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Content 7

 

The Doctor and the Pharmacist

Radio Show Articles:
November 22, 2014

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Do Artificial Sweeteners Cause Glucose Intolerance?
Hospice Care Is Associated with Lower Costs for Patients with Terminal Cancer
Quality, Not Quantity, of HDL Is Associated with CVD
Evidence-Based Recommendations for Diagnosing and Treating Uncomplicated
   Urinary Tract Infections
Epidural Steroids for Cervical Radicular Pain: Little Benefit
Utility of Aspirin in Primary Prevention of Cardiovascular Events
Mastectomy Use on the Rise in Women Eligible for Breast Conservation Surgery
Calcium-Channel Blockers Not Linked with Breast Cancer Risk, Analysis Suggests
Statin Use Beneficial Only in Gram-Negative Infections?
Stressful Police Duties Linked to Sudden Cardiac Death
NSAID Use an Independent Predictor of Bleeding in Patients with Atrial Fibrillation

MM: This research is dramatic and frightening. We have postulated for a long time that non-caloric sweeteners actually increase sugar cravings but this is the first time that I have seen that they impair glucose tolerance. If this holds true in future human studies, you can bet that the food/artificial sweetener industry will rally against it. It will be an interesting development to observe.
  
Nature 2014 Oct 9; 514:181
Do Artificial Sweeteners Cause Glucose Intolerance?
In mice, artificial sweeteners lead to alterations in the microbiome and changes in glucose absorption
Noncaloric artificial sweeteners, such as saccharine, sucralose, and aspartame, were introduced to control body weight and lower risk for diseases linked to obesity. Yet the epidemic of type 2 diabetes and obesity has coincided with introduction of noncaloric sweeteners. Most of us assume that the epidemic of obesity and type 2 diabetes led to more use of noncaloric sweeteners. However, researchers in Israel report that the opposite might be true: Use of noncaloric sweeteners might have contributed to the epidemic.
Mice that are given noncaloric sweeteners develop glucose intolerance quickly, compared with mice that are given sucrose or glucose. Introduction of dietary noncaloric sweeteners promptly alters the mouse microbiome to favor biochemical pathways that enhance absorption of calorie-rich glucose and short-chain fatty acids. Giving antibiotics to the glucose-intolerant mice eliminated glucose intolerance, and transplanting feces from sweetener–fed animals into germ-free animals produced glucose intolerance in these control animals, whereas feces transplanted from glucose-fed mice into controls didn't produce glucose intolerance.
Seven healthy human volunteers who did not regularly consume noncaloric sweeteners were placed on a diet that contained noncaloric sweeteners. Within 1 week, four participants developed glucose intolerance. Stool from these people, when transplanted to mice, also produced glucose intolerance. Stool from the three humans who did not develop glucose intolerance did not produce glucose intolerance in mice.
Comment This report argues that, although artificial sweeteners lack calories, they can change the gut microbiome in a way that leads to absorption of more calories and that compromises glucose tolerance. That surprising claim surely will be tested.
Citation(s): Suez J et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 2014 Oct 9; 514:181.
(http://dx.doi.org/10.1038/nature13793)
  
http://www.ncbi.nlm.nih.gov/pubmed/25231862?access_num=25231862&link_
type=MED&dopt=Abstract

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MMM: I spoke with my father this week and we discussed our inevitable demise. We differ significantly in age and in the places that we are in our lives but we were in agreement that when our respective times come to leave this life, although neither of us are anxious to do so, we will welcome that time with open arms and do not wish to fight or deny the inevitable. This approach and attitude may seem fatalistic but we both believe that it is realistic. Many people - especially medical professionals - are reluctant to accept the simple fact that death is inevitable and will often try to hold it off as long as possible with dramatic measures, especially at the very end of life. Does this approach deny death with dignity? I want to clarify that throughout our lives, I believe that we should do our utmost best to engage in healthful activities that give us the best chance for a long, healthy and fulfilling life but my dad and I have to question heroic efforts when it comes to the very end. Once again, the question of quality vs. quantity arises.
  
JAMA 2014 Nov 12; 312:1888
Hospice Care Is Associated with Lower Costs for Patients with Terminal Cancer
But hospice patients still experienced substantial and costly medical care of uncertain value.
Use of hospice care for patients who are terminally ill has increased during the past few decades, but whether hospice care is more or less expensive than nonhospice care is unclear. To explore this issue, investigators used a Medicare database to identify 18,165 patients with poor-prognosis cancer who enrolled in hospice and matched them by age, sex, location, and disease severity (i.e., survival duration after cancer diagnosis) with 18,165 patients who did not choose hospice care. Patients in both groups lived for about 7 months after initial diagnosis.
Mean duration of hospice care was 11 days. During hospice care (or the equivalent period for those not enrolled in hospice), hospice patients were significantly less likely than nonhospice patients to be hospitalized (42% vs. 65%), to be admitted to intensive care (15% vs. 36%), to undergo invasive procedures (27% vs. 51%), or to die in the hospital (3% vs. 50%) or in a skilled nursing facility (11% vs. 24%). Also, mean total cost of care during the last year of life was significantly lower for hospice patients (US$63,000 vs. $72,000).
Comment: I'm not surprised that patients who were enrolled in hospice experienced less resource-intensive care than did nonhospice patients. But the real story here, at least to me, is the remarkably high rate of admissions to the hospital and intensive care even among hospice patients. This study's most encouraging finding is the low likelihood of hospice patients dying in acute-care or long-term care facilities.
Citation(s): Obermeyer Z et al. Association between the Medicare hospice benefit and health care utilization and costs for patients with poor-prognosis cancer. JAMA 2014 Nov 12; 312:1888.
(http://dx.doi.org/10.1001/jama.2014.14950)
  
http://www.ncbi.nlm.nih.gov/pubmed/25387186?access_num=25387186&link_
type=MED&dopt=Abstract

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MM: In our healthcare scheme, we tend to focus on numbers. This may be the case due to our need to measure change. But, what if we are looking at the wrong numbers? We know that higher natural HDL and lower LDL tends to show better outcomes relative to CV risk. We also know that by just increasing the HDL, there does not seem to be any significant clinical benefits. What if we've been looking at the wrong type of HDL? It would certainly make sense that if we are looking at the wrong parameter, then our premise about HDL and changing the level of HDL may also be intrinsically flawed. I am excited to see where this research will lead and if we are ultimately able to enhance cholesterol efflux capacity, what will the clinical results be?
  
N Engl J Med 2014 Nov 18
Quality, Not Quantity, of HDL Is Associated with CVD
Cholesterol efflux capacity might be a better biomarker of cardiovascular risk.
In several large clinical trials, therapies to raise high-density lipoprotein (HDL) levels have not been associated with cardiovascular risk reduction, and questions remain as to whether HDL cholesterol (HDL-c) concentration plays a causal role in cardiovascular disease (CVD). Some researchers have suggested that HDL cholesterol efflux capacity, the functional ability of HDL to accept cholesterol as part of reverse cholesterol transport, may be a more important biomarker of risk. Therefore, investigators in an industry-supported analysis assessed the association of HDL cholesterol efflux capacity and CVD in 2416 participants without baseline CVD (median age, 42; 57% women; 49% black) from the large multiethnic Dallas Heart Study.
The primary outcome of interest was atherosclerotic CVD (first nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or CVD-related death). At a median follow-up of 9.4 years, 132 participants had experienced a primary outcome.
Multiple traditional risk factors and metabolic variables were associated with HDL-c level, but not with HDL cholesterol efflux capacity. In contrast, HDL-c level was not associated with CVD. However, in an adjusted model that included HDL-c level, the highest quartile of cholesterol efflux capacity was associated with a 67% reduction in the primary outcome, compared with the lowest quartile. Adding cholesterol efflux capacity to traditional risk factors improved discrimination-improvement and reclassification indexes.
Comment: These data provide important new information regarding cholesterol efflux capacity and its potential as a new biomarker for CV risk. Whether future therapies targeting this biomarker will improve clinical outcomes remains to be determined. Based on these data, however, the quality of HDL likely matters more than quantity in determining the level of CV risk.
Citation(s): Rohatgi A et al. HDL Cholesterol efflux capacity and incident cardiovascular events. N Engl J Med 2014 Nov 18; [e-pub ahead of print].
(http://dx.doi.org/10.1056/NEJMoa1409065
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MM: I don't disagree with the findings that lab tests may not be required to diagnose uncomplicated UTI's. However, I do disagree with the recommended first line treatment and the cavalier attitude towards antibiotic resistance developing with lax guidelines. I recommend the use of D-Mannose capsules or powder for patients who experience these uncomplicated UTI's. The most common bacterial infection (>80% in the general population) is E. coli, and this bug is very susceptible and responsive to D-Mannose. The protocol is more than just 1-2 times a day but the results are impressive. Also, there is very little chance of a downside. Most people respond quickly and definitively. For more information, please contact the staff at Mark Drugs.
  
JAMA 2014 Oct 22/29; 312:1677
Evidence-Based Recommendations for Diagnosing and Treating Uncomplicated Urinary Tract Infections
UTIs can be diagnosed without office visits or urine cultures; treatment with simple first-line antibiotics is best.
To address best practices on outpatient diagnosis and treatment of urinary tract infections (UTIs) in light of concern about increasing antibiotic resistance, researchers conducted an evidence review of 44 randomized, controlled trials; observational cohort studies; and systematic reviews. These studies focused largely on uncomplicated UTIs in younger women (age, ≤65).
Key findings from the evidence review are:

The most appropriate antibiotic choices are trimethoprim-sulfamethoxazole (160/800 mg twice daily for 3 to 7 days), nitrofurantoin (100 mg twice daily for 5 to 7 days), or fosfomycin (Monurol; 3 g in a single dose; used rarely by U.S. physicians and much more expensive than the other choices). Fluoroquinolones offered no advantage in cure rates; β-lactam antibiotics, such as amoxicillin-clavulanate, are less effective than the first-line recommendations. Most patients who delay antibiotic treatment to encourage spontaneous resolution eventually receive antibiotics and have longer times to resolution. Men with uncomplicated UTIs should be treated as above but for 7 to 14 days.
Comment: These recommendations are consistent with those of other expert guidelines. The antibiotic recommendations often are violated (particularly regarding inappropriate use of fluoroquinolones), but in real-world practices, we often find adherence difficult, especially in middle-aged and older patients. For example, many patients have sulfa allergies or take medications that can increase sulfa toxicity (NEJM JW Gen Med Nov 7 2014), and nitrofurantoin is contraindicated in patients with glomerular filtration rates <60 mL/minute/1.73 m2.
Citation(s): Grigoryan L et al. Diagnosis and management of urinary tract infections in the outpatient settings: A review. JAMA 2014 Oct 22/29; 312:1677. (http://dx.doi.org/10.1001/jama.2014.12842)
  
http://www.ncbi.nlm.nih.gov/pubmed/25335150?access_num=25335150&link_
type=MED&dopt=Abstract

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MM: It's not surprising that the benefits of steroidal injections to the upper spine do not show longitudinal benefit. Other studies have demonstrated that these same steroidal injections into the lumbar region show little to any benefit and they have the added problem of suppressing the immune system for up to six months. This is another example of clinicians using expensive technologies that simply don't work rather than using physical treatments such as stretching, gentle weight resistance, massage , acupuncture and manipulation; that are less invasive and dangerous and may show greater benefits.
  
Anesthesiology 2014 Nov; 121:1045
Epidural Steroids for Cervical Radicular Pain: Little Benefit
In a nonblinded, randomized trial, epidural steroid injections were not significantly better than conservative treatment
Data on epidural steroid injections for cervical radiculopathy are largely observational, and results of the few small randomized trials have been inconclusive. In this multicenter trial, U.S. investigators randomized 169 patients with arm pain attributed to cervical radiculopathy to receive either single initial epidural steroid injections (which could be repeated at 1 month and 3 months, if needed), drug therapy (gabapentin or nortriptyline) plus physical therapy, or both interventions. Criteria for enrollment included pain duration of 1 month to 4 years (median duration, 0.8 years) and magnetic resonance imaging findings that supported clinical presentation.
At 1 month, arm-pain scores (the primary outcome) improved in all three groups, with no statistically significant differences between groups. Additionally, the groups did not differ in patient-reported satisfaction and global improvement in pain. On various other secondary endpoints at 1, 3, and 6 months, some trends favored combination treatment over epidural steroid injections alone or oral medication plus physical therapy alone, but most differences did not reach statistical significance.
Comment In this nonblinded study, most patients with cervical radiculopathy derived little or no benefit from cervical epidural steroid injections. Over the years, I've referred only a few patients for these injections, and always as a last resort; this study's findings support that practice.
Citation(s): Cohen SP et al. Epidural steroid injections, conservative treatment, or combination treatment for cervical radicular pain: A multicenter, randomized, comparative-effectiveness study. Anesthesiology 2014 Nov; 121:1045. (http://dx.doi.org/10.1097/ALN.0000000000000409)
  
http://www.ncbi.nlm.nih.gov/pubmed/25335172?access_num=25335172&link_type=
MED&dopt=Abstract

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MM: This a great example of how a treatment is potentially underestimated in its potential harm in the general population but has shown consistent benefit to groups that are at a higher CV risk. We must always weigh the potential risks against the potential benefits of a treatment. This approach should apply to assessing all treatments and activities. we encourage exercise but too much may be harmful. We encourage drinking plenty of fluids but although rare, drowning is a potential problem. Finally, I encourage higher than typical doses of vitamin D3 but there is date that supports that a level in excess of 400ng/ml may be detrimental. None of these statements should prevent a person from making thoughtful and reasonable choices but as in most things, moderation seems to be the best approach.
  
JAMA 2014 Nov 17
Utility of Aspirin in Primary Prevention of Cardiovascular Events
Low-dose aspirin had no benefit in older Japanese patients with risk factors.
Aspirin has been the mainstay of cardiovascular treatment for over a century, but its role in primary prevention is uncertain in certain populations. The Japanese Primary Prevention Project was a multicenter, open-label trial to determine whether low-dose aspirin reduces the incidence of cardiovascular events in older patients with multiple atherosclerotic risk factors. More than 14,000 people aged 60 to 85 with hypertension, dyslipidemia, or diabetes mellitus were randomized to 100 mg aspirin daily or no aspirin and were followed for up to 6.5 years. The primary outcome was the composite of death from cardiovascular causes (myocardial infarction [MI], stroke, and other cardiovascular causes), nonfatal stroke (ischemic or hemorrhagic, including undefined cerebrovascular events), and nonfatal MI.
After a median follow-up of 5 years, the study was terminated when interim analyses indicated unlikely benefit. There was no significant difference in the cumulative primary outcome event rate (2.77% for aspirin vs. 2.96% for no aspirin). Fifty-six fatal events occurred in each group. While aspirin significantly reduced the risk for nonfatal MI and transient ischemic attack, it significantly increased the risk for extracranial hemorrhage requiring transfusion or hospitalization.
Comment: Daily aspirin did not lower risk for adverse cardiovascular events among older Japanese patients with atherosclerotic risk factors. However, in the end, this turned out to be a low-risk population: The 5-year cumulative event rate was <3% despite the patients' older age and risk factors. The findings add to a growing body of evidence that helps refine our decision-making: Patients at very low risk for vascular events or high risk for bleeding should not take aspirin for primary prevention of vascular events, even at low doses. In ongoing studies (ARRIVE, ASCEND, ASPREE) researchers are assessing the role of aspirin in presumably higher-risk people without vascular disease. For now, clinicians must individualize decision-making based on potential benefits (including noncardiovascular benefits) as well as bleeding risk
Citation(s): Ikeda Y et al. Low-dose aspirin for primary prevention of cardiovascular events in Japanese patients 60 years or older with atherosclerotic risk factors: A randomized clinical trial. JAMA 2014 Nov 17; [e-pub ahead of print].
(http://dx.doi.org/10.1001/jama.2014.15690)
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MM: This data has to make one wonder about the thought process behind these decisions. Is there any impact from decisions of celebrities who have had unique situations such as HER+ conditions? It is unfortunate when a decision making process is potentially influenced by social pressure or the idea that if a movie actress made this decision then it must be right for me. The bottom line is that each person and story is unique and the decision to preserve or remove breast tissue is an important one that can have emotional as well as physical implications. Mark Drugs empathizes with these difficult decisions and offers the Rose Garden Mastectomy Boutique to our patients. No matter what your treatment protocol choice is, we have products to help you with your personal, physical and emotional well-being. These range from mastectomy products to a broad selection of natural and synthetic wigs. Please call our staff for more information and guidance.
  
Mastectomy Use on the Rise in Women Eligible for Breast Conservation Surgery
By Kelly Young, Edited by Susan Sadoughi, MD, and Richard Saitz, MD, MPH, FACP, FASAM
Women with early-stage breast cancer who are eligible for breast conservation surgery are increasingly opting for mastectomies, according to a JAMA Surgery study.
Researchers used national cancer registry data to identify surgical trends in 1.2 million women with early-stage breast cancer. From 1998 to 2011, the percentage of women who were eligible for breast conservation surgery and underwent mastectomy increased from 34% to 38%. Most of this increase could be attributed to a rise in bilateral mastectomies for unilateral cancer, from 2% to 11% of all women who were eligible for breast-conserving surgery.
http://archsurg.jamanetwork.com/article.aspx?articleid=1921808
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MM: Even well designed studies may get fouled by selection bias. This may be unintentional and may simply be a result of a particular population that is unusually homogenous in a particular dimension. No matter what the reason, it is typically better to look at the reproducibility of a study and see if the results are consistent with a variety of demographics.
  
Calcium-Channel Blockers Not Linked with Breast Cancer Risk, Analysis Suggests
By Amy Orciari Herman, Edited by Susan Sadoughi, MD, and Richard Saitz, MD, MPH, FACP, FASAM
Calcium-channel blockers do not appear to be associated with increased risk for breast cancer, a new study finds, calling into question a 2013 study suggesting a potential association. Findings from the new study were presented on Wednesday at the American Heart Association meeting in Chicago.
Using two databases comprising over 3700 women aged 50 to 70 with no history of breast cancer, researchers compared women who were prescribed calcium-channel blockers with those who were not. One database showed a small but significant increase in risk for developing breast cancer with calcium-channel blockers, while the other showed a 50% reduction in risk with the drugs.
The research group's press release notes that given "the contrasting results found in these two independent analyses ... it is likely not the medication that caused the changes in breast cancer risk but other factors (e.g., selection biases)."
http://intermountainhealthcare.org/hospitals/imed/services/heart-institute/about/Pages/news.aspx?NewsID=1867
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MM: I read a recent article in the local paper touting the wide and long lasting benefits of statin drugs in people with mild to moderate elevated LDL cholesterol. The article claimed that a retrospective study of 5 years of medium dose statin use conferred a decrease in all types of long term mortality and morbidity long after the drugs had been ceased. A couple of things in the article were noteworthy. The benefits were only present with low to moderate doses of statins. The higher doses were not as beneficial long term and demonstrated greater adverse effects in the short term and long term. This study introduces another confounding parameter to the discussion. Before recommending a product or simply making it a "standard protocol" we. as clinicians must make a complete assessment of the patient to determine how much benefit is present and what, if any, the risks are.
  
Eur J Clin Microbiol Infect Dis 2014 Nov 6
Statin Use Beneficial Only in Gram-Negative Infections?
Results from a prospective, observational study suggest a protective effect of prior statin use on mortality from gram-negative — but not gram-positive — bloodstream infections.
Several previous investigations have suggested that prior statin use has a protective effect on sepsis outcome (NEJM JW Infect Dis Feb 14 2007). However, such studies were often limited by small sample size and uncontrolled design, leaving opportunity for confounders such as failure to differentiate between gram-positive and gram-negative infections.
To address one such issue, researchers in Norway conducted a prospective, observational study involving adults with bloodstream infections (BSIs; 746 gram-negative and 572 gram-positive) who were treated at their institution between 2002 and 2011. Eighteen percent of those with gram-negative and 17% of those with gram-positive BSIs had taken statins the week preceding the positive blood culture. For both gram-negative and gram-positive BSIs, statin users had a higher burden of comorbid conditions such as diabetes, hypertension, and cardiovascular disease and a higher Charlson comorbidity index score. Severity of infection at time of diagnosis and distribution of pathogens were similar between groups.
For gram-negative BSIs, all-cause 90-day mortality was 10% in statin users and 21% in nonusers (P=0.002), whereas for gram-positive BSIs, the rate was similar between users and nonusers (29% and 27%; P=0.90). The beneficial effect of prior statin use in patients with gram-negative infections remained significant in a logistic regression analysis that controlled for various potential confounding variables (odds ratio, 0.4; P=0.003)
Comment: This study confirms previous investigations suggesting a protective effect of statin use on mortality — albeit apparently only in gram-negative infections. The underlying mechanism should be investigated, because it might reveal important, unrecognized details about host–microbe interaction. Unfortunately, the findings do not help us much in the management of individual patients: Benefit has not been demonstrated for newly started statin treatment in patients with ongoing infection.
Citation(s): Mehl A et al. Prior statin use and 90-day mortality in gram-negative and gram-positive bloodstream infection: A prospective observational study. Eur J Clin Microbiol Infect Dis 2014 Nov 6; [e-pub ahead of print].
(http://dx.doi.org/10.1007/s10096-014-2269-6)
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MM: Most of us have jobs that induce stressful conditions "on occasion". Those stressful conditions are frequently self-induced or induced by perceived pressures from our bosses, deadlines or clients. Police and fire fighters have a much different set of challenges. Their stressors are real and not just perceived. This constant threat of real visible or unknown danger places their bodies in a constant state of pressure and potentially increases their blood pressure and other risk factors of CV incident. Typical, socially accepted releases may include smoking or drinking alcohol and these may serve to only increase these risk factors. It tends to be a vicious circle. More emphasis, education and adjustment tools should be offered to these professions regarding diet, exercise and lifestyle modification in addition to in-house programs. If these professionals fail to engage in these programs, then perhaps more inducements towards self-preservation should be added as these preventive actions and costs should show long term benefit and decreased overall community costs.
  
Stressful Police Duties Linked to Sudden Cardiac Death
By Amy Orciari Herman, Edited by David G. Fairchild, MD, MPH, and Lorenzo Di Francesco, MD, FACP, FHM
Police officers face increased risk for sudden cardiac death during physically and psychologically stressful duties, a BMJ study finds.
Researchers identified 441 on-duty sudden cardiac deaths from U.S. law enforcement databases. These deaths occurred most frequently during restraints/physical altercations (25% of deaths), non-emergency activities, physical training, and pursuits of suspects.
After accounting for how much time police officers typically spend on certain duties, the researchers estimated duty-specific relative risks for sudden cardiac death. They found that, compared with non-emergency activities, restraints/physical altercations carried up to 69 times the risk for sudden death, pursuits up to 51 times the risk, and physical training up to 23 times the risk.
The authors note that cardiovascular risk factors (e.g., smoking, hypertension) are relatively common among police officers, making them particularly susceptible to stress-induced cardiac events. "Our findings," they conclude, "suggest that primary and secondary cardiovascular prevention efforts are needed among law enforcement officers."
http://www.bmj.com/content/349/bmj.g6534
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MM: Yet another CV reason to avoid oral NSAIDs arises. Healthcare Providers have been aware of the dangers inherent to the use of oral NSAIDs in the CV patient for several years but the A. Fib patient has not been frequently addressed. Fortunately there are options for non-malignant pain management that include compounded neuropathic pain creams and gels and oral herbal combinations such as All Flex Pro, available from Mark Drugs, that uses a combination of glucosamine, Cetyl myristoleate, Boswelia, Bromelain, Type II collagen, Probiotics, minerals and several other complementary components.
  
NSAID Use an Independent Predictor of Bleeding in Patients with Atrial Fibrillation
By Amy Orciari Herman, Edited by David G. Fairchild, MD, MPH, and Jaye Elizabeth Hefner, MD
Use of nonsteroidal anti-inflammatory drugs — with or without concomitant antithrombotic therapy — is associated with increased risks for bleeding and thromboembolism in patients with atrial fibrillation, an Annals of Internal Medicine study finds.
Using national patient and prescription registries, Danish researchers studied over 150,000 adults with new diagnoses of atrial fibrillation. One third filled prescriptions for NSAIDs during roughly 6 years' follow-up.
Overall, the risk for serious bleeding was significantly higher within 14 days of continuous NSAID exposure than without NSAID exposure (3.5 vs. 1.5 bleeding events per 1000 patients). NSAIDs were associated with increased risks for serious bleeding and thromboembolism when taken with an oral anticoagulant, an antiplatelet, or both, but they also conferred increased risks when taken alone. Higher NSAID dosages were associated with higher bleeding risks.
The authors conclude that "physicians should exercise caution with NSAIDs" when treating patients with atrial fibrillation.
http://annals.org/article.aspx?articleid=1935053

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