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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
September 13, 2014

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Low-Carb Diet Linked to Greater Weight Loss Than Low-Fat
Popular Diets Similar in Terms of Weight Loss, Meta-Analysis Finds
New Data on the Relation Between Excess Weight and Cancer Incidence
Consumer Reports: Pregnant Women Should Avoid All Tuna
Shorter Intervals Between Pregnancies Do Not Appear to Increase Adverse Outcomes
Capturing Circulating Tumor Cells to Ascertain Drug Sensitivity
Drugs That Raise HDL Cholesterol Levels Don't Change All-Cause Mortality or Prevent
   Fatal Cardiac-Related Events
Parents Who Refuse Neonatal Vitamin K Prophylaxis Are More Likely to Refuse
   Childhood Immunizations
Origin of the Ebola Outbreak
Lack of Protective Gear Contributing to Ebola Toll Among Healthcare Workers
Teaching Parents How to Nurture May Improve Children's Long-Term Health
Topiramate for Comorbid Post-Traumatic Stress and Alcohol Use Disorders

MM: It is reassuring that this study demonstrates the weight loss benefits of a low carb diet vs a low fat diet however, it is curious that the researchers further question the long term benefits of this dietary approach. Other examples of the benefits of a low carb approach( a Mediterranean Diet) may be seen in a variety of illnesses from chronic inflammation to seizure disorders (a Ketogenic diet).
Low-Carb Diet Linked to Greater Weight Loss Than Low-Fat
By Kelly Young, Edited by David G. Fairchild, MD, MPH, and Jaye Elizabeth Hefner, MD
A low-carbohydrate diet is associated with greater weight reduction than a low-fat diet among obese adults, according to an Annals of Internal Medicine study.
Roughly 150 obese adults who were otherwise healthy were randomized to eat either a low-fat (<30% fat) or low-carbohydrate (<40 g/day of digestible carbohydrates) diet. Participants were provided diet-specific handbooks with recipes and meal-planning tips in addition to a daily meal-replacement shake or bar.
At 12 months, the low-carb group had lost 3.5 kilograms more than the low-fat group, even though caloric intakes were similar. The low-carb group also saw greater improvements in body composition, CRP levels, HDL cholesterol, and triglycerides.
NEJM Journal Watch Cardiology editor-in-chief Harlan Krumholz comments: "This study, a welcome trial in an area where we need them, supports the new conventional wisdom that low carb is better than low fat for losing weight — what we do not yet know is which diet is better for lowering risk. That information will require larger trials with much longer follow-up — but we desperately need that information."
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MM: I find it interesting that the same data may be interpreted in many ways and quite often these interpretations disclose the individual bias of the reviewer.
Popular Diets Similar in Terms of Weight Loss, Meta-Analysis Finds
By Amy Orciari Herman, Edited by David G. Fairchild, MD, MPH, and Lorenzo Di Francesco, MD, FACP, FHM
Popular branded low-carbohydrate and low-fat diets lead to significant weight loss, with little difference between the two approaches, according to a network meta-analysis in JAMA.
Researchers examined data from 48 randomized trials that studied various popular diets among roughly 7300 overweight or obese adults. They found that all diets were superior to no intervention. In particular, low-carb programs (e.g., Atkins) and low-fat approaches (e.g., Ornish) yielded the greatest weight loss at 6 months (roughly 8 kg versus no diet), with minimal differences among the individual diets. Weight loss at 6 months was somewhat lower with moderate macronutrient diets (e.g., Weight Watchers), at just under 7 kg.
The authors say their analysis "supports the practice of recommending any diet that a patient will adhere to in order to lose weight."
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MM: For a long time diabetes, colon cancer, breast cancer and CV disease have been associated with obesity but this data supporting the increased relationship between uterine, gall bladder, kidney, cervical, thyroid. liver ovarian and leukemia forms of cancer is mind blowing. Weight loss is not easy but it very well may mean the difference in life, death and the emotional and financial well-being of one's family. For these and many more reasons I continue to endorse the HCG Weight Loss and Metabolic Syndrome program.
Lancet 2014 Aug 14
New Data on the Relation Between Excess Weight and Cancer Incidence
Increasing body-mass index was associated with increasing incidences of certain cancers.
A 2008 meta-analysis deepened our understanding of associations among body-mass index (BMI), sex, and incidences of a variety of malignancies (NEJM JW Gen Med Feb 28 2008). Now, using data collected from British general practices, researchers have analyzed >160,000 new cancers that occurred in a population of 5 million people (age, ≥16) during a mean follow-up of 7.5 years. The investigators evaluated the relations between baseline BMI and cancer incidence and the contributions of other factors such as age, smoking, and menopausal status.
Increasing BMI was associated with increasing incidences of cancers of the uterus, gallbladder, kidney, cervix, thyroid, liver, colon, ovary, and breast (postmenopausal) and with leukemia. Overall, cancers of the lung and oral cavity were more common in patients with lower BMIs, but these associations were driven entirely by smoking history; BMI was unrelated to incidence of these cancers in never-smokers. Assuming causality, 41% of uterine cancers and more than 10% of several other cancers could be attributed to excess weight.
Comment: The effects of BMI on cancer incidence vary based on organ and patient subgroup, which suggests a diversity of underlying mechanisms. These data might help elucidate some of these pathways, and they add yet more urgency for developing strategies to prevent excessive weight gain and to treat overweight and obesity.
Citation(s): Bhaskaran K et al. Body-mass index and risk of 22 specific cancers: A population-based cohort study of 5·24 million UK adults. Lancet 2014 Aug 14; [e-pub ahead of print].
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MM: I find it tragic that a food that is so beneficial in so many ways is such a great risk in so many other ways. I love sushi and tuna is my favorite form of it. Fortunately I am neither a child nor a pregnant woman but all of us must be cognizant of what we introduce into our bodies as heavy metal exposure may lead to cognitive decline and potentially contribute to conditions such as Alzheimer's Disease (AD). The moniker "brain food" may now have several meanings.
Consumer Reports: Pregnant Women Should Avoid All Tuna
By Kelly Young
Pregnant women should avoid eating tuna altogether because of the risk for mercury exposure, says Consumer Reports. The recommendation is at odds with the FDA and EPA, which recently proposed that pregnant women eat 8-12 oz. of low-mercury seafood, including canned light tuna, weekly.
The agencies recommended limiting consumption of albacore tuna to 6 oz. per week. But Consumer Reports' analysis of FDA data found that a 125-pound woman could exceed the EPA's recommended mercury consumption limit by eating just 4 oz. weekly. Canned light tuna does, on average, contain less mercury than albacore, but FDA data indicate that 20% of canned light tuna samples contained double the average level of mercury.
In addition, Consumer Reports recommends that young children, women of childbearing age, and people who eat 24 oz. of fish per week or more should not eat yellowfin and big eye tuna in sushi since these are high-mercury fish.
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MM: As much of our higher socio-economic, American population tends to have children later in life due to educational and professional goals being achieved first, and with that there is the tendency to have multiple births in a relatively close time proximity to each other, this is reassuring news.
Shorter Intervals Between Pregnancies Do Not Appear to Increase Adverse Outcomes
By Kelly Young, Edited by Susan Sadoughi, MD, and Richard Saitz, MD, MPH, FACP, FASAM
Having pregnancies in quick succession was not associated with increased risk for adverse birth outcomes in a study in the BMJ. The World Health Organization recommends a minimum of 2 years between birth and subsequent pregnancy.
Using Australian healthcare databases, researchers studied over 40,000 women who had three births. The time between a women's first and second pregnancy was compared with that between her second and third, allowing each woman to be her own control.
Compared with 18 to 23 months between pregnancies, shorter interpregnancy times were not significantly associated with increased risk for preterm birth, small for gestational age, or low birth weight in fully adjusted models.
The authors write: "Our study suggests that adverse birth outcomes are not the result of short interpregnancy intervals in themselves but are due to correlated maternal risk factors … such as socioeconomic and lifestyle factors."
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MM: Less invasive diagnostic techniques reduce costs and risk of spreading a disease within a specific patient. Taking venous blood is a relatively simple approach and may soon be replaced with a process similar to checking blood glucose levels. This could make cancer screening and specific tumor identification as easy as a simple home testing kit.
Science 2014 Jul 11; 345:216
Capturing Circulating Tumor Cells to Ascertain Drug Sensitivity
Breast cancer cells isolated from venous blood in six patients were cultured and evaluated for mutations.
Both primary tumors and metastatic tumor deposits shed malignant cells into the circulation. Capturing an individual's circulating tumor cells and studying them for genetic mutations and drug sensitivity could lead to more-effective, targeted treatment. Moreover, if a less invasive method of collecting such tumor cells, via venipuncture rather than biopsy, were developed, both patients and physicians would benefit. The problem, however, is that tumor cells are shed in very small numbers. Finding the tumor cell “needle” in the “haystack” of white blood cells has been difficult.
A team from Harvard-affiliated institutions has developed a specialized cell sorting technique and has extracted circulating breast cancer cells from six patients. The researchers grew the extracted tumor cells in culture and evaluated them for genetic mutations (through rapid genome sequencing) and drug sensitivities.
Comment: This encouraging report indicates that we might be able to determine the biology of an individual's cancer via simple venipuncture. This approach would allow us to monitor mutational changes in a tumor and to individualize drug therapies throughout the clinical course without having to obtain additional tumor material invasively. However, this study is very preliminary, and the researchers did not attempt to prove that isolating circulating tumor cells would improve clinical care for patients.
Citation(s): Yu M et al. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility. Science 2014 Jul 11; 345:216. (http://dx.doi.org/10.1126/science.1253533)

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MM: It seems that although having a higher intrinsic level od HDL is heart protective, the artificial or drug induced raising of HDL fails to demonstrate significant benefits. Therefore, as simplistic as the recommendation may be, its best to modify diet and exercise routines rather than tryinfg to rely on medicine and supplements for optimal CV health.
BMJ 2014 Jul 18; 349:g4379.
Drugs That Raise HDL Cholesterol Levels Don't Change All-Cause Mortality or Prevent Fatal Cardiac-Related Events
In patients not taking statins, risk for nonfatal myocardial infarction was lower among those taking niacin or fibrates.
HDL cholesterol levels are associated inversely with cardiovascular (CV) risks. In this meta-analysis of nearly 40 randomized, controlled trials, investigators determined whether drugs that raise HDL cholesterol levels lower risk for adverse CV outcomes in >117,000 patients.
All of the drugs — niacin, fibrates, and cholesteryl ester transfer protein (CETP) inhibitors — raised HDL cholesterol levels significantly. However, across all trials, none of the drugs lowered all-cause mortality, coronary heart disease–related mortality, or risk for stroke, compared with control treatments (mostly placebo). In statin-naive patients, risk for nonfatal myocardial infarction was significantly lower among those who took niacin (odds ratio, 0.7) or fibrates (OR, 0.8), and niacin was associated with lower risk for stroke (OR, 0.8). None of the drugs lowered risk for adverse CV outcomes in statin-treated patients.
Comment: Although niacin, fibrates, and CETP inhibitors raised HDL cholesterol levels significantly, none of these drugs lowered risk for all-cause death, death from coronary heart disease, or stroke. Notably, CETP inhibitors are unavailable for clinical use. Do niacin and fibrates have roles in selected patients? Probably not for niacin: Recent studies have shown that niacin is ineffective in statin-treated patients with vascular disease (NEJM JW Gen Med Jul 16 2014). In contrast, evidence from subgroups embedded in larger randomized trials suggests that fibrates might lower risk for adverse CV outcomes in statin-treated patients with both high triglyceride and low HDL cholesterol levels (Atherosclerosis 2011; 217:492). A trial devoted to low-HDL, high-triglyceride patients would be appropriate.
Citation(s): Keene D et al. Effect on cardiovascular risk of high density lipoprotein targeted drug treatments niacin, fibrates, and CETP inhibitors: Meta-analysis of randomised controlled trials including 117 411 patients. BMJ 2014 Jul 18; 349:g4379. (http://dx.doi.org/10.1136/bmj.g4379)

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MM: I find it interesting that the correlation of refusal of "general" injections was consistent for parents on typically uncomplicated births. Please note that there was no increased incidence of complications, overall, compared to children who did receive the injections. Also, the authors indemnify the potential problems associated with lack of Vitamin K injection but merely allow the reader to make the same association of vaccines that their refusal may lead to death.
Pediatrics 2014 Sep 15; 134:497
Parents Who Refuse Neonatal Vitamin K Prophylaxis Are More Likely to Refuse Childhood Immunizations
In Canada, more parents are declining intramuscular vitamin K prophylaxis and this decision correlates with vaccine refusal
Intramuscular administration of vitamin K at birth prevents late vitamin K deficient bleeding, and parental refusal of prophylaxis has rare but devastating consequences (NEJM JW Pediatr Adolesc Med Dec 4 2013). Researchers examined parent refusal rates, patient characteristics, and compliance with subsequent immunization in a retrospective review of all infants born in Alberta, Canada, between 2006 and 2012.
Most (99.3%) of the 282,378 infants received intramuscular vitamin K and 0.4% received oral vitamin K. During the 6-year period, the refusal rate rose significantly from 0.21% to 0.32%. Factors associated with vitamin K refusal included delivery at home or birthing center and delivery by a midwife (4.9, 3.5, and 8.4 times higher than delivery at hospitals and by physicians, respectively). Mothers who delivered vaginally without epidurals had a significantly higher refusal rate than those who delivered vaginally with epidurals. Nonimmunization rates in infants who did and did not receive vitamin K were about 5% vs. 75% for DTaP-IPV-Hib, meningococcal, and pneumococcal primary series and 20% vs. 85% for MMR and VZV vaccines. At age 15 months, children who did not receive neonatal vitamin K prophylaxis were 15 times more likely to have not received any childhood vaccinations than children who did receive vitamin K.
Comment: Although refusal of intramuscular neonatal vitamin K prophylaxis is not common, the trend seems to be increasing and correlates with vaccine refusal. The risks for both infectious and noninfectious preventable diseases are clear and need to be communicated to all who care for children.
Citation(s): Sahni V et al. Neonatal vitamin K refusal and nonimmunization. Pediatrics 2014 Sep 15; 134:497.
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MM: Patient "Zero" appears to have been a "healer" aka a healthcare person. As in our own culture, those who provide care are also at risk. We must always focus on caregiver and patient health and well-being. If we ignore either aspect, risks to all are increased.
Science 2014 Aug 29; 345:989
Origin of the Ebola Outbreak
Detailed genomic analysis helps to define the origin and spread of Ebola virus in West Africa.
With today's unprecedented outbreak of Ebola virus (EBOV) disease in West Africa (NEJM JW Infect Dis Jul 1 2014), understanding how the outbreak began and how the virus may be evolving can benefit prevention and control efforts. To obtain this information, a multinational research team sequenced EBOV genomes from 78 patients in Sierra Leone.
The first case of EBOV disease in Sierra Leone was confirmed on May 25, and epidemiologic analysis linked this case to the burial of a traditional healer who had treated EBOV disease patients in the neighboring country of Guinea. Tracing revealed 13 additional cases in women attending the burial. Investigators obtained 15 inactivated EBOV samples from 12 of these patients, as well as 84 samples from 66 other EBOV disease patients, totaling >70% of cases diagnosed in Sierra Leone through mid-June.
Phylogenetic comparison of the Sierra Leonean genomes with 20 from previous outbreaks in central Africa and 3 from cases in Guinea suggests that the strains responsible for the three most recent outbreaks diverged from a common ancestor in about 2004. The genetic similarity among EBOV strains from the current outbreak suggests a single transmission from a natural reservoir to humans, then ongoing human-to-human transmission. It appears that two distinct viral strains that had likely diverged in mid-April in Guinea were introduced into Sierra Leone at the time of the burial ceremony. The observed substitution rate within the 2014 outbreak is roughly twice as high as that between outbreaks.
Comment: An editorialist highlights the importance of this work in efforts to control the current outbreak. The high mutation rate of EBOV already has implications for the diagnosis of this infection (even now, the Sierra Leonean genomes differ from polymerase chain reaction probes used for 5 different EBOV diagnostic assays) and could complicate the development of effective vaccines and antibody-mediated treatment. The authors wish to honor the memory of five co-authors of this study who succumbed to EBOV disease in the course of their public health and research efforts in Sierra Leone. Editor Disclosures at Time of Publication Disclosures for Richard T. Ellison III, MD at time of publication Grant / research support NIH-NIAID CLOS
ECitation(s): Gire SK et al. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science 2014 Aug 28; [e-pub ahead of print]. (http://dx.doi.org/10.1126/science.1259657) Vogel G.Genomes reveal start of Ebola outbreak. Science 2014 Aug 29; 345:989.
(http://dx.doi.org/10.1126/science.345.6200.989) - See more at:

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MM: Lack of trained professionals is a problem that seems to pervade areas of lower income for these professionals. This is true in the U.S. and abroad. when it comes to areas of epidemics, these conditions seem to get worse. The lack of proper Personal Protective Equipment (PPE) and education on the proper use of this equipment would violate OSHA requirements in this country and for that reason alone American healthcare workers have this equipment and are at reduced risk of danger from their work environment. It would seem that efforts to provide this type of PPE to African nations and proper instruction of its value and use might be an effective means to limit some of the spread of this disease and improve its care.
Lack of Protective Gear Contributing to Ebola Toll Among Healthcare Workers
By Kelly Young
Edited by David G. Fairchild, MD, MPH, and Lorenzo Di Francesco, MD, FACP, FHM
The World Health Organization estimates that more than 240 healthcare workers have been infected with the Ebola virus since the outbreak began, and over half of these have died.
The affected countries were struggling with a dearth of physicians before the outbreak: in Sierra Leone, Guinea, and Liberia, there are only one or two doctors for every 100,000 people, according to WHO estimates. In Liberia, which had only 51 total physicians, 36 healthcare workers have died, according to an Annals of Internal Medicine commentary.
The Annals commentators emphasize two factors that are contributing to the high infection rate among healthcare workers: there is a scarcity of personal protective equipment (PPE), and when it is available, workers are not always following the proper procedure in putting it on and taking it off.
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Proc Natl Acad Sci U S A 2014 Aug 5; 111:11287
Teaching Parents How to Nurture May Improve Children's Long-Term Health
A 7-week intervention for families of low socioeconomic status seems to lead to less low-grade inflammation in the children 8 years later.
Early exposure to stress appears to increase vulnerability to psychiatric and medical conditions years later. Low socioeconomic status during childhood also increases this risk although some children seem less vulnerable, with better parenting apparently modifying the risk. Researchers examined peripheral blood measures of inflammation in children 8 years after a 7-week family intervention to improve parenting, strengthen family relationships, and build youth competencies.
The intervention consisted of weekly group meetings; separate 1-hour parent and youth skill-building sessions were followed by 1-hour family sessions (14 hours total). Parents learned nurturant-involved techniques and other strategies; children were taught the importance of household rules and socially adaptive behaviors. Rural families (667 mothers and their 11-year-old children; 46% were below the federal poverty threshold) were randomized to the intervention or a control (leaflets on child development, stress management, and exercise). Parents completed questionnaires at baseline and 3 months later.
In 272 youths at age 19, blood levels of six cytokines were obtained. The intervention was associated with significantly less inflammation than the control on all indicators. This finding was partially explained by improved parenting, but not by children's obesity or smoking. The more disadvantaged a family was, the more strongly changes in parenting were related to improved inflammatory markers.
Comment: Jonathan M. Silver, MD These results appear amazing: A 7-week intervention affected inflammatory markers 8 years later. Many questions remain: Did the groups have baseline differences in inflammatory markers that affected the findings? Do the marker changes translate into improved long-term health? Would other markers of chronic stress, such as telomere length (NEJM JW Psychiatry May 13 2013) show similar changes? If the results are confirmed in studies addressing these questions, we could have an important cost-effective intervention to improve the health of a vulnerable population.
Comment: Barbara Geller, MD From a child psychiatry viewpoint, these findings are consistent with the earlier developmental literature. In a classic study (Child Develop 1949; 20:145), Spitz showed that infants raised by mothers in prison, where mother–child interactions were warm and playful, had better developmental outcomes than babies raised in convents with minimal interaction with humans or toys; 37% of convent babies died by age 2. More recently, child adversity was associated with higher stress-related biomarkers in adulthood (NEJM JW Pediatr Adolesc Med Jan 27 2010). Overall, data support incorporating parenting interventions into pediatric practices in areas with low socioeconomic status
Citation(s): Miller GE et al. A family-oriented psychosocial intervention reduces inflammation in low-SES African American youth. Proc Natl Acad Sci U S A 2014 Aug 5; 111:11287.

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MM: Topiramate seems to rapidly be becoming the favorite drug in a number of categories. It has recently been approved for use in conjunction with phentermine for weight loss and now PTSD and Alcohol related disorders. This is not a side effect free drug and we will need to keep an eye on it as its projected uses start to expand.
Alcohol Clin Exp Res 2014 Aug 4;
Topiramate for Comorbid Post-Traumatic Stress and Alcohol Use Disorders
Topiramate shows promise, but causes transient cognitive side effects.
Co-occurrence of alcohol use disorders and post-traumatic stress disorder (PTSD) is common and leads to poorer outcomes and functioning than either disorder alone. Based on demonstrated efficacy of topiramate for each disorder, these researchers tested the effects of adjunctive use of the drug in 30 veterans with current DSM-IV-TR PTSD and alcohol dependence (28 men; mean age, 50) who expressed the desire to reduce their alcohol consumption.
The 12-week, randomized, controlled study used flexible dosing (25–300 mg daily). Attrition was low (10%) and similar in both groups. Mean daily topiramate dose was 286 mg. Compared with baseline and with placebo, topiramate significantly reduced the number of drinking days and craving for alcohol and showed a trend toward decreased amount of alcohol consumed. Topiramate also reduced PTSD symptoms from baseline levels. However, the medication impaired learning and memory (assessed by neuropsychological testing) during the first 6 weeks, with significant, but not complete, recovery by 12 weeks. Other adverse effects were similar in the two groups.
Comment: Findings from this pilot study indicate that topiramate has promise in treating comorbid alcohol use disorders and PTSD. As a commentator points out, this population lacks pharmacological treatment options. Also, further studies are needed to confirm the finding and determine the relative effectiveness of topiramate as monotherapy, adjunctive medication, and/or combined with particular psychotherapies. However, clinicians could consider topiramate for this complicated comorbidity in a difficult-to-treat population
Citation(s): Batki SL et al. Topiramate treatment of alcohol use disorder in veterans with posttraumatic stress disorder: A randomized controlled pilot trial. Alcohol Clin Exp Res 2014 Aug 4; [e-pub ahead of print]. (http://dx.doi.org/10.1111/acer.12496) Petrakis IL.A commentary on topiramate treatment of alcohol use disorder in veterans with PTSD: A randomized controlled pilot trial. Alcohol Clin Exp Res 2014 Aug 4; [e-pub ahead of print]

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