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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
August 16, 2014

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Vaccine Safety in Children: Huge Benefit, Minimal Risks
Squaric Acid Sensitization Therapy for Pediatric Warts
Pound It: Fist Bumps More Hygienic Than Handshakes
Running News: Short Distances Count; Heat Stroke a Bigger Danger than Arrhythmia
Most Overweight Kids Misperceive Their Size
Matching Patients and Donors for Stem-Cell Transplantation
Sodium Intake, Potassium Intake, Blood Pressure, and Cardiovascular Events
Sodium Consumption and Worldwide Cardiovascular Mortality
Decline in Stroke Incidence Rates: Cause for Cautious Optimism

MM: Beware of he who doth protest too much. If a person continually feels the need to tell you that he is honest, should that raise red flags that there may be a reason to do so? When we are constantly being reassured that vaccines are the greatest thing since sliced bread, should we become more vigilant regarding vaccines? I find it interesting that these studies proclaim the safety of vaccines yet manufacturers are exempt from litigation if a person is injured by these same safe vaccines. What am I missing here?
Pediatrics 2014 Jul 1
Vaccine Safety in Children: Huge Benefit, Minimal Risks
In a systematic review, serious adverse events were rare, not unexpected, and mostly resolved completely.
The Rand Corporation updated a 2011 Institute of Medicine consensus report on vaccine safety (National Academies Press 2011). To do so, they performed a systematic review of evidence published from 2010 to August 2013. Of 20,478 possible articles, 67 met inclusion criteria.
The combined data revealed the following:
Concerning adverse events associated with vaccines:

 Equally important: What is not associated with vaccines:

Comment This study should reassure everyone that vaccines are safe, that adverse events are rare, and in most cases will resolve completely. Transparency about adverse events may provide reassurance of the benefit of immunizations. If these data do not reassure parents, at least clinicians can speak with confidence of the safety and importance of vaccines for the health of children.
Citation(s): Maglione MA et al. Safety of vaccines used for routine immunization of US children: A systematic review. Pediatrics 2014 Jul 1; [e-pub ahead of print]
Byington CL.Vaccines: Can transparency increase confidence and reduce hesitancy? Pediatrics 2014 Jul 1; [e-pub ahead of print].
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MM: warts are one of those conditions that are life tormenting. They may be uncomfortable, are certainly unsightly and unquestionable socially unacceptable. Many people are plagued by these dermal eruptions and feel lost and confused when various treatments fail. Mark Drugs has been preparing Squaric acid topical treatments for recalcitrant warts for many years and is an expert on this product. Please contact your physician for a prescription if you or your children suffer from this condition.
Pediatr Dermatol 2014 Jul 14
Squaric Acid Sensitization Therapy for Pediatric Warts
A retrospective analysis suggests that this treatment can be effective and safe when other treatments have failed.
Warts, caused by the human papilloma virus, are one of the most frequent complaints in the dermatologist's office, particularly in children. Cryotherapy or other painful procedures are difficult for the young child. Squaric acid dibutyl ester (SADBE) contact immunotherapy has been studied for alopecia areata since the 1970s but is less well researched for treating warts. Now, investigators have performed a retrospective chart review of 72 consecutive patients (age range, 3–18 years) treated with SADBE over a 10-year period in a pediatric dermatology clinic. All had recalcitrant warts. Many had failed conventional therapies, including salicylic acid, cantharidin, candida antigen immunotherapy, and imiquimod. Patients were sensitized with 2% SADBE on the upper volar arm under occlusion for one day. Two weeks later, parents applied 0.4% SADBE three times per week to the warts and gradually increased application frequency to daily to elicit a mild dermatitis. At monthly clinic visits, the concentration of SADBE was changed if needed.
Of 48 patients with obtainable treatment outcomes, 40 (83%) had complete wart resolution, 79% of whom used a maximum concentration of 0.4%. Average time to response was 2.6 months; mean treatment course of responsive patients was 8 months. Average follow-up was 34 months. Of 34 patients asked, 68% said they would do SADBE treatment again if needed. In 52 patients with safety data, adverse effects included erythema, pruritus, dermatitis, irritation, and blisters; 60% reported no adverse effects. Occurrence of adverse effects was unrelated to treatment response. Resolution rates were statistically the same in immunocompromised patients (4 of 5) and immunocompetent patients.
Comment This large study, like previous case series, was uncontrolled; some of the improvement may have been placebo effect or spontaneous resolution. Nevertheless, the findings demonstrated safety and efficacy of home SADBE sensitization therapy for pediatric warts, even in immunocompromised patients. Treatment adherence affects efficacy, and office-based application may yield faster results. Home application with monthly doctor's appointments can be successful, but parents should not give up too soon, as 10 weeks of therapy may be needed to see a response.
Citation(s): Pandey S et al. Examining the efficacy and safety of squaric acid therapy for treatment of recalcitrant warts in children. Pediatr Dermatol 2014 Jul 14; [e-pub ahead of print].
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MM: I like the avant garde flair of a fist bump when I see my college buddies or a high five when I play softball with a bunch of friends and make a good play or get a hit but it sort of loses something for me when I enter a business meeting or am introduced to someone. I can only hope that in spite of the decreased bacterial transfer of the fist bump or the high five, it will not overtake the traditional handshake. I may be an old fuddy duddy but at this point in my life and career, I will probably stick with a handshake and in those cases where I am already friendly to a person, I will not rule out a hug..
Pound It: Fist Bumps More Hygienic Than Handshakes
By Kelly Young
Edited by David G. Fairchild, MD, MPH, and Jaye Elizabeth Hefner, MD
Fist bumps spread far less bacteria that handshakes do, according to research being published in the American Journal of Infection Control.
To test whether shaking hands, fist-bumping, or high-fiving would transfer the most bacteria, one researcher wore a glove dipped in a broth rich in E. coli, while another researcher's glove was sterilized. Following each greeting, the researchers measured how much bacteria had been transferred to the sterilized glove.
Handshakes conferred the highest bacterial transfer. Compared with handshakes, high-fives cut bacterial transfer by more than half, and fist-bumping reduced it by 90%.
The researchers say their results might be explained by the high speed and low surface area of the fist bump.
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MM: It is nice to know that in our very busy lives, even if we can only carve out a brief workout, there may be benefits. The typical recommendation is that a person exercises several hours each week in order to gain any significant benefit. This study demonstrates a significant benefit from much less exercise. I have been a runner since I was 12 years old but also live a very busy life. I have always felt guilty if I went for a run of less than 30 minutes. That feeling of guilt may not change any time in the near future but at least I now have the hope that I am still getting some benefit from my abbreviated workouts when that is all that I can squeeze in.
Running News: Short Distances Count; Heat Stroke a Bigger Danger than Arrhythmia
By Larry Husten
Edited by David G. Fairchild, MD, MPH, and Jaye Elizabeth Hefner, MD
Running just 5 minutes a day can extend one's life span. For endurance runners, heat stroke may be a bigger danger than cardiac disorders. These are the lessons learned from two new studies in the Journal of the American College of Cardiology.
In the first, researchers analyzed data from more than 55,000 adults. Compared with people who did not run, runners had a 30% reduction in all-cause mortality and a 45% reduction in cardiovascular mortality, resulting in a 3-year increase in life expectancy. Findings did not differ significantly based on running distance, duration, speed, or frequency. Editorialists advise physicians to offer a simple exercise prescription to patients: "15 min of brisk walking or 5 min of running is all it takes for most clinic patients."
In the second study, researchers retrospectively reviewed data from more than 137,000 runners who participated in endurance races in Tel Aviv. They found only two serious cardiac cases: one myocardial infarction and one hypotensive supraventricular tachycardia. However, serious cases of heat stroke (core body temperature above 104-105 degrees associated with multiorgan dysfunction) occurred in 21 runners; two cases were fatal, and 12 were life-threatening. The researchers say the diagnosis of heat stroke can be missed and mistaken for a cardiac disorder unless the core temperature — which can only be reliably obtained with a rectal measurement — is taken immediately.
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MM: Body Dysmorphia is a condition where a person can't stop thinking about a flaw in their appearance. They may think that they are too tall, fat, short or thin. This can take a huge toll on their personal life and certainly on their self-perception. It has the potential of both short and long term negative outcomes. Having a misperception of one's stature in the other direction may be just as potentially detrimental. Failure to act upon being overweight and making appropriate diet and lifestyle changes or being anorexic and failing to modify the diet to include better nutritional choices can lead to long term life diminishing results. These results, which may be additionally related to socio-economic levels, make them even more disturbing than their raw data value alone.
Most Overweight Kids Misperceive Their Size
By Kelly Young
Edited by Susan Sadoughi, MD, and Richard Saitz, MD, MPH, FACP, FASAM
Roughly 81% of overweight boys and 71% of overweight girls consider themselves to be "about the right weight," according to a new CDC report.
As part of the National Health and Nutrition Examination Survey, U.S. children aged 8 to 15 years were asked, "Do you consider yourself now to be fat or overweight, too thin, or about the right weight?" Their answers were compared with their BMIs.
In children who were obese, 48% of boys and 36% of girls said they were about the right weight. Children from families with lower incomes were more likely to misclassify their weight status than those from higher-income families.
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MM: There is a significant drop in the number of non-white registrants in these national databases. This creates a significant downstream shortage of potential matches and the likelihood of stem cell transplantation cures for these various racial and ethnic groups. At the present time, if successful treatments are to be found, using the current technology, it will be imperative that registration efforts are increased in these various populations. The best way to improve this registration is through information and education. This will help to eliminate much of the fear associated with a medical procedure and will help to decrease the various misconceptions of danger associated with being a donor of any sort.
N Engl J Med 2014 Jul 24; 371:339
Matching Patients and Donors for Stem-Cell Transplantation
Identifying highly matched donors remains a challenge for most nonwhite populations.
Allogeneic hematopoietic stem-cell transplantation (HSCT) represents the only curative approach for many patients with high-risk or relapsed hematologic malignancies. However, only about 30% of patients have a human leukocyte antigen (HLA)-matched related donor.
To assess the likelihood of identifying unrelated-matched (8/8 HLA loci) or minimally mismatched (7/8 loci) donor or cord blood in the U.S. National Marrow Donor Program (NMDP), investigators used a population-based model to determine the frequency of donor availability among 21 racial and ethnic groups. The NMDP registry contains approximately 11 million donors and nearly 200,000 cord-blood units. The latter require less-stringent matching (6/6 or 5/6 loci), but single-cord units often lack an adequate cell dose for transplantation in patients older than 20 years of age.
White patients of European descent had a 75% probability of donor identification (excluding cord blood), whereas white patients of Middle Eastern or North African descent had a 46% probability. Black patients had only a 16% to 19% probability, whereas Hispanics, Asians, and Native Americans had probabilities ranging from 27% to 52%. Although the overall results of this analysis suggested that a donor could ultimately be identified from the registry, most nonwhites lacked a matched or minimally mismatched stem-cell source, putting these patients at risk for poorer outcomes and lower survival following HSCT.
Comment: Approximately 6000 unrelated-donor HSCTs were facilitated by the NMDP in 2012. However, the ability to rapidly identify highly matched donors remains a challenge for most nonwhite populations. Some of this need is being served by cord-blood transplantation, including double cord unit transplants, and the use of related haplo-identical donors. As the authors suggest, recruiting individuals from racial and ethnic populations is key for expanding the NMDP donor pool to address this critical need.
Citation(s): Gragert L et al. HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry. N Engl J Med 2014 Jul 24; 371:339.
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MM: Going to extremes does not seem like the best approach in most cases. This same tenet seems to apply when it comes to sodium restriction. The "U-shaped" curve associated with both high and low sodium diets seems to support this premise. I have never bought into the premise that sodium must be eliminated in hypertensive patients. Excessive sodium intake should be considered but sodium and sodium chloride specifically, provides a number of very important functions in the human body including muscle contraction and relaxation, gastric acid balance and digestion and electrolyte and fluid homeostasis. All of which are necessary for the existence and continuation of life.
N Engl J Med 2014 Aug 14; 371:601
Sodium Intake, Potassium Intake, Blood Pressure, and Cardiovascular Events
In an observational study of 100,000 people, the associations were complex.
Considerable controversy exists about relations among sodium intake, blood pressure (BP), and adverse cardiovascular events. Researchers explored this issue in an observational study of about 100,000 adults from a mix of 18 high- and low-income countries. Using fasting urinary sodium and potassium measurements, the researchers estimated daily sodium and potassium excretion — a surrogate for intake.
Key BP findings were:

Key findings for a primary composite outcome (death or major adverse cardiovascular event) during mean follow-up of 3.7 years were:

Comment: For some observers, these findings might suggest that a low-sodium, high-potassium diet will lower BP substantially and promote favorable clinical outcomes; however, the study's observational nature precludes strong inferences about causality or the effects of dietary intervention. The U-shaped association between sodium excretion and adverse clinical outcomes has been noted in previous studies and could represent reverse causality if higher-risk patients are more likely to restrict sodium intake. Alternatively, the authors speculate that excessive sodium restriction could promote harm by activating the renin-angiotensin-aldosterone system in vulnerable patients.
Citation(s): Mente A et al. Association of urinary sodium and potassium excretion with blood pressure. N Engl J Med 2014 Aug 14; 371:601.
(http://dx.doi.org/10.1056/NEJMoa1311989) O'Donnell M et al.
Urinary sodium and potassium excretion, mortality, and cardiovascular events. N Engl J Med 2014 Aug 14; 371:612.
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MM: In the fairness of providing a balance approach to controversial topics, I felt that it was only appropriate to provide the other argument for sodium restriction thereby demonstrating the overall confusion in the medical field on this topic.
N Engl J Med 2014 Aug 14; 371:624.
Sodium Consumption and Worldwide Cardiovascular Mortality
According to a modeling study, high sodium intake accounts for approximately 1 in 10 cardiovascular deaths globally.
The association of high sodium intake with hypertension and cardiovascular disease is well established; however, little is known about the global effect of high sodium on cardiovascular mortality. Therefore, investigators used data from surveys on sodium intake (based on urinary excretion and diet) from 66 countries to quantify global intake of sodium according to age, sex, and country. They conducted a meta-analysis of 107 randomized studies to determine the effects of sodium intake on blood pressure; derived cause-specific mortality from the Global Burden of Disease Study 2010; and developed a model to assess the effects of current sodium intake, compared with a reference of 2.00 g of sodium daily, on cardiovascular mortality.
The estimated mean level of global sodium intake in 2010 was 3.95 g daily; mean regional estimates ranged from 2.18 to 5.51 g daily. Nearly 1 in 10 cardiovascular deaths (1.65 million; 62% men) were attributable to sodium consumption above the reference level. Most of these deaths (84.3%) occurred in low- and middle-income countries, and more than 40% occurred in people younger than 70.
Comment: These findings highlight the substantial global burden of high sodium intake and support population-based initiatives to reduce dietary sodium. In preventive care, extrapolative analyses such as this also might help clinicians persuade their patients that minimizing sodium consumption according to guideline recommendations can lower their cardiovascular risk.
Citation(s): Mozaffarian D et al. Global sodium consumption and death from cardiovascular causes. N Engl J Med 2014 Aug 14; 371:624.
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MM: This data suggests that the most significant lifestyle change that affects the incidence of stroke may be smoking cessation. This may be deduced by the fact that of the conditions examined, obesity, diabetes, hypertension and coronary heart disease, all increased significantly over the time period but smoking diminished.
JAMA 2014 Jul 16; 312:259
Decline in Stroke Incidence Rates: Cause for Cautious Optimism
The decline is attributable largely to lower incidence in elders, whereas mortality but not incidence has declined in younger patients.
Over the past three decades, several modalities have been shown to reduce risk for stroke, including antihypertensive therapy, statins, smoking cessation, and lifestyle modification. If these measures are being used in the community, then one would expect declining rates of stroke incidence. Investigators for the Atherosclerosis Risk in Communities (ARIC) study longitudinally followed stroke-free participants from four geographic regions for more than 2 decades. The investigators tracked 14,357 participants with a mean age of 54.1 years at the first study visit (between 1987 and 1989). Participants were followed for a maximum of 25 years, with 282,097 person-years of follow-up overall. The researchers found a decrease in age-adjusted stroke incidence of 24% per 10-year period (absolute decrease, 0.93 per 1000 person-years). The decrease was seen in participants older than 65 years (31% reduction) but not in younger participants (a nonsignificant 3% decrease). The decrease in stroke incidence was seen in both blacks and whites and both sexes. Hypertension and diabetes prevalence increased by 40% and coronary heart disease by 80%; the smoking rate declined. Mortality following stroke decreased by 20%, with the reduction most prominent in patients younger than 65 years.
Comment: The reduction in stroke incidence documented in this study is certainly good news. It correlates with the well-documented increased control of hypertension and more-widespread treatment of dyslipidemia. One note of caution concerns the lack of reduction in stroke incidence rates in patients younger than 65. This group has had a surge in diabetes and obesity and needs more-vigorous risk factor treatment in the future. A limitation of these data is the lack of information on Hispanics or other ethnicities that are growing rapidly in the U.S.
Citation(s): Koton S et al. Stroke incidence and mortality trends in US communities, 1987 to 2011. JAMA 2014 Jul 16; 312:259.

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