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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
September 15, 2012

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Exercise and Home Safety Interventions Prevent Falls in Older Adults
Hypothyroidism Guidelines Released
Is Helicobacter pylori Eradication Sufficient for Bleeding Ulcers?
Sports and Energy Drinks Erode Tooth Enamel
Recipe for Postmenopausal Weight Loss
Montelukast Reduces Severity of Obstructive Sleep Apnea in a Randomized Trial
Should HbA1c Cutoffs Differ for Blacks and Whites?
Strong Evidence for Cancer Stem Cells
Growth Hormone–Releasing Hormone for Cognition
Women Strengthened by Omega-3s

MM: Strength building exercise that involves core strength as well as balance and peripheral muscle tone will decrease the risk of falling and providing home safety adaptations are laudable but I think the Cochrane Collaboration misses the boat when it comes to vitamin D supplementation. First, a significant portion of the elderly population is vitamin D deficient or insufficient. The report states that those individuals with “normal” levels do not benefit from supplementation. Second, there is a broad array of data that indicates that people of all ages in the highest quartile of vitamin D levels compared to the lowest quartile have superior balance, muscle and fatigue revovery.
Exercise and Home Safety Interventions Prevent Falls in Older Adults
Group and home-based exercise programs, as well as home safety interventions, help prevent falls among community-dwelling older adults, according to a review by the Cochrane Collaboration.
In an update of its 2009 review, the group assessed 159 randomized trials of fall prevention interventions with nearly 80,000 participants aged 60 and older.
Among the other interventions that helped reduce the rate of falls or risk for falls:

Some of the interventions that did not have an effect include:


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MM: Although this review is almost 180 pages in length it still ignores the fact that a significant number of patients do not do well on L-thyroxine monotherapy and “feel” much better when using Armour thyroid or another natural or balanced thyroid supplement. Their clinical signs as well as their actual symptoms are far better when using the complete product. It is befuddling that the guidelines ignore the patients in lieu of the endocrinologist researchers.
Hypothyroidism Guidelines Released
New guidelines on managing hypothyroidism in adults have been issued by the American Association of Clinical Endocrinologists and the American Thyroid Association.
Published online in Thyroid, the guidelines comprise 52 evidence-based recommendations. These include:

The authors write that "while there is no consensus about population screening for hypothyroidism there is compelling evidence to support case-finding for hypothyroidism" in patients with automimmune disease and psychiatric disorders, among other conditions.
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MM: One of the interesting things about these study results is that they mirror the clinical results that we have experienced with probiotics and the use of our Betten-aid (Heartburn Away) product. We have seen that the use of this chewable product that contains probiotics and digestive enzymes, over an extended period of time tends to relieve both short and long term symptoms of gastritis, GERD and general dyspepsia. The puzzling thing has always been what provided the residual benefits of the product long after the patient stopped using it. Now we seem to have an answer.
Am J Gastroenterol 2012 Aug; 107:1197
Is Helicobacter pylori Eradication Sufficient for Bleeding Ulcers?
A prospective study suggests that peptic ulcer rebleeding is very unusual after H. pylori eradication and that maintenance antiulcer therapy may not be needed.
Helicobacter pylori infection is associated with peptic ulcer disease, and eradication of the infection reduces ulcer recurrence. The need for maintenance acid-reduction therapy in this setting is controversial.
To explore this issue, investigators at 10 university hospitals in Spain prospectively studied 1000 patients with endoscopically documented bleeding peptic ulcers and H. pylori infection. Participants were treated until eradication of the infection was confirmed by breath test. Thereafter, they received no acid-reduction therapy and were told not to take aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs). They returned at 1-year intervals for a clinical examination and a breath test for H. pylori. If signs or symptoms of upper gastrointestinal bleeding occurred, urgent endoscopy was performed.
All participants were followed for at least 12 months (total, 3253 patient-years of follow-up). Recurrence of peptic ulcer bleeding was rare, occurring in three participants during year 1 and two during year 2. All five cases of rebleeding involved either H. pylorireinfection or NSAID use. The cumulative incidence of rebleeding was 0.5% (95% confidence interval, 0.16%–1.16%) overall and 0.15% (95% CI, 0.05%–0.36%) per patient-year of follow-up.
Comment: These findings provide excellent evidence that H. pylori eradication is sufficient therapy for peptic ulcer patients — even if they had bleeding — in the absence of other causes for ulcers. Forty-one percent of the patients in this study had previously used NSAIDs or aspirin. Without a control group in which NSAIDs are continued, we cannot assess the effect of H. pylori eradication alone, but if such agents are avoided, H. pylorieradication appears to be definitive ulcer therapy. The real clinical challenge is to keep these patients from taking NSAIDs and identify those at high risk for H. pylori reinfection to determine who should be considered for continued antiulcer therapy.
— David J. Bjorkman, MD, MSPH (HSA), SM (Epid.)
 Journal Watch Gastroenterology September 14, 2012
Citation(s): Gisbert JP et al. Long-term follow-up of 1,000 patients cured ofHelicobacter pylori infection following an episode of peptic ulcer bleeding. Am J Gastroenterol 2012 Aug; 107:1197.
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Gen Dent 2012 May/Jun; 60:190.
Sports and Energy Drinks Erode Tooth Enamel
In laboratory simulations, energy drinks eroded twice as much tooth enamel as sports drinks.
The ability of acidic liquids to erode tooth enamel is well known, but the effects of regular consumption of sports and energy drinks on tooth enamel has not been well studied. Investigators analyzed the physiochemical properties (fluoride content, pH, titratable acidity) of 13 sports and 9 energy drinks. They also measured the capacity of a subset of drinks to erode tooth enamel by immersing enamel specimens from extracted molars in 100 mL of the sample beverage for 15 minutes 4 times daily for 5 days. Each 15-minute cycle alternated with a 2-hour immersion in 100 mL of artificial saliva. Enamel samples were weighed before and after immersion cycles to calculate enamel weight loss.
Both energy and sports drinks had lower fluoride levels than the recommended optimum level for drinking water (mean, 0.16 ppm and 0.28 ppm, respectively, vs. 0.7–1.0 ppm). Energy drinks (e.g., Rockstar, Von Dutch, Monster Assault, Red Bull Sugar Free, 5-Hour Energy) had four times the titratable acidity level as sports drinks (Propel, Powerade, Gatorade). Exposure to energy drinks also resulted in twice as much enamel weight loss as exposure to sports drinks (3.1% vs. 1.5%). Acidity varied among groups of energy and sports drinks; Gatorade Blue and Hydr8 ranked highest among sports drinks and Red Bull Sugar Free, Monster Assault, 5-Hour Energy, Von Dutch, and Rockstar ranked highest among energy drinks.
Comment: If sports and energy drinks replace a large proportion of water consumed daily by adolescents, their teeth could be harmed in two ways: inadequate fluoride intake and enamel erosion. Previous laboratory research by the author indicates that carbonated beverage consumption also reduces tooth enamel. Using a straw reduces tooth exposure to any liquid.
— Alain Joffe, MD, MPH, FAAP Published in Journal Watch Pediatrics and Adolescent Medicine
September 12, 2012
Citation(s): Jain P et al. A comparison of sports and energy drinks—Physiochemical properties and enamel dissolution. Gen Dent2012 May/Jun; 60:190.
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J Acad Nutr Diet 2012 Sep; 112:1347
Recipe for Postmenopausal Weight Loss
Pass the veggies, but skip dessert and soda.
Weight control can be particularly challenging for postmenopausal women. To identify the dietary changes most conducive to long-term weight loss in overweight and obese women, U.S. investigators analyzed data from 419 postmenopausal participants in the WOMAN Study. Women were randomized to "lifestyle change" intervention (regular group meetings facilitated by nutritionists, exercise physiologists, and psychologists) or a health education control group.
At 48 months of follow-up, 57% of intervention participants and 29% of controls had maintained at least a 5-pound weight loss. In multivariable analysis that combined both groups, increased consumption of fruits and vegetables and decreased consumption of desserts, sugar-sweetened beverages, and meat and cheese were associated with long-term weight control.
Comment: Given that more than one third of people in the U.S. are now obese, clinicians are frequently asked for advice about weight control. This study confirms that the recommended recipe for weight loss requires little modification as women age. Unfortunately, however, these guidelines are harder for women to practice than for clinicians to preach.
— Eleanor Bimla Schwarz, MD, MS Published in Journal Watch Women's Health September 13, 2012
Citation(s): Gibbs BB et al. Short- and long-term eating habit modification predicts weight change in overweight, postmenopausal women: Results from the WOMAN Study. J Acad Nutr Diet 2012 Sep; 112:1347.
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MM: This is interesting because montelukast is a mast cell stabilizer and much like the activity ofthis drug, probiotics have similar effects on mast cells and reduce inflammation. This offers a natural adjunct or alternative to the drug. Whenever these opportunities arise, its nice to be aware of them.
Pediatrics 2012 Sep 1; 130:e575
Montelukast Reduces Severity of Obstructive Sleep Apnea in a Randomized Trial
Children with nonsevere OSA had significantly improved sleep study results, adenoid size, and sleep symptoms.
Obstructive sleep apnea (OSA) can lead to cardiopulmonary and neurobehavioral consequences in children. Adenotonsillectomy is the most common surgical treatment for this condition, but some medical therapies have shown promise, including the leukotriene modifier montelukast in an open-label study. In this placebo-controlled, double-blind study, researchers in Israel randomized 46 nonobese children (age range, 2–10 years) who were referred for habitual snoring and were diagnosed with mild or moderate OSA by sleep study to receive daily oral montelukast (4 mg for ages 2–5 years and 5 mg for ages 6–10 years) or placebo for 12 weeks.
Children who received montelukast had a significant reduction in the number of sleep study-documented obstructive apneic events (from about 4 to 2 per hour) and in the adenoidal/nasopharyngeal ratio measured from lateral neck radiographs taken before and after the trial. In contrast, children who received placebo had no reductions in these outcomes. Parent questionnaires completed before and after the trial showed significant subjective improvements in witnessed apnea, breathing difficulties, snoring, awakenings, and restless sleep in the montelukast group and no improvements in the placebo group. No adverse events were reported.
Comment: This industry-supported study is the first randomized, placebo-controlled study of montelukast for mild to moderate OSA. The results demonstrate convincing objective and subjective improvements in nonobese children with mild to moderate OSA after 12 weeks of montelukast treatment. The authors hypothesize that montelukast interacts with leukotriene receptors on adenotonsillar tissue. Without a sleep study, it can be hard to know whether a child's OSA is mild or severe, but a time-limited therapeutic trial of montelukast seems worthwhile before deciding on surgery. Nasal steroids are another anti-inflammatory nonsurgical alternative. Of note, these findings do not apply to obese children with OSA or children with severe OSA.
— Cornelius W. Van Niel, MD Published in Journal Watch Pediatrics and Adolescent Medicine
September 12, 2012
Citation(s): Goldbart AD et al. Montelukast for children with obstructive sleep apnea: A double-blind, placebo-controlled study. Pediatrics 2012 Sep 1; 130:e575.
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Ann Intern Med 2012 Aug 7; 157:153
Should HbA1c Cutoffs Differ for Blacks and Whites?
Using retinopathy as a marker, researchers argue against a higher glycosylated hemoglobin cutoff for diagnosing diabetes in black patients.
At any given glucose level, glycosylated hemoglobin (HbA1c) measurements consistently are higher in black patients than in white patients, and many experts have debated the appropriateness of diagnostic cutoffs that fail to account for this racial difference. To examine the clinical relevance of this observation, researchers compared the relation between HbA1clevel and prevalence of retinopathy among blacks and whites. Cross-sectional data from the National Health and Nutrition Examination Survey (2005–2008) were used; more than 3800 individuals (age, ≥40) were included in the analysis, and all participants underwent retinal imaging.
After adjustment for multiple variables, including age, blood pressure, body-mass index, and use of antidiabetes medications, prevalence of retinopathy was significantly higher when HbA1c levels were ≥5.5% for blacks and ≥6.0% for whites, relative to the reference group (participants with HbA1c levels <5.5%).
Comment: Although blacks have a higher HbA1c level for any given glucose measurement, retinopathy is more common at lower HbA1c levels in blacks than in whites. This finding argues against raising the HbA1c cutoff for diagnosing diabetes in black patients. The reasons for this finding are unclear; one possibility, not addressed in the study, might be poorer blood pressure control among hypertensive blacks than among hypertensive whites at any given HbA1c level.
— Jamaluddin Moloo, MD, MPH Published in Journal Watch General Medicine September 13, 2012
Citation(s): Tsugawa Y et al. Should the hemoglobin A1c diagnostic cutoff differ between blacks and whites? A cross-sectional study. Ann Intern Med 2012 Aug 7; 157:153.
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Nature 2012 Aug 23; 488:522.
Strong Evidence for Cancer Stem Cells
A small number of cells give rise to all new cancerous cells in a tumor.
Most of us were taught that all malignant cells in a tumor have the potential for uncontrolled growth. However, in the past decade, some cancer biologists have postulated that only a few cells in a tumor have such potential. These cells, called cancer stem cells, have different genetic and phenotypic characteristics than the much larger mass of tumor cells that they spawn. Failure to kill these cancer stem cells might explain why therapies that kill a large fraction of the tumor burden fail to cure cancer.
The evidence for cancer stem cells has come largely from experiments in which cells from primary mouse tumors are transplanted into different mice. Critics have argued that such experiments do not reflect the normal biology of how cancers arise. Responding to that criticism, several teams now report on experiments in mouse strains that form tumors spontaneously. Using novel in vivo imaging techniques, these researchers confirm that a small fraction of cells in such tumors give rise to new cells that cause tumors growth.
Comment: If a small fraction of a tumor's cells (cancer stem cells) is responsible for tumor growth and metastasis, and if molecular markers distinguish these cells (as many experiments indicate), then these cells could be targeted directly — and the cancer could be cured. Prior research indicates this hope might not be unfounded
(JW Gen Med Jan 31 2012JW Gen Med Aug 27 2009, and JW Gen Med Aug 24 2006).
— Anthony L. Komaroff, MD Published in Journal Watch General Medicine September 11, 2012
Citation(s): Chen J et al. A restricted cell population propagates glioblastoma growth after chemotherapy. Nature 2012 Aug 23; 488:522.
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Arch Neurol 2012 Aug 6
Growth Hormone–Releasing Hormone for Cognition
GHRH improves cognitive performance and some endocrine values in healthy elderly people and in those with MCI.
Somatotrophic hormones, including growth hormone (GH), insulinlike growth factor 1 (IGF-1), and growth hormone–releasing hormone (GHRH), decrease with aging and may have a role in cognitive impairments. In a double-blind, placebo-controlled study, researchers examined the effect of manufacturer-supplied GHRH (1 mg/day) administered subcutaneously before bed for 20 weeks in 66 participants with amnestic mild cognitive impairment (MCI) and 86 healthy participants (mean age, 68). Researchers performed multiple assessments of IGF-1 levels, endocrine assessments at baseline and at week 20, and neuropsychiatric assessments at baseline, at weeks 10 and 20, and at 10 weeks after discontinuation (week 30).
In both healthy and MCI groups, GHRH was associated with benefits in overall cognitive performance and executive function and with a trend toward improved verbal memory. GHRH also increased lean muscle mass by 3.7% and decreased body fat by 7.4%. Changes in plasma insulin levels and body composition were not related to improvement. Increases in IGF-1 (occurring in the normal range) were associated with higher executive function scores (which showed a trend toward enduring improvement at week 30).
Comment: Growth hormone–releasing hormone had a beneficial effect on several cognitive measures in both normal elderly and those with amnestic mild cognitive impairment. Unfortunately, researchers did not measure the clinical significance of these changes: Did participants and their families notice them? More-sensitive measures of GH function (i.e., stimulation tests) than those used here might reveal whether actual GH deficiency correlates with response. This is a promising but expensive intervention ($50/injection), with unknown long-term safety and efficacy. We shouldn't forget inexpensive interventions, such as exercise and decreasing calorie intake, for cognitive stability (JW Psychiatry Mar 21 2011 and Mar 9 2009).
— Jonathan Silver, MD Published in Journal Watch Psychiatry August 27, 2012
Citation(s): Baker LD et al. Effects of growth hormone–releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults: Results of a controlled trial. Arch Neurol2012 Aug 6; [e-pub ahead of print].
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Arch Intern Med 2011 Aug 8/22; 171:1363
Women Strengthened by Omega-3s
Older women who took fish oil and exercised gained about twice as much leg muscle and strength.
Could fish oil help protect against aging-related muscle deterioration? Last year, we reported on the results of a small clinical study from Washington University, suggesting that fish oil may do just that ... see “Omega-3s May Reduce Age-Related Muscle Loss”. The second such trial, from Britain, supports the potential for fish oil to enhance the muscle-building effects of exercise in older people. In addition to strength and stability, skeletal muscle plays key roles in determining overall wellbeing.

During normal aging, muscle size shrinks by up to two percent a year … a process known as sarcopenia that can degrade quality of life and impair independence. U.S. health data suggests that one in four Americans aged 50 to 70 have sarcopenia, and that it afflicts more than half of those over 80 years of age.

As you’d expect, muscle is best built and maintained through resistance exercise using free weights or exercise machines.
However, as we age, our bodies are less able to boost muscle mass through exercise alone, with women being a bit more vulnerable to sarcopenia, compared with men.

UK study finds greater muscle gains with fish oil
Researchers from Scotland’s University of Aberdeen reported the results of small, “pilot” clinical trial last week, at the British Science Festival in Aberdeen.

They recruited 14 women aged over 65 years to participate in a small clinical trial lasting 12 weeks. Every day, the women performed an exercise program consisting of two 30-minute sessions of standard leg muscle exercises. Half the women were given fish oil providing the omega-3 fatty acids EPA and DHA, while the other half received a placebo pill containing olive oil. The women's leg muscle strength was measured at the start and end of the three-month trial … with compelling results:

Lead researcher Dr. Stuart Gray commented on possible reasons for the gains in the omega-3 fish oil group: “We believe the benefits of fish oil are due to a number of factors. Older people tend to have low-level inflammation in the body, which interferes with the muscles’ ability to increase strength and mass. The anti-inflammatory qualities found in fish oil may reduce this inflammation and therefore inhibit this interference.” (BSF 2012)

“Also the omega-3s found in fish oil help make muscles more fluid and proteins involved in increasing muscle mass function at a higher level in the body. We hope that providing new mechanistic insights into the benefits of fish oil on muscles could lead to the development of new pharmacological treatments to prevent against the loss of muscle with age.” (BSF 2012)  He announced the launch of a larger follow up study at the British Science Festival: “We will ask both males and females over the age of 65 to undertake an 18 week program of resistance training, where half the participants will also take fish oil supplements and half a placebo supplement. We will also analyze if males and females respond differently to the fish oil and resistance exercises in the study.” (BSF 2012)

Dr. Gray said the study will seek to determine the reasons why omega-3s help: “We will monitor changes in muscle mass, volume and fat content in the participants using MRI; insulin sensitivity and inflammation in blood samples; and changes in protein synthesis and molecular signaling in muscle biopsies. These changes will indicate to us the impact of fish oil on the body in helping prevent against sarcopenia.” (BSF) Men and women differ in their ability to make new muscle protein and in their responses to exercise. As Dr. Gray told the BBC, “Older women have similar levels of protein synthesis to younger women whereas older men have lower levels compared to younger men. Older men adapt to exercise and increase their protein synthesis. Older women don't do this to a great extent, although their basal levels of synthesis are higher.” (BBC 2012)

The pilot study was funded by a grant from the UK’s Biotechnology & Biological Sciences Research Council (BBSRC), as will the larger follow up trial.

Sources: Ball J. Fish oils 'help slow age decline'. September 6, 2012. Accessed at http://www.bbc.co.uk/news/science-environment-19494801. British Science Festival (BSF). Could fish oil be key in protecting the elderly against muscle deterioration? September 5, 2012. Accessed at http://www.abdn.ac.uk/news/details-13096.php

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