Misdiagnosis, noncompliance often culprits in refractory celiac disease

Refractory celiac disease is often the result of patients having either received an incorrect diagnosis, or their noncompliance, according to Dr. Joseph Murray of the Mayo Clinic in Rochester, Minn. “When faced with such a patient, it’s important to reconfirm the original diagnosis,” said Dr. Murray, who made his remarks during a clinical track presentation at a conference on inflammatory bowel. In cases in which the diagnosis can be confirmed and the patient is compliant, discovering if there are other conditions, and whether to intervene and how, are the important next steps, according to Dr. Murray. When patients present with symptoms of nonresponsive celiac disease, besides taking the patient’s history, which should include whether the patient has any first-degree family members with “true” celiac disease, not just family members who have chosen to stop eating gluten, “I will always ask for the original biopsies,” said Dr. Murray. In addition, original serology tests, if they were done, can confirm whether there are celiac-specific antibodies. “Gliadin antibodies are not celiac specific,” said Dr. Murray. “You can get gliadin antibodies in virtually every other disorder that affects the intestines, so they are pretty much worthless.” Better specificity comes from tissue transglutaminase or endomysial antibodies, he said at the meeting diseases sponsored by the Crohn’s & Colitis Foundation of America. Human leukocyte antigen genotyping, and whether the patient had a clinically obvious response to a gluten-free diet also will help the clinician puzzle out if the original diagnosis was correct, according to Dr. Murray. Worth noting is whether the patient has dermatitis herpetiformis, “That’s pathognomonic for celiac disease,” said Dr. Murray. For example, in the case of a 90-year-old woman whose biopsy 10 years before had been interpreted as presumptive celiac disease and who had had an initial response to a gluten-free diet, had symptoms that persisted for a decade because she’d contracted tropical sprue from annual visits to Indonesia that were not noted in her original patient history. Treated properly, her symptoms abated entirely, according to Dr. Murray. “She wasn’t exactly happy about her 10 years of living gluten free,” he said. Dangers of noncompliance As for patients who claim to follow a gluten-free diet, “That’s not true most of the time,” said Dr. Murray. “A positive serology test in a patient who’s been following a gluten-free diet for a year or more means they’re not just getting a little gluten. They’re getting a lot of gluten.” It can either be advertent or inadvertently, he said. However, serology is insensitive for lower levels of gluten contamination, but a gram of gluten, roughly one-half a slice of bread per day, can be detected, according to Dr. Murray. If noncompliance is the reason for the refractory condition, patients are at greater risk for increased mortality, osteoporosis, lymphomas, and other cancers, and psychological effects such as depression. “Eliminating the gluten may take time. Often we have to use behavioral counselors to help,” said Dr. Murray. Also key is to stay in touch with the patient. “Follow-up in patients with celiac disease is abysmal,” Dr. Murray said, “It’s almost like once the disease is diagnosed, it’s forgotten about medically.” “The complicating thing about celiac disease can be that autoimmune disorders and like disorders hang out together,” said Dr. Murray. “Complications of celiac disease also can occur in multiples.” Bacterial overgrowth, microscopic colitis, lymphoma, and systemic sclerosis associated–dysmotility are all concurrent conditions Dr. Murray reported seeing in his own practice when treating refractory celiac disease. Because lactose intolerance is also common in celiac disease, Dr. Murray said he will often advises patients to avoid dairy for a year, and then gradually add that back into the diet with good results. “Often, that will work, so I don’t even test for lactose intolerance initially,” he said. Despite all the possible etiologies for nonresponsive celiac disease, gluten exposure was found in more than a third of cases, while “true refractory celiac disease really makes up only about 10% or 11% of these nonresponsive patients,” said Dr. Murray, referring to a study on the topic (Clin. Gastroenterol. Hepatol. 2007;5:445-50). Patients with celiac disease also can have multifocal strictures in the proximal duodenum that reach the jejunum, “but rarely affect the ileum,” according to Dr. Murray. Possible lymphomas “The first thing that I think about when I see a really sick patient previously diagnosed with celiac disease several years before is, ‘Does the patient have lymphoma?’” said Dr. Murray. Ulcerative jejunoileitis typically indicates that lymphoma is imminent, although shallower ulcers are often linked to the use of NSAIDs, he said. Giant cavitating lymphadenopathy, while rare, is also a consideration, according to Dr. Murray. “A premalignant type of disorder, sometimes will respond to immunosuppressives, but often can presage the development of lymphoma,” he said. True refractory celiac disease involves symptomatic malabsorption, severe enteropathy, and a primary or secondary nonresponse to a gluten-free diet. “By definition, there should be no lymphoma,” said Dr. Murray. Refractory celiac disease is either characterized as type 1, which has a normal T-cell population and responds well to immunosuppression, or as type 2 with clonal T cells. Dr. Murray said he often uses topical budesonide to treat type 1 patients, with good results, since there is about a 90% recovery rate in this patient population. Type 2 is the most pernicious, with nearly half of patients dying within 5 years of diagnosis, either from malignant or infectious complications, according to Dr. Murray. “Type 2 refractory disease is not a trivial disease,” he said. Although most adults with celiac disease don’t heal, many are asymptomatic; however, this does not mean a patient’s risk of mortality from the disease has improved. Patients are also at greater risk for malignant complications. (Am. J. Gastroenterol. 2010;105:1412-20 [doi:10.1038/ajg.2010.10]). “We really don’t know what we should do about those asymptomatic patients,” said Dr. Murray. He noted that, “Failure to heal is not entirely benign, but it’s not refractory celiac disease,” said Dr. Murray.

Thrombosis precautions in IBD not met in two-thirds of high-risk cases

HOLLYWOOD, FLA. (FRONTLINE MEDICAL NEWS) – The relative risk of thromboembolic events is greater in inpatient inflammatory bowel disease patients than in the general population, but prophylactic treatment is still not standard, according to a speaker at a conference on inflammatory bowel diseases. “It’s a relatively rare problem, only about 1 to 1.5 percent,” said Dr. Athos Bousvaros, of Boston Children’s Hospital. “So, why worry about it so much? Because it really is a major source of morbidity in the IBD population. It usually happens in the sick patients, the ones at risk for strokes; and it usually happens at the worst time, when you’re thinking about colectomy.” However, Dr. Bousvaros said only about a third of IBD patients at risk for a thromboembolic event are given prophylactic treatment in the inpatient setting, especially in severe colitis, and it is generally recommended. Although pharmacologic prophylaxis is included in the American College of Gastroenterology guidelines, Dr. Bousvaros cited a recent study that found only 35% of gastroenterologists in the United States actually do so (J. Clin. Gastroenterol. 2013;47:e1-e6). “In the inpatient setting, especially in severe colitis, [prophylaxis] is generally recommended,” Dr. Bousvaros said. “It is included in the AGA [American Gastroenterological Association] physician performance measure set.” In the outpatient setting, data do not support it, he said. Relative risk high While the absolute risk is low, the relative risk of a venous thromboembolic event is six times greater in IBD, particularly in patients aged 20 years or less, said Dr. Bousvaros, citing a cohort study that used Danish administrative data (Gut 2011;60:937-43). “It’s mainly patients with flares, and mainly those with colitis, either Crohn’s or severe ulcerative colitis,” Dr. Bousvaros said. In a prospective study of about 2,800 IBD patients (mean age, 42 years) recruited over 2.5 years, matched with non-IBD controls, and followed for several years, about 4% developed de novo venous thromboembolism (Gastroenterol. 2010;139:779-787.e1). Dr. Bousvaros emphasized that IBD was an independent risk factor for VTE recurrence in the study. “They were typically treated with long-standing prophylaxis. And if any anticoagulation was involved, the risk of recurrence was high,” he said at the meeting, which was sponsored by the Crohn’s & Colitis Foundation of America. High-risk criteria Overall, the relative risk for VTE was found by a just-published meta-analysis of more than 200,000 IBD patients to be 2.4 for deep vein thrombosis, 2.5 for pulmonary embolism, 1.3 for ischemic heart disease, and 3.4 for mesenteric ischemia (J. Crohns Colitis 2013 Oct 29 [doi: 10.1016/j.crohns.2013.09.021]). Dr. Bousvaros said the investigators did not find an increased risk for arterial thromboembolic events in IBD, but that VTEs “were highly significant in this population.” Patients with IBD should be considered high risk for VTE if they are being treated in hospital for severe colitis and have a personal or family history of thrombosis, have known thrombophilia, have been taking oral contraceptives, have a history of smoking, are obese, or have had a PICC line. “Any of those makes you a particularly high-risk patient,” Dr. Bousvaros said.

Bariatric surgery benefits in type 2 diabetes linked to disease duration

MELBOURNE (FRONTLINE MEDICAL NEWS) – The benefits of bariatric surgery in people with type 2 diabetes are significantly reduced with longer disease duration at the time of surgery and with time since surgery, a long-running, prospective, controlled study has found. The Swedish Obese Subjects study showed that 72% of surgery patients achieved remission at 2 years after treatment, compared with 16% of control patients. Furthermore, 15 years after surgery, 31% of the surgery patients remained in remission, compared to 7% of control patients, according to data presented at the International Diabetes Federation world congress. When stratified by disease duration at baseline, newly diagnosed patients maintained significantly higher remission rates at 2, 10 and 15 years’ follow-up (roughly 94%, 60%, and 47%, respectively) than did those who had had diabetes for more than 3 years at baseline (about 39%, 12%, and 9%). These data came from the SOS (Swedish Obese Subjects) study, a nonrandomized, prospective, observational study involving 2,010 obese subjects who underwent bariatric surgery in 1987-2001, when they were 37-60 years old. A total of 68% of the bariatric surgery recipients had vertical band gastroplasty, 19% underwent gastric banding, and 13% had a Roux en-Y gastric bypass. They were extensively matched by 18 variables to 2,037 obese controls. The SOS study is being conducted at 25 surgical departments and 480 primary care clinics across Sweden. Follow-up is ongoing. There were 343 individuals with type 2 diabetes in the surgical group and 260 in the control group, enabling a secondary analysis of the impact of bariatric surgery in type 2 diabetes. Presenter Markku Peltonen said that although bariatric surgery achieves impressive results in the short-term, there is considerable relapse in the longer term. “It’s typical of bariatric surgery that you achieve the greatest weight loss initially, after 2 years, then there is a slow regain again and this was observed in this study,” said Dr. Peltonen, director of the department of chronic disease prevention at the National Institute for Health and Welfare, Helsinki. “Even in the long term, they are doing much better than the controls who were treated with traditional weight management means,” he said in an interview. This also extended to the microvascular and macrovascular complications of diabetes, with the study showing a significant 47% lower incidence of complications in the surgery group, compared with the control group. However, these benefits were also attenuated by disease duration. Patients who had had diabetes for more than 3 years and were treated with surgery showed no significant differences in diabetes complication rates, compared with the patients given medical care only. Dr. Peltonen said he was surprised by the degree of impact that disease duration had on the outcomes of surgery. “Somehow the expectation would be that we would see an effect even in those people with long diabetes duration, because they have a serious, advanced disease but it looks like, based on our results, that maybe it’s so that the disease has advanced for so long that bariatric surgery cannot reverse that development.” Session chair John Dixon said the SOS study represented the pinnacle of long-term data for bariatric surgery, and offered impressive insights. “The fact that 31% of these patients are still in remission from diabetes some 15 years down the track is extraordinary, because we know the deterioration of beta cells is significant and this group has held it off for a long time,” said Dr. Dixon, head of clinical obesity research at the Baker IDI Heart and Diabetes Institute in Melbourne. Dr. Dixon said the finding that patients treated early fared better and had a reduction in long-term complications was also a very important clinical finding, suggesting that bariatric surgery should be considered earlier in obese patients not getting good control with conventional therapy. SOS was supported by the Swedish Research Council, the Swedish Foundation for Strategic Research, and the Swedish government. Some study investigators authors had received paid lectureships, held stock in, or were on the advisory boards for pharmaceutical companies.

DOs and DON’Ts in Managing GERD ( GastroEsophageal Reflux Disease ) :

DO eat a healthy diet, rich in fruits, vegetables, and low-fat dairy products. Lower your intake of saturated and total fats. DO raise the head of your bed 6 to 8 inches with wooden blocks. DO maintain a healthy body weight. DO take medicines recommended by your doctor. DON’T eat refl ux-inducing foods, such as citrus fruits and juices, coffee, peppermint, chocolate, and spicy foods. DON’T eat large meals. DON’T eat meals late in the day. DON’T lie down just after eating. DON’T wear tight-fi tting clothing. DON’T smoke or use tobacco products.

Restrictions on use of diabetes drug rosiglitazone lifted after FDA re-examines cardiovascular risk data

ST LOUIS - On November 25, 2013, the US Food and Drug Administration (FDA) issued a safety alert stating that it is requiring the removal of certain restrictions on prescribing and use of Avandia (rosiglitazone), a drug used in the treatment of diabetes. This new label information concerns cardiovascular risk. The FDA is also requiring the same modifications be made to the labels for any other drugs that contain rosiglitazone. The decision to remove the previous prescribing and dispensing restrictions for rosiglitazone-containing medicines was made on the basis of results from the FDA's review of data of a large, long-term clinical trial. Moreover, the decision to change the restrictions was supported by a comprehensive, outside, expert re-evaluation of the data conducted by the Duke Clinical Research Institute. In 2010, in response to data from a meta-analysis of placebo-controlled randomized trials that suggested an elevated risk of cardiovascular events in association with rosiglitazone use, the FDA announced it would restrict the drug to use in patients with type 2 diabetes who could not manage their disease with other medications. The FDA also required GlaxoSmithKline, the manufacturer of Avandia, to convene an independent group of scientists to readjudicate key aspects of the trial known as Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD). This trial evaluated the cardiovascular safety of Avandia compared with standard diabetes drugs. The original evaluation of data from RECORD suggested an increase in myocardial infarctions (MIs) and decreases in the rates of death and stroke in patients treated with rosiglitazone. These results were not statistically significant. During the course of the FDA's original 2010 review of the RECORD trial, important questions had arisen about potential bias in the identification of cardiovascular events. The readjudicated results could not dismiss an increased risk of MI with rosiglitazone versus placebo, because the trial did not use a placebo. However, the readjudicated results did assess rosiglitazone versus the standard-of-care diabetes drugs metformin and sulfonylurea and confirmed the original RECORD finding that did not show an increased risk of MI associated with the use of rosiglitazone. In the trial, patients treated with rosiglitazone experienced fewer deaths from a cardiovascular cause, from a stroke, and from an MI; fewer nonfatal strokes; and fewer deaths from any cause compared with patients treated with metformin and sulfonylurea. Patients treated with metformin and sulfonylurea experienced fewer nonfatal MIs compared with patients treated with rosiglitazone. However, none of these results were statistically significant. On the basis of the results from the readjudicated RECORD trial, the FDA is requiring modifications to the rosiglitazone Risk Evaluation and Mitigation Strategy (REMS) program to remove the requirements for restricted distribution. After the changes to the REMS are finalized, health care professionals, pharmacists, and patients will no longer be required to enroll in the rosiglitazone REMS program to prescribe, dispense, or receive rosiglitazone medicines. Patients will also be able to receive rosiglitazone through regular retail pharmacies and mail order pharmacies.

FDA warns of risk of myocardial infarction and death with use of certain cardiac stress test drugs

On November 20, 2013, the US Food and Drug Administration (FDA) issued a warning concerning the rare risk of myocardial infarction (MI) and death with use of the cardiac nuclear stress test agents Lexiscan (regadenoson) and Adenoscan (adenosine). The FDA has approved changes to the drug labels to reflect these serious events and has updated its recommendations for use of these agents. The FDA has reviewed the FDA Adverse Event Reporting System (FAERS) database and the medical literature for cases of MI and death from all causes associated with the use of Lexiscan and Adenoscan. Information about Lexiscan included that dating from June 24, 2008, to April 10, 2013, and for Adenoscan, from May 18, 1995, to April 10, 2013. The beginning dates correlated with the start of marketing for each drug. The FAERS database contained 26 MI cases and 29 cases of death occurring after Lexiscan administration, and 6 cases of MI and 27 cases of death after Adenoscan administration. Reports did not always specify when deaths or MIs occurred. When reported, these adverse events tended to occur within 6 hours after Lexican or Adenoscan administration. A few deaths occurred when Lexiscan or Adenoscan was administered with exercise stress testing, which is not an FDA approved use of the drugs. With Lexiscan, the most common adverse events associated with death were cardiac arrest, MI, loss of consciousness, respiratory arrest, electrocardiography ST-segment depression, pulmonary edema, and ventricular fibrillation. With Adenoscan, the most common adverse events associated with death were cardiorespiratory arrest, dyspnea, cardiac arrest, respiratory arrest, and ventricular tachycardia. A review of the medical literature also identified 2 case reports of MI associated with Lexiscan use. However, published studies from the medical literature have not documented an increased incidence of cardiovascular adverse events with Lexiscan compared with Adenoscan. Lexiscan and Adenoscan are FDA approved for use during cardiac nuclear stress tests in patients who cannot exercise adequately. Both products help identify coronary artery disease by dilating these arteries and increasing blood flow to help identify obstructions. Lexiscan and Adenoscan cause blood to flow preferentially to the healthier, unblocked, or unobstructed arteries, which can reduce blood flow in obstructed arteries. In some cases, this reduced blood flow can lead to an MI, which can be fatal. The use of both drugs should be avoided in patients with signs or symptoms of unstable angina or cardiovascular instability because these patients may be at greater risk for serious cardiovascular adverse reactions. Cardiac resuscitation equipment and trained staff should be readily available before administering Lexiscan or Adenoscan.

High schoolers smoking more cigars, pipes, e-cigarettes

BY RICHARD FRANKI Overall use of tobacco among high school students decreased from 2011 to 2012, but cigar and pipe smoking went up, as did the use of some nonconventional products, the Centers for Disease Control and Prevention reported. In 2012, 23.3% of high school students surveyed reported current tobacco use, compared with 24.3% in 2011. Use of cigars, driven largely by a significant increase among non-Hispanic black students, went from 11.6% in 2011 to 12.6% in 2012, and pipe use rose from 4.0% to 4.5%, according to data from the National Youth Tobacco Survey. “Youths are known to have higher rates of cigar use than adults, which might be related to the lower price of some cigars (e.g., cigarillos and ‘little cigars’) relative to cigarettes, or the marketing of flavored cigars that might appeal to youths,” the report said (MMWR 2013;62;893-7). Significant increases in use were seen for electronic cigarettes (1.5% in 2011 to 2.8% in 2012) and hookahs (4.1% to 5.4%), but the use of other nonconventional products such as bidis (small brown cigarettes wrapped in a leaf), kreteks (clove cigarettes), and snus declined, the CDC noted.

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.