Gastric bypass induces diabetes remission in obese patients

WASHINGTON (IMNG) – Gastric bypass surgery resulted in significantly more weight loss and also improved measures of glycemic control significantly more than did other forms of bariatric surgery, Dr. John Morton reported at the annual clinical congress of the American College of Surgeons.

However, he noted, while remission did correlate with weight loss in patients who had gastric banding or sleeving, it appeared to be independent of weight loss in those who had the bypass surgery. While he didn’t speculate on the reasons for this finding, he did affirm his belief that gastric bypass is the best option for most obese patients with comorbid diabetes.

“I feel very comfortable recommending it” for these patients, said Dr. Morton of the Stanford (Calif.) University. “There are, of course, other clinical conditions to consider when deciding [among] bypass, banding, and sleeve, but if the only consideration is around diabetes, I’m 100% comfortable in recommending it for obese diabetics.”

He presented the 1-year follow-up data on 1,792 obese patients who underwent bariatric surgery. Of these, 1,364 had a Roux-en-Y bypass; 264 had a sleeve gastrectomy; and 164 had adjustable gastric banding.

The patients were a mean of about 46 years old. Body mass index was statistically, but not clinically, different between the groups (bypass 47 kg/m2; band 44 kg/m2; sleeve 44 kg/m2). Waist circumference ranged from 51 to 53 inches. About 75% of the group was female and more than half, white.

Overall, about one-third of each group had type 2 diabetes. Most were taking only oral medications. About 5% took only insulin, and about a quarter took both oral agents and insulin. At baseline, the mean HbA_1c was more than 7% in each group. The mean fasting insulin was 36 microU/mL in the bypass group, 28 microU/mL in the band group, and 32 microU/mL in the sleeve group.

By 12 months after surgery, patients with diabetes who had bypass had lost the most weight – a mean of 71% of their excess body weight, compared with 38% in the banding group and 50% in the sleeve group.

Those who had the bypass surgery also experienced the biggest change in their HbA_1c – dropping almost 16% to a mean of 5.8%. Patients in the other two groups experienced a mean drop of 10%, resulting in HbA_1c levels of right around 6%.

Fasting insulin levels also improved significantly more in the bypass group, falling from a baseline mean of 56 microU/mL to 7.8 microU/mL – a decrease of 68%. In the band group, the level fell from 28 microU/mL to 12 microU/mL – a 52% decrease. In the sleeve group, levels fell from 32 microU/mL to 10 microU/mL – a 61% decrease.

“Fasting insulin is also considered an independent marker of cardiac risk,” Dr. Morton added, indicating that the risk of cardiovascular problems would fall along with insulin levels.

Blood glucose improved significantly more in the bypass group, falling from a baseline mean of 149 mg/dL to 101 mg/dL – a 22% change. In the band group, the level fell from 140 mg/dL to 125 mg/dL (8%) and in the sleeve group, from 130 mg/dL to 118 mg/dL (5.6%).

A multivariate analysis controlled for surgery type, sex, body mass index, race, age, and insurance status. Of these factors, surgery type was the strongest predictor, with bypass patients three times more likely to achieve that goal than those undergoing banding or sleeve placement.

Dr. Morton did not present his complication data. However, during the discussion period, he said the three procedures were similarly safe. The gastric sleeve group had a higher leak rate than did the other groups, but that remained less than 1%. Readmission rates were comparable, he said, but he did not provide that number.

“Any time you consider this, it has to be a risk/benefit analysis,” he said. “It’s our philosophy that for obese patients with severe diabetes, we approach them first with the bypass because it has the most proven track record over time.”

Dr. Morton has up to 7 years of data on some of the patients, and said he is now analyzing that. But when questioned about durability, he agreed that diabetes can recur in the rather common scenario of a patient regaining weight. “At the end of the day, though, what’s important is that the obese patient with diabetes gets treatment. All three surgeries demonstrated some improvement, and I believe that any surgery is better than no surgery at all.”

Dr. Morton has received research support from Covidien.

Gestational diabetes linked to sleep apnea

Women with gestational diabetes are nearly seven times more likely to have sleep apnea and to sleep an average of one hour less nightly than do expectant mothers without the condition, a small observational study has shown.

“It is common for pregnant women to experience sleep disruptions, but the risk of developing obstructive sleep apnea increases substantially in women who have gestational diabetes,” Dr. Sirimon Reutrakul of Rush University Medical Center in Chicago, said in a statement. “Nearly 75% of the participants in our study who had gestational diabetes also suffered from obstructive sleep apnea.”

Reports in the literature link sleep apnea in pregnancy to complications such as preeclampsia, hypertension, low birth weights, preterm delivery, and other pregnancy-related adverse outcomes.

Use of continuous positive airway pressure (CPAP) early in pregnancy for women with hypertension and chronic snoring was noted by the investigators to be associated with better blood pressure control and pregnancy outcomes. CPAP treatment in nonpregnant type 2 diabetes patients with sleep apnea has been shown occasionally effective in improving glucose control. Because there are currently no data on the effects of sleep apnea treatment in gestational diabetes, whether CPAP treatment might affect glucose metabolism and pregnancy outcomes is unknown.

Dr. Reutrakul and his associates cited previous studies that increased sleep apnea leads to poor glycemic control, as well as reports that sleep apnea is a major risk factor for insulin resistance regardless of body mass index (BMI). With these data in mind, the investigators compared metabolic and sleep apnea measures in 15 pregnant women who did not have gestational diabetes; 15 pregnant women with gestational diabetes; and 15 obese controls (BMI = 31.0 +/– 4.3 kg/m²) who were neither pregnant nor diabetic. The groups were matched for age, race, and in the pregnant groups, and prepregnancy BMI.

All gestating women were expecting singletons and were either in the latter part of their second term, or the early part of their third. The average gestational age was 28.2 +/– 3.7 weeks in the women with gestational diabetes, and 30.9 +/– 2.0 weeks in the pregnant group without.

The women with gestational diabetes had notably higher measures of prepregnancy BMI than did the pregnant women without gestational diabetes. The BMI of the gestational diabetes cohort at the time of the sleep apnea monitoring also tended to be higher. Most of the pregnant women were overweight (BMI 25.0-29.9 kg/m²) or obese (BMI = 30 kg/m²) based on the prepregnancy BMI (93% of those with gestational diabetes; 67% of those without).

The number of apneas and hypopneas per hour of sleep were measured using polysomnography. Sleep apnea was diagnosed in the women if their apnea-hypopnea index (AHI) score was greater than or equal to 5. Dr. Reutrakul and his colleagues wrote that theirs was the first study to use polysomnography to evaluate overall sleep quality, including apnea, in women with gestational diabetes, compared with pregnant women without gestational diabetes, controlling for confounding factors. Wake time after sleep onset equaled the number of minutes participants were awake between sleep onset and end of the session.

There were a number of statistically significant findings:

After they adjusted for prepregnancy BMI, Dr. Reutrakul and his associates found that a diagnosis of gestational diabetes was strongly associated with a diagnosis of sleep apnea (odds ratio, 6.60; 95% confidence interval, 1.15-37.96). The researchers also found that pregnant women with gestational diabetes slept a median average of 1 hour less than the other pregnant women did (397 minutes vs. 464 minutes). The gestational diabetes cohort also had a median AHI approximately four times higher than the pregnant women without gestational diabetes had (8.2 vs. 2.0), and a higher overall rate of sleep apnea than did the nongestational diabetes group (73% vs. 27%). Compared with controls, a higher AHI was found in pregnant women without gestational diabetes (2.0 vs. 0.5), as was more disrupted sleep as reflected by a higher wake time after sleep onset (66 vs. 21 minutes). Their median microarousal index was also higher (16.4 vs. 10.6).

The researchers noted that women with gestational diabetes gained less weight during pregnancy than the pregnant women without gestational diabetes (BMI increased respectively by 2.2 +/– 2.0 vs. 4.6 +/– 1.9 kg/m²), ruling out any “strong association” between gestational weight gain, gestational diabetes, and sleep apnea.

According to the authors, the study also was limited by its cross-sectional design, which does not indicate whether sleep apnea causes gestational diabetes, or vice versa. Regardless, Dr. Reutrakul stated, “Based on these findings, women who have gestational diabetes should be considered for evaluation for obstructive sleep apnea, especially if other risk factors such as hypertension or obesity are present, and women already diagnosed with sleep apnea should be monitored for signs of gestational diabetes during pregnancy.”

A member of the research team reported financial ties with Pfizer and other industry-related research grant support. See study for list of disclosures. This study was supported by the ResMed Foundation; the diabetes research training center at the University of Chicago, a specialized center of research on Women’s Health; and the National Institutes of Health.

Call to restrict PPI use in hospitals

Proton pump inhibitors substantially raise the risk of hospital-related C. difficile infection and clinicians “should strongly consider restricting” their use, US researchers say.
Hospital patients were almost twice as likely to contract a C. difficile infection (CDI) if they had received a PPI, the study of 200 CDI patients and matched controls showed.
There was a dose response, with the likelihood of a CDI increasing with longer durations of PPI therapy, the authors from the Midwestern University College of Pharmacy found.
Other factors significantly associated with CDI were prior hospitalisation within 30 days, 

Studies show long-term benefits of colorectal cancer screening

Both colonoscopy and fecal occult-blood testing lead to lasting reductions in the risk of death from colorectal cancer, according to a pair of studies in the September 19, 2013, issue of The New England Journal of Medicine. 

One study used data from long-term follow-up studies of health care professionals to analyze the impact of sigmoidoscopy and colonoscopy on colorectal cancer incidence and death. The analysis included a total of 88,902 participants followed up for 22 years. The lead author was Reiko Nishihara, PhD, of Dana-Farber Cancer Institute, Boston. 

On multivariate analysis, hazard ratios (HRs) for colorectal cancer were 0.57 for patients undergoing endoscopy with polypectomy, 0.60 for those with negative sigmoidoscopy, and 0.44 for those with negative colonoscopy. Patients with negative colonoscopy also had a lower incidence of proximal colon cancer, HR 0.73. Colorectal cancer mortality was reduced after both sigmoidoscopy and colonoscopy: HR 0.59 and 0.32, respectively. Only colonoscopy was associated with reduced mortality from proximal colon cancer: HR 0.47. 

The second study evaluated data on 46,551 patients, aged 50 to 80 years, from a randomized trial of annual or biannual fecal occult blood testing versus usual care. The lead author was Dr Aasma Shaukat of Minneapolis Veterans Affairs Health Care System. 

At 30 years' follow-up, the rate of death from colorectal cancer was 1.8% with annual screening, 2.2% with biennial screening, and 2.7% with usual care. Relative risks were 0.68 with annual screening and 0.78 with biennial screening. The mortality benefit of biennial screening was greater in men compared to women; all-cause mortality was not significantly different between groups. 

"[B]oth colonoscopy and fecal occult-blood testing are effective for colorectal-cancer screening, and these new studies support current screening guidelines," according to an accompanying editorial by Drs Theodore R. Levin and Douglas A. Corley. They emphasize that the differing nature of the 2 studies "makes direct comparisons of effectiveness difficult." Forthcoming randomized trials will help in determining which test is better over a 10-year follow-up interval, as well as the overall effectiveness of colorectal cancer screening.

Diabetics’ stroke risk post MI has plummeted

September 23, 2013

BY BRUCE JANCIN

AMSTERDAM (IMNG) – The risk of ischemic stroke following an acute myocardial infarction in diabetes patients dropped markedly during a recent 10-year period, according to a nationwide Swedish study.

Indeed, the reduction in ischemic stroke risk during the first year after an MI was significantly larger in diabetic than in nondiabetic patients over the course of a decade, Stina Jakobsson said at the annual congress of the European Society of Cardiology.

“We believe that the larger risk reduction seen in the diabetic patients may indicate that they have gained more from the increased use of evidence-based secondary preventive treatment,” added Ms. Jakobsson, a medical student at Umea (Sweden) University.

She presented an analysis of all 173,233 patients discharged from Swedish coronary care units after an acute MI during 1998-2008. A total of 19% of them had a previous diagnosis of diabetes.

Among diabetes patients with an MI in 1998-2000, ischemic stroke occurred in 7.1% within 1 year after their coronary event. However, the 1-year ischemic stroke rate in such patients whose MI occurred in 2007-2008 dropped to 4.7%. This was a much more impressive improvement than occurred in the same time span among nondiabetic patients, where the ischemic stroke rate during the first year after an acute MI was 4.2% in 1998-2000, nudging downward to 3.7% in 2007-2008.

Ms. Jakobsson stressed that there is definitely room for improvement in the use of reperfusion therapy and secondary preventive medications among diabetes patients with an MI. Although the use of these key interventions increased over time in both diabetic and nondiabetic MI patients, rates still remained lower in the diabetic group in the most recent study years.

The 4.7% 1-year incidence of ischemic stroke among Swedish diabetes patients with an acute MI in 2007-2008 was significantly greater than the 3.7% rate among nondiabetic patients. Moreover, even among patients on optimized secondary prevention therapies, the ischemic stroke rate was higher in the diabetic group. That’s not surprising because they more often had a history of prior cardiovascular disease at the time of their acute MI.

“They were sicker to start with,” Ms. Jakobsson observed.

The most powerful predictors of increased risk of ischemic stroke post MI included older age, atrial fibrillation, an ST-elevation MI, and prior ischemic stroke.

This study was supported by Swedish governmental research funds. Ms. Jakobsson reported having no financial conflicts of interest.

Almost 2 million try to quit smoking in wake of CDC campaign

Almost 2 million Americans tried to quit smoking in the wake of a 2012 government educational campaign, and at least 100,000 of them have quit permanently.

That’s according to an analysis of the Centers for Disease Control and Prevention’s (CDC’s) Tips From Former Smokers campaign that was published online in the Lancet on Sept. 9 (doi: 10.1016/S0140-6736(13)61686-4). The analysis by CDC officials estimates that 1.6 million Americans tried to quit after the campaign’s launch in March 2012. By June 2012, when it ended, at least 100,000 of them could be defined as having permanently quit.

“These are really minimal estimates,” said Dr. Thomas Frieden, director of the CDC, in a briefing with reporters. “We think the actual impact may have been even larger than this.”

The Tips From Former Smokers campaign was made possible by a $54 million grant from the Affordable Care Act’s Public Health and Prevention Fund. Print ads featured graphic photos of former smokers with stomas, or scars from open heart surgery. Former smokers also described tobacco’s toll on their health in broadcast and radio ads and videos posted to the CDC website. The TV ads directed viewers to the 1-800-QUIT-NOW quit line or to the National Cancer Institute’s quit assistance website, www.smokefree.gov.

A testimonial from former smoker Terrie Hall has been the most-visited page on the entire CDC site, receiving 2.5 million hits so far, Dr. Frieden said. In it, Ms. Hall tells smokers: “Record your voice for loved ones while you still can.” Ms. Hall was diagnosed with throat cancer, had her larynx removed, and now speaks with the aid of an artificial voice box.

Overall, the tips campaign was seen by four out of five smokers, the Lancet report estimated.

To assess how well the campaign worked, the CDC used a nationally representative online survey. Current smokers – those who had smoked at least 100 cigarettes in their lifetime and now smoked every day or some days – and nonsmokers (all others) were compared. There was a baseline survey before the campaign started and another immediately after the campaign ended.

Of the invited smokers, 70% (4,108) responded, and 58% (3,000) of the invited nonsmokers responded to the baseline survey. After the campaign ended, 74% (3,058) of the smokers and 74% (2,220) of the nonsmokers responded. About 75% of the smokers and nonsmokers said they recalled seeing at least one tips ad.

The prevalence of smokers who tried to quit in the past 3 months increased from 31% before the tips campaign to 35% after the campaign. At the end of the 12-week campaign, 13% of smokers who tried to quit said they had not smoked again.

After stratifying the results of the overall response to the campaign, the CDC researchers found that there were more quit attempts among younger smokers, lighter smokers, African American smokers, and smokers with less education.

Calls to the 1-800-QUIT-NOW line increased 132% during the 12-week campaign, 200,000 more calls than during the same period the previous year. There were also 500,000 unique visitors to the www.smokefree.gov website.

The analysis showed that the campaign spurred a large number of nonsmokers to talk to their friends or family about the dangers of smoking and quitting. Applying the findings to the U.S. population, the researchers reported that almost 5 million nonsmokers recommended a smoking cessation service to a friend or family member, and 6 million discussed the dangers of smoking.

Lisha Hancock was one of those smokers who heard from a family member about quitting, but she also said that she was influenced greatly by Terrie Hall’s story. Ms. Hancock told reporters that she smoked for 17 years, starting at age 21. Family and peer pressure did not motivate her to quit. But her 5-year-old son’s questions and response to Ms. Hall’s ads, along with her own impressions from Ms. Hall’s testimonial, moved her. “You can see the regret and sadness in her eyes,” said Ms. Hancock, in a conference call.

After seeing the ads and online testimonials, Ms. Hancock decided to make a plan, made some diet and exercise changes, and used nicotine lozenges to help her quit. She has gone about 6 months without smoking, she said.

The CDC report found that thanks to more people quitting, the campaign may have added 500,000 quality-adjusted life-years to the U.S. population, which suggests a cost per life-year saved of less than $200. That ranks the campaign “among the most cost-effective preventive interventions,” said the CDC authors.

Meanwhile, the $54 million spent on the campaign is less than what the tobacco industry spends for 3 days of marketing, according to the report. The industry’s $8 billion in annual spending far outweighs the federal government’s capabilities, but Dr. Frieden said he was optimistic. “We’re going to win that David and Goliath battle,” he told reporters.

Dr. Frieden said that the study results validated a large, national educational antismoking campaign. The CDC will continue to find ways to alert the public to the dangers of smoking, he said. The agency ran additional Tips From Former Smokers ads between March and June this year. That campaign included exhortations for smokers to talk to their physicians about quitting.

No inverse link found between H. pylori and gastroesophageal reflux disease

Helicobacter pylori was found to have a strong inverse link with Barrett’s esophagus, but not with symptoms of gastroesophageal reflux disease. Erosive esophagitis also was seen to trend toward an inverse association withH. pylori.

Previous reports have attributed a protective effect against gastroesophageal reflux disease (GERD), esophageal adenocarcinoma, and Barrett’s esophagus to H. pylori infection, particularly the cytotoxin-associated gene A (cagA+) strain. Having determined the studies associating H. pylori with GERD either yielded weak support for an inverse relationship, were prone to bias, or were otherwise flawed, a team lead by Dr. Joel Rubenstein of the Veterans Affairs Center for Clinical Management Research, Washington, and the University of Michigan Medical School in Ann Arbor analyzed the associations of the three disease outcomes occurring in the same populations with the bacterium.

They constructed a case-controlled study of men between the ages of 50 and 79 years (n = 533), who had colorectal cancer screening at one of two tertiary medical centers in Michigan between 2008 and 2011, and who were recruited to have upper endoscopy. The study served as a secondary analysis of the Newly Diagnosed Barrett’s Esophagus Study, and included three non–mutually exclusive case groups: Barrett’s esophagus, erosive esophagitis, and GERD symptoms. An additional group of men in the same age group (n = 80) found to have Barrett’s esophagus during clinically indicated upper endoscopy exams was also assessed.

Using logistic regression, the investigators estimated any associations between serum antibodies against H. pylori and cagA+ in the study group, and GERD symptoms, esophagitis, and Barrett’s esophagus. These results were compared with a control group of randomly selected men (n = 177) who did not have any of the three conditions and who were having colorectal screens.

Women were not studied, because of their typically low rates of Barrett’s esophagus. Also excluded were men with any history of upper endoscopy, Barrett’s esophagus, or esophagectomy; diagnostic indication for colonoscopy; irritable bowel disease; known ascites or esophageal varices; any cancers other than melanoma in the previous 5 years; or notable coagulopathy.

The study did include consecutive men between the ages of 50 and 79 years, newly diagnosed at either of the two study sites with Barrett’s esophagus by way of a clinically indicated upper endoscopy.

To determine the presence of GERD, the study group was given a survey that was not formally validated, about their use of proton pump inhibitors (PPI) and histamine₂ receptor agonists (HR₂A) in relation to the frequency they experienced heartburn and regurgitation. Patients who reported weekly heartburn and regurgitation while not using medication were considered to have GERD. A validated survey, the Mayo Clinic’s Gastroesophageal Reflux Questionnaire (GERQ), was applied during the last quarter of the study, although because the GERQ does not address the role of acid-reducing medications, the investigators wrote that there is the chance that patients with GERD managed by medication could have been misclassified by the questionnaire as non-GERD controls.

The study group also underwent colonoscopy, followed by upper endoscopy. If Barrett’s esophagus was suspected, biopsies were obtained. Using the Los Angeles Classification scheme, if class C or D esophagitis was found, patients repeated the endoscopy while taking a PPI before investigators determined if the patient had Barrett’s esophagus. Patients who were not taking any acid-reducing medications at the time of the endoscopy who reported at least weekly symptoms of GERD and had a normal endoscopy without erosive esophagitis or Barrett’s esophagus were considered to have nonerosive reflux symptoms. Patients with Barrett’s esophagus identified on a clinically indicated upper endoscopy were included with the same as those identified among the the people screened for colorectal cancer. Blood samples were drawn from all subjects and assayed for H. pylori.

The results were that 822 of the colorectal cancer patients had upper endoscopy; 328 were randomly selected for descriptive analysis of assays, 22.3% of which were found to have antibodies against H. pylori, with 1.8% equivocal for H. pylori on two assays. Of those positive for H. pylori, nearly half (49.3%) were found to have antibodies against cagA while none of those who were equivocal for H. pylori were found to have antibodies against cagA. Compared with study group members who were seropositive for H. pylori, those who were seronegative were less likely to be smokers and to have higher education and income.

Noting that classification errors for GERD might have biased the estimated associations with H. pylori toward the null, the investigators discovered that while there was a strong inverse connection between H. pylori, especially the cagA+ strain, and erosive esophagus (H. pylori adjusted odds ratio, 0.63; 95% confidence interval: 0.37-1.08 and cagA+ OR, 0.47; 95% CI: 0.21-1.03) and Barrett’s esophagus (OR, 0.53; 95% CI: 0.29 -0.97), especially the cagA+ strain (OR, 0.36; 95% CI: 0.14-0.90), they could not make a decisive link between GERD symptoms and H. pyloriinfection (OR, 0.948; 95% CI: 0.548-1.64 and cagA+ OR, 0.967; 95% CI: 0.461-2.03) (Clin. Gastroenterol. Hepatol. 2013 [doi: 10.1016/j.cgh.2013.08.029]).

Dr. Rubenstein and his colleagues theorized that since the GERD link was not found, the mechanism of H. pylori’s negative association with Barrett’s esophagus might be from the direct impact of the bacteria on the inflammatory or mucosal response; its indirect effects on the production of leptin or ghrelin; or a confounding effect created by genetic regulation of cytokines or prior alterations in the esophageal and gastric microbiota.

The study was underwritten by the National Institutes of Health and by a senior marketing grant from the American Society for Gastrointestinal Endoscopy. Dr. Rubenstein and his associates reported no relevant disclosures.

Abraxane approved for late-stage pancreatic cancer

September 10, 2013

ST LOUIS (MD Consult) - On September 6, 2013, the US Food and Drug Administration (FDA) approved Abraxane (paclitaxel protein-bound particles for injectable suspension, albumin-bound) for the treatment of patients with metastatic pancreatic cancer. The drug is intended for use with gemcitabine. Abraxane has been previously approved for the treatment of breast cancer and non-small cell lung cancer.

The safety and effectiveness of Abraxane for use in pancreatic cancer were established in a clinical trial with 861 participants who were randomly assigned to receive either Abraxane plus gemcitabine or gemcitabine alone. Participants treated with Abraxane plus gemcitabine survived, on average, 1.8 months longer than patients treated with gemcitabine alone. Additionally, participants who received Abraxane plus gemcitabine experienced progression-free survival that was, on average, 1.8 months later than the participants who only received gemcitabine.

Common adverse effects observed in Abraxane plus gemcitabine-treated participants included neutropenia, thrombocytopenia, fatigue, peripheral neuropathy, nausea, alopecia, peripheral edema, diarrhea, pyrexia, vomiting, rash, and dehydration. The most common serious adverse effects were pyrexia, dehydration, pneumonia, and vomiting. 

Hospital Clostridium difficile cases nearly doubled during 2000s

DENVER (IMNG) – The incidence of Clostridium difficile infections in United States hospitals nearly doubled between 2001 and 2010, with little evidence of recent decline. In addition, there does not appear to be a significant decline in mortality or hospital length of stay among patients with the infection, an analysis of national data showed.

“These data underscore the importance of directing resources to the prevention of [C. difficile infection], as well as developing public policy for reducing the incidence of these infections in U.S. hospitals,” Kelly R. Daniels, Pharm.D., said in an interview prior to the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the study was presented.

“Judicious use of antibiotics is essential to reducing these infections, as antibiotics are the main risk factor for the development of CDI,” she noted. “Compliance with other infection control measures, such as hand washing, is also key. Further research is needed to identify effective measures for preventing CDI and improving outcomes in patients with CDI.”

Dr. Daniels, a graduate student in the translational science PhD program at the University of Texas, Austin, and her associates retrospectively reviewed U.S. National Hospital Discharge Surveys from 2001 to 2010. They included patients aged 18 years and older who were discharged from the hospital with an ICD-9-CM diagnosis code for CDI (008.45) and used data weights to determine national estimates. They presented incidence rates as CDI cases per 1,000 hospitalizations, and they used multivariable logistic and linear regression models to compare mortality and hospital length of stay between primary and secondary CDI.

Over the 10-year study period, 2.2 million patients were discharged from the hospital with CDI. Their median age was 75 years, most (86%) were white, and more than half (59%) were female. One-third of cases (33%) were primary CDI, while the remainder were secondary CDI. The three most common concomitant infectious diagnoses were urinary tract infection (21%), pneumonia (14%), and sepsis/septicemia (12%).

Dr. Daniels reported that the incidence of CDI increased from 4.5 cases/1,000 hospitalizations in 2001 to 8.2 cases/1,000 hospitalizations in 2010. Similar trends were observed in patients with primary and secondary CDI.

The overall mortality rate was 7.1% for the study period and was significantly higher among patients with secondary CDI, compared with those who had primary CDI (8.8% vs. 3.3%, respectively; relative risk, 1.8). The median hospital length of stay was 8 days and was significantly higher among patients with secondary CDI, compared with those who had primary CDI (9 days vs. 5 days, respectively; RR, 13.3).

“We found that in-hospital mortality among patients with primary CDI is decreasing, while mortality among patients with secondary CDI is increasing,” Dr. Daniels said. “This trend is different from prior studies, which demonstrated increases in CDI-related mortality from the 1990s to the early 2000s.”

The decline in in-hospital mortality among patients with primary CDI might reflect improvements in care in recent years, she explained. In contrast, the increase in mortality among those with secondary CDI may be caused by changes in the frequency or severity of other comorbid illnesses. However, “this was not specifically examined as part of our study,” Dr. Daniels added.

She acknowledged certain limitations of the analysis, including the fact that it relied on administrative codes to identify cases of CDI. “Although CDI codes have high accuracy for identifying CDI, they cannot be considered equivalent to medical chart reviews,” Dr. Daniels explained. Also, “the use of administrative codes precludes our ability to confirm the CDI diagnosis using laboratory methods or to identify the causative strain of C. difficile.” In addition, the National Hospital Discharge Surveys don’t include federal hospitals and long-term care hospitals. “Therefore, our estimates may not be generalizable to those settings and may underestimate the true burden of CDI in the United States,” Dr. Daniels explained.

No outside funding was obtained for the conduct of this study. Dr. Daniels disclosed that she is supported by the National Institutes of Health National Center for Advancing Translational Sciences Loan Repayment Program.

Gastroenterologists generating less revenue for hospitals

Average annual hospital revenue generated by gastroenterologists dropped 4.5% from 2010 to 2013, according to a survey by physician job placement firm Merritt Hawkins.

Average revenue of $1.39 million was reported for gastroenterologists in 2013, down from $1.45 million in 2010.

The 4.5% drop for gastroenterologists is smaller, however, than the decreases reported for all specialists (–9.7%) and all physicians (–6.2%). Mean hospital revenue generated in 2013 for all specialists was $1.42 million, which is the lowest Merritt Hawkins has reported since it started the survey in 2002, the report noted.

The average net revenue generated for all physicians was $1.45 million, which is, again, the lowest average since 2002, Merritt Hawkins said in its analysis.

The survey was sent to more than 3,000 hospitals in January 2013 and was completed by 102 hospital chief financial officers.

Half of patients relapsed after infliximab cessation

December 8, 2011

BY DENISE NAPOLI Roughly half of Crohn’s disease patients who are in remission while being treated with infliximab will relapse after discontinuing this drug, reported Dr. Edouard Louis and colleagues reported online in the journal Gastroenterology.
However, following retreatment with infliximab, “almost all” patients were once again in remission 1 month later, “and none experienced a significant acute or delayed infusion reaction, despite a drug holiday longer than 6 months for half of them.”
Dr. Louis of the Centre Hospitalier Universitaire de Liège, Belgium, and his associates studied 115 adult patients with active luminal Crohn’s disease (CD) who had received at least 1 year of therapy with infliximab and an antimetabolite (azathioprine, 6-mercaptopurine, or methotrexate).
All patients had received at least two infliximab infusions during the 6 months prior to study inclusion, and patients’ concurrent antimetabolite doses had been stable for at least 3 months, with corticosteroid-free remission for the last 6 months before inclusion.
“Clinical response was defined by a decrease in the Crohns Disease Activity Index (CDAI) of at least 70 points, and 25% from CDAI at relapse,” whereas remission was defined as a CDAI below 150.
Overall, there were 62 reported relapses at the study centers. Five of these relapses were invalidated by the authors, and another five were not retreated with infliximab because of patient or physician decision, leaving 52 relapses which were retreated per study protocol (Gastroenterology 2011 [doi:10.1053/j.gastro.2011.09.034]).
Factors significantly associated with relapse included male gender, with a hazard ratio of 3.7 (95% confidence interval, 1.9-7.4; P less than .001) and baseline hemoglobin levels less than 145 g/L at study inclusion (such as infliximab cessation), with a hazard ratio of 6.0 (95% CI, 2.2-16.5; P less than .001).
A leukocyte count greater than 6 x 10⁹/L (hazard ratio, 2.4, 95% CI 1.2-4.7; P = .01) and a high sensitivity C-reactive protein level greater than or equal to 5 mg/L (HR, 3.2, 95% CI 1.6-6.4; P less than .001) were also associated with relapse, as were a lack of previous surgical resection and a fecal calprotectin level greater than or equal to 300 mcg/g.
By 30 days after restarting infliximab, 37 of the 40 patients with complete data available (93%) were in remission once again, and 39 of 40 (98%) had clinical response.
Of the remaining 12 patients, there was one consent withdrawal and 11 patients were assessed at alternate time points, with 9 found to be in remission and with clinical response, 1 with response only, and 1 patient not in remission or showing clinical response.
“No infusion reaction or significant delayed reaction was reported in the retreated patients up to third retreatment, despite a median drug holiday of 6.6 months,” wrote Dr. Louis, adding that no other serious adverse event was reported during the study.
“In clinical practice, stopping infliximab may still be considered for various reasons including cost, fear of long-term side effects, and concerns about pregnancy,” concluded the authors.
“However, simple parameters may be used to identify a subgroup of patients with a low risk of relapse and in whom infliximab withdrawal may be considered,” they wrote, pointing out that “when patients relapsed, retreatment with infliximab was effective and well tolerated in the vast majority.”
Dr. Louis reported receiving consultancy fees as well as research and educational grants from several pharmaceutical companies, as did several other authors. The research was sponsored by the Association François Aupetit and the Société Nationale Française de Gastroentérologie.

HCV infection may predict coronary artery disease

December 9, 2011

BY HEIDI SPLETE NATIONAL HARBOR, MD. (EGMN) – Coronary artery disease was significantly more prevalent in patients with hepatitis C virus infection, compared with control subjects, based on a retrospective review. The findings were presented at the annual meeting of the American College of Gastroenterology.
“An association of coronary artery disease [CAD] with hepatitis C has been suggested, but definitive data are still lacking,” said Dr. Sanjaya Satapathy, who conducted the study while at Long Island Jewish Medical Center in New Hyde Park, N.Y.
To estimate the prevalence of CAD in hepatitis C patients, Dr. Satapathy and his colleagues reviewed data from 934 individuals with hepatitis C infection who were seen at a single center between May 2002 and December 2008. Of these patients, 63 had undergone coronary angiography. The investigators compared their data with data from 63 matched controls without hepatitis C.
Overall severity of CAD according to the combined Reardon severity score was significantly greater in the hepatitis C virus (HCV) group than in the controls (6.3 vs. 2.6, respectively), suggesting that being HCV-positive increases the severity of, or risk for, CAD, Dr. Satapathy said.
The researchers defined CAD in two different ways for their analysis. CAD defined as stenosis greater than 50% was found in 44 of the HCV cases (70%) compared with 30 controls (48%). CAD defined as stenosis greater than 75% was found in 42 patients with hepatitis C (67%) compared with 29 controls (46%).
In addition, the prevalence of multivessel coronary artery disease was significantly higher in the HCV patients compared with the controls (57% vs. 16%, respectively). The prevalence of single-vessel involvement was greater in the control group.
“HCV seropositive status is a strong predictor for CAD,” Dr. Satapathy said. However, “HCV patients are more likely to remain undertreated with antiplatelet and lipid-lowering agents,” he noted.
The study was limited by the retrospective design and small sample size, said Dr. Satapathy. However, the findings suggest that CAD is significantly more common and severe in HCV-positive patients, and this should be considered by clinicians treating these patients, he said.
Dr. Satapathy said he had no financial conflicts to disclose.

Outcomes of transplant for acute liver failure improve steadily

December 12, 2011

BY SUSAN LONDON SAN FRANCISCO (EGMN) – Outcomes after liver transplantation for acute liver failure steadily improved during a recent period spanning about 2 decades, researchers reported at the annual meeting of the American Association for the Study of Liver Diseases.
An analysis of data from nearly 5,000 European patients found that rates of both graft survival and patient survival increased over time, even as the mean age of donors and recipients was rising.
However, rates of graft loss and death remained high during the first year after surgery, driven mainly by infection, rejection, and primary delayed function or nonfunction of the graft.
“A progressive and constant improvement in the survival rate after liver transplantation for acute liver failure has been achieved in the last 20 years despite an increase in donor and recipient age,” commented lead investigator Dr. Giacomo Germani. “High mortality and graft loss still persist, especially within the first year posttransplant.”
Importantly, deaths and graft losses due to social causes – mainly nonadherence to therapy and suicide – were much more common among patients who underwent transplantation because of paracetamol (known as acetaminophen in the United States) toxicity than among other patients. And more than half of these events occurred in the first year, suggesting that early psychiatric and related intervention for this group of recipients could be beneficial, according to Dr. Germani.
For the study, the investigators analyzed data from the European Liver Transplant Registry, which captures data on liver transplants done in 23 countries. The authors identified 4,903 patients older than 16 years who underwent isolated liver transplantation for fulminant or subfulminant acute liver failure between 1988 and 2009.
Temporal trends showed that the annual number of transplantations for acute liver failure increased until approximately 1994 and then remained essentially stable thereafter, reported Dr. Germani, who is a research fellow with the Royal Free Hospital and University College London, and a physician with the Padova (Italy) University Hospital.
On average, recipients were 39 years old and donors were 41 years old, but the age of both groups increased during the study period.
“The most important change [over time] was the increase in the donor age,” Dr. Germani maintained. For example, donors older than 60 years made up merely 2% of all donors in 1988-1993 but 21% in 2004-2009.
There was a shift in the etiology of the acute liver failure leading to transplantation during the study period that most likely reflected more effective diagnosis, he said. The proportion of cases recorded as having an unknown etiology fell from 60% in 1988-1993 to just 33% in 2004-2009. Meanwhile, there were increases in the proportions attributed to paracetamol toxicity, other drug toxicity, and other known causes (for example, traumatic or operative liver injury).
For the entire study period, the cumulative 10-year rates of graft and patient survival were 50% and 63%, respectively, “almost comparable with [those for] transplantation for other etiology,” Dr. Germani observed.
Both outcomes improved significantly during the study period. For example, the cumulative 5-year rate of graft survival improved steadily from about 50% in 1988-1993 to about 70% in 2004-2009 (P less than .001).
Social causes accounted for just 1% of all deaths and graft losses for the entire cohort. But they accounted for nearly 8% of those among patients who underwent transplantation because of paracetamol toxicity.
Temporal trends in the causes of death or graft loss showed increases in the proportions that were due to cardiovascular causes (likely related to increasing recipient age) and to primary delayed function or nonfunction of the graft (likely related to increasing use of livers from donors having less favorable characteristics), according to Dr. Germani.
After determining that mortality and graft loss were most common in the first year after transplantation and particularly in the first 3 months, the investigators identified independent risk factors for these outcomes and incorporated them into predictive models.
There was generally good correspondence between observed and model-predicted mortality and graft loss, according to Dr. Germani.
When applied to older adults, the models identified those at especially high risk for poor outcome. For example, among the cohort of patients older than 50 years of age, the risk of graft loss or death in the first year after transplantation was 44% to 61% if the patient was older than 60 years, was male, or had an incompatible ABO match with the donor, depending on the factor. With all three factors combined, the risk jumped to 80%.
“It is therefore important to reevaluate the selection of older patients with acute liver failure as potential recipients for liver transplantation in order to avoid futile transplants,” Dr. Germani recommended.

More Nonalcoholic Steatohepatitis Requiring Transplant

Neil Canavan

November 28, 2011 (San Francisco, California) — Nonalcoholic steatohepatitis (NASH) as an indication for liver transplantation rose 5-fold from 2002 to 2009. Although metabolic changes related to NASH risk have increased in the general population as a whole, the criteria for establishing risk for NASH-related liver failure remain unclear, according to data presented here at The Liver Meeting 2011: American Association for the Study of Liver Diseases 62nd Annual Meeting.
"NASH is increasingly an indication for liver transplant," said Danielle Brandman, MD, from the University of California at San Francisco. "Factors for this include the addition of NASH as a diagnosis in the UNOS [United Network for Organ Sharing] database, and increased awareness of NASH as a cause of end-stage liver disease." Up to half of all cases of cryptogenic cirrhosis are likely a result of unrecognized NASH, although Dr. Brandman noted that there are no uniform diagnostic criteria to define cryptogenic cirrhosis caused by NASH.
To identify the NASH-related risk factors driving this increase, the researchers conducted a comparison of pre- and post-MELD score measures.
The findings suggest that steep increases in the incidence of obesity and insulin resistance are the culprits, as opposed to the recorded rates of hypertension and dyslipidemia, which have remained essentially stable since 2002.
In addition to these changes occurring over time in the general population, "we must think about how patients with NASH undergoing liver transplant may be changing over time," said Dr. Brandman. This study is an investigation of changes in the characteristics of liver transplant recipients secondary to NASH over time, as well as patient survival after transplantation for NASH.
The data for this retrospective investigation were drawn from the UNOS database. The inclusion criteria included being 18 years or older and undergoing liver transplantation from 2002 to 2009. Exclusion criteria included retransplantation, HIV positivity, fulminant hepatic failure, and rare liver diseases.
Cases of NASH and "probably NASH" were combined for the analysis. NASH was determined using primary diagnostic code at liver transplantation, and probably NASH was defined as preliver transplant diabetes mellitus, preliver transplant hypertension, and/or a body mass index (BMI) of 40 kg/m² or higher.
After reviewing 30,182 charts, Dr. Brandman's team identified 1355 cases of NASH and 1537 cases of probably NASH. In the probably NASH group, 70% had diabetes, 32% were hypertensive, and 9% had a BMI of 40 kg/m² or higher. Many patients had more than 1 condition, and half of the remaining liver transplant recipients were positive for hepatitis C virus infection.
There were more females in the NASH/probably NASH group than in the no NASH group (43% vs 29%), more patients with a BMI of 40 kg/m² or higher (31.7% vs 27.5%), more white patients (31.7 vs 27.5), more preliver transplant diabetes (67% vs 19%), and more hypertension (43% vs 16%). Patients in the NASH/probably NASH group had a low prevalence of hepatocellular carcinoma but a high requirement for renal replacement therapy just before transplantation.
Five-year survival rates after liver transplantation in the 2 groups were the same (81.1%).
Matching temporal trends of these measures to risk and outcome has been problematic. "Since 2002, NASH is an increasing indication for liver transplant; it was responsible for just over 4% of transplants in 2002 and more than 12% in 2009," said Dr. Brandman. "At the same time, those identified as having NASH/probably NASH exhibited less preliver transplant diabetes and pretransplant hypertension over time, despite increases in these conditions in the general population."
Dr. Brandman surmises that the selection criteria for liver transplantation are likely being applied. "Additional studies are needed to determine what these criteria are, and which are the strongest predictors of outcome."
There's Something Happening Here
"NASH can definitely kill an individual," said Arun Sanyal, MD, chair of gastroenterology, hepatology, and nutrition at Virginia Commonwealth University in Richmond. Patients with NASH have a 15% to 20% risk of progressing to cirrhosis and end-stage liver disease, and there is increasing evidence that NASH may be connected to the development of hepatocellular carcinoma, even in the absence of cirrhosis. "That has huge public health implications because this cancer has one of the fastest rising incidences in the country."
Dr. Sanyal concurs with Dr. Brandman that the factors driving the increase in NASH are not clear.
"The increasing incidence of obesity and insulin resistance are 2 factors certainly." Other suggested contributors are the consumption of high-fructose corn syrup and environmental exposure to pollution. "There are studies that have linked exposure to various hydrocarbons to the development of fat in the liver — one of the defining characteristics of NASH."
Genetics also play a role. "We know that African Americans have a high incidence of hypertension and diabetes, but seem to be protected from fatty liver disease. In contrast, Hispanics have a high rate of metabolic syndrome and fatty liver disease," Dr. Sanyal said.
What is the clinician to do for the obese or hypertensive patient regarding NASH? "This is an emerging trend, so we're not quite there yet with a general clinical recommendation." There is no set diagnostic criteria for the disease, and other than lifestyle interventions, there is no approved treatment, although vitamin supplements can help. "We published a study last year showing that vitamin E at 800 units/day reverses NASH in roughly 40% of patients [N Engl J Med. 2010;362:1675-1685]," Dr. Sanyal noted.
Dr. Brandman and Dr. Sanyal have disclosed no relevant financial relationships.
The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting. Abstract 12. Presented November 8, 2011.

Hepatitis screening offered with routine colonoscopy accepted by 75%

November 23, 2011

BY HEIDI SPLETE NATIONAL HARBOR, MD. (EGMN) – A screening colonoscopy can provide a convenient opportunity to simultaneously test older adults for hepatitis, based on a study of 500 patients, 75% of whom agreed to blood tests for hepatitis A, B, and C.
Adults aged 50-65 years (the “baby boomers”) represent a high-risk population for hepatitis, and hepatitis C in particular, because of possible exposure to high-risk activities in their teens and twenties, said Dr. Dawn Sears of Scott & White Hospital in Temple, Tex. The findings were presented at the annual meeting of the American College of Gastroenterology.
Men make up 70% of chronic hepatitis cases, and they are less likely to see a doctor regularly than women, she noted. “Colorectal cancer screenings are often the only physician encounter for men aged 50 to 60 years,” she said.
To increase hepatitis screening in older adults, Dr. Sears and her colleagues tested whether combining hepatitis testing with routine colonoscopy appointments would be effective.
Patients were mailed information about hepatitis along with their instructions for colonoscopy preparation. On the day of their colonoscopies, patients met with a research nurse, signed a consent form, and completed a patient risk form. Blood was drawn for hepatitis screening when the IV was placed prior to the colonoscopy.
A total of 376 of 500 patients (75%) undergoing colonoscopies agreed to hepatitis testing. The study population was 42% male and 58% female. Risk factors in the patients’ histories included high-risk sexual activity, getting a tattoo prior to the year 2000, injecting or snorting drugs, having a blood transfusion before 1992, having a sexual partner with known hepatitis, being a health care worker who had been stuck with a needle, and spending at least 2 days in jail.
None of the patients had hepatitis B surface antigens, and 77% did not have antibodies against hepatitis A and B. Four patients had results suggesting previously undiagnosed hepatitis C, and all four complied with the recommended follow-up polymerase chain reaction (PCR) testing. One patient had a positive PCR follow-up, and that patient is beginning triple therapy, Dr. Sears said. All patients who were found to have hepatitis C antibodies had risk factors for hepatitis C infection, she noted.
“We should ask about risk factors and consider screening for hepatitis B and C," Dr. Sears said. “Gastroenterologists see most baby boomers at least once. We understand the [test] results, and this provides the highest quality, most efficient health care for our patients.”

Meta-analysis supports lower colorectal cancer risk with high fiber intake

November 26, 2011

ST LOUIS (MD Consult) - A high intake of dietary fiber—especially cereals and whole grains—is associated with a lower risk of colorectal cancer, according to a study published in the November 26, 2011, issue of the British Medical Journal.

A systematic review was performed to identify cohort and case-control studies of the relationship between fiber and whole-grain intake and the incidence of colorectal cancer. Data from 25 prospective studies were pooled for meta-analysis. The lead author was Dagfinn Aune of Imperial College London.

Based on data from 16 studies, the summed relative risk of colorectal cancer at a total daily fiber intake of 10 g was 0.90. There was no significant reduction in colorectal cancer risk at the same daily intake of fruit or vegetable fiber, based on 9 studies each; or legume fiber, based on 4 studies.

However, higher intake of cereal fiber was associated with a significant reduction in colorectal cancer: summary relative risk 0.90, based on 8 studies. For an increase of 3 servings per day of whole grain, the summary relative risk of colorectal cancer was 0.83, based on 6 studies.

It has been suggested that increased intake of dietary fiber may reduce the risk of colorectal cancer, although studies of this issue have reached conflicting results. With the addition of recent studies, the available evidence base is large enough to clarify this association, including the dose-response relationship.

The results show a significant reduction in colorectal cancer incidence for individuals with a high intake of dietary fiber. The protective effect appears particularly strong for intake of cereal fiber and whole grains. The investigators conclude, "Our results indicate a 10% reduction in risk of colorectal cancer for each 10 g/day intake of total dietary fibre and cereal fibre and about a 20% reduction for each three servings (90 g/day) of whole grain daily, and further reductions with higher intake."

Endoscopist training program boosts polyp detection rate

November 29, 2011

BY HEIDI SPLETE NATIONAL HARBOR, MD. (EGMN) – Polyp detection rates were significantly higher among endoscopists who completed a quality-improvement training program, compared with rates of those who did not in a randomized, controlled trial of 15 endoscopists and 2,400 procedures. The findings were presented at the annual meeting of the American College of Gastroenterology.
Adenoma detection rate is a key quality indicator for colonoscopy, and previous studies have shown associations between physicians’ behavior (such as looking behind folds, and the time spent inspecting the colon) and rates of adenoma detection, said Dr. Susan Coe of the Mayo Clinic in Jacksonville, Fla.
However, attempts at improving polyp detection rates, including discussions with low-performing physicians, required withdrawal times, and financial penalties, have proven unsuccessful, she said.
Dr. Coe and her colleagues, including senior investigator Dr. Michael B. Wallace, designed a prospective, randomized educational intervention to determine whether targeted endoscopist training would increase polyp detection rates.
“This is the first study to our knowledge to prospectively show that adenoma detection rate can be significantly improved through an intensive, structured endoscopist training program,” Dr. Coe said.
In the first phase of the study, the endoscopists performed 1,200 colonoscopies to determine their baseline detection rates. The average baseline rate was 36% among endoscopists randomized to both the training and non-training groups.
In the second phase of the study, the endoscopists performed another 1,200 colonoscopies after half of them had completed the training program. Among endoscopists in the training group, the average adenoma detection rate increased significantly to 47%, compared to 35% in the non-training group.
The Endoscopic Quality Improvement Program consisted of two 1-hour small group sessions. The first session included literature, photo, and video examples of polyps, explanations of techniques from high-detecting endoscopists, and information about subtle lesions such as flat and serrated polyps.
The second session consisted of a validated surface pattern recognition exercise. The participants in the training program received monthly feedback on their adenoma detection rates, withdrawal times, and group averages after completing the program.
The baseline characteristics of the endoscopists who underwent training and those who did not were similar overall. Median age in the trained and untrained groups was 45 years and 50 years, respectively.
Dr. Coe noted that the findings were limited by the small number of endoscopists and the single setting, but the study is ongoing to see whether the improvements associated with training persist. Larger studies are also planned, she said.

Excessive vitamin D intake may elevate AF risk

November 30, 2011

BY MITCHEL L. ZOLER ORLANDO (EGMN) – People with an excessive blood level of vitamin D from overdosing with supplements had a 2.5-fold increased incidence of atrial fibrillation, based on a study of 132,000 residents of Utah and southeastern Idaho.
The finding “suggests the need for caution with vitamin D supplementation and the need for careful assessment of serum levels if high doses [of vitamin D] are used,” Megan B. Smith said at the annual scientific sessions of the American Heart Association.
The finding also suggests that patients identified with new-onset atrial fibrillation should be evaluated for a possible extremely high vitamin D level, said Ms. Smith, although in the results she reported, the high blood level of vitamin D linked with a significantly elevated incidence of atrial fibrillation, greater than 100 ng/dL, was extremely unusual, occurring in just 291 of the 132,000 people (0.2%) included in the study.
Although the mechanism linking such an extremely elevated blood level of vitamin D to a markedly increased rate of new-onset atrial fibrillation remains unclear, a likely explanation is the hypercalcemia that vitamin D toxicity can cause. Hypercalcemia can, in turn, reduce cardiac conduction velocity and shorten cardiac refractory time, said Ms. Smith, a dietician at Utah State University in Logan.
“Utah [residents have] tremendous use of supplements. From what we’ve seen in the charts we have, excessive use of vitamin D supplements is the primary driver” of the high levels seen, said Dr. T. Jared Bunch, director of electrophysiology research at the Intermountain Medical Group in Murray, Utah, and lead investigator for the study. “The few patients [with very high vitamin D levels] who I have seen got vitamin D in their milk, from a multivitamin, and from vitamin D pills. They get it from multiple sources,” but added that the low prevalence of levels above 100 ng/dL also showed that it is a difficult level for a person to reach.
“Utah has an enormous problem with vitamin D deficiency, so we had this large group of people” who were members of Intermountain Healthcare, and had their vitamin D level measured once as part of their routine care. A survey by Dr. Bunch and his associates showed that unless asked, people don’t usually tell their physician that they take a vitamin D supplement, and that physicians at Intermountain Health do not usually ask patients about their vitamin D intake.
The measurement numbers documented the extent of the vitamin D deficiency problem, with 38,000 of the 132,000 people measured (29%) having a blood level below 20 ng/dL. This group with vitamin D deficiency showed significantly elevated prevalence rates of diabetes, hypertension, coronary artery disease, heart failure, and depression, compared with people in the designated “normal” vitamin D range of 41-60 ng/dL. But notably the incidence of atrial fibrillation in the deficiency group was not significantly different than the rate in the reference group with a normal vitamin D level at baseline.
“There is something unique” about the excess, toxic level, for atrial fibrillation incidence, Dr. Bunch said in an interview.
To better examine the potential role of vitamin D in elevating atrial fibrillation risk, Dr. Bunch and his associates are now regularly measuring blood vitamin D levels in Intermountain Healthcare members and prospectively tracking their atrial fibrillation incidence.
The results reported by Ms. Smith came from a retrospective analysis of the one-time vitamin D measurement by an immunoassay, and atrial fibrillation incidence tallied over an average 584 days of follow-up based on ECG testing and ICD-9 codes in each person’s medical record. The most common vitamin D level measured was 21-40 ng/dL, in 73,547 people (56%). Another 17,234 people (13%) had a level of 41-60 ng/dL, which the researchers considered normal and which they used as the reference group.
During follow-up, the incidence of new-onset atrial fibrillation was about 1.5% in all subgroups based on their baseline vitamin D level, except for those with a level above 100 ng/dL, who had an incidence of about 4%. A multivariate analysis that controlled for baseline differences in demographics identified a significantly elevated atrial fibrillation rate only in people with a baseline vitamin D level greater than 100 ng/dL.
Ms. Smith and Dr. Bunch said that they had no disclosures.

No increase in cardiovascular risks for obese kids who become normal-weight adults

November 17, 2011

ST LOUIS (MD Consult) - Among children who are overweight or obese, cardiovascular risk factors are not increased for those are nonobese in adulthood, according to a study in the November 17, 2011, issue of The New England Journal of Medicine.

The researchers analyzed data from 4 prospective studies of cardiovascular risk factors involving children with follow-up into adulthood. The analysis included a total of 6,328 participants, with a mean follow-up of 23 years. All underwent assessment of body mass index (BMI) in childhood and adulthood.

Cardiovascular risk factors at follow-up were compared for participants who were normal-weight in both childhood and adulthood (4,742 participants), overweight or obese in childhood but nonobese in adulthood (274 participants), overweight or obese in childhood and obese in adulthood (500 participants), and normal-weight in childhood but obese in adulthood (812 participants). The lead author was Dr Markus Juonala of University of Turku and Turku University Hospital, Finland.

Cardiovascular risk factors were significantly increased for participants who had high adiposity in both childhood and adulthood, compared to those who had normal BMI in childhood and were nonobese in adulthood. Relative risks were 5.4 for type 2 diabetes, 2.7 for hypertension. 1.8 for elevated low-density lipoprotein cholesterol, 2.1 for reduced high-density lipoprotein cholesterol, 3.0 for elevated triglycerides, and 1.7 for increased carotid artery intima-media thickness.

In contrast, none of these risks was increased for participants who had high BMI in childhood but were nonobese in adulthood. For obese adults who had been normal-weight in childhood, risks were similar to those who had been overweight or obese in childhood.

Childhood obesity has been linked to an increased risk of cardiovascular disease and death. It is unclear whether childhood obesity increases risks independently of the effects of obesity in adulthood.

The new study confirms the increased rates of cardiovascular risk factors among overweight or obese children who become obese adults. However, for children who have high BMI but are not obese as adults, risks are similar to those with normal BMI at both times. Although no clinical recommendations can be made from the observational study, the researchers write, "[W]e hypothesize that reducing BMI in children and adolescents who are overweight or obese could reduce their cardiovascular risk."

NSAIDs Can Raise Risk for Crohn's Disease

November 2, 2011 (National Harbor, Maryland/Washington, DC) — High doses of nonsteroidal anti-inflammatory drugs (NSAIDs), longer duration of use, or greater frequency of use are all associated with an increased risk for Crohn's disease and ulcerative colitis, according to findings of a study presented here at the American College of Gastroenterology (ACG) 2011 Annual Scientific Meeting.

In contrast, although both aspirin and NSAIDs are associated with ulcerations in the gastrointestinal tract, dose, duration, and frequency of aspirin use were not associated with risk for Crohn's disease or ulcerative colitis. The authors distinguished between aspirin and other NSAIDs in their study.

"So this suggests that there may be pathways uniquely affected by NSAIDs and not by aspirin," Ashwin Ananthakrishnan, MD, MPH, a gastroenterologist on staff at Massachusetts General Hospital, Boston, and an instructor at Harvard Medical School, told Medscape Medical News. "Such pathways could potentially be important in explaining why some people get Crohn's and ulcerative colitis."

Compared with nonusers, women who used NSAIDs for more than 15 days a month faced a greater risk for Crohn's disease and ulcerative colitis. Women who used more than 5 tablets of NSAIDs per week also saw an elevated risk for Crohn's disease compared with women with more than 6 years of NSAID use.

Although significant advances have been made in understanding the genetics of Crohn's disease and ulcerative colitis, with up to 99 genetic variations associated with the 2 conditions, genetic changes explain only about one third of the risk for the diseases, suggesting that environment has a big influence on why someone gets either Crohn's disease or ulcerative colitis, said Dr. Ananthakrishnan, who was lead author on the study.

The researchers conducted a prospective cohort study of 76,814 women enrolled in the Nurses' Health Study (NHS). Since 1990, the NHS has captured data on aspirin and NSAID use. Gastroenterologists subsequently confirmed diagnoses of Crohn's disease or ulcerative colitis.

The data drew upon more than 18 years of data, including 123 confirmed incident cases of Crohn's disease and 117 cases of ulcerative colitis. The mean age of the cohort in 1990 was 57 years. The researchers used Cox proportional hazards models to examine the relative risks for Crohn's disease and ulcerative colitis after adjusting for possible confounders, including smoking, menopausal status, and hormone use. In all, 44% of women reported regular use of aspirin and 37% said they regularly used NSAIDs at baseline.

Dr. Ananthakrishnan cautioned against overinterpreting the results of the study. "It's very important to recognize you have to weigh the risks and benefits," he said. For someone who doesn't have Crohn's or ulcerative colitis, the absolute risk is fairly small. Perhaps 15 in 100,000 people risk getting the conditions.

More studies are needed to compare the safety of these agents, he said, noting that people are more likely to take high-dose NSAIDs and take NSAIDs more frequently for pain relief. Those who take aspirin for cardiac protection tend to take low doses. "We don't know if you take the same dose of NSAIDs or aspirin, if they are equally safe or equally dangerous," he said.

Bruce Sands, MD, MS, chief of the Division of Gastroenterology and Burrill B. Crohn professor of medicine at Mount Sinai Hospital in New York, New York, said he found the study "a very provocative, interesting, and well-done work."

"The risk of NSAIDS for IBD [inflammatory bowel disease] has long been speculated due to their effects in decreasing barrier function of the gut epithelium. This is the first study to prospectively assess that risk in advance of onset of disease to my knowledge," he told Medscape Medical News.

Dr. Ananthakrishnan has disclosed no relevant financial relationships. Dr. Sands has financial relationships with Abbott Immunology, Avaxia Biologics, Bristol-Myers Squibb, Elan Pharmaceuticals, Emmi Solutions, GlaxoSmithKline, Novartis Pharmaceuticals, Pfizer, and Prometheus Laboratories.

American College of Gastroenterology (ACG) 2011 Annual Scientific Meeting and Postgraduate Course. Abstract #6. Presented October 31, 2011.