Should we screen extensively for cancer after unprovoked venous thrombosis?

What you need to know

  • The prevalence of occult cancer in patients with a first unprovoked venous thromboembolism seems to be lower (~4%) than previously reported (10%)

  • There is limited evidence to recommend extensive cancer screening with computed tomography in such patients

  • Consider history and physical examination, basic laboratory tests, and results from routine age-specific cancer screening to guide further testing as an alternative to extensive screening

How far to go in screening patients with an unprovoked venous thromboembolism (VTE) for an occult cancer is a clinical dilemma. Unprovoked VTE, either deep vein thrombosis or pulmonary embolism, can be the first manifestation of an undiagnosed cancer. Until recently, the literature suggested that up to 10% of such patients would be diagnosed with a cancer in the year after their diagnosis of VTE.1 However, the incidence of occult cancer in patients studied in two recent, high quality, randomised controlled trials was only about 4%.23 This drop in the proportion of people with occult cancer may require an adjustment in the clinical approach.

Fig 1⇓ outlines a conservative approach and a more detailed approach to investigating such patients. Extensive screening has become the standard of care, though it is based on limited data.

 However, high quality data from recently completed trials discussed below suggest that extensive screening strategies may not provide additional value over routine cancer screening in the frequency of cancer detection in these patients.

What is the evidence of uncertainty?

Search strategy and study selection

We searched PubMed (from inception to 31 December 2016) for randomised controlled trials and systematic reviews using the search terms “cancer screening,” “venous thromboembolism,” “unprovoked,” “meta-analysis,” and “randomized controlled trial.” We reviewed articles published in English between 2012 (publication of NICE guidelines) and 2016.


Risk of serious atrial fibrillation and stroke with use of bisphosphonates: evidence from a meta-analysis.

Clinical studies have suggested an association between bisphosphonate use and the onset of atrial fibrillation (AF). However, data on the risk of developing AF, stroke, and cardiovascular mortality with the use of bisphosphonate are conflicting. The objective of this study was to evaluate the risk of serious AF (events that required hospital admission), stroke, and cardiovascular mortality with the use of bisphosphonates through a systematic review of the literature.
METHODS: We searched the PubMed, CENTRAL, and EMBASE databases for observational studies and randomized controlled trials (RCTs) on the use of bisphosphonates from 1966 to April 2012 that reported the number of patients who developed serious AF, stroke, and cardiovascular mortality at follow-up. The random-effects Mantel-Haenszel test was used to evaluate relative risk-adverse cardiovascular outcomes with the use of bisphosphonates.
RESULTS: Six observational studies (n = 149,856) and six RCTs (n = 41,375) were included for analysis. On pooling observational studies, there was an increased risk of AF (OR, 1.27; 95% CI, 1.16-1.39) among bisphosphonate users. Further, analysis of RCTs revealed a statistically significant increase in the risk of serious AF (OR, 1.40; 95% CI, 1.02-1.93) and no increase in the risk of stroke (OR, 1.07; 95% CI, 0.85-1.34) or cardiovascular mortality (OR, 0.92; 95% CI, 0.68-1.26) with the use of bisphosphonates.
CONCLUSIONS: Evidence from RCTs and observational studies suggests a significantly increased risk of AF requiring hospitalization, but no increase in risk of stroke or cardiovascular mortality, with the use of bisphosphonate.


Alopecia With Endocrine Therapies in Patients With Cancer.


Background. Whereas the frequency of alopecia to cytotoxic chemotherapies has been well described, the incidence of alopecia during endocrine therapies (i.e., anti-estrogens, aromatase inhibitors) has not been investigated. Endocrine agents are widely used in the treatment and prevention of many solid tumors, principally those of the breast and prostate. Adherence to these therapies is suboptimal, in part because of toxicities. We performed a systematic analysis of the literature to ascertain the incidence and risk for alopecia in patients receiving endocrine therapies.

Methods. An independent search of citations was conducted using the PubMed database for all literature as of February 2013. Phase II–III studies using the terms “tamoxifen,” “toremifene,” “raloxifene,” “anastrozole,” “letrozole,” “exemestane,” “fulvestrant,” “leuprolide,” “flutamide,” “bicalutamide,” “nilutamide,” “fluoxymesterone,” “estradiol,” “octreotide,” “megestrol,” “medroxyprogesterone acetate,” “enzalutamide,” and “abiraterone” were searched.

Results. Data from 19,430 patients in 35 clinical trials were available for analysis. Of these, 13,415 patients had received endocrine treatments and 6,015 patients served as controls. The incidence of all-grade alopecia ranged from 0% to 25%, with an overall incidence of 4.4% (95% confidence interval: 3.3%–5.9%). The highest incidence of all-grade alopecia was observed in patients treated with tamoxifen in a phase II trial (25.4%); similarly, the overall incidence of grade 2 alopecia by meta-analysis was highest with tamoxifen (6.4%). The overall relative risk of alopecia in comparison with placebo was 12.88 (p < .001), with selective estrogen receptor modulators having the highest risk.

Conclusion. Alopecia is a common yet underreported adverse event of endocrine-based cancer therapies. Their long-term use heightens the importance of this condition on patients’ quality of life. These findings are critical for pretherapy counseling, the identification of risk factors, and the development of interventions that could enhance adherence and mitigate this psychosocially difficult event.


Source: The Oncologist.



The Ugly Side of Statins.

Story at-a-glance

  • A review of the published statin research revealed a categorical lack of evidence to support the use of statin therapy in primary prevention of heart attacks
  • Statins may actually increase cardiovascular risk in women, the young and people with diabetes
  • The cholesterol-lowering drugs are also linked to an increased risk of cataracts, memory impairment, diabetes, erectile dysfunction and over 300 adverse health effects
  • Lifestyle changes were far more effective, and safer, for primary heart attack prevention than statin drugs.
  • Statin cholesterol-lowering drugs are among the most widely prescribed drugs on the market, bringing in $20 billion a year.1 They are a top profit-maker for the pharmaceutical industry, in part due to relentless and highly successful direct-to-consumer advertising campaigns.


    One in four Americans over the age of 45 now takes statins, typically for theprimary prevention of heart attacks and strokes. Traditionally, primaryprevention usually involves healthy lifestyle choices that support heart health, things like eating right and exercising, yet here we have millions of Americans taking pills instead.

    Has anyone unbiased stopped to find out if these drugs are really the best method for heart attack prevention? After all, as researchers noted in theOpen Journal of Endocrine and Metabolic Diseases (OJEMD):2

    “…naive indiscriminate acceptance of novel mainstream therapies is not always advisable and prudence is required in unearthing harmful, covert side effects.”

    This is precisely the task that researchers from Ireland took on by completing an objective review of Pubmed, EM-BASE and Cochrane review databases.3Their results speak volumes…

    It is beginning to dawn on some clinicians that contemporary treatments are not only failing to impact on our most prevalent diseases, but they may be causing more damage than good. A perfect example of such an issue is the statin saga.”

    The Evidence Is In: Lifestyle Trumps Statins for Primary Heart Attack Prevention

    For a drug therapy that appears to offer little by way of primary prevention, the risks were alarming. For every 10,000 people taking a statin, there were:

    • 307 extra patients with cataracts
    • 23 additional patients with acute kidney failure
    • 74 extra patients with liver dysfunction

    The landmark review revealed “a categorical lack of clinical evidence to support the use of statin therapy in primary prevention.” They also found that statins actually increase cardiovascular risk in women, the young and people with diabetes. The review also showed that statin therapy increased:

    • Muscle fatigabilty by 30% with more than 11% incidence of rhabdomyolysis (a life-threatening muscle condition) at high doses
    • Coronary artery and aortic calcification
    • Erectile dysfunction, which is 10 times more common in young men taking the lowest dose of statin.
    • Diabetes
    • Cancer

    The researchers noted:

    There is increased risk of diabetes mellitus, cataract formation, and erectile dysfunction in young statin users, all of which are alarming. Furthermore there is a significant increase in the risk of cancer and neurodegenerative disorders in the elderly plus an enhanced risk of a myriad of infectious diseases. All side effects are dose dependent and persist during treatment.

    Primary prevention clinical results provoke the possibility of not only the lack of primary cardiovascular protection by statin therapy, but highlight the very real possibility of augmented cardiovascular risk in women, patients with diabetes mellitus and the young. Statins are associated with triple the risk of coronary artery and aortic calcification.

    These findings on statins’ major adverse effects had been under-reported and the way in which they [were] withheld from the public, and even concealed, is a scientific farce.

     Cardiovascular primary prevention and regeneration programmes, through life style changes and abstaining from tobacco use have enhanced clinical efficacy and quality of life over any pharmaceutical or other conventional intervention.”

    If You Take Statins, Your Vision Could Be at Risk

    The featured review found an increased risk of cataracts with statin use, and this was supported by a new JAMA study,4 which further revealed that the risk of cataracts is increased among statin users, compared with non-users. As a main cause of low vision among the elderly, cataract is a clouding of your eye lens.

    It has previously been hypothesized that statin antioxidant effects may slowthe aging process of the lens, but the current study revealed that they, instead, raise cataract risk, again calling into question the usefulness of statins for primary prevention of heart attacks. The researchers concluded:

    The risk-benefit ratio of statin use, specifically for primary prevention, should be carefully weighed, and further studies are warranted.”

    Certain Statins May Impair Your Memory and May Even Lead to Amnesia

    Still more research revealed that rats taking the statin Pravachol (pravastatin) had impaired learning, with lower abilities to perform simple learning and memory tasks.5 This isn’t exactly news, as in 2012, the US Food and Drug Administration (FDA) announced it would be requiring additional warning labels for statins, one of which warned that statins may increase the risk of memory loss and confusion. The warnings, particularly the one for memory loss, came as the result of anecdotal reports compiled over the previous year…

    Interestingly, the animal study found no association between another statin drug, Lipitor, and impaired memory in the rats. But Dr. Duane Graveline, a medical doctor and former astronaut, has written an entire book on this very topic, titled Lipitor: Thief of Memory.

    In my interview with him, Dr. Graveline shared his powerful story about how Lipitor caused him severe global transient amnesia, which is what brought him out of retirement to investigate statins. There have been thousands of cases of transient global amnesia and other types of cognitive damage associated with statin use, reported to the FDA’s MedWatch site. It is believed that statin drugs damage your brain by creating a cholesterol deficiency.

    Insufficient cholesterol results in your brain not having the raw materials it needs to make biochemicals critical for memory and cognitive function, including coenzyme Q10 and dolichols, the latter of which carry the genetic instructions from your DNA to help create specific proteins in your body that are crucial for cognitive function, emotions and mood.

    High Cholesterol Levels May Be Protective

    Any discussion of statins would be incomplete without a discussion of cholesterol – the ‘villain’ that these drugs mercilessly lower. Many buy into the conventional belief that lower cholesterol equals a lower risk of heart disease, but this is not always the case. And, in fact, high cholesterol levels are indeed protective in some cases, whereas low cholesterol levels are very clearly linked to chronic disease. Writing in OJEMD, researchers explained:

    “Cholesterol is crucial for energy, immunity, fat metabolism, leptin, thyroid hormone activity, liver related synthesis, stress intolerance, adrenal function, sex hormone syntheses and brain function. When prescribing HMGCoA reductase inhibitors [statins] one needs to be cognizant of the fact that the body had increased its’ cholesterol as a compensatory mechanism and investigate accordingly.

    We seem to have fallen into the marketing trap and ignored the niggling side effects with regard to the HMGCoA reductase inhibitors. The only statin benefit that has actually been demonstrated is in middle-aged men with coronary heart disease. However, statins were not shown to best form of primary prevention.

    … In actual fact, high cholesterol levels have been found to be protective in elderly and heart failure patients and hypo-cholestereamic [low cholesterol] patients had higher incidence of intra-cerebral bleeds, depression and cancer. … We are observing the revealing of the utmost medical tragedy of all time. It is unprecedented that the healthcare industry has inadvertently induced life-threatening nutrient deficiency in millions of otherwise healthy people. What is even more disparaging is that not only has there been a failure to report on these negative side-effects of statins, there has actually been active discouragement to publish any negative studies on statins.”

    This is, in large part, why so many people are completely unaware that statin drugs have been directly linked to over 300 side effects,6 which include:

    Cognitive loss Neuropathy Anemia
    Acidosis Frequent fevers Cataracts
    Sexual dysfunction An increase in cancer risk Pancreatic dysfunction
    Immune system suppression Muscle problems, polyneuropathy (nerve damage in the hands and feet), and rhabdomyolysis, a serious degenerative muscle tissue condition Hepatic dysfunction. (Due to the potential increase in liver enzymes, patients must be monitored for normal liver function)

    Ask Yourself – and Your informed Physician — if You Really Need to Be Taking Statins

    I’ve long stated that the odds are very high — greater than 100 to 1 — that if you’re taking a statin, you may not even need it, as cholesterol is NOT the cause of heart disease. To further reinforce the importance of cholesterol, I want to remind you of the work of Dr. Stephanie Seneff, who works with the Weston A. Price Foundation.

    One of her theories is that cholesterol combines with sulfur to form cholesterol sulfate, and that this cholesterol sulfate helps thin your blood by serving as a reservoir for the electron donations you receive when walking barefoot on the Earth (also called grounding). She believes that, via this blood-thinning mechanism, cholesterol sulfate may provide natural protection against heart disease.

    In fact, she goes so far as to hypothesize that heart disease is likely the result of cholesterol deficiency — which of course is the complete opposite of the conventional view. So if your physician is urging you to check your total cholesterol, know that this test will tell you virtually nothing about your risk of heart disease, unless it is 330 or higher. HDL percentage is a far more potent indicator for heart disease risk. Here are the two ratios you should pay attention to:

    1. HDL/Total Cholesterol Ratio: Should ideally be above 24 percent. If below 10 percent, you have a significantly elevated risk for heart disease.
    2. Triglyceride/HDL Ratio: Should be below 2.

    Additional risk factors for heart disease include:

    • Your fasting insulin level: Any meal or snack high in carbohydrates like fructose and refined grains generates a rapid rise in blood glucose and then insulin to compensate for the rise in blood sugar. The insulin released from eating too many carbs promotes fat production and makes it more difficult for your body to shed excess weight, and excess fat, particularly around your belly, is one of the major contributors to heart disease
    • Your fasting blood sugar level: Studies have shown that people with a fasting blood sugar level of 100-125 mg/dl had a nearly 300 percent increase higher risk of having coronary heart disease than people with a level below 79 mg/dl
    • Your iron level: Iron can be a very potent oxidative stress, so if you have excess iron levels you can damage your blood vessels and increase your risk of heart disease. Ideally, you should monitor your ferritin levels and make sure they are not much above 80 ng/ml. The simplest way to lower them if they are elevated is to donate your blood. If that is not possible you can have a therapeutic phlebotomy and that will effectively eliminate the excess iron from your body

    Try This Instead for Primary Heart Attack Prevention

    Make no mistake about it, statin drugs are some of the most side effect-ridden medications on the market, and they frequently do more harm than good. Of utmost importance, statins deplete your body of CoQ10, which accounts for many of its devastating results. Therefore, if you take a statin, you MUST take supplemental CoQ10, or better, the reduced form called ubiquinol. If you are interested in optimizing your cholesterol levels (which doesn’t necessarily mean lowering them) and lowering your risk of heart disease and heart attacks, there are natural strategies available for doing so.

    • Reduce, with the plan of eliminating, grains and sugars in your diet, replacing them with mostly whole, fresh vegetable carbs and healthy fats. Also try to consume a good portion of your food raw.
    • Make sure you are getting enough high-quality, animal-based omega-3 fats, such as krill oil.
    • Other heart-healthy foods include olive oil, coconut and coconut oil, organic raw dairy products and eggs, avocados, raw nuts and seeds, and organic grass-fed meats.
    • Optimize your vitamin D levels.
    • Exercise daily, especially with high-intensity interval training (HIIT) exercises.
    • Avoid smoking or drinking alcohol excessively.
    • Be sure to get plenty of good, restorative sleep.

HPV Vaccine Linked to Premature Menopause in Young Girls.

Dr. Deirdre Little, a pediatrician in Australia, was the first one to sound the alarm over the HPV vaccine causing premature menopause when she observed it in one of her 16 year old patients in 2012. Dr. Little published a paper in the British Medical Journal warning that the premature menopause of a healthy 16-year-old girl may be linked to the Gardasil vaccination.



Now, a new study has just been recently published in the American Journal of Reproductive Immunology documenting three more cases of “Primary Ovarian Failure,” where three young girls stopped having periods and showed signs of menopause. The study confirms Dr. Little’s experience, and was conducted in Israel and Italy. The authors concluded:

We documented here the evidence of the potential of the HPV vaccine to trigger a life-disabling autoimmune condition. The increasing number of similar reports of post HPV vaccine-linked autoimmunity and the uncertainty of long-term clinical benefits of HPV vaccination are a matter of public health that warrants further rigorous inquiry.

Countries Outside of the U.S. are Discovering the Dangers of the HPV Vaccine

It is not surprising that this study was not conducted in the U.S. As Dr. Deirdre Little observed back in 2012, the Gardasil manufacturer did not conduct studies on ovarian effects of the vaccine or any studies regarding ongoing fertility effects. Gardasil has become a huge financial success, and is one of the most lucrative vaccines in the market.

But the side effects to Gardasil, which are more than just Primary Ovarian Failure, are becoming more and more known as sales of Gardasil might be slowing down, or at least not increasing as fast as the manufacturers would like them to. In countries where the vaccine is not produced, studies like the one referenced above are being conducted since it is apparent they will probably not be done in the U.S. The health ministry of Japan recently issued a nationwide notice that HPV vaccinations should no longer be recommended for girls aged 12 to 16 because so many adverse reactions have been reported.


Why Aren’t the Dangers of the HPV Vaccine Being Investigated in the U.S.?

So while other countries are beginning to put the brakes on the HPV vaccine and doing their own research, what is happening in the U.S.? The mainstream media, apparently simply reprinting press releases directly from the pharmaceutical companies, is actually portraying the HPV vaccines as one of the safest vaccines around, and lamenting the fact that more girls are not getting it! Here are some examples:

Doctors say HPV vaccine is safe and “grossly underutilized” – Need for vaccine ‘not understood’ by parents – from Medical News Today, July 27, 2013

HPV vaccination rate stalls. ‘We’re dropping the ball,’ CDC says – ”The vaccine is safe and effective,” Schuchat said. “We need doctors to recommend it and deliver it.” – from Los Angeles Times, July 25, 2013

Parents’ Worries About HPV Vaccine on the Rise: Study – from U.S. News and World Report, March 18, 2013 Quote:

Both Darden and Cunningham said it’s puzzling that parents’ safety worries about the HPV vaccine would grow so much, so fast. It’s not clear from the study, but Cunningham said he suspects many parents get misinformation online.

“There’s a lot of unreliable vaccine information out there,” he said. As for safety, he suggested that parents with concerns go to reliable online sites, like the CDC website, and talk with their child’s doctor.

As for the Israeli/Italian peer-reviewed study which is indexed on PubMed, the NIH website, linking HPV vaccines to causing girls to go into premature menopause? Not a peep in the U.S. mainstream media….

Earlier this year, Jeffry John Aufderheide of revealed that Merck, the manufacturer of Gradasil, paid out over $18 million in speaking fees to doctors to promote their drugs, including Gardasil. So are medical doctors in the U.S. really the best source of knowledge on the side effects of a vaccine they are paid to promote??

As far as trusting the CDC website: Julie Gerberding was in charge of the CDC from 2002 to 2009, which includes the years the FDA approved Gardasil as a vaccine. Soon after she took over the CDC, she reportedly completely overhauled the agency’s organizational structure, and many of the CDC’s senior scientists and leaders either left or announced plans to leave. Some have claimed that almost all of the replacements Julie Gerberding appointed had ties to the vaccine industry.

Gerberding resigned from the CDC on January 20, 2009, and is now the president of Merck’s Vaccine division, a $5 billion dollar a year operation, and the supplier of the largest number of vaccines the CDC recommends (article here).

Do you think this might be one reason why the U.S. is not investigating or even reporting the negative side effects of the HPV vaccine?

Then there is the issue of how much money the government makes off of royalties from the HPV vaccines. In November 2010, Dr. Eric Suba submitted a Freedom of Information Request to the Office of Government Information Services to discover the amount of money the U.S government earns from Merck’s sale of Gardasil. But apparently the government is immune from revealing those figures, as you can read for yourself the response Dr. Suba received here.

So not only is the CDC not publishing the dangers of the HPV vaccine, but two years ago they recommended young boys get the vaccine also, and there is a push on now to start giving it to infants. In the state of California, a bill funded by Gardasil producer Merck was passed allowing schools to administer the HPV vaccine to girls without their parent’s consent or knowledge.

In the United States, there are several websites and Facebook pages that tell the stories of young women who have suffered from the effects of the HPV vaccine, or even worse, have died. You won’t likely get this information from your doctor, and you will certainly not find it on government websites. Here are a few:

Sane Vax, Inc.

One More Girl

Gardasil Kills



Radioactive seed localization for non-palpable breast cancer.

Radioactive seed localization (RSL) is an alternative to wire localization for guiding surgical excision of non-palpable breast cancer. This review provides an overview of the available evidence on the accuracy of RSL in patients undergoing breast-conserving surgery.

METHODS: PubMed, Embase and the Cochrane Library were searched systematically in January 2012 for studies that addressed localization of non-palpable breast cancer using an iodine-125-labelled seed. Studies were deemed eligible if they reported on the proportion of patients with tumour-positive margins after RSL, the proportion of patients needing re-excision after RSL, and procedural complications.
RESULTS: Six studies reported data on RSL in 1611 patients with non-palpable breast lesions. Overall complete resection rates ranged from 73 to 96.7 per cent. Three studies included over 300 patients, and complete resection rates in these studies varied between 89.5 and 96.7 per cent. The risk of seed migration and failure of seed placement ranged from 0 to 0.6 per cent and 0 to 7.2 per cent respectively.
CONCLUSION: Available scientific evidence suggests that RSL is a safe and accurate technique for localization of non-palpable breast lesions.

Source: British journal Of Surgery


Antibiotic prophylaxis for urinary tract infections after removal of urinary catheter: meta-analysis.


Objective To determine whether antibiotic prophylaxis at the time of removal of a urinary catheter reduces the risk of subsequent symptomatic urinary tract infection.

Design Systematic review and meta-analysis of studies published before November 2012 identified through PubMed, Embase, Scopus, and the Cochrane Library; conference abstracts for 2006-12 were also reviewed.

Inclusion criteria Studies were included if they examined antibiotic prophylaxis administered to prevent symptomatic urinary tract infection after removal of a short term (≤14 days) urinary catheter.

Results Seven controlled studies had symptomatic urinary tract infection after catheter removal as an endpoint; six were randomized controlled trials (five published; one in abstract form) and one was a non-randomized controlled intervention study. Five of these seven studies were in surgical patients. Studies were heterogeneous in the type and duration of antimicrobial prophylaxis and the period of observation. Overall, antibiotic prophylaxis was associated with benefit to the patient, with an absolute reduction in risk of urinary tract infection of 5.8% between intervention and control groups. The risk ratio was 0.45 (95% confidence interval 0.28 to 0.72). The number needed to treat to prevent one urinary tract infection was 17 (12 to 30).

Conclusions Patients admitted to hospital who undergo short term urinary catheterization might benefit from antimicrobial prophylaxis when the catheter is removed as they experience fewer subsequent urinary tract infections. Potential disadvantages of more widespread antimicrobial prophylaxis (side effects and cost of antibiotics, development of antimicrobial resistance) might be mitigated by the identification of which patients are most likely to benefit from this approach.


In our meta-analysis of pooled data from seven studies (six of which were randomized), there were significantly fewer symptomatic urinary tract infections in patients receiving prophylaxis during removal of a urinary catheter than in those not receiving prophylaxis. Our finding in favor of antibiotic prophylaxis, however, must be tempered by possible publication bias toward positive studies, the limitations of the included studies, and practical considerations about encouraging more widespread antibiotic use.

Indwelling urinary catheters pose several risks to patients, including urethral trauma, discomfort, and urinary tract infection.31 In an era of increasingly constrained fiscal resources and evolving antibiotic resistance, evidence based antimicrobial prescribing is essential to promote antimicrobial stewardship.32 Unfortunately, there is no consensus on whether clinicians should prescribe antibiotic prophylaxis to patients when an indwelling urinary catheter is removed.


This meta-analysis of available data indicates an overall benefit of antibiotic prophylaxis at the time of removal of a urinary catheter to prevent subsequent urinary tract infections. The number needed to treat indicates that 17 patients would need to receive prophylaxis to prevent one symptomatic urinary tract infection. We know little, however, about the potential negative consequences of implementing antibiotic prophylaxis in this setting in a wider frame or indeed which types of patients would be most likely to benefit. Increasing antimicrobial resistance, healthcare costs for antibiotics, and the potential for side effects of antibiotic administration are disadvantages that merit careful review. From a public health standpoint, we should be careful not to encourage antibiotic use when it might not be necessary. The healthcare provider of a catheterized patient, however, might consider antibiotic prophylaxis before catheter removal, after taking individual risk factors into account. Future studies should better characterize who is at risk of developing symptomatic urinary tract infection after catheter removal (whether bacteriuric or not) and then examine antibiotic prophylaxis in those at greatest risk.

What is already known on this topic

  • Catheterization of the urinary tract is associated with an increased risk of bacteriuria and symptomatic urinary tract infection
  • Antibiotic administration at the time of removal of a urinary catheter might effectively reduce urinary tract infections, but guidelines for catheter associated infections note insufficient evidence to support this practice
  • Antibiotic prophylaxis at the time of urinary catheter removal in general surgery, prostatectomy, and medical patients effectively reduced the incidence of symptomatic urinary tract infections with a number needed to treat of 17
  • The effect size of antibiotic prophylaxis in this meta-analysis was stable to sensitivity analyses with exclusion of non-randomized trials and two studies in non-surgical patients

What this study adds.


Source: BMJ



e wind: �x �� �� -border-alt:none windowtext 0in; padding:0in’>12 1314 16 Although other studies have examined the links between acute kidney injury and mortality and end stage renal disease in people admitted to hospital with myocardial infarction treated with either invasive or medical management,18 33 these studies have not compared renal outcomes on the basis of treatment strategies.


Our findings show that acute kidney injury is a relatively common complication in people with non-ST elevation acute coronary syndrome and chronic kidney disease and increases substantially with lower baseline estimated glomerular filtration rate. However, the difference in the incidence of acute kidney injury between people who receive early invasive management and similar patients treated conservatively is relatively small. Importantly, despite the modestly higher risk of acute kidney injury associated with early invasive management at all levels of estimated glomerular filtration rate, our findings suggest that this strategy is not associated with higher risks of more clinically relevant renal outcomes (including acute dialysis or progression to end stage renal disease), which occurred much less often at all levels of baseline estimated glomerular filtration rate, regardless of treatment strategy. Since early invasive management seemed to be consistently associated with a long term survival advantage at all levels of baseline estimated glomerular filtration rate, these findings (interpreted in light of their consistency with results from randomised trials showing that early invasive management improves long term survival in high risk patients3 4) suggest that restricting or delaying access to invasive coronary procedures may not avoid most cases of clinically relevant acute kidney injury and could deny high risk individuals (including those with pre-existing chronic kidney disease) important benefits.

There are several potential mechanisms for the higher risk of acute kidney injury associated with early invasive management. People who received early invasive management were more likely to receive coronary angiography, percutaneous coronary intervention, coronary artery bypass grafting surgery, and angiotensin converting enzyme inhibitors or angiotensin receptor blockers, placing them at risk of acute kidney injury from contrast exposure, perioperative ischaemia, and haemodynamic effects. Furthermore, patients who received invasive management had a longer hospital stay and more measurements of creatinine during follow-up, which may have increased the probability that acute kidney injury would be ascertained. However, the magnitude of the increased risk associated with invasive management strategies was small, suggesting that patients’ characteristics such as age, comorbidity, pre-existing chronic kidney disease, drug use (including diuretics and inhibitors of the renin angiotensin system), and haemodynamic instability are more important contributors to the risk of acute kidney injury in patients with acute coronary syndrome than whether or not they are managed invasively or medically.

The better survival associated with early invasive management of non-ST elevation acute coronary syndrome in this cohort are in keeping with the clinical benefits of angiography and revascularisation reported in clinical trials, including subgroups with pre-existing chronic kidney disease.2 3 4 Although episodes of acute kidney injury have been linked to an increased risk of end stage renal disease,18 19 34 we did not observe a higher risk of end stage renal disease in people with otherwise similar characteristics who received early angiography despite the higher risk of acute kidney injury, even among strata with lower baseline estimated glomerular filtration rate. Radiocontrast associated acute kidney injury is typically manifested by a small change in serum creatinine levels, rarely leads to acute dialysis, and is usually reversible.10 Our findings suggest that the majority of such additional episodes of acute kidney injury associated with invasive procedures may confer relatively low risks of progression to end stage renal disease, although further studies are needed to help predict those at risk of progressive chronic kidney disease after acute kidney injury.


In conclusion, early invasive management of non-ST elevation acute coronary syndrome is associated with a small increase in the risk of acute kidney injury compared with a conservative management approach but is not associated with higher risks of in-hospital acute kidney injury requiring dialysis or long term risk of end stage renal disease. Given the improvement in cardiovascular outcomes and long term survival observed with early invasive management, these results suggest that invasive treatments should not be withheld solely because of concern they might increase the risk of kidney injury.

What is already known on this topic

  • Acute kidney injury after invasive coronary procedures is associated with adverse outcomes, including end stage renal disease and death
  • Fear of precipitating contrast induced acute kidney injury possibly contributes to underuse of invasive treatments for acute coronary syndrome in people at high risk of kidney disease
  • Comparisons of renal outcomes between people treated with invasive versus conservative management are lacking
  • People who received early invasive management for non-ST segment elevation acute coronary syndrome were modestly more likely to develop acute kidney injury
  • After early invasive management the risks of requiring dialysis and long term risk of end stage renal disease were similar, and patients had better long term survival than those treated conservatively
  • These findings were consistent across varying levels of baseline kidney function, suggesting similar relative risks and benefits of early invasive management in people with and without pre-existing kidney disease

What this study adds


Source: BMJ


Intake of fish and marine n-3 polyunsaturated fatty acids and risk of breast cancer: meta-analysis of data from 21 independent prospective cohort studies.


Objectives To investigate the association between intake of fish and n-3 polyunsaturated fatty acids (n-3 PUFA) and the risk of breast cancer and to evaluate the potential dose-response relation.

Design Meta-analysis and systematic review of prospective cohort studies.

Data sources PubMed and Embase up to December 2012 and references of retrieved relevant articles.

Eligibility criteria for selecting studies Prospective cohort studies with relative risk and 95% confidence intervals for breast cancer according to fish intake, n-3 PUFA intake, or tissue biomarkers.

Results Twenty six publications, including 20 905 cases of breast cancer and 883 585 participants from 21 independent prospective cohort studies were eligible. Eleven articles (13 323 breast cancer events and 687 770 participants) investigated fish intake, 17 articles investigated marine n-3 PUFA (16 178 breast cancer events and 527 392 participants), and 12 articles investigated alpha linolenic acid (14 284 breast cancer events and 405 592 participants). Marine n-3 PUFA was associated with 14% reduction of risk of breast cancer (relative risk for highest v lowest category 0.86 (95% confidence interval 0.78 to 0.94), I2=54), and the relative risk remained similar whether marine n-3 PUFA was measured as dietary intake (0.85, 0.76 to 0.96, I2=67%) or as tissue biomarkers (0.86, 0.71 to 1.03, I2=8%). Subgroup analyses also indicated that the inverse association between marine n-3 PUFA and risk was more evident in studies that did not adjust for body mass index (BMI) (0.74, 0.64 to 0.86, I2=0) than in studies that did adjust for BMI (0.90, 0.80 to 1.01, I2=63.2%). Dose-response analysis indicated that risk of breast cancer was reduced by 5% per 0.1g/day (0.95, 0.90 to 1.00, I2=52%) or 0.1% energy/day (0.95, 0.90 to 1.00, I2=79%) increment of dietary marine n-3 PUFA intake. No significant association was observed for fish intake or exposure to alpha linolenic acid.

Conclusions Higher consumption of dietary marine n-3 PUFA is associated with a lower risk of breast cancer. The associations of fish and alpha linolenic acid intake with risk warrant further investigation of prospective cohort studies. These findings could have public health implications with regard to prevention of breast cancer through dietary and lifestyle interventions.


In this meta-analysis dietary intake of marine n-3 polyunsaturated fatty acids (PUFA), but not alpha linolenic acid (ALA), was associated with a lower risk of breast cancer. Fish consumption was not associated with risk. Dose-response analyses indicated a 5% lower risk of breast cancer per 0.1g/day or 0.1% energy/day increment of dietary marine n-3 PUFA, but no significant trend for ALA or fish intake. To the best of our knowledge, this is the first time meta-analysis has systematically and quantitatively evaluated the association between intake of fish and n-3 PUFA and risk of breast cancer.

Source: BMJ

One hundred years of congenital adrenal hyperplasia in Sweden: a retrospective, population-based cohort study.


Congenital adrenal hyperplasia due to 21-hydroxylase deficiency results in cortisol and aldosterone deficiency and is, in its most severe form, lethal. We aimed to assess the effect of historical medical improvements in the care of patients with this disorder over time and to assess the effects of neonatal screening in Sweden.


For this retrospective, population-based cohort study, we collected data for all known patients with congenital adrenal hyperplasia in Sweden between Jan 1, 2010, and Dec 31, 2011. Data sources included the registry at the Swedish national screening laboratory, patients identified via the Swedish neonatal screening programme, late-diagnosed patients reported to the laboratory, and patients who underwent genetic diagnostics or became known to us through clinical contacts. All known patients were included in a population-based cohort study of the distribution of clinical severity, genotype, sex, and the effect of nationwide neonatal screening.


We identified 606 patients with the disorder, born between 1915 and 2011. The CYP21A2 genotype (conferring deficiency of 21-hydroxylase) was known in 490 patients (81%). The female-to-male ratio was 1·25 in the whole cohort, but close to 1 in patients detected by the screening. We noted a sharp increase in the number of patients diagnosed in the 1960s and 1970s, and after the introduction of neonatal screening in 1986 the proportion of patients with the salt-wasting form of congenital adrenal hyperplasia increased in both sexes, from 114 (47%) of 242 individuals between 1950 and 1985 to 165 (57%) of 292 individuals between 1986 and 2011 (p=0·038). On average, five to ten children were missed every year before 1970. The non-classic form of the disorder was diagnosed more often in women than in men, which accounts for the female preponderance in our cohort.


Our findings suggest that, contrary to current belief, boys and girls with salt-wasting congenital adrenal hyperplasia were equally missed clinically. Neonatal screening improved detection of the salt-wasting form in girls as well as boys, saving lives in both sexes. The non-classic form was diagnosed more often in women than it was in men, leading to the female preponderance in this cohort.


Our findings show a substantial increase in the apparent incidence of congenital adrenal hyperplasia during the past century, with increases in line with improvements in diagnosis and treatment over time. The absence of a female preponderance has previously been interpreted as a sign of good medical care and diagnosis. However, our data show that both male and female patients with the salt-wasting form are missed clinically—even in a country such as Sweden with a developed health-care system—and that neonatal screening improves survival in both sexes. A large proportion of patients were not detected by neonatal screening. Non-classic congenital adrenal hyperplasia is diagnosed more often in women than it is in men, explaining the overall female preponderance despite the fact that male and female patients with salt-wasting congenital adrenal hyperplasia are diagnosed equally via screening.

To our knowledge, this study is the most extensive description of the changing apparent incidence of the different clinical forms of the disorder over time (panel). The sharp rise in the apparent incidence during the 1960s (figure 1) can be interpreted as the effect of not only the introduction of treatment with glucocorticoids in the 1950s, but also the concomitant increasing awareness of the disorder and its symptoms. Availability of a treatment generally results in increasing motivation among physicians to identify and diagnose a disease. However, in 1950, when glucocorticoids were introduced, there was only one active paediatric endocrinologist in Sweden, and little knowledge and awareness of congenital adrenal hyperplasia. Despite the obstacles, a few patients in the country were identified and started on glucocorticoid supplementation in the early 1950s. Laboratory diagnosis was difficult in both the 1950s and the 1960s, relying on measurements of urinary steroids. The amount of 17-ketosteroids was used as a measure of the level of androgens, and 17-hydroxysteroids as a measure of cortisol. Gonadotropins were measured with a mouse bioassay:extract from urine was given to prepubertal female mice and the uterine weight was subsequently measured as an indirect indication of the amount of gonadotropins.33


Research in context

Systematic review

We searched PubMed and Web of Science for research articles and reviews written in English with no restriction to year of publication. We used the search terms “congenital adrenal hyperplasia”, “21-hydroxylase deficiency”, and “CYP21A2”. We also searched the reference lists of retrieved articles. We identified no other studies describing the incidence of congenital adrenal hyperplasia related to the progress of diagnostics and treatment covering the past 100 years. The first effective treatment with glucocorticoids was introduced in the 1950s and improved patients’ survival. Mineralocorticoid treatment for patients with salt-wasting forms of the disorder was introduced shortly thereafter. Diagnosis has developed from clinical examination to laboratory markers and genetic analyses. Most publications report a skewed sex ratio, with more girls than boys diagnosed, in the prevalence of congenital adrenal hyperplasia, which is widely interpreted as more girls surviving the neonatal period.


Our findings show how medical development during the past 100 years has improved the survival of patients with congenital adrenal hyperplasia, first by the introduction of glucocorticoid and mineralocorticoid treatment and later with the introduction of neonatal screening. Our findings contradict previous ideas about the disorder: many have postulated that the female preponderance among patients with congenital adrenal hyperplasia is caused by missed diagnosis and increased mortality in boys. However, our data show that both male and female babies with the severe form of the disorder were missed clinically and that neonatal screening improved survival in both sexes equally. Non-classic congenital adrenal hyperplasia is diagnosed more often in women than in men, which accounts for the female preponderance in this cohort.

Since the 1950s, once diagnosis was made, treatment was still difficult. Treatment for congenital adrenal hyperplasia has changed little over time, with the exception of the introduction of mineralocorticoid treatment. The first mineralocorticoid, 11-desoxycorticosterone acetate, was given as sublingual tablets or subcutaneous implants that lasted for 3 months, at which point patients were at risk of adrenal crisis. Improved surgical techniques and more centralised surgical care have led to better surgical outcomes. However, these modern techniques also have shortcomings, such as strictures, reduced sensitivity, and impaired sexual function.153435

We detected no substantial decrease in the female-to-male ratio after the introduction of screening in our population. However, and more importantly, the proportion of salt-wasting forms of congenital adrenal hyperplasia increased substantially after the introduction of the nationwide neonatal screening programme. This finding should be taken into consideration when assessing the need for neonatal screening in a population. Specifically, the incidence of the salt-wasting form seems to be a more important and adequate measure for improvement of the situation for patients with congenital adrenal hyperplasia compared with the sex ratio alone. In the cohort of patients identified through the neonatal screening programme the female-to-male ratio was close to one. Mild forms of the disorder, presenting later in life and with no risk of salt loss, are detected more often in women. Hence, the female preponderance among the late-diagnosed patients is largely the reason for the high proportion of female patients in the whole cohort (figure 1), and there is a time lag before these patients contribute to the incidence. This occurrence explains the drop in apparent incidence as well as the equal sex ratio after the year 2000 (figure 1). The classification of patients by genotyping—81% had a known genotype—in combination with the nationwide coverage since 1986 made these conclusions possible.

The carrier frequency, and therefore the actual incidence of congenital adrenal hyperplasia has probably been stable over time because available data do not suggest a large global variance in the incidence of the salt-wasting form, with the exception of a few populations.3 On the assumption that all patients with salt-wasting congenital adrenal hyperplasia born after screening began have been diagnosed, the number of patients not identified in the pre-screening era can be reliably calculated because the birth rate in Sweden since 18th century is known (figure 3). Patients with the salt-wasting form of the disorder most likely did not survive the neonatal period whereas patients with the simple virilising form might have had adrenal crises during later infections,35 or might not have been diagnosed at all, as would also have been the case with patients with the non-classic form of the disorder. However, the estimated number of non-salt-wasting patients might be less reliable, because these individuals might have been missed in the screening and not all patients with a non-salt-wasting form of the disorder might have been reported to the registry. Additionally, the proportion of non-classic cases could have increased with the increasing immigration to Sweden since the late 1960s.

The apparent increase in incidence in the 1970s might suggest, to some extent, increased interest in the disorder and the fact that one of the investigators of this paper (AT) made a concurrent survey to identify all diagnosed patients. Neonatal screening could, in itself, have increased awareness of the disease and thereby also improved clinical diagnoses in patients with milder forms of the disease. More identified patients and an increased apparent incidence result in better awareness of the disease.

With screening in combination with the possibility of doing CYP21A2 mutation analyses, physicians no longer have to await electrolyte disturbances in a newborn baby to be able to assess the severity of their disease. Hence, the patients might escape the possible negative effects on brain development. The oldest patients mostly underwent CYP21A2 genotyping, which might be indicative of the fact that they are followed up more often at specialised clinics at university hospitals.

Some of the patients born before 1950 with congenital adrenal hyperplasia were initially assigned a male sex, with or without a hypospadias diagnosis. A physically detectable symptom, the virilisation of external genitalia, aided diagnosis and increased survival. In the 1950s, our knowledge of chromosomes and chromosomal determination of sex increased, and the analysis of Barr bodies became routine clinical practice in the 1950s.36 This development led to the general idea that all 46XX individuals with congenital adrenal hyperplasia should be raised as girls when the patients were diagnosed early.

In the middle of the 20th century, the focus was on the survival of the patients. With improved treatment, other aspects of the patients wellbeing can be addressed. The many patients with a known CYP21A2 genotype has enabled retrospective analyses of treatment outcomes in relation to disease severity—ie, cortisol deficiency and extent of androgen exposure.11,1334 The increased awareness of the psychological effects of prenatal exposure to androgens and disappointing surgical results in the more virilised patients, even using improved, modern techniques, have led to discussions about how treatment should be optimised and what sex the more virilised patients should be brought up as. The discussion about sex assignment has just begun.37

The integration of clinical work with molecular genetics and improved specialised care has been instrumental in improving the medical competence and the outcome for patients with congenital adrenal hyperplasia. Improvements in surgical and psychological care are some of the main challenges for the future.

Source: Lancet


Effectiveness of a bundled intervention of decolonization and prophylaxis to decrease Gram positive surgical site infections after cardiac or orthopedic surgery: systematic review and meta-analysis.


Objective To evaluate studies assessing the effectiveness of a bundle of nasal decolonization and glycopeptide prophylaxis for preventing surgical site infections caused by Gram positive bacteria among patients undergoing cardiac operations or total joint replacement procedures.

Design Systematic review and meta-analysis.

Data sources PubMed (1995 to 2011), the Cochrane database of systematic reviews, CINAHL, Embase, and were searched to identify relevant studies. Pertinent journals and conference abstracts were hand searched. Study authors were contacted if more data were needed.

Eligibility criteria Randomized controlled trials, quasi-experimental studies, and cohort studies that assessed nasal decolonization or glycopeptide prophylaxis, or both, for preventing Gram positive surgical site infections compared with standard care.

Participants Patients undergoing cardiac operations or total joint replacement procedures.

Data extraction and study appraisal Two authors independently extracted data from each paper and a random effects model was used to obtain summary estimates. Risk of bias was assessed using the Downs and Black or the Cochrane scales. Heterogeneity was assessed using the Cochran Q and I2 statistics.

Results 39 studies were included. Pooled effects of 17 studies showed that nasal decolonization had a significantly protective effect against surgical site infections associated with Staphylococcus aureus (pooled relative risk 0.39, 95% confidence interval 0.31 to 0.50) when all patients underwent decolonization (0.40, 0.29 to 0.55) and when only S aureus carriers underwent decolonization (0.36, 0.22 to 0.57). Pooled effects of 15 prophylaxis studies showed that glycopeptide prophylaxis was significantly protective against surgical site infections related to methicillin (meticillin) resistant S aureus (MRSA) compared with prophylaxis using β lactam antibiotics (0.40, 0.20 to 0.80), and a non-significant risk factor for methicillin susceptible S aureus infections (1.47, 0.91 to 2.38). Seven studies assessed a bundle including decolonization and glycopeptide prophylaxis for only patients colonized with MRSA and found a significantly protective effect against surgical site infections with Gram positive bacteria (0.41, 0.30 to 0.56).

Conclusions Surgical programs that implement a bundled intervention including both nasal decolonization and glycopeptide prophylaxis for MRSA carriers may decrease rates of surgical site infections caused by S aureus or other Gram positive bacteria.


Although multiple studies have assessed the efficacy of interventions to prevent surgical site infections caused by Gram positive bacteria, these interventions are not uniformly applied to surgical patients. Our results showed that nasal decolonization was associated with decreased rates of Gram positive surgical site infections andStaphylococcus aureus surgical site infections among patients undergoing cardiac or orthopedic surgical procedures. However, these results remained statistically significant for S aureus surgical site infections, though not all Gram positive surgical site infections, when the meta-analysis was limited to randomized controlled trials. Additionally, a bundle that included nasal decolonization and glycopeptide prophylaxis for patients who carried methicillin (meticillin) resistant S aureus (MRSA) was associated with significantly decreased rates of surgical site infections caused by Gram positive bacteria and by S aureus.

We also found that routine use of prophylactic glycopeptides protected against MRSA infections but not against all Gram positive surgical site infections. Additionally, dual prophylaxis with a glycopeptide and another antimicrobial agent seemed to be more protective against Gram positive surgical site infections than prophylaxis with glycopeptides alone. This finding is consistent with studies of methicillin susceptible S aureus (MSSA) bacteremia, which found that vancomycin is less effective than a β lactam antibiotic for treating MSSA infections.63 64 These results are similar to the conclusions of a recent review article, which stated that vancomycin is not recommended for preoperative prophylaxis but may be considered as a component of an MRSA bundle to prevent surgical site infections.65

Our meta-analyses were the first to assess a bundle that included nasal decolonization and targeted glycopeptide prophylaxis for MRSA carriers. Other meta-analyses have assessed nasal decolonization or glycopeptide prophylaxis alone,66 67 68 and our results confirm the findings of the previous studies and extend these by including the results of recent studies. Future meta-analyses should assess other outcomes associated with these interventions. These outcomes could include duration of hospital stay since one group of researchers found that the mean duration of hospital stay was significantly shorter in those randomized to mupirocin and chorhexidine gluconate rather than to placebo.27 Future meta-analyses should also confirm our preliminary findings that these interventions do not open a niche for pathogens other than S aureusto fill, and should also analyze other patient populations such as those requiring trauma surgery to determine if these findings are generalizable to other surgical specialties.

Nasal decolonization protected against S aureus surgical site infections when all patients were decolonized and when only S aureus carriers were decolonized. Routine nasal decolonization of all surgical patients may be easier to implement and more cost effective than using cultures or polymerase chain reaction testing to screen patients preoperatively.69 None the less, it may be prudent to reserve mupirocin decolonization for patients who carry S aureus to prevent widespread mupirocin resistance.70Similarly, it may be prudent to do further research on targeted prophylaxis with vancomycin before including this bundle in clinical practice. Of note, the pooled relative risks assessing Gram positive surgical site infections were identical for both the decolonization studies and the bundle studies. Thus high quality studies such as cluster randomized trials are still needed to determine whether adding glycopeptide prophylaxis to nasal decolonization will further decrease the incidence of Gram positive surgical site infections.

In our sensitivity analyses we found that nasal decolonization was associated with a 1% risk difference and the bundle was associated with a 0.5% risk difference in Gram positive surgical site infections. Although these differences seem small, they are clinically significant considering that cardiac and orthopedic operations are common and surgical site infections are associated with considerable morbidity. Each year, approximately 300 000 cardiac operations and approximately 900 000 total joint arthroplasties are done in the United States alone.71 Thus these interventions could prevent 6000 to 12 000 surgical site infections per year in the United States and even more worldwide.

Limitations of this study

Our study has some limitations. Firstly, meta-analyses are only as valid as the studies that contribute to the pooled risk ratio. We included many studies that were simple before and after quasi-experimental studies. Additionally, none of the included studies adjusted statistically for potential confounders, thus confounding may be problem, especially among the observational studies. To mitigate this limitation, we performed subset analyses on the results of only randomized controlled trials. Secondly, we did not include studies that did not report or could not provide specific data on Gram positive infections, thus we may have excluded important decolonization and prophylaxis studies. However, nine of 15 contacted investigators submitted additional data for inclusion in the analyses. Thirdly, studies of the association between interventions and Gram positive surgical site infections were heterogeneous, and thus some of the meta-analysis results should be interpreted with caution. Once these studies were stratified by potential sources of heterogeneity, the stratified subsets were homogeneous. For example, nasal decolonization aims to decrease the incidence of endogenous S aureus surgical site infections. The association between nasal decolonization and Gram positive surgical site infections may have been different for studies in which S aureus caused most Gram positive surgical site infections compared with studies in which surgical site infections due to other Gram positive pathogens were common. Thus we limited heterogeneity by doing subset analyses that separated studies focusing on S aureus surgical site infections from those focusing on all Gram positive surgical site infections.


Surgical site infections caused by Gram positive bacteria may be prevented by decolonizing patients who carry S aureus in their nares and potentially by adding a glycopeptide to the usual prophylaxis using β lactam antibiotics for MRSA carriers. High quality randomized controlled trials or cluster randomized trials should be performed to further assess this bundle.

What is already known on this topic

  • Surgical site infections (SSIs) are potentially preventable adverse events of cardiac and orthopedic operations
  • SSIs significantly increase hospital length of stay, readmission rates, healthcare costs, and mortality rates
  • Clinicians and researchers have debated whether nasal decolonization or glycopeptide antibiotic prophylaxis reduce SSIs caused by Gram positive bacteria
  • Among patients undergoing cardiac or orthopedic surgery:
  • Nasal decolonization with mupirocin ointment was protective against Gram positive SSIs
  • Preoperative prophylaxis with anti-methicillin (meticillin) resistant Staphylococcus aureus (MRSA) antibiotics when given to all patients was not protective against Gram positive SSIs
  • A bundle that included nasal decolonization and anti-MRSA prophylaxis for MRSA carriers was significantly protective against Gram positive SSIs

What this study adds


  • Among patients undergoing cardiac or orthopedic surgery:
  • Nasal decolonization with mupirocin ointment was protective against Gram positive SSIs
  • Preoperative prophylaxis with anti-methicillin (meticillin) resistant Staphylococcus aureus (MRSA) antibiotics when given to all patients was not protective against Gram positive SSIs
  • A bundle that included nasal decolonization and anti-MRSA prophylaxis for MRSA carriers was significantly protective against Gram positive SSIs

Source: BMJ