Exercise May Beat Drugs in Lowering Some Disease Death Rates

Medscape Medical News

Tinker Ready

Oct 02, 2013

Exercise may be just as effective as many drugs in lowering risk for death in the secondary prevention of coronary heart disease, rehabilitation after stroke, and prevention of diabetes, according to an analysis of randomized controlled trials published online October 1 in the British Medical Journal.

Although the researchers note that they were able to find a limited number of randomized controlled trials of exercise, their analysis of combined trial data found no detectable differences in death rates between exercise and drug interventions in the secondary prevention in coronary heart disease and in prediabetes. For stroke patients, the findings suggest that physical activity is more effective at preventing death than drug treatments, including anticoagulants and antiplatelets. However, diuretics appear more effective than exercise in preventing death in cases of heart failure.

The research was conducted by Huseyin Naci, MHS, from the London School of Economics and Political Science in the United Kingdom and the Drug Policy Research Group, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts, and John P.A. Ioannidis, MD, from the Stanford Prevention Research Center, Stanford University School of Medicine in California.

The researchers looked at 16 meta-analyses including research that combines data from multiple research studies. Four of the studies looked at exercise and 12 measured the effect of drug treatment. The researchers added 3 new exercise trials for a review that included 305 randomized controlled trials with 339,274 participants. For the 4 conditions with evidence on the effectiveness of exercise on mortality, 14,716 participants were included in 57 trials.

The authors note that the lack of exercise trials is a limitation of their study.

"Evidence from randomized controlled trials on the mortality benefits of exercise is scarce," they write. "Even in treatment areas where such evidence exists, exercise trials evaluating mortality outcomes were at a disadvantage in two ways: considerably fewer trials evaluated exercise than drugs...and fewer people participated in exercise trials."

For example, although there is much evidence that drugs such as simvastatin lower death rates in the secondary prevention of cardiovascular disease, research on the mortality benefits of exercise is limited, they write. In addition, evidence on how physical activity compares with drug interventions "is lacking."

Their analysis found that in coronary heart disease, the odds of mortality was reduced with use of statins (odds ratio [OR], 0.82; 95% credible interval [Crl], 0.75 - 0.90), β blockers (OR, 0.85; 95% Crl, 0.78 - 0.92), angiotensin-converting enzyme inhibitors (OR, 0.83; 95% Crl, 0.72 - 0.96), and antiplatelets (OR, 0.83; 95% Crl,0.74 - 0.93) compared with controls. Exercise produced similar results, but with wider credible intervals (OR, 0.89, 95% Crl, 0.76 - 1.04).

Exercise was more effective than any drug intervention in reducing the death rate among patients with stroke (OR, 0.09; 95% Crl, 0.01 - 0.72). However, the researchers note "considerable uncertainty" in that finding because of the small number of events in exercise trials.

Neither exercise nor drugs were clearly effective in reducing death rates in prediabetes, the authors found. In heart failure, fewer deaths occurred with diuretics (OR, 0.19; 95% Crl, 0.03 - 0.66) and β blockers (OR, 0.71; 95% Crl, 0.61 - 0.80) compared with controls. Diuretics were more effective than exercise (OR, 0.24; 95% Crl, 0.04 - 0.85), angiotensin-converting enzyme inhibitors (OR, 0.21; 95% Crl, 0.03 - 0.76), β blockers (OR, 0.27; 95% Crl, 0.04 - 0.93), and angiotensin receptor blockers (OR, 0.21; 95% Crl, 0.03 - 0.73).

"Given the scarcity of financial resources to fund future trials of exercise interventions, one option would be to require such evidence from pharmaceutical companies," the authors write. "In cases where drug options provide only modest benefit, patients deserve to understand the relative impact that physical activity might have on their condition."

The authors have disclosed no relevant financial relationships.

BMJ. Published online October 2, 2013. 

Midlife Stress May Trigger Dementia, Alzheimer's in Women

Medscape Medical News > Psychiatry

Deborah Brauser

Oct 02, 2013

Common psychosocial stressors experienced by women during midlife may lead to a higher risk of developing dementia and Alzheimer's disease (AD), new research suggests.

The population study included 800 women from Sweden who were first examined in 1968 and then followed up periodically for 38 years.

Results showed that the number of stressors, such as workplace problems, serious illness, divorce, and widowhood, experienced at baseline was associated with a 21% higher risk of developing AD and a 15% higher risk of developing dementia during the follow-up period. It was also associated with significantly increased later-life distress.

The findings show that accumulated stress from common events "may have severe and long-standing physiological and psychological consequences," write Lena Johansson, PhD, RN, from the Neuropsychiatric Epidemiology Unit at the Institute of Neuroscience and Physiology at Gothenburg University in Mölndal, Sweden, and colleagues.

They add that these physiologic consequences can include adverse reactions in the central nervous, cardiovascular, endocrine, and immune systems.

However, the investigators point out that more studies are now needed for replication and to investigate whether interventions such as stress management and behavioral therapy should be started in patients who are experiencing these stressors.

The study was published online September 30 in BMJ Open.

Impact of Common Stressors

Although previous research has shown that severe stressors such as combat and natural disasters can influence both physical and mental health throughout the life course, the long-term impact of more common stressors is unclear.

In the current analysis, the researchers assessed 800 participants in the larger Prospective Population Study of Women in Gothenburg, Sweden. It began in 1968, when the women were in their late 30s, mid 40s, or 50s.

Follow-up assessments were conducted in 1974, 1980, 1992, 2000, and 2005.

At baseline, the women were asked whether they had experienced any of 18 specific stressors, which included death of a child, unemployment for themselves or a partner, or alcoholism or mental illness in a close family member.

They were also asked at baseline and at each follow-up point about having ever experienced symptoms of distress (such as sleep disturbances, irritability, and fear) lasting for at least 1 month or longer.

A psychiatric examination, including tests and a neuropsychiatric assessment, was also given at all times of measurement, and medical records for all of the women were collected.

Biological Response

Results showed that 25% of the women reported at baseline having experienced at least 1 of the listed stressful events, and 16% reported having experienced 4 or more of the events.

Interestingly, the most commonly reported stressors were mental illness in a sibling (31.9%) and mental illness in a mother (26.5%).

During the follow-up period, 19.1% of all participants developed dementia; the average age at time of diagnosis was 78 years. A total of 68% of the women who developed dementia went on to develop AD.

"The mean time from the baseline examination in 1968 to dementia onset was 29 years," report the investigators.

The number of stressful events reported at baseline was associated with a higher incidence of the development of AD (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.08 - 1.36) or all- type dementia (HR, 1.15; 95% CI, 1.05 - 1.27) at some point during follow-up, as well as having symptoms of distress at each time of measurement.

"We have previously reported that long-standing distress in midlife increase risk of AD and structural brain changes," write the researchers.

"These findings are now extended by showing that number of psychosocial stressors and report of distress independently predicted AD, that is, increased distress could not completely explain the association between midlife stressors and dementia," they write.

They note that this may be because of the different ways individuals respond to stressors.

"Thus, biological responses may develop as a reaction to psychosocial stressors."

The study was funded by several organization, which are listed in the original article. The study authors have disclosed no relevant financial relationships.

BMJ Open. Published online September 3, 2013. Abstract

Busting Obesity Myths

Medscape Internal Medicine > Medicine Matters

Sandra Adamson Fryhofer, MD

Oct 01, 2013 

 Magazines are filled with fad diets promising quick and easy ways to lose weight. The truth is, when it comes to losing weight ,there is a lot of misinformation. A new study conducted by an international team of doctors, dieticians, and experts, funded by the National Institutes of Health, debunks some of these weight loss myths.

The first myth was picked up by the media big time. The myth? Having sex burns lots of calories. The truth? Sex may be great, but it's not that great for burning calories. This opinion is based on a study done in 1984, which measured calories burned during this activity for 30 men. According to this study, the 300-calories-for-sex rule is a myth. Six minutes of sex -- and that is on average how long it takes -- burns only about 21 calories, which is only 14 more calories than watching TV.

Next myth: Breastfeeding protects your child from obesity later in life. Breastfeeding is best for baby; there is no doubt about that. It creates a special bond between mother and child. Breast milk has all the nutrients baby needs to be healthy. It contains substances that help your baby fight infections, but it won't keep your baby from getting fat, says a 6-year randomized clinical trial that followed more than 13,000 children.This myth was also dispelled by a recent JAMA study of 17,000 mothers and their infants who were breastfed. Follow-up when the kids turned 12 found that breastfeeding did not prevent them from becoming obese or overweight. That is why we moms have to lead by example and encourage exercise activity and healthy eating habits for our children.

Next is one that we have all heard: It is best to set reasonable, sensible, attainable goals. You will be more successful because you won't get frustrated. Sounds reasonable enough, but the expert panel said, "Malarkey." Sometimes bigger goals can mean better results. In fact, people who set more ambitious expectations often lose the most weight even if they don't reach their goal.

This study also undermines presumptions that snacking leads to weight gain and that eating breakfast protects against obesity.

The expert panel did come up with their own list of obesity truths. Genetic factors play a role, but they are not the whole story. Environmental changes can make a difference. Regardless of your weight, exercise is a win-win to help lose weight and gain health. Involving parents and focusing on home settings can help overweight children.

Combatting obesity takes constant attention and it should be treated like it is a chronic condition. Structured meal plans and meal replacements can be helpful. The panel also acknowledged that medications and weight loss surgery are necessary for some. At the end of the day, you are left with an equation: the difference between calories in and calories burned. Losing weight means using more calories than you consume each day, but with many complex variables. And as you lose weight, those variables change. Losing weight isn't easy.

Yoga recommended for Backache

Medscape Psychiatry Minute. 

by Dr. Peter Yellowlees. 

Clinicians frequently advise patients with chronic back pain to take up yoga as part of a multimodal approach to therapy. Although we know that yoga can improve physical function, does it also reduce pain? Now a team of investigators^[1] from the University of Duisburg-Essen in Germany has systematically reviewed and meta-analyzed the literature on the effectiveness of yoga for low back pain. Ten randomized controlled trials with a total of 967 chronic low back pain patients were included in the study. The investigators found strong evidence for short-term effectiveness, and moderate evidence for long-term effectiveness, of yoga for chronic low back pain. Of importance, yoga was not associated with any serious adverse events. It is safe to conclude that yoga can be recommended as an additional therapy to chronic low back pain patients. Perhaps we should also be using it more ourselves because of its positive global effect on health. This article is selected from Medscape Best Evidence.I'm Dr. Peter Yellowlees.

Abstract

Statins Linked to Cataracts in Large, Retrospective Study

Heartwire

Shelley Wood

Sep 20, 2013

SAN ANTONIO TX — Another large study is linking statin use to the development of cataracts

The latest, following on a Canadian analysis last year, is a propensity score-matched analysis of over 45 000 subjects in a military healthcare system, published this week in JAMA Ophthalmology .

As Dr Jessica Leuschen (Wilford Hall Ambulatory Surgery Center, San Antonio, TX) and colleagues point out, observational studies of statins have been conflicting, with some suggesting an increased risk of cataracts with statin usewhile others appear to show a beneficial effect of statins on cataract risk. At the recent European Society of Cardiology(ESC) 2013 Congress , Dr John B Kostis (Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ) presented the results of a random-effects meta-analysis, showing a 20% lower rate of cataracts with statin use compared with no statin use, with a more pronounced benefit seen when statins were started in younger patients.

The meta-analysis published today, however, found the opposite. It matched 6972 statin users with nonusers within the San Antonio Military Multi-Market Area health system using propensity scores based on variables that increased the likelihood of receiving statins and increased the risk of developing cataracts. Statin users had to have been on the drugs for more than 90 days; simvastatinwas prescribed in almost three-quarters of the patients.

They found that statin users in the propensity-matched analysis had a 9% increase in cataracts. In secondary analyses that looked at all patients with no comorbidities (based on the Charlson index) at baseline, the risk of developing cataracts was 29% higher in the statin users. Results were consistent regardless of whether patients had been taking statins for two, four, or six years, authors note.

The study is the first to use propensity matching to try to eliminate baseline confounding--making it a key contribution to the relatively recent research into this potential interaction. To heartwire , senior author Dr Ishak Mansi (VA North Texas Health Care System, Dallas) noted that there are a number of ways in which statins could be a marker for important confounders, including accessible healthcare and health insurance, as well as underlying risk factors such as smoking, diabetes, and older age--all of which are also risk factors for cataract.

That kind of confounding may have been a factor in the Kostis et al meta-analysis at ESC, Mansi commented, when asked about the divergent findings, adding that since the paper is not yet published, he hasn't had a chance to review its methodology.

"Without knowing the specifics of the paper . . . I can generally say the following: During the mid-1990s and early 2000s, there were many papers that associated statin use with improved outcomes of many diseases such as cataract, fracture, infection, dementia, etc; however, recently, it was realized that statin use was associated with 'healthy-user bias.' That is to say, individuals who are health-conscious are more likely to take statins, and better outcomes may be secondary for their health consciousness and not due to the statin itself. . . . Therefore, if this meta-analysis included large-volume studies that date back to this period of time, their results may be affected by these biases of these studies."

Cardiologists have had plenty of experience with seemingly contradictory studies, he added. "Historically, we have been through these controversies on several topics, such as the use of hormonal-replacement therapy, treatment of chronic systolic heart failures with antiarrhythmic drugs, etc. We will have to study and search for our best capabilities until we reach an answer.

"Statins are very effective medications; therefore, side effects are expected. Healthcare providers should make sure that there is justifiable indication to prescribe statins according to guidelines and that the potential benefits outweigh the potential risks of side effects for individual patients. These medications should not be prescribed lightly."

For the public, however, the message is slightly different. "For some patients, these medications have been a main tool in treatment of heart disease and should not be stopped because of a small higher risk of association with other diseases," Mansi said. All effective medications can be expected to have side effects, he continued. "It is much better to do your best to lower your own risk of cardiovascular disease (if feasible) by stopping smoking and keeping physically active than to take a pill to lower your risk of heart disease."

Vitamin B Supplements May Lower Stroke Risk

Medscape Medical News > Neurology

Pauline Anderson

Sep 18, 2013

Unlike other similar reports that failed to find a significant effect of vitamin B supplementation on stroke risk, an updated meta-analysis has shown that taking these vitamins to lower homocysteine levels significantly reduces the stroke rate.

Folate (vitamin B₉) and vitamin B₁₂ are important regulators of homocysteine metabolism. In several jurisdictions, cereals are fortified with folate. Folic acid is a supplemental form of folate.

Several biological factors may affect whether vitamin B supplements will affect stroke risk, the study showed.

"Based on our results, the ability of vitamin B to reduce stroke risk may be influenced by a number of other factors, such as the body's absorption rate, the amount of folic acid or vitamin B₁₂ concentration in the blood, and whether a person has kidney disease or high blood pressure," said Yuming Xu, MD, Department of Neurology, The First Affiliated Hospital of Zhengzhou University, China, in a press release.

The study is published online September 18 in Neurology.

Updated Analysis

Researchers searched for randomized controlled trials published before August 2012 that compared vitamin B supplementation with placebo, very-low-dose B vitamins, or usual care; had a minimum follow-up of 6 months; and included stroke events as a study endpoint.

Since 2010, several important meta-analyses have been published on the effects of therapy to lower homocysteine levels with B vitamin supplementation on vascular disease risk. The new meta-analysis included studies that were omitted from previous reports and adopted stricter inclusion criteria (it excluded several studies because of small samples, zero rates of outcome events, ill-defined endpoints events, and inappropriate control group design).

The updated analysis included 14 trials, all double-blind, with a mean age ranging from 52 to 68.9 years, and involving a total of 54,913 participants. Study follow-up ranged from 24 months to 87 months. One study, the Atherosclerosis and Folic Acid Supplementation Trial (ASFAST), had just folic acid as the intervention, while the rest adopted combined intervention with B vitamins.

In these 14 reports, there were 2471 stroke events. The researchers noted a reduction in overall stroke events resulting from lowered homocysteine levels following B vitamin supplementation (risk ratio, 0.93; 95% confidence interval, 0.86 - 1.00; P = .04).

However, several strictly designed trials reported increased stroke events even with B vitamin supplementation.

In a subgroup analysis, the researchers found no significant differences between intervention and control groups regarding primary or secondary stroke prevention, stroke type (hemorrhagic, ischemic), or stroke severity.

Results were also not significant in a subgroup analysis for changes of stroke risks in response to various doses of folic acid supplementation or various baseline blood homocysteine concentrations. Previous studies had shown that 0.4 or 0.8 mg of folic acid is beneficial for lowering homocysteine levels and improving vascular endothelial function.

The researchers did find a benefit in the subgroup with 3 or more years of follow-up.

Subgroups of patients with chronic kidney disease were included in 5 of the 14 studies and 1 subanalysis. Some trials reported decreased glomerular filtration rate with B vitamin supplements.

As for analyses specific to vitamin B₁₂, the report did not find significant benefit for reduction of stroke events in subgroups according to intervention dose, reduction of homocysteine level, or baseline blood vitamin B₁₂ concentration. An analysis of populations with folate fortification of cereal products also failed to obtain significant results regarding B₁₂ dose. Other research had reported that 1 mg of B₁₂ is beneficial.

Vitamin B₁₂ Deficiency

The authors explored the issue of pre-existing metabolic B₁₂ deficiency. A subanalysis of the Vitamin Intervention for Stroke Prevention (VISP) trial that excluded participants with low baseline B₁₂concentrations due to malabsorption and high B₁₂ levels following B₁₂ injection found beneficial results of B vitamin supplementation for reduction of stroke risk. The current analysis showed a beneficial trend although not a significant benefit in the group with baseline median B₁₂ concentrations of 322 to 400 pmol/L.

"Our clinical implication is that metabolic B₁₂ deficiency should be more thoroughly followed and treated, so that such deficiencies are found and treated appropriately with B vitamin intervention," the authors write. "In future, we should consider adoption of specific administration routes rather than a single oral route, e.g. oral route in populations with inadequate dietary intake or injection route in populations with B₁₂ malabsorption to obtain effective intervention results."

As for baseline blood pressure levels, the meta-analysis identified a benefit of B vitamins in study participants with baseline high blood pressure. Hyperhomocysteinemia is known to promote hypertension. In China, guidelines for hypertension recommend reducing homocysteine levels to manage blood pressure.

The analysis did not find a significant increase in cancer incidence.

Asked to comment, Ralph L. Sacco, MD, professor and Olemberg Chair of Neurology, executive director, McKnight Brain Institute, and chief of neurology, Jackson Memorial Miller School of Medicine, University of Miami, Florida, said he found the meta-analysis interesting but that the reduction in stroke events among those treated with vitamin B is only slight, albeit significant.

"The effects are quite small and greatest among those with elevated Hcy [homocysteine] over 20 and among subjects who do not have a diet with folate supplementation," Dr. Sacco told Medscape Medical News.

The addition of some new studies since the last meta-analysis explains the different findings, said Dr. Sacco, adding that the change is not sufficient to alter current guidelines.

"When one examines the largest clinical trials individually, there is no significant effect of vitamin B supplementation for primary or secondary stroke prevention, so it's difficult to use a meta-analysis to change evidence-based guidelines. There may be some subgroups of patients who could benefit from vitamin B supplementation, but unfortunately the effects are small and limited."

Dr. Xu serves as an editorial board member for the Chinese Journal of Neurology and Life Science Journal and on the Scientific Advisory Board for the Chinese Medical Association and the Neural Immune Professional Committee of Hunan Province.

Airport X-Rays: How Worried Should We Be?

Medscape Internal Medicine > Medicine Matters

Sandra Adamson Fryhofer, MD

Sep 10, 2013

The topic: the safety of airport security scanners. Here is why it matters. Airport security is a must for public safety, but are the methods used to scan safe? Could the radiation emitted hurt us? What about privacy issues?

These questions and more were answered in a new report from the AMA Council on Science and Public Health.^[1]Exposure to ionizing radiation can damage DNA. Infants are more sensitive to cancer-causing effects of radiation than are adults. For fetuses, radiation exposure in the womb can increase the risk for birth defects. Cancer risk from radiation exposure decreases as we get older, but one should understand that not all scanners are the same.

The so-called backscatter models use low levels of ionizing radiation to create images. The newer millimeter wave models use radio waves instead, so there is no ionizing radiation. But even radiation exposure from the backscatter units is low intensity. Most exposure is to the skin and most of the rays are reflected back by the skin. Some radiation is absorbed by internal organs, but not that much.

The amount of radiation exposure from one backscatter x-ray security scan is very small: less than a tenth of a microsievert, which is less radiation exposure than you get from eating a banana. The radiation you get from a regular chest x-ray is 20 microsieverts. A mammogram is 400 microsieverts. A chest CT is 7000 microsieverts. The reality is that all of us are exposed to background radiation from the atmosphere. High altitudes from air travel increase radiation exposure due to cosmic rays. You get 700 times more radiation exposure from a transatlantic flight, 70 microsieverts, than you do from 1 backscatter scan.

Privacy issues are another matter. They are a concern. These scanners produce detailed images of your body -- very detailed images. Some might call them R-rated. This has been passengers' concern. It also has the attention of Congress, which is why Congress mandated special scanner software to make these images more generic and less embarrassing.

Note that the company that makes the backscatter machines could not meet the software deadline, so its contract was not renewed. This means that the backscatter scanners are now history, at least in airports. The Transportation Security Administration (TSA) was supposed to replace them all with millimeter wave machines as of June 2013.

For Medicine Matters, I'm Dr. Sandra Fryhofer.