Category "Health"

For the first time, updated results from the European Randomized Study of Screening for Prostate Cancer (ERSPC), the largest randomized prostate cancer screening trial in the world, show a significant survival advantage with prostate-specific antigen (PSA) screening for men from 50 to 74 years of age.

The new data come from a follow-up of 13 years, and were presented during a late-breaking abstract session here at the European Association of Urology 29th Annual Congress. An initial analysis of the ERSPC results, reported in 2009, provided the first proof that PSA screening saves lives from prostate cancer.

This update “offers the most robust data yet in support of the effectiveness of PSA-based early detection efforts to reduce prostate cancer metastases and mortality,” said Matthew Cooperberg, MD, MPH, associate professor of urology, epidemiology, and biostatistics at the University of California, San Francisco, who was asked by Medscape Medical News for comment.

According to Dr. Cooperberg, who was not involved in the research, the ERSPC, together with the Göteborg trial “provides the only contemporary insights on the question of benefits of early detection.”

He said that the screening study conducted in the United States — the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial — “is now broadly acknowledged only to address the question of annual vs opportunistic screening, given a screening rate of more than 75% in the usual care arm.”

The updated ERSPC results were presented by Jonas Hugosson, MD, professor of urology at the Sahlgrenska Academy, University of Gothenburg, in Sweden. He cautioned that screening with the PSA test “should not start too late,” emphasizing that the weight of screening benefits fall to men whose screening begins before the age of 60.

“In our data from the Göteborg Trial, the Swedish arm of ERSPC, we found a prostate cancer mortality reduction of 20% in men who started PSA screening after age 60, while men who started to screen before age 60 had a reduction of 50%,” Dr. Hugosson told Medscape Medical News.

The ERSPC, which began 20 years ago, was a randomized study of more than 180,000 men, only half of whom underwent regular PSA testing. Results from the 11-year follow-up of the ERSPC were published in 2012.

The gap between screened and unscreened groups is decreasing; the relative risk for prostate cancer between the screening and control groups at 9-year follow-up was 1.91, at 11-year follow-up was 1.66, and at a median of 13 years of follow-up was 1.57, Dr. Hugosson reported.

However, he noted, “we still have a 57% increased incidence of prostate cancer in the screening group, compared with the control group.”

This is one of the downsides of PSA screening — the risk for overdiagnosis of prostate cancer that might not affect the individual’s health in the time he has left to live. However, once it is detected, it might be treated, or at least followed with further screening.

The most recent update from the trial shows that the absolute difference in prostate cancer mortality per 1000 patient-years has increased from 9 years (0.31 vs 0.37) to 11 years (0.35 vs 0.46) to 13 years (0.43 vs 0.54). However, the difference in the relative risk for mortality has stabilized in favor of screening; it was 0.85 at 9 years, 0.78 at 11 years, and 0.79 at 13 years.

The number of men needed to invite for screening to prevent 1 prostate cancer death has decreased from 979 at 9 years and is 781 at 13 years. The number needed to diagnose to prevent 1 death has decreased from 35 at 9 years to 27 at 13 years.

As previously reported by this group, large differences between centers in prostate cancer mortality persist.

“For example, in Finland, our largest center has a 9% mortality reduction, whereas Sweden, our neighbor with the same kind of healthcare system, has more than a 4-fold better mortality reduction (38%),” he said. “The largest mortality reduction was seen in Spain (46%), but an increase in mortality was seen in Switzerland (–14%).

An initial analysis suggested that these differences in outcomes between centers stem from differences in screening protocols, such as rate of biopsy, median PSA per invited man, and duration of screening, which ranged from 4 to 10 years.

“It seems like the intensity of screening is very closely related to the effect of prostate cancer mortality reduction,” he said.

Dr. Cooperberg predicts that the benefits from PSA screening will increase with longer follow-up, and he noted that “for a man in his 50s, the relevant time horizon is 30 years or more, not 13 years.”

“The risk of overdiagnosis with screening is still, of course, very salient,” he explained. “The solution is to focus early detection efforts on the detection of high-risk prostate cancer, with broad implementation of active surveillance as the default strategy for low-risk disease.”

Dr. Cooperberg said he disagrees with efforts to stop or reduce PSA screening in healthy men. “A policy of discouraging all early detection efforts runs counter to the growing body of high-quality evidence, and puts thousands of men at risk of avoidable suffering and early mortality,” he said.

Referring to the 2012 recommendation from the US Preventive Services Task Force (USPSTF) against PSA screening for prostate cancer,he noted that “the USPSTF will update its evidence review in the near future to reflect the increasingly incontrovertible message of the ERSPC: that PSA-based early detection saves lives, period.”

Source: Medscape

Individuals prescribed statin therapy for high cholesterol levels have increased their caloric intake by nearly 10% and their intake of fat by 14% over a recent 10-year period, while no changes in eating habits have been observed among statin nonusers, a new study shows.

In addition, researchers report that individuals prescribed a statin had a larger increase in body-mass index (BMI) than those who weren’t taking the lipid-lowering medication.

Presenting their findings April 24, 2014 here at the Society of General Internal Medicine Meeting , the researchers say the study showed that statin users were consuming an extra 192 kcal per day in 2009–2010 than they were in 1999–2000, and this could have contributed to the increase in BMI, which was the equivalent of a 3- to 5-kg weight gain.

“Since the guideline recommends that patients should prevent weight gain, the observed increase in caloric intake and more rapid increase in BMI among statin users are of concern,” write Dr Takehiro Sugiyama (University of Tokyo, Japan) and colleagues in JAMA: Internal Medicine, where the study was published to coincide with the presentation. “According to the guidelines, people who receive statin therapy also should take steps to reduce fat intake, but we did not observe a pattern of combining statin use with dietary control.”

Dr Rita Redberg (University of California, San Francisco), the editor of JAMA: Internal Medicine, said she has treated many patients with statins over the years and has observed a “false reassurance” among those who receive the cholesterol-lowering medications. There is a perception, she writes, that “statins can compensate for poor dietary choices and a sedentary life.” The new data raise concerns of a potential hazard with statins, where the focus on “cholesterol levels can be distracting from the more beneficial focus on healthy lifestyle to reduce heart-disease risk,” suggests Redberg.

Using data from the National Health and Nutrition Examination Survey (NHANES), Sugiyama and colleagues examined the temporal trend in food intake among statin users and nonstatin users between 1999 and 2010. During this time period, the proportion of patients taking statins increased from 7.5% in 1999 to 16.5% in 2010. Statin users tended to be older, male, and white and have less education, a diagnosis of diabetes, and a higher BMI than their counterparts not taking statins.

In 1999–2000, statin users consumed 2000 kcal/day and ate 71.7 g/day of fat, both of which were significantly less than that consumed by individuals not taking statins. By 2009–2010, however, there was a significant increase in the number of calories consumed and the amount of fat eaten by statin users, whereas dietary habits were unchanged among those not taking the cholesterol-lowering medications. In 2009–2010, there was no significant difference in the amount of food consumed by statin users and nonusers, nor was there any difference in the amount of fat consumed. Similar findings were observed when the researchers restricted the analysis to saturated fat and cholesterol intake.

Regarding obesity, there was a 1.3-kg/m² increase in BMI from 1999–2000 to 2009–2010 in the statin users and a 0.4-kg/m² increase among statin nonusers.

Although the paper is limited by its cross-sectional design, Sugiyama and colleagues state that it is reasonable to conclude the average American treated with statins is eating more calories and more fat than the average American taking statins was doing a decade ago. At present, they can only speculate as to the reasons for this.

“One possibility is that statin use may have undermined the perceived need to follow dietary recommendations. Patients who recognized that their LDL-cholesterol levels were lowered drastically by statins may have lost the incentive to pursue dietary modifications,” write the researchers. “Physicians might have contributed to this process by shifting the focus of consultations from diet to statin regimen adherence once statin treatment had begun.”

Dr Mahesh Patel (Duke University School of Medicine, Durham, NC), who was not affiliated with the study, said the new analysis is interesting because it explores something that is rarely studied in medicine, that being the interaction between medication and lifestyle habits. However, he is cautious about making firm conclusions based on the data.

“It is tempting to conclude that patients prescribed statins adopted a more liberal diet than the individuals who were not taking the drugs, but the study only reflects population averages” and does not track the same patients over the 10-year period, he told heartwire .

Dr Sekar Kathiresan (Massachusetts General Hospital Heart Center, Boston) agreed with the need for caution. The analysis, which is based on a somewhat “sexy hypothesis,” tends to fit with people’s preconceived notions about the ill effects of medication use. The lament often heard is that people will simply abandon moderation when it comes to diet because they are now being treated with a statin.

“The flaw is that this is a nonrandomized, observational study, and the statin use might simply be marking a subset of patients who ate more over a 10-year period,” Kathiresan told heartwire . As such, the observational nature of the NHANES analysis makes it impossible to imply causality, whereby taking a statin had the unintended effect of people eating more. Like Patel, Kathiresan noted that the researchers did not follow the same group of patients from 1999 to 2010, a major limitation of the data.

Previous studies have shown that the use of statins is associated with a modestly increased risk of diabetes. Kathiresan said that an increased BMI might be one of the possible reasons for this association but again urged restraint about reading too much into the data.

Both Patel and Kathiresan agreed that physicians need to be vigilant in getting patients to understand their risk factors. To heartwire , Patel said that patients should be reminded “they are not off the hook because they’re on a statin and their LDL-cholesterol levels are better” and that physicians should not “let off the gas” once their patients are treated with a moderate- or high-dose statin as recommended by the clinical guidelines.

Source: Medscape

Garcinia cambogia is yet another entrant in the growing list of natural supplements being marketed as the answer to obesity. G. cambogia is most well-known for its use as a spice. This product, which is classified as a fruit, is naturally found throughout southeastern Asia, India and western Africa.

One of nearly 300 species of Garcinia, G. cambogia is the one most studied for its weight-loss potential. G. cambogia grows as a small tree and produces a rusty-red round fruit.² It is the rind of this fruit that is used for both culinary and therapeutic purposes.

Obesity is a tremendous health problem, not just in the United States but globally as well. An estimated 1 billion adults worldwide are overweight, and nearly one-third of those are considered clinically obese. In the United States alone, the overall cost of obesity was estimated by the CDC to be nearly $150 billion per year.

G. cambogia became popular as a weight-loss aid when it was noted to enhance satiety in its native regions. A secondary effect of the fruit is its potent laxative action.⁶ The active ingredient of G. cambogia is hydroxycitric acid (HCA).
The mechanism of fat metabolism is complex, and the role of G. cambogia in this process is debatable.

Metabolically, HCA appears to be the source of early satiety. This acid enters the energy-production process of the Kreb’s cycle and ultimately increases hepatic glycogen synthesis and inhibits formation of low-density lipoproteins.
This is thought to signal to our brains that we have had enough to eat. Some suggest that HCA interacts with the production of the adipose-controlling hormone leptin, but these claims have yet to be substantiated by clinical trials.

In a meta-analysis literature review, researchers identified only 23 trials that met review criteria. Fewer than half of those ultimately met the proper standards for well-done randomized, placebo-controlled trials.

After the final data analysis, use of G. cambogia was associated with a very slight (0.88 kg) weight loss over control groups, but also with twice the number of adverse GI effects.

Korean researchers studied the effects of G. cambogia, placebo, and another weight-loss supplement in 86 overweight adults in a 10-week randomized trial.  At the end of the study, no statistically significant weight loss was found in any of the three groups.

In another small trial, researchers studied 24 overweight adults over two weeks of daily intake of G. cambogia HCA extract. In addition to actual weight loss being monitored, 24-hour energy intake was tracked. By the end of the trial, energy intake was reduced by 15% to 30% in the 
G. cambogia group over placebo, with a very modest trend in weight loss.

Finally, a study in India focused on 60 obese individuals who were randomized to HCA plus two other supplements, or placebo. At the end of eight weeks, both HCA groups had a 5% to 6% reduction in weight and BMI. Food intake, total cholesterol, LDL cholesterol, and triglycerides all decreased in the HCA groups, and HDL levels increased.

Unfortunately, evidence-based literature demonstrates the potential for adverse events in G. cambogia/HCA. In addition to significant GI upset, increasing reports of hepatic injury are surfacing.

For example, researchers found that daily feeding with HCA supplement did result in decreased fat accumulation and glucose resistance in obese mice, but at the expense of significant hepatic fibrotic changes and inflammation.

Source: MPR

The World Health Organization (WHO) has released its first report on global antimicrobial resistance, including antibiotic resistance. The organization now considers antibiotic resistance a major threat to public health worldwide. The report discusses resistance to various infectious agents but emphasizes 7 bacteria responsible for common and serious diseases like bloodstream infections (sepsis), diarrhea, pneumonia, urinary tract infections, and gonorrhea.

Key points from the report include:

• A common intestinal bacteria, Klebsiella pneumoniae, has developed resistance to last resort treatment for life-threatening infections caused by hospital-acquired infections such as pneumonia, bloodstream infections, infections in newborns and intensive-care unit patients. This resistance has spread worldwide; in certain countries, carbapenem antibiotics would not work in more than half of people treated for K. pneumoniae infections due to resistance.

• For the treatment of urinary tract infections caused by E. coli, fluoroquinolone resistance is extremely widespread globally. Resistance was virtually zero when these drugs were first introduced in the 1980s, but this treatment is now ineffective in more than half of patient in countries in many parts of the world.

• Over 1 million people are infected with gonorrhea worldwide each day and treatment failure to the last resort of treatment for gonorrhea (3rd generation cephalosporins) has been confirmed in Austria, Australia, Canada, France, Japan, Norway, Slovenia, South Africa, Sweden and the United Kingdom.

• Antibiotic resistance causes longer duration of illness in patients and increases the risk of death. Individuals with MRSA (methicillin-resistant Staphylococcus aureus) are estimated to be 64% more likely to die than people with a non-resistant form of the infection. Health care costs also increase with lengthier stays in hospital and the requirement of more intensive care.

The WHO also outlines several strategies for fighting antibiotic resistance from multiple fronts. Consumers are encouraged to use antibiotics only when prescribed by a physician, complete all doses of prescribed antibiotics, and refrain from sharing prescribed antibiotics with others.

Healthcare professionals and pharmacists are advised to increase infection prevention and control, limit prescribing and dispensing of antibiotics only when necessary, and prescribing and dispensing the correct antibiotic(s) based on the patient’s illness. Policymakers and industries can strengthen resistance tracking and laboratory capacities, regulate and promote appropriate antibiotic use, encourage innovation and research of new tools, and foster cooperation and information among all stakeholders.

Source: MPR

Prostate cancer (PC) is the most common male-related malignancy in the United States, the second most common cause of cancer-related death among US men, and the fourth most prevalent male malignancy worldwide.

Clinical aspects of PC vary widely, and two men with similar PC stage and PSA values may develop sharply different outcomes. The fact that most men are asymptomatic at diagnosis is a reflection of the tendency of PC to arise in the peripheral aspect of the prostate, distant from the urethra.

Obstructive and irritative urinary symptoms are consistent with larger-volume tumors involving the central tissue zone. Such symptoms are by no means restricted to PC and may be mimicked by such conditions as benign prostatic hyperplasia (BPH), urinary tract infection, and prostatitis. Progressive bone pain involving the spine, pelvis, or hips may herald the presence of metastases.

Currently, the most typical initial scenario is an older asymptomatic man with an elevated PSA who is found at subsequent biopsy to have an unanticipated histologic surprise in the form of PC. Fortunately, 90% of PC cases detected today are at a clinically localized stage.

PC screening tools include the PSA blood test and the digital rectal examination (DRE). Since the introduction of PSA testing in 1987, PC incidence has increased sharply, and mortality rates have trended downward.

Yet the cumulative risk/benefit comparisons for screening are not consistently persuasive due to the disturbing lack of randomized controlled trials (RCTs) demonstrating reduced mortality in screened populations. In fact, the US Preventive Services Task Force currently recommends against PSA-based screening.

In 1995, the Office of Technology Assessment concluded that available evidence indicated that PSA testing was of no proven mortality benefit. The CDC, American Cancer Society, and American Urological Association endorse testing with PSA and DRE annually in men reaching age 50 years, with earlier screening at age 40 years for black men or those with a family history of PC.

Since 90% of men with elevated PSA and normal DRE will be proven at biopsy to have disease confined to the prostate, most men can anticipate a favorable prognosis and a wide array of treatment options.

PSA is a serine protease that functions to liquefy the ejaculate. The prostate gland is the predominant source of PSA in serum. Elevations of PSA occur with architectural disruption of the gland as in PC, BPH, prostatitis, prostate biopsy or massage, transurethral resection of prostate, and (transiently) ejaculation.

PC detection and treatment strategies are influenced by current scientific data, recommended therapies with narrow risk/benefit profiles, quality-of-life concerns, and personal perceptions and values prior to initiating treatment. Patient involvement in treatment choice is especially important in early-stage, low-risk PC, where WW is a viable option, especially in older men with limited life expectancy

Although evidence is conflicting, RP appears more appropriate for younger men with organ-confined malignancy and higher Gleason scores, in which case curative resection is clinically attractive for preventing disease progression, distant metastasis, and tumor recurrence in anticipation of >10 years of life expectancy. Large-scale RCTs are underway to further clarify treatment decisions for men with PC.

The Prostate, Lung, Colorectal, and Ovary study, involving 76,693 US men over the span of 13 years, and the European Randomized Screening for Prostate Cancer study, involving 182,160 men in Europe over the span of nine years, are promising and intended to further define relative mortality benefits of PC screening.

Criteria are being evaluated for selective identification of tumors destined to become more aggressive and metastatic, thereby warranting closer surveillance or more intensive oncologic intervention at earlier dates. New candidate biomarkers in prostate tissue may become useful in creating a genetic fingerprint of tumors likely to become aggressive and invasive.

Current genes are still research-based and include such sequenced peptides as GSTP-1, RASSFIA, AMACR, PBOV1, hepsin, DD3, and NMP48.18 Future laboratory developments may allow complementary determination of histologic features and molecular biology panels to predict transformation of PC from indolent to important clinical status. It is worth noting that the researcher who discovered PSA, Richard Ablin, PhD, has decreed overdiagnosis of PC by PSA “a hugely expensive public health disaster.”

Emerging data and applied technologies are being developed to predict which PCs will awaken to progression and which will remain dormant. Such techniques should allow the PSA screening debate to settle considerably. Clinical insights are emerging toward consensus for patients and providers searching for answers to the dilemma of whether to screen for PC or not.

Criteria are being evaluated for selective identification of tumors destined to become more aggressive and metastatic, thereby warranting closer surveillance or more intensive oncologic intervention at earlier dates. New candidate biomarkers in prostate tissue may become useful in creating a genetic fingerprint of tumors likely to become aggressive and invasive.

Current genes are still research-based and include such sequenced peptides as GSTP-1, RASSFIA, AMACR, PBOV1, hepsin, DD3, and NMP48.⁸ Future laboratory developments may allow complementary determination of histologic features and molecular biology panels to predict transformation of PC from indolent to important clinical status.

It is worth noting that the researcher who discovered PSA, Richard Ablin, PhD, has decreed overdiagnosis of PC by PSA “a hugely expensive public health disaster.”

Emerging data and applied technologies are being developed to predict which PCs will awaken to progression and which will remain dormant. Such techniques should allow the PSA screening debate to settle considerably. Clinical insights are emerging toward consensus for patients and providers searching for answers to the dilemma of whether to screen for PC or not.

Source: MPR

Here’s a tip for those who managed to duck the flu’s first punch: Watch out for the next one.

Many communities are experiencing an increase in flu, part of a second wave that is hitting some regions of the country particularly hard, health officials say. Most of the effects are in the northeast — New England, New York and New Jersey –  but some parts of the mid-Atlantic are seeing increased flu activity.

Federal health officials say it’s common for an uptick in flu to occur in March and April. Often, that is caused by an increase in the influenza B virus, a strain different from the ones that dominated earlier in the flu season.

“We are experiencing a second wave of flu, and that second wave is influenza B,” said Lyn Finelli, chief of influenza surveillance and outbreak response at the U.S. Centers for Disease Control and Prevention. “In some communities in the Northeast, they tell us that they’re experiencing more influenza now than during the peak of the flu season in late December and early January.”

Six states — Connecticut, Delaware, Maine, New Jersey, New York and Rhode Island — reported widespread influenza activity for the week ending April 12, the most recent data available.

In the Washington, D.C., region, doctors and hospitals say they are seeing patients with flu-like illnesses, some of whom are testing positive for influenza B. George Washington University Hospital has had a slight increase in influenza B cases in the past month and a half, said spokesman Steven Taubenkibel. In March, 11 patients tested positive for influenza B; this month, the hospital has had 16 patients test positive for the illness.

This season’s flu vaccine covers two strains of the influenza A virus, including the H1N1 “swine flu” responsible for the 2009 global pandemic, and two strains of influenza B. All four strains were included in the quadrivalent vaccine available for the first time this season. The H1N1 virus has dominated during this flu season, but influenza B viruses now account for the largest proportion of viruses that are circulating, according to the CDC.

Although it may seem odd to get a flu shot in April, health officials said those who haven’t been vaccinated should do so.

The rest of the country is experiencing fairly normal flu activity for this time of year, according to CDC data. For the week ending April 12, 1.5 percent of patient visits to doctors were for flu-like illnesses nationally. But in New York, flu-like illnesses accounted for more than 4 percent of all visits, increasing slightly over the previous week. In New Jersey, those illnesses accounted for more than 3 percent of visits, also edging up from the previous week, the data show.

The second wave of flu typically ends in May. But even into the summer, flu still lingers. “It never completely disappears,” Finelli said.

Source: Washington Post

Among men with high cholesterol and erectile dysfunction, a short course of statin therapy was associated with improvements in both measures, shows a new meta-analysis. The study was presented at the American College of Cardiology (ACC) 2014 Scientific Sessions and simultaneously published online in the Journal of Sexual Medicine

These findings “may improve adherence to statin therapy . . . [because] we know that in primary prevention a large proportion of patients stop talking [a statin] or take a much lower amount than prescribed,” lead investigator Dr John B Kostis (Rutgers Robert Wood Johnson Medical School New Brunswick, NJ) said during a press briefing. For example, in a 90 000-patient study, 35% took less than a quarter of prescribed statins and 60% took less than half, and in an 11 000-patient study, 47% of patients stopped taking the statin, he said.

Erectile dysfunction is often the first sign of CVD, like the canary in the coal mine, Kostis pointed out. “What do you do with a person who has erectile dysfunction? You evaluate them for CVD.”

“Over the years, it’s become apparent that erectile dysfunction is an indication of decreased vascular health in men and is considered by many to be a significant CV risk factor,” moderator Dr Jeffrey Kuvin (Tufts Medical Center, Boston, MA) echoed. “Whether erectile function improves due to a reduction in LDL-C or perhaps other pleiotropic effects of statins still remains unclear. I think [this] meta-analysis strongly shows that statin therapy improves erectile dysfunction after only a short duration of therapy.”

Erectile dysfunction affects an estimated 18 to 30 million American men, more often after age 40, and common causes include heart disease, high cholesterol, high blood pressure, diabetes, obesity, tobacco use, depression, and stress, according to an ACC statement.

Many older men have erectile dysfunction along with diabetes and atherosclerotic disease, for which they are frequently prescribed statins, Kostis noted. Previous research has suggested, however, that statin therapy may lower testosterone levels.

The investigators searched for randomized controlled trials that examined the effect of statin therapy on erectile function. They identified 11 such trials in which men completed the International Inventory of Erectile Function survey, which consists of five questions, each scored on a five-point scale, where low values represent poor sexual function.

The trials had an average of 53 patients per study, for a total of 647 patients. Men had an average age of 57.8 years and received statins for about 3.8 months.

During this time, average LDL-C levels dropped significantly from 138 to 91 mg/dL in the treated men but were virtually unchanged in control groups.

In men who took statins, erectile-function scores increased by 3.4 points, from 14.0 to 17.4 points—a 24.3% increase. The increase in erectile-function score was about one-third to one-half of that reported with phosphodiesterase inhibitors, such as sildenafil (Viagra, Pfizer), tadalafil (Cialis, Lilly), or vardenafil (Levitra, Bayer/GlaxoSmithKline), and larger than the effect of lifestyle modification or testosterone, Kostis said.

Some people have called statins a “double-edged sword,” he noted. On one hand, they improve endothelial function, which may improve blood flow to the penis; but on the other hand, they lower the level of cholesterol, a precursor of testosterone. However, these 11 studies showed that “the beneficial effect [of statins on erectile dysfunction] predominates.”

Strengths of the meta-analysis were that it included all published randomized trials about the topic, and the benefit remained after multiple sensitivity analyses. However, limitations were the inclusion of small studies with few participants and diverse statins, treatment duration (1.5 to six months), and patient types.

“A well-powered, placebo-controlled trial with a factorial design (for example, phosphodiesterase inhibitors, testosterone, and statin) would clarify the effect of statins in relevant patient subsets,” Kostis concluded. These drugs are not recommended as a primary treatment for erectile dysfunction in patients with normal cholesterol levels, he cautioned—another potential area for further rigorous research.

Source: Medscape

A popular and controversial sports supplement widely sold in the USA and other countries is secretly spiked with a chemical similar to methamphetamine that appears to have its origins as an illicit designer recreational drug, according to new tests by scientists in the USA and South Korea.

The test results on samples of Craze, a pre-workout powder made by New York-based Driven Sports and marketed as containing only natural ingredients, raise significant health and regulatory concerns, the researchers said. The U.S. researchers also said they found the same methamphetamine-like chemical in another supplement, Detonate, which is sold as an all-natural weight loss pill by another company: Gaspari Nutrition.

“These are basically brand-new drugs that are being designed in clandestine laboratories where there’s absolutely no guarantee of quality control,” said Pieter Cohen, an assistant professor at Harvard Medical School and a co-author of the analysis of Craze samples being published today in the peer-reviewed scientific journal Drug Testing and Analysis.

“It has never been studied in the human body,” Cohen warned. “Yes, it might make you feel better or have you more pumped up in your workout, but the risks you might be putting your body under of heart attack and stroke are completely unknown.”

Craze, which is marketed as giving “unrelenting energy and focus” in workouts, was named 2012’s “New Supplement of the Year” by Bodybuilding.com. A USA TODAY investigation published in July reported on other tests detecting amphetamine-like compounds in Craze.

While Walmart.com and several online retailers have stopped selling Craze in the wake of USA TODAY’s investigation, the product has continued to be sold elsewhere online and in GNC stores. In recent weeks, Driven Sports’ website, which offers Craze for sale, has said the product is out of stock. Detonate is sold by a variety of online retailers.

An attorney for Driven Sports, Marc Ullman, said the company had no comment on the latest findings that the compounds are actually more closely related to methamphetamine.

Cohen said researchers informed the FDA in May about finding the new chemical compound in Craze. The team found that the compound — N,alpha-diethylphenylethylamine — has a structure similar to methamphetamine, a powerful, highly addictive, illegal stimulant drug. They believe the new compound is likely less potent than methamphetamine but greater than ephedrine.

“There are suggestions about how it’s tweaked that it should not be as addictive as meth,” Cohen said. But because it hasn’t been studied, he said, its dangers aren’t known. The team said it began testing Craze in response to several failed urine drug tests by athletes who said they had taken Craze.

Driven Sports has issued repeated statements in recent months that Craze does not contain any amphetamine-like compounds, including posting test results on its website that it says prove the product is clean. In July, a USA TODAY investigation revealed that a top Driven Sports official — Matt Cahill — is a convicted felon who has a history of selling risky dietary supplements, including products with ingredients linked to severe liver injury and at least one death. Cahill is currently facing federal charges in California involving his introduction of another supplement, Rebound XT, to the market in 2008 that contained an estrogen-reducing drug, and this spring a grand jury was also investigating, USA TODAY has reported.

The newspaper’s investigation, which focused on several products sold over the years by Cahill’s changing series of companies, reported that tests by the U.S. Anti-Doping Agency in June 2012 and a government-affiliated forensic lab in Sweden in April 2013 had detected undisclosed amphetamine-like compounds in samples of Craze.

A month after USA TODAY published its report about Cahill and Craze, a team of South Korean scientists published an article in a journal of the Japanese Association of Forensic Toxicology saying they had found a methamphetamine-like compound in samples of Candy Grape flavor and Berry Lemonade flavor Craze.

The researchers, from the National Forensic Service in South Korea and the National Institute for Public Health and the Environment in the Netherlands, noted that the compound found in Craze was the same as that found in a crystalline powder seized by narcotics agents in December 2011 as a suspected illicit designer drug. In that case the powder was found in an unclaimed lost package shipped from Vietnam to South Korea, according to an earlier journal article published by the team in late 2012. “It appeared that the recipient of this article sought to abuse this chemical in the same way as amphetamines. There is a possibility that this chemical will be widely abused for recreational use in the near future,” they wrote at the time.

Instead, the same team soon found the compound in Craze.

The researchers noted that the compound had been patented in 1988 by Knoll Pharmaceuticals with claims of psychoactive effects, such as enhancing mental activities and pain tolerance. While it was never developed into a medicine, the patent described tests on animals and suggested an intended oral dose of 10 mg to 150 mg, with a target of 30 mg.

A suggested serving size of Craze yielded a dose of the compound of about 23 mg, the Japanese journal article said, and “it could be assumed that NADEP was added to the supplements intentionally for its pharmacological effects without adequate labeling.” The U.S. research team also found the meth-like substance at levels of 21 mg to 35 mg per serving in each of the samples tested from three separate lots of Craze.

Craze’s label does not disclose the compound found by the researchers. Instead it says the product contains dendrobium orchid extract that was concentrated for different phenylethylamine compounds. Phenylethylamines include a variety of chemicals “that range from benign compounds found in chocolate to synthetically produced illicit drugs,” according to the U.S. researchers.

The U.S. researchers noted that an “extensive” search of scientific literature does not find any evidence that the compound listed on Craze’s label has ever been documented as a component of dendrobium orchid extract. The U.S. research team included Cohen; John Travis, a scientist at NSF International, a Michigan-based testing and standards organization that has a dietary supplement certification program; and Bastiaan Venhuis of the National Institute for Public Health and the Environment in the Netherlands.

Although not part of the journal article being published today, NSF International announced that in separate testing they also have detected the same methamphetamine-like compound in the weight-loss supplement Detonate sold by Gaspari Nutrition. “Regulators may want to consider taking action to warn consumers,” NSF International said in a statement. Gaspari markets Detonate as containing “dendrobium extract.”

Last year Driven Sports posted a series of blog items on its website alerting customers that counterfeit versions of Craze were being sold. “Could there be counterfeit products, of course,” Cohen said. “Chances are this is more likely an effort by the manufacturer to distract regulators and consumers from what’s really going on here.”

Source: USA Today

Read more at Food Poisoning Bulletin.

The higher temperatures, humidity and rainfall associated with climate change have intensified outbreaks of West Nile virus infections across the United States in recent years, according to a study published this week.

One of the largest surveys of West Nile virus cases to date links warming weather patterns and increasing rainfall–both projected to accelerate with global warming–to outbreaks of the mosquito-borne disease across 17 states from 2001 to 2005.

The authors predict the pattern will only get worse. “If temperature and precipitation are influential in determining West Nile virus infection risk, such changes would likely increase the burden of this disease in coming decades,” the authors note in the study, published online Monday in the journal Environmental Health Perspectives.

In the study, Jonathan Soverow of the Beth Israel Deaconess Medical Center in Boston and colleagues at Toronto’s Hospital for Sick Children and the Harvard School of Public Health matched more than 16,000 confirmed West Nile cases in 17 states to local meteorological data.

The team found that warmer temperatures had the greatest effect on the virus’ transmission to humans.  Higher humidity, heavier rainstorms and increased precipitation were also tied to higher rates of West Nile virus infection, according to the study.

“A lot of the trends we see depend on local conditions,” said Roger Nasci, an entomologist at the U.S. Centers for Disease Control and Prevention who studies vector-borne diseases but was not involved with the study.  “West Nile virus is a very focal disease.  It’s not uniformly distributed across the U.S.”

West Nile virus led to 43 deaths in 2008 in the United States.  More than 1,300 infections were diagnosed last year, according to the CDC.

Humans can become infected if bitten by a mosquito carrying West Nile virus.  Around 20 percent of infected people show symptoms of the disease, such as fever, headache and nausea.  Of those, about one percent develop neurological symptoms such as numbness, convulsions and paralysis.

Warmer weather helps spread West Nile virus because it extends the length of the mosquito season, said Vicki Kramer, chief of the vector-borne disease section at the California Department of Public Health.

Higher temperatures also let mosquitoes reach biting age sooner and speed multiplication of the virus within insects, said Kramer.  Thus in a warmer climate not only are there more biting mosquitoes, but those mosquitoes carry more copies of the West Nile virus, making them more likely to infect their human targets.

“It takes a while for the disease to build up,” says Kramer.  “That’s why we see more cases in August than in June.”

Rainfall’s effects on mosquitoes and West Nile virus are more complicated, cautioned Bill Landesman, an ecologist at Rutgers University.  For example, although their eggs need standing water to hatch, mosquito populations often flourish after a drought because mosquitoes can re-colonize faster than other insects.

“We’re wrestling with this interplay of abiotic (physical) factors, mosquito populations and the West Nile virus,” said Landesman, “and that sometimes makes things difficult to understand.”
The new study by Soverow’s team may help researchers make sense of some of these complex interactions.

For example, the study found that a single rainstorm resulting in at least two inches of rain could increase infection rates by 33 percent, while smaller storms did not.  Heavy rainfall increases humidity, which can stimulate mosquitoes to bite; it also creates pools of water in which mosquitoes can breed.

Total weekly rainfall had a smaller effect on West Nile virus infections, the study found.  An increase of 0.75 inch of rainfall increased the number of infections by about five percent.

Only a few mosquito species carry the West Nile virus, and each has specific habitat requirements, according to Nasci of the CDC.  Warmer, wetter weather patterns will likely expand the niches of these species.

California health officials have already observed this, as some mosquito species carrying the West Nile virus have extended their ranges into higher elevations and coastal areas as temperatures warmed.

Along with mosquitoes, certain species of birds are reservoirs for the West Nile virus.  Changing weather patterns also affect bird populations, which can impact the number of human infections.

For example, droughts can drive birds into urban areas, making human West Nile virus outbreaks more likely, said Kramer.

Southern states with high home foreclosure rates also face a unique West Nile virus threat, added Kramer and Landesman, since neglected swimming pools act as mosquito breeding grounds.

“The take-home message is that these systems are really complex,” said Landesman.  “Climate changes won’t make them any easier to understand.”

Source: Scientific American

It’s possible that some of us are born not to run. According to an eye-opening new genetics study of lab rats, published in The Journal of Physiology, the motivation to exercise — or not — may be at least partly inherited.

For years, scientists have been bedeviled by the question of why so few people regularly exercise when we know that we should. There are obvious reasons, including poor health and jammed schedules. But researchers have begun to speculate that genetics might also play a role, as some recent experiments suggest. In one, published last year, sets of fraternal and identical adult twins wore activity monitors to track their movements. The results indicated that the twins were more alike in their exercise habits than a shared upbringing alone would explain. Their willingness to work out or sit all day depended to a large extent on genetics, the researchers concluded.

But which genes might be involved and how any differences in the activity of those genes might play out inside the body were mysteries. So scientists at the University of Missouri recently decided to delve into those issues by creating their own avid- or anti-exercising animals.

They accomplished this task by inter-breeding normal rats that had voluntarily run on wheels in the lab. The male rats that had run the most were bred with the female rats that also had run the most; those that had run the least were likewise mated. This scheme continued through many generations, until the scientists had two distinct groups of rats, some of which would willingly spend hours on running wheels, while the others would skitter on them only briefly, if at all.

In their first experiments with these rats, the researchers found some intriguing differences in the activity of certain genes in their brains. In normal circumstances, these genes create proteins that tell young cells to grow up and join the working world. But if the genes don’t function normally, the cells don’t receive the necessary chemical messages and remain in a prolonged, feckless cellular adolescence. Such immature cells cannot join the neural network and don’t contribute to healthy brain function.

In general, these genes worked normally in the brains of the rats bred to run. But their expression was quite different in the non-runners’ brains, particularly in a portion of the brain called the nucleus accumbens, which is involved in reward processing. In humans and many animals, the nucleus accumbens lights up when we engage in activities that we enjoy and seek out.

Presumably as a result, when the scientists closely examined the brains of the two types of rats, they found that by young adulthood the animals bred to run had more mature neurons in the nucleus accumbus than did the non-runners, even if neither group had actually done much running. In practical terms, that finding would seem to indicate that the brains of pups born to the running line are innately primed to find running rewarding; all those mature neurons in the reward center of the brain could be expected to fire robustly in response to exercise.

Conversely, the rats from the reluctant-running line, with their skimpier complement of mature neurons, would presumably have a weaker innate motivation to move.

Those results would be disheartening, except that in the final portion of the experiment the scientists had reluctant runners exercise by setting them on running wheels, while also providing some born-to-run animals with wheels. After six days, the unwilling runners had accumulated far less mileage, about 3.5 kilometers (two miles) per rat, compared to almost 34 kilometers each by the enthusiasts.

But the halfhearted runners’ brains were changing. Compared to others in their family line that had remained sedentary, they now showed more mature neurons in their nucleus accumbens. That part of their brain remained less well developed than among the naturally avid rat runners, but they were responding to exercise in ways that would seem likely to make it more rewarding.

What, if anything, these findings mean for people is “impossible to know at this point,” said Frank Booth, a professor of biomedical sciences at the University of Missouri who oversaw the study. Rat brains are not human brains, and rat motivations are at best opaque.

Even so, Dr. Booth said, his group’s data would seem to suggest “that humans may have genes for motivation to exercise and other genes for motivation to sit on the couch,” and over generations, one set of these genes could begin to predominate within a family. But predispositions are never dictatorial.

“People can decide to exercise,” whatever their inheritance, Dr. Booth said, and, as his study’s final experiment suggests, they could rewire their brains so that moving becomes a pleasure.

Source: New York Times