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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
February 16, 2013

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High Calcium Intake Linked to Increased CV and Mortality Risks in Women
Maternal Folic Acid Intake Early in Pregnancy Associated with Reduced Autism Risk
A Strategy to Avoid Surgery for Acute Anterior Cruciate Ligament Tears
Hip-Shopping Exposes U.S. System's Pricing Opacity
Lancet Series Focuses on Reducing Global Burden of Noncommunicable Diseases
Alcohol a Major Contributor to Cancer Mortality in U.S.
Synthetic Cannabinoids Associated with Acute Kidney Injury
No CV Benefit from Vitamin and Antioxidant Supplements
Sexual Dysfunction with Aromatase Inhibitor Therapy: An Underestimated Problem?
Neurostimulation in Parkinson's Seen Beneficial in Early Disease
FDA Asked to Determine Safe Levels of Added Sugars

MM: It appears that it may not be beneficial and possibly harmful to take what many practitioners consider an appropriate daily supplement of calcium. One theory that was previously espoused when looking for a friendly meeting place RE calcium intake was that if it was obtained solely from foods, then there would not be any increased CV danger. This may not be the case at all. We must continue to examine the data to discover if calcium supplementation is truly beneficial or potentially harmful.
High Calcium Intake Linked to Increased CV and Mortality Risks in Women
By Christine Sadlowski
Calcium intake above 1400 mg a day was associated with increased risks for cardiovascular disease and mortality among women in a prospective Swedish study in BMJ.
More than 60,000 women aged 39 to 73 at baseline completed a diet questionnaire starting in 1987. Over a median follow-up of 19 years, women who consumed 1400 mg or more of calcium daily (through diet or supplements) had 40% higher mortality, 51% higher cardiovascular mortality, and nearly double the ischemic heart disease mortality, compared with those who consumed 600 to 999 mg. Among women with 1400 mg daily intake, those who took calcium supplements had even higher all-cause mortality (adjusted hazard ratio, 2.57).
The authors conclude that efforts to prevent bone fractures in elders should focus "on people with a low intake of calcium rather than increasing the intake of those already consuming satisfactory amounts."
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MM: There appear to be many reasons for and theories about how autism may develop. Whether it results from experiences in utero or from post-partum external/environmental stimuli or a combination of events, the fact remains that it is an ever increasing problem that has grown by epidemic proportions in the past 20 years. Could the provision of more folic acid in early pregnancy improve a child's defense against autism? This is an interesting question and deserves a closer look.
Maternal Folic Acid Intake Early in Pregnancy Associated with
Reduced Autism Risk

By Kelly Young
Folic acid supplementation among women is associated with a reduced risk for autism in their offspring, according to a JAMA study.
Researchers studied a cohort of 85,000 infants from Norway, 0.13% of whom were later diagnosed with autistic disorder. Their mothers reported whether they took folic acid supplements during the 4 weeks before to 8 weeks after the beginning of pregnancy. (Food was not fortified with folic acid during this study.) After adjustment for potential confounders, mothers who took folic acid during this interval had children who were less likely to have autistic disorder, relative to mothers who did not use folic acid (adjusted odds ratio, 0.61). There was no association with Asperger syndrome or other autism spectrum disorders.
A secondary analysis done with fish oil supplements did not find a similar association with autism, suggesting that the effect was not attributable to general health-conscious behaviors.
CDC editorialists call the study "encouraging" and "provocative," but say it "seems at odds with the continued increases in [autism spectrum disorder] diagnoses observed in the United States since the folic acid food fortification program began in 1998."
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MM:With the increases to healthcare costs it makes sense to examine alternative approaches to treatment that are potentially as effective as surgery at a greatly reduced cost. Joints throughout the body have similarities as do connective tissues and if knees have a similar response to rehab and time to that of spines and backs, then it certainly makes sense to take a wait and see attitude in more cases to determine if or when surgery is appropriate
BMJ 2013 Jan 24; 346:f232
A Strategy to Avoid Surgery for Acute Anterior Cruciate Ligament Tears
Among young active patients, 5-year outcomes were no worse for optional later reconstruction than for early reconstruction.
In a recent study, European investigators found no differences in patient-reported 2-year outcomes between early reconstruction and optional later reconstruction among young active patients with acute anterior cruciate ligament (ACL) tears (JW Gen Med Aug 3 2010). Now, the same investigators report outcomes at 5 years.
Overall, 121 patients (mean age, 26) with acute ACL tears in previously uninjured knees participated in the trial. All patients received structured rehabilitation and were randomized to early reconstruction or optional later reconstruction. Thirty of the 59 patients (51%) in the latter group underwent delayed reconstruction (7 of these after year 2). At 5 years, no differences were noted between the groups in the results of knee injury, osteoarthritis, activity, and health scales. In addition, no differences were found in incident radiographic knee osteoarthritis or the number of knees that required meniscus surgery (about half in each group).
Comment: This study confirms earlier findings that rehabilitation plus early reconstruction does not result in better outcomes than rehabilitation with optional later reconstruction in young active patients with acute ACL tears. Using the latter strategy, about half of these patients could avoid surgery. The authors note that the results do not apply to less-active patients or to professional athletes, "but they should encourage clinicians and young active adult patients to consider rehabilitation as a primary treatment option."
Paul S. Mueller, MD, MPH, FACP  Published in Journal Watch General Medicine February 8, 2013
Citation(s): Frobell RB et al. Treatment for acute anterior cruciate ligament tear: Five year outcome of randomised trial. BMJ 2013 Jan 24; 346:f232.
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MM: This data blew me away. Most of us are aware that insurance companies and Medicare assign reimbursements (prices) to services and procedures. Hip replacement has become a pretty common practice and I was rather surprised to see such a significant price range on this procedure, especially if no "complications" were anticipated. I guess it's like anything else. The institutions have to make up the difference between what they fail to receive from Medicare and other insurance from the payers who are willing to foot the bill as it is presented but a 10 fold difference is rather substantial.
Hip-Shopping Exposes U.S. System's Pricing Opacity
By Christine Sadlowski
Patients may ask about a study in JAMA Internal Medicine highlighting the difficulty of obtaining price estimates for medical procedures.
A researcher posed as the grandchild of a 62-year-old woman without insurance who needed total hip replacement and would pay out-of-pocket. She called 20 top-ranked hospitals, and also two hospitals chosen randomly from each state, to request "bundled" pricing information — i.e., hospital plus physicians' fees. Top-ranked hospitals were more likely than the others to provide total cost information up front, but less than two thirds of each hospital type provided such information, even after multiple requests.
Price quotes ranged from about $10,000 to over $100,000 at both top-ranked hospitals and other hospitals.
The New York Times reports that the findings "are likely to fan the debate on the unsustainable growth of American health care costs and an opaque medical system in which prices are often hidden from consumers."
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MM: These diseases are the chronic healthcare issues that must be met. Obesity is a potential contributor to all of these conditions. Improvements to our food chain and distribution, a new approach to our "nutrition pyramid" and encouragement towards physical activity with appropriate nutritional supplementation to enhance and maintain optimal health are all important tools to batting these health epidemics and crises.
Lancet Series Focuses on Reducing Global Burden of Noncommunicable Diseases
By The Journal Watch Editors
The Lancet offers a series on how countries can achieve the World Health Assembly target of reducing mortality caused by noncommunicable diseases — cardiovascular disease, cancer, chronic respiratory disease, and diabetes — by 25% by 2025. The series includes papers that touch on low-cost interventions; ways to reduce inequalities; the tactics of big food, alcohol, and beverage companies; and using more generic drugs to treat more people.
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Alcohol a Major Contributor to Cancer Mortality in U.S.
By Kelly Young
Alcohol use was responsible for about 3.5% of all cancer deaths in the U.S. in 2009, according to a study in the American Journal of Public Health.
Researchers combined results of population surveys about alcohol use with the relative risks for cancer mortality observed in meta-analyses. In men, the majority of the alcohol-related cancer deaths were due to cancers of the oral cavity, pharynx, larynx, and esophagus. In women, the majority were due to breast cancer. Each cancer death resulted in roughly 18 years of potential life lost. Roughly 30% of the alcohol-attributable cancer deaths occurred in people who drank about 1.5 or fewer drinks per day.
As to the mechanism for these effects, the authors offer: "genotoxic effects of acetaldehyde, production of reactive oxygen or nitrogen species, changes in folate metabolism, increased estrogen concentration, or serving as a solvent for tobacco metabolites."
The authors call for clear statements of the danger from healthcare organizations, emphasizing that "there is no safe level at which there is no cancer risk."
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Synthetic Cannabinoids Associated with Acute Kidney Injury
By Cara Adler
Acute kidney injury can be added to the list of toxicities associated with use of synthetic cannabinoids (also called "spice" or "K2"), according to an MMWR article.
Between March and December of last year, 16 previously healthy young people from six states presented to emergency departments with symptoms including nausea, vomiting, and flank, back, or abdominal pain within days or hours after smoking synthetic cannabinoids. All were hospitalized. Peak serum creatinine levels ranged from 3.3 to 21.0 mg/dL. Kidney function recovered in most patients within 3 days of the creatinine peak. Five patients required hemodialysis. No patients died.
Toxicologic analysis in seven cases identified a new synthetic cannabinoid called XLR-11 in five, but the authors note that there was no single product that explained all cases.
The authors advise clinicians to ask otherwise healthy young patients with unexplained acute kidney injury about use of synthetic cannabinoids, and to report suspected cases to poison centers (1-800-222-1222) and health departments
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BMJ 2013 Jan 18; 346:f10
No CV Benefit from Vitamin and Antioxidant Supplements
Taking vitamins and antioxidants does not prevent major adverse cardiovascular events.
Although observational studies have linked higher intakes of vitamin- and antioxidant-rich fruits and vegetables with lower cardiovascular (CV) risk, randomized trials of vitamin and antioxidant supplements have yielded conflicting results. Most prior meta-analyses of these trials have involved individual vitamin or antioxidant supplements, and no meta-analysis has included comprehensive randomized trial data on this topic. In this meta-analysis, investigators reviewed data from 50 randomized, controlled trials that involved 295,000 participants to assess the efficacy of vitamin and antioxidant supplements in preventing major adverse CV events.
In the overall analysis, supplemental vitamins and antioxidants had no effect on risk for CV-related death, myocardial infarction, angina, stroke, sudden cardiac death, or transient ischemic attack. Similarly, these supplements had no effect overall on CV risk in subgroup analyses by type of prevention trial (primary or secondary), type of vitamins and antioxidants, CV outcomes, duration of treatment, supplements given singly or in combination, study design, study quality, or funding source.
Comment: In this large meta-analysis, which included data from a recently published randomized trial (JW Gen Med Nov 15 2012), vitamin and antioxidant supplementation did not prevent major adverse CV events. The study authors reasonably conclude, "There is no evidence to support the use of vitamin or antioxidant supplements in the prevention of cardiovascular disease." Nonetheless, these supplements might have other benefits, such as cancer prevention (JW Gen Med Oct 25 2012).
Paul S. Mueller, MD, MPH, FACP  Published in Journal Watch General Medicine February 14, 2013
Citation(s): Myung S-K et al. Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: Systematic review and meta-analysis of randomised controlled trials. BMJ 2013 Jan 18; 346:f10.
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Menopause 2013 Feb; 20:162
Sexual Dysfunction with Aromatase Inhibitor Therapy: An Underestimated Problem?
Swedish study shows AI use is associated with low sexual desire, inadequate vaginal lubrication, and sexual dissatisfaction.
Aromatase inhibitor (AI) therapy has become a standard adjuvant endocrine treatment for postmenopausal women with hormone receptor–positive tumors; however, its impact on sexuality remains to be investigated. In this cross-sectional study, Swedish investigators enrolled 82 women with receptor-positive breast cancer and 105 age-matched women without breast cancer (mean age of all participants at entry, 62). Sexual function was assessed in four groups: women with breast cancer who were using tamoxifen or AIs, and women without breast cancer who were or were not using vaginal or systemic estrogen.
Overall, 60% to 68% of participants reported being sexually active. Distressing low sexual desire was nonsignificantly more prevalent in AI users (21%) than in tamoxifen users (10%) or breast cancer–free women using estrogen (14%) or not using estrogen (6%). Distressing insufficient vaginal lubrication was significantly more prevalent in AI users (60%) than in any other group (range, 17%–28%). Fully 42% of AI users expressed dissatisfaction with their sex lives compared with 18% of tamoxifen users (P<0.05), 27% of estrogen users, and 14% of estrogen nonusers (P<0.05).
Comment: As use of aromatase inhibitors grows, more attention should be paid to the effects of these medications on sexuality. These findings suggest that inadequate vaginal lubrication is more common in AI users than previously reported. Women who experience severe dyspareunia might also avoid other forms of intimate contact, leading to further stress in their relationships with partners. Because both the 2-mg estradiol vaginal ring and 25-µg estradiol vaginal tablets raise serum estradiol levels in women receiving AIs (J Oncol Practice 2012; 8:144), medical oncologists have been cautious about use of vaginal estrogen in such patients. Although over-the-counter vaginal lubricants and moisturizers should be encouraged in these women, the efficacy of these agents is limited. As part of the effort to provide an effective, safe option, a clinical trial of 10-µg estradiol vaginal tablets in AI users is under way.
Andrew M. Kaunitz, MD  Published in Journal Watch Women's Health February 14, 2013
Citation(s): Baumgart J et al. Sexual dysfunction in women on adjuvant endocrine therapy after breast cancer. Menopause 2013 Feb; 20:162.
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MM: This is one of those science geek things that I love to hear about. Imagine if we could hook up a simple battery pack with robot guided electrodes into the brain to diminish the progression of Parkinsonian diseases. If this is truly beneficial it could not only slow progression but prevent any drug related side effects in the process.
Neurostimulation in Parkinson's Seen Beneficial in Early Disease
Stimulation of the subthalamic nucleus with implanted electrodes earlier than is customary in the course of Parkinson's disease improves quality-of-life measures better than medical therapy alone, according to a New England Journal of Medicine study.
Conducted in Germany and France, the study randomized some 250 patients to treatment either with neurostimulation plus medication or to drug therapy alone. All patients were in relatively early stages of disease — i.e., all were under 60, their mean duration of symptoms was 7.5 years, and all had severity ratings below stage 3 on a scale of 0 to 5.
After 2 years, the neurostimulation group had quality-of-life improvements 8 points higher than the drug therapy group (on a 100-point scale). Major depression was more common with neurostimulation.
An editorialist comments that "for carefully chosen, highly functioning patients, [neurostimulation] may provide many additional years of good functioning."
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FDA Asked to Determine Safe Levels of Added Sugars
By Cara Adler
The Center for Science in the Public Interest has petitioned the FDA to set limits for safe amounts of added sugars in foods and beverages.
Citing America's overconsumption of sugar and its contribution to obesity, heart disease, and other health problems, the petition requests that the FDA:

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