• ... a quote for the day:
• Correcting Low Vitamin D Levels in Obese Adolescents Improves Insulin Sensitivity
• Drug Research Lab Faked Data, but Drugs Still on Shelves
• Midlife Cardiorespiratory Fitness Might Attenuate Later-Life Dementia
• Higher Potassium Intake Lowers Blood Pressure and Is Associated with Less Risk for Stroke
• Antibiotic Development 'Alarmingly Slow'
• Influenza Can Sneak Past Surgical Masks
• Sunshine and Tuberculosis: Is There a Relationship?
• Kids with Migraines Likely to Have Been Colicky Babies
• Measuring Coronary Artery Calcium in People with Type 2 Diabetes Identifies a
Low-Risk Subset
• New Neurosurgical Guidelines Warn of Harm from Steroids in Acute Spinal Injury
• FDA Admits to Lack of Aggressive Response in NECC Situation
... a quote for the day:
Today, too many depend upon the "vision" of others and copy their select attributes and behaviors. Pharmaceutical compounding is experiencing some difficult times due to the ignorance, selfishness, and self-centeredness of a few. Despite that, we must retain our vision of "quality compounding" to serve patients and prescribers and the healthcare needs of the nation.
- Dr Lloyd Allen
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MM: We have seen this data in the past but it is worth repeating. Obesity across all areas of our society has become the number one health problem as it is insidious, frequently unrecognized as a problem or simply ignored and accepted. It leads to a myriad of other debilitating health concerns and affects all age groups, genders and ethnic groups. Furthermore, when it is present in our young people it becomes a lifelong problem. The simple addition of a Vitamin D3 supplement that costs pennies a day can improve the quality of life for a lifetime and can decrease the health costs of an individual and a nation for decades to come.
Am J Clin Nutr 2013 Feb 13;
Correcting Low Vitamin D Levels in Obese Adolescents Improves Insulin Sensitivity
Adolescents who took 4000 IU of vitamin D3 daily had lower fasting insulin levels and insulin resistance than controls.
Obese adolescents often have insufficient vitamin D levels, and poor vitamin D status has been associated with abnormal glucose metabolism and insulin resistance. Investigators assessed the effect of correcting low vitamin D levels on inflammatory and metabolic abnormalities in 35 obese adolescents (mean age, 14 years; mean body-mass index [BMI], 39.8 kg/m2; mean serum 25-hydroxyvitamin D [25(OH)D], 19 ng/mL) who were randomized to receive vitamin D3 (4000 IU/day) or placebo for 6 months.
At 3 months, serum 25(OH)D concentrations increased significantly in the supplement group and all adolescents reached normal levels while levels in the placebo group did not change significantly. At 6 months, no differences were noted between the two groups in fasting plasma glucose, BMI, and three inflammatory markers. However, fasting insulin levels, two measures of insulin resistance, and the leptin-to-adiponectin ratio (a possible marker of insulin resistance) fell significantly more in the supplemented group than in the placebo group.
Comment: The vitamin D3 dose used in this study is higher than the recommended daily allowance of 600 IU for adolescents, but other research has shown such doses are safe for correcting deficiency (Curr Opin Pediatr 2009 Aug; 21: 465). The authors note that this is the first randomized study in obese adolescents to use a vitamin D dose high enough to increase serum 25(OH)D concentrations to levels associated with improvement in metabolic markers. They postulate that correction of vitamin D insufficiency may someday play a role in the treatment of insulin resistance that often accompanies obesity.
— Alain Joffe, MD, MPH, FAAP Published in Journal Watch Pediatrics and Adolescent Medicine March 20, 2013
Citation(s): Belenchia AM et al. Correcting vitamin D insufficiency improves insulin sensitivity in obese adolescents: A randomized controlled trial. Am J Clin Nutr 2013 Feb 13; [e-pub ahead of print].
(http://dx.doi.org/10.3945/ajcn.112.050013)
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Drug Research Lab Faked Data, but Drugs Still on Shelves
By Kelly Young
Much of a Texas laboratory's work in testing drug safety has been determined to be fraudulent, but many of the drugs it studied have remained on the shelf 2 years after the revelation, according to a story by ProPublica, an investigative journalism group.
Some 100 drugs, mostly generics, relied on Cetero Research's data for FDA approval. ProPublica confirmed the following five drugs were among those affected: the injectable form of the chemotherapy drug Temodar (temozolomide), the injectable form of the renal cell carcinoma drug Torisel (temsirolimus), and the painkillers Lazanda (fentanyl) nasal spray, generic tramadol, and generic ibuprofen in capsule form.
The FDA has declined to list the affected drugs, saying that doing so would reveal company secrets. The agency has required retests of the drugs tested by the lab. Meanwhile, the European Medicines Agency pulled seven of the drugs off the shelves.
The FDA says the potential for patient harm is "quite low," and it has not found any problems in the drugs it has finished reviewing.
Fraudulent Research on FDA-approved Drugs Stay on the Market
Key Points:
- In 2011, the FDA announced that years' worth of studies from a major drug research lab were discovered to be potentially worthless.
- About 100 drugs were on the U.S. market based in part on these studies.
- The FDA allowed the drugs stay on the market with no new testing (in some cases until now).
- As the FDA investigated and ordered re-tests, its European equivalent pulled seven drugs from the market.
- The FDA says it has no evidence that any of the drugs were unsafe or that any patient has been harmed.
- The FDA has never named the drugs, saying to do so would reveal trade secrets.
Instead, the agency decided to handle the matter quietly with virtually no public disclosure of what it had discovered. None of the drugs were pulled from the market, even temporarily, while not knowing for sure they were safe and effective. To this day, some drugs remain on the market despite the FDA having no additional scientific evidence to back up the safety and efficacy of these drugs. By contrast, the European Medicines Agency, has pulled seven Cetero-tested medicines from the market.
http://www.propublica.org/article/fda-let-drugs-approved-on-fraudulent-research-stay-on-the-market
http://www.propublica.org/article/no-substitute-when-a-generic-drug-isnt-what-it-seems
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MM: Once again we see that simple exercise of moving around that elevates the heart rate and breathing rate can have long term benefits. We readily acknowledge the benefits of exercise to the cardiovascular system but now we see that cognitive function may be enhanced long term throughout life with exercise. This is further support of lifestyle modification benefits that include dietary changes, exercise and simply taking responsibility for our own health and wellness.
Ann Intern Med 2013 Feb 5; 158:162
Midlife Cardiorespiratory Fitness Might Attenuate Later-Life Dementia
Later dementia was less common among people who were more fit before age 65.
Does exercise in midlife protect against dementia later in life? To evaluate this association, researchers used data from the Cooper Clinic in Dallas, Texas — a practice whose participants generally are healthy and either self-referred or employer-referred for preventive health examinations. The study cohort was >19,000 participants who underwent exercise treadmill tests between 1971 and 2009 (before age 65); their long-term incidence of dementia was determined from Medicare administrative claims data.
A total of 1659 cases of incident dementia were identified during a median follow-up of 25 years. Lower fitness at midlife was associated with higher prevalence of elevated body-mass index, hypertension, diabetes, hyperlipidemia, and smoking. After controlling for these risk factors, individuals in the highest quintile of fitness at midlife had a significantly lower incidence of all-cause dementia than those in the lowest quintile (hazard ratio, 0.64).
Comment: This observational study suggests that higher levels of midlife fitness are associated with lower risk for later dementia. The authors hypothesize that exercise lowers risk for developing diabetes and hypertension, which are associated with developing dementia. Of note, a recent NIH consensus statement concluded that evidence was insufficient to recommend physical activity as a method of attenuating risk for later-life dementia (Ann Intern Med 2010; 153:176).
— Jamaluddin Moloo, MD, MPH Published in Journal Watch General Medicine March 19, 2013
Citation(s): DeFina LF et al. The association between midlife cardiorespiratory fitness levels and later-life dementia: A cohort study. Ann Intern Med 2013 Feb 5; 158:162.
(http://annals.org/article.aspx?articleid=1567851)
http://www.ncbi.nlm.nih.gov/pubmed/23381040?dopt=Abstract
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MM: It's all well and good to increase dietary potassium intake but care must be taken not to overdose on this critical mineral. Hyperkalemia can have detrimental effects on the body including at first nausea, fatigue, muscle weakness or tingling sensations. However at higher levels Hyperkalemia may lead to slow heart rate (bradycardia), weak pulse and cardiac standstill aka heart stoppage.
BMJ 2013 Apr 4; 346:f1378
Higher Potassium Intake Lowers Blood Pressure and Is Associated with Less Risk for Stroke
A BP-lowering effect was noted in hypertensive people and those with high sodium intake.
Low potassium intake is associated with hypertension and stroke. In new meta-analyses, investigators assessed whether higher potassium intake protects against hypertension and adverse cardiovascular (CV) events, including stroke.
Overall, 1600 individuals participated in 22 randomized trials; trial interventions were provision of potassium supplements in 20 trials and dietary advice in the other 2. Higher potassium consumption significantly reduced systolic blood pressure (SBP) by a mean 5.9 mm Hg and diastolic blood pressure (DBP) by a mean 3.8 mm Hg. However, subgroup analyses revealed that higher potassium intake lowered BP only in patients with hypertension (i.e., not in patients with normal or low BP). Daily potassium intake of 90 to 120 mmol was associated with the largest reductions in SBP (mean, 7.2 mm Hg) and DBP (mean, 4.0 mm Hg). Notably, higher potassium intake lowered SBP regardless of baseline potassium intake and antihypertensive drug use. When trials were grouped by participants' sodium intake, the greatest decrease in SBP (mean, 6.9 mm Hg) was seen in studies with the highest daily mean sodium intake (>4 g). In 11 cohort studies that involved 127,000 patients, high potassium intake was associated with less risk for stroke (risk ratio, 0.76) but not with lower risk for incident CV disease or coronary heart disease.
Comment: In these meta-analyses, higher potassium intake lowered SBP and DBP and was associated with less stroke risk. Patients, especially those with hypertension, should be advised to not only reduce their sodium intake but also to increase their potassium intake.
— Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine April 18, 2013
Citation(s): Aburto NJ et al. Effect of increased potassium intake on cardiovascular risk factors and disease: Systematic review and meta-analyses. BMJ 2013 Apr 4; 346:f1378.
(http://dx.doi.org/10.1136/bmj.f1378)
http://www.ncbi.nlm.nih.gov/pubmed/23558164?dopt=Abstract
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MM: The take away from this article should be
a.) new antibiotics are slow in coming to market due to increased toxicity and danger associated with those that have either been developed in the past 6-7 years or actually made it to the market; and
b.) The authors emphasize that infection prevention is a key component to health.
Some simple ways that we have readily available to us to prevent infection are vitamin D3 and Probiotics. Both of these non-prescription products have shown a history of both safety and efficacy.
Antibiotic Development 'Alarmingly Slow'
By Kelly Young
A survey by the Infectious Diseases Society of America finds "tangible progress" in the development of new antibiotic drugs, but this progress has been "alarmingly slow."
The report, published in Clinical Infectious Diseases, finds that only two new antibiotics — telavancin and ceftaroline fosamil — have been approved since 2009. IDSA has called for 10 new antibiotics to be developed by 2020.
Seven intravenous drugs against multidrug-resistant gram-negative bacilli (GNB) are in phase II or III clinical trials, including four β-lactam plus β-lactamase inhibitor combination drugs, two protein synthesis inhibitors, and one peptic mimetic. However, none of these covers the entire spectrum of GNB resistance.
The authors conclude: "In the meantime, the preservation of the miracle of antibacterials will not be possible without a determined focus on protecting our currently available antibacterial drugs via strong antibiotic stewardship and infection prevention."
http://cid.oxfordjournals.org/content/early/2013/04/16/cid.cit152.full
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J Infect Dis 2013 Apr 1; 207:1037
Influenza Can Sneak Past Surgical Masks
Air samples yielded small-particle viral RNA as far as 6 feet from infected patients.
We know that influenza virus can be transmitted by airborne particles, but many details remain to be unraveled. Researchers evaluated viral dispersal patterns under ordinary clinical circumstances by stationing air sampling machines at various distances from the heads of sick patients admitted to a tertiary care teaching hospital in North Carolina. Air samples then were assayed for influenza virus RNA with quantitative polymerase chain reaction (PCR).
Among 61 patients with influenza confirmed by rapid testing, aerosolized virus was detected in the vicinity of 26 "emitters" (43%), 5 of whom were "super-emitters," who generated aerosolized virus in quantities orders of magnitude higher than other emitters. Emitters had more virus in their nasopharyngeal samples than non-emitters but were otherwise relatively similar on symptom scores; no clinical characteristics distinguished super-emitters from emitters. The air samples obtained 1 foot from emitters' heads had the highest concentrations of viral RNA. However, air samples obtained from 6 feet away still contained viral RNA, almost all of which was contained in particles small enough to elude standard surgical masks.
Comment: These data come with the caveat that PCR testing cannot distinguish infectious virus from inert RNA. However, they do imply that, in about half of hospitalized influenza patients, standard infection-control measures might be inadequate. An editorialist suggests that the intensity and severity of the community outbreak should be taken into account when discussing whether standard surgical masks should be replaced with the respirator masks and eye protection required to combat small-particle aerosols.
— Abigail Zuger, MD Published in Journal Watch General Medicine April 9, 2013
Citation(s): Bischoff WE et al. Exposure to influenza virus aerosols during routine patient care. J Infect Dis 2013 Apr 1; 207:1037.
(http://dx.doi.org/10.1093/infdis/jis773)
http://www.ncbi.nlm.nih.gov/pubmed/23372182?dopt=Abstract
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PLoS ONE 2013 Mar 6; 8:e57752
Sunshine and Tuberculosis: Is There a Relationship?
What does a seasonal variation in TB incidence mean with regard to sun exposure and vitamin D status?
An estimated 9 million cases of tuberculosis occur each year, worldwide, with 1.7 million associated deaths. Vitamin D has been reported to contribute to host defenses against TB, and sun exposure is an important source of vitamin D. Investigators evaluated the relationship between fluctuations in sun exposure and incidence of TB in Birmingham, England.
From 1980 to 2010, 9739 new cases of pulmonary and extrapulmonary TB were reported. Reports of new cases were 24% higher in the summer than in the winter (95% confidence interval, 15.8–32.8; P<0.001). Winter dips in sunshine correlated with peaks in TB incidence 6 months later (4.7% increase in incidence for each 100 hours decrease in sunshine, P<0.001). This variation in seasonal incidence was significant in both pulmonary and extrapulmonary TB, and among U.K.-born patients. A similar trend was seen in individuals born outside the U.K., although there were too few such cases to assess statistical significance.
Comment: Seasonal occurrence of tuberculosis has been reported by other investigators. It is tempting to conclude that this phenomenon is related to sun exposure. In fact, one of the first Nobel Prizes in Medicine was given to Niels Finsen for his discovery that ultraviolet radiation was an effective therapy for cutaneous TB. However, it is important to emphasize that these findings identify an association between sun exposure and TB incidence, rather than cause and effect. It is common but incorrect to conclude that any association of a disease with season or sun exposure is caused by variations in vitamin D status. Many other factors can cause seasonal variation in disease. As the authors point out, a hypothesis generated by these observations should be followed by further investigation. The bottom line is that a seasonal variation in TB incidence exists; whether this variation is related to aspects of sun exposure or vitamin D is unclear.
— Craig A. Elmets, MD Published in Journal Watch Dermatology April 5, 2013
Citation(s): Koh GC et al. Tuberculosis incidence correlates with sunshine: An ecological 28-year time series study. PLoS ONE 2013 Mar 6; 8:e57752.
(http://dx.doi.org/10.1371/journal.pone.0057752)
http://www.ncbi.nlm.nih.gov/pubmed/23483924?dopt=Abstract
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Kids with Migraines Likely to Have Been Colicky Babies
By Amy Orciari Herman
Nearly three quarters of children with migraine experienced colic as infants, according to a case-control study in JAMA.
Some 200 children and adolescents (aged 6 to 18 years) who were diagnosed with migraine in three European emergency departments were compared with roughly 470 children of the same age with minor trauma (controls). Those with migraine were more likely than controls to have a history of colic (73% vs. 27%), as determined by parental report and medical record review. The increased prevalence of colic was observed for migraine with and without aura. In a separate analysis, tension headache was not associated with infant colic.
Editorialists, noting that sleep disruption can trigger migraine, speculate: "It is plausible that the lack of a fully established endogenous circadian rhythm of melatonin production during an infant's first months of life may play a role in both sleep disruption and gastrointestinal motility and trigger migraine in a vulnerable infant that is then diagnosed as colic."
http://jama.jamanetwork.com/article.aspx?articleid=1679399
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MM: I investigated the measuring of coronary artery calcium plaque several years ago and was impressed by the testing and the projections that there was a relationship between these calcium plaque levels and cardiovascular (CV) disease. This study investigates an added relationship with type 2 diabetes that is quite interesting.
BMJ 2013 Mar 25; 346:f1654
Measuring Coronary Artery Calcium in People with Type 2 Diabetes Identifies a Low-Risk Subset
Coronary calcium scores might help stratify risk for adverse cardiovascular events.
A promising cardiovascular (CV) risk stratification tool is computed tomography (CT) measurement of coronary artery calcium. But how well does this tool perform in people with type 2 diabetes? In this meta-analysis of eight prospective studies, investigators evaluated the association of coronary artery calcium scores with all-cause mortality and adverse CV events (e.g., myocardial infarction) in more than 6500 patients.
Overall, 29% of participants had coronary calcium scores <10. After a mean follow-up of 5.2 years, 802 events (fatal and non-fatal CV events and all-cause mortality) had occurred. Compared with coronary calcium scores <10, scores 
10 were associated with significantly elevated risk for the composite outcome of all-cause mortality, adverse CV events, or both (relative risk, 5.5) and for adverse CV events alone (RR, 9.2). The sensitivity and specificity of a coronary calcium score 
10 for the composite outcome were 94% and 34%, respectively; for adverse CV events alone, sensitivity was 95% and specificity was 43%. For coronary calcium scores <10, post-test probability of the composite outcome was less than 2% (a nearly 7-fold reduction from pretest probability). Similar results were obtained for adverse CV events only.
Comment: In this meta-analysis, coronary artery calcium scoring identified people with type 2 diabetes who were at low risk for cardiovascular events. Whether it improves outcomes or is cost-effective should be evaluated in randomized trials.
— Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine April 9, 2013
Citation(s): Kramer CK et al. Coronary artery calcium score prediction of all cause mortality and cardiovascular events in people with type 2 diabetes: Systematic review and meta-analysis. BMJ 2013 Mar 25; 346:f1654.
(http://dx.doi.org/10.1136/bmj.f1654)
http://www.ncbi.nlm.nih.gov/pubmed/23529983?dopt=Abstract
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Neurosurgery 2013 Mar; 72:1
New Neurosurgical Guidelines Warn of Harm from Steroids in Acute Spinal Injury
Comprehensive consensus guidelines contain 112 evidence-based recommendations, including that methylprednisolone should not be used for treatment of acute spinal cord injury.
The Congress of Neurological Surgeons and the American Association of Neurological Surgeons released a revised version of the original 2002 evidence-based guidelines for management of acute cervical spine and spinal cord injuries (http://journals.lww.com/neurosurgery/toc/2013/03002). Of 112 recommendations (the previous version contained 76), 19 are classified as level I recommendations, 16 as level II, and 77 as level III. Due to lack of evidence, the panel offered no recommendations on certain topics of interest such as, for example, the benefit or harm of hypothermia in patients with spinal cord injury.
Changes most relevant to emergency medicine include:
- Methylprednisolone is not recommended for acute spinal cord injury, because no class I or II evidence supports its benefit. Class I, II, and III evidence indicate a higher incidence of infection, sepsis, complications, increased intensive care unit length of stay, and death with steroid use. (Level 1 recommendation)
- Computed tomography is the imaging study of choice for obtunded or un-evaluable patients with potential cervical spine injuries. (Level I)
- Computed tomographic angiography is recommended to assess for vertebral artery injury in selected patients who meet the modified Denver Screening Criteria after blunt cervical trauma. (Level I)
- Spinal immobilization and imaging are not recommended in patients with penetrating or blunt trauma who have normal mentation, no neck pain or tenderness, no focal neurologic findings, and no distracting injuries. (Level II)
Comment: Another indication for steroids bites the dust! For those of us who were not convinced by the original data, we now have expert consensus to put an end, once and for all, to the misguided notion that steroid treatment is indicated for patients with acute spinal injury.
— Kristi L. Koenig, MD, FACEP, FIFEM Published in Journal Watch Emergency Medicine April 12, 2013
Citation(s): Resnick DK. Updated guidelines for the management of acute cervical spine and spinal cord injuries. Neurosurgery 2013 Mar; 72:1.
(http://dx.doi.org/10.1227/NEU.0b013e318276ee7e)
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FDA Admits to Lack of Aggressive Response in NECC Situation
The FDA chief conceded on Tuesday that the agency could have been more aggressive in its oversight of the compounding pharmacy at the center of a deadly meningitis outbreak. FDA Commissioner Margaret Hamburg said a confusing legal landscape, combined with resistance from compounding pharmacies, had hampered her agency's ability to act on a myriad of complaints against the New England Compounding Center and its sister company, Ameridose LLC. "I wish we had acted earlier," Hamburg told a House Energy and Commerce subcommittee looking into the outbreak, which has killed 53 people and sickened more than 700. This was the second hearing held by the committee to determine whether the FDA could have prevented the outbreak and whether it needs greater powers to regulate pharmacies that compound drugs tailored for specific patients.
http://www.reuters.com/article/2013/04/16/us-usa-health-meningitis-idUSBRE93F1FW20130416
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