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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
July 11, 2015

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Menopausal Hormone Therapy After Treatment for Cervical Cancer
Challenges to Optimal Local Therapy in Breast Cancer
U.S. Breast Cancer Screening Data lead to questions about the value
   of Mammography
Vaginal Wind and Pelvic Floor Disorders
Which SSRIs are safest in pregnancy? New findings may help guide treatment decisions
Medicare has proposed reimbursement to physicians for End-of-Life Conversations
Is Mild Thyroid Hormone Insufficiency during pregnancy associated with
   ADHD symptoms?
ARE you eating enough Fruits and Veggies? Most Americans aren't
Poor Health in adolescence affects education and employment in adulthood

MM: One of the most often asked questions that I receive is whether a woman can use hormones after a treatment or diagnosis of a sex organ related cancer. This study demonstrates that the answer may be "yes"! Most women in the United States who are receiving Hormone Therapy (HT) are receiving either estradiol or conjugated estrogens (Premarin). In Europe, the hormone, Estriol(E3) has been available for decades and it is certainly possible that this is the HT that many of the women studied received. Estriol(E3) is generally considered a much safer estrogen than either of the others typically administered and this may reflect the attitude of those in this Swedish study. In the United States, Estriol is only available from a compounding pharmacist.
Menopause 2015 Jun; 22:633
Menopausal Hormone Therapy After Treatment for Cervical Cancer
Swedish report shows low use of HT in women with early menopause arising from treatment for cervical malignancy.
Many women with cervical cancer are premenopausal at diagnosis, and bilateral salpingo-oophorectomy (BSO) and radiation therapy induce menopause. In this retrospective national cohort study, investigators identified Swedish women aged ≤45 treated for cervical cancer between 2005 and 2009 and assessed subsequent use of hormone therapy (HT) among those rendered menopausal by treatment.
Of  867 women treated for cervical cancer, 257 had menopause induced because of BSO or radiation therapy. In the 6- to 12-month interval following diagnosis, systemic HT or vaginal estrogen had been dispensed at least once to 67% (systemic) and 17% (vaginal) of these women; overall, 71% had received HT of any type at least once. Younger women were more likely to have received HT. However, less than half (46%) of women overall were dispensed HT at least 75% of the time during this interval (a proxy for ongoing HT use). In women age 22 to 29 at diagnosis, prevalence of ongoing HT use was approximately twice that in women aged 40 to 45. HT use declined with follow-up time, such that only one in five women maintained ongoing use 4.5 to 5 years after diagnosis.
Comment: Given that cervical neoplasia is not considered a hormone-responsive malignancy, professional guidelines (e.g., Obstet Gynecol 2002; 99:855) recommend HT for young cervical cancer survivors with induced menopause, as these women are at excess risk for osteoporosis, coronary or cerebrovascular disease, and cognitive decline. The global decline in HT use among the general menopausal population following initial publication of Women's Health Initiative findings in 2002 has probably contributed to the low prevalence of HT use among cervical cancer survivors. In these women with early menopause, HT's benefit–risk profile is likely to be more favorable than in women experiencing spontaneous natural menopause. In the absence of specific contraindications, HT is appropriate (and important) for young menopausal women, including those who have been treated for cervical cancer.
Citation(s): Everhov ÅH et al. Hormone therapy after uterine cervical cancer treatment: A Swedish population-based study. Menopause 2015 Jun; 22:633. (http://dx.doi.org/10.1097/GME.0000000000000357)

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MM: Breast conserving therapy is an option open to many women but those same women may not realize that when a portion of the breast is removed from a single side or even bi-laterally, the person becomes physically out of balance and can develop headaches, backaches and other physical conditions. This is an example of where a patient can benefit from a breast prosthetic and appropriate bra for that prosthetic. This is not merely an aesthetic approach. It is a health approach. additionally, Medicare and most private insurance will provide these prosthetics, balancers and bras on a regular schedule for weight changes or over specific time periods.
Contact Mark Drugs Roselle and The Rose Garden Boutique for more information.
JAMA Surg 2015 Jun 17
Challenges to Optimal Local Therapy in Breast Cancer
Obstacles to breast-conserving therapy include age, socioeconomic factors, and proximity to treatment centers.
Breast-conserving therapy (BCT) that combines lumpectomy and breast irradiation has been the preferred treatment for most women with early-stage breast cancer (EBC) since multiple randomized trials have shown equivalent survival with BCT compared with mastectomy. To examine recent trends in the use of BCT, investigators accessed the National Cancer Data Base to study more than 700,000 women treated for early-stage breast cancer between 1998 and 2011.
The use of BCT increased from 54.3% to 60.1% overall during this period. However, there were persistent and disturbing differences based on age, socioeconomic factors, and proximity to treatment centers. The use of BCT was greater in patients aged 52 to 61 years (62.8%) compared with younger patients (57.8%) and in women with more education (61.7%). Rates of BCT were lower in patients without insurance (49.3%) compared with those with private insurance (62.3%) and with the lowest median income (51.1%). BCT was more commonly used in the Northeast than in the South, at academic centers, and in close proximity to treatment centers.
Comment: These findings, put into context by an accompanying editorial, point to the pragmatic issues of daily life that can be obstacles for some patients to receive BCT. Patients with low income, lack of family support, childcare issues, or lack of reliable transportation may make the choice of mastectomy a necessity.
Citation(s):Lautner M et al. Disparities in the use of breast-conserving therapy among patients with early-stage breast cancer. JAMA Surg 2015 Jun 17; [e-pub]. (http://dx.doi.org/10.1001/jamasurg.2015.1102)
Newman LA.Ongoing consequences of disparities in breast cancer surgery. JAMA Surg 2015 Jun 17; [e-pub].
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MM: The question of value of mammography has been raised in the past and most vociferously by my dear friend, mentor and co-host, Dr Mayer Eisenstein, but this study brings up an alarming statistic that although mammography has been associated with a higher rate of small-cancer diagnoses, a higher rate of large-cancer diagnoses there were no fewer cancer-specific deaths. This once again brings in the question of the actual value of mammography. The problem still exists, however, do we have anything that is better and that will save lives as that is the true measurement of a successful practice?
JAMA Intern Med 2015 Jul 6
U.S. Breast Cancer Screening Data Lead to Questions About the
Value of Mammography

Higher uptake of mammography is associated with more cancer diagnoses but not with lower cancer-specific mortality.
Despite some trials showing lower breast cancer–related mortality associated with screening mammography, controversy about its benefit persists, because most trials were conducted decades ago, and screening practices and treatments have changed. Researchers used data on 16 million women (age, ≥40) from 547 U.S. counties to identify the percentage who had undergone mammography in 1999 or 2000 (range, 39%–78% across counties). In these same counties, about 53,000 women were diagnosed with breast cancer in 2000 and were followed for at least 10 years.
Significant correlation was noted between the proportion of county residents screened by mammography and the rate of breast cancer diagnoses, with a 10–percentage-point increase in screening associated with a 16% increase in breast cancer diagnoses. Mammography use was associated significantly with the diagnosis rate of both small (≤2 cm) and large (>2 cm) cancers. No association was found between rate of mammography and 10-year breast cancer–associated mortality.
Comment: An ideal screening program should lead to detection of more small cancers and fewer large cancers over time and should be associated with lower cancer-specific mortality. In this study, mammography was associated with a higher rate of small-cancer diagnoses, but also with a higher rate of large-cancer diagnoses and no fewer cancer-specific deaths. Although several explanations for these epidemiological findings are possible, the most compelling is that widespread mammography leads to overdiagnosis of clinically unimportant cancers that have no effect on mortality. According to editorialists, these findings should encourage clinicians who are counseling patients about mammography to be more explicit about overdiagnosis risk.
Citation(s):Harding C et al. Breast cancer screening, incidence, and mortality across US counties. JAMA Intern Med 2015 Jul 6; [e-pub].
Elmore JG and Etzioni R.Effect of screening mammography on cancer incidence and mortality. JAMA Intern Med 2015 Jul 6; [e-pub].
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MM: An otherwise annoying or inconvenient symptom may indicate a more serious condition. This is often the way that serious medical conditions are discovered so the lesson to learn from this article is you are not a hypochondriac if you are listening to your body and discover that something is strange or out of order. Vaginal wind may simply be a dysbiosis of the area or some other dysfunction locally. But, it may also be a rectovaginal fistula that has the potential of being life threatening.
Obstet Gynecol 2015 Jul; 126:136
Vaginal Wind and Pelvic Floor Disorders
Audible passage of air from the vagina is a common, sometimes bothersome, consequence of pelvic dysfunction.
The prevalence and consequences of vaginal wind — audible passage of vaginal air — have not been well characterized. Investigators queried 110 women (54% with pelvic organ prolapse) seen at a clinic specializing in pelvic floor disorders.
Overall, 69% of participants reported vaginal wind occurring a mean of twice weekly. Higher prevalence was associated with younger age, premenopausal status, and longer vaginal length, but not with pelvic organ prolapse. Vaginal wind occurred most commonly during intercourse, other sexual activities, and exercise. Women who experienced this event more often found it more bothersome, although fewer than one quarter reported a negative effect on sexual satisfaction. In a subset of women who underwent pelvic reconstructive surgery, 65% of those with vaginal wind prior to surgery reported resolution.
Comment: Vaginal wind was commonplace in this population of women with pelvic floor dysfunction, but it's unclear whether the phenomenon is as common among women who are not seeking specialty care. For most respondents, this symptom had small effects on quality of life. If further studies in a general population confirm the frequency and degree of bother suggested here, perhaps routinely asking patients about vaginal wind would be reasonable. Because passing gas through the vagina is a cardinal sign of a rectovaginal fistula, a careful pelvic examination is warranted in women with this complaint.
Citation(s):Miranne JM et al. Prevalence and resolution of auditory passage of vaginal air in women with pelvic floor disorders. Obstet Gynecol 2015 Jul; 126:136. (http://dx.doi.org/10.1097/AOG.0000000000000921)
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MM: It is important to have information when a decision needs to be made concerning the risks and benefits of certain medications and pregnancy. This information may be a helpful guideline to patients and clinicians in answering these very important questions.
Which SSRIs Are Safest in Pregnancy?
New Findings May Help Guide Treatment Decisions

By Amy Orciari Herman, Edited by Susan Sadoughi, MD, and Richard Saitz, MD, MPH, FACP, FASAM
A new study in the BMJ may help guide clinicians' and patients' choice of antidepressant in pregnancy.
Using data from a large U.S. study, researchers identified nearly 18,000 birth defect cases and 10,000 controls. The mothers of 660 cases and 300 controls had used selective serotonin reuptake inhibitors (SSRIs) in the month before or first 3 months of pregnancy.
Among the findings:

The authors note that if the associations observed are causal, the absolute risks are small. For example, for babies exposed to paroxetine, the absolute risk for anencephaly would increase from 2 to 7 per 10,000.Allison Bryant, associate editor with NEJM Journal Watch Women's Health, said: "Any risk ... cannot yet be entirely separated from risks attributed to the underlying condition. Women and their providers should keep this in mind when considering the risk-benefit balance for treating maternal depression."
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MMM: It is a sad commentary that recognition of value through monetary reimbursement can be the deciding factor for humanistic treatments and communications. It is unfortunate that clinicians are so harried and busy that unless they receive remuneration for these discussions they may not feel that they can financially afford to provide these services to patients and their loved ones. This new approach may relieve a great deal of psychological suffering to patients and their families.
Medicare Has Proposed Reimbursement to Physicians for End-of-Life Conversations
By the Editors
Medicare has proposed a rule that would allow clinicians to be reimbursed for providing advance care planning for seniors.
This service includes early counseling for patients to decide the type of care they prefer both before an illness progresses and during treatment. Medicare currently covers this counseling only when patients first enroll, a time when they may not need or want end-of-life counseling.
The change is expected to take effect Jan. 1.
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MM: The commentary section of this article is short sighted in that it looks at the only treatment for gestational hypothyrioidism is thyroid hormone replacement. It fails to acknowledge other supportive approaches that can address the starting point of a hypothyroid situation. Things such as diet, nutrition, hydration, selenium, zinc, iodine and probiotics and digestive enzymes to stabilize the gut and immune system may be the proper recommendations and guidelines for pregnant moms to "treat" or prevent the condition in the first place.
JAMA Pediatr 2015 Jul 6
Is Mild Thyroid Hormone Insufficiency during Pregnancy associated
with ADHD Symptoms?
The effect was modest, but the study should be interpreted with caution.
Hypothyroxinemia (a mild decrease in free thyroid hormone without an increase in thyrotropin levels) occurs transiently in some women during pregnancy. This condition is associated with mild decrease in neurocognitive functions in children. The effect on behavior is uncertain.
In a population-based birth cohort study in the Netherlands, researchers studied 3873 mother-child pairs to determine the behavioral effect of transient maternal hypothyroxinemia during pregnancy. Thyroid function was measured at the beginning of the second trimester (mean, 13.6 weeks). Attention-deficit/hyperactivity disorder (ADHD) symptoms in children were assessed by the Conners' Parent Rating Scale when the children were 8 years old.
Hypothyroxinemia occurred in 127 mothers. ADHD symptom scores in children exposed to gestational hypothyroxinemia were 7% higher than in unexposed children (P=0.04) when adjusted for maternal age, education, and income. Results were similar after exclusion of mothers with elevated thyroid peroxidase antibodies. There was no association between maternal hypothyroxinemia and oppositional behavior scores on the Conners' Scale.
Comment: I am cautious in interpreting the clinical significance of this study. First, the effect of maternal hypothyroxinemia was modest. Second, the determination of ADHD symptoms from parent report alone is not sufficient for a diagnosis of ADHD. Teacher reports, duration of symptoms, and knowing about a child's functional impairments would have strengthened the study. Third, measurement of thyroid hormone was performed at only one point during pregnancy. Mild low levels of thyroid hormone are known to be transient during gestation. Would frequent monitoring of changes in thyroid levels during pregnancy have produced the same results? We cannot conclude from this study that prescribing thyroid hormone during pregnancy in women with transient hypothyroxinemia has a behavioral benefit for the child.
Citation(s):Modesto T et al. Maternal mild thyroid hormone insufficiency in early pregnancy and attention-deficit/hyperactivity disorder symptoms in children. JAMA Pediatr 2015 Jul 6; [e-pub].
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MM: It's been well publicized that the predominant fruits and veggies that we eat as Americans are Tomatoes as Ketchup, Corn as high fructose corn syrup and other additives and sweeteners and the Potato as french fries. This is a sad commentary on our Standard American Diet (SAD). I have heard too many times the comment from adults, "I don't eat anything GREEN." This directly reflects our nationalistic aversion to fresh or frozen fruits and vegetables and needs to show a reversal in order to stay many of the chronic illnesses that we experience ranging from diabetes, cancer, heart disease, obesity and an array of autoimmune diseases and conditions. Additionally, if we are truly concerned with the health and well-being of the "next generation" then we must teach by example.
ARE You eating Enough Fruits and Veggies? Most Americans Aren't
By Cara Adler, Edited by André Sofair, MD, MPH, and William E. Chavey, MD, MS
More than 85% of adults in the U.S. do not eat the recommended amounts of fruits and vegetables, according to an MMWR analysis of national survey data from 2013.
Roughly 13% of respondents met USDA intake recommendations for fruit (1.5–2 cups for those with less than 30 minutes of physical activity daily) and 9% for vegetables (2–3 cups daily). Percentages ranged from 8% in Tennessee to 18% in California for fruit, and from 6% in Mississippi to 13% in California for vegetables.
The authors note that the survey did not include consumption of fried potatoes or juice that is not 100% fruit.
Veggie Rec's:    http://www.choosemyplate.gov/printpages/MyPlateFoodGroups/Vegetables/food-groups.vegetables-amount.pdf
Fruits rec's:      
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MM: We all want our children to be healthy and happy but when they are not the problems may extend well into adulthood. This is a reason that, as parents and grandparents, we may need to be more supportive for a longer period of time if our kids experience longitudinal illnesses.
Pediatrics 2015 Jul; 136:128
Poor Health in Adolescence Affects Education and Employment in Adulthood
A systematic review finds stronger evidence for a negative impact of mental health than physical health problems.
The extent to which chronic health conditions during adolescence affect educational achievement and employment in adulthood is not well studied. Investigators conducted a systematic review to address the issue. They identified 27 longitudinal case-controlled studies (15 conducted in the U.S.) that included 70 analyses of potential associations between chronic conditions and education and employment outcomes.
The mean age of adolescents with chronic conditions was 14.6 years (range, 10.5–18) and the mean age at adult follow-up was 23.1 (range, 18.5–35). Of the 70 analyses, 61 showed poorer educational and employment outcomes in adolescents with chronic health conditions compared with healthy controls.

Comment: The authors note that some of these findings might be attributable to confounding socioeconomic variables, but they also propose direct causal mechanisms by which poor health affects outcomes. These include increased school absenteeism, deficits in academic abilities (e.g., for those with ADHD), social isolation, and insufficient time left for school and work. Maximizing adult socioeconomic outcomes requires addressing chronic health conditions (especially mental health problems) during adolescence.
Citation(s):Hale DR et al. Adolescent health and adult education and employment: A systematic review. Pediatrics 2015 Jul; 136:128.

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