A desire to continue providing colonoscopy, combined with a lack of resources, led one physician to offer the procedure without sedation. Now, that solution may lead to no-sedation colonoscopy becoming a more widely considered option.

A few years ago, the Sepulveda Ambulatory Care Center in North Hills, Calif., experienced a nursing shortage, and Felix Leung, MD, a staff gastroenterologist, was faced with two options. He could stop performing the procedure, or he could start offering it without sedatives. The Sepulveda center is part of the Veterans Affairs Greater Los Angeles Healthcare System. In response to patients who didn't want to travel 15 miles to another facility, he offered the no-sedation approach. Quite a few -- 30% between 2002 and 2005 -- accepted.

"The veterans asked if there was an alternative, and we found out that unsedated colonoscopy is done in many parts of the world," said Dr. Leung, who also is a professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles. "The U.S. seems to be unusual in that we, by and large, only do sedated colonoscopy."

He has since documented his experiences in a series of papers, including one in the December 2008 Journal of Family Practice. This article reported that, from September 2002 to June 2005, 145 out of 483 eligible patients opted to undergo colonoscopy without sedation. Of this group, 112 were able to complete it. Twenty-six could not, because of the discomfort, and later underwent sedated colonoscopy or barium enema. Another seven had poor bowel preparation or obstructing lesions that blocked the procedure. Some physicians said these numbers indicated that unsedated colonoscopy is a viable alternative.

"It's not going to be for everyone, but it's an option that I think patients would want to consider," said Thomas Kintanar, MD, a family physician in Fort Wayne, Ind. "There are some patients who will do just great without any anesthetic." He is also a board member of the American Assn. for Primary Care Endoscopy, although he was speaking for himself.

Colonoscopies without sedation are common in Europe and Asia.

Colonoscopy without sedation is common in Europe and Asia, and efficacy is comparable.

"There have been several studies that show that if you have motivated patients, a significant fraction of them can have a colonoscopy without sedation," said Douglas Rex, MD, past president of the American College of Gastroenterology. "But what has to be kept in mind is that most American patients actually prefer to be sedated. If you use sedation, there is better patient satisfaction and better physician satisfaction. That's really important."

Dr. Rex, who is also professor of medicine at Indiana University School of Medicine and director of endoscopy at Indiana University Hospital, has performed a small number of colonoscopies on unsedated patients and has undergone one without sedation himself. "For the great majority, having sedation offers a lot of advantages and a lot of positives," he said.

But with the demand for colonoscopy growing, performing it without sedation could reduce both associated work force needs and costs to the health care system. In his efforts, for instance, Dr. Leung eliminated the need for two registered nurses.

Also, a report released Jan. 7 by the Lewin Group, a health care consulting firm, projected that demand for gastroenterologists would grow at a rate nearly double the supply. If this projection bears out, it could impact the availability of traditional colorectal cancer screening, thereby increasing interest in the no-sedation option.

Neither the American Gastrological Assn. nor the ACG has policy regarding no-sedation colonoscopy. In broader terms, ACG policy notes that a well-trained endoscopist is key to a good colonoscopy. The American Academy of Family Physicians takes the position that family physicians trained in colonoscopy should be allowed to perform them and that specialty should not affect privileging.

Going without sedation also could provide some benefits for patients. Dr. Leung discovered many preferred being able to communicate and remember the conversations with the physician during and after. In addition, the unsedated approach is less expensive and does not require patients to have an escort or restrict activities afterward.

"Some patients just didn't have anybody to shuttle them around, and these patients would not have been able to have screening by colonoscopy if this option was not available," Dr. Leung said.

Additionally, this approach cuts to zero the already very low risk of complications associated with the sedative medications and significantly reduces the chance of a perforation.

"You cannot perforate [the bowel of] an awake patient. They will get off the table and smack you," said Ricardo G. Hahn, MD, professor of family medicine at the University of Southern California in Los Angeles. Unsedated colonoscopy is "not a comfortable procedure, but it's only once every five to 10 years."

Dr. Hahn co-authored a paper in the September-October 2007 Journal of the American Board of Family Medicine comparing unsedated colonoscopy with flexible sigmoidoscopy in a family medicine clinic.

Several physicians, however, expressed caution, because unsedated colonoscopy may not be possible or appropriate for everyone. Data from a VA population, which tends to be older and predominantly male, may not apply to the wider world. For example, female physiology tends to make this procedure more difficult.

Experts also worry that an uncomfortable experience may keep a patient from completing this screening.

"The key for us is to ensure a good exam, a comfortable exam for the patient and one that they are willing to repeat," said David A. Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia School of Medicine. He also is an ACG past president.

Dr. Leung's upcoming projects will look at colonoscopy techniques, such as using water infusion without air insufflation, to reduce the discomfort related to the procedure and allow more patients to have it done without or with less sedation.

The print version of this content appeared in the Jan. 19, 2009 issue of American Medical News.

Washington -- The Food and Drug Administration is asking the manufacturers of new drugs and biologics for type 2 diabetes to be more diligent in determining if their therapies pose cardiovascular risks.

Until now, manufacturers had only to show that their drugs reduced blood sugar levels.

"We need to better understand the safety of new antidiabetic drugs," said Mary Parks, MD, director of the agency's Division of Metabolism and Endocrinology Products at the Center for Drug Evaluation and Research. She released a guidance document outlining the agency's recommendations for doing such an assessment Dec. 17, 2008.

More than 23 million people in the U.S. have been diagnosed with type 2 diabetes, which places them at a two- to four-times greater risk of heart disease than their nondiabetic counterparts. None of the currently approved antidiabetic therapies has been proven convincingly to reduce that risk, the FDA said.

The guidance, which is effective immediately, asks that phase II and III clinical trials demonstrate that new therapies do not increase cardiovascular risk in comparison with existing therapies.

More than 23 million people in the U.S. have type 2 diabetes.

The FDA also recommends to manufacturers that any cardiovascular events occurring in their trials be analyzed by committees of outside cardiologists.

The FDA already has placed black-box warnings on one class of type 2 diabetes drugs, thiazolidinediones, or TZDs, after they were found in postmarketing studies to increase the risk of heart failure. Two drugs, Avandia, or rosiglitazone, and Actos, or pioglitazone, are in that class.

Alarms about Avandia's association with increased heart risks were raised in a May 2007 New England Journal of Medicine article by Steven Nissen, MD, chair of Cleveland Clinic's Dept. of Cardiovascular Medicine. At the time, Dr. Nissen noted that because of this risk, Avandia is not a drug he recommends to patients.

GlaxoSmithKline, the manufacturer of Avandia, strongly disagreed with the conclusions in the NEJM article, faulting the authors' reliance on a meta-analysis rather than on long-term trials that Glaxo said showed no increased cardiovascular risk associated with Avandia.

Meanwhile, in a study published online Dec. 10, 2008, by the Canadian Medical Assn. Journal, researchers found that the risk of fractures doubled among older women who take TZDs for one year or more to control their diabetes.

"We knew going into this study there was an association between thiazolidinediones and fracture risk. However, the magnitude of the risk had not been evaluated," said Sonal Singh, MD, MPH, an assistant professor of internal medicine at Wake Forest University School of Medicine in Winston-Salem, N.C., and a co-researcher for the study.

Glaxo responded that the bone fracture risk had been reported previously and is noted on the Avandia label. A study to evaluate the effects of the drug on bone in women with type 2 diabetes is now enrolling participants, a spokesman said.

But in a commentary published online Dec. 10, 2008, in the CMA journal, Lorraine L. Lipscombe, MD, an adjunct researcher at the Institute for Clinical Evaluative Sciences in Toronto, recommended that TZDs not be considered a first-line therapy for type 2 diabetes.

"If a patient is unable to take other therapies or if other therapies have failed, there may be a role for thiazolidinediones in carefully selected patients duly informed of the potential adverse effects," she wrote.

The print version of this content appeared in the Jan. 19, 2009 issue of American Medical News.

Inhalers such as Serevent Diskus and Foradil Aerolizer, which contain only a long-acting beta agonist, are not good choices for treating asthma. The reason: The chance they will be used without an inhaled corticosteroid is too great, according to three Food and Drug Administration advisory committees that gathered in December 2008. The benefits of inhalers that deliver both types of medicines -- Advair Diskus and Symbicort -- are worth the risks.

"The single agent, long-acting beta agonists should no longer be approved for use in the treatment of asthma. The combination dispensers should continue to be approved for all age groups," said Marsha Rappley, MD, chair of the FDA's Pediatric Advisory Committee and dean of the College of Human Medicine at Michigan State University. Members of the Pulmonary-Allergy Drugs as well as the Drug Safety and Risk Management advisory committees were also in attendance.

The agency is not required to follow its advisory panels' recommendations but generally does.

This is the latest in the checkered history of long-acting beta agonists. Several studies showed that these medications increase the risk of severe exacerbations. Because they seem to reduce symptoms without addressing inflammation, treatment guidelines urge that they be used only with inhaled corticosteroids, which appear to mediate their negative effects. The beta agonists also are not recommended for patients able to control their illnesses on other medications. Prior FDA advisory committee deliberations have led to the drugs remaining on the market, but with stronger warnings about possible adverse events.

Most asthma specialists received news of the latest action with trepidation. On one hand, the combination products are far more commonly prescribed than the inhalers with only a long-acting beta agonist. Also, even if the single products lose an indication for asthma, they are still expected to be labeled for chronic obstructive pulmonary disease -- so they could still be used off-label for asthma patients.

On the other hand, physicians worried about losing the single-drug products as an option or the possibility that all products containing a long-acting beta agonist drug would be pulled from the market. Many physicians view these drugs as very valuable.

"I think their conclusions were conservative and consistent with trying to optimize the safety and the use of these medications. I can see their rationale. But I'm a bit concerned that they're overcautious about the safety signal," said Stanley Szefler, MD, head of pediatric clinical pharmacology at National Jewish Health in Denver. He was speaking personally, although he testified at the joint advisory committee meeting on behalf of the American Academy of Allergy, Asthma and Immunology and the American College of Allergy, Asthma & Immunology.

Concern also stemmed from the idea that this move might limit patient access and affect the cost of treating asthma. These drugs in two inhalers are less expensive than are the combined products.

"From a clinical standpoint, it's nice to have more options. And, from a patient standpoint, I'm concerned about cost. These medications are fairly expensive," said Richard Gower, MD, president of ACAAI. "We live in an imperfect world. All drugs have potential benefits and side effects."

Manufacturers cheered the conclusion that the benefits of combination products outweighed the risks but disagreed with the conclusion that those with only a long-acting beta agonist should no longer be used for asthma.

Statements issued by these companies said these products provided more dosing flexibility and were safe when used as directed.

"We welcome the committee's endorsement of Advair as a safe and effective treatment for asthma. ... Serevent, when used with an [inhaled corticosteroid], is an important treatment option for some patients as outlined in national guidelines," said Ellen Strahlman, MD, chief medical officer for GlaxoSmithKline.

The advisory panels also called for more studies to determine the safety of the combination products in children.

The print version of this content appeared in the Jan. 19, 2009 issue of American Medical News.

Researchers investigating an experimental malaria immunization are moving it into a large phase III trial in response to recent positive results.

"We are closer than ever before to having a malaria vaccine," said Dr. Christian Loucq, director of the PATH Malaria Vaccine Initiative. "The world urgently needs a safe and effective vaccine. Even a partially effective vaccine has the potential to save hundreds of thousands of lives each year."

Data from phase II projects investigating the RTS,S/AS01E and the RTS,S/AS02D malaria vaccines were published in the Dec. 11, 2008, New England Journal of Medicine and presented at last month's American Society of Tropical Medicine and Hygiene meeting in New Orleans.

These two-shot formulas contain the same antigen but have different adjuvants.

One study randomized 894 infants and toddlers in Kenya and Tanzania to receive either RTS,S/AS01E or rabies shots. The RTS,S/AS01E vaccine reduced the incidence of illness caused by the malaria parasite by 53% over eight months. Those receiving the investigation product also experienced fewer serious adverse events than did those who received the rabies vaccine.

A second study randomized 340 infants in Tanzania to receive either three doses of RTS,S/AS02D or the hepatitis B vaccination, in conjunction with the usual immunization schedule. The RTS,S/AS02D vaccine reduced the risk of being infected with the malaria parasite by slightly more than 65% over a six-month period. Also, it did not interfere with the effect of the other vaccines.

"These results are very exciting and give me renewed hope of having a malaria vaccine in the not-too-distant future," said Dr. Salim Abdulla, lead author on the second paper and head of the Bagamoyo Branch of the Ifakara Health Institute in Bagamoyo, Tanzania.

Multicenter phase III efficacy trials are expected to start early this year, pending approval by national regulatory agencies and ethics committees.

The print version of this content appeared in the Jan. 5, 2009 issue of American Medical News.

Denise Bunning had no idea that switching her 6½-month-old son from breast milk to a milk-based formula would threaten his life. But Bryan's first sips proved perilous. His lips and tongue swelled, and his eyes rolled back. "I didn't know what was happening," says Bunning, who, with her husband, David, co-founded the Food Allergy Project in Chicago.

Bryan was diagnosed with life-threatening allergies to milk, eggs, tree nuts and sesame seeds. So when their second son, Daniel, was born, the Bunnings took precautions. Still, at 9 months he also had an anaphylactic reaction after a babysitter inadvertently put a milk-soiled bib around his neck. "His allergies are even worse," she says. "In addition to milk, eggs and tree nuts, he is also allergic to beef, turkey and shellfish."

For reasons scientists cannot yet explain, food allergies are increasing, especially among children. According to the Centers for Disease Control and Prevention, the number of food or digestive allergies in those younger than 18 increased 18% in the last decade. In an October 2008 report, the CDC estimated that 3 million U.S. children and teenagers have a food or digestive allergy, compared with just more than 2.3 million in 1997. And more than 9,000 annual pediatric hospital discharges had a food allergy diagnosis.

But the problem goes beyond children -- 1% to 2% of adults have food allergies, which can emerge at all ages for many reasons. Recent studies focus on pediatric patients, but many of the themes are applicable. The key differences involve patterns. For instance, the most common food allergies among adults are shellfish, fish, peanuts, tree nuts and eggs. For kids, it's cow's milk, eggs, peanuts, tree nuts and sesame seeds. Also, while children often outgrow these issues, adults do not.

"There's an epidemic of allergies," says Clifford Bassett, MD, assistant clinical professor of medicine at Long Island College Hospital in Brooklyn and medical director of Allergy and Asthma Care of New York. He also is the vice president of public education for the American Academy of Allergy, Asthma & Immunology. "Today, one in 26 children has a food allergy, up from one in 30 in 1997."

According to the CDC, eight foods -- milk, eggs, peanuts, tree nuts, fish, shellfish, soy and wheat -- account for 90% of allergies. With reactions ranging from tingling around the mouth and lips to hives and even death, management can be challenging. "There are 200 fatalities each year from food allergies. This is an important problem," Dr. Bassett says. "There needs to be more education of physicians and patients. Parents need a plan, an EpiPen, and we need to teach them how to be label detectives."

The hardest part, says the Food Allergy Project's David Bunning, is unexpected exposure. It can be a bite of a cookie, peanut shell dust at a ballgame or a dairy-coated pill. But all can lead to an anaphylactic reaction or even death. "Avoidance becomes all-encompassing," he says. "And regardless of how careful we are, every year or so we have an accidental cross-contamination."

A little bit of dirt and other theories

Corresponding to this increase in food allergies is an increase in allergies overall, says David L. Rosenstreich, MD, director of the division of allergy and immunology at Montefiore Medical Center in New York. "There is clearly more asthma, there is clearly more rhinitis. Why is this happening?"

While possible explanations abound, not enough evidence exists to pinpoint a cause, says Jonathan Field, MD, director of the pediatric allergies and asthma clinic at New York University's Langone Medical Center, in Bellevue.

8 foods account for 90% of food allergies.

Food-specific theories question if our diets have changed in subtle ways, maybe with nutrients that push more toward allergic responses. Others note that eating more or maybe even less of specific allergenic foods is to blame. Some theories even center on how a food is processed. For example, maybe roasting peanuts makes them more allergenic than boiling or frying, a common preparation in Asia, where peanuts are frequently eaten but peanut allergy rates appear lower, says Scott H. Sicherer, MD. He is associate professor of pediatrics at the Jaffe Food Allergy Institute, Mount Sinai School of Medicine in New York. Other theories blame a lack of sun exposure and decreased vitamin D, he adds, noting data indicating that more people with anaphylaxis live in northern climates.

The hygiene theory also is popular. Some experts say society is too clean, keeping kids' immune systems from maturing as they did in the past. "The hygiene hypothesis says that we are oversanitizing the early environment of the child," Dr. Bassett says. "The immune system has less exposure to dirt, germs and bugs."

In support of this perspective, researchers point to Eastern Germany before the fall of the Berlin Wall. "They had much lower rates of allergy," Dr. Field says. "As they were westernized, they had more."

Maybe a little dirt is not so bad, Dr. Rosenstreich says. "In the farm studies, children who live on farms in close proximity to animals and are exposed to endotoxins have fewer allergies. And it looks like a pet in the home in the first year of life may well protect children from asthma. This is the opposite of what we've been teaching."

According to a release by the American Academy of Allergy, Asthma & Immunology, new research casts doubt on food avoidance recommendations -- specifically, that infants and new mothers avoid eating peanuts. The study, published in the November 2008 Journal of Allergy and Clinical Immunology, found that children who avoided peanuts in infancy and early childhood were 10 times as likely to develop peanut allergy as those who were exposed to them.

Researchers measured the incidence of peanut allergy in 8,600 Jewish school-age children in the United Kingdom and Israel. Prevalence of the allergy in the U.K. was estimated at 1.85% versus 0.17% in Israel. "Actually, peanut is eaten at an earlier age in Israel, lending argument to the idea that perhaps earlier exposure is not a problem," Dr. Sicherer says.

Food or digestive allergies in children increased 18% in the last decade.

Nonetheless, the AAAAI cautions that, although the results are promising, they shouldn't translate to changes in treatment just yet. "While this study's findings provide optimism for prevention of peanut allergy in the future, randomized, controlled trials are needed to verify that early introduction of peanut is indeed effective," says Jacqueline A. Pongracic, MD, vice chair of the allergy academy's Adverse Reactions to Foods Committee.

Similarly, a study published in the Oct. 28, 2008, Journal of Allergy and Clinical Immunology explored milk exposure and milk allergies. Investigators from Johns Hopkins Children's Center and Duke University found that giving children increasingly higher doses of milk over time may ease milk allergy. "They were able to greatly increase tolerance to milk," Dr. Rosenstreich says. "Total avoidance may also be a mistake."

In another twist, a recent study found evidence that early cat ownership may help protect young children against developing asthma symptoms. The research was conducted by scientists at the Columbia Center for Children's Environmental Health at Columbia's Mailman School of Public Health, in New York.

Education and research

Clinical signs of food allergy often are confused with other reactions, most commonly intolerance. "The question is are they truly food allergic," says Jonathan Bernstein, MD, professor of medicine in the division of immunology and allergy, Dept. of Internal Medicine at the University of Cincinnati College of Medicine.

Guidelines published in the March 2007 Annals of Allergy, Asthma & Immunology help clarify food allergy diagnosis and management, which begin with a detailed history, confirmatory testing and education about day-to-day living. The diagnostic gold standard is the double-blind, placebo-controlled food challenge. "For children, many food allergies are outgrown, so repeated evaluations are needed," Dr. Sicherer says.

In a study in the September 2008 BMC Medical Education, however, researchers found that primary care physicians are not trained adequately in food allergy management. This survey and others found a majority of respondents were unable to identify risk factors for anaphylaxis.

"Our previous studies also showed that too many doctors did not know, for example, exactly how to teach people how and when to use self-injectable epinephrine," Dr. Sicherer says. "We were funded by the U.S. Dept. of Agriculture to create an educational program for doctors who care for teenagers and adults with food allergy. The program focuses on nuances. ... There are a lot of things the doctor must keep up on, including new labeling laws, for example."

Dr. Bernstein says it's important for primary care physicians to ask patients what happens when they eat the suspected food. "We don't want to create hysteria," he says. "It's important to find out if it is an allergy, and sending someone for a consult to clarify is not bailing from your patient."

The print version of this content appeared in the Jan. 5, 2009 issue of American Medical News.