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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
May 3, 2014

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Vitamin D Blood Levels and Supplementation and Cause-Specific Death
WHO: Antibiotic Resistance a Major Public Health Threat Globally
Outpatient Antibiotic Prescription Trends in the U.S., 2006–2010
Medicare Advisers Vote Against Paying for lung Screening in High-Risk Patients
Updated Guidelines for preventing Recurrent Stroke
FDA Approves Novel Implantable Device for Sleep Apnea
A Combination Antibiotic Regimen for Active Ulcerative Colitis
Unreliable Parent, Impulsive Child Barbara
Benefits of Family Routines
Modest Midlife Exercise Seems Able to Ward Off Disability, Early Death
Dietary Fiber After MI Linked to Improved Survival
Cynicism in Medicine
Pediatrics Academy Offers Clinical Guide for ACL Injuries

MM: This is an impressive study. 850,000 individuals were observed. Comparisons were made between those with the highest and those with the lowest blood levels of vitamin D. The very impressive result was that all cause mortality or risk of death was decreased by 16% for every 10ng/ml that vitamin D levels were raised. This included cardiovascular (CV)-related death), cancer-related death, and all-cause death. In the medical community, there is a lot of misinformation regarding vitamin D. In my opinion, blood level goals, in general, of 25(OH)D should at minimum be in the 60-80ng/ml range but according to most of the peer-reviewed published literature that I have read and reviewed, there is little to no danger if levels are higher; and most people are completely safe if their levels are in the 100-140ng/ml range. Adverse effects, that are typically reversible, will rarely occur with blood levels up to 250ng/ml.
BMJ 2014 Apr 1; 348:g1903
Vitamin D Blood Levels and Supplementation and Cause-Specific Death
Vitamin D3 seems like the better choice for supplementation.
Despite considerable research, the health benefits of vitamin D supplementation in the general population remain controversial. In this systematic review and meta-analysis, investigators determined whether blood vitamin D levels and vitamin D supplementation were associated with risk for death.
One analysis involved 73 observational studies (mean follow-up, 0.3–29 years) that involved 850,000 participants (median age, 63; median baseline blood 25-hydroxyvitamin D [25(OH)D] level, 20.7 ng/mL). Overall, compared with participants whose blood 25(OH)D levels were in the top third, those whose levels were in the bottom third had significantly greater risks for cardiovascular (CV)-related death (adjusted relative risk, 1.4), cancer-related death (ARR, 1.1), and all-cause death (ARR, 1.4). For each 10 ng/mL lower increment of 25(OH)D, risk for all-cause death increased by 16%.
Another analysis involved 22 randomized, placebo-controlled trials (31,000 older participants; mean follow-up, 0.4–6.8 years) with data on the effect of vitamin D supplementation on all-cause mortality; 8 trials provided vitamin D2 (dose range, 208–4500 IU/day), and 14 trials provided vitamin D3 (dose range, 10–6000 IU/day). Vitamin D3 supplementation significantly lowered mortality risk (relative risk, 0.9), but vitamin D2 supplementation did not.
Comment: In this analysis, the observational data showed an inverse association between blood 25-hydroxyvitamin D levels and death, but reverse causality is possible (i.e., ill people having low vitamin D levels rather than low vitamin D levels causing illness). In randomized trials, vitamin D3 supplementation modestly lowered all-cause mortality risk; however, the optimal dose and duration of vitamin D3 supplementation are unknown. Thus, widespread vitamin D supplementation should not be recommended.
Citation(s): Chowdhury R et al. Vitamin D and risk of cause specific death: Systematic review and meta-analysis of observational cohort and randomised intervention studies BMJ 2014 Apr 1; 348:g1903.

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MM: When I was first licensed as a pharmacist in 1983, most of these antibiotics were not yet on the market. In a mere 30 years the medical profession coupled with the manufacturers of antibiotics have irresponsibly managed to set in motion a healthcare problem that has the dangerous potential of being an apocalypse. In the Reagan era there was a popular program promoted by the first lady, "Just say No!" Maybe we have to use think of those same words before we order or accept a prescription for an antibiotic. There is no better time to start this approach than the present.
WHO: Antibiotic Resistance a Major Public Health Threat Globally
By Kelly Young
Antibiotic resistance "has reached alarming levels in many parts of the world" and is now a major public health threat, according to a World Health Organization report.
The WHO surveyed member nations for antibiotic resistance in seven common bacteria. Among the findings:

The WHO says that proper surveillance to antimicrobial resistance is lacking in much of the world. It plans to develop tools and standards for tracking drug resistance, taking cues from its programs to fight malaria, tuberculosis, and HIV.
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MM: I think that it is wonderful that fewer antibiotic Rx's are being written but let's get real. There are about 250 million people in the U.S. If each and every person received the same number of antibiotic Rx's then each person would be getting between 5 and 6 Rx's annually. And that is only for non-hospitalized patients. This is simply ridiculous. If there is that high a frequency of bacterial infections then we are failing in our preventive measures as healthcare providers and as a society. There are several simple things that may be performed to improve this situation in addition to simply delaying how quickly we administer antibiotics. These may include vitamin D3 use achieving blood levels that are in the 60-80ng/ml range, increase vitamin C consumption to 2-3 grams daily, increasing our consumption of whole, fresh or frozen foods, increasing the percentage of our diet that are fruits and vegetables when compared to starches and sugars, decreasing sugar and high glycemic carbohydrates in our diets, taking daily probiotics in the 20-50 billion units/day range. All of these approaches may be beneficial but if people will only choose one, then we will see an improvement in our health as a society.
Antimicrob Agents Chemother 2014 May; 58:2763
Outpatient Antibiotic Prescription Trends in the U.S., 2006–2010
During the study period, antibiotic prescription rates declined by 3% overall but were 25% higher in the winter than in the summer.
Antibiotic resistance is a major problem today and is clearly related to antibiotic overprescription and misuse. To design programs for promoting prudent use of anti-infective drugs, knowledge about current prescription patterns is essential. Toward this end, researchers analyzed records for 2006 through 2010 from the IMS Health Xponent database, which captures >70% of all dispensed outpatient prescriptions in the U.S. From these data, they determined trends and seasonal variation in antibiotic use.
Between 2006 and 2010, more than 1.34 billion antibiotic prescriptions were dispensed. Penicillins, macrolides, cephalosporins, and quinolones were the classes prescribed most commonly. The overall outpatient prescription rate decreased by 2.8% over the 5-year period, mainly due to reduced prescribing of penicillins and cephalosporins (and despite an increase in macrolide use). An average of 24.5% more antibiotic prescriptions were dispensed in the winter months (October through March) than in the summer, with seasonal variation greatest for macrolide and penicillin prescriptions (100% and 75% more prescriptions, respectively, in winter). Prescriptions for cephalosporins and quinolones increased only moderately during the winter months; those for sulfonamides, tetracyclines, urinary anti-infectives, and miscellaneous antibacterial classes demonstrated little seasonality.
Comment: The modest decline in overall antibiotic prescription is appreciated and may reflect slowly changing attitudes of physicians and patients regarding liberal antibiotic use. However, the reverse trend of increasing macrolide use, especially in winter months, likely suggests inappropriate antibiotic prescribing for infections of viral origin — a potential target for future interventions.
Citation(s): Suda KJ et al. Trends and seasonal variation in outpatient antibiotic prescription rates in the United States, 2006 to 2010. Antimicrob Agents Chemother 2014 May; 58:2763.
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MM: I do not disagree with the Medicare advisers. I feel that there are too many tests performed in American healthcare for High Risk patients to confirm what may already be known or to justify treatments that are potentially very expensive and show little benefit. We spend more than twelve times most other modern countries on our older patients and have a worse quality of life and care for these patients than most other countries. Our efforts and expenditures are being inappropriately directed. Additionally, we see a very high level of misdiagnosis and false positives leading to inappropriate surgeries and other treatments. We have seen this in other areas that test potential patients who are not at high risk including breast and prostate. Until we develop better, less invasive and more reliable testing; and change our overall lifestyles in an effort to become healthier from the start and less self-destructive, we should curtail much of the less productive testing.
Medicare Advisers Vote Against Paying for lung Screening in High-Risk Patients
By Amy Orciari Herman
A Medicare advisory panel voted on Wednesday against paying for annual lung CT screening in heavy smokers — despite the fact that the U.S. Preventive Services Task Force issued a grade B recommendation in favor of screening high-risk groups in December 2013.
Advisory panel members said that "they had little confidence that the benefits of subjecting Medicare beneficiaries to regular scans outweighed the risks of the psychological trauma or unnecessary surgeries that could result from false positives," Modern Healthcare reports.
The panel's vote is nonbinding, with patient advocates hopeful that Medicare will disagree. A final coverage determination is expected in early 2015.
Modern Healthcare notes that under the Affordable Care Act, the USPSTF's endorsement means that private insurers must cover the screening themselves, with no out-of-pocket costs for their non-Medicare members.
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MM: An ounce of prevention is worth a pound of cure. These are sensible approaches, in general, are achievable with limited effort and expense, and for the most part make sense for patients who fall into these high risk categories.
Updated Guidelines for preventing Recurrent Stroke
By Kelly Young
The American Heart Association and the American Stroke Association have released updated guidelines for preventing recurrent stroke in patients who've experienced a stroke or transient ischemic attack.
Here are a few of the changes from the groups' 2011 guidelines:

Additional recommendations on medical and surgical management are included.

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MM: This is an interesting device and it treats a condition that is in reality a symptom of another or multiple underlying conditions. These conditions are frequently associated with systemic inflammation. Lifestyle changes have been demonstrated to also be beneficial for people with sleep apnea. Elimination of foods that people may be sensitive to or are generally inflammatory, such as bananas, gluten, dairy or corn can show major improvements in sleep apnea as well as a variety of other conditions that are affected by inflammation.
FDA Approves Novel Implantable Device for Sleep Apnea
By Kristin J. Kelley
The FDA has approved a new treatment — Inspire Upper Airway Stimulation therapy — for patients with moderate-to-severe obstructive sleep apnea who cannot use a continuous positive airway pressure machine.
The device is implanted in the upper chest, senses breathing patterns, and mildly stimulates the airway muscles, keeping the airway open. The device is turned on and off using a handheld remote.
In a study published in the New England Journal of Medicine, some 125 patients (83% men, mean age: 55 years) had the device implanted. At 12 months, the number of apnea events per hour decreased by 68% and oxygen desaturation events decreased by 70%.
The procedure to implant the device has a shorter recovery time than surgery to alter airway or facial anatomy, according to the manufacturer. It is expected to be available to patients by the end of 2014.
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MM: Triple antibiotic therapy seems to have fallen out of favor compared to how it was accepted a decade ago for the treatment of ulcers and ulcerative colitis (UC).Although correction of the flora within the GI tract is a large part of reducing inflammation, other approaches that are potentially less damaging to the body than aggressive antibiotic treatment may be a possibility. Dr Jill Smith has done extensive research with Low Dose Naltrexone (LDN) and the treatment of pediatric Crohn's disease. Her results may be extended to treatment of UC and have been by many clinicians..
Aliment Pharmacol Ther 2014 May; 39:949
A Combination Antibiotic Regimen for Active Ulcerative Colitis
Response rates continue to be promising for amoxicillin, tetracycline, and metronidazole.
Bacteria are widely suspected to be one of the inciting antigens in ulcerative colitis (UC). As such, antibiotics, probiotics, and fecal microbiota transplantation have all been established or proposed as treatments for UC.
In the current open-label, multicenter trial, researchers assessed the efficacy of a combination of amoxicillin (500 mg), tetracycline (500 mg), and metronidazole (250 mg) 3 times daily for 2 weeks to induce and maintain remission in patients refractory to or dependent on steroids. The same researchers had previously designed this regimen to treat elevated levels of Fusobacterium varium observed in inflamed colonic mucosa of patients with ulcerative colitis and serum antibodies to F. varium. The regimen was effective for short-term control of UC in a randomized, double-blind, placebo-controlled study (NEJM JW Gastroenterol Aug 27 2010).
Among 30 patients with steroid-refractory, active UC (severe, 10; moderate, 19; mild, 1) and 64 patients with steroid-dependent, active UC (severe, 6; moderate, 51; mild, 7), a clinical response was achieved in 63.3% and 73.4%, respectively, within 2 weeks of completing therapy. At 3 and 12 months after completion, respective rates of clinical remission were 60.0% and 66.6% in steroid-refractory patients and 56.3% and 51.6% in steroid-dependent patients. At 3 and 12 months after completion, respective mucosal healing rates were 46.7% and 53.3% for steroid-refractory patients and 32.8% and 35.9% for steroid-dependent patients. In steroid-dependent patients, 60.9% were able to discontinue steroid therapy and remain in remission for ≥3 months.
Comment: The obvious weakness of this study is the lack of placebo control. However, the biologic plausibility based on prior studies of Fusobacterium varium, the previous short-term outcomes in a randomized trial, and the minimal cost and toxicity of this treatment compared with conventional alternatives indicate that this regimen is worth following closely for its potential to treat ulcerative colitis. It is also reasonable for use in clinical practice pending additional research.
Citation(s): Kato K et al. Adjunct antibiotic combination therapy for steroid-refractory or -dependent ulcerative colitis: An open-label multicentre study. Aliment Pharmacol Ther 2014 May; 39:949.

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MM: This was not a particularly well designed study but is interesting none the less. Being consistent is important irrespective of the environment. Employees and co-workers perform better if they get consistent responses to their actions or activities. Pets train better if the system of rewards and admonishments are consistent. It only makes sense that children would have a consistent response as these other groups.
Transl Psychiatry 2014 Apr 15; 4:e382
Unreliable Parent, Impulsive Child Barbara
Children's perceptions of parents' inconsistency in giving rewards are linked to greater impulsivity
Do inconsistent parental rewards contribute to the environmental pathogenesis of teenagers' impulsive and addictive behaviors? To learn more, investigators used a delay discounting (DD) paradigm combined with functional magnetic resonance imaging in 48 healthy teenagers (mean age, 14). DD refers to an individual's lower valuing of promised versus immediate awards.
In baseline questionnaires, teenagers self-reported substance use and assessed parents' reward consistency. At baseline and at 2 weeks, teens completed the DD test and were rated on whether they chose a lower, but immediate, reward or a later, larger one. Also, teens completed another study, which required them to send e-mails describing a good experience that day; they were told that each e-mail would receive an award. By design, half of the group did not receive the promised rewards.
At baseline, teenagers with higher DD reported greater alcohol use in the previous year (too few used cannabis or tobacco for analyses). Parental inconsistency and higher DD at both time points were associated with lower activation of the nucleus accumbens and ventromedial prefrontal cortex.
Comment: Even preschoolers differ in the ability to delay gratification, and children who can delay their rewards have better cognitive and social outcomes during adolescence (Science 1989; 244:933). Thus, finding the etiology of delay discounting is important. Because only adolescents' reports of parental reward behaviors were available, it is not possible to discern whether parental inconsistency was actual or whether physiologically impulsive teenagers misinterpreted reward fulfillment, perhaps due to a genetically transmitted trait. Nevertheless, these data make such great intuitive sense that clinicians should consider educating parents that keeping their promises of reward affects their children's' future impulsivity and alcohol use
Citation(s): Schneider S et al. Parental inconsistency, impulsive choice and neural value representations in healthy adolescents. Transl Psychiatry 2014 Apr 15; 4:e382.
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MM: I have to wonder is moms who spent more time engaging their kids were more likely to demonstrate a bias towards assessing the outcomes. I do find it interesting that moms assessed that reading didn't have a positive impact on SEH. I have to wonder if this was possibly a reflection of the moms or the actual impact on the kids. In any case, there is no question in my mind that children who are socialized and engaged have a better opportunity to be well rounded and have an enhanced sense of self worth than those who are not.
J Dev Behav Pediatr 2014 Feb/Mar; 35:93
Benefits of Family Routines
Social and emotional health of young children who engaged in home-based family routines were rated higher by mothers.
The quality of a home environment influences the development of cognitive, social, and emotional skills, especially in young children. In a secondary analysis of data from a nationally representative sample of 8550 children followed from birth in 2001 to kindergarten entry, investigators evaluated the association between home activities and social and emotional health (SEH).
Information on family routines was collected by maternal interviews when children were ages 2 and 4 months, 4 years, and at kindergarten entry. Family routines were defined as family dinners ≥5 days/week; reading, storytelling, or singing ≥3 times/week; and playing at least a few times weekly. At kindergarten entry, mothers rated their children's SEH on two standardized scales; a total score >1 standard deviation above the mean was considered high SEH.
Approximately 75% of children participated in ≥3 family routines; 73% regularly ate dinner together, 71% read regularly, 51% participated in storytelling, 77% participated in singing, and 67% participated in playing. At kindergarten entry, 17% of children were rated with high SEH scores. Four family routines were associated with increased odds of a high SEH score: family dinners, storytelling, singing, and playing. Reading was not associated with high SEH.
Comment: Young children who frequently engaged in home-based family routines were rated higher by their mothers on standard social and emotional health measures. The results would be stronger if the children had been evaluated by standardized interview at school entry rather than by maternal report. Nonetheless, the study is a valuable reminder to encourage these specific family routines. Noting the association with higher SEH might encourage some parents to engage in these routines. It is surprising that reading with children ≥3 times/week was not associated with higher SEH. Previous studies have demonstrated the benefits of reading routines on early childhood development (NEJM JW Pediatr Adolesc Med Sep 9 2005).
Citation(s): Muñiz EI et al. Family routines and social-emotional school readiness among preschool-age children. J Dev Behav Pediatr 2014 Feb/Mar; 35:93.
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MM: The premise of this article is excellent. The recommendation that to get started on exercise is simple to get up during a commercial while watching TV and walk around the house to a destination other than the kitchen is a sad commentary on how much time is spent watching TV but probably a good suggestion. On the other hand, it sort of takes away some of the joy of having DVR'd your favorite shows.
Modest Midlife Exercise Seems Able to Ward Off Disability, Early Death
By Joe Elia
Two BMJ studies illustrate the dangers of inactivity in middle age, as well as show a simple way to get more activity.
The first study used accelerometers to monitor 7 days of physical activity (light or moderate in intensity) among some 1800 adults over age 49 who had knee osteoarthritis or were at risk for it. At 2 years' follow-up, even light-intensity activities were significantly related to avoidance of disability onset or progression.
The second study examined the prognostic value of grip strength, chair-rise speed, and standing balance in some 2800 adults (age at baseline, 53 years) followed up after 13 years. Those in the lowest quintile of composite scores had nearly quadruple the risk for all-cause mortality, compared with those in the highest quintile of achievement.
To avoid disability or early death, an editorialist suggests that increasing light activity by over an hour a day (say, by walking around during television commercials) "might do the trick."
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MM: Although I do not agree with the prevailing food pyramid/plate, I do agree that westerners - not just Americans - are eating a diet that is unbalanced and ultimately detrimental to their health. This is a condition that pervades the U.S., Canada, Mexico, Japan and western Europe. The excessive proportion of fats, carbohydrates and prepared foods has contributed to this condition. Nutritional education about portions and content will go a long way towards improving this situation.
Dietary Fiber After MI Linked to Improved Survival
By Larry Husten
Consuming more dietary fiber after myocardial infarction is associated with a reduced risk for death, a BMJ study finds.
Researchers analyzed long-term data about diet and other risk factors from more than 4000 healthcare professionals who had an MI. Nine years after the MI, people who were in the highest quintile of fiber consumption had a 25% lower risk for death from any cause. Overall, there was a 15% reduction in mortality risk associated with every 10-g/day increase in fiber intake.
The strongest association was observed for fiber derived from cereals and grains. A strong benefit was also found for people with the largest increases in fiber consumption after their MI. The findings remained significant after adjustment for other factors known to influence survival after MI. However, the authors acknowledge that they were unable to "fully adjust for all known or unknown healthy lifestyle changes."
The authors note that less than 5% of people in the U.S. consume the minimum recommended amount of fiber (25 g/day for women and 38 g/day for men).
Adapted from CardioExchange.
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MM: This is a sad commentary on medicine and healthcare in general. The increased demands upon clinicians while respect, reimbursement and overall quality of life are being diminished has been leading to this unfortunate result. What is so sad is that doctors who are the new entries into the field are already experiencing this attitude. These young clinicians are to be the future and yet they are demoralized at the very start of their careers.
Cynicism in Medicine
When a group of residents were recently asked whether they were more or less cynical now than at the start of their residency, many expressed increased cynicism toward the healthcare system — but not toward patients.
Akhil Narang poses the same question to readers, adding: "If you're more cynical, why and how much of this was a result of modifiable factors in your training program?"
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MM: I sort of liked this article due to its' simplistic suggestion to decrease the risk of injury while it identified the problem. It seems that we all too often see the identification of a problem but a solution is not offered. This was a refreshing change.
Pediatrics Academy Offers Clinical Guide for ACL Injuries
A guide from the American Academy of Pediatrics focuses on injuries of the anterior cruciate ligament, including diagnosis, treatment, and prevention.
The document, available for free in Pediatrics, shows that girls are especially vulnerable to these injuries and are more prone to suffer them at a younger age than boys. ACL injury, regardless of the treatment used, predisposes the patient to degenerative arthritis of the knee. However, neuromuscular training — particularly repetitive jumping exercises to strengthen the lower extremity — can greatly reduce injury risks.

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