• What's Behind the Link Between Early Antibiotic Exposure and Wheezing?
• Smoking Bans: You've Come a Long Way, Baby
• Effects of Smoking During Pregnancy Are Long-Lasting
• Higher-Dose statins Linked to Moderate Increase in Diabetes Risk
• Who Said Statins Work for Everything?
• Statins Linked to Reduced Physical Activity in Older Adults
• Pour It On: Extra-Virgin Olive Oil Could Reduce AF Risk
MM: I was recently at a OSHA review presentation for my staff and the presenter mentioned that germs can be our friends. She referenced a study that demonstrated that our children are the least healthy and the most hyper-sensitive to their environment than ever before in recorded history. One theory is that this is due to hyper-exposure to hand sanitizers and other antibiotics that prevent children from being exposed to allergens at an early age when their immune systems are immature and developing. This theory has merit in that every organism and biological system is typically made stronger and more resilient through challenges. If we place our kids in a plastic bubble, then we are not serving their long term health needs.
Lancet Respir Med 2014 May 15
What's Behind the Link Between Early Antibiotic Exposure and Wheezing?
The association might not be causative but rather explained by impaired host defense or genetic polymorphisms.
Early antibiotic exposure has been associated with wheezing and asthma in children, but whether the relation is causative or the result of reverse causation (asthma symptoms lead to antibiotic use) or confounding by indication (another hidden variable causes antibiotic use and is a risk for asthma) is uncertain. In a population-based birth cohort, investigators in the U.K. examined this link in 800 children born between 1995 and 2000 who were followed until age 11 years.
Most children (71%) received antibiotics during the first year of life and 51% of children had at least one physician-diagnosed wheezing episode. Children who received antibiotics during the first year had a 1.71 increased risk for wheezing or asthma. The risk was greatest during the 2 years after antibiotic administration. Early antibiotic use was not associated with risk for atopy defined by positive skin pricks, although atopic patients had a fourfold increased risk for asthma exacerbations at age 3 years. Early antibiotic exposure was associated with impaired viral host defense (measured by cytokine induction) and polymorphisms on 17q21 (a known risk factor for asthma).
Comment: The association between antibiotic use and wheezing in young children might not be causative. These researchers suggest the apparent association might reflect confounding by indication with decreased host immune defense and genetic polymorphisms.
Citation(s): Semic-Jusufagic A et al. Assessing the association of early life antibiotic prescription with asthma exacerbations, impaired antiviral immunity, and genetic variants in 17q21: A population-based birth cohort study. Lancet Respir Med 2014 May 15; [e-pub ahead of print].
(http://dx.doi.org/10.1016/S2213-2600(14)70096-7)
Crane J and Wickens K.Antibiotics and asthma: A tricky tributary of the hygiene hypothesis. Lancet Respir Med 2014 May 15; [e-pub ahead of print].
(http://dx.doi.org/10.1016/S2213-2600(14)70109-2
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MM: Second hand smoke has been recognized for several decades as a health risk or hazard. The challenge to smoke free legislation arises when the argument is made that greater restriction of people's personal freedom of choice is not the responsibility or right of government. Another argument is that the repression of smoking will have the trickle down effect of hurting he economy of those tobacco producing areas and that is unfair to the growers. In my opinion, tobacco growers are subject to the same supply and demand economics as other industries that are highly taxed and regulated by the government. In the case of tobacco though, 2nd hand smoke affects not the4 user but those around him and it deprives these people the right of choice regarding their environment. So, yes, gevernment is too much in our business but in this case, a responsibility of government is to protect those who are at risk or danger and those who are proximal to 2nd hand smoke deserve that protection.
Lancet 2014 May 3; 383:1549
Smoking Bans: You've Come a Long Way, Baby
Preterm birth rates dropped by 10% following enactment of smoke-free legislation in Europe and North America.
Despite the well-known harms of secondhand smoke, many communities have yet to enact smoke-free legislation. To assess the effects of such policies on pregnancy outcomes and risk for childhood asthma, researchers conducted a meta-analysis of five North American and six European studies involving >2.5 million pregnancies and 247,168 asthma exacerbations.
Following the introduction of smoke-free policies, reductions of 10% were promptly seen in rates of preterm birth and very-small-for-gestational-age birth. In addition, rates of pediatric asthma exacerbations fell by 10%.
Comment: Given the significant social and healthcare costs of caring for children born too soon or too small — as well as those who develop asthma — smoke-free policies could save us billions of dollars each year. As an editorialist notes, California's tobacco control program provided a 100 to 1 return on investment. Nonetheless, many states still have a long way to go toward implementing comprehensive tobacco control policies.
Citation(s): Been JV et al. Effect of smoke-free legislation on perinatal and child health: A systematic review and meta-analysis. Lancet 2014 May 3; 383:1549. (http://dx.doi.org/10.1016/S0140-6736(14)60082-9)
http://www.ncbi.nlm.nih.gov/pubmed/24680633?access_num=24680633&link_
type=MED&dopt=Abstract
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MM: Encouraging pregnant women to stop smoking during pregnancy has long been considered a good recommendation. Most of the data is associated with lower birth weights, cardiovascular risks and other complications. This data shows more long term ill effects on the offspring and should be considered as even stronger evidence of the benefits of smoking cessation during pregnancy and thereafter.
JAMA Psychiatry 2014 May 14
Effects of Smoking During Pregnancy Are Long-Lasting
Young adults who were exposed prenatally to smoking show poorer response inhibition.
Smoking during pregnancy has been linked to higher rates of externalizing disorders in offspring. These disorders, such as attention-deficit/hyperactivity disorder (ADHD) and conduct disorder are associated with decreased inhibitory control. Researchers examined the relationship of prenatal smoking to activity and structure of brain regions involved in response inhibition.
Participants were 178 young adults (73 men) who had been followed prospectively since birth, including four ADHD assessments between ages 2 and 11. In the group, 13.5% had mothers who smoked >5 cigarettes per day during pregnancy. Prenatal exposure to smoking was associated with higher rates of parental postnatal smoking and higher rates of offspring's nicotine dependence, psychosocial adversity, and lifetime ADHD symptoms.
At age 25, participants underwent functional magnetic resonance imaging during a response inhibition (“NoGo”) task. Study results were controlled for sex, psychosocial and obstetric adversity, lifetime nicotine dependence, parental postnatal smoking and prenatal stress, ADHD symptoms, and novelty seeking, which was measured at age 19. Prenatal smoking was associated with lower activity during the task in the anterior cingulate cortex, inferior frontal gyrus (IFG), and supramarginal gyrus, and with smaller volume of the right IFG.
Comment: This study did not control for parental diagnoses like ADHD or alcohol use disorder. However, the findings of lower activity in brain regions related to response inhibition in adults exposed prenatally to smoking are consistent with previous associations between prenatal smoking and externalizing disorders. This study reinforces the importance of strongly discouraging smoking in pregnant women and aggressively encouraging them to quit.
Citation(s): Holz NE et al. Effect of prenatal exposure to tobacco smoke on inhibitory control: Neuroimaging results from a 25-year prospective study. JAMA Psychiatry 2014 May 14; [e-pub ahead of print].
(http://dx.doi.org/10.1001/jamapsychiatry.2014.343)
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MM: It's certainly possible that people with higher cholesterol levels are at greater general risk for co-morbid conditions. That being said, we must not discount the potential problems associated with statins in general and must recognize that adverse effects are commonly increased in medications as the dose is increased irrespective of the medication class that they belong to.
Higher-Dose statins Linked to Moderate Increase in Diabetes Risk
By Kelly Young
Edited by Susan Sadoughi, MD, and Jaye Elizabeth Hefner, MD
Higher doses of statins are associated with greater risk for incident diabetes than lower doses, according to a BMJ study.
Using healthcare databases from Canada, the UK, and the US, researchers identified 137,000 patients who were prescribed statins after hospitalization for a major cardiovascular event. At 2 years, patients prescribed a higher-dose statin (rosuvastatin, 10 mg and up; atorvastatin, 20 mg and up; simvastatin, 40 mg and up) had a 15% higher rate of new diabetes diagnoses than lower-dose statin users. Incidence rates were highest in the first 4 months.
The authors conclude: "Clinicians should consider our study results when choosing between lower potency and higher potency statins in secondary prevention patients, perhaps bearing in mind that head-to-head randomized trials of higher potency versus lower potency statins have not shown a reduction in all-cause mortality or serious adverse events in secondary prevention patients with stable disease."
http://www.bmj.com/content/348/bmj.g3244
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MM: Once again the highly touted statins fall short of expectations and in fact fail to show benefit for a life-threatening condition. Since statins are touted to be just that, life saving, it is extremely important that this distinction be made. They confer no other benefits to Quality of Life (QOL) so there is only a single marker and this one is insufficient in its performance.
Lancet Neurol 2014 May 16
Who Said Statins Work for Everything?
A disappointing result for patients with subarachnoid hemorrhage
Delayed ischemic deficits are an important cause of morbidity and mortality for patients who survive a subarachnoid hemorrhage (SAH). Current options to limit the incidence of delayed deficits include calcium channel blockers and hypervolemic therapy. Phase II study outcomes suggested that statins may be useful in reducing the incidence of delayed ischemic deficits. Potential mechanisms include the anti-inflammatory properties of statins and upregulation of endothelial nitric oxide synthase.
In this phase III trial, researchers enrolled 803 patients who could be treated within 96 hours after SAH onset. Patients were randomly assigned to treatment with 40 mg per day of simvastatin or placebo, for 21 days. The primary endpoint was neurologic outcome at 6 months, determined by the modified Rankin scale score (favorable outcome, ≤2).The odds ratio for the primary endpoint with simvastatin versus placebo was not significantly different (0.97; 95% confidence interval, 0.75–1.25). The rate of clinical delayed ischemic deficits in both groups was 16%. The 6-month death rate was 10% in the simvastatin group versus 9% in the placebo group (a nonsignificant difference).
Comment: These findings refute the earlier, promising phase II study results. This is an illustrative case wherein testing in a larger sample size did not confirm an earlier plausible hypothesis. Some may claim the study population was “too mild,” with a lower than expected rate of delayed ischemic deficits and death. However, the lack of even a trend for benefit with statin treatment makes it clear that statins are beneficial for ischemic stroke, not for SAH.
Citation(s): Kirkpatrick PJ et al. Simvastatin in aneurysmal subarachnoid haemorrhage (STASH): A multicentre randomised phase 3 trial. Lancet Neurol 2014 May 16; [e-pub ahead of print].
(http://dx.doi.org/10.1016/S1474-4422(14)70084-5)
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MM: It's not a big surprise that as we age, we tend to be less mobile and less active. This goes along with general wear and tear on the joints, muscles and bones. It is also not a surprise that if we are hurting then we are less inclined to engage in the activities that we intellectually understand will intensify that discomfort. This isn't rocket science. Yet, a big push for the use of statins is that they may reduce inflammation. They increase myopathy or muscle pain in what seems to be a majority of patients and these pains tend to increase with increasing statin doses and duration yet they might decrease joint pain in some patients. It's sort of a balancing act.
Statins Linked to Reduced Physical Activity in Older Adults
By Kelly Young
Edited by David G. Fairchild, MD, MPH, and André Sofair, MD, MPH
Statin use in older adults is associated with a slight reduction in physical activity, according to an observational study in JAMA Internal Medicine.
Researchers assessed physical activity in some 4000 men aged 65 and older. Based on survey data, overall physical activity decreased over the 7-year-study, regardless of the patient's statin use. New statin users experienced the largest drop in physical activity, compared with nonusers and prevalent users. After adjustment for other factors, statin users had 9.6% fewer minutes (or, 5.4 fewer minutes) of daily moderate physical activity than nonusers, based on accelerometry.
The authors say that possible reasons for the lower physical activity may be "general muscle pain caused by statins (a well-known adverse effect), exercise-endured myopathy, or muscular fatigue."
http://archinte.jamanetwork.com/article.aspx?articleid=1878470
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MM: So, in addition to the good flavor bestowed on many foods by using EVOO, we see that it also protects the pacemaker aspect of our heartbeats and may prevent atrial fibrillation.(AF). This is reassuring hat a simple lifestyle change that is not at all painful and in fact enjoyable is also potentially beneficial..
Circulation 2014 Apr 30
Pour It On: Extra-Virgin Olive Oil Could Reduce AF Risk
Post-hoc PREDIMED study findings suggest antiarrhythmic as well as anti-ischemic benefits of a Mediterranean diet with an extra helping of EVOO.
Some studies suggest that improved dietary habits or nutritional supplements have a role in reducing the incidence of atrial fibrillation (AF). To find out more, investigators conducted a secondary analysis of data from the PREDIMED trial (NEJM JW Gen Med Mar 12 2013), in which individuals without prevalent cardiovascular disease at baseline were randomly assigned to one of three diets: Mediterranean diet supplemented with extra-virgin olive oil (EVOO), Mediterranean diet supplemented with mixed nuts, or advice to follow a low-fat diet (control group). Incident AF, although not a primary endpoint, was adjudicated during follow-up by an events committee blinded to the intervention group. The present study involved 6705 participants without AF at randomization.
During a median follow-up of 4.7 years, 72 patients in the EVOO group developed AF, compared with 92 in the mixed-nuts group and 89 in the control group. Relative to the control diet, the Mediterranean diet with EVOO significantly reduced the risk for AF (hazard ratio, 0.62; 95% confidence interval, 0.45–0.85). The Mediterranean diet with nuts had no significant effect on AF risk (HR, 0.89; 95% CI, 0.65–1.20).
Comment: Adhering to a traditional Mediterranean diet is known to lower risk for several cardiovascular outcomes. This post-hoc analysis from the PREDIMED trial suggests that supplementing a Mediterranean dietary pattern with extra-virgin olive oil also reduces the risk for atrial fibrillation. We already have plenty of evidence to recommend a heart-healthy diet; adding another potential benefit may help to convince our patients. Note to readers: At the time NEJM Journal Watch reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.
Citation(s): Martínez-González MÁ et al. Extra-virgin olive oil consumption reduces risk of atrial fibrillation: The PREDIMED trial. Circulation 2014 Apr 30; [e-pub ahead of print]. (http://dx.doi.org/10.1161/CIRCULATIONAHA.113.006921)
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