Home  |  Patients  |  Physicians  |  In the News  |  Hours/Location  |  Contact
        Bio-Identical Hormones
             Hormones for Women
             Hormones for Men
             Hormone Drug Info
      • Erectile Dysfunction
      • HCG Weight Loss
      • NasoNeb & Sinus Meds
      • Pain Management
      • LDN, MS & Autoimmune
      • Sterile Clean Room
      • Veterinary Compounding

             Drug Shortages
             AMA Recognition
             Legal Information
             Insurance Services
        Nutritional Products
             Product Review Process
             Synergy Blends
        Veterinary Products
             Drug Shortages
        What is the Rose Garden
        Compression Hosiery
        Bras & Camisoles
        Swim Suits
        Hats & Turbans
        Lymphedema Garments

     • Rental, Repair, Sales
     • NasoNeb & Sinus Meds
     Breast Pumps & Nursing
     • Product List

        Product List
        Product Review Process
        Synergy Blends
        Veterinary Products
        •  Compounds
        •  Supplements

        PCAB Accreditation
        Legal Information
      • Staff Members
        History of Mark Drugs

Content 7


The Doctor and the Pharmacist

Radio Show Articles:
April 30, 2011

Back to Specialties button

Aspirin and NSAIDs Are Potential Chemopreventive Agents for Melanoma
Which Vitamin D Supplement Boosts Levels More — D2 or D3?
Oral Food Challenges Distinguish Food Sensitization from Allergy
Body Dissatisfaction Trumps Weight in Predicting Emotional Distress in Adolescents
Levothyroxine Dosing Associated with Increased Fracture Risk in the Elderly
An Encouraging Intervention for Obese Children
Vitamin B for PMS?
Vaginal Progesterone Lowered Preterm Birth Rates in Women with Short Cervices
Screening for Autism Could Begin at the 1-Year Well-Baby Visit
Long-Acting Naltrexone for Opioid Withdrawal: Data and Questions
Longer Working Hours and Risk for CHD
Can Weight Gain Be Predicted in Adolescent DMPA Users?
Yet Another Prostate Cancer Screening Study
Obesity and Overweight Are Associated with Diastolic Dysfunction
Bowel Preparation for Colonoscopy: GoLYTELY vs. MiraLAX
Lucentis vs Avastin Study to Be Released Soon
Follow-Up: Interview on the Cardiovascular Risks of Calcium Supplements
Long-Term Outcomes of Ductal Carcinoma in Situ
Oral Contraceptives Containing Drospirenone Carry Higher Thrombosis Risk
   Than Those with Levonorgestrel
Vitamin D’s Vision-Protection Potential Affirmed
Tangy Aid to Weight Control?
Omega-3s praised, sugars panned, in newest scientific statement from the
   American Heart Association by Craig Weatherby
Clinical trial finds strawberries reduced risk from precancerous lesions of the esophagus;
   animal studies found same effect from other berries
How Many Infants Are Born to HIV-Infected Women in the U.S.?
Clusterin and Alzheimer Disease
Omega-3s Associated with Some Prostate Cancers
Occipital Nerve Stimulation for Chronic Migraine?
Phentermine plus Topiramate for Weight Loss?
Breakup sought of CVS Caremark, Groups cite harm to consumers

MM: If inflammation is a major culprit RE Melanoma and other cancers, and that is the basis of recommending ASA, NSAIDS or Statin drugs, why not use a safer, no-side-effect approach such as probiotics and digestive enzymes. These provide a 24/7 approach to combatting inflammation.
J Invest Dermatol 2011 Mar 10
Aspirin and NSAIDs Are Potential Chemopreventive Agents for Melanoma
Long-term use of nonsteroidal anti-inflammatory drugs was associated with a decreased risk.
Sunscreens, photoprotective clothing, and avoidance of tanning beds and sun exposure have all been advocated to prevent melanoma. Despite these measures, melanoma rates have continued to rise, while the incidence of most malignancies has stabilized or declined. Additional approaches to melanoma prevention are desperately needed.
     Prompted by earlier findings suggesting that regular use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) and statins reduce the development and progression of cutaneous melanoma, investigators performed a case-control study to evaluate the efficacy of aspirin, other NSAIDs, and lipid-lowering agents as chemoprevention. Using patient interviews, the researchers compared drug use in 400 patients, aged 40 or older, who had had a melanoma and in 600 controls. Statin and NSAID use were meticulously assessed in inquiries about medications prescribed (with reference to all known drug names) and conditions for which the drugs were administered.
     Statin use did not differ between patients and controls, even when the analysis was limited to subjects with >5 years of regular statin use. On the other hand, aspirin and nonaspirin NSAID use was more common among controls who had not had melanomas, even after adjustment for potential confounders. Individuals with >5 years of aspirin and nonaspirin NSAID use had nearly 50% fewer melanomas than those without. Those who took aspirin alone were about 25% less likely to develop melanoma. Even among the smaller group who had taken NSAIDs but not aspirin, those with ≥5 years of nonaspirin NSAID use had significantly less melanoma than those with ≤2 years of use.
     Comment: Chemopreventive agents have been identified for a number of cancers, but melanoma has been an exception. Statin drugs inhibit some of the signal transduction pathways involved in melanoma development, but were not found effective in this study. Because aspirin and NSAIDs have known anti-inflammatory effects and have been shown to protect against other types of cancer, including nonmelanoma skin cancer (see JW Dermatol Dec 10 2010), they may be protective for individuals with multiple dysplastic nevi, prior melanomas, extensive sun damage, or familial syndromes associated with increased melanoma risk. These findings provide the scientific rationale for prospective, interventional clinical trials of these agents for melanoma prevention in high-risk patients.
Craig A. Elmets, MD Published in Journal Watch Dermatology April 22, 2011
     Citation(s):Curiel-Lewandrowski C et al. Long-term use of nonsteroidal anti-inflammatory drugs decreases the risk of cutaneous melanoma: Results of a United States case-control study. J Invest Dermatol 2011 Mar 10; [e-pub ahead of print]. (http://dx.doi.org/10.1038/jid.2011.58)
Top of Page

J Clin Endocrinol Metab 2011 Apr; 96:981
Which Vitamin D Supplement Boosts Levels More — D2 or D3?
D3 (cholecalciferol) has the edge.
     In the U.S., vitamin D supplements are available over-the-counter as D3 (cholecalciferol; usually in 400–1000 IU doses) and by prescription as vitamin D2 (ergocalciferol; Drisdol and others; often prescribed at 50,000 IU doses). In previous research, D3 supplements raised blood levels of 25-hydroxyvitamin D (25[OH]D) more than D2 did at equivalent doses. In two new studies, researchers reach the same conclusion.
     In a randomized trial, 64 older adults received daily D2 or D3 (1600 IU) or monthly D2 or D3 (50,000 IU). Mean 25(OH)D levels were about 33 ng/mL at baseline. At 1 year, mean 25(OH)D levels had increased by 9 ng/mL in both the daily and monthly D3 groups; mean levels increased by 6 and 4 ng/mL in the daily and monthly D2 groups, respectively. The increase was significantly greater with D3 than with D2.
     In another randomized trial, 33 adults received 50,000 IU weekly of either D2 or D3; mean baseline 25(OH)D was about 28 ng/mL. After 12 weeks, increases in 25(OH)D levels were significantly greater with D3 than with D2 (increase from baseline, about 40 vs. 22 ng/mL).
     Comment: On average, oral supplemental vitamin D3 — the form made naturally after exposure to sunlight — raises 25(OH)D blood levels more than does vitamin D2. The authors of the second study conclude, with good reason, that D3 is preferable for correcting vitamin D deficiency. Note, however, that U.S. clinicians often give D2 by prescription to vitamin D–deficient patients: One reason might be the availability of high-dose D2 capsules that can be taken weekly or monthly; another might be a mistaken impression that prescription D2 is "stronger" than an equivalent dose of D3.
Allan S. Brett, MD Published in Journal Watch General Medicine April 26, 2011
     Citation(s):Binkley N et al. Evaluation of ergocalciferol or cholecalciferol dosing, 1600 IU daily or 50,000 IU monthly in older adults. J Clin Endocrinol Metab 2011 Apr; 96:981.
Top of Page

J Pediatr 2011 Apr; 158:578.e1
Oral Food Challenges Distinguish Food Sensitization from Allergy
Most children on elimination diets based on immunoassay results have negative oral food challenge tests.
Numerous studies suggest that many children are inappropriately labeled as allergic to specific foods. In a retrospective record review, investigators assessed the response to oral food challenges in 125 children (age range, 1–19 years; median age, 4 years) with atopic dermatitis who were referred to a major center for evaluation of food allergy. Oral food challenges were not performed in patients with a history of life-threatening reactions; a convincing history of a recent reaction; an associated large wheal size on skin prick test; or an immunoassay level above the 95% predictive value for milk, eggs, peanuts, or fish.
     Among 44 children who were avoiding 111 foods because of previous positive immunoassays or skin tests, 103 (93%) food challenges were negative. Among 67 children who were avoiding 122 foods because of previous reactions, 102 (84%) food challenges were negative. The foods that were most likely to be associated with a positive food challenge were peanuts (23% of challenges in children avoiding peanuts were positive), wheat (22%), and eggs (18%). Milk was not among the foods most likely to be associated with a positive food challenge (13%).
     Comment: Although this study included a highly selected referral population of children with atopic dermatitis, most of whom did not have a significant history or lab findings of food allergy, the results are an important reminder that many children are placed on restricted diets with little or no evidence of food allergies.
Howard Bauchner, MD Published in Journal Watch Pediatrics and Adolescent Medicine
April 27, 2011
Citation(s): Fleischer DM et al. Oral food challenges in children in with a diagnosis of food allergy. J Pediatr 2011 Apr; 158:578.e1.
Top of Page

J Adolesc Health 2011 Apr; 48:373
Body Dissatisfaction Trumps Weight in Predicting Emotional Distress in Adolescents
Body dissatisfaction but not obesity correlates with emotional distress in adolescents.
     Whether obese adolescents are more likely than nonobese peers to have emotional distress is controversial. To determine whether body dissatisfaction mediates the relation between obesity and emotional well-being, investigators analyzed data from a racially and ethnically diverse sample of 366 boys and 440 girls in Minnesota who were surveyed in early and late adolescence (at mean ages of 13 and 17 years, respectively). At each time point, participants completed measures of body shape satisfaction, self-esteem, and depressive mood. Self-reported and actual heights and weights were measured in early adolescence, but only self-reported height and weight were assessed during late adolescence. Obesity was defined as body-mass index (BMI) ≥95% for age.
     The initial regression model (controlled for age, socioeconomic status, and ethnicity/race) examined weight alone as a predictor of emotional distress. In this model, being obese significantly correlated with lower self-esteem in males and females in both early and late adolescence. Being obese also correlated significantly with depressed mood at both time points in males, but not females. However, when the body dissatisfaction variable was added to the analysis, being obese no longer correlated with self-esteem or depressed mood in either sex. Rather, body dissatisfaction alone significantly correlated with lower self-esteem in both sexes at both time points and with depressed mood in males in late adolescence and females in early and late adolescence.
     Comment: These results support the authors' hypothesis that body dissatisfaction mediates any proposed effect of obesity on adolescents' emotional well-being. Calculating an adolescent's BMI helps determine what kind of metabolic assessment he or she will need; assessing an adolescent's level of body dissatisfaction can be a window to determining his or her level of emotional well-being.
Alain Joffe, MD, MPH, FAAP Published in Journal Watch Pediatrics and Adolescent Medicine April 27, 2011
     Citation(s): Mond J et al. Obesity, body dissatisfaction, and emotional well-being in early and late adolescence: Findings from the Project EAT study. J Adolesc Health 2011 Apr; 48:373.
Top of Page

Levothyroxine Dosing Associated with Increased Fracture Risk in the Elderly
Elderly patients receiving levothyroxine show a dose-related increased risk for fracture,
according to a BMJ study. An accompanying editorial says that the risk is small and the main concern is defining the proper "normal" thyroid-stimulating hormone (TSH) level in this age group.
    Using Ontario's prescription-benefit database, researchers conducted a case-control study among more than 200,000 adults (mean age, 82) who were using thyroxine any time over a 5-year period. Current and recent thyroxine use (within the past 6 months) were both associated with an increased risk for fracture, compared with remote use (discontinued more than 6 months previously). Both high and medium cumulative doses showed increased fracture risk over low doses.
     Editorialists criticize the lack of TSH data — a limitation the authors acknowledge — and point out that "elderly people need relatively low thyroxine doses, so serum TSH should be regularly monitored and a suppressed TSH should be avoided in such patients."
Top of Page

Pediatrics 2011 Apr; 127:619.
An Encouraging Intervention for Obese Children
A parent-centered dietary-modification intervention was more effective than a child-centered activity intervention.
     In a randomized clinical trial, researchers compared the effectiveness of a 6-month child-centered physical-activity program, a parent-centered dietary-modification program, or both interventions in 165 prepubertal overweight children (age range 5.5–9.9 years) in Australia. Both interventions included weekly 2-hour face-to-face sessions for 10 weeks and a monthly relapse-prevention program available by telephone for 3 months.
     At 24 months, mean body-mass index (BMI) z scores were significantly reduced in all three groups, with significantly greater reductions in the combined intervention and parent-centered diet intervention groups than in the child-centered activity intervention group. Waist circumference and most metabolic outcomes also were significantly improved in the three groups with no differences among groups.
     Comment: These results are encouraging, although the clinical significance of the change in BMI z score is difficult to determine. My nutrition colleagues estimate that the mean weight loss was equivalent to about 2 kg, which is less than the 5% of total body weight that usually is considered clinically important weight loss. Obviously, assessing outcomes after longer follow-up is important. The finding that the parent-centered diet intervention was more effective than the child-centered activity intervention demonstrates that childhood obesity is a family problem and that focusing on the child alone is unlikely to be as effective.
Howard Bauchner, MD Published in Journal Watch Pediatrics and Adolescent Medicine
April 27, 2011

     Citation(s): Collins CE et al. Parent diet modification, child activity, or both in obese children: An RCT. Pediatrics 2011 Apr; 127:619.
Top of Page

Am J Clin Nutr 2011 May; 93:1080
Vitamin B for PMS?
Higher dietary intake of thiamine and riboflavin was associated with lower risk for new-onset premenstrual syndrome.
     The etiology of premenstrual syndrome (PMS) remains elusive. To evaluate possible associations between dietary B vitamin intake and development of PMS, investigators conducted a case-control study nested within the Nurses' Health Study, a longitudinal cohort of women who provide biennial reports of diet and lifestyle factors and health outcomes. During 10 years of follow-up, PMS was diagnosed in 1057 participants (36%); 1968 women were identified who did not have PMS or other menstrual symptoms.
     Women in the highest quintile of thiamine intake were 25% less likely to develop PMS than were those in the lowest quintile, and women in the highest quintile of riboflavin intake were 35% less likely to develop PMS. Intake of B vitamins from supplements did not lower risk for PMS — probably a reflection that such supplements often are prescribed for management of PMS.
     Comment: Several studies have shown benefits, albeit inconsistent, of using vitamin B supplements to treat PMS. This study suggests that high dietary intake of thiamine and riboflavin is associated with diminished risk for PMS. However, my enthusiasm for the findings is dimmed by the lack of correction for multiple comparisons, strong correlations among intake of individual B vitamins, and exclusion of women without PMS who reported any menstrual symptoms besides PMS. In general, women should be counseled to consume a wide variety of foods that contain high levels of B vitamins, such as seafood, legumes, and green leafy vegetables, as part of a healthy diet.
Anna Wald, MD, MPH Published in Journal Watch Women's Health April 28, 2011
     Citation(s): Chocano-Bedoya PO et al. Dietary B vitamin intake and incident premenstrual syndrome. Am J Clin Nutr 2011 May; 93:1080.
Top of Page

Ultrasound Obstet Gynecol 2011 Apr 6;
Vaginal Progesterone Lowered Preterm Birth Rates in Women with Short Cervices
But efficacy did not seem to extend to women with histories of PTB.
     Preterm birth (PTB) is a major contributor to perinatal morbidity and mortality. In a phase III randomized trial, researchers evaluated vaginal progesterone (90 mg daily) compared with placebo for preventing PTB in 458 asymptomatic women with short cervix (10–20 mm) identified sonographically before 24 weeks' gestation (72 participants had histories of PTB). Participants self-administered 1 gel applicator daily until delivery or 37 weeks. The primary outcome was preterm birth before 33 weeks.
     Rates of PTB before 33 weeks were 45% lower in women who received progesterone compared with those who received placebo (8.9% vs. 16.1%; P=0.02), and the authors calculated that 14 women with short cervix would need to be treated to prevent 1 case of PTB before 33 weeks. However, the reduction in rate of PTB among participants with histories of PTB did not reach statistical significance (15.8% vs. 20.6%; P=0.60). Among newborns, overall incidence of respiratory distress syndrome (RDS) was substantially lower in the progesterone group than in the placebo group (3.0% vs.7.6%; P=0.03).
     Comment: Cervical length is a powerful predictor of preterm birth in the index pregnancy. These results show that vaginal progesterone is useful for lowering rates of PTB as well as RDS in asymptomatic singleton pregnancies at high risk because of sonographically identified short cervical length. However, its worth in women with histories of PTB (a high-risk, refractory group) remains uncertain.
Diane J. Angelini, EdD, CNM, FACNM, FAAN, NEA-BC Published in Journal Watch Women's Health April 28, 2011
     Citation(s): Hassan SS et al. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: A multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol 2011 Apr 6; [e-pub ahead of print].
Top of Page

Screening for Autism Could Begin at the 1-Year Well-Baby Visit
     A simple checklist can detect autism spectrum disorders, language delays, and developmental delays as early as the 1-year well-baby visit, according to a Journal of Pediatrics study.
     Thirty pediatrics offices in San Diego County participated in a program that screened all infants for autism and related disorders at the 1-year checkup. Screening involved a 24-item checklist that parents completed in about 5 minutes in the waiting room. Of some 10,500 screened infants, 184 failed and were tracked every 6 months for 3 years. Some 40 infants who passed served as controls.
     During follow-up, 32 of the 184 infants were diagnosed with autism spectrum disorders, 56 with language delays, 9 with developmental delays, and 36 with "other" delays. The positive predictive value of the checklist was calculated at 75%. All controls continued to test normally throughout follow-up.
[Editor's note: The journal has not yet posted this article online, although the embargo has passed. We've linked to the early-release page, where the article should appear shortly.]
Top of Page

Long-Acting Naltrexone for Opioid Withdrawal: Data and Questions
     A long-acting formulation of naltrexone shows effectiveness in promoting opioid abstinence, but a strongly worded commentary in the Lancet questions its safety and criticizes the FDA's approval of the drug.
     Researchers, some of whom were employees of the drug's manufacturer, randomized 250 recently detoxified Russian patients to monthly injections of either depot naltrexone or placebo. After 6 months — during which about half the subjects left the trial — patients on extended-release naltrexone showed test-proved opioid abstinence a median of 90% of weeks, while placebo recipients had 35% abstinence.
     An accompanying comment says the study is striking "for the questions it raises about the FDA's approval processes and clinical trial ethics." In addition to the high rate of noncompletion of the protocol, the writers worry that the study apparently did not evaluate the rate of overdose after completion of treatment. (Overdose after relapse is especially high among detoxified heroin-dependent patients receiving oral naltrexone.)
Top of Page

Ann Intern Med 2011 Apr 5; 154:457
Longer Working Hours and Risk for CHD
Risk rose when workdays stretched beyond 10 hours.
     Several psychosocial factors, including stress, have been associated with elevated risk for coronary heart disease (CHD). In this study, researchers evaluated whether long working hours predict CHD risk beyond that provided by the Framingham risk model. Data on the working hours of more than 7000 British civil servants without known heart disease were obtained between 1991 and 1993, with follow-up through 2004. The primary endpoint was incident CHD, defined as coronary-related death or nonfatal myocardial infarction.
     After adjusting for Framingham risk score, participants with workdays of 10 hours (hazard ratio, 1.45) or ≥11 hours (HR, 1.67) had higher rates of CHD than those with workdays of 7 to 8 hours. The addition of working hours to the Framingham risk score led to a net reclassification of approximately 5% of participants from a lower-risk to a higher-risk group.
     Comment: In this interesting study, long workdays were associated with higher risk for incident CHD (after controlling for Framingham risk factors). The researchers did not evaluate whether long working hours are a marker of CHD risk or a causal factor in development of CHD. Regardless, the study reminds us that we could be underestimating the effect of psychosocial factors in development of CHD.
Jamaluddin Moloo, MD, MPH Published in Journal Watch General Medicine April 26, 2011
     Citation(s):Kivimäki M et al. Using additional information on working hours to predict coronary heart disease: A cohort study. Ann Intern Med 2011 Apr 5; 154:457. (http://www.annals.org/content/154/7/457.long) http://www.ncbi.nlm.nih.gov/pubmed/21464347?dopt=Abstract
Top of Page

Obstet Gynecol Obstet Gynecol 2011 Apr; 117:793
Can Weight Gain Be Predicted in Adolescent DMPA Users?
Early weight gain foretold continued or excessive weight gain with prolonged use of this contraceptive method.
     Depot medroxyprogesterone acetate (DMPA) is used commonly for contraception in adolescent populations. This 3-month injectable agent affords efficacy, convenience, and privacy but has been associated with concerns about weight gain. Clinicians have attempted to identify reliable predictors of weight gain to better inform patients who seek guidance about DMPA. In a subset of a larger study aimed at investigating bone-density changes in users of hormonal contraception, researchers addressed the issue of weight gain in 97 adolescent DMPA users (age range, 12 to 18). Body-mass index was assessed at baseline, 6, 12, and 18 months.
     At 6 months, 20% of participants had experienced >5% weight gain (early gainers). Compared with nonearly gainers (those who gained ≤5% of body weight during the first 6 months), early gainers were much more likely to continue to gain weight during the next 12 months of DMPA use (P<0.01).
     Comment: These results, which suggest that identifying early weight gain is a strategy for predicting subsequent excessive weight gain in young DMPA users, echo similar findings in older women (mean age, 24; JW Womens Health Sep 3 2009). Notably, however, most participants (4 out of 5) did not experience substantial weight gain within 6 months of initiating DMPA. Counseling women about the advantages, disadvantages, and potential adverse effects associated with DMPA (as well as other forms of contraception) is important in promoting informed decision making about available options.
Anne A. Moore, WHNP/ANP-BC, FAANP Published in Journal Watch Women's Health April 21, 2011
     Citation(s): Bonny AE et al. Early weight gain related to later weight gain in adolescents on depot medroxyprogesterone acetate. Obstet Gynecol 2011 Apr; 117:793. http://www.ncbi.nlm.nih.gov/pubmed/21422849?dopt=Abstract
Top of Page

BMJ 2011 Mar 31; 342:d1539
Yet Another Prostate Cancer Screening Study
In a 20-year study, screening resulted in overdiagnosis but not lower prostate cancer mortality.
     In a recent meta-analysis of six randomized trials, prostate cancer screening resulted in overdiagnosis of prostate cancer and did not lower prostate cancer–specific or overall mortality (JW Gen Med Oct 7 2010). In this population-based trial, investigators assessed whether screening lowers prostate cancer–specific mortality at 20 years after enrollment.
Participants were all 9026 men in Norrköping, Sweden, who were between the ages of 50 and 69 in 1987; 1494 were randomized to prostate cancer screening at 3-year intervals; the remaining 7532 men were controls. Screening in 1987 and 1990 consisted of digital rectal examination (DRE); prostate-specific antigen (PSA) testing was added in 1993 and 1996. Data collection ceased at the end of 2008. Men with abnormal DREs and PSA levels >4 µg/L underwent prostate biopsy. Prostate cancer was diagnosed in 5.7% of screened men and in 3.9% of controls. However, 2.0% of screened men and 1.7% of controls died from prostate cancer; this difference was not significant.
     Comment: Strengths of this trial (the early [2004] results of which were included in the aforementioned meta-analysis) include its population-based design and its long-term follow-up. Overall, the results are consistent with those of prior studies, taken together: Screening for prostate cancer results in overdiagnosis of prostate cancer and does not lower prostate cancer–specific mortality.
Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine April 21, 2011
     Citation(s): Sandblom G et al. Randomised prostate cancer screening trial: 20 year follow-up. BMJ 2011 Mar 31; 342:d1539. (http://dx.doi.org/10.1136/bmj.d1539) http://www.ncbi.nlm.nih.gov/pubmed/21454449?dopt=Abstract
Top of Page

J Am Coll Cardiol 2011 Apr; 9:326
Obesity and Overweight Are Associated with Diastolic Dysfunction
This finding held even when other risk factors were taken into account.
     Obesity is a risk factor for heart failure. To investigate whether this risk is mediated by diastolic dysfunction, U.S. researchers studied a population-based cohort of 950 patients (mean age, 72). Diastolic function was assessed by echocardiography.
     The incidence of diastolic dysfunction was 51% in normal-weight patients, 54% in overweight patients (body-mass index [BMI], 25.0–29.9 kg/m2), and 57% in obese patients (BMI, >30); these differences were not significant. However, after adjustment for age and clinical risk factors, obesity (odds ratio, 1.6) and even overweight (OR, 1.5) were independent predictors of diastolic dysfunction. Conversely, mean left ventricular ejection fraction was actually slightly higher in the obese group than in the normal-weight group (64.5% vs. 62.2%).
     Comment: In this population-based analysis, obesity and overweight were associated with a significantly elevated risk for diastolic dysfunction, even when the higher incidence of risk factors such as hypertension and diabetes was taken into account. The authors postulate that metabolic and neurohormonal derangements associated with obesity are responsible for this finding and that diastolic dysfunction represents a pathophysiologic link between obesity and heart failure.
Kirsten E. Fleischmann, MD, MPH Published in Journal Watch General Medicine April 21, 2011
     Citation(s): Russo C et al. Effect of obesity and overweight on left ventricular diastolic function: A community-based study in an elderly cohort. J Am Coll Cardiol 2011 Mar 22; 57:1368. (http://dx.doi.org/10.1016/j.jacc.2010.10.042)
Top of Page

Clin Gastroenterol Hepatol 2011 Apr; 9:326
Bowel Preparation for Colonoscopy: GoLYTELY vs. MiraLAX
In a randomized, blinded, controlled trial, MiraLAX — although more tolerable — proved inferior.
     MiraLAX — polyethylene glycol (PEG) 3350 without electrolytes — is commonly used for bowel cleansing before colonoscopy. However, it is not FDA approved for this indication; furthermore, it is typically mixed with Gatorade, which makes it hypotonic compared to PEG-based solutions with electrolytes (e.g., GoLYTELY). Data on the efficacy and safety of MiraLAX are mostly anecdotal.
     Now, researchers have conducted a randomized, blinded, controlled trial to compare the efficacy and tolerability of MiraLAX with those of GoLYTELY. Adults scheduled for screening colonoscopy received one of the following four bowel preparations, given in split-dose fashion (i.e., half the evening before and half the morning of colonoscopy):

     Of the 425 patients enrolled, 403 (evenly distributed among the study arms) completed the colonoscopy. The total Ottawa score for bowel-cleansing effectiveness was significantly better with GoLYTELY than with MiraLAX either alone, plus lubiprostone, or plus bisacodyl (average, 5.1 vs. 6.9, 6.3, and 6.8, respectively). The scores were also better for GoLYTELY in each segment of the colon. The proportion of patients with excellent preparation quality was significantly higher in the GoLYTELY arm than in the MiraLAX arms (49%, vs. 15%, 19%, and 20%). The number of polyps detected and the number of patients with at least one polyp were similar among the arms; the mean procedure duration was nonsignificantly longer in the MiraLAX arms. Overall, tolerability was better in the MiraLAX arms, although individual symptoms such as nausea, cramping, and bloating were similar among all the arms.
     Comment: The principal result here is not surprising; the literature suggests that any 2-L prep given properly (split dose) is less effective than any 4-L prep given in the same manner. One might ask whether 2-L preps, despite their increased tolerability, should be used at all or only in select groups of patients who are easy to prepare for colonoscopy. Although the current study did not compare results between constipated and nonconstipated patients, anecdotal experience and previous studies suggest that chronic constipation and use of constipating drugs predict poor preparation. Defining a subset of patients for whom low-volume preparations are appropriate is a reasonable target for study.
     Although hyponatremia occurs (rarely) with essentially all bowel preparations, MiraLAX mixed with Gatorade is hypotonic and theoretically increases the risk for this complication. Given all of these considerations, clinicians who still prescribe MiraLAX should probably use it only for nonconstipated patients and for younger, healthier individuals who do not have kidney disease or other complicating factors and are unlikely to experience clinically significant hyponatremia from ingestion of 2 L of Gatorade during a 2-day period.
Douglas K. Rex, MD Published in Journal Watch Gastroenterology April 22, 2011
     Citation(s): Hjelkrem M et al. MiraLAX is not as effective as GoLytely in bowel cleansing before screening colonoscopies. Clin Gastroenterol Hepatol 2011 Apr; 9:326.
Top of Page

Lucentis vs Avastin Study to Be Released Soon
     The results of a key study comparing Lucentis with low doses of Avastin will determine if Lucentis is better than Avastin; if not, Lucentis use may be decreased. The trial is sponsored by the U.S. National Eye Institute.
     Billions of dollars of Lucentis sales hinge on the head-to-head comparison. If Avastin proves as good as Lucentis, it will offer an alternative for age-related eye disease at a fraction of the cost. Most analysts expect Avastin to prove as effective as Lucentis in the 1,200-patient test. Avastin is not indicated for ophthalmic use but it works in a similar way to Lucentis, and the tiny amount needed for an eye injection costs only around $50, against a U.S. price of $1,950 for Lucentis.
Top of Page

Follow-Up: Interview on the Cardiovascular Risks of Calcium Supplements
     Clinical Conversations interviews Prof. Ian Reid, the senior author on a BMJ meta-analysis published last week that showed a modestly increased cardiovascular risk in postmenopausal women who took calcium supplements.
     Dr. Reid is satisfied he's demonstrated the connection, and he says that "people with remaining doubts" are going to have to make their decisions whether to recommend the supplements on the basis of the currently available data, since new trials aren't likely.
Top of Page

J Clin Oncol J Natl Cancer Inst 2011 Mar 16; 103:478
Long-Term Outcomes of Ductal Carcinoma in Situ
Breast-conserving treatments for DCIS are associated with excellent prognoses.
Incidence of ductal carcinoma in situ (DCIS) has risen substantially during the last 2 decades as a result of screening mammography. However, mammographically detected DCIS is often clinically silent and substantially less extensive than the large DCIS lesions that once were common at diagnosis. In addition, therapeutic approaches to DCIS have evolved: For most patients, breast conservation (i.e., lumpectomy and radiation therapy with or without tamoxifen as appropriate) is feasible.
     The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-17 and B-24 trials were designed to assess outcomes of breast-conserving treatments for DCIS. In the B-17 trial, 818 patients with localized DCIS were randomized to lumpectomy only (LO) or lumpectomy plus radiation therapy (LRT). In the B-24 trial, 1804 patients were randomized to LRT with or without tamoxifen. Now, NSABP investigators provide long-term data from B-17 (median follow-up, 207 months) and B-24 (median follow-up, 163 months) in participants who did or did not experience invasive ipsilateral breast tumor recurrence (I-IBTR). The key issue addressed was influence of I-IBTR on overall outcomes by treatment mode.
     Fifteen-year cumulative incidence of I-IBTR was 19.4% for LO, 8.9% for LRT (B-17), 10% for LRT plus placebo (B-24), and 8.5% for LRT plus tamoxifen. I-IBTR (but not DCIS recurrence) was associated with excess risk for death (hazard ratio, 1.75; P<0.001). Risk for dying of breast cancer in either trial (with or without I-IBTR) was very low: 15-year cumulative incidence was 3.1% for LO, 4.7% for LRT (B-17), 2.7% for LRT plus placebo (B-24), and 2.3% for LRT plus tamoxifen.
     Comment: That invasive ipsilateral breast tumor recurrence ultimately affects survival should not come as a revelation. On a more positive note, these data reaffirm that optimal treatment of DCIS attenuates risk for death from breast cancer. In short, breast-conserving treatment for DCIS is associated with excellent long-term prognosis.
William J. Gradishar, MD Published in Journal Watch Oncology and Hematology April 19, 2011
     Citation(s):Wapnir IL et al. Long-term outcomes of invasive ipsilateral breast tumor recurrences after lumpectomy in NSABP B-17 and B-24 randomized clinical trials for DCIS. J Natl Cancer Inst 2011 Mar 16; 103:478. (http://dx.doi.org/10.1093/jnci/djr027)
Top of Page

Oral Contraceptives Containing Drospirenone Carry Higher Thrombosis Risk Than Those with Levonorgestrel
     Women who use oral contraceptives containing the newer progesterone drospirenone (e.g., Yaz, Angeliq) face a two- to threefold higher risk for venous thromboembolism (VTE) than those using contraceptives containing levonorgestrel, according to two case-control analyses in BMJ.
     Researchers used U.S. and U.K. databases to identify cases of idiopathic VTE in women using oral contraceptives containing drospirenone or levonorgestrel, and then matched those women with controls using the same contraceptives who did not develop VTE.
     The U.S. cohort, which included 186 cases and 681 controls, showed higher VTE risk with drospirenone than with levonorgestrel (odds ratio, 2.4). Similarly, the U.K. cohort, comprising 61 cases and 215 controls, showed higher risk with drospirenone (OR, 3.3).
     The researchers conclude: "These findings support more recent studies that suggest that drospirenone oral contraceptives are not as safe as levonorgestrel oral contraceptives with respect to venous thromboembolism and, in the absence of other considerations, should not be the first choice in oral contraception." An editorialist agrees.
Top of Page

Article from Vital Choices Newsletter
April 28, 2011
Vitamin D’s Vision-Protection Potential Affirmed
Study links higher blood levels to reduce rate of macular degeneration in women under 75
by Craig Weatherby

Age-related macular degeneration (AMD) is the leading cause of blindness and irreversible vision loss. Several epidemiological studies have linked higher intakes of fish and omega-3s to reduced rates of AMD.
For more on that research, see the articles in the “Omega-3s & Eye Health” section of our news archive. And four years ago, an analysis of data from the huge National Health and Nutrition Examination Survey found that Americans whose blood levels of vitamin D ranked in the top one-fifth were 36 percent less likely to develop “dry”, early stage AMD (Parekh N et al 2007). And people who reported eating lots of fish enjoyed an even more dramatic 59 percent drop in the risk of “wet” (later-stage, blinding) AMD … presumably because of added eye support from the omega-3s in fish. For our full report on that 2007 study, see “Vitamin D Adds Eye Health to Roster of Recent Accolades”.) Now, a new analysis of data from participants in the Carotenoids in Age-Related Eye Disease Study (CAREDS) suggests that vitamin D may help prevent AMD.
Higher vitamin D levels linked to 44 percent lower eye risk
     The new analysis found that women under the age of 75 with high vitamin D blood levels were less likely to have “early” AMD (Millen AE et al. 2011). The results showed that women younger than 75, whose vitamin D levels were lower than 38 nanomoles per liter (nmol/L) were more likely to have AMD, compared with women whose blood levels were above that mark. Specifically, women with a vitamin D blood level above 38 nmol/L were 44 percent less likely to have AMD. This statistical correlation between higher D levels and lower risk does not prove that vitamin D prevents AMD, which only rigorous clinical trials can do.
     According to lead author Amy E. Millen, Ph.D., “The take-home message from this study is that having very low vitamin D status [below 38 nanomoles per liter] may be associated with increasing your odds of developing age-related macular degeneration.” But as she noted, “being at a higher vitamin D level than 38 nanomoles per liter does not appear to be more protective.”  
     Professor Millen said that people can increase their vitamin D levels by spending moderate amounts of time in sunlight, and eating foods rich in vitamin D, such as fatty fish, by taking supplements, and eating D-fortified cereals and dairy foods. The research was funded by the National Institutes of Health (NIH) and by Research to Prevent Blindness.
How much D is enough?
     Scientists and doctors can measure and express vitamin D levels either as nanomoles per liter (nmol/L) or nanograms per liter (ng/L). The U.S. Institute of Medicine (IOM) considers vitamin D blood levels below 30 nmol/L deficient and a level below 50 nmol/L inadequate. These nmol/L figures equate to 12 nanograms per liter (ng/mL) and 20 ng/mL, respectively. Actually, the IMO says that levels below 30 nmol/L and 50 nmol/L these put people “at risk for” deficiency or inadequacy, respectively.
     But as John Cannell, M.D., president of the Vitamin D Council says, it is misleading to say that blood levels below these put people “at risk for” deficiency or inadequacy, since these blood levels virtually define deficiency and inadequacy.  
Most leading vitamin D researchers recommend much higher minimum blood levels ranging from 90 to 120 nmol/L (36 to 48 ng/mL), to ensure optimal health. In November of 2010, the IOM’s Food and Nutrition Board tripled the recommended daily allowance (RDA) for people from age one through 50, from 200 IUs to 600 IUs. Unfortunately, the IOM panel retained its prior recommended minimum blood level of 20 ng/mL (i.e., 50 nmol/L), which is well above the 38 nmol/L now associated with a 44 percent lower risk of AMD. In contrast, virtually all of the world’s leading vitamin D researchers recommend a minimum blood level of 30 ng/mL (i.e., 75 nmol/L), because this much-higher-than-average level is associated with lower risk of major diseases. For example, leading vitamin D researcher Michael F. Holick, M.D., Ph.D., of Boston University says the evidence supports keeping vitamin D levels above 30 ng/mL (75 nmol/L). And he notes that levels up to 100 ng/mL are safe for everyone except sarcoidosis patients. For more on the experts’ intake and blood level recommendations, see “Vitamin D RDAs Raised Substantially” and “Vitamin D May Boost Aging Brains”.
     Sources: Millen AE, Voland R, Sondel SA, Parekh N, Horst RL, Wallace RB, Hageman GS, Chappell R, Blodi BA, Klein ML, Gehrs KM, Sarto GE, Mares JA; for the CAREDS Study Group. Vitamin D Status and Early Age-Related Macular Degeneration in Postmenopausal Women. Arch Ophthalmol. 2011 Apr;129(4):481-489. Parekh N, Chappell RJ, Millen AE, Albert DM, Mares JA. Association between vitamin D and age-related macular degeneration in the Third National Health and Nutrition Examination Survey, 1988 through 1994. Arch Ophthalmol. 2007 May;125(5):661-9.
Top of Page

Article from Vital Choices Newsletter
April 21, 2011
Tangy Aid to Weight Control?
Newly discovered antioxidant in tangerines blocked metabolic declines in mice fed junky diets
by Craig Weatherby
     A newly discovered flavonoid-type antioxidant from tangerines prevented obesity in mice fed a junk-food diet. 
Better yet, the compound – called Nobiletin – sparked metabolic changes that should reduce the risk of diabetes and atherosclerosis … the underlying condition responsible for most heart disease.
     The study was led by Murray Huff, Ph.D., a vascular biologist at The University of Western Ontario’s School of Medicine.  Two years ago, Huff’s team made headlines when they discovered a related flavonoid (naringenin) in grapefruit , which also offered protection against obesity and other signs of metabolic syndrome in mice (Mulvihill EE et al. 2009).(Flavonoids constitute most of the antioxidants in plant foods … they’re a subset of the larger group of plant-source antioxidants called polyphenols.) And, as Huff says, “What’s really interesting to us is that Nobiletin is ten times more potent in its protective effects compared to Naringenin, and this time, we’ve also shown that Nobiletin has the ability to protect against atherosclerosis.” (UWO 2011)
Tangerine agent seen as potential ally against diabetes and heart disease
     The study employed mice genetically prone to developing metabolic syndrome in response to sugary, starchy, fatty diets (Mulvihill EE et al. 2009). People and animals are said to have metabolic syndrome when they show any three out of six undesirable signs linked to diabetes and heart disease:

     The mice were divided into two groups, both of which were fed a “western” diet high in fats and sugars … but one group had Nobiletin added to their chow. The control group became obese and showed all the signs associated with metabolic syndrome: elevated cholesterol and triglycerides, high blood levels of insulin and glucose, and a fatty liver. These metabolic abnormalities greatly increase the risk of cardiovascular disease and type 2 diabetes. The second group of mice, fed the exact same diet but with Nobiletin added, experienced no rise in their levels of cholesterol, triglycerides, insulin or glucose, and gained weight normally. The Nobiletin-fed mice also became much more sensitive to the effects of insulin … a good thing.
     Nobiletin was shown to prevent the buildup of fat in the liver by stimulating the expression of genes involved in burning excess fat, and inhibiting the genes responsible for manufacturing fat.“The Nobiletin-treated mice were basically protected from obesity,” said Dr. Huff. “And in longer-term studies, Nobiletin also protected these animals from atherosclerosis, the buildup of plaque in arteries, which can lead to a heart attack or stroke.”
Genetic effects support findings; human potential seen
    When the team exposed isolated mouse cells to Nobiletin, they detected “nutrigenomic” effects that explain the metabolic protections it produced in the animal’s bodies. Huff went on to note the experiments’ human implications: “This study really paves the way for future studies to see if this is a suitable treatment for metabolic syndrome and related conditions in people.” That prospect for drug development probably helps explain why, although most of the funding came from the Heart and Stroke Foundation of Ontario, the research was funded in part by the Pfizer Corporation’s Canada Cardiovascular Research Program.
     Whether or not a drug based on Nobiletin ever sees the light of day, it will still make sense for most people to favor the whole tangerine fruit, which contains many other beneficial antioxidants as well as fiber. Plus, it’ll be free of side effects, and will always taste far better than any pill!
     Sources: Mulvihill EE, Assini JM, Lee JK, Allister EM, Sutherland BG, Koppes JB, Sawyez CG, Edwards JY, Telford DE, Charbonneau A, St-Pierre P, Marette A, Huff MW. Nobiletin Attenuates VLDL Overproduction, Dyslipidemia, and Atherosclerosis in Mice With Diet-Induced Insulin Resistance. Diabetes. 2011 Apr 6. [Epub ahead of print]. Mulvihill EE, Allister EM, Sutherland BG, Telford DE, Sawyez CG, Edwards JY, Markle JM, Hegele RA, Huff MW. Naringenin prevents dyslipidemia, apolipoprotein B overproduction, and hyperinsulinemia in LDL receptor-null mice with diet-induced insulin resistance. Diabetes. 2009 Oct;58(10):2198-210. Epub 2009 Jul 10. Schulich School of Medicine & Dentistry, The University of Western Ontario (UWO). Substance in tangerines fights obesity and protects against heart disease. April 6th, 2011. Accessed at: http://www.fmd.uwo.ca/news/index.php?article=001444
Top of Page

Article from Vital Choices Newsletter
April 25, 2011
Heart Group Touts Lifestyle for Triglycerides
Omega-3s praised, sugars panned, in newest scientific statement from the American Heart Association
by Craig Weatherby
     We don’t buy everything the American Heart Association (AHA) says about diet and cardiovascular disease (CVD). But – aside from an unscientific, broad-brush swipe at saturated fats – we applaud their new statement on the ability of lifestyle changes to lower high blood triglyceride levels and the risk of cardiovascular disease (CVD).  
Rather than announcing new research, the new statement stresses the proven but under-recognized implications of what we already know about the impacts of lifestyle on triglyceride levels. Here’s the key sentence from the AHA’s press release: “Diet and lifestyle changes that include substituting healthy fats for unhealthy saturated and trans fats, engaging in regular physical activity and losing excess weight can reduce triglycerides – a blood fat – by 20 percent to 50 percent.” (AHA 2011) As the full statement makes clear, by “healthy fats”, they mean polyunsaturated fats … especially the omega-3 fatty acids (EPA and DHA) that abound in oily fish like salmon, tuna, and sardines.
     We take issue with the implication that saturated fats are inherently unhealthful, or that unsaturated fats are always healthful. Saturated fats and cholesterol from foods are not unhealthful when consumed in moderation as part of a balanced whole-foods diet. Instead, the extremely excessive omega-6 fat intake typical of American diets clearly is dangerous … see our sidebar, “AHA’s cardio advice: A mixed bag”, below, visit the “Omega-3 / Omega-6 Balance” section of our news archive, and see “Cholesterol Fiasco Undermines Accepted Theory”.
AHA statement advises fishy whole-food diets
     In short, the AHA urges Americans to be physically active and adopt nutritious, whole-food diets:

     While this list has become official U.S. policy – see “Eating More Fish Advised in U.S. Diet Guidelines” – people may be more motivated to follow it if they know it drastically reduces a major risk factor for heart disease.
New focus on triglycerides
     Statement co-chair Neil J. Stone, M.D., put these blood fats in perspective:
“Triglycerides are an important barometer of metabolic health. When the clinician sees an elevated triglyceride level, there needs to be an important conversation about risk factors and the need to eat less, eat smarter, and to move more on a daily basis to improve triglycerides and the metabolic profile.” (AHA 2011) And, as the AHA statement notes, high triglyceride levels are “… not a target for drug therapy because there has not been adequate study to show that drug therapy to lower triglycerides to this level [100 mg/dL] is helpful.” (This quote reflects a regrettable bias toward drug therapies over lifestyle-based disease prevention and amelioration … a slant that’s sadly typical of mainstream, pharma-focused and funded medicine.)
     Accordingly, the AHA statement advises that instead of taking marginally effective drugs, “Many people can reduce their triglycerides as well as other metabolic risk factors such as blood sugar and blood pressure with diet, weight loss and increased physical activity.”
     Nearly one in three American adults has high triglyceride levels (i.e., above 150 mg/dL). Triglyceride levels have continued to rise in adults aged 20-49 … an ongoing uptick that’s been paralleled by rising rates of obesity and diabetes in that age range … and increasingly among adolescents as well. In the AHA statement, “elevated triglycerides” remains defined as it has been, at 150 mg/dL or higher … but it sets a new “optimal” level of 100 mg/dL.
     Omega-3s praised, sugars panned
The AHA statement recommends these specific dietary targets for people with high triglycerides (AHA 2011):

     Again, we take issue with insinuations that saturated fats are inherently unhealthful, and that unsaturated fats – specifically, omega-6 fatty acids – are always healthful. The new statement complements recent AHA scientific statements on childhood and adolescent obesity and dietary sugar intake. In the 2009 AHA statement on sugar, their expert panel wrote, “High intakes of dietary sugars in the setting of a worldwide pandemic of obesity and cardiovascular disease have heightened concerns about the adverse effects of excessive consumption of sugars.” (Johnson RK et al. 2009) Most of the added sugar consumed by Americans comes from sweetened beverages. The AHA now recommends drinking no more than 36 ounces of sugar-sweetened beverages per week, based on a 2000-calorie-per-day diet.
     The AHA statement encourages people with triglyceride levels at or above 150 mg/dL to engage in physical activities of at least moderate intensity (such as brisk walking) for at least 150 minutes per week, saying “… these activities may contribute an additional 20-30 percent triglyceride-lowering effect.” (AHA 2011)
Sources: American Heart Association (AHA). Dietary, lifestyle changes can significantly reduce triglycerides. American Heart Association Rapid Access Journal Report. April 18, 2011. Accessed at http://www.newsroom.heart.org/index.php?s=43&item=1315. Daniels SR et al. Overweight in children and adolescents: pathophysiology, consequences, prevention, and treatment. Circulation. 2005;111:1999 –2012.. Johnson RK et al. Dietary sugars intake and cardiovascular health: a scientific statement from the American Heart Association. Circulation. 2009;120: 1011–1020. Miller M et al. Triglycerides and Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circulation. 2011 Apr 18. [Epub ahead of print]
Top of Page

Article from Vital Choices Newsletter
April 25, 2011
Strawberries Curbed Throat-Cancer Risk
Clinical trial finds strawberries reduced risk from precancerous lesions of the esophagus; animal studies found same effect from other berries
by Craig Weatherby
     Esophageal cancer is the sixth most frequent cause of cancer death in the world, and the third most common kind of gastrointestinal cancer. According to the American Cancer Society, more than 16,000 new cases of esophageal cancer will be diagnosed in the United States this year. Last year, researchers from Ohio State University (OSU) reported that raspberries, strawberries, blueberries, Brazilian açaí berries, and Chinese goji berries inhibited the growth of esophageal tumors in rats, equally well (Stoner GD et al. 2010).Now, results from a clinical trial led by OSU researchers and colleagues in China suggest that strawberries may help people at risk of esophageal cancer decrease that danger. Lead author Dr. Tong Chen of OSU presented the findings on April 6 at the American Association for Cancer Research (AACR) 102nd meeting 2011 in Orlando, Florida. As she said, “We concluded from this study that six months of strawberry treatment is safe and easy to consume. In addition, our preliminary data suggests that strawberries decreased histological grade of precancerous lesions and reduced cancer-related molecular events.” (OSU 2011)
     Based on the 2010 results in rats, the researchers embarked on a clinical trial in China to investigate the effects of freeze-dried strawberries on patients with precancerous esophageal lesions. (Most patients with precancerous lesions in their esophagus will develop esophageal cancer.) “We found that daily consumption of strawberries suppressed various biomarkers involved in esophageal carcinogenesis, including cell proliferation (uncontrolled cell growth), inflammation and [pro-cancer] gene transcription,” Chen said. (OSU 2011). Each of 36 study participants ate 60 grams (about two ounces) of freeze-dried strawberries daily for six months. The researchers biopsied tissue samples from participants’ esophaguses, before and after the strawberry consumption. Encouragingly, 29 out of 36 participants showed a decrease in “histological grade” of the precancerous lesions during the study. (Histological grading is a measure of the progress of a tumor, and is used to estimate a patient’s prognosis and plan their treatment.). As Dr. Chen said, “Our study is important because it shows that strawberries may slow the progression of precancerous lesion in the esophagus. Strawberries may be an alternative, or may work together with other chemopreventive drugs, for the prevention of esophageal cancer. But, we will need to test this in randomized placebo-controlled trials in the future.” (OSU 2011)
     Chen and her team are studying esophageal squamous cell carcinoma, which makes up 95 percent of cases of esophageal cancer worldwide. The survival rate is very low, with only 10 percent of patients living 5 years after diagnosis. In the United States, Canada, and Europe, the risk factors for developing esophageal cancer include tobacco and alcohol use, along with diets lacking in fruits and vegetables.  In Asia, additional risk factors include dietary intake of salty food and food contaminated with various mycotoxins; deficiencies in dietary vitamins and minerals; and throat injuries from hot beverages.
     The study received funding from the California Strawberry Commission.
Sources Ohio State University (OSU). Strawberries May Slow Precancerous Growth in Esophagus. April 6, 2011. Accessed at:
Stoner GD, Wang LS, Seguin C, Rocha C, Stoner K, Chiu S, Kinghorn AD. Multiple berry types prevent N-nitrosomethylbenzylamine-induced esophageal cancer in rats. Pharm Res. 2010 Jun;27(6):1138-45. Epub 2010 Mar 16. Erratum in: Pharm Res. 2010 Sep;27(9):2031. Stoner GD, Chen T, Kresty LA, Aziz RM, Reinemann T, Nines R. Protection against esophageal cancer in rodents with lyophilized berries: potential mechanisms. Nutr Cancer. 2006;54(1):33-46.
Top of Page

J Acquir Immune Defic Syndr 2011 Mar 3
How Many Infants Are Born to HIV-Infected Women in the U.S.?
An estimated 9000 infants were born to HIV-infected women in 2006, reflecting an increase of up to 30% from 2000.
     Guidelines to prevent perinatal HIV transmission have been implemented successfully in the U.S., resulting in a dramatic decline in the estimated number of infants born with HIV infection (1650 in 1991 vs. 138 in 2004). However, transmission events still occur, and in many areas of the U.S., transmission rates exceed the achievable goal of <1%. According to CDC estimates, approximately 2.8% of infants born to HIV-positive mothers in 2005 were infected. In the present study, researchers estimated the number of infants who were born to HIV-infected women in the U.S. in 2006 and were thus at risk for perinatal acquisition of HIV.
     Using a variety of statistical methods, the researchers estimated that 171,400 women of childbearing age were living with HIV disease in the U.S. in 2006 and that 8700 infants were born to these women. This latter number reflects an increase of up to 30% from the estimate previously reported for 2000 — an increase that is likely attributable to an overall rise in the number of women living with HIV infection in the U.S.
     Comment: A major limitation of this study is that these are estimated numbers of HIV-exposed infants, rather than reported data on known pregnancies among HIV-infected women. The figures likely overestimate the number of live births to HIV-infected women, because the investigators were unable to account for stillbirths and induced or spontaneous abortions. Similarly, pregnancy rates among HIV-infected women may actually have declined significantly between 2001 (which served as the basis for the estimates) and 2006; in at least one state referenced in this paper, reported births of HIV-exposed infants decreased by approximately 60% from 1990 to 2003. Understanding national and statewide perinatal exposure trends over time, with detailed analyses of sociodemographic differences, is crucial for targeting intervention efforts and ensuring that we reach the women who are most likely to transmit HIV to their infants.
Sonia Nagy Chimienti, MD Published in Journal Watch HIV/AIDS Clinical Care April 25, 2011
     Citation(s): Whitmore SK et al. Estimated number of infants born to HIV-infected women in the United States and five dependent areas, 2006. J Acquir Immune Defic Syndr 2011 Mar 3; [e-pub ahead of print]. (http://dx.doi.org/10.1097/QAI.0b013e3182167dec)
Top of Page

JAMA 2011 Apr 6; 305:1322
Clusterin and Alzheimer Disease
Elevated plasma levels of the protein clusterin were associated with AD prevalence and severity, but they did not predict AD incidence or distinguish between AD and vascular dementia.
     Plasma clusterin has been reported to be associated with baseline severity of Alzheimer disease (AD) and with the speed of AD progression and brain atrophy. Furthermore, the locus of the gene that encodes for this protein has been implicated in AD.
     To assess the value of plasma clusterin as an AD biomarker, researchers analyzed data from a randomly selected subcohort of 926 participants in the large, prospective, population-based Rotterdam Study. Each participant had undergone brief cognitive screening with the Mini-Mental State Examination and the Geriatric Mental State Schedule; subsequent neuropsychological testing was conducted in those with an MMSE score <26 or a GMSS organic level above zero.
     During a mean follow-up of 7.2 years, 61 of the 926 participants in the subcohort were diagnosed with dementia according to standard criteria. To these 61, the researchers added 178 people from the larger cohort who developed dementia during follow-up and another 77 who had a dementia diagnosis upon study entry. After adjustment for multiple dementia risk factors (e.g., older age, less education, apolipoprotein E {varepsilon}4 carrier status, vascular risk factors), no clear association between incident dementia and plasma clusterin levels was found. Plasma clusterin also did not discriminate effectively between AD and vascular dementia. Elevated plasma clusterin levels were, however, significantly associated with AD diagnosis at the time of study entry (i.e., with AD prevalence) and with greater AD severity.
     Comment: The authors acknowledge that, given their data, plasma clusterin is not a useful biomarker for predicting the development of AD. However, the current findings point to a possible neuroprotective role of clusterin in dementia. Harnessing clusterin in AD therapy may warrant exploration.
Brandy R. Matthews, MD Published in Journal Watch Neurology April 26, 2011
     Citation(s): Schrijvers EMC et al. Plasma clusterin and the risk of Alzheimer disease. JAMA 2011 Apr 6; 305:1322.
Top of Page

Omega-3s Associated with Some Prostate Cancers
     Patients may ask about a study that unexpectedly links anti-inflammatory omega-3 fatty acids with high-grade prostate cancer. Proinflammatory trans-fatty acids showed — also unexpectedly — a protective effect. The results appear in the American Journal of Epidemiology.
     In a nested, case-control study within the Prostate Cancer Prevention Trial, researchers examined the proportions of serum fatty acids in 1800 men with invasive prostate cancer and 1800 matched controls. At the outset of the 7-year study, all participants had been cancer-free.
     For the omega-3 fatty acid docosahexaenoic acid, each quartile of serum concentration above the lowest quartile "was associated with an approximate doubling of high-grade disease." For the 18:1 and 18:2trans-fatty acids, a protective effect was found.
     Calling their findings "disconcerting," the authors say that much more study will be needed before changing dietary recommendations.
Top of Page

Cephalalgia 2011 Feb; 31:271
Occipital Nerve Stimulation for Chronic Migraine?
A prospective, sham-controlled, feasibility study suggests that ONS may be safe and effective for intractable chronic migraine.
     Occipital nerve stimulation (ONS) may reduce pain directly within the distribution of the occipital nerve and may lessen activation of the trigeminocervical complex. Open-label studies of ONS for migraine treatment have shown promising results. Investigators have now conducted a blinded safety and feasibility study of ONS, sponsored by the stimulator manufacturer. A total of 75 patients with intractable chronic migraine were randomized, in a 2:1:1 ratio, to receive fully active stimulation with an ONS device, sham stimulation with a device that was active for only 1 minute per day, or continued medical management.
     Data on safety and efficacy were available for 66 patients at 3 months. Given the goals of this study, multiple outcomes were analyzed independently. Treatment response, defined as 50% reduction in number of headache days per month or a ≥3-point reduction in average pain intensity on a scale of 0 to 10, was 39% in the active-stimulation group, compared with 6% in the sham-stimulation group and 0% in the medical-management group. The average decline in the number of headache days per month was 6.7 days in the active-stimulation group (from 22.4 to 15.7 days), compared with average declines of 1.5 and 0.9 days in the other two groups, respectively. The active-stimulation group also had advantages over the other groups on several measures of disability. Adverse device-related events were common. For example, 24% of device recipients experienced lead migration, and 14% developed implant-site infections.
     Comment: Occipital nerve stimulation may be an effective therapy for treating patients with intractable chronic migraine. These trial findings justify further study of this treatment modality. Lower complication rates are likely to be achieved as experience with this treatment grows.
— Todd J. Schwedt, MD Dr. Schwedt is Director, Washington University Headache Center, and Assistant Professor of Neurology and Anesthesiology, Washington University School of Medicine, St. Louis.
Published in Journal Watch Neurology April 26, 2011
     Citation(s): Saper JR et al. Occipital nerve stimulation for the treatment of intractable chronic migraine headache: ONSTIM feasibility study. Cephalalgia 2011 Feb; 31:271.
Top of Page

Lancet 2011 Apr 16; 377:1341
Phentermine plus Topiramate for Weight Loss?
The combination resulted in weight loss but caused substantial side effects.
     Many candidate weight-loss drugs have been abandoned because they caused unacceptable side effects. However, drug combinations in moderate doses might have synergistic weight-loss effects with fewer adverse effects.
     U.S. researchers randomized 2487 obese adults (body-mass index, 27–45 kg/m2) with two or more comorbidities to combinations of phentermine (an FDA-approved weight loss drug) and topiramate (an antiseizure drug that causes anorexia and weight loss) at low or high doses or to matching placebo once daily for 56 weeks. All patients were counseled about changing their diets and lifestyles. Previously diagnosed mild depression or antidepressant prescriptions were reported for 17% of patients.
     Forty-three percent of placebo patients and 34% of active-treatment patients discontinued study drugs early; 69% of patients were assessed at week 56. In an intent-to-treat analysis, patients who received high- or low-dose treatment lost significantly more weight on average than did those who received placebo (10.2 kg, 8.1 kg, and 1.4 kg, respectively), and those who received active therapy were significantly more likely to lose at least 10% of baseline body weight (48%, 37%, and 7%, respectively). Compared with placebo patients, patients in both active-treatment groups had significantly greater mean reductions in waist circumference, systolic blood pressure, and total cholesterol, triglyceride, fasting glucose, and glycosylated hemoglobin levels. Active treatment was associated significantly with dry mouth, paresthesia, constipation, dysgeusia, dizziness, and irritability but not with depression or suicidality.
     Comment: The FDA has been increasingly cautious in evaluating new drugs for treating obesity. This study, sponsored by the developer of a combined formulation of these two drugs, was considered by the FDA before it rejected the drug combination in 2010 (pending further safety studies). Experience with other weight-loss remedies that showed initial promise tells us that enthusiasm for this one should be tempered until further safety data are available.
Bruce Soloway, MD Published in Journal Watch General Medicine April 26, 2011
     Citation(s): Gadde KM et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): A randomised, placebo-controlled, phase 3 trial. Lancet 2011 Apr 16; 377:1341. (http://dx.doi.org/10.1016/S0140-6736(11)60205-5)
Top of Page


Breakup sought of CVS Caremark, Groups cite harm to consumers
By Reed Abelson and Natasha Singer  New York Times / April 15, 2011
     CVS Caremark is coming under increasing pressure from consumer groups and shareholders to split up, at the same time that federal and state regulators are looking into accusations of anticompetitive behavior by the merged company.The four-year-old merger of the drug store chain and the pharmacy benefit manager is the subject of an investigation by the Federal Trade Commission and by the attorneys general of 24 states, according to earlier disclosures by CVS Caremark. The company says it is “cooperating fully’’ with the inquiries. “We remain confident that our business practices and service offerings are being conducted in compliance with antitrust laws,’’ said Carolyn Castel, a company spokeswoman. But yesterday, five consumer groups wrote a letter to Jon Leibowitz, the commission’s chairman, claiming “there is strong evidence that the CVS Caremark merger has harmed consumers.’’
     The groups, which called for breaking up the $27 billion merger, also accused the company of using confidential patient information from Caremark, which manages prescription benefits for health plans, to steer consumers to CVS pharmacies. The company’s practices effectively gave the Woonsocket, R.I., company an unfair advantage over other pharmacies, reducing competition and limiting consumer choice, according to the letter, which was signed by Community Catalyst, Consumer Federation of America, Consumers Union, the National Legislative Association on Prescription Drug Prices, and US PIRG.
     CVS Caremark denied accusations it had engaged in improper business practices, saying they were “false, unfounded, and misleading.’’ It defended its privacy protections, saying it maintained a firewall to ensure that Caremark and CVS did not share “certain competitively sensitive information,’’ Castel wrote in an e-mail. The company did not improperly steer patients to CVS pharmacies, she said. She also said “there are no plans to split up the company.’’ A spokeswoman for the FTC, Cecelia Prewett, confirmed the commission had received the letter, but said it could not comment on an open investigation. Consumer groups as well as independent pharmacists, who have argued they are now at a competitive disadvantage, have been calling for regulators to review the merger.
     CVS Caremark says the merger is helping its customers by reducing costs and improving health outcomes. “The innovative products we have introduced into the marketplace since the merger are gaining traction,’’ Castel said, and will “enhance shareholder value.’’ The company also said it “places a high priority on protecting the privacy of its customers and plan members.’’ Castel said CVS Caremark used patient data internally for “appropriate purposes,’’ like identifying potentially adverse drug reactions.

Top of Page

Home | Contact | Roselle (630) 529-3400 | Deerfield (877) 419-9898 | Careers | Sitemap