Clinical Health Updates

Probiotic yogurt prevents antibiotic-associated diarrhea in hospitalized patients

Clinical Question:
Can a yogurt product prevent diarrhea in older, hospitalized patients treated with antibiotics?

Bottom Line:
A probiotic yogurt drink containing active bacterial cultures — perhaps only the specific types and species used in this study — decreased the likelihood of diarrhea following initiation of antibiotic therapy (number needed to treat [NNT] = 5). It also prevented Clostridium difficile-associated diarrhea. The yogurt drink, marketed as Actimel (Danone, France) was given twice a day.

Reference:
Hickson M, D’Souza AL, Muthu N, et al. Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial. BMJ 2007;335:80.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
The authors determined the efficacy of a probiotic drink containing Lactobacillus for the prevention of any diarrhoea associated with antibiotic use and that caused by Clostridium difficile. They did a randomised double blind placebo controlled study. It was participated by 135 hospital patients (mean age 74) taking antibiotics. Exclusions included diarrhoea on admission, bowel pathology that could result in diarrhoea, antibiotic use in the previous four weeks, severe illness, immunosuppression, bowel surgery, artificial heart valves, and history of rheumatic heart disease or infective endocarditis. Consumption of a 100 g (97 ml) drink containing Lactobacillus casei, L bulgaricus, and Streptococcus thermophilus twice a day during a course of antibiotics and for one week after the course finished. The placebo group received a longlife sterile milkshake. Primary outcome: occurrence of antibiotic associated diarrhoea. Secondary outcome: presence of C difficile toxin and diarrhoea. 7/57 (12%) of the probiotic group developed diarrhoea associated with antibiotic use compared with 19/56 (34%) in the placebo group (P=0.007). Logistic regression to control for other factors gave an odds ratio 0.25 (95% confidence interval 0.07 to 0.85) for use of the probiotic, with low albumin and sodium also increasing the risk of diarrhoea. The absolute risk reduction was 21.6% (6.6% to 36.6%), and the number needed to treat was 5 (3 to 15). No one in the probiotic group and 9/53 (17%) in the placebo group had diarrhoea caused by C difficile (P=0.001). The absolute risk reduction was 17% (7% to 27%), and the number needed to treat was 6 (4 to 14).

Pantoprozole more effective than somatostatin for peptic ulcer rebleeding

Clinical Question:
Is somatostatin more effective than pantoprazole for reducing peptic ulcer bleeding following endoscopic hemostasis?

Bottom Line:
In patients with a bleeding ulcer, after successful endoscopic hemostasis, despite equipotent acid suppression, pantoprazole continuous infusion was superior to somatostatin to prevent bleeding recurrence and quick disappearance of the endoscopic stigmata. Nevertheless, no differences were seen in the need for surgery and mortality.

Reference:
Tsibouris P, Zintzaras E, Lappas C, et al. High-dose pantoprazole continuous infusion is superior to somatostatin after endoscopic hemostasis in patients with peptic ulcer bleeding. Am J Gastroeneterol 2007;102:1192-1199.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
The best antisecretory treatment after endoscopic hemostasis in patients with ulcer bleeding is still in quest. The authors compared pantoprazole and somatostatin continuous infusion after endoscopic hemostasis in patients with bleeding peptic ulcers. A total of 164 consecutive patients with a bleeding peptic ulcer, after successful endoscopic hemostasis, were randomly assigned to receive, double blindly, continuous IV infusion of pantoprazole 8 mg/h for 48 h after a bolus of 40 mg (group P) or somatostatin 250 microg/h for 48 h after a bolus of 250 microg (group-S). Twenty-four-hour pH-metry was performed in the last 30 patients in each group. Endoscopy was performed, in case of bleeding nonrecurrence, every 48 h until disappearance of stigmata. Bleeding recurrence: group S 14 patients (17%) versus group P 4 (5%) (P=0.046). In multivariate analysis, bleeding recurrence was 4.57 (CI 1.31-15.91) times more frequent in group S (P=0.02). There was no difference in the need for surgery and mortality. Acid suppression over pH 6: group S 82.9% of the time versus group P 81.5% (P=0.97). Acid suppression over pH 6 for >85% of the time: group S 14 (47%) patients versus group P 17 (57%) (P=0.44). Disappearance of endoscopic stigmata after 48 h: group S 25/68 patients (37%) versus group P 72/78 (92%) (P<0.0001). No major side effects identified in either study group.

Folic acid does not reduce risk of colorectal adenomas

Clinical Question:
Does folic acid supplementation reduce the risk of colorectal cancer in adults?

Bottom Line:
Folic acid supplementation (1 mg/d) does not reduce the risk of colorectal adenoma. Interestingly, daily folic acid actually increased the risk of advanced colorectal lesions, suggesting supplementation might actually increase the risk of cancer.

Reference:
Cole BF, Baron JA, Sandler RS, et al, for the Polyp Prevention Study Group. Folic acid for the prevention of colorectal adenomas. A randomized clinical trial. JAMA 2007;297:2351-2359.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
Laboratory and epidemiological data suggest that folic acid may have an antineoplastic effect in the large intestine. To clear about this laboratory finding the authors assessed the safety and efficacy of folic acid supplementation for preventing colorectal adenomas. They did 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. 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). 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). 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.

Sequential H. pylori tx increases cures

Clinical Question:
Is a sequential antibiotic treatment for Helicobacter pylori more effective than a continuous 10-day regimen?

Bottom Line:
Response to H. pylori eradication has dropped to approximately 80% because of resistance. Ten days of pantoprazole (Protonix) 40 mg with amoxicillin 1 g twice daily for the first 5 days followed by tinidazole (Tindamax) 500 mg twice daily and clarithromycin (Biaxin) 500 mg twice daily for the remaining 5 days is more effective than 10 days of continuous triple drug treatment.

Reference:
Vaira D, Zullo A, Vakil N, et al. Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: a randomized trial. Ann Intern Med 2007;146:556-563.

Study Design:
Randomized controlled trial (double-blinded)
Funding:

Synopsis:
Antimicrobial resistance has decreased eradication rates for Helicobacter pylori infection worldwide. The authors determined whether sequential treatment eradicates H. pylori infection better than standard triple-drug therapy for adults with dyspepsia or peptic ulcers. They did a randomized, double-blind, placebo-controlled trial. In a two Italian hospitals between September 2003 and April 2006. PATIENTS: 300 patients with dyspepsia or peptic ulcers. (13)C-urea breath test, upper endoscopy, histologic evaluation, rapid urease test, bacterial culture, and assessment of antibiotic resistance. A 10-day sequential regimen (40 mg of pantoprazole, 1 g of amoxicillin, and placebo, each administered twice daily for the first 5 days, followed by 40 mg of pantoprazole, 500 mg of clarithromycin, and 500 mg of tinidazole, each administered twice daily for the remaining 5 days) or standard 10-day therapy (40 mg of pantoprazole, 500 mg of clarithromycin, and 1 g of amoxicillin, each administered twice daily). The eradication rate achieved with the sequential regimen was significantly greater than that obtained with the standard treatment in the intention-to-treat analysis (89% vs. 77%; P = 0.0134; difference, 12% [95% CI, 3% to 20%]), the modified intention-to-treat analysis (91% vs. 78%; P = 0.0022; difference, 13% [CI, 5% to 21%]), and the per-protocol analysis (93% vs. 79%; P = 0.0013; difference, 14% [CI, 6% to 21%]). Sequential therapy was significantly more effective in patients with clarithromycin-resistant strains (89% vs. 29%; P = 0.0034). The incidence of major and minor side effects did not differ between therapy groups (17% in both groups). One patient (0.7%) in the standard therapy group discontinued treatment because of side effects. LIMITATIONS: Follow-up was incomplete in 4.6% and 2.7% patients in the sequential therapy and standard therapy groups, respectively. The results may not be generalizable to other countries. Sequential therapy may be more effective because it includes 1 additional antibiotic (tinidazole) that is not contained in standard therapy.

MRI = contrast enhanced CT for assessment of acute pancreatitis

Clinical Question:
Is nonenhanced magnetic resonance imaging comparable with contrast enhanced computed tomography for assessing severity and predicting outcome in patients with acute pancreatitis?

Bottom Line:
NEMRI is comparable to CECT in the early assessment of the severity of AP, and both methods are equally efficient in predicting local and systemic complications of AP. MRI has a potential advantage over CT in detecting bile duct lithiasis and pancreatic hemorrhage.

Reference:
Stimac D, Miletic D, Radic M, et al. The role of nonenhanced magnetic resonance imaging in the early assessment of acute pancreatitis. Am J Gastroenterol 2007;102:997-1004.

Study Design:
Diagnostic test evaluation

Synopsis:
Consecutive patients admitted with acute pancreatitis were included. Between the third and fifth hospital days, patients underwent spiral computed tomography with intravenous contrast and NEMRI, including MR cholangiopancreatography (MRCP). Fourteen patients were excluded because of contrast allergy, metal implants, and inability to undergo MRI because of mechanical ventilation. Two radiologists who were masked to patients’ clinical data independently reviewed both imaging studies. Disease severity on imaging was graded by the Balthazar grade, a scoring system based on radiographic findings of pancreatic enlargement, inflammation, fluid collections, and percent necrosis. This was compared with clinical disease severity, as assessed primarily with the Atlanta criteria, and secondarily with several other prognostic measures including the Ranson score, the Acute Physiology and Chronic Health Outcomes (APACHE) II score, and C-reactive protein levels.

A total of 101 patients were studied. The patients’ median age was 62 years and the causes of acute pancreatitis were primarily biliary (63%) and alcoholic (18%). Pancreatitis was classified as severe according to the Atlanta score in approximately 33% of patients, and by the Ranson score in 64% (Ransom score > 2). CECT and NEMRI showed significant correlation for Balthazar grade, assessment of pancreatic necrosis, and combined severity indices (Balthazar grade plus points for percent necrosis). Magnetic resonance severity indices also correlated with the Ranson score, systemic complications, and length of hospital stay. Using CECT as the gold standard, NEMRI had a sensitivity of 79% and specificity 92% for detection of severe pancreatitis (positive likelihood ratio = 10; negative likelihood ratio = 0.23).

Aspirin prevents colon cancer

Clinical Question:
Does aspirin prevent colon cancer?

Bottom Line:
Use of 300 mg or more of aspirin a day for about 5 years is effective in primary prevention of colorectal cancer in randomised controlled trials, with a latency of about 10 years, which is consistent with findings from observational studies. Long-term follow-up is required from other randomised trials to establish the effects of lower or less frequent doses of aspirin.

Reference:
Flossmann E, Rothwell PM; British Doctors Aspirin Trial and the UK-TIA Aspirin Trial. Effect of aspirin on long-term risk of colorectal cancer: consistent evidence from randomised and observational studies. Lancet 2007;369:1603-1613.

Study Design:
Systematic review

Synopsis:
Randomised trials have shown that aspirin reduces the short-term risk of recurrent colorectal adenomas in patients with a history of adenomas or cancer, but large trials have shown no effect in primary prevention of colorectal cancer during 10 years’ follow-up. However, the delay from the early development of adenoma to presentation with cancer is at least 10 years. The authors assessed the longer-term effect of aspirin on the incidence of cancers. They studied the effect of aspirin in two large randomised trials with reliable post-trial follow-up for more than 20 years: the British Doctors Aspirin Trial (N=5139, two-thirds allocated 500 mg aspirin for 5 years, a third to open control) and UK-TIA Aspirin Trial (N=2449, two-thirds allocated 300 mg or 1200 mg aspirin for 1-7 years, a third placebo control). We also did a systematic review of all relevant observational studies to establish whether associations were consistent with the results of the randomised trials and, if so, what could be concluded about the likely effects of dose and regularity of aspirin use, other non-steroidal anti-inflammatory drugs (NSAID), and the effect of patient characteristics. In the randomised trials, allocation to aspirin reduced the incidence of colorectal cancer (pooled HR 0.74, 95% CI 0.56-0.97, p=0.02 overall; 0.63, 0.47-0.85, p=0.002 if allocated aspirin for 5 years or more). However, this effect was only seen after a latency of 10 years (years 0-9: 0.92, 0.56-1.49, p=0.73; years 10-19: 0.60, 0.42-0.87, p=0.007), was dependent on duration of scheduled trial treatment and compliance, and was greatest 10-14 years after randomisation in patients who had had scheduled trial treatment of 5 years or more (0.37, 0.20-0.70, p=0.002; 0.26, 0.12-0.56, p=0.0002, if compliant). No significant effect on incidence of non-colorectal cancers was recorded (1.01, 0.88-1.16, p=0.87). In 19 case-control studies (20 815 cases) and 11 cohort studies (1 136 110 individuals), regular use of aspirin or NSAID was consistently associated with a reduced risk of colorectal cancer, especially after use for 10 years or more, with no difference between aspirin and other NSAIDs, or in relation to age, sex, race, or family history, site or aggressiveness of cancer, or any reduction in apparent effect with use for 20 years or more. However, a consistent association was only seen with use of 300 mg or more of aspirin a day, with diminished and inconsistent results for lower or less frequent doses.

Pretreatment with omeprazole (Losec) before endoscopy reduces bleeding

Clinical Question:
Does an infusion of omeprazole before endoscopy reduce the likelihood of bleeding that will require treatment?

Bottom Line:
An overnight infusion of omeprazole prior to endoscopy in patients with acute upper gastrointestinal hemorrhage reduces the need for intervention and speeds discharge from the hospital.

Reference:
Lau JY, Leung WK, Wu JC, et al. Omeprazole before endoscopy in patients with gastrointestinal bleeding. N Engl J Med 2007;356:1631-1640.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
An infusion of proton pump inhibitor after endoscopy has been shown to reduce the likelihood of recurrent bleeding and has become standard care. The authors wondered whether an infusion before endoscopy could be just as useful. They identified 638 patients with an upper gastrointestinal bleed who were hemodynamically stable (including those who could be readily stabilized with intravenous fluids). Unstable patients and those taking aspirin long term were excluded. Patients were randomized (allocation concealed) to receive either an 80 mg bolus of intravenous omeprazole followed by a drip of 8 mg per hour or matching placebo. The average age of patients was 62 years, 35% were women, and approximately 60% in each group had a peptic ulcer as the source of bleeding. All patients then underwent endoscopy the following morning. Patients with spurting or oozing hemorrhage and those with a nonbleeding visible vessel had appropriate endoscopic therapy to stop the bleeding. Patients who received omeprazole were less likely to require endoscopic treatment of bleeding than those who received placebo (19% vs 28%; P = .007; number needed to treat [NNT] = 11). They were also more likely to go home in less than 3 days (60% vs 49%; P = .005; NNT = 9) and no more likely to have recurrent bleeding or subsequent blood transfusion.

Oats are safe for patients with celiac disease

Clinical Question:
Can persons with celiac disease safely include oats in their diet?

Bottom Line:
Oats can safely be consumed by patients with celiac disease. A small amount of wheat contamination is common in rice, corn, and oat products but generally does not reach the threshold of mucosal damage. Patients on a gluten-free diet may try adding oats, but should stop if they develop symptoms.

Reference:
Garsed K, Scott BB. Can oats be taken in a gluten-free diet? A systematic review. Scand J Gastroenterol 2007;42:171-178.

Study Design:
Systematic review

Synopsis:
There has long been doubt about the need to exclude oats from a gluten-free diet (GFD). The authors reviewed the literature in order to arrive at a firm recommendation. Electronic databases were searched up to February 2006 using the terms “oats” and “coeliac disease”. Twenty relevant studies were found and presented. Early studies were small and uncontrolled and mostly indirect. In 10 studies involving 165 patients, only 1 patient was shown to have histological damage as a result of consuming oats.

High volume of AAA repairs associated with lower mortality

Clinical Question:
Are patients with abdominal aortic aneurysms better off if they go to institutions with higher surgical volumes?

Bottom Line:
Patient survival after repair of abdominal aortic aneurysms (elective or urgent) is higher when the patient is treated in an institution with a high surgical volume. This argues in favor of a central approach to managing patients with abdominal aortic aneurysms. Additionally clinicians who diagnose these patients may wish to consider altering their referral process taking these data into account. (LOE = 1a)

Reference:
Holt PJ, Poloniecki JD, Gerrard D, Loftus IM, Thompson MM. Meta-analysis and systematic review of the relationship between volume and outcome in abdominal aortic aneurysm surgery. Br J Surg 2007;94:395-403.

Study Design:
Systematic review

Synopsis:
The authors investigated the volume-outcome relationship for abdominal aortic aneurysm (AAA) surgery and quantified critical volume thresholds. PubMed, EMBASE and the Cochrane library were searched for articles on the operation volume-outcome relationship in elective and ruptured AAA surgery. UK Hospital Episode Statistics data were also considered. Elective and ruptured AAA repairs were dealt with separately. The data were meta-analysed, and the odds ratios (95 per cent confidence interval) for mortality at higher- and lower-volume hospitals were compared. Volume thresholds were identified from each paper. The analysis included 421,299 elective and 45,796 ruptured AAA operations. Significant relationships between mortality and annual volume were noted for both groups. Overall, the weighted odds ratio was 0.66 (0.65 to 0.67) for elective repair at a threshold of 43 AAAs per annum and 0.78 (0.73 to 0.82) for ruptured aneurysm repair at a threshold of 15 AAAs per annum, both in favour of high-volume institutions.

Harms outweigh benefits of aspirin/NSAID for colon cancer prevention

Clinical Question:
Should patients be advised to take aspirin or a nonsteroidal anti-inflammatory drug to prevent colorectal cancer?

Bottom Line:
The US Preventive Services Task Force recommends against routine use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) to prevent colorectal cancer. The beneficial decrease in colorectal adenoma, cancer incidence, and possibly cancer-related mortality is more than offset by the harm associated with their use. Ulcers leading to gastrointestinal bleeding, renal impairment, and an increase in cardiovascular events are the main problems.

Reference:
U.S. Preventive Services Task Force. Routine aspirin or nonsteroidal anti-inflammatory drugs for the primary prevention of colorectal cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med 2007;146:361-364. Rostom A, Dube C, Lewin G, et al. Nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors for primary prevention of colorectal cancer: A systematic review prepared for the U.S. Preventive Services Task Force. Ann Intern Med 2007;146:376-389.

Study Design:
Practice guideline

Synopsis:
The authors examined the benefits and harms of nonaspirin (non-ASA) nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX-2) inhibitors for the prevention of colorectal cancer (CRC) and adenoma. They searched on MEDLINE (1966 to 2006), EMBASE (1980 to 2006), Cochrane Central Register of Controlled Trials, Cochrane Collaboration’s registry of clinical trials, and Cochrane Database of Systematic Reviews. The authors focused on randomized, controlled trials and case-control and cohort studies of the effectiveness of NSAIDs for the prevention of CRC and colorectal adenoma were identified by multilevel screening by 2 independent reviewers. Systematic reviews of harms were sought. Data abstraction, checking, and quality assessment were completed in duplicate. A single cohort study showed no effect of non-ASA NSAIDs on death due to CRC. Colorectal cancer incidence was reduced with non-ASA NSAIDs in cohort studies (relative risk, 0.61 [95% CI, 0.48 to 0.77]) and case-control studies (relative risk, 0.70 [CI, 0.63 to 0.78]). Colorectal adenoma incidence was also reduced with non-ASA NSAID use in cohort studies (relative risk, 0.64 [CI, 0.48 to 0.85]) and case-control studies (relative risk, 0.54 [CI, 0.4 to 0.74]) and by COX-2 inhibitors in randomized, controlled trials (relative risk, 0.72 [CI, 0.68 to 0.77]). The ulcer complication rate associated with non-ASA NSAIDs is 1.5% per year. Compared with non-ASA NSAIDs, COX-2 inhibitors reduce this risk but, in multiyear use, have a higher ulcer complication rate than placebo. Cyclooxygenase-2 inhibitors and nonnaproxen NSAIDs increase the risk for serious cardiovascular events (relative risk, 1.86 [CI, 1.33 to 2.59] for COX-2 inhibitors vs. placebo).