Clinical Health Updates

Esophageal cancer occurs in 7/1000 per year

Clinical Question:
How many patients with Barrett’s esophagus will develop esophageal cancer?

Bottom Line:
Approximately 7 per 1000 (0.7%) patients with Barrett’s esophagus will develop esophageal cancer per year. The low incidence of Barrett’s, followed by this low incidence of esophageal cancer, may make routine evaluation of patients with chronic gastroesophageal reflux less important.

Reference:
Thomas T, Abrams KR, De Caestecker JS, Robinson RJ. Meta analysis: cancer risk in Barrett’s oesophagus. Aliment Pharmacol Ther 2007;26(11-12):1465-1477.

Study Design:
Meta-analysis (other)

Synopsis:
Risk of cancer in Barrett’s oesophagus is reported to vary between studies and also between countries, where the studies were conducted as per several systematic reviews. Cancer incidence has implications on surveillance strategies. The authors performed a meta-analysis to determine the incidence of oesophageal cancer in Barrett’s oesophagus. Articles retrieved by MEDLINE search (English language, 1966-2004). Studies had to necessarily include verified Barrett’s oesophagus surveillance patients, documented follow-up and cancer identified as the outcome measure. A random effects model of meta-analysis was chosen and results were expressed as mean (95% CI). Forty-one articles selected for conventional Barrett’s oesophagus (length >3 cm); eight included short segment Barrett’s oesophagus (one additional article including only short segment Barrett’s oesophagus). Cancer incidence was 7/1000 (6-9) person-years duration of follow-up (pyd), with no detectable geographical variation [UK 7/1000 (4-12) pyd, USA 7/1000 (5-9) pyd and Europe 8/1000 (5-12) pyd]. Cancer incidence in the UK was 10/1000 (7-14), when two large studies were excluded. Cancer incidence in SSBO was 6/1000 (3-12) pyd. When short segment Barrett’s oesophagus compared to conventional Barrett’s oesophagus, there was a trend towards reduced cancer risk [OR 0.55, (95% CI: 0.19-1.6), P = 0.25].

Acupuncture may have value in treating GERD

Clinical Question:
Is adding acupuncture more effective than doubling the dose of proton pump inhibitor in patients with heartburn symptoms despite treatment?

Bottom Line:
In this small, short-term study, adding twice weekly acupuncture to standard-dose proton pump inhibitor (PPI) treatment was more effective in controlling symptoms than doubling the PPI dose. Acupuncture may be useful for some patients, but the long-term benefits, if any, have not been established.

Reference:
Dickman R, Schiff E, Holland A, et al. Clinical trial: acupuncture vs. doubling the proton pump inhibitor dose in refractory heartburn. Aliment Pharmacol Ther 2007;26(10):1333-1344.

Study Design:
Randomized controlled trial (nonblinded)

Synopsis:
The authors enrolled 30 adult patients with a 3-month history of symptoms related to gastroesophageal reflux disease despite taking a standard-dose PPI (omeprazole 20 mg daily). These patients were also willing to undergo endoscopy (and did so). To minimize the variability of the 2 groups because of the small sample size, the researchers matched participants by age, sex, and body mass index. The patients were randomized, allocation concealment unknown, to receive either a double dose of omeprazole or 10 acupuncture sessions over 4 weeks while continuing the standard-dose PPI. Acupuncture consisted of 5 points selected to “calm” or “regulate” the stomach (CV 12, 17, Per.6, Sp.9, and St.36). Although acupuncturists were instructed to minimize interaction with patients, 10 sessions so closely spaced are likely to exert a significant placebo effect and the study would have been much better had it employed a double-dummy approach using sham acupuncture and placebo omeprazole in the opposite groups. Another issue: The investigators used statistical tests that typically are not believed to be valid for small numbers of patients.

In this short-term study, the addition of acupuncture to standard dose PPI therapy significantly decreased symptoms of daytime and nighttime heartburn, acid regurgitation, dysphagia, and chest pain, whereas there was no change with double-dose PPI. Quality of life, assessed at the end of the study using the SF-36 general health scale was significantly improved in the acupuncture group as compared with the increased dose group.

7 days of tx good for H. pylori

Clinical Question:
What is the optimum duration of treatment for Helicobacter pylori eradication?

Bottom Line:
Seven days of treatment with triple therapy — a proton pump inibitor (PPI) + clarithromycin (Biaxin) + amoxicillin or metronidazole — produces rates of eradication that are nearly as good as 10 days to 14 days of treatment, and are equally good if only high-quality research is considered.

Reference:
Fuccio L, Minardi ME, Zagari RM, Grilli D, Magrini N, Bazzoli F. Meta-analysis: Duration of first-line proton-pump inhibitor-based triple therapy for Helicobacter pylori eradication. Ann Intern Med 2007;147(8):553-562.

Study Design:
Meta-analysis (randomized controlled trials)

Synopsis:
Researchers conducting this meta-analysis searched 3 databases to find research comparing different durations of triple therapy for H. pylori eradication. They also searched conference proceedings, but limited all of their choices to articles in English. Two researchers independently abstracted the data and assessed study quality via the commonly used Jadad criteria. Their search yielded 21 studies comparing 7, 10, and 14 days of treatment using regimens of a PPI with clarithromycin and amoxicillin or a PPI with clarithromycin and metronidazole. Most of the studies evaluated patients with peptic ulcer disease (n = 15). Only 4 of the studies had a quality score of 4 or 5 of a possible 5, with only 3 studies clearly described concealed allocation and only 4 studies were double blinded.

The 11 studies comparing 7 days with 10 days of treatment collectively showed a slightly higher cure rate with 10 days of therapy, though the difference is not likely clinically relevant (77% vs 81% cure; relative risk = 1.05). Differences between 7 days and 14 days of treatment were similar in 13 studies: 73% versus 78%; relative risk = 1.07. There was heterogeneity among the study results that could be explained by the use of antibiotic. The difference in outcome between durations of therapy were present in studies using amoxicillin but not in studies using metronidazole. The outcomes were not different based on duration of therapy when only the high-quality studies were analyzed.

Blatchford score more sensitive than Rockall in GI bleeding

Clinical Question:
Is the Blatchford score more reliable than the Rockall score in predicting which patients with nonvariceal upper gastrointestinal bleeding will require clinical interventions?

Bottom Line:
The Blatchford score identified more patients who needed transfusion or interventions to stop bleeding among those with nonvariceal upper gastrointestinal (GI) bleeding.

Reference:
Chen IC, Hung MS, Chiu TF, Chen JC, Hsiao CT. Risk scoring systems to predict need for clinical intervention for patients with nonvariceal upper gastrointestinal tract bleeding. Am J Emerg Med 2007;25(7):774-779.

Study Design:
Cohort (retrospective)

Synopsis:
Several risk score systems are designed for triage patients with acute nonvariceal upper gastrointestinal bleeding (UGIB). Blatchford score, which relies on only clinical and laboratory data, is used to identify patients with acute UGIB who need clinical intervention (before endoscopy). Clinical Rockall score, which relies on only clinical variables, is used to identify patients with acute UGIB who have adverse outcome, such as death or recurrent bleeding. Complete Rockall score, which relies on clinical and endoscopic variables, is also used to identify patients with acute UGIB who died or have recurrent bleeding. In this studies the authors defined patients who need clinical intervention (ie, blood transfusion, endoscopic or surgical management for bleeding control) as high-risk patients. Our study aims to compare Blatchford score with clinical Rockall score and complete Rockall score in their utilities in identifying high-risk cases in patients with acute nonvariceal UGIB. International Classification of Diseases, Ninth Revision, Clinical Modification codes for admission diagnosis were used to recognize a cohort of patients (N = 354) with acute UGIB admitted to a tertiary care, university-affiliated hospital. Medical record data were abstracted by 1 research assistant blinded to the study purpose. Blatchford and Rockall scores were calculated for each enrolled patient. High risk was defined as a Blatchford score of greater than 0, a clinical Rockall score of greater than 0, and a complete Rockall score of greater than 2. Patients were defined as needing clinical intervention if they had a blood transfusion or any operative or endoscopic intervention to control their bleeding. Such patients were defined as high-risk patients. The Blatchford score identified 326 (92.1%) of the 354 patients as those with high risk for clinical intervention (ie, blood transfusion, endoscopic or surgical management for bleeding control). The clinical Rockall score identified 289 (81.6%) of the 354 patients as high-risk, and the complete Rockall score identified 248 (70.1%) of the 354 patients as high-risk. The yield of identifying high-risk cases with the Blatchford score was significantly greater than with the clinical Rockall score (P < .0001) or with the complete Rockall score (P < .0001). In our total 354 patients, 246 (69.5%) patients were categorized as those with high risk for clinical intervention (ie, blood transfusion, endoscopic or surgical management for bleeding control, as aforementioned) in our study. The Blatchford score identified 245 (99.6%) of 246 patients as high-risk. Only 1 patient who met the study definition of needing clinical intervention was not identified via Blatchford score. This patient did not have recurrent bleeding nor die and did not receive blood transfusion. The clinical Rockall score identified 222 (90.2%) of 246 patients as high-risk. Twenty-four patients who met the study definition of needing clinical intervention were not recognized via clinical Rockall score. Of these patients, 0 died, 7 developed recurrent bleeding, and 6 needed blood transfusion. The complete Rockall score identified 224 (91.1%) of 246 patients as high-risk. Twenty-two patients who met the study definition of needing clinical intervention were not recognized via complete Rockall score. Of these patients, 2 died, 3 developed recurrent bleeding, and 20 needed blood transfusion.

Benign course for symptomatic uncomplicated diverticular disease

Clinical Question:
What is the prognosis for adults with symptomatic uncomplicated diverticular disease?

Bottom Line:
The vast majority (more than 95%) of adults diagnosed with symptomatic uncomplicated diverticular disease described their symptoms as none or mild and as not affecting their daily activities after a 5-year follow-up.

Reference:
Salem TA, Molloy RG, O’Dwyer PJ. Prospective, five-year follow-up study of patients with symptomatic uncomplicated diverticular disease. Dis Colon Rectum 2007;50(9):1460-1464.

Study Design:
Cohort (prospective)

Synopsis:
To evaluate the natural history of diverticular disease, these investigators identified 163 adults, aged 64 to 80 years, diagnosed with symptomatic, uncomplicated diverticular disease. All patients were referred to a surgical outpatient clinic by their primary care clinician for the assessment of large bowel symptoms. Symptoms included lower left quadrant pain and/or change in bowel habits without evidence of inflammation (no fever, tenderness, or increased inflammatory markers). The diagnosis of diverticular disease was confirmed using colonoscopy, flexible sigmoidoscopy, or barium enema. Outcomes were assessed using a computerized database of hospital records, telephone contact with patients, and from primary care clinicians. A total of 25 patients were excluded from follow-up as a result of having left-sided colon cancer or rectal bleeding secondary to polyps or hemorrhoids. Nineteen patients died; none of the deaths were considered secondary to diverticular disease and an additional 18 patients (14%) were lost to follow-up. Of the remaining 119 patients who were followed up for a median of 5.5 years, 2 (1.7%) were successfully treated for acute diverticulitis and 1 additional patient underwent surgery for recurrent symptoms. The other 116 patients (97%) described their symptoms as either none or mild and as not affecting their daily activities after a median follow-up of 66 months.

PEG more effective than tegaserod for chronic constipation

Clinical Question:
Which is the more effective treatment for chronic constipation, tegaserod or polyethylene glycol?

Bottom Line:
Based on the results of this nonmasked trial, polyethylene glycol (PEG) is more effective, better tolerated, and less expensive in the short-term than tegaserod for the treatment of chronic constipation in adults.

Reference:
Di Palma JA, Cleveland MV, McGowan J, Herrera JL. A randomized, multicenter comparison of polyethylene glycol laxative and tegaserod in treatment of patients with chronic constipation. Am J Gastroenterol 2007;102:1964-1971.

Study Design:
Randomized controlled trial (nonblinded)

Synopsis:
Polyethylene glycol (PEG) 3350 (MiraLax) and tegaserod (Zelnorm), a serotonin subtype 4 receptor partial agonist, are currently approved for treatment of constipation. The authors compared the efficacy of each product over a 4-wk treatment period. They study patients who met defined criteria for chronic constipation were randomized in this open-labeled, parallel, multicenter study to receive the PEG laxative as a single daily dose of 17 g or tegaserod tablets 6 mg b.i.d., for 28 days. As a primary end point, treatment success was defined for each patient as relief of modified ROME criteria for constipation for 50% or more of their treatment weeks. Various secondary measures were also assessed. An interactive voice response system (IVRS) recorded patient reported daily bowel movement experience and study efficacy and safety information. A total of 237 patients were enrolled and received treatment at one of 25 centers. Successful treatment according to the primary end point was seen in 50.0% of the PEG and 30.8% of tegaserod patients (P= 0.003). By treatment weeks 3 and 4, significantly more PEG patients were successfully treated according to primary and secondary response definitions. PEG patients experienced more bowel movements per week (P= 0.019) and had significantly greater improvement in constipation symptoms (P= 0.016) based on results from a validated patient self-reported questionnaire. Tegaserod patients experienced a significantly higher incidence of headaches. Otherwise, there were no significant differences in adverse events.

For severe secondary peritonitis, on-demand relaparotomy > planned relaparotomy

Clinical Question:
In patients with secondary peritonitis who undergo initial emergent laparotomy, does planned relaparotomy reduce morbidity, mortality, and costs over on-demand relaparotomy?

Bottom Line:
Mortality rates did not differ between the 2 approaches, but on-demand laparotomy resulted in reduced intensive care unit (ICU) length of stay, reduced overall hospital length of stay, and decreased costs.

Reference:
van Ruler O, Mahler CW, Boer KR, et al, for the Dutch Peritonitis Study Group. Comparison of on-demand vs planned relaparotomy strategy in patients with severe peritonitis. JAMA 2007;298:865-873.

Study Design:
Randomized controlled trial (nonblinded)

Synopsis:
In patients with severe secondary peritonitis, there are 2 surgical treatment strategies following an initial emergency laparotomy:
1. planned relaparotomy
2. relaparotomy

Only when the patient’s condition demands it (“on-demand”). The on-demand strategy may reduce mortality, morbidity, health care utilization, and costs. However, randomized trials have not been performed.

The investigators compared
1. patient outcome
2. health care utilization
3. costs of on-demand and planned relaparotomy.

They did a randomized, nonblinded clinical trial of patients who had severe secondary peritonitis and an Acute Physiology and Chronic Health Evaluation (APACHE-II) score of 11 or greater
1. 2 academic teaching hospitals in the Netherlands from November 2001 through February 2005
2. 5 regional teaching hospitals in the Netherlands from November 2001 through February 2005

End Points are.
1. The primary end point was death and/or peritonitis-related morbidity within a 12-month follow-up period.
2. Secondary end points included health care utilization and costs.

A total of 232 patients (116 on-demand and 116 planned) were randomized. One patient in the on-demand group was excluded due to an operative diagnosis of pancreatitis and 3 in each group withdrew or were lost to follow-up. There was no significant difference in primary end point (57% on-demand [n = 64] vs 65% planned [n = 73]; P = .25) or in mortality alone (29% on-demand [n = 32] vs 36% planned [n = 41]; P = .22) or morbidity alone (40% on-demand [n = 32] vs 44% planned [n = 32]; P = .58). A total of 42% of the on-demand patients had a relaparotomy vs 94% of the planned relaparotomy group. A total of 31% of first relaparotomies were negative in the on-demand group vs 66% in the planned group (P <.001). Patients in the on-demand group had shorter median intensive care unit stays (7 vs 11 days; P = .001) and shorter median hospital stays (27 vs 35 days; P = .008). Direct medical costs per patient were reduced by 23% using the on-demand strategy.

Bariatric surgery reduces all-cause mortality in morbidly obese

Clinical Question:
Does bariatric surgery reduce all-cause mortality?

Bottom Line:
This nonrandomized controlled trial showed that bariatric surgery results in sustained weight loss of 14% to 25% after 10 years and also reduces all-cause mortality.

Reference:
Sjostrom L, Narbro K, Sjostrom CD, et al, for the Swedish Obese Subjects Study. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 2007;357:741-752.

Study Design:
Non-randomized controlled trial

Synopsis:
Obesity is associated with increased mortality. Weight loss improves cardiovascular risk factors, but no prospective interventional studies have reported whether weight loss decreases overall mortality. In fact, many observational studies suggest that weight reduction is associated with increased mortality. They did a prospective, controlled Swedish Obese Subjects study involved 4047 obese subjects. Of these subjects, 2010 underwent bariatric surgery (surgery group) and 2037 received conventional treatment (matched control group). We report on overall mortality during an average of 10.9 years of follow-up. At the time of the analysis (November 1, 2005), vital status was known for all but three subjects (follow-up rate, 99.9%). The average weight change in control subjects was less than +/-2% during the period of up to 15 years during which weights were recorded. Maximum weight losses in the surgical subgroups were observed after 1 to 2 years: gastric bypass, 32%; vertical-banded gastroplasty, 25%; and banding, 20%. After 10 years, the weight losses from baseline were stabilized at 25%, 16%, and 14%, respectively. There were 129 deaths in the control group and 101 deaths in the surgery group. The unadjusted overall hazard ratio was 0.76 in the surgery group (P=0.04), as compared with the control group, and the hazard ratio adjusted for sex, age, and risk factors was 0.71 (P=0.01). The most common causes of death were myocardial infarction (control group, 25 subjects; surgery group, 13 subjects) and cancer (control group, 47; surgery group, 29).

Celiac disease common in primary care patients with chronic GI symptoms

Clinical question
Can a case-finding strategy identify more patients with celiac disease?

Bottom line
This study tells us that celiac disease (CD) is relatively common in primary care practice, particularly in patients with gastrointestinal symptoms, chronic fatigue, or thyroid disease. Patients with persistent symptoms should be evaluated for CD using the strategy described in this study, and the diagnosis should be confirmed either by intestinal biopsy or a successful trial of a gluten-free diet.

Reference
Catassi C, Kryszak D, Louis-Jacques O, et al. Detection of celiac disease in primary care: a multicenter case-finding study in North America. Am J Gastroenterol 2007;102:1454-1460.

Study design: Cohort (prospective)

Synopsis
Celiac disease (CD) is one of the most common lifelong disorders in western countries. However, most cases remain currently undiagnosed in North America, mostly due to poor awareness of CD by primary care physicians. The authors determined whether an active case-finding strategy in primary care could increase the frequency of CD diagnosis and to determine the most common clinical presentations of the condition. This was a multicenter, prospective study involving adult subjects during the years 2002-2004, attending one of the participating practices. All individuals with symptoms or conditions known to be associated with CD were tested for immunoglobulin A anti-transglutaminase (tTG) antibodies, and those with elevated anti-tTG were subsequently tested for IgA antiendomysial antibodies (EMA). All subjects who were positive for EMA were advised to undergo an intestinal biopsy and HLA typing. The study group included 737 women and 239 men, with a median age of 54.3 yr. A positive anti-tTG test was found in 30 out of 976 investigated subjects (3.07%, 95% CI 1.98-4.16). CD was diagnosed in 22 patients (18 women, 4 men). The most frequent reasons for CD screening in these 22 cases were bloating (12/22), thyroid disease (11/22), irritable bowel syndrome (7/22), unexplained chronic diarrhea (6/22), chronic fatigue (5/22), and constipation (4/22). The prevalence of CD in the serologically screened sample was 2.25% (95% CI 1.32-3.18). The diagnostic rate was low at baseline (0.27 cases per thousand visits, 95% CI 0.13-0.41) and significantly increased to 11.6 per thousand visits (95% CI 6.8-16.4, P < 0.001) following active screening implementation.

Vancomycin > metronidazole for severe C. difficile-associated diarrhea

Clinical question
Is metronidazole or vancomycin more effective for treating CDAD based on disease severity?

Bottom line
In this small study, metronidazole and vancomycin are equally effective for the treatment of mild CDAD, but vancomycin is superior for treating patients with severe CDAD.

Reference
Zar FA, Bakkanagari SR, Moorthi KM, Davis MB. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis 2007;45:302-7.

Study design: Randomized controlled trial (double-blinded)

Synopsis
The incidence and severity of Clostridium difficile-associated diarrhea (CDAD) has been increasing, and there have been recent reports of metronidazole treatment failure. Metronidazole is still commonly used as first-line treatment for CDAD but has never been compared with vancomycin in a prospective, randomized, double-blind, placebo-controlled trial. The authors conducted such a trial, stratifying patients according to disease severity, to investigate whether one agent was superior for treating either mild or severe disease. From October 1994 through June 2002, patients with CDAD were stratified according to whether they had mild or severe disease based on clinical criteria and were randomly assigned to receive oral metronidazole (250 mg 4 times per day) or oral vancomycin (125 mg 4 times per day) for 10 days. Both groups received an oral placebo in addition to the study drug. Patients were followed up for 21 days to assess cure, treatment failure, relapse, or intolerance. One hundred seventy-two patients were enrolled, and 150 of these patients successfully completed the trial. Among the patients with mild CDAD, treatment with metronidazole or vancomycin resulted in clinical cure in 90% and 98% of the patients, respectively (P=.36). Among the patients with severe CDAD, treatment with metronidazole or vancomycin resulted in clinical cure in 76% and 97% of the patients, respectively (P=.02). Clinical symptoms recurred in 15% of the patients treated with metronidazole and 14% of those treated with vancomycin.