• Does Vitamin D in Pregnancy Affect Maternal and Neonatal Outcomes?
• High-Potency Statins Associated with Acute Kidney Injury
• New York Times Magazine Looks at Breast-Cancer 'Overawareness'
• 3D Breast Scanning Improves Detection, Lowers False-Positives, Study Finds
• Pediatricians Urged to Talk to Kids About the 'Cinnamon Challenge'
• Maternal Valproate Use During Pregnancy Linked to Autism in Children
• The Best First-Line Treatment of ADHD in Very Young Children
• NIH Trial of Chelation Therapy Yields Surprising Results
• Loperamide Improves Results of Evening-Before Bowel Preparation
• Upper vs. Lower GI Delivery of Fecal Transplant for C. difficile Infection
• A New Approach to Clostridium difficile
• Intravaginal Washing and Insertion of Commercial Products Are Common —
Should They Be?
MM: This data clearly indicates that Vitamin D3 has benefits in pregnancy other than offspring bone density.
BMJ 2013 Mar 26; 346:f1169
Does Vitamin D in Pregnancy Affect Maternal and Neonatal Outcomes?
Vitamin D insufficiency during pregnancy was associated with maternal and neonatal morbidities, but did not affect bone density in children.
Although observational data suggest associations between vitamin D deficiency during pregnancy and adverse outcomes, both for women and their offspring, the need for vitamin D during pregnancy remains controversial. Canadian investigators conducted a meta-analysis of 31 studies assessing the effects of maternal serum vitamin D on maternal and neonatal outcomes. Another study concerned the effects of maternal vitamin D on bone density in offspring.
The meta-analysis showed that pregnant women with vitamin D insufficiency (<75 nmol/L = 30ng/ml) were at significantly elevated risk for preeclampsia and gestational diabetes. Analysis limited to studies that reported birth variables showed a significant association between maternal vitamin D insufficiency (defined in these studies as <37.5 nmol/L=15ng/ml) and small-for-gestational-age infants. Low birth weight, but not birth length or head circumference, was also associated with low maternal vitamin D. Findings in the second study (a prospective, population-based study of 3960 mother-offspring pairs in southwest England) showed no association between the mothers' vitamin D levels during any trimester and bone mineral density in their children (mean age, 10 years).
Comment: Results of the meta-analysis do not imply causality or define the appropriate level of vitamin D during pregnancy. Inconsistent reporting of confounders undermined the overall conclusions, and because many of the studies were case-controlled, effect size could have been overestimated. Future research should account for factors such as nutrition, lifestyle, skin pigmentation, and sun exposure, as well as addressing any dose-response relations between low vitamin D and clinical outcomes. Nonwhite populations and those in geographic areas with minimal sun exposure or with excessive pollution should also be further studied.
— Diane J. Angelini, EdD, CNM, FACNM, FAAN, NEA-BC Published in Journal Watch Women's Health April 25, 2013
Citation(s): Aghajafari F et al. Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: Systematic review and meta-analysis of observational studies. BMJ 2013 Mar 26; 346:f1169.
(http://dx.doi.org/10.1136/bmj.f1169)
http://www.ncbi.nlm.nih.gov/pubmed/23533188?dopt=Abstract
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BMJ 2013 Mar 19; 346:f880
High-Potency Statins Associated with Acute Kidney Injury
Risk is greatest during the first 4 months of treatment.
Several reports have suggested that statins occasionally affect kidney function, but this association requires confirmation. In this retrospective analysis, investigators used administrative databases in Canada, the U.K., and the U.S. to assess the association between new statin use and acute kidney injury (AKI) in 2 million people between 1997 and 2008. They compared high-potency statins (
10-mg rosuvastatin, 
20-mg atorvastatin, and 
40-mg simvastatin) with low-potency statins to eliminate confounding by indication (i.e., patients to whom statins are prescribed are more likely to have multiple comorbidities), and they used propensity scores to adjust further for differences between high- and low-potency users. Overall, 33% received high-potency statins.
During the first 120 days of treatment, 4700 patients without chronic kidney disease (CKD) and 1900 patients with CKD were hospitalized for AKI. Among patients without CKD, those started on high-potency statins were 34% more likely to be hospitalized within 120 days than those who began treatment with low-potency statins. Between 120 days and 2 years, the increased risk was smaller (10%–15%) but still significant. Among patients with CKD, high-potency statin use was associated with a nonsignificant 10% higher risk for AKI hospitalization.
Comment: In this study, new high-potency statin use was associated with elevated risk for hospitalization for AKI. If the association is valid, potential mechanisms mentioned by the authors include rhabdomyolysis, suppression of coenzyme Q10 production, and pleiotropic effects of statins. The authors acknowledge that absolute risk is small: Roughly 1700 patients without CKD would have to be treated for 120 days to cause one additional hospitalization for AKI. Nonetheless, clinicians should prescribe the lowest effective statin dose of statins to avoid this and other possible complications.
— Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine April 11, 2013
Citation(s):Dormuth CR et al. Use of high potency statins and rates of admission for acute kidney injury: Multicenter, retrospective observational analysis of administrative databases. BMJ 2013 Mar 19; 346:f880.
(http://dx.doi.org/10.1136/bmj.f880)
http://www.ncbi.nlm.nih.gov/pubmed/23511950?dopt=Abstract
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New York Times Magazine Looks at Breast-Cancer 'Overawareness'
By Kelly Young
The New York Times Magazine's cover story this week, "Our Feel-Good War on Breast Cancer," examines problems related to the nation's focus on early detection.
The story says mammograms do not easily detect the more lethal forms of the disease when they are still treatable; they do find cancers that might not spread but are treated anyway.
One researcher says that compared with Europe, the U.S. has a "mastectomy craze;" women who might not need a mastectomy medically might opt for one to regain a sense of self control. The researcher says, "There is so much 'awareness' about breast cancer in the U.S. I've called it breast-cancer overawareness. It's everywhere. There are pink garbage trucks. Women are petrified."
The author, who's had breast cancer herself, concludes: "All that well-meaning awareness has ultimately made women less conscious of the facts: obscuring the limits of screening, conflating risk with disease, compromising our decisions about health care, celebrating 'cancer survivors' who may have never required treating."
http://www.nytimes.com/2013/04/28/magazine/our-feel-good-war-on-breast-cancer.html?_r=0
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3D Breast Scanning Improves Detection, Lowers False-Positives, Study Finds
By Joe Elia
In a direct comparison with conventional two-dimensional screening mammography, using a series of 2D images to construct a three-dimensional (3D) breast image finds more cancers, yet lowers the false-positive rate, according to a Lancet Oncology study.
Researchers, partially sponsored by the equipment manufacturer, did both 2D and 3D screening on some 7300 women. The resulting scans were compared separately for cancer detection and the proportion of false-positive recalls.
Of the 59 cancers detected, 39 were found on both 2D and 3D screening; 20 were found only on 3D screening, and none only with 2D screening. The detection rate was 5.3 cancers per 1000 screens with 2D, and 8.1 with 3D screening. Some 400 screens (5.5%) resulted in false-positive recalls, with significantly less attributable to 3D screening. The authors estimate the rate of false-positive recalls would be 20% lower with 3D screening.
The authors conclude their results "show the urgent need" for randomized trials comparing the two techniques.
http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70134-7/abstract
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Pediatricians Urged to Talk to Kids About the 'Cinnamon Challenge'
By Amy Orciari Herman
"Pediatricians should be encouraged to discuss with children the Cinnamon Challenge and its possible harmful effects, especially with children having cinnamon hypersensitivity, asthma, pulmonary cystic fibrosis, or chronic lung disease," according to a perspective published in Pediatrics.
People attempting the Cinnamon Challenge try to swallow a tablespoon of cinnamon within 60 seconds, without drinking anything; they frequently videotape the results, which typically include coughing and gagging, and then post them online. As of August 2012, there were over 50,000 such videos posted on YouTube, the authors report.
In addition to coughing, burning of the mouth, and vomiting, more serious events may occur — for example, pulmonary inflammation, aspiration pneumonia, and lung collapse requiring ventilator support.
In the first half of 2012, some 30 people required medical attention following the Cinnamon Challenge.
http://pediatrics.aappublications.org/content/early/2013/04/16/peds.2012-3418.full.pdf+html
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Maternal Valproate Use During Pregnancy Linked to Autism in Children
By Kelly Young
Children whose mothers use the antiepileptic valproate during pregnancy face an increased risk for autism, according to a JAMA study.
Using Danish registries, researchers identified roughly 500 children whose mothers filled prescriptions for valproate while pregnant and 650,000 who were not exposed to the drug. Over 14 years' follow-up, some 5400 children were diagnosed with autism spectrum disorders, including 2100 with autism.
Children exposed to valproate prenatally had nearly three times the risk for autism spectrum disorders and five times the risk for autism, compared with unexposed children. Risks were increased even when parental psychiatric disease and epilepsy were taken into account. In addition, risks were elevated among exposed children compared with children whose mothers stopped taking valproate at least 30 days before conception.
Editorialists conclude: "Given the accumulating evidence linking fetal valproate exposure to congenital malformations, cognitive impairments, and autism, the use of valproate in women of childbearing potential should be minimized. Alternative medications should be sought."
http://jama.jamanetwork.com/article.aspx?articleid=1681408
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Pediatrics 2013 Apr 1
The Best First-Line Treatment of ADHD in Very Young Children
Preschoolers with attention-deficit/hyperactivity disorder or disruptive behaviors seem to do well with parent behavior training.
Behavior problems in preschoolers are increasingly acknowledged, especially in structured day care and preschools where nonprimary caretakers notice the aberrant behaviors. To assess the best treatment approaches for children under 6 years old with attention-deficit/hyperactivity disorder (ADHD) or disruptive behaviors that predict later ADHD, these authors reviewed interventional studies. To analyze studies with the greatest methodological strength, the authors identified only eight sufficiently strong studies on parent behavior training (PBT) and one on methylphenidate, and no multicomponent, nonpharmacological studies.
Significant improvement in child behavior with PBT, which does not use teachers' ratings or child observations, was consistently strong, and benefits persisted over 6-month follow-up.
The methylphenidate study — the National Institute of Mental Health's multisite Preschool ADHD Treatment Study — included only participants who had failed PBT. Methylphenidate worked well, but only in children with no or only one comorbidity; improvement was greater on clinician ratings than on those by parents or teachers. Preschoolers on methylphenidate had higher rates of adverse effects than older children, including low mood, irritability, somatic complaints, and insomnia.
Comment: Even though parent behavior training is effective, it requires trained personnel. But it is safe and relatively easy to administer and thus is a useful first-line approach. Methylphenidate is less effective and has more adverse effects in preschoolers than in school-age children. Still, it is useful in uncomplicated ADHD after PBT has failed. Whether early treatment for ADHD with methylphenidate might alter abnormal pathways in the central nervous system, as shown in school-age children (JW Psychiatry Mar 25 2013), is a compelling research question. A corollary question: Does PBT alter developmental trajectories in the CNS?
— Barbara Geller, MD Published in Journal Watch Psychiatry April 22, 2013
Citation(s): Charach A et al. Interventions for preschool children at high risk for ADHD: A comparative effectiveness review. Pediatrics 2013 Apr 1; [e-pub ahead of print].
(http://dx.doi.org/10.1542/peds.2012-0974)
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JAMA 2013 Mar 27; 309:1241
NIH Trial of Chelation Therapy Yields Surprising Results
Compared with placebo, a much-maligned alternative treatment demonstrates a modest benefit, prompting an editorialist to cry foul.
Chelation therapy for coronary artery disease consists of a series of infusions containing ethylenediaminetetraacetic acid (EDTA), which facilitates urinary excretion of divalent and trivalent cations. Although the evidence supporting this therapy is weak, and it is far out of the cardiology mainstream, a national survey indicated that in 2007 more than 100,000 adults received chelation therapy. Therefore, the NIH sponsored the double-blind, placebo-controlled, randomized Trial to Assess Chelation Therapy to determine if a chelation regimen reduces cardiovascular events. Patients with a history of myocardial infarction (MI) were assigned to receive an infusion of EDTA, ascorbate, B vitamins, electrolytes, procaine, and heparin (n=839) or a placebo solution (n=869). The infusion was administered weekly for 30 weeks, and then 10 additional infusions were administered 2 to 8 weeks apart.
At a median follow-up of 55 months, the Kaplan-Meier 5-year estimates for the primary endpoint (total mortality, recurrent MI, stroke, coronary revascularization, or hospitalization for angina) were 32.8% for chelation therapy and 38.5% for placebo (hazard ratio, 0.82; 95% confidence interval, 0.69–0.99; P=0.035). Point estimates for the individual endpoint components, although nonsignificant, trended toward benefit. The benefit was significantly greater in patients with anterior MI and those with diabetes than in patients without these conditions.
Comment: This trial is very controversial. Citing numerous study limitations, an editorialist quite strongly decried the trial and rejected its findings. However, the trial is being conducted by outstanding investigators, and I find it hard to dismiss the results. They merit consideration. But, given the absence of a presumed mechanism of this treatment and my low pretrial expectation of the intervention's effectiveness, I agree with the authors that the findings warrant further investigation but are not strong enough to suggest that we should add this treatment to our current arsenal.
— Harlan M. Krumholz, MD, SM Published in Journal Watch Cardiology April 24, 2013
Citation(s): Lamas GA et al. Effect of disodium EDTA chelation regimen on cardiovascular events in patients with previous myocardial infarction: The TACT randomized trial. JAMA 2013 Mar 27; 309:1241.
(http://dx.doi.org/10.1001/jama.2013.2107)
http://www.ncbi.nlm.nih.gov/pubmed/23532240?dopt=Abstract
Bauchner H et al. Evaluation of the Trial to Assess Chelation Therapy (TACT): The scientific process, peer review, and editorial scrutiny. JAMA 2013 Mar 27; 309:1291.
(http://dx.doi.org/10.1001/jama.2013.2761)
Nissen SE. Concerns about reliability in the Trial to Assess Chelation Therapy (TACT). JAMA 2013 Mar 27; 309:1293.
(http://dx.doi.org/10.1001/jama.2013.2778)
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MM: The use of an anti-diarrheal prior to a bowel prep seems almost counter-intuitive but when you consider that it decreases migration from the small bowel into the colon it makes a lot of sense.
Dis Colon Rectum 2013 Jan; 56:120
Loperamide Improves Results of Evening-Before Bowel Preparation
Fewer patients randomized to loperamide had a dirty or bile-coated cecum than did patients randomized to placebo.
About 15 years ago, researchers demonstrated that a delay between taking bowel preparation and performance of colonoscopy worsened the quality of cecal and ascending colon preparation (Dis Colon Rectum 1998; 41:1223). Subsequently, many studies have confirmed that administration of half (i.e., split dosing) or all (i.e., same-day dosing) of the preparation on the day of colonoscopy provides superior bowel preparation, particularly in the ascending colon, compared with evening-before dosing (JW Gastroenterol Sep 28 2012). Split or same-day dosing has been endorsed by the American College of Gastroenterology and the U.S. Multi-Society Task Force on Colorectal Cancer as the optimal means of bowel preparation for colonoscopy.
Now, the same group that originally described the effect has assessed whether a pharmacologic intervention might improve the quality of colon preparation with use of evening-before dosing. In a preliminary study, they demonstrated that taking Imodium immediately after completing the pre-colonoscopy preparation would impede the movement of small bowel contents into the right colon. The optimal dose appeared to be 4 mg, and 2 mg was insufficient.
To investigate further, the authors randomized 200 patients to take two 2-mg loperamide tablets or two placebo tablets after consuming 4 liters of polyethylene glycol electrolyte lavage solution on the evening before colonoscopy. Tablets were taken as soon as participants stopped passing liquid stools. The cecum was then photographed and its preparation quality judged by the senior author, who was blinded to treatment status.
Loperamide successfully improved right colon preparation. Thirteen of 102 (12.7%) participants in the placebo group had a dirty or coated cecum compared with 2 of 98 (2.0%) in the loperamide group. Overall preparation was fair or poor in 18.6% of the placebo group compared with 9.2% of the loperamide group.
Comment: If this effect is confirmed, randomized, controlled trials will be needed to compare split dosing and evening-before dosing with loperamide. However, this study suggests a very simple and clever way to improve the quality of evening-before bowel preparation.
— Douglas K. Rex, MD Published in Journal Watch Gastroenterology April 26, 2013
Citation(s): Church J et al. Keeping the cecum clean: A randomized, prospective, placebo-controlled trial of loperamide as part of preparation for colonoscopy. Dis Colon Rectum 2013 Jan; 56:120.
(http://dx.doi.org/10.1097/DCR.0b013e3182707d27)
http://www.ncbi.nlm.nih.gov/pubmed/23222289?dopt=Abstract
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MM: As this transplant becomes more and more accepted in conventional medical circles it becomes more important that patients are comfortable with the process. It is my opinion that patients will find the lower delivery route more acceptable than the upper route.
Am J Gastroenterol 2013 Apr; 108:500.
Upper vs. Lower GI Delivery of Fecal Transplant for C. difficile Infection
Results suggest that lower gastrointestinal administration might resolve more infections.
Despite cure rates of >90% shown in studies of fecal microbiota transplantation for Clostridium difficile infection (JW Gastroenterol Mar 30 2012), no randomized controlled trials have yet been conducted, and published meta-analyses have methodological limitations. The current systematic review and meta-analysis assessed current evidence of efficacy for fecal microbiota transplantation in C. difficile infection.
Researchers identified 11 studies with a total of 273 patients in whom fecal microbiota transplantation was performed. Delivery methods varied: Colonoscopy was used exclusively in five studies, nasogastric or nasojejunal tube was used in three studies, and enema was used in one. Colonoscopy, gastroscopy, or gastrostomy tube was used in the other two studies.
The clinical resolution rate was 89.1% overall. In a priori subgroup analyses, the clinical resolution rate was 91.2% in patients with lower gastrointestinal delivery (colonoscopy and enema) and 80.1% in patients with upper gastrointestinal delivery (nasogastric/nasojejunal tube or gastroscopy). The difference was statistically nonsignificant. Rates did not vary by whether the donor was anonymous or patient-selected. No adverse events were reported.
Comment: These findings suggest that enema or colonoscopic administration of fecal transplantation is preferred, pending the results of randomized controlled trials.
— Douglas K. Rex, MD Published in Journal Watch Gastroenterology April 26, 2013
Citation(s): Kassam Z et al. Fecal microbiota transplantation for Clostridium difficile infection: Systematic review and meta-analysis. Am J Gastroenterol 2013 Apr; 108:500.
(http://dx.doi.org/10.1038/ajg.2013.59)
http://www.ncbi.nlm.nih.gov/pubmed/23511459?dopt=Abstract
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J Infect Dis 2013 May 15; 207:1498
A New Approach to Clostridium difficile
Mice treated with an agent that prevents sporulation were protected against infection.
The spore is Clostridium difficile's secret weapon, accounting for its tenacity as a pathogen, its longevity on inanimate surfaces, and its ability to cause multiple relapses. None of the current treatments for C. difficile–associated disease (CDAD) specifically address this aspect of infection. Now, researchers have inaugurated a paradigm shift with CamSA, a bile salt derivative that is a strong inhibitor of C. difficile spore germination.
Antibiotic-treated mice were administered CamSA in various doses before, during, or after challenges with oral C. difficile spores. Within 48 hours of receiving the spores, all untreated control mice developed signs of severe CDAD. However, mice who received CamSA were protected in a dose-dependent fashion; those who received single oral doses at the highest concentration were protected completely from infection and excreted intact C. difficile spores with very few vegetative (bacterial) forms. Mice that were challenged with C. difficile in bacterial form were not protected reliably by CamSA.
Comment: Bile salts sometimes are used in patients with C. difficile infection to bind the organism's toxin, despite worry that they might bind the treating antibiotics instead. This research opens an entirely new potential role for related compounds — still far away from use in humans, but, as an editorialist points out, a very attractive option for both prevention and treatment.
— Abigail Zuger, MD Published in Journal Watch General Medicine April 25, 2013
Citation(s): Howerton A et al. A new strategy for the prevention of Clostridium difficile infection. J Infect Dis 2013 May 15; 207:1498.
(http://dx.doi.org/10.1093/infdis/jit068)
http://www.ncbi.nlm.nih.gov/pubmed/23420906?dopt=Abstract
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Obstet Gynecol 2013 Apr; 121:773
Intravaginal Washing and Insertion of Commercial Products Are Common — Should They Be?
Petroleum jelly was associated with bacterial vaginosis.
Bacterial vaginosis (BV), a condition marked by alterations in the vaginal microbiome, is associated with adverse pregnancy outcomes and increased risk for HIV acquisition. The etiology of BV is not fully understood, but both sexual activity and intravaginal practices such as douching are thought to play roles. Investigators enrolled 141 women (median age, 32) in Los Angeles who completed surveys at entry and at 12 months about their intravaginal practices; participants were also tested for BV and sexually transmitted infections. Women were counseled about the distinction between the vagina (the region beyond the introitus) and the vulva (part of the external genitalia).
Fully 81% of women reported washing inside their vaginas or inserting products other than tampons during the past year, and 45% reported washing inside the vagina during the past month. Compared with white or Latina women, black women were twice as likely to report vaginal washing. In women who used intravaginal products, the most common were commercial sexual lubricants (70%), petroleum jelly (17%), oils (13%), and antifungal creams (20%). BV was detected in 21% of participants at enrollment, and multivariable analysis showed that women who used petroleum jelly intravaginally during the past month were 2.2 times more likely to test positive for BV than those who did not use petroleum jelly. The association between intravaginal washing and BV incidence was modest and not statistically significant.
Comment: I was surprised that four out of five study participants reported washing intravaginally or inserting products into their vaginas. Although establishing and maintaining healthy vaginal microbiota can be elusive, the bulk of data suggests that douching and inserting vaginal products shifts the balance toward bacterial vaginosis. This study's strengths include its prospective design and careful analysis of the relation between vaginal symptoms and use of intravaginal products to determine whether these products caused BV or were used in response to the condition. In providing counsel about intravaginal cleansing practices beyond a general discouraging of douching, clinicians should recommend that woman avoid intravaginal use of petroleum jelly.
— Anna Wald, MD, MPH Published in Journal Watch Women's Health April 25, 2013
Citation(s): Brown JM et al. Intravaginal practices and risk of bacterial vaginosis and candidiasis infection among a cohort of women in the United States. Obstet Gynecol 2013 Apr; 121:773.
(http://dx.doi.org/10.1097/AOG.0b013e31828786f8)
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