HHAL MEDICAL NEWS AUGUST 2011

Meta-Analysis: Chocolate Appears to Be Heart-Healthy

Higher levels of chocolate intake "seem to be associated with a substantial reduction in the risk of cardiometabolic disorders," a BMJ meta-analysis reports.

Researchers examined seven observational studies, encompassing nearly 115,000 adult participants, that measured chocolate intake and cardiometabolic outcomes. Compared with the lowest level of chocolate consumption, the highest intake was associated with a roughly one third decrease in the risk for any cardiovascular disease or stroke. There was no benefit, however, with regard to heart failure.

The authors offer several cautions with their findings, including the fact that high levels of fat and sugar are found in most commercial preparations of chocolate. They also note that the present evidence only points to an association between chocolate and heart health.

BMJ article (Free)

Moderate Chocolate Consumption Linked to Lower Risk for Heart Failure in Women

Moderate chocolate consumption might lower a woman's risk for heart failure (HF), according to a study in Circulation: Heart Failure.

More than 30,000 middle-aged and older Swedish women without histories of diabetes, HF, or myocardial infarction completed food-frequency questionnaires and then were followed for roughly 9 years. During that time, 1.3% were hospitalized for, or died from, HF.

Compared with women who didn't eat chocolate, those who consumed one to three servings a month had about a 25% reduction in HF risk, while those who consumed one to two servings a week had a 30% risk reduction. Higher intake did not appear to have a protective effect.

The authors point out that chocolate is a good source of flavonoids, which might improve cardiovascular risk factors. They note, however, that chocolate consumed in the U.S. likely contains less cocoa (known to be cardioprotective) than that consumed by women in this study.

Circulation: Heart Failure article (Free PDF)

Dark Chocolate Associated with Lowered Blood Pressure

Small amounts of dark chocolate can modestly lower blood pressure in people with untreated hypertension, a small randomized trial in JAMA concludes.

Researchers studied 44 older adults who were assigned to eat either 6.3 grams of dark or white chocolate daily. The patients had untreated blood pressures in the upper prehypertension range or were in stage 1 hypertension. After 18 weeks, systolic blood pressure fell about 3 mm and diastolic 2 mm in those eating dark chocolate but did not change in the control group. The authors point to dark chocolate's role in increasing the production of nitric oxide in the vascular endothelium as a possible mechanism.

The authors note that the improvements were similar to those seen with comprehensive dietary modifications. Eating a little chocolate is easier and "may be a promising behavioral approach to lower blood pressure in individuals with above-optimal blood pressure," the authors write.

JAMA article

Cranberries vs. TMP-SMX to Prevent Urinary Tract Infections

Trimethoprim-sulfamethoxazole was better, at the expense of greater antibiotic resistance.

Premenopausal women who experience recurrent urinary tract infections (UTIs) are sometimes prescribed low-dose antibiotic prophylaxis. Growing concern about antibiotic resistance, coupled with many patients' desire for nonpharmacologic remedies, has led to renewed interest in cranberry consumption for UTI prophylaxis. The presumed mechanism is prevention of bacterial adhesion to uroepithelial cells by proanthocyanidins, a constituent of cranberries.

In a double-blind study, Dutch investigators randomized 221 women (median age, 35) who reported having a median of 6 to 7 UTIs in the previous year to receive either cranberry extract (500 mg twice daily) or trimethoprim-sulfamethoxazole (TMP-SMX; 480 mg nightly). During 12 months of treatment, cranberry-extract recipients had a mean of 4 symptomatic UTIs compared with a mean of 1.8 in the TMP-SMX group — a significant difference; the median time to first recurrence was 4 months in the cranberry group and 8 months in the antibiotic group. Adverse events did not differ between groups, but the dropout rate was about 50% in both.

Daily Bisacodyl Effective for Chronic Constipation 

Whether tolerance will develop after more-prolonged therapy — and whether intermittent treatment might produce better results for some patients — remains to be determined.

 Kamm MA et al. Clin Gastroenterol Hepatol 2011 Jul 9:577

Vertebroplasty Isn't Effective for Vertebral Compression Fractures

A meta-analysis showed no benefit over sham injection.

 Staples MP et al. BMJ 2011 Jul 12; 343:d3952

Wilson DJ. BMJ 2011 Jul 12; 343:d3470

Stroke Risk-Stratification Scores Have Limited Prognostic Value in Elders with AF

The authors suggest anticoagulation for all elders with atrial fibrillation.

 Hobbs FDR et al. BMJ 2011 Jun 23; 342:d3653

Stenting for Symptomatic Extracranial Vertebral Artery Stenosis

Rates of periprocedural stroke, transient ischemic attack, and restenosis are low, according to a systematic literature review.

 Stayman AN et al. Stroke 2011 Jun 23;

Endovascular Coiling vs. Surgical Clipping for Unruptured Cerebral Aneurysms: Does Patient Age Matter?

Outcomes were significantly better after coiling than after clipping in all age groups, and coiling's advantage increased with advancing age.

 Brinjikji W et al. Stroke 2011 May 42:1320

Are Hospitalists Really Cost-Effective?

A retrospective cohort study suggests that hospitalist care leads to higher total expenditures and more medical utilization following hospital discharge.

 KuoY-F and Goodwin JS. Ann Intern Med 2011 Aug 2; 155:152

Chen LM and Saint S. Ann Intern Med 2011 Aug 2; 155:194

Wellness index ranks the happiest states
The latest Gallup-Healthways Well-Being Index puts Hawaii and North Dakota at the top of its list of happiest states, while West Virginia is in last place, a spot it has occupied for several years. The index, based on surveys of more than 177,000 U.S. adults earlier this year, looks at emotional health, work environment, healthy behaviors, physical health and access to basic necessities. The New York Times (tiered subscription model)/Economix blog 

August 22, 2011

Hawaii Continues to Lead in Wellbeing; North Dakota Second

Southern states still struggle with low wellbeing

by Dan Witters

WASHINGTON, D.C. -- Americans in Hawaii continued to set the national standard in wellbeing in the first half of 2011, followed closely by North Dakota. West Virginia and Kentucky maintained their status as the states with the lowest wellbeing. Nebraska, which showed the biggest gains in wellbeing rank from 2009 (25^th) to 2010 (10^th), continued to move up, landing in the top five.

These state-level data, from the Gallup-Healthways Well-Being Index, are meant to provide a preliminary reading on the wellbeing of U.S. states in anticipation of the complete 2011 rankings, to be released early next year.

The Well-Being Index score for the nation and for each state is an average of six sub-indexes, which individually examine life evaluation, emotional health, work environment, physical health, healthy behaviors, and access to basic necessities. The January through June 2011 aggregate includes more than 177,000 interviews conducted among national adults, aged 18 and older.

The midyear Well-Being Index score for the country so far in 2011 is 66.4, a slight decline from 66.8 for all of 2010. The Well-Being Index is calculated on a scale of 0 to 100, where a score of 100 would represent ideal wellbeing. Well-Being Index scores among states vary by a range of 8.7 points.

Southern States Continue to Struggle With Low Wellbeing

More states in the South than anywhere else in the country have wellbeing scores in the lower range, as has been true in the past. Eight of the bottom 11 states in wellbeing (Missouri is classified as a Midwestern state) are Southern states.

Many Western states, in contrast, thrive in wellbeing, with four out of the top seven -- Hawaii, Alaska, Colorado, and Utah -- located in that region of the country. Five Midwestern states -- North Dakota, Nebraska, Minnesota, Kansas, and Iowa -- are also in the top 12, as are three Eastern states: New Hampshire, Vermont, and Maryland.

North Dakota's Well-Being Index composite score has moved up proportionally more than any other state since last year, to 70.5 from 68.4. Wellbeing in Wyoming has declined the most, dropping to 66.5 thus far in 2011 from 69.2 last year, though Wyoming has a relatively small sample size at the halfway point of the year, and thus, a larger margin of error. (See page 2 for a complete list of state Well-Being Index scores.)

Hawaii Again Tops List in Emotional and Physical Health

On the sub-indexes that make up the broader Well-Being Index, Hawaii is tops in Emotional Health and Physical Health, two domains in which it perennially leads the nation. Alaska does the best on Life Evaluation, North Dakota on Work Environment, and Vermont on Healthy Behavior, typically its strongest area. Massachusetts, which is always at or near the top in Basic Access, is once again leading on that dimension thus far in 2011.

At the bottom, West Virginia fares worst on Life Evaluation and Physical Health -- two areas in which residents of this state have seriously struggled since the launch of the Well-Being Index in 2008. Kentucky performs worst on Emotional Health, and Mississippi is again at the bottom on Basic Access, consistent with three previous years of tracking. Louisiana has the lowest Work Environment score so far in 2011, replacing Delaware for the first time since 2009 in that bottom spot. Oklahomans exhibit the unhealthiest behaviors.

Implications

The overall wellbeing of the nation has thus far trended down 0.4 points in 2011, representing a modest decline from 2010 in Americans' collective wellbeing. At midyear, many of the usual Western, Midwestern, and Eastern states top the country in wellbeing, while Southern states are again more prevalent toward the bottom of the list. The states at the very top and very bottom have remained largely unchanged since 2008, demonstrating highly consistent patterns over time.

View and export complete wellbeing data by metro area using Gallup's U.S. City Wellbeing Tracking interactive.

About the Gallup-Healthways Well-Being Index

The Gallup-Healthways Well-Being Index tracks U.S. wellbeing and provides best-in-class solutions for a healthier world. To learn more, please visit well-beingindex.com.

Survey Methods

Results are based on telephone interviews conducted as part of the Gallup-Healthways Well-Being Index survey Jan. 2-June 30, 2011, with a random sample of 177,600 adults, aged 18 and older, living in all 50 U.S. states and the District of Columbia, selected using random-digit-dial sampling.

For results based on the total sample of national adults, one can say with 95% confidence that the maximum margin of sampling error is ±0.2 percentage points. The margin of sampling error for most states is ±1-2 percentage points, but is as high as ±4 points for smaller states such as Wyoming, North Dakota, South Dakota, Nebraska, and Hawaii.

Interviews are conducted with respondents on landline telephones and cellular phones, with interviews conducted in Spanish for respondents who are primarily Spanish-speaking. Each daily sample includes a minimum quota of 400 cell phone respondents and 600 landline respondents, with additional minimum quotas among landline respondents for gender within region. Landline respondents are chosen at random within each household on the basis of which member had the most recent birthday.

Samples are weighted by gender, age, race, Hispanic ethnicity, education, region, adults in the household, and phone status (cell phone only/landline only/both, cell phone mostly, and having an unlisted landline number). Demographic weighting targets are based on the March 2010 Current Population Survey figures for the aged 18 and older non-institutionalized population living in U.S. telephone households. All reported margins of sampling error include the computed design effects for weighting and sample design.

In addition to sampling error, question wording and practical difficulties in conducting surveys can introduce error or bias into the findings of public opinion polls.

For more details on Gallup's polling methodology, visit www.gallup.com.

Treatment With Vitamin C Dissolves Toxic Protein Aggregates In Alzheimer's Disease

Researchers at Lund University have discovered a new function for vitamin C. Treatment with vitamin C can dissolve the toxic protein aggregates that build up in the brain in Alzheimer's disease. The research findings are now being presented in the Journal of Biological Chemistry.

The brains of people with Alzheimer's disease contain lumps of so-called amyloid plaques which consist of misfolded protein aggregates. They cause nerve cell death in the brain and the first nerves to be attacked are the ones in the brain's memory centre.

"When we treated brain tissue from mice suffering from Alzheimer's disease with vitamin C, we could see that the toxic protein aggregates were dissolved. Our results show a previously unknown model for how vitamin C affects the amyloid plaques", says Katrin Mani, reader in Molecular Medicine at Lund University.

"Another interesting finding is that the useful vitamin C does not need to come from fresh fruit. In our experiments, we show that the vitamin C can also be absorbed in larger quantities in the form of dehydroascorbic acid from juice that has been kept overnight in a refrigerator, for example".

There is at present no treatment that cures Alzheimer's disease, but the research is aimed at treatments and methods to delay and alleviate the progression of the disease by addressing the symptoms.

That antioxidants such as vitamin C have a protective effect against a number of diseases, from the common cold toheart attacks and dementia, has long been a current focus of research.

"The notion that vitamin C can have a positive effect on Alzheimer's disease is controversial, but our results open up new opportunities for research into Alzheimer's and the possibilities offered by vitamin C", says Katrin Mani.

Sources: Lund University, AlphaGalileo Foundation. 

Older Women with Sleep-Disordered Breathing at Higher Risk for Cognitive Impairment

Older women with sleep-disordered breathing are more likely to develop cognitive impairment, according to a prospective study in JAMA.

Some 300 U.S. women aged 65 or older without dementia underwent in-home polysomnography for one night; about one third demonstrated sleep-disordered breathing.

During roughly 5 years' follow-up, 35% of all participants developed mild cognitive impairment or dementia. The incidence was significantly higher among women with than without sleep-disordered breathing (45% vs. 31%). Intermittent hypoxia (but not sleep fragmentation or duration) appeared to account for the elevated risk.

Editorialists call for more research but conclude that "physicians of patients with mild cognitive impairment and sleep-disordered breathing for whom treatment with CPAP [continuous positive airway pressure] may be indicated should consider these results."

JAMA article (Free)

Soy Isoflavones and Menopause: No Benefit

Soy provided no improvement in bone density or hot flashes.

Levis S et al. Arch Intern Med 2011 Aug 8/22; 171:1363

Newton KM and Grady D. Arch Intern Med 2011 Aug 8/22; 171:1369

Weight Loss Boosts Libido Of Obese Men With Diabetes

A recent investigation has confirmed sexual desire and performance can be significantly improved in obese diabetic men if they lose weight on a high protein or low calorie diet. Just published in the Journal of Sexual Medicine, Will Williams, scientific advisor to the All About Weight organization, explained that the clinical investigation found that sexual function improved drastically and faster in obese men with Type 2 diabetes after they lost weight. Other investigations have discovered that the more overweight a male is, the lower his level of testosterone.

Williams explains:

"If you're overweight, losing that excess fat and exercising will probably increase your testosterone levels. Put that together with the improved self-esteem that comes with losing weight and it is not surprising that the sex drive is re-invigorated."

The recent study involved 31 men who lost between 5% and 10% of their body weight in eight weeks. A feature of the investigation was that it compared two types of diet. One group were put on a low-calorie, meal-replacement diet, while the others followed a high-protein low-carbohydrate diet. In both groups libido and sexual function improved. 

As the men lost weight, both groups also experienced the additional benefits of improving their insulin sensitivity,cholesterol levels and reducing systemic inflammation (a risk factor for heart disease). 

Mr Williams said:

"This is good news for men with diabetes, who often find that libido and sexual function is reduced as their diabetes progresses. It's important to select the right sort of diet to suit your health and lifestyle requirements."

Statins cut risk of stroke recurrence in young adults
People ages 15 to 49 who suffered an ischemic stroke and were treated with a statin at any point after the stroke had a 77% reduced risk of another stroke or blocked arteries compared with counterparts who never took a statin, a study in the journal Neurology found. "This study suggests that the drugs should be considered even when the cause of the stroke is unknown and the cholesterol levels are not high," said researcher Jukka Putaala. WebMD 

Body functionality becomes more important with age, study suggests
Researchers found that people's idea of body satisfaction changes from appearance to functionality as they age, with men giving functionality more importance than women do. The study in the Annals of Behavioral Medicine indicated that higher body satisfaction based on appearance and function translated to lower depressive symptoms among older adults. United Press International 

Constipation -- A cardiovascular risk? And for whom?
In postmenopausal women, constipation is a marker for cardiovascular risk factors and increased cardiovascular risk. Because constipation is easily assessed, it may be a helpful tool to identify women with increased cardiovascular risk. The American Journal of Medicine 

Holter Monitoring in Octogenarians with Syncope

11% of patients had symptomatic arrhythmias.

 Kühne M et al. J Am Geriatr Soc 2011 Jul 59:1293

Bacterial vaginosis: Test the partner, too
These authors report that a gram stain (Nugent) score for bacterial vaginosis greater than eight is associated with incident sexually transmitted infections. American Journal of Obstetrics & Gynecology

CT Angiography Predicts Prognosis in Symptomatic Patients

These computed tomography results, however, cannot be generalized to asymptomatic populations.

Computed tomographic angiography (CTA) is used increasingly for detection of obstructive coronary disease, but do the findings predict prognosis and future adverse cardiovascular events? Investigators addressed this issue in a meta-analysis of 11 studies, each with a minimum enrollment of 100 patients and minimum follow-up of 1 year. All patients had symptoms that were suggestive of coronary artery disease.

In nine studies (total enrollment, >3500), having at least one marked stenosis ( 50%) was associated with an annualized rate of mortality, myocardial infarction, unstable angina, and revascularization of 11.9%, but revascularization accounted for 62% of the 252 events. Left main stenosis, assessed in four studies, was associated with a hazard ratio of 6.6, and any atherosclerotic plaque, including subocclusive plaque, was associated with an HR of 4.5. Interestingly, in the three studies in which the incremental value of marked coronary stenosis over coronary artery calcium scoring was examined, the association remained highly significant (HR, 11.2).

Medline abstract (Free)

CCTA in Low-Risk Patients: Some Benefit, but at a Price

Coronary computed tomographic angiography resulted in more use of preventive medications — and more follow-up testing.

McEvoy JW et al. Arch Intern Med 2011 Jul 25; 171:1260

Lauer MS. Arch Intern Med 2011 Jul 25; 171:1268

Coronary artery calcium: A better predictor in more ways than one
CAC seems to further stratify risk in patients eligible for JUPITER, and could be used to target subgroups of patients who are expected to derive the most, and the least, absolute benefit from statin treatment. Focusing of treatment on the subset of individuals with measurable atherosclerosis could allow for more appropriate allocation of resources. (Free registration required.) The Lancet

Coronary Artery Calcium Beats C-Reactive Protein In Predicting Who Might Benefit From Statins

According to this week's European Society of Cardiology special issue of The Lancet, a study team led by Dr Michael J Blaha, Ciccarone Center for the Prevention of Heart Disease at the Johns Hopkins Hospital in Baltimore, MD, USA, discovered that coronary artery calcium (CAC) is a much better predictor of heart attack and stroke in apparently healthy adults compared to the level of C-reactive protein (CRP). Therefore, CAC levels, which directly measure atherosclerosis in coronary arteries, may be better at identifying those patients most likely to benefit from statin treatment. 

The initial use for statins was for the treatment of patients with high cholesterol levels; however, a previous study (JUPITER trial) established that healthy patients with normal cholesterol, but higher levels of CRP (an inflammatory marker), also benefited from statin treatment. 

Researchers conducted this new study using 950 patients from the Multi-Ethnic Study of Atherosclerosis (MESA) who would have been eligible for JUPITER, and looked at how CAC could establish risk. CAC levels were obtained by using a CT scan of the heart. 

The researchers discovered, that 47% of MESA patients eligible for JUPITER had CAC scores of 0 with extremely low rates of coronary heart disease events (0.8 per 1000 person-years) in this group. 

A group of 25% of participants had CAC scores of more than 100 (20 per 1000 person-years) registering 74% of all coronary events. 

95% of all heart attacks in the study population occurred in people with some measurable level of CAC. 

In contrast to 13% of those with the highest levels of coronary calcium (scores >100) suffering from a heart attack or stroke during the study, only 2% of those with high CRP but no detectable levels of CAC did so. 

The authors calculated that to prevent one heart attack in people with a CAC score of 0, 549 people would need treatment with statins for 5 years, compared with only 24 for those with CAC scores over 100. The statistics were calculated by using the 46% cardiovascular event reduction observed with statins in JUPITER. 

The researchers calculated that 124 patients, including those with heart attacks or stroke, would need statin treatment for 5 years to prevent one event, but this number decreases to 19 for those with the highest CAC scores. 

To sum up the study, simple presence of CAC was linked to a 4.3 times higher risk of coronary heart disease (interruption of the blood supply to the heart muscle due to fatty deposits in the coronary arteries, leading to heart attacks) and a 2.6 times increased risk of cardiovascular disease (heart attacks or stroke). High levels of CRP were not linked to adverse events after accounting for routinely measured risk factors. It is significant to mention, that CAC predicts heart attacks and strokes equally well regardless of the CRP level. 

The authors say, "Future guidelines for primary prevention of cardiovascular disease and coronary heart disease should include CAC for those patients that have normal cholesterol but some other risk factor, including obesity, pre-diabetes/metabolic syndrome, or a family history of heart disease." Dr Blaha added, "We think that it is time to move past traditional risk factors and blood tests and toward incorporation of direct measures of subclinical atherosclerosis in risk prediction. This makes sense because CAC uses modern technology to directly measure the disease we propose to treat with statins."

Researchers state that their results support previous studies that CAC has better predictive value than CRP, but extends that finding specifically to patients with normal cholesterol levels. 

Stopping Aspirin Raises Risk for Nonfatal Myocardial Infarction in Patients with Cardiovascular Disease

However, risk for coronary heart disease death did not increase.

 García Rodríguez LA et al. BMJ 2011 Jul 19; 343:d4094

Aspirin 50 mg or 100 mg: No difference in platelet response?
This study revealed no difference in antiplatelet response to either aspirin of 50 vs. 100 mg or cardiovascular events over five years in patients with coronary artery disease. The American Journal of Cardiology

What's most cost-effective to diagnose hypertension?
These researchers found that ambulatory monitoring was the most cost-effective strategy for the diagnosis of hypertension for men and women of all ages. It was cost-saving for all groups and resulted in small but significant improvements in quality of life. The authors recommend ambulatory monitoring before the start of antihypertensive treatment. (Free registration required.) The Lancet

Clinic-Based BP Measurement Is Inaccurate for Diagnosing Hypertension

Compared with ambulatory blood pressure measurements, those obtained in the clinic or at home are far less accurate.

Most clinicians rely on clinic- or home-based measurement of blood pressure (BP) for diagnosing hypertension. However, whether such measurements are accurate is unclear. In this systematic review and meta-analysis of 20 studies that involved 5700 patients, U.K. investigators determined how accurately clinic- and home-based BP measurements diagnosed hypertension; daytime ambulatory BP measurements were the reference standard.

The studies varied in the number of BP measurements obtained for ambulatory (24–111), clinic (2–18), and home (18–56) monitoring. Compared with a mean daytime ambulatory BP of >135/85 mm Hg for diagnosing hypertension (the reference standard), a mean clinic BP of >140/90 had a sensitivity of 75% and a specificity of 75%, and a mean home BP of >135/85 had a sensitivity of 86% and a specificity of 62%. How often these differences affected clinical accuracy depended on the prevalence of hypertension: If prevalence was 10% (e.g., in people  40), only one in four diagnoses of hypertension based on clinic BP measurements would be correct, whereas, if prevalence was 50% (e.g., in people  65), then three in four diagnoses of hypertension would be correct.

Original article (Subscription may be required)

Medline abstract (Free)

Depression Associated with Increased Risk for Stroke in Older Women

Both depression and antidepressant use are associated with increased risk for stroke, according to a prospective study in Stroke.

More than 80,000 Nurses' Health Study participants aged 54 to 79 without a history of stroke were assessed for depression; nearly one quarter were considered depressed.

During 6 years' follow-up, about 1000 strokes occurred. After multivariable adjustment, the risk for stroke was 29% higher among depressed than nondepressed women (0.3% for those reporting current depression vs. 0.2% without depression). In addition, antidepressant use, regardless of depression diagnosis, was associated with a significantly increased risk for stroke; the elevated risk was seen mainly with SSRIs.

The authors say their findings "provide additional evidence that depression is associated with a moderately increased risk of incident stroke." They call for more research "to determine whether the risk associated with depression can be reduced by other therapies or preventive strategies."

Stroke article 

Cholesterol-lowering foods beat low-fat diet alone in study
A Canadian study found that people who were advised to eat cholesterol-lowering foods, such as soy milk and nuts, achieved a greater than 13% reduction in LDL cholesterol, compared with a 3% decrease for those told to follow a low-fat, high-fiber diet. The study found that food with viscous fiber, such as barley and oats, and food with plant sterols, such as enhanced margarine, are among the most likely to lower cholesterol. The findings appear in the Journal of the American Medical Association. HealthDay News

Well-Being Index: Healthy behaviors are at low ebb in U.S.
The June Well-Being Index from Healthways and Gallup showed low ratings for healthy behaviors among Americans, with 66.5% of survey respondents reporting they ate healthy the entire day before. Only 55.7% got the recommended five servings of fruits and vegetables for four of the previous seven days, and 53.4% reported they exercised for at least 30 minutes on three of seven days the week before. Zacks

Azithromycin Prevents COPD Exacerbations

Select patients with frequent exacerbations of chronic obstructive pulmonary disease despite optimal therapy might benefit from prophylaxis.

 Albert RK et al. N Engl J Med 2011 Aug 25; 365:689

Does Gabapentin Prevent Postherpetic Neuralgia?

Researchers believe so, but their uncontrolled trial doesn't prove it.

Lapolla W et al. Arch Dermatol 2011 Aug 147:901

In a first of its kind study, assessing anti-cancer properties of ginger as a whole instead of the plant's individual components, scientists at Georgia State University have discovered, that whole ginger extract has promising cancer-preventing activity in prostate cancer. 

According to an online article in FirstView published in theBritish Journal of Nutrition, Associate professor of Biology, Ritu Aneja discovered in her lab, that ginger extract had significant effects in stopping the growth of cancer cells, as well as in inducing cell death in a spectrum of prostate cancer cells. 

In addition, animal studies revealed that the extract did not show significant toxicity to normal tissues, such as bone marrow. Research revealed very good tumor regression by up to 60 percent, and no toxicity whatsoever. 

Despite much research having been performed on anti-cancer properties in ginger, Aneja's lab prefers to take a more holistic approach to investigate the types of molecules involved. She does not believe individual compounds are solely responsible for the extract's anti-cancer properties and considers it to be a synergistic interplay of components, enabling scientists to use much smaller amounts of extract to benefit from its properties instead of using a single chemical. 

Data evaluation shows that humans would have to consume only about 3½ ounces of whole ginger extract in their daily diet to achieve the beneficial effects. 

Aneja's lab prefers to seek natural, non-toxic ways to combat cancer, using kinder, gentler drugs and plant compounds because current approaches cause major and debilitating side effects. 

To detect beneficial properties in plant extracts is a high lywork-intensive process in order to establish what exact chemical compounds in the extract provide the preventative effect, or kill cancer cells. 

Aneja said:

"Although it might seem easy to work with plant extracts, it is not so, because there are zillions of compounds and other complex derivatives in there, and we don't know which ones are the good ones. Moreover, the compounds we are seeking to identify may be low in abundance, but they may be very important and cannot be disregarded."

The work was started by dedicated and persistent undergrad, Vibhuti "Simran" Sharma, now an environmental chemist for the Southern Company; one of Aneja's numerous undergraduate research students she mentored. 

Sharma said:

"I did a lot of background research, and found several published papers on ginger, but discovered that there was nothing much done on the whole extract, especially in prostate cancer - a slow growing, long-latency cancer amenable to chemopreventive strategies. Most of the literature focused on only one compound found in ginger."

To enable undergraduate students to study independently in a stimulating and motivational environment, Aneja combines guidance with independent exploration. Sharma continued to educate herself about techniques and protocols and took it upon herself to convert three pounds of ginger into the extract for the study. 

Getting the extract to freeze dry was a three-week process of trial and error for Sharma as it turned from ice into a solid but reverted into a liquid, initially. 

After experimenting with prostate, breast and cervical cancer cells, she discovered that most cells responded positive to the extract. Aneja's lab took the research further in prostate cancer and Sharma, a graduate herself now, continues to assist in Aneja's lab with the production of more whole ginger extract for further fractionation and ongoing efficacy studies. 

Vegetarians Have Lower Risk for Symptomatic Diverticular Disease

Results support earlier findings on the protective effects of dietary fiber intake and vegetarianism on diverticular disease.

Crowe FL et al. BMJ 2011 Jul 19; 343:d4131

Fatal Outcomes of Eating Disorders

In a meta-analysis of studies with an average of 13 years of follow-up, anorexia nervosa was associated with a standardized mortality ratio of 5.86.

Arcelus J et al. Arch Gen Psychiatry 2011 Jul 68:724

Is Folic Acid a Risk Factor for CRC?

No type of folate, including folic acid, increased the risk for colorectal cancer.

Stevens VL et al. Gastroenterology 2011 Jul 141:98

Lee JE et al. Gastroenterology 2011 Jul 141:16

Do Fruits and Veggies Reduce Risk for Colorectal Cancer?

A weak inverse association was seen between CRC risk and fruit and vegetable consumption; risk reduction was greatest when intake increased from low levels.

Instructions to patients with regard to diet and colorectal cancer (CRC) often include decreasing consumption of dietary fat — especially animal fat — and increasing consumption of fiber, fruits, vegetables, and low-fat dairy products. However, increased intake of whole grains has not been effective in reducing the recurrence of adenomas, and epidemiologic data on the effect of fruits and vegetables have been mixed.

Now, researchers have conducted a meta-analysis of 19 cohort studies investigating fruit and vegetable intake and CRC risk. All 19 studies were included in a comparison between highest and lowest intakes; 15 were included in a dose-response analysis. Five studies were conducted in Europe, 10 in the U.S., and 4 in Asia.

The relative risk for CRC with highest versus lowest intake was 0.92 (95% confidence interval, 0.86–0.99) for fruits and vegetables and 0.90 (95% CI, 0.83–0.98) for fruits alone. For fruits, the dose-response analysis suggested a nonlinear association, with most of the risk reduction occurring when low intake increased to about 100 g per day. High vegetable intake also offered significant protection (RR, 0.91; 95% CI, 0.86–0.96). The benefits were restricted to colon cancer, and the risk reduction was nonlinear, with the greatest reduction occurring when low intake increased to about 100 g per day.

Comment: Gastroenterologists are often asked about drugs, supplements, and lifestyle or dietary factors that can reduce the risk for CRC. I encounter these questions most often in the recovery area after colonoscopy. Regular use of aspirin and other nonsteroidal anti-inflammatory drugs has the clearest and strongest benefit but also carries a risk for bleeding. Calcium supplementation seems beneficial, with some increased risk for kidney stones. Folate supplementation has a modest benefit, with negligible risk, particularly in patients who have already undergone clearing colonoscopy. Lifestyle factors — including normalization of body weight, regular exercise, and cessation of smoking — can be strongly recommended. Increased intake of fruits and vegetables might have some benefit, and the current study provides a new finding that the greatest advantage is in individuals with very low current intake. Of course, eating more fruits and vegetables could bring other health benefits as well.

Aune D et al. Nonlinear reduction in risk for colorectal cancer by fruit and vegetable intake based on meta-analysis of prospective studies. Gastroenterology 2011 Jul; 141:106.

·         Medline abstract (Free)

Leptin: A new treatment for brittle bones?
In a pilot study involving leptin replacement therapy for two years and its effect on bone, researchers found a significant increase in bone mineral density and bone mineral content in the lumbar spine. These results suggest that leptin may be a promising new treatment option for improving bone health in strenuously exercising young women with low circulating leptin levels at baseline. Metabolism -- Clinical and Experimental 

Smoking and coronary heart disease: A higher risk for women
These authors point out that it is unclear if the mechanisms underlying the sex difference in risk of coronary heart disease are biological or related to differences in smoking behaviour between men and women. Tobacco-control programmes should consider women, particularly in those countries where smoking among young women is increasing in prevalence. (Free registration required) The Lancet

Smoking and Bladder Cancer: Half of Cases in Women Attributable to Smoking

Women have caught up with men in their risk for smoking-related bladder cancer, according to aJAMA study.

In a prospective 10-year study, more than 450,000 participants aged 50 to 71 reported their smoking histories and then were followed through cancer registries for the development of bladder cancer.

Current smokers had four times the relative risk, and ex-smokers had twice the relative risk, of never smokers. Men had a higher rate of bladder cancer regardless of smoking history: Those who never smoked had four times the risk of women who never smoked. However, for the first time the proportion of cancers attributable to smoking was equal for men and women, at roughly 50% each.

JAMA article 

USPSTF: Evidence Insufficient to Weigh Pros and Cons of Bladder Cancer Screening

Evidence is inadequate to evaluate the benefits and harms of bladder cancer screening in asymptomatic adults, according to a new recommendation statement (grade I) from the U.S. Preventive Services Task Force.

The statement, published in the Annals of Internal Medicine, updates the task force's 2004 recommendation (grade D) against bladder cancer screening. The USPSTF notes that in its review of the current evidence, it found "epidemiologic data that suggested heretofore undemonstrated benefits of screening" — as well as insufficient data on the accuracy of screening tests (e.g., urinalysis for hematuria), the effectiveness of treatment, and the harms of screening and treatment.

Annals of Internal Medicine article (Free PDF)

Pravastatin-paroxetine combo raises blood glucose levels in study
Combining the drugs pravastatin and paroxetine significantly increased blood glucose levels by up to 48 mg/dL in patients with diabetes, experts reported in the Clinical Pharmacology & Therapeutics journal. The findings underscore the importance of carefully monitoring the effects of drugs on blood glucose metabolism, researchers said. Drug Topics

Why Stress Causes DNA Damage

For years, researchers have published papers that associate chronic stress with chromosomal damage. 

Now researchers at Duke University Medical Center have discovered a mechanism that helps to explain the stress response in terms of DNA damage. 

"We believe this paper is the first to propose a specific mechanism through which a hallmark of chronic stress, elevated adrenaline, could eventually cause DNA damage that is detectable," said senior author Robert J. Lefkowitz, M.D., James B. Duke Professor of Medicine and Biochemistry and a Howard Hughes Medical Institute (HHMI) investigator at Duke University Medical Center. 

The paper was published in the Aug. 21 online issue of Nature. 

In the study, mice were infused with an adrenaline-like compound that works through a receptor called the beta adrenergic receptor that Lefkowitz has studied for many years. The scientists found that this model of chronic stress triggered certain biological pathways that ultimately resulted in accumulation of DNA damage. 

"This could give us a plausible explanation of how chronic stress may lead to a variety of human conditions and disorders, which range from merely cosmetic, like graying hair, to life-threatening disorders like malignancies," Lefkowitz said. 

P53 is a tumor suppressor protein and is considered a "guardian of the genome" - one that prevents genomic abnormalities. 

"The study showed that chronic stress leads to prolonged lowering of p53 levels," said Makoto Hara, Ph.D., a postdoctoral fellow in the Lefkowitz laboratory. "We hypothesize that this is the reason for the chromosomal irregularities we found in these chronically stressed mice." 

Lefkowitz earlier had proved the existence of isolated, and characterized the G-protein-coupled receptors (GPCRs) such as the beta adrenergic receptor. These receptors, which are located on the surface of the membranes that surround cells, are the targets of almost half of the drugs on the market today, including beta blockers for heart disease, antihistamines and ulcer medications. 

Now he is continuing studies along another pathway,stemming from the GPCRs, that was discovered in his lab, which is known as the beta-arrestin pathway. At first, the theory was that beta-arrestin proteins turned off or desensitized the G-protein pathways, but evidence is accumulating that these proteins are also responsible for causing certain biochemical activities in their own right. 

In the current study, the scientists found a molecular mechanism through which adrenaline-like compounds acted through both G-protein and the beta-arrestin pathways to trigger DNA damage. 

The Nature publication showed that the infusion of an adrenaline-like compound for four weeks in the mice caused degradation of p53, which was present in lower levels over time. 

The study also showed that the DNA damage was prevented in mice lacking beta-arrestin 1. Loss of beta-arrestin 1 stabilized cellular levels of p53 both in the thymus, an organ that strongly responds to acute or chronic stress, and in the testes, where paternal stress might affect an offspring's genome. 

Future studies planned by the Lefkowitz laboratory include studying mice that are placed under stress (restrained), thus creating their own adrenaline or stress reaction to learn whether the physical reactions of stress, rather than an influx of adrenaline in the lab as was done in the current study, also leads to accumulation of DNA damage. 

Other authors include Jeffrey J. Kovacs, Erin J. Whalen, Sudarshan Rajagopal, Ryan T. Strachan, Seungkirl Ahn, Barbara Williams, Christopher M. Lam, Kunhong Xiao, and Sudha K. Shenoy, all of the Duke Department of Medicine; Aaron J. Towers and Simon G. Gregory of the Department of Medicine and the Center for Human Genetics at Duke; and Wayne Grant and Derek R. Duckett of the Translational Research Institute, The Scripps Research Institute, Jupiter, Fla.. 

Calcium Tests Necessary? May Protect From Harmful Statin Side Effects

New calcium tests are understood to be able to accurately determine if a patient needs to be prescribed anticholesterol drugs known as statins, which work well but often produce dramatic side effects. This new test using a CT scanner in tandem provides insight into the likelihood that certain patients at moderate risk of heart problems will have a heart attack or stroke. 

The new study released this week sought to determine whether a test of calcium in the arteries is more helpful at estimating risk than a blood test that examines levels of C-reactive protein. 

The researchers tracked 2,083 people for six years. They found that 13% of those with the highest levels of calcium in their arteries had a heart attack or stroke during that time period. But just 2% of those with high levels of C-reactive protein, and no calcium buildup, had a heart attack or stroke.

Not everyone needs a calcium test, said lead study author Dr. Michael J. Blaha, a cardiology fellow at the Johns Hopkins University School of Medicine: 

"We believe looking for calcification in coronary vessels in certain patients makes sense in order to predict who may benefit from statin therapy, because the test gets right to the heart of the disease we want to treat."

The main intent of the test is for people who fall into the middle area between those who are at high risk of heart problems due to factors like high blood pressure and those who are at low risk. 

Dr. Roger Blumenthal, director of the Ciccarone Center for the Prevention of Heart Disease at Johns Hopkins University continues: 

"Our data support recent American Heart Association guidelines, which say it is reasonable to order a coronary calcium scan for adults who are considered to be at intermediate risk of a heart attack over the next 10 years. A high coronary calcium score would indicate that statin therapy would likely be a useful strategy to lower that person's cardiovascular risk."

A blood calcium test is usually ordered to screen for, diagnose, and monitor a range of conditions relating to the bones, heart, nerves, kidneys, and teeth. Blood calcium levels do not directly tell how much calcium is in the bones, but rather, how much calcium is circulating in the blood. 

A total calcium level is often measured as part of a routine health screening. It is included in the Comprehensive Metabolic Panel (CMP) and the Basic Metabolic Panel (BMP), groups of tests that are performed together to diagnose or monitor a variety of conditions. When an abnormal total calcium result is obtained, it is viewed as an indicator of an underlying problem. To help diagnose the underlying problem, additional tests are often done to measure ionized calcium, urine calcium, phosphorous, magnesium, vitamin D, and parathyroid hormone (PTH). PTH and vitamin D are responsible for maintaining calcium concentrations in the blood within a narrow range of values. 

Measuring calcium and PTH together can help determine whether the parathyroid glands are functioning normally. Measuring urine calcium can help determine whether the kidneys are excreting the proper amount of calcium and testing for vitamin D, phosphorus, and/or magnesium can help determine whether other deficiencies or excesses exist. Frequently, the balance among these different substances, and the changes in them, are just as important as the concentrations. 

Cardiologist Dr. Vijay Nambi, an assistant professor at Baylor College of Medicine, said that most insurance companies feel that these tests can help patients make their own decisions about the direction of treatment although these are often not covered by insurance companies: 

One-Time Sigmoidoscopy Reduces Colorectal Cancer Incidence, Mortality

A single flexible sigmoidoscopy can reduce colorectal cancer incidence and mortality, according to a study in the Journal of the National Cancer Institute.

Nearly 35,000 adults (aged 55 to 64) in Italy were randomized to sigmoidoscopy or to no screening. Just over half of intervention patients actually underwent sigmoidoscopy.

During 11 years' follow-up, colorectal cancer was diagnosed in 251 intervention patients and 306 controls, and colorectal cancer–related death occurred in 65 and 83, respectively. In intention-to-treat analyses, sigmoidoscopy was associated with a significant, 18% reduction in cancer incidence and a nonsignificant, 22% reduction in mortality. In per-protocol analyses, the reductions in incidence and mortality were both significant (31% and 38%, respectively).

Despite these findings, an editorialist concludes that the overall evidence doesn't suggest a large difference in effectiveness of FOBT, flexible sigmoidoscopy, and colonoscopy, so "the U.S. approach of recommending all three screening strategies seems sound."

JNCI article (Free abstract)

Implications of False-Negative Clostridium difficile Tests

Patients with false-negative results can be just as sick as those with positive results.

Clostridium difficile infections (CDI) commonly are diagnosed with commercial enzyme immunoassays (EIAs) that identify bacterial toxin, but the tests' sensitivity seldom exceeds 80%. No one has established yet whether this poor performance reflects differences among patients (Are milder infections, for instance, more likely to be missed by EIA?), reflects differences among organisms, or is simply a test characteristic.

Investigators prospectively identified 42 hospitalized patients with diarrhea and negative C. difficiletoxin EIAs in whom CDI had been confirmed with a two-step strategy using a more accurate polymerase chain reaction (PCR) assay for the toxin genes. These patients were indistinguishable from 90 patients with positive EIAs across more than two dozen clinical variables, ranging from underlying medical conditions and previous antibiotic use to severity of diarrhea and likelihood of recurrence.

All organisms isolated from stool of EIA-negative patients produced toxin in culture, and skin and environmental cultures were no less likely to yield C. difficile than those of EIA-positive patients. The one difference: EIA-negative patients were less likely to harbor the ribotype 027 strain, a particularly virulent C. difficile strain.

Guerrero DM et al. Clinical and infection control implications of Clostridium difficile infection with negative enzyme immunoassay for toxin. Clin Infect Dis 2011 Aug 1; 53:287. (http://dx.doi.org/10.1093/cid/cir361)

Original article (Subscription may be required)

Medline abstract (Free)

Is Insomnia a Disease?

Or, is it a normal part of life that's been medicalized by available treatment?

We generally identify a disease before we look around for its treatment. Observers argue that, these days, the sequence sometimes is reversed: The marketing of a pharmaceutical agent gives birth to a disease, often by "medicalizing" what is actually a natural part of human existence. Has this process created an epidemic of insomnia in the U.S.?

Researchers examined recent trends in the diagnosis and treatment of sleeplessness, using data from an annual population-based survey of U.S. outpatient visits. Between 1993 and 2007, patient complaints of sleeplessness more than doubled, and ICD-9 diagnoses of insomnia rose more than sevenfold. Both these increases, however, were dwarfed by the skyrocketing number of prescriptions written for sedative hypnotics. Benzodiazepine prescriptions increased modestly (by about 50%) from 1993 to 2007, whereas prescriptions for non-benzodiazepine sedative hypnotics (zolpidem [Ambien and others] and similar drugs) soared 30-fold.

The results in 2007: an estimated 5.7 million complaints of sleeplessness, 6.1 million diagnoses of insomnia, and 16 million prescriptions written. The authors suggest that these divergent curves imply that "life problems are being treated with medical solutions," without much attention being given to anything but the prescription pad.

Switching Antipsychotics May Reduce Metabolic Problems

Even so, monitoring for new adverse effects and the possible loss of antipsychotic effectiveness is critical.

Atypical antipsychotic medications are clinically effective, but often induce metabolic problems and weight gain. To assess the safety and effectiveness of switching antipsychotics to reverse these adverse effects, investigators conducted a multisite, NIH- and industry-funded, randomized, controlled, 24-week study.

The 215 clinically stable patients with schizophrenia or schizoaffective disorder had moderately increased cardiovascular risk, measured by metabolic indicators and elevated body-mass index (BMI), and were taking olanzapine (average dose, 18.5 mg/day), quetiapine (average, 502 mg/day), or risperidone (average, 4.1 mg/day). The study protocol involved staying on the current medication or switching to manufacturer-supplied aripiprazole in a gradual, 4-week cross-taper (mean dose during study, 16.9 mg/day). All patients received a behavioral intervention directed at diet and exercise; none took statins or weight-loss medications.

At 24 weeks, compared with controls, switchers to aripiprazole showed significantly greater decreases in non-HDL cholesterol (by 9.4 mg/dL), weight (by 2.9 kg), and BMI (by 1.1) and significantly improved trigylceride levels (difference of 32.7 mg/dL). The two groups showed no differences in symptom scores or treatment failures. However, significantly more switchers than controls stopped the protocol-specified treatment prematurely (47.7% vs. 27.4%). More switchers than controls reported insomnia and serious adverse effects.

Published in Journal Watch Psychiatry August 22, 2011

Sleep-Disordered Breathing Raises Risk for Cognitive Decline in Older Women

Risk might be related to hypoxic episodes.

Yaffe K et al. JAMA 2011 Aug 10; 306:613

Canessa N and Ferini-Strambi L. JAMA 2011 Aug 10; 306:654

Guidelines for Diagnosing and Treating COPD Updated

Updated guidelines on diagnosing and treating stable chronic obstructive pulmonary disease (COPD) have been released by the American College of Physicians and three respiratory societies in the Annals of Internal Medicine.

Among the changes since 2007:

• Inhaled bronchodilators may be used for symptomatic patients with an FEV1 between 60% and 80% of predicted values, in addition to those with an FEV1 below 60%.
• Clinicians should base the choice of monotherapy with long-acting inhaled anticholinergics or long-acting inhaled beta-agonists on cost, patient preference, and potential adverse effects.
• Symptomatic or exercise-limited patients with an FEV1 greater than 50% of predicted may be considered for pulmonary rehabilitation.
• Patients with severe hypoxemia at rest should receive continuous oxygen therapy.

The guidelines reaffirm that combination therapy may be used, but there is not enough evidence to recommend when it should be chosen over monotherapy.

Annals of Internal Medicine article (Free abstract)

Kids Might Be Able to Forgo Fasting Before Lipid Screening

Fasting appears to have little effect on cholesterol values among children, according to a cross-sectional study in Pediatrics. (In 2008, the American Academy of Pediatrics recommended fasting lipid panels for high-risk children.)

Researchers examined data on nearly 13,000 children aged 3 to 17 years who underwent lipid screening as part of the National Health and Nutrition Examination Survey. Fasting before screening varied across the sample.

After adjustment for weight and other confounders, lipid measurements changed little according to fasting status. For example, the researchers calculate that LDL cholesterol in an average child would be about 5 mg/dL lower postprandially versus after a 12-hour fast.

The authors say such changes in lipid values are "likely not clinically important." They conclude that "physicians might be able to decrease the burden of childhood cholesterol screening by not requiring prescreening fasting."

Pediatrics article (Free PDF)