Clinical Question:
Does antioxidant vitamin supplementation reduce the risk of preeclampsia?

Bottom Line:
Concomitant supplementation with vitamin C and vitamin E does not prevent pre-eclampsia in women at risk, but does increase the rate of babies born with a low birthweight. As such, use of these high-dose antioxidants is not justified in pregnancy.

Reference:
Poston L, Briley AL, Seed PT, Kelly FJ, Shennan AH; Vitamins in Pre-eclampsia (VIP) Trial Consortium. Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial. Lancet 2006;367:1145-1154.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
Oxidative stress could play a part in pre-eclampsia, and there is some evidence to suggest that vitamin C and vitamin E supplements could reduce the risk of the disorder. The aim was to investigate the potential benefit of these antioxidants in a cohort of women with a range of clinical risk factors. The author did a randomised, placebo-controlled trial to which we enrolled 2410 women identified as at increased risk of pre-eclampsia from 25 hospitals. We assigned the women 1000 mg vitamin C and 400 IU vitamin E (RRR alpha tocopherol; n=1199) or matched placebo (n=1205) daily from the second trimester of pregnancy until delivery. Our primary endpoint was pre-eclampsia, and our main secondary endpoints were low birthweight (<2.5 kg) and small size for gestational age (<5th customised birthweight centile). Analyses were by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 62368611 . Of 2404 patients treated, we analysed 2395 (99.6%). The incidence of pre-eclampsia was similar in treatment placebo groups (15% [n=181] vs 16% [n=187], RR 0.97 [95% CI 0.80-1.17]). More low birthweight babies were born to women who took antioxidants than to controls (28% [n=387] vs 24% [n=335], 1.15 [1.02-1.30]), but small size for gestational age did not differ between groups (21% [n=294] vs 19% [n=259], 1.12 [0.96-1.31]).

Clinical Question:
Does praying for patients decrease the patients’ risk of complications following heart surgery?

Bottom Line:
Intercessory prayer itself had no effect on complication-free recovery from CABG, but certainty of receiving intercessory prayer was associated with a higher incidence of complications.

Reference:
Benson H, Dusek JA, Sherwood JB, et al. Study of the therapeutic effects of intercessory prayer (STEP) in cardiac bypass patients: A multicenter randomized trial of uncertainty and certainty of receiving intercessory prayer. Am Heart J 2006;151:934-942.

Study Design:
Randomized controlled trial (single-blinded)

Synopsis:
Intercessory prayer is widely believed to influence recovery from illness, but claims of benefits are not supported by well-controlled clinical trials. Prior studies have not addressed whether prayer itself or knowledge/certainty that prayer is being provided may influence outcome. The author evaluated whether (1) receiving intercessory prayer or (2) being certain of receiving intercessory prayer was associated with uncomplicated recovery after coronary artery bypass graft (CABG) surgery. Patients at 6 US hospitals were randomly assigned to 1 of 3 groups: 604 received intercessory prayer after being informed that they may or may not receive prayer; 597 did not receive intercessory prayer also after being informed that they may or may not receive prayer; and 601 received intercessory prayer after being informed they would receive prayer. Intercessory prayer was provided for 14 days, starting the night before CABG. The primary outcome was presence of any complication within 30 days of CABG. Secondary outcomes were any major event and mortality. In the 2 groups uncertain about receiving intercessory prayer, complications occurred in 52% (315/604) of patients who received intercessory prayer versus 51% (304/597) of those who did not (relative risk 1.02, 95% CI 0.92-1.15). Complications occurred in 59% (352/601) of patients certain of receiving intercessory prayer compared with the 52% (315/604) of those uncertain of receiving intercessory prayer (relative risk 1.14, 95% CI 1.02-1.28). Major events and 30-day mortality were similar across the 3 groups.

Clinical Question:
Are angiotensin-converting enzyme inhibitors effective in decreasing mortality and morbidity in patients with heart disease but without heart failure or systolic dysfunction?

Bottom Line:
Angiotensin-converting enzyme inhibitors reduce total mortality and major cardiovascular end points in patients who have CAD and no left ventricular systolic dysfunction or heart failure.

Reference:
Danchin N, Cucherat M, Thuillez C, Durand E, Kadri Z, Steg PC. Angiotensin-converting enzyme inhibitors in patients with coronary artery disease and absence of heart failure or left ventricular systolic dysfunction. Arch Intern Med 2006;166:787-796.

Study Design:
Meta-analysis (randomized controlled trials)

Synopsis:
Results of randomized trials of angiotensin-converting enzyme inhibitors in patients with coronary artery disease (CAD) and preserved left ventricular function are conflicting. We undertook this study to determine whether long-term prescription of angiotensin-converting enzyme inhibitors decreases major cardiovascular events and mortality in patients who have CAD and no evidence of left ventricular systolic dysfunction. The author searched MEDLINE, EMBASE, and IPA databases, the Cochrane Controlled Trials Register (1990-2004), and reports from scientific meetings (2003-2004), and we reviewed secondary sources. Search terms included angiotensin-converting enzyme inhibitors, coronary artery disease, randomi(s)zed controlled trials, clinical trials, and myocardial infarction. Eligible studies included randomized controlled trials in patients who had CAD and no heart failure or left ventricular dysfunction, with follow-up omicronf 2 years or longer. Of 1146 publications screened, 7 met our selection criteria and included a total of 33 960 patients followed up for a mean of 4.4 years. Five trials included only patients with documented CAD. One trial included patients with documented CAD (80%) or patients who had diabetes mellitus and 1 or more additional risk factors, and another trial included patients who had CAD, a history of transient ischemic attack, or intermittent claudication. Treatment with angiotensin-converting enzyme inhibitors decreased overall mortality (odds ratio, 0.86; 95% confidence interval, 0.79-0.93), cardiovascular mortality (odds ratio, 0.81; 95% confidence interval, 0.73-0.90), myocardial infarction (odds ratio, 0.82; 95% confidence interval, 0.75-0.89), and stroke (odds ratio, 0.77; 95% confidence interval, 0.66-0.88). Other end points, including resuscitation after cardiac arrest, myocardial revascularization, and hospitalization because of heart failure, were also reduced.

Clinical Question:
Can regular treatment with Lactobacillus GG prevent relapse in patients with ulcerative colitis?

Bottom Line:
Lactobacillus GG seems to be effective and safe for maintaining remission in patients with ulcerative colitis, and it could represent a good therapeutic option for preventing relapse in this group of patients.However, the study was unblinded and a confirmatory study would be helpful.

Reference:
Zocco MA, Dal Verme LZ, Cremonini F, et al. Efficacy of Lactobacillus GG in maintaining remission of ulcerative colitis. Aliment Pharmacol Ther 2006;23:1567-1574.

Study Design:
Randomized controlled trial (nonblinded)

Synopsis:
These Italian researchers enrolled 187 consecutive patients with ulcerative colitis for an average of 8 years into this study of the probiotic LGG. This species has been used successfully to treat traveler’s diarrhea and antibiotic-associated diarrhea. The patients were randomly assigned (allocation concealment uncertain) to receive one of the following regimens for 12 months: LGG 18 billion viable bacteria per day in 2 doses; mesalazine 2400 mg daily; or the combination. The primary outcome was the appearance of ulcerative colitis signs or symptoms that required additional treatment. This study did not blind the patients or the investigators, which is a serious limitation because the clinical outcome in this study makes blinding especially important. Relapse occurred in approximately 17% of patients over the course of the study. Using intention-to-treat analysis, the investigators found similar relapse rates across the 3 treatment groups (15%, 20%, and 16%). Similar findings occurred when patients were evaluated by endoscopy for the presence of colitis.

Clinical Question:
Can a questionnaire be used to differentiate between urge and stress incontinence?

Bottom Line:
The 3IQ questionnaire is a simple, quick, and noninvasive test with acceptable accuracy for classifying urge and stress incontinence and may be appropriate for use in primary care settings. Similar studies are needed in other populations. We also need a clinical trial comparing the outcomes of treatments based on the 3IQ and the extended evaluation.

Reference:
Brown JS, Bradley CS, Subak LL, et al, for the Diagnostic Aspects of Incontinence Study (DAISy) Research Group. The sensitivity and specificity of a simple test to distinguish between urge and stress urinary incontinence. Ann Intern Med 2006;144:715-723.

Study Design:
Diagnostic test evaluation

Synopsis:
Urinary incontinence is common in women. Because treatments differ, urge incontinence should be distinguished from stress incontinence. To make this distinction, current guidelines recommend an extensive evaluation that is too time-consuming for primary care practice. To test the accuracy of a simple questionnaire to categorize type of urinary incontinence in women the author did a multicenter, prospective study of the accuracy of the 3 Incontinence Questions (3IQ) compared with an extended evaluation to distinguish between urge incontinence and stress incontinence to 5 academic medical centers in the United States. Participants are 301 women enrolled from April to December 2004 who were older than 40 years of age (mean age, 56 years [SD, 11]) with untreated incontinence for an average of 7 years (SD, 7) and a broad range of incontinence severity. All participants included in the analyses answered the 3IQ questionnaire, and a urologist or urogynecologist who was blinded to the responses performed the extended evaluation. Sensitivity, specificity, and likelihood ratios were determined for the 3IQ. For classification of urge incontinence and with the extended evaluation as the gold standard, the 3IQ had a sensitivity of 0.75 (95% CI, 0.68 to 0.81), a specificity of 0.77 (CI, 0.69 to 0.84), and a positive likelihood ratio of 3.29 (CI, 2.39 to 4.51). For classification of stress incontinence, the sensitivity was 0.86 (CI, 0.79 to 0.90), the specificity was 0.60 (CI, 0.51 to 0.68), and the positive likelihood ratio was 2.13 (CI, 1.71 to 2.66). LIMITATIONS: Participants were enrolled by urologists and urogynecologists at academic medical centers.

Clinical Question:
Does lifestyle changes are effective in patients with gastroesophageal reflux disease?

Bottom Line:
There is no evidence supporting an improvement in GERD measures after cessation of tobacco, alcohol, or other dietary interventions.

Reference:
Kaltenbach T, Crockett S, Gerson LB. Are lifestyle measures effective in patients with gastroesophageal reflux disease? Arch Intern Med 2006;166:965-971.

Study Design:
Systematic review

Synopsis:
This systematic review assembled all English-language research on the value of lifestyle changes on the symptoms of GERD. Their search was severely flawed by limiting to only English-language articles and only searching one database back to the year 1975. Once the studies were identified, 2 authors independently reviewed every study; that is, they did not limit their review by quality of the study. Although smoking was associated with an increase in GERD symptoms, short-term (1-2 days) smoking cessation was not shown to decreased GERD symptoms in 3 low-quality studies. Alcohol use may or may not be associated with reflux symptoms. There is insufficient research supporting recommendations to abstain from citrus juices, carbonated beverages, coffee and caffeine, chocolate, spicy foods, fatty foods, or late evening meals. One study supports the effectiveness of raising the head of the bed, though other studies have not found a difference. Another study supported a wedge to elevate the head. Several studies have shown some association between weight loss or left lateral decubitus sleeping position and improved symptoms.

Clinical Question:
Does gastric acid suppression increase the risk of pneumonia in children?

Bottom Line:
This is the first prospective study performed in pediatric patients showing that the use of GA inhibitors was associated with an increased risk of acute gastroenteritis and community-acquired pneumonia in GERD-affected children. It could be interesting to underline that they observed an increased incidence of intestinal and respiratory infection in otherwise healthy children taking GA inhibitors for GERD treatment. On the contrary, the majority of the previous data showed that the patients most at risk for pneumonia were those with significant comorbid illnesses such as diabetes or immunodeficiency, and this points to the importance of GA suppression as a major risk factor for infections. In addition, this effect seems to be sustained even after the end of therapy. The results of their study are attributable to many factors, including direct inhibitory effect of GA inhibitors on leukocyte functions and qualitative and quantitative gastrointestinal microflora modification. Additional studies are necessary to investigate the mechanisms of the increased risk of infections in children treated with GA inhibitors, and prophylactic measures could be considered in preventing them.

Reference:
Canani RB, Cirillo P, Roggero P, et al, for the Working Group on Intestinal Infections of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP). Therapy with gastric acidity inhibitors increases the risk of acute gastroenteritis and community-acquired pneumonia in children. Pediatrics 2006 May;117:e817-820.

Study Design:
Case-control

Synopsis:
Gastric acidity (GA) inhibitors, including histamine-2 receptor antagonists (H2 blockers) and proton pump inhibitors (PPIs), are the mainstay of gastroesophageal reflux disease (GERD) treatment. A prolonged GA inhibitor-induced hypochlorhydria has been suggested as a risk factor for severe gastrointestinal infections. In addition, a number of papers and a meta-analysis have shown an increased risk of pneumonia in H2-blocker-treated intensive care patients. More recently, an increased risk of community-acquired pneumonia associated with GA inhibitor treatment has been reported in a large cohort of adult patients. These findings are particularly relevant to pediatricians today because so many children receive some sort of GA-blocking agent to treat GERD. To test the hypothesis that GA suppression could be associated with an increased risk of acute gastroenteritis and pneumonia in children treated with GA inhibitors, we conducted a multicenter, prospective study. The study was performed by expert pediatric gastroenterologists from 4 pediatric gastroenterology centers. Children (aged 4-36 months) consecutively referred for common GERD-related symptoms (for example, regurgitation and vomiting, feeding problems, effortless vomiting, choking), from December 2003 to March 2004, were considered eligible for the study. Exclusion criteria were a history of GA inhibitors therapy in the previous 4 months, Helicobacter pylori infection, diabetes, chronic lung or heart diseases, cystic fibrosis, immunodeficiency, food allergy, congenital motility gastrointestinal disorders, neuromuscular diseases, or malnutrition. Control subjects were recruited from healthy children visiting the centers for routine examinations. The diagnosis of GERD was confirmed in all patients by standard criteria. GA inhibitors (10 mg/kg ranitidine per day in 50 children or 1 mg/kg omeprazole per day in 50 children) were prescribed by the physicians for 2 months. All enrolled children were evaluated during a 4-month follow-up. The end point was the number of patients presenting with acute gastroenteritis or community-acquired pneumonia during a 4-month follow-up study period. They obtained data in 186 subjects: 95 healthy controls and 91 GA-inhibitor users (47 on ranitidine and 44 on omeprazole). The 2 groups were comparable for age, gender, weight, length, and incidence of acute gastroenteritis and pneumonia in the 4 months before enrollment. Rate of subjects presenting with acute gastroenteritis and community-acquired pneumonia was significantly increased in patients treated with GA inhibitors compared with healthy controls during the 4-month follow-up period. In the GA inhibitor-treated group, the rate of subjects presenting with acute gastroenteritis and community-acquired pneumonia was increased when comparing the 4 months before and after enrollment. No differences were observed between H2 blocker and PPI users in acute gastroenteritis and pneumonia incidence in the previous 4 months and during the follow-up period. On the contrary, in healthy controls, the incidence of acute gastroenteritis and pneumonia remained stable.

Clinical Question:
Can a self-help guidebook help patients with irritiable bowel syndrome?

Bottom Line:
Self-help guidebook results in a reduction in primary care consultations, a perceived reduction in symptoms, and significant health service savings. This suggests that patients attending their primary care physician with functional abdominal symptoms should be offered self-help information as part of their management.

Reference:
Robinson A, Lee V, Kennedy A, et al. A randomised controlled trial of self-help interventions in patients with a primary care diagnosis of irritable bowel syndrome. Gut 2006;55:643-648.

Study Design:
Randomized controlled trial (nonblinded)

Synopsis:
Adult primary care patients (N=420) given a diagnosis by their primary care physician or a gastroenterologist of irritable bowel syndrome were enrolled in a study of self-help. The primary intervention was a self-help guidebook with information about lifestyle, diet, medications, and alternative therapies. Patients were randomly assigned (allocation concealed) to 1 of 3 groups: self-help guidebook alone; the same guidebook plus a self-help group meeting; or usual care. Groups were balanced at the start of the study and analysis was by intention to treat. The patients’ mean age was 40 years, 89% were women, and they had experienced bowel symptoms for a mean of 6 years. Patients receiving the guidebook made fewer visits to their primary care physician than did patients in the usual care group (1.6 fewer visits after 1 year). The self-help group meeting conferred no additional benefit over the guidebook alone. Symptoms improved in all 3 groups, although the greatest improvement was seen in patients receiving the guidebook (0.5 additional points on a 7-point scale, which is of unlikely clinical significance).

Clinical Question:
Does a combination of helium and oxygen improve exercise capacity in patients with chronic obstructive lung disease?

Bottom Line:
Reducing inspired gas density can improve exercise performance in COPD as much as increasing inspired oxygen. These effects can be combined as Heliox28 and are most evident in patients with more severe airflow obstruction.

Reference:
Laude EA, Duffy NC, Baveystock C, et al. The effect of helium and oxygen on exercise performance in chronic obstructive pulmonary disease: a randomized crossover trial. Am J Respir Crit Care Med 2006;173:865-870.

Study Design:
Cross-over trial (randomized)

Synopsis:
Breathing supplemental oxygen reduces breathlessness during exercise in patients with chronic obstructive pulmonary disease (COPD). Replacing nitrogen with helium reduces expiratory flow resistance and may improve lung emptying. Combining these treatments should be independently effective. The author study the effect of changing oxygen or helium concentration in inspired gas during exercise in patients with stable COPD. In 82 patients (mean age, 69.7 yr; mean FEV(1), 42.6% predicted), we measured endurance shuttle walking distance, resting and exercise oxygen saturation, and end-exercise dyspnea (Borg scale) while patients breathed Heliox28 (72% He/28% O(2)), Heliox21 (79% He/21% O(2)), Oxygen28 (72% N(2)/28% O(2)), or medical air (79% N(2)/21% O(2)). Gases were administered using a randomized, blinded, crossover design via a face mask and an inspiratory demand valve. Breathing Heliox28 increased walking distance (mean+/-SD, 147+/-150 m) and reduced Borg score (-1.28+/-1.30) more than any other gas mixture. Heliox21 significantly increased walking distance (99+/-101 m) and reduced dyspnea (Borg score, -0.76+/-0.77) compared with medical air. These changes were similar to those breathing Oxygen28. The effects of helium and oxygen in Heliox28 were independent. The increase in walking distance while breathing Heliox28 was inversely related to baseline FEV(1) breathing air.

Clinical Question:
Does esomeprazole (Nexium) improve symptoms and quality of life in patients with asthma?

Bottom Line:
In this study, esomeprazole (Nexium) was no better than placebo in improving peak expiratory flow, asthma symptoms, or quality of life in patients with stable asthma. Furthermore, esomeprazole was no better than placebo in patients with reflux, either.

Reference:
Kiljander TO, Harding SM, Field SK, et al. Effects of esomeprazole 40 mg twice daily on asthma: a randomized placebo-controlled trial. Am J Respir Crit Care Med 2006;173:1091-1097.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
Gastroesophageal reflux disease (GERD) is common in patients with asthma, suggesting an interaction between the two conditions. To assess the effect of gastric acid suppression with the proton pump inhibitor esomeprazole on asthma outcomes in subjects with persistent moderate to severe asthma treated with antiinflammatory asthma medication. The author did a double-blind study, subjects were randomized to receive esomeprazole 40 mg or placebo twice daily for 16 wk. According to nocturnal respiratory symptoms (NOC) and GERD, subjects were divided into three strata: GERD-/NOC+, GERD+/NOC-, and GERD+/NOC+. A total of 770 subjects were randomized. There was no statistically significant improvement in morning peak expiratory flow (PEF) over placebo in the overall study population: 6.3 L/min (p = 0.061). Over the whole treatment period, in GERD+/NOC+ subjects (n = 350), esomeprazole provided an 8.7-L/min improvement (p = 0.03) in morning PEF, and a 10.2-L/min improvement (p = 0.012) in evening PEF over placebo. Among 307 subjects taking long-acting beta2-agonists, improvements over placebo were observed in morning PEF (12.2 L/min, p = 0.017) and in evening PEF (11.1 L/min, p = 0.024); these improvements were more pronounced in GERD+/NOC+ subjects. Esomeprazole 40 mg twice daily was well tolerated and no safety concerns were noted.