Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding.

OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of proton pump inhibitors (PPIs) in the prevention and treatment of acute upper gastrointestinal (UGI) haemorrhage, as well as to compare this with H2-receptor antagonist (H2RA), Helicobacter pylori eradication (in infected patients) or no therapy, for the prevention of first and/or subsequent bleeds among patients who continue to use non-steroidal anti-inflammatory drugs (NSAIDs). Also to evaluate the clinical effectiveness of PPI therapy, compared with other treatments, for the prevention of subsequent bleeds in patients who had previously experienced peptic ulcer (PU) bleeding. DATA SOURCES: Electronic databases and major conference proceedings were searched up to February 2006. REVIEW METHODS: Data were collected from the systematic reviews addressing each research objective. These were then entered into an economic model to compare the costs and quality-adjusted life-days of alternative management strategies over a 28-day period for patients who have had UGI bleeding. A Markov model with a Monte Carlo simulation used data from the systematic reviews to identify the most cost-effective treatment strategy for the prevention of UGI bleeding (first and subsequent) among NSAID users using an outcome of costs per quality-adjusted life-years (QALYs) over a lifetime from age 50 years. RESULTS: PPI treatment initiated after endoscopic diagnosis of PU bleeding significantly reduced re-bleeding and surgery compared with placebo or H2RA. Although there was no evidence of an overall effect of PPI treatment on all-cause mortality, PPIs significantly reduced mortality in subgroups when studies conducted in Asia were examined in isolation or when the analysis was confined to patients with high-risk endoscopic findings. PPI treatment initiated prior to endoscopy in UGI bleeding significantly reduced the proportion of patients with stigmata of recent haemorrhage (SRH) at index endoscopy compared with placebo or H2RA, but there was no evidence that PPI treatment affected clinically important outcomes. Giving oral PPI both before and after endoscopy, with endoscopic haemostatic therapy (EHT) for those with major SRH, is preferred to all others on cost-effectiveness grounds at any threshold over 25,000 pounds per QALY, even if only short-term effects are taken into account, and at any threshold over 200 pounds per life-year gained if long-term effects are included. The risk of NSAID-induced endoscopic gastric and duodenal ulcers was reduced by standard doses of PPI and misoprostol, and double doses of H2RAs. Standard doses of H2RAs reduced the risk of endoscopic duodenal ulcers. PPIs reduced NSAID-induced dyspepsia. PPIs were superior to misoprostol in preventing recurrence of NSAID-induced endoscopic duodenal ulcers, but PPIs were comparable to misoprostol in preventing the recurrence of NSAID-induced endoscopic gastric ulcers. Full-dose misoprostol reduced bleeding, perforation or gastric outlet obstruction due to NSAID-induced ulcers, but misoprostol was poorly tolerated and associated with frequent adverse effects. H. pylori eradication treatment was equally effective with PPI treatment for the primary or secondary prevention of endoscopic ulcers in NSAID users. H. pylori eradication treatment was more effective than placebo for the primary prevention of endoscopic PU and for the prevention of re-bleeding from PU in NSAID users. With regard to primary and secondary prevention of bleeding PU in NSAID users, the two most cost-effective strategies are H. pylori eradication alone, and H. pylori eradication followed by misoprostol (substituted by a PPI, if misoprostol is not tolerated) at an additional 4810 pounds per QALY. In patients who had previously experienced a bleed from a PU, re-bleeding was less frequent after H. pylori eradication therapy than after non-eradication antisecretory therapy, whether or not the latter was combined with long-term maintenance antisecretory therapy. CONCLUSIONS: PPI treatment compared with placebo or H2RA reduces mortality following PU bleeding among patients with high-risk endoscopic findings, and reduces re-bleeding rates and surgical intervention. PPI treatment initiated prior to endoscopy in UGI bleeding significantly reduces the proportion of patients with SRH at index endoscopy but does not reduce mortality, re-bleeding or the need for surgery. The strategy of giving oral PPI before and after endoscopy, with EHT for those with major SRH, is likely to be the most cost-effective. Treatment of H. pylori infection was found to be more effective than antisecretory therapy in preventing recurrent bleeding from PU. H. pylori eradication alone or eradication followed by misoprostol (with switch to PPI, if misoprostol is not tolerated) are the two most cost-effective strategies for preventing bleeding ulcers among H. pylori-infected NSAID users, although the data cannot exclude PPIs also being cost-effective. Further large randomised controlled trials are needed to address areas such as PPI administration prior to endoscopic diagnosis, different doses and administration of PPIs, as well as the primary and secondary prevention of UGI bleeding.

Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding.

BACKGROUND: There is conflicting evidence regarding the clinical efficacy of proton pump inhibitors (PPI) initiated prior to endoscopy in patients with upper gastrointestinal bleeding. OBJECTIVES: We aimed to systematically review evidence from randomised controlled trials (RCTs) that studied PPI treatment initiated before endoscopy in patients with upper gastrointestinal bleeding. SEARCH STRATEGY: A search was undertaken according to the Cochrane Upper Gastrointestinal and Pancreatic Diseases model using CENTRAL, (The Cochrane Library), MEDLINE, EMBASE and CINAHL databases and major conference proceedings up to September 2005. The literature search was re-run in February 2006. SELECTION CRITERIA: Types of studies: Randomised controlled trials (RCTs). TYPES OF PARTICIPANTS: Hospitalised patients with unselected upper gastrointestinal bleeding. Types of interventions: Active treatment with a PPI (oral or intravenous) and control treatment with either placebo or an histamine-(2) receptor antagonist (H(2)RA). Types of outcome measures: Assessed at 30 days: mortality, rebleeding and surgery. Also assessed were stigmata of recent haemorrhage at index endoscopy, length of hospital stay and blood transfusion requirements. DATA COLLECTION AND ANALYSIS: At least two reviewers assessed the eligibility criteria of each study and extracted data regarding outcomes and factors affecting methodological quality. MAIN RESULTS: Five RCTs were included for review. No further RCTS were identified in an updated literature search. Four trials comprising a total of 1512 patients in total reported data for all randomised patients. There was no statistical heterogeneity among trials for the outcomes of mortality, rebleeding and surgery. There were no statistically significant differences in rates of mortality, rebleeding or surgery between PPI and control treatment. Pooled mortality rates were 6.1% and 5.5% respectively (odds ratio (OR)1.12; 95% CI 0.72 to 1.73). Pooled rebleeding rates were 13.9% and 16.6% respectively (OR 0.81; 95%CI 0.61 to 1.09). Pooled rates for surgery were 9.9% and 10.2% respectively (OR 0.96 95% CI 0.68 to 1.35). PPI treatment compared to control significantly reduced the proportion of patients with stigmata of recent haemorrhage at index endoscopy; pooled rates were 37.2% and 46.5% respectively (OR 0.67; 95% CI 0.54 to 0.84). For the continuous outcomes, namely length of hospital stay and blood transfusion requirements, quantitative analysis could not be performed. AUTHORS' CONCLUSIONS: PPI treatment initiated prior to endoscopy in patients with upper gastrointestinal bleeding significantly reduces the proportion of patients with stigmata of recent haemorrhage at index endoscopy. However, there is no evidence that PPI treatment affects clinically important outcomes, namely mortality, rebleeding or need for surgery.

Review article: the clinical pharmacology of proton pump inhibitors.

Proton pump inhibitors inhibit the gastric H+/K+-ATPase via covalent binding to cysteine residues of the proton pump. All proton pump inhibitors must undergo acid accumulation in the parietal cell through protonation, followed by activation mediated by a second protonation at the active secretory canaliculus of the parietal cell. The relative ease with which these steps occur with different proton pump inhibitors underlies differences in their rates of activation, which in turn influence the location of covalent binding and the stability of inhibition. Slow activation is associated with binding to a cysteine residue involved in proton transport that is located deep in the membrane. However, this is inaccessible to the endogenous reducing agents responsible for restoring H+/K+-ATPase activity, favouring a longer duration of gastric acid inhibition. Pantoprazole and tenatoprazole, a novel proton pump inhibitor which has an imidazopyridine ring in place of the benzimidazole moiety found in other proton pump inhibitors, are activated more slowly than other proton pump inhibitors but their inhibition is resistant to reversal. In addition, tenatoprazole has a greatly extended plasma half-life in comparison with all other proton pump inhibitors. The chemical and pharmacological characteristics of tenatoprazole give it theoretical advantages over benzimidazole-based proton pump inhibitors that should translate into improved acid control, particularly during the night.

Proton pump inhibitor treatment for acute peptic ulcer bleeding.

BACKGROUND: Randomised controlled trials (RCTs) evaluating the clinical effect of proton pump inhibitors (PPIs) in peptic ulcer (PU) bleeding yield conflicting results. OBJECTIVES: To evaluate the efficacy of PPIs in acute bleeding from PU using evidence from RCTs. SEARCH STRATEGY: We searched CENTRAL, The Cochrane Library (Issue 4, 2004), MEDLINE (1966 to November 2004), EMBASE (1980 to November 2004), proceedings of major meetings to November 2004, and reference lists of articles. We contacted pharmaceutical companies and experts in the field. SELECTION CRITERIA: RCTs of PPI treatment (oral or intravenous) compared with placebo or H(2)-receptor antagonist (H(2)RA) in acute bleeding from PU. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data independently, assessed study validity, summarised studies and undertook meta-analysis. The influence of study characteristics on the outcomes was examined by subgroup analyses and meta-regression. MAIN RESULTS: Twenty-four RCTs comprising 4373 participants in total were included. Statistical heterogeneity was found among trials for rebleeding (P = 0.04), but not for all-cause mortality (P = 0.24) or surgery (P = 0.45). There was no significant difference in all-cause mortality rates between PPI and control treatment; pooled rates were 3.9% on PPI versus 3.8% on control (odds ratio (OR) 1.01; 95% CI 0.74 to 1.40). PPIs significantly reduced rebleeding compared to control; pooled rates were 10.6% with PPI versus 17.3% with control treatment (OR 0.49; 95% CI 0.37 to 0.65). PPI treatment significantly reduced surgery compared with control; pooled rates were 6.1% on PPI versus 9.3% on control (OR 0.61; 95% CI 0.48 to 0.78). There was no evidence to suggest that results on mortality and rebleeding were dependent on study quality, route of PPI administration, type of control treatment or application of initial endoscopic haemostatic treatment. PPIs significantly reduced surgery compared with placebo but not when compared with H(2)RA. There was no evidence to suggest that study quality, route of PPI administration or application of initial endoscopic haemostatic treatment influenced results on surgery. PPI treatment appeared more efficacious in studies conducted in Asia compared to studies conducted elsewhere. All-cause mortality was reduced only in Asian studies; reductions in rebleeding and surgery were quantitatively greater in Asian studies. Among patients with active bleeding or non-bleeding visible vessel, PPI treatment reduced mortality (OR 0.53; 95% CI 0.31 to 0.91), rebleeding and surgery. AUTHORS' CONCLUSIONS: PPI treatment in PU bleeding reduces rebleeding and surgery compared with placebo or H(2)RA, but there is no evidence of an overall effect on all-cause mortality.

Systematic review and meta-analysis: enhanced efficacy of proton-pump inhibitor therapy for peptic ulcer bleeding in Asia--a post hoc analysis from the Cochrane Collaboration.

BACKGROUND: Proton-pump inhibitors reduce re-bleeding rates after ulcer bleeding. However, there is significant heterogeneity among different randomized-controlled trials. AIM: To see whether proton-pump inhibitors for ulcer bleeding produced different clinical outcomes in different geographical locations. METHODS: This was a post hoc analysis of our Cochrane Collaboration systematic review and meta-analysis of proton-pump inhibitor therapy for ulcer bleeding. Sixteen randomized-controlled trials conducted in Europe and North America were pooled and re-analysed separately from seven conducted in Asia. We calculated pooled rates for 30-day all-cause mortality, re-bleeding and surgical intervention and derived odds ratios and numbers needed to treat with 95% confidence intervals. RESULTS: There was no significant heterogeneity for any outcome. Reduced all-cause mortality was seen in the Asian randomized-controlled trials (odds ratios = 0.35; 95% confidence interval: 0.16-0.74; number needed to treat = 33), but not in the others (odds ratios = 1.36; 95% confidence interval: 0.94-1.96; number needed to treat--incalculable). There were significant reductions in re-bleeding and surgery in both sets of randomized-controlled trials, but the effects were quantitatively greater in Asia. CONCLUSIONS: Proton-pump inhibitor therapy for ulcer bleeding has been more efficacious in Asia than elsewhere. This may be because of an enhanced pharmacodynamic effect of proton-pump inhibitors in Asian patients.

Review article: oesophageal complications and consequences of persistent gastro-oesophageal reflux disease.

The major oesophageal complications associated with persistent gastro-oesophageal reflux disease (GERD) include erosive oesophagitis, ulceration, strictures and gastrointestinal (GI) bleeding. Although the causes of these complications are uncertain, studies indicate that erosive oesophagitis may progress to the development of ulcers, strictures and GI bleeding. Pharmacological treatment with proton pump inhibitors is favoured over that with H(2)-receptor antagonists for the treatment of strictures. The treatment of strictures is accomplished with dilation and many favour the concomitant use of proton pump inhibitors. Most gastroenterologists are seeing far fewer oesophageal strictures these days since the introduction of proton pump inhibitors. In addition, research has shown that oesophageal complications have a greater impact on patients suffering from night-time GERD than on those suffering from daytime GERD. Barrett's oesophagus is a significant complication associated with persistent GERD and those at risk generally experience a longer duration of symptoms, especially those with a high degree of severity. In addition, there is a strong relationship between Barrett's oesophagus and oesophageal adenocarcinoma. This is in part due to the association of obesity and the development of hiatal hernias. Furthermore, endoscopic screening is being used to detect Barrett's oesophagus and oesophageal adenocarcinoma in persons suffering from chronic GERD, even though screening may not have an impact on outcomes (Sharma P, McQuaid K, Dent J, et al. A critical review of the diagnosis and management of Barrett's esophagus: The AGA Chicago Workshop. Gastroenterology 2004; 127: 310-30.).

Proton pump inhibitor treatment for acute peptic ulcer bleeding.

BACKGROUND: Peptic ulcer (PU) bleeding is associated with substantial morbidity, mortality and healthcare cost. Randomised controlled trials (RCTs) evaluating the clinical effect of proton pump inhibitors (PPIs) in peptic ulcer bleeding have yielded conflicting results. OBJECTIVES: To evaluate the efficacy of PPIs in the management of acute bleeding from PU using evidence from RCTs. SEARCH STRATEGY: We performed a search of CENTRAL, The Cochrane Library (Issue 3, 2003), MEDLINE (1966 to February 2003) and EMBASE (1980 to February 2003) and proceedings of recent major meetings through to February 2003. We searched the reference lists of articles and contacted pharmaceutical companies and experts in the field for additional published or unpublished data. SELECTION CRITERIA: RCTs of PPI treatment (oral or intravenous) compared with either placebo or H(2)-receptor antagonist (H(2)RA) in patients with acute bleeding from PU were included if they met pre-defined criteria. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data independently on a purpose-designed data extraction form. Validity of included studies was assessed by adequacy of randomisation method and other pre-defined criteria. Studies were summarised and meta-analysis was undertaken. The influence of factors on the outcomes was assessed. MAIN RESULTS: Twenty-one RCTs with a total of 2915 participants were included. Statistical heterogeneity was found among trials for rebleeding (P = 0.05), but not for mortality (P = 0.26) or surgery (P = 0.42). There was no significant difference in mortality rates between PPI and control treatment; pooled rates were 5.2% on PPI versus 4.6% on control (odds ratio (OR) 1.11; 95% CI 0.79 to 1.57). PPI treatment significantly reduced rates of surgical intervention compared with control; pooled rates were 8.4% on PPI versus 13.0% on control (OR 0.59; 95% CI 0.46 to 0.76). PPIs significantly reduced rebleeding compared to control; pooled rates were 10.6% with PPI (range: 0% to 24.4%) versus 18.7% with control treatment (range: 2.3% to 39.1%), the OR was 0.46 (95% CI 0.33 to 0.64). Results on mortality and rebleeding rates were independent of route of PPI administration, type of control treatment or application of initial endoscopic haemostatic treatment. Surgical intervention rates varied with type of control (PPI significantly reduced surgical intervention rates compared with placebo and not when compared with H(2)RA) but not with route of PPI administration or application of initial endoscopic haemostatic treatment. REVIEWERS' CONCLUSIONS: PPI treatment in PU bleeding reduces rebleeding and surgical intervention rates in studies comparing treatment with placebo or H(2)RA, but there is no evidence of an effect on mortality.

Review article: management of peptic ulcer bleeding-the roles of proton pump inhibitors and Helicobacter pylori eradication.

Peptic ulcer bleeding is associated with substantial morbidity and mortality. The goals of management are to control any active bleeding and prevent re-bleeding and then to heal the ulcer and prevent its recurrence. Initial management strategies are guided by the patient's clinical condition and endoscopic findings. Thus, treatment may consist of endoscopic and medical therapy and, sometimes, surgery. Control of acid secretion, preferably with proton pump inhibitor therapy in the initial management continues to evolve; it has also been used as both an adjunct to endoscopic therapy and as primary treatment. These agents have been found to be effective in some trials in the reduction of re-bleeding and the need for surgery, although there is no clear benefit demonstrated for overall mortality. Proton pump inhibitors have been administered either intravenously or orally in different trials. The long-term management of patients with peptic ulcer, after the initial bleeding episode, should include patient stratification based upon risk factors for ulcer recurrence (i.e. Helicobacter pylori infection, use of aspirin or nonsteroidal anti-inflammatory drugs). Elimination or modification of these risk factors reduces the risk of ulcer recurrence and, hence, of recurrent ulcer bleeding.

Meta-analysis: the efficacy of intravenous H2-receptor antagonists in bleeding peptic ulcer.

BACKGROUND: Although a previous meta-analysis found that intravenous H2-receptor antagonists were only weakly beneficial in bleeding gastric ulcer and of no benefit in bleeding duodenal ulcer, patients with ulcer bleeding continue to receive such treatment. AIM: To re-evaluate the efficacy of intravenous H2-receptor antagonists in ulcer re-bleeding, surgery and mortality by updating the previous meta-analysis. METHODS: After two independent literature searches, randomized, placebo-controlled trials of intravenous H2-receptor antagonists in bleeding ulcer published between 1984 and 2000 were added to those from the initial meta-analysis. Pooled rates of re-bleeding, surgery and death were re-calculated, together with the relative risk reduction, absolute risk reduction, number needed to treat and Mantel-Haenszel odds ratio. RESULTS: Intravenous H2-receptor antagonists did not significantly reduce re-bleeding, surgery or death in bleeding duodenal ulcer. There were small but significant reductions in re-bleeding, surgery and death in bleeding gastric ulcer; the absolute risk reductions were 7.2%, 6.7% and 3.2%, respectively. CONCLUSIONS: Intravenous H2-receptor antagonists are of no value in bleeding duodenal ulcer, although they may be mildly beneficial in bleeding gastric ulcer. Because proton pump inhibitors have a greater inhibitory effect on gastric acid secretion than H2-receptor antagonists, they may be more effective in ulcer bleeding and should be further evaluated for that indication.

Current indications for acid suppressants in Helicobacter pylori -negative ulcer disease.

Although Helicobacter pylori infection remains the single most common cause of peptic ulcer, an increasing proportion of patients have H. pylori -negative ulcers. The proportion is higher in the USA--and possibly Australia--than elsewhere. Although the precise aetiology of these ulcers is often unknown, some are caused by the use of aspirin or non-steroidal anti-inflammatory drugs. In areas with a high prevalence of H. pylori -negative ulcers, the empirical treatment of H. pylori infection for newly diagnosed peptic ulcer disease should be discouraged. All such patients should have documentation of their H. pylori status before treatment. Patients with H. pylori -negative ulcers may have the more serious ulcer diathesis and are likely to require long-term management with acid-suppressing drugs. Proton pump inhibitors are likely to be the drugs of choice; patients may be relatively refractory to H(2)-receptor antagonists. The optimal duration of treatment is undefined but might be lifelong. There are no prospective studies of the efficacy of surgery or mucosal-protective agents in the treatment of H. pylori -negative ulcers.

The utility of urgent colonoscopy in the evaluation of acute lower gastrointestinal tract bleeding: a 2-year experience from a single center.

OBJECTIVE: Urgent colonoscopy is often recommended to evaluate acute rectal bleeding. However, it may not identify a source because of blood in the lumen or inadequate preparation. Our aim was to determine the utility of urgent colonoscopy as the initial test for acute rectal bleeding. METHODS: This was a retrospective chart review of all patients discharged in 1997 and 1998 with an International Classification of Diseases, 9th Revision, code for hematochezia or rectal bleeding. RESULTS: We identified 514 charts but excluded 424 because of inaccurate coding. In the 90 with confirmed acute rectal bleeding, colonoscopy was the initial test in 39; age, sex, and race distributions were similar to those who did not have colonoscopy. A definite source of bleeding was seen at colonoscopy in only three patients, a probable source in 26, and no source in 10. Therapeutic intervention in four patients with a definite or probable source was successful in three. The commonest reasons for not performing urgent colonoscopy were bleeding from presumed hemorrhoids or bleeding that was clinically insignificant. Spontaneous resolution of bleeding and length of hospital stay were not affected by urgent colonoscopy. Five patients had surgery for unrelated reasons. In-hospital mortality was 2% and was unrelated to bleeding. CONCLUSION: Urgent colonoscopy as the initial investigation in acute lower GI tract bleeding probably does not alter the outcome in most cases. Identification of a definite bleeding source leading to successful therapeutic intervention is rare. Spontaneous resolution is frequent, length of hospital stay is similar, and clinical outcome is excellent regardless of whether or not urgent colonoscopy is performed.

An audit of the utility of in-patient fecal occult blood testing.

OBJECTIVES: Recent surveys of physician practice have suggested the existence of excessive, inappropriate use of the fecal occult blood test (FOBT). We studied the implementation of this test in hospitalized patients. METHODS: We performed a retrospective chart review of 1000 randomly selected patients who had been discharged from the Medicine service at four teaching hospitals. Patient demographics, clinical presentation, presence or absence of overt GI bleeding, and use of medications that might affect the FOBT were recorded. Reviewers assessed whether patients who had FOBT would have been candidates for colon resection if asymptomatic colon cancer had been found. RESULTS: Digital rectal examination was documented in 44.8% of patients; the findings were recorded in only 9%. A total of 421 patients had FOBT on admission, usually on stool obtained at digital rectal examination. Of the patients with a positive FOBT, 17% had active GI bleeding. Only 41.1% of patients with a positive FOBT were referred to the gastroenterology service. In 70.5% of patients, FOBT could be considered inappropriate because of factors such as age, active GI bleeding, or use of aspirin or other nonsteroidal anti-inflammatory drugs. CONCLUSIONS: The FOBT, which is validated only for colorectal cancer screening, is often performed inappropriately in patients admitted to the hospital. This test should be restricted in hospital practice. It would be preferable to identify patients who are appropriate candidates for colorectal cancer screening at the time of hospital discharge and to advise them about the appropriate performance of the FOBT at home.

The effect of stimulant laxatives and polyethylene glycol-electrolyte lavage solution for colonoscopy preparation on serum electrolytes and hemodynamics.

We have previously shown that magnesium citrate or bisacodyl before polyethylene glycol electrolyte lavage solution (PEG-ELS) improves colonoscopy preparation. Patients prefer this to preparation with full-volume PEG-ELS alone. However, such combinations might cause undesirable changes in hemodynamics or serum electrolytes. This study examined the effects of these combinations on heart rate, blood pressure, and serum electrolytes. We randomized 68 consecutive patients undergoing colonoscopy to one of three preparations. Group 1 received 4 L of PEG-ELS, group 2 received 2 L of PEG-ELS with 20 mg bisacodyl, and group 3 received 2 L of PEG-ELS preceded by 296 mL of magnesium citrate. Heart rate, blood pressure, and serum electrolytes were measured before starting the preparation and immediately before colonoscopy. Mean serum magnesium fell by 0.01 mg/dL and 0.11 mg/dL in groups 1 and 2, respectively, and rose by 0.06 mg/dL in group 3 (p = 0.044). There were no other significant changes. Statistically significant changes in serum magnesium after preparation with PEG-ELS and a stimulant laxative are minor and probably of no clinical relevance. Two liters of PEG-ELS with a stimulant laxative is safe and effective for colonoscopy.

Differing attitudes toward virtual and conventional colonoscopy for colorectal cancer screening: surveys among primary care physicians and potential patients.

OBJECTIVES: To investigate attitudes among primary care physicians and potential patients concerning "virtual" and conventional colonoscopy for colorectal cancer screening. METHODS: We sent 1000 questionnaires to primary care physicians by electronic or postal mail and administered 400 to potential patients. Questionnaires contained progressively detailed information about the tests and asked for choices based on information presented. RESULTS: One hundred eight-eight primary care physicians and 323 potential patients were included. Results indicated the following: 76.6% of potential patients and 47.3% of physicians initially preferred virtual colonoscopy because of its noninvasive nature; 23.6% of potential patients and 52.9% of physicians valued the ability of conventional colonoscopy to visualize the mucosa directly; and 67.4% of potential patients and 51.6% of physicians preferred virtual colonoscopy because it does not require sedation. Considering all information, most potential patients preferred virtual to conventional colonoscopy (60.2% vs 25.7%), whereas more physicians preferred conventional to virtual colonoscopy (44.9% vs 30.3%). Additionally, 82.3% of potential patients would comply more with recommendations for colorectal cancer screening, and 61.7% of physicians would refer more patients for screening, if virtual colonoscopy was available. CONCLUSIONS: Potential patients preferred virtual to conventional colonoscopy, whereas physicians favored conventional colonoscopy. Physicians placed more importance on the ability of conventional colonoscopy to visualize the mucosa directly, the opportunity for therapy, and cost. Potential patients were more encouraged than physicians by the availability of virtual colonoscopy for improving participation in colorectal cancer screening.

Meta-analysis of randomized, controlled trials of antibiotic prophylaxis before percutaneous endoscopic gastrostomy.

OBJECTIVES: We sought to review the published literature on the value of antibiotic prophylaxis for the prevention of wound infection that occurs after percutaneous endoscopic gastrostomy. We also sought by meta-analysis to estimate the efficacy of antibiotic prophylaxis in preventing wound infection. METHODS: We performed a fully recursive literature search for randomized, controlled trials of antibiotic prophylaxis against wound infection occurring after percutaneous endoscopic gastrostomy. Relative and absolute risk reductions and the numbers needed to treat were derived for individual trials and pooled data. RESULTS: We identified seven trials, two of which did not find a statistically significant benefit of antibiotic prophylaxis. After pooling, antibiotic prophylaxis was found to reduce the relative and absolute risk of wound infection by 73% and 17.5%, respectively. The number needed to treat to prevent one wound infection was 5.7 (95% confidence interval = 4.4-8.0). CONCLUSION: A single intravenous dose of a broad-spectrum antibiotic, given approximately 30 min before percutaneous endoscopic gastrostomy is effective in reducing the incidence of peristomal wound infections.

Survey of internal medicine residents' use of the fecal occult blood test and their understanding of colorectal cancer screening and surveillance.

OBJECTIVE: Primary care physicians have imperfect understanding of current colorectal cancer screening guidelines and recommendations. Furthermore, compliance with colorectal cancer screening by internal medicine residents has been demonstrated to be poor. We sought to identify whether current trainees in internal medicine had adequate understanding of colorectal cancer screening and surveillance and test utilization. METHODS: We applied a structured questionnaire about colorectal cancer screening and the use of fecal occult blood tests to 168 internal medicine residents at four accredited programs in the U.S. They were also asked for recommendations about six hypothetical patients who may have been candidates for screening or surveillance. RESULTS: Seventy-one percent identified 50 yr as the currently recommended age to commence screening in an average-risk individual; 64.3% would begin screening with fecal occult blood testing and flexible sigmoidoscopy and 4.8% with colonoscopy. Most perform fecal occult blood testing on stool obtained at digital rectal exam and without prior dietary restrictions. Many use fecal occult blood testing for indications other than colorectal cancer screening. Only 29% recommended colonoscopy to evaluate a positive fecal occult blood test. Most residents plan to be screened for colorectal neoplasia at the appropriate age; significantly more opted for colonoscopy than recommended it for their patients. CONCLUSIONS: Internal medicine residents have many misperceptions regarding colorectal cancer screening and the utility of the fecal occult blood test. Educational efforts should be directed at internal medicine residents, many of whom plan careers in primary care, where most colorectal cancer screening is currently performed.

Colorectal cancer screening and surveillance practices by primary care physicians: results of a national survey.

OBJECTIVE: Screening for colorectal cancer reduces its morbidity and mortality and is cost-effective. Screening is usually the responsibility of primary care physicians who may be unsure about its implementation. We aimed to assess primary care physicians' knowledge and practice regarding colorectal cancer screening, and to compare their responses with those of three national experts and with published guidelines. METHODS: We mailed a postal questionnaire to 2,310 primary care physicians regarding demographics, nature of practice, use of screening tests, and six hypothetical patients who may have been candidates for screening or surveillance. We used published national guidelines and the collective opinions of the three external experts as the so-called "gold standard." RESULTS: Of all respondents, 85.1% offered colorectal cancer screening. Most used suitable tests, starting at an appropriate age; 49.8% continued screening indefinitely irrespective of patients' age and 43.6% performed fecal occult blood testing without appropriate dietary advice to patients. Also, respondents frequently performed this test for inappropriate indications. Only 51.8% would follow a positive fecal occult blood test with colonoscopy. CONCLUSIONS: Colorectal cancer screening practices by primary care physicians vary considerably from those recommended. Many offer screening to individuals in whom it is not appropriate, and continue it into advanced age. Frequent, inappropriate use of fecal occult blood tests will produce many false positives. Primary care physicians often do not appropriately follow a positive test. Further educational efforts are needed in an attempt to improve practice and further reduce the morbidity and mortality from colorectal cancer.

Vitamin B12 levels during prolonged treatment with proton pump inhibitors.

Reduced serum vitamin B12 (cobalamin) levels have been documented occasionally during long-term treatment with a proton pump inhibitor (PPI) in selected groups of patients. This has largely been confined to patients being treated for Zollinger-Ellison syndrome who have sustained drug-induced achlorhydria, which does not ordinarily occur during treatment with a PPI. An appreciation of normal cobalamin metabolism and the pharmacological action of the PPIs adequately explain the mechanism for this reduction. PPIs do not promote the development of pernicious anemia.

Changes in colorectal cancer over a 15-year period in a single United States city.

OBJECTIVE: The aim of this study was to identify colorectal cancer trends in different patient groups in one region. METHODS: We reviewed the records of all patients with colorectal cancer who were seen at two hospitals in Columbia, SC, between 1981 and 1995. Patients were divided into three 5-yr cohorts (cohort 1, 1981-1985; cohort 2, 1986-1990; and cohort 3, 1991-1995). We recorded demographic data, histological type, tumor stage, grade, and survival. RESULTS: A total of 1395 patients were diagnosed, of whom 1252 had adenocarcinoma. Mean age of diagnosis was 64.5 yr in black and 66 in white patients (p = 0.036). Adenocarcinoma proximal to the splenic flexure was found in 62% of women and 49% of men (p < 0.001), and in 51% of black and 44% of white patients (p = 0.08). Proximal cancers accounted for 61%, 48%, and 32% of cohorts 1, 2, and 3, respectively. The proportions of patients with advanced stage (III and IV) adenocarcinoma in the three cohorts were 54%, 47%, and 40%, respectively (p = 0.001). Median survival for adenocarcinoma was 23.7, 23.5, and 23.1 months in cohorts 1, 2, and 3 (p = 0.9). CONCLUSIONS: The prevalence and demographics of colorectal cancer have been fairly stable at this center. There has been a significant decrease in proximal cancers. Although adenocarcinoma is being diagnosed at an earlier stage, this has not affected survival. Colonoscopy may be the most appropriate screening method in women and in black patients, in whom proximal cancers are more often found.