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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
September 29, 2012

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The Key to Longevity After Age 75?
Low Blood Pressure Isn't Associated with Lower Mortality in Patients with Newly
   Diagnosed Diabetes
PHARMA Companies Paid $6.6 Billion This Year to Settle Fraud Claims
Drug giants fined $11bn for criminal wrongdoing
Benzodiazepines Tied to Dementia in Elders
Detoxification Program for Narcotic Bowel Syndrome
Meta-Analysis: Progesterone Levels Can Reliably Predict Viability in Early Pregnancy
Is Early Antibiotic Exposure Associated with Increases in Body Mass?
Sugar-Sweetened Soft Drinks Contribute Significantly to Weight Gain
Cardiovascular-Risk Indicators Elevated in Overweight, Obese Children
"Safe" Blood Lead Levels Are Associated with Gout
Obama Administration Warns Hospitals Not to 'Game the System' Through EMRs
White or Whole Grain: Does Glycemic Index Matter During Pregnancy?
Are Organic Foods More Nutritious Than Conventional Foods?
Gabapentin for Refractory Chronic Cough?
Sleep and Working Memory in Parkinson Disease
Does Diagnostic Radiation Increase Breast Cancer Risk in Women with BRCA Mutations?
Is Pregnancy-Associated Cancer Becoming More Common?
Does Moderate Drinking Harden Bones?
Vitamin D Heart-Health Link Affirmed

MM: IT seems that the old adage, “Eat, drink and make merry “ may actually be the key to a long and healthy life. This information bodes best for the social butterflies and non-smokers among them.
BMJ 2012 Aug 30; 345:e5568
The Key to Longevity After Age 75?
Don't smoke, have rich social interactions, and engage in leisure activities.
In very few studies have researchers examined the association between modifiable risk factors (e.g., smoking, alcohol consumption, and weight) and longevity in elders. Swedish investigators identified and examined these associations in a prospective, population-based, cohort study of more than 1800 older people (age, ≥75) who were followed for 18 years; half the participants lived beyond age 90.
In age-adjusted analyses, the median age at death was 1.1 years higher for normal-weight versus underweight participants; 1.3 years higher for never smokers versus current smokers; 1.3 years higher for alcohol drinkers versus never drinkers; 1.6 years higher for participants with rich social networks versus those with limited or poor networks; and 1.0 to 2.3 years higher for participants who engaged in mental, social, physical, and productive leisure activities versus those who did not. Multivariate analyses affirmed the salutary effects of not smoking and of social, physical, and productive (e.g., gardening, sewing, volunteer work) leisure activities. The median survival of participants with low-risk profiles (i.e., healthy behaviors, rich social network, and participation in leisure activities) was 5.4 years longer than that of participants with high-risk profiles. These associations were present in men and women, the oldest age group (≥85), and those with chronic diseases.
Comment: In this study, not smoking, having rich social networks, and engaging in mental, social, physical, and productive leisure activities were associated with longevity among elders including the oldest age group and those with chronic diseases. Older patients should be encouraged to engage in these healthy behaviors.
— Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine September 27, 2012
Citation(s): Rizzuto D et al. Lifestyle, social factors, and survival after age 75: Population based study. BMJ 2012 Aug 30; 345:e5568.
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MM : Moderate control of blood pressure , just like moderate control of blood sugar seems to be a better choice for improved mortality and longevity when compared to aggressive control. For a long time it has been preached that more stringent and aggressive parameters are necessary for those with diabetes. This study indicates that this is not entirely true. Yes, blood pressure must be monitored and maintained but apparetly the reins must be loosened on this patient group.
BMJ 2012 Aug 30; 345:e5567
Low Blood Pressure Isn't Associated with Lower Mortality in Patients with Newly Diagnosed Diabetes
Type 2 diabetic patients whose blood pressure was <110/75 had excess risk for mortality at 3.5 years.
An American Diabetes Association guideline recommends that "most patients with diabetes" receive treatment to reach a systolic blood pressure (SBP) target of <130 mm Hg (although exceptions are allowed for "higher or lower SBP targets" based on patients' characteristics and treatment responses) and a diastolic BP (DBP) target of <80 mm Hg (Diabetes Care 2012; 35 (Suppl 1):S11). Little evidence, however, supports these recommendations. In this retrospective study, investigators used the U.K. General Practice Research Database to examine the effects of SBP and DBP on all-cause mortality in 126,000 adults with newly diagnosed type 2 diabetes.
BP was determined during the first year after diagnosis of diabetes. After median follow-up of 3.5 years, 20% of patients had died. In patients with cardiovascular (CV) disease, those whose SBP was lower than 110 mm Hg were significantly more likely to die than were those whose SBP was 130 to 139 mm Hg (hazard ratio, 2.8); mortality among patients with SBP of 110 to 129 mm Hg was similar to that among patients with SBP of 130 to 139. Participants whose DBP was 70 to 74 mm Hg and those whose DBP was <70 mm Hg were significantly more likely to die than were those whose DBP was 80 to 84 mm Hg (HRs, 1.3 and 1.9, respectively). Similar results were found in patients without CV disease.
CommentIn this study, BP lower than 130/80 mm Hg was not associated with lower risk for 3.5-year all-cause mortality in patients with newly diagnosed type 2 diabetes. In fact, BP lower than 110/75 mm Hg was associated with excess risk. Notably, these observational results are similar to those from the randomized ACCORD blood pressure trial, which showed that, in patients with long-standing type 2 diabetes at high risk for adverse CV events, an SBP target of <120 mm Hg, compared with a target of <140 mm Hg, did not lower incidence of a composite endpoint of fatal and nonfatal CV events
(JW Cardiol Mar 14 2010).
— Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine September 27, 2012
Citation(s): Vamos EP et al. Association of systolic and diastolic blood pressure and all cause mortality in people with newly diagnosed type 2 diabetes: Retrospective cohort study. BMJ 2012 Aug 30; 345:e5567.
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PHARMA Companies Paid $6.6 Billion This Year to Settle Fraud Claims
GSK, J&J and other pharmaceutical companies have paid $6.6 billion this year to settle claims of defrauding U.S. health programs, more than double the amount of 2011, advocacy group Public Citizen said. Common frauds include overcharging government programs such as Medicare and pushing doctors to prescribe drugs for unapproved uses.
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Drug giants fined $11bn for criminal wrongdoing
Fines are not enough to reform drug industry, warn lawyers
The global pharmaceutical industry has racked up fines of more than $11bn in the past three years for criminal wrongdoing, including withholding safety data and promoting drugs for use beyond their licensed conditions.
In all, 26 companies, including eight of the 10 top players in the global industry, have been found to be acting dishonestly. The scale of the wrongdoing, revealed for the first time, has undermined public and professional trust in the industry and is holding back clinical progress, according to two papers published in today's New England Journal of Medicine. Leading lawyers have warned that the multibillion-dollar fines are not enough to change the industry's behaviour.
The 26 firms are under "corporate integrity agreements", which are imposed in the US when healthcare wrongdoing is detected, and place the companies on notice for good behaviour for up to five years. The largest fine of $3bn, imposed on the UK-based company GlaxoSmith-Kline in July after it admitted three counts of criminal behaviour in the US courts, was the largest ever. But GSK is not alone – nine other companies have had fines imposed, ranging from $420m on Novartis to $2.3bn on Pfizer since 2009, totalling over $11bn.
Kevin Outterson, a lawyer at Boston University, says that despite the eye watering size of the fines they amount to a small proportion of the companies' total revenues and may be regarded as a "cost of doing business". The $3bn fine on GSK represents 10.8 per cent of its revenue while the $1.5bn fine imposed on Abbott Laboratories, for promoting a drug (Depakote) with inadequate evidence of its effectiveness, amounted to 12 per cent.
Mr Outterson said: "Companies might well view such fines as a quite small percentage of their global revenue. If so, little has been done to change the system. The government merely recoups a portion of the financial fruit of firms' past misdeeds."
He argues that penalties should be imposed on executives rather than the company as whole. He cites a Boston whistleblower attorney, Robert Thomas who observed that GSK had committed a $1bn crime and "no individual has been held responsible".
Following GSK's admission that it had withheld safety data about its best-selling diabetes drug Avandia, the company pledged to make more clinical trial information available. But the pledge has "disturbing exceptions", according to Mr Outterson, and in any case is made under the corporate integrity agreement, which expires in five years.
Trust in the industry among doctors has fallen so low that they dismiss clinical trials funded by it, even when the trials have been conducted with scientific rigour, according to a second paper in the journal by researchers at Brigham and Women's Hospital, Boston. This could have serious implications because most medical research is funded by the drug industry and "if physicians are reluctant to trust all such research, it could hinder the translation of … research into practice," said Aaron Kesselheim, who led the study.
Andrew Witty, the chief executive of GSK, said at the time of the $3bn settlement last July that it had resolved "difficult, long-standing matters" for the company and that there had since been a "fundamental change in procedures" including the removal of staff engaged in misconduct and changes to incentive payments.
The Association of the British Pharmaceutical Industry said practices in the industry had improved and more changes to "build greater levels of trust" would be made. The UK Medicines and Healthcare Products Regulatory Agency said it monitored the conduct of companies and took "appropriate action" when it uncovered malpractice.
Alzheimer's funding 'must continue'
Governments, universities and charities should step in to ensure funding is maintained for research into Alzheimer's disease, following a series of failed drug trials, experts said yesterday.
They were responding to a report in The Independent that the world's leading drug companies are giving up on the search for a cure, scaling back their neuroscience departments and focusing on symptomatic, rather than disease-modifying, treatments.
A spokesman for the Alzheimer's Society said: "This is not the time to back away from dementia research. Despite costing the economy more than cancer and heart disease, funding for research into dementia is only a fraction of these conditions. More funding is urgently needed if we are to defeat it."
Jeremy Laurance
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Benzodiazepines Tied to Dementia in Elders
Benzodiazepine drugs are associated with increased risk for dementia, according to a BMJstudy.
The study included nearly 1100 community-dwelling, older adults in France who were free of dementia; 9% were considered new users of benzodiazepines — that is, they began using the drugs after the third year of follow-up.
During the next 15 years, dementia was diagnosed significantly more often in new benzodiazepine users than in nonusers (32% vs. 23%). After adjustment for confounders such as age, diabetes, and depression, new users had a 60% increased risk for dementia. A complementary, nested case-control analysis found a similar increase in risk.
The researchers argue against the idea that benzodiazepine use is simply a marker for other conditions (e.g., anxiety) that are linked to dementia — for example, the association between the drugs and dementia increased after 7 years of use. However, they acknowledge that such a theory cannot be "entirely ruled out."
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Am J Gastroenterol 2012 Sep; 107:1426
Detoxification Program for Narcotic Bowel Syndrome
Researchers describe outcomes for 39 patients.
Narcotic bowel syndrome (NBS) is characterized by unexplained abdominal pain that is treated with opioids and persists or worsens while opioid doses are maintained or increased. NBS can be — but is not necessarily — associated with opioid-related dysmotility (e.g., constipation, gastroparesis, ileus). University of North Carolina researchers describe outcomes for 39 patients (34 inpatients, 5 outpatients) treated in their NBS detoxification program. Patients had been receiving opioids for an average of 5 years; at enrollment, the mean dose was 75 mg of intravenous morphine equivalents daily, with oral drugs (e.g., Oxycontin, MS Contin, hydromorphone) or fentanyl patches.
Opioids were tapered off during an average of 7 days for inpatients and 39 days for outpatients. Immediately after detoxification, pain scores had decreased by 35%. Unfortunately, half the patients were again receiving prescription opioids at 3 months; however, among those not using opioids at 3 months, pain scores had decreased by about 75%.
Comment: This report draws attention to a syndrome that might be underrecognized in clinical practice. Although the high rate of recidivism is discouraging, a comprehensive detoxification program can be effective in some patients. In a four-page appendix, the authors describe their protocol, which focuses not only on opioid dosing, but also on communication with patients and managing anxiety and depression.
— Allan S. Brett, MD Published in Journal Watch General Medicine September 27, 2012
Citation(s): Drossman DA et al. Diagnosis, characterization, and 3-month outcome after detoxification of 39 patients with narcotic bowel syndrome. Am J Gastroenterol 2012 Sep; 107:1426.
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Meta-Analysis: Progesterone Levels Can Reliably Predict Viability
in Early Pregnancy

In evaluating early pregnancy, a single progesterone measurement can rule out viability, depending on the cutoff levels used and whether ultrasound is available, according to a BMJmeta-analysis.
Researchers examined data from 26 cohort studies including some 9500 pregnant women, some with symptoms and inconclusive ultrasound results, and others with only symptoms.
In studies with inconclusive ultrasound results, a progesterone cutoff level between 3.2 and 6 ng/mL gave a sensitivity of 75% and a specificity of 98% for predicting a nonviable pregnancy.
In studies with symptoms alone, a progesterone cutoff of 10 ng/mL gave a sensitivity of 67% and a specificity of 96%.
The authors conclude that the test "is more accurate when it follows an inconclusive ultrasound."
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Int J Obes (Lond) 2012 Aug 21
Is Early Antibiotic Exposure Associated with Increases in Body Mass?
Exposure during the first 6 months of life was associated with increased body mass at ages 10 to 38 months, but the effect disappeared by age 7 years.
Exposure to low-dose antibiotics early in life is known to fatten animals. Is the same true for children? Investigators in the U.K. explored potential associations between exposure to antibiotics at three age intervals (<6 months, 6–14 months, and 15–23 months) and morphometric measures in a longitudinal birth cohort of 11,532 infants weighing ≥2500 gm (mean, 3477 gm) at birth. The cohort was 93% white, and 26% were breast-fed.
Nearly one third of the cohort had received antibiotics by 6 months of age, and only 26% had no reported antibiotic exposure by age 24 months. Infants who received antibiotics during the first 6 months had significantly greater body-mass index and weight-for-length measures at ages 10 to 38 months than children who were not exposed to antibiotics during the first 2 years of life. However, the difference disappeared by age 7 years. In stratified analysis with adjustment for confounders, the effect of exposure before age 6 months was greater among children with normal-weight mothers than among children with overweight or obese mothers. Exposure after 6 months was not associated with overweight or obesity. Exposure to antipyretics was not associated with increased body mass.
Comment: Restraint in prescribing antibiotics is always prudent. In this cohort of presumably healthy babies, early exposure to antibiotics was associated with greater body mass at age 3 years but not at age 7 years. These data call for greater understanding of the mechanism of the association between antibiotics and body mass, as well as the influence of early antibiotic exposure on the human microbiome.
— F. Bruder Stapleton, MD
Published in Journal Watch Pediatrics and Adolescent Medicine September 26, 2012
Citation(s): Trasande L et al. Infant antibiotic exposures and early-life body mass. Int J Obes (Lond) 2012 Aug 21; [e-pub ahead of print].
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Sugar-Sweetened Soft Drinks Contribute Significantly to Weight Gain
Three New England Journal of Medicine studies on the consumption of sugar-sweetened beverages suggest that the drinks have an important role in the risk for obesity.
One study, in a large cohort of initially nonobese adults, looked at patterns of drink consumption and their relation to subjects' genetic predisposition to obesity. Researchers found that incident obesity increased with increasing drink consumption within the same level of genetic risk; similarly, obesity increased with increasing genetic risk within the same level of consumption.
Two other studies examined the effects of replacing sugar-sweetened drinks with sugar-free drinks, one in normal-weight children and the other in adolescents who were overweight or obese. Among normal-weight children, those randomized to one masked sugar-free drink/day for 18 months gained significantly less weight and body fat, compared with those randomized to a sugar-containing drink. Among overweight adolescents, a 1-year intervention aimed at reducing sugary drink consumption lowered gains in BMI at 1 year, but not at 2 years, relative to controls.
An editorialist says that the studies "provide a strong impetus to develop recommendations and policy decisions to limit consumption of sugar-sweetened beverages."
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Cardiovascular-Risk Indicators Elevated in Overweight, Obese Children
Overweight and, particularly, obese school-aged children show significant increases in measures of cardiovascular risk relative to their normal-weight peers, a BMJ meta-analysis shows. Editorialists remind readers that although the results are "worrying," it is unknown whether those risks follow the children into adulthood, independent of adult weight.
The analysis looked at 63 studies including almost 50,000 children aged 5 to 15 years from highly developed countries. Average systolic blood pressure was 4.54 mm Hg higher among overweight children and 7.49 mm Hg higher among obese children, compared with their normal-weight peers. Obese children also had increased total cholesterol, fasting glucose, fasting insulin, and insulin resistance, as well as a 19-g increase in left ventricular mass.
The editorialists liken childhood obesity to climate change, which "is at times in danger of inciting an ennui borne out of a repetition of problems without answers."
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Ann Intern Med 2012 Aug 21; 157:233
"Safe" Blood Lead Levels Are Associated with Gout
Even at levels well below 25 µg/dL, gout incidence rose as blood lead levels rose.
Elevated blood lead levels are associated with gout, but we know less about risk for gout among people with "normal" blood lead levels. Using data from more than 6000 participants the National Health and Nutrition Examination Survey (NHANES; 2005–2008), researchers determined whether blood lead levels that the CDC considers to be safe for adults (<1.21 µmol/L [25 µg/dL]) were associated with gout. The analysis excluded people younger than 40 and those with glomerular filtration rates (GFR) <10 mL/minute/1.73 m2. Diagnoses of gout were self-reported.
After controlling for multiple factors, including age, renal function, and use of diuretics, prevalence of gout was 1.76% among individuals in the lowest quartile of blood lead level (mean, 0.04 µmol/L) versus 6.05% among those in the highest quartile (mean, 0.19 µmol/L).
CommentIn this population-based study, blood lead levels that are considered to be safe by the CDC were associated with excess risk for gout. The authors suggest that even low levels of lead are associated with health risks and that current guidelines likely are inadequate and require refinement.
— Jamaluddin Moloo, MD, MPH Published in Journal Watch General Medicine September 25, 2012
Citation(s): Krishnan E et al. Low-level lead exposure and the prevalence of gout: An observational study. Ann Intern Med 2012 Aug 21; 157:233.
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Obama Administration Warns Hospitals Not to 'Game the System'
Through EMRs

The Obama administration is cautioning hospitals against attempting to "game the system" by using electronic medical records to fraudulently bill Medicare.
In a letter obtained by the New York Times that was sent to five hospital and academic associations, the Department of Justice and the Department of Health and Human Services warn specifically against "cloning" medical records to inflate providers' payments and "upcoding" patients' conditions or intensity of care to qualify for higher payments without improving the quality of care.
The Centers for Medicare and Medicaid Services is conducting audits to identify improper billing and coding. "CMS has the authority to address inappropriate increases in coding intensity in its payment rules, and CMS will consider future payment reductions as warranted," the letter states.
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BMJ 2012 Aug 30; 345:e5605
White or Whole Grain: Does Glycemic Index Matter During Pregnancy?
Adherence to a low-glycemic–index diet curbed maternal weight gain but did not lower incidence of neonatal macrosomia.
Fetal macrosomia is intimately tied to the obesity epidemic: Maternal obesity raises risk for fetal macrosomia, which in turn is a risk factor for obesity later in life. Investigators at the National Maternity Hospital in Dublin conducted a randomized, controlled trial of a low-glycemic–index diet and its effects on neonatal macrosomia and maternal outcomes in 800 women with prior macrosomic deliveries but no histories of gestational diabetes. Participants were randomized during early pregnancy to receive dietary education (with a special focus on glycemic index) or routine prenatal care.
Compared with women in the control group, those in the intervention group achieved lower dietary glycemic indexes, gained less weight during pregnancy (mean difference, 1.3 kg;P=0.01), and were less likely to experience glucose intolerance. Although a significant proportion of women in each group exceeded recommended gestational weight gain goals, women in the intervention group were less likely to do so (38% vs. 48%;P=0.01). However, neither mean birth weight nor incidence of macrosomia differed between groups. Rates of preterm or cesarean delivery also did not differ.
Comment: Although counseling and adherence to a low-glycemic–index diet had no effect on neonatal birth weight, this study adds evidence that nutritional counseling can curb gestational weight gain. Excessive weight gain is associated with other adverse maternal outcomes that this study might not have been powered to detect, and probably has consequences for women's health both between pregnancies and in the long term. Providing culturally appropriate nutritional counseling during pregnancy is a high priority, particularly for women at greatest risk for adverse weight-related outcomes.
— Allison Bryant, MD, MPH Published in Journal Watch Women's Health September 27, 2012
Citation(s): Walsh JM et al. Low glycaemic index diet in pregnancy to prevent macrosomia (ROLO study): Randomised control trial. BMJ 2012 Aug 30; 345:e5605.
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MM: Many have stated that it is important to determine when it is beneficial to use organic vs conventional products. People who are environmentally sensitive may be the best choices to use predominantly organically produced products but there is no question in my mind that many of us will benefit from meats that are hormone and antibiotic free. When it comes to fruits and vegetables the question becomes more clouded. It comes down to the fact that we all need to be better educated and informed when it comes to making these choices and decisions.
Ann Intern Med 2012 Sep 4; 157:348.
Are Organic Foods More Nutritious Than Conventional Foods?
This systematic review does not support the common belief that organic foods are more nutritious, but evidence suggests they reduce exposure to pesticides and multiresistant bacteria.
Organic food sales reached US$26.7 billion in 2010. Researchers conducted a systematic analysis of peer-reviewed studies published from 1966 to 2011 to examine whether organic foods are more nutritious and safer than conventionally produced foods.
Of 5908 potentially relevant studies identified by searching 7 databases, 237 studies met the criteria for inclusion. Most studies (223) compared organic and conventional fruits, vegetables, grains, meats, poultry, milk, or eggs directly. Overall, no evidence was found to support the hypothesis that organic foods are more nutritious than conventionally produced food. No differences were found in vitamin content, beneficial fatty acids, or other nutrients. Many studies (52% of produce studies) examined sampled food that was grown on experimental farms where conditions could be controlled. Only 29% of sampled food was grown on commercial farms.
In terms of safety, pesticides were detected on the surface of 7% of organic produce samples and 38% of conventionally grown produce samples. No studies were found that compared pesticide levels among adult consumers of organic versus conventional foods. The prevalence of Escherichia colicontamination was equivalent in organic and conventionally grown produce (7% and 6%, respectively). Bacterial contamination was common for both organic and conventionally produced meats and poultry. For example, about 65% of organic and conventional chicken was contaminated withCampylobacter. However, conventionally produced chicken and pork were 33% more likely than organic alternatives to be contaminated with three or more bacteria resistant to antibiotics.
Comment: Based on the evidence, it appears that organic foods are not more nutritious and are contaminated with bacteria at about the same rate as conventional foods. Exposure to pesticide residues is lower in organic foods, but the associated health risks in adults and children are unclear, and all levels of pesticides in organic and conventional foods were within acceptable government standards.
— Louis M. Bell, MD Published in Journal Watch Pediatrics and Adolescent Medicine September 26, 2012
Citation(s): Smith-Spangler C et al. Are organic foods safer or healthier than conventional alternatives? A systematic review. Ann Intern Med2012 Sep 4; 157:348.
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Lancet 2012 Aug 28
Gabapentin for Refractory Chronic Cough?
Patients with hypersensitive central cough reflex responded well to 10 weeks of therapy.
Refractory chronic cough might be related to sensitization of the central cough reflex. Gabapentin can alleviate neuropathic pain by modifying central pain sensitization, and two small case series previously suggested that gabapentin might also be effective against chronic cough.
Australian investigators randomized 62 adults with at least 8 weeks of refractory chronic cough to gabapentin (titrated to a maximum dose of 1800 mg daily) or placebo for 10 weeks. Participants had no known respiratory disease and no response to inhaled or oral steroids, nasal steroids or antihistamines, or proton-pump inhibitors; these or other drugs for cough could be continued throughout the trial.
Compared with placebo patients, gabapentin patients showed significantly greater improvements on validated scales that measured cough severity and cough-specific quality of life and a significantly greater decrease in measured cough frequency; these between-group differences became nonsignificant after treatment ended. Patients with central cough sensitization (defined by cough triggers, such as abnormal throat sensation, talking on the phone, or air conditioning, and by response to standardized doses of capsaicin aerosol) exhibited a greater response to gabapentin than patients without central cough sensitization. One patient in each group withdrew from the study due to adverse effects.
CommentThese data lend support to the hypothesis that a hypersensitive central cough reflex is one mechanism of chronic refractory cough. Opioids often are effective for refractory cough but have obvious disadvantages for chronic use; gabapentin might be a safer alternative if larger studies support its efficacy, although it might sometimes cause central nervous system side effects.
— Bruce Soloway, MD Published in Journal Watch General Medicine September 25, 2012
Citation(s): Ryan NM et al. Gabapentin for refractory chronic cough: A randomised, double-blind, placebo-controlled trial. Lancet 2012 Aug 28; [e-pub ahead of print].
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MM: Sometimes looking at a relatively simple solution to improve a condition eludes us. It may be possible that such a simple stop gap solution to PD deterioration exists as suggested obliquely in this article. A c-pap machine providing open breathing passages and oxygen may be a viable treatment to slow the progression or improve the condition transiently.
Brain 2012 Sep; 135:2789.
Sleep and Working Memory in Parkinson Disease
Slow-wave sleep may be an important modulator of dopamine-related improvement in working memory among patients with PD.
To investigate whether sleep parameters are associated with improvement in working memory among patients with Parkinson disease (PD) or dementia with Lewy bodies (DLB), researchers conducted overnight polysomnography for 2 nights, followed by cognitive testing, in 53 patients with PD (most without dementia) and 10 patients with DLB. After each night of polysomnography, participants performed digit-span testing four times, beginning 2 hours after awakening and repeated every 2 to 3 hours. The digit-span forward task tested short-term memory, and the digit-span backward task tested working memory.
Sleep parameters did not differ among PD patients who were or were not taking dopaminergic medication and DLB patients. Based on the mean difference in digit-span scores from day 1 and day 2, the PD patients who were taking dopaminergic medications improved significantly on the digit-span backward task; the PD group not taking dopaminergic medications and the DLB patients did not show improvement. On the digit-span forward test, the PD patients did not improve significantly and the DLB patients' scores declined significantly. In PD patients taking dopaminergic medication, improvement in digit-span backward performance correlated positively with the percentage of sleep that was slow-wave sleep and correlated negatively with duration of time with an oxygen saturation level <90%.
The authors concluded that (1) improvements in working memory based on digit-span backward performance can be seen in PD patients, particularly in those taking dopaminergic medications; (2) slow-wave sleep may be important for these improvements; and (3) nocturnal oxygen desaturation may impede these improvements.
Comment: These findings offer insight into the potential for cognitive improvement in patients with Parkinson disease, particularly those who do not have dementia and who are taking dopaminergic medications. Slow-wave sleep may be an important modulator of this improvement. Increasing slow-wave sleep may improve working memory in people with PD, although the clinical utility of using dopaminergic medications specifically to enhance cognition requires further investigation. Future research should examine the exact mechanisms by which dopamine may enhance working memory, determine whether dopaminergic medications increase slow-wave sleep, and clarify how nocturnal oxygen desaturation can impede this cognitive process.
— Jennifer Rose V. Molano, MD Dr. Molano is Assistant Professor of Neurology, University of Cincinnati College of Medicine.
Published in Journal Watch Neurology September 25, 2012
Citation(s): Scullin MK et al. Nocturnal sleep enhances working memory training in Parkinson's disease but not Lewy body dementia.Brain 2012 Sep; 135:2789.
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BMJ 2012 Sep 6; 345:e5660.
Does Diagnostic Radiation Increase Breast Cancer Risk in Women with BRCA Mutations?
European questionnaire-based study leaves the question unanswered.
Because ionizing radiation can damage DNA, diagnostic x-ray exposure in individuals with defects in DNA repair mechanisms (such as those associated with BRCA1 and BRCA2mutations) could lead to excess risk for cancer. Investigators surveyed women with documented BRCA1/2 mutations in the Netherlands, France, and the U.K. to evaluate any association between radiation exposure and later development of breast cancer. Questionnaires were administered to BRCA1/2 carriers from 2006 to 2009 to elicit their recollections of the type and number of diagnostic procedures they had received in their lifetimes. Estimates of radiation doses to the breast during each type of diagnostic procedure (mammography, fluoroscopy, and computed tomography and conventional radiography of the chest or shoulder) were used to determine total cumulative dose. Cases that were diagnosed >5 years before completion of the study questionnaire were excluded to prevent survival bias.
Of the 1993 participants, 43% (mean age, 49.7) had received diagnoses of breast cancer. Self-reported exposure to any form of diagnostic radiation before age 30 was associated with significantly higher risk for breast cancer (hazard ratio, 1.90; 95% confidence interval, 1.20–3.00), and risk rose with increasing cumulative dose. A history of mammography before age 30 was associated with nonsignificantly increased risk for breast cancer (HR, 1.43; 95% CI, 0.85–2.40). No evidence of excess risk was found for diagnostic radiation exposure between ages 30 and 39.
CommentAs with other epidemiologic studies of diagnostic radiation and risk for breast cancer in BRCA1/2 mutation carriers, the results of this study are inconclusive. The retrospective questionnaire design is subject to recall bias, especially given that women were asked to recollect events occurring up to 30 years earlier. Moreover, no attempt was made to document the date and type of radiologic tests that were reported. Furthermore, estimates of cumulative radiation dose were hypothetical and subject to wide variation based on factors in individuals as well as facilities. Until further data are obtained, theNational Comprehensive Cancer Network recommendation of screening with magnetic resonance imaging and mammography in BRCA mutation carriers beginning at age 25 should be followed.
— Henry Mark Kuerer, MD, PhD, FACS Published in Journal Watch Oncology and Hematology September 25, 2012
Citation(s): Pijpe A et al. Exposure to diagnostic radiation and risk of breast cancer among carriers of BRCA1/2 mutations: Retrospective cohort study (GENE-RAD-RISK). BMJ 2012 Sep 6; 345:e5660.
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BJOG 2012 Sep 5
Is Pregnancy-Associated Cancer Becoming More Common?
In an Australian study, rising incidence was only partially accounted for by advancing maternal age.
Pregnancy-associated cancers are those that are initially diagnosed during pregnancy or within 12 months of delivery. To determine trends in pregnancy-associated cancer and related maternal and pregnancy outcomes, investigators linked data from an Australian cancer registry, a perinatal database, and hospital records of 781,907 women who delivered from 1994 to 2008.
In all, 1798 pregnancy-associated cancers were identified, most commonly melanoma, breast cancer, and thyroid cancer (46, 29, and 17 per 100,000 pregnancies, respectively). A total of 499 cancers were diagnosed during pregnancy and 1299 were diagnosed postpartum. Pregnancy-associated cancer was almost 50% more common than would have been expected in the general female population of reproductive age. From 1994 to 2007, the crude incidence of pregnancy-associated cancer rose from 112 to 192 per 100,000 pregnancies. Only 14% of this increase was explained by advancing maternal age. Women with cancer diagnosed during pregnancy were 10 times as likely as those without pregnancy-associated cancer to experience a thromboembolic event and 4 times as likely to experience sepsis.
Comment: Notably, these data were not adjusted for maternal smoking or obesity, two risk factors for cancer and thromboembolism. Although more-frequent interactions with clinicians during pregnancy could account for some of the increase in cancer diagnosis, pregnancy-associated immune changes also could affect oncogenesis and tumor growth. Given that cancer is the second most common cause of death among women of reproductive age — and that contraception lowers risk for many cancers (e.g., JW Womens Health Apr 26 2012) — these findings should encourage a renewed commitment to making every pregnancy a wanted pregnancy.
— Eleanor Bimla Schwarz, MD, MS Published in Journal Watch Women's Health September 27, 2012
Citation(s): Lee YY et al. Incidence and outcomes of pregnancy-associated cancer in Australia, 1994–2008: A population-based linkage study. BJOG 2012 Sep 5; [e-pub ahead of print].
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Menopause 2012 Sep; 19:974
Does Moderate Drinking Harden Bones?
Short-term abstention and resumption of alcohol intake affected markers of bone turnover in postmenopausal women.
Although alcoholism is associated with low bone mineral density (BMD) in women, moderate alcohol consumption has been associated with increased BMD. Investigators assessed the effect of short-term alcohol withdrawal in 40 menopausal women (mean age, 56) who consumed alcohol moderately, did not have osteoporosis, and were not receiving hormone therapy. Serum markers of bone turnover were assessed at baseline, after 2 weeks of abstention from drinking, and 24 hours after resumption of ethanol intake at baseline levels.
Mean baseline alcohol consumption in the group was 19 g ethanol daily, equivalent to 1.4 standard drinks. After 14 days of abstinence from alcohol, markers of both bone resorption and bone formation were significantly higher than at baseline. One day after women resumed moderate alcohol intake (day 15), their levels of bone turnover markers returned to baseline. Serum estradiol levels were low (consistent with menopause) in participants and did not change with alcohol abstinence or resumption.
CommentAlthough small and short-term, this study provides reasonable evidence that moderate alcohol consumption decreases bone turnover — a finding that is consistent with other reports and might explain why women who are moderate drinkers tend to have higher bone mineral density than nondrinkers. Although moderate alcohol consumption is associated with improved cardiovascular and all-cause mortality in women, such consumption is also associated with increased risk for breast cancer. Furthermore, it is uncertain whether moderate alcohol consumption lowers risk for osteoporotic fractures.
— Andrew M. Kaunitz, MD Published in Journal Watch Women's Health September 27, 2012
Citation(s): Marrone JA et al. Moderate alcohol intake lowers biochemical markers of bone turnover in postmenopausal women.Menopause 2012 Sep; 19:974.
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Vitamin D Heart-Health Link Affirmed
Danish study links low levels of vitamin D to higher risks of heart attack and early death By Craig Weatherby
Until recently, vitamin D was an overlooked nutrient … an oversight that likely harmed public health. When it comes to bone health, it’s become clear that maintaining adequate vitamin D levels is more important than taking big doses of calcium. But numerous population studies link lack of vitamin D to higher risk for infections, various cancers, and certain auto-immune disorders … findings that fit with vitamin D’s broad, hormone-like effects in the body.
Most recently, several population studies – and a few clinical trials – linked low vitamin D levels to a higher risk of heart attack, arteriosclerosis, and angina (Danik JS et al. 2012; Pilz S et al. 2012). Other studies show that vitamin D deficiency may increase blood pressure, which raises the risk of heart attack. Heart disease is the most common cause of adult death, according to the World Health Organization (WHO), which estimates that it kills at least 17 million people annually.
For our coverage of some of the prior research, see “Vitamin D Lack Raises Heart-Death Risk”, “Vitamin D Linked Closely to Heart Health” … and other articles in the Vitamin D & Heart Health and Vitamin D & Metabolic Health sections of our News Archive.
The connection between low vitamin D levels and heightened risk of heart disease seen in population studies must be confirmed by clinical trials … a number of which are now underway. But it can’t hurt – and would help overall health – to use diet and supplements to ensure adequate levels. (See our sidebar, “Fish fit the vitamin D bill; Sockeye salmon stand out”.) Now, Danish researchers have affirmed the heart-health role of vitamin D in the largest study to date, which used blood tests to determine people’s vitamin D status … as opposed to very rough estimates based on diet/lifestyle questionnaires.
Danish study supports heart-vitamin D link
The new analysis relied on data from 10,170 Danes who participated in the Copenhagen City Heart Study in the early 1980’s, and provided blood samples as part of that study. The authors of the new study measured the vitamin D levels in those samples, and compared those levels to the participants’ health records over the ensuing 29 years (Brøndum-Jacobsen P et al. 2012).
The results of that comparison linked low levels of vitamin D with markedly higher risks of heart attack, heart disease, and early death. Low blood levels of vitamin D were linked to these increased risks:

Ischemic heart disease (IHD) is characterized by reduced blood supply to the heart muscle, usually due to coronary artery disease caused by atherosclerosis (clogged arteries). The risk of IHD rises with age, smoking, eating meat, high levels of certain kinds of cholesterol, diabetes, and high blood pressure. The scientists compared people whose vitamin D levels fell in the bottom five percent – less than 15 nmol/L (6 ng/mL) – to those whose vitamin D levels exceeded 50 nmol/L (20 ng/mL).
 (The U.S. Institute of Medicine recommends a minimum blood level of 50 nmol/L, but leading researchers recommend higher levels … see our sidebar, “Vitamin D: Recommended RDAs and blood levels”.)
 The higher risks remained after the results were adjusted to account for several factors that can influence the level of vitamin D and the risk of heart disease and death.  As co-author Børge Nordestgaard said, “… we can ascertain that there is a strong statistical correlation between a low level of vitamin D and high risk of heart disease and early death. The explanation may be that a low level of vitamin D directly leads to heart disease and death.” (UC 2012)
 Of course, no population study can prove a cause-effect relationship, which he noted: “However, it is also possible that vitamin deficiency is a marker for poor health generally.” (UC 2012) Dr. Nordestgaard noted that sun exposure is the primary source of vitamin D, but cautioned against overdoing it:
“The cheapest and easiest way to get enough vitamin D is to let the sun shine on your skin at regular intervals. There is plenty of evidence that sunshine is good, but it is also important to avoid getting sunburned, which increases the risk of skin cancer.” (UC 2012)
 Companion evidence review affirms vitamin D’s heart role
Additionally, the Danish group performed a “meta-analysis” in which they reviewed 35 prior studies on vitamin D and heart health (Brøndum-Jacobsen P et al. 2012). Their meta-analysis covered 18 studies investigating the risk of ischemic heart disease and 17 studies looking at vitamin D and early death. The Danish team compared people who fell in the lowest quartile (one-quarter) of vitamin D blood levels to those in the highest quartile. The results showed that the risk of ischemic heart disease and early death rose by 39 percent and 46 percent respectively, for those in the lowest quartile versus those in the highest quartile of vitamin D status.
 Given the accumulating evidence linking vitamin D to heart health, one would seem foolish not to take steps to ensure adequate intakes and blood levels.
 Sources: Brøndum-Jacobsen P, Benn M, Jensen GB, Nordestgaard BG. 25-Hydroxyvitamin D Levels and Risk of Ischemic Heart Disease, Myocardial Infarction, and Early Death: Population-Based Study and Meta-Analyses of 18 and 17 Studies. Arterioscler Thromb Vasc Biol. 2012 Aug 30. [Epub ahead of print] Danik JS, Manson JE. Vitamin d and cardiovascular disease. Curr Treat Options Cardiovasc Med. 2012 Aug;14(4):414-24. Pilz S, Kienreich K, Tomaschitz A, Lerchbaum E, Meinitzer A, März W, Zittermann A, Dekker JM. Vitamin D and cardiovascular disease: update and outlook. Scand J Clin Lab Invest Suppl. 2012 Apr;243:83-91. Review. University of Copenhagen (UC). Vitamin D deficiency increases risk of heart disease. September 24, 2012. Accessed at:

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