SpaceX Dragon to Carry 23 Student Experiments to Space Station.

Twenty-three microgravity experiments designed by participants of the Student Spaceflight Experiment Program (SSEP) will become part of space history Oct. 7. They will be launched to the International Space Station aboard the SpaceX Dragon, the first commercially developed and built American spacecraft to fly a resupply cargo resupply mission to the station.

Twelve of the SSEP experiments are getting a second flight opportunity. They were delivered to the space station on a SpaceX demonstration mission in May, but were not completed. The other 11 experiments are new.

Each experiment will study the effects of microgravity on physical, chemical and biological systems. The students have been immersed in every facet of research, from defining investigations to designing experiments, writing proposals, and submitting to a formal NASA review for selection of flight experiments. The 23 experiments represent more than 7,000 students and almost 2,000 proposals.

“SSEP offers a unique flight opportunity that allows students to experience both the excitement and the challenges inherent in conducting research in a microgravity environment,” said Roosevelt Johnson, deputy associate administrator for education at NASA Headquarters in Washington. “It really is STEM [science, technology, engineering and mathematics] in action, using the International Space Station — which has America’s only orbiting National Laboratory — to host these students’ science experiments.”

SSEP began in June 2010 as a cooperative venture by the National Center for Earth and Space Science Education (NCESSE) and NanoRacks LLC, a national STEM education initiative. The organizations work together to give hundreds of students across a community the opportunity to design and propose real experiments to fly in low Earth orbit. Teams submit formal flight experiment proposals, and a formal proposal review process selects the flight experiment for the community. A suite of programs leverages the flight experiment design competition to engage the entire community, including a mission patch art and design competition.

SSEP payloads were flown in 2011 aboard space shuttles Endeavour and Atlantis on their respective STS-134 and STS-135 missions. The third round of experiments in May was the first to be conducted in orbit by space station astronauts. Next week’s Dragon launch is the fourth flight opportunity. A fifth suite of experiments is scheduled for spring 2013.

More than 100 SSEP students, teachers, and family members will travel to Florida to attend the SpaceX launch from Cape Canaveral Air Force Station.
SSEP is one of many programs that use NASA’s science and exploration missions to encourage students to pursue a STEM-centric school curriculum. NASA’s Office of Education is committed to inspiring and developing the next generation of scientists and engineers through experiential, hands-on learning.

To learn more about the SSEP, including future opportunities for student participation, visit:

Source: NASA



NASA Offers Opportunities for Biological Research on Space Station.

NASA invites scientists from around the country to submit proposals to perform biological research aboard the International Space Station. The NASA Research Announcement (NRA), “Research Opportunities in Space Biology,” opened Sept. 30.

This NRA challenges scientists to propose experiments that could provide answers to questions about how life adapts and responds to microgravity. Selected investigators will have the opportunity to take advantage of new cell, plant and animal research facilities being developed for the space station. Proposals should demonstrate benefits to astronauts living and working in the harsh environment of space during long-duration missions. They also should improve medicine and health care for humans on Earth.

The NRA also focuses on ground-based research designed to lead to new space biology investigations aboard the orbiting laboratory. The investigations should use microgravity and other characteristics of the space environment effectively to enhance our understanding of basic biological processes and develop the scientific and technological foundations for a safe, productive human presence in space for extended periods in preparation for exploration beyond low Earth orbit. The investigations should apply this knowledge and technology to improve the nation’s competitiveness, education and quality of life.

NASA’s selection of research projects is guided by recommendations from the National Research Council’s 2011 Decadal Survey Report, “Recapturing a Future for Space Exploration: Life and Physical Sciences Research for a New Era.” The NASA-developed “Fundamental Space Biology Science Plan” provides an implementation strategy and roadmap based on available flight and fiscal resources.

read the complete NRA, click on “Solicitations” at NASA’s NSPIRES website:


Source: NASA


Intricate Interplay.

In our latest Clinical Problem-Solving article, a 55-year-old man presented with sinus congestion, headaches, chills, mild nausea, fatigue, and a “foggy” sensation that had lasted approximately 1 week. He reported darker urine than usual and had noticed that his eyes were turning yellow.

Although generally regarded as a chronic liver disease, autoimmune hepatitis is manifested as an acute illness in about 25% of patients.

Clinical Pearls

What is the differential diagnosis for severe aminotransferase elevations?

In contrast to the broad differential diagnosis for elevations in serum aminotransferase levels that are less than 5 times the upper limit of the normal range, the causes of severe aminotransferase elevations (>20 times the upper limit of the normal range) are more limited and include Wilson’s disease, acute biliary obstruction, and viral, toxic, ischemic, and autoimmune hepatitis.

What are the two types of autoimmune hepatitis?

Two types of autoimmune hepatitis have been proposed; type 1 is defined by positive results on testing for antinuclear antibodies and smooth-muscle antibodies, and type 2 by positive results on testing for antibodies against liver-kidney microsome type 1 and liver cytosol type 1. Type 2 autoimmune hepatitis has been described mainly in children in Europe and is rare in the United States. Among patients with type 1 disease, the reported prevalence of antinuclear antibodies alone is 13%, smooth-muscle antibodies alone 33%, and both 54%. Autoantibodies develop later in the disease in some patients who are seronegative on initial evaluation. Autoantibody-negative autoimmune hepatitis is important to recognize because patients with this condition typically have a favorable response to glucocorticoid therapy.

Morning Report Questions

Q: What is the standard treatment for severe cases of autoimmune hepatitis?

A: Treatment with either prednisone alone (at a dose of 60 mg daily) or a combination of prednisone (at a dose of 30 mg daily) and azathioprine (at a dose of 50 mg, or 1 to 2 mg per kilogram of body weight, daily) is recommended in cases of severe autoimmune hepatitis, on the basis of data from randomized clinical trials; combination therapy is generally preferred because the lower dose of glucocorticoid reduces side effects. Prednisolone in equivalent doses can be substituted for prednisone. Glucocorticoids are tapered over a 4-week period to a level required to maintain a biochemical remission, and this maintenance regimen is then continued until disease resolution (defined as biochemical remission for a minimum of 24 months), unless there is treatment failure or drug toxicity.

Q: What are the characteristics of nonalcoholic fatty liver disease?

A: Nonalcoholic fatty liver disease is one of the most common causes of asymptomatic aminotransferase elevations and chronic liver disease in Western countries. It encompasses a spectrum of disorders, from simple steatosis to fibrosing steatohepatitis that can progress to cirrhosis and its complications, including hepatocellular carcinoma. Aminotransferase levels can wax and wane, often into the normal range. Associated features include insulin resistance, central adiposity, dyslipidemia, and hypertension. The diagnosis of nonalcoholic fatty liver disease requires that there is no history of substantial alcohol consumption, although the definition of substantial alcohol consumption and the effect of obesity on thresholds for the development of alcoholic fatty liver disease remain unclear. Statins can be safely used in patients with nonalcoholic fatty liver disease and, in the majority of patients with this condition, are associated with improvement in liver enzyme abnormalities.

Source: NEJM





Benzodiazepine Use Linked to Dementia Risk.

Older adults who use benzodiazepines have about a 50% greater chance of developing dementia than their peers who don’t use benzodiazepines, French researchers observed in a large population-based study.

This finding, added to evidence of increased risk for falls and fractures in elderly who use benzodiazepine, “should incite (health providers) to carefully assess expected benefits versus putative risks, and to limit prescriptions to a few weeks,” lead author of the study and PhD student Sophie Billioti de Gage, PharmD, from the University of Bordeaux Segalen in France, told Medscape Medical News.

“In any case, uncontrolled use should be cautioned against,” she said.

The study was published online September 27 in the British Medical Journal.

“Bad Drugs for Older Adults”

Greg A. Sachs, MD, who reviewed the study for Medscape Medical News, said it is “yet another study that suggests that benzodiazepines are bad drugs for older adults.”

Dr. Sachs is chief of the Division of General Internal Medicine and Geriatrics, Indiana University School of Medicine, and investigator at the IU Center for Aging Research, Regenstrief Institute, Indianapolis. He was not involved in the study.

“Many of these drugs,” Dr. Sachs said, “are on ‘Do Not Prescribe’ lists for older adults. If used at all, they should be used for short periods of time (10 days or less) and in the lowest dose possible to achieve benefit for the target symptom.” Benzodiazepines “should not be used long term for either sleep or anxiety; safer alternatives exist.”

The analysis included 1063 men and women (mean age, 78.2 years) from the PAQUID (Personnes Agées Quid) project, a prospective, population-based study of cognitive aging and dementia involving a total of 3777 participants from France. The study started in 1987 and follow-up lasted 20 years, with clinic visits every 2 to 3 years.

All participants in the current analysis were free of dementia at the outset and did not start taking benzodiazepines until at least the third year of follow-up. Ninety-five (8.9%) reported benzodiazepine use at the 5-year visit, indicating new use between years 3 and 5. Year 5 was baseline for the analysis.

During the 15-year follow-up period, 253 (23.8%) cases of dementia were confirmed: 30 (32%) in benzodiazepine users and 223 (23.0%) in nonusers.

The 15-year incidence rate of dementia per 100 person-years was higher in benzodiazepine users than nonusers (4.8 vs 3.2).

The multivariable adjusted hazard ratio (HR) for dementia with new use of benzodiazepines was 1.60 (95% confidence interval [CI], 1.08 – 2.38). This result was unchanged when further adjusted for depressive symptoms (HR, 1.62; 95% CI, 1.08 – 2.43).

The result “remained robust” in a secondary pooled analysis of patients who initiated a benzodiazepine between follow-up visits 8 and 15 (HR, 1.46; 95% CI, 1.10 – 1.94). This added a total of 116 additional new users during follow-up to the 95 new users at year 5.

Similarly, in a nested-case control study (467 case-patients with dementia and 1810 controls), the adjusted odds ratio (OR) with ever use vs never use was 1.55 (95% CI, 1.24 – 1.95). The results were similar in past users (OR, 1.56; 95% CI, 1.23 – 1.98) and recent users (OR, 1.48; 95% CI, 0.83 – 2.63).

The PAQUID investigators say their findings are consistent with 3 recent case-control studies that found an increased risk for dementia in benzodiazepine users.

Two of the studies from Taiwan (Wu et al, 2011, Wu et al, 2009) used health insurance data and showed an increased risk for dementia in long-term users ( > 6 months; adjusted OR, 1.24; 95% CI, 1.01 – 1.53) and current users (adjusted OR, 2.71; 95% CI, 2.46 – 2.99).

The third study, a nested case-control study among French people, found an increased risk for dementia in former users (adjusted OR, 2.3; 95% CI, 1.2 – 4.5).

Other studies, however, have not found an increased risk for dementia among elderly people using benzodiazepines.

Dr. Billioti de Gage told Medscape Medical News that “contrary to most of the previous study on the topic, our study is based on a long period of follow-up (up to 15 years) and was carried out in a large representative cohort of elderly participants. This allows to take into account the somewhat long prodromal period of dementia and to generalize the conclusions.”

“Positive Distinguishing Factors”

Dr. Sachs said there are several “positive distinguishing factors about this study.” It was large; it followed patients over many years with little dropout; it was prospective and longitudinal rather than cross-sectional; the diagnosis of dementia involved both neuropsychological testing and examination by a neurologist; and the researches had excellent information about drug use from patients, he explained.

The exclusion of people who were already receiving benzodiazepines at time of study entry and for a period of a few years “run in” is another key strength, he said.

“This is important regarding the notion of ‘reverse causation’ — that people could end up taking benzodiazepines because of symptoms of depression or anxiety that are early symptoms relating to a developing dementia. Without doing that, it could bias the study toward people with dementia already brewing getting benzodiazepines at a higher rate, instead of the notion that it is contributing to dementia development,” Dr. Sachs said.

The analyses were “carefully done” and the findings were “explored and confirmed using more than one approach. The PAQUID study is one of the higher quality cohort studies examining dementia,” he added.

Dr. Billioti de Gage said, “patients should be told about the potential adverse effects of these drugs, including long-term risk when initiating benzodiazepines and about the necessity of gradual discontinuation when stopping the treatment.”

She and her colleagues say further study is needed to determine whether long-term use of benzodiazepines in people younger than age 65 years is also associated with an increased risk for dementia and uncover possible correlations between dosage or cumulative length of exposure and dementia.

Dr. Sachs agrees. The analysis “cannot tell us anything about long versus short acting meds, specific meds, dose, or duration of therapy,” he told Medscape Medical News. Also, the small numbers of people on benzodiazepines in the study is a limitation, he added.

Another limitation, he said, is that the analysis is primarily focused on “ever use” of benzodiazepines, “and that means we do not have information here on whether stopping the meds would help prevent dementia. In fact, because of the ‘ever use’ approach to analysis, I’d be concerned that someone misinterpret this and think ‘why bother stopping’ once someone has been exposed.”

Dr. Sachs also noted that “far greater numbers of people who developed dementia had not been exposed to benzodiazepines than those who had; so while it increases relative risk, how much it contributes to development of dementia should not be overplayed; this still was an observational study, so assigning causation is hard to do no matter how well the study is done.”




Beta Blockers of No Use in Stable CAD Patients.

New registry data indicate that beta blockers do not appear to be of any benefit in three distinct groups of stable outpatients: those with coronary artery disease (CAD) but no history of MI; those with a remote history of MI (one year or more); and those with coronary risk factors only [1].

Lead author Dr Sripal Bangalore (New York University School of Medicine, NY) told heartwire that the evidence for beta-blocker use has mainly been based on old post-MI trials that antedate modern reperfusion or medical therapy and heart-failure trials. People have extrapolated from these trials and assumed that the drugs are also beneficial in those with CAD and even those with just risk factors for CAD, he says, but it is not known if this is justified. Bangalore and colleagues decided to investigate further; they report their findings in the Journal of the American Medical Association, published online October 2, 2012.

Whether they used beta blockers or not in each of these three distinct patient cohorts, we did not see an association with reduced CV events, even in the prior-MI group.

“What we found was pretty interesting. Whether they used beta blockers or not in each of these three distinct patient cohorts, we did not see an association with reduced CV events, even in the prior-MI group. And for some of the outcomes, being on a beta blocker was associated with worse outcomes; for example, there was an increased risk of the primary composite end point–CV death, nonfatal MI, or nonfatal stroke–in patients with just risk factors but no CAD,” he notes.

He says that the answer to how long a patient should continue to take a beta blocker after an acute MI is not really known: “As of now, we don’t have enough data to answer this. If a patient after a year [following MI] can no longer tolerate beta blockers for any reason, and they don’t have heart failure, the data would suggest there is no harm in stopping. If they do have heart failure, however, I would be more inclined to push them a bit further and say, ‘This is a great medication; it saves lives.’ ”

To this end, he stresses that “it is important to understand what this study is not about. It’s definitely not about patients who come in after an acute MI or those who have HF–we know there is plenty of data to suggest that beta blockers are beneficial in HF–and also it’s not about patients who are on a beta blocker for any other reason, be that for arrhythmias or migraine prophylaxis.”

REACH Registry: Data in Almost 45,000 Patients Show Mostly No Benefit

Bangalore and colleagues analyzed data from the Reduction of Atherothrombosis for Continued Health (REACH) registry of 44 708 participants, 14 043 (31%) of whom had prior MI, 12 012 (27%) had documented CAD but without MI, and 18 653 (42%) had CAD risk factors only.

The primary study outcome was a composite of CV death, nonfatal MI, or nonfatal stroke. The secondary outcome was the primary outcome plus hospitalization for atherothrombotic events or a revascularization procedure; and there were a number of tertiary outcomes. Overall median follow-up was 44 months.

Researchers found that event rates were not significantly different in patients with vs those without beta-blocker use for any of the outcomes tested, even in the prior-MI cohort (16.9% vs 18.6%; hazard ratio [HR] 0.90, p=0.14).

In the CAD-without-MI group alone, rates of the primary end point were not significantly different among those with vs those without beta-blocker use (12.9% vs 13.6%; HR 0.92, p=0.31). And for the secondary end point in this patient group, outcomes were actually worse among those who used beta blockers compared with those who didn’t (OR 1.14, p=0.01); this was also the case for the tertiary outcome of hospitalization (OR 1.17, p=0.01).

The same applied to the cohort with risk factors alone, in which rates of the primary end point were higher among those who used beta blockers than those who didn’t (14.2% vs 12.1%; HR 1.18, p=0.02), as were rates of the secondary outcome (22.0% vs 20.2%; OR 1.12, p=0.04), but not the tertiary outcomes of MI and stroke.

Randomized Clinical Trials Needed to Define Subgroups of CAD Patients Who Will Benefit

Bangalore says there is somewhat of a disconnect between what current guidelines recommend–which is broadly in line with what he and his colleagues found–and what doctors on the ground are actually doing.

The most recent American Heart Association guidance on secondary prevention, for example, gave beta blockers only a class IIa recommendation for longer-term therapy and a class IIb recommendation for patients with coronary or other vascular disease, note he and his colleagues. And the latest European Society of Cardiology guidelines recommend long-term beta-blocker therapy only in patients with reduced left ventricular systolic dysfunction (class I), he says.

The message is we do need randomized trials in this era of modern medical and reperfusion therapy, even in patients with prior MI, to actually define who is best for beta-blocker therapy and to identify the optimal duration of treatment.

“Though the guidelines are kind of aligned with what we are showing, in practice that’s not true. It’s common to see beta blockers being prescribed because of the perception that they are perhaps beneficial. But we should be extra careful in making those extrapolations,” he told heartwire .

“There are a lot of patients who have had even a remote MI and who are still on beta blockers. And they are prescribed even for people who have had PCI and CABG but who have not had an MI,” he notes. And he adds that this drug class is still widely used for high blood pressure despite the fact that it has been downgraded by many hypertension societies to a fourth-line agent for the treatment of this condition.

“The message is we do need randomized trials in this era of modern medical and reperfusion therapy, even in patients with prior MI, to actually define who is best for beta-blocker therapy and to identify the optimal duration of treatment,” he concludes.


Gout Guidelines From ACR Include New Drugs, Diet.

New gout guidelines from the American College of Rheumatology are meant to improve gout management by providing clinicians with clear, readily implemented guidance on urate-lowering therapy (including diet and lifestyle changes), chronic tophaceous gouty arthropathy (CTGA), analgesic and antiinflammatory management of acute gouty arthritis, and drug prophylaxis of acute attacks.

The guidelines, reported in the October issue of Arthritis Care & Research in two parts, and include guidance on the new drugs febuxostat and pegloticase, recently approved for gout management and not yet addressed in the European League Against Rheumatism or British Society for Rheumatology gout guidelines.

Senior author Robert Terkeltaub, MD, told Medscape Medical News,”This is the first time in the 78-year history of ACR that there have been guidelines for the management of gout. This indicates how seriously people in rheumatology take this and how common the problem has become, with more than 8 million cases in the US, affecting 3.9% of adults. What we have here is a disease that is very well understood but ridiculously poorly managed.” Dr. Terkeltaub is chief of rheumatology at the Veterans Affairs Medical Center in San Diego, California, and professor of medicine and associate division director at the University of California in San Diego.

Old Disease, New Management

Part 1 of the guidelines focuses on hyperuricemia and CTGA. The top recommendation is for more intensive education of patients on diet, lifestyle choices, treatment objectives, and management of concomitant diseases; this includes recommendations on specific dietary items to encourage, limit, and avoid.

“We provide a comorbidity check-list for the clinician that I expect will be very useful in day-to-day practice,” Dr. Terkeltaub said. “We have also provided a cohesive set of diet and lifestyle recommendations. This has been a problem because of the fact and fiction mixed in to diet and lifestyle approaches to gout. The guideline is an advance because it provides a more actionable set of recommendations for physicians to talk about with their patients.”

Table. Comorbidity Checklist for Patients with Gout

Obesity, dietary factors
Excessive alcohol intake
History of urolithiasis
Chronic kidney disease
Potential genetic or acquired causes of uric acid overproduction (inborn error of purine metabolism, psoriasis, myeloproliferative or lymphoproliferative disease)
Lead intoxication


Dr. Terkeltaub added, “Many patients feel that diet and moderation alone should be sufficient to manage their gout. Diet is important, but what is really important is getting the serum urate to a target appropriate for that patient. At a bare minimum it should be < 6 mg/dL. In clinical practice the serum uric acid level is no longer part of the routine metabolic panel, but it is inexpensive and should be monitored regularly in gout patients.”

Dr. Terkeltaub noted that dietary or alcohol excess can increase uric acid and trigger acute gout attacks in susceptible individuals, but he said that dietary restrictions alone may not reduce serum urate levels enough to prevent joint damage in gout patients.

“The average age gout patient in our clinical trials has a serum uric acid level between 9.5 and 10 mg/dL. Even ideal diet and alcohol intake will likely lower that by only 10% to 15%, which will not bring the typical gout patient to a serum uric acid of 6 mg/dL. Often people need urate-lowering drugs to get them to the target level and keep them there. People feel that if they have fewer gout attacks, they are better, but the disease will progress unless serum uric acid is reduced to a level where deposits of urate crystals in the joint tissues will disappear,” Dr. Terkeltaub said.

Start Low, Go Slow With Allopurinol

The ACR guidelines recommend treating patients with a xanthine oxidase inhibitor, such as allopurinol, as the first-line pharmacologic urate-lowering therapy approach. The recommended goal is to reduce serum urate to less than 6 mg/dL, and the initial allopurinol dosage should be no greater than 100 mg/d, the guidelines say. This should be followed by gradual increase of the maintenance dose, which can safely exceed 300 mg even in patients with chronic kidney disease.

“Clinicians often start allopurinol at doses that are too high but maintain allopurinol at doses that are too low,” Dr. Terkeltaub said. “We give specific guidance on start low, go slow dose escalation.”

To avoid allopurinol toxicity, the guidelines recommend considering HLA-B*5801 prescreening of patients at particularly high risk for severe adverse reaction to allopurinol (eg, Koreans with stage 3 or worse kidney disease and all patients of Han Chinese and Thai descent).

For CTGA, the guidelines recommend combination therapy, with 1 xanthine oxidase inhibitor (allopurinol or febuxostat) and 1 uricosuric agent, when target urate levels are not achieved. They advise using probenecid as an alternative first-line urate-lowering drug in the setting of contraindication or intolerance to at least 1 xanthine oxidase inhibitor (except in patients with creatinine clearance below 50 mL/min). They also recommend pegloticase in patients with severe gout disease who do not respond to standard, appropriately dosed urate-lowering therapy.

“We provide guidance for dose-escalation of urate-lowering therapy for specific case scenarios of mild, moderate, and severe disease including for patients with destructive joint disease that is chronic to their gout. These provide ways to assess the patient in an office setting on clinical findings alone, with serum uric acid. Pictorial representation of most severe patients should help identify who needs more intensive uric acid-lowering therapy,” Dr. Terkeltaub said.

Acute Gout Requires Prompt Treatment

Part 2 of the guidelines covers therapy and prophylactic antiinflammatory treatment for acute gouty arthritis. These guidelines recommend initiating pharmacologic therapy within 24 hours of onset of acute gouty arthritis attack while continuing urate-lower therapy without interruption.

Nonsteroidal antiinflammatory drugs (NSAIDs), corticosteroids, or oral colchicine are the recommended first-line treatment for acute gout, and combinations of these medications can be used for severe or unresponsive cases.

To prevent the acute gout flares that may accompany the early stages of urate-lowering therapy, the guidelines recommend oral colchicine or low-dose NSAIDs as long as there is no medical contraindication or lack of tolerance.

Dr. Terkeltaub advised caution with colchicine dosing. “One of the major problems in quality of care is that people were getting drowned in colchicine for acute gout. We assessed the evidence and decided to go with the FDA [Food and Drug Administration]-approved regimen of low-dose colchicine for early acute gout flare. That is a major recommendation. When people get drowned in high doses of colchicine for a long time for acute gout, the rate of adverse events is quite high.”

The recommendations were prepared during a 2-year project by an ACR task force panel that included 7 rheumatologists, 2 primary care physicians, a nephrologist, and a patient representative. The draft guidelines then went through 3 rounds of peer review, Dr. Terkeltaub said.

“I’d like to see better education of physicians and other primary caregivers, including nurse practitioners and physician assistants, and then better education of gout patients. If we only accomplish that, we’ll have accomplished a lot. There has been a systematic failure of both quality of care and patient education in gout,” Dr. Terkeltaub said.

Doug Campos-Outcalt, MD, scientific analyst for the American Academy of Family Physicians, reviewed the new guidelines for Medscape Medical News. Dr. Capos-Outcalt is chair of the Department of Family Medicine at the University of Arizona College of Medicine in Phoenix.

Dr. Campos-Outcalt said, “This is a reasonable, limited number of guidelines that are implementable. You don’t like to see guidelines that have 50 recommendations. The ACR guidelines also present, from a family physician perspective, no major changes in standard-of-care.” However, Dr. Campos-Outcalt suggested that a broader effort to disseminate the guidelines to primary care physicians will be needed because few of them regularly read the journal in which the guidelines appear.

Dr. Campos-Outcalt told Medscape Medical News that the guidelines seem reasonable but that before being influenced by them, he would like to take a closer look at the level of evidence each recommendation is based on. “We don’t like to see recommendations based on low-level evidence,” he said. Only about 20% of the ACR recommendations were based on top-quality “level A” evidence (supported by more than 1 randomized clinical trial or meta-analysis). About half of the recommendations were based on level C evidence (consensus opinion of experts, case studies, or standard of care).




One Pill to Cure Them All: Single-Drug Polypharmacy in Cardiovascular Disease.

 Dr Richard Smith (UnitedHealth, London, UK), a longtime editor of BMJ, doesn’t know his own blood pressure or LDL levels, but he believes he’s keeping cardiovascular disease at bay by taking a polypill every day. Smith, who was enrolled in one of the early polypill trials, says he’s done this since he was 56 years old.


“If I had to go to the doctor every three months to get my blood pressure measured and my lipids measured and have to go back to have my drugs titrated, I couldn’t be bothered with all that,” he said. “Because I get [my polypills] through the post, and I just take it every night, it’s extremely simple.”

Low-dose combination tablets go by many names–the term “polypill” was trademarked by an enterprising US pharmacist. Cardiovascular researchers working in this area have settled on “polypharmacy” or single-tablet multidrug combination therapy, but like its name, the ideal makeup for a polypill is still largely undecided. Proponents of the polypharmaceutical approach, where a single tablet contains a statin, ACE inhibitor, beta blocker, diuretic, and aspirin, say it might one day form the cornerstone of primary- and secondary-prevention treatment for cardiovascular disease.

Smith was just one high-profile name attending the Global Summit on Combination Polypharmacy for Cardiovascular Disease, organized by Dr Salim Yusuf (McMaster University, Hamilton, ON). Calling cardiovascular disease the biggest epidemic the world has ever known, “bigger than HIV,” affecting nearly one in three individuals, Yusuf believes the magnitude of the problem and the ensuing worldwide shortage of cardiologists and specialists to treat cardiovascular morbidities cry out for new treatment paradigms.

“This is not about a pill,” Yusuf told heartwire . “This is about a strategy to reduce cardiovascular disease by 50% globally in a cost-effective manner.”

The two-day summit took place this week at the McMaster University Population Health Research Institute and included some of cardiology’s biggest names grappling with the medical, scientific, legal, regulatory, economic, and social issues of trying to get polypharmacy treatments on the market for patients with existing cardiovascular disease, as well as for those at high risk for cardiovascular disease.

The Wald and Law BMJ Paper

The polypill concept gained notoriety in a 2003 paper by Sir Nicholas Wald and Dr Malcolm Law (University of London, UK) in BMJ that provocatively claimed a combination polypill with a statin, three blood-pressure-lowering medications at half doses, an ACE inhibitor, aspirin, and folic acid could reduce the risk of ischemic heart disease by 88% and stroke by 80%. The British doctors raised the possibility of one day using the drug to treat all patients with cardiovascular disease as well as those 55 years of age and older, without measuring any risk factors.

This is about a strategy to reduce cardiovascular disease by 50% globally in a cost-effective manner.

“There is merit in the idea of treating all patients 55 years of age and older with a polypill, but right now there is too much resistance,” Yusuf told heartwire . “That is a bridge that we might cross five years from now, but it will be debated. If you start to think of prevention and treatment paradigms, think about LDL cholesterol. The targets have been coming down and treatment has become more aggressive. And the targets have been getting closer and closer for the whole population. Right now, the low-hanging fruit is in secondary prevention for the implementation of the polypill, high-risk primary prevention for research, and the whole population for the future.”

Dr Sidney Smith (University of North Carolina, Chapel Hill), the president of the World Heart Federation, told heartwire that one of the greatest challenges is simply getting patients to change their lifestyle, including stopping smoking, increasing physical activity, and eating healthier foods. The challenge after that monumental task is get these same individuals to adhere to those changes.

“I personally do not think that taking medication should be a substitute for changing lifestyle,” said Smith. “Now, in many areas, the cost of medication, when it is needed, is high and in many instances patients need to take more than one pill. I think the broadest initial application for a multidrug pill, the so-called polypill, will be in populations that are at high risk or have known disease and in countries that are low income or middle income and developing. Large populations of patients, such as in China and India, where the economies are developing and the healthcare systems are not set up to practice individualized medicine as we see in the US, might be best suited to the delivery of multidrug therapy by other healthcare workers.”

Dr Srinath Reddy (Public Health Foundation, India) agreed there is concern the use of the polypill would overshadow the needed changes to lifestyle and diet. He said the use of the polypill raises the specter of two competing visions of society. In the first, social and personal changes are used to bring about intergenerational benefits, such as tobacco-cessation programs, so that each successive generation has a lower risk of cardiovascular disease than the one preceding it. The other vision would be a more medicalized society, one in which ailments and disease are treated with drug therapies. While such a strategy has the potential to reduce the risk of cardiovascular disease and stroke, it provides no health benefits to the following generations.

Experts All Gathered in One Room

Throughout the meeting, the major discussions surrounding polypharmacy centered on who should be treated, what doses and formulations should be included in the polypill, how would the drug get approved by various regulatory agencies, who should administer medical treatment, and how the drugs would be distributed in low- to middle-income countries that lacked sufficient healthcare infrastructure. Aside from these massive hurdles, the experts agreed that adherence to medical treatment, whether the drug was in a single pill or treatment requiring multiple tablets, remains the elephant in the room.

I personally do not think that taking medication should be a substitute for changing lifestyle.

Dr Valentin Fuster (Mount Sinai School of Medicine, New York) noted that adherence to medical therapy declines 40% in the first six months after starting treatment. Fuster cited data from the Prospective Urban Rural Epidemiology(PURE) study showing large treatment gaps between affluent and underdeveloped countries with regard to proven secondary-prevention therapies. In addition, data from other trials, including the soon-to-presented FREEDOM trial of patients with diabetes mellitus, shows that just one in five patients had their cardiovascular risk factors controlled at follow-up. Similar rates of risk-factor control were observed in COURAGE and BARI 2D.

“We have a problem,” said Fuster. “We can talk about any intervention we want, from stents to surgery to anything at all, but 80% of people are not reaching the risk-factor profile they are supposed to reach.” The abysmal control of risk factors is occurring in clinical trials, Fuster pointed out, including the FREEDOM trial, where investigators were reminded every week to make sure patients were taking statins, aspirin, and other medications.

The underlying assumption of polypharmacy for cardiovascular disease is that a single drug with multiple compounds would improve risk-factor control because patients would be more likely to adhere to one medication. That, however, has not yet been proven in clinical trials. As Smith pointed out, adherence is a complex issue involving access, cost, and patient motivation, among other things. In the MI FREEE trial, for example, eliminating the copay for evidence-based cardiovascular medicines resulted in an adherence rate of less than 50%, a figure that was significantly higher than patients who had to make copayments, but low nonetheless.

Dr Susan Shurin (National Heart, Lung, and Blood Institute, Bethesda, MD), who spoke on the North American perspective of incorporating combination polypharmacy into a national strategy, believes that the development of a polypill belongs in the hands of the pharmaceutical companies and not the US government, but if such a multidrug strategy is to be approved or sanctioned, researchers would have to show the treatment had a “high impact” in that access and adherence were better and the single-combination tablet solved a problem the other generically available medicines could not.

Some of the Concerns About the Polypill

Despite acknowledging the gap between ideal and real-world risk factor control across all types of cardiovascular disease and the fact that 15% of the world’s population consumes 90% of the medicine, a discrepancy that afflicts poor and middle-income countries most, many of the summit’s speakers said there are concerns about the limitations of single-drug polypharmacy. In fact, resistance to the polypill often comes from physicians who are concerned about side effects, the inability to titrate the individual drugs, and the risks if a patient misses multiple days of treatment or if they decide to take “drug holidays.”

While titrating the doses of drugs, especially blood-pressure drugs, can further reduce individual risk factors, the net result would be a minimal reduction in overall clinical events, argued the researchers, and simply not worth the trade-off of increased side effects. Dr Anthony Rodgers (George Institute, Sydney, Australia) called such fiddling with doses “rapidly diminishing marginal returns in the pursuit of perfection.”

If you use complicated risk-scoring systems or just age, you end up treating almost the same people.

At the extreme end of the polypill debate–prescribing the medicine to patients 55 years of age and older regardless of risk factors–many physicians would be reluctant to ignore cardiovascular risk scoring systems in favor of a one-size-fits-all approach to healthcare.

Former BMJeditor Smith, however, argues that age alone can be used to treat a vast majority of patients. “If you go around and use complicated risk-scoring systems, like Framingham, or use just age, in men and women, you end up treating almost the same people,” said Smith. “There are some differences, but there aren’t that many.” And the simplicity of the concept, he pointed out, ultimately reduces costs.

To heartwire , Smith said he believes, as do other physicians, that there is currently enough available evidence to approve a polypill today for secondary prevention given that each individual component of the drug has been shown to reduce cardiovascular risk factors and clinical events. In secondary prevention, the collective wisdom is that treatment with a polypill would reduce clinical events by 50% to 60%. In primary prevention, however, the panelists, speakers, and audience members all agreed that more research needs to be done. The state of evidence right now is that there is sufficient rationale for starting new trials, but many expect outcome studies will be needed for a primary-prevention polypill to see the regulatory light of day.

The Next Stages

During the summit, Dr Norman Stockbridge (Food and Drug Administration, Bethesda, MD) noted that the agency has not previously approved anything like the polypill. While there are at least 44 two-drug combinations for hypertension, there is no precedent for a three-, four-, or five-drug combination tablet. He added that the polypill concept also changes the practice of medicine, whereby physicians maximize the effectiveness of one drug before moving on to another. Dr Peter Mol (Medicines Evaluation Board, Utrecht, the Netherlands) said that regulatory agencies in Europe would likely want confirmatory clinical trials, and these studies vary depending on how the drug is to be used (first- vs second-line therapy).

Currently, there are a host of ongoing clinical trials, including the 600-patient FREEDOM study in patients with diabetes and the 4000-patient FOCUS study. One study, Use of a Multidrug Pill in Reducing Cardiovascular Events (UMPIRE), scheduled to be presented at the American Heart Association meetingin November, is part of a collaborative effort called Single Pill to Avert Cardiovascular Events (SPACE) being run by the George Institute in Sydney, Australia. Other trials in the SPACE collaboration include the Kanyini Guidelines Adherence with the Polypill (GAP) study, which is completed but unpublished, and the Improving Adherence Using Combination Therapy(IMPACT) trial, which is ongoing in New Zealand.

The HOPE-3 study is also testing polypharmacy in patients at moderate risk for cardiovascular disease (based on age and one other risk factor) and will include cardiovascular death, nonfatal MI, and stroke as the primary outcome. TIPS-3 is ongoing, and TIPS-4 is scheduled to launch in three months.

Another possibility of gaining regulatory approval is to bypass the agencies altogether and appeal to the World Health Organization to get a multidrug combination tablet on the “Essential Medicines” list. Before that, however, there is a need to develop a consensus statement about the unmet healthcare need, the safety and efficacy of the polypill in the intended population, including the minimum data required for secondary-prevention patients, and its relative cost-effectiveness compared with other agents.



Cherries May Prevent Gout Flares.

Patients with gout were less likely to report acute attacks after 2 days of eating cherries or imbibing cherry extract than during periods after no cherry intake, according to data reported in Arthritis & Rheumatism by Yuqing Zhang, DSci, and colleagues from Boston University School of Medicine in Massachusetts.

Dr. Zhang, who is professor of medicine and epidemiology at Boston University School of Medicine, told Medscape Medical News that cherry intake during a 2-day period was associated with a 35% lower risk for gout attacks and that cherry extract intake was associated with a 45% lower risk.

Risk for gout attacks was reduced by 75% when cherry intake was combined with allopurinol use. Dr. Zhang said, “We found that if subjects took allopurinol alone, it reduced the risk of gout attack by 53%; if subjects took cherry alone, it reduced the risk by 32%; if they took both, the risk of gout attack was reduced by 75%.”

These associations were discovered in a case-crossover study of 633 individuals with physician-diagnosed gout who were prospectively recruited and followed online for 1 year. When a participant reported a gout attack, the researchers asked about the onset date of the gout attack, symptoms and signs, medications, and potential risk factors (including daily intake of cherries and cherry extract) during the 2 days before the attack. Patients served as their own controls, so the same information was assessed for 2-day control periods not associated with gout attacks. A cherry serving was defined as one-half cup or 10 to 12 cherries.

Participants had a mean age of 54 years; 88% were white and 78% were male. Of patients with some form of cherry intake, 35% ate fresh cherries, 2% ingested cherry extract, and 5% consumed both fresh cherry fruit and cherry extract. Researchers documented 1247 gout attacks during the 1-year follow-up period, with 92% occurring in the joint at the base of the big toe.

Factors associated with increased serum uric acid levels, such as increased alcohol consumption and purine intake, or use of diuretics, were associated with increased risk for recurrent gout attacks.

“Our findings indicate that consuming cherries or cherry extract lowers the risk of gout attack,” Dr. Zhang said in a press release. “The gout flare risk continued to decrease with increasing cherry consumption, up to three servings over two days.” Further cherry intake was not associated with additional benefit.

“However, the protective effect of cherry intake persisted after taking into account patients’ sex; body mass (obesity); purine intake; and use of alcohol, diuretics, and antigout medications,” according to the release.

The authors speculate that cherries may decrease serum uric acid levels by increasing glomerular filtration or reducing tubular reabsorption. They also note that cherries and cherry extract contain high levels of anthocyanins, which possess anti-inflammatory properties.

Dr. Zhang told Medscape Medical News, “While our study findings are promising, randomized clinical trials should be conducted to confirm whether cherry products could provide a nonpharmacological preventive option against grout attacks. Until then we would not advocate on the basis of the current findings that individuals who suffer from gout abandon standard therapies and opt for cherry extract products as an alternative.”

In an accompanying editorial, Allan Gelber, MD, from Johns Hopkins University School of Medicine in Baltimore, Maryland, and Daniel Solomon, MD, from Brigham and Women’s Hospital and Harvard University Medical School in Boston, write that the findings are promising but reiterates the need for randomized clinical trials to confirm that consumption of cherry products could prevent gout attacks.

Dr. Gelber told Medscape Medical News, “For the patient who asks his/her doctor ‘Doc, what can I do, myself, to decrease my chance of developing another gout attack, above and beyond the medications you have prescribed for me?’ our response would include that one of the options is dietary modification. Previously, physician recommendations included advocating for moderation in alcohol consumption, weight reduction, and decreasing high-purine foods from the diet…but now there are new data supporting a beneficial role in eating cherries to reduce one’s risk for recurrent gout attacks.”

Dr. Gelber noted that the most definitive support for the recommendation to eat cherries as a strategy to reduce gout risk would come from a randomized clinical trial. “Just as with new medications that come down the pipeline, dietary interventions ought also be subject to the rigor of a clinical trial. Such a study could be undertaken. There is logistical challenge to undertaking such a trial since cherry fruit is broadly available. But, in a controlled setting, such a trial would be feasible,” he said.





New EASD/ADA Position Paper Shifts Diabetes Treatment Goals?

A new position statement for the treatment of type 2 diabetes takes an approach much more focused on the individual patient compared with the “one number fits all” target of glycated hemoglobin (HbA1c) used up to now.

These new recommendations from the European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA), announced here today in a news conference at the European Association for the Study of Diabetes (EASD) 48th Annual Meeting, put the patient’s condition, desires, abilities, and tolerances at the center of the decision-making process about the goals and methods of treatment. “Our recommendations are less prescriptive than and not as algorithmic as prior guidelines,” the authors write.

In light of the increasing complexity of glycemic management in type 2 diabetes and the wide array of antidiabetic agents now available, as well as uncertainties about the benefits of intensive glycemic control on macrovascular complications, a joint task force of the EASD and the ADA sought to develop recommendations for the treatment of nonpregnant patients with type 2 diabetes to help clinicians determine optimal therapies. Their aim was to take into account the benefits and risks of glycemic control, the efficacy and safety of the drugs used to achieve it, and each patient’s situation. The resulting guidelines are published simultaneously in Diabetes Care (2012;35:1364-1379) and Diabetologia (2012;55:1577-1596) by the EASD and the ADA and are available on the EASD Web site.

“What we’re trying to do is encourage people to really engage in a complex world with the patient, given the variety of choices,” said David Matthews, MD, DPhil, from the Oxford Centre for Diabetes, Endocrinology and Metabolism at Churchill Hospital and the National Institute for Health Research, Oxford Biomedical Research Centre, United Kingdom, and cochair of the Position Statement Writing Group of the EASD and ADA. “And the algorithmic approach, in our view, has finally had its day. We can’t do that anymore.”

Dr. Matthews said the EASD and ADA writing group decided not to issue guidelines but rather to take positions and issue recommendations. “Published guidelines tend to be algorithmic, yet few clinicians prescribe by algorithms…and so there’s a lot of lip service to explicit guidelines,” he said.

Furthermore, there’s a danger in guidelines in that some payers and regulatory bodies focus on them as an absolute measure of success or failure and pay accordingly, or not. So for this reason, the authors did not put a specific HbA1c number in their position statement, and in addition, they did not want to give the impression that it is all right for the number to drift upward if it is below a certain level.

On the other hand, a lower HbA1c value may not be best for some patients. “We’ve got trial data challenging the simplistic view of the lower-the-better approach to glycemic control…. That tells us we need to be careful about just using numbers, however important they may be, to treat patients,” Dr. Matthews said.

So the plan is to have the physician and patient combine the best available evidence with clinical expertise and patient preferences to determine the course of treatment, which may include lifestyle interventions such as physical activity, dietary advice, and oral or injectable antidiabetic drugs, including insulin.

Main Points to New Approach

The position statement lays out 7 key points:

  • Individualized glycemic targets and glucose-lowering therapies
  • Diet, exercise, and education as the foundation of the treatment program
  • Use of metformin as the optimal first-line drug unless contraindicated
  • After metformin, the use of 1 or 2 additional oral or injectable agents, with a goal of minimizing adverse effects if possible (despite limited data to guide specific therapy)
  • Ultimately, insulin therapy alone or with other agents if needed to maintain blood glucose control
  • Where possible, all treatment decisions should involve the patient, with a focus on “patient preferences, needs and values”
  • A major focus on “comprehensive cardiovascular risk reduction”

The authors highlight several elements that need to be gauged for making decisions about the appropriate levels of effort to reach glycemic targets. Patient attitudes and expected efforts may range from highly motivated with good adherence and self-care abilities to poor motivation, nonadherence, and poor self-care abilities. The potential risks for hypoglycemia and other adverse effects are another element in decision-making.

The recommendations also focus on duration of disease, life expectancy, significant comorbidities, established vascular complications, and the patient’s resources and support system.

The authors make the point that although the recommendations focus on glycemic control, clinicians and patients should also pay attention to other risk factors, and specifically, “aggressive management of cardiovascular risk factors” in light of the increased risk for cardiovascular morbidity and mortality among patients with type 2 diabetes. Physicians should encourage as much physical activity as possible, aiming for a minimum of 150 min/week, consisting of aerobic, resistance, and flexibility training if possible.

If newly diagnosed patients are at or near the HbA1c target of less than 7.5% and they are highly motivated, they should be given a trial of lifestyle changes for 3 to 6 months with a goal of avoiding pharmacotherapy. But for patients with moderate hyperglycemia or for whom lifestyle changes are expected to be unsuccessful, antidiabetic drug therapy, usually with metformin, should be initiated. If lifestyle efforts are eventually successful, drug therapy may be modified or discontinued.

Information to Guide Pharmacotherapy

Many of the drugs to control blood glucose have similar efficacy, said Writing Group cochair Silvio Inzucchi, MD, professor of medicine, clinical director of the Section of Endocrinology, and director of the Yale Diabetes Center at the Yale School of Medicine in New Haven, Connecticut.

Based on an extensive review of more than 500 articles, “all of these drugs work more or less to the same extent,” he said. “In the grand scheme of things, when you’re talking about a patient taking a medication for years, perhaps decades, and being faced with side effects of medications, the differences in hemoglobin A1c may actually pale in comparison to how they experience that medication.”

To guide choices of glucose-lowering agents, the authors provide in tabular form summaries of the cellular mechanisms, physiological actions, advantages, disadvantages, and costs of classes of agents and drugs within the classes. They also show an algorithm for escalating treatment, starting with lifestyle changes and progressing to initial drug monotherapy, 2- and then 3-drug therapy, and finally to basal and then more complex insulin strategies.

The recommendations end with considerations of the effects of age, weight, sex/racial/ethnic/genetic differences, the comorbidities of coronary artery disease, heart failure, chronic kidney disease, liver dysfunction, and concerns about hypoglycemia. The authors also point out several areas where data are insufficient and therefore where research efforts should be aimed.

When asked if the new recommendations are feasible given the time allotted to seeing a patient, Andreas Pfeiffer, MD, DrMed, chief of the Department of Clinical Nutrition at the German Institute of Human Nutrition Potsdam-Rehbruecke in Nuthetal, Germany, and professor of internal medicine and director of the Department of Endocrinology, Diabetes and Nutrition at Charité Universitaetsmedizin Berlin, Germany, was cautious in his answer.

“If you calculate the time a doctor has per patient, it’s something like 7 minutes or so, and most patients are used to the physician telling him what he’s supposed to do,” Dr. Pfeiffer said. “In some ways it’s unrealistic” for a physician to explore a patient’s desires, capabilities, tolerances, and social support systems in that amount of time. On the other hand, patients return to the doctor several times over the course of a year, so there are more chances to expand the discussion.

But Dr. Pfeiffer worries whether diabetes specialists may become lax if they are not trying to treat to a specific goal. “Diabetologists have average HbA1c’s in Germany of around 7%, which is pretty good, actually…. And now if you relax the guidelines and say, ‘You don’t really have to care so much about it,’ so where do they go?” he wondered.


Gut Bacteria Can Affect Fat Absorption, and Act in Accordance to “Social Structures”.

Much new research is now emerging on the importance of bacteria – intestinal bacteria, to be more exact. These are commonly referred to as probiotics, and are the antithesis to antibiotics, both of which I’ll discuss below.

These microscopic critters are also known as your microbiome.

Around 100 trillion of these beneficial bacterial cells populate your body, particularly your intestines and other parts of your digestive system. In fact, 90 percent of the genetic material in your body is not yours, but rather that of bacteria, fungi, viruses and other microorganisms that compose your microflora.

We’re now discovering that the composition of this microflora has a profound impact on your health. For example, we now know that your intestinal bacteria influence your:

  • Genetic expression
  • Immune system
  • Brain development, mental health, and memory
  • Weight, and
  • Risk of numerous chronic and acute diseases, from diabetes to cancer

Certain Gut Microbes Affect Absorption of Dietary Fats

Most recently, a research team that includes Carnegie’s Steve Farber and Juliana Carten has revealed that certain gut microbes increase the absorption of dietary fats.1 According to the authors:

Diet-induced alterations in microbiota composition might influence fat absorption, providing mechanistic insight into how microbiota-diet interactions regulate host energy balance.”

Medical News Today2 recently reported on the findings, stating:

“Previous studies showed gut microbes aid in the breakdown of complex carbohydrates, but their role in dietary fat metabolism remained a mystery, until now… ‘This study is the first to demonstrate that microbes can promote the absorption of dietary fats in the intestine and their subsequent metabolism in the body,’ said senior study author John Rawls of the University of North Carolina. ‘The results underscore the complex relationship between microbes, diet and host physiology.'”

The bacteria identified as instrumental in increasing fat absorption are called Firmicutes, which, incidentally, have previously been linked to obesity, as they’re found in greater numbers in the guts of obese subjects. The researchers also found that the abundance of Firmicutes was influenced by diet. This adds weight to previous research postulating that gut bacteria can increase your body’s ability to absorb fat, and therefore extract more calories from your food compared to others who have a different composition of bacteria in their intestines – even when consuming the same amount of food.

Now, more recent research published in the journal Science3 reveals that bacteria may have “social structures similar to plants and animals.” According to the authors:

“In animals and plants, social structure can reduce conflict within populations and bias aggression toward competing populations; however, for bacteria in the wild it remains unknown whether such population-level organization exists. Here, we show that environmental bacteria are organized into socially cohesive units in which antagonism occurs between, rather than within, ecologically defined populations.

By screening approximately 35,000 possible mutual interactions among Vibrionaceae isolates from the ocean, we show that genotypic clusters known to have cohesive habitat association also act as units in terms of antibiotic production and resistance.

Genetic analyses show that within populations, broad-range antibiotics are produced by few genotypes, whereas all others are resistant, suggesting cooperation between conspecifics. Natural antibiotics may thus mediate competition between populations rather than solely increase the success of individuals.”

What this means is that certain bacteria have the ability to produce chemical compounds that inhibit the growth of other bacteria, while not harming their own kind or “close relatives.” These chemical compounds or natural antibiotics act as a type of chemical warfare, allowing the bacteria in question to gain a competitive edge by killing off the competition. Meanwhile, other “allies” are spared, as they are resistant to the antibiotic chemicals produced.

As reported by Medical News Today:4

“‘The research has the potential to bridge gaps in our understanding of the relationships between plants and humans and their non-disease- and disease-causing bacterial flora,’ said Robert Fleischmann, a program director in the Division of Biological Infrastructure for the National Science Foundation.

‘We use antibiotics to kill pathogenic microbes, which cause harm to humans and animals,’ said Polz. ‘As an unfortunate side effect, this has lead to the widespread buildup of resistance, particularly in hospitals where pathogens and humans encounter each other often.’

In addition, the results help scientists make sense of why closely related bacteria are so diverse in their gene content. Part of the answer, they say, is that the diversity allows the bacteria to play different social roles. Social differentiation, for example, could mitigate the negative effects of two species competing for the same limiting resource – food or habitat, for instance – and generate population level behavior that emerges from the interaction between close relatives.”

Beware of Fluoridated Antibiotics that Can Ruin Your Gut Flora and Your Health

Your lifestyle can and does influence your gut flora on a daily basis. All of these common exposures can wreak havoc on the makeup of bacteria in your gut, but researchers are now increasingly looking at the cascading ill effects of antibiotic drugs in particular. For example, your gut bacteria are extremely sensitive to:

Antibiotics are severely overused – not just in medicine, but also in food production. In fact, about 80 percent of all the antibiotics produced are used in agriculture – not only to fight infection, but to promote unhealthy (though profitable) weight gain in the animals. Hence, if you want to avoid overexposure to antibiotics, it’s also crucial to avoid conventionally-raised meats.

That said, certain antibiotics prescribed in medicine are so harmful they probably shouldn’t be used at all. Medications such as Avelox, Cipro, and Levaquin have been named in over 2,000 drug injury lawsuits.5

These are all fluoroquinolones, a class of fluoridated antibiotics associated with a number of serious side effects, such as potentially blinding retinal detachment, kidney failure, and permanent tendon damage. Fluoroquinolones do carry a black box warning for tendonitis, ruptured tendons, and its potentially detrimental effect on neuromuscular activity, but many patients simply do not read the warning labels before taking the drug. Other serious injuries linked to fluoroquinolones include:

Injury to central nervous system Injury to your heart Liver problems
Gastrointestinal problems Injury to musculoskeletal system Injury to renal system
Injury to visual and/or auditory system Altered blood sugar metabolism Depression
Psychotic reactions and hallucinations Phototoxicity Disfiguring rashes
Staphylococcus aureus infection C. difficile infection Severe diarrhea

Learn More about the Dangers of Fluoroquinolone Antibiotics

Shockingly, despite all these risks, fluoroquinolones are one of the most commonly prescribed classes of antibiotics in the world. John Fratti, who was hired by the FDA in a part-time position as an FDA Patient Representative for drug safety, is on a quest to raise awareness on the dangers of fluoroguinolone toxicity. He filed a Freedom of Information (FOI) request with the FDA on two of the top fluoroquinolones, Levaquin and Cipro, and learned that they are associated with over 2,500 deaths.

A non-profit organization called Quinolone Vigilance Foundation, established by Mr. David Melvin, was created to spread awareness of the dangers associated with this class of drugs, and the Foundation’s website contains both information and support for those injured by these drugs. Fortunately, fluoroquinolones have started getting some well-deserved media attention as of late.

According to a recent article in The New York Times:6

“A half-dozen fluoroquinolones have been taken off the market because of unjustifiable risks of adverse effects. Those that remain are undeniably important drugs, when used appropriately. But doctors at the Centers for Disease Control and Prevention have expressed concern that too often fluoroquinolones are prescribed unnecessarily as a ‘one size fits all’ remedy without considering their suitability for different patients.

Experts caution against giving these drugs to certain patients who face higher than average risks of bad reactions – children under age 18, adults over 60, and pregnant and nursing women – unless there is no effective alternative. The risk of adverse effects is also higher among people with liver disease and those taking corticosteroids or nonsteroidal anti-inflammatory drugs.

When an antibiotic is prescribed, it is wise to ask what the drug is and whether it is necessary, what side effects to be alert for, whether there are effective alternatives, when to expect the diagnosed condition to resolve, and when to call if something unexpected happens or recovery seems delayed.”

Last year, PBS NewsHour7 aired a segment highlighting the dangers of fluoroquinolones. Fratti, who is himself a victim of fluoroquinolone toxicity, was interviewed. He was prescribed Levaquin a few years ago for a minor bacterial infection. The drug caused nerve damage, tendon damage and damage to his central nervous system.

How to Optimize Your Gut Flora

The good news is that positively influencing the bacteria growing in your body is relatively easy. Aside from reserving antibiotics for serious cases of infection only, one of the most important steps you can take is to stop consuming sugary foods. When you eat a healthy diet that is low in sugars and processed foods, one of the major benefits is that it causes the good bacteria in your gut to flourish and build up a major defense against the bad bacteria getting a foothold in your body in the first place.

This is one of the many reasons I highly recommend reducing, with the plan of eliminating, sugars and most grains from your diet. Following my recently updated nutrition plan will help you optimize your diet in a systematic step-by-step fashion. A healthy diet is the ideal way to maintain a healthy gut, and regularly consuming traditionally fermented or cultured foods is the easiest way to ensure optimal gut flora. Healthy options include:

Fermented vegetables of all kinds (cabbage, carrots, kale, collards, celery spiced with herbs like ginger and garlic) Lassi (an Indian yogurt drink, traditionally enjoyed before dinner) Tempeh
Fermented raw milk such as kefir or yogurt, but NOT commercial versions, which typically do not have live cultures and are loaded with sugars that feed pathogenic bacteria Natto Kimchee


Just make sure to steer clear of pasteurized versions, as pasteurization will destroy many of the naturally-occurring probiotics. For example, most of the “probiotic” yogurts you find in every grocery store these days are NOT recommended. Since they’re pasteurized, they will be associated with all of the problems of pasteurized milk products instead. They also typically contain added sugars, high fructose corn syrup, dyes, and/or artificial sweeteners; all of which are detrimental to your health.

Consuming traditionally fermented foods will also provide you with the following added benefits:

  • Important nutrients: Some fermented foods are excellent sources of essential nutrients such as vitamin K2, which is important for preventing arterial plaque buildup and heart disease. Cheese curd, for example, is an excellent source of both probiotics and vitamin K2. You can also obtain all the K2 you’ll need (about 200 micrograms) by eating 15 grams, or half an ounce, of natto daily. They are also a potent producer of many B vitamins
  • Optimizing your immune system: Probiotics have been shown to modulate immune responses via your gut’s mucosal immune system, and have anti-inflammatory potential. Eighty percent of your immune system is located in your digestive system, making a healthy gut a major focal point if you want to maintain optimal health, as a robust immune system is your number one defense system against ALL disease
  • Detoxification: Fermented foods are some of the best chelators available. The beneficial bacteria in these foods are very potent detoxifiers, capable of drawing out a wide range of toxins and heavy metals
  • Cost effective: Fermented foods can contain 100 times more probiotics than a supplement, so just adding a small amount of fermented foods to each meal will give you the biggest bang for your buck
  • Natural variety of microflora: As long as you vary the fermented and cultured foods you eat, you’ll get a much wider variety of beneficial bacteria than you could ever get from a supplement

When you first start out, you’ll want to start small, adding as little as half a tablespoon of fermented vegetables to each meal, and gradually work your way up to about a quarter to half a cup (2 to 4 oz) of fermented vegetables or other cultured food with one to three meals per day. Since cultured foods are efficient detoxifiers, you may experience detox symptoms, or a “healing crisis,” if you introduce too many at once.

Learn to Make Your Own Fermented Vegetables

Fermented vegetables are easy to make on your own. It’s also the most cost-effective way to get high amounts of healthful probiotics in your diet. To learn how, review the following interview with Caroline Barringer, a Nutritional Therapy Practitioner (NTP) and an expert in the preparation of the foods prescribed in Dr. Natasha Campbell-McBride’s Gut and Psychology Syndrome (GAPS) Nutritional Program. In addition to the wealth of information shared in this interview, I highly recommend getting the book Gut and Psychology Syndrome, which provides all the necessary details for Dr. McBride’s GAPS protocol.

Although you can use the native bacteria on cabbage and other vegetables, it is typically easier to get consistent results by using a starter culture. Caroline prepares hundreds of quarts of fermented vegetables a week and has found that she gets great results by using three to four high quality probiotic capsules to jump start the fermentation process.

Source: Dr. Mercola