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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
December 2, 2017

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How Long Should Patients Receive Opioids After Surgery?
Focus on Parents for Better Outcomes in Some Adolescents with Anorexia Nervosa
Severe Obesity in Childhood Predicts High Risk for Obesity in Adulthood
Whole Grains Diet Reduces Systemic Inflammation and Body Weight vs. a Refined
   Grains Diet
Does Cognition in Children Born Extremely Preterm Catch Up by Early Adulthood?
Can We Identify Adolescents Most Likely to Bring Weapons to School?
Management of Pediatric Gastroesophageal Reflux
Dietary Approaches to Treating EoE: A Meta-Analysis
Trial of Labor After Cesarean: A Powerful Clinical Option
Breast-Feeding Associated with Reduced Risk for Developing Multiple Sclerosis
Is Impedance pH Testing Useful in Diagnosing Noncardiac Chest Pain in GERD?
Helicobacter pylori Eradication Does Not Prevent Metachronous Gastric Cancer
Abortion, Cash, and Subsequent Contraceptive Use

JAMA Surg 2017 Sep 27
How Long Should Patients Receive Opioids After Surgery?
For common surgical procedures, 7 days usually sufficed for opioid-naive patients, but duration depended on the type of procedure performed.
Surgeons vary considerably in the dose and duration of opioids they prescribe to patients postoperatively. To better define optimal postoperative opioid prescribing, researchers used a U.S. Department of Defense Military Health System database to identify opioid-naive patients (age range, 18–64) who had undergone one of eight common surgical procedures between 2005 and 2014.
More than 215,000 patients filled at least one prescription for opioids within 14 days of their procedures, and 19% received at least one refill. Although 7-day durations sufficed for most patients, significant variability in duration of opioid consumption was noted among types of procedures: Patients who underwent musculoskeletal procedures (e.g., anterior cruciate ligament repair, discectomy) generally required longer duration and more frequent refills than those who underwent women's health procedures (e.g., mastectomy, hysterectomy) or general surgery procedures (e.g., appendectomy, cholecystectomy).
COMMENT: A 7-day limit on initial opioid prescription might be adequate for many common general surgery and gynecologic procedures, but for patients undergoing orthopedic interventions, such a limit might be inappropriately restrictive. This study did not include amount of daily morphine milligram equivalents (MMEs) prescribed or consumed or patients' expected goals for pain control (tolerable vs. “pain free”). However, these findings reinforce that the degree and duration of acute pain depends on several factors, including type of surgery. As we strive to curb opioid prescribing, studies like this are vital to developing safe and effective evidence-based postsurgical pain-management recommendations.
CITATION(S): Scully RE et al. Defining optimal length of opioid pain medication prescription after common surgical procedures. JAMA Surg 2017 Sep 27; [e-pub]. (http://dx.doi.org/10.1001/jamasurg.2017.3132)
Rogers SO Jr.Addressing variability in opioid prescribing. JAMA Surg 2017 Sep 27; [e-pub]. (http://dx.doi.org/10.1001/jamasurg.2017.3166)
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Eur Eat Disord Rev 2017 Nov 03
Focus on Parents for Better Outcomes in Some Adolescents with
Anorexia Nervosa

When mothers have high expressed emotion, outcomes are better when a specific family therapy is administered to the parents alone.
Although family-based treatment (FBT), a specific family therapy administered in a conjoint format, can be effective for anorexia nervosa in adolescents, so can treating parents alone via parent-focused FBT (PFT). In such cases, poor treatment response and treatment dropout have been associated with high parental expressed emotion (EE), manifested by criticizing the patient, emotional overinvolvement, or both. Researchers analyzed data from an Australian randomized, controlled trial to compare the effects of the two therapies on parental EE and on patient outcomes.
There were 102 patient-family units (patients' mean age, 15.5; mean of 15 treatments in 6 months). At baseline, high EE was seen in 44% of mothers and 26% of fathers; high maternal criticism correlated with longer illness duration.
At end of treatment in 63 families, remission was seen in 15 of 30 patients with consistently low EE mothers, 6 of 14 whose mothers changed from high to low, 3 of 9 whose mothers changed from low to high, and none of 10 with consistently high EE mothers.
Mothers changing from high to low criticism were more likely to have received PFT vs. FBT (88% vs. 12%). Shifting from low to high criticism occurred in 27% of mothers after FBT and 0% of mothers receiving PFT. No significant associations were found for paternal EE.
COMMENT: Although this study is small, its findings reinforce associations of high EE with poorer outcomes. They also suggest that for families starting with high maternal EE, treating the parents with FBT apart from their children is preferable to conjoint family FBT for reducing maternal criticism and improving outcomes.
CITATION(S): Allan E et al. Parental expressed emotion during two forms of family-based treatment for adolescent anorexia nervosa. Eur Eat Disord Rev 2017 Nov 03; [e-pub]. (http://dx.doi.org/10.1002/erv.2564)
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N Engl J Med 2017 Nov 30; 377:2145
Severe Obesity in Childhood Predicts High Risk for Obesity in Adulthood
Simulation models predict that obese 2-year-olds have a 75% probability of obesity at age 35 years.
How childhood obesity translates into adult obesity is unknown. Using five U.S. national health data sets that include roughly 177,000 body-mass index (BMI) observations in 42,000 children (age 2–19 years) and adults, researchers developed models to predict risk of obesity at age 35 years. Severe obesity was defined as BMI ≥35 in adults and ≥120% of the 95th percentile for age in children.
Among the model's findings and predictions:

COMMENT: These simulated trends are very interesting and suggest that identifying obesity early in childhood and instituting interventions should be given high priority in attempting to avoid obesity later in life.
CITATION(S): Ward ZJ et al. Simulation of growth trajectories of childhood obesity into adulthood. N Engl J Med 2017 Nov 30; 377:2145.
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Gut 2017 Nov 1
Whole Grains Diet Reduces Systemic Inflammation and Body Weight vs. a Refined Grains Diet
Findings supply evidence to back up dietary recommendations.
Investigators in Denmark examined whether replacing a refined grain diet with a whole grain diet would alter the gut microbiome and insulin sensitivity or affect biomarkers of metabolic health and gut functionality. In this randomized, controlled cross-over study, 50 patients were randomized to a whole grain diet for 8 weeks, with crossover following a washout period to a refined grain diet for 8 weeks. During the whole grain period, participants were given a target of consuming ≥75 grams per day of whole grains, compared with a target of <10 grams whole grains per day during the refined grain period.
During the whole grain period, body weight decreased slightly, which correlated with lower energy intake. Inflammatory markers decreased with the whole grain diet: serum C-reactive protein dropped from 6.3 to 4.2 mg/L, and interleukin-6 from 1.6 to 1.4 pg/mL, both highly significant changes. Insulin sensitivity was not improved by the whole grain diet, and consuming whole grains did not affect intestinal permeability. Neither diet had major effects on the fecal microbiome.
COMMENT; Increasingly, gastroenterologists have evidence on which to base dietary recommendations. These data support whole grains over refined grains for weight management and in patients with inflammatory conditions.
CITATION(S): Roager HM et al. Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: A randomised cross-over trial. Gut 2017 Nov 1; [e-pub].
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Arch Dis Child Arch Dis Child 2017 Nov 16
Does Cognition in Children Born Extremely Preterm Catch Up by Early Adulthood?
Cognitive impairments in infants born before 26 weeks persisted through age 19 years, neither improving nor deteriorating.
Cognitive impairments in extremely preterm infants have been shown to persist into childhood, but adult outcomes have not been studied rigorously. To describe cognitive development from infancy to early adulthood in extremely preterm individuals, researchers prospectively followed a cohort of 315 infants born in the U.K. or Ireland at or before 25 weeks' gestation. Standardized cognitive testing (IQ tests with mean scores of 100) was performed at ages 2.5, 6, 11, and 19 years. From 6 years on, scores were compared to those of 160 matched term-born peers.
Extremely preterm individuals had significantly lower cognitive scores than term-born peers over the study period (25.2 points lower, on average). Although there was some catch-up in the preterm group (0.5 points per year), score trajectories in both groups were essentially stable over time, showing little change from age 6 to 19 years. In the preterm group, boys had significantly lower scores than girls (8.8 points lower, on average), and individuals born at 25 weeks had higher scores than those born earlier (4.4 points higher, on average). Moderate to severe neonatal brain injury was associated with lower IQ in the preterm group; higher maternal education level was associated with higher IQ in both the preterm and term groups.
COMMENT: Although it is difficult to give parents an accurate prediction of their premature infant's developmental future, it can be helpful to explain what we know about children like theirs. The sobering results from this study reflect group outcomes and should be presented as such. In my experience, parents want to know the range of typical outcomes but also need to know that individual development varies widely and that we will offer support to help realize their child's full developmental potential.
CITATION(S): Linsell L et al. Cognitive trajectories from infancy to early adulthood following birth before 26 weeks of gestation: A prospective, population-based cohort study. Arch Dis Child 2017 Nov 16; [e-pub].
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Pediatrics 2017 Nov 27
Can We Identify Adolescents Most Likely to Bring Weapons to School?
Based on U.S. survey data, having additional experiences with peer aggression on top of being bullied heightens risk for weapon carrying.
Victims of bullying are more likely to experience mental and physical health problems and academic issues and were recently found to be more likely to bring a weapon to school. Now, researchers have assessed whether additional past experiences of peer aggression (apart from being bullied) increase the likelihood of bringing a weapon to school, using recent U.S. survey data from over 15,000 high school students. Results were as follows:

COMMENT: School gun violence makes everyone feel powerless, but this study suggests that pediatricians might be able to help prevent it by identifying the highest-risk teens. Sex-specific analyses indicating that girls' weapon carrying is strongly influenced by peer aggression experiences highlight that this is not only a problem among boys.
When screening for bullying experiences during visits with adolescents, three helpful follow-up questions might be: How often do you get in fights at school? Have you been threatened or injured at school? Have you skipped school because you felt unsafe? Teens endorsing one or more of these should be connected with additional mental health or educational supports.
CITATION(S): Pham TB et al. Weapon carrying among victims of bullying. Pediatrics 2017 Nov 27; [e-pub].
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Pediatrics 2013 May; 131:e1684
Management of Pediatric Gastroesophageal Reflux
Guidelines stress the importance of distinguishing between physiologic gastroesophageal reflux and gastroesophageal reflux disease.
Sponsoring Organization: This American Academy of Pediatrics clinical report is based on 2009 evidence-based guidelines developed by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Purpose and Objective: To help pediatric clinicians identify patients with simple gastroesophageal reflux (GER) whom they can manage with minimal testing and conservative treatment and those with gastroesophageal reflux disease (GERD) who require consultation with a gastroenterologist.
Key Points:

COMMENT: This useful evidence-based approach to diagnosis and management of infants and children with GER and GERD includes algorithms for management of infants with recurrent vomiting/regurgitation and weight loss or recurrent vomiting/regurgitation and poor weight gain, and children or adolescents with chronic heartburn. Infants require careful assessment to distinguish common physiologic GER from GERD. Providing reassurance to parents of infants diagnosed with GER is recommended to avoid unnecessary diagnostic procedures and pharmacologic therapy.
CITATION(S): Lightdale JR and Gremse DA.Gastroesophageal reflux: Management guidance for the pediatrician. Pediatrics 2013 May; 131:e1684.
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Gastroenterology d 2014 Jun; 146:1639
Dietary Approaches to Treating EoE: A Meta-Analysis
Results were best with the elemental diet but strong and more generalizable with the less onerous six-food elimination diet.
Eosinophilic esophagitis (EoE) has been categorized as a food allergy because of evidence of disease remission with dietary elimination, which should be considered as an initial therapy in both children and adults with EoE (NEJM JW Gastroenterol Jun 7 2013). In choosing the optimal dietary intervention (elemental, empiric elimination, or targeted elimination) for patients, clinicians are currently hampered by variable findings on their effectiveness.
In a systematic review and meta-analysis, researchers evaluated the efficacy of dietary interventions to induce histologic remission in EoE (peak eosinophil counts <15 eosinophils per high-power field).
Results based on data from 23 articles and 10 abstracts were as follows:

COMMENT: Results from trials of six-food (milk, egg, wheat, soy, nuts, and seafood) elimination diets showed high homogeneity and thus are widely generalizable for patients of all ages. This diet also avoids the many disadvantages of the elemental diet. When embarking on the six-food elimination diet, counseling from a dietitian is strongly recommended to ensure that adequate nutrition is maintained. Also, similar to specific-food elimination diets, patients must be very comfortable with reading ingredient labels.
Although dietary modification is clearly an effective nonpharmacologic intervention in patients with EoE, further research is needed that addresses the lack of controlled trials, temporal variability in the definition of EoE, and the need for more-accurate assessment of durability of effect.
CITATION(S): Arias Á et al. Efficacy of dietary interventions for inducing histologic remission in patients with eosinophilic esophagitis: A systematic review and meta-analysis. Gastroenterology 2014 Jun; 146:1639.
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Obstet Gynecol 2017 Nov; 130:1167
Trial of Labor After Cesarean: A Powerful Clinical Option
ACOG updates its guidance on individualized counseling about the risks and benefits of TOLAC.
Sponsoring Organization: American College of Obstetricians and Gynecologists (ACOG)
Target Population: Obstetric care providers
Background and Objective: A safe birth for both mother and newborn is often best achieved with vaginal birth. Some women may choose to attempt a trial of labor after cesarean (TOLAC) to achieve vaginal birth after cesarean (VBAC); alternatively, they may plan a repeat cesarean delivery (RCD). This ACOG practice bulletin updates guidance for providing individualized counseling about the risks and benefits of TOLAC and RCD. In the absence of randomized trials, observational data have played an essential role in developing these guidelines.
Key Recommendations

COMMENT: Clinicians who provide care for pregnant women are deeply committed to achieving the lowest possible rates of cesarean delivery while protecting the safety of mothers and neonates. TOLAC is a powerful clinical option for optimizing cesarean delivery rates. Although all birthing decisions should be individualized, for women with a predicted rate of successful TOLAC as low as 40%, planned RCD may be the safer option. For those with a predicted rate of successful TOLAC of ≥60%, a TOLAC may be the optimal plan; however, a predicted success rate of <60% is not a contraindication to attempting a TOLAC. Women who are likely to achieve a successful TOLAC should be encouraged to pursue this birth plan.
CITATION(S): The American College of Obstetricians and Gynecologists.Practice bulletin no. 184: Vaginal birth after cesarean delivery. Obstet Gynecol 2017 Nov; 130:1167.
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Neurology 2017 Aug 8; 89:563
Breast-Feeding Associated with Reduced Risk for Developing Multiple Sclerosis
For mothers who breast-fed for a cumulative duration of ≥15 months, risk for MS was half that of those who breast-fed for <15 months.
Having more than one pregnancy has been shown to protect against developing multiple sclerosis (MS). Does prolonged breast-feeding play a similar role? In an analysis utilizing the Kaiser Permanente Southern California system, investigators selected 397 patients with recent MS diagnoses and matched them with 433 disease-free controls. Total cumulative duration of breast-feeding and total ovulatory years were determined through interviews. Sixty percent of women had ≥1 child, and breast-feeding data were available for 239 cases and 262 controls. Socioeconomic factors included household income, race/ethnicity, education, and smoking.
Women who breast-fed for ≥15 months were half as likely to receive diagnoses of MS as those who breast-fed for <15 months. No dose response was found for breast-feeding for 4 to 14 months. MS risk was not associated with age, gravidity, parity, age at first birth, contraceptive use, menstrual years, or ovulatory years.
COMMENT: These investigators have previously suggested that prolonged exclusive breast-feeding is associated with reduced risk for disease reactivation in patients with MS (NEJM JW Neurol Nov 2015 and JAMA Neurol 2015; 72:1132). The current study found that cumulative breast-feeding for ≥15 months may be protective (although only 26% of the eligible population reported doing so). Surprisingly, number of pregnancies, children, and ovulatory years were not associated with MS risk. Other studies have suggested numerous benefits of breast-feeding (such as protection against breast and endometrial cancers). Breast-feeding may be a proxy for socioeconomic status and other healthy behaviors, and controlling for all of these is difficult. Although these findings need replication, we should continue to encourage mothers to breast-feed for a variety of known and theoretical benefits.
CITATION(S): Langer-Gould A et al. Breastfeeding, ovulatory years, and risk of multiple sclerosis. Neurology 2017 Aug 8; 89:563.
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Am J Gastroenterol 2017 Nov; 112:1671
Is Impedance pH Testing Useful in Diagnosing Noncardiac Chest Pain in GERD?
A low observed positive symptom-associated probability of chest pain with gastroesophageal reflux disease suggests not.
Although the characteristic symptoms of gastroesophageal reflux disease (GERD) are heartburn and regurgitation, chest pain is a variable symptom in some. To investigate factors associated with the occurrence of noncardiac chest pain during a GERD episode, researchers retrospectively assessed data from 120 patients with a primary GERD symptom of retrosternal pain who had undergone ambulatory 24-hour pH-impedance monitoring. Proton-pump inhibitors (PPIs) were discontinued at least 7 days before monitoring.
Baseline heartburn and regurgitation were reported in 49% and 24%, respectively, and 42% of participants reported one of these symptoms during the pH monitoring. Among over 4000 reflux episodes observed, 76% were acidic and 24% were weakly acidic. Noncardiac chest pain was reported in 86% but was considered to be associated with reflux in only 13%, i.e., with a positive symptom-associated probability (SAP). Chest pain episodes associated with GERD were mostly acidic (89%), versus weakly acidic (11%). These episodes also had significantly higher proximal extent and a delayed volume clearance time compared with episodes without chest pain.
COMMENT: Although establishing a definitive diagnosis of GERD prevents unnecessary testing and may reduce related functional disability in patients with noncardiac chest pain, the relatively weak association of chest pain with reflux events calls into question whether pH-impedance testing is needed. What is not defined among patient characteristics in this study is the percentage with a history of noncardiac chest pain whose symptoms were controlled with PPI therapy. Notably, two thirds of patients with a positive SAP for chest pain also had typical symptoms of GERD. Although impedance pH monitoring is a very useful tool in evaluating nonresponse to PPIs, its specific use in investigating noncardiac chest pain seems limited.
CITATION(S): Herregods TVK et al. Determinants of the association between non-cardiac chest pain and reflux. Am J Gastroenterol 2017 Nov; 112:1671.
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Gut Liver 2017 Oct 27
Helicobacter pylori Eradication Does Not Prevent Metachronous Gastric Cancer
Among patients who underwent resection for early gastric cancer, those who were negative for H. pyloriinfection had the highest rate of metachronous cancers.
Helicobacter pylori infection is a known risk factor for gastric cancer (GC). Eradication of the infection may reverse some GC precursor states, such as gastric mucosal atrophy and intestinal metaplasia, but will it reduce the incidence of metachronous GC?
To find out, investigators in Korea retrospectively reviewed 565 patients from a single center who underwent endoscopic resection of early GC. Follow-up endoscopy was performed at 3, 6, and 12 months after resection, and annually thereafter.
At median follow-up of ≥60 months, 157 patients were negative for H. pylori infection at the time of resection, 212 underwent successful H. pylori eradication after resection, and 196 had persistent H. pylori infection after resection. Antral mucosal atrophy was present in 70% of patients at the time of resection and did not vary among groups during follow-up. Corpus atrophy was more common in those with persistent infection than in those with eradicated infection (P=0.015) or no infection (P<0.001). Intestinal metaplasia did not vary among groups during follow-up.
Metachronous GC occurred in 12.7% of patients who were negative for H. pylori infection, 9.2% with persistent infection, and 5.7% with eradicated infection. Among patients younger than 70 years, fewer metachronous cancers developed in those with eradicated infection than in those with persistent infection (P=0.018) or those who were negative for infection (P=0.001). Age, but not H. pylori status, was associated with a slight increased risk for metachronous cancers (hazard ratio, 1.06; 95% confidence interval, 1.00–1.12; P=0.045).
COMMENT: The authors conclude that H. pylori eradication might prevent progression of corpus atrophy and metachronous cancers in patients younger than 70 years of age. However, interpretation of this paper is limited by its retrospective nature and possible selection bias at a single center. The results for age are barely statistically significant and are probably clinically insignificant. Also, the H. pylori–negative group had the highest rate of metachronous cancers, casting doubt on the causative role of H. pylori.
CITATION(S): Han SJ et al. Long-term effects of Helicobacter pylori eradication on metachronous gastric cancer development. Gut Liver 2017 Oct 27; [e-pub].
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Obstet Gynecol 2017 Dec; 130:1338
Abortion, Cash, and Subsequent Contraceptive Use
Insurance coverage is key to preventing repeat abortions.
Most women seeking abortion services want to avoid early repeat pregnancy. To evaluate the role of insurance coverage on women's use of postabortion contraception, researchers analyzed data collected from some 19,700 women who had a first-trimester abortion at one of 28 California clinics that offered same-day initiation of all forms of reversible contraception.
Overall, 94% of women left the abortion clinic with a form of contraception (21% with a highly effective method). In adjusted analyses, compared with uninsured (“self-pay”) clients, low-income women who qualified for state-funded healthcare were more than 3 times as likely to initiate postabortion contraception, and more than twice as likely to receive a highly effective reversible method.
COMMENT: Postabortion use of highly effective reversible contraceptives such as intrauterine devices (IUDs) or subdermal implants has been shown to lower the likelihood of repeat abortion by two thirds (Contraception 2008; 78:143). Women who must pay out of pocket for abortion services can rarely afford the added expense of contraception. These findings are noteworthy because, in California, public funds are available for low-income women who need abortions and contraception; elsewhere in the U.S., discrepancies in uptake of contraception after abortion are probably even larger.
CITATION(S): Biggs MA et al. Role of insurance coverage in contraceptive use after abortion. Obstet Gynecol 2017 Dec; 130:1338.

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