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.