Early Exposure to Anesthesia

Repeated exposure to anesthesia for early-life surgeries may lead to neurodevelopmental problems in children, new research suggests. A large cohort study showed that children who underwent 2 or more anesthetic/surgery episodes before the age of 2 years had a nearly 2-fold increased risk for developing learning disabilities (LDs) by their late teens compared with their counterparts who had not received anesthesia. Receiving multiple early-age exposures was also significantly associated with the need for school-based individualized educational programs (IEPs) related to speech and language impairment and for lower scores on tests of cognitive ability and academic achievemen "It's important to reassure parents that single exposures to anesthesia don't seem to be associated with a problem and that the need for repeated surgeries among young children is relatively unusual," added Dr. Flick. "This is likely to affect a relatively small number of children. Nonetheless, it's quite concerning." According to the researchers, studies of young animals have shown than most anesthetic drugs can cause neurodegeneration. However, previous research examining the link between anesthetics/surgery and cognition in human children "have been few, have relied on single outcome measures, and have not controlled for comorbidity." A population-based, matched cohort study, first published by the Mayo Clinic investigators in 2001, included 8548 children born in Rochester, Minnesota, between January 1976 and December 1982. As reported in 2009 by Medscape Medical News, the investigators examined the link between anesthesia exposure and LDs in some of these participants. However, Dr. Flick said that a criticism of that study was that it did not control for health status. "After it was published, some people said that the problem we were measuring was not anesthesia exposure but comorbidity. In other words, the kids who required multiple surgeries were not healthy. And because they were not healthy, then they had [LDs]. So the US Food and Drug Administration [FDA] asked us to do a study that would control for the effects of comorbidity." For the analysis, the investigators evaluated data on 350 of the participants who were exposed to anesthesia before the age of 2 years (68% male) and then age-matched each of these "cases" to 2 healthy controls who were not exposed (n = 700, 68% male). The controls were also matched according to "factors known to influence the incidence of LDs," including sex, mother's education, birthweight, and gestational age. Health status was determined through the use of the American Society of Anesthesiologists Physical Status and the Johns Hopkins adjusted clinical groups Case-Mix System. All children underwent the group-administered Test of Cognitive Skills and California Achievement Test, as well as the individually administered Wechsler Intelligence Scale for Children and Woodcock-Johnson Battery test for academic achievement through their schools. Study outcome measures included the need for an IEP for emotion/behavior (such as anxiety, depression, unusual behavior patterns, aggression, and impulsivity), LDs before the age of 19 years (in reading, written language, and/or mathematics), and achievement and cognition scores. Results showed that 286 of the children exposed to general anesthesia before surgery by the age of 2 years received it only once, whereas 64 were exposed more than once. The median duration of anesthetic exposure was 75 minutes, and combinations using halothane (87.5%) or nitrous oxide (88.1%) were the most frequently used anesthetic medications. Of the children exposed to anesthesia/surgery just once, 23.6% developed LDs by the age of 19 years vs 21.3% of the unexposed participants. However, 36.6% of those with multiple exposures developed LDs. After adjustment for health status, this translated into a significantly increased risk for LDs in those with the multiple exposures (hazard ratio [HR], 2.12; 95% confidence interval [CI], 1.26 - 3.54), but not for those with just 1 exposure.
"The size of the study was not sufficient to differentiate what specific type of [LD] may occur. There's a good deal of overlap; kids who have 1 type often have another type as well," explained Dr. Flick. Although exposure was not a significant factor in children receiving an IEP for emotion/behavior, multiple exposures were found to be a significant risk factor for the need for an IEP for speech/language (HR, 4.76; 95% CI, 2.48 - 9.12). "We cannot exclude the possibility that multiple exposures to anesthesia/surgery at an early age may adversely affect human neurodevelopment with lasting consequences," write the study authors. Because regional anesthesia seems to be free of risk from neurotoxicity, this option should be explored…in appropriate cases. However, most surgical procedures will require general anesthesia, and neither surgery nor anesthesia should be withheld from children in need.

Healthy Brain

A combination of brain exercises and healthy lifestyle changes can improve memory performance in healthy elderly adults, new research suggests. In a sample study of 115 participants from 2 live-in retirement communities, those who underwent a new educational program (that included memory training, physical activity, stress reduction, and better diet) showed significant improvements on a variety of measures after just 6 weeks, including word recognition and recall. Gary Small, MD, professor of aging at the University of California–Los Angeles (UCLA) and director of the UCLA Longevity Center noted that the investigators wanted to test whether this intervention improved both objective and subjective memory performance. "Subjective memory is a person's self-perception of how they're doing, and objective is how well they do on a pen-and-paper test. It was gratifying to see that this program seemed to be helping people in day-to-day memory challenges." Lead author Karen Miller, PhD, associate clinical professor at the Semel Institute for Neuroscience and Human Behavior at UCLA, said in a release that "it was exciting" to see the subjects' participation, as well as their improvements in the memory fitness program. "The study demonstrates that it's never too late to learn new skills to enhance one's life," added Dr. Miller. "Despite the effectiveness of memory training interventions in clinical trials, few community-based programs exist, and their effects have not been systematically tested," write the investigators. The new memory training program, which was created by Dr. Small and Dr. Miller, uses a standardized curriculum consisting of brain exercises for association and visual imagery, education on a "healthy brain diet" and stress reduction, physical activity, and even assigned memory exercises to be performed at home. The investigators have previously offered this program in a number of settings, including the UCLA campus and senior centers. However, this is the first time it was offered in a retirement living community, which made participation easier because "users did not have to drive to a class off-site," said Dr. Small. "Our group tends to study memory training and healthy lifestyle techniques from the point of view of first developing a program that we think is user friendly and then testing it out. However, many times there's the approach where a scientific study is done first. So a program may be proven to be effective or not, but the question is: Will people use it? And will it be adaptable to a lot of communities?" he said. For the study, 115 residents of 2 continuing-care communities in Maryland older than 62 years (mean age, 80.9 years; 79% women; 98% white) who had slight memory complaints but no diagnosis of dementia were enrolled and tested for memory performance. After testing, participants were randomly assigned either to undergo the memory fitness program, consisting of 12 twice-weekly, hour-long sessions (15 - 20 per class), or to be placed on a waiting list for the program and considered study controls. Objective cognitive measures during the pretesting phase, as well as at baseline and at study's end, assessed changes in immediate and in delayed verbal memory, retention of verbal information, memory recognition, and verbal fluency. Subjective measures evaluated domains of memory self-awareness, including frequency and severity of forgetting, mnemonics use, and retrospective functioning. Results showed that the patients who underwent the memory fitness program showed significant improvements postintervention on recognition memory for word pairs (P < .001) and retention of verbal list learning (P < .01). In addition, their retrospective functioning scores increased (P < .0001), "indicating a belief in having a better memory," write the investigators.
"These findings indicate that a 6-week healthy lifestyle program can improve both encoding and recalling of new verbal information as well as self-perception of memory ability in older adults," they write, noting that it may be generalizable to a real-world setting.
"As a community-based educational intervention, the program has the potential to meet the community's need for an affordable and sustainable memory program over time."
John Parrish, PhD, executive director of the Erickson Foundation, which oversees the retirement communities used in this study, said in a release that the foundation is now offering the program in all 16 of their communities across the country.
"The study suggests that the memory fitness program may be a cost-effective means of addressing some memory-related concerns of healthy older adults," he said.
Dr. Small said that he hopes that clinicians will see from this study and others that mild, age-related memory complaints can improve with specific training.
"There are a lot of ways to learn memory techniques. I think physicians should first ask people about their memory concerns and then try to refer them to get some help," he said.
"It's important to empower people and teach them about healthy brain lifestyle. Although there's no absolute proof that you can prevent Alzheimer's disease, we know that physical exercise and healthy diet can prevent diabetes, which is itself a major risk factor for Alzheimer's. So it all seems to tie together."

A powerful antioxidant: epigallocatechin-3-gallate – or EGCG

Researchers first discovered evidence of a “longevity gene” about 20 years ago. It’s a gene that may increase your life span. There’s a few ways you can turn on this “longevity gene.” One way is by calorie restriction.
Researchers found that giving mice a diet with very few calories significantly extended their life spans.1 Later studies found the same was true with a wide range of living creatures from single-celled organisms to plants and animals. The results showed that taking in fewer calories does turn on the longevity gene, and the organisms live longer.2
It wasn’t until recently an explanation was found. Researchers isolated a family of life-protecting genes called sirtuins (silent information protein regulators).
Under conditions of severe stress, such as starvation, the sirtuins are turned on. And they transmit signals to every cell in your body to cancel out the effects of aging.
This would be a great solution to aging … if starving were an option.
That’s where EGCG comes in.
EGCG helps switch on your longevity genes similar to restricting your eating. Mentioned in the medical journal Rejuvenation Research, “The protective effects of high-dose EGCG against oxidative stress were comparable with the effects of caloric restriction, a well-established dietary intervention that retards aging.”
EGCG can also help slow the aging process because it:
• Zaps harmful free radicals
• Supports DNA, leaving cells stable and healthy
• Helps boost your exercise capacity
• Is 25 to 100 times more potent than vitamins C and E
• Wards off the problems that come with aging

Prostate Surgery

Nearly half of men who undergo surgery for prostate cancer find themselves with greater incontinence problems and less sexual function than they anticipated, according to a new poll. Before the surgery, some men in the study had expected to have better urinary and sexual function a year after the procedure than before it -- a misbelief the researchers say is out of step with reality. As part of the new survey, 152 men undergoing radical prostatectomy filled out a questionnaire before they had surgery but after they had received counseling on the risks of the procedure. The questions asked about their expectations of urinary, bowel and sexual function a year after the surgery. About half of men expected the same function after surgery as before, but 17% anticipated better sexual function after the surgery. On a follow-up survey one year later, just 36% of the men said their expectations for urinary function matched the true outcomes, and 40% said their expectations for sexual function matched reality. Daniela Wittmann, the sexual health coordinator in the urology department at the University of Michigan and the lead author on the study, noted it's hard to predict how likely a patient is to recover his urinary and sexual function. "We can only (inform them) in terms of overall statistics, we can't predict for the individual man" how well he will recover, Wittmann said, "which means that, if in doubt, people tend towards being hopeful and optimistic." One recent study showed that, one year after surgery, only one out of four men recovered the ability to have intercourse. (See Reuters Health report, April 21, 2011.) Another research team recently found that some degree of incontinence was common, too, although men tended not to be significantly bothered by it. (See Reuters Health report, June 3, 2011.) Dr. Tracey Krupski of the University of Virginia, who wrote an editorial published along with the study online June 15th in the Journal of Urology, said men's unrealistic expectations can be a double-edged sword. On the one side, she told Reuters Health, optimism is known to help people heal, but on the other side, "it may ultimately lead to disappointment when adjusting to a long term disability." A different study, published along with Wittman's, found that when men were educated about the risks and benefits of nerve sparing prostatectomy, and then given the power to choose the type of procedure, they were likely to make choices similar to their surgeons'. In this study, by Dr. Hugh Lavery and colleagues at Ohio State University, the men had both a routine pre-operative counseling session and a separate appointment with a surgeon to discuss the risks and benefits of each procedure. Dr. Krupski said additional pre-operative visits would be beneficial, but are generally not covered by insurance plans. She said that a network of men who have been through the experience and can support new cancer patients might help them understand the realities of life after surgery. Wittmann said that involving patients' partners is also vital to successfully regaining sexual relationships. "Sex is a partnered activity for most people. The partner can be very effective as part of an intimate team recovering from the side effects of this surgery," she told Reuters Health. The study did not examine whether men would make a different treatment decision given their hindsight after the surgery. Wittmann said she thinks only a small proportion of men would choose not to have surgery if they fully understood the potential for erectile dysfunction, because there are other cancer-related reasons that drive their decision.

Chronic NSAID in Elderly

Older patients with hypertension and coronary artery disease who use nonsteroidal anti-inflammatory drugs (NSAIDs) chronically for pain are at significantly increased risk of cardiovascular events, a new post hoc analysis from the International Verapamil-Trandolapril Study (INVEST) demonstrates [1]. The research is published in the July 2011 issue of the American Journal of Medicine. "We found a significant increase in adverse cardiovascular outcomes, primary driven by an increase in cardiovascular mortality," lead author Dr Anthony A Bavry (University of Florida, Gainesville) told heartwire . "This is not the first study to show there is potential harm with these agents, but I think it further solidifies that concern." He says the observational study, conducted within the hypertension trial INVEST, is particularly relevant to everyday practice because the patients included were typical of those seen in internal-medicine, geriatric, and cardiology clinics--they were older, with hypertension and clinically stable CAD. Bavry and colleagues were not able to differentiate between NSAIDs in the study--most people were taking ibuprofen, naproxen, or celecoxib--and he says until further work is done, he considers the risks of NSAIDs "a class effect," and their use should be avoided wherever possible. However, "Patients should not terminate these medicines on their own," he says. "They should have a discussion with their physician. When I see patients like these taking NSAIDs I will have an informed discussion with them and tell them there is evidence that these agents may be associated with harm. I try to get them to switch to an alternative agent, such as acetaminophen, or if that's not possible I at least try to get them to reduce the dose of NSAID or the frequency of dosing. But ultimately, it's up to them if this potential risk is worth taking depending upon the indication for their use." Within the large cohort of more than 22 000 patients in INVEST, Bavry and colleagues identified patients who reported taking NSAIDs at every follow-up visit and termed them chronic users (n=882). Most often, patients were taking these agents for conditions such as rheumatoid arthritis, osteoarthritis, and lower back pain, Bavry said. They compared the chronic NSAID users with those who only intermittently (n=7286) or never (n=14 408) used NSAIDs over an average of 2.7 years and adjusted the findings for potential confounders. The primary outcome--a composite of all-cause death, nonfatal MI, or nonfatal stroke--occurred at a rate of 4.4 events per 100 patient-years in the chronic-NSAID group vs 3.7 events per 100 patient-years in the nonchronic group (adjusted hazard ratio 1.47; p=0.0003). As noted by Bavry, the end point was primarily driven by a more than doubling in the risk of death from CV causes in the chronic-NSAID group compared with never or infrequent users (adjusted HR 2.26; p<0.0001). The association did not appear to be due to elevated blood pressure, the researchers say, because chronic NSAID users actually had slightly lower on-treatment BP over the follow-up period. They note that a recent American Geriatrics Society panel on the treatment of chronic pain in the elderly recommends acetaminophen as a first-line agent and suggests that nonselective NSAIDs or COX-2 inhibitors be used only with extreme caution. "Our findings support this recommendation," they state.

H1N1 Flu Vaccine

The risk for Guillain-Barré syndrome is not increased after use of adjuvanted pandemic influenza (H1N1) 2009 vaccine, but the upper limit does not exclude a potential increase in risk up to 2.7-fold, according to the results of a multinational case-control study reported online July 12 in the BMJ. "A concern with the pandemic influenza A (H1N1) 2009 vaccine was the possible occurrence of neuroimmunological adverse events, including Guillain-Barré syndrome," write Jeanne Dieleman, senior pharmacoepidemiologist from the Department of Medical Informatics at Erasmus University Medical Center in Rotterdam, the Netherlands, and colleagues. "A more than sevenfold increased risk of Guillain-Barré syndrome was observed with the swine origin influenza A (H1N1) subtype A/NJ/76 vaccine applied in the United States in 1976, when the vaccination campaign had to be discontinued abruptly. Subsequent prospective surveillance studies and retrospective epidemiological studies on seasonal influenza vaccines used in 1978, 1979, 1980, 1992, 1993, and beyond showed no or modest increases (up to twofold) in risk of Guillain-Barré syndrome." The goal of this case-control study, performed in 5 European countries, was to evaluate the relationship between pandemic influenza A (H1N1) 2009 vaccine and Guillain-Barré syndrome. Patients (n = 104) with Guillain-Barré syndrome or its variant Miller-Fisher syndrome were classified according to the Brighton Collaboration definition and matched to 1 or more control participants by age, sex, index date, and country. The primary study endpoint was the relative risk estimate for Guillain-Barré syndrome after vaccination with pandemic influenza vaccine. Countries varied substantially in case recruitment and vaccine coverage. Adjuvanted vaccines (Pandemrix and Focetria) were used most commonly. For all countries, the unadjusted pooled risk estimate was 2.8 (95% confidence interval [CI], 1.3 - 6.0). However, vaccination with pandemic influenza vaccine was not associated with a heightened risk for Guillain-Barré syndrome after adjustment for influenza-like illness or upper respiratory tract infection and seasonal influenza vaccination (adjusted odds ratio [OR], 1.0; 95% CI, 0.3 - 2.7). On the basis of the 95% CI, the absolute effect of vaccination could vary from 1 less case of Guillain-Barré syndrome within 6 weeks after vaccination in 1 million people, to up to 3 excess cases. "The risk of occurrence of Guillain-Barré syndrome is not increased after pandemic influenza vaccine, although the upper limit does not exclude a potential increase in risk up to 2.7-fold or three excess cases per one million vaccinated people," the study authors write. "When assessing the association between pandemic influenza vaccines and Guillain-Barré syndrome it is important to account for the effects of influenza-like illness/upper respiratory tract infection, seasonal influenza vaccination, and calendar time." Study limitations include the fact that the study was performed in a pandemic situation; under-reporting of cases in the Netherlands; substantial delays in inclusion of cases in Sweden and France; possible residual confounding; and some missing information on vaccination, mostly in control participants. In an accompanying editorial, Frank DeStefano, from the Immunization Safety Office (MS-D26), Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention in Atlanta, Georgia, and colleagues discuss the safety of adjuvanted pandemic influenza A (H1N1) 2009 vaccines. "Although pandemic influenza A (H1N1) 2009 monovalent vaccines are no longer being used, data on their safety are relevant to current clinical practice because the H1N1 strain in the pandemic vaccine has been incorporated into the currently recommended trivalent seasonal vaccine," the editorialists write. "Most of the trivalent seasonal flu vaccines currently used in Europe do not contain an adjuvant, and no adjuvanted flu vaccines are used in the US. Nonetheless, the safety findings on adjuvanted flu vaccines will be important if such vaccines become more common in the future, whether in seasonal flu vaccines or for the next pandemic."
This study was funded by the European Centre for Disease Prevention and Control. Some of the study authors have disclosed various financial relationships with GSK, SPMSD, Wyeth/Pfizer, Boehringer, Lilly, AstraZeneca, and/or Baxter. The editorialists have disclosed no relevant financial relationships.

Your memory

As we age, most of us will find our short-term memory and ability to process new information “not what it used to be.” This is the cognitive equivalent of creaky knees , an inconvenient reminder that we’re getting older. Dementia, though, is something different. With dementia, multiple areas of thinking are compromised and the deficits are likely to get worse. By definition, dementia means memory and other cognitive areas deteriorate to the point that everyday tasks and decisions become difficult, and sometimes impossible. The causes of dementia are many, but in this country, Alzheimer’s disease is responsible for between 60% and 80% of dementia cases. Are there ways to avoid Alzheimer’s disease? Not according to the 2010 National Institutes of Health conference on preventing Alzheimer’s disease and cognitive decline. The group’s consensus statement said there is no evidence of “even moderate scientific quality” that nutritional supplements, herbal preparations, diet, or social and economic factors can reduce the chances of getting Alzheimer’s. Interventions intended to delay the onset of Alzheimer’s didn’t fare much better. In terms of staying sharp (versus developing dementia) as we get older, the outlook was a little better, according to the group. Diet and nutritional supplements still didn’t pass muster, and no medication was billed as preventing cognitive decline, but physical activity and cognitive “engagement” seem to hold some promise. Why the difference? For one thing, by the time people are diagnosed with Alzheimer’s disease (even mild or moderate cases), there may already be too much brain damage for exercise and other interventions to do much good. In some studies depression has been associated with mild cognitive impairment and cognitive decline. Successful treatment of depression may not alter Alzheimer’s, but the aspects of a person’s thinking clouded by depression may improve with treatment. A healthy mind relies on a healthy body. Elevated blood pressure and cholesterol, diabetes, excess weight, smoking, and a sedentary lifestyle all contribute to cognitive declines. Working to stay healthy helps you stay sharp. Stop smoking. In 2010, a National Institutes of Health panel noted that current smokers were 41% more likely to exhibit cognitive declines than former smokers or nonsmokers. Challenge your mind. Engaging in challenging board games, reading, working crossword puzzles, playing a musical instrument, and acquiring new skills may help keep your mind fit. These activities seem to expand the web of neuronal connections in the brain and help keep neurons nimble and alive. Challenge your body. Brain cells crave a steady diet of oxygen. Physically active people lower their risk for developing dementia and are more likely to stay mentally active. Get your rest. Too little sleep can affect memory. Six hours may be the minimum needed, although researchers testing college students found those who had eight hours were better able to learn new skills. Watch your weight. Staying within a normal weight range lowers your risk for illnesses such as diabetes, hypertension, metabolic syndrome, and stroke, which can compromise the brain to varying degrees. Check with your doctor. Are there any factors — such as medication side effects, vitamin deficiencies, depression, or chronic conditions — that could be better managed to help you stay as mentally sharp as possible? Discuss these issues with your doctor.