• Myths About Obesity
• Low Total-Fat Intake Is Associated with Lower Weight, Body-Mass Index, and
Waist Circumference
• The Drug-Dose Gender Gap
• Assets of Owners of Meningitis-linked Pharmacy Frozen
• In Patients with Hyperlipidemia, Exercise and Statins Both Lengthen Life
• Pravastatin in Pregnancy? Stay Tuned.
• How Much Do Women Know About Breast Cancer Overdiagnosis?
• Early Introduction of Complementary Foods Might Prevent Allergic Disease
• No Relation Between Length of Treatment for UTIs and Early Recurrence in Men
• Treatment Mode Has Little Effect on Long-Term Function in Prostate Cancer
• Quadruple-Dose Influenza Vaccine for HIV-Infected Patients
• Antibiotics for Acute Lower Respiratory Tract Infection?
• Pediatrics Type 2 Diabetes Guidelines Published
MM: There are lots of myths about what may lead to or what can eliminate obesity. Its amazing how few actual effective approaches there are in today's medical community that actually work. It's even more amazing how few health care practitioners recognize a truly effective approach to battling obesity and Metabolic Syndrome: The HCG Weight Loss Protocol. Give us a call at Mark Drugs and we will happily provide more information about this outstanding protocol or visit our website at http://markdrugs.com/weightloss.html
Myths About Obesity
By Kelly Young
Researchers identify a variety of myths about obesity and deliver sometimes-unpleasant countervailing facts in the New England Journal of Medicine. Among them:
Myth: Sexual activity is a good form of exercise.
Fact: It may be intense, but it's not long-lasting enough to be much better than watching television, calorically speaking.
Myth: Breast-feeding infants protects them from obesity later in life.
Fact: Studies that controlled for confounding found no evidence of a protective effect.
Myth: Patients should set realistic goals for weight loss. Otherwise they might become frustrated and not lose as much.
Fact: Studies have shown that patients who set more ambitious goals are likely to lose more weight.
http://www.nejm.org/doi/full/10.1056/NEJMsa1208051
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MM: It this a surprise? No, but unfortunately most low fat prepared foods add empty carbohydrates such as high fructose corn syrup and these are just as detrimental if not more so that the high fat content of prepared foods. A balanced diet of natural, whole foods is the unparalleled best approach to a dietary regimen. Whether the foods that we eat are organic or not, they are best for us if they are the "whole, natural versions of those foods"
BMJ 2012 Dec 6; 345:e7666
Low Total-Fat Intake Is Associated with Lower Weight, Body-Mass Index, and Waist Circumference
A meta-analysis backs up observations about fat intake.
Surprisingly, the relation between fat intake and body weight is unclear. In a World Health Organization–sponsored meta-analysis of randomized trials and cohort studies, investigators determined the effect of reducing total-fat intake on body weight in people who did not intend to lose weight (e.g., studies to lower cardiovascular risk).
Thirty-three randomized trials (duration, 0.5–8.1 years; 74,000 participants) were included in the meta-analysis. The mean final weight of participants randomized to low-fat diets (most allowed 
30% fat intake) was 1.6 kg lower than that of participants randomized to usual-fat diets — a significant difference. Greater reductions in fat intake and lower fat intake at baseline were associated with greater weight loss. Participants who were randomized to low-fat diets also had significantly lower final mean body-mass index (BMI; by 0.5 kg/m2) and waist circumference (by 0.3 cm) than did those randomized to usual-fat diets. The cohort studies yielded similar results. Finally, low-fat diets also had salutary effects on lipids and blood pressure.
Comment: In this meta-analysis, low total-fat intake was associated with lower weight, BMI, and waist circumference in people who did not intend to lose weight. On average, the improvements were modest, but many participants likely achieved clinically important responses. These results have public health implications and support the authors' claim that attempts should be made to reduce total-fat intake in populations where mean total-fat intake is 
30% of energy. Clinicians should remain steadfast in recommending the same for their individual patients.
— Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine January 3, 2013
Citation(s): Hooper L et al. Effect of reducing total fat intake on body weight: Systematic review and meta-analysis of randomised controlled trials and cohort studies. BMJ 2012 Dec 6; 345:e7666.
(http://dx.doi.org/10.1136/bmj.e7666)
http://www.ncbi.nlm.nih.gov/pubmed/23220130?dopt=Abstract
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MM: This is an interesting article as it continues to define the physiological differences between men and women. Most medication dosing relies on height and weight as well as age but frequently fails to address gender.
The Drug-Dose Gender Gap
Many sleep aids are designed to last up to eight hours. When evaluating a new short-acting sleep aid for individuals to take when waking up in the middle of the night, the FDA scientists wanted to know how much of the drug would still demonstrate a blood level in the morning.
What they found was a gender gap: men metabolized the drug, zolpidem (Intermezzo), faster than women; therefore, the FDA approved a 3.5-milligram dose for men, and a 1.75-milligram dose for women. Zolpidem is used in other sleeping aids, including Ambien, and, recently, the FDA reduced doses of Ambien for women by half.
Sleep aids are not the only medications that may have unexpected, even dangerous, effects in women; this phenomenon also occurs in many drugs, from aspirin to anesthetics. Many believe that as a result, women may experience a disproportionate share of adverse, often more severe, side effects.
http://well.blogs.nytimes.com/2013/01/28/the-drug-dose-gender-gap/?partner=rss&emc=rss
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MM: For the most part I have avoided the issue of the NECC compounding pharmacy in Massachusetts and how they killed dozens of people through sloppy preparation and abysmal maintenance of their production labs and facilities. Unfortunately these scummy individuals have given pharmacy in general and compounding pharmacy specifically, a black eye. This article demonstrates that these people were not typical pharmacists. That they were conniving, greedy, selfish individuals and not typical of the majority of pharmacists worldwide.
Assets of Owners of Meningitis-linked Pharmacy Frozen
A bankruptcy judge has just frozen the assets of the owners of the pharmacy linked to a deadly U.S. meningitis outbreak. The orders signed by U.S. Bankruptcy Judge temporarily restrict the owners of New England Compounding Center (NECC) from selling their luxury homes or spending up to $21 million they received last year in salary and shareholder distributions.
Recent disclosures show how privately-held NECC's largest shareholder Carla Conigliaro, for example, received nearly $9 million in 2012, Barry Cadden, NECC's chief pharmacist, received about $3.2 million in 2012, his wife Lisa Cadden received about $2.8 million, and Greg Conigliaro, a recycling entrepreneur, who is Lisa Cadden's brother and Carla Conigliaro's brother-in-law, received about $1.6 million.
http://www.reuters.com/article/2013/01/28/us-usa-health-meningitis-necc-idUSBRE90R0XI20130128
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Lancet 2012 Nov 28
In Patients with Hyperlipidemia, Exercise and Statins Both Lengthen Life
Moderate fitness or statin use led to about the same 10-year mortality.
Both taking statins and increasing physical activity lower mortality in patients at risk for cardiovascular disease, but few data exist on the comparative or synergistic effects of these interventions. Researchers followed more than 10,000 military veterans (97% men; 52% black) with dyslipidemia who received care through the U.S. Veterans Administration and underwent exercise tolerance tests between 1986 and 2011. Each patient was assigned to one of four fitness strata, based on peak exercise capacity at cohort entry (from 
5.0 to >9.0 metabolic equivalents [MET]) and was classified as a statin user (for at least 3 months) or nonuser. Patients were followed prospectively for a median of 10 years.
After adjustment for potential confounders, statin use and better fitness were associated independently with lower mortality. Among nonusers, the most-fit patients had significantly lower mortality than the least-fit patients (adjusted hazard ratio, 0.37). Similarly, among statin users, the most-fit patients had significantly lower mortality than the least-fit patients (AHR, 0.32). Moderately fit nonusers (exercise tolerance, 5.1–7.0 MET) had mortality risk approximately equivalent to the least-fit statin users.
Comment: In this observational study, better fitness lowered mortality in hyperlipidemic patients, whether or not they were taking statins, and moderate fitness in nonusers lowered mortality as much as statin use. Physical activity is safe and effective, and an inexpensive alternative or adjunct to statin therapy. Why don't we advocate more strongly for it?
— Bruce Soloway, MD Published in Journal Watch General Medicine January 15, 2013
Citation(s):Kokkinos PF et al. Interactive effects of fitness and statin treatment on mortality risk in veterans with dyslipidaemia: A cohort study. Lancet 2012 Nov 28; [e-pub ahead of print].
(http://dx.doi.org/10.1016/S0140-6736(12)61426-3)
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MM: We frequently look for the easy way to achieve a goal but this is not always the best way. Preeclampsia has been successfully addressed in many cases by providing bio-identical progesterone during pregnancy. This is an inexpensive, simple, safe and effective natural approach and it is surprising that it has not been seen more prominently in the treatment of preeclampsia. It is even more surprising when you realize that most of the statins are already available in their generic form so that means that it is unlikely that a big drug company is pushing this particular agenda.
Obstet Gynecol 2013 Feb; 121:349
Pravastatin in Pregnancy? Stay Tuned.
A potential strategy for preventing preeclampsia
Statins are a cornerstone of cardiovascular disease prevention. Most clinicians recommend discontinuing these drugs during pregnancy because of their FDA Category X status (risk for fetal abnormalities outweighs potential benefits of use). However, postmarketing surveillance has not indicated that statins are teratogenic — and as one of the hydrophilic statins, pravastatin is unlikely to cross the placenta.
Preeclampsia, which complicates 3% to 5% of U.S. pregnancies, has many pathogenic similarities to cardiovascular disease. In a recent study, pravastatin restored angiogenic balance without apparent harm in a rodent model of preeclampsia. Now, 128 women in the U.K. have been enrolled in a proof-of-concept study of pravastatin's ability to restore angiogenic balance in early-onset preeclampsia. In the U.S., investigators at the Eunice Kennedy Shriver National Institute of Child Health and Human Development have launched a double-blind, placebo-controlled pilot study to collect pharmacokinetic and maternal–fetal safety data on daily pravastatin in 40 high-risk pregnant women.
Comment: Although it's premature to recommend initiating prophylactic pravastatin use during pregnancy, as we await these study results, I plan to more actively engage my high-risk patients in shared decision making about the pros and cons of continuing statins while they are pregnant. Preeclampsia remains a major cause of maternal and neonatal morbidity; therefore, safe and effective treatments are a public health priority.
— Eleanor Bimla Schwarz, MD, MS Published in Journal Watch Women's Health January 31, 2013
Citation(s): Costantine MM et al. Pravastatin for the prevention of preeclampsia in high-risk pregnant women. Obstet Gynecol 2013 Feb; 121:349.
(http://viajwat.ch/XVjnWQ)
http://www.ncbi.nlm.nih.gov/pubmed/23344286?dopt=Abstract
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BMJ 2013 Jan 23; 346:f158
How Much Do Women Know About Breast Cancer Overdiagnosis?
Most participants in an Australian study were unaware of the potential for overdiagnosis with screening mammography.
About one third of breast cancers diagnosed with screening mammography will not progress to advanced disease (JW Womens Health Nov 21 2012). However, estimates of overdiagnosis rates vary widely. Investigators in Australia conducted focus groups in mid-2011 to assess women's awareness of breast cancer overdiagnosis; participants also were asked how published prevalence estimates of such overdiagnosis would affect their screening choices. Eight age-stratified focus groups comprised a total of 50 women from diverse cultural and socioeconomic backgrounds.
Before participating, few women were aware of breast cancer overdiagnosis, although some knew about overdiagnosis associated with prostate cancer screening. By the end of the sessions, most women seemed to understand the concept. Many expressed surprise that distinguishing between cases needing versus cases not needing treatment is so difficult. Some participants (particularly younger women with limited screening experience) exhibited skepticism about the value of screening. Women indicated that low (1%–10%) or intermediate (30%) overdiagnosis rates would have only a modest effect on their attitudes about screening. In contrast, if the overdiagnosis rate were 50%, some women questioned whether they would choose to be screened — and whether, if breast cancer were diagnosed, they would follow all treatment recommendations.
Comment: As is true of the debate over prostate-specific antigen screening for prostate cancer (JW Gen Med Jul 12 2012), breast cancer overdiagnosis is a potentially contentious issue. Gaining a better understanding of women's perceptions about and reactions to overdiagnosis will help us improve how we inform them about the benefits and risks of screening mammography.
— Andrew M. Kaunitz, MD Published in Journal Watch Women's Health January 31, 2013
Citation(s): Hersch J et al. Women's views on overdiagnosis in breast cancer screening: A qualitative study. BMJ 2013 Jan 23; 346:f158.
(http://dx.doi.org/10.1136/bmj.f158)
http://www.ncbi.nlm.nih.gov/pubmed/23344309?dopt=Abstract
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J Allergy Clin Immunol 2013 Jan; 131:78
Early Introduction of Complementary Foods Might Prevent Allergic Disease
Duration of total breast-feeding is more important than exclusive breast-feeding for prevention of asthma and allergies.
The timing of the introduction of complementary foods in infants is confusing for parents and clinicians alike. Older guidelines recommended avoidance of dairy until age 1 year; eggs until age 2 years; and peanuts, nuts, and seafood until age 3 years. Currently, the American Academy of Pediatrics recommends exclusive breast-feeding until age 4 to 6 months, followed by introduction of complementary foods without providing a timeline for when to introduce specific foods. Investigators followed 3781 Finnish children for 5 years to examine the association between duration of breast-feeding and timing of introduction of complementary foods (based on parent report) and the development of allergic disease and specific IgE (sIgE) sensitization to foods and inhalants.
Introduction of wheat, rye, oats, and barley before age 5.5 months, fish before age 9 months, and egg before age 11 months was associated with lower rates of asthma, allergic rhinitis, and sIgE sensitization. Total breast-feeding duration of 9.5 months or more was associated with lower risk for nonatopic asthma, and the benefit seemed to correlate with the duration of total breast-feeding rather than exclusive breast-feeding.
Comment: By telling parents for years to delay the introduction of allergenic complementary foods, we might have caused more harm than good. On the basis of these results and recent guidelines (J Allergy Clin Immunol: In Practice 2013;1:29), I recommend exclusive breast-feeding for only 4 months followed by continued breast-feeding with complementary foods until age 12 months. Grains should be started at age 4 months, followed by all other foods during the first year. A recent randomized trial showed similar growth rates and better iron status in breast-fed infants when complementary grains were started at 4 versus 6 months of age. (JW Pediatr Adolesc Med Jan 9 2013)
— David J. Amrol, MD Dr. Amrol is an Associate Professor of Clinical Internal Medicine and Director of the Division of Allergy and Immunology at the University of South Carolina School of Medicine in Columbia.
Published in Journal Watch Pediatrics and Adolescent Medicine January 30, 2013
Citation(s): Nwaru BI et al. Timing of infant feeding in relation to childhood asthma and allergic diseases. J Allergy Clin Immunol 2013 Jan; 131:78.
(http://dx.doi.org/10.1016/j.jaci.2012.10.028)
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JAMA Intern Med 2013 Jan 14; 173:62
No Relation Between Length of Treatment for UTIs and Early Recurrence in Men
How long to continue antibiotics in men with urinary tract infections is still up for debate.
Most research to examine length of antibiotic treatment for uncomplicated urinary tract infections (UTIs) has been conducted in women, for whom clinical guidelines are well established. In a retrospective study of 33,336 veterans with uncomplicated UTIs (all outpatients; mean age, 68; median antibiotic-therapy duration, 10 days), researchers explored whether length of antibiotic therapy was associated with recurrence in men. Most patients received ciprofloxacin or trimethoprim-sulfamethoxazole; about one third were treated for 
7 days, and the rest were treated for >7 days.
Researchers found 1373 cases of early recurrence (at 
30 days; 4% of the cohort) and 3313 cases of late recurrence (at >30 days; 10%). In multivariate analyses, no difference was noted in risk for early recurrence between men who received longer- or shorter-duration initial treatment; risk for late recurrence was significantly higher among those who received longer-duration treatment than among those who received shorter initial courses (11% vs. 8%).
Comment: This retrospective study involved an administrative database that could not capture fully the many factors that influence clinical decision making and that also might be associated with recurrence (i.e., catheter use). However, this study does suggest that the same clinical trials that were conducted in women would be justified in men to develop more precise guidelines on length of treatment.
— Thomas L. Schwenk, MD Published in Journal Watch General Medicine January 31, 2013
Citation(s): Drekonja DM et al. Urinary tract infection in male veterans: Treatment patterns and outcomes. JAMA Intern Med 2013 Jan 14; 173:62.
(http://dx.doi.org/10.1001/2013.jamainternmed.829)
Trautner BW. New perspectives on urinary tract infection in men. JAMA Intern Med 2013 Jan 14; 173:68.
(http://dx.doi.org/10.1001/jamainternmed.2013.1783)
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Treatment Mode Has Little Effect on Long-Term Function in Prostate Cancer
By Joe Elia
The long-term functional outcomes of localized prostate cancer are similar whether patients undergo prostatectomy or radiotherapy, although the 2- and 5-year outcomes vary, according to a New England Journal of Medicine study.
Researchers examined 15-year outcomes in some 1700 men diagnosed between the ages of 55 and 74 with clinically localized cancers. Patients were grouped by primary therapy, either prostatectomy or radiotherapy, regardless of their use of androgen deprivation.
Prostatectomy was associated with higher risk for urinary incontinence and erectile dysfunction, and lower risk for bowel urgency at the 2- and 5-year marks, than radiotherapy. However by 15 years, functions declined across both groups, and there were no significant differences in functional outcomes between them.
The authors conclude: "Considering the often long duration of survival after treatment for prostate cancer, these data may be used to counsel men considering treatment for localized disease."
http://www.nejm.org/doi/full/10.1056/NEJMoa1209978
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Ann Intern Med 2013 Jan 1; 158:19
Quadruple-Dose Influenza Vaccine for HIV-Infected Patients
Seroprotection was better overall with a high-dose vaccine than with the standard-dose one, but questions about application to clinical practice remain.
Up to 40% of HIV-infected patients who receive the recommended standard-dose, inactivated, trivalent seasonal influenza vaccine do not respond to it. Researchers have now randomized 195 HIV-infected patients (70% men; 70% black; 89% on antiretroviral therapy) to receive high-dose (60-µg) influenza vaccine or the standard 15-µg vaccine. A serum hemagglutinin inhibition assay was used to measure antibody response.
Seroprotection rates were significantly higher with the high-dose than with the standard-dose vaccine for the H1N1 (96% vs. 87%) and influenza B strains (91% vs. 80%) — and nonsignificantly higher for the H3N2 strain (96% vs. 92%). Seroconversion rates followed that same pattern, and postvaccination geometric mean antibody titers for all three strains were significantly higher in the high-dose group. Both preparations were well tolerated overall, although local-site reactions and the occurrence of more than one adverse event were more common in the high-dose group. Among the 11% of participants with CD4 counts <200 cells/mm3, a nonsignificant trend toward higher response to the high-dose vaccine than to the standard-dose vaccine emerged.
Comment: The FDA has approved high-dose influenza vaccination for HIV-uninfected people aged 65 and older. This new evidence of the high-dose vaccine's advantage in HIV-infected patients is tempered by the lack of clinical endpoints in the trial and by the small number of participants with CD4 counts <200 cells/mm3, which likely contributed to the overall high response rates. Additionally, the true effectiveness of seasonal influenza vaccines relies on the antigenic match to circulating strains and, of course, patients' acceptance of vaccination — factors not captured in an immunogenicity trial.
Despite these caveats, any improvement in influenza protection would greatly benefit our patients. A plus of this trial's design is that it used a commercially available vaccine and a strategy that would be easy to implement, and the tolerability of the quadruple-dose vaccine is promising. We must wait to see whether this study's findings lead to revised influenza-vaccine recommendations for HIV-infected patients. In my experience, clinical practice regarding use of high-dose hepatitis B vaccine varies widely, indicating that consistent guidelines for use of these high-dose vaccines are needed.
— Brian R. Wood, MD Dr. Wood is Assistant Professor of Medicine in the Division of Allergy and Infectious Diseases at the University of Washington in Seattle. He reports no conflicts of interest.
Published in Journal Watch HIV/AIDS Clinical Care January 28, 2013
Citation(s): McKittrick N et al. Improved immunogenicity with high-dose seasonal influenza vaccine in HIV-infected persons: A single-center, parallel, randomized trial. Ann Intern Med 2013 Jan 1; 158:19.
http://www.ncbi.nlm.nih.gov/pubmed/23277897?dopt=Abstract
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Lancet Infect Dis 2013 Feb; 13:123
Antibiotics for Acute Lower Respiratory Tract Infection?
Amoxicillin was largely ineffective in patients with acute cough and sputum production who had no evidence of pneumonia.
Although most patients with "acute bronchitis" have viral infections, many receive antibiotics. Now, European researchers have conducted a multinational antibiotic trial that involved 2061 adults with so-called acute "lower-respiratory-tract infections" (LRTIs) — a term sometimes used interchangeably with bronchitis — in whom pneumonia was not suspected. Patients were included whether cough was (or was not) the most prominent symptom, as long as LRTI was considered to be likely. At enrollment, 79% of participants produced sputum (discolored in about half); mean duration of illness was 9 days.
Patients received amoxicillin (1 g, thrice daily) or placebo for 1 week and recorded daily symptom scores for 4 weeks. For the primary outcome — duration of symptoms, rated as moderately bad or worse — researchers found no significant difference between the antibiotic and placebo groups. One secondary outcome — the proportion of patients with new or worsening symptoms —was slightly lower in the amoxicillin group (16% vs. 19%; P=0.043; number needed to treat, 30). Gastrointestinal side effects were more common with amoxicillin (29% vs. 24%; P=0.025). Outcomes were similar in older and younger adults.
Comment: One problem here is the LRTI terminology: The anatomic demarcation point between upper and lower respiratory tract wasn't defined clearly, and, even if it were, clinicians often can't tell whether a nonpneumonic infectious cough is originating in the oropharynx, trachea, or upper bronchi or even in the nasopharynx (with cough resulting from postnasal drainage). Indeed, some of these patients probably had what we call "the common cold." However, whether we call this entity LRTI or acute bronchitis, antibiotics (or at least amoxicillin) confer minimal or no benefit.
— Allan S. Brett, MD Published in Journal Watch General Medicine January 24, 2013
Citation(s): Little P et al. Amoxicillin for acute lower-respiratory-tract infection in primary care when pneumonia is not suspected: A 12-country, randomised, placebo-controlled trial. Lancet Infect Dis 2013 Feb; 13:123.
(http://dx.doi.org/10.1016/S1473-3099(12)70300-6)
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Pediatrics Type 2 Diabetes Guidelines Published !
The American Academy of Pediatrics has issued a clinical practice guideline for the management of newly diagnosed type 2 diabetes in those aged 10 to 18 years. Published in Pediatrics, the guideline recommends that clinicians:
- start insulin therapy for patients with ketosis or ketoacidosis, patients in whom type 1 and type 2 disease can't be distinguished, and patients with blood glucose at or above 250 mg/dL or HbA1c >9%;
- initiate a lifestyle modification program and metformin therapy for other patients;
- monitor HbA1c concentrations every 3 months and intensify treatment if HbA1c and blood glucose goals are not met;
- advise finger-stick blood glucose monitoring for patients who are on medications that can cause hypoglycemia, are starting or changing diabetes treatment, have not met treatment goals, or have other illnesses;
- counsel patients about diet and nutrition;
- encourage patients to exercise for at least 1 hour a day.
http://pediatrics.aappublications.org/content/early/2013/01/23/peds.2012-3494.full.pdf+html
