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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
December 9, 2017

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Low Accuracy of Clinician Suspicion for Lyme Disease
Does Physician Denial of Patient Requests Affect Patient Satisfaction?
High Rates of Marijuana Use in Cancer Patients
Healthy Life, Healthy Brain: Lifestyle Factors and the Dementia Process
Risk Factors for Gastric Cancer in the United States
Anemia in the Elderly: A Review
Managing Seasonal Allergic Rhinitis with Medications
Does Use of Hormonal Contraception Affect Risk for Breast Cancer?

Pediatrics 2017 Nov 24
Low Accuracy of Clinician Suspicion for Lyme Disease
Clinicians tend to overdiagnose and underdiagnose Lyme disease, making it prudent to confirm the disease with serologic testing.
To assess the accuracy of clinician's suspicion of Lyme disease, researchers followed a cohort of children aged 1 to 21 years undergoing evaluation for Lyme disease at five emergency departments in endemic areas.
Children were eligible if they had an erythema migrans lesion (Bull's-eye Rash) or the clinician ordered Lyme disease serology (blood/serum testing). Before serology results were available, the clinician estimated the likelihood of Lyme disease on a 10-point scale. The disease was diagnosed if the child had positive serology or clinical signs compatible with Lyme disease: erythema migrans lesion (Bull's eye rash) ; early disseminated disease (cranial neuritis, headache and/or neck pain or stiffness, electrocardiogram changes consistent with carditis); or late disease (arthritis). Patients with only nonspecific symptoms, such as fever or fatigue, were classified as not having Lyme disease, regardless of serologic results.
Of 1021 children enrolled (median age, 9 years), 4% presented with a single EM lesion, 47% with early disseminated disease, 46% with late disease, and 3% with nonspecific symptoms. Overall, 238 children (23%) had Lyme disease. For patients without an erythema migrans lesion, clinician suspicion had minimal accuracy for the diagnosis (area under the receiver operating characteristics curve, 0.75). Of 554 children judged “unlikely” to have Lyme disease (score of 1–3), 12% had the disease, and of 127 children judged “very likely” to have Lyme disease (score of 8–10), 31% did not have the disease.
COMMENT: A single erythema migrans lesion — present in only 4% of cases in this study — is all that is needed to diagnose Lyme disease, making serologic testing unnecessary. This study shows that clinician suspicion results in both overdiagnosis and underdiagnosis of Lyme disease. My recommendation is to examine patients carefully for the presence of erythema migrans lesions (sometimes they are hidden under hair!), and in patients without lesions who have Lyme-compatible signs, send samples for serologic testing to confirm your suspicion.
CITATION(S): Nigrovic LE et al. Accuracy of clinician suspicion of Lyme disease in the emergency department. Pediatrics 2017 Nov 24; [e-pub].
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JAMA Intern Med 2017 Nov 27
Does Physician Denial of Patient Requests Affect Patient Satisfaction?
Denying requests for pain medications, referrals, and laboratory tests was associated with lower patient satisfaction.
Many physicians are concerned that denying patients' requests for various services or treatments might lessen patient satisfaction, which can have consequences for physician ratings and income. In this study, investigators examined 1319 visits made by 1141 adults (mean age, 46; 68% women) to 51 physicians in an academic medical center clinic in northern California. Validated questionnaires administered to patients immediately after the visits were used to assess patient requests made to physicians and patient satisfaction with the visits.
Patients reported that they made 1691 requests, and that 1441 (85%) were fulfilled. Most requests were for laboratory tests (34%), referrals (21%), pain medications (20%), and other new medications (nonpain, nonantibiotic; 20%), or for antibiotics, radiology tests, and other tests (≈10% each). Compared with visits in which requests for laboratory tests, referrals, pain medications, and other new medications were fulfilled, those in which such requests were denied were associated significantly with lower patient satisfaction.
COMMENT: These results are exploratory but suggest that a clinical practice style of “choosing wisely” and avoiding tests and medications that are deemed unnecessary might have unintended consequences.
Jerant A et al. Association of clinician denial of patient requests with patient satisfaction. JAMA Intern Med 2017 Nov 27; [e-pub].
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Cancer 2017 Nov 15; 123:4488.
High Rates of Marijuana Use in Cancer Patients
In a state with legalized marijuana, 24% of patients had used marijuana in the last year, primarily for pain, nausea, stress, anxiety, and depression.
Medicinal use of marijuana is increasingly common in the U.S. despite limited evidence of efficacy and ambiguous boundaries between medicinal and recreational use (NEJM JW Psychiatry Feb 2017 and JAMA2017; 317:209). In this survey-based study, researchers examined use in outpatients from a Seattle cancer center after state legalization of marijuana.
Of 2737 patients approached, 926 responded (34%; median age, 58; >50% college-educated; 66% with solid tumors). About 66% had a history of lifetime marijuana use, and 24% were “active users.” Although 74% preferred to learn about marijuana from their cancer team, most got their information elsewhere (e.g., friends, websites, or other patients).
Among active users, two thirds used marijuana before cancer diagnosis. Three quarters consumed weekly; over half consumed daily. Intake was by inhalation, edibles, or both. Almost two thirds had told their physicians about their marijuana use. They used marijuana largely to treat pain, nausea, and appetite (75%) or cope with stress, anxiety, and depression (63%). About 26% said they used it to help treat their cancer.
COMMENT: The rate of marijuana use was surprisingly high in this group of cancer patients; the findings suggest that clinicians should routinely ask our patients with chronic illness about marijuana use. Much of the use seems to be driven by neuropsychiatric distress arising naturally from the burden of illness; stress and anxiety also powerfully affect pain and nausea/appetite. Ease of access to legalized marijuana may have facilitated marijuana use. Whether these patients pursued established treatments for neuropsychiatric distress, or did not because of their marijuana use, is unknown.
CITATION(S): Pergam SA et al. Cannabis use among patients at a comprehensive cancer center in a state with legalized medicinal and recreational use. Cancer 2017 Nov 15; 123:4488.
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Exp Gerontol 2017 Dec 15; 100:100
Healthy Life, Healthy Brain: Lifestyle Factors and the Dementia Process
A healthy lifestyle is associated with better cognition and may delay dementia onset.
As the quest to cure dementia continues, lifestyle modification is an emerging strategy to prevent or modify the dementia process. With the number of individuals with dementia expected to increase from 47 million in 2015 to 66 million by 2030, preventing or delaying the onset of dementia may reduce the global burden. One third of risk factors for dementia are potentially modifiable, including education in early life; hearing loss, hypertension, and obesity in midlife (45–65 years); and smoking, depression, physical activity, social engagement, and diabetes mellitus in late life (>65 years) (NEJM JW Neurol Oct 2017 and Lancet 2017 Jul 19; [e-pub]).
Lifestyle Risk Factors for Dementia
Longitudinal studies have provided intriguing results on the effect of lifestyle factors on the dementia process. Vascular risk factors in midlife, when people are more likely to be asymptomatic, may be critical in the development of an underlying dementia process, including Alzheimer disease (AD). An elevated body-mass index (BMI ≥30 kg/m2) at midlife was associated with twofold increased odds of elevated brain amyloid deposition in late life. Increased brain amyloid deposition in late life was also associated with the number of midlife vascular risk factors (body-mass index, smoking history, hypertension, diabetes, and high cholesterol); the adjusted odds ratio for ≥2 risk factors versus no risk factors was 2.88 in the entire cohort and 9.15 in apolipoprotein E ℇ4 carriers. Late-life vascular risk factors were not associated with increased brain amyloid deposition in late life (NEJM JW Neurol Jun 2017 and JAMA 2017; 317:1443).
Vascular risk factors for dementia also may be influenced by gender (NEJM JW Neurol Dec 2017 and Neurology 2017; 89:1886). With hypertension defined as a blood pressure of ≥140/90 mm Hg and dementia diagnoses determined by inpatient and outpatient diagnostic codes, women with midlife hypertension had a 65% increased dementia risk compared with normotensive women, but the association did not hold in men. For women, compared with those who remained normotensive, a change to hypertension status and persistent hypertension from early to mid-adulthood were associated with a 73% and 63% increased risk for dementia, respectively. Hypertensive females who remitted to normotensive status did not have an increased dementia risk. Changes in hypertension status did not affect dementia risk in men.
Lifestyle factors also may contribute to incident mild cognitive impairment (MCI). In six low- and middle-income countries in the World Health Organization's Study on Global Aging and Adult Health, a diagnosis of MCI was associated with 28% increased odds of not meeting recommended physical activity criteria of 150 minutes of moderate-to-vigorous physical activity per week.1
Preliminary data show that aerobic exercise with three 1-hour sessions a week for 6 months may lead to short-term improvements in general cognitive performance, general cardiovascular capacity, and resting diastolic blood pressure in patients with vascular cognitive impairment (NEJM JW Neurol Jan 2017 and Neurology2016; 87:2082). A target systolic blood pressure of <120 mm Hg may also improve cognition, particularly in black people (NEJM JW Neurol Dec 2017 and JAMA Neurol 2017; 74:1199).
In late life, mentally stimulating activities such as craft activities, computer use, and social activities were associated with a 25% reduction in risk for amnestic MCI in cognitively normal individuals (median baseline age, 77 years); computer use was also associated with decreased risk for nonamnestic MCI. The lowest MCI risk was seen in apolipoprotein E ℇ4 noncarriers who performed mentally stimulating exercises (except for craft activities), and the highest MCI risk was seen in apolipoprotein E ℇ4 carriers who did not perform mentally stimulating activities (NEJM JW Neurol Jun 2017 and JAMA Neurol 2017; 74:332).
Cross-sectional studies using neuroimaging and cognitive testing more directly inform the relationship between lifestyle factors and brain health. Low adherence to the Mediterranean diet was associated with a significantly larger decrease in total brain volume in older adults after adjusting for age, sex, body-mass index, medical comorbidities, education, intellectual abilities, cognitive performance, and apolipoprotein E ℇ4 carrier status (NEJM JW Neurol Mar 2017 and Neurology 2017; 88:449).
Influence on Alzheimer Disease Biomarkers
Lifestyle factors may influence AD biomarkers. People with hypertension, hyperlipidemia, cardiac arrhythmias, coronary artery disease, congestive heart failure (CHF), diabetes mellitus, or stroke had greater neurodegeneration identified by MRI and fluorodeoxyglucose positron emission tomography (PET) compared with those without vascular or metabolic conditions. Although cerebral amyloid deposition (based on Pittsburgh Compound B [PiB] PET) and entorhinal cortex tau uptake (based on tau-PET) were not different between those with and without vascular or metabolic conditions, hyperlipidemia was associated with entorhinal cortex tau uptake; and diabetes mellitus, CHF, and cardiac arrhythmias were associated with neurodegeneration.2
The Dominantly Inherited Alzheimer's Disease study showed changes in AD biomarkers among presymptomatic AD mutation carriers with low versus high exercise level (<150 minutes/week vs. more). The exercise groups did not differ in cerebral amyloid load (based on PiB-PET), cerebrospinal fluid (CSF) amyloid-beta 42 level, or CSF tau level. However, in presymptomatic mutation carriers who already had amyloid pathology, higher cerebral amyloid levels were seen in the low-exercise group than in the high-exercise group.3
Lifestyle Interventions May Improve Cognition
The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability used a multidomain lifestyle intervention in participants aged 60 to 77 years who had an increased risk for dementia later in life and cognitive abilities at the mean or slightly lower than expected for age. The control group received information and advice on lifestyle modification. The intervention group received additional training on nutrition, exercise, cognition, and management of vascular risk factors (hypertension, dyslipidemia, and diabetes). After 24 months, the intervention group showed improvements in total cognitive scores, executive functioning, and processing speed compared with the control group, even after accounting for sociodemographic factors, socioeconomic status, baseline cognition, cardiovascular risk factors, and cardiovascular comorbidity at baseline.4
How to Advise Patients
Many questions remain, including regarding the effects of sleep and alcohol on brain health. More studies that incorporate combined outcomes with both biomarker status and neuropsychological testing will further inform the field. But given what we know, how should we advise our patients? A recent presidential advisory report from the American Heart Association (AHA)/American Stroke Association, which provides practical metrics from the AHA's Life Simple 7, helps answer this question.5 To optimize patients' brain health, clinicians can focus on four ideal health behaviors — not smoking, achieving the advised physical activity goal, eating a healthy diet, maintaining BMI <25 kg/m2 — and three ideal health factors — having a blood pressure <120/<80 mm Hg, a total cholesterol <200 mg/dL, and a fasting glucose of <100 mg/dL. Pursuing mentally stimulating activities is also advised. While the quest to cure dementia continues, clinicians can empower patients with the information that a healthy life leads to not only a healthy body but also a healthy brain.
CITATION(S): 1. Vancampfort D et al. Mild cognitive impairment and physical activity in the general population: Findings from six low- and middle-income countries. Exp Gerontol 2017 Dec 15; 100:100.
2. Vemuri P et al. Age, vascular health, and Alzheimer disease biomarkers in an elderly sample. Ann Neurol 2017 Nov; 82:706.
3. Brown BM et al. Habitual exercise levels are associated with cerebral amyloid load in presymptomatic autosomal dominant Alzheimer's disease. Alzheimers Dement 2017 Nov; 13:1197.
4. Rosenberg A et al. Multidomain lifestyle intervention benefits a large elderly population at risk for cognitive decline and dementia regardless of baseline characteristics: The FINGER trial. Alzheimers Dement 2017 Oct 19; [e-pub].
5. Gorelick PB et al. Defining optimal brain health in adults: A presidential advisory from the American Heart Association/American Stroke Association. Stroke 2017 Oct; 48:e284.
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Gastrointest Endosc 2017 Nov 16
Risk Factors for Gastric Cancer in the United States
Having intestinal metaplasia and being an East Asian immigrant could be factors used as screening criteria in the U.S.
Screening and surveillance guidelines for gastric cancer exist in Asia but not in the U.S. To help determine which patients should undergo surveillance in the U.S., investigators retrospectively compared characteristics of 152 patients with biopsy-proven gastric cancer and 456 matched controls who had undergone endoscopy.
Results were as follows:

COMMENT: The lower incidence of gastric cancer in the U.S. suggests that screening and surveillance protocols similar to those in Asia would not be cost-effective in the U.S. In the absence of guidelines, information on patients who are at the highest risk for gastric cancer allows an individualized approach. Because of its small size, this study may have missed associations with other ethnicities and family history observed in other studies. Surveillance of patients with intestinal metaplasia who have a family history of gastric cancer or who immigrated from East Asian or other countries with a high risk for gastric cancer may be appropriate. Additional studies to determine the cost-effectiveness of endoscopic surveillance in specific populations are needed.
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): Choi AY et al. Association of gastric intestinal metaplasia and east Asian ethnicity with the risk of gastric adenocarcinoma in a U.S. population. Gastrointest Endosc 2017 Nov 16; [e-pub].
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Blood 2017 Nov 15
Anemia in the Elderly: A Review
Etiologic classification, evaluation, and treatment of older patients
The prevalence of anemia (hemoglobin <13 g/dL in men and <12 g/dL in women) is increasing as the population ages and is currently estimated at 17% in those over 65. The diagnostic categories and treatment of anemia in the elderly are discussed in a recent review and summarized as follows:

COMMENT: Epidemiologic studies report that anemia in the elderly hastens cognitive decline, contributes to cardiovascular and other diseases, and impairs the quality of life. Therefore, intensive efforts to identify treatable causes are appropriate, especially in those with refractory anemias and transfusion dependency. However, the vigor of the investigations should always be commensurate with the overall goals of patient management.
CITATION(S): Stauder R et al. Anemia at older age: Etiologies, clinical implications and management. Blood 2017 Nov 15; [e-pub].
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Arch Intern Med 2017 Nov 28
Managing Seasonal Allergic Rhinitis with Medications
Updated guidelines from the 2017 Joint Task Force on Practice Parameters recommend initial treatment with an intranasal corticosteroid alone.
Sponsoring Organizations: American Academy of Allergy, Asthma, and Immunology (AAAAI); American College of Allergy, Asthma, and Immunology (ACAAI)
Target Audience: Primary care providers, otolaryngologists, allergists, and pulmonologists
Seasonal allergic rhinitis affects as many as 14% of adults in the U.S. Most patients either self-treat or see primary care clinicians; only a minority of patients see allergists. Patients and physicians alike often express confusion about the best medication or combination of medications to use. This update of a 2008 guideline from the AAAAI and ACAAI provides specific guidance on pharmacologic treatment for seasonal allergic rhinitis, including for initial therapy.
Key Recommendations

COMMENT: Patients tend to prefer oral medications over nasal sprays, but if an intranasal corticosteroid is used regularly, it is the most effective medication for addressing all allergic rhinitis symptoms, with no need to add an oral antihistamine. However, because many patients seem to feel better while taking oral antihistamines, I suggest using them only as needed and stressing daily use of their nasal steroid. For patients with mild nasal symptoms (especially mild itching, rhinorrhea, or sneezing) or systemic itching or urticaria, an oral antihistamine is appropriate first-line therapy. For patients whose allergic rhinitis is not controlled adequately with intranasal corticosteroids alone or who have severe symptoms and want quicker onset of action, intranasal antihistamines such as azelastine can be added to their nasal steroid, albeit at the expense of dysgeusia.
CITATION(S): Wallace DV et al. Pharmacologic treatment of seasonal allergic rhinitis: Synopsis of guidance from the 2017 Joint Task Force on Practice Parameters. Ann Intern Med 2017 Nov 28; [e-pub].
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N Engl J Med 2017 Dec 7; 377:2228
Does Use of Hormonal Contraception Affect Risk for Breast Cancer?
Danish national observational analysis suggests modest excess risk, but methodologic concerns cloud credibility.
Many women and clinicians are concerned that hormonal contraception might raise risk for breast cancer. In a prospective cohort study, investigators used Danish national data to assess the association between use of hormonal contraception and risk for invasive breast cancer in women aged 15 to 49. Some 1.8 million women were followed for a mean of 10.9 years (1995–2012); 11,517 breast cancers were diagnosed. Findings were adjusted for duration of hormonal contraceptive use, age, calendar year, education, parity, polycystic ovary syndrome, endometriosis, and family history of breast or ovarian cancer.
Most hormonal contraceptives were oral formulations, followed by the progestin-releasing intrauterine device (IUD). Relative risk for breast cancer in current or recent users of any hormonal contraceptives compared with never-users was 1.20 (95% confidence interval, 1.14–1.26), an absolute risk of 13 additional cases of breast cancer per 100,000 person-years. Current or recent use of the progestin-releasing IUD was associated with an RR of 1.21 (95% CI, 1.11–1.33). Breast cancer diagnoses were uncommon among users of contraceptive implants or injections.
COMMENT: Given that >80% of invasive breast cancers are diagnosed in women older than 49 (for U.S. data, see American Cancer Society), I was surprised that these authors limited their analysis to women between 15 and 49 (despite using a database that tracks all Danish women aged 15 to 79). Clinical breast examinations, screening mammograms, and lactation history all contribute to the diagnosis of breast cancer; thus, I was also surprised that the authors did not adjust their findings for these potential confounders. Epidemiologists caution that, in cohort studies, RRs of less than 2 or 3 should not be interpreted as suggesting causation (Obstet Gynecol 2012; 120:920). It's therefore baffling that neither the investigators nor an editorialist mentioned what constitutes a fundamental limitation of this report. Lastly, an NIH-funded case-control study conducted by CDC investigators — considered by many to be among the definitive studies on this topic — found no suggestion of excess risk for breast cancer with use of oral contraceptives (N Engl J Med 2002; 346:2025). The findings of this Danish study will not alter the way in which I counsel patients about the benefits and risks of hormonal birth control: While we cannot rule out the possibility of a small increase in risk for breast cancer, the best available data suggest that use of hormonal contraceptives does not have an impact on this risk.
CITATION(S): Mørch LS et al. Contemporary hormonal contraception and the risk of breast cancer. N Engl J Med 2017 Dec 7; 377:2228.
Hunter DJ.Oral contraceptives and the small increased risk of breast cancer. N Engl J Med 2017 Dec 7; 377:2276.

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