• FDA looks to reduce use of Unapproved Animal Drugs
aka Compounded Medications Docket No. FDA-2010-N-0528
• Storytelling to Improve Blood Pressure
• FDA Approves Drug to Prevent Preterm Delivery
• Behavioral Therapy Alleviates Chronic Insomnia
• Impaired Balance After Taking Zolpidem (Ambien®)
• Sun Exposure Decreases Risk for Multiple Sclerosis
• Stroke Prevalence Rising in Young Adults and Children
• Topical Botulinum Toxin for Wrinkles
• Prenatal Exposure to Diagnostic X-Rays Associated with Nonsignificant Increase
in Pediatric Cancers
• The Inside Scoop on the Wakefield Fiasco
• Omega-3 Blocked Key Blindness Cause
• Safety of Tamoxifen vs. an Aromatase Inhibitor as Adjuvant Therapy for Breast Cancer
• Influence of Subspecialty Care on Survival in Women with Endometrial Cancer
• Male Circumcision for Preventing Transmission of Human Papillomavirus to Women
• Vitamin D and Cancer Mortality: Not to Be Taken Lightly
PLEASE ACT NOW ON THIS IMPORTANT ISSUE
FDA looks to reduce use of Unapproved Animal Drugs aka Compounded Medications
Docket No. FDA-2010-N-0528
AVMA disapproves of time allotment
Comments Not Accepted after Friday, February 18!
Compounded medicines = Unapproved Animal Drugs. According to Wade Siefert, RPh of Preckshot Professional Pharmacy (Peoria IL) and faithful annual exhibitor at the ISVMA’s annual conventions, the FDA defines all compounded medications – as well as the extra-label use of commercially available products – to be “unapproved” animal drugs.
On December 20, the FDA published a request for comments in the Federal Register on Unapproved Animal Drugs. For veterinarians who rely upon custom preparations of medicines using Active Pharmaceutical Ingredients, or bulk ingredients, speak up and be counted. The FDA wants only FDA-approved finished products to be used in veterinary products; they’re concerned that the safety and effectiveness of animal drug products marketed in the US without FDA approval has not been demonstrated.
As stated in the Federal Register, the types of unapproved animal drugs marketed include, but are not limited to: injectable vitamins; various topical solutions, shampoos, and liniments; electrolyte and glucose solutions; and antidotes. In addition, there are a variety of anti-infective and other animal drug products marketed for use in a variety of animal species.
The FDA affirms that many unapproved animal drugs are, and some continue to be, the standard of care in treating animals,
and some are essential to protecting animal health and ensuring an adequate food supply; however, they are seeking ways to increase the number of approved animal drugs to minimize the “unapproved” drugs used for animals.
“The FDA’s intended actions will eliminate most of the veterinary compounding that takes place currently in this country,”
says Siefert, who is also Vice President of the The International Academy of Compounding Pharmacists. “Treatment options will be mostly eliminated, and the quality of medications that could still be prepared would be negatively impacted severely.”
Siefert learned of the notice published by the FDA just this week, and was astonished that the opportunity for comments was so limited. So is the AVMA. On December 28 an official request was made by the AVMA to extend the comment period.
(To access the AVMA’s official correspondence, go to www.regulations.gov/#!documentDetail;D=FDA-2010-N-0528-0012.)
In his letter to the Division of Dockets Management, Executive Vice President of the AVMA W. Ron DeHaven emphasizes this brevity of opportunity. “We believe that the notice, which seeks to explore possible new mechanisms that would increase the number of approved or otherwise legally marketed animal drugs, warrants thoughtful consideration due to the complexity of the subject matter.”
Post a comment online BEFORE FRIDAY, FEBRUARY 18, 2011 when the comments window closes. Let the FDA know how additional limits placed on veterinary compounding from commercially-available, finished drug products will impact the ability to effectively treat, and the quality of care administered to, the animals requiring medical care.
Open the link at http://www.regulations.gov/#!submitComment;D=FDA-2010-N-0528-0001 today.
FDA is soliciting public comment on potential actions the Agency can take to help achieve the goal of obtaining legal marketing status, as appropriate, for unapproved animal drugs that are currently being marketed in the United States.
The Agency asks that comments be as detailed as possible.
FDA is also specifically requesting comments and information on the questions and subjects below.
1. Monographs: Certain over-the-counter (OTC) drugs for humans are marketed under monographs that establish the conditions under which these drugs are generally recognized as safe and effective and not misbranded. The monographs specify active ingredients, dosage forms, product strengths, indications for use, labeling, and other conditions.
Does published literature of sufficient quality exist for some currently marketed unapproved animal drugs such that monographs might be a feasible approach? For which drugs might this be feasible? What are the attributes that make the published literature suitable for this purpose? What criteria should be used to determine whether an animal drug is potentially suitable for a monograph to ensure that quality, safety and effectiveness would not be compromised in the absence of premarket review?
2. Use of Publicly Available Information:
In some cases, human prescription drugs have been approved and marketed after FDA reviewed the existing
literature and data regarding a particular drug or class of drugs.
Does published literature of sufficient quality exist for some animal drugs that could be used to support safety
and effectiveness evaluations for these currently unapproved marketed drugs? For which drugs might this be feasible?
What attributes make published literature of sufficient quality to contribute to such an evaluation?
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Ann Intern Med 2011 Jan 18; 154:77
Storytelling to Improve Blood Pressure
Benefits of a culturally appropriate storytelling intervention were similar to those of antihypertensive drugs.
Can patient-to-patient storytelling, i.e., narrative communication, help to lower blood pressure? In this study of hypertensive black patients in Alabama, researchers identified patients in focus groups who clearly and persuasively described their experiences with hypertension; selected patients served as storytellers on DVDs and offered lessons about how to interact with physicians and how to achieve better medication adherence, diet, and exercise. The 231 study participants randomly received either the storytellers' DVDs or DVDs about general health issues unrelated to hypertension. Intervention patients spent an average of 88 minutes watching the storytellers' DVDs.
Patients in both groups who had controlled hypertension at baseline exhibited no significant changes in blood pressure 6 to 9 months later. However, intervention patients with uncontrolled hypertension at baseline exhibited significant reductions in mean blood pressure — 15 mm Hg systolic (vs. 3 mm Hg in controls) and 3 mm Hg diastolic (vs. no change in controls).
Comment: In this randomized trial, storytelling by black patients for black patients achieved dramatic reductions in blood pressure — 15 mm Hg systolic and 3 mm Hg diastolic relative to controls. With this approach, the authors note, "listeners may be influenced if they actively engage in a story, identify themselves with the storyteller, and picture themselves taking part in the action." The magnitude of the effect is similar to that of antihypertensive medications. If the study can be replicated and if the benefits are sustained over time, the intervention would be a substantial achievement — one that would also force us to reevaluate how we deliver messages to our increasingly diverse patient populations.
— Jamaluddin Moloo, MD, MPH Published in Journal Watch General Medicine February 10, 2011
Citation: Houston TK et al. Culturally appropriate storytelling to improve blood pressure: A randomized trial. Ann Intern Med 2011 Jan 18; 154:77. (http://www.annals.org/content/154/2/77.long)PMID: 21242364
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http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm242234.htm
FDA Approves Drug to Prevent Preterm Delivery
Hydroxyprogesterone caproate (Makena) has been approved to reduce the risk for preterm delivery, the FDA announced.
The drug is intended for women with a singleton pregnancy who have had at least one spontaneous preterm delivery. It is not approved for women with a multiple pregnancy or other risk factors for preterm delivery.
Makena is injected into the hip once a week, beginning at 16 weeks of pregnancy and up to 21 weeks. In a trial of some 460 women, rates of delivery before 37 weeks were 37% in women randomized to Makena and 55% in controls. A follow-up study showed no developmental differences between children born to mothers in the two groups.
Reported side effects include pain, swelling, and itching at the injection site and hives, nausea, and diarrhea. Serious adverse reactions were uncommon: one case each of infection at the injection site and pulmonary embolism.
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Arch Intern Med 2011 Jan 24
Behavioral Therapy Alleviates Chronic Insomni
Behavioral therapy is effective but not widely available
As many as 30% of patients in primary care practices report difficulty falling asleep or maintaining sleep. Brief behavioral therapies are effective for alleviating sleep problems but are difficult to standardize and disseminate, especially in patients with medical comorbidities.
To test the effect of behavioral intervention in this population, researchers randomized 82 older adults (mostly white women; mean age, 72; mean comorbidities, 6) to receive brief behavioral therapy or basic sleep information (control). The intervention focused on (1) reducing amount of time in bed, (2) getting up at the same time every day, (3) going to bed only when sleepy, and (4) staying in bed only when asleep. The therapy group received 2 hours of counseling that was delivered in person and in telephone sessions during 3 weeks by a nurse practitioner who was not trained in sleep medicine.
At 4 weeks, sleep parameters (including sleep quality, sleep onset latency, wakefulness after sleep onset, and sleep efficiency) were significantly better in therapy patients than in controls. Total sleep time was similar between therapy and control patients. Fifty-five percent of intervention patients and 13% of controls no longer met insomnia criteria at 4 weeks.
Comment: According to these findings, only two or three patients would need brief behavioral therapy to achieve benefit in one patient. This highly effective intervention — provided by a nurse without specialized sleep medicine training — is not widely available. However, these compelling results argue for further development of this approach and for testing its value in less-controlled practice-based trials.
— Thomas L. Schwenk, MD Published in Journal Watch General Medicine February 10, 2011
Citation(s): Buysse DJ et al. Efficacy of brief behavioral treatment for chronic insomnia in older adults. Arch Intern Med 2011 Jan 24; [e-pub ahead of print]. (http://dx.doi.org/10.1001/archinternmed.2010.535)
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J Am Geriatr Soc 2011 Jan; 59:73
Impaired Balance After Taking Zolpidem (Ambien®)
The effect was particularly striking among older adults.
Injurious falls among older patients often occur in the middle of the night. In this study, conducted in a sleep laboratory, researchers examined whether the commonly prescribed hypnotic drug zolpidem (Ambien and generics) impairs balance and cognition when sleep is interrupted.
Eleven younger (mean age, 22) and 12 older (mean age, 67) participants all received 5-mg bedtime doses of zolpidem on one occasion and placebo on another occasion, in random order. After 2 hours of sleep, participants were awakened and asked to perform tandem walking on a balance beam; stepping off the beam was deemed a failed test. One young adult failed the balance test after placebo, and three failed after zolpidem. No older adults failed the balance test after placebo, but 7 of 12 failed after zolpidem. On brief cognitive tests — also administered after participants were awakened in the middle of the night — performance was worse after zolpidem than after placebo in both age groups.
Comment: Not surprisingly, zolpidem impaired balance and cognition when sleep was interrupted 2 hours after bedtime dosing; the effect on balance was particularly striking among older people. Although many elders perceive benefit when they take hypnotic drugs for insomnia, this study reminds us of the potential perils of that practice.
— Allan S. Brett, MD Published in Journal Watch General Medicine February 8, 2011
Citation(s): Frey DJ et al. Influence of zolpidem and sleep inertia on balance and cognition during nighttime awakening: A randomized placebo-controlled trial. J Am Geriatr Soc 2011 Jan; 59:73. (http://dx.doi.org/10.1111/j.1532-5415.2010.03229.x)PMID: 21226678
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Neurology 2011 Feb 8; 76:540
Sun Exposure Decreases Risk for Multiple Sclerosis
A convergence of survey, examination, and biological data further implicates sunlight as a factor
Several lines of evidence suggest that relative reductions in both sunlight exposure and vitamin D levels are associated with increased risk for multiple sclerosis (MS). In this case–control study, researchers examined sun-exposure factors in 216 patients with a first demyelinating event (FDE) and 395 controls from across regions of Australia ranging from latitudes 27°S to 43°S. Participants completed a validated questionnaire that quantified lifetime sun exposure, and they provided serum samples for vitamin D measurement. Examination data included skin and eye color, ethnicity, nevi count, melanin density in a non–sun-exposed site, and estimates of actinic skin damage. The researchers estimated lifetime ambient ultraviolet (UV) light exposure from residence and ozone satellite map data and from reported leisure-time sun exposure from age 6 years through the previous 3 years.
Higher self-reported sun exposure and greater actinic damage were each associated with significantly reduced risks for an FDE after adjustments for physical activity, smoking, history of mononucleosis, and melanin density. Patients with an FDE had lower serum vitamin D levels despite taking more vitamin D supplements than controls in the previous year. The annual incidence of FDE ranged from 2.1 per 100,000 people at 27°S to 8.7 per 100,000 at 43°S. The authors estimated that 32% of the latitudinal gradient was explained by a combination of serum vitamin D, lifetime leisure-time UV dose, and skin melanin density.
Comment: The attention to detail in the study is impressive, and the sum is greater than its parts. For instance, incident case patients were interviewed and examined by a neurologist close to diagnosis to insure the disease was asymptomatic before presentation. This process reduced self-report bias from recall and disease effects. Moreover, numerous measurements estimated sunlight exposure in a large number of participants from a region with notable variation in latitude. These findings lend further support for roles of both sunlight and vitamin D in MS risk, but the relationship is complex and may also involve genetic factors. Although telling our patients to sunbathe and take megadose vitamin D would be premature, longitudinal studies may provide insights into whether UV exposure is associated with a more favorable disease course.
— Robert T. Naismith, MD Published in Journal Watch Neurology February 7, 2011
Citation(s): Lucas RM et al. Sun exposure and vitamin D are independent risk factors for CNS demyelination. Neurology 2011 Feb 8; 76:540.
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http://www.newsroom.heart.org/index.php?s=43&item=1250
Stroke Prevalence Rising in Young Adults and Children
The number of hospitalizations for acute ischemic stroke is dramatically increasing among people under age 35, according to CDC research presented at the International Stroke Conference.
In males aged 15 through 34, the prevalence of hospitalizations for stroke increased by over 50% (9.8 to 14.8 per 10,000 hospitalizations) from 1994 to 2007. Among women in this age group, the increase was 17%.
The increases were still noticeable when broken down into smaller age groups (36% increase in boys and 31% increase among girls aged 5 to 14 years). Researchers were not certain what is behind the trend in children, but better detection of ischemic stroke with MRI may play a role and "the role of obesity and hypertension will prompt a big discussion," said study author Xin Tong in a conference interview.
In the same study, researchers found that stroke rates were declining among middle-aged and older patients.
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Dermatol Surg 2010 Dec; 36:2111
Topical Botulinum Toxin for Wrinkles
No need to frown if you don't like needles.
Botulinum toxin A (BTX-A) injection is the most popular cosmetic procedure in the U.S. The main medical limitations of BTX-A treatment include the need for injection and the resultant bruising. In this randomized, double-blind, repeat-dose, placebo-controlled, manufacturer-sponsored study, a topical BTX-A preparation (RT001) was applied under occlusion for 30 minutes to the crow's feet of 19 subjects, and placebo ointment was applied to the crow's feet of another 17 subjects. The treatments were repeated at 4 weeks. The degree of improvement was assessed in patients at rest on a 5-point wrinkle scale at 4 and 8 weeks after the first treatment.
At 4 and 8 weeks, 95% of RT001 subjects had at least a 1-point improvement in their wrinkle score, compared with only 15% of placebo subjects. Improvement of at least 2 points was noted in 29% of RT001 recipients at 4 weeks and in 50% of RT001 recipients at 8 weeks, compared with none of the placebo recipients. On self-ratings at 8 weeks, 84% of the RT001-treated subjects and 41% of the placebo-treated subjects rated their crow's feet to be improved. All comparisons were statistically significant. There were no treatment-related adverse events.
Comment: Topical BTX-A produced a significant therapeutic benefit for crow's feet. Whether it would be effective in areas of thicker skin and deeper muscles, such as the glabella or glabrous skin, remains to be seen. If this preparation receives FDA clearance, it may make BTX-A treatment accessible to patients who do not like needles or the associated discomfort. It could dramatically change the way BTX-A treatment is delivered, certainly moving it from the dermatologist's office and possibly even from under physician supervision. If not used correctly, however, very large doses of BTX-A could be delivered with adverse consequences or undesired therapeutic effects.
— George J. Hruza, MD Published in Journal Watch Dermatology February 11, 2011
Citation(s): Brandt F et al. Efficacy and safety evaluation of a novel botulinum toxin topical gel for the treatment of moderate to severe lateral canthal lines. Dermatol Surg 2010 Dec; 36:2111 . (http://dx.doi.org/10.1111/j.1524-4725.2010.01711.x)
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BMJ 2011; 342:d472 doi: 10.1136/bmj.d472 (Published 10 February 2011)
Prenatal Exposure to Diagnostic X-Rays Associated with Nonsignificant Increase in Pediatric Cancers
A BMJ study suggests a slightly — albeit nonsignificant — increased risk for childhood cancer from diagnostic x-rays in utero and in early childhood.
Researchers assessed prenatal and early childhood exposure to radiation and ultrasounds through parental interviews and medical records of some 2700 children with cancer and 4900 age- and sex-matched controls in the U.K.
They found a modestly increased risk for all cancers after prenatal exposure to x-rays, but this result was not statistically significant. Similarly, they found a nonsignificant increase in cancer risk after exposure to diagnostic radiography in early infancy (0 to 100 days). With radiographs in early infancy, the risk for lymphoma reached statistical significance, but it was only based on seven cases. Ultrasound scans were not associated with cancer.
The authors conclude that their results, "which indicate possible risks of cancer from radiation at doses lower than those associated with computed tomography scans, suggest a need for cautious use of diagnostic radiation imaging procedures to the abdomen/pelvis of the mother during pregnancy and in children at very young ages."
http://www.bmj.com/content/342/bmj.d472.full
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BMJ 2011 Jan 5; 342:c5347
The Inside Scoop on the Wakefield Fiasco
A journalist's investigation of how the falsification of a vaccine–autism link was perpetrated and perpetuated.
In 1998, Andrew Wakefield and colleagues published a now discredited paper in the Lancet that described 12 children with a syndrome of regressive autism and gastrointestinal disorders and linked it to the patients' recent receipt of the measles, mumps, and rubella (MMR) vaccine. Since that time, multiple large studies have shown no association between MMR and autism, and, as a result, the original paper has been retracted, first by several coauthors and eventually by the Lancet. The British General Medical Council (GMC) has erased Wakefield and one of his coauthors from the medical register. Unfortunately, the publicity surrounding Wakefield's initial claim was extraordinarily effective in fueling the antivaccine movement before the fraud was fully brought to light.
Journalist Brian Deer has just published a three-part series in the British Medical Journal detailing the history of this debacle. The first article highlights some of the more egregious errors in the ethics and science of the work itself and the lack of oversight at the Royal Free Hospital. A review of the 12 pertinent medical records shows that the data in Wakefield's original article cannot be verified. The patients were subjected to multiple unnecessary procedures, many patients were referred by antivaccine activist groups, and the work was largely sponsored by a lawyer involved in antivaccine litigation. The second article details financial conflicts of interest and Wakefield's failed attempt to fund a business that would develop a "safe" vaccine, test bowel tissue with polymerase chain reaction, and patent a diagnostic test for Crohn disease. The final chapter reports about the lengthy investigation carried out by the Lancet (from 2004 to 2010) after Deer first presented evidence of this widespread deception to the editor, Richard Horton.
Comment: This series, along with accompanying editorials should be mandatory reading for medical students and for any practitioner involved in patient-related research. It highlights the importance of (1) personal responsibility, (2) mandatory safety and patient-protection policies, and (3) reporting all conflicts of interest. For all of us, another key take-home message is to always consider the biological plausibility of a result and the need to verify the unexpected. In this instance, there were many clues along the way — we just needed to see them.
— Peggy Sue Weintrub, MD Dr. Weintrub is on the Speakers' Bureau for Merck & Co., Inc
Published in Journal Watch Pediatrics and Adolescent Medicine February 9, 2011
Citation(s): Deer B. How the case against MMR vaccine was fixed. BMJ 2011 Jan 5; 342:c5347. (http://dx.doi.org/10.1136/bmj.c5347)PMID: 21209059
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Article from Vital Choices Newsletter
(http://newsletter.vitalchoice.com/e_article002016958.cfm?x=bj5Gvnb,b1h1R7NC)
February 10, 2011
Omega-3 Blocked Key Blindness Cause
Mouse study supports epidemiological and clinical studies and reveals key mechanisms by which omega-3 DHA prevents vascular overgrowth in the macula by Craig Weatherby
Four years ago, a team at Children’s Hospital Boston published a mouse study showing that omega-3 DHA from fish oil retards a leading cause of blindness called retinopathy. A follow-up study from the same researchers reveals exactly how omega-3s provide protection against retinopathy (Sapieha P et al 2011). The results also provide reassurance that widely used non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin and ibuprofen don’t blunt omega-3 DHA’s apparent preventive powers. Retinopathy is caused by a proliferation of tortuous, leaky blood vessels in the retina, and it counts as a leading cause of blindness.
Study finds omega-3 DHA rebuffs retinopathy in mice
Vascular overgrowth in the retina affects 4.1 million Americans with diabetes – a number expected to double over the next 15 years – and many premature infants. Another 7 million-plus Americans have age-related macular degeneration (AMD), whose blinding “wet” form is typically caused by the same kind of abnormal blood vessel growth.
“The ability to prevent these ‘neovascular’ eye diseases with omega-3 fatty acids could provide tremendous cost savings”, said Children’s Hospital ophthalmologist Lois Smith, MD, PhD, senior investigator on the study (CHB 2011). “The cost of omega-3 supplementation is about $10 a month, versus up to $4,000 a month for anti-VEGF therapy,” she noted, referring to drugs such as Macugen and Lucentis used in AMD and diabetic retinopathy. “Our new findings give us new information on how omega-3s work that makes them an even more promising option.”
Boston team pinpoints one source of DHA’s anti-blindness effect
In the new study, the Boston group detected a new protective mechanism – namely, a direct effect on blood vessel growth (Sapieha P et al. 2011). Amazingly enough, omega-3 DHA selectively promoted the growth of healthy blood vessels and inhibited the growth of abnormal vessels. In addition, Smith and colleagues isolated both the DHA metabolite (4-HDHA) that exerts these beneficial effects and the enzyme that produces it, called 5-lipoxygenase or 5-LOX. They showed that the COX enzymes involved in inflammation-related pain are not involved in omega-3 breakdown … which suggests that the aspirin and other NSAIDs taken by millions of Americans daily should not interfere with omega-3 DHA’s eye benefits. "This is important for people with diabetes, who often take aspirin to prevent heart disease, and also for elderly people with AMD who have a propensity for heart disease," says Smith (CHB 2011). (An asthma drug called zileuton does interfere with 5-LOX and could negate the benefits of omega-3 DHA.) Finally, the study demonstrated that 5-LOX acts by activating the PPAR-gamma receptor, the same receptor targeted by “glitazone” drugs such as Avandia, taken by diabetics to increase their sensitivity to insulin. Since these drugs also increase the risk for heart disease – the FDA nearly banned Avandia in 2010 – boosting omega-3 intake might be a safer way to improve insulin sensitivity.
Findings add to the risks of America’s gross “omega-imbalance”
The retinas of mice and men alike are packed with omega-3 fatty acids, which are lacking in the average American’s diet. Americans’ diets tend to be extremely high in omega-6 fatty acids, compared with typical human diets prior to the industrial and agricultural revolutions of the 1800s. (To read about research regarding the ill effects of this “omega-imbalance”, see the “Omega-3 / Omega-6 Balance” section of our news archive.) For example, in Dr. Smith's previous study, mice fed diets rich in omega-3s had nearly 50 percent less damaging vessel growth in the retina than mice fed omega-6-rich diets. The results of that 2007 study also showed that the omega-3-rich diet decreased pro-inflammatory cellular “messaging” in the eye. Smith plans to continue seeking beneficial ways in which omega-3s might help deter retinopathy, while looking for the most harmful omega 6 metabolites. “We found the good guys, now we'll look for the bad ones,” says Smith. “If we find the pathways, maybe we can selectively block the bad [omega-6] metabolites.” (CHB 2011)
Clinical trials underway to test DHA in people
Smith works closely with scientists at the National Eye Institute who are conducting an ongoing trial of omega-3 supplements in patients with AMD, known as AREDS2, which will end in 2013. An earlier “retrospective” study, called AREDS1, linked higher self-reported intake of fish to a lower likelihood of developing AMD. In addition, Smith is collaborating with a group in Sweden that’s conducting a clinical trial of omega-3s in premature infants, who are often deficient in omega-3.
That study will measure infants' blood levels of omega-3 products and follow the infants to see if they develop retinopathy. If results are promising Smith will seek FDA approval to conduct a clinical trial in premature infants at Children’s Hospital.
For our coverage of prior research on the role of omega-3s in eye health, see the “Omega-3s & Eye Health” section of our news archive.
Sources: Children's Hospital Boston (CHB). Omega 3's – more evidence for their benefit. Feb. 9, 2011. Accessed at http://www.eurekalert.org/pub_releases/2011-02/chb-o3020411.php. Children's Hospital Boston (CHB). Can blindness be prevented through diet? Increasing omega-3 intake in mice reduces damaging vessel growth in the eye. June 24, 2007. Accessed at: http://www.childrenshospital.org/newsroom/Site1339/mainpageS1339P1sublevel309.html. Sapieha P et al. 5-Lipoxygenase Metabolite 4-HDHA Is a Mediator of the Antiangiogenic Effect of ω-3 Polyunsaturated Fatty Acids. Sci Transl Med 9 February 2011: Vol. 3, Issue 69, p. 69ra12. DOI: 10.1126/scitranslmed.3001571
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Lancet 2011 Jan 22; 377:321
Safety of Tamoxifen vs. an Aromatase Inhibitor as Adjuvant Therapy
for Breast Cancer
An international randomized trial shows differing safety profiles for tamoxifen and exemestane.
Recently updated guidelines from the American Society of Clinical Oncology recommend that adjuvant therapy for postmenopausal women with hormone receptor–positive breast cancer include an aromatase inhibitor (AI; JW Womens Health Feb 3 2011). In the manufacturer-sponsored Tamoxifen Exemestane Multinational (TEAM) trial of the AI exemestane (Aromasin), investigators randomized almost 10,000 menopausal women with hormone receptor–positive breast cancer to receive exemestane alone or sequentially after 2.5 to 3 years of tamoxifen. Now, the authors report results at mean follow-up of 5.1 years.
Five-year disease-free survival was almost identical in both treatment arms (about 85.5% overall), but safety profiles of the exemestane-only versus sequential regimens were distinct. Rates of uterine bleeding (3% vs. 5%) and rates of venous thrombosis (<1% vs. 2%) were lower in the exemestane-only group than in the sequential-treatment group. By contrast, osteoporosis (10% vs. 6%) and fractures (5% vs. 3%) occurred more commonly in the exemestane-only group (P<0.0001 for all comparisons).
Comment: Given the similar efficacy of the AI-only and the tamoxifen-AI sequential regimens, the contrasting safety profiles shown in this large, phase III trial warrant close attention. Recognition of these distinct safety profiles (which arise from the differential estrogenic and antiestrogenic activities of AIs and tamoxifen) can inform clinicians' choice of agent. For example, tamoxifen might represent an appealing choice for women who have undergone hysterectomies, as they are not at risk for endometrial proliferation. AIs might have safety advantages for obese women, who are at excess risk for venous thrombosis. Finally, although the report does not detail financial costs, tamoxifen (available generically in the U.S.) is substantially less expensive than AIs.
— Andrew M. Kaunitz, MD Published in Journal Watch Women's Health February 10, 2011 Citation(s): van de Velde CJH et al. Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): A randomised phase 3 trial. Lancet 2011 Jan 22; 377:321.PMID: 21247627
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J Clin Oncol 2011 Jan 24
Influence of Subspecialty Care on Survival in Women with Endometrial Cancer
Women with advanced disease had better outcomes when care was provided by
gynecologic oncologists.
Although women with ovarian cancer have longer survival when cared for by gynecologic oncologists (GOs) rather than general obstetrician-gynecologists or surgeons (JW Womens Health May 8 2008), the influence of subspecialty care in the setting of endometrial cancer is not known. To address this question, researchers used U.S. national cancer data to identify more than 18,000 women with endometrial cancer (median age at diagnosis, 70; 90% white) and to analyze outcomes in relation to type of care received.
From 1991 to 2002, the proportion of women with endometrial cancer who received treatment from GOs rose from 10.7% to 27.5%. Women whose surgeries were performed by GOs were more likely to present with advanced disease, to have more-aggressive tumor histopathology, to receive more-extensive lymph node dissections, and to have received chemotherapy and radiation therapy (P<0.001 for all comparisons). Among women with stage I cancer, 5-year disease-specific survival rates were similar (about 95%) whether or not treatment was provided by GOs; however, among women with stage II, III, or IV cancer, 5-year survival rates were higher when GOs provided care (79% vs. 73%; P=0.001). In analysis adjusted for age, type of surgery, cancer stage, tumor grade, and histopathology, GO-provided care was associated with improved survival.
Comment: The enhanced survival associated with subspecialty care for endometrial cancer likely reflects more-complete surgical staging and cytoreduction as well as better guidance about postoperative adjuvant therapies. More than two thirds of endometrial cancers are stage I at diagnosis, and such tumors are associated with favorable outcomes whether or not a GO provides care. However, because preoperative assessment does not reliably predict the presence of advanced tumors, referral to a GO — when feasible — is appropriate whenever endometrial cancer is diagnosed.
— Andrew M. Kaunitz, MD Published in Journal Watch Women's Health February 10, 2011
Citation(s): Chan JK et al. Influence of gynecologic oncologists on the survival of patients with endometrial cancer. J Clin Oncol 2011 Jan 24; [e-pub ahead of print]. (http://dx.doi.org/10.1200/JCO.2010.31.2124)
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Lancet 2011 Jan 15; 377:209
Male Circumcision for Preventing Transmission of
Human Papillomavirus to Women
In Ugandan trials, adult male circumcision was associated with a 28% reduction in prevalence of high-risk HPV in female partners.
Male circumcision lowers risk for transmission of HIV, herpes simplex virus type 2 (HSV-2), and human papillomavirus (HPV) in men (and acquisition of bacterial vaginosis and trichomoniasis by their female sex partners). In a study of participants in two circumcision trials in Uganda, investigators asked whether male circumcision lowers risk for HPV acquisition in participants' regular female partners. Circumcision was performed at trial entry (intervention group) or at 24 months (control group). At enrollment, 12 months, and 24 months, women self-collected vaginal swabs for HPV testing and genotyping.
At enrollment, 35% of 648 women with partners in the intervention group and 37% of 595 women with partners in the control group tested positive for high-risk HPV genotypes (i.e., those linked to development of cervical cancer). At 24 months, high-risk HPV prevalence was 28% in the intervention group versus 39% in the control group (risk ratio, 0.72); thus, immediate male circumcision was associated with a 28% reduction in prevalence of high-risk HPV in female partners. In addition, a 23% reduction in incidence of new high-risk HPV infections was observed.
Comment: In observational studies, women with circumcised partners have been less likely to develop cervical cancer than women with uncircumcised partners. The relation between HPV infection and cervical cancer has been firmly established; however, because of the long delay from HPV acquisition to development of malignancy, efforts to stop the spread of HPV will not yield benefits for many years. In addition, because most women whose partners are circumcised as adults are likely to have preexisting HPV infection, neonatal circumcision is a more effective means to prevent HPV infection on a population basis. Nonetheless, as editorialists note, circumcision and HPV vaccination have emerged as two key strategies for lowering incidence of cervical cancer.
— Anna Wald, MD, MPH Published in Journal Watch Women's Health February 10, 2011
Citation(s): Wawer MJ et al. Effect of circumcision of HIV-negative men on transmission of human papillomavirus to HIV-negative women: A randomised trial in Rakai, Uganda. Lancet 2011 Jan 15; 377:209.PMID: 21216000
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Cancer Res 2010 Nov 1; 70:8587
Vitamin D and Cancer Mortality: Not to Be Taken Lightly
The association is not clear-cut, according to an assessment of data from the Third National Health and Nutritional Examination Survey.
Ultraviolet radiation has various deleterious effects but a positive influence on vitamin D metabolism. Dermatologists typically recommend that patients use sunscreen and take other precautions to prevent sunburn, nonmelanoma skin cancer, melanoma, and cutaneous photoaging. This practice is increasingly being scrutinized because much of the population is vitamin D deficient and because several healthful effects have been attributed to vitamin D, including a potential cancer-protection effect. To assess the association between baseline serum 25-hydroxyvitamin D levels (25[OH]D) and cancer mortality, researchers prospectively examined data on 16,819 participants in the Third National Health and Nutritional Examination Survey (NHANES III). Levels of 25(OH)D were measured once, in spring or summer in higher latitudes and in fall or winter in lower latitudes.
During a mean follow-up of 13.4 years, 884 participants died of cancer. Cancer mortality did not correlate with serum 25(OH)D in the total population or in men and women analyzed separately. However, men with 25(OH)D levels >80 nmol/L had a significantly higher cancer mortality rate than those with levels <50 nmol/L. Among women in the summer/higher-latitude group, the overall cancer risk trended significantly lower with higher 25(OH)D level. Serum 25(OH)D levels were not associated with cancer mortality among non-Hispanic white, non-Hispanic black, and Mexican-American subgroups. Colon cancer deaths trended nonsignificantly lower with higher 25(OH)D levels. In men, but not women, elevated baseline serum 25(OH)D was associated with increased deaths from lung cancer and from digestive tract cancers other than colorectal cancer. No clear trend was apparent for female breast cancer, prostate cancer, or combined deaths from non-Hodgkin lymphoma or leukemia.
Comment: The large NHANES III database provides a unique opportunity to evaluate in detail the relation between vitamin D and diseases in the U.S. Study limitations include the measurement of vitamin D levels only at baseline. The findings suggest that we don't yet have the final word on the relationship between vitamin D and human health and that claims that vitamin D protects against specific cancers are not necessarily supported by the facts. Dermatologists can use this information to counter people's presumption that sun exposure or tanning bed use will protect against cancer mortality; in fact, such exposure may actually increase deaths from some cancers.
— Craig A. Elmets, MD Published in Journal Watch Dermatology December 10, 2010
Citation(s): Freedman DM et al. Serum 25-hydroxyvitamin D and cancer mortality in the NHANES III study (1988–2006). Cancer Res 2010 Nov 1; 70:8587.PMID: 20847342
