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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
November 14, 2015

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Prescription Drug Use, Polypharmacy jump since 1999
Can Animals help kids grow up without Asthma?
Iron Dosing for Optimal Absorption
Mediterranean Diet might Preserve Brain Volume
MRI might detect Late-Onset Alzheimer disease decades before symptoms start
Higher Physician spending tied to Lower Risk for Malpractice Claims
Central Obesity tied to Increased CV Mortality Risk in Normal-Weight Adults
Does Total Joint Replacement improve Long-Term Cardiovascular Outcomes?
SPRINT: Intensive Blood Pressure Control tied to lower Adverse CV Events
Energy Drink Associated with Increased Blood Pressure
WHO Declares end to Ebola in Sierra Leone
Acupuncture and Alexander Technique help alleviate Chronic Neck Pain
Most Women do not gain Appropriate Weight during Pregnancy

Prescription Drug Use, Polypharmacy Jump Since 1999
By Joe Elia, Edited by David G. Fairchild, MD, MPH, and Lorenzo Di Francesco, MD, FACP, FHM
Almost 60% of U.S. adults take a prescription drug, and 15% take five or more, according to an analysis of national survey data in JAMA.
Using household interviews conducted during the National Health and Nutrition Examination Surveys, researchers found that use of at least one prescription drug over the past 30 days had increased from 51% in 1999–2000 to 59% in 2011–2012. Polypharmacy — the use of five or more prescription drugs — rose from 8% to 15% over the same period.
Drug classes with the greatest increases in use included antihypertensives, statins, and antidepressants, while antibiotic use declined. Narcotic analgesic use increased from about 4% to about 6%. In 2011–2012, the most commonly used prescription drug was simvastatin.
The authors say that age shifts don't explain the increase. They propose more likely explanations: national policy changes, including the advent of Medicare Part D, and the increase in obesity, necessitating wider use of cardiometabolic drugs.
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JAMA Pediatr 2015 Nov 2
Can Animals Help Kids Grow Up Without Asthma?
Swedish infants living with dogs or farm animals had decreased risk for asthma at ages 3 to 6 years.
The hygiene hypothesis posits that exposure to a greater variety of microorganisms during childhood may decrease the risk for chronic inflammatory diseases. However, previous studies of the associations between animal exposure and childhood asthma risk have been contradictory, with the exception of living in a farm environment, which seems protective. In a new study, researchers used Swedish registry data to assess whether exposure to dogs or farm animals in infancy was associated with childhood asthma.
In a cohort of roughly 276,000 children, 8.2% were exposed to dogs and 0.3% to farm animals (mostly cattle and sheep) during the first year of life. At age 6 years, 4.2% of the cohort had asthma. Adjusting for location, socioeconomic factors, and parental history of asthma, asthma at age 6 years was significantly inversely associated with exposure to dogs (odds ratio, 0.87) and farm animals (OR, 0.48).
In a separate cohort of roughly 377,000 children followed through the preschool years, exposure to dogs during infancy was associated with a significantly lower risk for developing asthma at age 3 to 5 years (adjusted hazard ratio, 0.90), but not at 1 or 2 years. Children exposed to farm animals during infancy had a significantly lower risk at all preschool ages (adjusted hazard ratio, 0.69). Dog exposure in the preschool cohort was associated with increased risk for pneumonia (hazard ratio, 1.13).
COMMENT: This large prospective study confirms a notable reduction in asthma risk among children who grow up in farm environments. Dogs also appear to be somewhat protective, whether or not there is a family history of asthma. These results are likely generalizable to other European and North American societies. When parents of infants ask about the pros and cons of having a dog, we can talk about a potential mild decrease in asthma risk.
CITATION(S): Fall T et al. Early exposure to dogs and farm animals and the risk of childhood asthma. JAMA Pediatr 2015 Nov 2; [e-pub]. (http://dx.doi.org/10.1001/jamapediatrics.2015.3219)
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Blood 2015 Oct 22; 126:1981
Iron Dosing for Optimal Absorption
Current schedules may need to be revised from daily to every-other-day dosing.
Ferrous sulfate is prescribed for patients with iron deficiency in doses of 60 mg of elemental iron given orally two or three times daily. The absorption of iron is decreased by hepcidin, a peptide that blocks the transport of iron from intestinal epithelial cells to the blood.
To examine the factors that affect hepcidin levels and iron absorption, investigators studied 54 nonanemic young women who received ferrous sulfate in successive daily and twice-daily dosing schedules. They report the following:

COMMENT: The authors of this study concluded that oral iron doses of ≥60 mg result in higher fractional iron absorption when spaced by 48 hours and that giving iron more frequently increases the absolute amount of iron absorbed. Their observations suggest that current daily dosing schedules might need to be revised in favor of every-other-day dosing; less-frequent dosing would likely be more acceptable to patients and would probably increase compliance. The authors did not evaluate the impact of hepcidin on iron absorption in patients with iron deficiency anemia. A study of iron repletion in severe iron deficiency should be next on the research agenda.
CITATION(S): Moretti D et al. Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. Blood 2015 Oct 22; 126:1981.

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Neurology 2015 Oct 21
Mediterranean Diet Might Preserve Brain Volume
Elders who adhered to the Mediterranean diet did not lose brain volume as fast as their nonadherent compatriots.
Long-term adherence to the Mediterranean diet has been linked in many (but not all) epidemiological studies to a lowered risk for developing Alzheimer disease; in addition, in a 2015 randomized trial, cognition seemed to improve in a group that followed a Mediterranean diet (NEJM JW Gen Med Aug 15 2015 and JAMA Intern Med 2015; 175:1094). A team from Columbia University looked for possible anatomical correlates of this observation.
In an ongoing community-based, multi-ethnic study of 674 older patients (mean age, 80) without dementia, researchers collected dietary information and obtained magnetic resonance images. Participants who adhered most closely to the Mediterranean diet were compared with those who were least adherent. The two groups were remarkably similar with regard to age, sex, ethnicity, disease history, and cognitive performance. After adjusting for multiple possible confounding factors, the investigators found the Mediterranean-diet group had significantly larger total brain volume, total gray matter volume, and total white matter volume than the nonadherent group. Higher fish intake and lower red meat intake were the specific dietary factors associated most strongly with higher brain volumes. Parts of the brain associated most strongly with dietary factors were the cingulate cortex, parietal lobe, temporal lobe, and hippocampus. Brain volumes of Mediterranean-diet elders were equivalent to brain volumes seen in nonadherent participants who were 5 years younger.
COMMENT: These findings are consistent with other evidence indicating that the Mediterranean diet is “brain healthy.” Citing these results might help persuade patients to adopt this diet.
CITATION(S): Gu Y et al. Mediterranean diet and brain structure in a multiethnic elderly cohort. Neurology 2015 Oct 21; [e-pub].
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Science 2015 Oct 23; 350:430
MRI Might Detect Late-Onset Alzheimer Disease Decades Before Symptoms Start
Anthony L. Komaroff, MD reviewing Kunz L et al. Science 2015 Oct 23.
Adults who carry the APOE-4 mutation show impaired grid-cell activity on functional magnetic resonance imaging.
In people who are destined to suffer from late-onset Alzheimer's disease (AD), the entorhinal cortex begins to develop deposits of tau protein by age 30. Grid cells that help humans navigate in space are associated closely with the entorhinal cortex (a brain area in the medial temporal lobe), and grid-cell activity can be assessed by functional MRI (fMRI).
A multicenter European team studied 38 healthy young adults who carried one copy of the APOE-4 gene (a risk factor for late-onset AD) and 37 similar volunteers who carried no copies. fMRI (blood oxygenation level-dependent [BOLD] type) revealed that the high-risk group had impaired grid-cell activity and elevated hippocampal activity. The investigators interpreted the elevated hippocampal activity as compensating for difficulties in spatial navigation. The APOE-4 carriers also demonstrated deficits in tests of spatial navigation.
COMMENT: These researchers describe a technique for identifying young adults who are at risk for developing late-onset AD. Increasingly, research is directed at preventing accumulation of tau protein and β-amyloid protein ― both thought to be central to AD pathology ― early in life, in hopes that such treatment would be more successful if begun before symptoms appear. This new technique for detecting young adults at risk for AD could aid in selecting participants for such treatment trials.
CITATION(S): Kunz L et al. Reduced grid-cell-like representations in adults at genetic risk for Alzheimer's disease. Science 2015 Oct 23; 350:430. (http://dx.doi.org/10.1126/science.aac8128)

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MM: This is a sad commentary that physicians have to do more testing, perform "heroic" measures to extend life and increase patient and insurance expenditures to reduce their risk of being sued. This ratio appears to be present irrespective of the percentage of successful outcomes. More testing and use of resources does not necessarily guarantee better outcomes but apparently it does reduce the risk of being sued. If we are ever going to meet the clinical needs of patients and avoid national bankruptcy, then this attitude of being a litigious society must alter its' course or we will continue to head for a healthcare inspired financial apocalypse.
Higher Physician Spending Tied to Lower Risk for Malpractice Claims
By Kelly Young, Edited by Susan Sadoughi, MD, and Richard Saitz, MD, MPH, FACP, FASAM
Physicians who spend more money per patient are at lower risk for subsequent malpractice claims than those who spend less, potentially bolstering the case for defensive medicine, suggests a BMJ study.
Researchers matched the spending of 25,000 Florida physicians in 2000–2009 to their malpractice claims. In all specialties, higher resource use was associated with lower rates of malpractice claims in the following year. For instance, in internal medicine, 1.5% of physicians in the bottom fifth of spending incurred a malpractice claim, compared with 0.3% in the top fifth.
In addition, in an analysis of some 225,000 caesarean deliveries, nearly 6% of obstetricians in the bottom fifth of caesarean deliveries had a malpractice claim the following year, compared with 3% in the top fifth.
The authors conclude: "Without evidence on rates of errors associated with greater resource use, we cannot definitively conclude that defensive medicine ... reduces the number of malpractice claims. However, our findings still suggest that greater resource use is associated with fewer claims, which is consistent with physician beliefs that higher resource use, more generally, is associated with reduced liability of malpractice."
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Central Obesity Tied to Increased CV Mortality Risk in Normal-Weight Adults
By Jenni Whalen, Edited by Jaye Elizabeth Hefner, MD
Patients who have normal body mass index but central obesity are at high risk for cardiovascular mortality, according to an Annals of Internal Medicine study.
Using National Health and Nutrition Examination Survey data, researchers studied more than 15,000 adults with BMIs greater than 18.5.
After a mean follow-up of 14 years, waist-to-hip ratio (WHR), but not BMI, was associated with higher overall mortality risk. Among men with normal BMI, those with central obesity had an 87% higher total mortality risk than men without central obesity. Similarly, women with normal-weight central obesity had a 48% higher mortality risk than women with similar BMI but no central obesity.
An editorialist concludes: "To better target persons at greatest risk, such as those who already have excess or increasing levels of adiposity or those with disproportionate abdominal fat in relation to BMI, these new data provide evidence that clinicians should look beyond BMI.
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Arthritis Rheumatol 2015 Oct; 67:2771
Does Total Joint Replacement Improve Long-Term Cardiovascular Outcomes?
A new study challenges a previous one that suggested long-term cardiovascular benefit after hip or knee replacement.
Worldwide, approximately 1.8 million total knee and hip replacements are performed annually. In a 2013 observational study, investigators reported lower long-term risk for adverse cardiovascular events during a median 7-year follow-up after hip or knee replacement; they speculated that more exercise and less nonsteroidal anti-inflammatory drug use after surgery might explain their findings (NEJM JW Gen Med Dec 15 2013 and BMJ 2013; 347:f6187). However, that study has been criticized because short-term adverse events after surgery were excluded.
In a new observational U.K. study, researchers analyzed both short-term and long-term risks for myocardial infarction (MI) in about 40,000 patients (age, ≥50) with knee or hip osteoarthritis. Patients who underwent joint replacement were propensity-matched to patients who did not undergo surgery, and the surgical and nonsurgical cohorts were compared. The incidence of MI was significantly higher in surgical patients during the first month after surgery than in nonsurgical controls during their 1-month index period. However, shortly thereafter, cumulative risk for MI in the nonsurgery group “caught up” with that in the surgical group, and no significant difference in cumulative MI incidence was noted between groups for the rest of the follow-up period.
COMMENT: This study did not confirm the 2013 study, which suggested a long-term cardioprotective benefit for total hip or knee replacement. The new study demonstrates what we already know — that older patients who undergo major surgery incur excess short-term risk for postoperative MI. After the early postoperative period, overall long-term cardiovascular risk in osteoarthritis patients who undergo joint replacement appears to be similar to that of patients who do not undergo surgery.
CITATION(S):Lu N et al. Total joint arthroplasty and the risk of myocardial infarction: A general population, propensity score–matched cohort study. Arthritis Rheumatol 2015 Oct; 67:2771. (http://dx.doi.org/10.1002/art.39246)

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SPRINT: Intensive Blood Pressure Control Tied to Lower Adverse CV Events
By Allan S. Brett, MD
Dr. Brett is editor-in-chief of NEJM Journal Watch General Medicine,from which this summary was adapted. See full coverage at the link below.
Treating to a systolic blood pressure target of 120 mm Hg lowered the incidence of adverse cardiovascular events in a high-risk population, according to the SPRINT study published in the New England Journal of Medicine and presented at the American Heart Association's annual meeting.
Researchers enrolled roughly 9400 patients (age 50 or older) with a systolic BP of 130 to 180 mm Hg and high cardiovascular risk but without diabetes or stroke. Patients were randomized to either intensive or standard treatment (systolic BP targets, 120 or 140 mm Hg, respectively). The researchers were permitted discretion in choosing drug regimens.
The trial was terminated early after a median follow-up of 3.3 years, during which participants' average systolic BPs were 121.5 mm Hg and 134.6 mm Hg in the intensive- and standard-treatment groups, respectively. The primary composite outcome (myocardial infarction, non-MI acute coronary syndrome, stroke, heart failure, or CV-related death) occurred in 5.2% of intensive-treatment patients and 6.8% of standard-treatment patients. Two individual components of the composite outcome were significantly lower with intensive treatment — heart failure (1.3% vs. 2.1%) and CV-related death (0.8% vs. 1.4%). All-cause mortality also was significantly lower with intensive treatment (3.3% vs. 4.5%).
Several serious adverse events were significantly more common with intensive than with standard treatment: incidences of hypotension, syncope, and electrolyte abnormalities were each about 1 percentage point higher, and incidence of acute kidney injury was about 2 percentage points higher. Among patients without CKD at baseline, the incidence of a >30% decline in glomerular filtration rate was significantly greater with intensive treatment (3.8% vs. 1.1%).
SPRINT has demonstrated that aiming for a systolic BP of 120 mm Hg can lower the rate of adverse cardiovascular events; to prevent 1 event, 61 patients had to be treated for 3.3 years. Keep in mind that SPRINT was limited to middle-aged and older patients at above-average CV risk and that diabetic patients were excluded. Whether the decline in GFR associated with intensive treatment represents a harmless hemodynamic effect or more-serious renal injury is unclear.
Clinicians must understand that BP measurements in this study were based on the average of the three readings, taken automatically at 5-minute intervals with no clinician in the room. This method yields substantially lower readings than does a single measurement by a clinician. If SPRINT is applied without attention to proper BP measurement, substantial overtreatment — with a higher rate of adverse events — likely will occur.
Finally, note that the average achieved systolic BP in the intensive-treatment group (121.5 mm Hg) remained higher than the 120 mm target. This likely represents judicious balancing by treating clinicians who tried to approximate the 120 mm goal while avoiding side effects and excessive polypharmacy.

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Energy Drink Associated with Increased Blood Pressure
By Kelly Young, Edited by Susan Sadoughi, MD, and André Sofair, MD, MPH
Consumption of the energy drink Rockstar was followed by increases in blood pressure and norepinephrine levels in a small pilot study published in JAMA and presented at the American Heart Association's annual meeting.
Twenty-five adults (mean age, 29 years) were randomized to first consume either a 16-ounce Rockstar energy drink or a placebo drink that tasted similar but didn't contain caffeine or other stimulants. Within 2 weeks, participants consumed the other beverage.
Within 30 minutes of consuming the energy drink, participants' systolic blood pressure increased an average of 6.2%, compared with 3.1% after consuming the placebo drink. The energy drink was also associated with significant increases in diastolic blood pressure (6.8% vs. 0%) and serum norepinephrine levels (74% vs. 31%).
The authors say it is too soon to know whether these changes translate to an increase in cardiovascular risk
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WHO Declares End to Ebola in Sierra Leone
Sierra Leone is now free of Ebola virus, the World Health Organization announced on Friday, November 6, 2015. Two Ebola incubation periods (42 days) have passed since the last person with confirmed infection in the country had a second negative blood test.
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Acupuncture and Alexander Technique Help Alleviate Chronic Neck Pain
By Jenni Whalen
Both acupuncture and the Alexander Technique can improve chronic neck pain, according to a study in the Annals of Internal Medicine.
Over 500 U.K. patients with nonspecific neck pain of at least 3 months' duration were randomized to one of three strategies: 12 acupuncture sessions plus usual care, 20 one-to-one Alexander Technique lessons plus usual care, or usual care alone. The Alexander Technique is a method of changing how one carries out daily activities, with a focus on reducing tension through coordination, balance, posture, and spatial awareness.
At 12 months, both the acupuncture and Alexander Technique groups had significantly greater reductions in a score measuring neck pain and disability (about a 30% reduction from baseline), compared with usual care alone (23%). The pain/disability reductions with acupuncture and the Alexander Technique were considered clinically significant.
Alexander Technique Website: http://www.amsatonline.org/
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Most Women Do Not Gain Appropriate Weight During Pregnancy
By Cara Adler
More than two-thirds of pregnant women in the U.S. either gain too much or too little weight during pregnancy, according to a study inMMWR.
Using data from birth certificates and the Pregnancy Risk Assessment Monitoring System for full-term singletons born in 2012 or 2013, researchers calculated mothers' prepregnancy body mass index and weight gained during pregnancy.
The Institute of Medicine recommends a gain of 28 to 40 pounds during pregnancy for underweight women, 25 to 35 pounds for normal-weight women, 15 to 25 pounds for overweight women, and 11 to 20 pounds for obese women. Based on these recommendations, weight gained was considered appropriate in 32% of pregnancies, inadequate in 20%, and excessive in 48%. Women who were overweight or obese before pregnancy had the highest prevalence of excessive gain, whereas those who were underweight before pregnancy had the highest prevalence of inadequate gain.
The authors recommend interventions to promote appropriate weight gain, including calculating BMI at first prenatal visit and counseling on diet and physical activity.
What Amount is Healthy?
Website: http://iom.nationalacademies.org/About-IOM/Leadership-Staff/IOM-Staff-Leadership-Boards/Food-and-Nutrition-Board/HealthyPregnancy.aspx

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