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Content 7

 

The Doctor and the Pharmacist

Radio Show Articles:
March 12, 2016

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Gut Dysbiosis may play a role in Nonalcoholic Fatty Liver Disease
Low Vitamin D in Pregnancy and increased MS risk in Offspring: New Study
   Supports Potential Link
Vitamin D Supplementation shows no Benefit in Knee Osteoarthritis
FDA allows Omega-3 Company to Market Product for Unapproved Use
High HDL Cholesterol not always "Good," Study Suggests
Children who are Young for their Grade more likely to be Diagnosed with ADHD
N95 Respirators might not be Better than Surgical Masks in Clinical Settings
Two Studies point to lower Food Allergy Risk when Allergenic Foods Consumed early in life
Carpal Tunnel Syndrome Guidelines Published
Relatively High Suicide Rate among People with Chronic Fatigue Syndrome
Social-Media Use and Depression: What is the Connection?

Hepatology 2016 Mar; 63:764
Gut Dysbiosis may play a role in Nonalcoholic Fatty Liver Disease
Levels of three genera of gut microbiota are associated with severity of nonalcoholic steatohepatitis and fibrosis.
Gut dysbiosis — a microbial imbalance implicated in obesity, cardiovascular disease, and metabolic syndrome — has recently been suggested in animal studies to play a role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD).
To determine whether gut dysbiosis is associated with severity of nonalcoholic steatohepatitis (NASH) and liver fibrosis, investigators studied 57 consecutive adults (60% male; median age, 60; 81% had metabolic syndrome) with biopsy-proven NAFLD at a single medical center in France. Thirty patients (53%) had no fibrosis or mild fibrosis (stage 0 or 1); 10 of these (33%) had NASH. The remaining 27 (47%) had significant fibrosis (stage ≥2); 25 of these (93%) had NASH. Stool samples were collected at the time of liver biopsy. Taxonomic composition of gut microbiota in the samples was assessed using 16S ribosomal RNA gene sequencing.
Results were as follows:

COMMENT: This study of a well-characterized population of adult NALFD patients showed that three genera of gut microbiota — BacteroidesPrevotella, and Ruminococcus — were associated with NASH and fibrosis. A potential mechanism that might explain the association is that Bacteroides-associated increases in stachyose and deoxycholic acid can promote NASH. In the future, information regarding the gut microbiome could allow clinicians to risk-stratify NAFLD patients and could lead to the development of novel prebiotic and probiotic therapies.
CITATION(S): Boursier J et al. The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota. Hepatology 2016 Mar; 63:764.
(http://dx.doi.org/10.1002/hep.28356)
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Low Vitamin D in Pregnancy and increased MS Risk in Offspring: New Study Supports Potential Link
By Amy Orciari Herman, Edited by David G. Fairchild, MD, MPH, and Jaye Elizabeth Hefner, MD
Markedly deficient vitamin D levels during pregnancy are associated with increased risk for multiple sclerosis in one's offspring, suggests a case-control study in JAMA Neurology.
Using the Finnish Maternity Cohort, researchers identified nearly 200 young adults with confirmed MS and over 300 unaffected controls. Serum samples from participants' mothers, collected during pregnancy, were assessed for 25-hydroxyvitamin D (25[OH]D).
The average maternal 25(OH)D level was considered insufficient in both groups, and was somewhat lower among case mothers than controls (13.86 vs. 15.02 ng/mL). In multivariable-adjusted analyses of a subset of participants matched for region and date of birth, "clearly deficient" maternal 25(OH)D levels (<12.02 ng/mL) were associated with a near doubling of risk for MS in offspring, compared with higher levels.
An editorialist discusses potential mechanisms, including the possibility that vitamin D deficiency during myelinogenesis could lead to "weak myelin" that is particularly susceptible to the damage seen in MS.
Dr. Robert Naismith of NEJM Journal Watch Neurology notes: "While it is too early to recommend vitamin D during pregnancy for the prevention of MS, some groups are advocating for the more routine use of vitamin D within a pregnant population for a variety of potential health benefits."
http://archneur.jamanetwork.com/article.aspx?articleid=2499458
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Vitamin D Supplementation shows no benefit in Knee Osteoarthritis
By Thomas L. Schwenk, MD    
Among patients with knee osteoarthritis and low vitamin D levels, supplementation offered no benefit over placebo in terms of pain scores or cartilage structure. The findings appear in JAMA.
Researchers in Australia conducted a trial involving over 400 vitamin D-deficient but otherwise healthy older adults (mean 25-hydroxyvitamin D levels, 18 ng/mL) with symptomatic knee osteoarthritis. Participants were randomized to receive oral vitamin D3 supplements (cholecalciferol; 50,000 IU monthly) or placebo for 24 months.
At 24 months, vitamin D levels had increased by 16 ng/mL and 3 ng/mL in the supplementation and placebo groups, respectively. However, changes from baseline in pain scores or knee architecture did not differ between groups.
Comment: These results do not support the use of vitamin D to improve pain or cartilage structure in patients with knee osteoarthritis.
http://jama.jamanetwork.com/article.aspx?articleid=2499277
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FDA allows Omega-3 Company to market Product for Unapproved Use
By Amy Orciari Herman, Edited by Susan Sadoughi, MD, and Richard Saitz, MD, MPH, FACP, FASAM
The FDA on Tuesday agreed to allow the makers of the omega-3 pill Vascepa (icosapent ethyl) to market it for an unapproved use — to lower triglycerides in patients with high levels — the New York Times reports. The drug is currently approved to lower triglycerides only in those with extremely high levels (≥500 mg/dL).
The company, Amarin, sued the FDA in 2015 for the right to market Vascepa to a larger group of patients. In August, a federal judge said the agency "could not prohibit Amarin from using truthful information to promote its drug, even for unapproved uses, because doing so would violate the company's right to free speech," the Times reports.
Dr. Michael Carome of Public Citizen told the Times: "This really sends a signal to other companies that if you want to engage in off-label promotion, you can negotiate with the FDA."
In a statement, the FDA said Tuesday's settlement "is specific to this particular case and situation, and does not signify a position on the First Amendment and commercial speech."
http://www.nytimes.com/2016/03/09/business/fda-deal-allows-amarin-to-promote-drug-for-off-label-use.html?_r=0
  
http://www.reuters.com/article/us-amarin-fda-settlement-idUSKCN0WA2PK
  
http://www.vascepa.com/vascepa-pi-ppi-(clean)-P00120G-6-15.pdf
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High HDL Cholesterol not always "Good," study suggests
By Amy Orciari Herman, Edited by André Sofair, MD, MPH, and William E. Chavey, MD, MS
High HDL cholesterol levels don't always protect against coronary heart disease. In fact, one particular genetic mutation appears to raise both HDL cholesterol and heart disease risk, according to a study in Science.
Researchers analyzed the lipid-modifying regions of the genomes in over 300 individuals with extremely high HDL levels (mean, 107 mg/dL). They identified a particular mutation in SCARB1 — a gene that encodes the major HDL receptor on cell surfaces. This mutation disrupted HDL receptor function.
Applying their findings to population-based studies, the researchers found that heterozygous carriers of the variant had not only elevated HDL levels but also significantly increased risk for coronary heart disease.
http://science.sciencemag.org/content/351/6278/1166
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Children who are Young for their Grade more kikely to be Diagnosed with ADHD
By Cara Adler, Edited by André Sofair, MD, MPH, and William E. Chavey, MD, MS
The youngest children in a school grade are more likely than the oldest to be diagnosed with attention-deficit/hyperactivity disorder and to receive treatment, according to a study from Taiwan in the Journal of Pediatrics.
Using national health insurance data from 1997 to 2011 for roughly 380,000 children, researchers compared ADHD diagnoses and medication use between children born in August (youngest in a grade) and those born in September (oldest).
In adjusted analyses, the youngest children were significantly more likely than the oldest to be diagnosed with ADHD (odds ratio, 1.65) and to receive ADHD medications (OR, 1.73). When stratified by age group, the increased risk for ADHD diagnosis was seen among preschool and school-age children, but not among adolescents. The findings were consistent in boys and girls.
Dr. Louis Bell of NEJM Journal Watch Pediatrics and Adolescent Medicine offered his opinion: "Interestingly, the impact of relative age on increasing the likelihood of an ADHD diagnosis disappeared by the teenage years. The message seems to be that neurocognitive immaturity, as demonstrated by the youngest children in a grade, does not equal ADHD, so proceed with caution when considering the diagnosis."
http://www.jpeds.com/article/S0022-3476(16)00160-8/fulltext
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N95 Respirators might not be better than Surgical Masks in Clinical Settings
By Kelly Young, Edited by David G. Fairchild, MD, MPH, and Jaye Elizabeth Hefner, MD
N95 respirators don't offer a clear advantage over surgical masks in preventing respiratory infection among healthcare workers, according to a meta-analysis in CMAJ.
Researchers analyzed the results of six studies comparing the effectiveness of N95 respirators with surgical masks in clinical settings. There were no significant differences between the two devices in rates of laboratory-confirmed respiratory infection, influenza-like illness, or workplace absenteeism. The authors note that the confidence intervals were wide for the outcomes, preventing them from drawing strong conclusions about the devices.
Separate analyses, however, did suggest that N95 respirators were associated with less filter penetration and less inward leakage under lab conditions.
The authors conclude: "Although N95 respirators appeared to have a protective advantage over surgical masks in laboratory settings, our meta-analysis showed that there were insufficient data to determine definitively whether N95 respirators are superior to surgical masks in protecting health care workers against transmissible acute respiratory infections in clinical settings."
http://www.cmaj.ca/content/early/2016/03/02/cmaj.150835.full.pdf+html
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Two Studies point to lower Food Allergy Risk when Allergenic Foods Consumed Early in Life
By Christine Judge and Kelly Young, Edited by Susan Sadoughi, MD, and André Sofair, MD, MPH
Early introduction of allergenic foods in infancy continues to show promise in reducing risk for developing food allergies, suggest two studies in the New England Journal of Medicine presented at the American Academy of Allergy, Asthma & Immunology's annual meeting.
In the first study, children with severe eczema or egg allergy who were randomized to consume peanuts before age 11 months had reduced risk for peanut allergy at age 5 years, compared with those asked to avoid peanuts. As a follow-up, roughly 550 children were asked to avoid peanuts for an additional 12 months.
The prevalence of peanut allergy at age 72 months (primary outcome) was higher in the avoidance versus consumption groups (named for primary trial assignments; 19% vs. 5%). In the consumption group, the percentage with peanut allergy was similar at the end of the two studies (3.6% and 4.8%).
Dr. David Amrol, with NEJM Journal Watch General Medicine,comments: "Although we don't know how long it takes to develop this tolerance, ... we should encourage consumption of peanut products in high-risk (and probably all) children by age 11 months and at a frequency of several times weekly for 4 years to produce long-lasting tolerance."
In the second study, U.K. researchers randomized 1300 breastfed infants to start introducing allergenic foods either at 3 or after 6 months of age.
Among the 56% of participants who adhered to their assigned regimen, prevalence of food allergy from ages 1–3 years was lower in the early-introduction than the standard-introduction group (2.4% vs. 7.3%). However, the difference wasn't significant when nonadherent patients were included. Peanut and egg allergies were also less common in adherent, early-introduction children.
Dr. Amrol offers this advice: "It is too early to say this early food introduction strategy works, and it is definitely difficult to implement.... Try to introduce allergenic foods as early as possible, but parents don't need to create feeding battles or lose sleep if their baby is not ready to consume them regularly."
http://www.nejm.org/doi/10.1056/NEJMoa1514209
  
http://www.jwatch.org/na37033/2015/02/23/early-peanut-introduction-reduces-risk-peanut-allergy?query=pfw&jwd=%24db.getCUSTOMERID%28%29&jspc=
%24db.getSPECIALTY%28%29

  
http://www.nejm.org/doi/full/10.1056/NEJMoa1514210
  
http://www.nejm.org/doi/full/10.1056/NEJMe1601412
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Carpal Tunnel Syndrome Guidelines Published
By Kelly Young
The American Academy of Orthopaedic Surgeons has issued new guidelines on managing carpal tunnel syndrome.
To diagnose carpal tunnel syndrome, the group does not recommend routinely using magnetic resonance imaging or ultrasound. The following are recommended: a thorough patient history, certain physical examination maneuvers, observation, and specific diagnostic tests, such as the hand-held nerve conduction study device. The authors emphasize that no single element should be used alone to make a diagnosis.
Thenar atrophy is associated with carpal tunnel syndrome, but the syndrome cannot be ruled out in the absence of thenar atrophy.
For treatment, the group recommends immobilization, oral or injectable steroids, and ketoprofen phonophoresis gel, and recommends against magnet therapy. It also recommends surgery to release the transverse carpal ligament to help restore hand function and ease symptoms.
file:///C:/Users/Mark/Downloads/CTS%20CPG_3.7.2016.pdf
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Lancet 2016 Feb 9
Relatively High Suicide Rate among People with Chronic Fatigue Syndrome
Depression that develops in some CFS patients is the most likely explanation for this excess risk.
Some reports have suggested that people who suffer from chronic fatigue syndrome (CFS) have higher risks for suicide and cancer-related mortality than does the general population.
Researchers identified 2147 patients with CFS in a large population registry. During a 7-year window, all-cause and cancer-associated mortality in CFS patients was not different from age- and sex-standardized mortality ratios in the overall population. However, the suicide rate was nearly sevenfold higher in people with CFS, and, not surprisingly, suicide incidence was particularly elevated in CFS patients with concomitant depression. However, the absolute annual rate of suicide for people with CFS was about 1 suicide per 1000 people — a rate lower than that reported for people with affective disorders, personality disorders, or alcohol dependence.
COMMENT: The authors acknowledge that many of their registry-identified cases of CFS did not meet the most widely used criteria for diagnosing CFS. Risk for suicide probably is higher in people with CFS than in the general population, but the absolute number of suicides in this study was small enough that the confidence intervals were wide. The depression that develops in the years after the onset of CFS in many, but by no means all, patients is the most likely explanation for excess suicide risk.
CITATION(S): Roberts E et al. Mortality of people with chronic fatigue syndrome: A retrospective cohort study in England and Wales from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Clinical Record Interactive Search (CRIS) Register. Lancet 2016 Feb 9; [e-pub].
(http://dx.doi.org/10.1016/S0140-6736(15)01223-4)
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Depress Anxiety 2016 Jan 19
Social-Media Use and Depression: What Is the Connection?
Young adults with greatest social-media use have more depressive symptoms.
Social-media use is common in young adults. Its relationship with mood symptoms is unclear, with conflicting study results. Investigators have now examined depressive symptoms in a nationally representative sample of 1787 young adults (age range, 19–32) who responded to a survey on depressive symptoms and use of a wide variety of social media.
Of the participants, 50% were female, 58% were white, and 56% were in a committed relationship; about two thirds had attended at least some college. Median time using social media was 61 minutes per day and 30 visits per week. Only 3% reported no social-media use.
On a four-item, five-point, validated scale, 26% of respondents reported depressive symptoms in the previous week at a level that has been linked to a high likelihood of clinical depression. Being female, having a lower education level, and being in the oldest age group (27–32 years) were associated with higher depression scores. In analyses adjusting for demographic variables, participants in the highest quartiles for both social-media time and visits per week had significantly greater odds for having high depression scores than participants in the lowest quartiles.
COMMENT: This large national study associated higher rates of depressive symptoms with greater use of social media. As a cross-sectional study, it cannot establish causality. In addition, social-media use varies (e.g., active vs. passive use; positive vs. negative emotional valence). Clinicians should be alert to high social-media use in depressed young adults and ascertain the type of use. From a public-health standpoint, social media can also facilitate connecting with depressed people and providing information and resources.
CITATION(S): Lin LY et al. Association between social media use and depression among U.S. young adults. Depress Anxiety 2016 Jan 19; [e-pub].
(http://dx.doi.org/10.1002/da.22466)

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