• CVS to Stop Selling Tobacco
• Another Study Suggests Excess Cardiovascular Risk with Testosterone
• Does Xylitol Syrup Prevent Recurrent Otitis Media in Children?
• Influenza Is More Virulent Among Cancer Patients
• Acute Otitis Externa Guidelines Released
• Overweight and Obesity at Age 5 Years Increases Risk for Obesity at Age 14
• Diet and the Microbiome
• More Evidence Links Gut Microbiome to Autism
• New Autism Guidelines Released
• One-Year Update on H7N9 Flu in China Finds No Definite Human-to-Human Spread
• Songbirds and Parakeets: Possible Sources of Influenza A (H7N9) Virus Transmission
• A Two-Way Interaction Between Nature and Nurture
• ACIP Releases 2014 Adult Immunization Schedule
MM: CVS is to be applauded for this approach to health. Mark Drugs made this move in 1990! Unfortunately we were not big enough to catch the eye of anyone other than the customers who were irked that we no longer sold tobacco. I find it interesting that the FDA has finally learned that you are more likely to get a positive result from youth by appealing to their vanity rather than to their concern with longevity.
CVS to Stop Selling Tobacco
By Kelly Young
CVS Caremark has announced plans to stop selling tobacco products at all of its pharmacies by Oct. 1. A JAMA viewpoint, co-written by CVS's chief medical officer, notes that pharmacy chains, including CVS, are adding retail health clinics to assist in treating chronic conditions like hypertension, hyperlipidemia, and diabetes, "all conditions exacerbated by smoking." The article continues: "Although the sale of tobacco products in CVS pharmacies produces more than $1.5 billion in revenues annually, the financial gain is outweighed by the paradox inherent in promoting health while contributing to tobacco-related deaths."
Several medical societies, including the American Lung Association, came out in support of the move and encouraged other pharmacies to follow suit.
In other anti-smoking news, the FDA is about to release a new anti-smoking campaign aimed at high-risk youth aged 12 to 17. "The Real Cost" will target teens' concerns, such as the cosmetic consequences of smoking.
http://jama.jamanetwork.com/article.aspx?articleID=1828530&utm_source=
Silverchair%20Information%20Systems&utm_medium=email&utm_campaign=
JAMA%3AOnlineFirst02%2F05%2F2014
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MM: The cavalier position of many men and many physicians who want or order PDE5 drugs is a reason that testosterone products are frequently ordered without sufficient assessment, testing or follow-up. This is similar to how estrogen supplementation was first ordered in the 1950's. Many clinicians are unaware that testosterone has estradiol (E2) as one of its breakdown products and that E2 must be considered and monitored in follow-up testing. Pharma has neglected to educate physicians on the appropriate patient history to obtain, testing, side effects and follow-up that is appropriate with these drugs in order to appropriately prescribe them. This is another example of corporate greed at the expense of the consumer.
PLoS ONE 2014 Jan 29; 9:e85805
Another Study Suggests Excess Cardiovascular Risk with Testosterone
The FDA has announced that it is reassessing the safety of testosterone products.
In a recent observational U.S. study, testosterone therapy was associated with excess cardiovascular risk in older men with risk factors (NEJM JW Gen Med Nov 19 2013). In this new study, NIH-supported researchers examined the same issue, using a large database with information from employer-sponsored insurance plans.
Nearly 56,000 men received new prescriptions for testosterone. Their annualized rate of myocardial infarction (MI) during the 3 months after initiating testosterone therapy was significantly higher (by 36%) than the rate during the previous year. In contrast, MI rates were not significantly different before and after initiation of phosphodiesterase type 5 (PDE5) inhibitors (sildenafil and tadalafil [Cialis]) prescribed for erectile dysfunction.
Next, the testosterone and PDE5 cohorts were compared after extensive adjustment for baseline differences. In younger patients (age, <65) without MI histories, testosterone use (compared with PDE5 use) was not associated with excess MI risk. However, in younger patients with previous MIs, and in older patients (regardless of MI history), testosterone use was associated with roughly twice the risk for MI, compared with PDE5 use.
Comment: In this observational study, the incidence of myocardial infarction rose in at-risk subgroups within 3 months after initiating testosterone therapy; absolute risk was roughly 5 to 10 excess MIs per 1000 person-years. Because these results are consistent with findings from the aforementioned U.S. study and from a recently published meta-analysis (BMC Medicine 2013; 11:108), the FDA has announced that it is reassessing the safety of testosterone products. An NIH-sponsored 1-year randomized trial (the “T Trial”) with 800 participants is under way, but it might not be sufficiently powered to settle concerns about cardiovascular risk.
Citation(s): Finkle WD et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS ONE 2014 Jan 29; 9:e85805.
(http://dx.doi.org/10.1371/journal.pone.0085805)
http://www.ncbi.nlm.nih.gov/pubmed/24489673?access_num=
24489673&link_type=MED&dopt=Abstract
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MM: Herbal products do not occur in nature in convenient dosing schedules. If it takes constant exposure of a product (5x/day vs 3x/day) to have an effective result then it is necessary to suffer that inconvenient approach to treatment. I find the condescending approach of the reviewer to be ignorant and mal-informed. The bottom line is that suffering this inconvenience does not put our children at increased risk of super-infection and antibiotic resistance that occurs with chronic antibiotic use.
Pediatrics 2014 Jan 6
Does Xylitol Syrup Prevent Recurrent Otitis Media in Children?
Xylitol given three times daily was no better than placebo.
Xylitol, a sugar alcohol with known antibacterial properties, has been shown to prevent episodes of acute otitis media (AOM) in children when given as a gum or syrup five times per day. In a practice-based trial, 326 children (mean age, 22 months) with at least three AOM episodes in the prior year were randomized to receive 12 weeks of xylitol (5 g in an oral syrup, 3 times/day) or sorbitol as placebo. (Sorbitol does not have antibacterial properties.) This is the first study to use a xylitol solution with added mucosal adherence agents to optimize its effect.
Time to first AOM episode (in the medical record or by parent report) after the start of xylitol versus placebo was not significantly different in a proportional hazards model and intent-to-treat analysis (hazard ratio, 0.88; 95% confidence interval, 0.61–1.27). Compliance with treatment did not affect the results, even when those taking xylitol as directed were compared with children taking placebo combined with noncompliant children in the xylitol group (HR, 0.93). Within 3 months after starting the study, about one third of children in each group had had an AOM episode, and the total number of AOM episodes and days of antibiotic use were similar between groups. Rates of gastrointestinal adverse effects were similar and led to discontinuation in 11% and 7% of the xylitol and placebo groups, respectively.
Comment: This study was somewhat underpowered so a larger study might show a difference between xylitol and placebo, especially if acute otitis media is diagnosed in a standardized manner by experts. But, I like this real-world practice-based study in which compliance was not perfect and primary care pediatricians made diagnoses and prescribed antibiotics — outcomes that really matter to me as a practicing pediatrician. Previous studies have shown prophylactic benefit from xylitol in children who did and did not have recurrent AOM; it may work when bacterial colonization is lighter and middle ear effusions are absent. However, I agree with the authors that parents are unlikely to give a child without recurrent ear infections anything 3 or 5 times per day
Citation(s): Vernacchio L et al. Xylitol syrup for the prevention of acute otitis media. Pediatrics 2014 Jan 6; [e-pub ahead of print].
(http://dx.doi.org/10.1542/peds.2013-2373)
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MM: This is even more support to provide non-invasive measures to strengthen a cancer patient's immune system. Most Cancer treatments totally destroy the immune system and make the patient more susceptible to viruses and disease. Introduction of Vitamin D, Vitamin C, direct sunlight exposure and Low Dose Naltrexone (LDN) may make the difference between recovery and failure
Clin Infect Dis 2014 Jan 15; 58:214
Influenza Is More Virulent Among Cancer Patients
Yet many of the most common flu symptoms are less common in this group.
Influenza is particularly virulent among immunocompromised people, but studies have been largely retrospective, without point-by-point comparisons with immunologically normal people during the same flu season. Now, NIH investigators have prospectively evaluated 32 immunocompromised patients (25 with hematologic malignancies, 7 with solid tumors) who presented with culture-confirmed influenza between 2008 and 2011. Compared with 54 nonimmunocompromised influenza patients (a group that included patients with well-controlled HIV infection) treated during the same years, immunocompromised patients were less likely to be overweight and to be current smokers and also less likely to be vaccinated (25% vs. 60%).
Fever was reported by about 80% of both groups, but most other flu symptoms were significantly less common among the immunocompromised, including dry cough (78% vs. 96%), chills (52% vs. 81%), shortness of breath (37% vs. 62%), and myalgias (40% vs. 68%). Conversely, radiologic abnormalities were more common among immunocompromised patients, more of whom also required intensive care unit admission, and the single fatality in the study was an immunocompromised patient. Average durations of viral shedding were significantly longer in the immunocompromised group.
Comment: No surprises here regarding the increased virulence of the flu and the higher likelihood of pneumonia in severely immunocompromised people. The relative dearth of common symptoms in this group is interesting and suggests that clinicians should consider flu in these patients even in the absence of many of the usual clinical indicators
Citation(s): Memoli MJ et al. The natural history of influenza infection in the severely immunocompromised vs nonimmunocompromised hosts. Clin Infect Dis 2014 Jan 15; 58:214. (http://dx.doi.org/10.1093/cid/cit725)
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Acute Otitis Externa Guidelines Released
By Kelly Young
The American Academy of Otolaryngology — Head and Neck Surgery Foundation has released updated guidelines on diagnosing and treating acute otitis externa (AOE) in patients aged 2 years and older.
Among the recommendations:
- Patients with diffuse AOE should be assessed for factors that modify management, such as tympanostomy tube or nonintact tympanic membrane.
- Clinicians should use topical treatments as first-line therapy for uncomplicated AOE.
- Initial treatment with systemic antibiotics is not recommended unless there's extension outside the ear canal or other signs that systemic therapy is needed.
- Clinicians should instruct patients on how to apply topical treatments (the guidelines include a table of patient instructions).
- If the canal is obstructed, clinicians should insert a wick or perform aural toilet.
- If the tympanic membrane is perforated, a nonototoxic topical preparation should be prescribed.
- If patients fail to respond to initial therapy within 48 to 72 hours, they should be reassessed to rule out other potential causes of illness.
http://oto.sagepub.com/content/150/2/161.full
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MM: These are scary numbers and reinforce that we need to start thinking about and promoting healthy eating from the womb and onwards.. Mothers who are more fit will have babies who are more fit and as the child progresses these healthy approaches should become ingrained from the very start and will hopefully follow them throughout their lives and into future generations.
N Engl J Med 2014 Jan 30; 370:401
Overweight and Obesity at Age 5 Years Increases Risk for Obesity at Age 14
Overweight 5-year-olds were four times more likely to be obese at age 14 years than their normal-weight counterparts.
Although childhood obesity is a major health problem, relatively little is known about its incidence. Investigators examined weight and body-mass index (BMI) in 7738 kindergarten children followed for 9 years in the Early Childhood Longitudinal Study (1998–2007).
At a mean age of 5.6 years, 15% of children were overweight (BMI >85th percentile), and 12% were obese (>95th percentile). The prevalence of obesity reached 21% by eighth grade (mean age, 14 years); prevalence had increased by 65% in non-Hispanic white children, 50% in Hispanic children, and 120% in non-Hispanic black children. At all ages, children in the next-to-poorest socioeconomic quintile and children with the highest birth weight (>4000 g) had the highest prevalence of obesity. Between ages 5 and 14 years, 12% of children became obese. At age 14 years, four times more overweight kindergartners were obese than normal-weight kindergarteners (32% vs. 8%). The authors calculated that 72% of kindergarteners at the 99th percentile would still be obese by eighth grade.
Comment: Early overweight and obesity in kindergarten are risk factors for obesity in eighth grade, especially among high-birth-weight, wealthy, and minority children. These data should motivate us to develop strategies to prevent early obesity and to limit further weight gain in high-risk groups.
Citation(s): Cunningham SA et al. Incidence of childhood obesity in the United States. N Engl J Med 2014 Jan 30; 370:401.
(http://dx.doi.org/10.1056/NEJMoa1309753)
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MM: There are numerous reasons that people will follow a plant based diet however those who have extreme food and gut sensitivities now have evidence of how they are benefitting from that diet. It is not necessary for everyone to eliminate animal based products but there may be many Nature 2014 Jan 23; 505:559
Diet and the Microbiome
The human gut microbiome can be altered quickly by dietary modification.
Recent work has shown that antibiotics can induce sustained changes in the gut microbiome and that such alterations increase the risks for colonization with antibiotic-resistant pathogens (NEJM JW Infect Dis Jun 25 2013) and for Clostridium difficile disease. The ability to reliably restore a normal gut microbiome after antibiotic treatment would clearly be of great benefit.
Now, researchers (with partial support from the food industry) have examined whether dietary modifications can quickly alter the predominant human gut microbiota in a diet-specific manner. They gave 10 volunteers “plant-based” and “animal-based” diets for 5 days each, assessing each individual's gut microbiota daily using 16S ribosomal RNA sequencing on samples collected for the 4 days before, 5 days during, and 6 days after each diet.
A consistent alteration in the gut microbiota occurred 1 day after the animal-based diet reached the distal gut, with a return to each individual's baseline microbiota structure 2 days after this diet ended. Statistical analysis identified 22 clusters of bacterial species whose abundance changed with the animal-based diet and 3 clusters whose abundance changed with the plant-based diet. Microbial gene expression strongly correlated with the changes noted in the gut microbiota; the transcriptional responses to the two diets were consistent with known differences in gene abundance between herbivorous and carnivorous mammals. The animal-based diet also appeared to introduce foreign microorganisms associated with cheese and cured meats, with an increase seen in the prevalence of bacteria and fungi characteristic of these foods. Finally, the animal-based diet also altered the composition of fecal bile salts.
Comment: This work has extensive implications for our understanding of nutrition, normal gut physiology, and the pathogenesis of multiple conditions, including inflammatory bowel disease. It also gives hope that a rational approach can now be used to develop effective probiotics that could correct the deleterious effects of antibiotic therapy on the human microbiome.
Citation(s): David LA et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 2014 Jan 23; 505:559.
(http://dx.doi.org/10.1038/nature12820)
http://www.ncbi.nlm.nih.gov/pubmed/24336217?access_num=24336217&link_
type=MED&dopt=Abstract
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MM: Parents of autistic children have long noted that dietary changes, digestive enzymes and probiotics have seemed to make variable differences in their children's behavior. This mouse study is additional evidence that changing the intestinal environment of these children should be beneficial.
Cell 2013 Dec 19; 155:1451
More Evidence Links Gut Microbiome to Autism
In a mouse model, specific bacterial metabolites are linked to the behavioral syndrome.
The microbiome of the gut has been linked to several important diseases (NEJM JW Gen Med Dec 31 2013), including autism. A new study adds provocative evidence in favor of this hypothesis.
A CalTech team studied a mouse model of autism — affected animals display behaviors similar to those of autistic humans. These mice have a characteristic unusual microbiome and a compromised gut mucosal barrier, which leads to absorption and high blood levels of several gut bacterial metabolites. One of these metabolites is related chemically to a metabolite that has been reported to be elevated in urine of autistic children (Biomarkers 2011; 16:252). Parenteral treatment of normal mice with another of these metabolites produced “autistic” behavior. Treating the autistic-model mice with probiotic Bacteroides fragilis reversed the abnormal microbiome, the high blood levels of the unique metabolites, and the behavioral abnormalities.
Comment: If this mouse model of autism truly reflects pathology similar to autism in humans, these researchers might have identified yet another major human illness that is linked to the gut microbiome. Moreover, the identification of two specific metabolites that induce autistic behavior could provide molecular targets for therapy. Finally — although it seems too good to be true — the suggestion that probiotic therapy might cure autism surely would be a remarkable event if it proves to be valid.
Citation(s): Hsiao EY et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 2013 Dec 19; 155:1451.
(http://dx.doi.org/10.1016/j.cell.2013.11.024)
http://www.ncbi.nlm.nih.gov/pubmed/24315484?access_num=24315484&link_
type=MED&dopt=Abstract
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New Autism Guidelines Released
By Kelly Young
The American Academy of Child and Adolescent Psychiatry has updated its guidelines on diagnosing and treating autism spectrum disorder in the pediatric population.
The guidelines, published in the Journal of the American Academy of Child & Adolescent Psychiatry, recommend the following:
- Questions about autism symptoms should be routinely included in developmental assessments of young children and psychiatric assessments of all children.
- In children who screen positive for symptoms, the clinician should conduct a thorough diagnostic evaluation.
- A multidisciplinary assessment of children with autism spectrum disorder should include a physical exam, hearing screening, genetic testing, a Wood's lamp exam, communication assessment, and psychological assessment.
- Clinicians should refer families to appropriate structured educational and behavioral interventions.
- Drugs may be offered to alleviate specific symptoms or comorbidities.
- Clinicians should help families with long-term planning.
- Clinicians should ask about the patient's use of complementary and alternative medicines and explain their potential risks and benefits.
http://www.jaacap.com/article/S0890-8567(13)00819-8/fulltext
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One-Year Update on H7N9 Flu in China Finds No Definite
Human-to-Human Spread
By Joe Elia
In the year since avian influenza A(H7N9) appeared in China, there have been no definite cases of human-to-human transmission, although it cannot be ruled out, according to a New England Journal of Medicine study.
As of Dec. 1, 2013, 139 cases had been confirmed, according to the China CDC. Most occurred among city dwellers and were associated with exposure to live chickens. Almost all patients were hospitalized, and the case fatality rate was 34%.
Over 2500 close contacts (excluding four family clusters) all tested negative for the virus. Investigation of the family clusters could not rule out person-to-person spread.
In an editorial postscript to the paper, NEJM's editors note that 65 more cases have been identified "in this ongoing outbreak" since Dec. 1.
http://www.nejm.org/doi/full/10.1056/NEJMoa1304617
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MM: If this news hits the lay press then it becomes an important piece of information that these domesticated birds are used in various Chinese religious ceremonies where they are held next to the face, kissed and released. This is a unique set of circumstances that could impact the relevancy of this study in western nations.
Emerg Infect Dis 2014 Feb
Songbirds and Parakeets: Possible Sources of Influenza A (H7N9) Virus Transmission
Influenza A (H7N9) viruses from humans can replicate in songbirds and parakeets, be shed into the environment, and infect other birds.
Avian-origin influenza A (H7N9) virus continues to cause sporadic human infections in China; older men have experienced disproportionate rates of illness and death. To assess whether wild and domesticated small birds can be infected with and transmit this pathogen, researchers inoculated finches, sparrows, and parakeets with fluid containing H7N9 virus originating from a patient in China. A sample of birds tested preinoculation were influenza antibody negative.
All inoculated birds shed virus via the oropharynx. Most showed no clinical signs of disease, although two died; all surviving birds cleared the virus by day 8 postinoculation. Virus was detected on multiple days in the communal water trough shared by the birds. Among inoculated birds, all society finches and sparrows, 75% of zebra finches, and 80% of parakeets seroconverted. Among birds that had direct contact with the inoculated birds, a smaller proportion seroconverted, and some shed virus.
Comment: This study confirms that songbirds and parakeets are susceptible to influenza H7N9, contaminate water, and can transmit the virus to uninfected birds. The authors speculate that these birds could transmit virus to domesticated poultry or to other wild birds if they share common water sources. The authors comment that keeping pet birds in China is associated with luck and is common among older men, who often carry caged birds with them on strolls. They also describe religious ceremonies that involve purchase of a songbird that is held to the face, kissed, and released. They conclude that such birds may be intermediate hosts and sources of virus for wild birds, domestic poultry, and humans. Future studies should focus on the role of songbirds and parakeets in the ecology, maintenance, and transmission of H7N9 virus.
Citation(s): Jones JC et al. Possible role of songbirds and parakeets in transmission of influenza A(H7N9) virus to humans. Emerg Infect Dis 2014 Feb; [e-pub ahead of print].
(http://dx.doi.org/10.3201/eid2003.131271)
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Nat Neurosci 2014 Jan; 17:89
A Two-Way Interaction Between Nature and Nurture
Findings of intergenerational epigenetics in mammals
In an animal study, researchers examined epigenetic transmission of learned behavior across three generations.
The investigators conditioned 2-month-old male mice (F0 generation) to develop an exaggerated startle response to a specific odor (acetophenone) paired with a foot shock. Mating with nonexposed females produced the F1 generation, which exhibited the same enhanced startle to the odor acetophenone (and not to another nonconditioned control odor [propanol]), plus enhanced sensitivity to acetophenone, even though F1 mice had never been exposed to it. The same phenomena occurred in offspring of mothers conditioned to acetophenone before conception. Nonexposed F1 offspring of conditioned parents had more olfactory receptors for acetophenone than offspring of nonconditioned parents. Similar neuroanatomy was found in F1 mice produced through in vitro fertilization. F0 and F1 sperm contained markers of hypomethylation of the gene for the olfactory receptor.
The same behavioral and neuroanatomical changes were found in F2 offspring of conditioned F1 animals, but not in F2 offspring of nonconditioned mice fostered from birth by conditioned mothers. Generalized sensitivity to odor or reactivity to stress did not explain these results.
Comment: According to classical evolutionary theory, the environment selects random mutations that convey better adaptation, and we accumulate generations of genetic influences that may or may not be appropriate to a new environment. An editorialist points out that circulating substances produced by the central nervous system during conditioning alter the methylation and structure of genes — and thus their expression — in sperm or eggs. Therefore, changes in gene expression (i.e., epigenetics) produced in one generation can be passed to subsequent generations, for better or worse. If this phenomenon occurs in people, treatments that alter epigenetic effects of adverse experience may eventually prove useful to the children of ill parents.
Citation(s): Dias BG and Ressler KJ.Parental olfactory experience influences behavior and neural structure in subsequent generations. Nat Neurosci 2014 Jan; 17:89.
(http://dx.doi.org/10.1038/nn.3594)
http://www.ncbi.nlm.nih.gov/pubmed/24292232?access_num=24292232&link_
type=MED&dopt=Abstract
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ACIP Releases 2014 Adult Immunization Schedule
By Kelly Young
The CDC's Advisory Committee on Immunization Practices (ACIP) has released its 2014 immunization schedule for adults.
Among the changes for this year:
- Haemophilus influenzae type B (Hib) vaccine should no longer be considered for unvaccinated adults with HIV because of their low risk for Hib infection.
- The inactivated influenza vaccine can be used in patients with hives-only allergy to eggs, but only with additional safety precautions. The recombinant influenza vaccine, which does not contain egg protein, can be safely used in patients with egg allergy of any severity.
- Patients aged 11 years and older who have not received tetanus, diphtheria, and acellular pertussis (Tdap) vaccine should receive a dose of Tdap, followed by a tetanus and diphtheria toxoids (Td) booster every 10 years thereafter.
http://annals.org/article.aspx?articleid=1819123
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