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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
April 2, 2011

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Human Chorionic Gonadotropin May Relieve Intractable Pain
Atorvastatin (Lipitor®) Linked to Small Increase in Risk for Type 2 Diabetes
Misoprostol Vaginal Insert for Labor Induction: Not Ripe Yet
Don't Just Eat Dirt, Breathe Dirt!
FDA Chemist and Son Charged with Insider Trading
KV slashes price of Makena
FDA, KV, and Over-the-top Pricing on Makena
KV Hydroxyprogesterone Caproate Loses Exclusivity
KV Shares Slide After FDA Announcement
Does Waist Circumference Measure Up?
Low Amounts of Radioactive Iodine Found in Milk in Washington
EPA: Radiation in U.S. from Japan's Reactor Breakdowns Not a Public Health Concern
Are Diet and IQ Linked in Children?
Vitamin D Intakes Called too Low to Nix Cancer
Omega-3s Bolster Hip Bones, Omega-6s Hurt
Group Visits for Patients with Diabetes
Hot Flashes and Cardiovascular Risk: A Matter of Timing?
Growth Hormone and Estrogen for Girls with Turner Syndrome
AAP: Pediatricians Should Advise Parents to Monitor Children's Online Behavior
Longer Survival of Patients with Cystic Fibrosis
Chronic Fatigue Syndrome: Pessimism Doesn't Help
Behavioral Interventions Lead to Modestly Better Outcomes in CFS Patients
Does Cardiac Screening of Athletes Really Save Lives?
Screening for Dementia Made Ridiculously Simple

Human Chorionic Gonadotropin May Relieve Intractable Pain
     "Human chorionic gonadotropin (hCG), frequently used in fertility therapy, relieved intractable pain for most patients," according to a study presented at the American Academy of Pain Medicine meeting. In fact, "after a year of hCG therapy, seven out of eight patients were able to reduce opiate use by 30% to 50%," researchers found.
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Atorvastatin (Lipitor®) Linked to Small Increase in Risk for Type 2 Diabetes
     Atorvastatin seems to carry a "slight increase in the risk" for new-onset type 2 diabetes, according to an analysis of three large trials published in the Journal of the American College of Cardiology. (The trials, as well as this analysis, were sponsored by atorvastatin's manufacturer.)
     Researchers were responding to a 2010 Lancet meta-analysis, which found a small but measurable risk for new-onset diabetes after all statin use. The current analysis focuses on atorvastatin's effects in the TNT, IDEAL, and SPARCL trials. It found that atorvastatin, when compared with placebo in the SPARCL trial, carries a higher risk for diabetes. In the other trials, there was a slightly increased risk when an 80-mg dose was compared with lower doses (10-mg atorvastatin in TNT, 20-mg simvastatin in IDEAL), but the differences did not achieve statistical significance.
     The JACC authors conclude (as did the authors of the Lancet meta-analysis) that the benefits of statins "far outweigh the risks."
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A Compounded Option is presently available in suppository form that is supported
by this article
Obstet Gynecol 2011 Mar; 117:533
Misoprostol Vaginal Insert for Labor Induction: Not Ripe Yet
In a dose-ranging study, 200-µg dose was most effective but was associated with excess risk for adverse events secondary to uterine tachysystole.
     Vaginal misoprostol tablets are used off-label to induce cervical ripening for induction of labor; however, controlled-release drug delivery would be preferable. In a manufacturer-sponsored phase II dose-ranging study, U.S. investigators randomized 374 pregnant women (greater than or equal to 36 weeks' gestation) who required labor induction to undergo cervical ripening with 100-µg, 150-µg, or 200-µg misoprostol vaginal inserts (MVIs). The primary outcome was proportion of vaginal births within 24 hours of misoprostol administration; continuous uterine and fetal heart rate monitoring were performed.
     Women who received 200-µg MVI entered active labor fastest and had shortest median time to any delivery mode. In all, 24% of women in the 200-MVI group, compared with 36% in the 100-MVI group, failed to achieve vaginal delivery within 24 hours (P=0.057). Oxytocin augmentation was required by 49% of women in the 200-MVI group compared with 71% of women in the 100-MVI group (P<0.001). Uterine tachysystole occurred substantially more often in the 200-MVI group (41%) than in the 100-MVI group (20%), as did nonreassuring fetal heart rate patterns secondary to tachysystole. Rates of cesarean delivery for nonreassuring fetal status related to misoprostol were 1.7% and 3.8% in the 100-MVI and 200-MVI groups, respectively.
     Comment: In this relatively small study, 200-µg misoprostol vaginal inserts substantially shortened time to delivery and lessened the need for oxytocin; however, this dose was most likely to cause adverse events secondary to uterine tachysystole. The drug reservoir and retrieval tape of the MVI delivery system are identical to those of the dinoprostone vaginal insert (Cervidil); both offer the ability to remove the insert at the onset of labor or if an adverse reaction (e.g., tachysystole) occurs. The availability of a misoprostol insert that allows for controlled drug release as well as easy removal would be an advantage. However, this product will not be ready for marketing without further trials aimed at addressing tachysystole and associated adverse events.
Diane J. Angelini, EdD, CNM, FACNM, FAAN, NEA-BC Published in Journal Watch Women's Health March 24, 2011
Citation(s): Wing DA et al. Misoprostol vaginal insert for successful labor induction: A randomized controlled trial. Obstet Gynecol 2011 Mar; 117:533. http://www.ncbi.nlm.nih.gov/pubmed/21343755?dopt=Abstract
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N Engl J Med 2011 Feb 24; 364:701
Don't Just Eat Dirt, Breathe Dirt!
Colonization with a variety of microbes from early childhood appears to be important for balanced immunologic development.
     Studies have shown that growing up on a farm is associated with reduced risk for asthma, possibly through stimulation of the innate immune system in early life. These data are supportive of the so-called hygiene hypothesis (see N Engl J Med 2002; 347:869, 347:930).
Recently, researchers in Germany analyzed data from two large cross-sectional studies comparing microbial exposures of farm-dwelling and non–farm-dwelling children in central Europe.
     In the PARSIFAL study (6843 participants), researchers analyzed mattress dust samples for environmental bacteria via DNA signatures, which detect bacteria that cannot be measured by culture. In the GABRIELA study (9668 participants), researchers used culture techniques to evaluate bacterial and fungal taxa in dust from children's rooms. Both studies showed that farm-dwelling children had a lower incidence of asthma and atopy and were exposed to a larger variety of environmental microorganisms than non–farm-dwellers. Microbial diversity was inversely related to asthma risk. An inverse relationship was seen between asthma incidence rates and exposure to certain fungal and bacterial species.
     Atopy, also significantly less prevalent among farm-dwelling children, was only weakly affected by microbial diversity.
     Comment: These findings remind us that the lungs, like the skin and gut, do not have sterile surfaces. We are colonized with a variety of microbes from early childhood, which appears to be important for balanced immunologic development. The necessary mechanism may entail colonization or symbiosis, with pathogenic strains crowded out by "good" microbial strains, but it may also entail infection by "bad" microbes, which stimulates development of the innate immune system and balances Th1 and Th2 systems.
     Long-term follow-up of the children in GABRIELA and PARSIFAL would be interesting. If the hygiene hypothesis is correct, these farm-dwelling children should have a lower incidence of autoimmune diseases (e.g., diabetes, celiac disease, Crohn disease) than the non–farm-dwelling reference population.
     We can't all raise our children on farms, so should we raise our urban children differently — should we let them get more "dirty"? Should we vaccinate them less, or differently? As a parent and a physician, I am eager to know.
Mary Wu Chang, MD Published in Journal Watch Dermatology April 1, 2011
     Citation(s): Ege MJ et al. Exposure to environmental microorganisms and childhood asthma. N Engl J Med 2011 Feb 24; 364:701. http://www.ncbi.nlm.nih.gov/pubmed/21345099?dopt=Abstract
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FDA Chemist and Son Charged with Insider Trading
     An FDA chemist and his son were charged with using inside information about drug approvals to reap more than $3.6 million in profits, in an embarrassing blow to the health industry regulator.
     The SEC has charged Cheng Yi Liang with illegally trading in advance of at least 27 public announcements about 19 publicly held companies. "Liang's conduct was calculated, repeated, and egregious. Liang was a serial insider trader who violated the public's trust for his own profit on numerous occasions," the SEC said in its complaint filed in federal court in Maryland.
     The Justice Department has charged Liang and his 25-year-old son Andrew with conspiracy, securities fraud, and wire fraud for making $2.27 million in trades involving five pharmaceutical companies between November 2007 and March 2011.
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KV slashes price of Makena
     KV Pharmaceutical has just announced it is reducing the price of the drug, sold as Makena, to $690 an injection. KV has also stated it is expanding its program to help women who still are having trouble affording the medication.
     The company was taking the steps because of the "concerns" that have been raised, including the tight budgets state Medicaid programs were facing.
     "While the new price may represent a significant reduction, it remains excessively inflated given that the original price was stratospheric compared to the compounded drug's price," said George Saade, president of the Society for Maternal-Fetal Medicine.
     The March of Dimes, which has come under criticism for praising the drug's approval before the price was made public, announced it was severing its ties with the company, which had provided about $1 million in donations to the organization.
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FDA, KV, and Over-the-top Pricing on Makena
     KV Pharmaceutical, armed with exclusive rights to an FDA-approved drug for pregnant women, speculated that it had the market tied up. They slapped a big price tag on the drug and put it on the market for sale. At $1,500 a dose, the company thought it stood to take in significant sales. However, they didn't count on the expectant mothers-and their doctors and government representatives-to fight back (as they were used to getting their doses at $10 to $15 each). The FDA entered into the fray; however, the agency doesn't have the power to tell KV Pharmaceuticals to lower the price, but it can allow pharmacists to keep on compounding the drug as they have for many years. The FDA released their official statement on Wednesday morning (March 30) of this week.
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KV Hydroxyprogesterone Caproate Loses Exclusivity
     In a rare move for any regulatory agency, the FDA announced it would not enforce the monopoly status it had given KV Pharmacuetical's Makena amid its controversial plans to charge $1,500 per dose. The company's stock fell after the FDA's announcement that it would continue to use its enforcement discretion for other makers of the same drug that sell it for $10 or $15 a dose.
     Resulting from this was a growing chorus of KV critics that lauded the FDA action as a fitting response to what they view as the drug marketer's greedy overreach. The pricing for Makena is "profiteering at its worst," said Dr. George Hubbell, the Missouri chair of the American College of Obstetricians and Gynecologists.
     U.S. Senator Sherrod Brown, D-Ohio, who has castigated KV's pricing as "irresponsible," called the FDA decision "a victory for pregnant women, consumers, and taxpayers. This drug, which was developed with extensive taxpayer support, is too important to fall out of reach for pregnant women."
     Doctors have for years widely prescribed the drug to help prevent pre-term births. KV merely paid another company to push an already existing and widely used drug over the bureaucratic hurdles to win approval. They had purchased the marketing rights for about $200 million. The FDA said it would not enforce KV's market protections unless others produced unsafe or substandard versions of the drug.
     KV's investments can't justify the company's high price, according to a statement from Senator Brown's office, which concluded that -- at $1,500 a shot -- KV could recoup its $200 million investment 18 times in the first year, netting a $3.7 billion profit.
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KV Shares Slide After FDA Announcement
     Shares of KV Pharmaceutical Co. fell 27 percent Wednesday after federal regulators said it "does not intend to take enforcement action against pharmacies that compound hydroxyprogesterone caproate based on a valid prescription for an individually identified patient."
     "This announcement by the FDA will ensure that women with high-risk pregnancies continue to have access to a safe, effective, and affordable treatment option to prevent premature births," AHIP President and CEO Karen Ignagni said in a statement.
     AHIP recently sent a letter to the FDA seeking clearer guidance on the availability of compounded drugs for high-risk pregnant women. The letter raised concerns "about the potential for patients' loss of access to the longstanding therapy as a result of the exclusivity granted to the newly approved drug and the extraordinary price increase established by the manufacturer" and requested that the FDA "provide clearer guidance on the availability of compounded drugs that may be needed to ensure affordable access for vulnerable populations." KV's Makena price hike has caused a backlash from lawmakers, consumers, and doctors.
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Am J Clin Nutr 2011 Feb; 93:392
Does Waist Circumference Measure Up?
Independent of body-mass index, increases in waist circumference predicted changes in cardiovascular disease risk factors in postmenarcheal white adolescents.
     Cross-sectional studies suggest that visceral fat, measured by magnetic resonance imaging, is positively related to cardiovascular risk factors in children and adolescents. To determine whether changes in waist circumference — an indirect measure of central adiposity — predicts longitudinal change in cardiovascular risk factors, investigators analyzed data from 2379 black and white girls (age range, 9–10 years) enrolled in the National Heart, Lung, and Blood Institute Growth and Health Study in 1987–1988. Girls who had at least two postmenarcheal study visits during the 10 years of follow-up were included in the analysis.
     After adjustment for body-mass index (BMI) z score, steeper age-related increases in waist circumference were significantly associated with greater increases in LDL cholesterol, systolic and diastolic blood pressure, and insulin resistance (homeostasis model assessment) in white but not black girls. Changes in waist circumference were not related to changes in HDL cholesterol, triglycerides, insulin, or glucose concentrations in either white or black girls. Changes in waist circumference were not related to changes in HDL cholesterol, triglycerides, insulin, or glucose concentrations in either white or black girls.
      Comment: This is one of many studies to suggest that monitoring waist circumference might identify adolescents at risk for emergence of certain cardiovascular disease risk factors. Although this might be true, I remain skeptical about its clinical usefulness. The authors don't tell us whether measuring waist circumference identifies girls who by BMI criteria would not be targeted for intervention or whether it simply identifies a subset of overweight/obese girls at particular risk. To the extent that girls in the highest percentiles of waist circumference are already identified as being overweight/obese, ongoing monitoring of blood pressure and LDL levels would already be indicated and such patients would also receive the same counseling: Exercise more and control weight, both of which would improve cardiovascular disease risk factors. Finally, until studies demonstrate that measuring waist circumference will not trigger or exacerbate disordered eating in teenage girls, we need more-compelling evidence before it is incorporated into routine care.
Alain Joffe, MD, MPH, FAAP Published in Journal Watch Pediatrics and Adolescent Medicine March 16, 2011
Citation(s): Tybor DJ et al. Independent effects of age-related changes in waist circumference and BMI z scores in predicting cardiovascular disease risk factors in a prospective cohort of adolescent females. Am J Clin Nutr 2011 Feb; 93:392. http://www.ncbi.nlm.nih.gov/pubmed/21147855?dopt=Abstract
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Low Amounts of Radioactive Iodine Found in Milk in Washington
     The FDA and the Environmental Protection Agency say they have detected small amounts of a radioactive iodine isotope in milk in Washington state. The radiation is related to problems at the Japanese nuclear power plant.
     A sample taken March 25 from Spokane, Wash., was found to contain 0.8 picocuries per liter of iodine-131, which the FDA says is "far below the levels of public health concern." Because of iodine's short (8-day) half-life, officials expect the radiation in the milk supply to drop quickly.
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EPA: Radiation in U.S. from Japan's Reactor Breakdowns Not a
Public Health Concern

     The levels of radiation in the U.S. from Japan's nuclear incident do not currently pose a public health problem, according to an analysis from the EPA.
     The agency analyzed data from 12 air monitor locations across the U.S. and found "trace amounts" of radiation related to damage at Japan's Fukushima nuclear plant. While some levels are a bit higher than they were in the past 2 weeks, the EPA says they remain "far below levels of public health concern."
RADIATION LEVELS BY STATE: http://epa.gov/japan2011/rert/radnet-data-map.html#results
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J Epidemiol Community Health 2011 Feb 7
Are Diet and IQ Linked in Children?
A healthy diet was positively associated with IQ at age 8 years.
     Most studies of long-term effects of nutrition in early childhood focus on cardiovascular and metabolic outcomes. Less is known about the effect of children's diet on intelligence. In a prospective cohort study, researchers examined this association using data from parent-reported food-frequency questionnaires collected at ages 3, 4, 7, and 8.5 years for 13,988 children in England. At age 8.5 years, 7044 children (the study group) completed the Wechsler Intelligence Scale; these children were more likely to be girls, to have been breast-fed, and to have older mothers with higher levels of education than children without IQ data.
     Three consistent dietary patterns were found at each time point: processed (convenience foods with high fat and sugar content), traditional (meat, poultry, potato, and vegetable), and health conscious (salad, fruit, vegetables, fish, pasta, and rice). A snacking dietary pattern (finger foods such as fruit, biscuits, bread, and cakes) was also found at age 3 years. In a fully adjusted analysis that controlled for many factors including mother's education and social class, the processed dietary pattern at age 3 years was negatively associated with IQ at age 8.5 years; each 1-standard deviation (SD) increase in processed-food score was associated with a 1.7- point decrease in IQ (P<0.0001). The health-conscious dietary pattern at age 8.5 years was positively associated with IQ; a 1-SD increase in health-conscious dietary pattern score was associated with a 1.2-point increase in IQ (P=0.001). The snacking pattern at age 3 years was associated with a significant 1-point increase in IQ at age 8.5 years (P<0.0001).
     Comment: In this study, a diet high in fat, sugar, and processed food in early childhood was associated with a small reduction in IQ in school-age children, and a healthy diet of fruit, vegetables and fish in school-age children was associated with a small increase in IQ. Although the change in individual IQ scores was small, the effect on large populations of children could have greater significance (similar to the positive association between low lead levels and IQ). Do we need proof of a few additional IQ points to encourage healthy nutrition in children? Probably not, but the possibility might motivate some parents (and school cafeteria staff) to provide children with a healthy diet.
Martin T. Stein, MD Published in Journal Watch Pediatrics and Adolescent Medicine March 2, 2011
     Citation(s): Northstone K et al. Are dietary patterns in childhood associated with IQ at 8 years of age? A population-based cohort study. J Epidemiol Community Health 2011 Feb 7; [e-pub ahead of print]. (http://dx.doi.org/10.1136/jech.2010.111955)
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March 31, 2011
Vitamin D Intakes Called too Low to Nix Cancer
Analysis finds higher intakes needed to impact disease risk; news explains simultaneous report of mixed anti-cancer evidence
by Craig Weatherby
     We’ve reported on some of the many studies that have associated higher vitamin D intakes or blood levels with reduced rates of breast, colon, and other cancers.  Now the coincidence of two simultaneous studies explains why the evidence remains mixed, albeit mostly positive. One, from the New England Journal of Medicine, was a review of the abundant epidemiological evidence – and much smaller amount of clinical evidence – that vitamin D intake affects cancer risk. As the authors wrote, there's good reason to think that vitamin D should help prevent cancer: “The theory that vitamin D can help prevent cancer is biologically plausible.” (Manson JE et al. 2011). But as they also noted, some studies find no link between higher vitamin D levels and lower cancer risk, and that having low vitamin D blood levels could logically be associated with also having one of more of four risk factors for cancer:

The other study, by leading vitamin D researchers, was an analysis of how much dietary vitamin D is needed to reach blood levels associated with reduced risk of cancer in epidemiological and clinical studies (Garland CF et al. 2011).
Let’s look at that study,which examined evidence related to minimum protective blood levels .. whose results would explain the mixed anti-cancer evidence cited in the New England Journal of Medicine paper.
     Leading researchers find D intakes too low to consistently curb cancer
     Compared to the intake levels thought adequate, researchers at the University of California and Omaha’s Creighton University found that markedly higher intakes of vitamin D are needed to reach blood levels that might cut the incidence of major cancers and other diseases. While these levels are higher than traditional intakes, they are largely in a range deemed safe for daily use in a December 2010 report from the National Academy of Sciences Institute of Medicine.
     “We found that daily intakes of vitamin D by adults in the range of 4000-8000 IU are needed to maintain blood levels of vitamin D metabolites in the range needed to reduce by about half the risk of several diseases – breast cancer, colon cancer, multiple sclerosis, and type 1 diabetes,” said Cedric Garland, DrPH, professor of family and preventive medicine at UC San Diego’s Moores Cancer Center. (UCSD 2011) “I was surprised to find that the intakes required to maintain vitamin D status for disease prevention were so high – much higher than the minimal intake of vitamin D of 400 IU/day that was needed to defeat rickets in the 20th century.” (UCSD 2011) “This result was what our dose-response studies predicted, but it took a study such as this, of people leading their everyday lives, to confirm it”, said Robert P. Heaney, MD, of Creighton University, a distinguished scientist who’s studied vitamin D needs for decades. (UCSD 2011)
     Garland, Heaney, and their co-authors analyzed data from a survey of several thousand volunteers who were taking vitamin D supplements in the dosage range from 1000 to 10,000 IU/day. Blood studies were conducted to determine the level of vitamin D circulating in their blood. “Most scientists who are actively working with vitamin D now believe that 40 to 60 ng/ml is the appropriate target concentration of 25-vitamin D in the blood for preventing the major vitamin D-deficiency related diseases, and have joined in a letter on this topic,” said Garland. “Unfortunately,” he added, “according a recent National Health and Nutrition Examination Survey, only 10 percent of the US population has levels in this range, mainly people who work outdoors.” (UCSD 2011)
     Recommended daily doses found too low ... even after being raised
     Last year, a U.S. Institute of Medicine (IOM) committee identified 4000 IU per day as a safe supplemental intake level for adults and children nine years and older … with intakes in the range of 1000-3000 IU per day safe for infants and children through eight years of age. While the IOM committee declared 4000 IU per day a safe dosage, their recommended minimum daily intake was only 600 IU. “Now that the results of this study are in, it will become common for almost every adult to take 4000 IU per day,” Garland said. “This is comfortably under the 10,000 IU per day that the IOM Committee Report considers as the lower limit of risk, and the benefits are substantial.”(UCSD 2011).  Garland added that people who may have contraindications should discuss their vitamin D needs with their family doctor.
     “Now is the time for virtually everyone to take more vitamin D to help prevent some major types of cancer, several other serious illnesses, and fractures,” said Heaney. (UCSD 2011)
     Other co-authors of the article were Leo Baggerly, Ph.D., and Christine French.
     We recommend viewing the video interviews conducted by breast cancer survivor Carole Baggerly, founder of Grassroots Health … a non-profit organization that collects and disseminates scientifically accurate information on vitamin D.
     (If you don’t see them on the Grassroots Health home page, you can view them on YouTube … click here for the interview with Dr. Garland, and here for the interview with Dr. Heaney.)
     Grassroots Health is advised by the world’s leading vitamin D researchers, including scientists from the University of California, Emory University, Harvard University, Boston University, University of Toronto, and more.
     Mixed evidence is due to participants’ relatively low vitamin D intakes
     When you examine the two studies side-by-side, it seems apparent that the amount of dietary vitamin D needed to affect cancer risk is much higher than previously thought, and much higher than the amounts consumed by people in most epidemiological and clinical studies. In other words, it's not much of a surprise that the New England Journal of Medicine review found the evidence mixed and inconclusive. This is not to say that the available evidence, while compelling, is conclusive, because it is not.  However, few of the many populations studied consumed enough vitamin D to reach the blood levels associated with reduced cancer risk. So it's no surprise that the evidence from epidemiological and clinical studies, while generally positive, is mixed. If you presume that vitamin D exerts real anti-cancer effects, people in most studies just aren't getting enough vitamin D from their diets or sun exposure to consistently produce reduced cancer risk.
     When it comes to epidemiological evidence, it’s critical to observe the central scientific caveat, “correlation is not causation”. Just because a particular lifestyle factor or blood nutrient level is statistically associated with lower rates of a particular disease does not mean it is responsible for that risk reduction. That said, when a large amount of epidemiological evidence is accompanied by lab evidence showing why a food or nutrient could prevent cancer, it becomes harder to dismiss the association as mere chance. And the landmark findings by Dr. Garland and his colleagues would explain why the evidence is mixed.
     Sources: Garland CF, French CB, Baggerly LL, Heaney RP. Vitamin d supplement doses and serum 25-hydroxyvitamin d in the range associated with cancer prevention. Anticancer Res. 2011 Feb;31(2):607-11. Accessed at:
Manson JE, Mayne ST, Clinton SK. Vitamin D and Prevention of Cancer - Ready for Prime Time? N Engl J Med. 2011 Mar 23. [Epub ahead of print] University of California - San Diego (UCSD). Higher vitamin D intake needed to reduce cancer risk. Feburary 22, 2011. Accessed at:
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March 28, 2011
Omega-3s Bolster Hip Bones, Omega-6s Hurt
Study links higher fish intake to healthier bone mineral levels in hips and upper thighs; high omega-6 intakes may weaken bones unless omega-3 intake is also high
by Craig Weatherby

     Vitamin D and long-chain omega-3s (EPA and DHA) are the essential nutrients in which fish – especially fatty fish – are uniquely rich.  And both of these relatively uncommon food factors support bone health … see the “Omega-3s & Bone Health” and “Vitamin D & Bone Health” section of our news archive. Scientists suspect that dietary omega-3s reduce the risk of osteoporosis by reducing inflammation, decreasing activation of osteoclasts (cells that break down bone), and helping the body absorb calcium.
     As Iranian researchers wrote three years ago, the evidence that omega-3s enhance bone health is encouraging, but needs more confirmation from human clinical trials: “Generally, animal studies support the beneficial effects of omega-3 fatty acids on bone health and osteoporosis; however, the dissimilar lipid [fat] metabolism in human and animals, varying [human] study designs, and controversies over human study outcomes make it difficult to draw a definite conclusion.” (Salari P et al. 2008)
     In the meantime, an analysis of health and diet data from the large Framingham Osteoporosis Study adds substantial epidemiological evidence in favor of omega-3s (Farina EK et al. 2011). Just as important, it supports prior indications that Americans’ grossly excessive intake of omega-6 fatty acids has bone-weakening effects. That warning sign about high omega-6 intakes has been detected in animal studies (see “Omega-3 Fats Built Rats’ Bones: Omega-6s Weakened Them”). And it was seen in findings from the University of California’s Rancho Bernardo Study, conducted among 1,532 people aged 45 to 90.
     As the UC San Diego team wrote six years ago, “A higher ratio of omega-6 to omega-3 fatty acids is associated with lower BMD [bone mineral density] at the hip in both sexes.” (Weiss LA et al. 2005).
     Study supports value of omega-3s and risks of excess omega-6s
     The new findings come from Tufts University researchers in Boston, who analyzed diet surveys and bone-health data from more than 600 volunteers in the Framingham Osteoporosis Study (Farina EK et al. 2011). Their analysis found that older adults who reported consuming the most omega-3 fatty acids were more likely to have maintained adequate bone mineral density in their hips four years later. The study's authors came to this conclusion after analyzing dietary surveys and bone scans from 623 adults enrolled in the Framingham Osteoporosis Study (average age 75).  Only the long-chain omega-3s in fish and fish oil (EPA and DHA) appear to have this effect. In contrast, when omega-3 intakes are low, high intake of either the long-chain omega-6 fat in animal foods (AA) or the short-chain omega-6 in plants foods (LA) may weaken bones.
     The current study found that, as a general principle, people who ate the most fish – three or more servings per week – were more likely to have healthy bone mineral levels in the hips, as measured by bone mass density scans of their upper femurs. However, the team found distinctions when they looked at varying intakes of omega-3s and omega-6s in relation to each other:

     In other words, omega-6 AA seems to promote bone loss when your diet is low in omega-3s. In contrast, diets high in omega-3s from fish and omega-6 AA may confer a slight hip-bone advantage over diets high in omega-3s that contain less omega-6 AA. The USDA-funded Tufts team concluded that frequently consuming fish may delay the onset of osteoporosis, and that AA’s positive effects only appear when people are getting more omega-3s than the average American.
      Sources: Farina EK, Kiel DP, Roubenoff R, Schaefer EJ, Cupples LA, Tucker KL. Protective effects of fish intake and interactive effects of long-chain polyunsaturated fatty acid intakes on hip bone mineral density in older adults: the Framingham Osteoporosis Study. Am J Clin Nutr. 2011 Mar 2. [Epub ahead of print]. Högström M, Nordström P, Nordström A. n-3 Fatty acids are positively associated with peak bone mineral density and bone accrual in healthy men: the NO2 Study. Am J Clin Nutr. 2007 Mar;85(3):803-7. Orchard TS, Cauley JA, Frank GC, Neuhouser ML, Robinson JG, Snetselaar L, Tylavsky F, Wactawski-Wende J, Young AM, Lu B, Jackson RD. Fatty acid consumption and risk of fracture in the Women's Health Initiative. Am J Clin Nutr. 2010 Dec;92(6):1452-60. Epub 2010 Oct 27. Salari P, Rezaie A, Larijani B, Abdollahi M. A systematic review of the impact of n-3 fatty acids in bone health and osteoporosis. Med Sci Monit. 2008 Mar;14(3):RA37-44. Review. Weiss LA, Barrett-Connor E, von Mühlen D. Ratio of n-6 to n-3 fatty acids and bone mineral density in older adults: the Rancho Bernardo Study. Am J Clin Nutr. 2005 Apr;81(4):934-8.
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Arch Intern Med 2011 Mar 14; 171:453.
Group Visits for Patients with Diabetes
Physician-led groups focused on specific goals to improve glycemic control
     Group visits have been proposed as an efficient approach to chronic disease management, but the specific features and effectiveness of such groups vary widely. In this comparative effectiveness trial from Texas, 87 Veterans Affairs patients with diabetes mellitus (DM; mean age, 63; mean glycosylated hemoglobin [HbA1c] level, 8.8%) who had previously received extensive routine primary care and DM education were randomized to one of two forms of group visits for 12 weeks.
     The intervention patients received four 1-hour group sessions led by a physician; these sessions focused on goal-setting and action plans and provided advice on how to talk to and work with physicians. Each session was followed by a 10-minute individual consultation with the study physician. The control group received two 2-hour sessions led by a nurse educator and a dietician; these sessions focused on typical DM education, and each was followed by a routine 20- to 30-minute physician visit.
     At 12 weeks, HbA1c levels had dropped significantly in the intervention group (from 8.86% to 8.04%) but had not changed in the control group. The between-group difference was maintained at 1-year follow-up.
     Comment: Although this "open-label" comparative effectiveness trial involved only a single site and a committed group of clinicians, the results are sufficiently impressive to warrant replication and generalization to other clinical settings. A focus on goal-setting and specific behavioral action plans appears to result in better glycemic control than just general education.
Thomas L. Schwenk, MD Published in Journal Watch General Medicine March 31, 2011
     Citation(s): Naik AD et al. Comparative effectiveness of goal setting in diabetes mellitus group clinics: Randomized clinical trial. Arch Intern Med 2011 Mar 14; 171:453. (http://dx.doi.org/10.1001/archinternmed.2011.70)
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Menopause 2011 Feb 19
Hot Flashes and Cardiovascular Risk: A Matter of Timing?
Early-occurring vasomotor symptoms were associated with lower CV risk, and late symptoms with excess risk.
     Most women experience peri- or postmenopausal vasomotor symptoms (VMS), although symptom onset and duration vary. To address the relative contributions of early- versus late-onset VMS to risk for cardiovascular disease (CVD), investigators analyzed data on VMS, CVD events, and all-cause mortality in 60,000 participants in the Women's Health Initiative Observational Study (mean age at enrollment, 63.3; mean years since menopause, 14.4; median follow-up, 9.7 years). Women were stratified into four cohorts based on timing of VMS onset: no VMS, early VMS (present at menopause onset but not at study enrollment), persistent VMS (present at both times), or late VMS (not present at menopause onset but present at enrollment). Evaluated outcomes were major coronary events, stroke, total CVD events, and all-cause mortality. Fully adjusted models included several factors (e.g., age, body-mass index, smoking status, use of hormone therapy, physical activity, hypertension, hypercholesterolemia, diabetes).
     Analyses in fully adjusted models showed that women with early VMS had lower risk for stroke, total CVD events, and all-cause mortality than did those with no VMS. In models adjusted only for age and ethnicity, women who experienced late VMS compared with those who had no VMS showed excess risk for all four outcomes; after full adjustment, elevated risk for major coronary events and all-cause mortality persisted. HT use did not seem to predict CVD events or all-cause mortality in women with early or late VMS.
     Comment: Precisely when vasomotor symptoms occur in relation to menopause seems to confer differing degrees of CVD risk. Early VMS, as a probable consequence of perimenopausal hormonal fluctuations, might not be an independent CVD risk factor. Women with late VMS had higher prevalence of traditional CV risk factors, yet excess CVD risk persisted after adjustment for such factors; thus, perhaps late VMS is not causally related to CVD risk, but, instead, is a consequence of some other mechanism. Further studies must be performed to characterize the physiologic differences between early- and late-occurring VMS; meanwhile, late VMS should alert clinicians to assess modifiable CVD risk factors carefully and to initiate aggressive intervention.
Wendy S. Biggs, MD Published in Journal Watch Women's Health March 31, 2011
Citation(s): Szmuilowicz ED et al. Vasomotor symptoms and cardiovascular events in postmenopausal women. Menopause 2011 Feb 19; [e-pub ahead of print].
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N Engl J Med 2011 Mar 31; 364:1230.
Growth Hormone and Estrogen for Girls with Turner Syndrome
Combining the two had a synergistic effect that improved growth.
     Turner syndrome is caused by a missing or incomplete X chromosome. People who have Turner syndrome develop as females. The genes affected are involved in growth and sexual development, which is why girls with the disorder are shorter than normal and have abnormal sexual characteristics. http://learn.genetics.utah.edu/content/disorders/whataregd/turner/
Growth hormone (GH) increases adult height in girls with Turner syndrome, but does prepubertal low-dose estrogen add to the growth benefit? In a double-blind, placebo-controlled clinical trial, researchers randomized 149 girls with Turner's syndrome (age range, 5.0–12.5 years) to one of four groups: GH injection plus oral estrogen, GH injection plus oral placebo, placebo injection plus oral estrogen, or double placebo. GH (0.1 mg/kg three times per week) was given until growth velocity slowed to <1.5 cm/year and low-dose estrogen (ethinyl estradiol, 25–50 ng/kg/day) was given until age 12, when patients began estrogen-replacement therapy.
     At a mean age of 17 years, GH increased adult or estimated adult height by about 5 cm compared with placebo injection. Girls who received GH were significantly more likely to reach an adult height in the normal range (40% vs. 4%). The combination of GH and estrogen increased adult height by an additional 2.1–2.3 cm. Mean adult height in the estrogen-alone group was similar to that in the placebo group. Adverse events were similar in all groups.
     Comment: The new finding in this study is the synergistic effect of estrogen and GH on adult height in girls with Turner's syndrome. However, final adult height was not available for 39% of patients, most of whom withdrew from the study. In addition, the effect of estrogen was quite modest, and because of the small number of patients, safety is uncertain. The authors note that the relatively small height gain in their study might reflect the low dose of GH (0.3 mg/kg/week vs. the current recommended dose of 0.375 mg/kg/week) and the fact that prior studies that reported greater height gain used historical controls that might have overestimated the effect of GH.
Howard Bauchner, MD Published in Journal Watch Pediatrics and Adolescent Medicine March 30, 2011
Citation(s): Ross JL et al. Growth hormone plus childhood low-dose estrogen in Turner's syndrome. N Engl J Med 2011 Mar 31; 364:1230.
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AAP: Pediatricians Should Advise Parents to Monitor Children's
Online Behavior

     Pediatricians should urge parents to take a central role in their children's online activities, according to a new report from the American Academy of Pediatrics. The report, published in Pediatrics, cites a survey finding that a fifth of teens visit social media sites more than 10 times a day.
     Among the recommendations for pediatricians:

     The AAP also notes that pediatricians should learn about digital technologies so they are better equipped to have relevant discussions with patients and their families.
AAP’s Internet Safety Website: http://safetynet.aap.org
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BMJ 2011 Feb 28; 342:d1008
Longer Survival of Patients with Cystic Fibrosis
In the past 2 decades, DNase therapy has made a difference.
     During the past 2 decades, survival among patients with late-stage cystic fibrosis (CF) has lengthened substantially. In this retrospective cohort study, U.K. investigators evaluated survival of 276 patients (53% male; mean age, 26) with CF whose lung function had deteriorated to forced expiratory volume in 1 second (FEV1) <30% of predicted.
     Patients were divided into seven 2-year cohorts (1990–1991, 1992–1993, etc.) from 1990 to 2003 according to the time when their FEV1 was first recorded as <30% of predicted. Median survival increased from 1.2 years in the 1990–1991 group to 5.3 years in the 2002–2003 group, with a marked difference in survival after 1994 — the year that nebulized recombinant human (NRH) DNase was licensed for use in the U.K. Overall, use of NRH DNase was associated with significantly lower risk for death (hazard ratio, 0.6), whereas body-mass index <19 kg/m2, long-term oxygen treatment, and use of nebulized antibiotics were associated with excess mortality.
     Comment: During the past 2 decades, survival has lengthened for patients with CF whose lung function is poor, and the results of this study suggest that NRH DNase has played an important role. The DNA in purulent sputum, which derives from disintegrated neutrophils, forms a viscous gel that contributes to the high viscosity of sputum in patients with CF. NRH DNase greatly lowers the viscosity of sputum in these patients.
Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine March 29, 2011
Citation(s): George PM et al. Improved survival at low lung function in cystic fibrosis: Cohort study from 1990 to 2007. BMJ 2011 Feb 28; 342:d1008.
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Lancet 2011 Mar 5; 377:823
Chronic Fatigue Syndrome: Pessimism Doesn't Help
Two behaviorally based therapies perform better than adaptive pacing therapy, but response remains suboptimal.
     Several treatments have been suggested for chronic fatigue syndrome (CFS). Cognitive-behavior therapy (CBT) focuses on patients' fears that activity would induce exacerbations. Graded exercise therapy (GET) addresses patients' deconditioning and activity avoidance by gradually increasing exercise. Some patient advocacy groups recommend "adaptive pacing therapy" (APT), which assumes that patients should not exceed an "energy envelope" but should instead adapt to the illness by reducing and prioritizing activities. This multicenter, randomized study compared efficacy of CFS specialist medical care (SMC; mainly, advice and pharmacotherapy; greater than or equal to 3 sessions in 12 months) alone or added to APT, CBT, or GET (less than or equal to 14 sessions in 23 weeks, optional "booster" at 36 weeks).
     The 640 participants (mean age, 38; 77% women) met recognized criteria for CFS; 34% had depressive disorders. Patient-rated scales were used to assess fatigue and physical functioning. More patients improved with CBT/SMC (59%) and GET/SMC (61%) than with APT/SMC (42%) or SMC alone (45%). Recovery (i.e., scores within the average range) was more common with CBT/SMC (30%) and GET/SMC (28%) than with APT/SMC (16%) and SMC alone (15%). Response was not linked to treatment satisfaction (SMC alone, 50%; all other therapies, 82%–88%). Subjects had more confidence in APT/SMC (72%) and GET/SMC (70%) than in CBT/SMC (57%) and SMC alone (41%).
     Comment: In this carefully conducted study, CBT and GET were superior to APT despite patients' comfort with APT. CBT and GET focus on positive psychological factors — i.e., decreasing avoidance and improving stamina. It would be difficult to devise a more pessimistic name for a disorder than CFS, and APT's rationale, while interesting, appears to reinforce the idea of disability while ignoring the physical and cognitive benefits of exercise (see JW Psychiatry Mar 21 2011). The next step is to determine whether combining CBT and GET would improve response, which remains suboptimal.
Jonathan Silver, MD Published in Journal Watch Psychiatry March 21, 2011
     Citation(s): White PD et al. Comparison of adaptive pacing therapy, cognitive behavior therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): A randomised trial. Lancet 2011 Mar 5; 377:823.
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Lancet 2011 Feb 18
Behavioral Interventions Lead to Modestly Better Outcomes in CFS Patients
But these benefits do not exclude an organic cause for chronic fatigue syndrome.
     In small trials, people with chronic fatigue syndrome (CFS) have benefited from cognitive-behavioral therapy (CBT; focused on overcoming fear of activity) and graded exercise therapy (GET; focused on gradually improving exercise tolerance). Some patient organizations, however, have reported that CBT and GET can be harmful, and they favor adaptive pacing therapy (APT; focused on optimizing expenditure of limited energy).
U.K. researchers randomized 641 patients with CFS to receive specialist medical care (including education and symptomatic pharmacotherapy) alone or with added CBT, GET, or APT. During 1 year, all patients received at least three sessions of specialist care. Patients randomized to CBT, GET, or APT were offered as many as 14 therapy sessions in the first 23 weeks. Primary outcomes were patient-reported fatigue (using a 33-point questionnaire) and physical function (on a 100-point scale).
     After 1 year, 45% of specialist care–only patients improved by greater than or equal to 2 points for fatigue and greater than or equal to 8 points for function, compared with 42%, 59%, and 61% of patients who also received APT, CBT, or GET; 15% of specialist care–only patients reached normal levels on both outcomes, compared with 16%, 30%, and 28% of patients who also received APT, CBT, or GET. In both comparisons, APT did not differ significantly from specialist care alone, whereas outcomes with CBT and GET were both significantly better than with either APT or specialist care alone.
     Comment: The authors recommend either CBT or GET as first-line therapy for CFS patients, and they stress that the moderate benefits of these behavioral interventions do not exclude an organic cause of CFS.
Bruce Soloway, MD Published in Journal Watch General Medicine March 1, 2011
     Citation(s): White PD et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): A randomised trial. Lancet 2011 Feb 18; [e-pub ahead of print].
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J Am Coll Cardiol 2011 Mar 15; 57:1291
Does Cardiac Screening of Athletes Really Save Lives?
In Israel, mandatory electrocardiography and stress testing for athletes failed to reduce sudden cardiac death rates.
     Death on an athletic field is troubling and often seized upon by the media as evidence of the high purported risk of some sports. Most individuals who die suddenly without obvious trauma during athletic events have a structural heart disease such as hypertrophic cardiomyopathy or arrhythmogenic right ventricular dysplasia.
     In 1997, after a 2-year surge in sudden cardiac death (SCD) in athletes, Israel implemented a mandatory screening procedure that includes a yearly electrocardiogram (ECG) and Bruce protocol stress testing every 4 years for all participants in organized sporting activities. Investigators have now compared the incidence of SCD in athletes during the 12 years before the implementation of mandatory screening with SCD incidence during the 12 years afterward. The researchers found no significant difference in SCD risk between the two periods (2.54 vs. 2.66 events per 100,000 athlete years).
     Comment: Based on positive results from one Italian retrospective study (JW Cardiol 2006 Oct 18), screening ECGs are mandated before participation in organized sports in many European countries, and calls for such testing are widespread elsewhere. Although the goal of reducing the number of athletic field deaths is laudable, the current findings underline the lack of convincing evidence that including an ECG in the screening process decreases the risk for sudden cardiac death. ECG screening is quite expensive and often results in false-positive findings and occult diagnosis of benign conditions; therefore, based on the present data, I do not support mandatory ECG screening for participation in sports.
Mark S. Link, MD Published in Journal Watch Cardiology March 30, 2011
     Citation(s): Steinvil A et al. Mandatory electrocardiographic screening of athletes to reduce their risk for sudden death: Proven fact or wishful thinking? J Am Coll Cardiol 2011 Mar 15; 57:1291.
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Arch Intern Med 2011 Mar 14; 171:432
Screening for Dementia Made Ridiculously Simple
This screening test is quicker and easier than the Mini-Mental State Exam — and just as effective.
     Cognitive screening for dementia in the hospital and in elderly or medically ill patients, is often done with the Mini-Mental State Exam (MMSE), the mainstay in psychiatric practice. However, the MMSE is somewhat insensitive to subcortical processes affecting cognition, can be influenced by educational level or visuomotor deficits, and cumbersomely requires time (10–15 minutes) and props (paper and pencil). A new, simple 16-item screening battery, the " Sweet 16," takes 2 to 3 minutes and tests only orientation (8 items), attention (2 digit span items), and memory (3 registration and 3 delayed memory items).
     After its development and testing in 774 patients post acute hospitalization, researchers validated the Sweet 16 against the MMSE in a representative sample (709 participants) from the Aging Demographics and Memory Study. The Sweet 16 correlated highly with the MMSE (r=0.94). The researchers determined the sensitivity and specificity of both measures (cut-off values: the Sweet 16, 14; MMSE, 24) against a gold standard (IQCODE). The Sweet 16 had higher sensitivity than MMSE (80% vs. 60%), but was less specific (70% vs. 86%).
     Comment: Clinicians already use the items on this battery to screen for dementia when the full MMSE is too cumbersome or lengthy to administer. This study provides cut-offs and sensitivity and specificity data to inform use of these common cognitive testing items. The brevity and lack of need for pencil and paper are huge advantages for the Sweet 16, which actually identifies more cases than the MMSE, although it may create a few more false positives. It does not adequately screen for the cognitive deficits in subcortical illnesses like HIV and Parkinson dementias, but it could become the standard for the future. The authors warn that the Sweet 16 should be used only as a screen; more extensive testing is warranted for those with positive results.
Peter Roy-Byrne, MD Published in Journal Watch Psychiatry March 21, 2011
Citation(s): Fong TG et al. Development and validation of a brief cognitive assessment tool: The Sweet 16. Arch Intern Med 2011 Mar 14; 171:432. http://www.ncbi.nlm.nih.gov/pubmed/21059967?dopt=Abstract

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