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.

Combination Therapy Gives Patients With IBD Another Option

November 4, 2011 (National Harbor/Washington, DC) — Combination therapy with allopurinol and low-dose thiopurines is an effective and well-tolerated treatment for inflammatory bowel disease (IBD), according to a study presented here at the American College of Gastroenterology 2011 Annual Scientific Meeting and Postgraduate Course.

This combination therapy gives another treatment option for patients with IBD who fail conventional thiopurine therapy, lead author Frank Hoentjen, MD, PhD, told Medscape Medical News. He is assistant professor of medicine at Raboud University Medical Center in Nijmegen, the Netherlands.

The researchers wanted to see whether they could lower the discontinuation rate for thiopurine by optimizing therapy before increasing the dosage.

"In patients with a skewed thiopurine metabolism who have either adverse reactions or an inability to achieve remission, allopurinol plus low-dose thiopurines should be considered before escalating maintenance therapy," Dr. Hoentjen said.

The "long-term effectiveness and tolerability of allopurinol and thiopurine combination therapy in inflammatory bowel disease patients" confirm previous small studies, which have shown the benefit of combination therapy, he said. The cohort size and follow-up time in this study were double those of the largest previous study.

Physicians have puzzled over the problems associated with thiopurines for a few decades, but only in the past 10 years have they learned that levels of metabolites correlate with efficacy and adverse effects, Dr. Hoentjen explained. Some of the adverse reactions that have caused patients to discontinue thiopurine therapy are nausea, vomiting, headaches, muscle aches, leucopenia, transaminitis, and pancreatitis.

The study looked at 85 patients with an average follow-up time of 20.4 months. Most of the patients were diagnosed with Crohn's disease or ulcerative colitis. Patients started combination therapy because of previous thiopurine refractoriness (54%), an inability to achieve or maintain remission despite optimized thiopurine therapy, hepatotoxicity (47%), nonhepatic adverse reactions (8%), or for other reasons (5%).

Participants were adults with IBD from 2 tertiary referral IBD centers who failed monotherapy with thiopurines; they were subsequently treated with allopurinol plus low-dose thiopurine. Therapeutic effectiveness was assessed by calculating the cumulative number of patients still using combination therapy at 6, 12, 24, and 60 months and who were still in clinical remission, based on Physician's Global Assessment and on laboratory, radiologic, and/or endoscopic findings.

The percentage of patients still using combination therapy at 6, 12, 24, and 60 months was 88%, 84%, 76%, and 73%, respectively.

The genetic background in this subgroup of patients might be an area for future research, Dr. Hoentjen said. If researchers can genetically identify patients who will develop a skewed thiopurine metabolism (and possibly the consequences, like hepatotoxicity or lack of clinical remission), they will be able to start combination therapy without trying monotherapy with thiopurines first, he said. Although physicians already use thiopurine methyltransferase genotyping in clinical practice, it is not 100% predictive.

James Lewis, MD, MSCE, chair elect of the National Scientific Advisory Committee of the Crohn's and Colitis Foundation of America, told Medscape Medical News that he finds the study "very interesting."

Although thiopurines are commonly used to treat IBD, data on the use of allopurinol to modify thiopurine metabolism toward the production of 6-thioguanine nucleotides are limited, and long-term data on the combination are even harder to come by. "These data suggest that in selected patients who preferentially metabolize mercaptopurine to 6-methylmercaptopurine, this may be an effective long-term strategy," he said.

Dr. Lewis, who is also associate professor of medicine and epidemiology at the University of Pennsylvania in Philadelphia, offered up some warnings. Patients and physicians who consider using this combination need to be aware of the risks for bone marrow suppression and perhaps liver injury, he cautioned. Leukopenia occurred in 13% of these patients. We know that it is challenging to closely monitor patients treated with azathioprine or 6-mercaptopurine for bone marrow suppression, he said. "This combination raises the stakes even higher, and an optimal monitoring frequency has not been established."

Dr. Hoentjen has disclosed no relevant financial relationships. Dr. Lewis reports providing consulting/research support services to Roche, Amgen, Centocor, Dark Canyon Laboratories, Millennium Pharmaceuticals, Pfizer, Shire, Takeda, and United Biosource Corporation.

American College of Gastroenterology (ACG) 2011 Annual Scientific Meeting and Postgraduate Course. Abstract 27. Presented November 1, 2011.

Turmeric Enema May Equal Vancomycin for C. Difficile Colitis

NEW YORK (Reuters Health) Nov 03 - Turmeric enemas may be as tolerable and effective as vancomycin enemas for treating Clostridium difficile colitis, a small new study suggests.

Turmeric, a plant belonging to the ginger family, produces a bright yellow spice that has been used for thousands of years in food and as medicine. Curcumin is its major component.

Turmeric is known to have antioxidant, anti-inflammatory and anti-microbial properties, and it also slows cell proliferation, according to Dr. P. Patrick Basu of North Shore Forest Hills Hospital and Columbia University College of Physicians and Surgeons in New York.

Dr. Basu told Reuters Health that after reading about the use of turmeric enemas for ulcerative colitis, he hoped to find a similar benefit for patients with moderate to severe C. difficile colitis.

He reported Monday at the American College of Gastroenterology's annual meeting in Washington, DC that he and his colleagues randomly assigned 36 patients to twice-daily enemas containing either vancomycin (250 mg), turmeric (1 g), or placebo, for 10 days. Patients also took 500 mg metronidazole orally three times a day for two weeks.

The infection was eradicated in similar proportions of patients in the vancomycin and turmeric groups (83% and 76%, respectively), compared to 66% in the placebo group.

At 21 days after the end of treatment, the ATLAS score for clinical severity (Age, Temperature, Leukocytes, Albumin, and Systemic antibiotics) was reduced by 60% in the vancomycin and turmeric groups, compared to 38% in the placebo group. In addition, the endoscopic appearance of luminal ulcers was improved with vancomycin and turmeric compared to placebo.

Recurrence developed in 10% of patients treated with vancomycin, 9% of those in the turmeric group, and 29% of patients who received the placebo.

While the treatment was generally tolerable, two patients given the turmeric enema complained of stained fomites. Dr. Basu and his team addressed the issue of leakage by giving patients non-medical suppositories after the enema was administered.

"The people who got vancomycin, they did very well, and curcumin, they did equally well," Dr. Basu said. "The beauty of it was that the curcumin was much, much less expensive." He estimated the cost of the turmeric enemas at $150 for 14 days of twice-daily enemas.

Dr. Basu said he and his colleagues are running a larger trial with 120 patients, which they plan to submit for publication next year.

Many different cancers show increased risk after organ transplantation

November 2, 2011

ST LOUIS (MD Consult) - Organ transplant recipients are at increased risk of a wide range of cancers, including cancers unrelated to infection, reports a study in the November 2, 2011, issue of The Journal of the American Medical Association.

National, regional, and state cancer registries were used to evaluate overall patterns of cancer risk after solid organ transplantation. The linked registries provided data on 175,732 solid organ transplant recipients—about 58% received kidney transplants, 22% liver transplants, 10% heart transplants, and 4% lung transplants.

Relative and absolute risks of cancers associated with organ transplantation were assessed, compared to the general population. The analysis included the risks of 32 cancers known to be associated with infections, such as anal cancer and Kaposi sarcoma; as well as cancers with no known relationship to infections. The lead author was Dr Eric A. Engels of the National Cancer Institute.

Organ transplant recipients had an increased overall cancer risk, with an incidence of 1,375 per 100,000 person-years. The standardized incidence ratio (SIR) was 2.0, with an excess absolute risk of 719.3 per 100,000 person-years.

The most common cancers occurring at increased rates in organ transplant recipients were non-Hodgkin lymphoma, SIR 7.54; lung cancer, SIR 1.97; liver cancer, SIR 11.56; and kidney cancer, SIR 4.65. Excess absolute risks were 168.3, 85.3, 109.6, and 76.1 per 100,000 person-years, respectively.

Lung transplant recipients had the greatest increase in lung cancer risk, SIR 6.14. However, lung cancer risk was also significantly increased for other groups of transplant recipients. The increase in liver cancer risk was limited to liver recipients: SIR 43.83. This risk was extremely high in the first 6 months after liver transplantation, SIR 508.97; but much lower with long-term follow-up of 10 to 15 years, SIR 2.22.

Kidney cancer risk was increased for kidney recipients: SIR 6.66, with a bimodal pattern in onset time. Liver and heart transplant recipients were also at increased risk of kidney cancer: SIR 1.80 and 2.90, respectively.

Because of immunosuppression and oncogenic viral infections, organ transplant recipients are at increased risk of cancer. Most studies of this issue have focused on kidney transplant recipients. There are also questions about the risks of non-infection-related cancers.

The new study shows an overall increase in cancer risk after solid organ transplantation, including kidney, liver, heart, and lung recipients. Significant increases are observed for both infection and non-infection related cancers. The researchers conclude, "The elevated risk for a broad range of malignancies among transplant recipients, coupled with improvements in long-term survival, should encourage further development of approaches to prevention and early detection of cancer targeted to this population."

JAMA. 2011;306:1891-1901.