JAMA

doi: 10.1001/jama.2010.227pmid: N/A

CLINICIAN'S CORNER Aspirin and Prevention of Vascular Events A low ankle brachial index (ABI) has been associated with an increased risk of incident cardiovascular and cerebrovascular events. In an analysis of data from the randomized, placebo-controlled Aspirin for Asymptomatic Atherosclerosis trial, Fowkes and colleagues Article examined the effectiveness of daily low-dose aspirin (100 mg) for the prevention of major cardiovascular and cerebrovascular events among persons aged 50 to 75 years who were free of clinical cardiovascular disease but had a low ABI (≤ 0.95) at a screening visit. The authors report that there was no statistically significant reduction in vascular events among persons who were randomly assigned to receive aspirin compared with persons who were assigned to receive placebo during a mean (SD) follow-up of 8.2 (1.6) years. In an editorial, Berger Article discusses aspirin therapy for prevention of cardiovascular events. Long-term Outcomes After ICU Stay In an analysis of Medicare claims data, Wunsch and colleagues assessed 3-year outcomes among Medicare beneficiaries who were hospitalized in an intensive care unit (ICU) and survived to hospital discharge and compared these with 2 matched control groups: hospitalized patients who survived to discharge and the general population. The authors found that Medicare patients who survived an ICU stay had high rates of mortality over the subsequent 3 years, in excess of that seen in comparable controls. Patients who received mechanical ventilation had substantially increased mortality, particularly in the early months after hospital discharge. Article Anemia Management in End-Stage Renal Disease The optimal management of anemia in end-stage renal disease (ESRD) is not clear. In an analysis of data from Medicare's ESRD program, Brookhart and colleagues examined the safety of erythropoiesis-stimulating agents and iron therapy in patients with ESRD. The authors characterized each US dialysis center's typical use of erythropoiesis-stimulating agents and intravenous iron for patients in 4 hematocrit categories and found that mortality rates were highest among patients with hematocrit less than 30% and found that greater use of erythropoiesis-stimulating agents and iron was associated with decreased mortality risk among patients in this group. However, greater use of erythropoiesis-stimulating agents and iron was associated with an increased risk of mortality among patients with hematocrit levels of 36% or higher. Article End-Expiratory Pressure in Lung Injury and ARDS In a meta-analysis of individual-patient data from 3 randomized clinical trials, Briel and colleagues Article examined the association of higher vs lower levels of positive end-expiratory pressure (PEEP) with mortality among adults with acute lung injury or acute respiratory distress syndrome (ARDS) who were receiving ventilation with low tidal volumes. Overall, the authors found that patients receiving higher levels of PEEP had similar hospital mortality as patients receiving lower levels of PEEP. However, among the subgroup of patients with ARDS, higher levels of PEEP were associated with improved survival. In an editorial, Rubenfeld Article discusses the implications of the analysis for critical care research and patient care. A Piece of My Mind “I wonder . . . if living in a condemned building with no utilities is the same as being homeless.” From “HIV Clinic.” Article Medical News & Perspectives In an interview with JAMA, A. Thomas McLellan, PhD, deputy director of the White House Office of National Drug Control Policy, explains US antidrug efforts are placing a new emphasis on prevention, screening, and treatment. Article Commentaries The Healthcare Innovation Zone: a platform for reform Article Rethinking the sedation continuum Article Real-time investigation of influenza drugs Article Literatim Abraham Flexner and education Article Author in the Room Teleconference Join Frank Davidoff, MD, Wednesday, March 17, from 2 to 3 PM eastern time to discuss how insights from health care improvement initiatives can reduce ambivalence about heterogeneity in determining efficacy of treatment. To register, go to http://www.ihi.org/AuthorintheRoom. Readers Respond How would you manage a 31-year-old woman with a transformed low-grade glioma? Go to www.jama.com to read the case, and submit your response, which may be selected for online publication. Submission deadline is March 7. JAMA Patient Page For your patients: Information about mechanical ventilation. Article

doi: 10.1001/jama.303.9.815pmid: N/A

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Cole, Thomas B.

doi: 10.1001/jama.2010.214pmid: 20197519

At an early age, William-Adolphe Bouguereau (1825-1905) mastered a classical and popular style, and against the advice of the avant-garde, he stuck to it, producing more than 800 paintings in his lifetime and accumulating award after award from the official art establishment. In time Bouguereau became a prominent member of the art establishment himself, earning a life membership in the Académie des Beaux-Arts of the Institut de France. As a painter, referee, and teacher, he achieved greatness in the official art world and willingly passed along its traditions to a new generation of artists. William-Adolphe Bouguereau (1825-1905), Homer and His Guide, 1874, French. Oil on canvas. 209×143 cm. Courtesy of the Milwaukee Art Museum (http://www.mam.org/), Milwaukee, Wisconsin; Layton Art Collection, gift of Frederick Layton, L1888.5. Photograph by Larry Sanders. However, these traditions were under attack from a group of outsiders who valued innovation over allegiance to the accepted standards of excellence in painting. These artists had their own ideas of how to advance the art of painting, and they resented the official art world's lack of interest in their discoveries. Some of their resentment was directed against Bouguereau personally, because he had a major role in selecting paintings for official exhibitions. The new-style painters criticized his work as being artificial rather than natural, and sentimental rather than realistic. One of the most vocal of these innovators, the French painter Edgar Degas, made up a word for everything he thought was hidebound and static about conventional critical taste: “Bouguereauté.” From his own perspective, Bouguereau was only paying homage to the time-tested classical style of Michelangelo and Raphael, and he had trouble understanding what it was that people saw in the work of his detractors: “As for the impressionists, the pointillists, etc., I cannot discuss them. I do not see the way they see, or claim to see.” Eventually, Degas and other painters with new ideas, including Édouard Manet, Camille Pissarro, and Paul Cézanne, left the academic art world behind and organized their own exhibition of paintings, but their departure had little or no effect on the critical success (or the sales) of Bouguereau's paintings until well into the next century. One of Bouguereau's most successful works was Homer and His Guide (cover), painted in 1874, the same year that Degas and his colleagues organized their first independent exhibition. The subject of the painting is the blind poet Homer, the legendary author of The Iliad and The Odyssey, whom classical painters of the 19th century considered the father of Western culture ( JAMA cover January 6, 2010). In the painting, Homer is on his way to sing his poems in a nearby town. When a pack of dogs attacks him, three shepherds chase them away and lead him by the arm to his destination. The painting is full of action, and the colors are deep and arresting. To understand why this style of painting appealed to art lovers of the 19th century but rankled the avant-garde, it may be useful to compare it to the work of Degas. Homer and His Guide features a classical subject, a straight-on view, a pyramidal design with Homer's sightless eyes at the apex and the lesser figures toward the base, three-dimensional modeling of the human figures, strong contrasts of dark and light to allow the figures to step out of the background, a glossy painted surface, and emotional, perhaps sentimental, gestures and facial expressions. These are hallmarks of the academic style of painting in 19th-century France. By comparison, Degas often played with or even ignored these conventions ( JAMA cover April 15, 2009). The subjects of his paintings were racy rather than lofty, the viewer's perspective was anything but straight-on, the human figures often blended into the background, and their facial expressions, captured in private moments, conveyed little emotion. Each of these painters considered his own work to be a closer approximation of reality than the other’s. Bouguereau's style has been described as “photorealism,” because at first glance his paintings look as lifelike as photographs. However, on closer inspection, many of his scenes appear staged or just plain improbable. For example, if Homer and his shepherd guide were photographed rather than painted as they walked along a dusty road, would their robes be so tidy and their backs so straight? In Bouguereau's defense, he never claimed to be a “photorealist.” His aim was to make beautiful pictures in the classical style, not to confront the viewer with the strengths and weaknesses of human nature or offer new opinions on the way that people see the world. In his lifetime, Bouguereau's audience was content. However, by the 1920s, art audiences were beginning to expect more than pretty pictures and perfect technique, and popular demand for the paintings of Degas and his colleagues began to overtake demand for the work of Bouguereau. Today, Degas and Bouguereau are seldom spoken of in the same breath. The idealism of the 19th century has given way to the cynicism of the 21st, and Bouguereau's paintings are best regarded as windows into an antique world that daydreamed about myths and legends and took pride in the elements of classical design.

Wells, Sarah

doi: 10.1001/jama.2010.170pmid: N/A

Touch this one inch of skin and send a thousand nerve endings to their knees. Prick it and risk the run of twenty blood vessels. Sever this layer to enter the dark territory of the interior—a six-inch scar lets nothing out that ought to stay in. And how about those sixty thousand melanocytes per inch that determine the color of me and when overexposed to UV rays, can bring the death of me. This one really gets under my skin—sweat glands in my palms begin to kick in. Praise, anyway, to the maker of the excess folds around my knuckles, ankles, and knees so I can sit cross-legged and curtsy with no pain, hold a pen without tears between bones, metacarpals popping out to be tucked back in. Glory to the lord of fingerprints, heart lines, head lines, life lines, indents and cavities fashioned in the womb. How particular your carvings, how precise your instrument to etch that patterned Arch, Whorl, or Loop unique in every instance. Plastic surgeon of the heavens, how I delight in a furrowed brow, crow's feet, age spots— wrinkle me up a dozen times to show I lived hard, good, funny—after all beauty, being what it is, is only skin deep—may my soul seep through dry scales of later hands, resting tranquil in my lap. O omniscient dermatologist, what ingenuity, past hurts evident in scrapes and scars— a clumsy stumble down uneven concrete stairs, knees and ankle raw and dripping; pockmarked cheeks from teenage zits—all healed, in the end, but not forgotten. How often we need reminders of where we’ve been.

Walker, Eric P.

doi: 10.1001/jama.2010.209pmid: 20197520

We met in February, and like many patients in this clinic she had chronic pain. I will try to help but, as for so many in this clinic, the pain is not just physical. The medications you gave me are helping my pain and it is time for me to pick up a refill. My knee is hurting bad today but to get my medicine I will have to walk to the pharmacy since I have no one to give me a ride and my voucher for the bus is expired. She is here to pick up her prescription, and we meet in the lobby. I hope it is okay to eat crackers in here. I saw the gas station on my walk here and remembered that I had not eaten anything since yesterday. My stomach pain is worse and I am still bleeding a lot, but they say I can't get surgery because I don't have an address to be discharged to from the hospital. I wonder to myself if living in a condemned building with no utilities is the same as being homeless. Weeks pass and she calls the clinic. My pain is worse. Can we increase my pain medications? I can't afford to buy my medicine, so will you help me? My phone does not have any minutes, so I will have to call you back and trust that you will be working to help me and that when I call you will have an answer. She is back in clinic today after several missed appointments. The new pain medicine is working better. It is not time for a refill, but my husband stole my pain medicine. Here is the police report. Can I get a refill to relieve my pain or will I have to wait? Who can I trust when the one person in the world who says he loves me is stealing from me? It is December now and time for another refill. I am feeling pretty sick today but need a refill on my pain medicine. I will have to walk to pick up the prescription if you can call it in. This was the last day that I or anyone talked to her. The requested prescription was never filled. The last day of her life and one final request to relieve her suffering or, possibly, a last effort to experience one small pleasure. Is there a difference?

Kuehn, Bridget M.

doi: 10.1001/jama.2010.210pmid: 20197521

Just a few months after his appointment by President Obama as the new director of the White House Office of National Drug Control Policy (ONDCP), R. Gil Kerlikowske, former chief of the Seattle Police Department announced that after 4 decades, the “war on drugs” was over. “It's time to recognize drug abuse and addiction for what it is—not just a criminal justice issue, but also a very complex and dynamic public health challenge, one that demands a systematic, comprehensive, and evidence-led approach if we are going to be equal to the task,” Kerlikowske said in a December speech (http://www.whitehousedrugpolicy.gov/news/speech09/121009_Stockholm.pdf). Such statements and the appointment of a 35-year veteran of addiction treatment research, A. Thomas McLellan, PhD, as deputy director of ONDCP have lead to optimism that drug treatment would play a larger role in US drug policy. McLellan, cofounder of the Treatment Research Institute, a nonprofit organization that promotes the translation of addiction research into therapy, and editor in chief of the Journal of Substance Abuse Treatment from 2000-2009, recently discussed with JAMA the new direction at ONDCP. A. Thomas McLellan, PhD JAMA:There has been considerable progress in understanding the biological underpinnings of addiction in recent years. What role will this science play in the new policy? Dr McLellan: On the demand-reduction side of the ONDCP strategy, we are going to be pushing prevention, early intervention, treatment, and recovery. Across all of those areas, the emphasis is evidence-based practice. JAMA:What kinds of prevention strategies is the ONDCP planning? Dr McLellan: There are some very good, clear indicators that addiction has an at-risk period. It is basically adolescence, somewhere between age 10 and 21. If you don't become addicted to tobacco, alcohol, cocaine, or opiates by that time, you probably are not going to be. That's very important, especially from a policy perspective, because that means that's where you focus your efforts. The second thing we’ve learned from the science is that you get greater impact from prevention if you combine evidence-based interventions from multiple sectors—parents, the health care field, schools, church, and the police—that influence adolescents. We are arguing for prevention-prepared communities—communities that get the relevant sectors together and do a comprehensive assessment of the risks that are affecting their adolescents. The next thing is for communities to become smart consumers, look in the literature for those interventions that have been shown to be effective in preventing the harms that they see as most salient in their community. For our part, we are organizing the federal government to consolidate across agencies to try to preferentially fund communities that have shown this level of preparation. JAMA:What role will treatment play in the new drug control policy? DR MCLELLAN: You are not always able to prevent, but you can identify substance use and intervene early. Here's the problem—it's not happening. It's especially not happening in the health care field, where it really ought to happen. There is almost no area within health care, from primary care right through to the emergency room, where there isn't at least a 20% prevalence of substance use disorders. Yet the health care community has been really slow to embrace the simple act of asking people about their substance use and giving them the facts about what unhealthy substance use is. We see this as an important opportunity to improve the overall quality of medicine. Lots of work now has shown that even subdiagnostic levels of use of alcohol and other drugs complicate the diagnosis, the course, the management, the outcomes, and the cost of virtually every chronic disease that there is. I’m not talking about people who are in the most serious forms of addiction, but the great majority of these problems are simply excess use and for those people a simple discussion can have lasting effects on reducing substance use, improving the quality of care, and reducing costs. This is not my opinion, there is a big evidence base on this. JAMA:What can ONDCP do to promote the use of screening and brief interventions? Dr McLellan: One of the things we're going to be doing is urging medical schools, nursing schools, and pharmacy schools to devote courses to substance use disorders. It's very important to be clear that substance use disorders are public health problems. Even the most serious form of these substance use disorders, the addictions, affect about 23 to 25 million people. That is about the same number of people who have diabetes. This is one of those areas that physicians, nurses, and pharmacists are not adequately trained in. We also think that screening has been sold the wrong way. Physicians have been told to do this so they can find addicted people. Why the hell would you do that if you don't know how to treat an addicted person? So it's understandable that they didn't do this with great gusto. But we think that's been the wrong message. We think there are 3 reasons to screen for substance use disorders. One, to find emerging problems that even brief interventions are likely to arrest and improve. Two, if you are about to prescribe virtually any medication, we think it is just responsible medical practice to know what other drugs, including alcohol, are on board so you can prevent drug-drug interactions and possibly overdoses. The third reason is that there are very few things in life that are better predictors of failure to adhere to a medical regimen than the use of alcohol and other drugs. So a doctor is just doing himself or herself a favor by asking about substance use and raising it as a health issue. They are going to do better medicine. Finally, we think clinicians have been inadequately compensated for these services, so we're calling for an increase in compensation for screening and brief interventions. JAMA:If there is more screening, more individuals with addiction will be identified. Where will they go for treatment? Dr McLellan: Addiction treatment in this country is one of a few areas where there has always been specialty care but no meaningful involvement of primary care. There are a lot of reasons for that. Meanwhile, substance use disorders are compromising virtually every area of medicine, including treatment for chronic pain, sleep disorders, and diabetes. Not nearly enough people with substance use disorders are being treated. Rather than increase the specialty sector, we’ve called for a substantial expansion of substance use treatment into federally qualified health centers—in other words, right into mainstream health care. We're starting with the federal system because we can, but the goal is to integrate substance use and addiction treatment right into mainstream health care. JAMA:You alluded to the abuse of opioid medication prescribed for pain management. Does the ONDCP have specific plans to tackle this issue? Dr McLellan: Prescription drug overdose is the second leading cause of accidental death in this country. It's amazing. The number one cause is automobile accidents. In fact, there are 16 states where prescription opiate overdose deaths were the number one cause of accidental death [http://www.cdc.gov/nchs/data/databriefs/db22.pdf]. That is something we can fix and that's a big priority for us. JAMA:But some physicians argue that efforts to curb opioid abuse could deter physicians from prescribing and reduce patients' access to pain control. What will be the ONDCP's approach to these issues? Dr McLellan: ONDCP is just as concerned as everyone else that we do not do anything to minimize appropriate care of pain. We are working closely with the Department of Health and Human Services, the National Institute on Drug Abuse, the US Food and Drug Administration, and the 4 largest primary care medical societies on this issue. Our hope is that in the near future, a consensus can be developed on standard pain management protocols that, number one, protect patients. Patients sometimes are reluctant to take an opioid analgesic because they are afraid of getting addicted, and they need more education. We think that ought to be part of the protocol. Two, physicians should use patient contracts and just good old-fashioned sitting down with patients and telling them that they have responsibility in the management of any of these medications. They have to safely store them. They can't give them to their friends and neighbors because that happens quite a bit. Three, we are trying to integrate prescription drug monitoring into electronic health information systems. We think that's going to solve a big concern for doctors—doctor shopping. Then we want to come to an agreement on prescription refill policies. ONDCP will try to convene these groups to develop a consensus way to manage pain, given all the available facts. JAMA:Where will law enforcement fit into the new policy? Dr McLellan: There is an appropriate role for law enforcement. There are a few physicians breaking laws and they are willfully doing it. But of course, most physicians aren't [breaking laws]. We want a consensus to emerge that creates clear guidelines that will give physicians and patients confidence, and of course, law enforcement an appropriate role. It's the ambiguity now that is creating difficulty. JAMA:Are there any other priorities that we haven't discussed that you’d like to highlight? Dr McLellan: Those are our main priorities in the health care area. We, of course, have other priority areas in terms of supply reduction. We're still quite committed to keeping our borders secure and preventing the entry of drugs into this country and the production of drugs in this country.

Voelker, Rebecca

doi: 10.1001/jama.2010.211pmid: 20197522

As public health experts get a better handle on the high incidence of repeated infections with Chlamydia trachomatis among US adolescents, the need for better screening and intervention has become obvious. Now research has revived the notion that inadequate screening among boys and young men has helped push the revolving door of repeated chlamydia infection. Experts have known for years that repeated chlamydia infections are common in young women. But few studies have examined whether these are reinfections or treatment failures, or whether repeated infection is as common in young men as in young women. Studies of adolescents in clinics and school-based screening programs are beginning to fill in some of these knowledge gaps. Some experts say the persistent cycle of repeated chlamydia infection could be addressed more effectively if screening programs included boys and young men. A study published in January examined chlamydia infections in 210 adolescent girls treated in Indianapolis, Ind, primary care clinics. Researchers evaluated clinical samples and documentation of the girls' sexual activity every 3 months for 3 years. More than half (121) of the girls had subsequent infections after being treated. Based on genotyping of the ompA gene in C trachomatis clinical samples, the researchers reported that 84% of the repeated infections were reinfections, 14% were attributable to antibiotic failure, and 2% were persistent infections without documented treatment (Batteiger BE et al. J Infect Dis. 2010;201[1]:42-51). J. Dennis Fortenberry, MD, one of the study's authors and professor of pediatrics at the Indiana University School of Medicine, Indianapolis, said the findings trump the common assumption that screening programs will reduce infections. Despite intensive screening and treatment, Fortenberry said, the girls “kept getting chlamydia.” Fortenberry observed that expectations of what screening programs can accomplish may be too high. But he also noted that many current screening programs are not reaching enough high-risk adolescents. “That means we should give better attention to the male partners,” he said. “Part of it has to do with challenging our belief that just by screening young women we're doing enough.” Epidemiologist Greta Anschuetz, MPH, agreed. “I do believe that men should be screened,” she said. Data that she and her colleagues at the Philadelphia Department of Public Health in Pennsylvania collected from 14 862 local high school students from 2002 to 2006 show that chlamydia and Neisseria gonorrhoeae infection rates were 2.5 times higher in females than males—6.0 vs 2.4 cases per 100 person-years. The vast majority (90%) of infections were chlamydia (Anschuetz GL et al. Sex Transm Dis. 2009;36[1]:4-8). The reinfection rates in male and female students were perhaps more telling. During the school years studied, the reinfection rate was 19 per 100 person-years in male students compared with 17.7 in female students. So even though females had higher overall infection rates, more of the males were repeatedly infected. The finding has implications for screening recommendations. The US Preventive Services Task Force (USPSTF) has concluded that current evidence does not support screening of boys or young men. However, the Centers for Disease Control and Prevention (CDC) in Atlanta suggests that if programs do screen males, individuals who test positive should be rescreened 3 months later for reinfection. The USPSTF and CDC recommend that only sexually active women younger than age 26 years be screened for chlamydia; the CDC suggests that those who are infected be retested about 3 months after treatment. But the screening rate in young, sexually active women is low—41.6% in 2007 (Centers for Disease Control and Prevention. MMWR Morb Mortal Wkly Rep. 2009;58[14]:362-365). The federal government's Healthy People 2010 objectives set a target goal to screen 62% of sexually active young women. Screening is recommended just for women because untreated chlamydia can leave them with complications such as pelvic inflammatory disease and infertility, but few, if any, complications occur in men. “In areas where there are high prevalence rates, specifically in clinics where there are a lot of infections, it's important to screen males and females annually,” said Gale Burstein, MD, MPH, associate professor of clinical pediatrics at the State University of New York at Buffalo. “In our clinic in Buffalo we routinely screen the men, and we find a lot of chlamydia.” But Kathleen Tebb, PhD, of the Department of Pediatrics at the University of California at San Francisco, said controversy still brews around the idea of screening boys and men for chlamydia, especially in the current climate of resources stretched to their limits. In a study of 711 sexually active, asymptomatic adolescent boys who visited pediatric clinics in 10 geographic regions in Northern California, Tebb and her colleagues reported a chlamydia prevalence of 4%, which is similar to the overall prevalence rate in Anschuetz's study of high school students (Tebb KP et al. J Adolesc Health. 2004;34[3]:166-168). While overall prevalence may have been high enough to warrant screening in boys, Tebb said her study found wide geographic variations in prevalence. In regions where no infections in boys were reported, resources spent on routine screening would have been wasted. But geographic variations raise a chicken-and-egg scenario: screening without knowing local prevalence may waste resources, but local prevalence cannot be determined without screening. Her work is politically neutral, but Tebb noted that public funding for sex education during the Bush administration focused on abstinence-only programs. Consequently, she said, funds were cut for more comprehensive programs that explain safer sex options and screening for disease. “This bigger national policy issue really hindered progress in this area at both the scientific and program implementation levels,” she said. Fortenberry of Indiana University is not optimistic that clinical recommendations will change anytime soon to include screening of boys and young men. But he said a larger issue looms: “There are some people who might argue that this is ongoing gender discrimination that still makes women bear a greater part of the burden of something that our entire society has to be interested in [for] our reproductive health.”

Voelker, Rebecca

doi: 10.1001/jama.2010.219pmid: 20197523

Consider this clinical scenario: an elderly patient with strong risk factors for heart disease takes a daily aspirin as a preventive measure. Lately, she has become a little forgetful and begins taking Ginkgo biloba because she read in a magazine that the herbal supplement can improve cognition. Several months later she falls on a loose piece of carpeting. Fortunately, she does not fracture her hip. But a protruding carpet nail leaves her with a deep gash in her arm. On the way to the emergency department, paramedics have difficulty controlling her bleeding, and she is at risk for substantial blood loss. If the patient had known she should tell her primary care physician that she started taking G biloba—or if her physician had routinely asked about any new vitamins or supplements she took—the woman might have been spared a potentially dangerous bleeding episode. Patients, physicians, pharmacists, and other health care professionals “need to know about the potential harm these herbs can have,” said Arshad Jahangir, MD, professor of medicine and consultant cardiologist at the Mayo Clinic Arizona in Scottsdale. Jahangir is a coauthor of a new review that spells out the risks of adverse events that herbal supplements pose for patients with cardiovascular disease and those who take cardiovascular medications (Tachjian A et al. J Am Coll Cardiol. 2010;55[6]:515-525). “We can see the effect of some herb-drug interactions—some which can be life-threatening—on tests for blood clotting, liver enzymes, and, with some medications, on electrocardiograms,” Jahangir added. The review encourages physicians to have a solid knowledge base about herbal products and to carefully question patients about herbal supplements they may use. Discussions with patients should note the products' potential to cause adverse effects when taken alone or in combination with the medications they already take. Scarce scientific evidence of herbal supplements' safety and efficacy as well as scant regulatory oversight put patients with cardiovascular disease who take these products at risk of adverse events, including increases in bleeding, blood pressure, and heart rate. Herbal supplements such as fumitory and kelp can increase the effects of β-blockers, calcium channel blockers, and antihypertensive and anticoagulant agents. Jahangir and colleagues note how ubiquitous herbal supplement use has become: more than 15 million individuals in the United States use herbs or high-dose vitamins for health purposes. In addition, visits to complementary and alternative medicine practitioners increased by nearly 50% during the 1990s, while visits to physicians remained unchanged.

Mitka, Mike

doi: 10.1001/jama.2010.212pmid: 20197524

The problem of medication adherence typically gets little attention compared with other, more pressing issues in health care. Yet higher adherence rates could dramatically improve patient outcomes while reducing overall health care spending. Poor adherence accounts for an estimated 33% to 69% of medication-related hospital admissions, costing about $100 billion (Osterberg L and Blaschke L. N Engl J Med. 2005;353[5]:487-497). Harder to measure, but no less real, are the premature deaths and reduced quality of life for patients; increased patient and physician anger, frustration, and hopelessness; and skewed findings for clinical research. Adherence can be especially difficult when a medication is prescribed as part of a primary prevention strategy, such as the use of statins for lowering cholesterol levels to reduce cardiovascular risk. “We ask people to take a pill every day for 20 years that will not make them feel better, and may make them feel worse, with the goal of preventing something 20 years from now,” said Walid Gellad, MD, an associate scientist at the RAND Corporation who has researched the adherence issue. “It is like exercising and eating right; they offer long-term benefits but involve immediate hassles, and people stop.” Medication adherence remains a problem for many patients, especially those taking pills daily to avoid such adverse events as a myocardial infarction decades in the future. But for many patients who give up on statins, the consequence is a greater chance of a future cardiovascular event and possible death. That means, to reduce mortality from cardiovascular events, the health care community should place greater effort on improving adherence rather than focusing on such strategies as expanding the eligible patient population or developing ever-more-powerful medications, said Amir Shroufi, PhD, a public health doctor with the National Health Service in Cambridge, England. Using computer modeling, Shroufi and a colleague found evidence that improving the 5-year adherence rate for statin use seen in patients at high risk of a cardiovascular event from 50% to 75% would avert twice as many cardiovascular deaths than would equivalent increases in prescribing statins for those at lower risk (Shroufi A and Powles JW. J Epidemiol Community Health. 2010;64[2]:109-113). “We're not saying that statin prescribing should not be extended to lower thresholds; we are just trying to quantify the benefits of improved adherence,” Shroufi said. “Adherence is neglected, considering how important it is and how many billions are spent developing new drugs. Such spending does not matter if people do not take them.” Developing strategies to improve patients' adherence to their statin medication regimens sounds good in theory, but has yet to be implemented successfully in the real world, said Steven E. Nissen, MD, chairman of the Department of Cardiovascular Medicine at the Cleveland Clinic Foundation. “How do you achieve the fabulous results you see in randomized clinical trials? We do not have answers to this question,” said Nissen. He emphasized the difficulties of using medications in primary prevention. “Often patients will take a statin for 6 months, 9 months, or a year, and since they do not feel sick, they lose interest and stop. It is much easier to give an arthritis medication, because if you do not take it, you will soon not feel well.” Gellad, who is also an assistant professor of medicine at the University of Pittsburgh in Pennsylvania, said modifying patient behavior is difficult, but other barriers to adherence can be changed. In his RAND report (http://www.rand.org/pubs/technical_reports/TR765), Gellad and colleagues conducted a literature review and identified evidence-based, potentially modifiable barriers, including cost sharing, regimen complexity, medication beliefs, and depression (in patients with diabetes). The report was prepared as a background paper for a conference last summer that focused on public policy options to improve medication adherence. The result of the conference was the release in October of 5 policy recommendations to improve medication adherence, presented by the American College of Cardiology, the National Association of Chain Drug Stores, the National Consumers League, the Pharmaceutical Research and Manufacturers of America, and GlaxoSmithKline plc. Gellad said promoting policy changes is important to keep the conversation about adherence alive, but he does not think these barriers will come down until economics forces the issue. “When people understand the financial losses from poor adherence, that is when they will make changes—especially when it hurts the bottom line,” Gellad said. “When Medicare realizes it is losing huge sums of money in the long term because of adverse complications from poor adherence, then adherence may become a more important issue in Washington.”

Taccone, Paolo;Polli, Federico;Gattinoni, Luciano

doi: 10.1001/jama.2010.184pmid: N/A

In Reply: Dr Russell suggests that baseline assessment of gas exchange may have been biased by cardiovascular dysfunction and use of vasoactive agents, affecting patients' enrollment as well as severity stratification in our trial. While this hypothesis is physiologically correct, assessment of cardiovascular status once cardiogenic edema has been excluded is not currently considered in the diagnostic criteria of ARDS.1 Russell correctly states that hemodynamic impairment is common in patients with ARDS and that it may affect the application of prone positioning, and he asks for details regarding cardiovascular treatment. In our study, we did not collect detailed information regarding hemodynamic status and cardiovascular support because our primary aim was to study a positional strategy during mechanical ventilation. Therefore, our information on cardiovascular dysfunction was collected together with information on other organ dysfunction as a cumulative index of severity (the Sequential Organ Failure Assessment [SOFA] score2). Based on the cardiovascular component of SOFA, the percentage of patients treated at baseline with vasoactive agents (SOFA cardiovascular subscore ≥2) was similar in the 2 study groups, considering either the entire population (85/168 [50.6%; 95% confidence interval {CI}, 43.0%-58.1%] in the prone vs 81/174 [46.6%; 95% CI, 39.1%-54.0%] in the supine group; P = .45) or the moderately hypoxemic subgroup (45/94 [47.9%; 95% CI, 37.4%-58.4%] vs 43/98 [43.9%; 95% CI, 33.9%-54.3%]; P = .58) and the severely hypoxemic subgroup (40/74 [54.0%; 95% CI, 42.0%-65.7%] vs 38/76 [50.0%; 95% CI, 38.3%-61.7%]; P = .62). The median (interquartile range) days of vasopressor infusion for the prone vs supine groups was 4 (1-8) vs 3 (0-7) days (P = .12) for the entire study population; 4 (1-8) vs 2 (0-6) (P = .09) in patients with moderate hypoxemia; and 4 (1-8) vs 4 (1-8) (P = .63) in patients with severe hypoxemia. Prone positioning was not applied because of severe hemodynamic instability in only 48/1445 (3.3%) patient-days (33 patient-days in patients with moderate hypoxemia). Russell also comments that potential imbalances between the study groups in the use of some treatments currently suggested by the Surviving Sepsis Campaign3 might have biased the results of our trial. Our study protocol was written and approved by local institutional review boards in 2003, before the release of the first Surviving Sepsis Campaign guidelines in 2004. Therefore, we did not include those treatments in our collection forms. However, in our study protocol we strongly recommended that any cotreatments be applied using the same criteria in the prone and supine groups, in which patients with severe ARDS were equally represented as stratified at randomization. We also believe that the effects of many of these cotreatments on the primary outcome of our study are questionable, owing to the uncertainty of their effects on mortality (eg, intensive insulin therapy4 and steroids5), as also suggested in the most recent guidelines.3 Back to top Article Information Financial Disclosures: Dr Gattinoni reported receiving a fee of US $1500 for a single meeting 5 years ago at KCI Medical Products headquarters, as a member of an advisory board. The other authors reported no financial disclosures. References 1. Bernard GR, Artigas A, Brigham KL, et al. The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. 1994;149(3, pt 1):818-8247509706PubMedGoogle ScholarCrossref 2. Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA. 1993;270(24):2957-29638254858PubMedGoogle ScholarCrossref 3. Dellinger RP, Levy MM, Carlet JM, et al; International Surviving Sepsis Campaign Guidelines Committee; American Association of Critical-Care Nurses; American College of Chest Physicians; American College of Emergency Physicians; Canadian Critical Care Society; European Society of Clinical Microbiology and Infectious Diseases; European Society of Intensive Care Medicine; European Respiratory Society; International Sepsis Forum; Japanese Association for Acute Medicine; Japanese Society of Intensive Care Medicine; Society of Critical Care Medicine; Society of Hospital Medicine; Surgical Infection Society; World Federation of Societies of Intensive and Critical Care Medicine. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008;36(1):296-32718158437PubMedGoogle ScholarCrossref 4. Brunkhorst FM, Engel C, Bloos F, et al; German Competence Network Sepsis (SepNet). Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med. 2008;358(2):125-13918184958PubMedGoogle ScholarCrossref 5. Sprung CL, Annane D, Keh D, et al; CORTICUS Study Group. Hydrocortisone therapy for patients with septic shock. N Engl J Med. 2008;358(2):111-12418184957PubMedGoogle ScholarCrossref