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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
August 20, 2011

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Implications of False-Negative Clostridium difficile Tests
Lactation Support Can Help Fend Off Postpartum Depression
Illegal Online Pharmacies Using Consumer-Search-Engine Manipulation to
   Redirect Shoppers to Unauthorized Drug Sites
Drug Shortages Lead to Price Gouging
Inspection Deal Aims to Improve Generic Drugs
Study Finds Slim Isn't Always Best
Chinese Herbs as Efficient as Oseltamivir (Tamiflu®) for Shortening Flu Symptoms
Good Delivery Outcomes for Expectant Mothers with Multiple Sclerosis
Clinical study using MRI scans and mental tests linked fish oil to better, bigger brains …
   benefits were absent in the miniority carrying the APOE4 “Alzheimer’s gene
Revisiting High-Dose Chemotherapy for Breast Cancer
Twins with Autism: A Focus on Environmental Factors
A Look Back at the Effect of Varicella Vaccination on Varicella Deaths

MM: Testing is a great thing and can frequently rule out or identify problems. A problem with testing is when we allow the tests to deny the clinical signs and symptoms. In any case, one of the greatest causes of death worldwide is micro-organism associated diarrhea. The use of Saccharomyces Boulardii (SB) is a safe, effective and inexpensive treatment that is in many cases potentially life-saving.
Clin Infect Dis 2011 Aug 1; 53:287.
Implications of False-Negative Clostridium difficile Tests
Patients with false-negative results can be just as sick as those with positive results.
     Clostridium difficile infections (CDI) commonly are diagnosed with commercial enzyme immunoassays (EIAs) that identify bacterial toxin, but the tests' sensitivity seldom exceeds 80%. No one has established yet whether this poor performance reflects differences among patients (Are milder infections, for instance, more likely to be missed by EIA?), reflects differences among organisms, or is simply a test characteristic.
     Investigators prospectively identified 42 hospitalized patients with diarrhea and negative C. difficile toxin EIAs in whom CDI had been confirmed with a two-step strategy using a more accurate polymerase chain reaction (PCR) assay for the toxin genes. These patients were indistinguishable from 90 patients with positive EIAs across more than two dozen clinical variables, ranging from underlying medical conditions and previous antibiotic use to severity of diarrhea and likelihood of recurrence.
     All organisms isolated from stool of EIA-negative patients produced toxin in culture, and skin and environmental cultures were no less likely to yield C. difficile than those of EIA-positive patients. The one difference: EIA-negative patients were less likely to harbor the ribotype 027 strain, a particularly virulent C. difficile strain.
     Comment: The high false-negative rate of EIA for C. difficile toxin apparently reflects nothing but the variability of a poor test. A better test is urgently needed. (The PCR test used in this study is accurate but very expensive for routine use.)
Abigail Zuger, MD Published in Journal Watch General Medicine August 18, 2011
      Citation(s):Guerrero DM et al. Clinical and infection control implications of Clostridium difficile infection with negative enzyme immunoassay for toxin. Clin Infect Dis 2011 Aug 1; 53:287. (http://dx.doi.org/10.1093/cid/cir361)
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MM: Post partum depression (PPD) is a very scary thing. At a time when one should be joyful about the new addition to a family and the miracle of life, a person can be thrust into the depths of an unending nightmare.  Breast feeding may mute the effects of a change in pregnancy levels of progesterone. Progesterone supplementation in the form of injection, transdermal cream or buccal lozenge has been demonstrated in many patients to provide relief from PPD.
Obstet Gynecol 2011 Aug; 118:214.
Lactation Support Can Help Fend Off Postpartum Depression
Help for breast-feeding pain while in the hospital was associated with lower risk for developing postpartum depression.
     Postpartum depression, which affects 13% of mothers during the first 12 weeks postpartum, adversely affects infant development and can result in adverse outcomes including maternal suicide. To examine how mothers' early breast-feeding experiences affect risk for postpartum depression, investigators analyzed data from the CDC's nationally representative Infant Feeding Practices Study II that was prospectively collected from 2586 mothers who reported ever breast-feeding.
     At 1 week postpartum, only 2% of mothers reported no pain with breast-feeding, and 23% reported severe pain; at 2 weeks, 11% of mothers reported no pain, and 12% reported severe pain. Women who experienced severe pain during their first 2 weeks of breast-feeding were twice as likely to be depressed by 2 months postpartum as were mothers who experienced no pain with early breast-feeding. Mothers who received lactation support for moderate or severe pain with early breast-feeding were significantly less likely to develop postpartum depression (adjusted odds ratios, 0.22 and 0.17, respectively) than were those who did not receive lactation support.
     Comment: Although the authors adjusted for many potential confounders (e.g., parity; maternal age; education; ethnicity; participation in a Women, Infants and Children agency program), they were not able to adjust for maternal body-mass index, histories of depression, or whether pregnancies were planned. In addition, they were not able to distinguish the effects on maternal wellbeing of lactation support from those of overall support. Nonetheless, given the multiple maternal and infant benefits of breast-feeding, consideration should be given to expanding lactation support for mothers who experience pain with early breast-feeding; moreover, mothers who have difficulties with breast-feeding should be monitored carefully for postpartum depression.
Eleanor Bimla Schwarz, MD, MS Published in Journal Watch Women's Health August 18, 2011
     Citation(s):Watkins S et al. Early breastfeeding experiences and postpartum depression. Obstet Gynecol 2011 Aug; 118:214.
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Illegal Online Pharmacies Using Consumer-Search-Engine Manipulation to Redirect Shoppers to Unauthorized Drug Sites
     Consumers attempting to buy prescription medications over the Internet may fall victim to one of the many illegal online pharmacies popping up on the web according to cyber-security experts at Carnegie Mellon University. Their report says that infected websites are redirecting online shoppers to dangerous unauthorized pharmacies.
      The study reported the top results for 218 drug-related web searches over the course of nine months in 2010 and 2011. They found the search results were being manipulated to promote unauthorized pharmacies. In the past, it has been known that unauthorized online pharmacies have been using email spam to take advantage of unwary online consumers; however, this did not cover enough customers so now the online thieves are infecting websites to redirect unwary consumers to hundreds of illegal online pharmacies http://consumer.healthday.com/Article.asp?AID=655839
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MM: There seem to be more cases of drug shortages at the hospital level than I can remember in my 30 years of pharmacy practice. It is especially distressing at the number of injectible products that appear to be in short supply. Mark Drugs is the only Accredited Compounding Pharmacy in the state of Illinois and can help to close the gap for many of these products. If your institution is in need of an item, please contact us.
Drug Shortages Lead to Price Gouging
     Scalping tickets to a sporting event or a rock concert can get you arrested; but reselling drugs in short supply at a hefty markup is a thriving business. As an example, Propofol is in short supply at a cost of 3,161% more than regular price.
     Being in the midst of a record shortage of prescription drugs, unscrupulous marketers are stockpiling hard-to-find drugs and attempting to sell them back to hospitals at up to 50 times their normal prices. However, even though pharmaceutical price gouging isn't illegal, it is unethical and potentially dangerous.
     Among backordered drugs with the biggest markups are (1) Labetalol-4,533%, (2) Cytarabine-3,980%, (3) Dexamethasone-3,857%, (4) Leucovorin-3,170 %, (5) Propofol- 3,161%, (6) Papavarine-2,979%, (7) Protamine-2,752%, (8) Levophed-2,642%, (9) Sodium chloride concentrate-2,350%, and (1) Furosemide-1,721%.
     Looking at the labetalol example that is reported to cost $25 a dose, hospitals have been asked to pay $1,200. The FDA has listed 180 drugs in short supply. Hospitals have responded, in some cases, by delaying surgeries or turning to less-effective drugs. Purchasing from unauthorized dealers can put patients at risk by circulating counterfeit or stolen medications; also these drugs may not have been stored and handled properly, which can adversely affect their stability.

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Inspection Deal Aims to Improve Generic Drugs
     An agreement between pharmaceutical manufacturers and the FDA will force the scrutiny of overseas plants. Over 80 percent of the active ingredients for drugs sold in the US are made overseas, mostly in a network of facilities in China and India that are rarely visited by government inspectors, who sometimes cannot even find the plants.
     After decades of failed attempts, the federal government and the generic drug industry have reached an agreement that should pass Congress and will lead to routine inspections of these overseas plants. Under this agreement, expected to be completed within weeks, generic drug companies (which make 75 percent of the prescription medicines sold in the US) would pay $299 million in annual fees to underwrite inspections of foreign manufacturing plants every two years, the same frequency required of domestic plants.
     At the present rate of inspection, the FDA would need more than 13 years to inspect every foreign drug plant exporting to the US. Some plants have never been inspected, saving huge sums in cleanup and other compliance costs. This is one reason that drug manufacturing is disappearing from the United States.
     OTC medications and vitamins are not affected. Aspirin and vitamin C supplements, among others, are now made almost entirely in uninspected plants in China.
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Study Finds Slim Isn't Always Best
     York University has published a study in Applied Physiology, Nutrition and Metabolism showing that obese people who are otherwise healthy live just as long as their slim counterparts, and are less likely to die of cardiovascular causes.
     These findings challenge the idea that all obese individuals need to lose weight according to lead author Jennifer Kuk, assistant professor in York's School of Kinesiology & Health Science, Faculty of Health. "Moreover, it's possible that trying - and failing - to lose weight may be more detrimental than simply staying at an elevated body weight and engaging in a healthy lifestyle that includes physical activity and a balanced diet with plenty of fruits and vegetables," she says.
     The study looked at 6,000 obese Americans over a 16-year span, comparing their mortality risk with that of lean individuals finding that obese individuals who had no (or only mild) physical, psychological or physiological impairments had a higher body weight in early adulthood, were happier with this higher body weight, and had attempted to lose weight less frequently during their lives. These individuals were also more likely to be physically active and consume a healthy diet.
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Chinese Herbs as Efficient as Oseltamivir (Tamiflu®) for
Shortening Flu Symptoms

     Traditional Chinese herbal therapy resolves fever in influenza as quickly as oseltamivir, according to an Annals of Internal Medicine study.
     Researchers studied some 400 adults and adolescents in 11 Chinese hospitals who had uncomplicated 2009 H1N1 influenza A. Patients, who remained in the hospital for quarantine purposes and not the severity of their illness, were randomized to one of four groups: maxingshigan-yinqiaosan, oseltamivir, maxingshigan-yinqiaosan plus oseltamivir, or no treatment. (Maxingshigan-yinqiaosan comprises 12 herbs, including ephedra, which is restricted in the U.S.)
     The median time to fever resolution was significantly shorter with oseltamivir (20 hours), maxingshigan-yinqiaosan (16), and combination therapy (15) than with no treatment (26). Symptomatic improvement did not differ among the treatment groups. Two patients using maxingshigan-yinqiaosan had nausea and vomiting.
     The authors conclude that the herbal treatment can be used as an alternative when oseltamivir is not available.
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Ann Neurol 2011 Jul; 70:41.
Good Delivery Outcomes for Expectant Mothers with Multiple Sclerosis
A large, population-based cohort study found no increase in adverse neonatal and delivery outcomes
     Studies of pregnancy outcomes in women with multiple sclerosis (MS) have been limited and have had inconsistent results. Aiming to provide more-reliable data, investigators in British Columbia used a perinatal registry that included >99% of births in the region during an 11-year period. They cross-referenced these data by personal health number to an MS registry that included 80% of the region's MS patients. Each MS birth was compared with several demographically matched control births. Detailed information about demographics, obstetrical history, and medical conditions ensured that potential confounders were minimized.
     A total of 432 births to 321 women with MS were included, along with 2975 births to 2958 women without MS. Maternal MS was not statistically associated with gestational age, birth weight, forceps- or vacuum-assisted vaginal delivery, caesarean section, or Apgar scores.
     Comment: Women of childbearing age with MS often ask whether pregnancy is medically advised. The neurologist typically focuses on the mother's health in explaining the risks and benefits of stopping MS medication, advising on whether to breast-feed, and discussing when to restart therapy after delivery. However, these women are also interested in what will happen to their babies. Until now, we lacked data on this important question. We can now reassure women with MS about the delivery and immediate perinatal outcome. As currently managed, MS is not associated with an increased likelihood of a premature delivery, delivery complications, or lower birth weight and does not affect short-term neonatal outcomes.
Robert T. Naismith, MD Published in Journal Watch Neurology August 16, 2011
     Citaation: van der Kop ML et al. Neonatal and delivery outcomes in women with multiple sclerosis. Ann Neurol 2011 Jul; 70:41.
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Clinical study using MRI scans and mental tests linked fish oil to better,
bigger brains … benefits were absent in the miniority carrying the
APOE4 “Alzheimer’s gene”

Fish Oil Aided Size and Health of Aging Brains
by Craig Weatherby
     Omega-3 fish oil may keep aging brains from shrinking and dimming, according to a study presented in June at the International Conference on Alzheimer’s Disease in Paris. Researchers at Rhode Island Hospital reported that their study linked fish oil supplements to better cognitive functioning as well as to bigger brains. The study was led by Lori Daiello, PharmD, at the Rhode Island Hospital Alzheimer’s Disease and Memory Disorders Center. The data for the analyses was obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a large, NIH-funded study that followed older adults with normal cognition, mild cognitive impairment, and Alzheimer’s Disease. The 819 study participants were followed for more than three years, and underwent periodic memory testing and brain MRIs.

Study links fish oil to better thinking, bigger brains
     Among the volunteers, 117 – or 14 percent – reported taking fish oil supplements regularly, before and during the three-year study. The researchers compared cognitive functioning and brain atrophy (shrinkage) in those who reported that they routinely took omega-3 fish oil, versus the 702 (86 percent) who said they took no fish oil. Ms. Daiello’s team reported that compared to non-users, use of fish oil supplements was associated with better cognitive functioning during the study. However, this association was significant only in those who showed normal thinking and memory capacity at the start of the study. And better cognition was not seen in individuals who had a genetic risk factor for Alzheimer’s Disease, known as APOE4. The unique, novel finding of this study was a clear association between fish oil supplements and bigger brain volume.
     As Daiello said, “We found a significant positive association between fish oil supplement use and average brain volumes in two critical areas utilized in memory and thinking – cerebral cortex and hippocampus – as well as smaller brain ventricular volumes compared to non-users at any given time in the study.  “In other words,” she continued, “fish oil use was associated with less brain shrinkage in patients taking these supplements during the ADNI study compared to those who didn’t report using them.” But, as with the thinking and memory advantages, the brain-size benefit was not seen in those who had the APOE4 gene variation. Daiello continues, “These observations should motivate further study of the possible effects of long-term fish oil supplementation on important markers of cognitive decline and the potential influence of genetics on these outcomes.”
Prior findings render results plausible
     This was not a controlled clinical trial, in which people would have been assigned to take fish oil or a placebo. But its positive findings seem plausible, given the prior evidence showing that omega-3s can improve thinking/memory capacity, increase brain volume, and stimulate growth of new networks among brain cells (neurons). The brain-volume benefit has been seen in some but not all prior studies (Puri BK et al. 2001; Quinn JF et al. 2010; McNamara RK 2010) … including three we reported on: “Omega-3s Boost Brain Networks Critical to Memory”, “Harvard Team Finds Key Cause of Age-Related Brain Fog”, and the “Study 1” section of “Omega-3s Display More Brain-Mood Benefits.”
Gene variation regulates Alzheimer’s risk … and omega-3 benefit
     The finding that fish oil did not benefit people with the APOE4 gene fits with most research related to late-onset Alzheimer’s. However, fish oil has may reduce agitation symptoms in APOE4 carriers, and improve symptoms of depression in patients who carry APOE2 or APOE3. See “Omega-3 DHA Alleviates Agitation in Early-Onset Alzheimer’s” and the “Study #4” section of “Brain Benefits of Fish (and Veggies) Gain Support”. Most cases of Alzheimer’s disease (AD) are the “late-onset” form, which develops after age 60. The APOE gene comes in several different forms, or alleles, three of which – APOE2, APOE3, and APOE4 – occur most often. People who develop Alzheimer's are more likely to have an APOE4 allele than people who do not develop the disease. APOE4 is present in about 25 to 30 percent of all people, and in about 40 percent of people with late-onset Alzheimer's. People who inherit one or two APOE4 alleles also tend to develop the disease at an earlier age than those who do not have any APOE4 alleles. Carriers of two E4 alleles have between 10 and 30 times the risk of developing AD by 75 years of age, compared to those not carrying any E4 alleles.
     Why would the APOE variant matter? Alzheimer’s disease is characterized by – though not necessarily caused by – build-up of beta-amyloid protein plaque and tau protein tangles in the brain. And some evidence suggests that people with APOE4 alleles are not as efficient at removing amyloid plaque. The jury is still out, however, until research finds the link(s) between APOE4 and Alzheimer's risk and severity.
 Sources: Calderon F, Kim HY. Docosahexaenoic acid promotes neurite growth in hippocampal neurons. J Neurochem. 2004 Aug;90(4):979-88. Erratum in: J Neurochem. 2004 Sep;90(6):1540. Cansev M, Watkins CJ, van der Beek EM, Wurtman RJ. Oral uridine-5'-monophosphate (UMP) increases brain CDP-choline levels in gerbils. Brain Res. 2005 Oct 5;1058(1-2):101-8. Epub 2005 Aug 29. Cao D, Xue R, Xu J, Liu Z. Effects of docosahexaenoic acid on the survival and neurite outgrowth of rat cortical neurons in primary cultures. J Nutr Biochem. 2005 Sep;16(9):538-46. Darios F, Davletov B. Omega-3 and omega-6 fatty acids stimulate cell membrane expansion by acting on syntaxin 3. Nature. 2006 Apr 6;440(7085):813-7. Issa AM, Mojica WA, Morton SC, Traina S, Newberry SJ, Hilton LG, Garland RH, Maclean CH. The efficacy of omega-3 fatty acids on cognitive function in aging and dementia: a systematic review. Dement Geriatr Cogn Disord. 2006;21(2):88-96. Epub 2005 Dec 9. Review. Lim WS, Gammack JK, Van Niekerk J, Dangour AD. Omega 3 fatty acid for the prevention of dementia. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD005379. Review. Marszalek JR, Lodish HF. Docosahexaenoic acid, fatty acid-interacting proteins, and neuronal function: breastmilk and fish are good for you. Annu Rev Cell Dev Biol. 2005;21:633-57. Review. McEvoy LK, Holland D, Hagler DJ Jr, Fennema-Notestine C, Brewer JB, Dale AM; Alzheimer's Disease Neuroimaging Initiative. Mild cognitive impairment: baseline and longitudinal structural MR imaging measures improve predictive prognosis. Radiology. 2011 Jun;259(3):834-43. Epub 2011 Apr 6. McNamara RK. DHA deficiency and prefrontal cortex neuropathology in recurrent affective disorders. J Nutr. 2010 Apr;140(4):864-8. Epub 2010 Feb 10. Puri BK, Counsell SJ, Hamilton G, Richardson AJ, Horrobin DF. Eicosapentaenoic acid in treatment-resistant depression associated with symptom remission, structural brain changes and reduced neuronal phospholipid turnover. Int J Clin Pract. 2001 Oct;55(8):560-3. Quinn JF, Raman R, Thomas RG, Yurko-Mauro K, Nelson EB, Van Dyck C, Galvin JE, Emond J, Jack CR Jr, Weiner M, Shinto L, Aisen PS. Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. JAMA. 2010 Nov 3;304(17):1903-11. Rhode Island Hospital (RHI). Rhode Island Hospital Study Identifies Fish Oil’s Impact On Cognition And Brain Structure. August 17, 2011. Accessed at http://www.lifespan.org/news/2011/08/17/rhode-island-hospital-study-identifies-fish-oils-impact-on-cognition-and-brain-structure/ Shrivastava R, Vincent B, Gobron S, Cucuat N, John GW. Evidence for growth-promoting effects of omega n - 3 fatty acids alone and in combination with a specific vitamin and mineral complex in rat neuroblastoma cells. Nutr Neurosci. 2005 Oct-Dec;8(5-6):317-21. Tosun D, Schuff N, Mathis CA, Jagust W, Weiner MW; Alzheimer's Disease NeuroImaging Initiative. Spatial patterns of brain amyloid-beta burden and atrophy rate associations in mild cognitive impairment. Brain. 2011 Apr;134(Pt 4):1077-88. Epub 2011 Mar 22. Wang L, Pooler AM, Albrecht MA, Wurtman RJ. Dietary uridine-5'-monophosphate supplementation increases potassium-evoked dopamine release and promotes neurite outgrowth in aged rats. J Mol Neurosci. 2005;27(1):137-45. Wurtman R, Ulus I, Cansev M, Watkins W, Wang L, Marzloff G. Increased dendritic spine density in adult gerbil hippocampus following oral UMP and DHA supplementation. The International Academy of Nutrition & Aging 2006 SYMPOSIUM II Nutrition and Alzheimer’s Disease/Cognitive Decline. Oral Presentation May 2, 2006, InterContinental Chicago. Wurtman RJ, Ulus IH, Cansev M, Watkins CJ, Wang L, Marzloff G. Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally. Brain Res. 2006 Apr 19; [Epub ahead of print]
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J Clin Oncol 2011 Jul 18
Revisiting High-Dose Chemotherapy for Breast Cancer
Meta-analyses show that overall survival was not prolonged in the adjuvant or metastatic setting.
     Some clinicians might find it difficult to remember that high-dose chemotherapy (HDC) was once heralded as the answer to treating patients with high-risk or advanced breast cancer. An entire industry developed around this therapeutic approach, which evolved largely as a result of promising phase II trials. Patients clamored to receive HDC, and lawsuits against insurers multiplied if the treatment was denied. All this activity occurred prior to the completion of phase III randomized trials that addressed the efficacy of HDC. The general mind-set at the time was that HDC worked; thus, accrual to ongoing key randomized trials was slowed.
     Now, researchers have assembled a single database from six randomized clinical trials in which HDC plus autologous stem-cell support (ASCS) was compared with a less intense chemotherapy regimen without ASCS in 866 women with metastatic breast cancer. Patients' disease characteristics were generally well defined, although human epidermal growth factor receptor 2 (HER2) status was largely unknown. HDC with ASCS resulted in longer progression-free survival (median, 11.0 vs. 8.3 months) than did nonbone marrow ablative approaches, but no improvements in overall survival (OS) were seen. No clinical subset of patients benefited from HDC plus ASCS.
     In a second report, the same group conducted a meta-analysis of 15 randomized trials that involved 6210 patients (mostly premenopausal) with high-risk primary breast cancer who were randomized to HDC plus ASCS or to nonbone marrow ablative chemotherapy that did not require ASCS. HER2 status was unknown in most patients. HDC plus ASCS prolonged relapse-free survival (hazard ratio, 0.87; P<0.001) but not OS. Again, no subset of patients seemed to benefit from HDC plus ASCS.
     Comment: As results of phase III trials of HDC plus ASCS in breast cancer were published, enthusiasm for this therapeutic approach all but disappeared. Now, with even longer follow-up and a deeper understanding of breast cancer biology, most believe that this approach met an appropriate end. However, the findings resulted in greater emphasis on managing adverse effects, the introduction of cytokines to support blood counts, development of tools to measure quality of life, and development of translational work to characterize residual disease. One of the most important lessons learned is that phase II trials are no substitute for carefully conducted, randomized phase III trials.
William J. Gradishar, MD Published in Journal Watch Oncology and Hematology August 16, 2011
     Citation(s):Berry DA et al. High-dose chemotherapy with autologous stem-cell support as adjuvant therapy in breast cancer: Overview of 15 randomized trials. J Clin Oncol 2011 Jul 18; [e-pub ahead of print]. (http://dx.doi.org/10.1200/JCO.2010.32.5910)
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Arch Gen Psychiatry 2011 Jul 4
Twins with Autism: A Focus on Environmental Factors
The concordance rates in dizygotic twins and shared environmental liabilities are higher than expected.
     The burgeoning number of studies of genetic and environmental risk factors for autism (e.g., Nature Genetics 2010; 42:489; and Arch Gen Psychiatry 2011 Jul 4 (e-pub ahead of print)) have paralleled the growing number of reports of increased prevalence among U.S., European, and Asian populations (e.g., JW Psychiatry Jun 6 2011). Genetic variations alone are unlikely to increase prevalence because population genomes would not change so quickly.
     These researchers investigated environmental versus inherited effects in a birth cohort of twin pairs from the California developmental disabilities system, of whom at least one was diagnosed with autism. The investigators used research criteria (comprehensive parental interviews and child assessments) to reevaluate the twins for autism spectrum disorder (ASD) and strict autism. Of 1156 potential twin pairs, 192 met diagnostic criteria and had family consent to the study; 143 pairs had at least one twin with strict autism.
     The pairwise concordance rates in dizygotic twins were unexpectedly high both for strict autism (sex-concordant female and male dizygotic pairs, 0.21–0.27; female and male monozygotic pairs, 0.58–0.60) and for ASD (dizygotic pairs, 0.31–0.36; monozygotic pairs, 0.50–0.77). Variance due to shared environment was 55% for strict autism and 58% for ASD; variance due to genetic factors was 37% and 38%, respectively.
     Comment: As the authors note, these concordance rates in dizygotic twins and shared environmental liabilities are higher than previously reported, but unlike some previous investigations, this study used rigorous diagnostic measures, including direct observation of the children. When discussing causes of autism with families, clinicians can inform them that at this time no specific causes of autism have been identified and that various inherited and environmental causes may be involved. There may also be genetic–environmental interactions, analogous to severe sunburn in genetically vulnerable, fair-haired, blue-eyed individuals, which is manifested only with an environmental trigger (sun exposure).
Barbara Geller, MD Published in Journal Watch Psychiatry August 15, 2011
     Citation(s):Hallmayer J et al. Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry 2011 Jul 4; [e-pub ahead of print].
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Pediatrics 2011 Aug; 128:214
A Look Back at the Effect of Varicella Vaccination on Varicella Deaths
In just over a decade, the average annual mortality rate for varicella-related deaths in the U.S. has declined 88%.
     During the first 6 years after the 1995 licensure of the varicella vaccine, varicella-related mortality in the U.S. dropped 66% (from 105 annual deaths to 39 deaths). This study examined varicella mortality from 2002 through 2007 — a period when vaccine coverage increased to about 90% in children aged 19 to 35 months.
     In 2002, varicella was listed in 32 records as the underlying cause of death. The annual number of varicella deaths in 2003 through 2007 ranged from 13 to 19; this represents an 88% decline in the average mortality rate from 0.41 per million population in the immediate prevaccine years (1990–1994) to 0.05 per 1,000,000 in 2005–2007. The decline was greatest in patients younger than 20 (97%) but also was apparent in older patients (age, 20–49: 90%; age, >50: 67%). Only 11% of patients whose deaths were related to varicella had preexisting high-risk medical conditions (all were malignancies).
     Comment: Varicella vaccination has had an enormous effect on varicella-related mortality. In 2007, the American Academy of Pediatrics recommended a second dose for children aged 4 to 6 years that can be expected to further decrease the number of varicella cases and deaths. Although this study did not address varicella morbidity, controlling varicella also reduces numerous nonfatal complications (e.g., infectious, neurological, hematologic). A critical finding is that most fatal cases were not in patients with known risk for severe disease. This report provides more fodder for discussions about the value of vaccination. For those in the trenches, keep up the good work and keep vaccinating! For those who are not familiar with what varicella looks like, hone your visual skills so you don't miss the appropriate window to diagnose and manage varicella when it does crop up.
Peggy Sue Weintrub, MD Published in Journal Watch Pediatrics and Adolescent Medicine August 17, 2011
     Citation(s):Marin M et al. Near elimination of varicella deaths in the US after implementation of the vaccination program. Pediatrics 2011 Aug; 128:214.

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