Weight loss surgery is twice as effective as lifestyle changes at preventing type 2 diabetes in people who are obese, a new study found.
The Swedish study followed more than 3,400 obese men and women, roughly half of whom had bariatric surgery, for up to 15 years. It found that bariatric surgery reduced the risk of type 2 diabetes by 78 percent
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Bariatric surgery reduces the size of the stomach, which results in significant weight loss. Most patients in the new study had undergone a procedure called Roux-en-Y gastric bypass.
Previous studies had shown that many obese people who have this procedure improve their health and reduce the cost of their care. In this group of patients, however, costs did not go down, the researchers said.
"These three-year findings suggest that the return on investment for bariatric surgery isn't seen," said lead researcher Matthew Maciejewski, from the Center for Health Services Research in Primary Care at the Durham VA Medical Center, in North Carolina.
"It is possible, however, that if we could follow these
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Previous animal research demonstrated that ingestion of a high-fat diet produces weight gain and profoundly affects the gut microbiota composition, resulting in a greater abundance of one type of bacteria called Firmicutes, and a decrease in Bifidobacteria spp and Bacteroidetes. A similar pattern has also been found in obese humans. Feeding of prebiotics, substances that enhance the growth of beneficial bacteria, changes the composition and/or the activity of the gastrointestinal microbiota, to promote the release of gut peptides and to improve glucose and lipid metabolism in diet-induced obese and type 2 diabetic mice.
Roux-en-Y gastric bypass (RYGB) surgery is considered the most effective treatment of morbid obesity and diabetes. Recent studies reported substantial shifts in the composition of the gut microbiota towards lower concentrations of Firmicutes and increased Bacteroidetes in obese subjects after RYGB. Most of the human studies on gut microbiota have been carried out using fecal samples which may not accurately represent how RYGB surgery affects the gut microbiota profile along different parts of the intestine.
Because RYGB may affect how nutrients are absorbed in different portions of the intestine, a new study conducted by researchers at the University of Zurich measured the bacterial composition and the amounts of different peptides that affect food intake along different intestinal segments after RYGB in rats. They found that 14 weeks after surgery, Bifidobacteria spp, and Bacteroides-Prevotella spp content were significantly increased in several portions of the intestine in RYGB rats compared to control animals. In fact, the changes in gut microbe populations after RGYB resembled those seen after treatment with prebiotics. Gut microbiota changes were also associated with altered production of gastrointestinal hormones known to control energy balance.
The lead author on this study, Melania Osto, Ph.D. said "Our findings show that RYGB surgery leads to changes in gut microbiota that resemble those seen after treatment with prebiotics. The results of this study suggest that postsurgical gut microbiota modulations may influence gut peptide release and significantly contribute to the beneficial metabolic effects of RYGB surgery."
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When patients seek out cosmetic surgery from New York-based Dr. Oliver Zong, they're often looking to remove fat, but not from their bellies or thighs.
Zong is a podiatrist, and one of his specialties is slimming down people's fat toes -- "toe-besity," he calls it.
He's been in practice for about a decade, and when he started, toe reshaping was unheard of.
"When people first started asking, I said 'What?'" said Zong, who is surgical director at NYC FootCare. "We were mostly doing toe shortenings in the begining."
Now, he said, more and more people are zoning in on the smaller details of their feet, like the width of their toes.
For many patients, an odd-looking toe is a source of great embarrassment.
E.R., a patient of Zong's, said he hid his fat right big toe for years.
"I always had issues with it," said E.R., who asked to remain anonymous. "It was one of those things that you're just not comfortable with and try to hide it."
On top of being unattractive, the toe also caused discomfort.
"The bone was pushing the nail up, and the nail curved up a little bit, so it was hitting the shoe," he said.
Three weeks ago, the 37-year-old New Yorker had surgery to shave off some fat and bone. His second toe was also a hammertoe, so Zong shaved down the bone of that toe as well.
There's still a lot of swelling, but E.R. said he already feels better about his foot.
The results will be presented Tuesday at The Endocrine Society's 94th Annual Meeting in Houston.
"This is particularly important prior to bariatric surgery where weight loss and decreased calcium and vitamin D absorption in some procedures may place these patients at further risk," said study lead author Marisa Censani, M.D., pediatric-endocrinology fellow at Columbia University Medical Center, in New York City. "These results provide insight into prevalence and risk factors for pre-existing vitamin D deficiency in obese adolescents prior to bariatric surgery."
In the United States, weight-loss surgery is becoming an increasingly common procedure due to the obesity epidemic, which affects people of all ages, including children. One of the most common types is gastric-bypass surgery, which involves surgically removing a portion of the stomach, thereby reducing its size and ability to hold large amounts of food. While highly effective at controlling weight, weight-loss surgery presents certain challenges. One of the greatest post-surgical difficulties is maintaining adequate nutrition, particularly with respect to factors associated with bone development since adolescents have not yet reached their peak bone mass.
Vitamin D is found in foods such as eggs, milk, and fish, as well as the sun. The vitamin plays an essential role in regulating the amount of the minerals calcium and phosphorus circulating in the blood.
While previous studies have found an increased risk of vitamin D deficiency among adults evaluated for weight-loss surgery, whether this deficiency also occurred among morbidly obese adolescents remained unclear. Morbid obesity is defined in adults as having a weight-to-height ratio, or BMI, greater than 40; a healthy BMI is no more than 24.9.
In one of the first studies of its kind, Censani and her co-investigators found that more than half of adolescents undergoing evaluation for weight-loss surgery were vitamin D deficient, and 8 percent had severe deficiencies. Slightly less than one-fifth had adequate vitamin D levels. Patients with the highest BMIs were the most likely to be vitamin deficient.
In other findings, investigators identified several racial differences. African Americans were the most likely to be vitamin D deficient, while Caucasians were the least likely to have a deficiency. Specific percentages of vitamin D deficiency among racial subgroups were:
• 82 percent of African Americans
• 59 percent of Hispanics
• 37 percent of Caucasians
"These results support screening all morbidly obese adolescents for vitamin D deficiency, and treating those who are deficient, particularly prior to bariatric procedures that could place these patients at further risk," Censani said.
Investigators analysed the medical records of 236 adolescents who were being considered for bariatric surgery between March 2006 and June 2011. Of these patients, 219 provided medical records that included data on vitamin D levels. Sixty-five percent were female, their average age was 16 years, and average BMI was about 48. Forty-three percent were Caucasian, 35 percent were Hispanic, and 15 percent were African American.
Censani was supported by the NIH National Institute of Diabetes and Digestive and Kidney Diseases 5T32 DK 06552-07 in Pediatric Endocrinology.
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The study, presented recently as a late-breaking abstract at the American Diabetes Association's 72nd Scientific Sessions, strongly counters the popular view that people generally cannot maintain long-term the weight loss achieved during lifestyle intervention programs.
"The notion that most people in the medical field have is that when you apply intensive lifestyle interventions, the majority of patients gain all or most of the weight back in a year," said Osama Hamdy, M.D., Ph.D., Medical Director of the Obesity Clinical Program and Director of Inpatient Diabetes Management at Joslin and lead author of the paper.
"People have been pessimistic," he added. "They think they may need bariatric surgery. But we are sending an optimistic message. Think again. There is something else that can work effectively in real-world clinical practice and save money too. This is a very important observation."
The study showed that around 50 percent of the 120 patients who enrolled in the Weight Achievement and Intensive Treatment (Why WAIT) program for 12 weeks were able to maintain an average of 9.5 percent weight loss at four years, while the total group maintained 6.3 percent at four years.
Why WAIT is a multidisciplinary diabetes weight management program designed for clinical practice. The program included a change in diabetes medications to enhance weight reduction, structured dietary intervention with lower carbohydrates and higher protein and meal replacement, an exercise program, with emphasis on strength training and weekly educational and support sessions.
Although subjects in this study were followed for four years, they were on their own after the initial 12-week program. The study found that about half of the subjects did not regain the weight -- on average 24 pounds -- after four years. This group also maintained a significant improvement in their metabolic control as measured by hemoglobin A1c and the improvement in other vascular risk factors like blood pressure and lipids.
It also found that those who maintained at least seven percent of their weight loss at one year were most likely to continue the weight reduction over the long term.
"This is very important information," Dr. Hamdy said. "It tells us not everyone gains the weight back. In reality, these are similar numbers to the weight loss gained by some bariatric surgeries at that time frame."
Those who had lost at least seven percent of their body weight after one year lost an average of 29 pounds -- or 11.9 percent of their body weight -- at 12 weeks and maintained an average loss of 31.5 pounds -- or 12.6 percent -- at one year.
A second group included those who lost an average of 19.6 pounds -- or eight percent -- at 12 weeks but was down to a loss of just 5.6 pounds -- or 2.3 percent -- at one year.
Those in the first group maintained weight losses of 23.9 pounds at two years, 23.5 pounds at three years and 24.1 pounds at four years. Those in the second group only maintained losses of 6.9 pounds at two years, 6.3 pounds at three years and 8 pounds at four years.
Blood sugar levels in the first group dropped over the four year period, but levels in the second group rebounded after dropping initially. However, there were no differences in the groups when reductions in blood pressure, HDL cholesterol and triglyceride levels were compared at the end of the four years.
"Those who gained the weight back still got some benefits," Dr. Hamdy said.
He said the findings of this study are more robust than the four-year results initially reported from the National Institutes of Health's Look Ahead (Action for Health and Diabetes) study, designed to assess the long-term health consequences of intentional weight loss in overweight and obese individuals with type 2 diabetes.
He said this probably due to the fact that patients in the Why WAIT study received an optimal intensive lifestyle intervention, which included close evaluation at the outset, and that all interventions were in group format. In addition, diabetes medications were also adjusted by diabetologists at the start and during the follow-up, and patients were fed less carbohydrates and exercised more -- up to 300 minutes per week, he said.
Subjects in Why WAIT were able to cut their diabetes medications by half on average at the end of the 12 week program. It saved them $561 a year on diabetes medications alone, he said. Based on other valid cost-effective analysis, patients in the program saved $2,000 per year or 27 percent on overall health care costs and around $1,000 or 44 percent on diabetes-related costs, he added.
Dr. Hamdy said the study proves that intensive lifestyle intervention is at least as effective as some common bariatric surgeries in helping people lose weight and deal with their diabetes issues, with less cost and fewer short and long-term side effects.
"Surgery carries a lot of long-term risks," he said. "And a significant number of surgical patients gain their weight back after one or two years."
He also said that bariatric surgery costs in the range of $20,000 while the optimal intensive lifestyle intervention through the Why WAIT model cost just $2,700. After those results, "we are ready to debate them on the long-term value," he added.
He concluded: "So many physicians have been telling the governmental authorities that weight loss in clinical practice is a waste of money and that they will never keep the weight off. We now have a message for them. It is very effective in at least half of people in terms of weight loss and cost savings. Intensive lifestyle intervention can be a very valid option."
Dr. Hamdy said a new study involving Joslin and Brigham and Women's Hospital in Boston is underway that aims to compare the Why WAIT model directly to bariatric surgery.
Co-authors included Amy Rossi, MD; Adham Abdel Mottalib, MD; Nuha El Sayed, MD; Ann Goebel-Fabbri, Gillian Arathuzik, Jacqueline Shahan, Joan Beaton, Pamela Needle, Amanda Kirpitch, John Zrebiec, Michael Seem Catherine Carver, Jo-Anne Rizzotto and Martin Abrahamson, M.D..
The study was internally funded by Joslin Diabetes Center.
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A 28-year-old woman who had 60 percent of her lung removed is giving Zeddie Little, better known as “ridiculously photogenic guy,” a run for his money.
The woman, known only as Rachel, was nicknamed “ridiculously photogenic surgery girl” after posting photos from her hospital bed on Reddit.
“I’m currently in the ICU of the Cleveland Clinic,” she wrote. “My pain is being reasonably managed, but I cannot fall asleep. Anyone care to entertain me?”
Judging by the response, the answer was yes. The post amassed 612 comments in 11 days, many about her beauty, and spurred the Internet meme, “Lose 60% of her lung … wins 100% of my heart.”
Rachel, an Army wife and mother from Dayton, Ohio, said she has congenital emphysema, a lung disease she’s had since birth that became problematic after she contracted pneumonia.
“I’ve had it my entire life and didn’t know,” she wrote.
The genetic form of emphysema is caused by a deficiency in alpha-1 antitrypsin, a protein that helps give lungs their elasticity. Rachel said 60 percent of her right lung was damaged.
“I begged my surgeon to let me see it when he got it out,” she wrote. “He took pics, though, and I will get to see them today. Anyone want to check them out after I get them??”
Rachel said even she was surprised by how great she felt – and looked – just hours after major surgery.
“I am just as surprised as everyone else that I managed to look like that,” she wrote. “I know exactly what it is, too. It was taken when I was still on so many pain meds that I couldn’t feel anything but happiness!”
When the painkillers wore off, it was a different picture, she said.
“My incisions and tubes and lungs were on fire. I wanted to scream but moving and making noise made it worse,” she wrote. “I can assure you that happy glow isn’t there today!”
But the flood of comments like, “Damn, I wish I had looked this good after my surgeries,” and “You are beautiful! Good luck with the recovery,” may give Rachel the boost she needs to power through the pain.
“WOW!!!! I can’t believe how many people responded to my little post!!! I was thinking 25-50. My mind has been blown!” she wrote. “It is going to take awhile to respond to all of this, but I’m really touched that so many people cared enough to say anything at all.”
SHOWS: Good Morning AmericaA team led by Dr. Tony Lam and Dr. Danna Breen, a post- doctoral fellow in the lab of Dr. Lam, used a rat model to study novel nutrient-sensing signals in the jejunum, located in the middle of the intestine. Dr. Lam and his team demonstrate that duodenal-jejunal bypass surgery activates novel nutrient-sensing signals in the jejunum and rapidly lowers blood sugar levels in non-obese rats with uncontrolled diabetes. DJB surgery is a type of bariatric surgery which excludes the duodenum and proximal jejunum, the first section of the small intestine, and instead redirects food into the distal jejunum, the middle to last section of the intestine. This latter section of the intestine, as demonstrated by Dr. Lam and his team, can sense glucose and signal to the brain to let the liver know that it must lower glucose production, leading to better control of blood sugar in the diabetic rats.
The study showed for the first time that a surgical intervention induces a rapid glucose-lowering effect in non-obese type 1 uncontrolled diabetic rats, independent of a reduction in food intake and body weight as well as changes in blood insulin levels.
The research was published in a paper entitled, "Jejunal nutrient sensing is required for duodenal-proximal jejunal bypass surgery to lower glucose levels in uncontrolled diabetes," in the May 20, 2012 on-line edition of the international journal Nature Medicine.
"We report that shortly after a meal, the influx of nutrients into the jejunum of DJB surgical diabetic rats activates novel sensing mechanisms to lower blood sugar levels. Importantly, this occurs in the presence of insulin-deficiency and is independent of weight loss," says Dr. Lam, who holds The John Kitson McIvor (1915 -- 1942) Endowed Chair in Diabetes Research and the Canada Research Chair in Obesity at the Toronto General Research Institute and the University of Toronto. He is also Associate Director of Research at the Banting and Best Diabetes Centre at the University of Toronto.
Currently, patients with Type 1 diabetes lower their glucose through insulin injections (usually several times a day) and must regularly monitor blood glucose levels. High or uncontrolled glucose levels can result in damage to eyes, nerves and kidneys and increase the risk of heart attack, stroke, blindness, erectile dysfunction, foot problems and amputations. Many laboratories around the world are in a race to find alternative and effective ways in which to lower and better control glucose levels because of the severe complications which can result from high sugar levels.
Dr. Lam's laboratory is a world pioneer in exploring the role of the gut in regulating blood sugar. "The gut is an easier and therefore more promising therapeutic target in regulating blood sugar than the brain or liver, due to their potential side effects, " says Dr. Danna Breen, who is the lead author in the study. Dr. Breen adds that this type of surgery may potentially have therapeutic value in lowering glucose (sugar) levels in non-obese individuals with type 2 or 1 diabetes, but that many more years of future studies are required to determine whether this approach is effective and safe in humans who have diabetes.
In healthy individuals, insulin is a hormone whose primary role is to regulate blood sugar. It is produced by cells located on the pancreas in response to sugar intake, and it acts to bring blood sugar to appropriate levels, allowing the body to have the energy it needs to function properly. In persons with type 1 diabetes, the pancreas does not produce insulin, resulting in elevated blood sugar levels due to lack of insulin which cannot signal to the liver to reduce sugar production. People with type 1 diabetes need to take daily insulin shots and carefully monitor their blood sugar levels.
"If new medicines or surgical interventions can be developed that stimulate this sensing mechanism in the gut, we may have an effective and alternative way of slowing down the body's production of sugar, thereby lowering blood sugar levels in diabetes," says Dr. Lam, who is also an Associate Professor of Medicine and Physiology at the University of Toronto. Other ongoing studies of Dr. Lam's lab reveal novel molecular targets in the gut that effectively lower blood sugar in obesity and type 2 diabetes.
Studies reported in the New England Journal of Medicine this year have challenged medical therapy as the prevailing method of treating patients with type 2 diabetes. Two studies reported that bariatric surgery induced remission in severely obese patients with type 2 diabetes, and was associated with significant improvement in metabolic control over and above medical therapy, both conventional and intensive. An accompanying April 26, 2012 editorial by Drs. Zimmet and Alberti, states that "surgeons may now be able to claim greater success in achieving metabolic control," in these patients, although long-term studies with greater numbers of patients still need to be completed. No studies have yet reported on surgical interventions as treatments for patients with type 1 diabetes.
"More than two million Canadians have diabetes. Diabetes is an epidemic in Canada and around the world that is growing at an alarming rate," says Dr. Philip M. Sherman, Scientific Director of the Institute of Nutrition, Metabolism and Diabetes at the Canadian Institutes of Health Research. "Since many people are undergoing bariatric surgery in an attempt to manage morbid obesity and the associated health problems, such as diabetes, it is critical that we understand how it works. The Canadian Institutes of Health Research is pleased to support Dr. Lam's work which increases our understanding and may offer a new approach to managing morbidity and premature mortality resulting from this illness."
Working with rats, Drs. Lam, Breen and colleagues designed and performed a series of elegant experiments on two different groups of rats: rats whose insulin-producing pancreatic islet cells were destroyed by toxins; and genetically-altered rats which experienced spontaneous autoimmune destruction of islet cells -- similar to what happens in humans with type 1 diabetes.
Non-obese rats induced with uncontrolled diabetes or autoimmune type 1 diabetes had an experimental DJB surgery, a variation of the Roux-en-Y gastric bypass, the most common surgical method currently used to treat obese patients. Two days after DJB surgery, blood sugars were normal in the insulin-deficient diabetic rats.
Dr. Breen emphasized that further studies need to be undertaken to determine the long-term effects of this intervention in rodents, as well as to ensure the safety and efficacy of this procedure in humans.
Other researchers involved in the study include Brittany A. Rasmussen, Andrea Kokorovic and Grace W.C. Cheung from the Toronto General Research Institute and the Department of Physiology, University of Toronto; and Dr. Rennian Wang, from the Departments of Physiology and Pharmacology, University of Western Ontario.
The work was funded by the Canadian Institutes of Health Research, as well as a fellowship from the University Health Network and the Banting and Best Diabetes Centre, University of Toronto.
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"Obesity is a huge problem in the United States," said study author Chandhana Paka, a fellow in minimally invasive gynecological surgery at Stanford University School of Medicine. "We wanted to see if bariatric surgery
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Autoregulation monitoring is a noninvasive technique that can determine when blood flow to the brain may be low. The other method, a blood test, uses a small sample of blood to detect brain-tissue injury during surgery.
Doctors previously had no way to detect brain injuries as they occurred during heart surgery.
Details of the research are to be presented Wednesday during an American Heart Association press briefing.
Brain injury occurs in 30 percent to 70 percent of infants and children who have surgery to repair congenital heart defects, which are heart abnormalities present at birth. For each 1,000 live births in the United States, about eight babies will have some type of heart defect, according to a heart association news release.
This was a pilot study to evaluate the feasibility of new ways to monitor for brain damage while children have surgery to repair heart defects. The researchers plan to conduct another study to assess the effectiveness of these brain monitoring techniques 18 months after surgery.
Researchers' data and conclusions should be considered preliminary until published in a peer-reviewed medical journal.
More information
The March of Dimes has more about congenital heart defects.
The findings suggest that a patient's gender, along with other factors, should be taken into account to provide the best possible estimates of risk for patients scheduled for neurosurgery, the University of Michigan Medical School researchers said.
The researchers analyzed data on more than 900 people who had brain or spinal surgery between 2006 and 2009. The overall complication rates within 30 days after surgery were 18.6 percent for brain surgery patients and 10.8 percent for spinal surgery patients.
The complication rate for men was 20.3 percent, compared to 11.3 percent for women. The rate for men remained twice that of women even after the researchers adjusted for other factors such as age, tobacco and alcohol use, and health problems such as high blood pressure, coronary artery disease and diabetes.
Complications also were more common in older patients and in those with coronary artery disease.
Men spent an average of 7.5 days in the hospital, compared with 5.7 days for women. But gender did not affect the average length of stay in the intensive care unit after surgery.
Multiple factors likely contribute to the different complication rates in men and women, including "psychosocial, hormonal or underlying disease differences," the researchers said.
For example, the lower complication rate in women could be due to better social support, "neuroprotective" effects of estrogen or lower rates of cardiovascular disease.
The study appears in the April issue of the journal Neurosurgery.
More information
MedlinePlus has more about neurosurgery.
The study, which covered nearly 3,000 women, focused on so-called ductal carcinoma in situ, or DCIS - abnormal cells in the milk ducts that are considered the earliest stage of breast cancer. The most common treatment involves removing only the abnormal tissue and conserves the breast.
But researchers said the findings, which appeared in the Journal of the National Cancer Institute, pointed to a downside of breast-conserving surgery for DCIS.
"Women making treatment decisions about DCIS need to understand that many women will need additional surgery or invasive intervention after breast-conserving surgery," said Joshua Fenton, an assistant professor at the University of California, Davis, who co-wrote an editorial published with the study.
The most common invasive procedure is usually a biopsy to remove abnormal tissue in the same breast.
Of the 2,948 women in the study, all of whom had breast-conserving surgery for DCIS between 1990 and 2001, 41 percent had at least one mammogram to check out symptoms or a suspicious lump. And 66 percent had at least one invasive procedure.
But only eight percent actually had a DCIS recurrence and another eight percent were found to have invasive breast cancer.
Larissa Nekhlyudov at Harvard Medical School and Harvard Vanguard Medical Associates in Boston, who led the study, said women should be aware that breast conserving surgery can come with a long follow-up.
"We're not suggesting that women have a mastectomy instead," she said.
"The good news is that the majority of these women will not have a (cancer) recurrence. But the work-ups for a possible recurrence are likely to continue for years."
The findings fit into the bigger issue of the pros and cons of mammography screening. In the United States, the government-backed U.S. Preventive Services Task Force recommends screening women ages 50 to 74 every other year. Some medical groups, though, call for regular mammograms for all women from age 40.
Since mammograms came into widespread use in the 1980s, the number of DCIS diagnoses has shot up. About one in five newly-diagnosed breast cancers is DCIS.
The problem is that DCIS may or may not progress to tumors that invade the breast tissue, and currently there is no way to predict which cases will progress.
So women with DCIS almost always receive treatment, which for some may be unnecessary.
When it comes to early prostate cancer, which is also usually caught through screening, men have the option to delay treatment and choose "active surveillance" - where the cancer is monitored to see if it's progressing.
That's because prostate cancer is frequently slow-growing and may never threaten a man's life.
But this is not an option for DCIS yet since there's no way of telling which tumors might progress quickly, although it could become one if researchers find certain tumor characteristics that strongly predict it's benign, Fenton said.
This will also probably take a "cultural shift," Nekhlyudov noted, since people typically want aggressive treatment for cancer, even if it's early stage. SOURCE: http://bit.ly/IEYv3o
(Reporting from New York by Amy Norton at Reuters Health; editing by Elaine Lies and Bob Tourtellotte)
In certain very rare genetic cases, the common painkiller codeine can be lethal. The gene mutation causes the body to metabolize codeine into morphine at levels 50 percent to 70 percent higher than normal. Among such patients, an otherwise standard amount of codeine can unpredictably turn into a toxic overdose.
After undergoing tonsillectomies for sleep apnea, three children with the gene mutation ultimately died, while the fourth patient barely survived.
"Codeine has been around for the better part of a century as a medication, including as a syrup for children," said study lead author Dr. Gideon Koren, a professor of pediatrics, pharmacology, pharmacy and medical genetics at the University of Toronto. "That's the drug that is used by most surgeons in the U.S. to control pain. But codeine is not actually the analgesic. To deal with pain it has to be transformed in the liver into morphine. And that happens with everyone who takes it to some degree," he explained.
"Most people take 10 molecules of codeine and make one molecule of morphine," added Koren, who is also a professor at the University of Western Ontario. "The problem is that our knowledge of genetics has revealed that there are people who are ultra-rapid metabolizers. They take 10 molecules of codeine and make two, three or even five molecules of morphine. In other words, they take the right doses but end up poisoning themselves."
Koren and his colleagues described the cases of the three recent pediatric codeine overmetabolizers in the April 9 online and May print issue of Pediatrics. The earlier case was reported in 2009 in the New England Journal of Medicine.
"Tragically," Koren said, "we have found that once in 2009 and again now in three additional cases, toddlers who underwent tonsillectomies for sleep apnea and then were treated with codeine were in that ultra-rapid metabolizer group that produce too much morphine. And we have every reason to believe there have been many more such cases, which of course almost certainly occurred in the past, but before anyone knew how to uncover the reason genetically."
About 2 percent to 3 percent of children have obstructive sleep apnea syndrome, which involves structural airway issues that interfere with breathing and, in turn, sleeping. And among those whose sleep apnea is caused by enlarged tonsils, tonsillectomy is often the treatment of choice.
In 70 percent to 80 percent of cases, such surgery successfully improves the patient's sleep apnea condition. And for the children in the recent case studies -- a 3-year old girl, a 4-year-old boy and a 5-year old boy -- the surgery itself was not the problem.
Instead, because of their unidentified ability to overmetabolize codeine, their problems began with the codeine prescribed for pain management after the procedure.
After they were discharged from the hospital, lethargy and signs of heavy sedation set in, as well as other symptoms, including fever, impaired breathing and vomiting. Both boys died within 24 hours after being released from the hospital, while the girl was able to survive after readmission and mechanical ventilation support.
The researchers noted that screening tests for metabolizing mutations are available. But, many medical facilities remain unaware of the risks posed by such mutations. The tests are expensive, amounting to several hundred dollars each. As a result, such screenings are not currently a routine feature of preoperative hospital protocol.
Koren said that in Europe, physicians have long since replaced codeine with nonsteroidal anti-inflammatory drugs (NSAIDs) for post-tonsillectomy pain management. This is because, along with the metabolizing issue, one effect of codeine is to inhibit breathing, which is a problem for the roughly one-fifth of pediatric patients who will still experience sleep apnea even after surgery.
But concerns about the increased bleeding that can result from NSAID usage has complicated discussions about a similar switch in the United States.
"So this situation is by no means settled yet," Koren said. "We just want to bring attention to the fact that some kids may be exposed to an unacceptable risk, and parents should know about that risk. And perhaps request and pay for a screening before an operation. People spend money on far less important things."
Dr. Dennis Woo, an associate professor of pediatrics at the University of California, Los Angeles David Geffen School of Medicine, said that while the risk of such cases is low there is a need to raise awareness.
"In the big scheme of things this affects a very small number of kids," Woo said. "But the message to the medical profession is that you need to be careful and monitor all these kids closely."
Dr. Jerry Schreibstein, a partner with the Ear, Nose & Throat Surgeons of Western New England, stressed that it should be made clear that this "very rare and unusual complication is related to the medication and not the procedure."
Schreibstein said there are risks with any surgical procedure. "And these need to be discussed fully with a physician," he said. "But there are alternatives for pain relief, with few side effects, that can be used for children. And these should be reviewed and considered. Because I'd hate to have parents walk away with the notion that it's the tonsillectomy that caused these deaths."
More information
For more on codeine and children, visit the U.S. National Library of Medicine.
Of 127 women who had their surgeries at one Utah medical center, about half told researchers their pain control was falling short three days after leaving the hospital.
Two weeks later, 23 percent of women whose surgery had involved cutting into the abdomen were still feeling their pain wasn't controlled -- as were five percent of those who had vaginal surgery.
Even more were still in need of narcotic painkillers at the two-week mark: one-third of women who'd had abdominal surgery, and 10 percent of those who'd had vaginal surgery.
The study, reported in the journal Obstetrics & Gynecology, is a rare inquiry into how women fare during at-home recovery from gynecologic surgery.
"It's just amazingly understudied," said lead researcher Dr. Ingrid Nygaard, of the University of Utah School of Medicine in Salt Lake City.
One reason it's so important to understand what goes on during home recovery is that hospital stays are now much shorter than they were years ago.
The women in this study were discharged from the hospital an average of one or two days after surgery, depending on whether it was vaginal or abdominal. Most often, the surgery was a hysterectomy (removal of the uterus) or a procedure to correct prolapse -- when weakened tissue in the pelvis allows one or more organs to protrude into the vagina.
All of the women kept diaries at home to record their pain control after surgery.
Based on the results, Nygaard's team concluded pain relief was "suboptimal" for some women.
"I'm not advocating more narcotics," Nygaard said, referring to the powerful painkillers, like hydrocodone and oxycodone, that surgery patients typically need for a period of time after their procedures.
But, she said, there's a need for more research into how to best control women's pain after gynecologic surgery.
"We can see that it's a problem. Now we need to see what helps," Nygaard said.
For now, better patient education on pain control might make a difference, she said. Some women, for example, might find that it's best to take non-narcotic painkillers -- namely, non-steroidal anti-inflammatory drugs like ibuprofen -- "round-the-clock," and save narcotics for more-occasional use.
Attention to relieving constipation could help too, Nygaard said.
Many patients have constipation after surgery, and narcotics tend to make the problem worse. Having smaller meals, eating more fiber or getting light exercise might help get the bowels moving -- and ease any pain from the constipation, Nygaard said.
In theory, "complementary" remedies like massage or gentle stretching exercises could also help, she noted. But there's still a need for studies to show whether that's actually the case.
How do you know if your discomfort after surgery is "normal" or not?
According to Nygaard, one "red flag" is if you're still in need of narcotics after two weeks. But each patient has to talk with her own doctor about the best way to manage her pain.
One "striking" finding from the study, Nygaard noted, is that about half of the women said they still did not feel generally "recovered" six weeks after surgery.
So if you're still not feeling yourself at that point in recovery, you're not alone. "It's not abnormal to not feel fully recovered at six weeks," Nygaard said.
SOURCE: http://bit.ly/IiQLma Obstetrics & Gynecology, April 2012.
Of 127 women who had their surgeries at one Utah medical center, about half told researchers their pain control was falling short three days after leaving the hospital.
Two weeks later, 23 percent of women whose surgery had involved cutting into the abdomen were still feeling their pain wasn't controlled -- as were five percent of those who had vaginal surgery.
Even more were still in need of narcotic painkillers at the two-week mark: one-third of women who'd had abdominal surgery, and 10 percent of those who'd had vaginal surgery.
The study, reported in the journal Obstetrics & Gynecology, is a rare inquiry into how women fare during at-home recovery from gynecologic surgery.
"It's just amazingly understudied," said lead researcher Dr. Ingrid Nygaard, of the University of Utah School of Medicine in Salt Lake City.
One reason it's so important to understand what goes on during home recovery is that hospital stays are now much shorter than they were years ago.
The women in this study were discharged from the hospital an average of one or two days after surgery, depending on whether it was vaginal or abdominal. Most often, the surgery was a hysterectomy (removal of the uterus) or a procedure to correct prolapse -- when weakened tissue in the pelvis allows one or more organs to protrude into the vagina.
All of the women kept diaries at home to record their pain control after surgery.
Based on the results, Nygaard's team concluded pain relief was "suboptimal" for some women.
"I'm not advocating more narcotics," Nygaard said, referring to the powerful painkillers, like hydrocodone and oxycodone, that surgery patients typically need for a period of time after their procedures.
But, she said, there's a need for more research into how to best control women's pain after gynecologic surgery.
"We can see that it's a problem. Now we need to see what helps," Nygaard said.
For now, better patient education on pain control might make a difference, she said. Some women, for example, might find that it's best to take non-narcotic painkillers -- namely, non-steroidal anti-inflammatory drugs like ibuprofen -- "round-the-clock," and save narcotics for more-occasional use.
Attention to relieving constipation could help too, Nygaard said.
Many patients have constipation after surgery, and narcotics tend to make the problem worse. Having smaller meals, eating more fiber or getting light exercise might help get the bowels moving -- and ease any pain from the constipation, Nygaard said.
In theory, "complementary" remedies like massage or gentle stretching exercises could also help, she noted. But there's still a need for studies to show whether that's actually the case.
How do you know if your discomfort after surgery is "normal" or not?
According to Nygaard, one "red flag" is if you're still in need of narcotics after two weeks. But each patient has to talk with her own doctor about the best way to manage her pain.
One "striking" finding from the study, Nygaard noted, is that about half of the women said they still did not feel generally "recovered" six weeks after surgery.
So if you're still not feeling yourself at that point in recovery, you're not alone. "It's not abnormal to not feel fully recovered at six weeks," Nygaard said.
SOURCE: http://bit.ly/IiQLma Obstetrics & Gynecology, April 2012.
