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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
February 17, 2018

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Hormone Therapy to Prevent Depression in Menopausal Women?
Resolving the Paradox of Obesity and Risk for Cervical Cancer
Does Curbing Out-of-Pocket Costs Encourage Women to Access
   Mammography Screening?
Balance Training for Multiple Sclerosis
Thalamic Atrophy in Multiple Sclerosis
Improved College Graduation Rates Through Early Education Enrichment
Why Parents Should Not Provide Alcohol to Adolescents
Pot Smoking Is Still Bad for Teenage Mental Health
Choosing Wisely: What Not to Do in Pediatric Orthopedics
How Well Does Urinalysis Perform in Diagnosing Urinary Tract Infection in Young Infants?
What If Your Peers Don't See Your Gender Identity As You Do?

JAMA Psychiatry 2018 Jan 10
Hormone Therapy to Prevent Depression in Menopausal Women?
We need to be very cautious in interpreting the conclusions of this study.
Hormone therapy (HT) has been theorized to attenuate the increased risk for depression around menopause. In a 1-year trial, 172 euthymic women (mean age, 51) were randomized to transdermal estradiol plus oral progesterone or to placebo.
Participants rated their depression symptoms on a scale seven times during the study. Significantly more placebo recipients than HT recipients had scores at least once at a level deemed to be “potential clinical depression.” The placebo group had significantly more visits with this cutoff score and significantly higher mean scores (by ≈1.5 points) at 6 and 12 months. Results favored active treatment more clearly among women with recent stressful life events and in early than in late perimenopause or actual menopause. Vasomotor symptoms or previous histories of depression or abuse did not explain the results.
COMMENT: HT improves insomnia and hot flashes, which can aggravate depression. Furthermore, estradiol might (or might not) improve symptoms in women with perimenopause-associated depression. However, without information about persistence of these symptoms and self-rated depressive symptoms, impairment, distress, and actual depressive illness, one cannot know whether HT prevented depressive episodes or even persistent bothersome depressive symptoms in this trial. Depression tends to recur around menopause, but a previous depression history did not influence results, suggesting that HT did not benefit actual depressive disorders. As editorialists note, the estradiol dose was higher and the progesterone dose was lower than current recommendations. Additionally, the U.S. Preventive Services Task Force recently found “no net benefit” of HT for primary prevention of most chronic disorders that appear in menopause; “convincing evidence” of risks such as invasive breast cancer, venous thromboembolism, and cardiovascular disease; and insufficient evidence of differential benefit at different menopausal phases (JAMA 2017; 318:2224). HT to prevent depression during menopause in women not known to be at risk requires much more study.
CITATION(S): Gordon JL et al. Efficacy of transdermal estradiol and micronized progesterone in the prevention of depressive symptoms in the menopause transition: A randomized clinical trial. JAMA Psychiatry 2018 Jan 10; [e-pub].
Joffe H and Hickey M. Should hormone therapy be used to prevent depressive symptoms during the menopause transition? JAMA Psychiatry 2018 Jan 10; [e-pub].
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J Clin Oncol 2018 Jan 22
Resolving the Paradox of Obesity and Risk for Cervical Cancer
Study suggests underdiagnosis of preinvasive disease is the root of the problem.
Obesity's prevalence in the U.S. has tripled in the last 30 years. Has this trend affected screening for and prevalence of cervical cancer? Investigators at Kaiser Permanente of Northern California conducted a retrospective cohort study to assess the association between body-mass index (BMI) and cervical cancer screening outcomes. The Kaiser system implemented triennial cytology and human papillomavirus cotesting in 2003 for women aged ≥30; this study involved some 944,000 women (age range, 30–49) screened for cervical precancer (cervical intraepithelial neoplasia grade 3 and adenocarcinoma in situ) and cervical cancer (squamous cell carcinoma, adenocarcinoma, and microinvasive cancer) from 2003 through 2015. Overall, 40% of participants were white and 31% were obese (BMI, 30–80 kg/m2). Mean follow-up was 4.4 years; mean number of screening tests was 2.9 regardless of BMI.
Cervical precancer was diagnosed in 0.48% of participants and cervical cancer in 0.05%. Risk for precancer was highest among women with BMI <25 and fell as weight increased, with the lowest 5-year cumulative risk in obese women. In contrast, risk for cancer rose with increasing BMI (P for trend <0.001 for both outcomes). The authors estimated that, if screening for precancer were as effective in obese women as in those with lower BMI, 20% of cancers could have been prevented.
COMMENT: In this patient population, differential adherence to screening does not explain the study's findings. If obesity is a risk factor for invasive cancer, it should also raise risk for precancer. Consequently, the apparent paradoxical decrease in risk for precancer among higher-BMI women suggests screening for cervical precancer is less effective in such women. I agree with the authors that adequate visualization and sampling of the cervix is more challenging in higher-BMI women, and that this may explain these findings. Using an appropriately sized vaginal speculum and adequately separating the vaginal walls may improve efficacy of cervical cancer screening in our increasingly obese patient population.
CITATION(S): Clarke MA et al. Epidemiologic evidence that excess body weight increases risk of cervical cancer by decreased detection of precancer. J Clin Oncol 2018 Jan 22; [e-pub].
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N Engl J Med 2018 Jan 18; 378:262
Does Curbing Out-of-Pocket Costs Encourage Women to Access
Mammography Screening?

Evidently so: The Affordable Care Act's elimination of cost sharing was associated with higher biennial screening rates among older women.
Even for individuals with health insurance, incurring out-of-pocket costs diminishes use of health care services. From 2009 through 2011, passage of the Affordable Care Act (ACA) eliminated cost sharing (i.e., copayments) for screening mammography among women enrolled in Medicare Advantage plans. Now, investigators have assessed rates of biennial screening mammography in women aged 65 to 74 (a population for which the U.S. Preventive Services Task Force recommends biennial screening) who were enrolled in plans that initially required, then eliminated, cost sharing in accord with the ACA (intervention plans) compared with plans that fully covered mammograms before and after the ACA directive (control plans). Characteristics of women enrolled in either type of plan were similar (mean age, 68; 9% black; 15% below poverty level).
For women covered by intervention plans, rates of biennial screening increased from 60% to 65% during the 2-year periods before and after cost sharing was eliminated. For women with control plans, rates of screening were 73% before and after the ACA mandate.
COMMENT: This report adds to earlier findings that older women's tendency to access mammography is susceptible to out-of-pocket cost. Results such as these predict that, if the ACA is repealed, likelihood of screening mammography will decline among such women.
CITATION(S): Trivedi AN et al. Elimination of cost sharing for screening mammography in Medicare Advantage plans. N Engl J Med 2018 Jan 18; 378:262.
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Neurology 2018 Jan 31
Balance Training for Multiple Sclerosis
Dizziness and disequilibrium were reduced after a specialized 14-week rehabilitation program.
Patients with multiple sclerosis (MS) have numerous challenging symptoms with limited pharmacologic options, including impaired balance, dizziness, blurred dynamic vision, and fatigue. Investigators tested an exercise program that specifically addresses sensory/motor integration, the Balance and Eye Movement Exercises for People with Multiple Sclerosis (BEEMS) program, in patients with such symptoms. Eighty-eight patients were recruited for this randomized, controlled trial. The 16-week protocol included a 2-week baseline, 6 weeks of therapy administered twice per week with daily home exercises (phase 1), and an additional 8 weeks of supervised sessions once per week with daily home exercises (phase 2).
More than 85% of participants in each treatment group completed both phases. The computerized dynamic posturography–sensory organization test composite score was improved significantly more in BEEMS than in control patients at 6 weeks (the primary outcome; 4.89-point difference) and 14 weeks (8.32-point difference). Those with brainstem or cerebellar lesions, as determined either by MRI or neurologic exam, appeared to improve more than those without brainstem or cerebellar findings at 6 weeks (5.26-point difference), but this difference was not sustained at 14 weeks. Additional endpoints of fatigue and mental and physical quality of life improved more with BEEMS.
COMMENT: Twenty supervised sessions in a vestibular rehabilitation program, with daily home exercises, had positive benefits on balance, quality of life, and fatigue in patients with MS. The effect was seen with as few as 12 sessions and increased even further with an additional 8 sessions. Although outcomes did not differ at 14 weeks between those with and those without brainstem or cerebellar findings, patients with such findings seemed to improve even with 12 sessions. This type of program could be a welcome addition to your local rehabilitation program.
CITATION(S): Herbert JR et al. Efficacy of Balance and Eye-Movement Exercises for Persons with Multiple Sclerosis (BEEMS). Neurology 2018 Jan 31; [e-pub].
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Ann Neurol d 2018 Jan 12
Thalamic Atrophy in Multiple Sclerosis
Thalamic volume decline begins early and progresses steadily, regardless of MS subtype.
Thalamic atrophy is an early imaging feature of multiple sclerosis (MS) and is thought to reflect neurodegenerative processes.
To examine the evolution of thalamic atrophy in MS, investigators conducted a prospective longitudinal study involving 520 patients with relapse-onset MS and 81 healthy controls who received annual MRI brain scans. MS patients received 2485 scans during a mean follow-up of 4.1 years; controls received 147 scans during a mean follow-up of 1.3 years.
Results were as follows:
·         The annual thalamic volume loss from baseline was significantly greater in MS patients than in controls (−0.71% vs. −0.28%).
·         A linear decline in thalamic volume was seen in each 5-year epoch during a disease duration of 20 years.
·         The annual thalamic volume loss by MS subtype was −0.58% for clinically isolated syndrome, −0.74% for relapsing remitting MS, and −0.59% for secondary progressive MS.
·         Lower thalamic volume at baseline correlated modestly with worse baseline disability and functional measures of cognition, ambulation, and upper extremity function (correlations ranged from 0.15 to 0.37).
·         Thalamic volume atrophy correlated moderately with whole brain volume (r=0.6 over 2 years).
COMMENT: Thalamic atrophy begins early and has a relatively steady rate of decline across MS disease duration, regardless of disease subtype. This finding suggests that the degenerative process of MS starts early and does not accelerate as patients transition to secondary progressive MS. Thalamic atrophy is more sensitive to change compared with whole brain volume and may be a better surrogate for shorter clinical trials of neuroprotective agents.
Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.
CITATION(S): Azevedo CJ et al. Thalamic atrophy in MS: An MRI marker of neurodegeneration throughout disease. Ann Neurol 2018 Jan 12; [e-pub].
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JAMA Pediatr 2018 Jan 29
Improved College Graduation Rates Through Early Education Enrichment
Positive effects of a preschool-to-third-grade program for underserved children were evident 30 years later in higher postsecondary education rates.
Greater educational attainment predicts better outcomes in almost every aspect of health, making it an important public health objective. In the current study, researchers examined whether an early childhood educational enrichment program can influence rates of postsecondary degree completion into participants' thirties.
The program was developed in the 1980s as a large-scale, school-based, multicomponent, early-childhood intervention in high-poverty neighborhoods of Chicago. It provided high-quality educational enrichment to nearly 1000 children (93% black, 7% Hispanic) in preschool through third grade and featured reduced class sizes, family support services including parent involvement at school and home visits, and comprehensive nutritional and health supports.
When surveyed at age 35, those with longer participation in the CPC program showed higher rates of educational attainment, from high school graduation to advanced degrees. For example, compared with children participating for <4 years, those who participated for 4 to 6 years showed significantly better outcomes for:
·         High school graduation: 60% vs. 50%
·         Years of education: 13.0 vs. 12.5
·         College attendance: 63% vs. 56%
·         Associate degree or higher: 19% vs. 13%
·         Bachelor's degree or higher: 14% vs. 8%
COMMENT: Pediatric providers can play a role in improving the college graduation rates of low-income children. When possible, it is helpful to steer families towards schools that have an educational enrichment program or more parent support, as these were important components of this early childhood educational intervention. Local schools may also list statistics such as class sizes and enrichment opportunities on their websites. Although increases in degree completion rates in this study might seem small, only 30% of Americans complete a four-year degree, so these effects are rather substantial.
CITATION(S): Reynolds AJ et al. A multicomponent, preschool to third grade preventive intervention and educational attainment at 35 years of age. JAMA Pediatr 2018 Jan 29; [e-pub].
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Lancet Public Health 2018 Jan 25 2018 Jan 29
Why Parents Should Not Provide Alcohol to Adolescents
Doing so increases the risk for subsequent alcohol-related problems.
To determine if parental provision of alcohol is associated with reduced risk for alcohol-related harms, investigators conducted a longitudinal study of 1927 adolescents from secondary schools in three Australian cities (mean age, 13; 45% female). Adolescents and their parents independently completed surveys annually for 6 years about source of alcohol supply and alcohol-related outcomes. At each survey, adolescents were classified as having no alcohol supply or supply from parents only, parents plus other source, or other source only. Analyses were controlled for potential confounders, such as parental alcohol consumption, family alcohol problems, and having an older sibling.
Compared with adolescents reporting no supply, those reporting parent-only supply were significantly more likely at the next survey to report binge drinking (odds ratio, 2.6), any alcohol-related harms (OR 2.5), and alcohol use disorder (OR, 2.5). Odds were even higher for adolescents whose supply was from parents plus other source or other source only. Regardless of source, there was a dose-response relationship between number of years of alcohol provision and alcohol-related harms. Parental supply was associated with doubled odds of supply from other sources at the next survey.
COMMENT: In a recent systematic review (Int J Environ Res Public Health 2017; 14:287), the authors (including four from the current study) concluded that parental supply of alcohol is associated with increased risk for alcohol-related harms but cautioned that the studies had significant flaws (e.g., different measures of exposure [sips versus whole drinks], publication bias). The current study avoids many of those flaws yet reaches the same conclusion, which is also consistent with conclusions from three U.S. studies. Based on current evidence, parents should not supply alcohol to their adolescent children.
CITATION(S): Mattick RP et al. Association of parental supply of alcohol with adolescent drinking, alcohol-related harms, and alcohol use disorder symptoms: A prospective cohort study. Lancet Public Health 2018 Jan 25; [e-pub].
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JAMA Psychiatry 2018 Jan 17
Pot Smoking Is Still Bad for Teenage Mental Health
A longitudinal study distinguishes between the effects of using marijuana and smoking cigarettes.
Cannabis use is usually accompanied by cigarette smoking, and both tobacco and cannabis have been associated with psychosis; but whether the link to psychosis is attributable to marijuana or tobacco is unknown. Researchers examined longitudinal data on 5300 U.K. adolescents who repeatedly self-reported their cigarette and cannabis use between ages 14 and 19 and were assessed on structured interviews for psychotic experiences at ages 12 and 18.
Compared with no use of cigarettes or cannabis (66% of the sample), both cigarette use (without cannabis use) beginning only early in adolescence and marijuana use (typically with cigarette use) beginning either early or late in adolescence were significantly associated with psychotic symptoms at age 18. Adjusting for many variables (e.g., family substance-use history, IQ, childhood trauma, and alcohol use) did not alter these results. However, after adjustment for confounding factors (sex, maternal education, mother's prenatal smoking, and child's emotional and behavioral problems), tobacco was no longer associated with later psychotic symptoms, but the association with early- and later-onset cannabis use (adjusted ORs, 3.70 and 2.97) remained significant. There was little evidence that psychotic experiences at age 12 predicted later cannabis use.
COMMENT: That the association of later psychosis with cannabis use (but not cigarette use) survived adjustment of intermediate variables suggests that it is marijuana (and not nicotine or other elements of smoking that often accompany cannabis use) that predisposes to psychosis. The lack of evidence that early psychosis predicts later cannabis use contradicts the theory that the latter is a form of self-treatment for the former. Despite widespread acceptance of marijuana use, it should be discouraged by clinicians treating patients who are vulnerable to psychosis.
CITATION(S): Jones HJ et al. Association of combined patterns of tobacco and cannabis use in adolescence with psychotic experiences. JAMA Psychiatry 2018 Jan 17; [e-pub].
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Choosing Wisely: What Not to Do in Pediatric Orthopedics
By Kelly Young
The American Academy of Pediatrics-Section on Orthopaedics and the Pediatric Orthopaedic Society of North America have released their list of five practices to reconsider as part of the Choosing Wisely campaign. Among them:

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Pediatrics d 2018 Jan 16
How Well Does Urinalysis Perform in Diagnosing Urinary Tract Infection
in Young Infants?

Urinalysis had high sensitivity and specificity for UTI, especially in infants with concomitant bacteremia.
Urinalysis has shown variable performance as a screening test for urinary tract infection (UTI) in young febrile infants, particularly those aged <60 days. The current guidelines from the American Academy of Pediatrics define UTI for infants aged >2 months as the presence of pyuria and a urinary bacterial colony count of >50,000 colony-forming units (CFUs)/mL. Criteria for infants younger than 2 months are not established.
As part of a larger cross-sectional study in febrile infants aged ≤60 days presenting to emergency departments across the U.S., researchers assessed the performance of urinalysis in detecting UTI (defined as a urine culture obtained by catheterization with growth ≥50,000 CFUs/mL). Results were as follows:
·         In over 4000 infants tested, 7% had a UTI, of which 9% were bacteremic.
·         Of the urinalysis components, leukocyte esterase was the most sensitive (92%) and specific (96%) for predicting UTI.
·         The presence of nitrates had low sensitivity (38%) but high specificity (99%).
·         Pyuria (>5 white blood cells/high-power field) was also a good predictor (82% sensitive, 94% specific).
·         Performance of the aggregate urinalysis result (positive if any component is positive) was better in infants who had UTI associated with bacteremia, and the presence of leukocyte esterase had a sensitivity of 100% for UTI with bacteremia.
COMMENT: Counter to the teaching that urinalysis is not predictive for diagnosing UTI in very young infants, these results demonstrate high sensitivity and specificity of urinalysis, particularly the aggregate test (presence of any leukocyte esterase, nitrate, or pyuria), and especially in infants with bacteremic UTI. When interpreting urine culture, especially those with lower colony count (i.e., 10,000–15,000), clinicians should also consider the urinalysis component findings.
CITATION(S): Tzimenatos L et al. Accuracy of the urinalysis for urinary tract infections in febrile infants 60 days and younger. Pediatrics 2018 Jan 16; [e-pub].
Roberts KB and Wald ER. The diagnosis of UTI: Colony count criteria revisited. Pediatrics 2018 Jan 16; [e-pub].
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Pediatrics 2018 Feb 5
What If Your Peers Don't See Your Gender Identity As You Do?
Among transgender/gender nonconforming youth, those whose gender presentation was perceived by peers as less than fully congruent with their birth-assigned sex reported lower levels of physical and mental health.
To provide a more nuanced examination of health disparities for transgender/gender nonconforming youth (TGNC), investigators analyzed data from the 2016 Minnesota Student Survey (81,000 9th and 11th grade students). Students reported their biologic sex; whether they considered themselves transgender, gender queer, genderfluid or unsure (grouped together for analysis as TGNC); and how others at school viewed their gender expression (very or mostly feminine, somewhat feminine, equally feminine/masculine, somewhat masculine, very masculine).
Almost 3% of students described themselves as TGNC. Compared to cisgender peers, TGNC students were significantly more likely to report long-term physical health problems, long-term mental health problems, staying at home sick in the past 30 days, and visiting a nurse in the past 30 days. TGNC students were significantly less likely to report having a preventive medical or dental check-up in the last year. Of TGNC students assigned a male gender at birth, 80% perceived that peers viewed their gender expression as other than very masculine; this 80% rated their physical and mental health as poorer than the 20% who perceived that others viewed them as very masculine. Among TGNC students assigned female gender at birth, 88% perceived that peers viewed their gender expression as other than very feminine; these 88% reported lower levels of physical and mental health than the 12% who perceived that others viewed them as very feminine.
COMMENT: A possible explanation for these findings is that youth who are perceived by peers as having a gender expression that is less than fully congruent with their birth-assigned sex experience discrimination from or feel less than fully accepted by peers. This same dynamic may apply when seeking healthcare. As providers, we can make every effort to create a welcoming office environment for TGNC youth and frame our interactions with them in ways that affirm the expression/definition of gender identity that is most comfortable for them.
CITATION(S): Rider GN et al. Health and care utilization of transgender and gender nonconforming youth: A population-based study. Pediatrics 2018 Feb 5; [e-pub].

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