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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
September 1, 2012

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Management of Thyroid Disease During and After Pregnancy
Vitamin D Supplementation Does Not Reduce Depression Risk in Older Women
Nearly 1600 Cases of West Nile Virus Reported
More Good News for Men Who Love Chocolate
How Obesity, Diabetes, and Infection Interact After Total Joint Replacement
Can We Safely and Effectively Vaccinate Patients Receiving Biologic Therapies
   for Immune-Mediated Disease?
Fracture Risk After Bariatric Surgery
Patients Taking Antihypertensive Drugs Show Increase in Lip Cancer
Benefits of Circumcision Outweigh Harms, AAP Says
Skin Cancer: Another Reason to Stop Smoking
AAP Offers Guidelines for Sleep Apnea in Children
Sex Differences in Statin Benefits
Medical Errors: Major Problem
Physical Therapy Has Short-Term Clinical Benefits in Patients with Parkinson Disease
What to Do with NGU That Fails to Respond to Treatment?

MM: I’ve talked about the likelihood of thyroid disorders at length to moms who have experienced this phenomenom for many years and its amazing how many of them state that their doctor had not told them of this potential problem. We see that many of these women with post-partum hypo- or hyperthyroid conditions experience a reversal of either condition with the introduction of oral iodine/iodide supplementation. We always recommend that this is monitored by their physician but it is a simple and typically safe alternative or complementary treatment that may be considered.
J Clin Endocrinol Metab 2012 Aug; 97:2543
Management of Thyroid Disease During and After Pregnancy
Updated guidelines explicitly address several issues related to thyroid dysfunction and pregnancy.
The Endocrine Society has revised its 2007 guidelines for managing thyroid disease during pregnancy and postpartum. Highlights of the updated guidelines are as follows:

Comment: These guidelines are important because pregnancy is associated with profound changes in thyroid function, and the developing fetus is at risk for harm if maternal thyroid function is abnormal. All clinicians who care for pregnant women should stay current on how to manage thyroid dysfunction during pregnancy; to do so, they should review these guidelines in detail and seek consultation as appropriate.
Robert W. Rebar, MD Published in Journal Watch Women's Health August 30, 2012
Citation(s): De Groot L et al. Management of thyroid dysfunction during pregnancy and postpartum: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012 Aug; 97:2543.
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MM: Here is where confusion of what helps what tends to arise. Yes, there is a correlation of low vitamin D and depression. No, small doses of vitamin D do NOT improve depression. Yes, sunlight improves depression and vitamin D levels. But that is where the yes, no answers end. Sunlight also increases endogenous levels of serotonin, the feel good neurotransmitter. So, intense Daily Exposure to sunlight or “light box” exposure may improve depression and especially Seasonal Affective Disorder (SAD). For more information about Full Spectrum Light Bulbs or Light Boxes please contact Mark Drugs.
Am J Epidemiol 2012 Jul 1; 176:1
Vitamin D Supplementation Does Not Reduce Depression Risk in Older Women
Results from a very large, population-based, randomized study
Although observational studies have linked symptoms of depression to low vitamin D levels, few randomized, controlled trials have tested whether vitamin D supplementation can treat or prevent depression. These studies had modest and, often, selective samples and yielded conflicting results. Researchers have now analyzed data from the Women's Health Initiative Calcium and Vitamin D Trial in 36,282 women aged 50 to 80 who were randomized to 400 IU vitamin D (with 1000 mg calcium) or to placebo. Depression symptoms and antidepressant use (as proxy for depression) were measured at randomization and 2 years later (symptoms measured at follow-up in only 2263 women).
The two groups had low baseline levels of antidepressant use (7%), threshold depression (10%), and total vitamin D intake (mean, 366 IU). Supplementation for 2 years had absolutely no effect on risk for depressive symptoms above threshold or on antidepressant use either in the entire group or in the subgroup without threshold depression at baseline.
Comment: This extremely large and meticulously done study found no benefit from vitamin D for depression. The results suggest that observed links between low vitamin D and depression may be due to confounding effects of lifestyle and diet. Although the vitamin D dose might have been too small, the authors note that when added to intake from food, it achieved the daily dose recommended by the Institute of Medicine. This study does not address the question of whether depressed patients with low vitamin D levels would improve with vitamin D supplements. Adequate vitamin D is still important for optimal health in multiple ways, but patients with depression will have to do more than raise their vitamin D levels to feel better.
Peter Roy-Byrne, MD Published in Journal Watch Psychiatry August 30, 2012
Citation(s): Bertone-Johnson ER et al. Vitamin D supplementation and depression in the Women's Health Initiative Calcium and Vitamin D Trial. Am J Epidemiol 2012 Jul 1; 176:1.
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Nearly 1600 Cases of West Nile Virus Reported
The number of people infected by West Nile virus in the United States has reached 1590, a 40% increase in the past week, according to new data from the CDC. Sixty-six of those cases have been fatal. This year is still on pace to be one of the worst for West Nile virus infections.
Over half the reported cases had neuroinvasive disease.
Nearly half of all cases have been from Texas, but Louisiana, Michigan, Mississippi, Oklahoma, and South Dakota have also been disproportionately affected.
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MM: Simply put… Hooray!!!
More Good News for Men Who Love Chocolate
A new study adds to the evidence that moderate chocolate consumption might lower stroke risk — this time, among middle-aged and older men.
Over 37,000 Swedish men aged 45 to 79 without a history of cardiovascular disease completed dietary questionnaires and then were followed for roughly 10 years. During that time, 5% experienced a first stroke.
After multivariable adjustment, those in the highest quartile of chocolate consumption (62.9 g/week) had a significant, 17% reduction in stroke risk compared with those in the lowest quartile (0 g/week).
Writing in Neurology, the researchers note that the flavonoids in chocolate may protect against stroke "through several biological mechanisms, including antioxidant, anti-platelet, and anti-inflammatory effects."
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MM: Here is a remarkably good reason to consider the HCG Metabolic Syndrome and Weight Loss protocol prior to considering knee or hip joint replacement. As this protocol combats both obesity and diabetes, it literally gets 2 birds with a single stone.
J Bone Joint Surg Am 2012 Jul 18; 94:e1011.
How Obesity, Diabetes, and Infection Interact After Total Joint Replacement
Periprosthetic infection was associated with severe obesity and, to a lesser extent, diabetes.
Some orthopedists insist that patients with diabetes have tight glycemic control before they undergo total hip or knee replacement, presumably to prevent postoperative infection. To examine the interplay between diabetes and obesity as risk factors for periprosthetic joint infection, Finnish researchers analyzed a single-center database of 7181 primary hip or knee replacement operations. Both deep incisional infections and joint (or joint space) infections that occurred during the first postoperative year were counted.
The overall incidence of infection was 0.7% (52 cases). After multivariate analysis with adjustment for diabetes, body-mass index (BMI), and several other variables, periprosthetic infection was associated significantly with both severe obesity (odds ratio, 6.4) and diabetes (OR, 2.3). The incidence of infection was zero in diabetic patients with BMIs <25 kg/m2 and was between 1% and 2% in diabetic patients with BMIs between 25 and 40. In patients with both diabetes and BMI ≥40, the incidence of infection was much higher — 10%.
Comment: In this study, severe obesity was associated more strongly with periprosthetic infection than was diabetes; when both factors were present, risk was substantially higher. The data presented in this study were insufficient to determine whether poor glycemic control among diabetic patients was an additional risk factor for infection. Moreover, controlled trials have not been performed to determine whether tightening glycemic control before or after orthopedic surgery improves postoperative outcomes.
Allan S. Brett, MD Published in Journal Watch General Medicine August 16, 2012
Citation(s): Jämsen E et al. Obesity, diabetes, and preoperative hyperglycemia as predictors of periprosthetic joint infection: A single-center analysis of 7181 primary hip and knee replacements for osteoarthritis. J Bone Joint Surg Am 2012 Jul 18; 94:e1011.
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MM: I still shy away from administering a live vaccine to a potentially immuno-compromised individual. The very premise of doing such an act is contradictory. The theory associated with the activity of a vaccine requires that an immune system be intact. If a person is immunocompromised, then, by definition, the system is NOT intact and therefore not a safe, effective or recommended action. Any other approach is irresponsible.
JAMA 2012 Jul 4; 308:43
Can We Safely and Effectively Vaccinate Patients Receiving Biologic Therapies for Immune-Mediated Disease?
Indications are promising but not definitive; nevertheless, we should discuss results with patients who request the herpes zoster vaccine.
This question is important, as the risk for herpes zoster is elevated in older adults, more so in patients with immunologically mediated diseases. Most labels for biologic therapies suggest that immunization with live vaccine is contraindicated because of a fear that these individuals may develop varicella infection. Therefore, clinicians are hesitant to administer the "shingles" shot, and I have followed this practice with patients who request the vaccine.
These authors retrospectively assessed the rate of herpes zoster infection within 42 days of vaccination in 463,541 Medicare beneficiaries older than 60 being treated for rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, or inflammatory bowel disease. They also compared long-term risks for developing zoster in vaccinated versus nonvaccinated patients. Vaccinated patients were statistically less likely to develop zoster in the long term, including the 633 who were receiving biologic therapies at the time of vaccination. No recipients of biologic therapies developed zoster within 42 days of vaccination.
Comment: This study took advantage of a large database, but was limited by the small number of vaccinated biologic therapy recipients. The findings suggest that vaccination was effective and not associated with adverse effects. The authors were unable to ascertain whether biologic therapy was interrupted at the time of vaccination. We should discuss this observation with our patients, but the data are insufficient to definitively determine the safety and efficacy of this live vaccine.
Although some study authors had ties to pharmaceutical companies, the data were collected and analyzed at a university center with support from the National Institutes of Health. An excellent audio author interview is available on the JAMA website
Jeffrey P. Callen, MD Published in Journal Watch Dermatology August 10, 2012
Citation(s): Zhang J et al. Association between vaccination for herpes zoster and risk of herpes zoster infection among older patients with selected immune-mediated diseases. JAMA 2012 Jul 4; 308:43.
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BMJ 2012 Aug 7; 345:e5085
Fracture Risk After Bariatric Surgery
Risk was not increased in the short term, but trended higher 3 to 5 years after surgery.
Both restrictive and malabsorptive bariatric surgeries affect bone remodeling adversely and reduce bone density. In this population-based retrospective cohort study, investigators determined fracture risk in nearly 2100 obese patients who had undergone bariatric surgery compared with risk in >10,400 obese patients (matched to cases by factors such as age, sex, and body-mass index [BMI]) who had not undergone such surgery.
After a mean follow-up of 2.2 years, neither osteoporotic nor nonosteoporotic fractures occurred more commonly in patients who underwent bariatric surgery than in controls. However, trends for excess fracture risk 3 to 5 years after bariatric surgery and in patients who had greater postsurgical reductions in BMI were observed.
Comment: These results suggest that, in the short term, fracture risk is not higher in patients who undergo bariatric surgery. The observed trend for excess fracture risk 3 to 5 years after surgery is concerning; as the authors note, these results "do not exclude a more protracted adverse influence [of bariatric surgery] on skeletal health in the longer term."
Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine August 28, 2012
Citation(s): Lalmohamed A et al. Risk of fracture after bariatric surgery in the United Kingdom: Population based, retrospective cohort study. BMJ 2012 Aug 7; 345:e5085.
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MM: Although this is a very low overall incidence of a particular type of cancer, when someone asks, “Why me?”, this may be part of an explanation.
Arch Intern Med 2012 Aug 6
Patients Taking Antihypertensive Drugs Show Increase in Lip Cancer
Hydrochlorothiazide, HCTZ-triamterene, and nifedipine were associated with a higher incidence of lip cancer.
Cancer of the lip (i.e., of the vermillion border, commissure, and labial mucosa) is a rare malignancy (yearly incidence in the U.S., 0.7/100,000 persons). Usually occurring on the lower lip, this cancer is much less common in the dark-skinned, suggesting that sun exposure is a major causative factor. Prompted by epidemiologic studies that linked some antihypertensive medications with cutaneous squamous cell carcinomas (SCCs; presumably through photosensitization), investigators looked for an association with lip cancer as well.
They reviewed more than 13 years of pharmacy records from a large HMO and identified 712 cases of lip cancer among non-Hispanic whites who were not HIV-positive or organ transplant recipients at diagnosis. They compared these cases with 22,904 matched controls without lip cancer. The hypertension drugs hydrochlorothiazide (HCTZ), HCTZ-triamterene, and nifedipine were associated with a higher incidence of lip cancer; the relative risk for HCTZ users was 2.2 (odds ratio, 1.76–2.79). As expected, lip cancer was also associated with smoking, but the higher risk in HCTZ, HCTZ-triamterene, and nifedipine users remained after multivariable analysis. Lisinopril recipients had no increased lip cancer incidence, indicating that risk was drug related rather than hypertension related. The likelihood of developing lip cancer correlated positively with duration of treatment with these drugs. Those with at least 5 years of HCTZ treatment had a fourfold increase in lip cancer.
Comment: Hydrochlorothiazide has been implicated as a risk factor for cutaneous SCCs; these findings add evidence that long-term treatment raises risks for epithelial neoplasms. Though it is plausible that the photosensitizing properties of HCTZ and nifedipine are responsible for the increased risk, such a mechanism cannot be proven by the available information here. However, long-term users of nifedipine and HCTZ medications should employ broad-spectrum sunscreens that block out both ultraviolet A and B and should be monitored carefully for skin and lip cancers.
Craig A. Elmets, MD Published in Journal Watch Dermatology August 30, 2012
Citation(s): Friedman GD et al. Antihypertensive drugs and lip cancer in non-Hispanic whites. Arch Intern Med 2012 Aug 6; [e-pub ahead of print].
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Benefits of Circumcision Outweigh Harms, AAP Says
The benefits of circumcision outweigh the harms, the American Academy of Pediatrics says in a policy statement in Pediatrics. The benefits include lower risk for urinary tract infections before 1 year of age, as well as reduced risk for sexually transmitted infections and penile cancer later in life.
However, the AAP stops short of recommending routine circumcision. The decision is best left to parents, the group says.
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Arch Dermatol 2012 Aug; 148:939.
Skin Cancer: Another Reason to Stop Smoking
Current and ever smokers had increased risk for developing cutaneous squamous cell carcinomas.
Although most skin cancers are caused by excessive sun exposure, environmental chemicals have also been implicated in their development. Tobacco smoke contains such chemicals — polyaromatic hydrocarbons, which are known to cause cancer in the skin and other organs. Investigators performed a meta-analysis of published studies on the relationship between tobacco use and nonmelanoma skin cancer.
A search of four electronic databases identified 25 cohort and case-control studies published between 1950 and October 2010 on tobacco use and skin cancer that met the inclusion criteria. Tobacco exposure included cigarettes, cigars, and chewing tobacco. The data were insufficient to establish a clear association between tobacco use and nonmelanoma skin cancer (basal cell carcinoma [BCC] and cutaneous squamous cell carcinoma [SCC] combined) or BCC alone, but they did show a consistent and significant increase in the risk for cutaneous SCC (odds ratio, 1.52; 95% confidence interval, 1.15–2.01). Current smokers and those who had ever smoked were at greater risk for developing cutaneous SCC than former smokers.
Comment: This analysis illustrates that although dermatologists focus on sun exposure as a cause of nonmelanoma skin cancers, other environmental agents should be considered as well. As the authors point out, the increased risk could be attributed to the carcinogenic properties of tobacco, to the immunosuppressive effects of tobacco, or to an action of ultraviolet radiation on the chemicals in tobacco smoke. If physicians needed another reason to counsel their patients to avoid smoking, here is one.
Craig A. Elmets, MD Published in Journal Watch Dermatology August 30, 2012
Citation(s): Leonardi-Bee J et al. Smoking and the risk of nonmelanoma skin cancer: Systematic review and meta-analysis. Arch Dermatol 2012 Aug; 148:939.
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AAP Offers Guidelines for Sleep Apnea in Children
The American Academy of Pediatrics has released guidelines for diagnosing and managing uncomplicated obstructive sleep apnea syndrome in children and adolescents. Among the recommendations, published in Pediatrics:

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Arch Intern Med 2012 Jun 25; 172:909.
Sex Differences in Statin Benefits
Secondary cardiac prevention in men and women was similar, but benefits for overall mortality and stroke might be different.
Statins clearly confer an overall benefit in preventing cardiovascular (CV) morbidity and mortality, but the relative benefits in men versus women are not as clear-cut. Researchers conducted a meta-analysis of 11 randomized, placebo-controlled, secondary-prevention trials of statins for adverse cardiovascular events (43,191 patients; 21% women) with follow-up ranging from 16 weeks to 6 years. Of the 11 studies, only 3 were rated as good quality, and the 4 largest studies were rated as fair.
In pooled analyses, relative risk for any adverse CV event was about 19% lower with statins in both women and men, but relative risk for all-cause mortality or stroke was lowered significantly (by 19%) in men and nonsignificantly (by 8%) in women. Mean LDL cholesterol-lowering (about 22%) was similar for men and women. Statin-related adverse events occurred with equal frequency in both sexes.
Comment: The authors support using statins for secondary prevention in both women and men, based on lower risk for adverse CV events, but they note the lack of significant benefit in women for all-cause mortality and stroke. However, editorialists point out various limitations of this analysis (some of which are acknowledged by the meta-analysis authors themselves), and they believe that statins can be recommended as benefiting women for all outcomes studied.
Thomas L. Schwenk, MD Published in Journal Watch General Medicine August 2, 2012
Citation(s): Gutierrez J et al. Statin therapy in the prevention of recurrent cardiovascular events: A sex-based meta-analysis. Arch Intern Med 2012 Jun 25; 172:909.
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Medical Errors: Major Problem
Earlier this year, a daughter stepped to the head of a class of medical students at the University at Buffalo-SUNY and proceeded to describe the cascade of events that killed her 88-year-old mother. The mother was independent and anything but frail when admitted to the hospital with a mild case of gout. The doctors prescribed a muscle relaxant that isn't used for gout—and in fact is prominently displayed on a list of drugs that should be avoided in the elderly. As a result, she suffered a scary fall in rehab and lost the ability to walk. While in the hospital, poor infection-control measures led to a series of infections, each one worse than the previous, and she died in a hospice of sepsis. The daughter said to the class, "Dear God, you shouldn't go into a hospital a fairly robust 88-year-old woman with gout and die 48 days later of sepsis," says the daughter, who directs a number of social services programs for a YWCA in the Buffalo area. "It shouldn't happen."
Click on the link below to read the remainder of this story on medication errors. Physicians and others are now looking closely at their practices to see how they can improve; something compounding pharmacists have been leaders in for the past ten to twelve years!
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BMJ 2012 Aug 6; 345:e5004
Physical Therapy Has Short-Term Clinical Benefits in Patients with Parkinson Disease
A meta-analysis showed that many functional outcomes improved with PT.
Despite optimal medical management, many patients with Parkinson disease (PD) experience progressive declines in physical function and mobility and decrease their participation in daily activities. Evidence suggests that physical therapy (PT) might mitigate such deterioration. In this meta-analysis, investigators assessed the effectiveness of PT versus no intervention in patients with PD.
Researchers evaluated data from 39 randomized controlled trials (trial-length range, 4–52 weeks) that involved more than 1800 patients. Compared with no intervention, PT was associated with significantly faster walking speed and longer distance walked in 2 or 6 minutes, significant improvements in timed up-and-go tests, functional reach tests, Berg Balance Scale, and freezing-of-gait questionnaire scores. PT also was associated with fewer falls and with improvements on the "unified Parkinson's disease rating scale." PT resulted in significant benefit for 9 of 18 assessed outcomes.
Comment: In this meta-analysis, PT yielded tangible short-term clinical benefits in patients with PD. Although the American Academy of Neurology guideline lists PT as an "alternative" therapy for PD (Neurology 2006; 66:976), it regards the magnitude of benefit from PT as small and nonsustainable after cessation. Nevertheless, in some patients, long-term PT might be beneficial — future trials should address this uncertainty.
Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine August 28, 2012
Citation(s): Tomlinson CL et al. Physiotherapy intervention in Parkinson's disease: Systematic review and meta-analysis. BMJ 2012 Aug 6; 345:e5004.
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J Infect Dis 2012 Aug; 206:357
What to Do with NGU That Fails to Respond to Treatment?
Nongonococcal urethritis treatment failures might be caused by mycoplasma infections.
Men with nongonococcal urethritis (NGU) usually are treated empirically with azithromycin or doxycycline. However, because specific microbiological diagnoses are made rarely and microbiological proof of cure is obtained even more rarely, clinicians often have difficulty interpreting persistent or recurrent symptoms.
Researchers analyzed pre- and posttreatment urinary nucleic acid amplification test results from a prospective, randomized, nonblinded study in which azithromycin was compared with doxycycline (with or without tinidazole) in 293 heterosexual men with symptomatic NGU. Among 169 men who returned for follow-up 3 to 4 weeks after treatment, 80 exhibited persistent symptoms, and of these, 56% had no organism identified on repeat testing. However, persistent infection was identified in 12% of men in whom Chlamydia trachomatis infections were diagnosed initially and in 44% of those in whom Mycoplasma genitalium infections were diagnosed initially. Persistence of both organisms was more likely in patients with visible urethral discharge on follow-up and in those with >15 polymorphonuclear neutrophils per high-power field seen on Gram stain of discharge. In addition, persistent chlamydia infection was more likely in men who were treated with azithromycin, and persistent mycoplasma infection was more likely in those who were treated with doxycycline.
Comment: As clinicians often operate in the dark when it comes to these infections, one of the take-home messages from this study might be helpful: Although many cases of clinical failure are of uncertain etiology, a fair percentage can be attributed to mycoplasma infection. Thus, if a patient was treated initially with doxycycline, retreatment with azithromycin or a quinolone might be helpful.
Abigail Zuger, MD Published in Journal Watch General Medicine August 21, 2012
Citation(s): Seña AC et al. Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis infections in men with nongonococcal urethritis: Predictors and persistence after therapy. J Infect Dis 2012 Aug; 206:357.

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