HHAL MEDICAL NEWS FEBRUARY 2013

Meta-analysis shows little association between egg consumption and coronary heart disease or stroke.

To lower blood cholesterol and cardiovascular disease risk, the American Heart Association (AHA) recommends consuming <300 mg of cholesterol daily (Circulation 2006; 114:82). Because chicken eggs are high in cholesterol (about 200 mg each), clinicians commonly advise patients with elevated blood cholesterol to avoid eating them. However, the association between egg consumption and cardiovascular disease is unclear. In a meta-analysis of 17 prospective cohort studies in which egg consumption was measured with food-frequency questionnaires, investigators assessed this association.

The analysis included nine reports on coronary heart disease (CHD) and eight reports on stroke, with 10 to 20 years of follow-up in most studies. No associations between egg consumption and risk for CHD or stroke were observed. However, subgroup analyses of diabetic patients in which highest and lowest egg consumption were compared showed excess risk for CHD (relative risk, 1.5) and less risk for hemorrhagic stroke (RR, 0.8).

Rong Y et al. Egg consumption and risk of coronary heart disease and stroke: Dose-response meta-analysis of prospective cohort studies. BMJ 2013 Jan 7; 346:e8539. (http://dx.doi.org/10.1136/bmj.e8539)

Original article

Medline abstract

Arthritis: Sun's Rays May Cut Risk in Women

Previously, some epidemiologic studies have found a correlation between an increased incidence of RA and other autoimmune diseases with higher latitude of residence. As well, experimental studies have demonstrated immunosuppressive effects of UV-B, which also increases vitamin D synthesis in the skin, that in turn, has immunomodulatory properties. Elizabeth V Arkema, from Harvard School of Public Health (Massachusetts USA), and colleagues analyzed cumulative UVB flux data for 106,368 women enrolled in the Nurses’ Health Study and 115,561 women in the subsequent Nurses’ Health Study II according to the state in which they lived. In NHS, which began in 1976, women (ages 30 to 55) living in states with the highest ultraviolet B (UVB) intensity had a 21% lower risk for RA compared with those living in states with low UVB levels. But in NHSII, initiated in 1989 in women ages 25 to 42, no significantly lower risk was seen. The study authors report that: "These results suggest that ambient UV-B exposure is associated with a lower RA risk in NHS, but not NHSII. Differences in sun-protective behaviours (eg, greater use of sun block in younger generations) may explain the disparate results."

http://www.medpagetoday.com/Rheumatology/Arthritis/37187

Study: Alternate walking and running to save energy, maintain endurance

Ohio State University (Ohio, USA) researchers submit that the human body has an innate sense of how to vary speed to optimize energy when it is on the move in the natural environment. As many exercise efficiency studies are conducted on treadmills, they do not necessarily reflect real-world situations as to energy expenditure and endurance preservation. Manoj Srinivasan and colleagues enrolled 36 college students were asked to travel a distance longer than a football field, either on pavement outdoors or inside a school hallway. Each was given a stopwatch, and told to arrive at the destination specific time, not before and not after – but exactly on-time. Subjects were not told whether to walk or run, and could set their own pace. The team instructed for the subjects to complete two extreme trips: at one extreme, the subjects were told to make the trip in 2 minutes – so they could do so at a leisurely pace if they chose; at the other extreme, they were allotted only 30 seconds, so they had to run at a very brisk pace. The team was most interested in what the subjects would do when they were allotted travel times between the two extremes, finding that a transition region existed where the subjects mixed the trip between walking and running. Regardless of any variable – fitness level, height, weight, leg length, amount of time given for the trip, whether they were indoors or out – all subjects employed a mixture of walking and running. The team observed that the subjects seem to naturally break into a run, or slow down to a walk, to save energy while ensuring they arrived at the destination on time. The study authors conclude that: " Humans and other animals might also benefit energetically from alternating between moving forward and standing still on a slow and sufficiently long treadmill.”

http://researchnews.osu.edu/archive/walkrun.htm

Good mood helps boost brain power in older adults

Previously, a number of studies suggest that younger adults are more creative and cognitively flexible when they are in a good mood. Stephanie M. Carpenter, from the University of Michigan (Michigan, USA), and colleagues enrolled 46 adults, ages 63 to 85 years, in a study to assess the role of mood on cognitive skill.. Half of the subjects were put into a good mood by receiving a thank-you card and two small bags of candy, tied with a red ribbon, when they arrived at the lab for the experiment. The other "neutral

mood" participants did not receive a card or candy. The participants completed a computer-based study. They also participated in a decision-making task, where the participants were given $3 in quarters and presented with eight virtual decks of cards over the course of experiment. The researchers wanted to see how quickly and accurately the participants would learn which decks generally won them money, and which decks lost them money. The findings were clear: older adults who were put into a good mood chose significantly better than those who were in the neutral mood. Later in the experiment, the researchers tested working memory -- how much information people can hold in their mind at any one time. Researchers read aloud a group of intermixed letters and numbers (such as T9A3) and participants were to repeat the group back in numeric and then alphabetic order (in this case, 39AT). The participants received groups with increasingly more letters and numbers. Results showed that the older adults who were induced into a good mood scored better on this test of working memory. The study authors conclude that: “These effects of positive-feeling induction have implications for affect theory, as well as, potentially, practical implications for people of all ages dealing with complex decisions.”

http://www.eurekalert.org/pub_releases/2013-01/osu-gmh012913.php

Could the timing of when you eat, be just as important as what you eat?

This is the first large-scale prospective study to demonstrate that the timing of meals predicts weight-loss effectiveness

Previous studies with animal models suggest a relationship between the timing of feeding and weight regulation. Frank Scheer, from Brigham and Women’s Hospital (Massachusetts, USA), and colleagues evaluate the role of food timing in weight-loss effectiveness in a group of 420 individuals who followed a 20-week weight-loss treatment. The participants were divided into two groups: early-eaters and late-eaters, according to the self-selected timing of the main meal, which in this Mediterranean population was lunch. During this meal, 40% of the total daily calories are consumed. Early-eaters ate lunch anytime before 3 p.m. and late-eaters, after 3 p.m. They found that late-eaters lost significantly less weight than early-eaters, and displayed a much slower rate of weight-loss. Late-eaters also had a lower estimated insulin sensitivity, a risk factor for diabetes. Researchers found that timing of the other (smaller) meals did not play a role in the success of weight loss. However, the late eaters—who lost less weight—also consumed fewer calories during breakfast and were more likely to skip breakfast altogether. Late-eaters also had a lower estimated insulin sensitivity, a risk factor for diabetes. Writing that: “Eating late may influence the success of weight-loss therapy,” the study authors submit that: “Novel therapeutic strategies should incorporate not only the caloric intake and macronutrient distribution—as is classically done—but also the timing of food.”

Boston, MA—Most weight-loss plans center around a balance between caloric intake and energy expenditure. However, new research has shed light on a new factor that is necessary to shed pounds: timing. Researchers from Brigham and Women's Hospital (BWH), in collaboration with the University of Murcia and Tufts University, have found that it's not simply what you eat, but also when you eat, that may help with weight-loss regulation.

The study will be published on January 29, 2013 in the International Journal of Obesity.

"This is the first large-scale prospective study to demonstrate that the timing of meals predicts weight-loss effectiveness," said Frank Scheer, PhD, MSc, director of the Medical Chronobiology Program and associate neuroscientist at BWH, assistant professor of medicine at Harvard Medical School, and senior author on this study. "Our results indicate that late eaters displayed a slower weight-loss rate and lost significantly less weight than early eaters, suggesting that the timing of large meals could be an important factor in a weight loss program."

To evaluate the role of food timing in weight-loss effectiveness, the researchers studied 420 overweight study participants who followed a 20-week weight-loss treatment program in Spain. The participants were divided into two groups: early-eaters and late-eaters, according to the self-selected timing of the main meal, which in this Mediterranean population was lunch. During this meal, 40 percent of the total daily calories are consumed. Early-eaters ate lunch anytime before 3 p.m. and late-eaters, after 3 p.m. They found that late-eaters lost significantly less weight than early-eaters, and displayed a much slower rate of weight-loss. Late-eaters also had a lower estimated insulin sensitivity, a risk factor for diabetes.

Researchers found that timing of the other (smaller) meals did not play a role in the success of weight loss. However, the late eaters—who lost less weight—also consumed fewer calories during breakfast and were more likely to skip breakfast altogether. Late-eaters also had a lower estimated insulin sensitivity, a risk factor for diabetes.

The researchers also examined other traditional factors that play a role in weight loss such as total calorie intake and expenditure, appetite hormones leptin and ghrelin, and sleep duration. Among these factors, researchers found no differences between both groups, suggesting that the timing of the meal was an important and independent factor in weight loss success.

"This study emphasizes that the timing of food intake itself may play a significant role in weight regulation" explains Marta Garaulet, PhD, professor of Physiology at the University of Murcia Spain, and lead author of the study. "Novel therapeutic strategies should incorporate not only the caloric intake and macronutrient distribution, as it is classically done, but also the timing of food."

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This research was supported by grants from Tomás Pascual and Pilar Gómez-Cuétara Foundations, Spanish Government of Science and Innovation (BFU2011-24720), Séneca Foundation from the Government of Murcia (15123/PI/10). National Heart, Lung, and Blood Institute grants HL-54776, National Institute of Diabetes and Digestive and Kidney Diseases, Grant Number DK075030 and by contracts 53-K06-5-10 and 58-1950-9-001 from the US Department of Agriculture Research, and by National Heart, Lung, and Blood Institute grant R01 HL094806, and by National Institute of Diabetes and Digestive and Kidney Diseases, grant R21 DK089378.

Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 3.5 million annual patient visits, is the largest birthing center in New England and employs nearly 15,000 people. The Brigham's medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, involving nearly 1,000 physician-investigators and renowned biomedical scientists and faculty supported by nearly $625 million in funding. BWH continually pushes the boundaries of medicine, including building on its legacy in organ transplantation by performing the first face transplants in the U.S. in 2011. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies, OurGenes and the Women's Health Initiative. For more information and resources, please visit BWH's online newsroom.

Iodine Concentration Studied in Type 2 Diabetes

A new study reports that urinary iodine concentration is related to insulin resistance in people with type 2 diabetes. Previous research indicates that individuals with type 2 diabetes are at increased risk for thyroid disease. Nearly 24 million Americans have diabetes, and type 2 diabetes accounts for 90 to 95 percent of cases.

The subjects included 109 individuals with type 2 diabetes and 157 healthy individuals between 18 and 55 years of age. The researchers measured fasting glucose, lipids, thyroid hormones including T3, T4 and thyroid stimulation hormone (TSH) and urine levels of creatinine and iodine. Additionally, investigators measured serum levels of inflammatory markers and hormones associated with insulin resistance including leptin, adiponectin, resistin, insulin, plasminogen activator inhibitor (aPAI), C-reactive protein (hsCRP), angiotensin II and tumor necrosis factor alpha (TNF-alpha). They also evaluated waist and hip circumference.

The researchers found that levels of urinary iodine were significantly lower in the subjects with type 2 diabetes compared to the healthy control subjects. The investigators showed that lower levels of urinary iodine were associated with greater waist and hip circumference, and levels of insulin, insulin resistance, glucose, triglycerides, resistin, angiotensin II and CRP. Lower levels of urinary iodine correlated with lower TSH.

The study authors stated, “The decreased levels of iodine concentration in type 2 diabetes patients and its likely deleterious effects on metabolic functions calls for a systematic approach to thyroid disease screening in diabetic patients. Routine annual urinary iodine determination is recommended and should target type 2 diabetes patients at risk of thyroid dysfunction.”

Reference:
Al-Attas OS, et al. Exp Clin Endocrinol Diabetes. 2012;10:618-22.

Study: Mediterranean-style diet reduces cardiovascular risks
A Mediterranean-style diet may prevent about 30% of heart attacks, strokes and deaths from cardiovascular disease in high-risk patients, according to a study published on the website of The New England Journal of Medicine. University of Vermont nutrition professor Rachel Johnson called the study from the University of Barcelona "really impressive" because it used meaningful end points rather than just risk factors such as cholesterol, hypertension or weight. The New York Times

Data analysis shows vitamin C may reduce duration of colds
Analysis of data from 72 trials found that regular use of vitamin C supplements may reduce the duration of colds but does not prevent them for most people, according to a report on the website of the Cochrane Database of Systemic Reviews. Researchers from the University of Helsinki said the supplements led to about an 8% reduction in the duration of cold symptoms for adults and a 14% reduction for children. Medscape (free registration)

Metanx therapy in type 2 diabetes

Research Design and Methods

This multicenter, randomized, double-blind, placebo-controlled trial involved 214 patients with type 2 diabetes and neuropathy (baseline vibration perception threshold [VPT]: 25-45 volts), who were randomly assigned to 24 weeks of treatment with either L-methylfolate calcium 3 mg, methylcobalamin 2 mg, and pyridoxal-5′-phosphate 35 mg or placebo. The primary end point was effect on VPT. Secondary end points included Neuropathy Total Symptom Score (NTSS-6) and Short Form 36 (SF-36), as well as plasma levels of folate, vitamins B₆ and B₁₂, methylmalonic acid (MMA), and homocysteine.

Results

There was no significant effect on VPT. However, patients receiving LMF-MC-PLP consistently reported symptomatic relief, with clinically significant improvement in NTSS-6 scores at week 16 (P = .013 vs placebo) and week 24 (P = .033). Improvement in NTSS scores was related to baseline MMA and inversely related to baseline PLP and metformin use. Quality-of-life measures also improved. Homocysteine decreased by 2.7 ± 3.0 μmol/L with LMF-MC-PLP versus an increase of 0.5 ± 2.4 μmol/L with placebo (P = .0001). Adverse events were infrequent, with no single event occurring in ≥2% of subjects.

CONCLUSION

LMF-MC-PLP appears to be a safe and effective therapy for alleviation of peripheral neuropathy symptoms, at least in the short term. Additional long-term studies should be conducted, as the trial duration in this study may have been too short to show an effect on vibration perception threshold. Further research on the effects in patients with cobalamin deficiency would also be useful. The American Journal of Medicine

http://www.amjmed.com/article/S0002-9343(12)00586-4/fulltext

Metabolic syndrome and cognitive function
At odds with what is found among the younger old members of society, the oldest old (90+) in this Chinese study who had metabolic syndrome showed better cognitive function. And among males aged 90 to 100, those with higher triglycerides and systolic blood pressure seemed to have better cognitive function. (Free abstract only.) Journal of the American Medical Directors Association

Study links cardiometabolic risk factors to premature death
Researchers looked at data on 9,245 people ages 12 to 39 and found that cardiometabolic risk factors such as central obesity, smoking and hyperglycemia were associated with a higher risk of death before age 55. Analysis also showed a higher risk of all-cause death related to hypertension and high total and non-HDL cholesterol in women, but not in men. The study appeared online in the journal Pediatrics.

Weight-loss program safe, effective among senior women
Older obese women who underwent a lifestyle intervention had lost as much weight as middle-age participants at six and 18 months, according to a study in the journal Clinical Interventions in Aging. Older women did not show higher risk of adverse events than middle-aged women, researchers noted, and better improvements in blood pressure were seen among the older women. DailyRx.com

Statin therapy in the elderly
Statin therapy in elderly patients with hypertension reduces the risk of new-onset atrial fibrillation. Statins are more beneficial in patients with CHADS2 (Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, prior Stroke or transient ischemic attack) score ≥2 than in those with score of 1. The American Journal of Medicine

Daily energy intake and obesity in children
Using a nationally representative sample from 1977-2010, authors examined the relative contribution of changes in daily total energy. They conclude that there was an increase in total energy intake (+108kcal/day) and the number of daily eating/drinking occasions. The average energy density per eating/drinking occasion reached its highest level in 2005–2010. (Available for CME credit.) American Journal of Preventive Medicine

Reasons for taking multivitamins vary among U.S. adults
Data on close to 12,000 adults from the 2007-2010 National Health and Nutrition Examination Survey show that 45% of Americans who took a multivitamin did so because they believed it would improve or maintain their health, while 23% did so because a doctor recommended it. Vitamin users reported better health but also more healthy lifestyles than non-users. The findings appear in the journal JAMA Internal Medicine. WebMD/HealthDay News

Intra-abdominal hypertension effect on the kidney
Abdominal compartment syndrome is an under-recognized cause of acute kidney injury (AKI). Matthew et al report a patient with severe lung disease who, while intubated for respiratory failure, developed abdominal compartment syndrome and oliguric AKI. Following cisatracurium-induced reduction in auto–positive end-expiratory pressure (PEEP) from 35 to 8 mm H2O, an immediate and dramatic improvement in kidney function occurred. American Journal of Kidney Diseases

How prevalent is diabetes in coronary disease?
This study concluded that the real incidence of new diabetes mellitus is very high in the coronary population, especially in those with prediabetes. It is necessary to use oral glucose tolerance test for diagnosis, but its indication can be optimized based on a risk model. The American Journal of Cardiology

Higher diabetes rates seen in Alzheimer's patients
Patients with Alzheimer's disease showed higher rates of clinically diagnosed and medically treated diabetes compared with the general population, a Finnish study indicated. However, the difference in diabetes rates between the two groups was small, researchers wrote in Diabetes Care. DailyRx.com

Major Psychiatric Disorders Linked to Genes Involved with Brain's Calcium Balance

Five major psychiatric illneses — autism, ADHD, bipolar disorder, depression, and schizophrenia — seem related to calcium-signaling pathways in the brain, according to a Lancet study.

Researchers performed genome-wide analyses on some 30,000 patients with the disorders and a roughly equal number of controls. They identified four genetic variants — all related to calcium signaling — that were significantly associated with the presence of one of the five disorders.

Commentators, noting the importance of calcium signaling to nerve growth and development, conclude that the results could help identify new targets for psychotropic drugs.

Lancet article

Compression-Only CPR Wins the Long Race

Bystanders, forget about the breaths — pump that chest!

A Circulation study combined data from two randomized trials comparing dispatcher instructions for resuscitation. Outcomes, measured up to 5 years after resuscitation, found compression-only CPR associated with a lower adjusted risk for death (0.91) relative to standard CPR. The results, writes J. Stephen Bohan "should encourage EMS dispatchers to instruct lay bystanders to initiate compression-only CPR in adult victims of cardiac arrest

Mediterranean Diet Lowers Cardiovascular Events in People at Risk

A Mediterranean diet, compared with a low-fat control diet, lowered the risk for major cardiovascular events by 30% in people at high risk for cardiovascular disease, according to a New England Journal of Medicine study.

Some 7500 people in Spain with risk factors for cardiovascular disease were randomized to a Mediterranean diet supplemented with extra-virgin olive oil (1 liter per week), a Mediterranean diet supplemented with mixed nuts (30 g per day), or a low-fat diet. Dietitians counseled all participants about how to follow their diet, and compliance was good in all three groups.

After a median follow up of 4.8 years, each of the two Mediterranean diet groups showed a 30% relative reduction in the rate of the primary outcome — myocardial infarction, stroke, or cardiovascular mortality — compared with the control group. Reductions in stroke accounted for most of the benefit.

The authors conclude that their results "support the benefits of the Mediterranean diet for the primary prevention of cardiovascular disease."

NEJM article

http://www.nejm.org/doi/full/10.1056/NEJMoa1200303?query=OF#t=articleResults

Glucagonlike peptide 1–based therapies for type 2 diabetes expose patients to greater risks for pancreatitis, according to a case-control study in JAMA Internal Medicine. Commentators worry that the results portend increased cancer risks for these widely used drugs.

Using insurance databases, researchers identified some 1300 diabetic patients taking either exenatide (Byetta) or sitagliptin (Januvia) and matched them with an equal number of controls based on age and diabetic complications. Current or recent use of the drugs was associated with a doubling of risk for hospitalization for acute pancreatitis, relative to nonusers.

Commentators remind readers that "antecedent pancreatitis is the commonest risk factor for subsequent pancreatic cancer." They point out that both drugs already carry black-box warnings on pancreatitis, and say that "despite large numbers of underpowered studies claiming the contrary," little is known about their long-term effects.

JAMA Internal Medicine article

Omalizumab Effective in Treating Chronic Hives

Omalizumab, an IgE monoclonal antibody approved to treat asthma, reduced itch severity in patients with chronic idiopathic urticaria in a phase III, industry-conducted trial published in the New England Journal of Medicine.

Roughly 325 adolescent and adult patients whose moderate-to-severe chronic idiopathic urticaria was uncontrolled by H₁-antihistamines were randomized to placebo or various doses of omalizumab in addition to an antihistamine. Omalizumab was administered by injection every 4 weeks.

After 12 weeks' treatment, patients taking the higher doses of omalizumab (150 and 300 mg) had significantly greater reductions in self-reported itch scores than the placebo group. The reduction with 75 mg was nonsignificant. Patients taking the higher doses also reported fewer hives.

Serious adverse events, including angioedema, nephrolithiasis, and melanoma, were most common in the 300-mg treatment group (6%). The authors say the sample size was too small to make definitive conclusions about the drug's safety.

NEJM article

Ramipril for Peripheral Arterial Disease?

PAD patients with intermittent claudication who took ramipril could walk longer and with less pain.

Currently, medical therapy is limited for patients with peripheral arterial disease (PAD) and intermittent claudication. To assess whether the angiotensin-converting–enzyme (ACE) inhibitor ramipril improves ambulatory function in PAD patients, researchers conducted a trial in which walking times on a treadmill and other measures of function were compared in 212 Australian PAD patients (mostly men; mean age, 65.5) who were randomized to daily ramipril (10 mg) or placebo for 6 months.

All patients underwent treadmill testing at baseline and at the end of the trial. At 6 months, pain-free and maximum walking times were 75 seconds and 225 seconds longer, respectively, in the ramipril group than in the placebo group. Ramipril recipients also reported greater improvements in walking distance, walking speed, stair climbing, and physical health–related quality of life.

Ahimastos AA et al. Effect of ramipril on walking times and quality of life among patients with peripheral artery disease and intermittent claudication: A randomized controlled trial. JAMA 2013 Feb 6; 309:453. (http://dx.doi.org/10.1001/jama.2012.216237)

Medline abstract

Antihypertensive Therapy plus Nonsteroidal Anti-Inflammatory Drugs Contribute to Risk for Kidney Injury

Triple therapy (a diuretic + an angiotensin-converting–enzyme inhibitor or angiotensin-receptor blocker + an NSAID) was associated with excess risk.

Patients with hypertension often have conditions for which nonsteroidal anti-inflammatory drugs (NSAIDs) are indicated. However, both NSAIDs and certain antihypertensive drugs (i.e., diuretics, angiotensin-converting–enzyme [ACE] inhibitors, and angiotensin-receptor blockers [ARBs]) have hemodynamic effects on the kidney. Investigators retrospectively studied a U.K. database to examine whether antihypertensive therapy in combination with regular NSAID use is associated with excess risk for acute kidney injury.

Nearly 490,000 users of antihypertensive drugs were included in the study. During a mean follow-up of 5.9 years, >2200 cases of kidney injury were identified (defined as first hospital admission related to kidney injury). Adjusted for multiple confounders, double therapy (an NSAID, plus either a diuretic, an ACE inhibitor, or an ARB) was not associated with any greater likelihood of kidney injury than was an antihypertensive drug alone. In contrast, triple therapy (an NSAID, plus a diuretic, plus an ACE inhibitor or an ARB) significantly heightened the incidence of kidney injury compared with the same therapy without an NSAID (rate ratio, 1.3). Notably, highest risk was observed during the first 30 days of triple therapy.

Lapi F et al. Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: Nested case-control study. BMJ 2013 Jan 8; 346:e8525. (http://dx.doi.org/10.1136/bmj.e8525)

Original article

Medline abstract

Dabigatran for Extended Treatment of Venous Thromboembolism

In clinical trials, the drug was compared with warfarin and placebo.

After an initial course of treatment for venous thromboembolism (VTE), extended warfarin therapy lowers risk for recurrent VTE — but at the expense of excess risk for bleeding. Dabigatran (Pradaxa) now has been examined for this indication in two placebo-controlled, industry-sponsored trials.

One trial included nearly 2900 VTE patients at especially high risk for recurrence; after initial treatment (mean, 7 months), they were randomized to receive either dabigatran or warfarin. During extended treatment that averaged 16 months, the incidence of symptomatic or fatal VTE was 1.8% with dabigatran and 1.3% with warfarin, a result that met criteria for "noninferiority" of dabigatran. Major or clinically relevant bleeding was significantly less common with dabigatran than with warfarin (5.6% vs. 10.2%).

Another trial included about 1300 VTE patients at lower risk for recurrence than patients in the first trial; after initial treatment (mean, 10 months), they were randomized to receive either dabigatran or placebo. During extended treatment that averaged 5.5 months, the incidence of symptomatic or fatal VTE was significantly lower with dabigatran than with placebo (0.4% vs. 5.6%). Major or clinically relevant bleeding was significantly more common with dabigatran than with placebo (5.3% vs. 1.8%).

Comment: Dabigatran's efficacy was similar to that of warfarin and superior to that of placebo; dabigatran caused less bleeding than warfarin but more bleeding than placebo. One worrisome observation was a small excess of adverse coronary events with dabigatran in the high-risk trial — an outcome that has been noted in previous dabigatran trials (Dabigatran has not yet been FDA approved for deep venous thrombosis treatment or prophylaxis.

Other options for extended treatment of patients with VTE include the following:

Rivaroxaban (Xarelto; FDA approved for this indication in 2012)

Apixaban (Eliquis; ; not yet FDA approved for this indication)

Aspirin (less effective than the aforementioned anticoagulants, but confers minimal bleeding risk

An editorialist has constructed a table comparing the results of clinical trials for dabigatran, rivaroxaban, and apixaban.

use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med 2013 Feb 21; 368:709. (http://dx.doi.org/10.1056/NEJMoa1113697)

· Medline abstract

- See more at: http://general-medicine.jwatch.org/cgi/content/full/2013/228/1?q=etoc_jwgenmed#sthash.Lvn87qaF.dpuf

Short-Term Folic Acid Supplementation Has No Effect on Cancer Incidence

However, effects on cancer risk beyond about 5 years are unknown.

Vollset SE et al. Lancet 2013 Jan 25;

Miller JW and Ulrich CM. Lancet 2013 Jan 25;

β-Blockers Improve Outcomes in Patients with Heart Failure and Low Left Ventricular Ejection Fraction

In a meta-analysis, no β-blocker was superior to any other.

Chatterjee S et al. BMJ 2013 Jan 16; 346:f55

Treating ADHD Without Drugs: A Meta-Analysis

Supplementation with free fatty acids showed positive effects in analyses of blinded assessments, after adjustment for medication use.

Medication has shown great benefit for symptoms of attention-deficit/hyperactivity disorder (ADHD) among children having this diagnosis, with a high effect size (0.9). Nevertheless, longitudinal outcomes in marital, employment, and legal domains are impaired, even among individuals without histories of conduct disorder In addition, some families prefer nonpharmacological interventions. Studies and meta-analyses of these have had mixed results, partly due to the use of unblinded assessors. To examine the value of such approaches, investigators conducted an industry-supported meta-analysis of all randomized, controlled trials on children with ADHD diagnoses (age range, 3–18).

Studies that combined nonpharmacological and medication interventions were excluded. Of 2904 screened records, 54 studies fit the meta-analysis criteria; one study had both cognitive and neurofeedback arms, yielding 55 analyzed trials.

In analyses of results from both unblinded and blinded assessments, supplementation with free fatty acids (11 studies) and diets excluding artificial food coloring (8 studies) were significantly better than comparison approaches. After adjustment for "treatment as usual" control arms using medication, only free fatty acid supplementation remained significant, with a low effect size (0.17). In analyses of blinded assessments, no other intervention (food elimination, 7 studies; behavioral, 15; neurofeedback, 8; cognitive, 6) showed significance.

- See more at: http://psychiatry.jwatch.org/cgi/content/full/2013/215/1?q=topic_nutrition#sthash.awx41HYL.dpuf

Anxiety May Accelerate Aging

Telomeres are the end caps of chromosomes, protecting the DNA complexes from deterioration during cell division. Telomere shortening is considered a marker of cellular aging, and prematurely shortened telomeres have been linked to increased risk of cancers, heart disease, dementia and death. Olivia Okereke, from Brigham and Women's Hospital (Massachusetts, USA), and colleagues completed a cross-section of study involving 5,243 women enrolled in the Nurses’ Health Study. The researchers obtained blood samples and analyzed telomere lengths, and surveyed the subjects regarding phobic symptoms. Having a high phobic anxiety level was associated with significantly shorter telomere lengths. The difference in telomere lengths for women who were highly phobic versus not, was similar to what was seen for an additional six years of age. Writing that: "Chronic psychological distress has been linked to shorter telomeres, an indication of accelerated aging,” the study authors conclude that: "In this large, cross-sectional study high phobic anxiety was associated with shorter telomeres.”

http://www.eurekalert.org/pub_releases/2012-07/bawh-alt070912.php

Tomato Compound May Reduce Heart Disease Risks

Lycopene is an antioxidant compound present in red-and pink-colored fruits and vegetables, most notably tomatoes. A number of previous studies suggest that circulating lycopene is inversely associated with cardiovascular disease risk. Paul F. Jacques, from Tufts University (Massachusetts, USA), and colleagues analyzed data collected on subjects enrolled in the Framingham Offspring Study, 314 of whom had cardiovascular disease, 171 people with coronary heart disease, and 99 people affected by stroke. The average lycopene intake among the study subjects was 7.9 mg per day. The team calculated the lycopene intake was inversely associated with a 17% reduction in cardiovascular disease incidence and a 26% decrease in coronary heart disease incidence; no association was observed for stroke incidence. The study authors submit that: "The present study of lycopene intake and [cardiovascular disease] provides supporting evidence for an inverse association between lycopene and [cardiovascular disease] risk.”

http://www.nutraingredients-usa.com/Research/Framingham-data-adds-to-accumulating-evidence-for-lycopene-s-heart-health-benefits/

Natural Approaches May Help Clear Brain Plaques

Alzheimer's brain tissue exhibits many fewer nerve cells and synapses than a healthy brain, due to the presence of plaques – abnormal clusters of protein fragments, build up between nerve cells; and tangles – twisted strands of proteins that comprise dead and dying nerve cells. In a small pilot study, Milan Fiala, from the University of California Los Angeles (UCLA; California, USA), and colleagues drew blood samples from both Alzheimer's patients and healthy controls, then isolated macrophages – blood components that are responsible for disposing of amyloid-beta and other waste products in the brain and body. The team incubated the immune cells overnight with amyloid-beta. They added either an active form of vitamin D3 called 1alpha,25–dihydroxyvitamin D3 or an active form of the omega-3 fatty acid DHA called resolvin D1 to some of the cells to gauge the effect they had on inflammation and amyloid-beta absorption. The researchers observed that both 1alpha, 25-dihydroxyvitamin D3 and resolvin D1 improved the ability of the Alzheimer's disease patients' macrophages to gobble-up amyloid-beta, and they inhibited the cell death that is induced by amyloid-beta. Researchers observed that each nutrition molecule utilized different receptors and common signaling pathways to do this. The lead researcher is hopeful that: "Our new study sheds further light on a possible role for nutritional substances such as vitamin D3 and omega-3 in boosting immunity to help fight Alzheimer's."

http://www.eurekalert.org/pub_releases/2013-02/uoc--vdo020513.php

Meditation Relieves Inflammation

Previous studies have suggested that psychological stress is a major influence in the symptoms of chronic inflammatory conditions, such as arthritis, inflammatory bowel disease, and asthma. Melissa A. Rosenkranz, from the University of Wisconsin (Wisconsin, USA), and colleagues compared to methods of reducing stress: a mindfulness meditation-based approach, and a program designed to enhance health in non-meditative ways including exercise and music therapy. The team induced psychological stress to the subjects, and measured changes in immune and endocrine markers. The results showed that mindfulness meditation was more effective at reducing stress-induced inflammation. The study authors conclude that: "These results suggest behavioral interventions designed to reduce emotional reactivity may be of therapeutic benefit in chronic inflammatory conditions. Moreover, mindfulness practice, in particular, may be more efficacious in symptom relief than the well-being promoting activities cultivated in the [non-meditative] program.

http://www.eurekalert.org/pub_releases/2013-01/uow-mmm011613.php

Soy Protein Improves Blood Vessel Health

Soybean protein is generally considered a healthy food, based on studies that suggest a favorable effect on cholesterol and blood pressure. C M Rebholz, from Tulane University School of Public Health and Tropical Medicine (Louisiana, USA), and colleagues examine the effect of soybean protein on biomarkers of inflammation, endothelial dysfunction and adipocytokines. 102 men and women were enrolled in a double-blind, three-phase crossover trial in which each subject was randomized to eight-week consumption phases of soy protein (40 g per day, containing 89.3 mg of isoflavones), milk protein (40 g per day), or complex carbohydrate (40 g per day, as placebo). Improvements in plasma levels of inflammation biomarkers (C-reactive protein, interleukin-6, tumor necrosis factor-α), endothelial dysfunction biomarkers (E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, thrombomodulin) and adipocytokines (high-molecular weight adiponectin, leptin, resistin) – signaling molecules produced by fat tissue all underwent significant improvement in the phase involving the soy protein.

http://www.nutraingredients-usa.com/Research/Soy-protein-shows-heart-health-benefits-RCT/

Big Health Gains from Small Steps

An active lifestyle approach, as compared to structured exercise, may be just as beneficial in improving health outcomes, including preventing metabolic syndrome, high blood pressure, and high cholesterol. Paul Loprinzi, from Oregon State University (Oregon, USA), and colleagues analyzed data collected on 6,321 participants, ranging in age from 18 to 85 years, in the NHANES 2003-2006 study. The researchers found that 43% of those who participated in the “short bouts” of exercise met physical activity guidelines of 30 minutes day. In comparison, less than 10% of those in the longer exercise bouts met those federal guidelines for exercise. The study data showed those in the shorter exercise group who met physical activity guidelines had an 89% chance of not having metabolic syndrome, compared to 87% for those meeting guidelines using the structured exercise approach.The study authors conclude that: “Engaging in [small amounts of activity], as opposed to bouts of [structured exercise], is just as strongly associated with several biologic health outcomes, suggesting that adults who perceive themselves as having little time to exercise may still be able to enhance their health by adopting an active lifestyle approach.”

http://oregonstate.edu/ua/ncs/archives/2013/jan/study-finds-taking-stairs-raking-leaves-may-have-same-health-benefits-trip-gym

Beef Up to Maintain Muscle

Sarcopenia, or the gradual loss of muscle mass, is a common consequence of aging, and poses a significant risk factor for disability in older adults. Stuart M. Phillips, from McMaster University (Canada), and colleagues enrolled 45 men, average age 59 years, in a study that found that eating a six-ounce (170 g) serving of 85% lean ground beef resulted in significant treatment the rate of muscle protein synthesis following exercise. This determination is double the current recommended serving sizes of meat in Canada. Study authors propose that: "Ingestion of 170 g of beef protein is required to stimulate a rise in myofibrillar [muscle protein synthesis] over and above that seen with lower doses.”

http://www.nrcresearchpress.com/doi/story/10.4141/news.2013.02.03.112#.US31jqLqkk0

Proper Nutrition Key to Maintaining Muscle Strength

Sarcopenia, or the gradual loss of muscle mass, is a common consequence of aging, and poses a significant risk factor for disability in older adults. As muscle strength plays an important role in the tendency to fall, sarcopenia leads to an increased risk of fractures and other injuries. While resistance training is an essential and effective intervention, adequate nutritional intake is also an important element. The International Osteoporosis Foundation (IOF) Nutrition Working Group has identified nutritional factors that contribute to loss of muscle mass, and conversely, are beneficial to the maintenance of muscle mass. The Group acknowledges that protein intake plays an integral part in muscle health, proposing an intake of 1.0–1.2 g/kg of body weight per day as optimal for skeletal muscle and bone health in elderly people without severely impaired renal function. As many studies indicate a role for vitamin D in the development and preservation of muscle mass and function, the Group also acknowledges that adequate vitamin D should be ensured through exposure to sunlight and/or supplementation if required. Vitamin D supplementation in seniors, and especially in institutionalized elderly, is recommended for optimal musculoskeletal health. The Group also recognizes emerging evidence that suggests that vitamin B12 and/or folic acid play a role in improving muscle function and strength.

http://www.iofbonehealth.org/which-nutritional-factors-help-preserve-muscle-mass-strength-and-performance-seniors

Vitamin D for Longevity

Many older women, particularly those in institutionalized care, are vitamin D deficient and at increased risk of falls and fractures. Goran Bjelakovic, from the University of Nis (Serbia), and colleagues completed a meta-analysis of 50 randomized trials that collectively involved 94,148 participants, with a mean age of 74 years. The team’s analysis suggested that vitamin D3 (cholecalciferol) supplementation reduces mortality by about 6%, equating to saving one life for every 200 people given vitamin D3 for two years. The researchers conclude that: “Vitamin D3 seems to decrease mortality in predominantly elderly women who are mainly in institutions and dependent care.”

http://www.eurekalert.org/pub_releases/2011-07/w-vdc070111.php

Alcohol a Major Contributor to Cancer Mortality in U.S.

Alcohol use was responsible for about 3.5% of all cancer deaths in the U.S. in 2009, according to a study in the American Journal of Public Health.

Researchers combined results of population surveys about alcohol use with the relative risks for cancer mortality observed in meta-analyses. In men, the majority of the alcohol-related cancer deaths were due to cancers of the oral cavity, pharynx, larynx, and esophagus. In women, the majority were due to breast cancer. Each cancer death resulted in roughly 18 years of potential life lost. Roughly 30% of the alcohol-attributable cancer deaths occurred in people who drank about 1.5 or fewer drinks per day.

As to the mechanism for these effects, the authors offer: "genotoxic effects of acetaldehyde, production of reactive oxygen or nitrogen species, changes in folate metabolism, increased estrogen concentration, or serving as a solvent for tobacco metabolites."

The authors call for clear statements of the danger from healthcare organizations, emphasizing that "there is no safe level at which there is no cancer risk."

Dietary Changes Prompt Swift Improvements in Inflammation

In the inflammation is a primary trigger for a number of chronic diseases ranging from cardiovascular disease to cancer, Alzheimer's disease to arthritis, a number of researchers are pursuing the role of changes in diet to reduce the inflammation response. Lynnette Ferguson, from The University of Auckland (New Zealand), and colleagues studied 30 healthy men and women, selected for their initially "poor" diets, who were encouraged to eliminate refined and processed foods and to follow a Mediterranean type diet over six weeks – featuring increased amounts of fish, vegetables, unrefined cereals, and "good" fats such as olive oil and avocado. A prominent feature of the diet was also that it was gluten-free. Recipes were supplied to the participants. After six weeks, the team observed that biomarkers of inflammation, most notably C-reactive protein (CRP), were markedly reduced.

http://www.foodnavigator-asia.com/Policy/Kiwi-study-shows-diet-change-can-have-rapid-impact-on-inflammation/

Green Tea Compounds Help to Protect Skin

Green tea contains between 30 and 40% of water-extractable polyphenols, and is particularly abundant catechins – most notably, epigallocatechn gallate (EGCG), for which some

studies

suggest a beneficial effect on cardiovascular health and weight management. Lesley E. Rhodes, from the University of Manchester (United Kingdom), and colleagues enrolled 14 healthy men and women, average age 42.5 years, with their skin, and gave them low-dose green tea catechin supplements added daily dose of 540 mg in combination with a vitamin C dose of 50 mg, for 12 weeks. The effects of the supplements were quantified by exposures to UV light before and after supplementation. Results showed that levels of metabolites of green tea catechins increase in skin fluid after supplementation, and erythema (skin redness) levels were reduced after the 12-week supplementation period. The team also observed that whereas UV exposure increased key markers of inflammation, green tea supplementation reduced that effect. The study authors submit that the data suggests that green tea exerts: "protection against sunburn inflammation and potentially longer-term UVR-mediated damage.”

http://www.nutraingredients-usa.com/Research/Green-tea-supplements-may-benefit-skin-from-within

Berries Boost Heart HealthBlueb

erries and strawberries contain high levels of naturally occurring compounds called dietary flavonoids – and, specifically the subclass of anthocyanins, which may help dilate arteries, counter the buildup of plaque, and provide other cardiovascular benefits. Eric Rimm, from Harvard School of Public Health (Massachusetts, USA), and colleagues analyzed data collected among g93,600 women, ages 25 to 42 years, enrolled in the Nurses' Health Study II. The women completed questionnaires about their diet every four years for 18 years. During the study, 405 heart attacks occurred. Women who ate the most blueberries and strawberries had a 32% reduction in their risk of heart attack, compared to women who ate the berries once a month or less – even in women who otherwise ate a diet rich in other fruits and vegetables. The study authors conclude that: “A high intake of anthocyanins may reduce [heart attack] risk in predominantly young women.”

http://www.eurekalert.org/pub_releases/2013-01/aha-sbm011013.php

Dual Blockade of the Renin-Angiotensin System Doesn't Prevent Mortality

Results of a meta-analysis argue against use of dual therapy.

The combination of an angiotensin-converting–enzyme (ACE) inhibitor plus an angiotensin-receptor blocker (ARB) sometimes is prescribed to patients with heart failure, hypertension, or diabetes, despite limited evidence of efficacy and lukewarm or no support from clinical guidelines. In this meta-analysis of 33 randomized controlled trials (mean duration, 52 weeks), investigators compared the outcomes of dual blockade with those of monotherapy in >68,000 patients (mean age, 61; 71% men).

Dual blockade consisted of an ACE inhibitor plus an ARB in 22 trials; the other trials included various combinations of an ACE inhibitor or an ARB with aliskiren (Tekturna). Compared with monotherapy, dual therapy did not prevent all-cause mortality or cardiovascular (CV)-related mortality. Although dual therapy was associated with a significant 18% lower relative risk for hospital admission precipitated by heart failure, it also was associated with significantly higher relative risks for hyperkalemia (55%), hypotension (66%), kidney failure (41%), and withdrawal because of drug-related adverse events (27%). In subgroup analyses, dual therapy did not prevent all-cause or CV-related mortality in patients with heart failure and was significantly associated with earlier all-cause mortality in patients without heart failure (relative risk, 1.1).

Makani H et al. Efficacy and safety of dual blockade of the renin-angiotensin system: Meta-analysis of randomised trials. BMJ 2013 Jan 28; 346:f360. (http://dx.doi.org/10.1136/bmj.f360)

Original article

Medline abstract

Antihypertensive Therapy plus Nonsteroidal Anti-Inflammatory Drugs Contribute to Risk for Kidney Injury

Triple therapy (a diuretic + an angiotensin-converting–enzyme inhibitor or angiotensin-receptor blocker + an NSAID) was associated with excess risk.

 Original article

 Medline abstract

Ascorbic Acid Supplements Linked to Kidney Stones

Use of vitamin C (ascorbic acid) supplements is associated with development of kidney stones in men, according to a study in JAMA Internal Medicine.

Nearly 50,000 men in Sweden completed questionnaires about their use of ascorbic acid. Over 11 years' follow-up, 0.9% developed kidney stones. Men who reported using ascorbic acid had nearly double the risk for incident kidney stones (adjusted relative risk, 1.92). Doses and brands were not available, but ascorbic acid supplements in Sweden typically contain 1000 mg per tablet.

The authors conclude: "Currently there are no well-documented benefits of high-dose ascorbic acid supplement use, and, therefore, it seems prudent to advise that high-dose preparations be avoided, particularly by those with a history of kidney stones."

JAMA Internal Medicine article

High Supplemental Calcium Intake Is Associated with Cardiovascular Death

But elevated risk was only in men and only for death from heart disease.

Xiao Q et al. JAMA Intern Med 2013 Feb 4;

Larsson SC. JAMA Intern Med 2013 Feb 4;

eGFR Levels Associated with Mortality in Patients with Kidney Disease

Associations between estimated glomerular filtration rate and death were different for men and women.

Nitsch D et al. BMJ 2013 Jan 29; 346:f324

Effect of Spironolactone on Diastolic Function and Exercise Capacity in Patients With Heart Failure With Preserved Ejection FractionThe Aldo-DHF Randomized Controlled Trial

JAMA. 2013;309(8):781-791. doi:10.1001/jama.2013.905.

Importance Diastolic heart failure (ie, heart failure with preserved ejection fraction) is a common condition without established therapy, and aldosterone stimulation may contribute to its progression.

Conclusions and Relevance In this randomized controlled trial, long-term aldosterone receptor blockade improved left ventricular diastolic function but did not affect maximal exercise capacity, patient symptoms, or quality of life in patients with heart failure with preserved ejection fraction. Whether the improved left ventricular function observed in the Aldo-DHF trial is of clinical significance requires further investigation in larger populations.

http://jama.jamanetwork.com/article.aspx?articleID=1656252&utm_source=Silverchair%20Information%20Systems&utm_medium=email&utm_campaign=MASTER%3AJAMALatestIssueTOCNotification02%2F26%2F2013

Surveillance Intervals for Small Abdominal Aortic AneurysmsA Meta-analysis

The RESCAN Collaborators*

JAMA. 2013;309(8):806-813. doi:10.1001/jama.2013.950.

Importance Small abdominal aortic aneurysms (AAAs [3.0 cm-5.4 cm in diameter]) are monitored by ultrasound surveillance. The intervals between surveillance scans should be chosen to detect an expanding aneurysm prior to rupture.

Results AAA growth and rupture rates varied considerably across studies. For each 0.5-cm increase in AAA diameter, growth rates increased on average by 0.59 mm per year (95% CI, 0.51-0.66) and rupture rates increased by a factor of 1.91 (95% CI, 1.61-2.25). For example, to control the AAA growth risk in men of exceeding 5.5 cm to below 10%, on average, a 7.4-year surveillance interval (95% CI, 6.7-8.1) is sufficient for a 3.0-cm AAA, while an 8-month interval (95% CI, 7-10) is necessary for a 5.0-cm AAA. To control the risk of rupture in men to below 1%, the corresponding estimated surveillance intervals are 8.5 years (95% CI, 7.0-10.5) and 17 months (95% CI, 14-22).

Conclusion and Relevance In contrast to the commonly adopted surveillance intervals in current AAA screening programs, surveillance intervals of several years may be clinically acceptable for the majority of patients with small AAA.

http://jama.jamanetwork.com/article.aspx?articleID=1656254&utm_source=Silverchair%20Information%20Systems&utm_medium=email&utm_campaign=MASTER%3AJAMALatestIssueTOCNotification02%2F26%2F2013

High Calcium Intake Linked to Increased CV and Mortality Risks in Women

Calcium intake above 1400 mg a day was associated with increased risks for cardiovascular disease and mortality among women in a prospective Swedish study in BMJ.

More than 60,000 women aged 39 to 73 at baseline completed a diet questionnaire starting in 1987. Over a median follow-up of 19 years, women who consumed 1400 mg or more of calcium daily (through diet or supplements) had 40% higher mortality, 51% higher cardiovascular mortality, and nearly double the ischemic heart disease mortality, compared with those who consumed 600 to 999 mg. Among women with 1400 mg daily intake, those who took calcium supplements had even higher all-cause mortality (adjusted hazard ratio, 2.57).

The authors conclude that efforts to prevent bone fractures in elders should focus "on people with a low intake of calcium rather than increasing the intake of those already consuming satisfactory amounts."

BMJ article (Free)

Beta-Blockers Less Effective in Heart Failure with Atrial Fibrillation

Patients with heart failure and atrial fibrillation do not benefit as much from beta-blocker therapy as those with sinus rhythm, according to a meta-analysis in the Journal of the American College of Cardiology: Heart Failure.

Researchers analyzed mortality outcomes from four studies including over 8500 patients with heart failure and reduced left-ventricular ejection fraction (<40%). Roughly 20% also had atrial fibrillation. Although those with atrial fibrillation who received beta-blockers had lower mortality risks than those receiving placebo (odds ratio, 0.86), patients with sinus rhythm fared much better (OR, 0.63). In addition, beta-blockers did not reduce hospitalizations for heart failure among patients with atrial fibrillation, whereas they did among those with sinus rhythm.

Editorialists call the study, "hypothesis-generating," and conclude that the results "at a minimum" suggest that treatment for those with heart failure and atrial fibrillation "should be approached differently" from those with sinus rhythm.

JACC: Heart Failure article

Maternal Folic Acid Intake Early in Pregnancy Associated with Reduced Autism Risk

Folic acid supplementation among women is associated with a reduced risk for autism in their offspring, according to a JAMA study.

Researchers studied a cohort of 85,000 infants from Norway, 0.13% of whom were later diagnosed with autistic disorder. Their mothers reported whether they took folic acid supplements during the 4 weeks before to 8 weeks after the beginning of pregnancy. (Food was not fortified with folic acid during this study.) After adjustment for potential confounders, mothers who took folic acid during this interval had children who were less likely to have autistic disorder, relative to mothers who did not use folic acid (adjusted odds ratio, 0.61). There was no association with Asperger syndrome or other autism spectrum disorders.

A secondary analysis done with fish oil supplements did not find a similar association with autism, suggesting that the effect was not attributable to general health-conscious behaviors.

CDC editorialists call the study "encouraging" and "provocative," but say it "seems at odds with the continued increases in [autism spectrum disorder] diagnoses observed in the United States since the folic acid food fortification program began in 1998."

JAMA article

Is Rhythm Control Better Than Rate Control for Atrial Fibrillation?

In a very large observational study, rhythm-control strategies resulted in fewer strokes and transient ischemic attacks than did rate-control strategies.

Tsadok MA et al. Circulation 2012 Dec 4; 126:2680

Rate Control for Atrial Fibrillation: What Is the Best Drug to Use?

In a small, randomized crossover trial of four commonly prescribed beta- and calcium-channel blockers, diltiazem emerged the winner.

Ulimoen SR et al. Am J Cardiol 2013 Jan 15; 111:225

No Link Between Bisphosphonate Use and Gastrointestinal Cancers

In case-control studies, bisphosphonate use of any dose did not confer risk.

Bisphosphonates, used for preventing and treating osteoporosis, can cause irritation of the gastrointestinal (GI) tract. However, whether use of these drugs is associated with excess risk for GI cancers is unclear. Using two large primary care databases, U.K. investigators conducted population-based, case-control studies to assess the association between bisphosphonate use (estimated from prescription data) and risk for GI cancers in older patients (age, 50).

Researchers matched each of 56,000 cases of colorectal, esophageal, or gastric cancer with as many as 5 controls in the same database. Adjusted for multiple confounders, overall bisphosphonate use ( 1 prescription) was not associated with excess risk for colorectal, esophageal, or gastric cancer in either database. Frequency and duration of bisphosphonate use and bisphosphonate type were not associated with excess cases of colorectal or esophageal cancer. In one database, short-term alendronate use (<1 year) was associated with excess risk for gastric cancer (odds ratio, 1.9), but long-term use was not.

Original article Medline abstract

Vinogradova Y et al. BMJ 2013 Jan 16; 346:f114

40-Year-Old Data Cast Doubt on Dietary-Fat Guidance

Data recovered from an old trial confirm the increased risks of substituting dietary omega-6 linoleic acid (ω-6 LA) for saturated fats, calling American Heart Association advice into question. The data appear in BMJ.

Cardiovascular outcome data from the 1966–1973 Sydney Diet Heart Study were analyzed for the first time. The trial, conducted among some 450 men with recent coronary events, tested the effect of replacing dietary saturated fats with ω-6 LA. Reports after the end of the trial showed increased all-cause mortality among those receiving ω-6 LA. The recovered data, which had been stored on tape, also show increased risks for mortality from cardiovascular disease (hazard ratio, 1.70) and coronary disease (1.74).

An editorialist writes: "These findings argue against the 'saturated fat bad, omega-6 [polyunsaturated fatty acid] good' dogma."

BMJ article (Free)

Mammograms in Older Women Better Done Biennially Than Annually

Older women undergoing mammography every 2 years versus annually are at lower risk for false-positive screens and at equal risk for advanced-stage disease, according to a study in the Journal of the National Cancer Institute.

Using data from the Breast Cancer Surveillance Consortium, researchers examined outcomes in some 140,000 older women who underwent mammography from 1999 to 2006. Roughly 3000 were diagnosed with breast cancer. The benefits of screening intervals were examined, along with adjustment for comorbidities.

The cumulative probability of a false-positive mammogram between ages 66 and 74 was 48% among those screened annually, versus 29% among the biennials. Tumor characteristics did not differ between the groups by comorbidity or screening interval.

JNCI article (Free abstract)

Antibiotics for COPD — Further Evidence of Benefit

Inpatients with chronic obstructive pulmonary disease exacerbations had better outcomes when treated with both steroids and antibiotics, according to a study in Chest.

Researchers retrospectively studied roughly 54,000 patients admitted to inpatient wards with acute exacerbations of COPD. Patients who received both steroids and antibiotics were compared with those who received steroids alone.

In-hospital mortality was low in both groups but was significantly lower in patients treated with antibiotics (1.0% vs. 1.8%). Rates of readmission by 30 days also were lower (5.4% vs. 6.8%).

How to Miss a Diagnosis in Primary Care

Diagnostic errors have a variety of contributing factors, but they most commonly occur during the encounter with the patient, according to aJAMA Internal Medicine study.

Researchers studied medical records from some 200 instances of unexpected return visits or emergency department use within 14 days of a primary care encounter — many due to missed diagnoses. The most commonly missed were pneumonia (7%), congestive heart failure (6%), and acute renal failure, cancer, and urinary tract infection (5% each). Faulty clinical encounters — involving, for example, bad history-taking, physical exam, or failure to review the existing record — were to blame in about 80% of cases.

Patients with missed diagnoses tended to be slightly older than those without errors. The medical records of the misdiagnosed tended to show no documentation of a differential diagnosis at the primary encounter. In addition, clinicians had often copied-and-pasted progress notes from the previous encounter into the electronic record.

JAMA Internal Medicine article

Brain Lesions Can Predict Alzheimer's Diagnosis
http://mnt.to/l/4bSv

Potential To Prevent And Treat Alzheimer's Disease Offered By Novel Herbal Compound
http://mnt.to/l/4bQH

Hormone Therapy Blocks Accelerated Biological Aging, Seen In Women With Alzheimer's Risk Factor
http://mnt.to/l/4bMV

Common Chemicals Linked To Osteoarthritis
http://mnt.to/l/4bPN

Alcohol Plays A Huge Role In Cancer Deaths In The U.S.
http://mnt.to/l/4bQ8

New Research Shows 'Flutter' Of Inactivity As Americans Ignore Warning Signs Of Atrial Fibrillation
http://mnt.to/l/4bRK

Analysis Links Ozone Levels, Cardiac Arrest
http://mnt.to/l/4bQK

Risk Of Cardiovascular Death Doubled In Women With High Calcium Intake - High Risk Only In Those Taking Supplements
http://mnt.to/l/4bLw

Vitamin C Helps Marathon Runners Reduce Risk Of Catching A Cold
http://mnt.to/l/4bMQ

Revolutionary Treatment Lowers Blood Pressure
http://mnt.to/l/4bQ3

Life-Saving Reduction In Sodium Consumption
http://mnt.to/l/4bJV

Music Lessons Before Age Seven Create Stronger Connections In The Brain
http://mnt.to/l/4bM8

Rewiring The Serotonin System
http://mnt.to/l/4bNB

How The Brain Unconsciously Processes Decision Information In Ways That Lead To Improved Decision Making
http://mnt.to/l/4bNs

Neither High Fructose Corn Syrup Nor Table Sugar Increases Liver Fat Under 'Real World' Conditions
http://mnt.to/l/4bM5

How To Get A Great Night's Sleep: Could Less Mean More?
http://mnt.to/l/4bNR

Exposure To Cold Air May Promote Longevity In Mammals
http://mnt.to/l/4bPQ

Bacteria Producing Nitric Oxide Extend Life In Roundworms
http://mnt.to/l/4bP6

Medical Professionals Should Consider How Marital Quality Affects Patients' Health
http://mnt.to/l/4bNK

Study Of Tiny Roundworms Provides Clue To Observed Human Health Benefits From Omega Fatty Acids
http://mnt.to/l/4bNF

Purified Extracts From Green Tea And Red Wine Interrupt Alzheimer's Disease Pathway In Cells
http://mnt.to/l/4bCf

Alzheimer's Amyloid Plaque Removal May Be Aided By Vitamin D And Omega 3
http://mnt.to/l/4bCD

Cognitive Impairment In Alzheimer's Disease Worsened By Damaged Blood Vessels Loaded With Amyloid
http://mnt.to/l/4bzG

Fitness And Dementia; Smarter PSA Testing For Prostate Cancer: Annals Of Internal Medicine Feb. 5, 2013
http://mnt.to/l/4bzB

Broken Down 'Motors' In The Brain Cause Anxiety
http://mnt.to/l/4bG4

Stress At Work Very Unlikely To Cause Cancer
http://mnt.to/l/4bGC

Giving May Shield Us From Stress And Help Us Live Longer
http://mnt.to/l/4bFM

Rapid Bone Loss Tied To Rib Fractures Treated With Steroids
http://mnt.to/l/4bCh

Your Ability To Master The Violin May Depend On The Functionality Of Your Small Finger
http://mnt.to/l/4bBf

Middle-Aged Men May Need More Protein To Maintain Muscle Mass
http://mnt.to/l/4bBc

Older Women Gain As Much Benefit From Mammograms Every 2 Years As Mammograms Every Year
http://mnt.to/l/4bCm

Tumour Blood Vessels Prevent The Spread Of Cancer Cells
http://mnt.to/l/4bJP

Sunlight Reduces The Risk Of Esophageal Cancer
http://mnt.to/l/4bFx

Men Experiencing Permanent Stress At Increased Risk For Type 2 Diabetes
http://mnt.to/l/4bGn

'Bad' Gut Bacteria May Help Control Diabetes
http://mnt.to/l/4bHy

Persistent Organic Pollutants In The Body Linked To The Development Of Type 2 Diabetes
http://mnt.to/l/4bD4

Risk For Type 1 Diabetes May Be Increased By Low Vitamin D Levels
http://mnt.to/l/4bBs

Patients Taking Insulin For Type 2 Diabetes May Be At Increased Risk Of Health Complications
http://mnt.to/l/4bzC

Unchecked Inflammatory Response Quelled By Zinc
http://mnt.to/l/4bFZ

Researchers Find The Cause Of Age-Related Cognitive Decline
http://mnt.to/l/4bGW

Fear Factor: Study Shows Brain's Response To Scary Stimuli
http://mnt.to/l/4bH9

Important New Insight Into The Neural Mechanisms Of Learning And Memory
http://mnt.to/l/4bBz

Unraveling The Brain's Vision Secrets
http://mnt.to/l/4bzh

Southern Diet Increases Risk Of Stroke
http://mnt.to/l/4bHb

Discussing Dietary Fats
http://mnt.to/l/4bFr

Canker Sore Drug Lowers Weight In Mice Without Diet, Exercise
http://mnt.to/l/4bJr

Obese Women Taking Certain Contraceptive May Be At Increased Risk For Type 2 Diabetes
http://mnt.to/l/4bGx

Possible Link Between Obesity And Gum Disease
http://mnt.to/l/4bDW

Getting Older Increases Risk Of Death From Excessive BMI, Correcting Flaw In Earlier 'Obesity Paradox' Research
http://mnt.to/l/4bCM

Obesity Causes Vitamin D Deficiency
http://mnt.to/l/4bFw

Exercise Linked With Reduced Prostate Cancer Risk In Caucasians But Not African Americans
http://mnt.to/l/4bGz

The Truth Behind Cupid's Arrow
http://mnt.to/l/4bHz

Potential Target Identified For Age-Related Cognitive Decline
http://mnt.to/l/4bFN

Sunshine Reduces Risk of Rheumatoid Arthritis
http://mnt.to/l/4bz7

Insight Into The Mechanics Of Arthritis
http://mnt.to/l/4btW

Lifelong Guide To Strong Bones
http://mnt.to/l/4bx8

Researchers Capture Key Moments In Cell Death
http://mnt.to/l/4byn

Changing Bioelectric Signals A Key To Halting Tumor Growth
http://mnt.to/l/4byf

Understanding 'Master Regulator' Genes Could Lead To Better Cancer Treatments
http://mnt.to/l/4bxR

How Cancer Cells Rewire Their Metabolism To Survive
http://mnt.to/l/4bxK

A New Mechanism That Contributes To The Evolution Of Cancer
http://mnt.to/l/4bxh

Avoid Eight Cancer Screenings, Says Consumer Reports
http://mnt.to/l/4by6

Blue Light Destroys Skin, Soft Tissue Infections
http://mnt.to/l/4bsZ

A Sedentary Lifestyle Can Reduce Sperm Quality
http://mnt.to/l/4bz9

Vitamin D Deficiency Likely Responsible For Flu Epidemic
http://mnt.to/l/4btr

Scientists Identify Culprit In Obesity-Associated High Blood Pressure
http://mnt.to/l/4bxM

Previously Unknown Mechanism Of Memory Formation Discovered
http://mnt.to/l/4bw7

Vegetarian Diet Reduces Risk Of Heart Disease By A Third
http://mnt.to/l/4bvf

Do The Health Benefits Of Berries Make It Past Your Mouth?
http://mnt.to/l/4bsg

BMI - Is The Body Mass Index Formula Flawed?
http://mnt.to/l/4bwD

Small Changes Like Taking Stairs, Raking Leaves May Equal A Trip To The Gym
http://mnt.to/l/4bsy

The Science Behind Satiety And Overeating
http://mnt.to/l/4bsv

Deep Fried Food Tied To Prostate Cancer
http://mnt.to/l/4bsY

Research Helps To Explain Early-Onset Puberty In Females
http://mnt.to/l/4bt

Stress Early In Life Can Affect Heart Function Early
http://mnt.to/l/4bXG

Exposure To Air Pollution Is Associated With Increased Deaths After Heart Attacks
http://mnt.to/l/4bTw

Pollution Linked To Increased Risk Of Death Among Heart Attack Patients
http://mnt.to/l/4bSC

Caught In The Act: Miniature Crime Scene Identifies The Culprit For Arrhythmia
http://mnt.to/l/4bRg

Hope For New Ways To Treat Diabetes And Cardiovascular Disease Following Discoveries Linking Gut Bacteria With Cholesterol Metabolism
http://mnt.to/l/4bRY

Obesity, Physical Inactivity Linked With Risk For Certain Molecular Subtype Of Colorectal Cancer
http://mnt.to/l/4bYz

For Colorectal Cancer Prevention, Resistant Starch Should Be On The Menu
http://mnt.to/l/4bTR

Halting Metastasis Of Colon Cancer
http://mnt.to/l/4bS9

Acne Linked To High Glycemic Index Foods And Dairy Products
http://mnt.to/l/4bTW

New Therapeutics Developed That Could Accelerate Wound Healing
http://mnt.to/l/4bTT

Pancreatic Cells Reprogrammed By Epigenetic Alterations To Secrete Insulin
http://mnt.to/l/4bXX

Glucagonlike Peptide 1-Based Therapies Associated With Acute Pancreatitis In Study
http://mnt.to/l/4bYN

Older African American Women At Increased Risk For Endocrine Disorder, The Most Common Cause Of Elevated Calcium Levels
http://mnt.to/l/4bXn

If Degenerative Cervical Spine Disease Doesn't Progress, Is Surgery Necessary?
http://mnt.to/l/4bTh

Mediterranean Diet Reduces Heart Attack, Stroke In High Risk Groups
http://mnt.to/l/4bZ4

Avocado Consumption May Be Associated With Better Diet Quality
http://mnt.to/l/4bWf

Red Wine And Red Grapes Help Protect Against Hearing Loss And Cognitive Decline
http://mnt.to/l/4bXS

High Fat Diets Maybe Linked To ADHD And Learning Problems
http://mnt.to/l/4bXN

Antioxidants Do Not Reduce Stroke Or Dementia Risk
http://mnt.to/l/4bW8

Diet Drinks Do Not Increase Appetite
http://mnt.to/l/4bV9

Caffeine Consumption And Mortality
http://mnt.to/l/4bTd

Organic Tomatoes Accumulate More Vitamin C, Sugars Than Conventionally Grown Fruit
http://mnt.to/l/4bTr

Modern Lifestyles Can Put Your Health At Risk
http://mnt.to/l/4bWN

"I'm Not Just Fat, I'm Old!"
http://mnt.to/l/4bTy

Decline In Walking Speed As We Age Likely Due To Thigh Fat
http://mnt.to/l/4bSZ

Time Spent Sitting Related To Risk Of Chronic Diseases
http://mnt.to/l/4bSf

Fish Oil Component Reduces Brain Damage In Newborns
http://mnt.to/l/4bVj

In Mouse Model, Omega-3 Lipid Emulsions Markedly Protect Brain After Stroke
http://mnt.to/l/4bVg

To attain knowledge, add things every day. To attain wisdom, subtract things every day."

--Laozi,
Chinese philosopher