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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
December 7, 2013

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Meta-Analysis Finds No Causal Relationship Between Vitamin D Status and Health
Pregnant, Ill, and Now a Clot
Meta-Analysis Dispels Myth of "Healthy" Obese
Management Guidelines for Overweight and Obesity in Adults
Addressing Insomnia Seems to Alleviate Depression
Exercise Interventions Can Prevent Injurious Falls in Elders
Antibiotic Treatment of Children Hospitalized with Pneumonia
Kangaroo Care in Preterm Infants Has Long-Term Benefits
How Common Is Hoarding Disorder?
Sleep and General Anesthesia Clear the Mouse Brain of Toxic Metabolites
The Importance of Interpregnancy Weight Control

MM: This type of analysis confuses me. On one side the studies show improvement in a variety of wide ranging conditions yet the analysis indicates that there is no statistical improvement of those with higher levels of Vitamin D. How can that be? If inflammation is the source of disease and Vitamin D can mediate inflammation then ipso facto, improved levels of vitamin D can influence/improve disease status. In our practice, we have seen frequent and consistent improvement in a wide variety of conditions when we increased the patients' Vitamin D level. Although I like and respect the LANCET, I believe that this analysis may be flawed.
Meta-Analysis Finds No Causal Relationship Between Vitamin D Status and Health
By Amy Orciari Herman
Vitamin D's frequently observed association with health conditions is not causal, according to a meta-analysis in the Lancet Diabetes & Endocrinology.
Researchers analyzed data from 290 prospective cohort studies and 172 randomized trials examining the relation between serum concentrations of 25-hydroxyvitamin D and nonskeletal health conditions. In the cohort studies, higher 25 (OH)D concentrations generally were associated with lower likelihood of cardiovascular disease, lipid disorders, glucose metabolism disorders, infectious diseases, multiple sclerosis, mood disorders, and total mortality. However, the randomized trials showed no effect of vitamin D supplementation on these outcomes.
The authors conclude that low serum vitamin D may simply be a marker of poor health. They speculate that low concentrations "could be the result of inflammatory processes involved in the occurrence and progression of disease."
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MM: Hardly a day goes by that I don't meet a pregnant woman who would benefit from graduated compression hosiery. These hosiery - when properly fitted - can make the difference in a pregnancy between comfort and discomfort and - as this article describes - life and death. Unfortunately, many clinicians lack education and understanding about Graduated Compression hosiery. Most clinicians only see compression hosiery in the hospital and these patients are bed-ridden aka non-ambulatory. For these non-ambulatory patients, the appropriate hosiery is constant compression hosiery, known as TED hose. For patients who are ambulatory (walking around), the appropriate hosiery are GRADUATED COMPRESSION hosiery. They are not the same, nor do they do the same thing. TED hose on an ambulatory patient can ultimately constrict the leg and restrict blood flow back to the heart. This can worsen a condition and is potentially deadly to a patient. MARK DRUGS ROSELLE is expert in the measuring and fitting of Graduated Compression Hosiery.
BMJ 2013 Nov 8; 347:f6099
Pregnant, Ill, and Now a Clot
Women hospitalized during pregnancy face increased risk for venous thromboembolism.
Venous thromboembolism (VTE) is one of the leading causes of maternal death in developed countries, but risk factors for antepartum VTE are not fully understood.
In an analysis of data from some 300,000 Danish births from 2003 through 2010, investigators found that VTE complicated 1.1 per 1000 pregnancies. In addition to known risk factors (e.g., overweight, history of VTE), hyperemesis gravidarum and use of benzodiazepines were associated with excess risk for antepartum VTE.In another study, U.K. researchers linked two national longitudinal databases in primary care and hospital admissions to assess the effects of hospitalization during pregnancy on VTE risk. Among 246,000 pregnancies, 18% of women required hospitalization; 22% of these hospitalizations lasted ≥3 days. Women with preexisting risk factors for VTE accounted for 27% of antepartum admissions. Risk for antepartum VTE was >17 times higher during hospitalization and 6 times higher during the month following discharge regardless of preexisting comorbidity. Thus, 1 of every 2000 antepartum hospitalizations (and 1 of every 1000 hospitalizations ≥3 days) was complicated by VTE. Hyperemesis gravidarum doubled risk for VTE. Overall, the rate of first VTE during pregnancy was four times higher than the rate in nonpregnant women.
Comment: Given that as many of 2% of pregnant women treated with low molecular weight heparins experience major bleeding, prophylaxis for venous thromboembolism is not routinely recommended during pregnancy. However, careful consideration of VTE risk against the potential benefits of prophylaxis is warranted in pregnant women who are hospitalized for longer than 3 days, especially when other VTE risk factors are present. Thromboprophylaxis is more commonly required in the postpartum setting, particularly following cesarean delivery.
Citation(s): Jensen TB et al. Risk factors for venous thromboembolism during pregnancy. Pharmacoepidemiol Drug Saf 2013 Oct 16; [e-pub ahead of print].
Sultan AA et al. Risk of first venous thromboembolism in pregnant women in hospital: Population based cohort study from England. BMJ 2013 Nov 8; 347:f6099.
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MM: A lot has been made of nominal weight loss and its benefits. Although weight loss in general is good, this analysis makes the point that being overweight and otherwise seeming to be in good health may actually be a deadly condition.
Meta-Analysis Dispels Myth of "Healthy" Obese
By Amy Orciari Herman
Having a healthy metabolic profile — for example, normal blood pressure, triglycerides, and blood glucose — does not appear to protect obese adults from increased risks for cardiovascular events or death, according to a meta-analysis in the Annals of Internal Medicine.
The analysis included eight observational studies comprising over 60,000 adults whose BMIs and metabolic profiles were assessed. Participants were defined as metabolically healthy if they did not meet criteria for the metabolic syndrome. (The syndrome was usually defined as having at least three of the following: increased waist circumference, high triglycerides, low HDL cholesterol, hypertension, and elevated blood glucose.)
In the four studies with at least 10 years' follow-up, metabolically healthy obese adults had a significant, 24% increased risk for the combined endpoint of cardiovascular events or death, relative to metabolically healthy normal-weight adults. Similarly, metabolically healthy overweight participants had a 21% increase in risk, but this did not reach statistical significance.
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J Am Coll Cardiol 2013
Management Guidelines for Overweight and Obesity in Adults
A thorough review of the current evidence base informs recommendations regarding dietary, pharmacologic, lifestyle, and surgical interventions.
Background and Objective: These recommendations stem from the work of an Expert Work Group convened by the National Heart, Lung, and Blood Institute to update the 1998 Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults — The Evidence Report.
The Work Group developed five critical questions to address in the revision: (1) What are the benefits of losing weight, and how much weight loss is needed to achieve them? (2) Are established cutpoints for overweight and obesity appropriate across different populations? (3) What is the best diet? (4) What is the best lifestyle intervention? (5) What are the benefits and risks of various bariatric surgical procedures?
Key Points

What's Changed
Current evidence regarding specific diets, lifestyle interventions, and surgical alternatives is thoroughly reviewed. Evidence for a continuous relationship between BMI and cardiovascular effects has led to some relaxation in the initial weight-loss target (≥5% vs. ≥10%).
Comment: These guidelines continue to emphasize the importance of moderate weight loss in improving cardiovascular outcomes in overweight or obese patients and underline the reality that there is no magic bullet when it comes to weight loss. In particular, the fact that no specific diet or diet plan is recommended sends an important message — many different strategies can be successful, provided that caloric intake is reduced. The authors recognize that integrated, intensive, yearlong lifestyle programs are the most likely to achieve good results and remind clinicians that bariatric surgery should be reserved for patients with a body-mass index of ≥40 without co-morbid conditions.
Citation(s): Jensen MD et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol 2013; [e-pub ahead of print].
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MM: There is no question that sleep is important for metabolic conditions and weight management. Also, that if a person constantly uses sleep aids, then their deep REM sleep and dream sleep can be disrupted and that can increase anxiety, diminish cognitive function and potentially influence depression. This article takes another look at an added approach to dealing holistically with depression.
Addressing Insomnia Seems to Alleviate Depression
By Joe Elia
Patients may ask about reports on the use of cognitive behavioral therapy to resolve insomnia, especially because the approach also seems to enhance the effectiveness of antidepressants. More than half of Americans with depression also suffer from insomnia, according to the New York Times.
Two Times reports describe a technique — not yet widely available but easily taught — called CBT-I (or cognitive behavioral therapy for insomnia). It involves about four sessions that emphasize control of stimuli around bedtime and keeping a sleep diary. Tactics include avoiding eating or watching television in bed, and getting up at the same time each day. If needed, cognitive therapy to challenge self-defeating thoughts (e.g., "If I don't sleep well, I can't function the next day") is added.
Four small studies under way use the technique as part of treating patients with depression. A preliminary report found that almost 90% of patients whose insomnia resolved after 8 weeks of CBT-I also had resolution of depression after 8 weeks of treatment with either an antidepressant or a placebo.
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MM: It's been said 'that the best way to prevent a broken hip is not to fall'. It makes sense that improved muscle tone and core strength is a good way to prevent falls in people of all ages but in the elderly this has an even greater significance since this group can sustain much greater injury and heal much more slowly than the younger population.
BMJ 2013 Oct 29; 347:f6234
Exercise Interventions Can Prevent Injurious Falls in Elders
Most exercise programs included balance training.
Falls cause substantial morbidity among elders and are costly. Although exercise interventions can prevent falls in older adults, whether such interventions also prevent fall-associated injuries is unclear. To determine the effects of fall-prevention exercise interventions on fall-related injuries, investigators in France conducted a meta-analysis of 17 randomized trials that involved 4300 community-dwelling elders (mean age, 77).
Most exercise programs included gait-, balance-, and strength-training components. Four outcomes were assessed: all injurious falls, falls resulting in medical care, severe injurious falls, and falls resulting in fractures. Compared with no intervention or placebo intervention (e.g., general health education class), exercise interventions significantly lowered the number of falls resulting in any injury (ranging from minor bruises to serious injuries such as fractures or head trauma; rate ratio, 0.6), falls resulting in medical care (RR, 0.7), falls resulting in serious injuries (RR, 0.6), and falls resulting in fractures (RR, 0.4). The interventions were effective regardless of baseline fall risk.
Comment: This meta-analysis convincingly shows that exercise interventions prevent falls and fall-related injuries — both minor and major — in elders. Elders should be encouraged to participate in such programs, because one in three elders falls every year, falls are a leading cause of nonfatal and fatal injuries, and falls are associated with US$30 billion in direct medical costs annually.
Citation(s): El-Khoury F et al. The effect of fall prevention exercise programmes on fall induced injuries in community dwelling older adults: Systematic review and meta-analysis of randomised controlled trials. BMJ 2013 Oct 29; 347:f6234.
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MM: As antibiotic (Ab)resistance is generally increasing across society, it makes more and more sense to try to be more specific when Ab's are truly needed. This study reinforces that approach. Using a broad spectrum antibiotic may seem to be a quick and easy treatment approach but in the long run, it can be extremely costly and not in the best interest of the patient or society in general.
Pediatrics 2013 Nov; 132:e1141
Antibiotic Treatment of Children Hospitalized with Pneumonia
Clinical outcomes associated with narrow-spectrum antibiotics and broad-spectrum antibiotics were equivalent.
In 2011, the Pediatric Infectious Diseases Society guidelines for management of community-acquired pneumonia (CAP) in infants (age >3 months) and children recommended use of narrow-spectrum antibiotics for outpatient (e.g., amoxicillin) and inpatient (e.g., ampicillin) management of uncomplicated CAP. Researchers retrospectively studied outcomes associated with this strategy using data from 43 free-standing children's hospitals in the Pediatric Health Information System database.
Between 2005 and 2011, nearly 150,000 children (age range, 6 months – 18 years) were hospitalized with CAP; of these, 15,564 children were included in the study after excluding children with complicated pneumonia, possible healthcare-associated pneumonia, and complex chronic conditions. Ninety percent of study children received broad-spectrum antibiotics and 10% received narrow-spectrum antibiotics. No significant differences were found between the two groups in median length of stay (3 days), transfer to the intensive care unit after 2 days of hospitalization (1.1% and 0.8%), readmissions within 14 days (2.3% and 2.4%), and median cost of hospitalization. Matched analysis of propensity scores in 1044 children in each exposure group also showed no difference between groups. Subgroup analysis of 4876 children with acute wheezing and pneumonia found no differences in outcomes between antibiotic groups or between wheezing and non-wheezing groups.
Comment: The results of this carefully done retrospective study suggest that narrow-spectrum antibiotics are just as effective as broad-spectrum antibiotics for otherwise healthy children requiring admission for uncomplicated community-acquired pneumonia. Judicious use of antibiotics in both the outpatient and inpatient arenas is important to prevent the development of resistant bacterial pathogens.
Citation(s): Williams DJ et al. Narrow vs broad-spectrum antimicrobial therapy for children hospitalized with pneumonia. Pediatrics 2013 Nov; 132:e1141.
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MM: Most people of all ages like a hug. It is not a surprise that pre-term infants would like and benefit from the same thing. The closeness of another human being, especially the comfort of a mother and the ability to hear and feel the familiar beat of her heart can have a soothing and apparently therapeutic effect on a patient/infant. Maybe we should consider a similar cuddling approach for a variety of diseases. All kidding aside, could this be a potential option to complement Obamacare?
Biol Psychiatry 2013 Oct 3
Kangaroo Care in Preterm Infants Has Long-Term Benefits
Postpartum maternal–infant skin-to-skin contact was associated with better cognition, sleep, and executive function at age 10 years.
Maternal–infant skin-to-skin contact in the form of kangaroo care (KC) in premature infants enhances neuromaturation. KC is associated with better autonomic function, electroencephalogram complexity, pain response, and physiologic stability, as well as improved mother–infant interactions/bonding and maternal mood. Whether these benefits are sustained long-term is not known.
Investigators in Israel prospectively examined the effects of KC in 146 premature infants (mean birth weight, 1270 g; mean gestation, 30.5 weeks); 73 infants were undressed and placed between the mothers' breasts for 1 hour daily for 14 days while the mother sat in a rocking chair, and 73 case-matched control infants received standard care in an incubator. All children were evaluated seven times during the first decade of life using standardized measurements for autonomic function (respiratory sinus arrhythmia), cognition, and parent mental health. Mother–child interactions at term, and at ages 3 months, 6 months, and 10 years were videotaped and assessed for maternal gaze, “motherese” high-pitched vocalizations, positive affect, and affective touch.
Compared with the control group, maternal attachment behavior and autonomic function were increased during the postpartum period in the KC group. From ages 6 months to 10 years, the KC group showed a sustained reduction in maternal anxiety and higher levels of cognitive development, organized sleep patterns, and executive functions. At age 10 years, KC children had lower cortisol levels in response to a standardized stress test (making a public speech and completing a complex math problem before an unfamiliar judge).
Comment: Kangaroo care for premature infants has come a long way from the initial observation in Bogotá, Colombia, where incubators were not available. The physiological and behavioral benefits derived from KC are thought to be a result of early and frequent skin-to-skin contact at a sensitive period of neurological maturation in premature infants. At a time when cost-effective interventions are valued, KC appears to be a good investment.
Citation(s): Feldman R et al. Maternal-preterm skin-to-skin contact enhances child physiologic organization and cognitive control across the first 10 years of life. Biol Psychiatry 2013 Oct 3; [e-pub ahead of print].
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Br J Psychiatry 2013 Oct 24
How Common Is Hoarding Disorder?
This new DSM-5 diagnosis is not rare, and hoarders are older, poorer, unpartnered, and less healthy and have more mental-health comorbidities.
Individuals with pathological hoarding refuse to discard objects and accumulate such clutter in their homes that these become close to uninhabitable. Previously thought to be a variant of obsessive-compulsive disorder (OCD), the syndrome has recently been viewed as distinct, difficult to treat, and extremely disabling. To determine its prevalence, researchers used a population-based health survey of 1698 London residents (age range, 16–90) and in-home interviews of 99 of 201 subjects screening positive on a single question about hoarding.
After in-home interviews and environment ratings, only 19% of respondents with positive screens met criteria for hoarding, giving a prevalence of 1.5%. Examination of descriptions of the in-home environment in screen-negative subjects yielded a potential 28 more cases. Hoarders were more likely to be older, poorer, and without a partner and to have a physical health condition and comorbid mental disorder. Only a third had sought help in the past year.
Comment: Hoarding disorder is as common as obsessive-compulsive disorder, schizophrenia, bipolar illness, and autism; often adversely affects family and caretakers; and yet has been infrequently investigated. No medications are known to help, although a recently developed approach using cognitive-behavioral therapy may hold some promise. Unfortunately, this study did not measure cognitive function, which has also been shown to be diminished in hoarders. The results remind clinicians that two thirds of patients volunteering that they are “hoarders” may not have this disorder, although those that do are likely to have considerable medical and psychiatric comorbidities.
Citation(s): Nordsletten AE et al. Epidemiology of hoarding disorder. Br J Psychiatry 2013 Oct 24; [e-pub ahead of print].
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Science 2013 Oct 18; 342:373
Sleep and General Anesthesia Clear the Mouse Brain of Toxic Metabolites
Does this phenomenon explain why we feel restored after a good night's sleep?
Without sufficient sleep, mood and cognition are impaired. Various central nervous system conditions, including migraines and seizures, become more frequent and severe. When animals are kept from sleeping, they ultimately die.
We need to sleep. But why? Investigators from New York developed a technique for measuring the interstitial space in the brains of living mice. That space is bathed by cerebrospinal fluid that is produced by the choroid plexus and pumped back into the blood in the meninges. The investigators found that, during sleep and anesthesia, the interstitial space increased by 60%. The functional result of this expansion is that many metabolites of neurons and glial cells that spill into the interstitial space are cleared from the space much more rapidly, enter the blood, and are detoxified by the liver. These molecules include β-amyloid and tau, which build up in the brains of patients with Alzheimer disease. When sleeping animals are aroused, clearance of toxic metabolites slows markedly.
Comment: The investigators speculate that, at least in mice, buildup of toxic metabolites in the brain's interstitial space is a trigger for sleep and that a key purpose of sleep is to clear such metabolites. Perhaps we feel restored in the morning because the brain has freed itself of toxins. This hypothesis is arresting in its simplicity and could prove to be profoundly important in human biology.
Citation(s): Xie L et al. Sleep drives metabolite clearance from the adult brain. Science 2013 Oct 18; 342:373.
Abstract/FREE Full Text Herculano-Houzel S.Sleep it out. Science 2013 Oct 18; 342:316. (http://dx.doi.org/10.1126/science.1245798)
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Obstet Gynecol 2013 Nov; 122:999
The Importance of Interpregnancy Weight Control
Second pregnancies had more complications if conception occurred before maternal return to original prepregnancy weight.
Obesity rates among women of reproductive age have risen in most developed countries. To examine the effects of changes in prepregnancy weight between consecutive pregnancies on complication rates in a second pregnancy, researchers analyzed data on body-mass index in 7897 women in northern Belgium who delivered their first two live-born singletons between 2009 and 2011 and who participated in a population-based cohort study by the Center for Perinatal Epidemiology.
Prevalence of overweight and obesity increased from 25% to 31% between first and second pregnancies. Interpregnancy weight retention was associated with increased risk during the second pregnancy for gestational diabetes and pregnancy-induced hypertension (even in women who were underweight or normal weight before their first pregnancies) and for cesarean delivery in women who were initially overweight or obese. These effects remained significant after accounting for maternal age and gestational weight gain. Longer interpregnancy intervals were associated with less weight retention.
Comment: Although this study did not include data on postpartum contraception or lactation, both of which play key roles in optimizing interpregnancy intervals, the findings suggest that mothers who are encouraged to return to their original prepregnancy weight before pursuing subsequent pregnancies may have better obstetric outcomes.
Citation(s): Bogaerts A et al. Interpregnancy weight change and risk for adverse perinatal outcome. Obstet Gynecol 2013 Nov; 122:999.

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