JAMA

doi: 10.1001/jama.300.15.1729pmid: N/A

Stress Testing to Document Ischemia Guidelines for elective percutaneous coronary intervention (PCI) for patients with stable coronary artery disease specify that myocardial ischemia should be documented on noninvasive testing before patients undergo elective PCI. In an analysis of 2004 Medicare claims data, Lin and colleagues Article determined the frequency and predictors of stress testing prior to elective PCI. The authors found that only 44.5% of the patients had stress testing within 90 days before elective PCI, and the authors report wide variation in rates of stress testing before PCI across geographic regions and across patient and physician characteristics. In an editorial, Diamond and Kaul Article discuss the effectiveness of PCI and anti-ischemic medical therapy and elaborate on the discord between practice guidelines and clinical practice. B Vitamin Supplementation and Cognitive Decline Elevated homocysteine levels have been associated with dementia and Alzheimer disease; however, evidence that homocysteine reduction can slow the rate of cognitive decline in persons with Alzheimer disease is inconclusive. In a randomized trial involving patients with mild to moderate Alzheimer disease and normal levels of folic acid, B12, and homocysteine at baseline, Aisen and colleagues Article investigated the effect of high-dose supplementation with folate (5 mg/d), vitamin B6 (25 mg/d), and vitamin B12 (1 mg/d) vs placebo on cognitive decline. The authors report that patients receiving high-dose B vitamin supplementation had a significant reduction in homocysteine levels but similar rates of cognitive decline as patients receiving placebo during the 18-month study. In an editorial, Clarke and Bennett Article discuss the evidence linking elevated homocysteine levels with dementia and review the lack of evidence that lowering homocysteine levels prevents or slows cognitive decline. Episodic Amiodarone for Atrial Fibrillation Amiodarone is an effective therapy for long-term prevention of atrial fibrillation (AF) but is associated with significant adverse events. In a randomized trial of patients with recurrent AF, Ahmed and colleagues tested the hypothesis that episodic amiodarone treatment—wherein amiodarone is discontinued after a month of sinus rhythm following electrical cardioversion and restarted if AF recurs—would be associated with fewer adverse events compared with continuous amiodarone treatment. The authors report that compared with patients who received continuous amiodarone, patients who received episodic amiodarone treatment had similar rates of a composite outcome of amiodarone-related and major cardiac adverse events but increased rates of AF recurrence, all-cause mortality, and cardiovascular hospitalizations. Article CLINICIAN'S CORNER Irritable Bowel Syndrome The Rational Clinical Examination In a systematic literature review of prospective studies involving adult patients with lower gastrointestinal tract symptoms, Ford and colleagues assessed the accuracy of individual symptoms and combinations of findings (Manning and Rome criteria, Kruis scoring system) to identify patients with irritable bowel syndrome. The authors found that individual symptoms had poor diagnostic accuracy and combinations of findings included in the diagnostic criteria and statistical models designed to distinguish irritable bowel syndrome from organic lower gastrointestinal tract diseases had only modest accuracy. Article A Piece of My Mind “In the maternity room, Sarah is flanked by her mother, who looks like she is about to burst into tears as she clutches Sarah's hand.” From “Babies Having Babies.” Article Medical News & Perspectives HIV/AIDS experts agree that antiretroviral therapy and other prevention strategies are needed to control a pandemic in which efforts to expand treatment worldwide are outpaced by new infections. Article Commentaries Ethics of billing and collections Article The food industry and obesity Article Transforming obesity prevention research Article JAMA Classics Evidence-based medicine Article Author in the Room Teleconference Join Rita F. Redberg, MD, MSc, November 19 from 2 to 3 PM eastern time to discuss stress testing to document ischemia before PCI. To register, go to http://www.ihi.org/AuthorintheRoom. Readers Respond How would you manage an 82-year-old woman with hypertension and renal artery stenosis? Go to www.jama.com, read the case, and submit your response by October 29. NEXT WEEK Theme Issue on the Health of the Nation JAMA Patient Page For your patients: Information about cardiac stress testing. Article

Smith, Jeanette M.

doi: 10.1001/jama.300.15.1734pmid: 18854522

The inviting weather on a recent September weekend left me with little choice but to while away the morning beside a shallow creek looking for the pawpaw fruit scattered throughout the forest canopy. Further diversions included the inspection of rocks in the creek bottom to identify interesting fossils. In these moments of focused contemplation of the natural world, all other reality seemed remote. A similar clarity and intensity of awareness of objects in nature typifies the luminous still life works by Edward Edmondson Jr (1830-1884). Edward Edmondson Jr (1830-1884), Still Life With Pawpaws, c 1870-1875, American. Oil on canvas. 35.6 × 43.2 cm. Courtesy of The Dayton Art Institute (http://www.daytonartinstitute.org), Dayton, Ohio; gift of Mrs Frank A. Brown (1969.81). Attainment of aesthetic ideals seemed doubtful in Edmondson's early days as an apprentice in the family tannery in Dayton, Ohio. In restrained rebellion against this fate, he is said to have bedecked the walls of his father's store and tanyard with paintings, using pigments such as fish oil and lampblack. The extent of any formal training is uncertain, although mentoring by a local portraitist reportedly occurred. However, the progressive polish seen in his work through time is suggestive of other edifying influences. One such influence was his studio partner, Thomas Walker Cridland, an English photographer, picture framer, and gilder, who had studied in New York City. Cridland had been exposed to the New York art world and was considered something of a “connoisseur.” Cridland's knowledge and photographs were conceivably a focal part of Edmondson's art. The sophisticated lighting that dramatized his still life works and portraits no doubt reflected this advantageous association. Trade routes such as the Miami and Erie Canal advanced Dayton's economy and enterprise in Ohio overall, which by 1850 was one of the most populous states in the Union. The increasing affluence and the appetite of the public for fruit and flower works as well as portraits ensured a livelihood for Edmondson. The progressive refinement of his methods was reflected in regional recognition at the Ohio State Fair in 1867 with awards such as Best Specimen Fruit Painting and Best in Portrait Oil. Edmondson's still life studies, which epitomized harmony and serenity, provided a semblance of rationality in contrast to the Dantean conflict rending the nation in the 1860s. In the aftermath of the Civil War, as the country struggled toward a new beginning, Edmondson turned a page in his own life with his marriage to Mollie Torrence of Dayton in 1867, followed by the birth of his son Robert in 1872. In Still Life With Pawpaws (cover), the almost incandescent jade green pawpaws are framed by emerald and olivine green hues of leaf and moss. The fruits appear in aqueous environs reflecting the propensity of the pawpaw tree for moist areas. Although one of its nicknames is “Indiana banana,” the pawpaw is found in a number of states largely east of the Mississippi River. The tropical tangy-sweet pudding-like center of the pawpaw is savored by wild animals and humans alike, and it has historical significance in its role in supplementing provisions for the Lewis and Clark expedition as recorded on Monday 15th of September 1806: “We landed one time only to let the men geather Pappaws or the Custard apple of which this Country abounds, and the men are very fond of.” The unpretentious but nutritious pawpaw is receiving increasing attention and is celebrated annually at the Ohio Pawpaw Festival, as well as being the subject of ongoing scientific study regarding its potential for commercial fruit production. Notable compositional elements of Pawpaws include the curious use of light and shading. The source of light suffuses in from the left side, leaving the backdrop on the left unilluminated, bringing the subject into conspicuous and objective focus, consistent with the aims of still life representation. The use of light and shadow in this manner is reminiscent of preceding still life works by the American painter Raphaelle Peale. In 1880, the Edmondson family moved to Santa Barbara, California, in hopes that the mild climate would restore Edmondson's worsening health related to a heart condition. While in California before his death in Santa Rosa in 1884, he appeared to favor painting landscapes, including several views of the Santa Barbara mission. This tanner's son came to be regarded as a leading Midwestern still life painter of his era. Perhaps his greatest achievement was a subtle unveiling of the elemental beauty of nature. The essence of these brief glimpses of the natural world, such as experienced by me on a sunny September day in the forest, have been thus exquisitely captured in time by Edmondson. Back to top Article Information Author's Note:The Paintings of Edward Edmondson (1830-1884) by Bruce H. Evans (Dayton, OH: Dayton Art Institute; 1972) was consulted in the preparation of this article. Editor's Note: This week's writer is Jeanette M. Smith, MD, Contributing Editor.

Brown, Grey

doi: 10.1001/jama.300.15.1736pmid: N/A

Bound by diagnosis, stranded mid-study, they make the most of it, as research takes a holiday. Beneath streamers of red, white and blue, they perch in the patient lounge, dutifully turn pages of last year's magazines, half-hearted attempts at jigsaw puzzles, someone suggests Monopoly. Home alone they abstractly figure the future, but here monthly changes align themselves in human form: those fresh to the disease noting tingles like stars bursting in limbs falling asleep, while slack-jawed neighbors coax conversation, and wheel-chaired pioneers forge ahead. The brave ones size each other up while spouses turn away. And who can deny the courage of the man who accepts a ride from his projected self, settles on the back of a scooter steered by one who has already lost the use of his legs.

Donovan, Cory A.

doi: 10.1001/jama.300.15.1739pmid: 18854523

Week by week I watch Sarah's belly grow. She is accompanied by her mother, and they are prompt for Sarah's prenatal visits. The 35-year-old mother and the 15-year-old girl sit side by side in the examination room chairs, Sarah getting bigger, rounder, and puffier week after week. Her mother listens earnestly to all of the instructions, sending sidelong glances at Sarah to punctuate the important information. Sarah's face is cherubic with big blue eyes and long lashes. She starts to waddle instead of walk. Her feet hanging off the examination table grow swollen, and she stops tying the laces of her sneakers. “Babies having babies,” my preceptor sighs as we watch mother and daughter make their way back to the lobby. I am in the middle of a nine-month elective during my third year of medical school at a clinic in rural Minnesota. Sarah seems so serious at every visit. Quiet and calm, she looks more at her hands on her belly than at anything else in the examination room. She nods but lets her mother ask the questions and make the plans. When asked directly about her body, even after 32 weeks of pregnancy, she turns her head to her shoulder, looks at the floor, and shrugs, embarrassed. She is not openly curious about the ordeal of childbirth. There is no expansive sigh when she rises from her chair or when she completes the climb onto the examination table. Sarah lacks the high drama and nervous tension of the other pregnant teenagers I’ve met. Her arms lie soft and still across the “I’m pregnant, what's your excuse?” sparkling T-shirt. I am pretty certain that the calm will vanish as contractions set in. Not long ago I witnessed a terrified patient as she delivered, her husband cowering beside the bed, her mother clutching the daughter's white-knuckled hand. She harshly and profanely rejected their encouraging and supporting words. Her yells echoed all the way to the pediatric wing. She physically struggled with the nurses and became deaf to my preceptor's instructions, ultimately pushing too hard too soon, causing a large tear that is still vivid in my memory. I don't want Sarah's delivery to be like that. By Friday, well into her 41st week, Sarah is scheduled for an early-morning induction. On the obstetrics floor a gaggle of 14- and 15-year-olds spills out of the family waiting room strangely transplanted from their school environment. Slouched against one another, braided and dressed in layers of pastel T-shirts, they speak enthusiastically over the noise they create. Backpacks sit against the tiled wall and US Weekly and People magazines are piled around them. I assume they’ve taken the day off from school; I imagine that it will be a long wait. First-baby inductions are often slow. Even with my relative inexperience, I predict an extended vigil, but judging from the way they’ve settled into the hall they seem prepared. In the maternity room, Sarah is flanked by her mother, who looks like she is about to burst into tears as she clutches Sarah's hand. Her mother scolds a mop-haired kid with acne when he backs into a vase as he attempts to make more room around the bed. “Time for a cervical check,” I say. I gather that he is the boyfriend when he grabs Sarah's hand possessively. “I think we can break the amniotic sac,” I say. My preceptor agrees and reaches for the crochet-like plastic hook. The boyfriend grimaces and sways from one foot to the other. Sarah smiles and thanks me. Shortly after one in the afternoon we get the call that Sarah is fully dilated and ready to push. We discard the clinic schedule and our laboratory coats and then hurry to the hospital. The wide-eyed teenagers, now armed with balloons and flowers in their hall fortress, grow quiet as my preceptor and I appear. In the birthing suite Sarah's legs are held aloft by her mother and a nurse. She smiles across her knees at me in recognition, no panic in her eyes, intrathecal anesthesia in place. As the contraction comes she focuses intensely on her breathing. Gowned and gloved, we wait 15 minutes until the baby's head is visible. Sarah pushes and yells in pain only once. “Keep focused on your breathing,” says the nurse, one of Sarah's feet supported in her experienced hands. We all begin unconsciously to mimic Sarah's rhythmic breathing, holding our breath as Sarah holds hers. Then Sarah takes a deep breath and pushes. Her face turns bright pink and mottled with her effort. She appears decades more mature than her peers in the hall. In the face of pain and a challenging new experience she becomes determined. Her mother trembles as she clutches Sarah's right foot. The teenaged father, also shaking, backs away from the scene before him. A few more breaths and pushes, then a gush of pink fluid; the head, shoulders, and legs slip into my extended arms. “Your daughter is beautiful,” I say as the infant wriggles in my lap. “Beautiful” takes into consideration the cone head, the white vernix, and the blue hands of the newly born. The baby is very large, a solid nine pounds eight ounces. The new grandmother starts crying, as does the father. Sarah closes her eyes for a moment and then peers over her knees to catch a glimpse of her new baby. The baby pinks up as she cries. With the vernix wiped off and her molded head covered with a knitted pink hat, she is picture ready in her mother's arms. Sarah beams, but is as quiet as ever. The boyfriend is overcome again with happy tears, and Sarah's mother snaps photographs. Between the flashes I watch Sarah watch her baby. She folds the newborn gently into her arms and rocks her slowly. She adjusts the hat and lets her baby's small fingers curl around her own. As she slips into her new role as mother, she stands in stark contrast to her peers in the hall. As I remove my gloves, I consider that women have delivered babies at 15 years of age since the beginning of humanity. However, this is no longer the norm, and I worry about this quiet young woman and her new daughter. High school is a difficult time, let alone adding the complications of a young, dependent life. Employment opportunities for young women without completing high school are few and far between. Her future now holds many additional challenges. What would have been different if Sarah had taken a different path, if her mom had brought her in for birth control, if the school had done a better job with sex education, if our culture were more open to dealing with the realities of teen sexuality? Will the inner strength Sarah demonstrated in the delivery last through the day-to-day challenges she will now face? I leave Sarah surrounded by her family, with her baby in her arms. I move through the group of excited teenagers, my mask dangling, the adrenaline spent. The girls prepare to visit their friend and hardly look up as I pass. I spot another pregnant belly beneath a long green T-shirt stretched tight. I hope that this other young woman, and I for that matter, will share her friend's inner strength when the time comes. Back to top Article Information Acknowledgment: Therese Zink, MD, assisted with the editing of this piece.

Stephenson, Joan

doi: 10.1001/jama.300.15.1745pmid: 18854524

Mexico City—When organizers of the XVII International AIDS Conference (IAC) designated “Universal Action Now” as the conference's theme, their intent was to emphasize the continued urgency of the pandemic and the need to take action toward universal prevention, treatment, care, and support to those living with HIV/AIDS. However, a less formal but perhaps more memorable theme took shape during the conference—a gathering of more than 20 000 researchers, health care workers, activists, and others, and the first IAC to be held in Latin America. “This conference will be recognized as the one . . . in which prevention and treatment got married,” said Pedro Cahn, MD, outgoing president of the International AIDS Society, which organizes the biennial meeting. In dealing with the HIV/AIDS pandemic, combination prevention, like combination treatment, “is the only feasible option,” said Peter Piot, MD, executive director of UNAIDS. A new report from the Joint United Nations Programme on HIV/AIDS (UNAIDS) released on July 29 (http://www.unaids.org/en/KnowledgeCentre/HIVData/GlobalReport/2008/) brought good news: a decline in the number of new HIV infections, from 3 million in 2001 to 2.7 million in 2007. In addition, about 3 million patients in low-income and middle-income countries currently receive treatment, as a result of a major push to expand access to antiretroviral therapy globally—an effort that has helped reduce the number of AIDS-related deaths to an estimated 2 million persons in 2007 after a peak in 2005 of 2.2 million deaths. But in conference session after session, experts agreed that expanding treatment, however important, is a Sisyphean task and that attempts to out-treat the epidemic will fail as more and more individuals become infected and require lifelong treatment with antiretroviral medications. “Every day, almost 3 times as many people become newly infected with HIV as those who start taking antiretroviral treatment,” said Peter Piot, MD, executive director of UNAIDS. “The end of AIDS is nowhere in sight.” In the long run, he noted, “the best way to stop people from dying of AIDS is to reduce the new infections in the first place.” But efforts to develop successful prevention tools have experienced some setbacks. Since the last IAC met in Toronto in 2006, trials of microbicides and studies of efforts to reduce HIV transmission by treating genital herpes showed no benefit, and a major HIV vaccine efficacy trial ended in disappointment in September 2007. Combination as key Despite such disappointments, researchers said it should be possible to reduce HIV transmission by emulating the treatment strategy that largely transformed HIV infection from a virtual death sentence into a chronic disease: using drugs in combination. On the prevention front, that strategy translates to exploiting all possible prevention tools and using them together, not in isolation. “The key word emerging from this conference is combination,” said Julio Montaner, MD, professor of medicine at the University of British Columbia in Vancouver, who became the International AIDS Society's new president at the close of the meeting. In fact, researchers are suggesting that one component of a suite of prevention strategies is treatment itself. Successful HIV treatment suppresses viral replication, and the drastic reduction in the body's viral load is thought to make the treated person less infectious. Supporting this is evidence that wide introduction of HIV therapy into a community translates into reductions in HIV incidence. For example, research in Taiwan found a 53% reduction in new positive HIV test results after free access to highly active antiretroviral therapy (HAART) was introduced there (Fang CT et al. J Infect Dis. 2004;190[5]:879-885). In British Columbia, Canada, Montaner and colleagues found that new yearly HIV infections also decreased by about half after HAART was introduced between 1995 and 1998 and has remained unchanged since then, despite an increase in the rate of syphilis infections, a surrogate measure of risk behavior (Montaner JSG et al. Lancet. 2006;368[9534]:531-536). Unintended consequences? While treatment as an HIV prevention strategy is appealing because it could be viewed as being a collateral benefit of treating those already infected to decrease HIV-related morbidity and mortality, the idea sparked controversy earlier this year and in sessions at the conference. In January, the Swiss Federal Commission for HIV/AIDS published a statement that indicated that a person with HIV infection who is taking antiretroviral drugs, who has achieved undetectable plasma levels of HIV for at least 6 months, and who has no other genital infection has a negligible risk of transmitting HIV through sexual contact (Vernazza P et al. Bull Médecins Suisses. 2008;89[5]:165-169). Not everyone was convinced that the risk is indeed negligible, however. Using a mathematical model, Australian researchers estimated that the cumulative risk of HIV transmission from an effectively treated person with HIV to that person's uninfected partner in unprotected encounters would quadruple the incidence that occurs with current rates of condom use (Wilson DP et al. Lancet. 2008;372[9635]:314-320). And although the Swiss statement did not explicitly indicate that condoms could be abandoned under the circumstances they outlined, public health experts were concerned that the document might be interpreted by patients receiving antiretroviral drugs that condom use was unnecessary, regardless of circumstances. “How we speak about treatment as prevention can have unintended consequences,” said Catherine Hankins, MD, MSc, chief scientific advisor for UNAIDS, at a special satellite session at the conference. Most patients living with HIV in low-income and middle-income countries do not have access to viral load testing, which means they would be unaware if their HIV levels were undetectable, she explained, and many have sexually transmitted infections, which means they would not meet the criteria of an absence of such infections. Nancy Padian, PhD, executive director of the Women's Global Health Imperative at the University of California, San Francisco, noted that while the statement was intended for physicians in Switzerland for use in counseling patients with undetectable viral loads and no sexually transmitted diseases who are in a monogamous relationship, the publicity surrounding the statement meant it was disseminated globally. “Sex workers [in Geneva] who are HIV-positive and on treatment interpreted it to mean that they did not have to use condoms and therefore could make more money,” she explained. The commission never thought of the statement as something that would be delivered worldwide, said Pietro Vernazza, MD, lead author of the document. “It was a statement that was delivered to Swiss physicians and it said it is okay to talk about risk estimates,” he explained. “It said under optimal conditions, the risk is in the range of daily life—we called it negligible.” In hopes of providing a more definitive answer to the question of risk of sexual transmission of HIV by individuals under treatment, researchers led by Myron Cohen, MD, of the University of North Carolina at Chapel Hill have launched a clinical trial involving 1750 couples in which 1 partner is infected and the other is not. However, results are not expected until 2015. Preexposure prophylaxis Studies also are under way to investigate the use of antiretroviral medications given orally or in a topical preparation as preexposure prophylaxis, or PrEP, for high-risk individuals. There is a strong rationale for their use in this context, including their effectiveness in preventing mother-to-child HIV transmission and in postexposure prophylaxis, as well as in studies of nonhuman primates showing the prevention of a simian form of HIV, said Timothy Mastro, MD, senior director of research for Family Health International in Research Triangle Park, NC. According to a report issued during the conference by the AIDS Vaccine Advocacy Coalition (http://www.avac.org/prep08.pdf), 7 randomized trials to test the concept are planned or already under way. These trials will test a once- daily dose of tenofovir or a combination of tenofovir plus emtricitabine in a variety of populations representing different routes of infection, including men who have sex with men, injection drug users, heterosexual men and women, heterosexual couples in which 1 person is infected with HIV, and women considered to be at high risk of infection. While scientists are hopeful that PrEP could have a substantial effect on HIV incidence, there are important unanswered questions for which researchers hope answers will emerge from the trials. Concerns include the possible emergence of drug-resistant HIV, particularly among individuals who take the drugs intermittently rather than consistently, as well as whether those who are given PrEP become less vigilant about avoiding behaviors that increase the likelihood of HIV infection. Circumcision, behavior change Results from some of the PrEP trials may be available in 2009, although findings from the largest studies (including a trial involving 4200 sexually active women in southern Africa that includes a vaginal gel in addition to oral PrEP) are not expected until 2010 or later. Whatever the outcome of studies of treatment's effects on HIV transmission, experts agreed that the new emphasis on a combination prevention approach will include expanding access to proven prevention methods. One such prevention strategy is male circumcision. An update of a seminal randomized controlled trial in Kenya demonstrating a 53% to 60% protective effect at 24 months of follow-up found the procedure's benefit lasts at least 3.5 years and showed a 64% protective effect. And a report released at the meeting by the Global HIV Prevention Working Group reminded the HIV/AIDS community that programs aimed at reducing high-risk behaviors should not be neglected as part of the mix of prevention strategies. “We carefully reviewed hundreds of scientific studies, assessing behavior change programs, and the overwhelming conclusion is that these programs work and can have a dramatic impact on preventing HIV infection,” said Helene Gayle, MD, MPH, president and CEO of Care USA and a working group member. “In all cases in which national epidemics have been reversed, broad-based behavioral change was central to that success.”

Hampton, Tracy

doi: 10.1001/jama.300.15.1748pmid: 18854525

Contrary to the widespread public assumption that routine breast self-examination is an important tool for detecting early stage breast cancer, a review of population-based studies indicates that engaging in this practice does not improve breast cancer mortality in women (http://www.cochrane.org/reviews/en/ab003373.html). Furthermore, the findings reveal that breast self-examination may lead to unnecessary biopsies. “As regular breast self-examination is not beneficial but harmful, it cannot be recommended as a routine practice for women,” said coauthor Jan Peter Kösters, MD, of the Nordic Cochrane Centre in Copenhagen, Denmark. Routine breast self-examination does not improve breast cancer mortality in women and may lead to unnecessary biopsies. While the findings, which are based on data that are several years old, indicate a lack of benefit of breast self-examination that is already well-known to many clinicians, the publicity surrounding the new review may confuse women who perform the procedcure with the hope of safeguarding themselves against cancer. Review's results For the review, Kösters and Peter Gøtzsche, MD, DrMedSci, also of the Nordic Cochrane Centre, searched the Cochrane Breast Cancer Group Specialised Register, the Cochrane Library, and PubMed in October 2007 for well-designed published trials that assessed this practice. They came up with no recent studies that fit their criteria; their findings were based on 2 large population-based studies from Russia and Shanghai, published in 1999 and 2002, respectively, that involved more than 388 000 women and compared outcomes for women who conducted breast self-examinations vs those who did not. “After a decade or more of follow-up, the women in the self-examination group in these trials were equally likely to have died from breast cancer as women in the group who did not practice breast self-examination,” said Kösters. The trials' results also revealed that breast cancer was more often suspected in the breast self-examination group because women who were randomly assigned to breast self-examination were almost twice as likely to undergo a biopsy. “Most women have lumps in their breasts and it is difficult to know whether a particular lump could be a cancer,” said Kösters. He also noted that lumps can often increase or decrease in size, which may prompt physicians to order tests such as biopsies to screen for cancer. Organizations, including the American Cancer Society, the World Health Organization, and the US Preventive Services Task Force, have not recommended breast self-examination for several years now. “Even though the existing studies had a lot of limitations, it's clear that if there is any benefit to breast self-exams, it's extremely small,” said Debbie Saslow, PhD, director of breast and cervical cancer for the American Cancer Society. Advice for women The American College of Obstetricians and Gynecologists takes a more neutral stance on the issue, stating that “despite a lack of definitive data for or against breast self-examination, this technique has the potential to detect palpable breast cancer and can be recommended.” “There's evidence that there's a benefit if you increase awareness so that a woman understands that she needs to see a doctor if she notices a change, because there's a chance that it could be breast cancer,” said Saslow. Kösters agreed, noting that if women “incidentally” find any changes in their breasts, they should see their physician for rapid assessment. Saslow also stressed that the potential for unnecessary biopsies should not be a reason for women to ignore any changes in their breasts or to keep from doing breast self-examinations if they so choose. “Mammograms have a lot of false-positives, too, but we still do them,” she said. Being aware of breast changes involves looking for discrepancies between both breasts, which might include any thickening, lumps, or skin changes in one of the breasts that does not change or that gets more pronounced with time, said Julie Gralow, MD, associate professor of medical oncology at the University of Washington in Seattle and chair of the American Society of Clinical Oncology's cancer communications committee. “There's nobody who knows your own body better than you,” she said. Gralow stressed that women should examine their breasts while looking in the mirror and should feel for changes while standing as well as lying down. Rather than weighing in on the pros and cons of routine breast self-examination with patients, physicians may find it more useful to discuss measures that are associated with a reduced risk for breast cancer and other diseases. “Maintaining a good body weight, getting physical activity, eating a healthy diet, and minimizing alcohol are going to impact not just your breast cancer risk but also your risk of heart disease, osteoporosis, and other things,” said Gralow. “Those are things you can do, and they have a real impact.”

Hampton, Tracy

doi: 10.1001/jama.300.15.1749pmid: 18854526

While considerable strides have been made in the diagnosis and treatment of breast cancer in the United States, many cases go undetected until later stages, and tens of thousands of people die from the disease each year. Several recent studies, presented in September at the 2008 Breast Cancer Symposium in Washington, DC, demonstrate researchers' ongoing efforts to improve those numbers. One study “offers new insight into a promising future alternative to mammography,” while another “will help us personalize care based on a better understanding of the molecular characteristics of a patient's tumor,” said Eric Winer, MD, professor of medicine at Harvard Medical School in Boston. Winer, who was not involved with the research, is also director of the Breast Oncology Center at the Dana-Farber Cancer Institute in Boston. Recent research reveals that molecular breast imaging is better than mammography for detecting breast cancer. The findings come at a time when researchers estimate that in 2008, more than 184 000 new cases of breast cancer will be diagnosed in the United States and nearly 41 000 people will die from the disease. The symposium was presented by the American Society of Clinical Oncology and other organizations. Molecular breast imaging Molecular breast imaging can detect 3 times as many cancers as mammography in women who have dense breasts and are at increased risk of breast cancer, 1 new study found. These women often need to undergo testing in addition to mammography because of difficulty distinguishing normal tissue from tumor tissue in dense breasts. “Molecular breast imaging detected more cancers than screening mammography but didn't produce more false-positive results,” said Carrie Hruska, PhD, lead author of the study and a research fellow in the department of radiology at the Mayo Clinic in Rochester, Minn. Molecular breast imaging, a relatively new screening method, involves injecting patients with a short-lived radioactive agent that is absorbed more readily by cancer cells than by healthy cells. In this study, 940 women with dense breasts who were also at an increased risk of breast cancer were screened with both molecular breast imaging and mammography. Of 13 tumors detected in 12 patients, 88 tumors were found by molecular breast imaging alone, 1 by mammography alone, 2 by both techniques, and 2 by neither. After molecular breast imaging, 7.7% of the women needed followup testing compared with 9.4% who needed follow-up testing after mammography. Of the 36 biopsies prompted by molecular breast imaging, 27.8% were positive for cancer vs 17.6% of the 17 biopsies prompted by mammography. The investigators have continued to follow up the patients in the study and have determined that the sensitivity and specificity for molecular breast imaging were 75% and 93.2%, respectively. The sensitivity and specificity for mammography were 25% and 91.3%, respectively. “Mammography is the best tool we have . . . to screen for breast cancer, but it is not perfect and we clearly need to have better tools,” said Winer. Her2 status Another study could help oncologists provide the most appropriate targeted therapy for their patients. The work involved women with breast cancers classified as positive for the human epidermal growth factor receptor 2 (HER2), a characteristic found in about one-quarter of breast cancers. These cancers express excessive amounts of the HER2 protein. HER2-positive breast cancer generally responds well to the anti-HER2 monoclonal antibody trastuzumab, but a significant number of cases eventually stop responding to the treatment. The study's 143 patients, who were treated at the University of Texas M. D. Anderson Cancer Center in Houston, were given a combination of chemotherapy and trastuzumab before undergoing surgery. Half of the patients achieved a pathologic complete response, with no evidence of invasive disease in the breast or lymph nodes. The investigators then examined pretreatment and posttreatment tissue from 23 patients who did not have a pathologic complete response. They found that 30.4% of these tumors had converted from HER2-positive to HER2-negative status by the time of surgery. The researchers also found that patients whose tumors did not have a complete response to trastuzumab were approximately 3 times more likely to experience a recurrence than those whose tumors did exhibit a complete response. “We believe that consideration should be given to reassessing HER-2 status in the residual tumor of patients who do not achieve a pathologic complete response in order to identify those patients who could be enrolled in a clinical trial to further investigate the most appropriate adjuvant therapy in this population,” said Elizabeth Mittendorf, MD, an assistant professor in the department of surgical oncology at the M. D. Anderson Cancer Center and the study's lead author.

Fontanarosa, Phil B.;DeAngelis, Catherine D.;Wong, John E. L.

doi: 10.1001/jama.300.15.1750pmid: 18854527

Singapore—JAMA and the National University Health System, Singapore (NUHS), cohosted the first-ever JAMA-themed international conference on “Recent Trends in Diabetes, Obesity, and Metabolic Syndrome” on August 1-2 in Singapore. The conference featured state-of-the-science discussions on the latest developments and clinical implications of these disorders, presented by an international, multidisciplinary panel of experts in epidemiology, research, medicine, and surgery, all but one of whom have published articles on these topics in JAMA. Collaboration in singapore The conference was the product of the vision and collaboration of Catherine D. DeAngelis, MD, MPH, Editor in Chief, JAMA and Archives Journals, and John E.L. Wong, MBBS, Dean, Yong Loo Lin School of Medicine, NUHS. According to DeAngelis, the goal was for JAMA to “cohost a world-class conference addressing one of the foremost challenges facing health care today—the prevention, diagnosis, and treatment of obesity, diabetes, and the myriad complications associated with these diseases” that increasingly are affecting populations all over the world. Wong noted that it was especially appropriate for the conference to take place in Singapore, considering that with regard to public health, “Singapore may serve as a harbinger for other Asian countries.” In one generation, Singapore has moved from “third world” to “first world” in terms of significantly elevating the standard of living and health of the population. However, as Wong pointed out, this rapid transformation also has presented important health challenges, such as a 4-fold increase in diabetes prevalence (from 1.9% in 1975 to 8.2% in 2004), which has substantial implications for health care expenditures. In an opening address for the conference, Singapore's Minister for Health, Mr Khaw Boon Wan, highlighted trends and progress in advancing the health of Singaporeans, including a comprehensive system of universal health care that accounts for only approximately 4% of Singapore's gross domestic product (GDP) (compared with expenditures for health care approaching 16% of GDP in the United States), as well as plans for having an electronic health record for every Singapore citizen in the near future. Khaw also acknowledged the importance and timeliness of the conference in helping to focus attention on the increasing rates of diabetes and obesity among the Singapore population. Epidemiology and prevention Three keynote presentations focused on recent data on the epidemiology of obesity and diabetes, as well as new concepts involving childhood obesity. Katherine M. Flegal, PhD, from the Centers for Disease Control and Prevention's National Center for Health Statistics in Atlanta, presented findings showing the steady increase in weight of the population and illustrated the complex relationship of obesity and body weight to morbidity and mortality and the difficulty predicting health effects associated with population shifts in overweight and obesity. Barbara V. Howard, PhD, from MedStar Research Institute in Hyattsville, Md, and Georgetown University in Washington, DC, presented data showing the increasing prevalence of diabetes and cardiovascular disease (CVD) throughout the world, such that patients with diabetes, who have numerous metabolic changes that confer increased cardiovascular risk, now account for half of all hospital admissions for CVD in some regions of the world. David S. Ludwig, MD, PhD, from Children's Hospital Boston and Harvard Medical School, also in Boston, pointed out that excessive body weight is now the most common chronic medical condition affecting children, that the causes are multidimensional, and that the effectiveness of dietary interventions and behavioral change programs for preventing and treating childhood obesity are being increasingly undermined by a “toxic environment” of overly plentiful, readily available unhealthful foods. Early detection and assessment The importance of early detection and accurate assessment of patients with diabetes was emphasized in 3 keynote presentations. Christopher D. Saudek, MD, from Johns Hopkins University School of Medicine in Baltimore, described the various approaches for assessing glycemia in patients with diabetes and emphasized that self-monitoring of serum glucose levels and periodic measurements of hemoglobin A1c levels are the preferred methods to monitor glycemic control. E. Shyong Tai, MB, ChB, FRCP, Singapore Health Services and the National University of Singapore, presented data showing that major risk factors for diabetes in Asian populations are similar to risk factors for populations in developed countries but that there appear to be important ethnic differences in some population groups in Singapore, such as Chinese, Malays, and Asian Indians, in terms of susceptibility to diabetes, as well as the associated phenotypes and patterns of complications. Tien Yin Wong, PhD, FRCSE, from NUHS, described how such early retinal vascular changes as isolated retinopathy and changes in retinal vascular caliber are not only biomarkers of risk of developing diabetes but also predict microvascular and macrovascular risk and diabetes complications, including cardiovascular and kidney disease. Therapeutic approaches Four keynote presentations highlighted the scientific underpinnings of current strategies for management of obesity, diabetes, and metabolic syndrome. David R. Flum, MD, MPH, from the University of Washington in Seattle, and a JAMA Contributing Editor, described current techniques for surgical management of obesity and obesity-related conditions, highlighted the relative benefits of surgery vs nonsurgical approaches for patients with extreme obesity, and emphasized the need for comprehensive evaluation of the effectiveness, safety, and long-term outcomes associated with surgical approaches to obesity. Using a case-based format, Irl B. Hirsch, MD, from the University of Washington, provided a practical approach for treatment strategies in patients with type 2 diabetes, including the use of oral agents as well as the appropriate use of basal, prandial, and correction-dose insulin to achieve glycemic control and help avoid hyperglycemic and hypoglycemic episodes. Norman Nor Chan, FRCP, MD, from the Chinese University of Hong Kong, described the importance of translating research on management of type 2 diabetes into clinical practice in Asia, emphasized the importance of evidence-based protocols that are relevant to and feasible for local health care setting and cultures, and discussed the need for reorganization of existing health care systems to provide more effective chronic disease management strategies. Xavier Pi-Sunyer, MD, MPH, from Columbia University's College of Physicians and Surgeons in New York City, presented findings illustrating the relationship of body fat distribution with metabolic disorders and CVD risk, emphasizing that excess fat deposition intra-abdominally, in skeletal muscle, in liver, or in the pancreas significantly increases health risks. Future jama conferences The Singapore conference, which attracted attendees from Singapore and 9 other countries, included a poster session presenting original research studies on diabetes, obesity, and metabolic syndrome. It also featured 12 special-interest sessions in which conference faculty focused on specific topics, such as economics of diabetes, conducting research on obesity, and understanding the biomedical publication process. Future international JAMA-themed conferences of comparable content, quality, and interest are anticipated. According to DeAngelis, “this conference, sponsored completely by JAMA and NUHS with absolutely no input, financial or otherwise, from any for-profit company, can serve as a model for how continuing medical education should be conducted.”

Stephenson, Joan

doi: 10.1001/jama.300.15.1752-bpmid: N/A

Chinese health officials launched a nationwide probe last month to investigate tainted infant formula produced in China that had caused illness in thousands of infants. According to news reports, milk powder formula and other milk products from 22 of China's dairy companies had been contaminated with melamine, a chemical that can be used to disguise diluted milk by giving an inflated reading on a test for protein content of food. Chinese law enforcement officers confiscate milk powder in a probe of tainted formula that caused illness in thousands of infants. As of September 21, the Chinese Health Ministry reported that nearly 53 000 infants had fallen ill and nearly 13 000 infants had been hospitalized, many with kidney stones or kidney failure. At least 3 deaths had been attributed to the consumption of tainted formula. Xinhua, the state-run news agency, said the Sanlu Group, a major producer of powdered infant formula, began receiving complaints about sick infants as early as December 2007 but did not make it publicly known until last month. The US Food and Drug Administration said that no Chinese manufacturer has met the requirements to sell infant formula in the United States, but the agency was investigating whether the products were being sold in specialty markets that serve the US Asian community (http://www.fda.gov/bbs/topics/NEWS/2008/NEW01883.html).

Stephenson, Joan

doi: 10.1001/jama.300.15.1752-apmid: N/A

Two teams of scientists report they have identified new targets in bacterial pathogens that might facilitate the development of novel drugs active against antibiotic-resistant bacteria. One team, in Japan, discovered a novel genetic pathway that some bacteria, including Chlamydia and Helicobacter pylori, use to synthesize a molecule called menaquinone they need to survive (Hiratsuka T et al. Science. 2008;321[5896]:1670-1673). Because human cells and intestinal bacteria lack this pathway, it might be possible to develop new drugs that specifically target these pathogens. A second team of scientists, in England, synthesized a small molecule called PC190723 that stops bacteria from reproducing by binding to a protein called FtsZ (Haydon DJ et al. Science. 2008;321[5896]:1673-1675). They found that this molecule was potent against different strains of staphylococci, including methicillin-resistant Staphylococcus aureus; they also found that mice given a normally lethal dose of S aureus were cured with PC190723, suggesting that drugs targeting FtsZ might help expand the current arsenal of antibiotics.