Thursday, January 28, 2010

Whole Diet May Ward Off Depression and Anxiety

From Medscape Medical News
Caroline Cassels

January 15, 2010 — A traditional or whole diet characterized by vegetables, fruit, whole grains, and high-quality meat and fish may help prevent mental illness — specifically, depression and anxiety. Conversely, a Western diet high in refined or processed foods and saturated fats may increase the risk of depression, new research suggests.

A large, cross-sectional study conducted by investigators at the University of Melbourne in Australia shows that women who regularly consume a so-called traditional diet were more than 30% less likely to have major depression, dysthymia, and anxiety disorders compared with their counterparts who consume a Western diet. In addition, the Western diet was associated with a 50% increased likelihood of depression.

"Simply put, if you habitually eat a healthy diet that includes fruit, vegetables, whole grains, and high-quality lean meat, then you may cut your risk of depression and anxiety," principal investigator Felice Jacka, PhD, told Medscape Psychiatry.

But one caveat here, said Dr. Jacka, is high-quality meat, which is difficult to come by in the United States. This is because most of the cattle in North America are raised — from birth to death — in feed lots, where they are fed a corn-based diet.

This method of raising cattle may have a "profound impact" on the quality of the meat, said Dr. Jacka. "It increases saturated fat and decreases very important good fatty acids. Whereas in Australia, red meat, such as beef and lamb, comes from pasture-raised animals, so it has a much healthier fatty acid profile," she said.

One of the findings that was not published in the article is that people who consumed more beef or lamb within Australia's recommended dietary guidelines (not more than 4 times per week) were less likely to have depression and anxiety.

According to Dr. Jacka, recent Australian studies show that a good proportion of individuals' dietary intake of omega-3 fatty acids actually comes from red meat.

"We've traditionally thought of omega-3s as only coming from fatty fish, but actually good-quality red meat, that is, naturally raised, has very good levels of omega-3 fatty acids, whereas red meat that comes from feedlots tends to be higher in omega-6 fatty acids — a fatty acid profile that is far less healthy and may in fact be associated with more mental health problems," she said.

The study was published online January 4 in the American Journal of Psychiatry.

Lack of Evidence

According to the investigators, unlike many medical conditions, most notably cardiovascular disease, psychiatric disorders lack evidence-based primary prevention and treatment strategies based on dietary modification. Previous studies that have looked at a potential link between diet and depressive illness have focused on individual nutrients or food groups, but they note that none has looked at the impact of a whole diet.

However, they add, that limiting studies to individual nutrients or foods may provide an incomplete picture of the relationship between diet and mental health. "We don't eat individual nutrients, we eat a whole diet," said Dr. Jacka.

"Up until very recently there really haven't been any studies that have looked at the impact of whole diet on common mental disorders, which is really interesting since over the past 10 years or so there's been a real burgeoning in the literature regarding the impact of diet on cardiovascular disease, diabetes, and the metabolic syndrome," she added.

Interestingly, many of the same underlying mechanisms that influence some of these conditions, such as immune dysfunction and subsequent inflammation, have also been shown to influence depression, Dr. Jacka pointed out.

To assess the association between individuals' regular diet and the prevalence of mental health disorders, the investigators used data from the Geelong Osteoporosis Study, a large epidemiologic study.

Unexpected Finding

The study included 1046 women ages 20 to 93 years. Participants' diets were assessed using the Cancer Council Victoria dietary questionnaire, a comprehensive food frequency tool that reports on 74 foods and 6 alcoholic beverages during the preceding 12 months on a 10-point frequency scale.

To diagnose current mental disorders, participants were assessed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) Research Version, Non-Patient Edition. In addition, psychological symptoms were measured with the 12-item version of the General Health Questionnaire (GHQ-12). Scores on the GHQ-12, major depressive disorder, dysthymia, and anxiety disorders were the study's primary outcomes.

After adjustment for age, socioeconomic status, education, and health behaviors, the results revealed that a traditional or whole food diet was associated with a reduction in depression and anxiety risk, with respective odds ratios (ORs) of 0.65 (95% confidence interval [CI], 0.43 – 0.98; P < .05) and 0.68 (95% CI, 0.47 – 0.99; P < .05).

In contrast, those who consumed a Western diet of processed or fried foods, refined grains, sugary products, and beer had higher GHQ-12 scores. Those who scored higher on the Western-type or processed food diet tended to be approximately 50% more like to have depression (OR, 1.52; 95% CI, 0.96 – 2.41). However the researchers found no link between the Western diet and an increased risk of anxiety.

In an unexpected finding, the researchers also found a tendency for a so-called modern diet — which consisted of foods such as fruits, salads, fish, tofu, beans, nuts, yogurt, and red wine — was associated with a higher, rather than lower, likelihood for depression among younger, more educated women.

The researchers speculate that this may be due to reverse causality. "We think these women may have been attempting to improve their depressive symptoms by consuming a healthier diet," said Dr. Jacka.

Growing Public Awareness

Dr. Jacka pointed out that recent research conducted in primary care practices in Australia show that up to 30% of individuals with depression change their dietary habits as a way of improving their depressive symptoms, a finding she views as an indication of a growing public awareness about the potential relationship between diet and mental health.

Although primary care physicians often encourage their patients to improve their diets and increase their exercise level to help improve cardiovascular risk factors, the field of psychiatry "is just not there yet," said Dr. Jacka.

In large part, she said, this is due to a lack of evidence to support the hypothesis that a healthy diet can help prevent and/or treat mental illness, but the tide is turning, said Dr. Jacka. Two recent studies published late in 2009 [Br J Psychiatry. 2009;195:408-413, Arch Gen Psychiatry. 2009;66:1090-1098] also support the link between diet and mental health and depression risk.

"The good thing about these studies is that they were able to rule out reverse causality as an explanation for their findings. In other words, they found if you had a poorer-quality diet you were more likely to develop depression over the ensuing years, which supports what we found in our cross-sectional study, but depression itself did not lead to a poorer diet," said Dr. Jacka.

Public Policy Implications?

"The data are fairly consistent, and I do think it's time we started a conversation about public health messages about the potential role of diet in prevention as well as the treatment of depression particularly and mental health in general," said Dr. Jacka.

She added that her group currently has a paper in press investigating a link between diet and depression in a cohort of adolescents that shows "a very clear" relationship between diet quality and the presence of depression.

"My feeling is that the negative impact of the processed food industry is really going to make itself felt [in terms of the physical and mental health] on the younger generation," she said. She pointed out that nutrition has an impact on the developing brain, adding that 75% of psychiatric illnesses begin before the age of 25 years.

"I believe that these dietary studies support the hypothesis that diet is causally related to depression, but we need to do more research to be sure that these just aren't chance findings. We also need to test whether [dietary] interventions in the early stages of depression may be of use," said Dr. Jacka.

Diet's 'Profound Impact'

Commenting on the study for Medscape Psychiatry, Fernando Gómez-Pinilla, PhD, at University of California Los Angeles' Neurotrophic Research Laboratory, said the study is impressive and makes an important contribution to the literature.

"This is a very well-controlled study and demonstrates the importance of a whole diet, not only on physical health, but also mental health," Dr. Gómez-Pinilla said.

Animal research by Dr. Gómez-Pinilla and colleagues has demonstrated that diet has a significant and rapid impact on brain-derived neurotrophic factor (BDNF), which plays a key role in psychiatric illness in general and depression in particular.

Boosting levels of neurotrophins appears to be one of the main ways antidepressant medications work. Dr. Gómez-Pinilla 's group has shown that feeding rats a Western diet high in refined sugars and saturated fats has a very immediate and obvious impact in reducing BDNF level, which has a resulting impact on learning and memory.

Like Dr. Jacka, Dr. Gómez-Pinilla said the psychiatric community has been somewhat reticent about advocating diet as a preventive and/or treatment strategy for mental illness. However, he said, this research, as well as other recent studies, may help convince clinicians about the "profound impact" diet can have on mood and psychiatric disorders in general and perhaps help shift clinical practice.

Dr. Jacka reports she has receive travel funding from Sanof-Synthelabo Australia and Organon and research support from an unrestricted educational grant from Eli Lilly. Disclosures of the other authors can be found in the original article.

Am J Psychiatry. Published online January 4, 2010.

Same Weight Loss, Better BP With Low-Carb Diet vs Drug/Diet Combo

From Heartwire
Shelley Wood

January 25, 2010 (Durham, North Carolina) — A new randomized trial comparing a low-carbohydrate diet with a low-fat diet in combination with the weight-loss drug orlistat has found that both strategies produced meaningful weight loss among hospital outpatients over a one-year period [1]. Strikingly, however, the low-carb diet appeared to produce significant improvements in blood pressure.

According to Dr William S Yancy Jr (Duke University, Durham, NC), lead author on the study, this is the first time the low-carb diet has been pitted against a diet drug in combination with a different diet. It is also one of the first studies to compare weight-loss strategies in patients who also have other known medical problems, including high blood pressure, diabetes, arthritis, etc.

Yancy et al's findings are published in the January 25, 2010 issue of the Archives of Internal Medicine.

Almost 10% Weight Loss at One Year

Yancy et al's study randomized 146 overweight or obese outpatients (mean age 52, mean body-mass index [BMI] 39.3) to either a low-carbohydrate, ketogenic diet, or to orlistat (120 mg, three times daily) and a low-fat diet over 48 weeks, with regular group meetings to boost diet adherence. At the end of the study period, weight loss was similar in both groups, at roughly 10% (approximately 20 to 25 pounds). Of note, almost 80% of the low-carb group and almost 90% of the orlistat/low-fat group completed the full 48-week follow-up.

Improvements in HDL and triglycerides were seen in both groups, LDL levels improved in the orlistat/low-fat diet group only, while glucose, insulin, and HbA1c levels improved in the low-carb group only, although none of these differences were statistically meaningful. By contrast, both systolic and diastolic blood-pressure levels declined in the low-carb group only, a statistically significant difference between weight-loss groups.

"It's not surprising that the blood pressure improved," Yancy told heartwire , adding that improvements in blood pressure are common in weight-loss trials. "But it was surprising that, with similar weight loss, blood pressure would improve more in one group than the other."

While there are a number of explanations for the blood-pressure differences between weight-loss strategies, Yancy speculated that it might be related to the known diuretic effect of low-carb diets.

"We've looked at that in the past, and it seems to occur in the first couple weeks of the diet and doesn't seem to be a big factor after that, but that could contribute to the differences seen here. The other thing is that low-carb diets are thought to reduce insulin levels more so than a high-carb diet. There are several different mechanisms that insulin has with the vascular system that might cause increased blood pressure, so if you decrease insulin your blood pressure might decrease as well."

No Significant Differences in Lipid Changes

Other low-carb diet studies have also reported improvements in lipid parameters compared with low-fat diets: something that was not seen in the current study to a statistically significant degree. Yancy attributes this in part to an aggressive attempt on the part of investigators to include as many patients as possible at the 48-week follow-up.

"A big criticism of other weight-loss trials is there are a lot of lost or missing data," he explained. "We tried to avoid that as much as possible, and as a result, some of these folks who came back for their final measurements who hadn't really been following their diets kind of watered down the results."

For example, in the paper, the authors report differences in heart-disease risk factors at interim time points and note that, out to 36 weeks, the two interventions "appeared to have differential effects on fasting serum lipid and lipoprotein levels over the first 36 weeks," but that "these differences converged by 48 weeks."

In another important finding, Yancy et al point out that while a small number of study participants initiated hypertension or diabetes medications over the course of the study in both diet groups, a much higher number actually decreased or discontinued their dosages, with a higher proportion of patients discontinuing or lowering their dosages in the low-carb group.

Referring to the blood-pressure effects of the low-carb diet, Yancy pointed out that investigators "don't really know the full effect of the diet intervention because patients were actually taking less medication."

Options for Patients

The key message from the paper is not that one diet is superior to another, Yancy concluded. "Different interventions appeal to different people," he told heartwire . "We have a big weight problem in our society, and this study gives us two different options, both of which worked quite well. And if you happen to have blood-pressure problems and you are trying to kill two birds with one stone, the low-carb option might be a better option than the orlistat option."

Of note, he added, orlistat is not associated with increases blood pressure, although other diet drugs are, including sibutramine, for which the FDA recently released an updated warning on CVD risks.

Yancy, as well as second author Dr Eric C Westman (Duke University Medical Center) disclosed having received clinical research grants from the Robert C Atkins Foundation.


Guidance for Relief Workers and Others Traveling to Haiti for Earthquake Response

Psychological/Emotional Difficulties

As a first responder or relief worker, you may encounter extremely stressful situations, such as witnessing a tremendous loss of life, serious injuries, missing and separated families, and destruction of whole areas. It is important to recognize that these experiences may cause you psychological or emotional difficulties.

Normal Reactions to a Disaster Event

Profound sadness, grief, and anger are common.
You may not want to leave the scene until the work is finished.
You will likely try to override stress and fatigue with dedication and commitment.
You may deny the need for rest and recovery time.
Ways to Help Manage Your Stress
Limit on-duty work time to no more than 12 hours per day.
Rotate work assignments between high stress and lower stress functions.
Drink plenty of water and eat healthy snacks and other energy foods.
Take frequent, brief breaks from the scene when you are able.
Keep an object of comfort with you such as a family photo, favorite music, or religious material.
Stay in touch with family and friends.
Pair up with another responder so that you can monitor one another's stress.
To learn about mental health resources, see:

Mental Health in Aid Workers Fact Sheet

Self-Care Tips for Stress
Download Podcasts on stress management for first responders: Stress Management for Emergency Responders - What Responders Can Do
NIOSH: Traumatic Incident Stress: Information for Emergency Response Workers
NIOSH: Estrés por sucesos traumáticos: Información para el personal de Emergencia
After You Come Home
If you are not feeling well, you should see your doctor and mention that you have recently returned from response and relief work in Haiti. Also tell your doctor if you were bitten or scratched by an animal while traveling.

Symptoms of malaria can develop up to one year after travel, so be alert for fever or flu-like symptoms.

Approximately one-third of aid workers report depression shortly after returning home, and more than half of returned aid workers have reported feeling predominantly negative emotions on returning home, even though many reported that their time overseas was positive and fulfilling. You might want to see a professional counselor to help you adjust back into your home environment.

More Information

Haiti destination page on the Travelers' Health website
Haiti country specific information from the US Department of State
United Nations Relief Web
Page last reviewed: January 16, 2010
Page last updated: January 16, 2010
Page created: January 14, 2010
Division of Global Migration and Quarantine National Center for Preparedness, Detection, and Control of Infectious Diseases
Centers for Disease Control and Prevention 1600 Clifton Rd. Atlanta, GA 30333, USA
800-CDC-INFO (800-232-4636) TTY: (888) 232-6348, 24 Hours/Every Day -

Sunday, January 24, 2010

Iraq Cabinet Approves Draft Law to Protect Doctors

From Reuters Health Information

BAGHDAD (Reuters) Jan 18 - Iraqi doctors would be allowed to carry weapons under a law approved by the cabinet on Sunday to help protect physicians subjected to kidnapping, murder and tribal demands for blood money from relatives of dead patients.

The law, which must still be passed by parliament, could help prevent doctors from fleeing war-shattered Iraq and encourage those abroad to come back.

Many doctors, particularly in the south, complain about a tribal tradition where the family of a patient who dies while in a doctor's care demands payment.

The draft law foresees a possible prison sentence of three years or a fine of no less than 10 million Iraqi dinars (around $8,000) against anyone who demands a tribal settlement from a doctor.

"The draft law is a gesture from the Iraqi government for doctors and specialists... to protect them from attacks and the tribal demands resulting from their medical work," government spokesman Ali al-Dabbagh said in a statement.

Doctors fled Iraq by the thousands during the explosion of violence between majority Shi'ites and minority Sunni Arabs in the years following the 2003 U.S.-led invasion that toppled Saddam Hussein.

Considered among the elite of Iraqi society, medical specialists became a target for insurgents, militias and kidnappers in search of rich ransoms. Hundreds have been killed since 2003.

The law would also allow the government to lift Iraq's usual retirement age of 63 and let doctors work until 70 if they are needed, and to build residential compounds for physicians near hospitals and other health institutions.

Green Vegetables Protect Smokers From Genetic Changes Associated With Lung Cancer Risk

From Medscape Medical News
Jacquelyn K. Beals, PhD

January 19, 2010 — A questionnaire on food intake combined with an analysis of DNA from the sputum of smokers shows that intake of leafy green vegetables, folate, and multivitamins protects smokers against the methylation of several genes often silenced in lung cancer. Methylation, the addition of methyl groups to cytosine bases of DNA, prevents a gene from being transcribed, essentially blocking its function.

Published in the January 15 issue of Cancer Research, this study leads to new conceptions of lung cancer prevention based on the influence of diet on the epigenome of patients' respiratory epithelium.

Although lung cancer most frequently results from the carcinogenic effects of tobacco, changes leading to cancer occur over the course of several decades. The 8 genes analyzed in this study are frequently "turned off" in lung cancer by promoter methylation, associated in previous studies with greater risk of developing the disease. Thus, higher methylation levels are associated with increased risk.

Of these 8 genes, 7 "are tumor suppressor genes, and the eighth is a gene involved in DNA repair," said senior author Steven A. Belinsky, PhD, director of the Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico, in his email to Medscape Oncology. "Most notably, one of the genes is p16, a critical gene for regulating cell cycle control."

Participants were drawn from the Lovelace Smokers Cohort. Cohort members are former and current smokers between 40 and 75 years old with at least 15 pack-years of smoking history. Individuals from the cohort filled out the Harvard University Food Frequency Questionnaire Dietary Assessment form to indicate their intake frequency of approximately 150 food items. After excluding individuals with caloric intakes exceeding sex-specific ranges, 1101 participants remained.

Foods with established or suspected connections with methylation or lung cancer were considered most carefully. The assessments included animal fat; vitamins C, E, and B9 (folate), among others; alcohol; cod liver oil; and multivitamins. Foods analyzed included 6 groups of potential relevance: yellow vegetables, leafy green vegetables (a major source of folate), cruciferous vegetables, tomatoes, fruit, and red or processed meats. The hypothesis was that animal fat and red and processed meats would be associated with greater methylation, whereas fruit, vegetable, and vitamin intake would be associated with lower methylation status.

The 8 genes — p16, MGMT, DAPK, RASSF1A, PAX5α, PAX5β, GATA4, and GATA5 — had previously established associations with the risk for lung cancer. DNA was obtained from cells isolated from each participant's sputum samples, and polymerase chain reaction was used to identify methylated forms of the genes of interest. Patients were "scored" by the number of methylated genes and were grouped into those having fewer than 2 genes methylated (low) and those with 2 or more genes methylated (high).

Significant Links Between Methylation Status and Dietary Variables

Statistical analysis found significant associations between methylation status and specific dietary variables. Intake of leafy green vegetables was associated with decreased risk for high methylation (odds ratio [OR], .84; 95% confidence interval [CI], .74 - .93; P < .001). Folate intake yielded similar results (OR, .84; 95% CI, .72 - .99; P = .04). Even current multivitamin use was significantly associated with methylation status: current use (OR, .57; 95% CI, .40 - .83; P = .01).

"There was a dose response with consumption of vegetables and sustained vitamin use, and increased duration was associated with better protection," observed Dr. Belinsky. "Multivitamins and leafy green vegetables have things other than folate, although that is the common link, and...the amount of folate varies by multivitamin and vegetable, so I don't know that there is a simple yes or no answer [regarding dose dependence]," he said.

The report summarizes their findings: "Green leafy vegetables were the only food item in this analysis to exhibit protection against methylation status." In addition, the use of multivitamins, which supply many of the same substances as leafy green vegetables, had a significant protective effect.

Should all smokers be told to increase their intake of spinach and kale? "Our findings certainly support yes for smokers," said Dr. Belinsky. "Most cancers arise through inactivating genes by methylation, so I don't think consumption of leafy green vegetables and a multivitamin would do anything negative, and it could help." He noted, however, that further studies are needed to validate their findings.

"Adequate folate intake is essential, because folate is a crucial cofactor in one-carbon metabolism and has an important role in DNA synthesis and replication," said Margaret R. Spitz, MD, MPH, clinical professor of epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, in her email replying to Medscape Oncology's request for independent commentary. "Also remember that folate deficiency is associated established risk factor for cardiovascular disease.

"I do not think we can make any clinical recommendations yet," said Dr. Spitz. With folate-fortified foods in the United States, many adults achieve their recommended allowance of folate from those sources alone. Nevertheless, "All smokers should be advised to quit, and everyone should follow common-sense dietary principles," Dr. Spitz concluded.

Dr. Belinsky is a consultant and has licensed intellectual property with Oncomethylome Sciences. Dr. Spitz has disclosed no relevant financial relationships.

Cancer Res. 2010;70(2):568-574. Abstract


Friday, January 22, 2010

High-Intensity Aerobics Improves Cognitive Performance in MCI, Especially for Women

From Medscape Medical News
Pam Harrison

January 21, 2010 — A high-intensity, supervised aerobic exercise program improves cognitive performance in older adults with mild cognitive impairment (MCI), a new study suggests. The effects are most pronounced in women despite comparable gains in cardiorespiratory fitness and body fat reduction in both sexes.

The results, published in the January issue of the Archives of Neurology, showed that a 6-month aerobic exercise program improved performance on multiple tests of executive function in women with MCI. The same exercise regimen also improved insulin sensitivity and reduced stress hormones in women but had much less effect in men.

"What we know is that generally with age or disease, we use glucose less efficiently and then we see cognitive problems," Laura Baker, PhD, University of Washington School of Medicine, Seattle, told Medscape Neurology. "So if we can increase the efficacy of glucose metabolism, we may be improving the efficacy with which glucose gets to the brain and therefore improve cognition. This happened for women but not for men."

Aerobics vs Stretching

For the study, 33 adults, of whom 17 were women, with amnestic MCI were randomized to either a high-intensity aerobic exercise program or a stretching control group. "The aerobic group exercised under the supervision of a fitness trainer at 75% to 85% of heart rate reserve for 45 to 60 minutes per day, 4 days per week for 6 months," the investigators note.

The control group followed the same schedule during which they performed supervised stretching activities but maintained their heart rate at or below 50% of their heart rate reserve. Glucometabolic and treadmill tests were done before and after the study on all participants, and blood was collected and the cognitive test administered at baseline and again at months 3 and 6.

The first 8 sessions were supervised by the trainer, and thereafter, the trainer supervised 1 session per week per participant. "Six months of controlled aerobic exercise vs stretching improved cardiorespiratory fitness indexed by exercise treadmill test measures of VO2 peak ... treadmill grade ... and treadmill time to exhaustion," the investigators report.

The same aerobic regimen also improved executive control processes of multitasking, cognitive flexibility, information processing efficiency, and selective attention. When sex was included in the model as a predictor variable, they write, "a significant interaction indicated that this treatment effect differed for men and women, [whereas] for women, increasing VO2 peak was associated with improved executive function."

Favorable effects of aerobic exercise were also apparent for Symbol-Digit Modalities and Verbal Fluency, measures of cognitive function, with analyses again revealing that the effect size was larger for women than for men on both tasks. Sex differences were also observed on the Stroop test, with aerobic exercise having no effect in men. The aerobic group was also faster to complete the Trails B test compared with baseline than the stretching control group; here, the effect was similar for women and men.

"Aerobic exercise was [also] associated with sex-specific improvements in glucoregulation and insulin sensitivity," the study authors note, "and for women, 6-month changes in insulin sensitivity predicted VO2 peak and executive function."

A sex-specific effect of aerobic exercise was again observed for plasma cortisol levels, increasing for women in the stretching control group over the study interval but not for women in the aerobic group. In men, cortisol levels decreased over time for those in the stretching group, whereas they remained stable for the aerobic group.

Aerobic exercise also reduced brain-derived neurotrophic factor (BDNF) in women but not in men.

Initiate and Organize

As Dr. Baker observes, the first cognitive ability to be affected in patients with MCI is their ability to initiate and to organize. "Generally, it's the little things like cleaning up or finishing off projects, and exercise is no different than any other task." Patients with MCI are also afraid to exercise, and they have no confidence that if they exercise they might do it right.

Thus, these people need help to "get the ball rolling," she adds. Once a structure is in place, however, and they get started on an exercise regimen, "they are really fine." Indeed, after the first 6 weeks of their exercise regimen during which patients were worked up to their target heart rate very slowly, "we were exercising them at a pretty high level, and by week 6, many of them were going over their target [heart rate]," Dr. Baker notes.

"Evidence already shows that there is a benefit from exercise for normal older adults with no specific memory problems, and our hope is that prolonged exercise may slow progression in cognitive decline in patients with MCI because even if we can't reverse cognitive decline altogether, if we can give someone a better quality of life for many months, that would be a huge accomplishment," Dr. Baker observes.

In a related but separate study published in the same issue of Archives of Neurology by Yonas Geda, MD, and colleagues at the Mayo Clinic in Rochester, Minnesota, moderate exercise done during mid or even later in life reduced the risk of MCI by 39% in adults with normal cognitive function at baseline.

Findings in this study were consistent among both men and women.

Important Gap

Art Kramer, PhD, University of Illinois at Urbana-Champaign, told Medscape Neurology that the study begins to fill an important gap toward a better understanding of the potential impact exercise may have in MCI patients. "There are many exercise studies with relatively healthy older individuals but very few with MCI or Alzheimer's disease, and rigorously controlled trials are important."

In their own meta-analysis of fitness and cognition (Psychol Sci. 2003;14:125-130), Dr. Kramer and colleagues also found that fitness positively affects cognition.

"Consistent across the many studies, the effect of exercise was larger for women than it is for men," he adds. On the other hand, the current study, although well controlled, still involves only a small sample and perhaps the lack of effect from aerobic exercise in men may be explained by the limited numbers of patients in the study overall.

"As the authors themselves suggest, this is preliminary data and it needs to be replicated ideally in a larger randomized controlled trial of MCI patients and perhaps even those further along with Alzheimer's disease," Dr. Kramer observes. Still, he adds, "the study attempts to relate the effects of exercise on cortisol and BDNF to animal work in which we have more physiological and neurological measures, which is a good step."

The study was supported by the Department of Veterans Affairs and the Alzheimer’s Association. The authors have disclosed no relevant financial relationships. Dr. Kramer has disclosed no relevant financial relationships.

Arch Neurol. 2010;67:71-79, 80-86.

Sibutramine Now Contraindicated in Patients With a History of Cardiovascular Disease

From Medscape Medical News > Medscape Alerts

Emma Hitt, PhD

January 21, 2010 — Sibutramine, marketed as Meridia in the United States by Abbott, (Reductil in UK) is now contraindicated in patients with a history of cardiovascular disease, the US Food and Drug Administration (FDA) announced today.

According to an alert posted today by MedWatch, the FDA's safety information and adverse event reporting program, the announcement is a follow-up to an ongoing safety review of preliminary results reported in November 2009, which first raised concerns about this issue.

According to the FDA, the drug label already warns against the use of sibutramine in patients with cardiovascular disease. "However, based on the serious nature of the review findings, FDA requested and the manufacturer agreed to add a new contraindication to the sibutramine drug label," stating that sibutramine should not be used in patients with a history of cardiovascular disease, including patients with a:

History of coronary artery disease (eg, myocardial infarction, angina)
History of stroke or transient ischemic attack
History of heart arrhythmias
History of congestive heart failure
History of peripheral arterial disease
Uncontrolled hypertension (eg, >145/90 mm Hg)
The safety review was based on data from the Sibutramine Cardiovascular Outcomes Trial (SCOUT), which enrolled more than 10,000 overweight or obese patients with diabetes or a history of coronary artery disease, peripheral vascular disease, or stroke, along with other cardiovascular risk factors.

An analysis of the trial's primary end point — a composite of myocardial infarction, stroke, resuscitated cardiac arrest, or death — found the rate to be 11.4% for patients receiving sibutramine and 10% for those receiving placebo.
The current review found that the risk for cardiovascular events with sibutramine was significantly increased only in patients with a history of cardiovascular disease (P = .023).

Healthcare professionals should regularly monitor blood pressure and heart rate in patients taking sibutramine, the FDA notes.

"If sustained increases in blood pressure and/or heart rate are observed, sibutramine should be discontinued," according to the FDA. "Additionally, sibutramine should be discontinued in patients who do not lose at least 5% of their baseline body weight within the first 3 to 6 months of treatment, as continued treatment is unlikely to be effective and exposes the patient to unnecessary risk."

The full study report for SCOUT is expected in March 2010, at which time an open public advisory committee meeting will be convened to determine whether additional regulatory actions should be taken to ensure the safe use of sibutramine.


Meanwhile, the European Medicines Agency (EMEA) also announced the results of its safety review of drugs containing sibutramine, citing the SCOUT data. According to a press release issued today, the EMEA concluded, "the risks of these medicines are greater than their benefits."

Sibutramine-containing brands in the United Kingdom and Europe include Reductil, Reduxade, and Zelium, among others.
The agency now "recommend[s] the suspension of marketing authorizations for these medicines across the European Union."

The EMEA statement goes on to say that physicians should no longer prescribe sibutramine-containing agents, pharmacists should no longer dispense them, and patients taking them should make an appointment to see their physicians "at the next convenient time."

More information is available on the FDA's MedWatch Web site and on the EMEA Web site.

Adverse events related to sibutramine should be communicated to MedWatch by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at, or by mail to 5600 Fishers Lane, Rockville, Maryland 20852-9787.

Green Tea May Help Cut Risk for Lung Cancer

From Medscape Medical News
Roxanne Nelson

January 19, 2010 (Coronado, California) — Consumption of green tea might reduce the risk for lung cancer, especially for individuals who smoke, according to a Taiwanese study presented here at the American Association for Cancer Research-International Association for the Study of Lung Cancer Joint Conference on Molecular Origins of Lung Cancer: Prospects for Personalized Prevention and Therapy.

Researchers found that individuals who did not drink green tea had a 5.16-fold increased risk for lung cancer, compared with those who drank at least 1 cup of green tea per day. When they narrowed the analysis to smokers, those who did not drink green tea at all had a 12.71-fold increased risk for lung cancer, compared with those who consumed at least 1 cup per day.

"Our results suggest that both smokers and nonsmokers could benefit by drinking green tea," lead author I-Hsin Lin, MS, a student at Chung Shan Medical University in Taiwan, told Medscape Oncology. "Green tea contains strong antioxidants called tea polyphenols, which have inhibitory effects of tumorgenesis, tumor proliferation, and tumor growth."

This is particularly true for smokers, she added. "Drinking green tea may provide a chance to lower the lung cancer risk in smokers, but it cannot reverse the toxic [effects] or carcinogenesis caused by smoking," said Ms. Lin. "Of course, we don't want smokers to use this as an excuse to keep smoking and thinking that they have a lower risk by drinking a cup of green tea every day."

Experimental studies have shown that tea polyphenols are potent antioxidants and can inhibit the development of a variety of malignancies, including lung cancer, but epidemiologic studies examining tea consumption and cancer are limited, and results have been inconclusive, according to the researchers.

Insulin-Like Growth Factor Might Play a Role

Previous experimental research has found that green tea might reduce cancer risk by decreasing the level of insulin-like growth factor (IGF)1 or increasing IGF-binding protein (IGFBP)3, said Ms. Lin.

The IGF signaling pathway plays a role in regulating cellular proliferation and apoptosis. The authors note that a high expression level of IGFBP3 suppresses the mitogenic action of IGFs and has been inversely associated with cancer risk. But there is only limited information available on the molecular role of IGF1, IGF2, and IGFBP3 in lung cancer.

"In our study, we analyzed the IGF1, IGF2, and IGFBP3 genotypes," Ms. Lin told Medscape Oncology. "Previous experimental research has shown that green tea might reduce cancer risk by decreasing IGF1 levels or increasing IGFBP3 levels."

"Also, previous studies and reviews have suggested that individuals who are carrying the cytosine-adenine (CA)19 allele might have lower IGF1 levels, so we confirmed our results based on those studies," she added.

Ms. Lin and colleagues designed a hospital-based case–control study to evaluate the effects of smoking, green tea consumption, and IGF1 (CA)n repeat, IGF2 820, and IGFBP3 –202 polymorphisms on the risk for lung cancer, and also examined the association between IGF1, IGF2, and IGFBP3 polymorphisms and lung cancer survival.

Highest-Risk Modulation in Smokers and Some Genotypes

The cohort consisted of 170 primary lung cancer patients and 340 healthy individuals who completed a questionnaire regarding cigarette-smoking habits, green tea consumption, dietary intake of fruits and vegetables, cooking practices, and family history of lung cancer.

The data for overall lung cancer survival was calculated from 136 lung cancer patients, and genotypes for IGF1 (CA)n repeat, IGF2 820, and IGFBP3 –202 were identified by polymerase chain reaction.

They found that smoking, consuming less than 1 cup of green tea per day, and exposure to cooking fumes for more than 3 hours per week were associated with an elevated risk for lung cancer. But after adjustment for the effects of exposure to cooking fumes, a significantly higher risk was observed in people who never drank green tea, particularly smokers.

Genotypes also played a role in modulating the risk. A 66% reduction in lung cancer risk was observed in green-tea drinkers with nonsusceptible IGF1 (CA)19/(CA)19 and (CA)19/X genotypes, compared with green-tea drinkers carrying the IGF1 X/X genotype (odds ratio, 0.34; 95% confidence interval, 0.17 - 0.69).

However, when looking at lung cancer survival, they did not find an association between the IGF1 (CA)n repeat, IGF2 820, and IGFBP3 –202 genotypes and overall survival.

"Our study [suggests] that, in the case of lung cancer, smoking-induced carcinogenesis could be modulated by green-tea consumption and the growth-factor environment," said Ms. Lin.

American Association for Cancer Research-International Association for the Study of Lung Cancer (AACR-IASLC) Joint Conference on Molecular Origins of Lung Cancer: Prospects for Personalized Prevention and Therapy: Abstract A21. Presented January 12, 2010.

Thursday, January 21, 2010

AMA Urges Restraint for Clinicians Seeking to Volunteer in Haiti

From Medscape Medical News
Martha Kerr

January 16, 2010 ( UPDATED January 17, 2010 ) —
"The spontaneous volunteer has no place in disaster response," asserted James J. James, MD, DrPH, MHA, director of the Center for Public Health Preparedness and Disaster Response, at the American Medical Association (AMA), during a webinar held today for medical and public health responders to assist them in preparing for the Haitian earthquake disaster relief effort.

The webinar was held in collaboration with the National Disaster Life Support Foundation Inc, the American Public Health Association, the Centers for Disease Control and Prevention Office of Injury Response, the American Nurses Association, and the AMA's peer-reviewed journal Disaster Medicine and Public Health Preparedness.

"Volunteers must be part of the solution, not the problem," Dr. James emphasized. In addition to today's webinar, the AMA is planning to develop a clearing house for appropriate volunteers.

The Federal Emergency Management Agency, part of the US Department of Homeland Security (DHS), recently devised the National Incident Management System (NIMS). NIMS "provides a systematic, proactive approach to guide departments and agencies at all levels of government, nongovernmental organizations, and the private sector to work seamlessly to prevent, protect against, respond to, recover from, and mitigate the effects of incidents, regardless of cause, size, location, or complexity, in order to reduce the loss of life and property and harm to the environment."

NIMS provides the template for the management of incidents, and the National Response Framework provides the structure and mechanisms for national-level policy for incident management.

For physicians and nurses who want to volunteer, Dr. James urged, "Don't go unless you are as part of an organized team or have assurance when you arrive that you will be joining one.

"In addition, he said, "note the following:

You will be entering an austere environment.
Personal security may be an issue.
Resources will be very scarce.
"Volunteers must be self-sufficient or they are a part of the problem," Dr. James emphasized.

Volunteers need to know the following:

Their local role.
Their group's organizer or local contact.
How to incorporate local assets.
"The most important message for health professionals who wish to volunteer to help in the wake of a disaster," asserts Cheryl Peterson, Senior Policy Analyst for the American Nurses Association (ANA), "is that they should never deploy outside of an organized response system."

Health professionals, including nurses, who just show up at an accident or disaster site (called "spontaneous" or "unaffiliated" volunteers) are unknown to command and control personnel and cannot be used to their full potential.

Those in charge of relief efforts will not know who you are, what your abilities or educational background are, or even if your license is valid, the webinar organizers pointed out. There is no on-site procedure for validating your professional status. In some cases, it merely creates more work for those leading the response operation to deal with spontaneous volunteers.

Organized response registries for healthcare professionals exist at both the state and federal levels.

This earthquake already has a high mortality rate, with estimates of around 100,000 already being reported. Médicins sans Frontièrs/Doctors Without Borders is also reporting incidences of looting and threats to the security of their personnel, causing them to change the site of one temporary hospital and hampering relief efforts in general.

The Sphere Project provides the handbook Humanitarian Charter and Minimum Standards in Disaster Response, which contains guidelines for handling disasters.

Those who wish to volunteer should check with their respective professional organizations for specific advice. There is also this message from Partners in Health (PIH):

"We are deeply grateful for the multitude of people who have contacted us wanting to provide medical assistance, medicine and supplies. While we wish we could use all of the support so generously offered, we urgently need the following: orthopedic surgeons, trauma surgeons, anesthesiologists, nurse anesthetists, OR nurses, post-op nurses, and surgical technicians."

"Unfortunately, we are unable to accommodate any volunteers without significant surgical or trauma training and experience. If your qualifications match our needs, please fill out this form."

PIH is also requesting orthopaedic supplies, surgical consumables (sutures, bandages, nonpowdered sterile gloves, syringes, etc) and large unopened boxes of medications. The group is unable to accept small quantities or unused personal medications.

Blankets, tents, and satellite phones with minutes are urgently needed. People with private planes willing to fly medical personnel and/or large quanities of supplies are also greatly needed. To donate any of these goods and services, complete this form.

Medical Relief Beginning to Arrive in Haiti

From Medscape Medical News
Martha Kerr

January 14, 2010 — As the airport at Port-au-Prince, Haiti, reopens and supplies begin to arrive after Tuesday's 7.0-magnitude earthquake, rescue workers on the ground are predicting the death toll to rise above 100,000. Approximately 3 million people — one third of the population of Haiti — have been affected.

Most of the damage is around the country's capital, and Port-au-Prince's 3 largest medical centers have been devastated.

The greatest need is for water and medical supplies, President Barak Obama said in a briefing Thursday morning, as he pledged $100 million in immediate assistance, with more to come in the days and months ahead.

"One of the largest relief efforts in recent history" is en route to Haiti, President Obama said, with 2000 US Marines being deployed from Camp LeJeune, North Carolina, today. The first waves of US rescue and relief workers are "on the ground and at work," he said.

"The president ordered a swift, coordinated, aggressive effort," Secretary of State Hilary Clinton told Meredith Viera on NBC's Today Show Thursday morning. "We've got the airport open, thanks to the US military. We've got our civilian search-and-rescue teams on the ground, thanks to [the US Agency for International Development] and [the Federal Emergency Management Agency]. We are doing all we can to figure out how best to attack the devastation all around."

"This is going to be a long-term effort," Secretary Clinton continued. "We have the immediate crisis of trying to save those lives that can be saved, to deal with the injured and the dead, to try to provide food, water, medical supplies, some semblance of shelter, and then to work with our Haitian partners, the government of Haiti, [nongovernmental organizations], others to begin the rebuilding process."

Médicins sans Frontièrs (MSF), or Doctors Without Borders, is in the process of establishing a 104-bed hospital with an inflatable surgical unit, 2 operating theaters, 7 hospitalization tents, and a staff of 70 physicians and healthcare providers. Neurologists will be sent as part of the team to deal with head and crush injuries.

"There are hundreds of thousands of people who are sleeping in the streets because they are homeless," said MSF coordinator Hans van Dillen in an article on the group's Web site. "We see open fractures, head injuries. The problem is that we cannot forward people to proper surgery at this stage."

Transportation is severely disrupted, and supplies and medical staff will be approaching the affected area through the Dominican Republic, said Mr. van Dillen.

MSF is working to get more staff into the country, and the organization is also concerned about the safety of its own staff of 800 in Haiti, some of whom have not yet been accounted for.

Call for Healthcare Workers

Partners in Health of Boston, Massachusetts, a nonprofit organization "focusing on delivery of quality health care in poor communities," with ties to Harvard Medical School and the Brigham and Women's Hospital, issued this statement:

"We are deeply grateful for the multitude of people who have contacted us wanting to provide medical assistance. As patients flood to our sites from Port-au-Prince, we're finding ourselves in need of both medical personnel and supplies. In particular, we need surgeons (especially trauma/orthopedic surgeons), ER doctors and nurses, and full surgical teams (including anesthesiologists, scrub and post-op nurses, and nurse anesthetists).

"If you are a health professional interested in volunteering, please send an email to with information on your credentials, language capabilities (Haitian Creole or French desired), availability, and contact information."

The Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, has an advisory for healthcare relief workers and volunteers.
The CDC cautions, "Because of their potential exposures, relief workers are at increased risk for illness and injuries.
In addition, they should be aware of potential hazards, such as downed power lines and security measures that may be imposed (e.g., curfews to prevent looting).
Those who provide assistance should also pay attention to their mental health needs before, during, and after their time in the field.
Moreover, because relief workers' services are desperately needed, it is essential that workers remain healthy during their trip.
In addition to this notice, relief workers should refer to the general regional travel recommendations for their specific travel destination."

The American Red Cross (ARC) says it is "contributing an initial $1 million from the International Response Fund to support the relief operation, and has opened its warehouse in Panama to provide tarps, mosquito nets and cooking sets for approximately 5,000 families."

The group is also sending 6 disaster management specialists to the disaster zone to help coordinate relief efforts.

"At this time, the [ARC] is only deploying volunteers specially trained to manage international emergency operations," ARC officials stress. "We are not accepting volunteers to travel to Haiti. If you would like to volunteer for the [ARC], please contact your local chapter." Ten dollars, charged to the sender's cell phone, can be donated to the Red Cross by texting "HAITI" to "90999." The group has received $3 million since that service was established 36 hours ago.

Thursday, January 14, 2010

Most Americans Overweight, and One-Third Are Obese

From Heartwire

Michael O'Riordan

January 13, 2010 (Hyattsville, Maryland) — Two new studies this week draw attention to the alarming number of individuals in the US considered overweight or obese [1,2]. Based on the latest surveys, more than two-thirds of US adults are overweight or obese, one-third are considered obese, and more than 10% of children and adolescents are also considered too heavy for their age.

The good news, however, is that the increasing obesity trends observed over the past decade appear to be leveling off, according to investigators.

"The levels are still very high, and obesity is a significant health concern," Dr Cynthia Ogden (Centers for Disease Control, Hyattsville, MD), an investigator on both studies, told heartwire . "On the other hand, we've seen a slowing down, if you will, in the rate of increase compared with what it was in the 1980s and 1990s, so that's a positive thing. But the prevalence remains very high, and significant disparities remain, and we did see an increase within this 10-year period. It's not as if there were no increase."

The data, from analyses of the National Health and Nutrition Examination Survey (NHANES), are published online January 13, 2010 in the Journal of the American Medical Association. In an editorial accompanying the studies [3], Dr J Michael Gaziano (Brigham and Women's Hospital, Boston, MA) argues that the despite the leveling off, the magnitude of the obesity problem threatens to undo gains made in recent years.

"Despite the many advances in preventive medicine and treatment that reduced cardiovascular disease, the new stage of the epidemiologic transition, the age of obesity and inactivity, emerged to threaten the progress made in postponing illness and death to later in adult life spans," he writes. "The steady gains made in both quality of life and longevity by addressing risk factors such as smoking, hypertension, and dyslipidemia are threatened by the obesity epidemic."

Two-Thirds of US Adults Obese or Overweight

Speaking with heartwire , Ogden, the first author of the study investigating trends in the prevalence of high body-mass index (BMI) in children and adolescents and an author, along with lead investigator Dr Katherine Flegal (Centers for Disease Control, Hyattsville, MD) of the study in adults, said NHANES provides enough data every two years to examine the natural prevalence of obesity in the US population. The purpose of these studies was to document trends over two-year periods for the past 10 years.

In the first study, they analyzed the prevalence of obesity and overweight in 5555 adult men and women based on height and weight measurements used to calculate BMI. Overweight was defined as a BMI of 25.0 to 29.9 kg/m2 and obesity defined as a BMI >30.0 kg/m2.

In 2007–2008, the overall prevalence of obesity was 33.8%, with more women than men, 35.5% vs 32.2%, considered obese. Combining obesity and overweight, the overall prevalence was 68.0%, this time with more men than women, 72.3% vs 64.1%, considered overweight and/or obese.
The prevalence of obesity varied by age group and by racial and ethnic groups.

Over the 10-year period, however, the prevalence of obesity did not significantly increase for women. There was a significant linear trend for men in the prevalence in 2007–2008 compared with the prevalence in 1999–2000, but the most recent figures were not statistically different when compared with data in 2003–2004 and 2005–2006.

In the second NHANES analysis, 11.9% of children and adolescents aged two to 19 years were considered obese, in this case defined as being at or above the 97th percentile of the BMI-for-age growth charts.
Using less stringent definitions, 16.9% and 31.7% of the kids were at or above the 95th and 85th percentile of the BMI-for-age growth charts. Like adults, disparities existed by age and by race and ethnic groups.

"In children, we saw no change over the 10-year period except for in boys six to 19 years of age," noted Ogden. "Here we saw an increase among the heaviest boys, among a cut point that is usually heavier than what we use to determine obesity. For those kids, the prevalence did increase, so there is a suggestion that the heaviest kids are getting even heavier. There is definitely still a concern."

Statistics Are Still Staggering

In his editorial, Gaziano writes that while a slowing of the steady upward trend in overweight and obesity is good news, "the statistics are still staggering," given that most Americans are overweight and one-third are obese.

The results of the survey are sobering, "given the wide variety of deleterious health effects strongly linked to excess weight," such as coronary heart disease, ischemic stroke, hypertension, dyslipidemia, type 2 diabetes, joint disease, cancer, sleep apnea, asthma, and other chronic conditions. Early obesity, he notes, strongly predicts later cardiovascular disease, and excess weight might help explain the dramatic increase in type 2 diabetes, a major risk factor for cardiovascular disease.

"If left unchecked, overweight and obesity have the potential to rival smoking as a public-health problem, potentially reversing the net benefit that declining smoking rates have had on the US population over the last 50 years," writes Gaziano.

Unlike smoking, high blood pressure, and dyslipidemia, however, the best approach to treating overweight and obese individuals is still unknown. The current approach involves changes in lifestyle, but as most clinicians are aware, promoting lifestyle changes to encourage weight reduction has been disappointing, according to the editorial.
Still, given the risk of obesity-related health concerns, a massive public-health campaign to raise awareness about the dangers is needed, and the longer the delay in doing so increases the likelihood of negating the significant progress achieved in decreasing chronic disease in the past four decades, writes Gaziano.

Tuesday, January 12, 2010

2009 H1N1: vaccine safety

From Medscape Infectious Diseases
2009 H1N1: What's New This Week -- December 7, 2009
Commentary by John G. Bartlett, MD
John G. Bartlett, MD

Posted: 12/09/2009

Safety of Influenza A (H1N1) 2009 Monovalent Vaccines
The CDC reports a review of swine flu vaccine safety data.[1] The methods summarized in this report are (1) the US Vaccine Adverse Event Reporting System (VAERS), with 3783 reports, and (2) data from the Vaccine Safety Datalink (VSD) for 438,376 patients in managed care organizations who received vaccines.

VAERS data. Through November 24, VAERS received 3783 reports of adverse events following H1N1 vaccination.

Serious reactions were reported in 204 of 46.2 million doses of H1N1 vaccines distributed. Table 1 indicates how swine flu reports compare with reports received from seasonal flu vaccine.
Table 1. Reported Reactions to Swine Flu: Vaccine vs Seasonal Flu Vaccine

Any Reaction Serious Reaction
Swine flu vaccine
Seasonal flu vaccine 82/million doses
47/million doses 4.4/million doses
2.9/million doses

Deaths: 13 reported to VAERS, including 3 after live virus vaccine. Nine of the 13 were associated with a serious underlying disease, 1 was a car crash, and 3 are under review.
Guillain-Barré syndrome: 12 possible cases identified: 4 confirmed, 4 not confirmed, and 4 under review.
Anaphylaxis: 19 possible anaphylaxis cases; 13 of these 19 have been confirmed.

VSD data review. As of November 21, 2009, 438,376 doses of H1N1 vaccine had been administered, including 323,345 injectable and 115,031 nasal spray.
During October 1-November 21, no cases of Guillain-Barré syndrome and only 1 case of anaphylaxis had been detected.

The increase in adverse event reports for swine flu vaccine over seasonal flu vaccine may represent efforts to enhance reporting. VSD has the ability to confirm signals from VAERS, but so far these show no increases above the background rates for monitored health events among recipients of H1N1 vaccines.

Commentary. There is considerable concern about the safety of the H1N1 vaccine, presumably because it is new and it was developed relatively quickly.

Patients need to know:

It is manufactured by the same methods used for all flu vaccines for the past 40 years. This vaccine has a different flu antigen, but the flu antigen in the vaccine changes nearly every year.
There is no adjuvant in this vaccine. Many people are concerned about the presence of an adjuvant.
Our experience with 438,000 doses is that no safety concerns have been identified to date.
An extensive series of studies monitors safety of the vaccine. The ones summarized here, VAERS and VSD, are only 2 of 11 safety monitoring surveillance systems.

Australia's Winter With Pandemic Influenza H1N1
The Australian experience[2] with swine flu is of interest because the pandemic hit simultaneously with seasonal flu (which might be expected to occur in the United States in the next 4 months), and Australia had careful planning and record keeping instated. The following are highlights:

The first wave of influenza hit in mid-May 2009 and lasted 18 weeks.
The pandemic strain of influenza A (H1N1) accounted for 90% of influenza isolates by week 8.
School absenteeism was the same as it was in 2007, which was Australia's worst influenza season.
13% of hospitalized patients were admitted to the ICU.
The highest rate of hospitalization was in children younger than 5 years old.
A relatively large number of "lung only" single organ failure patients received ECMO and two thirds survived.
A distinguishing feature was the young age of hospitalized patients -- the median age was 43 years. The median age of patients who died was 53 years compared with 83 years in previous flu seasons.

Commentary. The clinical features reported here are "old news." Most interesting is the dominance of swine flu H1N1 over seasonal flu strains and the relevance of this to influenza in the northern hemisphere. But we can't be certain that our experience will be like Australia's because we have already experienced 2 waves and many vaccinations have been given that may have created "herd immunity" to modify the distribution of strains in the influenza season.

For practical purposes, here is the bottom line:

The recommended vaccine strategy is easy:
Patients should get both vaccines if available and according to priority. A history of confirmed swine flu means that the patient should receive the seasonal flu vaccine only.
Prescribing antiviral agents will be challenging for practitioners because decisions must take into consideration the viral strain as well as epidemiologic patterns of sensitivity.
We know that the right drug should be given as quickly as possible and we also know that we often won't know the strain. The current sensitivity patterns are described in Table 2.

Table 2. Sensitivity Patterns

Oseltamivr Zanamivr Rimantadine
Swine flu A (H1N1) Sensitive Sensitive Resistant
Seasonal flu A (H1N1) Resistant Sensitive Sensitive
Seasonal flu A (H3N2) Sensitive Sensitive Resistant
Seasonal flu (type B) Sensitive Sensitive Resistant

The challenge will be simultaneous seasonal and pandemic H1N1 strains because they show opposite sensitivities to oseltamivir and rimantadine.
So far, these 2 strains have not surfaced together since pandemic H1N1 took over.

When to Consider the Use of Antibiotics in the Treatment of 2009 H1N1 Influenza-Associated Pneumonia
A difficulty arises when a patient has influenza or influenza with a bacterial superinfection that requires antibiotics.[3] A recent report showed that bacterial pathogens, including Staphylococcus aureus, were present in 17/53 (32%) of fatal cases of novel H1N1 infection, including 8 in children.[4] Table 3 summarizes the clinical features of influenza vs influenza with a bacterial superinfection.

Table 3. Detection of Agents of Pneumonia: Influenza vs Influenza + Bacterial Pathogen

Indicator Influenza Influenza + Bacterial Pathogen
Influenza identified Usually found Often found less because later in disease course
Fever Usually found Usually found after a period of defervescence
Respiratory specimen culture Normal flora Pathogen: usually S pneumoniae, S aureus or Group A strep
X-ray Diffuse Lobar consolidation
Onset of respiratory compromise Early: 1-2 days Later: 4-7 days

In regard to antimicrobial selection, these experts recommend coverage for methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae using a second- or third-generation cephalosporin with the addition of MRSA coverage if there is evidence of necrotizing pneumonia or if a Gram stain or culture of respiratory secretions suggests this pathogen. For outpatients, they suggest amoxicillin-clavulanate or a second- or third-generation cephalosporin.

Commentary. The clinical features suggesting bacterial superinfection are reminders of the well-known report of the 1957-1958 pandemic from NY Hospital-Cornell,[5] when the classic biphasic pattern with typical flu symptoms -- improvement and then rapid deterioration with lobar pneumonia -- was described. The main pathogens then and now are S pneumoniae, S aureus, and group A streptococci. The antibiotics preferred for hospitalized patients with suspected S pneumoniae would be cefotaxime or ceftriaxone. For S aureus (either MRSA or untested), the preference would be for vancomycin dosed to trough levels of 15-20 µg/mL or linezolid (which appears to have better lung penetration).

H1N1 Flu Still Down but 198 Children Dead
H1N1 remains at epidemic levels but is below its peak from October 2009. The Centers for Disease Control and Prevention estimates that more than 22 million Americans have been infected with H1N1 and 3900 have died. Since March 2009, 198 children in the United States have died from H1N1, many from associated bacterial infections.

Commentary. The question that I am asked most frequently is, "The swine flu vaccine is now pretty easy to get, but the cases are down; do I need to get vaccinated?" The answer: "Yes, cases are down, for the second wave that was predicted when school started. There may be a third wave that corresponds to seasonal flu, so you still need to get vaccinated."

Australia had seasonal flu and swine flu occur together because it is in the southern hemisphere. Swine flu H1N1 pushed out seasonal flu and was the dominant flu virus during their winter season. That is likely to happen here, but this is a guess. If it does, this is the window of opportunity to get vaccinated.
Tell patients to get both the swine flu vaccine and seasonal flu vaccine because they are complementary, reminding them that seasonal flu vaccine will not prevent swine flu and vice versa.

One additional point: Many patients tell me that they think they already had swine flu and do not need the vaccine. Only 20%-35% of people who have had flu-like illnesses during the second wave of influenza actually had positive tests for swine flu when they were tested. This means that 65%-80% had something else -- probably paraflu, RSV, adenovirus, rhinovirus, etc.
If they had a confirmed H1N1 test between April and December 2009, they only need to get the seasonal flu vaccine.
If they did not have a confirmed test, then they should be considered for both vaccines.
Note that these vaccines can be given at the same visit but are given at different injection sites.

H1N1 Epidemic Update
During influenza week 47 (November 22-28, 2009), influenza activity continued to decrease in the United States.[4] More than 99% of strains that were subtyped were 2009 influenza A (H1N1).


Virtually all influenza at this time is swine flu. Seasonal flu has not started.
The number of outpatient visits for influenza-like illnesses is 3.7%, which is above the national baseline of 2.3% but lower than earlier reports. Hospitalizations and deaths due to influenza are down.

Conclusion: The second wave is subsiding, but there is still widespread illness in 25 states.
Resistance testing shows that 15 of 1540 (less than 1%) 2009 H1N1 strains were resistant to oseltamivir. Nearly all 15 had previous exposure to oseltamivir.
Conclusion: Oseltamivir is still active against nearly all strains, especially in patients who have not had oseltamivir exposure.

Pediatric deaths attributed to this influenza strain in the United States now total 198, including 34 in children younger than 2 years of age. Of these, 89 had cultures of normally sterile sites and 28/89 (31%) showed bacterial superinfections involving a predictable menu of pathogens.

Conclusion: There is increasing concern and attention on bacterial superinfections. Clues are (1) biphasic course, (2) elevated WBC, (3) x-ray showing lobar consolidation, and (4) sputum showing the likely pathogens: pneumococcus, Staphylococcus aureus, or Group A streptococcus.

Friday, January 1, 2010

The Modern Face-lift

From Medscape Plastic Surgery & Aesthetic Medicine
An Expert Interview With Sherrell J. Aston, MD
Pippa Wysong

Face-lifts are popular procedures, and recent years have seen changes in the approach to this surgery and what surgeons and patients alike should expect. Medscape's Pippa Wysong spoke to Sherrell J. Aston, MD, who offers his thoughts on the state of the art in face-lifts. Dr. Aston is Director and Chairman of the Department of Plastic Surgery at Manhattan Eye, Ear and Throat Hospital (MEETH) in New York, NY. He is also a Professor of Surgery at the New York University School of Medicine, New York, NY, and is certified by the American Board of Surgery (ABS) and the American Board of Plastic Surgery (ABPS).

Medscape: Can you start by giving Medscape readers an overview of the modern concept of a face-lift?

Dr. Aston: Today's face-lift is a highly individualized procedure designed for each patient. Face-lift involves repositioning the underlying foundation and restoring tissues to their original position, without stretching of the overlying skin. We address the muscles in the neck and along the jawline, and the fat and fascia in the cheek.

We are concerned with fat and/or tissue redistribution, and fat atrophy. Most patients need tissue repositioning to help create the contours of the face that we're trying to achieve. Some people lose facial fat volume as part of the aging process, but people in their early 40s and 50s usually need volume redistribution rather than volume addition. When people have loss of tissue volume in the face, we will add fat, which is taken from another part of the body.

Medscape: Some people associate face-lifts with a "face-lift look," or windblown appearance. What causes that?

Dr. Aston: Today, that appearance can be avoided. The stretched look of earlier face-lifts was a result of the skin being pulled tight. Tightening or repositioning of the underlying foundation contours the face, without the need for stretching the skin. Stretching facial skin does not give a face-lift result that's considered appropriate anymore. Having said that, there are surgeons who do just tighten the skin, which can lead to that windblown look.

Medscape: Should anything be done with the hairline?

Dr. Aston: The hairline in the front and back and the sideburn area should be left in their normal positions. If there is an alteration in the hairline, it really shows when a woman wears her hair up in a ponytail. Today, there should be no alteration of the hairline, and scars behind the ear should not be obvious.

Medscape: Which parts of the face are involved in face-lifts?

Dr. Aston: A face-lift means correcting the aging process from the corner of the eyes down to the collarbone. That includes the midface, cheeks, jawline, and the neck. A forehead/eyebrow lift takes care of sagging from the corner of the eye upward. Not all face-lift patients need a forehead lift. In some people the eyebrows maintain an adequate position without anything being done to them.

Medscape: Is there such a thing as a "minilift"?

Dr. Aston: A minilift is a term that has been coined by the media. What is usually meant by this term is a procedure that's intended to correct the cheek, midface, and jawline with a small incision. The so-called minilift does not do much to help with laxity and sagging skin in the neck.

Plastic surgeons today perform, for some patients, a "short-scar" face-lift in which incisions begin in the temporal area above the ear, follow the contour of the cartilage of the ear, and then curve around the earlobe. A full face-lift incision continues from the earlobe, up behind the ear, and then goes into the hair in a way that is not seen. A short-scar face-lift works for people who do not have significant sagging in the neck. Through this short incision, we perform very sophisticated work on the underlying foundation.

Medscape: Noninvasive and minimally invasive procedures. How effective are they?

Dr. Aston: There is currently a lot of discussion about noninvasive and minimally invasive face-lift procedures, but the results obtained with those kinds of procedures do not last very long.

Medscape: What are some examples of minimally or noninvasive procedures?

Dr. Aston: Noninvasive procedures are primarily injectable procedures, in which doctors put filler substances or fat in the face to try to lift it. Recently, I saw a fashion magazine article discussing lifting the face with onabotulinumtoxinA (Botox®) and fillers. That can't happen. You can add volume to the face with fillers, and there are people who benefit from fillers. OnabotulinumtoxinA can stop crows' feet and frown lines between the eyebrows, but onabotulinumtoxinA and fillers cannot actually lift the face.

Some fillers are absorbable and disappear after 3 or 4 months. There are intermediate fillers that last longer, and so-called permanent fillers. Generally, the permanent fillers have a high degree of complications: cysts; bumps; and irregularities. There are reports in the literature describing significant problems with permanent fillers.

Medscape: How long does it take for patients to return to normal activities after getting a face-lift?

Dr. Aston: Most people can return to full social and athletic activities 3 weeks after surgery, although there is still some swelling in the tissue.

Medscape: Is it better to do face-lifts on patients when they are young?

Dr. Aston: Patients should not have a face-lift until they have changes in the face that are a result of the aging process that they wish to have corrected. People observe changes in their faces differently. Some people see the early changes -- a little bit of jowl or a little bit of sagging in the midface that troubles them a great deal. That is why we do a lot of face-lifts on patients in their mid- to late 40s. There are people in their early 50s who don't need a face-lift; we send them home.

Age is not the determining factor for when one should have a face-lift. The primary factors linked to the aging process are genetics; lifestyle, such as a lot of sun exposure; weight gain or loss; and smoking. Those 4 things affect appearance and changes associated with aging in most people.

However, it is better to have a face-lift when the tissue of the individual is as good as it can be. The better the material that you have to work with, the better that it is going to look, and the longer that it is going to last. Ideally, you want to do the work when the collagen in the skin has not broken down much.

Medscape: How long does a face-lift last?

Dr. Aston: Once you have a face-lift, you will look better than nature intended for the rest of your life. Mind you, 10 years after surgery you're not going to look as good as 4 or 5 years after surgery because aging does continue, but you will look better than if you did not have the procedure.

Medscape: Can a face-lift ever fall?

Dr. Aston: Many patients ask that. No; a true face-lift cannot fall. The changes that you make by repositioning the underlying foundation and tightening the deeper-layer tissues in the face are secure.

Medscape: What about reports that some face-lifts do fall?

Dr. Aston: There have been some attempts to lift the face by placing individual sutures in the tissue in the face -- single loops, usually under local anesthesia. If you attempt to lift the face with 1, 2, or 3 sutures and a suture breaks, then obviously the tissue will fall down. It's well known that threadlift faces return almost completely to their original appearance in a very short period of time.

Medscape: What is a "lunchtime face-lift"?

Dr. Aston: The meaning varies, but it's been described as a procedure done with local anesthesia in the doctor's office during one's lunch break. There are nonphysicians who do some of these procedures with very bad results. It's a so-called face-lift. Usually there are little undermining and trimming of the skin. Plastic surgeons around the world agree that these quickie procedures with local anesthesia that are done in 45 minutes to an hour do not give the results that most patients want.

Medscape: What kind of anesthesia is required for face-lifts?

Dr. Aston: Face-lifts can be done with local anesthesia and intravenous (IV) sedation or general anesthesia, and both are effective. The extent of the procedure often determines which kind of anesthesia should be used. Some people undergo face-lifts that are much more involved than others, and what we do to the underlying foundation varies. Modern general anesthetics are short acting; patients can be awake within a few minutes of the procedure being completed.

Every patient gets local anesthesia injected into the tissue regardless of whether they are having general anesthesia or IV sedation. With IV sedation, you need to give the local anesthetic to numb the tissue. The type of anesthesia used depends on the surgeon, the planned procedure, the facility where there surgery is performed, and the desires of the patient.

Medscape: Stem cells are a hot topic in medicine. Do they have a role in face-lifts?

Dr. Aston: Right now, there is no such thing as a stem cell face-lift, although the hope is that stem cells can help rejuvenate tissues and fill in volume. Stem cells are obtained with liposuction. We frequently inject fat into different areas of the face to return fat that is atrophied, or to improve the contour of the jawline, or over the cheekbones to improve contour. Stem cells show promise for the future, and I anticipate that we'll do more with stem cells as part of facial rejuvenation in the years to come.

No Benefit of Ginkgo Biloba for Age-Related Cognitive Decline

From Medscape Medical News

Susan Jeffrey

December 30, 2009 — Results of a randomized trial show no effect of ginkgo biloba supplements on the rate of cognitive decline in adults with either normal cognition or mild cognitive impairment.

The Ginkgo Evaluation of Memory (GEM) study, a large randomized trial, showed that use of the popular herbal supplement in a dose of 120 mg twice daily was no different than placebo in terms of cognitive outcomes during a median follow-up of 6 years.

"There were changes of normal aging in the general testing and in all 4 cognitive domains, but there was no separation between the 2 curves; they were virtually completely superimposable," senior author Steven T. DeKosky, MD, from the University of Pittsburgh, Pennsylvania, told Medscape Neurology.

The study is published in the December 23/30 issue of the Journal of the American Medical Association.

No Effect on Alzheimer's

Ginkgo biloba is among the most widely used complementary alternative medicines and is taken for a variety of reasons, among them the preservation of cognitive health in aging, the authors note. The primary analysis of the GEM study, published in 2008, showed that treatment with ginkgo in a dose of 120 mg twice daily had no effect in reducing the incidence of Alzheimer's dementia or all-cause dementia in subjects without dementia at baseline (DeKosky ST, et al. JAMA 2008;300:2253-2262).

In the present analysis, an a priori secondary outcome of the GEM study, the authors looked at data on the rate of change over time in cognitive outcomes among 3069 community-dwelling subjects who were aged 72 to 96 years and who had either normal cognitive function or mild cognitive impairment at baseline.

Participants were randomly assigned to receive a 120-mg dose twice daily of either ginkgo biloba extract or placebo and were followed-up for a median of 6.1 years. Outcomes of interest were rates of change over time in the Modified Mini-Mental State Examination and the cognitive subscale of the Alzheimer's Disease Assessment Scale and in the neuropsychological domains of memory, attention, visual-spatial construction, language, and executive functions, based on the sums of z scores of these individual tests.

"We did certainly find some changes in the normal group in their activities [and] in their overall cognitive function, as well as in memory, visual-spatial function, executive function, and so forth, but we found no differences between the performance in those who took the ginkgo and those who were on placebo," Dr. DeKosky said.

Rates of change on the Modified Mini-Mental State Examination and the cognitive subscale of the Alzheimer's Disease Assessment Scale varied by baseline cognitive status, but there were no differences in the rates of change between treatment groups. Similarly, there was no significant effect modification of treatment on the rate of decline by factors including age, sex, race, education, presence or absence of the APOE*E4 risk allele, or mild cognitive impairment at baseline.

Treatment appeared to be safe, however, with no evidence seen of gastrointestinal problems or increased bleeding risk with active treatment.

Dr. DeKosky pointed out that their results apply to an older population and to a largely Caucasian cohort. For this population, however, it seems clear that ginkgo does not have an effect — there was no separation of the curves at any point that might hint, for example, that an effect might have become clear with longer follow-up.

"I think we're more disappointed than anything, but we continue to look for things that work," Dr. DeKosky said in an interview. For example, another supplement, called huperzine — an extract of Chinese tea with properties similar to cholinesterase inhibitors — is under evaluation now for the treatment of Alzheimer's disease.

Still, some people will want to continue to take ginkgo, and as it is safe and relatively inexpensive, it probably would not be a problem to do so, Dr. DeKosky noted. "I don't believe in getting into disagreements with my patients who'd like to do something more than whatever we have to offer," he said. Instead, he encourages patients to go through a series of questions about the proposed treatment: Is it safe? Are there data to support its use? Does it cross-react with other medications they are taking? Is it sufficiently expensive to produce hardship?

Ginkgo biloba is still being investigated in a number of other indications, including cardiovascular disease and tinnitus, he added, "but so far, for the cognitive indications, we have not been able to determine a positive effect."

A "Nail in the Coffin"

Asked for comment on these findings, Ronald Devere, MD, director of the Alzheimer's Disease and Memory Disorders Center in Austin, Texas, and a fellow of the American Academy of Neurology, pointed out that ginkgo has been used for many years to prevent age-related cognitive decline. Possible mechanisms of action of ginkgo in this setting include increases in cerebral blood flow by cerebrovascular relaxation or a decrease in blood viscosity or in oxygen free radicals, among others, he noted.

The current analysis is part of the GEM study, the largest randomized trial of ginkgo biloba vs placebo to date that showed no effect of active treatment on slowing the development of either Alzheimer's disease or other dementias, Dr. Devere noted, or now in the rate of change in those with normal cognition or mild cognitive impairment.

"Numerous other, smaller studies have shown the same outcome but were limited by small size and shorter follow-up than reported in this article," Dr. Devere told Medscape Neurology. The only limitations of the study were that it did not include enough ethnic or other cultural groups to make conclusions about these populations and that it included a fairly highly educated group.

"Despite these mild limitations, it is a sound study and all but puts a final nail in the coffin of using [ginkgo biloba] to help prevent cognitive decline in the normal or mild cognitively impaired elderly," Dr. Devere concluded. "This study does not give us any definitive information in the normal younger or middle-aged population, some of whom may already be developing the early brain changes of Alzheimer's disease or other dementias."

JAMA. 2009;302:2663-2670.