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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
July 8, 2017

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Excessive Vitamin D Dietary Supplementation is Common in the U.S.
Nutrition and Social Decision Making
OB/GYN Group Revises Breast Screening Recommendations for Average-Risk Women
Have Breast Density Notification Laws affected Stage at Diagnosis?
Aspirin again bested Placebo for Preventing Preterm Preeclampsia in High-Risk Women
Lactation Support for Women with Diabetes
Is Glucose Self-Monitoring Worthwhile in Non–Insulin-Treated Diabetes?
Fathers' Roles in Family Food Environments
Sodium Content of Packaged Foods and Beverages is on the Decline
Even Moderate Alcohol Consumption is associated with Adverse Effects on the Brain
Firearm Deaths and Injuries among U.S. Children
USPSTF Recommends Screening for Obesity in Children Aged 6 Years and Older
Exercise Therapy for Knee Osteoarthritis in Patients with Major Comorbidities
Hepatitis C Infection is on the Rise in U.S. Women and Children

JAMA 2017 Jun 20; 317:2448
Excessive Vitamin D Dietary Supplementation Is Common in the U.S.
Almost one fifth of adults took daily supplements ≥1000 IU, and 3% ingested ≥4000 IU.
Known and purported benefits of sufficient vitamin D have caused some patients to believe that taking doses higher than the recommended daily intake (600 IU for adults ≤70, and 800 IU for those >70) adds even more value. In this study, investigators used a national health and nutrition survey database to identify about 5000 participants for each 2-year cycle of dietary assessment (from 1999 to 2014), for a total of 39,243 participants (mean age, 47).
In the 2013–2014 survey, the prevalence of daily supplemental intake ≥1000 IU vitamin D was 18.2%, and prevalence of intake ≥4000 IU was 3.2%. High intake was most common in women (25.9%), non-Hispanic whites (21.8%), and older participants (age, ≥70; 38.5%). Intake of ≥1000 IU increased significantly from the 1999–2000 survey (0.3%) to the 2013–2014 survey.
COMMENT: Prior studies have suggested several risks associated with high-dose vitamin D, including excess fractures, falls, renal calculi, and all-cause mortality. The increasing prevalence of high supplement intake suggests that clinicians should be asking specifically about supplemental vitamin D use. In fact, as I was preparing this summary, a colleague mentioned that one of his patients was taking 5000 IU of vitamin D daily and had a very high 25-hydroxyvitamin D level (84 ng/mL); my colleague called her, discussed excessive use of vitamin D supplements, and sent her a copy of this JAMA study.
CITATION(S): Rooney MR et al. Trends in use of high-dose vitamin D supplements exceeding 1000 or 4000 International Units daily, 1999–2014. JAMA 2017 Jun 20; 317:2448.
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Proc Natl Acad Sci U S A 2017 Jun 20; 114:6510
Nutrition and Social Decision Making
What we eat can change how we react to unfairness.
Nutritionally, all calories are not the same, in that calories from different sources (carbohydrates vs. fats, for example) have differential metabolic effects. In a two-part study, researchers explored whether macronutrients (protein and carbohydrates) differently influence social decisions as assessed in a behavioral paradigm, the ultimatum game [UG]). In this game, participants reject or accept monetary offers; rejection of an unfair offer has been interpreted as punishment.
First, researchers examined the relationship of the carbohydrate-protein ratio in 76 participants' usual breakfast to how they performed on the UG. The unfair offer was rejected by 24% of the group reporting a low-carbohydrate/high-protein breakfast and by 53% of the high-carbohydrate/low-protein group.
Then, 24 men were randomized to standardized breakfasts with either a low or a high carbohydrate ratio (50%–25% vs. 80%–10%, respectively). Rejection rates were significantly higher in the high-carbohydrate group. This diet was associated with significantly increasing postprandial plasma tryptophan level, lowered tyrosine levels, and higher peak glucose concentration. Tyrosine levels best predicted rejection rates.
COMMENT: The authors hypothesize that the changing plasma tyrosine level affects dopamine, which influences behaviors involving reward and social punishment. Thus, those with higher dopamine after the high-protein (higher-tyrosine) breakfast punished unfairness less often. There have been several interpretations of the UG; one can imagine different life situations where it may be advantageous, or less so, to be sensitive to perceived unfairness. Do you need to take action or, as a therapist, listen and not react to unfairness? Is it better to inhibit the desire to punish? In any case, we may need to consider diet in our patients and ourselves: does our diet affect our decisions?
CITATION(S):Strang S et al. Impact of nutrition on social decision making. Proc Natl Acad Sci U S A 2017 Jun 20; 114:6510.

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Obstet Gynecol 2017 Jul; 130:241
OB/GYN Group Revises Breast Screening Recommendations for
Average-Risk Women

ACOG takes into account personal values about benefits and risks of screening.
The American College of Obstetricians and Gynecologists (ACOG) has updated its guidance on breast cancer screening in average-risk women to emphasize shared decision making between the patient and provider.
Previously, the group recommended that average-risk women undergo annual screening mammography beginning at age 40. Now, the group advises the following:

COMMENT: These updated breast cancer screening guidelines from ACOG represent a welcome evolution. Given the harms and benefits associated with screening, it's appropriate that recommendations about mammography not be written in stone. The revisions bring ACOG's guidance more in line with the evidence-based recommendations of the U.S. Preventive Services Task Force (NEJM JW Womens Health Dec 2009 and Ann Intern Med 2009; 151:716). The focus on shared decision making (some might call this “negotiating”) about when to initiate screening, how often to be screened, and whether or not to undergo clinical breast examination makes sense — and should help improve healthcare for our adult female patients.
— Adapted from a Physician's First Watch article published Jun 23, 2017.
CITATION(S): American College of Obstetricians and Gynecologists.Practice Bulletin No. 179: Breast cancer risk assessment and screening in average-risk women. Obstet Gynecol 2017 Jul; 130:241.
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J Gen Intern Med 2017 Jun; 32:603
Have Breast Density Notification Laws Affected Stage at Diagnosis?
Legislation requiring breast density reporting did not reduce the incidence of advanced-stage breast cancer.
About 40% of women are reported to have dense breast tissue. Breast density is an independent risk factor for breast cancer, and the sensitivity of mammography to detect malignancy is diminished in dense breasts. Although evidence is insufficient to support supplemental screening with ultrasound or breast magnetic resonance imaging (MRI) in women with dense breasts, 28 states have passed breast density notification laws requiring women to be notified of their breast density on mammography (and in some states, to receive notification about possible supplemental imaging).
Investigators used U.S. breast cancer incidence data from 13 states, two of which (California and Connecticut) have breast density notification laws. They compared stage at diagnosis in Connecticut before and after legislation (2009) with that in states not having such legislation. Enactment of legislation was associated with a 1.4% increase in diagnosis of early-stage breast cancer in Connecticut women (vs. control states) and a 1.1% decrease in diagnosis of ductal carcinoma in situ. However, notification did not reduce the proportion of advanced or metastatic breast cancers.
COMMENT: Many women are shocked to learn that, despite many years of breast imaging, their mammograms could have low yield for detecting breast cancer. Although this study showed no obvious benefit of breast density notification, it has several limitations (no data on rate of supplemental screening, short 4-year follow up, and limited power to detect small effects). I look forward to the results of an ongoing Dutch randomized trial evaluating the addition of breast MRI to mammography in women with extremely dense breasts.
Dr. Samiian is an Assistant Professor of Surgery and Chief, Section of Breast Surgery, at the University of Florida College of Medicine, Jacksonville.
CITATION(S): Richman I et al. Breast density notification legislation and breast cancer stage at diagnosis: Early evidence from the SEER registry. J Gen Intern Med 2017 Jun; 32:603.
Tice JA and Kerlikowske K.Supplemental breast cancer screening: A density conundrum. J Gen Intern Med 2017 Jun; 32:593.
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N Engl J Med 2017 Jun 28
Aspirin Again Bested Placebo for Preventing Preterm Preeclampsia in
High-Risk Women

What prophylactic dose should be recommended?
Severe preeclampsia is a notable cause of maternal and perinatal morbidity and mortality, and many studies have indicated that aspirin, compared with placebo, can reduce risk for developing the condition. In an international European study of the effects of low-dose aspirin on risk for preterm (<37 weeks' gestation) preeclampsia, investigators identified 1620 women at high risk for the disease based on a screening algorithm that included medical history, baseline mean arterial blood pressure, uterine-artery pulsatility index, and serum concentrations of pregnancy-associated plasma protein A and placental growth factor. Participants were randomized at 11 to 14 weeks' gestation to receive aspirin (150 mg daily) or placebo until 36 weeks.
Rates of preterm preeclampsia were 1.6% in the aspirin group versus 4.3% in the placebo group (odds ratio, 0.38; 95% confidence interval, 0.20–0.74; P=0.004). Incidence of adverse events (placental abruption, spontaneous preterm delivery, stillbirth, or low birth weight) did not differ between groups.
COMMENT: This study bolsters the evidence that aspirin has a favorable benefit-risk ratio for women at increased risk for preterm preeclampsia, here determined with first-trimester screening that combined medical history with measurement of vascular function and selected biomarkers. In the U.S., low-dose aspirin is widely available as an 81-mg tablet; in Europe, low-dose aspirin for preventing preeclampsia is generally prescribed as a 150-mg tablet. As some evidence indicates that the magnitude of aspirin's beneficial effect is dose-dependent, U.S. clinicians recommending this agent to prevent preeclampsia should consider advocating two daily 81-mg tablets.
CITATION(S): Rolnik DL et al. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. N Engl J Med 2017 Jun 28; [e-pub].
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Lancet 2017 Jun 3; 389:2204
Lactation Support for Women with Diabetes
Antenatal breast-milk expression did not adversely affect perinatal outcomes in diabetic mothers otherwise at low risk for pregnancy complications.
Pregnant women with diabetes are at excess risk for complications such as delayed lactogenesis and difficulties with breast-feeding. Accordingly, some clinicians encourage women with diabetes to begin expressing colostrum during late pregnancy (despite limited supporting data and potential concerns that nipple stimulation might trigger contractions and preterm birth). To assess the safety of antenatal milk expression, Australian researchers conducted a randomized trial involving 635 diabetic women carrying “low-risk” singleton pregnancies. Beginning at 36 weeks' gestation, women in the intervention group were advised to hand-express breast milk twice daily for ≤10 minutes, freeze their milk, and bring it with them to the hospital. Women in the control group received standard obstetric care.
Mean gestational age at birth did not differ between groups, nor did the proportion of infants requiring neonatal intensive care. Infants of mothers in the intervention group were more likely to be exclusively breast-fed for their first 24 hours of life, but by 3 months, rates of breast-feeding were similar between groups.
COMMENT: Although this rigorous study provides reassurance that antenatal milk expression does not adversely affect low-risk pregnancies in women with diabetes, until we have clearer evidence that this practice has benefits, it should not be routinely recommended. Pregnant women — especially those with diabetes — have enough to worry about without adding milk expression to their “to-do” lists.
CITATION(S): Forster DA et al. Advising women with diabetes in pregnancy to express breastmilk in late pregnancy (Diabetes and Antenatal Milk Expressing [DAME]): A multicentre, unblinded, randomised controlled trial. Lancet 2017 Jun 3; 389:2204.
Berens P.Antenatal milk expression for women with diabetes in pregnancy. Lancet 2017 Jun 3; 389:2167.
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JAMA Intern Med 2017 Jun 10
Is Glucose Self-Monitoring Worthwhile in Non–Insulin-Treated Diabetes?
In a study with limitations, self-monitoring did not improve outcomes.
Most non–insulin-treated patients with type 2 diabetes perform self-monitoring of blood glucose (SMBG), but whether this practice improves glycemic control or quality of life is unclear. Researchers in North Carolina randomized 450 non–insulin-treated type 2 diabetics (glycosylated hemoglobin [HbA1c] level, 6.5%−9.5% within 6 months preceding randomization) to no SMBG, once-daily SMBG, or once-daily SMBG plus automated algorithm-derived messages designed to educate and motivate patients. Primary care providers received reports of SMBG data and continued routine management of their patients' diabetes. HbA1c and health-related quality of life were measured at baseline and 1 year later. Otherwise, the study team did not contact the patients or clinicians; interim HbA1c values were retrieved from patients' electronic medical records.
Among patients randomized to SMBG, adherence to daily testing decreased from about 90% at baseline to about 55% at 1 year, with less-frequent testing in patients who received automated messages than in those who did not. Mean HbA1c was significantly lower in both SMBG groups than in the no-SMBG group (mean difference, −0.33%) at 6 months. However, at 1 year, groups did not differ significantly in HbA1c levels or health-related quality of life.
COMMENT: Without consistent reinforcement, adherence to SMBG eroded rapidly; the authors suggest that this might have contributed to the disappearance of SMBG's early effect on HbA1c. In my experience, SMBG can be helpful for some non−insulin-treated patients, by providing daily reinforcement of lifestyle choices that enhance glycemic control. More rigorous studies could help us identify those patients with type 2 diabetes for whom SMBG might add measurable value.
CITATION(S): Young LA et al. Glucose self-monitoring in non–insulin-treated patients with type 2 diabetes in primary care settings: A randomized trial. JAMA Intern Med 2017 Jun 10; [e-pub].
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Appetite 2017 Jun 16; 117:98
Fathers' Roles in Family Food Environments
Fathers are perceived by family members (and themselves) as being less focused on and less committed to the creation of a healthy household food environment.
Studies of family food practices almost exclusively focus on mothers. To explore how fathers may affect the family food environment, a sociologist conducted 109 interviews with mothers, adolescents (ages 12–19 years), and fathers from 44 middle- and upper–middle-class one- and two-parent families from the San Francisco Bay area. Key findings:

COMMENT: While we cannot draw too many firm conclusions from a single small study from one geographic area, it is striking that fathers, mothers, and adolescents all generally agreed on how mothers and fathers differ in their attitudes toward a healthy food environment. Particularly given the prevalence of childhood obesity, it is important that fathers and mothers unite in creating a healthy food environment. At well child visits, pediatricians can remind fathers that they can and do play an important role in achieving this goal.
CITATION(S): Fielding-Singh P.Dining with dad: Fathers' influences on family food practices. Appetite 2017 Jun 16; 117:98.
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JAMA Intern Med 2017 Jun 5
Sodium Content of Packaged Foods and Beverages Is on the Decline
During the past 15 years, the decline was about 400 mg daily per person.
Most people in the U.S. consume more sodium than guidelines recommend, due in part to the sodium content of store-bought packaged foods. Researchers used a national database of household packaged food purchases from 2000 through 2014 to evaluate purchasing habits and the associated sodium content of packaged foods and beverages in about 170,000 households; household members used a barcode scanner to identify specific purchased foods and beverages, each of which was then linked to nutritional label data for nearly 1.5 million products. Whether foods actually were consumed was not assessed.
The amount of sodium acquired from purchased packaged foods, beverages, and table salt declined from about 2400 to 2000 mg daily per person from 2000 through 2014. The decline came mostly from decreases in the sodium content of packaged foods rather than decreases in the amount of foods purchased, but most packaged foods still exceeded optimal sodium density levels (≤1.1 mg/kcal). Most of the remainder of the decline came from a decrease in table salt purchases.
COMMENT: Lowering the sodium content of packaged foods is a positive step toward reducing sodium consumption, and might reflect consumer education and purchasing pressure on manufacturers. However, the sodium density of most packaged foods still is high. Also, this study was not designed to assess individual sodium intake, particularly with regard to restaurant food and other away-from-home sources.
CITATION(S): Poti JM et al. Sodium reduction in US households' packaged food and beverage purchases, 2000 to 2014. JAMA Intern Med 2017 Jun 5; [e-pub].
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BMJ 2017 Jun 6; 357:j2353
Even Moderate Alcohol Consumption Is Associated with
Adverse Effects on the Brain

No level of alcohol use was protective of cognitive function.
Evidence on the effects of light or moderate alcohol consumption on brain structure and function is mixed. In this U.K. study, researchers evaluated the relation between alcohol consumption and brain outcomes in 550 adults (mean age, 43) whose weekly alcohol use and cognitive function were evaluated at baseline and periodically from 1985 through 2015; brain magnetic resonance imaging was performed at the end of the study. Alcohol consumption was measured in “units,” defined as 8 g of alcohol per unit; in the U.S., a typical 12-ounce beer or 5-ounce glass of wine contains 14 g of alcohol (thus, nearly 2 units as defined here). No participants were alcohol dependent at baseline, and alcohol consumption was stable throughout the study.
During 30 years of follow-up, higher alcohol intake was associated with less grey-matter density. Compared with abstinence, drinking between 1 and 13 units weekly had no adverse or protective effects, whereas drinking 14 to 20 units weekly (a level deemed to be “moderate” for men), 21 to 29 units weekly, and ≥30 units weekly were associated with significantly higher odds of right-sided hippocampal atrophy (adjusted odds ratios, 3.4, 3.6, and 5.8, respectively). Higher average alcohol consumption was associated inversely with white matter integrity and lexical fluency (i.e., word retrieval characteristically associated with frontal lobe executive function).
COMMENT: In this long-term study, alcohol consumption up to 13 units weekly neither adversely nor favorably affected brain structure. However, even 14 to 20 8-g units weekly — a level typically viewed as “safe” — was associated with hippocampal atrophy (an outcome associated with cognitive impairment and dementia) and impairment in one measure of cognitive function. For optimal brain health, individuals should limit alcohol consumption.
CITATION(S): Topiwala A et al. Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: Longitudinal cohort study. BMJ 2017 Jun 6; 357:j2353. (http://dx.doi.org/10.1136/bmj.j2353)

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Pediatrics 2017 Jun 19
Firearm Deaths and Injuries Among U.S. Children
Over 90% of all pediatric firearm-related deaths in high-income countries occur in the U.S., with approximately 20 U.S. children being killed or injured from gunshot wounds each day.
Investigators used the National Electronic Injury Surveillance System and the National Violent Death Reporting System to assess the scale and characteristics of firearm-related deaths and injuries among U.S. children (0–17 years of age) from 2002 to 2014. Highlights of their findings include:

COMMENT: An editorialist provides a logical multipronged approach for addressing the problem of pediatric firearm injuries, including safe storage, physician counseling, public education, and gun safety legislation. I might have said the same thing on another day, but reading this today makes me mad. It makes me want our country to admit that the right to own a gun is more important to us than preventing the deaths of the numeric equivalent of a classroom full of children every week. Let's both take a well-reasoned approach and continue to speak the truth.
CITATION(S): Fowler KA et al. Childhood firearm injuries in the United States. Pediatrics 2017 Jun 19; [e-pub].
Nelson EW.Confronting the firearm injury plague. Pediatrics 2017 Jun 19; [e-pub].
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JAMA 2017 Jun 20; 317:2417
USPSTF Recommends Screening for Obesity in Children Aged 6 Years and Older
Screening for obesity using BMI allows for successful primary care behavioral interventions.
Obesity remains a serious childhood condition in the U.S., affecting nearly 20% of the pediatric population. To update its 2010 recommendations, the U.S. Preventive Services Task Force (USPSTF) reviewed the literature assessing screening and treatment for obesity in children and adolescents aged 2 to 18 years (NEJM JW Pediatrics and Adolescent Medicine Apr 2010 and Pediatrics 2010; 125:361).
Among the findings and recommendations:

COMMENT: These USPSTF recommendations support the 2010 recommendations to screen for obesity in children over 6 years old and add new information on the length of therapy shown to be successful as well as the limited value of medications. I agree with these recommendations, but also agree with editorialists that the issue is complex because of limited availability of behavioral intervention programs to primary care providers. We need to develop better resources, either within our primary care practices or our communities. In addition to individual obesity management, as one editorial suggests, we need to develop population-based interventions to address the obesity epidemic.


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Arthritis Care Res (Hoboken) 2017 Jun; 69:807
Exercise Therapy for Knee Osteoarthritis in Patients with Major Comorbidities
An exercise program tailored to patients' comorbidities improved physical function.
Exercise therapy is recommended for patients with knee osteoarthritis (OA). However, data are lacking on exercise therapy for patients with knee OA who also have chronic medical conditions, and these patients often are not referred to physical therapy. In this study, 126 patients (mean age, 63) with knee OA and at least one comorbid condition (i.e., coronary heart disease, heart failure, type 2 diabetes, chronic obstructive pulmonary disease, or obesity [body-mass index, ≥30 kg/m2]) were randomized to a tailored exercise program or to standard medical care for 20 weeks. The exercise program consisted of two 30- to 60-minute sessions weekly of strength training and aerobic exercise adapted to patients' comorbidities, and patients were encouraged to exercise at home at least five times weekly.
At the end of the intervention and 3 months after completing it, physical function scores (as measured on the WOMAC scale) and 6-minute walk distances improved significantly more in exercise patients than in standard-care patients. At the 3-month follow-up, exercise patients had mean improvements of 33% and 15% on the WOMAC scale and 6-minute walk test, respectively. No serious exercise-related adverse events occurred.
COMMENT: This study expands the population of patients with knee OA who should be referred to physical therapy to include those with substantial comorbidities. The findings are particularly important, because these comorbidities might preclude surgical intervention.
CITATION(S):de Rooij M et al. Efficacy of tailored exercise therapy on physical functioning in patients with knee osteoarthritis and comorbidity: A randomized controlled trial. Arthritis Care Res (Hoboken) 2017 Jun; 69:807.
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Ann Intern Med 2017 May 9
Hepatitis C Infection Is on the Rise in U.S. Women and Children
About 30,000 reproductive-aged women are reported to have HCV infection each year.
Until recently, the bulk of hepatitis C virus (HCV) infections occurred in persons born between 1945 and 1965 (baby boomers); thus, a one-time screening has been recommended for this group. To examine trends in younger women, investigators analyzed data on HCV cases in women and children reported to the National Notifiable Diseases Surveillance System (2006–2014) as well as those tested by Quest Laboratories (2011–2014).
The reported number of reproductive-aged women with HCV rose from 16,000 in 2006 to 31,000 in 2014. Among some 580,000 pregnant women who were tested, 0.73% had HCV. In addition, 0.76% of tested children had HCV. Infection rates varied with age and peaked at 1.62% in those aged 2 to 3 years.
COMMENT: As the authors speculate, the increasing number of HCV infections in younger women likely reflects the current opioid injection epidemic. While transmission to the neonates is infrequent, those born to women with high viral loads and concurrent HIV infection are at increased risk. Because routine testing in this age group — or in pregnancy — is not currently recommended, these numbers reflect only the testing performed when a high-risk history is elicited; therefore, we really do not know the extent of the problem. Population-based studies will be needed to evaluate HCV's scope and to devise screening strategies.
CITATION(S): Ly KN et al. Hepatitis C virus infection among reproductive-aged women and children in the United States, 2006 to 2014. Ann Intern Med 2017 May 9; [e-pub].
DeMaria A Jr et al. Hearing from the silent epidemic. Ann Intern Med 2017 May 9; [e-pub].

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