• Mortality Risks from Dietary Fats Detailed
• The Two Faces of Estrogen Therapy: Transdermal vs. Oral
• Some in Medicare Substituting Medical Marijuana for FDA-Approved Drugs
• Self-Administered Acupressure reduces Fatigue in Breast Cancer Survivors
• HPV-Associated Cancers Increased in 2008-2012
• Active Surveillance for Patients with Low-Risk Localized Prostate Cancer
• Oral Vancomycin Prophylaxis Effective for Prevention of Recurrent C. Diff Infection
• Use of H1- Antihistamines in Children is not Based on Good Evidence
• Can Neighborhood Greenspace Modulate Urban Youth Aggression?
• Metabolized B Vitamins may be an Effective Monotherapy for Depression
• Not Seeing the Light: An Effective Treatment for Mania?
• Obesity Patterns and Risk for Barrett Esophagus
Mortality Risks from Dietary Fats Detailed
By Amy Orciari Herman, Edited by David G. Fairchild, MD, MPH, and Lorenzo Di Francesco, MD, FACP, FHM
High intake of saturated fats and trans fats is tied to increased mortality, a JAMA Internal Medicine study finds.
Researchers examined diet and mortality among some 125,000 male and female health professionals who were free of cardiovascular disease, cancer, and diabetes at baseline. During roughly 30 years' follow-up, over 33,000 participants died. High intake of saturated fat — when replacing carbohydrates — was associated with an 8% increase in total mortality. Similarly, high trans fat intake conferred a 13% mortality increase. In contrast, high intakes of polyunsaturated fatty acids and monounsaturated fatty acids were associated with 19% and 11% reductions in mortality, respectively.
In addition, replacing 5% of calories from saturated fat with calories from polyunsaturated fatty acids and monounsaturated fatty acids was associated with mortality reductions of 27% and 13%, respectively.
The authors conclude: "Replacement of saturated fats with unsaturated fats ... should continue to be a key message in dietary recommendations. These findings also support the elimination of partially hydrogenated vegetable oils, the primary source of trans-fatty acids."
http://archinte.jamanetwork.com/article.aspx?articleid=2530902
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Menopause 2016 Jun; 23:600
The Two Faces of Estrogen Therapy: Transdermal vs. Oral
Transdermal estrogen therapy is associated with fewer VTE events than oral estrogen.
To compare the effects of transdermal and oral estrogen therapy on risk for cardiovascular events, investigators used an administrative insurance database in an industry-funded retrospective 10-year study of outcomes in 5102 women (mean age, 55) who initiated either form of hormone therapy. Exclusion criteria included prior venous thromboembolism (VTE) or coronary heart disease (CHD) or filling a prescription for any progestin, estrogen injection, gel, or spray, or a contraceptive pill during the study period or the 180 days prior to filling the initial prescription for the transdermal or oral estrogen.
Users of transdermal and oral estrogen were exposed to a mean of 471 and 524 days of hormone treatment, respectively. Among transdermal and oral estrogen users, 13 and 22 VTE events occurred, respectively (adjusted incidence rate ratio, 0.42; 95% confidence interval, 0.19–0.96) and 42 and 62 CHD or stroke events occurred (adjusted IRR, 0.85; 95% CI, 0.69–1.03).
COMMENT: This study's weaknesses include absence of some key clinical parameters in the dataset (e.g., body-mass index). However, the finding of lower VTE risk with transdermal estrogen is consistent with numerous observational studies; moreover, its biological plausibility (the transdermal path does not elevate hepatic production of clotting proteins) also supports the view that transdermal estrogen is indeed safer than the oral route with respect to VTE. As an editorialist notes, recent clinical guidelines acknowledge that VTE risk is probably lower with transdermal than with oral estrogen therapy for menopausal women. For example, the European Menopause Society (Maturitas 2011; 69:195) and the Endocrine Society (J Clin Endocrinol Metab 2015; 100:3975) both recommend the transdermal formulation for menopausal women at risk for VTE. In my practice, I routinely offer transdermal estradiol for moderate to severe vasomotor symptoms, and particularly encourage this formulation for women at elevated baseline VTE risk (including those who are obese). For women already taking oral estrogen for management of vasomotor symptoms, I explain the relative benefits of transdermal therapy and offer to transition them to this route of administration.
CITATION(S): Simon JA et al. Venous thromboembolism and cardiovascular disease complications in menopausal women using transdermal versus oral estrogen therapy. Menopause 2016 Jun; 23:600.
(http://dx.doi.org/10.1097/GME.0000000000000590).
Canonico M and Scarabin P-Y.Oral versus transdermal estrogens and venous thromboembolism in postmenopausal women: What is new since 2003? Menopause 2016 Jun; 23:587.
(http://dx.doi.org/10.1097/GME.0000000000000665)
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Some in Medicare Substituting Medical Marijuana for FDA-Approved Drugs
By Joe Elia, Edited by Susan Sadoughi, MD
Marijuana, classified as a Schedule I drug by the FDA, is being used in place of FDA-approved drugs in states that have legalized marijuana's medical use, according to a Health Affairs study.
Using Medicare Part D data, researchers examined prescribing patterns and drug-benefit costs between 2010 and 2013. Prescription-drug use in conditions thought to benefit from marijuana use — for example, anxiety, pain, and sleep disorders — dropped in states that had legalized medical marijuana, compared to states without legalization. The use of drugs in conditions not associated with a marijuana benefit, such as antibiotics and anticoagulants, did not differ between the groups of states.
The authors estimate that Medicare spending, both by the program and by its beneficiaries, fell by some $165 million in 2013 as the result of marijuana substitution. They point out that lowered costs are "not a sufficient justification" to legalize medical marijuana — a decision they call "complex and multidimensional."
http://content.healthaffairs.org/content/35/7/1230.abstract
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Self-Administered Acupressure reduces Fatigue in Breast Cancer Survivors
By Amy Orciari Herman, Edited by André Sofair, MD, MPH, and William E. Chavey, MD, MS
Breast cancer survivors with persistent fatigue could benefit from a course of acupressure, a JAMA Oncology study suggests.
Some 270 women who'd completed breast cancer treatment at least 12 months earlier and still had fatigue were randomized to perform self-administered acupressure daily or to receive usual care for 6 weeks. At baseline, women assigned to acupressure were trained briefly in either relaxing or stimulating acupressure.
At the end of the treatment period, significantly more women in the relaxing and stimulating acupressure groups achieved normal fatigue levels (66% and 61% of participants, respectively), compared with usual care (31%). The effect persisted after a 4-week washout period. Relaxing acupressure also improved sleep and quality-of-life.
The authors conclude: "Self-administered relaxing acupressure could offer an inexpensive, easy-to-learn intervention for improving fatigue, sleep, and quality of life in fatigued breast cancer survivors."
http://oncology.jamanetwork.com/article.aspx?articleid=2532352
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HPV-Associated Cancers Increased in 2008-2012
By Amy Orciari Herman, Edited by André Sofair, MD, MPH, and William E. Chavey, MD, MS
Roughly 39,000 human papillomavirus-associated cancers (those at anatomic sites associated with HPV) were diagnosed in the U.S. each year from 2008 through 2012, according to an analysis in MMWR. The rate — 11.7 per 100,000 people — represents an increase over the previous 5-year period, when the rate was 10.8 per 100,000.
CDC researchers analyzed 2008–2012 data from population-based cancer registries. The most common HPV-associated cancers were cervical and oropharyngeal. Cervical cancers were diagnosed more often among blacks and Hispanics than whites. Oropharyngeal cancers were more common among males than females, while anal and rectal cancers were more common among females.
Of the HPV-associated cancers diagnosed each year, roughly 80% were actually attributable to HPV; of these, nearly 93% were caused by HPV strains for which vaccines are available.
"Increasing vaccination coverage could decrease the cancer incidence ... in the United States," the authors urge.
https://www.cdc.gov/mmwr/volumes/65/wr/mm6526a1.htm
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J Clin Oncol 2016 Jun 20; 34:2182
Active Surveillance for Patients with Low-Risk Localized Prostate Cancer
For selected patients, this alternative to radical prostatectomy or radiation therapy is recommended.
Sponsoring Organization: American Society of Clinical Oncology (ASCO)
Target Audience: Oncologists, urologists, primary care physicians
Background: Active surveillance (AS) is used increasingly as an alternative to immediate treatment (e.g., radical prostatectomy, radiation therapy) for patients with low-risk localized prostate cancer. Recently, Cancer Care Ontario published a guideline entitled “Active Surveillance for the Management of Localized Prostate Cancer” (Can Urol Assoc J 2015; 9:171). ASCO now has formally endorsed most recommendations in that guideline.
Key Recommendations: AS, rather than immediate surgery or radiotherapy, is the recommended strategy for most patients with low-risk localized prostate cancer (Gleason score, ≤6). However, watchful waiting (i.e., simple observation without active monitoring for disease progression) should be considered for patients with limited life expectancy related to comorbidities or advanced age.
- Prostatectomy or radiation therapy is recommended for most patients with intermediate-risk cancers (Gleason score, 7). However, AS can be considered for patients with low-volume, intermediate-risk cancers (Gleason score, 3+4=7). Again, watchful waiting might be appropriate for Gleason-7 patients with limited life expectancy.
- AS should include prostate-specific antigen (PSA) testing every 3 to 6 months, annual digital rectal exam, “confirmatory” 12-core biopsy at 6 to 12 months after initial biopsy, and subsequent serial biopsies every 2 to 5 years.
- Ancillary tests (e.g., multiparametric magnetic resonance imaging, genomic testing) can be used selectively to guide management during AS, but these tests still are considered to be investigatory.
- AS patients who are reclassified to higher-risk disease based on follow-up biopsies should consider prostatectomy or radiation therapy.
COMMENT: No randomized trials designed to compare active surveillance with immediate prostatectomy or radiation therapy have been completed; thus, the quality of evidence for this guideline is considered to be poor by the Ontario group. In addition, optimal testing protocols during AS and criteria to trigger additional biopsies during AS have evolved by consensus and not by rigorous comparative study. One group uses a PSA doubling time of ≤3 years as a trigger for repeat biopsy (NEJM JW Oncol Hematol Feb 2010 and J Clin Oncol 2010; 28:126).
Most localized prostate cancers are discovered through PSA screening. Although the U.S. Preventive Services Task Force recommends against PSA screening, some patients choose to undergo screening (NEJM JW Gen Med Jul 1 2012 and Ann Intern Med 2012; 157:120). Therefore, primary care physicians should be familiar with the current practice of AS; indeed, some patients might involve their primary care physicians in AS, although urologists probably oversee most cases.
CITATION(S): Chen RC et al. Active surveillance for the management of localized prostate cancer (Cancer Care Ontario guideline): American Society of Clinical Oncology clinical practice guideline endorsement. J Clin Oncol 2016 Jun 20; 34:2182. (http://dx.doi.org/10.1200/JCO.2015.65.7759)
http://jco.ascopubs.org/content/34/18/2182?ijkey=
dec7fd5fac5d93914dd5205744d3a3dd3dcbe8b8&keytype2=tf_ipsecsha
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Clin Infect Dis 2016 Jun 17
Oral Vancomycin Prophylaxis Effective for Prevention of
Recurrent C. Diff Infection
In hospitalized patients receiving systemic antibiotics, the incidence of recurrent C. difficile infection was significantly reduced among those who received prophylaxis.
Oral vancomycin is used to treat episodes of Clostridium difficile colitis. To examine its use as a prophylactic agent, investigators retrospectively studied 203 patients with a prior history of C. difficile-associated diarrhea who were hospitalized and received systemic antibiotic therapy at a single community teaching hospital over a 4-year period.
Oral vancomycin prophylaxis had been used in 113 patients (at doses of 250 mg or 125 mg twice daily) and had not been used in 132 patients. Recurrent C. difficile infection occurred in 4% of those who received prophylaxis versus 27% of those who did not receive prophylaxis.
COMMENT: Oral vancomycin prophylaxis may be the way of the future for patients requiring antibiotic therapy and having a history of C. difficile colitis. However, the risk for promoting development of vancomycin-resistant enterococcus colonization or infection is a concern. Pending further study and cost-effectiveness analysis, oral vancomycin prophylaxis seems a good option in these patients.
CITATION(S):Van Hise NW et al. Efficacy of oral vancomycin in preventing recurrent Clostridium difficile infection in patients treated with systemic antimicrobial agents. Clin Infect Dis 2016 Jun 17; [e-pub].
(http://dx.doi.org/10.1093/cid/ciw401)
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Arch Dis Child 2016 Jun 22
Use of H1-Antihistamines in Children is not Based on Good Evidence
Only limited evidence supports use of commonly used first-generation antihistamines, which may have adverse side effects.
First-generation antihistamines are marketed for a number of allergic and nonallergic indications in children. Investigators from Belgium reviewed the literature from four major publication databases to assess evidence supporting use of three of these antihistamines — alimemazine, cyproheptadine, and dimethindene maleate — and to identify potential adverse drug reactions.
For alimemazine, licensed in some European countries for various indications in children, randomized, controlled trials examining efficacy for sleep disorders showed conflicting results. No randomized, placebo-controlled trials examined the use of alimemazine for pruritus. One randomized, controlled trial in children found benefit for reducing post-fundoplication emesis. For cyproheptadine, used to treat allergic rhinitis, cold urticaria, pruritus, migraine, and appetite stimulation, only one small randomized, controlled trial was found, which did not show benefit over comparators. For dimethindene maleate, used for pruritus treatment, only one randomized, controlled trial was identified and showed a reduction in the severity of itching. Use of these three classes of antihistamines for all indications was associated with adverse drug reactions, sedation being the most common.
COMMENT: First-generation antihistamines are often used in children, and some formulations are available over the counter without a prescription; yet, as findings of this literature review show, their use is generally not supported by clinical trial data. The authors cite a suggestion by two pediatric allergists that first-generation antihistamines be limited to severe pruritus or as adjunctive therapy with epinephrine for prophylaxis of anaphylaxis. Clearly, if being used, parents should be made aware of the lack of evidence for efficacy as well as potential adverse side effects.
CITATION(S): De Bruyne P et al. Are antihistamines effective in children? A review of the evidence. Arch Dis Child2016 Jun 22; [e-pub].
(http://dx.doi.org/10.1136/archdischild-2015-310416)
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J Am Acad Child Adolesc Psychiatry 2016 Jul; 55:591
Can Neighborhood Greenspace Modulate Urban Youth Aggression?
Living near parks and open fields significantly reduced aggressive behaviors.
Exposure to greenspace (parks, golf courses, and open fields) has been shown to improve the mental health of people living in urban environments. Can it also reduce aggression among urban-dwelling youth?
To find out, investigators conducted a prospective study involving a diverse cohort of 1287 adolescents (age range, 9–18 years) living in an urban community. A standardized parent report (the Child Behavior Checklist) was used to assess aggressive behaviors on at least two occasions. The results were correlated with a standardized index of vegetation derived from satellite imagery (the Normalized Difference Vegetation Index), a proxy for residential neighborhood greenspace.
Living within 1000 meters of greenspace was significantly associated with reduced aggressive behaviors in the short term (1–6 months) and long term (1–3 years). Specifically, the benefit of living near greenspace versus an area surrounded by housing complexes, shopping centers, or freeways was equivalent to 2.0 to 2.5 years of behavioral maturation. The associations were unaffected by age, gender, race, ethnicity, or socioeconomic status; perceived quality of the neighborhood environment; or maternal depression.
COMMENT: The principle that the environment matters is a foundation for optimal child and adolescent development. In our clinical work, we typically think about the quality of the home and school environment. These results are a reminder that the physical environment can also have a major effect on youth behavior. Although the effects of greenspace in this study were relatively small, when applied to an entire population, they could be substantial. From a public-health perspective, the authors suggest that interventions are needed to determine the efficacy of greenspace to reduce aggressive behaviors in urban environments. Pediatricians can effectively advocate for these interventions.
CITATION(S): Younan D et al. Environmental determinants of aggression in adolescents: Role of urban neighborhood greenspace. J Am Acad Child Adolesc Psychiatry 2016 Jul; 55:591. (http://dx.doi.org/10.1016/j.jaac.2016.05.002).,
Jensen PS.It takes a (green) village…. J Am Acad Child Adolesc Psychiatry 2016 Jul; 55:540. (http://dx.doi.org/10.1016/j.jaac.2016.05.004)
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J Clin Psychiatry 2016 May; 77:668
Metabolized B Vitamins may be an Effective Monotherapy for Depression
A proprietary compound shows promise, but many questions remain.
Once metabolized, B vitamins (i.e., “reduced B vitamins”) are important cofactors in neurotransmitter synthesis. Genetic polymorphisms can impair reduction of B vitamins, and reduced B vitamins (particularly methylfolate) may be effective adjunctively for treatment-resistant depression although the evidence is not strong (NEJM JW Psychiatry Jun 2016 and Am J Psychiatry 2016; 173:575). This manufacturer-sponsored, placebo-controlled study examined the 8-week efficacy of a proprietary formulation of multiple reduced B vitamins (EnLyte) as monotherapy for major depression in medication-free patients who had one of three MTHFR polymorphisms associated with impaired ability to reduce folate.
Compared with placebo, the formula was associated with significantly greater reduction in depression-rating scores beginning at week 2, with a large effect size by week 8. Remission rate was 42% with the formula; no rate with placebo was provided. By week 8, only the treated patients showed lower homocysteine levels, consistent with B-vitamin effects on homocysteine.
COMMENT; Reduced B vitamins may be a viable treatment for depression, especially in patients refusing medications. However, this study had several shortcomings: Whether depression in the participants was resistant to treatment is unknown, homocysteine reductions were not correlated with degree of response, and we don't know whether this proprietary compound (US$142/month) is uniquely required — methylfolate (US$98/month) alone may have worked in these patients. In addition, we do not know if the effect is confined to individuals with a MTHFR polymorphism (i.e., would reduced B vitamins work in individuals with adequate enzyme activity to metabolize their own B vitamins?). Nonetheless, the finding is noteworthy, especially for practicing clinicians whose patients want to try more “natural” treatments. Most insurers are unlikely to cover the treatment costs.
CITATION(S): Mech AW and Farah A.Correlation of clinical response with homocysteine reduction during therapy with reduced B vitamins in patients with MDD who are positive for MTHFR C677T or A1298C polymorphism: A randomized, double blind, placebo-controlled study. J Clin Psychiatry 2016 May; 77:668.
(http://dx.doi.org/10.4088/JCP.15m10166)
http://www.ncbi.nlm.nih.gov/pubmed/27035272?access_num=
27035272&link_type=MED&dopt=Abstract
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Bipolar Disord 2016 May; 18:221
Not Seeing the Light: An Effective Treatment for Mania?
Blue-blocking glasses seem to have an acute antimanic effect.
Seasonality and light conditions can affect bipolar-disorder episodes. Preliminary data have suggested antimanic effects of “dark therapy.” Blocking the blue-light spectrum signals the brain that there is total darkness, which orange-lensed glasses (blue blockers [BBs]) can accomplish; they also block melatonin-inhibiting effects of full-spectrum light. In a multicenter Norwegian trial, 24 hospitalized, treated patients with mania were randomized to wear BBs (https://www.lowbluelights.com/index.asp) or clear-lensed glasses from 6 p.m. to 8 a.m. for 7 consecutive days.
Healthy controls (n=35) were monitored for 7 days at baseline and wore BB glasses for 7 days. Participants removed glasses when the lights were out and were monitored with actigraphy. Clinicians rated patients' mania symptoms daily.
Pharmacologic treatment was less intense during the intervention week with BBs than with placebo. Mania scores were significantly lower after 3 days of BBs and continued to improve through 7 days, with a very large effect size. Individual symptoms improved, especially irritability and thought disorder. After the second night, average activity was lower.
Two patients using BBs experienced emerging depressive symptoms. One improved after decreasing BB duration by 2 hours; the other stopped it for one night, and mood rapidly elevated. One patient and three healthy controls reported headaches. Four healthy controls had uncomfortably low energy, and two had lowered mood.
COMMENT: In this randomized, controlled, but small study, mania symptoms improved acutely when patients wore glasses that blocked the blue-light spectrum, with a very large effect size (number needed to treat, >1.5). The authors believe that the antimanic effects were due to photo-responsive retinal ganglion cells directly influencing the limbic system, striatum, and brainstem.
This easily implemented intervention may be very effective for our patients with mania or, possibly, hypomania. Although more studies are necessary, there appears to be few reasons not to try it in the meantime.
CITATION(S): Henriksen TE et al. Blue-blocking glasses as additive treatment for mania: A randomized placebo-controlled trial. Bipolar Disord 2016 May; 18:221. (http://dx.doi.org/10.1111/bdi.12390)
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Clin Gastroenterol Hepatol 2016 Jun
Obesity Patterns and Risk for Barrett Esophagus
Abdominal obesity was positively associated with BE risk whereas gluteofemoral obesity was inversely associated but only among men.
Abdominal obesity has been independently associated with increased risks for Barrett esophagus (BE) and related esophageal adenocarcinoma (EAC), even after accounting for gastroesophageal reflux disease (GERD). Gluteofemoral obesity (increased subcutaneous fat in hip and thigh) has been associated with a protective effect against diabetes mellitus and cardiovascular disease but has not been evaluated with regard to BE risk.
In a pooled analysis of data from eight case-control studies comprising 1559 patients with BE, 2557 population-based controls, and 2064 control patients with GERD, researchers evaluated the associations between hip circumference and waist circumference and risk for BE, adjusting for other variable risks.
Waist circumference was significantly associated with BE risk in adjusted analyses using population-based controls (odds ratio per 5-cm increase, 1.18) or GERD controls (OR per 5-cm increase, 1.09). Hip circumference was significantly inversely associated with BE, but only after adjustment for waist circumference (OR per 5-cm increase, 0.88) and only in men (OR per 5-cm increase, 0.85); this association persisted even with adjustment of frequency of GERD symptoms.
COMMENT: The observation of decreased risk for BE with larger hip circumference is consistent with a proposed hypothesis in which adipose tissue in the gluteofemoral compartment serves as a “metabolic sink” that diverts the damaging effects of excess caloric intake. This would explain prior reports of a protective effect of gluteofemoral obesity against diabetes mellitus and cardiovascular disease. As the authors note, the lack of an observed protective effect in women (who have much lower BE and EAC rates) could be due to hormonal effects of estrogen, which regulates adipokine secretion from adipose. This, coupled with differential fat distribution patterns by gender, might explain men's higher risk for BE. The next steps are to evaluate whether these factors promote progression to EAC and whether related interventions could mitigate risk.
CITATION(S):Kendall BJ et al. Inverse association between gluteofemoral obesity and risk of Barrett's esophagus in a pooled analysis. Clin Gastroenterol Hepatol 2016 Jun 2; [e-pub]. (http://dx.doi.org/10.1016/j.cgh.2016.05.032)
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