Relationships

Each January, most of us make a list of New Year’s resolutions , maybe we want to strengthen our bodies, or our resolve to eat better, or the determination to quit smoking. As it turns out, strengthening your social relationships may be an effort worth adding to your list of New Year’s resolutions for the good of your health.

Social connections like these not only give us pleasure, they also influence our long-term health in ways every bit as powerful as adequate sleep, a good diet, and not smoking. Dozens of studies have shown that people who have satisfying relationships with family, friends, and their community are happier, have fewer health problems, and live longer.
Conversely, a relative lack of social ties is associated with depression and later-life cognitive decline, as well as with increased mortality. One study, which examined data from more than 309,000 people, found that lack of strong relationships increased the risk of premature death from all causes by 50% an effect on mortality risk roughly comparable to smoking up to 15 cigarettes a day, and greater than obesity and physical inactivity.
Scientists are investigating the biological and behavioral factors that account for the health benefits of connecting with others. For example, they’ve found that it helps relieve harmful levels of stress, which can adversely affect coronary arteries, gut function, insulin regulation, and the immune system. Another line of research suggests that caring behaviors trigger the release of stress-reducing hormones.
Research has also identified a range of activities that qualify as social support, from offers of help or advice to expressions of affection. In addition, evidence suggests that the life enhancing effects of social support extend to giver as well as to receiver.
All of this is encouraging news because caring involvement with others may be one of the easiest health strategies to access. It’s inexpensive, it requires no special equipment or regimen, and we can engage in it in many ways.
The quality of our relationships matters. For example, one study found that midlife women who were in highly satisfying marriages and marital-type relationships had a lower risk for cardiovascular disease compared with those in less satisfying marriages. Other studies have linked disappointing or negative interactions with family and friends with poorer health. One intriguing line of research has found signs of reduced immunity in couples during especially hostile marital spats.
Having a network of important relationships can also make a difference. A large Swedish study of people ages 75 and over concluded that dementia risk was lowest in those with a variety of satisfying contacts with friends and relatives.
For many of us, the recent holidays meant family gatherings, getting together with friends, and participating in special religious, community, and workplace activities. Such occasions are an opportunity to check in with each other, exchange ideas, and perhaps lend a supportive ear or shoulder. Now is a good time to strengthen your ties throughout the years to come. Here are some ways to start:
Focus on your most meaningful relationships.
Choose activities to do together that are most likely to bring joy to you and the people you care about.
Delegate or discard tasks that eat into your time, or do them together with family or friends.

Cloned meat

Are you eating cloned meat? You probably don’t know. It’s becoming common practice ... but the FDA doesn’t require labeling of cloned meat!

Birth defects in clones are quite common. Cloning has been found to produce unhealthy animals who suffer tremendously. Clones often die young, suffer birth defects, and commonly need antibiotics.

The Center for Food Safety says that as many as 50% of cow clones have what’s called “Large Offspring Syndrome.” Symptoms include unusually high birth weight that endangers the mother, and a long list of organ and systemic abnormalities, including heart problems and immature lung development.

The report also states that there is evidence that clones are not always exact duplicates of their gene donors. Clearly, cloning remains an unpredictable science.

And cloning scientists have warned that even small imbalances in these clones could result in hidden food safety problems in the cloned meat. A recent study found differences in the composition of the milk and meat of cloned animals.

But here’s what’s even more worrisome, the nation’s major cattle cloning companies admit that they have not been able to keep track of how many offspring of clones have entered the food supply.

So there’s no way of knowing if you are buying cloned meat or not! I don’t know about you, but I consider this extremely deceptive. We should have the right to choose, especially when it comes to what we eat.

It’s sad to think that the FDA approved cloned livestock food without completely knowing all of the risks involved. But they don’t exactly have a good track record…just look at all the drug recalls they’ve made over the last decade.

The whole idea of cloned meat is frightening if you ask me. That’s another reason why I choose grass-fed beef. I don’t have to worry about whether or not I am eating some science experiment developed in a test tube.

So when choosing meat for your next meal, consider the following two options.

• Cattle raised as nature intended – in an open field free to roam and feast on their natural diet of grass

Or

• Something developed in a scientific experiment that has not been properly researched, not to mention fed an unnatural diet of grain and given massive doses of antibiotics.

This should be an easy one, correct? Choose the grass-fed beef, of course. At least you’ll know exactly what you are getting – something that’s healthy and nutritious with no hidden food safety issues. It’s hormone-free, antibiotic-free, has no preservatives, and has a healthy ratio of omega-3 to omega-6 fats.

Osteoporosis Screening Recommendations

January 18, 2011 — The US Preventive Services Task Force (USPSTF) issued a B recommendation to routinely screen for osteoporosis in women 65 years of age or older and in younger women at comparable or greater fracture risk to that of a 65-year-old white woman with no additional risk factors. Current evidence was found to be insufficient to make a recommendation for or against screening men at this time (I statement).
This update to the 2002 USPSTF osteoporosis screening recommendation was published online January 17 in the Annals of Internal Medicine and is the first final recommendation statement to be published since the USPSTF implemented a new process for recommendation statements in July 2010. In this process, all draft recommendation statements are posted for public comment on the USPSTF Web site, as this draft was from July 6 to August 3, 2010, before being issued in final form.
"One half of all postmenopausal women will have an osteoporosis-related fracture during their lifetime, including 25% who will develop a vertebral deformity and 15% who will suffer a hip fracture," write USPSTF Chair Ned Calonge, MD, MPH, from the Colorado Trust in Denver, and colleagues. "Osteoporotic fractures, particularly hip fractures, are associated with chronic pain and disability, loss of independence, worsened quality of life, and increased mortality. Although hip fractures occur less commonly in men than in women, more than one third of men who sustain a hip fracture will die within 1 year."
Approximately 12 million Americans older than 50 years are expected to have osteoporosis by 2012. In addition to female sex and white race/ethnicity, other risk factors for osteoporosis include smoking, alcohol intake, low body mass, and parental history of fractures. To estimate 10-year risks for fractures, the USPSTF used the FRAX tool because it relies on easily obtainable clinical information, it was extensively validated in 2 large US cohorts, and it is freely accessible by clinicians and by the public.
Because the risk for fractures continues to rise with increasing age, the USPSTF did not specify an age limit at which screening should no longer be performed. When deciding whether to screen patients with significant morbidity, however, clinicians should consider the remaining lifespan.
The updated recommendations were based on a USPSTF assessment of available evidence on the diagnostic accuracy of instruments to determine osteoporosis and fracture risk, the utility of dual-energy x-ray absorptiometry (DXA) and peripheral bone measurement tests in predicting fractures, the potential harms of osteoporosis screening, and the potential benefits and harms of pharmacotherapy for osteoporosis in women and in men.
In terms of detecting osteoporosis, the USPSTF found convincing evidence that bone measurement tests such as DXA of the hip and lumbar spine and quantitative ultrasound of the calcaneus predict short-term risk for osteoporotic fractures in women, as well as in men. Evidence is adequate that clinical risk assessment instruments are only modestly predictive for low bone density or for fractures.
To date, no controlled studies have assessed whether screening for osteoporosis offers any benefits in terms of detection and early treatment, such as lower fracture rates or fracture-related morbidity or mortality.
Available evidence is convincing that drug treatment lowers the risk for fractures in postmenopausal women who have no previous osteoporotic fractures. The USPSTF determined that the magnitude of benefit of treating screening-detected osteoporosis is at least moderate in women 65 years of age or older, and in younger women whose fracture risk is at least as great as that of a 65-year-old white woman with no additional risk factors.
Treatment options include sufficient intake of calcium and vitamin D and weight-bearing exercise. Several drugs have been approved by the US Food and Drug Administration to prevent fractures, including bisphosphonates, parathyroid hormone, raloxifene, and estrogen.
"The choice of therapy should be an individual one based on the patient's clinical situation and the tradeoff between benefits and harms," the statement authors write. "Clinicians should provide patient education on how to use drug therapies to minimize side effects."
Because of the absence of randomized trials of primary fracture prevention in men who have osteoporosis, evidence was deemed inadequate to determine whether pharmacotherapy lowers fracture risk in men with no history of osteoporotic fractures.
Since publication of the 2002 USPSTF osteoporosis screening recommendation, the USPSTF has found no new studies evaluating harms of screening for osteoporosis in men or in women. DXA screening is associated with opportunity costs; namely, the time and effort expended by patients and by the healthcare system.
The specific agent used determines the potential harms of drug therapies for osteoporosis. For bisphosphonates, which are the most commonly prescribed treatments for osteoporosis, the USPSTF found adequate evidence that the harms are no greater than small. For estrogen and selective estrogen receptor modulators, however, the USPSTF found convincing evidence that the harms are small to moderate.
"The USPSTF concludes that for women ages 65 years and older, and for younger women whose fracture risk is equal to or greater than that of a 65-year-old white woman who has no additional risk factors, there is moderate certainty that the net benefit of screening for osteoporosis using DXA is at least moderate," the statement authors write. "The USPSTF concludes that for men, evidence of the benefits of screening for osteoporosis is lacking, and the balance of benefits and harms cannot be determined."

CHRONIC NEUROPATHIC PAIN

Chronic pain is not just a problem of incidence and pathophysiology; it is one of unique individual suffering. Chronic neuropathic pain (CNP) causes untoward amounts of suffering, and costs millions of dollars a year in lost work and healthcare costs. In terms of physiology, neuropathic pain is described by the International Association for the Study of Pain as, "pain initiated or caused by a primary lesion or dysfunction in the nervous system," and has an annual incidence of 1% in the general population.

Treatments for CNP

Unfortunately, our current treatments for CNP are limited. Although polypharmacy is common in the treatment of neuropathic pain, few studies have evaluated combination therapies. The current treatments do help some patients, but many patients do not respond and their suffering continues. Furthermore, current research tends to focus on disease states that can be clearly specified, eg, postherpetic neuralgia and HIV neuropathy. Many neuropathic pain states are either rare in incidence or poorly defined in presentation. It is not clear whether the results from current research for disorders, such as postherpetic neuralgia, will translate into similar outcomes for other neuropathic pain conditions.

A Search for New Treatment Options

The current limited treatment options and patient suffering have energized a search for new and more effective treatments. Research into the mechanisms of CNP has provided insight into some of these potential new treatment targets. Two such targets, the transient receptor potential (TRP) channel agonists (and antagonist) and cannabinoid agonists, are areas of increased excitement.

The TRP channels are a large family of cation channels. They influence a multitude of physiologic processes in the body from pain to thermosensation. There are 6 subfamilies, 1 of which is the TRPV(1-6). When activated, these receptors conduct mostly calcium, with some sodium and potassium conductance. The TRPV1 receptor, found in the central nervous system (CNS), in sensory ganglia (dorsal root ganglia), and peripheral C and A delta sensory fibers, is of particular interest. This receptor is activated by temperatures > 43°C (noxious), low pH ≤ 5.2, low voltage, and low lipid levels. Of note, the receptor is also activated by certain venomous insects and arachnids, although the exact mechanism for this is unknown.

Capsaicin

Capsaicin, the chemical that gives jalapeño peppers their "heat," has been found to be an exogenous agonist. The history of the use of capsaicin in pain goes back millennia. The benefits of capsaicin include the fact that it is lipophilic, readily crosses cell membranes, and is relatively easily synthesized.
Research in TRPV1 agonist has focused on topical, intravenous, intranasal, and oral routes of administration. The transdermal route has been shown to be the most effective and is now commercially available in an 8% transdermal patch under the trade name Qutenza®.

Clinical Trials of Capsaicin

Clinical trials with the 8% capsaicin patch have shown clinical efficacy. Unfortunately, meta-analyses for neuropathic pain treatments have continued to compare these studies, which used active controls (0.04%) and not placebos, with placebo-controlled trials. This artificially elevates the numbers needed to treat. The Cochrane Collaboration review and the recent review of neuropathic pain treatments by Finnerup and colleagues, published in the journal Pain, both compared 8% capsaicin clinical trials with placebo-controlled trials.

Indications and Use of Capsaicin

The 8% capsaicin patch has efficacy similar to other treatments, is topical, and avoids the systemic problems of daily medications. However, certain barriers accompany its application. It must be applied in a physician's office and takes 2-3 hours of a physician's (and patient's) time. In Europe, the 8% patch is indicated for neuropathic pain syndromes other than diabetic peripheral neuropathy. In the United States, the patch is indicated only for postherpetic neuralgia. It has been used, however, for trigeminal neuralgia (reported in case studies), and other neuropathic conditions. Research continues in the use of capsaicin for migraine (although the data have been conflicting), pruritus, musculoskeletal pain, osteoarthritis, and other pain conditions
In contrast to the history of capsaicin, the endocannabinoid signaling system was only recently discovered. These receptors are involved in a number of different physiologic processes, from food intake to immunomodulation. Two cannabinoid receptors have been identified, CB1 and CB2. Both of these receptors are 7-domain G protein-coupled receptors and affect cyclic adenosine monophosphate. Endocannabinoid agonists include both endogenous and exogenous substances. The endogenous cannabinoids, anandamide and 2-arachidonoylglycerol, were identified in the 1990s. Naturally occurring compounds are found solely in plants of the genus Cannabis. The most commonly known is delta⁹-tetrahydrocannabinol (THC). Exogenous endocannabinoid agonists include the "manufactured" drugs Sativex® (THC/cannabidiol) and nabilone.

Effects of Cannabinoids

Of interest, the endocannabinoid system interacts with a number of other pain control systems, eg, endorphins and TRPV receptors. They function mostly as neuromodulator agents and have potent anti-inflammatory effects. CB1 is expressed in the CNS, and CB2 is found on immune cells, but CB2 also has a role in pain and inflammation. CB2 receptors are found in the CNS, mainly in microglia, but in low densities. The CB1 receptor is low in density in the brainstem, which may account for its low lethality and toxicity. CB1 antagonists, when given to mice, result in hyperalgesia. Moreover, endocannabinoid deficiency may lead to certain conditions, such as migraine, irritable bowel syndrome, and fibromyalgia. In experimental models, cannabinoids inhibit release of glutamate, and it has been postulated that glutamate and glutamatergic systems are important for the maintenance of CNP.
Similar to capsaicin, cannabinoids have been used for centuries in the treatment of mood and pain. The naturally occurring THC has 20 times the anti-inflammatory potential of aspirin and nonsteroidal anti-inflammatory drugs. However, THC has no cyclooxygenase inhibitory capability. Cannabidiol, the second component in the product Sativex, is noneuphoriant, but has some of the same actions as THC. Of note, cannabidiol is also a TRPV1 agonist.

Clinical Trials

Cannabinoids have been evaluated in multiple animal models. Nerve injury models, streptozotocin-induced diabetic neuropathy, chemotherapy-induced neuropathy, HIV-associated sensory neuropathy, demyelination-induced neuropathy, multiple sclerosis-associated neuropathy, and postherpetic neuralgia animal models have all been used. Studies in all of these models have shown efficacy in suppression of hyperalgesia and allodynia.
In humans, both smoked and oral cannabinoids have been evaluated. Unfortunately, well-designed randomized, placebo-controlled trials are lacking for smoked cannabis. A recent study in the Canadian Medical Association Journal enrolled only 23 patients. Smoked cannabis was used and the design was a crossover randomized trial. This is one of the few well-designed studies with smoked cannabis. Unfortunately, to achieve a power of 80% the study needed to enroll 32 patients, a number that was not achieved.
In a study with THC/cannabidiol for diabetic neuropathic pain, the combination cannabinoids were no more effective than placebo. In a 2007 review, the THC/cannabidiol combination was shown to be effective in 125 patients with neuropathic pain of peripheral origin. In multiple sclerosis, Sativex was found to reduce spasticity. Furthermore, cannabinoids have not only been evaluated for the treatment of chronic pain, but also for dementia, some psychiatric illnesses, and chemotherapy-induced nausea and vomiting.

Pharmacologic vs Recreational Marijuana

The Cannabis sativa plant contains over 300 compounds, 66 of which are cannabinoids. Many of these are biologically active; some have unknown activity. The percentages of many of the metabolites of Cannabis can be dramatically influenced by where the plant is grown, how much water that it receives, and other factors. Of interest, GW Pharmaceuticals plc (Salisbury, United Kingdom) has genetically developed specific strains of Cannabis that produce single specific metabolites. It should be obvious that studies with smoked Cannabis, even if with standardized herbal material, cannot be translated to the marijuana shops of California. Therefore, the use of smoked marijuana for chronic pain cannot be supported by current data.

In conclusion, TRPV1 receptor agonists have shown efficacy in relieving pain of different neuropathic pain states. There is controversy over the use of smoked Cannabis in the treatment of pain; however, the use of specific cannabinoids agonists holds promise for the future. Additional mechanisms are being investigated as well.

References

1. International Association for the Study of Pain. IASP pain terminology. Irving GA, Backonja MM, Dunteman E, et al. A multicenter, randomized, double-blind, controlled study of NGX-4010, a high-concentration of capsaicin patch, for the treatment of postherpetic neuralgia. Pain Med. 2010 Nov 18. [Epub ahead of print].
2. Webster LR, Malan TP, Tuchman MM, Mollen MD, Tobias JK, Vanhove GF. A multicenter, randomized, double-blind, controlled dose finding study of NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia.
3. Derry S, Lloyd R, Moore RA, McQuay HJ. Topical capsaicin for chronic neurpathic pain in adults. Cochrane Database Syst Rev. 2009;(4):CD007393.
4. Finnerup NB, Sindrup SH, Jensen TS. The evidence for pharmacological treatment of neuropathic pain. Pain. 2010;150:573-581.
5. Ware MA, Wang T, Shapiro S. Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. CMAJ. 2010;182:E694-701.
6. Selvarajah D, Gandhi R, Emery CJ, Tesfaye S. Randomized placebo-controlled double-blind clinical trial of cannabis-based medicinal product (Sativex) in painful diabetic neuropathy. Diabetes Care. 2010;33:128-130.
7. Nurmikko TJ, Serpell MG, Hoggart B, Toomey PJ, Morlion BJ, Haines D. Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial. Pain. 2007;133:210-220.
8. Wade DT, Collin C, Stott C, Duncombe P. Meta-analysis of the efficacy and safety of Sativex (nabiximols), on spasticity in people with multiple sclerosis. Mult Scler. 2010;16:770-714. 

Είναι συνετό να έχεις πρόσβαση στα μυστικά του γενετικού σου κώδικα; Κάποιοι γιατροί φοβούνται ότι δε θα πάρεις τη σωστή απόφαση

συγγραφέας Δαλαμάγκα Μαρία

Το περιοδικό του Αμερικάνικου Ιατρικού συλλόγου (JAMA) πρόσφατα εξέφρασε τις ανησυχίες του σχετικά με το γονιδιακό test. Αυτό το test  δίνει τη δυνατότητα στον ενδιαφερόμενο να δει ένα χάρτη με τα χρωμοσώματα  του και με αυτό τον τρόπο και τις χρόνιες ασθένειες  , που έχει προδιάθεση να αναπτύξει αργότερα στη ζωή του.

Τι είναι αυτό που τόσο τους  ανησυχεί;  Οι πληροφορίες. Πιστεύουν ότι οι πληροφορίες μπορεί να είναι επικίνδυνες.

Οι γιατροί που γράφουν για το JAMA  φοβούνται ότι ίσως θα σπαταλάμε το πολύτιμο χρόνο του γιατρού και ότι θα θέσουμε σε δοκιμασία το σύστημα υγείας  , ζητώντας τους να ερμηνεύσουν τα αποτελέσματα του γονιδιακού test. Μπορεί  επίσης αυτό  να συνεπάγεται περιττές εξετάσεις και θεραπείες.

Έτσι καταλήγουμε στο συμπέρασμα ότι  το ιατρικό σύστημα λέει ότι τα φάρμακα είναι ασφαλή και οι πληροφορίες επικίνδυνες.

Πάνω από εκατό χιλιάδες Αμερικανοί πεθαίνουν από συνταγογραφούμενα φάρμακα κάθε χρόνο.

Η λειτουργία των γονιδίων είναι να δημιουργήσουν πρωτεϊνες , που χρησιμοποιούνται σε όλες τις λειτουργίες των κυττάρων. Ο ι πρωτεϊνες είναι επίσης σημαντικές για τη λειτουργία των οργάνων και των ιστών του σώματος.

Κάθε κύτταρο στο σώμα μας εξαρτάται από χιλιάδες πρωτεϊνες , οι οποίες πρέπει να δράσουν στο σωστό χρόνο και τόπο. Αλλά μερικές φορές μια μετάλλαξη σε ένα γονίδιο αποτρέπει τη σωστή λειτουργία των πρωτεϊνών. Ένα μεταλλαγμένο γονίδιο διαφοροποιεί τις οδηγίες για τη παραγωγή μιας πρωτεϊνης , και μπορεί να οδηγήσει σε δυσλειτουργία  ή και πλήρη απουσία αυτής. Όταν αυτό συμβεί σε μια πρωτεϊνη που έχει πρωτεύοντα ρόλο , μπορεί να οδηγήσει σε ασθένεια.

Είναι σημαντικό να αντιληφθούμε ότι τα γονίδια δεν προκαλούν ασθένεια. Με άλλα λόγια δεν υπάρχει το γονίδιο του καρκίνου. Αλλά μπορεί να  υπάρξει μια μετάλλαξη σε ένα γονίδιο,  που η λειτουργία των πρωτεϊνων  συντελεί στην εμφάνιση του καρκίνου.

Το γονιδιακό  test μπορεί να προσδιορίσει,  αν υπάρχει κάποια γονιδιακή μετάλλαξη.

Αν ανακαλύψεις ότι έχεις προδιάθεση για στεφανιαία νόσο ή καρκίνο του μαστού , αυτό δε σημαίνει ότι οπωσδήποτε θα αναπτύξεις την εν λόγω ασθένεια στο μέλλον.

Υπάρχουν πολλοί παράγοντες που καθορίζουν τη μεταγραφή των γονιδίων. Η διατροφή και η άσκηση παίζουν σημαντικό ρόλο.

Αν και ο γιατρός σας κρίνει  ότι τα αποτελέσματα  του test σχετίζονται με αυξημένο κίνδυνο για μια συγκεκριμένη ασθένεια ,  τότε μπορείτε να πάρετε προληπτικά μέτρα.

Pneumonia

Patients at risk for multidrug-resistant pathogens whose physicians followed guidelines from the American Thoracic Society and the Infectious Diseases Society of America to manage pneumonias with empirical antibiotic regimens had increased mortality compared with those patients receiving noncompliant therapy, new research suggests.
Daniel H. Kett, MD, from the University of Miami, Florida, and colleagues with the Improving Medicine through Pathway Assessment of Critical Therapy of Hospital-Acquired Pneumonia program published their findings online today in the Lancet Infectious Diseases.
In 2005, the American Thoracic Society and Infectious Diseases Society of America published updated guidelines for treating hospital-acquired pneumonia and related infections. These guidelines suggest that empirical treatment should be selected based on whether patients have recognized risk factors for multidrug-resistant pathogens.
The current study sought to evaluate the use of these guidelines and compare them with noncompliant treatment in 303 patients at 4 academic medical centers in the United States. All patients were in intensive care units and at risk for multidrug-resistant pneumonia.
Prescribed treatment was considered guideline compliant in 129 patients and noncompliant in 174 patients. Treatment was compliant if within 1 day of pneumonia recognition, therapy with a triple drug regimen as follows was implemented: cephalosporin, carbapenem, or β-lactam and β-lactamase inhibitor; an aminoglycoside or fluoroquinolone (in units with a high rate of carbapenem-resistant Acinetobacter spp, colistin was regarded as acceptable); and linezolid or vancomycin. Treatment not meeting these criteria was considered noncompliant.
Of the patients in the compliance group, 44 (34%) died before 28 days compared with only 35 (20%) in the noncompliance group. After adjusting for severity of illness and participants lost to follow-up, the estimated survival was significantly lower in the compliance group at 65% compared with 79% in the noncompliance group (P = .0042). Median length of stay and duration of mechanical ventilation were comparable between groups.
The most common reason for noncompliance was failure to use a secondary anti-Gram-negative drug (154 patients) and failure to empirically treat methicillin-resistant Staphylococcus aureus (MRSA) (24 patients). Another, less common, category of noncompliance was failure to use a primary anti-Gram-negative therapy.
"Despite our hopes to the contrary, we found that the use of guideline-compliant empirical treatment in patients in intensive-care units who were at risk for multidrug-resistant pathogens was associated with increased mortality," the authors conclude.
According to the researchers, the increased mortality associated with guideline-compliant empirical regimens may be explained by antibiotic-specific toxic effects. "Colistin and aminoglycoside use were associated with acute deterioration of renal function," they write. Neurotoxic effects have been described with aminoglycosides, colistin, and fluoroquinolones, and aminoglycosides contribute to critical illness polyneuropathy and myopathy. In addition, "prolongation of fluoroquinolone-induced QT interval can lead to life-threatening ventricular arrhythmias."
"[W]e suggest a comparison of regimens employing MRSA treatment and single versus dual Gram-negative coverage," the authors note.
Limitations include that the study was observational, lack of generalizability to inpatient wards, and incomplete information regarding prescribing practices.
In a related comment accompanying the article, Santiago Ewig, MD, from the Center for Thoracic Diseases of the Ruhrgebiet, Bochum, Germany, disputes the findings, although he agrees that the recommended triple approach is not supported by current evidence.
"All patients with septic shock, and probably severe sepsis, should receive dual coverage or triple coverage if MRSA is indicated," he writes. "Whether all haemodynamically stable patients with nosocomial pneumonia need such a wide coverage is questionable; at least, de-escalation [ie, monotherapy] treatment is mandatory, since it reduces selection pressure, organ toxic effects, and saves money. After all, de-escalation is what matters.
"The definition of non-adherence to American Thoracic Society guidelines should not read 'less than triple therapy' but rather 'less than long-term prognosis and risk-adjusted broad coverage and de-escalation according to culture and susceptibility results,' " he adds.
The study was supported by Pfizer. Dr. Kett and the other authors all have received financial support from or are employees of Pfizer. Several study authors have also declared financial relationships with the following institutions: Astellas, Cubist, Fallon Medica, GlaxoSmithKline, Johnson and Johnson, Madcat Healthcare, Merck, and Wyeth. Dr. Ewig has disclosed no relevant financial relationships.