeno/efeitos dos fármacos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Salicilatos/efeitos adversos , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase , Duodeno/patologia , Duodeno/fisiologia , Endoscopia , Mucosa Gástrica/patologia , Mucosa Gástrica/fisiologia , Humanos , Mucosa Intestinal/patologia , Mucosa Intestinal/fisiologia , Prostaglandina-Endoperóxido Sintases/fisiologia , Prostaglandinas/fisiologiaRESUMO
OBJECTIVES: Nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal (GI) toxicity remains the most frequent adverse drug event in the United States. The objective of this review is to update clinicians in recent advances in basic and clinical investigation regarding the pathogenesis and management of NSAID gastropathy. METHODS: Based upon an extensive review of the published literature and abstracts of key work within the past decade, the framework for new approaches to the prevention and treatment of NSAID-associated ulceration is summarized. RESULTS: The pathophysiology of NSAID-induced injury to the GI tract is multifaceted and includes both prostaglandin-dependent and independent components. The pharmaceutical industry has capitalized on the identification of two different isoforms of cyclooxygenase, enabling the development of specific inhibitors of one isoform that minimizes prostaglandin-dependent mechanisms that contribute to NSAID-induced injury. Clinical trials support the efficacy and reduced toxicity of these agents. Because acid exacerbates the injury initiated by NSAIDs, potent acid suppressive therapy, typically with proton pump inhibitors, is another common approach to the treatment of NSAID-related dyspepsia as well as NSAID-induced ulcer disease. CONCLUSIONS: Recent improvements in the understanding of NSAID-induced damage and new drug development have provided the opportunity for effective anti-inflammatory therapy with reduced GI toxicity. This illustrates the importance of identifying patients at risk for potential complications and the appropriate use of strategies to prevent and treat NSAID-induced complications.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Gastroenteropatias/induzido quimicamente , Anti-Inflamatórios não Esteroides/farmacologia , Ciclo-Oxigenase 1 , Ciclo-Oxigenase 2 , Sistema Digestório/efeitos dos fármacos , Gastroenteropatias/epidemiologia , Gastroenteropatias/fisiopatologia , Gastroenteropatias/prevenção & controle , Humanos , Isoenzimas/antagonistas & inibidores , Proteínas de Membrana , Prostaglandina-Endoperóxido Sintases , Substâncias Protetoras/uso terapêuticoRESUMO
UNLABELLED: Cyclooxygenase (COX)-2 expression and prostaglandin production is increased by Helicobacter pylori infection. Non-selective COX inhibitors reduce prostaglandins and mucosal proliferation in infected mucosa and may reduce gastric cancer risk, but ulceration precludes their use. COX-2 inhibitors cause fewer ulcers and may be chemopreventive. Physiological studies of COX-2 inhibitors in humans with H. pylori infection have not been performed. AIM: To study the impact of COX-2 specific inhibition on gastric prostaglandin levels, H. pylori gastritis and proliferation. METHODS: Twenty infected (eight males, 12 females; age 38 +/- 1.8) and six uninfected (four males, two females; age 36 +/- 3.5) healthy volunteers received rofecoxib 25 mg daily for 14 days. Endoscopic biopsies were evaluated for prostaglandin E2 (PGE2) content, gastritis and proliferation. RESULTS: Before drug therapy, compared to uninfected, H. pylori-infected subjects had significantly higher: (a) gastric mucosal PGE2 (pg/mg tissue) in the gastric body and antrum, (b) H. pylori score in body and antrum and (c) mid-gland proliferation index in antrum and body. The COX-2 inhibitor did not significantly affect PGE2 levels, gastritis scores or proliferation indices in the body or antrum in the H. pylori-positive or -negative subjects. CONCLUSION: The predominant source of increased gastric PGE2 in H. pylori infection appears to be COX-1-derived. In non-ulcerated H. pylori gastritis, COX-2 inhibition does not affect cellular proliferation. Rofecoxib's lack of effect on gastric prostaglandin levels and proliferation in H. pylori-infected mucosa may explain the absence of an increased ulcer risk among COX-2 inhibitor users with H. pylori infection. The lack of significant effect on intermediate biomarkers raises uncertainty regarding the potential of specific COX-2 inhibitors for chemoprevention of gastric cancer.
Assuntos
Dinoprostona/metabolismo , Gastrite/microbiologia , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori , Isoenzimas/antagonistas & inibidores , Neoplasias Gástricas/prevenção & controle , Adulto , Divisão Celular , Ciclo-Oxigenase 2 , Endoscopia Gastrointestinal , Feminino , Seguimentos , Mucosa Gástrica/metabolismo , Gastrite/metabolismo , Gastrite/patologia , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/patologia , Humanos , Lactonas/uso terapêutico , Masculino , Proteínas de Membrana , Prostaglandina-Endoperóxido Sintases , Antro Pilórico/metabolismo , SulfonasRESUMO
BACKGROUND: The benefits of the Helicobacter pylori test-and-treat strategy are attributable largely to the cure of peptic ulcer disease while limiting the use of endoscopy. AIM: To reappraise the test-and-treat strategy and empirical proton pump inhibitor therapy for the management of uninvestigated dyspepsia in the light of the decreasing prevalence of H. pylori infection, peptic ulcer disease and peptic ulcer disease attributable to H. pylori. METHODS: Using a decision analytical model, we estimated the cost per patient with uninvestigated dyspepsia managed with the test-and-treat strategy ($25/test; H.pylori treatment, $200) or proton pump inhibitor ($90/month). Endoscopy ($550) guided therapy for persistent or recurrent symptoms. RESULTS: In the base case (25%H. pylori prevalence, 20% likelihood of peptic ulcer disease, 75% of ulcers due to H.pylori), the cost per patient is $545 with the test-and-treat strategy and $529 with proton pump inhibitor, and both strategies yield similar clinical outcomes at 1 year. H. pylori prevalence, the likelihood of peptic ulcer disease and the proportion of ulcers due to H.pylori are important determinants of the least costly strategy. At an H. pylori prevalence below 20%, proton pump inhibitor is consistently less costly than the test-and-treat strategy. CONCLUSIONS: As the H. pylori prevalence, the likelihood of peptic ulcer disease and the proportion of ulcers due to H. pylori decrease, empirical proton pump inhibitor becomes less costly than the test-and-treat strategy for the management of uninvestigated dyspepsia. Given the modest cost differential between the strategies, the test-and-treat strategy may be favoured if patients without peptic ulcer disease derive long-term benefit from H.pylori eradication.
Assuntos
Antiulcerosos/uso terapêutico , Dispepsia/economia , Custos de Cuidados de Saúde , Infecções por Helicobacter/complicações , Helicobacter pylori , Antibacterianos/economia , Antibacterianos/uso terapêutico , Antiulcerosos/economia , Análise Custo-Benefício/métodos , Técnicas de Apoio para a Decisão , Quimioterapia Combinada , Dispepsia/tratamento farmacológico , Dispepsia/microbiologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Humanos , Modelos Econométricos , Úlcera Péptica/tratamento farmacológico , Úlcera Péptica/economia , Úlcera Péptica/microbiologia , Atenção Primária à Saúde/economia , Atenção Primária à Saúde/métodos , Inibidores da Bomba de Prótons , Estados UnidosRESUMO
Chronic ingestion of NSAIDs increases the risk for gastrointestinal complications, which range from dyspepsia to gastrointestinal bleeding, obstruction, and perforation. Among patients using NSAIDs, 0.1 to 2.0% per year suffer serious gastrointestinal complications. Patients who require analgesic therapy should be carefully assessed for the lowest possible dosage and shortest duration of NSAID use and for the potential of treatment with a non-NSAID pain reliever. These patients should also be assessed for factors that increase their risk of gastrointestinal complications, including increased age, concomitant anticoagulant or corticosteroid use, and past history of NSAID-associated gastrointestinal complications. The exact association between Helicobacter pylori infection and NSAID-related ulcer disease is unclear, and the routine testing and treatment of all NSAID using patients for H. pylori infection is not recommended at this time. NSAID-using patients who suffer from dyspepsia should have NSAIDs discontinued, the dosage changed, or be changed to a different class of NSAID. If NSAIDs cannot be discontinued, then an antisecretory agent should be initiated. Misoprostol prevents NSAID-associated gastrointestinal complications. Proton pump inhibitors are the most effective at healing NSAID-associated ulcers among patients who cannot discontinue NSAID therapy.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/terapia , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/prevenção & controle , Humanos , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
INTRODUCTION: Although it is incontrovertible that Helicobacter pylori causes peptic ulcer disease, controversy persists regarding the impact of H. pylori infection on the incidence of NSAID-related complications and whether H. pylori eradication reduces the rate of adverse events. METHODS: A symptom-driven decision analytic model was developed to compare the clinical and economic impact of H. pylori screening compared to a strategy of no H. pylori testing for individuals requiring chronic NSAID therapy. In the principal analysis, it was assumed that untreated H. pylori infection increased the ulcer risk by 50% and that successful eradication reduced the risk of adverse events to that of uninfected patients. Patients' ulcer risk and the protective effect of H. pylori eradication were evaluated using sensitivity analysis. RESULTS: When compared to no H. pylori testing, H. pylori screening led to fewer symptomatic ulcers (no test, 5.4; H. pylori test, 4.6 per 100 patient years) and ulcer complications (no test, 2.6; H. pylori test, 2.3 per 100 patient years) and a higher cost per patient (no test, $435; H. pylori test, $556). The incremental cost attributable to the H. pylori screening strategy to prevent a symptomatic and complicated ulcer was $16,805 and $31,842, respectively. The clinical and cost-effectiveness advantage of H. pylori screening improved as patients' ulcer risk increased or the protective effect of H. pylori eradication was enhanced. CONCLUSIONS: Based upon the available evidence, H. pylori screening has the potential to reduce NSAID-related adverse events for average-risk patients at an incremental cost. Until controlled investigations definitively quantify the effect of H. pylori eradication on clinically significant NSAID-related adverse events, a compelling argument can be made for H. pylori testing for chronic NSAID users at increased risk of ulcer disease.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Helicobacter pylori/isolamento & purificação , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Custos de Cuidados de Saúde , Humanos , Úlcera Péptica/induzido quimicamente , RiscoRESUMO
BACKGROUND: We report a clinical trial which evaluated the effectiveness of triple therapy containing low- and high-dose azithromycin to treat Helicobacter pylori infection. METHODS: From March 1997 to March 1998, patients infected with H. pylori were assigned to receive either: Treatment 1: ranitidine bismuth citrate (RBC) (400 mg b.d.) and amoxycillin (1 g b.d.) for 10 days with azithromycin 500 mg o.m. for 3 days: or Treatment 2: RBC and amoxycillin for 10 days with azithromycin 1 g o.m. for 3 days. H. pylori eradication was established by a urea breath test at least 4 weeks after therapy. Side-effects and compliance were assessed using a diary. RESULTS: Sixty-eight patients were enrolled. Fifty-seven per cent of patients were treated for active peptic ulcer disease or a history of peptic ulcer disease. Treatment 1 cured H. pylori in 44% and 44% by per protocol and intention-to-treat analysis, respectively. The corresponding eradication rates for Treatment 2 were 79% and 75%. Two patients taking Treatment 2 dropped out of the study because of side-effects. CONCLUSIONS: With RBC and amoxycillin for 10 days, azithromycin at a dose of 1 g/day for 3 days was significantly better at curing H. pylori infection than azithromycin 500 mg/day for 3 days.