• Severe Coinfection with Seasonal Flu and MRSA
• Antibiotic Resistance — More Than 4 Million Years Old!
• Aspirin to Prevent Cancer — The Story Continues to Evolve
• Prenatal PPI Exposure and Childhood Asthma
• Prempro Decision Orders Pfizer to Pay $4 Million in Damages to One Woman
• Future Technology: Sonic Screwdriver May have Multiple Uses
• Breast Cancer: Genomic Analysis Shows 10 Distinct Types
• High Intake of Some Berries Linked to Slower Cognitive Decline
• Optimizing Postmenopausal Vitamin D3 Supplementation
• Metformin Plus Insulin vs. Insulin Alone in Patients with Type 2 Diabetes
• The Higher the Body-Mass Index, the Higher the Risk for Adenoma
• Few Americans Meet Goals for Cardiovascular Health
• Neurology Group Updates Guidelines on Migraine Prevention
• Making the Case for Shots: 'The Clinician's Guide to the Anti-Vaccinationists' Galaxy'
• Meta-Analysis: Subclinical Hyperthyroidism Raises Total Mortality, CHD Risks
• In Alzheimer Disease, Antioxidants Hurt
• Headaches Are Common in Children with Tourette Syndrome
• Undetectable Viral Load — Not a Guarantee Against Transmitting HIV
• MRSA Is a Rare but Important Cause of Community-Acquired Pneumonia
MM: The funny thing about both seasonal flu and MRSA is that we have had tremendous clinical success with megadoses of Vitamin D3 with both of these conditions. When a patient comes down with the flu we recommend 1,000IU for every pound of body weight DAILY for 3-5 days. This typically reduces symptoms almost immediately and has demonstrated elimination of cold or flu within the first 24 hrs if caught early.
MRSA dosing is the same with a maintenance dose of 50,000IU daily for several months especially if the patient(s) demonstrate recurrence of the MRSA infection. The case that we had in FL several years ago had 7 seniors (ages 67-82) that demonstrated recurrent MRSA. After failure of Mupirocin nasal ointment and concomitant abtibiotic use they all agreed to use the 50,000 IU/day Vitamin D3 for 3 months. Three years later none of the 7 people have had a recurrence of MRSA.
Severe Coinfection with Seasonal Flu and MRSA
This week's MMWR describes the deaths of three family members in Maryland earlier this year — all were infected with seasonal influenza (H3N2) and two were coinfected with methicillin-resistant Staphylococcus aureus (MRSA).
All three patients had severe, rapidly progressing respiratory illness with bloody sputum. MMWR's editors note that in such circumstances, clinicians should "consider the possibility of influenza and S. aureus coinfection," and "empiric treatment for both organisms should be considered." They add that while such coinfections are uncommon, these cases are a reminder of their potentially deadly outcomes.
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6116a4.htm
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MM: Once again we see that we cannot beat micro-organisms. They are too adaptive for us to think that we can create an antibiotic that will kill all the “bad bugs”. No, we are better served in having the “bugs” work for and with us. This is the premise of using Probiotics symbiotically. We have co-existed with bacteria and other micro-organisms since the beginning of time. We must continue to use this experience and not ignore it. This is one of the reasons that Mark Drugs incorporates Probiotics in our Synergy Blends products. Probiotics appear to enhance the effects of our functional supplements. Whether they stabilize tissues, reduce local inflammation or alter local pH; supplements tend to work better when in the presence of probiotics.
PLoS ONE 2012 Apr 11; 7:e34953
Antibiotic Resistance — More Than 4 Million Years Old!
Bacteria from a cave in New Mexico, isolated for more than 4 million years, showed resistance to 14 commercially available antibiotics.
Recent reports suggest that genes encoding resistance to major classes of antibiotics existed long before development and use of such drugs. For example, they have been found in 30,000-year-old permafrost sediments in northwestern Canada (JW Infect Dis Sep 14 2011). Now, researchers have searched for resistance genes in the microbiota of Lechuguilla Cave, Carlsbad Caverns National Park, New Mexico — an ecosystem that has been isolated for >4 million years. This cave has been closed to human access without a permit since its discovery in 1986.
Samples, taken at three sites in deep, remote areas of the cave that have no connection to the surface and have probably never been visited by humans, yielded more than 500 unique bacterial strains. Ninety-three of these strains (33% gram-positive and 63% gram-negative) were selected at random for resistance testing against a panel of 26 antibiotics.
Seventy percent of the gram-positive strains and 65% of the gram-negative ones were resistant to three or four antibiotic classes. The highest resistance rates were observed for sulfamethoxazole and fosfomycin; low rates were seen for the semisynthetic or synthetic antibiotics minocycline, ciprofloxacin, and linezolid. Three strains (all of them Streptomyces species) were resistant to 14 commercially available antibiotics.
Comment: These data support a growing understanding that antibiotic resistance is an ancient phenomenon that is deeply embedded in the microbial pangenome. Several other studies have shown that the ever-increasing use of antibiotics in the clinic and in agriculture has been paralleled by a rising number of resistance-gene copies in bacteria in the environment. Together, these findings suggest that today's resistance problem reflects selection of naturally occurring genes that date back several million years.
— Thomas Glück, MD Published in Journal Watch Infectious Diseases April 25, 2012
Citation(s):Bhullar K et al. Antibiotic resistance is prevalent in an isolated cave microbiome. PLoS ONE 2012 Apr 11; 7:e34953.
(http://dx.doi.org/10.1371/journal.pone.0034953)
http://www.ncbi.nlm.nih.gov/pubmed/22509370?dopt=Abstract
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Lancet 2012 Mar 21
Aspirin to Prevent Cancer — The Story Continues to Evolve!
Daily aspirin reduced short-term risk for cancer incidence and death, and also lowered risk for metastasis.
Previous meta-analyses of long-term follow-up data from five large randomized trials of daily aspirin for prevention of vascular events showed that, compared with placebo or no treatment, aspirin lowered colon cancer incidence and mortality after 8 to 10 years and lowered mortality from other common solid cancers after 5 to 15 years (JW Gen Med Dec 29 2011). Now, these investigators have conducted two new meta-analyses of trials of aspirin for preventing vascular events: One, designed to assess the short-term effects of aspirin on cancer incidence and mortality, included in-trial data from 51 studies that involved more than 77,000 patients — and the other, aimed at studying aspirin's effects on risk for metastasis, included data from five U.K. studies that involved more than 17,000 patients.
In the first analysis, 34 trials in which cancer deaths were reported showed that significantly fewer such deaths occurred among patients who received aspirin (odds ratio, 0.85); this benefit was most pronounced 
5 years after randomization (OR, 0.63). In six primary-prevention trials, cancer incidence was significantly lower for patients who received aspirin (OR, 0.88), and this benefit was apparent after 3 years of follow-up. Meanwhile, aspirin's prevention of vascular events and its association with extracranial bleeds both waned, becoming nonsignificant after 3 years.
Aspirin's observed benefits after 3 to 5 years of follow-up suggest that it might inhibit metastasis, not just initial carcinogenesis. In the second meta-analysis, the investigators assessed time to diagnosis of solid cancers and identification of metastases. Aspirin slightly lowered the overall incidence of cancer; moreover, compared with cancers in the control group, more cancers in the aspirin group remained localized (OR, 1.24), whereas fewer cancers metastasized (OR, 0.64). Among patients who developed incident solid cancers, those taking aspirin were significantly less likely to have metastases at diagnosis or follow-up (OR, 0.59). This effect was significant only for colorectal cancers (OR, 0.36) and all adenocarcinomas (OR, 0.52). Among patients with initial diagnoses of localized cancer, those taking aspirin had significantly lower risk for subsequent metastasis (hazard ratio, 0.45) and better survival rates (HRs, 0.71 for cancer-related deaths and 0.81 for all-cause deaths).
Comment: The increasing benefit of aspirin for cancer prevention after 3 years of treatment — when the counterbalanced effects on risk for vascular disease and extracranial bleeding have been largely extinguished — strengthens the case for aspirin as primary prevention in at least some populations. Furthermore, its apparent effect on metastasis suggests that aspirin might, in the future, play a role in cancer therapy.
— Bruce Soloway, MD Published in Journal Watch General Medicine April 24, 2012
Citation(s):Rothwell PM et al. Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: Analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet 2012 Mar 21; [e-pub ahead of print].
(http://dx.doi.org/10.1016/S0140-6736(11)61720-0)
Rothwell PM et al. Effect of daily aspirin on risk of cancer metastasis: A study of incident cancers during randomised controlled trials. Lancet 2012 Mar 21; [e-pub ahead of print].
(http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2812%2960209-8/fulltext) Top of Page
Aliment Pharmacol Ther 2012 May; 35:1190
Prenatal PPI Exposure and Childhood Asthma
Maternal PPI use during pregnancy or the year thereafter is associated with an increased risk for asthma in the offspring but may not be causal.
The prevalence of childhood asthma is increasing in developed countries. The reason for this effect is not clear, but prenatal exposure to a variety of environmental or medicinal agents has been speculated to play a role. A recent study suggested a potential association between asthma and prenatal exposure to acid-reducing drugs, including proton-pump inhibitors (PPIs).
To explore this possibility, researchers conducted a population-based cohort study, using data previously collected for all singleton births from 1996 through 2008 in northern Denmark. Maternal use of acid-reducing medications — PPIs or histamine-2 receptor antagonists (H2RAs) — was determined from the prescription database that tracks outpatient medication dispensation in the same geographic area. Presence of asthma in the children was defined as a hospital diagnosis of asthma or at least two prescriptions of both a β-agonist and an inhaled glucocorticoid.
Among 197,060 eligible children, 2238 (1.1%) had prenatal exposure to a PPI and 24,506 (12.4%) developed asthma (median follow-up, 6.8 years). The adjusted incidence rate ratio (aIRR) of asthma among children with prenatal PPI exposure was 1.41 (95% confidence interval, 1.27–1.56). The risk did not vary by trimester of exposure, and PPI use initiated during the year after birth was also associated with an increased risk for asthma in offspring (aIRR, 1.32; 95% CI, 1.20–1.46). In a secondary analysis, prenatal H2RA exposure was also associated with an increased risk for asthma (aIRR, 1.47; 95% CI, 1.32–1.65).
Comment: Population studies commonly suggest an association between one or more exposures and outcomes. Because such studies cannot control for a host of potential confounding factors, the associations they uncover may raise hypotheses for further investigation, but they do not establish causation. In the present study, the acid-reducing medications could be a marker for an underlying maternal factor because even postnatal maternal use was associated with asthma in the offspring.
— David J. Bjorkman, MD, MSPH (HSA), SM (Epid.) Published in Journal Watch Gastroenterology April 27, 2012
Citation(s):Andersen ABT et al. Prenatal exposure to acid-suppressive drugs and the risk of childhood asthma: A population-based Danish cohort study. Aliment Pharmacol Ther 2012 May; 35:1190.
http://www.ncbi.nlm.nih.gov/pubmed/22443179?dopt=Abstract
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MM: Timing is everything. Just last month data came out of the Women’s Health Initiative (WHI) study that contended that women who took Premarin® had a lower incidence of breast cancer than those who took placebo or nothing at all.
(http://www.markdrugs.com/rs3-24-2012.html#anchor1) Hmm. I guess noone showed this study to the jury. I wonder what information will come out next week.
Prempro Decision Orders Pfizer to Pay $4 Million in Damages to One Woman
Pfizer must pay at least $4 million in damages to a woman who developed breast cancer after taking Prempro, a jury in Connecticut ruled. Jurors ruled that Pfizer's Wyeth unit was liable for causing Margaret Fraser's cancer and that Prempro was an "unreasonably dangerous product." The panel also found Wyeth should pay punitive damages over its handling of the drug. The jury concluded that Wyeth's handling of the drug "was reckless and they had misrepresented the risks and benefits of its drug to patients and doctors." A federal judge will decide later how much in punitive damages Pfizer must pay. Pfizer's Wyeth and Upjohn units have now lost 11 of 20 Prempro cases decided by juries since trials began in 2006.
http://www.bloomberg.com/news/2012-04-20/pfizer-ordered-to-pay-4-million-in-damages-in-prempro-case-1-.html
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MM: Here is another indulgence in my inner geekness. Please excuse my delving into these “techie” articles but I truly am a nerd and love this stuff. Thank you. ;-)
Future Technology: Sonic Screwdriver May have Multiple Uses
From Doctor Who to today, a team of physicists at the University of Dundee have taken equipment designed for MRI-guided focused ultrasound surgery and demonstrated a real Sonic Screwdriver—lifting and spinning a free-floating 10-cm diameter rubber disk with an ultrasound beam. The physicists used a targeted ultrasound beam to lift and spin a 90-gram, 10-centimeter rubber disk. By shaping the beam like a helix, the researchers were able to rotate the disk using only the energy of an ultrasound array. The vortex-shaped beam allows for angular momentum and the application of torque to an object without actually touching it.This may potentially have applications in the future for pharmacy. The Sonic Screwdriver can be viewed at:
www.youtube.com/watch?v=SeB69CcLEI8
http://www.fiercedrugdelivery.com/press-releases/sonic-screwdriver-tightens-fundamental-physics?utm_medium=nl&utm_source=internal#ixzz1tArQHNyL
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Breast Cancer: Genomic Analysis Shows 10 Distinct Types
Patients may ask about a widely reported, genomics-based investigation that further characterizes breast cancers into specific clinical subgroups. The work appears online in Nature.
Researchers first studied tumor samples from some 1000 patients with breast cancer. Good clinical follow-up data were available for all patients. On the basis of genomic analyses, the tumors fell into 10 distinct clinical subtypes — some carrying a higher mortality risk than others. The researchers then confirmed their findings in a validation set of another 1000 tumors.
The authors say their findings may help to better classify patients' tumors and could aid in examining how the different tumor types respond to various therapies.
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature10983.html
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High Intake of Some Berries Linked to Slower Cognitive Decline
Greater consumption of blueberries and strawberries — both rich in flavonoids — is associated with a slower rate of cognitive decline in older women, according to an industry-funded analysis from the Nurses' Health Study, published in the Annals of Neurology.
Some 16,000 women completed food-frequency questionnaires regularly beginning in middle age and then underwent cognitive assessments once they reached age 70 or older. Over 4 years' follow-up, higher intake of strawberries and blueberries was linked to slower cognitive decline. The strongest association was seen among women who ate at least one serving of blueberries or at least two servings of strawberries per week. Such intake, the researchers calculated, was associated with a delay in cognitive aging of up to 2.5 years. Total flavonoid intake was also associated with less decline.
The authors point to "substantial biologic evidence" in support of their findings — for example, several flavonoids may influence "reductions in neuroinflammation and enhanced neuronal viability."
http://onlinelibrary.wiley.com/doi/10.1002/ana.23594/abstract
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MM: The bottom line is that there is not a single daily dose that is right for everyone and people use up their Vitamin D3 at different rates. Therefore, either people need to be tested to determine an optimal dose or all the experts have to agree that this nutritional product has a very large therapeutic window, is very safe and little worry is necessary for the majority of the population when taking doses of 2,000-10,000 IU daily. Then maybe some of this debate can be put to rest.
Ann Intern Med 2012 Mar 20; 156:425
Optimizing Postmenopausal Vitamin D3 Supplementation
For white women, 600 IU of vitamin D3 daily appears to be sufficient.
Vitamin D deficiency is defined as a serum 25-hydroxyvitamin D (25[OH]D) level of <20 ng/mL (<50 nmol/L), and vitamin D insufficiency is defined as <30 ng/mL (<72.5 nmol/L; JW Gen Med Jun 23 2011). Although insuffiency is diagnosed frequently, no clear guidelines exist for determining the optimal replacement dose. In this randomized placebo-controlled trial, 163 healthy postmenopausal white women (mean body-mass index, 30 kg/m2) with vitamin D insufficiency (mean baseline 25[OH]D level, 16 ng/mL [39 nmol/L]) were assigned to receive placebo or various doses of daily vitamin D3 supplementation (ranging from 400–4800 IU). Participants were followed for 1 year.
Daily doses of 800 IU increased 25(OH)D levels to >20 ng/mL in 97.5% of women. Although a daily dose of 600 IU was not studied, modeling indicated it also would have been sufficient to achieve this level. Hypercalcemia occurred in 1 of 21 women who were randomized to 800 IU per day.
Comment: This randomized study of vitamin D3 supplementation for women with vitamin D insufficiency suggests that a daily dose of 600 to 800 IU is sufficient to correct this issue. However, this dose might not be applicable to nonwhite populations, severely obese people, or people with substantial comorbidities.
— Jamaluddin Moloo, MD, MPH
Published in Journal Watch General Medicine April 26, 2012
Citation(s):Gallagher JC et al. Dose response to vitamin D supplementation in postmenopausal women: A randomized trial. Ann Intern Med 2012 Mar 20; 156:425.
(http://www.annals.org/content/156/6/425.full)
http://www.ncbi.nlm.nih.gov/pubmed/22431675?dopt=Abstract
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BMJ 2012 Apr 19; 344:e1771
Metformin Plus Insulin vs. Insulin Alone in Patients with Type 2 Diabetes
Combination therapy led to lower insulin doses and better glycemic control.
Many patients with type 2 diabetes who are treated with metformin eventually require insulin. Although metformin often is continued in such patients, whether combining the drugs yields any benefit is unclear. In this meta-analysis of 23 randomized trials that involved more than 2100 participants (trial durations, 3–24 months), investigators compared metformin plus insulin with insulin alone.
Patients randomized to metformin plus insulin required less insulin (mean difference, –19 units/day), experienced better glycemic control (mean glycosylated hemoglobin [HbA1c] difference, –0.6%) and weighed less (mean difference, –1.7 kg) than did patients randomized to insulin alone. Hypoglycemia was more common in the metformin-plus-insulin group. All-cause and cardiovascular-related mortality, microvascular and macrovascular outcomes, and quality of life did not differ between the groups.
Comment: These results support the practice of continuing metformin in patients with type 2 diabetes who require insulin, rather than switching them to insulin alone. Nevertheless, despite the salutary effects of combination therapy on insulin dose, glycemic control, and weight, combination therapy was not superior to insulin alone for hard outcomes such as all-cause or cardiovascular-related mortality. Most trials included in the meta-analysis, however, were of short duration (<1 year). Long-term studies are needed to determine if continuing metformin in patients with type 2 diabetes who require insulin would prevent early death.
— Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine April 26, 2012
Citation(s): Hemmingsen B et al. Comparison of metformin and insulin versus insulin alone for type 2 diabetes: Systematic review of randomised clinical trials with meta-analyses and trial sequential analyses. BMJ 2012 Apr 19; 344:e1771.
(http://dx.doi.org/10.1136/bmj.e1771)
http://www.ncbi.nlm.nih.gov/pubmed/22517929?dopt=Abstract
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Gastroenterology 2012 Apr; 142:762
The Higher the Body-Mass Index, the Higher the Risk for Adenoma
A 5-unit increase in BMI was associated with a 19% increased risk for colorectal adenoma.
Obesity is considered a risk factor for colon cancer and adenomas. However, study results have been mixed on the magnitude of risk and whether it is limited to men. Now, researchers have conducted a meta-analysis to clarify the link between body-mass index (BMI) and colorectal adenoma.
Investigators identified 36 studies (16 case-control, 13 cross-sectional, and 7 cohort or nested case-control) appropriate for the meta-analysis. A 5-unit increase in body-mass index (BMI) was associated with a 19% increased risk for colorectal adenoma regardless of patient sex, study region (U.S., Europe, or Asia), or adjustment for physical activity, smoking, caloric intake, alcohol use, and nonsteroidal anti-inflammatory drug use in a subset of studies. In a meta-analysis based on BMI categories, obese patients (BMI 
30) but not overweight patients (BMI 
25 and <30) had an increased risk for colorectal adenoma compared with patients with normal BMI (<25). A subanalysis of 11 studies found that increased BMI was associated with increased risk for colon adenoma but not rectal adenoma.
Comment: This meta-analysis firms up the association between body-mass index and colon adenomas. Increased BMI has also been linked with increased risk for cancer of the colon but not the rectum. Current guidelines do not recommend adjustment of screening or surveillance intervals based on BMI.
— Douglas K. Rex, MD Published in Journal Watch Gastroenterology April 27, 2012
Citation(s):Ben Q et al. Body mass index increases risk for colorectal adenomas based on meta-analysis. Gastroenterology 2012 Apr; 142:762.
http://www.ncbi.nlm.nih.gov/pubmed/22245665?dopt=Abstract
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MM: Surprisingly this article has come out at the same time that data has been released that adult American males have significantly reduced their cholesterol since 1999. This reduction may largely be due to increased use of statin drugs. Yet , cardiovascular healthy lifestyle modifcations seem to have lagged behind drug use. In my opinion, the easy way is not always the best way. There is a time for medication solutions and there is a time to take responsibility for one’s health and to take action to improve it.
JAMA 2012 Mar 28; 307:1273
Few Americans Meet Goals for Cardiovascular Health
Healthy behaviors are significantly associated with decreased mortality, but recent decades have seen little progress toward improving those behaviors.
Cardiovascular disease remains the number-one killer in the U.S. Therefore, the American Heart Association has challenged the American public to improve cardiovascular health by (1) not smoking; (2) being physically active; achieving normal (3) blood pressure, (4) blood glucose and (5) total cholesterol levels, and (6) weight; and (7) eating a healthy diet. To examine trends in cardiovascular health, as related to all-cause and cardiovascular mortality risk, investigators studied National Health and Nutrition Examination Survey (NHANES) data from 1988–1994, 1999–2004, and 2005–2010, and from the NHANES III Linked Mortality File (through 2006).
Of nearly 45,000 participants, very few met all seven cardiovascular health goals (1988–1994, 2.0%; 2005–2010, 1.2%). Absolute mortality risks were significantly lower in participants meeting six or more goals than in those meeting one or fewer goals (see table). Compared with participants who met one or fewer goals, adjusted hazard ratios in those who met six or more goals were 0.49 for all-cause mortality and 0.24 for cardiovascular mortality.
Comment: Not unexpectedly, according to this large study, the more cardiovascular health goals we meet, the lower our risks for all-cause and cardiovascular mortality. Unfortunately — but also unsurprisingly — few Americans meet these goals. Importantly, the investigators did not study how changes in individuals' cardiovascular health profiles affect risk. Nonetheless, these findings should renew efforts to create and intensify primary prevention programs designed specifically to improve these metrics.
— JoAnne M. Foody, MD Published in Journal Watch Cardiology April 4, 2012
Citation(s):Yang Q et al. Trends in cardiovascular health metrics and associations with all-cause and CVD mortality among US adults. JAMA 2012 Mar 28; 307:1273.
(http://dx.doi.org/doi:10.1001/jama.2012.339)
http://www.ncbi.nlm.nih.gov/pubmed/22427615?dopt=Abstract
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Neurology Group Updates Guidelines on Migraine Prevention
The American Academy of Neurology and the American Headache Society have released updated guidelines on migraine prevention in Neurology.
Among the recommendations for prescription pharmacologic agents:
- Most antiepileptic drugs (divalproex sodium, topiramate, sodium valproate), certain beta-blockers (metoprolol, propranolol, timolol), and one triptan (frovatriptan) are effective and should be offered to patients.
- Certain antidepressants (amitriptyline, venlafaxine), other beta-blockers (atenolol, nadolol), and other triptans (naratriptan, zolmitriptan) are probably effective and should be considered.
- Lamotrigine is not effective and should not be given.
Among the guidance on NSAIDs and complementary therapies:
- Petasites (butterbur) is effective and should be offered.
- Several NSAIDs (fenoprofen, ibuprofen, ketoprofen, naproxen), riboflavin, magnesium, feverfew, and histamine SC are probably effective and should be considered.
- Montelukast is probably ineffective and should not be considered.
http://www.neurology.org/content/78/17/1337.full
http://www.neurology.org/content/78/17/1346.full
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Making the Case for Shots: 'The Clinician's Guide to the Anti-Vaccinationists' Galaxy'
The journal Human Immunology offers a brief review of the anti-vaccine movement and common misconceptions about vaccination.
Among the most common misperceptions:
- Antigenic overload. Anti-vaccinationists warn of cytokine storms and immune cascades, but there is no evidence to support the fear.
- Autoimmunity complications. The idea that diabetes, multiple sclerosis, and Guillain-Barré syndrome can result from vaccination is not supported by published evidence.
- Infection induces better immunity than vaccination. Measles kills in 1 case out of 3000; the vaccine for the disease has never killed anyone.
The authors say they hope that "clinicians can play a part in influencing health care practitioners, political leaders, the media, the public, and ultimately patients and parents, to consider the scientific method and peer-reviewed literature." They point out that "the available scientific data richly support the immunological value of vaccines in substantially decreasing morbidity and mortality owing to infectious diseases, and in improving the health of both individuals and populations."
http://www.sciencedirect.com/science/article/pii/S0198885912000821?v=s5
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Meta-Analysis: Subclinical Hyperthyroidism Raises Total Mortality, CHD Risks
Subclinical hyperthyroidism carries higher overall mortality and cardiovascular risks, a meta-analysis using patient-level data shows.
The study, published by the Archives of Internal Medicine, was designed to resolve conflicting results from earlier meta-analyses, which didn't use patient-level data. This analysis encompassed 10 prospective cohorts with data on over 50,000 people. Compared with euthyroid subjects, those with subclinical hyperthyroidism (defined as thyrotropin levels under 0.45 mIU/L with normal free thyroxine levels) showed higher hazard ratios for total mortality, coronary heart disease mortality, and incident atrial fibrillation. Risks for CHD mortality and atrial fibrillation were even higher at thyrotropin levels below 0.10.
The authors say their results support the advice of recent guidelines to treat subclinical hyperthyroidism. An editorialist recommends considering treatment "especially in elderly patients with cardiac risks, hyperthyroid symptoms, or osteoporosis."
http://archinte.ama-assn.org/cgi/content/full/archinternmed.2012.402
http://www.ncbi.nlm.nih.gov/pubmed/21510801?dopt=Abstract
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Arch Neurol 2012 Mar 19
In Alzheimer Disease, Antioxidants Hurt
Antioxidants do not improve AD biomarkers and adversely affect cognition.
Under the hypothesis that oxidative damage leads to Alzheimer disease (AD), some investigators have studied whether antioxidants (e.g., vitamins E and C, α-lipoic acid [ALA], and coenzyme Q [CoQ]) influence amyloid production. Results have generally been positive in animal models, but inconsistent in humans. Now, researchers have examined the effect of these antioxidants on cerebrospinal fluid (CSF) biomarkers and on changes in cognition (on the Mini-Mental State Exam [MMSE]) and function.
The 78 participants had mild-to-moderate AD (mean age, 73; 46% women; mean MMSE score, 23) and were taking memantine, an acetylcholinesterase inhibitor, or both. They were randomized to one of three treatments: a combination of vitamin E (800 IU/day), vitamin C (500 mg/day), and ALA (900 mg/day); CoQ (400 mg/day); or placebo. Four biomarkers (amyloid-β42 [Aβ42], total tau, a phosphorylated tau [P-tau181], and F2-isoprostanes) were assessed in CSF. Fifty-two participants completed the study.
After 16 weeks, there were no between-group differences or changes in Ab42, tau, and p-tau181. F2-isoprostanes decreased by 19% in the combination group. Cognition and function declined in all groups. Combination treatment was associated with significantly greater cognitive decline than placebo (MMSE, –2.8 vs. –0.9 points) and showed a trend toward greater functional deterioration.
Comment: Commonly used antioxidants showed no effect on several AD-related biomarkers (except F2-isoprostanes). However, cognitive scores in the combination group deteriorated clinically and statistically after 16 weeks. This finding raises concern that these agents may be detrimental to cognition. The authors do not propose a mechanism, but other researchers have previously hypothesized that antioxidants affect glucose regulation, as demonstrated by the decreased sensitivity of insulin to exercise with administration of antioxidants (JW Psychiatry Jun 8 2009).The take-home point: Do not take vitamins in the belief that "they couldn't hurt."
— Jonathan Silver, MD Published in Journal Watch Psychiatry April 23, 2012
Citation(s):Galasko DR et al. Antioxidants for Alzheimer disease: A randomized clinical trial with cerebrospinal fluid biomarker measures. Arch Neurol 2012 Mar 19; [e-pub ahead of print].
(http://dx.doi.org/10.1001/archneurol.2012.85)
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J Pediatr 2012 Mar 15
Headaches Are Common in Children with Tourette Syndrome
At Cleveland Clinic, 17% of children with TS reported having a migraine headache during the previous 6 months.
Tourette syndrome (TS), a condition characterized by motor or vocal tics, has several recognized comorbidities, but the prevalence of headache among children with TS is not well known. To learn more, researchers prospectively surveyed 109 children (age 
21 years; 83% male; 92% white/non-Hispanic) who were being seen for TS at Cleveland Clinic. Of this cohort, 58% also had attention-deficit/hyperactivity disorder, 23% had obsessive-compulsive disorder, 12% had anxiety disorder, and 4% had depression.
Headache of any type during the previous 6 months was reported by 60 children (55%), of whom 52 were male and 58 were white/non-Hispanic. Nineteen children (17% of the entire cohort) had experienced migraine headaches: 5 with aura, 9 without aura, 3 abdominal, and 2 sporadic hemiplegic. Of the children with migraine, 63% reported some disability in school, disability during activities, or interference with school attendance. About half of the 60 children with headache had tension headaches, but these interfered with school in only 4 cases. Headaches could not be classified in about one fifth of the 60 children. The most common headache triggers were labeled as "stress/excitement" and "missing sleep."
Comment: Headache appears to be a common comorbidity in childhood with Tourette syndrome. The prevalence of migraine was much higher than the 5% prevalence in the general pediatric population. Whether treatment for headache alters the symptoms of TS is not clear.
— F. Bruder Stapleton, MD Published in Journal Watch Pediatrics and Adolescent Medicine April 25, 2012
Citation(s):Ghosh D et al. Headache in children with Tourette syndrome. J Pediatr 2012 Mar 15; [e-pub ahead of print].
(http://dx.doi.org/10.1016/j.jpeds.2012.01.072)
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AIDS 2012 Feb 29
Undetectable Viral Load — Not a Guarantee Against Transmitting HIV
Detectable HIV RNA in semen concurrent with undetectable plasma HIV RNA is not an uncommon event, a finding which may have implications for HIV transmission.
Results from the HPTN 052 trial demonstrated antiretroviral therapy (ART) to be a powerful tool for both treatment and prevention, reducing the likelihood of HIV transmission by 96%. Some experts have suggested that suppression of HIV to undetectable levels in plasma virtually eliminates the risk for transmission, and in 2008, the Swiss Federal AIDS Commission declared that HIV-infected individuals on "effective ART" were "sexually noninfectious" if they did not have any other sexually transmitted infections (STIs). However, data from two recent studies suggest the need for caution.
Lambert-Niclot and colleagues evaluated 628 paired blood and semen samples collected from 304 HIV-infected men seeking assisted reproductive technology support between 2002 and 2011. Twenty men (6.6%) were found to have detectable HIV RNA in semen at the same time that they had undetectable HIV RNA in plasma, using an assay with a lower limit of detection of 20 to 40 copies RNA/mL. Seminal HIV RNA levels ranged from 135 to 2365 copies/mL. All 20 men had been on continuous suppressive ART for >6 months, and none had a concomitant STI. Sixteen had at least one subsequent concordant result (both samples with undetectable HIV RNA), most while on the same ART regimen as when the discordant result was noted. The prevalence of discordant blood/semen results did not change over time nor did it seem to be related to the specific antiretrovirals being used.
In a separate study, Politch and colleagues evaluated paired blood and semen samples from 101 HIV-infected men on stable ART, nearly all of whom reported sex with men. Overall, 21 (25%) of the 83 men with undetectable HIV in blood simultaneously had detectable virus in semen — a surprisingly high proportion attributed in part to the presence of STIs or urethritis in 10% of the men and genital inflammation in 24%. Men with STIs or urethritis were 29 times as likely as men without these conditions to have detectable HIV in semen despite undetectable virus in blood. Unprotected insertive anal intercourse and the presence of genital inflammation were also significantly associated with increased likelihood of a discordant blood/semen result.
Comment: Although there is no doubt that ART significantly decreases the likelihood of HIV transmission, these data indicate that the risk for HIV transmission is not eliminated by suppressive ART. Shedding of virus in the male genital tract is not uncommon, even in men with consistently undetectable plasma HIV RNA. Among such men, STIs, urethritis, and genital inflammation significantly increase the likelihood of HIV shedding in semen, and the timing and frequency of this shedding appear to be unpredictable. Furthermore, previous studies have shown no clear association between the presumed penetration of specific antiretrovirals into the genital tract and the likelihood of detectable virus in semen. Thus, despite the fact that the threshold level of genital-tract HIV necessary for transmission is not known, caution is warranted. Recommending safer sex (and procreation) practices for all HIV-infected patients, even those with suppressed plasma HIV RNA, seems prudent.
— Charles B. Hicks, MD Published in Journal Watch HIV/AIDS Clinical Care April 23, 2012
Citation(s):Lambert-Niclot S et al. Detection of HIV-1 RNA in seminal plasma samples from treated patients with undetectable HIV-1 RNA in blood plasma on a 2002–2011 survey. AIDS 2012 Feb 29; [e-pub ahead of print]. (http://dx.doi.org/10.1097/QAD.0b013e328352ae09)
Politch JA et al. Highly active antiretroviral therapy does not completely suppress HIV in semen of sexually active HIV-infected men who have sex with men. AIDS 2012 Mar 23; [e-pub ahead of print]. (http://dx.doi.org/10.1097/QAD.0b013e328353b11b)
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Clin Infect Dis 2012 Apr 15; 54:1126
MRSA Is a Rare but Important Cause of Community-Acquired Pneumonia
Patients known to carry methicillin-resistant Staphylococcus aureus and those with nursing home admission or exposure to skin infection were at highest risk for MRSA-caused pneumonia.
To determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infection and factors associated with it in patients hospitalized with community-acquired pneumonia, investigators prospectively enrolled a convenience sample of 627 adult patients with pneumonia who were admitted from 12 university-affiliated emergency departments during 2006–2007. Patients who were hospitalized or in long-term care facilities in the past month were excluded.
Among 595 patients (95%) who underwent blood cultures, respiratory cultures, or both, a pathogen was identified in 17% (11% of 579 blood cultures and 15% of 313 respiratory cultures). MRSA was identified in 2.4% of patients overall and in 4.8% of patients admitted to the intensive care unit. Two of 14 MRSA-infected patients died. Factors significantly associated with MRSA infection were patient history of MRSA, nursing home admission in the previous year, close contact with someone with a skin infection, multiple infiltrates or cavities on chest x-ray, and critical presentation (comatose state or intubation, pressors, or death in the ED).
Comment: Although the number of MRSA cases was small, this study supports the current Infectious Diseases Society of America pneumonia treatment guidelines, which recommend adding coverage for MRSA in patients with severe, life-threatening community-acquired pneumonia. Of note, the low yield from cultures (17%) reinforces the guideline revision that blood cultures should not routinely be drawn in patients with community-acquired pneumonia.
— Diane M. Birnbaumer, MD, FACEP Published in Journal Watch Emergency Medicine April 13, 2012
Citation(s):Moran GJ et al. Prevalence of methicillin-resistant Staphylococcus aureus as an etiology of community-acquired pneumonia. Clin Infect Dis 2012 Apr 15; 54:1126.
http://www.ncbi.nlm.nih.gov/pubmed/22438343?dopt=Abstract
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