No Getting Away From Clostridium difficile

Clostridium difficile (C difficile) is in the news again. This time, some of the news is good. In 3 state-led prevention programs, 71 hospitals that focused on prevention of C difficile infection (CDI) were able to cut their aggregate hospital-onset CDI rate by 20% in less than 2 years.^[1]

The bad news is that for most of the country, CDI rates are still at an all-time high and remain strongly associated with exposure to healthcare. According to Emerging Infections Program surveillance, in 2010, 94% of CDIs occurred in patients who had received healthcare as an inpatient, outpatient, or both in the preceding 12 weeks.^[1] C difficile infection is a rising cause of death in the most vulnerable patients. From 2000-2007, deaths from CDI increased 400% -- to 14,000 annually, at a cost of more than $1 billion.

It's time to reassess the way we think about C difficile.

C difficile infection is not just a frustratingly difficult-to-treat disease. It cannot be dismissed as a "hospital problem" or a "long-term care problem." It is a healthcare-wide patient safety problem. Like other patient safety problems, resolving CDI requires a multifaceted approach and a commitment to action from both multiple stakeholders and the individuals at the "sharp end" of patient care.

With the conviction that transmission of C difficile is avoidable but that no single action will be sufficient, the Centers for Disease Control and Prevention (CDC) outlined the 6 strategies that have the best chance of eradicating C difficile from healthcare. These strategies involve elements of antibiotic stewardship, testing for C difficile, isolation and infection control procedures, environmental cleaning, and communication^[2]:

1. Prescribe and use antibiotics carefully. About 50% of antibiotics that are given are not needed.
2. Test for C difficile when patients have diarrhea while taking antibiotics or within several months of taking them.
3. Isolate patients with C difficile immediately.
4. Wear gloves and gown when treating patients with C difficile, even during short visits. Hand sanitizer does not kill C difficile, and handwashing may not be sufficient.
5. Clean room surfaces with bleach or another Environmental Protection Agency (EPA)-approved spore-killing disinfectant after a patient with C difficile has been treated there.
6. When a patient transfers to another facility, notify the new facility if the patient has CDI.

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From U.S. Pharmacist

Statin-associated Myopathy

Jennifer Shannon, PharmD; Samuel John, PharmD; Jenna Ferrara, PharmD, BCPS; Sylvia Best, PharmD, BCPS; Shari N. Allen, PharmD

Authors and Disclosures

Posted: 03/20/2012; US Pharmacist © 2012 Jobson Publishing

Abstract and Introduction

Introduction

From 2006 to 2010, the number of dispensed prescriptions for lipid regulators, which primarily include statins, has continuously increased from 210.4 million to 255 million.^[1] The 3-hydroxy-3-methyl-glutaryl-CoA(HMG-CoA) reductase inhibitors, more commonly known as statins, are the most widely used medications for decreasing low-density lipoprotein (LDL) cholesterol. Statin use has been shown to decrease cardiovascular disease morbidity and mortality, but despite its advantages, over 40% of patients who have an indication for statin use are not receiving therapy. This may be secondary to a rare but major adverse event that is associated with the use of statins—myopathy.^[2,3]

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PPI-Associated Clostridium difficile Infection

The FDA recently alerted healthcare professionals and patients that use of proton-pump inhibitors may increase the risk for Clostridium difficile–associated diarrhea.

On reviewing published studies and information from the FDA's Adverse Event Reporting System, the FDA warned the public that use of proton-pump inhibitors (PPIs) may increase the risk for Clostridium difficile–associated diarrhea (CDAD). Although the strength of the association varied widely among studies, most studies found risk for C. difficile infection or disease to be 1.4 to 2.75 times higher in patients with PPI exposure than in those without. Many of the patients affected also had other risk factors, such as antibiotic use, older age, or certain comorbid conditions.

PPIs (and possibly histamine-2 antagonists) alter the gastric pH and can allow overgrowth of C. difficile. Several of these agents are now sold over the counter, without need for a prescription.

Patients taking PPIs should be advised to seek medical care promptly if they experience watery diarrhea that does not improve, abdominal pain, and fever. Those found to have C. difficile infection may require replacement of fluid and electrolytes and may need to discontinue or change a prescribed antimicrobial therapy. Uncommon but serious complications include kidney failure, toxic megacolon, bowel perforation, and even death.

Comment: The literature suggests that PPI use increases risk for several problems in addition to C. difficile infection — for example, nosocomial pneumonia, drug–drug interactions (because PPIs decrease absorption of several antimicrobial and antiretroviral agents), and electrolyte imbalances. The effects of dose and duration are not entirely clear, but using the lowest dose for the prescribed indication — and for no longer than necessary — makes sense.

Unfortunately, PPIs are often prescribed without good reason, such as for stress-ulcer prophylaxis in patients who don't qualify for this therapy. Furthermore, once started, these medications are often continued indefinitely. Over-the-counter availability of PPIs compounds the risk for adverse events by decreasing clinician oversight and, potentially, patient awareness of such risk.

— Lynn L. Estes, PharmD

Published in Journal Watch Infectious Diseases February 22, 2012

SUMMARY AND COMMENT

The Risks and Benefits of Aspirin in Primary Prevention of CVD

March 1, 2012 | Thomas L. Schwenk, MD | General Medicine

Risk for nontrivial bleeding roughly equals benefit in preventing nonfatal myocardial infarction.

Reviewing: Seshasai SRK et al. Arch Intern Med 2012 Feb 13; 172:209

Mora S. Arch Intern Med 2012 Feb 13; 172:217

Apixaban vs. Aspirin for Secondary Stroke Prevention in Atrial Fibrillation

This new oral anticoagulant drug significantly reduced the rate of thromboembolism without increasing the rate of intracranial hemorrhage.

Citation(s):

Diener H-C et al. Apixaban versus aspirin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: A predefined subgroup analysis from AVERROES, a randomised trial. Lancet Neurol 2012 Mar; 11:225.

Medline abstract (Free)

Keep an Eye on the Sodium-Potassium Ratio

Both the medical and lay literature have entertained much discussion about the role of diet in general and sodium intake specifically to minimize population risk for cardiovascular disease and mortality. We have demonstrated that high sodium intake is associated with greater risk^[1] and that lowering sodium intake lowers blood pressure, which may translate to a decreased risk for cardiovascular events and subsequent mortality.^[2] On the other hand, we have also demonstrated that low sodium intake can be associated with greater risk.^[3] We debate these relationships and the utility of the salt-restriction intervention because the ability to reduce blood pressure and the risk for clinical events and mortality have not all been demonstrated in the same study.

Is there really controversy here, or is it that the mechanism of risk between excess sodium intake and sodium reduction are more complex than previously realized? Perhaps it is the role of potassium intake that has been underinvestigated and underpresented to the public. Multiple studies demonstrate a link between the ratio of sodium-to-potassium intake and hypertension and cardiovascular disease,^[4-8] and that this ratio is a more powerful predictor of outcomes than the intake of either separately.

A recent analysis of the Third National Health and Nutrition Examination Survey examines the association between estimated intake of sodium and potassium and both cardiovascular and all-cause mortality among adults.^[9] Dietary intake of sodium and potassium were assessed using dietary recall, with estimation of quantities based on food descriptions. In examining the distribution of sodium and potassium intakes, it is noteworthy that the mean intake of sodium, at more than 4.3 g for men and 2.9 g for women, was impressively greater than that suggested in an unselected population. While statistically significant differences in race, ethnicity, education, smoking status, and alcohol intake were present in groups, age showed the greatest clinical differences in mean intake of sodium among participants. In men, sodium intake in those over 60 years was 3.6 g compared with 4.5 g in younger men; in older women, sodium intake was 2.5 g compared with 3.0 g in younger women (P < .001). Similar trends were seen among groups when the sodium-potassium ratio was compared. As with sodium alone, the sodium-potassium ratio was higher in men than in women and, in general, higher in younger patients compared with those aged 60 years (P <.001).

When correlated with risk for all-cause mortality and adjusted for factors such as age and gender, dose-risk relationships between both sodium and potassium were demonstrated. Mortality risk increased among respondents with increasing sodium intake (comparing lowest with increasing quartiles, hazard ratio [HR] = 1.17, 1.37, and 1.73, P = .02) and decreasing potassium intake (comparing lowest quartile with increasing quartiles HR= 0.86, 0.75, and 0.61; P = .01), independently. The strongest relationship between these parameters and mortality was seen, however, when quartiles of the sodium-potassium ratio were analyzed (comparing lowest with increasing quartile HR = 1.13, 1.25, and 1.46, P <.001). Similar relationships were seen when examining cardiovascular and ischemic causes of mortality.

As is well known, observational data can only demonstrate associations and cannot establish cause and effect. If we were tempted, however, to make the cause-effect leap, this study supports that we should instruct our patients that, without an increase in potassium, just reducing sodium may not be as effective in lowering their risk.

Serum Level vs Intake: Big Difference

Of note, we need to make it very clear to both our patients and colleagues that sodium and potassium intake are not the sole determinants of, and should not be confused with, sodium and potassium levels in the blood. It is well known that both hyponatremia and hypernatremia are linked to mortality,^[10,11] but they represent a disorder of water metabolism, not a reflection of sodium intake. On the other hand, it may be easy to become potassium depleted on a potassium-wasting medication with inadequate oral intake, but the relationship between levels and risk that exists for potassium, as does for sodium, is likely related to the physiology that predisposes an individual to be unable to maintain levels within a certain range.

Most recently, an observational study demonstrated a U-shaped relationship between postadmission serum potassium levels and in-hospital mortality among persons with acute myocardial infarction.^[12] The lowest mortality rates were seen among persons with serum potassium levels between 3.5 and 4.5 mEq/L. At values greater and less than this range, mortality risk increased. It should be remembered that the kidney tightly regulates potassium concentration in the blood until a disease process or medication taxes its ability to maintain homeostasis. Therefore, whether hypokalemia is a marker of aldosterone excess or directly confers risk of dysrhythmia cannot be discerned. Regardless, these relationships between both potassium level and potassium intake are likely independent and may be additive.

References

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This is a rather beautiful study linking mouse model work and cancer cell lines with their colorectal cancer biobank, making the link between inflammatory colorectal carcinogenesis and how it might be mediated by anti-inflammatory drugs.

We know that inflammation is one of the hallmarks of cancer. To me, that opens up a whole new world of therapeutic potential. We have been dabbling with aspirin for decades, and we have been looking at the newer generations of COX-2 inhibitors. However, Dubois and colleagues, who have made a very distinguished contribution to the understanding of the molecular events that link inflammation together, have given us some interesting new insights.

The study showed that prostaglandin E₂ (PGE₂), which is one of the key lipid mediators of inflammation, is linked to progression of colorectal cancer through methylation. Very simply, what they seem to have shown is that PGE₂ induces the synthesis of DNA methyltransferase enzymes. These are then responsible for methylating and transcriptionally silencing some tumor suppressor genes, and that could lead to progression. If you switch the tumor suppressor off, that could lead to tumor progression.

In a series of rather elegant and quite compelling experiments, they have shown the link. They have taken it from cell lines to elegant mouse model systems and made some correlations with human tumors. They then went on to show in the murine tumor models that, if we use celecoxib, a selective important inhibitor of cyclooxygenase-2, you can reduce the effect very markedly.

If you use azacitidine, which is a demethylating agent, you can also reduce this effect markedly. If you put the 2 drugs together, however, they seem to be truly pharmacologically synergistic. So, we have some fascinating insights into the mechanism of colorectal carcinogenesis. A really nice molecular study of what pathways might be involved sequentially. For those of us who are translational clinicians, as Dubois and colleagues pointed out in the article, it may give us some potential new therapeutic options.

I'm very keen on exploring new literature. It looks as if we might be able to identify patients with inflammatory tumors (ie, tumors in which inflammation contributes to the aggressive nature of the cancer and a worse phenotype) just by looking at some simple markers of inflammation. C-reactive protein may identify a subgroup of patients in whom the tumor is driven by this inflammatory process. A fantastic contribution has been made by Professor Donald McMillan, a friend of mine working at the University of Glasgow.

So again, if we apply this to personalized medicine, we might be able to identify patients in whom inflammation is important and patients in whom we might wish to use such drugs as celecoxib and aspirin, and potentially in combination with azacitidine with demethylating agents, to see what we can do to suppress inflammation. Through this, we might see what can be done to alter the natural history of established cancer and, perhaps in the future, see what we might be able to do to prevent colorectal cancer.

These were some beautiful laboratory insights. Dubois is contributing at the top of his game. I can see how these ideas could be taken into the clinic to test the hypotheses pretty quickly. Thanks for listening, and as always, we would be delighted to receive any of your comments or feedback. Thank you.

Which Foods Are Best for the Brain?

Diet is inextricably linked to conditions such as heart disease, obesity, and diabetes. However, what we consume also seems to have significant implications for the brain: Unhealthy diets may increase risk for psychiatric and neurologic conditions, such as depression and dementia, whereas healthy diets may be protective. Based primarily on recent Medscape News coverage, the following slideshow collects some of the more prominent investigations on nutrition and the brain into a single resource to aid in counseling your patients.

A study conducted in Spain^[6,7] reported that consumption of both polyunsaturated fatty acids (found in nuts, seeds, fish, and leafy green vegetables) and monounsaturated fatty acids (found in olive oil, avocados, and nuts) decreases the risk for depression over time. However, there were clear dose-response relationships between dietary intake of trans fats and depression risk, whereas other data support an association between trans fats and ischemic stroke risk.^[8] Trans fats are found extensively in processed foods, including many commercial chocolates (hence, check that label when considering the chocolate slide below). A deficiency in polyunsaturated fatty acids has been linked to attention deficit/hyperactivity disorder in children.^[9]

Make for Malta in Depression, Stroke, and Dementia

A 2009 study published in Archives of General Psychiatry found that people who follow Mediterranean dietary patterns -- that is, a diet high in fruits, vegetables, nuts, whole grains, fish, and unsaturated fat (common in olive and other plant oils) -- are up to 30% less likely to develop depression than those who typically consume meatier, dairy-heavy fare.^[1] The olive oil-inclined also show a lower risk for ischemic stroke^[2,3] and are less likely to develop mild cognitive impairment and Alzheimer disease, particularly when they engage in higher levels of physical activity.^[4,5]

Fat: The Good and the Bad

A study conducted in Spain^[6,7] reported that consumption of both polyunsaturated fatty acids (found in nuts, seeds, fish, and leafy green vegetables) and monounsaturated fatty acids (found in olive oil, avocados, and nuts) decreases the risk for depression over time. However, there were clear dose-response relationships between dietary intake of trans fats and depression risk, whereas other data support an association between trans fats and ischemic stroke risk.^[8] Trans fats are found extensively in processed foods, including many commercial chocolates (hence, check that label when considering the chocolate slide below). A deficiency in polyunsaturated fatty acids has been linked to attention deficit/hyperactivity disorder in children.^[

Fish Oil to Fend Off Psychosis?

Thanks to their high levels of polyunsaturated fatty acids, namely omega-3 fatty acids, fish can help fend off numerous diseases of the brain. A 2010 study correlated fish consumption with a lower risk for psychotic symptoms,^[10] and concurrent work suggested that fish oil may help prevent psychosis in high-risk individuals.^[11] Although data are conflicting, new research shows that the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid are beneficial in depression and postpartum depression, respectively, and other research suggests that omega-3 deficiency may be a risk factor for suicide.^[12-16] Oily,

Berries for Oxidative Stress

Polyphenols, namely anthocyanins, found in berries and other darkly pigmented fruits and vegetables may slow cognitive decline through antioxidant and anti-inflammatory properties. A study in rats from 2010 showed that a diet high in strawberry, blueberry, or blackberry extract leads to a "reversal of age-related deficits in nerve function and behavior involving learning and memory."^[17] In vitro work by the same group found that strawberry, blueberry, and acai berry extracts -- albeit in very high concentrations -- can induce autophagy, a means by which cells clear debris, such as proteins linked to mental decline and memory loss.^[18] Berry anthocyanins may also reduce cardiovascular disease risk by reducing oxidative stress and attenuating inflammatory gene expression.^[19]

A "Whole" Diet: Make Room for Red Meat?

A so-called "whole" diet high in fruits, vegetables, whole grains, and high-quality meats and fish results in a 30% risk reduction for depression and anxiety disorders, compared with consumption of a "Western diet" high in processed foods and saturated fats, according to a 2010 study.^[20] Even unprocessed red meat seems to be protective against depressive and anxiety disorders,^[21] in contrast to many studies in which red meat often falls into the category of "unhealthy" food. In speaking with Medscape News, principal investigator Dr. Felice Jacka specifically addressed the importance of farming practices: Despite the growing locavore movement, much of the livestock in the United States is still raised on industrial feedlots, which "...increases saturated fat and decreases very important good fatty acids...pasture-raised animals have a much healthier fatty acid profile." A "whole" dietary pattern may also reduce depression risk, as assessed at 5-year follow-up.^[22]

Alcohol: Always in Moderation

The Greeks touted "nothing in excess," a refrain that still rings true: Low to moderate* alcohol consumption has been associated with numerous potential physiologic benefits, including improved cholesterol profiles, beneficial effects on platelet and clotting function, and improved insulin sensitivity.^[23] According to a recent meta-analysis, limited alcohol use is associated with a lower risk for overall and Alzheimer dementia,^[24] a finding supported by a 2011 study of German primary care patients.^[23] Moderate alcohol intake may also protect against cerebrovascular disease, with wine potentially having added benefit because of its polyphenolic antioxidant components (ie, resveratrol).^[25-27] However, the health costs of alcohol consumption beyond low to moderate intake can quickly outweigh benefits to the brain, as heavy and long-term alcohol use can lead to alcohol abuse and dependence, impair memory function, contribute to neurodegenerative disease, and hinder psychosocial functioning.

*The US Food and Drug Administration defines "moderate alcohol consumption" as up to 1 drink per day for women and up to 2 drinks per day for men. One drink is equivalent to 12 fluid ounces of regular beer, 5 fluid ounces of 12% alcohol wine, or 1.5 fluid ounces of distilled spirits.

Brewed Awakening: Coffee for Depression and Stroke

The world's most widely used stimulant might do more than just wake us up: A 2011 meta-analysis^[28] found that consumption of 1-6 cups of coffee a day cut stroke risk by 17%. Although it may increase blood pressure, coffee beans contain antioxidant compounds that may reduce oxidation of low-density lipoprotein cholesterol, and coffee consumption has also been associated with increased insulin sensitivity and reduced concentrations of inflammatory markers.^[29] Another 2011 study^[30] reported that women who drink 2-3 cups of coffee per day have a 15% decreased risk for depression, compared with those who drink less than 1 cup per week. A 20% decreased risk was seen in those who drank 4 cups or more. The short-term effect of coffee on mood may be due to altered serotonin and dopamine activity, whereas the mechanisms behind its potential long-term effects on mood may relate to its antioxidant and anti-inflammatory properties, both factors that are thought to play a role in depressive illnesses.

Chocolate -- and Still More Antioxidants

Chocolate -- the darker the better -- seems to help scavenge free radicals and improve endothelial and platelet function, likely via flavanols (such as catechin), a group of plant-derived polyphenols.^[33] A 2010 cohort study published in European Heart Journal found that consumption of 6 g of chocolate daily -- a standard Hershey bar weighs 43 g -- was associated with a 39% lower combined risk for myocardial infarction and stroke in adults,^[34] whereas data collected from the Swedish Mammography Cohort demonstrated a 20% decreased risk for stroke in women who regularly consume chocolate.^[35] Although chocolate has been associated with a positive influence on mood, possibly mediated by the dopamine and opioid systems, an extensive review by Parker and colleagues^[36] suggests that the benefits are

What Not to Eat?

Saturated fats and refined carbohydrates have highly detrimental effects on the immune system, oxidative stress, and neurotrophins, all factors that are known to play a role in depression. The study by Akbaraly and colleagues cited previously^[22] showed that a diet rich in high-fat dairy foods and fried, refined, and sugary foods significantly increases risk for depression. Similar findings were seen in another study from Spain,^[7] showing that intake of such foods as pizza and hamburgers increased the risk for depression over time, and in another study, women with a diet higher in processed foods were more likely to have clinical major depression or dysthymia.^[17] Research published last year^[37] also showed for the first time that quality of adolescents' diets was linked to mental health: Healthier diets were associated with reduced mental health symptoms and unhealthy diets with increased mental health symptoms over time. Excess salt intake has been long known to increase blood pressure and stroke risk^[38,39]; however, recent data also correlate high salt intake, as well as diets high in trans or saturated fats, with impaired cognition.^[40,41]

Clinical Context

According to the current study by Crowell and colleagues, small intestinal bacterial overgrowth (SIBO) is characterized by clinical features resulting from competition between atypical and excessive bacteria in the small bowel and is defined as more than 10⁵ colony-forming units/mL of bacteria in an aspirate collected from the small intestine. Use of proton pump inhibitors (PPIs) has been associated with some adverse outcomes, and there is conflicting evidence about the effect of PPI use on the development of SIBO.

This retrospective study of patients who had glucose hydrogen breath testing (GHBT) performed for a variety of indications at a single center examines the association between PPI use and SIBO, as determined by abnormal GHBT results.

Study Synopsis and Perspective

Contrary to current thinking, a new study suggests that proton pump inhibitors (PPIs) do not predispose to small intestinal bacterial overgrowth (SIBO).

"The study was prompted by reports suggesting an association between PPI use and the development of SIBO," Dr. Michael Crowell of the Mayo Clinic, Scottsdale, Arizona, told Reuters Health by email.

"In our very busy motility laboratories, we test a substantial number of patients for SIBO — many are on PPIs. From my clinical observations, there did not appear to be any association between PPI use and SIBO positive breath tests. Therefore, we decided to test our hypothesis that there was no significant association using our database."

Altogether, Dr. Crowell and his colleagues looked at data on 1,191 patients (70% women) who had glucose hydrogen breath testing (GHBT) from 2004 to 2010. Slightly less than half — 556 patients, or 48% — were PPI users.

In all subjects, breath samples for hydrogen (H₂) and methane (CH₄) were collected before and every 20 minutes for 120 minutes following ingestion of a 50-g oral glucose load.

The following criteria were used to define a positive GHBT: an increase in H₂ greater than 20 parts per million (ppm) over baseline; a sustained increase in H₂ greater than 10 ppm over baseline; CH₄ greater than 15 ppm over baseline; and either an increase in H₂ greater than 20 ppm over baseline or CH₄ greater than 15 ppm.

In support of the team's hypothesis, they didn't find any differences in rates of abnormal breath tests between patients on or off PPI therapy. PPI use was not significantly associated with GHBT positivity.

In a paper online February 14 in the American Journal of Gastroenterology, they further report that subgroup analysis to evaluate the influence of PPI dose frequency on the proportion of patients with a positive breath test showed no significant differences between once-daily vs twice-daily PPI use based on any of the four criteria evaluated.

"Importantly," they say the lack of association between PPI use and GHBT remained strong after adjusting for potential confounding factors such as age, body mass index, diabetes, irritable bowel syndrome, and laxative/antidiarrheal use.

"Owing to the widespread use of PPIs and an increasing interest in the role of SIBO in a variety of conditions, the association of SIBO with PPI use has recently generated significant clinical interest," the authors note.

"The take-home message," Dr. Crowell said, "is that the probability that PPI use increases the risk of developing SIBO appears to be quite small in our clinic population."

In the past 10 years, studies using different tests for detecting SIBO have addressed the association between SIBO and PPI use and have yielded conflicting findings. "This means that it is quite likely that other factors may also influence GHBT positivity," the authors say.

"For example," they add, "it is easy to speculate that differences in diet might affect the study results. The majority of the studies suggesting a positive association between PPI use and SIBO were conducted in Europe, while the studies suggesting a negative association were from the United States raising the hypothesis that differences in dietary factors in different geographical location might affect the study results."

The conflicting study results may also stem, at least in part, from the lack of a true gold standard test to diagnose SIBO, the authors say.

The chief limitation of the study is the retrospective design, with its inherent issues of confounding, the authors admit, although they tried to control for potential confounding factors.

They also note that duration of PPI therapy may be associated with the probability of a positive GHBT, information that was not included in the analysis. However, they say in their tertiary care center most patients taking PPIs were on chronic acid suppression therapy that would be expected to increase the potential for an abnormal GHBT, rather than reduce the likelihood of GHBT positivity.

Strengths of the study include its large (adequately powered) size and use of multiple criteria to evaluate for breath test positivity, they say.

The study had no outside financial support, and the authors have declared no potential competing interests.

Am J Gastroenterol. Published online February 14, 2012.

February 28, 2012 (Silver Spring, Maryland) — Taking a statin can raise blood sugar and glycosylated hemoglobin HbA1c levels, according to a new labeling change approved by the Food and Drug Administration (FDA) today for the entire drug class [1].

As reported by heartwire , recent studies of popular statins showed a significant increase in the risk of diabetes mellitus associated with high-dose statin therapy. The Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) trial showed a 27% increase in diabetes mellitus in patients taking rosuvastatin compared to placebo. Also, the Pravastatin or Atorvastatin Evaluation and Infection Therapy: Thrombolysis In Myocardial Infarction 22 (PROVE-IT TIMI 22) substudy showed that high-dose atorvastatin can worsen glycemic control.

The labeling changes approved by the FDA also include new information on the potential for usually minor and reversible cognitive side effects. Also, the label for lovastatin has been significantly updated to provide information on contraindications and dose limitations for the drug in patients taking other medicines that may increase the risk for muscle injury.

The FDA says it is also eliminating the recommendation that patients on statins undergo routine periodic monitoring of liver enzymes, because this approach is ineffective in detecting and preventing the "rare and unpredictable" serious liver injuries related to statins. Statin therapy should be interrupted if the patient shows signs of serious liver injury, hyperbilirubinemia, or jaundice. The statin therapy should not be restarted if the drugs cannot be ruled out as a cause of the problems, the labeling will now state.

Summary and Comment Dabigatran Associated with Increased Bleeding During Atrial Fibrillation Ablation Until the effects of dabigatran use during ablation are clearer, it should be withheld for at least 24 hours before the procedure. In warfarin recipients with therapeutic international normalized ratios (INRs), uninterrupted warfarin treatment during radiofrequency ablation for atrial fibrillation (AF) has relatively convincingly been shown to reduce both thromboembolic and bleeding events. Dabigatran is increasingly prescribed as an alternative to warfarin in patients with nonvalvular AF. However, dabigatran's half life ranges from 12 to 14 hours and is prolonged in patients with renal insufficiency. Given the lack of an antidote to reverse its effects, the drug's safety and efficacy during ablation are not clear. Investigators used prospective data from a multicenter registry to compare the results of AF ablation in 145 patients taking dabigatran with the results in a matched cohort of 145 warfarin recipients with therapeutic INRs. Dabigatran was withheld on the day of surgery and restarted 3 hours after ablation; warfarin treatment was uninterrupted. The rate of major bleeding (pericardial tamponade) was 6% with dabigatran and 1% with warfarin (P=0.009). The rate of thromboembolic complications was also higher with dabigatran than with warfarin (2% vs. 0%), but this difference was not statistically significant. Comment: These findings are by no means definitive. All of the warfarin patients had therapeutic international normalized ratios — a more realistic control group would have been a matched sample of all warfarin recipients. The optimal role of dabigatran in patients with atrial fibrillation undergoing ablation has yet to be determined. We need more data before we open the floodgates, and an editorialist describes a number of alternative strategies for anticoagulation during AF ablation. Still, this report does provide some practical guidance: Dabigatran should be discontinued before the day of the ablation, probably for at least 24 hours. — Mark S. Link, MD Published in Journal Watch Cardiology February 29, 2012