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Content 7

 

The Doctor and the Pharmacist

Radio Show Articles:
March 23, 2013

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Correcting Low Vitamin D Levels in Obese Adolescents Improves Insulin Sensitivity
Bad Breast Cancer on the Rise in Young Women
Screening First-Degree Relatives for Colorectal Cancer Is Worthwhile
High-Potency Statins Associated with Acute Kidney Injury During First 120 Days' Use
Hepatitis C Virus Seldom Is Transmitted Sexually
ACOG Weighs In on Elective C-Section, Nonmedically Indicated Early-Term Delivery
Most People with Prediabetes Are Unaware of Their Condition
Pediatrics Group Supports Gay Marriage
Thiazides Might Be Less Cardioprotective in Lean Than in Overweight Hypertensive Patients
Placebo Prescribing High Among U.K. Primary Care Docs
Autism, Still Increasing in U.S., Associated with Maternal Trauma, Grandparent Age
Only Half of Children with Milk Allergy Outgrow It by Age 5 Years
Hyperbaric Oxygen for Diabetic Foot Ulcers?

MM: After reading this study I threw my fist in the air and shouted, "Yes!". The doses of vitamin D3 used in previous studies and the blood levels achieved tended to be insufficient. As a result, study results have ended up showing no or little benefit from Vitamin D3. This study used adequate doses to get clinical results. Kudos to the researchers who had the fortitude to use their heads and not bend their knees to convention that has previously forced both treatment and clinical studies to be grievously inadequate.
  
Am J Clin Nutr 2013 Feb 13
Correcting Low Vitamin D Levels in Obese Adolescents Improves
Insulin Sensitivity

Adolescents who took 4000 IU of vitamin D3 daily had lower fasting insulin levels and insulin resistance than controls.
Obese adolescents often have insufficient vitamin D levels, and poor vitamin D status has been associated with abnormal glucose metabolism and insulin resistance. Investigators assessed the effect of correcting low vitamin D levels on inflammatory and metabolic abnormalities in 35 obese adolescents (mean age, 14 years; mean body-mass index [BMI], 39.8 kg/m2; mean serum 25-hydroxyvitamin D [25(OH)D], 19 ng/mL) who were randomized to receive vitamin D3 (4000 IU/day) or placebo for 6 months.
At 3 months, serum 25(OH)D concentrations increased significantly in the supplement group and all adolescents reached normal levels while levels in the placebo group did not change significantly. At 6 months, no differences were noted between the two groups in fasting plasma glucose, BMI, and three inflammatory markers. However, fasting insulin levels, two measures of insulin resistance, and the leptin-to-adiponectin ratio (a possible marker of insulin resistance) fell significantly more in the supplemented group than in the placebo group.
Comment: The vitamin D3 dose used in this study is higher than the recommended daily allowance of 600 IU for adolescents, but other research has shown such doses are safe for correcting deficiency (Curr Opin Pediatr 2009 Aug; 21: 465). The authors note that this is the first randomized study in obese adolescents to use a vitamin D dose high enough to increase serum 25(OH)D concentrations to levels associated with improvement in metabolic markers. They postulate that correction of vitamin D insufficiency may someday play a role in the treatment of insulin resistance that often accompanies obesity.
Alain Joffe, MD, MPH, FAAP  Published in Journal Watch Pediatrics and Adolescent Medicine
March 20, 2013
Citation(s): Belenchia AM et al. Correcting vitamin D insufficiency improves insulin sensitivity in obese adolescents: A randomized controlled trial. Am J Clin Nutr 2013 Feb 13; [e-pub ahead of print].
(http://dx.doi.org/10.3945/ajcn.112.050013)
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MM: This is disturbing news. It would lead one to believe that we are poisoning our youth. Could it be a change in our diets such as High Fructose Corn Syrup (HFCS) or our use of medical products such as vaccines or the insidious increase of bromine in our environment that is replacing iodine in many people while supplanting iodine's natural presence in the breasts?My vote is IODINE. Iodine is found largely in breast and skin tissue. When this is replaced by Bromine people tend to have metabolic, hormonal, adrenal and immune system dysfunction.
  
JAMA 2013 Feb 27; 309:800
Bad Breast Cancer on the Rise in Young Women
In women aged 25 to 39, the incidence of stage IV disease has increased, on average, 2.07% per year from 1976 to 2009; no similar trend was observed in older women.
A new report analyzing the U.S. National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database suggests that the incidence of de novo metastatic (stage IV) breast cancer in young women is increasing. To identify this trend, investigators obtained data on breast cancer incidence, incidence trends, and survival rates as a function of age and extent of disease at diagnosis from three SEER registries spanning the years 1973 to 2009, 1992 to 2009, and 2000 to 2009.
The incidence of stage IV breast cancer at diagnosis for young women (aged 25 to 39) increased from 1.53 per 100,000 (95% confidence interval, 1.01–2.21) in 1976 to 2.90 per 100,000 (95% CI, 2.31–3.59) in 2009. This difference represents an absolute increase of 1.37 per 100,000 during the 34-year interval, or an average compounded increase of 2.07% per year (95% CI, 1.57%–2.58%; P<0.001). The incidence of stage IV disease in young women increased among all races and ethnicities evaluated, especially blacks and non-Hispanic whites, in both metropolitan and nonmetropolitan areas, and increased more for those with estrogen receptor–positive versus estrogen receptor–negative subtypes. In contrast, women in this age group did not experience similar increases in localized or regional disease. Women aged 40 to 54 also experienced a significant increase in stage IV disease, but all of the increases occurred before 1990, and no other age groups experienced significant increases in local, regional, or stage IV disease during the study period.
Comment: The results of the report are alarming, but some caveats are worth considering. Young women are thought to have more aggressive disease than older women, even when all other factors are equal. Also, the threshold for ordering additional staging studies (e.g., imaging) might have been progressively lower throughout the study period, which raises the possibility of acquisition bias and resulting disease up-staging. Finally, it is worrisome that, although nonendocrine-sensitive (i.e., triple-negative) breast cancer is thought to be more aggressive and more common in younger patients, the increase in stage IV disease at diagnosis in this study seems to influenced more by increases in estrogen receptor–positive disease. Determining what factors might account for the recent increase in stage IV disease among young women will require further study.
William J. Gradishar, MD  Published in Journal Watch Oncology and Hematology March 19, 2013
Citation(s): Johnson RH et al. Incidence of breast cancer with distant involvement among women in the United States, 1976 to 2009. JAMA 2013 Feb 27; 309:800.
http://www.ncbi.nlm.nih.gov/pubmed/23443443?dopt=Abstract
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MM: We frequently hear that everyone needs to be screened for various cancers and diseases. This is simply not true. Many times the results of screenings are simply wrong. Tests are not perfect and the testers are not perfect. This study emphasizes that those who are predisposed to various cancers should be screened as they are at higher risk.Those who are at low risk should be less wary of diseases and more wary of the screenings.
  
Gastroenterology 2013 Mar; 144:544
Screening First-Degree Relatives for Colorectal Cancer Is Worthwhile
Colonoscopy revealed a higher prevalence of adenomas and advanced neoplasms in siblings of patients with colorectal cancer than in matched controls.
Current guidelines vary on appropriate screening for first-degree relatives of patients with colorectal neoplasia. For patients with one first-degree relative who received a diagnosis of colorectal cancer (CRC) before age 60, or with two first-degree relatives with CRC, colonoscopy every 5 years is consistently recommended. For patients with only one first-degree relative who received a diagnosis of CRC after age 60, some guidelines suggest beginning screening at age 40 and others at age 50, and all recommend a 10-year interval. Some guidelines recommend the same strategy for patients with a family history of adenomas. The American College of Gastroenterology recommends counting adenomas like cancers only for first-degree relatives of patients with documented advanced adenomas. To date, few controlled studies have addressed the yield of lesions as detected by colonoscopy in this at-risk population.
Now, in a prospective screening colonoscopy study in China, investigators assessed the prevalence of adenomas detected by colonoscopy in 374 siblings of patients with CRC compared with 374 age- and sex-matched controls comprising siblings of patients with normal colonoscopies and no family history of CRC. Compared with controls, siblings of patients with CRC had a higher prevalence of adenomas ≥10 mm (5.9% vs. 2.1%), colorectal adenomas (31.0% vs. 18.2%), and advanced neoplasms (adenomas ≥10 mm in diameter or with high-grade dysplasia or villous or tubulovillous features; 7.5% vs. 2.9%). Six cancers were diagnosed among siblings of patients with CRC and none among controls. The risk for advanced neoplasms in siblings was higher when the index patient with CRC was female or aged ≥60 or had distal but not proximal colorectal cancer.
Comment: This study provides strong evidence in support of more aggressive screening in first-degree relatives of patients with colorectal cancer. Similar studies are needed in siblings of patients with adenomas, classified by whether adenomas are advanced. The finding of increased risk for cancer in siblings of patients aged ≥60 is surprising given that current guidelines call for more aggressive screening in siblings of patients who receive a diagnosis of CRC at a young age.
Douglas K. Rex, MD  Published in Journal Watch Gastroenterology March 22, 2013
Citation(s): Ng SC et al. Increased risk of advanced neoplasms among asymptomatic siblings of patients with colorectal cancer. Gastroenterology 2013 Mar; 144:544.
(http://dx.doi.org/10.1053/j.gastro.2012.11.011)
http://www.ncbi.nlm.nih.gov/pubmed/23159367?dopt=Abstract
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High-Potency Statins Associated with Acute Kidney Injury During
First 120 Days' Use

By Joe Elia
Use of high-dose statins is associated with an increased risk of hospitalization for acute kidney injury, according to a BMJ study.
Researchers used administrative databases — mainly Canadian but also U.S. and U.K. cohorts — to examine hospitalization rates for acute kidney injury in nearly 2.1 million patients newly prescribed a statin. High-potency statins were defined as at least 10 mg of rosuvastatin, at least 20 mg atorvastatin, and at least 40 mg simvastatin.
Among patients without chronic kidney disease, those taking high-potency statins were 34% more likely to be hospitalized for acute kidney injury during the first 120 days of therapy than those starting low-potency regimens. Patients with preexisting kidney disease showed a smaller (roughly 10%) increase in risk with high-dose treatment.
The authors estimate that 1700 patients without preexisting kidney disease would have to receive high-potency statins for 120 days to cause an additional hospitalization.
http://www.bmj.com/content/346/bmj.f880
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Hepatology 2013 Mar; 57:881
Hepatitis C Virus Seldom Is Transmitted Sexually
This study should reassure monogamous heterosexual couples who are discordant for the virus.
Although hepatitis C virus (HCV) infection can be acquired sexually, transmission rates are so low that quantifying them precisely has been difficult. Researchers evaluated partners of 500 monogamous heterosexual HCV-positive patients to determine frequency and correlates of transmission.
Most index patients were men (61%) and white (73%), and most reported histories of drug injection (54%) or blood transfusion before 1992 (32%). None were coinfected with HIV or hepatitis B virus. Twelve partners (2%) had histories of drug injection. Median duration of sexual relationships between partners was 15 years.
Overall, 20 of 500 partners (4%) had HCV antibodies, with circulating HCV RNA in 13. Genotyping and serotyping identified strain concordance in nine couples. Among six couples with circulating virus, strains were similar enough to implicate sexual transmission in three, for an overall estimated prevalence of sexually transmitted disease between 0.6% and 1.2%.
Estimates of transmission risk ranged from 1 to 2 per 380,000 episodes of sexual contact. Some specific practices, including sex during menses, anal intercourse, and lack of condom use, seemed to be associated with excess risk but did not achieve statistical significance.
Comment: HCV is highly infectious through blood exposures and remarkably noninfectious through sexual exposures, with risk for sexual transmission well below that documented for HIV and other blood-borne viruses. Low viral titers in genital secretions might explain this disparity. Clinicians will welcome these findings to reassure serodiscordant couples that transmission to their uninfected partners is unlikely.
Abigail Zuger, MD  Published in Journal Watch General Medicine March 19, 2013
Citation(s): Terrault NA et al. Sexual transmission of hepatitis C virus among monogamous heterosexual couples: The HCV Partners Study. Hepatology 2013 Mar; 57:881.
(http://dx.doi.org/10.1002/hep.26164)
http://www.ncbi.nlm.nih.gov/pubmed/23175457?dopt=Abstract
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ACOG Weighs In on Elective C-Section, Nonmedically Indicated Early-
Term Delivery

By Amy Orciari Herman
Committees from the American College of Obstetricians and Gynecologists have issued two statements: one on nonmedically indicated, early-term deliveries, and the other on elective cesarean delivery.
The first concludes that delivery at 37 to 38 weeks' gestation, when not medically indicated, "is not appropriate." The committee points to the greater morbidity and mortality among newborns and infants born before 39 weeks, including greater incidences of respiratory distress syndrome, pneumonia, and hypoglycemia.
The second statement, while acknowledging limitations to the data comparing elective cesarean and planned vaginal delivery, concludes: "In the absence of maternal or fetal indications for cesarean delivery, a plan for vaginal delivery is safe and appropriate and should be recommended." The committee adds that if elective cesarean delivery is planned, it should not be performed before 39 weeks' gestation, it should not be driven by concerns about pain, and it is especially not recommended for women who plan to have several children.
http://www.acog.org/Resources_And_Publications/Committee_Opinions/Committee_on_
Obstetric_Practice/Nonmedically_Indicated_Early-Term_Deliveries

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Most People with Prediabetes Are Unaware of Their Condition
By Cara Adler
Only one in nine U.S. adults with prediabetes are aware they have the condition, according to an MMWR study.
In an analysis of NHANES data, researchers found that the percentage who are aware they have prediabetes increased from 7.7% in 2005 to 11.1% in 2010. Awareness was low (below 14%) regardless of healthcare access, income, education, family history, and body mass index.
The authors write: "Persons with prediabetes, including those with regular access to health care, might benefit from efforts aimed at making them aware that they are at risk for developing type 2 diabetes and that they can reduce that risk by making modest lifestyle changes. Efforts are needed to increase awareness."
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6211a4.htm
http://www.cdc.gov/diabetes/prevention/factsheet.htm
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Pediatrics Group Supports Gay Marriage
By Kelly Young
The American Academy of Pediatrics has come out in support of gay marriage, saying that research indicates "that there is no causal relationship between parents' sexual orientation and children's emotional, psychosocial, and behavioral development."
In a policy statement in Pediatrics, the academy writes: "If a child has two living and capable parents who choose to create a permanent bond by way of civil marriage, it is in the best interests of their child(ren) that legal and social institutions allow and support them to do so."
The group also endorsed adoption and foster parenting by gays and lesbians.
http://pediatrics.aappublications.org/content/early/2013/03/18/peds.2013-0376.full.pdf+html
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MM: It's good to know that not all body types respond the same to different medications. As providers we will often look at a patient and make assumptions. This is part of our training and unfortunately it becomes a bias in many cases. This study shows that more data is necessary beyond the directives/guidelines that many insurance companies force practitioners to follow that state a standard approach to hypertension treatment. It is important to individualize treatments for all patients so that no harm is done in an effort to do good.
  
Lancet 2013 Feb 16; 381:537
Thiazides Might Be Less Cardioprotective in Lean Than in Overweight Hypertensive Patients
But amlodipine was equally effective in lean and overweight patients.
In several studies of patients with hypertension, obese patients have exhibited lower rates of adverse cardiovascular (CV) events than their nonobese counterparts. Does this "obesity paradox" vary with different antihypertensive therapies? In the 3-year, industry-sponsored ACCOMPLISH trial, patients with hypertension and additional CV risk factors who were randomized to receive benazepril and amlodipine had fewer adverse CV events (CV-related deaths or nonfatal myocardial infarctions or strokes) than those who received benazepril and hydrochlorothiazide. In a new analysis, investigators examined adverse CV event rates in this trial after categorizing participants by body-mass index (BMI).
The overall incidence of adverse CV events was significantly higher in normal-weight patients than in obese patients (7% vs. 5%). Among amlodipine recipients, event rates were similar by BMI category. But among hydrochlorothiazide recipients, event rates were significantly higher in normal-weight patients than in obese or overweight patients (and higher than rates in any amlodipine-treated BMI category).
Comment: Theoretically, the "obesity paradox" might be attributable to greater vasoreactivity in normal-weight hypertensive patients than in those who are obese (who tend to have more volume overload and vasodilatation). The authors suggest that thiazide diuretics might be less cardioprotective in lean patients because of the tendency of these agents to increase vasoconstriction and that other agents might be preferable in this group. Editorialists agree, and note that metabolic side effects might make thiazides suboptimal agents in some obese patients as well. But, some trials have shown thiazide diuretics to be as effective as other antihypertensive agents, the effects seen with relatively low doses of hydrochlorothiazide might not apply to higher doses or to other thiazides, and evidence from the ACCOMPLISH trial might not be generalizable to lower-risk populations.
Bruce Soloway, MD  Published in Journal Watch General Medicine March 21, 2013
Citation(s): Weber MA et al. Effects of body size and hypertension treatments on cardiovascular event rates: Subanalysis of the ACCOMPLISH randomised controlled trial. Lancet 2013 Feb 16; 381:537.
(http://dx.doi.org/10.1016/S0140-6736(12)61343-9)
http://www.ncbi.nlm.nih.gov/pubmed/23219284?dopt=Abstract
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Placebo Prescribing High Among U.K. Primary Care Docs
By Amy Orciari Herman
Twelve percent of general practitioners in the U.K. say they've used "pure" placebos — for example, sugar pills or saline injections — at some point in their careers, according to a PLoS One study.
Some 800 U.K. primary care providers completed Web questionnaires on placebo use. Among the other findings:

The researchers say their results are consistent with findings from other countries.
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0058247
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Autism, Still Increasing in U.S., Associated with Maternal Trauma,
Grandparent Age

By Joe Elia
Autism spectrum disorder (ASD) is becoming more prevalent, according to a government survey. Meanwhile, separate studies in JAMA Psychiatry find the condition associated with grandpaternal age and a mother's own childhood experience of abuse.
In a survey of parents, the National Center for Health Statistics found that the prevalence of ASD among school-aged children rose from 1.16% in 2007 to 2.00% by 2012.
Swedish birth registers reveal that, in addition to the known added risk for ASD from increasing paternal age, the increasing age of the grandfathers (both paternal and maternal) is also associated with a heightened risk.
And finally, Nurses' Health Study data reveal that mothers who reported being abused during their childhood were more likely to report having a child with ASD. That likelihood increased with the level of abuse they reported.
http://www.cdc.gov/nchs/data/nhsr/nhsr065.pdf
http://archpsyc.jamanetwork.com/article.aspx?articleid=1666655
http://archpsyc.jamanetwork.com/article.aspx?articleid=1666654
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J Allergy Clin Immunol 2013 Mar; 131:805
Only Half of Children with Milk Allergy Outgrow It by Age 5 Years
A new online tool predicts a young child's chance of resolution.
Milk allergy affects 2% to 3% of U.S. children and is the most common childhood food allergy. Previous studies indicated that 75% of children "outgrow" this allergy, but newer studies suggest much lower rates of resolution. Researchers examined the natural history of milk allergy in 293 children from age 3 to 15 months to a median age of 63 months.
By age 5 years, milk allergy fully resolved in only 53% of patients. Another 21% could tolerate milk in baked goods. Larger skin-prick test size, higher milk-specific IgE (sIgE) level, and moderate-to-severe eczema at baseline were associated with lower likelihood of resolution.
Comment: Unfortunately, only about half the children with milk allergy become tolerant by age 5 years, but another 21% could have milk in baked items which is a favorable sign of eventual tolerance. The authors created a valuable online tool based on the three predictors to estimate the likelihood of milk allergy resolution in individual patients younger than 15 months. By entering skin-prick size, sIgE level, and severity of eczema, you can print an individualized graph to demonstrate the chances of a child outgrowing his or her milk allergy. This study does not take into account recent research suggesting that patients who can tolerate baked milk products can hasten resolution by regularly consuming baked milk products
(JW Pediatr Adolesc Med Jun 22 2011).
— David J. Amrol, MD  Dr. Amrol is an Associate Professor of Clinical Internal Medicine and Director of the Division of Allergy and Immunology at the University of South Carolina School of Medicine in Columbia.
Published in Journal Watch Pediatrics and Adolescent Medicine March 20, 2013
Citation(s): Wood RA et al. The natural history of milk allergy in an observational cohort. J Allergy Clin Immunol 2013 Mar; 131:805.
(http://dx.doi.org/10.1016/j.jaci.2012.10.060)
http://www.jacionline.org/article/S0091-6749(13)00187-5/fulltext
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Diabetes Care 2013 Feb 19
Hyperbaric Oxygen for Diabetic Foot Ulcers?
Hyperbaric oxygen therapy does not appear to improve healing or prevent amputation in diabetic patients with foot wounds.
Hyperbaric oxygen (HBO) therapy, in which patients are exposed to 100% oxygen at two to three times ambient atmospheric pressure, has been used for the management of complicated wound infections for decades. However, its efficacy in healing wounds has remained unclear. Now, investigators have used longitudinal observational data from the National Healing Corporation (NHC) — a company with comprehensive wound-care centers across the U.S. — to assess HBO's effectiveness in the treatment of diabetic foot ulcers. They employed propensity scores to adjust for the lack of randomization.
Among 11,301 patients with 32,021 diabetic foot ulcers who received care at one of 83 participating NHC centers between November 2005 and May 2011, 6259 individuals had a wound persisting for 28 days and were included in the analysis. After adjustment for the probability that a patient would receive HBO, recipients of this therapy were less likely to experience wound healing (hazard ratio, 0.68; 95% confidence interval, 0.63–0.73) and more likely to have an amputation (HR, 2.37; 95% CI, 1.84–3.04) than were nonrecipients.
Comment: These results are subject to the limitations of the retrospective study design. In addition, the propensity-score methodology might not have adequately adjusted for the likelihood that patients who were referred for hyperbaric oxygen had more-severe disease. Nonetheless, the finding of worse outcomes for patients receiving HBO therapy argues strongly for randomized, controlled trials to assess its benefit.
Richard T. Ellison III, MD  Published in Journal Watch Infectious Diseases March 20, 2013
Citation(s): Margolis DJ et al. Lack of effectiveness of hyperbaric oxygen therapy for the treatment of diabetic foot ulcer and the prevention of amputation: A cohort study. Diabetes Care 2013 Feb 19; [e-pub ahead of print].
(http://dx.doi.org/10.2337/dc12-2160)

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