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Spring 2014
BMM Current Issue
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Question
By Anonymous
Carbapenem-resistant Enterobacteriaceae, better known as CRE, is only the latest family of antibiotic-resistant bacteria to grab headlines. Though infections are still rare and mostly confined to health care facilities, they’re extraordinarily difficult to treat, with a mortality rate around 50 percent. Are these “superbugs” becoming unstoppable? If so, where do we go from here?

Leonard Mermel, DO, ScM, medical director of Rhode Island Hospital’s Department of Epidemiology and Infection Control and a professor of medicine, takes the question.
Answer
By Leonard Mermel, DO, ScM
CRE are resistant to most currently available antibiotics. Bacteria multiply in minutes. When a population of bacteria is exposed to antibiotics (for example, in someone’s GI tract), those with molecular mechanisms that convey resistance will have a competitive advantage.

We live in a world where humans and the animals we eat are exposed to untold tonnage of antibiotics. If the world is a Petri dish, bacteria such as CRE will rise to the fore and present a formidable challenge when infection strikes. We know from the few cases seen in Rhode Island that our therapeutic antimicrobial armamentarium is extremely limited to thwart such microbes.

What can be done? We must limit antibiotic use to those people who truly need them, based on objective criteria of active bacterial infections. This can be achieved by robust antibiotic stewardship programs that assure judicious antibiotic use in acute and chronic health care settings. Antibiotic use as growth promoters in animals should be illegal. Health care facilities must have stringent infection prevention and control programs to mitigate risk of CRE spread from patient to patient.

We must motivate industry to develop new antibiotics and other treatments—but this cannot be the main thrust of our efforts to deal with the multi-drugresistant microbial pathogens in our midst, because drug development will never keep pace with bacterial evolution. We must reduce evolutionary pressure as good stewards of antibiotic use, and support infection prevention programs and research that will afford us a better understanding of transmission dynamics of such pathogens so prevention strategies can be applied with maximum effect. The advent of CRE is a clarion call to arms. Now we must boldly meet the challenge.

Question
By Name withheld
Given the recent United States Preventive Task Force (USPTF) recommendations against prostate-specific antigen (PSA) screening, Brown Medicine asked Assistant Professor of Surgery (Urology) (Clinical) Joseph Renzulli what he advises patients regarding screening for prostate cancer. Renzulli is certified in robot-assisted surgery and is a member of the urology staff at The Miriam Hospital and Rhode Island Hospital.
Answer
By Joseph Renzulli, MD
Acknowledging the limitations of the PSA test, the urologic community continues to recommend PSA screening in men over 40 years of age with a life expectancy of greater than 10 years. Prostate cancer represents the most common malignancy in men. It is estimated that there will be 241,740 new diagnoses and 28,170 deaths from the disease in 2012. This confers a 16 percent lifetime risk of prostate cancer being diagnosed in an American male. However, during the past three decades there has been a measurable reduction in mortality from prostate cancer. This reduction in death can be directly correlated to the introduction of PSA as a screening modality.

The USPTF has concluded that screening does not improve survival and therefore cannot be advocated for as a screening test. The European screening trial has demonstrated that PSA screening increases the overall number of prostate cancer diagnoses. However, the men diagnosed with prostate cancer through a screening regimen experienced a 27 percent reduction in prostate cancer specific mortality. Further, the PIVOT* trial recently reported that there was no significant difference in observation versus radical prostatectomy at 10 years of follow up in the low risk prostate cancer group (Gleason 6) but, there was a 31 percent reduction in prostate cancer mortality demonstrated in the intermediate risk group (Gleason 7) treated with prostatectomy. Therefore, we believe the real issue is not whether prostate cancer should be diagnosed but truly which cancers should be treated and which should be actively observed.

By selecting the appropriate patients for screening and treatment lives will be saved.
Question
By Name withheld

A recent large-scale study of adolescents in the US showed that significant numbers of young males experience unhealthy weight control behaviors. How are eating disorders in males different than in females? Are there special considerations for this population? Diane Dermarderosian, medical director of Hasbro Children’s Hospital Partial Hospital Program and assistant professor (clinical) of pediatrics, sheds some light.

Answer
By Diane Dermarderosian

Males develop eating disorders more frequently than previously understood. While the prevalence is controversial, most recent estimates are that 1 in 4 patients with eating disorders is male. The epidemiology is difficult to characterize, but we know that in males, there is frequently a more significant delay between emergence of symptoms and initiation of treatment. Factors contributing to this include shame about diagnosis, inadequate screening by providers, and a delay in referral to appropriate treatment even when the diagnosis has been made.

Males and females share many risk factors and clinical characteristics. Eating disorders are an outward expression of and coping mechanism for emotional distress. The factors causing them include genetic, psychological, biological, familial, environmental, and social influences. They are associated with significant morbidity and mortality for both genders.

That said, males are susceptible to a range of different risks than females. They are often more concerned with shape than weight, looking to optimize lean muscularity with minimal body fat. They tend to increase exercise rather than restrict calories. Risks include a history of being teased for childhood obesity, a desire to improve sports performance, an attempt to avoid medical illness, and an effort to improve a gay relationship. Exercise and athletic competition represent a particular risk. Although being gay increases the risk due to rigid sociocultural body image ideals, most men with eating disorders are not gay or bisexual.

While there is limited research about males and eating disorders, studies suggest that the prognosis is equal to or better than for females. The key to optimizing prognosis for all patients is prompt and comprehensive treatment. The core treatment principles for males and females include nutritional rehabilitation, medical stabilization, and psychological support to promote behavioral change. Establishing “male-only” support groups is key.

Question
By Anonymous

Last fall, biotech company Sequenom began marketing MaterniT21, a prenatal screening test for trisomy 21, or Down syndrome. Professor Jacob Canick, PhD, and Associate Professor (Research) Glenn Palomaki, PhD, in the Division of Medical Screening and Special Testing in the Department of Pathology and Laboratory Medicine at Women & Infants Hospital, published their study of the test in the journal Genetics in Medicine. In 1988, Canick and Palomaki were involved in the development of prenatal triple marker screening, which is now used throughout the world.

How does the new DNA-based screening test for Down syndrome work and who might take advantage of it?

Answer
By Professor Jacob Canick, PhD, and Associate Professor (Research) Glenn Palomaki

The test extracts the small fragments of maternal and fetal DNA that circulate in the mother’s blood. The DNA is analyzed, looking for a slight increase in the proportion of DNA fragments derived from chromosome 21, which signals Down syndrome. In our study, the test identified 98.6 percent (209/212) of the Down syndrome pregnancies, while only 0.2 percent of the normal pregnancies were mistakenly called positive. The mothers included in the study sample were all at high risk for having a child with Down syndrome—they were older than 38 years of age, had had abnormal ultrasound findings, or abnormal results for one of the maternal serum screening tests that are currently used.

The problem with current prenatal tests for Down syndrome is the false positive rate of 2 to 5 percent needed to identify about 90 percent of cases. After a positive screening result, pregnant women are offered either amniocentesis or chorionic villus sampling. These are diagnostic tests that will reliably identify any genetic anomalies in the fetus, but both are invasive procedures that carry about a 1 in 200 risk for fetal loss. With the new DNA-based test the number of these procedures is dramatically reduced because it would be unusual to have a woman originally at high risk who also has a positive DNA test have a normal pregnancy.

Right now, the DNA test is complex, resource intensive, and has not been validated as a primary screening test for every pregnant woman. But for women at high risk, it’s an effective tool that will prevent unnecessary procedures while maintaining high detection.
Question
By Bryan, Charlotte, NC
A recent study in Annals of Plastic Surgery found that while many who suffer from body dysmorphic disorder (BDD) seek cosmetic procedures, only 2 percent of procedures actually reduced its severity. Yet physicians continue to provide requested surgeries to people suffering from BDD. Should they? Katharine A. Phillips, professor of psychiatry and human behavior, director of the Body Dysmorphic Disorder Program at Rhode Island Hospital, and author of Understanding Body Dysmorphic Disorder: An Essential Guide, shares her thoughts.
Answer
By Katharine Phillips, MD
People with BD believe they look ugly or deformed when in fact they look normal. BDD is a common and severe disorder characterized by distressing or impairing preoccupation with nonexistent or slight defects in one’s physical appearance (e.g., perceived skin scarring, a “large” nose, or perceived balding). Compulsive behaviors (e.g., excessive mirror checking, excessive grooming) are common. People with BDD typically experience marked impairment in functioning, and suicidal thinking and behavior are common.

A majority of people with BDD receive cosmetic treatment for the defects they perceive— most often, dermatologic and surgical. These treatments appear to virtually never effectively treat BDD. Following cosmetic treatment, some BDD patients become even more distressed over their appearance. In a survey of cosmetic surgeons, 40 percent said they had been threatened legally and/or physically by a dissatisfied patient with BDD. Lack of improvement with cosmetic treatment isn’t surprising, because BDD involves distorted body image and a tendency to obsess about minor or nonexistent flaws.

Physicians are advised not to provide cosmetic treatment to people with BDD. Fortunately, serotoninreuptake inhibitor medications (antidepressant medications with anti-obsessional properties) and cognitive-behavioral therapy that specifically targets BDD are often effective for this disorder.
Question
By Karen, Coventry, RI
In March the Centers for Disease Control and Prevention released a report showing that cesarean deliveries rose 53 percent from 1996 to 2007 and now comprise a third of all deliveries. In Rhode Island, however, the number of c-sections rose by 82 percent, far more than the national average. Katharine D. Wenstrom, MD, professor of obstetrics and gynecology and director of the Division of Maternal-Fetal Medicine at Women & Infants Hospital, and Dwight J. Rouse, MD, professor of obstetrics and gynecology and a maternal-fetal medicine specialist, explain.
Answer
By Katharine D. Wenstrom, MD, and Dwight J. Rouse, MD
Although the rate of increase in the proportion of births by cesarean in Rhode Island did outpace the national rate of increase over this time period, this is because Rhode Island’s cesarean rate in 1996 was well below the national average (17.7 percent versus 21 percent). Since then, Rhode Island’s rate of cesarean delivery has caught up with rates around the nation and currently is fairly typical: in 2007 it was 32 percent, the same as the national rate. The cesarean rate varies considerably across the United States; it is lowest in Utah (22 percent) and highest in New Jersey (38 percent).

Clearly, the threshold for performing a cesarean delivery has decreased, and the myriad reasons for this include near universal cesarean delivery for fetuses in breech presentation, much wider utilization of labor induction (which increases the risk of cesarean), much lower rates of attempted vaginal birth after cesarean delivery, medical liability concerns (alleged failure to perform a timely cesarean delivery is a leading reason for medicolegal action against obstetricians), a heavier obstetric population (overweight and obese women are more likely to have abnormally progressive labor), and an acceptance of the concept of “patient choice cesarean” or cesarean with no medical indication.
Question
By Rick, Simi Valley, CA
Last January, the Journal of the American Medical Association (JAMA) published a study that concluded that for mild to moderate depression, most antidepressants are not more effective than placebos. Dr. Peter Kramer, clinical professor of psychiatry and human behavior and the author of Listening to Prozac and Against Depression, offers his perspective. What would you advise doctors whose patients have been taking antidepressants for mild to moderate depression? Should they discontinue the treatment on the assumption that the drugs are acting only as placebos?
Answer
By Peter Kramer, MD
The JAMA report is a meta-analysis, a statistical integration of individual research trials – in this instance, studies of antidepressant efficacy.

The mainstream press broadcasted the report’s conclusions—that medications’ utility “may be minimal or nonexistent, on average, in patients with mild or moderate symptoms”—as if they were decisive. But it is important to remember that meta-analyses are themselves experiments, limited by the choices researchers make as they prepare to combine data from existing studies.

Here, the authors began with 2164 research reports that they might have analyzed. The criteria that the researchers adopted caused them to discard all but six studies. Three involved imipramine, an older antidepressant, and three, paroxetine (Paxil). The winnowing was idiosyncratic. Because antidepressants have repeatedly been shown to work for chronic minor depression, the researchers chose to ignore studies targeting that condition. Also, many outcome trials begin with a washout period in which subjects who recover in a week or two are dropped, on the grounds that they do not really have the condition under study or they respond too readily to placebo. Washouts are especially important because of a problem called “rater inflation”; in their eagerness to enroll subjects and full up a study quickly, researchers may exaggerate subjects’ symptoms at intake; as a result, rapid apparent recoveries are common among the subjects with few initial symptoms. Since their interest was in placebo responses, the JAMA authors excluded studies with a washout phase. It is thus not surprising that in the handful of remaining studies, the scientists found strong placebo responses (along with strong medication responses) in less ill subjects. Among more severely ill patients, it was harder to find placebo effects, but the medication effects continued to be apparent. This pattern is the one that was summarized in the finding that medications had been shown to outperform placebos only in severely ill patients.

The conclusion that antidepressants work for severe acute depression and mild chronic depression but uniquely not for mild acute depression is one that would require further explanation. The JAMA study should serve as a stimulus to additional meta-analyses and, ideally, to clinical trials designed specifically to look how well or poorly antidepressants work in people with different levels of acute depression. In themselves, the JAMA findings should not transform clinical practice—although it is important to add that the broader literature and clinical consensus suggest that doctors should consider psychotherapy, alone or in combination with medications, in the treatment of minor depression.
Question
By Mary, Coventry, RI
What are you advising your patients in light of the government advisory panel guidelines?
Answer
By Robert Legare, MD, director of the Breast Health Center at Women & Infants
Acknowledging the limitations of mammography, we continue to recommend screening beginning at age 40 because this remains our best tool for early detection and successful treatment of breast cancer. In fact, screening mammography is a principal reason the U.S. breast cancer mortality rate has steadily declined since 1990. Annual mammographic screening realizes maximum effect in women aged 50 to 74, but most research indicates at least a 15 percent reduction in mortality in women aged 40 to 49. Women with personal risk factors or family history should begin screening at least at 40. If women delay mammography to age 50, there will definitely be delays in diagnosis which will impact survival. Mammography’s risk in younger women is “false positive” results that lead to additional imaging, needle biopsy, and more frequent follow up. This may add to some women’s anxiety, but may reassure others. We hope the recommendations continue to increase dialogue on the benefits and limitations of screening and acknowledge a great need for more effective screening approaches.
Question
By Joe K., Seattle
I am a health care provider. How can I reduce my risk of illness from swine-origin H1N1 influenza (S-O H1N1) virus?
Answer
By Leonard Mermel, DO, Professor of Medicine
Although many Americans have been affected by S-O H1N1, there’s not enough herd immunity to circumvent resurgence in the fall. To date, there does not appear to be any evidence of increasing virulence in the Southern Hemisphere where the virus is now spreading nor is there evidence of widespread oseltamivir (Tamiflu) resistance as of this time.
• All those with direct patient care responsibilities should, in my opinion, be required to receive both the seasonal flu vaccine and S-O H1N1 vaccine.
• Patients calling your office should be encouraged to stay home if their influenza-like illness (ILI) symptoms are mild. A voice mail message as such may be helpful.
• Patients coming to your office with ILI should be encouraged to put on a procedure or surgical mask and clean their hands upon entering the waiting room. This can be done using a cough etiquette station with appropriate signage in the waiting room (see CDC web site for educational information to put on/near the cough etiquette station). Masking of patients with ILI will reduce transmission risk. If you’re able to separate your waiting room with those with and without ILI that would be ideal. Also, spacing chairs at least 3 feet apart in the waiting room would help mitigate risk of transmission.
• Anyone within 6 feet of patients with ILI should adhere to Droplet Precautions: wear a procedure or surgical mask and scrupulous attention to hand hygiene. Eye protection should either be worn whenever within 6 feet of patients with ILI or if mucous membrane exposure to their respiratory secretions is anticipated. Your wearing a mask is particularly important if your patient with ILI (e.g., a 2-year-old or a confused/combative adult) is unable to keep a mask on during their visit.
• Minimizing potential aerosol-generating/cough-inducing procedures (e.g., jet nebulizer use; high-flow oxygen mask use; open airway suctioning; sputum induction; bronchoscopy) will also reduce risk of transmission. If such procedures must be done, they should be done with respiratory protection consisting of wearing an N95 respirator and eye protection or use of a PAPR and appropriate room ventilation. Crash carts in the office should also be stocked with such respiratory protection.
• A large number of U.S. health care workers who have so far been infected by S-O H1N1 acquired their illness from an ill colleague. Thus, if you have ILI symptoms stay home and don’t go to work.
It will be important to stay up to date with S-O H1N1 recommendations by checking the RI Department of Health web site on a regular basis http://www.health.ri.gov/news/flu/index.php. A pragmatic approach as noted above will reduce the risk of illness.
Question
By Marilyn M., Hilton Head
What are the risks involved in assisted reproductive technology, and how can they be avoided?
Answer
By Professor of Obstetrics and Gynecology John E. Buster
A possible outcome of assisted reproductive technology (ART) is high-order multiple births. But this problem can and should be avoided.

To overcome fertility problems with IVF, the ovary is stimulated to make multiple eggs, which are then fertilized in the laboratory. To make sure that a pregnancy occurs, there is a temptation to put in as many eggs as possible, but this is a delicate balance. We want to make sure couples have the best chance at pregnancy but also decrease the risk for multiples, which come with significant increased risks to the health of the mother and the outcome of the pregnancy.

Advances in laboratory methods and clinical protocols enable us to freeze better quality embryos and place fewer embryos. National standards about the number of embryos transferred – based on a patient’s age and her medical condition – have been set by the American Society for Reproductive Medicine and the Society of Assisted Reproductive Technology. Standards have also been set for careful monitoring of ovarian stimulation with drugs to prevent both complications and multiple pregnancy.

A new technique called in vitro maturation (IVM) enables specialists to recover and mature eggs without fertility drugs. This makes it possible to treat infertile women whose ovaries over-respond to fertility drugs and who have serious problems achieving pregnancy with standard IVF.
 
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