• Are Calcium Supplements Bad for the Heart?
• Dietary Fiber May Combat Obesity and Obesity-Related Inflammation in Adolescents
• Dietary Fats Are Associated with Cognition
• Low-Dose Aspirin Use Raises Risk for Major Bleeding
• Fetal Safety of Newer Antiepileptic Drugs During Pregnancy
• Cognitive Effects of Subconcussive Head Impact in Sports
• Contact Sports May Affect Learning in College Athletes
• Your Brain — Use It or Lose It
• Legal Medical Marijuana Poses Risks to Teens
• FDA Approves First New Weight-Loss Drug in 13 Years
• A New Approach to Insomnia
• Vegetables Might Reduce Risk for Acute Pancreatitis
• Botulinum Toxin A for Raynaud Syndrome
• Is Botulinum Toxin Type A Effective for Headache Prophylaxis?
• Five-Day, Levofloxacin-Based Concomitant Therapy for Helicobacter pylori
• High-Dose PPI, Amoxicillin, and Metronidazole for Primary Treatment of H. pylori Infection?
• Frozen Stool for Fecal Transplant in Refractory C. difficile Infection
• Cow, Soy, or Breast Milk: Does It Make a Difference in Developmental Outcome?
• FDA Causes Cancer Drug Shortages
• Supplementing Formula with Polyunsaturated Fatty Acids (DHA/Omega 3 & 6) Does
Not Enhance Infant Cognition
• Ibuprofen Reduces the Severity of Acute Mountain Sickness
• Eating Certain Fish Might Prevent Liver Cancer
MM: We have been saying for a long time that dietary sources of calcium are preferred. Here is a theory of why calcium supplements may be detrimental. Although it may make us squirm and uncomfortable to do so; it is often a good idea to challenge existing health and medical dogma. This is especially true if there is a lack of evidence or an abundance of contradictory data regarding that dogma. The use of high dose calcium supplementation may be one of those universally accepted practices that in fact, are detrimental to health and longevity.
Heart 2012 Jun; 98:920
Are Calcium Supplements Bad for the Heart?
Supplements, but not dietary calcium intake, were associated with elevated risk for myocardial infarction.
Calcium supplements are widely used to minimize risk for osteopenia and osteoporosis, especially by older women. But do supplements promote vascular calcification and therefore cardiovascular (CV) events? Using data for 24,000 participants in a German study of cancer and nutrition, investigators analyzed the effect of calcium intake, both dietary and supplemental, on CV events and CV mortality.
During an average follow-up of 11 years, there were 354 myocardial infarctions (MIs), 260 strokes, and 267 CV deaths. There was no evidence of increased risk for MI, stroke, or CV mortality with increasing dietary calcium intake. However, use of calcium supplements was associated with significantly elevated risk for MI (hazard ratio, 1.86), but not stroke (HR, 1.05) or CV death (HR, 1.02), although the number of events in supplement users was small.
Comment: This analysis is one of several to suggest that calcium supplementation is associated with elevated cardiovascular risk and that intake of dietary calcium is not. How to explain the discrepancy? Editorialists postulate that dietary calcium, taken in gradually with other foods, may not raise serum calcium levels to the same degree as supplements, so that supplements may lead to vascular calcium deposition over time. Although this analysis does not prove a causal link, it seems prudent to rely predominantly on dietary calcium whenever possible, reserving calcium supplements for situations where their benefits clearly outweigh their risks.
— Kirsten E. Fleischmann, MD, MPH Published in Journal Watch General Medicine June 26, 2012
Citation(s): Li K et al. Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition study (EPIC-Heidelberg). Heart 2012 Jun; 98:920.
(http://dx.doi.org/10.1136/heartjnl-2011-301345)
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MM: Mark Drugs now carries a high fiber, NO CARB, GLUTEN FREE bread for those who have entered phase II of the HCG (maintenance phase) weight loss and metabolic syndrome treatment protocol. It is delicious and holds up better than any no carb, low carb or gluten free bread I have ever tasted. I highly recommend it. Please call for more information.
J Clin Endocrinol Metab 2012 May 16
Dietary Fiber May Combat Obesity and Obesity-Related Inflammation in Adolescents
Greater consumption of dietary fiber was associated with lower visceral adiposity and markers of inflammation.
Dietary fiber has been suggested to mitigate systemic inflammation related to obesity. To examine the association between dietary fiber intake and inflammatory markers in adolescents, researchers examined dietary recalls, anthropometric and body composition measures, and fasting blood samples in 559 healthy adolescents (age range, 14–18 years; 49% female and 45% black) recruited from public schools in Georgia.
Boys consumed significantly more dietary fiber than and girls (12.4 vs. 9.4 g/day), but both consumed about 65% less than the recommended 14 g/1000 kcal. Mean plasma C-reactive protein (CRP) levels were 1.3 mg/L in girls and 0.9 mg/L in boys. In both girls and boys, fiber intake was inversely associated with leptin, CRP, fibrinogen, and fat mass, and positively associated with serum adiponectin. In analysis adjusted for age, race, Tanner stage, energy intake, and physical activity, dietary fiber was negatively associated with visceral adipose tissue (VAT) in both boys and girls. When fat mass or VAT measures were included as covariates in adjusted analyses, dietary fiber remained inversely associated with adiponectin and CRP levels. Fiber intake was not associated with plasma resistin.
Comment: This interesting study suggests that adding fiber to diets of adolescents might reduce visceral adiposity and inflammation. It might not be easy, but it is worth a try.
— F. Bruder Stapleton, MD Published in Journal Watch Pediatrics and Adolescent Medicine June 20, 2012
Citation(s):Parikh S et al. Adolescent fiber consumption is associated with visceral fat and inflammatory markers. J Clin Endocrinol Metab 2012 May 16; [e-pub ahead of print].
(http://dx.doi.org/10.1210/jc.2012-1784)
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MM: This study essentially states that trans fat and that which is found in red meat is not necessarily detrimental to cognitive function but that fish oil, olive oil and similar fats are beneficial. A relatively easy, but not fool proof way to determine what is good and what is bad is that if a fat is solid at room temperature it is more likely a bad one.
Ann Neurol 2012 May 17
Dietary Fats Are Associated with Cognition
In healthy older women, low saturated fat intake and high monounsaturated fat intake were beneficial.
"Unhealthy fats" — saturated fats and trans fats — promote cardiovascular disease, and "healthy fats" — monounsaturated and polyunsaturated fats — prevent cardiovascular disease. A new report from the Women's Health Study involved 6183 older women (mean age at study entry, 66) who provided detailed food-intake histories and underwent repeated cognitive testing (general cognition, verbal memory, and semantic fluency) during 4 years.
After adjusting for multiple confounding factors, higher saturated fat intake was associated significantly with worse global cognitive scores. In contrast, higher monosaturated fat intake was associated with better global cognitive scores. Researchers found a linear relation between the amount consumed of each fat consumed and the degree to which cognition changed. Women with the highest saturated fat intake were 60% to 70% more likely to develop poor cognition than were women with the lowest intake. In contrast, women with the highest monounsaturated fat intake had a 40% to 50% lower chance of poor cognition compared with those with the lowest intake. Contrary to the authors' hypothesis, neither trans fat nor polyunsaturated fat intake was associated with significantly worse or better cognition.
Comment: This large meticulously conducted observational study in older women shows a strong association between cognitive decline and both high saturated fat intake and low monounsaturated fat intake. In the absence of a randomized trial, the association cannot be considered causal; however, a randomized trial of this particular dietary pattern is unlikely to be conducted. The relatively low intake of trans fats in these generally healthy women might have led to the investigators' inability to establish an association with cognitive decline.
— Anthony L. Komaroff, MD Published in Journal Watch General Medicine June 5, 2012
Citation(s): Okereke OI et al. Dietary fat types and 4-year cognitive change in community-dwelling older women. Ann Neurol 2012 May 17; [e-pub ahead of print].
(http://dx.doi.org/10.1002/ana.23593)
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MM: It’s been pretty well accepted for a long time that those who are at risk for CV disease would benefit from daily Low Dose Aspirin (LDA). This study does not refute that. What is does say is that for those who are not at high risk, the potential benefits may not substantially outweigh the risks.
JAMA 2012 Jun 6; 307:2286
Low-Dose Aspirin Use Raises Risk for Major Bleeding
Results raise questions about aspirin use for primary prevention of adverse cardiovascular events in low-risk patients.
Low-dose aspirin use lowers risk for recurrent adverse cardiovascular (CV) events in patients with known CV disease. Its benefit for primary prevention of CV events, especially in low-risk patients (those with 10-year risk <10%), is less clear given the risk for complications, particularly major bleeding. In this Italian study, researchers used a population-based database to identify 186,425 patients (mean age, 69) who took low-dose aspirin (
300 mg) daily for at least 75 days and matched them to the same number of control patients who had the same bleeding propensity and did not use aspirin.
During median follow-up of 5.7 years, 6907 episodes of major bleeding requiring hospitalization in aspirin and control patients occurred; about two thirds of bleeds were gastrointestinal, and one third were intracranial. The incidence rate was 5.58 events per 1000 person-years in aspirin users and 3.60 for nonusers, an excess of 2 per 1000 person-years.
Comment: Based on these data and prior meta-analyses, an editorialist puts these risks into perspective with the calculation that, for 10,000 patients without known CV disease followed for 1 year, aspirin would prevent about seven major CV events and would cause four major bleeding events. This marginal benefit stands in sharp contrast to the calculation that, in 10,000 patients with known CV disease, aspirin use would prevent about 250 major CV events and would cause about 40 major bleeding events. Because this study was observational, confounding for which the authors could not adequately control might have occurred, but the results might shift clinicians and patients away from low-dose aspirin use in patients at low risk for CV disease.
— Thomas L. Schwenk, MD Published in Journal Watch General Medicine June 19, 2012
Citation(s): De Berardis G et al. Association of aspirin use with major bleeding in patients with and without diabetes. JAMA 2012 Jun 6; 307:2286.
(http://dx.doi.org/10.1001/jama.2012.5034)
http://www.ncbi.nlm.nih.gov/pubmed/22706834?dopt=Abstract
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Neurology 2012 May 22; 78:1692
Fetal Safety of Newer Antiepileptic Drugs During Pregnancy
Risk for major congenital malformations is low for most AEDs, although newer AEDs are not necessarily safer than older ones.
Increasing numbers of reproductive-aged women with epilepsy are being prescribed newer antiepileptic drugs (AEDs; lamotrigine, levetiracetam, and topiramate) over traditional AEDs (e.g., carbamazepine, phenytoin, valproate); however, fetal safety remains a concern. Researchers assessed rates of major congenital malformations (MCMs) diagnosed within 12 weeks after birth in offspring of North American AED Pregnancy Registry participants (enrolled from 1997 to 2011) who received monotherapy with old or new AEDs during the first trimester. An internal comparison group recruited through the registry consisted of pregnant women without epilepsy who were not taking AEDs.
In all, 4899 women receiving AED monotherapy (92% for epilepsy) and 442 unexposed women were eligible. Rate of fetal MCMs in the unexposed group was 1.1%. In women who received newer AEDs, MCM rates ranged from 2.0% to 4.2%. Relative risk for MCMs was 1.8 with lamotrigine (95% confidence interval, 0.7–4.6), 2.2 with levetiracetam (95% CI, 0.8–6.4), and 3.8 with topiramate (95% CI, 1.4–10.6). For older AEDs, MCM rates ranged from 2.9% to 9.3%. RR was 2.7 with carbamazepine (95% CI, 1.0–7.0), 2.6 with phenytoin (95% CI, 0.9–7.4), and 9.0 with valproate (95% CI, 3.4–23.3). Valproate was the only AED that showed a dose–response relation.
Comment: Although the confidence intervals associated with these findings are relatively wide, women with epilepsy who require anti seizure medication during pregnancy should find these results reassuring. For most antiepileptic drugs other than valproate, rates of major congenital malformations were low. Before conception, it should be determined whether a woman must take an AED during pregnancy. If so, the regimen should be simplified whenever possible to one AED that controls seizures at the lowest possible dose. For those women with epilepsy who are not planning to become pregnant, reliable contraception is critical.
— Autumn Klein, MD, PhD Published in Journal Watch Women's Health June 28, 2012
Citation(s): Hernández-Díaz S et al. Comparative safety of antiepileptic drugs during pregnancy. Neurology 2012 May 22; 78:1692.
http://www.ncbi.nlm.nih.gov/pubmed/22551726?dopt=Abstract
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Neurology 2012 May 29; 78:1777
Cognitive Effects of Subconcussive Head Impact in Sports
No clear cognitive concerns were noted.
Amid concerns about the neurological and psychiatric consequences of concussion in athletes comes a study on the cognitive effects of smaller head impacts that do not cause concussion. Researchers used a novel helmet technology to measure the number and force of head impacts experienced by 214 college football and ice-hockey players (men and women) during a single season. They then compared the results of pre- and postseason neurocognitive assessments between these athletes and 45 athletes in noncontact sports (track, crew, and Nordic skiing). In contact-sport athletes, the postseason assessment occurred an average of 25 days after the last head impact.
The contact-sport athletes experienced an average of 469 hits of at least 14 g (force of gravity) during the season (range, 1–2154). The maximum linear acceleration of each hit ranged from 17 g to 324 g. Neurocognitive scores did not differ significantly from preseason to postseason in either group of athletes, nor were any differences seen between the groups at preseason or postseason (except for better preseason performance by contact athletes on the Visual Memory Composite). A subgroup of participants underwent a more extensive battery of cognitive tests that showed some statistically significant differences, but the clinical significance of these findings was unclear.
Comment: Most contact-sport athletes have experienced prior concussions and subconcussive hits, so the lack of preseason differences between contact and noncontact athletes in this study was reassuring. The importance of some of the differences found here is unclear. The use of a relatively new technology to document strong but subconcussive head impacts in college athletes was perhaps the most important "outcome" of this study.
— Thomas L. Schwenk, MD Published in Journal Watch General Medicine June 28, 2012
Citation(s): McAllister TW et al. Cognitive effects of one season of head impacts in a cohort of collegiate contact sport athletes. Neurology 2012 May 29; 78:1777.
(http://dx.doi.org/10.1212/WNL.0b013e3182582fe7)
http://www.ncbi.nlm.nih.gov/pubmed/22592370?dopt=Abstract
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Neurology 2012 May 29; 78:1777
Contact Sports May Affect Learning in College Athletes
Even one season of repetitive head impacts might have a negative effect on cognitive performance.
Concussion and traumatic brain injury in athletes has been a frequent subject in the lay press recently, given growing interest in chronic traumatic encephalopathy as a distinct neurodegenerative entity; however, scientific studies on the topic are few and often contradictory. To assess the effect of repetitive head impacts on cognitive performance, researchers prospectively compared pre- and postseason neuropsychological test results between 214 Division I college athletes who played contact sports (ice hockey or football) and 45 such athletes who played noncontact sports. Contact-sport athletes wore helmets that recorded acceleration, duration, and location of head impact.
Contact-sport athletes were exposed to a mean of 469 distinct head impacts per season. None of the athletes studied suffered a concussion during the season. Comparison of pre- and postseason test results demonstrated that repetitive head impacts during a single season did not have a short-term detrimental effect overall. However, significantly more contact-sport athletes than noncontact-sport athletes (22% vs. 4%) performed more than 1.5 standard deviations below their predicted score on postseason tests of learning and memory (1.5 standard deviations was prospectively selected as a marker of "significantly poorer than expected" performance).
Comment: Most of the attention and discussion about contact sports has focused on concussion, not nonconcussive repetitive head impacts. Although it is possible and perhaps even intuitive that nonconcussive repetitive head impacts may have adverse effects on cognition, this study is too small and did not sufficiently address potential confounding variables to draw any conclusion other than a larger, controlled study is required. When reliable information is available, parents and young adults should be made aware to ensure informed decision making about contact-sport participation.
— Richard D. Zane, MD, FAAEM Published in Journal Watch Emergency Medicine June 22, 2012
Citation(s): McAllister TW et al. Cognitive effects of one season of head impacts in a cohort of collegiate contact sport athletes. Neurology 2012 May 29; 78:1777
http://www.ncbi.nlm.nih.gov/pubmed/22592370?dopt=Abstract
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MM: How many times have we heard that we should try something new to keep our brains functioning? Whether its learning a new language, doing crossword puzzles, playing “words with friends” on our smart phones or taking enrichment classes at our local universities and community colleges, it appears that it is both beneficial and important to keep our minds challenged in order to keep our brains fresh.
Biol Psychiatry 2012 May 1; 71:783
Your Brain — Use It or Lose It
An active cognitive lifestyle does not protect against Alzheimer disease pathology, but using cognitive abilities helps men and women minimize changes in aging in different ways.
Animal and human studies suggest that mental stimulation reduces the risk of cognitive decline. Researchers used data from a U.K. study of 13,004 older people (baseline age, 
65) who were followed for 14 years; the brains of 329 subjects who died during follow-up were autopsied. In the current analysis, researchers examined the relationship between neuropathology and Cognitive Lifestyle Score (CLS). The CLS measures years of education, occupational complexity, and social engagement.
After adjustment for relevant medical and vascular risk factors, men with high CLS (i.e., an active cognitive lifestyle) had an 80% relative reduction in risk for microvascular disease and associated deep white-matter lesions and a 70% relative reduction in risk for lacunar infarcts, compared with low-CLS men. High-CLS women had greater brain weight (but not less-frequent cerebrovascular disease) than low-CLS women. High CLS was associated with an 80% reduction in the risk for dementia at death in men but not women. In a subsample of 72 individuals, high CLS did not protect against neuronal loss in the hippocampus. However, after adjustment for other risk factors, high CLS was associated, in both men and women, with greater neuronal density and a thicker cortical ribbon in Brodmann area 9.
Comment: It is not yet known whether an active cognitive lifestyle and social engagement directly affect the brain and cerebral vasculature, whether people who are more resilient neurologically have more active cognitive lifestyles, or whether predisposition to greater resiliency is linked to predisposition to cognitive activity. However, improvement of cognitive decline by cognitive retraining (JW Psychiatry Oct 17 2011) suggests that a two-way interaction between the environment and the brain might protect against dementia via several mechanisms.
— Steven Dubovsky, MD Published in Journal Watch Psychiatry May 25, 2012
Citation(s): Valenzuela MJ et al. Multiple biological pathways link cognitive lifestyle to protection from dementia. Biol Psychiatry 2012 May 1; 71:783.
http://www.ncbi.nlm.nih.gov/pubmed/22055015?dopt=Abstract
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J Am Acad Child Adolesc Psychiatry 2012 May 28
Legal Medical Marijuana Poses Risks to Teens
A remarkable 74% of teens in two Colorado substance treatment programs admit to use of diverted marijuana.
Diversion of medical marijuana from legal prescriptions among teenagers is important to investigate for several reasons. The diversion of psychotropic drugs from parental and peer prescriptions is increasing (JW Psychiatry Apr 30 2007), and cannabis use during the teen years heightens the risk for psychosis (JW Psychiatry Jan 27 2005). Because many states now allow medical marijuana, researchers studied teenagers' use of marijuana diverted from legal prescriptions.
The study took place in Colorado, which houses approximately 40% of legal marijuana facilities in the U.S. and in which 2.3% of adults have registry cards for use of medical marijuana. The 164 subjects (age range, 14–18 years) from two substance-use treatment programs participated in comprehensive assessments that included items on diversion of legal marijuana. Teens with major psychiatric disorders were excluded.
Of the patients, 74% had used marijuana diverted from legal medical prescriptions; 80% of these users were male. Only one participant had a legal marijuana registry card. Diverters and nondiverters started marijuana use at a mean age of 12 years. Diverters had a significantly higher rate of marijuana use disorders (89% vs. 67%) and significantly more symptoms of conduct disorder.
Comment: Even taking into account the relatively easy availability of marijuana in Colorado, the use of diverted marijuana by 74% of teenagers in clinical treatment is remarkable. Child psychiatrists, especially in areas with legal medical marijuana (17 states and the District of Columbia), need to add cannabis to inquiries about diverted psychoactive drug use. Physicians treating patients receiving medical marijuana need to educate them about widespread diversion and precautions that may limit illegal use, such as secure home storage.
— Barbara Geller, MD Published in Journal Watch Psychiatry June 18, 2012
Citation(s): Salomonsen-Sautel S et al. Medical marijuana use among adolescents in substance abuse treatment. J Am Acad Child Adolesc Psychiatry 2012 May 28; [e-pub ahead of print].
(http://dx.doi.org/10.1016/j.jaac.2012.04.004)
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MM: It slays me that a product that shows such a marginal potential weight loss and other metabolic benefit is approved for weight loss yet both mis-information and dis-information persists regarding HCG. This drug already exhibits adverse effects and more will become evident with longitudinal and public use.
The FDA has approved lorcaserin (Belviq) as an adjunct to diet and exercise for ongoing weight management — the first new weight-loss drug to be approved in the U.S. in 13 years.
Lorcaserin is approved for use in adults with a BMI of 30 or more, or for those with a BMI of 27 or more who have at least one weight-related condition (type 2 diabetes, dyslipidemia, hypertension). In trials, lorcaserin recipients lost roughly 3.5% of body weight after 1 year.
Lorcaserin activates the brain's serotonin 2C receptor, which may help people feel full after eating smaller amounts. Treatment can cause serotonin syndrome, especially when taken with medications that raise serotonin levels or activate serotonin receptors, including antidepressants and migraine drugs.
Heart valve abnormalities, a concern with previous antiobesity drugs, did not appear to differ between patients treated with lorcaserin and those on placebo. However, the FDA warns that it should be used with caution in patients with congestive heart failure, because such patients may have higher levels of serotonin 2B receptors.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm309993.htm
http://www.reuters.com/article/2012/06/27/us-arena-obesity-idUSBRE85Q1AA20120627
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MM: Although almorexant is potentially promising, virtually all prescription sleep aid products that have been used in the past have fallen short of their promises and have shown adverse side effects. A wait and see attitude may be the best one to take with this class of drugs for the present.
Clin Pharmacol Ther 2012 Jun; 91:975
A New Approach to Insomnia
Orexin receptor antagonists may be effective in the treatment of primary insomnia.
Orexin (hypocretin) is a neurotransmitter involved in reward, eating, activity, arousal, and the sleep–wake cycle. Orexin levels in cerebrospinal fluid decrease during sleep. To examine whether almorexant — an antagonist of orexin-A and orexin-B (hypocretin 1 and 2) receptors — might improve sleep without daytime impairment, as occurs with many benzodiazepine receptor agonists, researchers conducted an international, manufacturer-sponsored, crossover trial. The 153 participants (mean age, 45) with chronic primary insomnia (including decreased total sleep, difficulty falling asleep, and daytime problems related to lack of sleep) received a single dose of almorexant or placebo, in random order, 1 week apart, and underwent all-night polysomnography.
Compared with placebo, doses of 100 mg or above were dose-dependently and significantly effective in increasing total sleep time. The best results occurred with 400 mg (70 minutes more total sleep, 54 minutes less time awake after sleep onset, decreased latency to all stages of sleep, and more time spent in stages 2, 3, and 4 and rapid eye movement [REM] sleep). The patients' subjective assessments showed similar improvements, but not in reduced waking after sleep onset. Daytime reaction time increased slightly (by 35 milliseconds) at 400 mg, and forward digit-span test scores were slightly lower at 200 mg, without any decrease in subjective alertness.
Comment: At 400 mg, almorexant primarily improved sleep maintenance and normalized the amount of REM sleep, improving sleep efficiency. The lack of clinically meaningful daytime impairment is encouraging. Decreased REM latency also occurs with antidepressants and some other medications, seeming to reflect REM rebound. However, because almorexant enhanced rather than suppressed REM sleep, some other mechanism of almorexant treatment probably affected REM latency. Cognitive-behavioral therapy remains the gold-standard treatment for primary insomnia, but orexin receptor antagonists hold promise.
— Steven Dubovsky, MD Published in Journal Watch Psychiatry June 11, 2012
Citation(s):Hoever P et al. Orexin receptor antagonism, a new sleep-enabling paradigm: A proof-of-concept clinical trial. Clin Pharmacol Ther 2012 Jun; 91:975.
(http://dx.doi.org/10.1038/clpt.2011.370)
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Vegetables Might Reduce Risk for Acute Pancreatitis
A diet high in vegetables is associated with reduced risk for acute pancreatitis, according to a study in Gut.
Using two Swedish cohorts, researchers assessed the fruit and vegetable consumption of some 80,000 healthy adults. During a mean 11-years' follow-up, 320 cases of non-gallstone-related acute pancreatitis were diagnosed.
Participants in the highest quintile of vegetable consumption had a 44% reduced risk for acute pancreatitis, relative to those in the lowest quintile. The risk was even lower in people who also drank more than one alcoholic beverage per day or were overweight. Fruit, however, was not associated with the risk reduction seen with vegetables.
The authors propose that high antioxidant intake through vegetables could benefit the pancreas by reducing the effect of oxidative stress, particularly in those with high baseline oxidative stress.
http://gut.bmj.com/content/early/2012/06/08/gutjnl-2012-302521.abstract
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MM: Raynaud syndrome is one of those life tormenting conditions that we have yet to determine a cause of, let alone a cure for. Botulinum toxin has shown usefulness in an increasing number of treatment options for a variety of conditions. It is encouraging to see the effect of this product for increasing local blood flow to decrease pain and discomfort in this patient group.
Arch Dermatol 2012 Apr; 148:426
Botulinum Toxin A for Raynaud Syndrome
Botulinum toxin treatment is worth trying as first-line treatment in Raynaud syndrome.
The treatment of digital ulcers has proven difficult in patients with severe Raynaud syndrome. It is always associated with an underlying autoimmune connective tissue disease, especially scleroderma, and often refractory to conventional therapies. Continuous, debilitating resting finger and hand pain and persistent ulcers prompted the exploration of alternative therapeutic options for a 52-year-old woman with treatment-resistant Raynaud syndrome.
The authors of this case report note that injection of 100 units of botulinum toxin A into the hand led to an immediate improvement in blood flow and pain, with eventual resolution of several digital ulcers. Although the exact mechanism by which botulinum toxin A exerts its effects in Raynaud syndrome has yet to be elucidated, the authors propose that it modulates expression of adrenergic receptors and neuropeptides, along with inhibiting contraction of vascular smooth muscle, thus improving tissue perfusion and pain.
Comment: Botulinum toxin treatment of Raynaud syndrome has been previously reported in the hand and plastic surgery literature and once in the dermatology literature as a felicitous outcome in a patient being treated for hyperhidrosis, but this appears to be the first report of intended use in a U.S. dermatology journal. The mechanism of action of botulinum toxin A treatment is as unclear in Raynaud syndrome as it is in wound healing and migraine headaches. However, the empirical evidence is impressive. Given the outstanding safety of low doses of botulinum, there appears to be no harm in trying it as a first-line treatment for Raynaud syndrome. Further investigations may help clarify the most helpful and cost-effective injection points and dosages.
— Murad Alam, MD, MSCI Published in Journal Watch Dermatology June 1, 2012
Citation(s): Smith L et al. Botulinum toxin-A for the treatment of Raynaud syndrome. Arch Dermatol 2012 Apr; 148:426.
http://www.ncbi.nlm.nih.gov/pubmed/22508867?dopt=Abstract
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JAMA 2012 Apr 25; 307:1736
Is Botulinum Toxin Type A Effective for Headache Prophylaxis?
A meta-analysis finds that it may be effective for chronic, but not episodic, migraine headache but not for any form of tension-type headache.
Headache is common in the community, with migraine and tension-type headache being the most common primary headache disorders to present to physicians (Headache 2004; 44:856). Frequent headache, called chronic daily headache, occurs on 15 or more days per month for 3 or more months (Curr Opin Neurol 2002; 15:287) and is the most challenging to treat. Chronic daily headache largely consists of chronic migraine (CM) and chronic tension-type headache (CTTH). Few controlled trials in these disorders have been conducted, largely because the definitions have been argued over for a long period and are only now standardized (Cephalalgia 2006; 26:742).
Botulinum toxin type A has been studied in both CM and CTTH and is the subject of a new meta-analysis of the evidence for its use in headaches in adults. The authors examined 27 placebo-controlled, randomized trials and 4 randomized studies comparing botulinum toxin type A with other medications. They demonstrate a reduction in headache days for CM and a less clear outcome for the umbrella diagnosis of chronic daily headache. There is no clear effect for either episodic migraine, defined as occurring on more than 15 days a month, or CTTH. As with any active treatment, there are adverse effects, such as blepharoptosis, skin tightness, and neck discomfort.
Comment: The results and conclusions in this meta-analysis are comparable to those of a pooled analysis of the chronic migraine studies (Headache 2010; 50:921) and recapitulate the rationale behind the U.S. Food and Drug Administration approval of botulinum toxin type A for the treatment of CM. Although one could quibble about the inclusion of studies that did not have a placebo injection arm in the CM analysis, since botulinum toxin type A administration would be completely unblinded, the overall outcome conclusions of the meta-analysis are not altered. The marginal effect in chronic daily headache illustrates, as the authors surmise, that the mixed population does less well. The meta-analysis underscores the importance of good medical history-taking and making a clear diagnosis to align patient presentation with the evidence. CM is a common, disabling, often life-ruining problem for patients, and a substantial public health problem. It requires more research into its pathophysiology and many more clinical trials to develop further evidence-based approaches.
— Peter J. Goadsby, MD, PhD, DSc Dr. Goadsby is a consultant for the manufacturer of Botox (botulinum toxin type A).
Published in Journal Watch Neurology May 15, 2012
Citation(s): Jackson JL et al. Botulinum toxin A for prophylactic treatment of migraine and tension headaches in adults: A meta-analysis. JAMA 2012 Apr 25; 307:1736.
http://www.ncbi.nlm.nih.gov/pubmed/22535858?dopt=Abstract
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Gastroenterology 2012 Jul; 143:55
Five-Day, Levofloxacin-Based Concomitant Therapy for Helicobacter pylori
This regimen was as effective as 10-day sequential treatment in eradicating H. pylori infection and slightly less expensive.
Resistance to antibiotic drugs, particularly clarithromycin (Biaxin ®), is a major limitation in the treatment of Helicobacter pylori infection in some geographic regions. Consensus guidelines have suggested bismuth-based therapy in such regions (Gut 2007; 56:772), but that approach is often poorly tolerated by patients.
To compare the efficacy of two nonbismuth treatment regimens in eradicating H. pylori infection in a region with high clarithromycin resistance, investigators conducted a randomized, controlled, noninferiority trial involving 180 treatment-naive patients with H. pylori infection from two hospitals in Italy. Participants received a 5-day concomitant regimen of esomeprazole (40 mg), amoxicillin (1 g), levofloxacin (500 mg), and tinidazole (500 mg) twice daily or a 10-day sequential regimen of esomeprazole (40 mg) and amoxicillin (1 g) twice daily for 5 days, followed by esomeprazole (40 mg), levofloxacin (500 mg), and tinidazole (500 mg) twice daily for 5 days. Eradication status was assessed by a breath test after treatment ended.
Eradication rates were similar between the two groups (92.2% for concomitant therapy and 93.3% for sequential therapy). Incidence of adverse events did not differ between groups. Approximately half the patients in each group underwent endoscopic biopsies and antibiotic resistance testing. Antibiotic resistance patterns were similar between groups. Concomitant therapy cost $9 less per patient than sequential therapy.
Comment: The authors conclude that 5-day, levofloxacin-based concomitant quadruple therapy is as effective as 10-day sequential therapy and less expensive for eradicating H. pylori infection in a region with high clarithromycin resistance. Antibiotic resistance to standard H. pylori eradication therapy is common and variable between regions. This resistance has made it difficult to find a therapy that achieves 95% eradication. The relative success of the 5-day, levofloxacin-based quadruple therapy is encouraging but may not be generalizable to other regions. Also, as with other antibiotics, resistance to levofloxacin could develop rapidly. As suggested by the authors, we may be better served by seeking alternative ways to eradicate H. pylori infection than by trying different antibiotic cocktails.
— David J. Bjorkman, MD, MSPH (HSA), SM (Epid.) Published in Journal Watch Gastroenterology June 29, 2012
Citation(s): Federico A et al. Efficacy of 5-day levofloxacin-containing concomitant therapy in eradication of Helicobacter pylori infection. Gastroenterology 2012 Jul; 143:55.
http://www.ncbi.nlm.nih.gov/pubmed/22484118?dopt=Abstract
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Aliment Pharmacol Ther Med 2012 Jul; 36:190
High-Dose PPI, Amoxicillin, and Metronidazole for Primary Treatment of H. pylori Infection?
In a multicenter study conducted in Spain, this regimen had a high cure rate and was well tolerated.
The standard treatment for Helicobacter pylori infection — triple therapy with a proton-pump inhibitor (PPI), clarithromycin (Biaxin ®), and either amoxicillin or metronidazole — is becoming less effective because of increasing clarithromycin resistance. Recommended alternative therapies have a variety of drawbacks. Investigators in Spain have suggested that the low eradication rates seen in earlier studies of metronidazole and amoxicillin could be explained by suboptimal dosing schedules, and that an appropriately dosed regimen might be successful in settings where clarithromycin resistance rates are high.
In a multicenter study involving 136 patients with documented H. pylori infection, these researchers used a strategy devised to sidestep clarithromycin resistance: 10 days of high-dose antibiotics (amoxicillin 1 g and metronidazole 500 mg, both 3 times daily) and very strong acid inhibition (esomeprazole 40 mg, twice daily), given with meals to increase adherence. Eradication was determined by urea breath test.
H. pylori was eradicated in 112 of the 127 patients who returned for follow-up, for an eradication rate of 88.2% (95% confidence interval, 81.2%–92.8%) in the per-protocol population and 82.4% (95% CI, 74.7%–88.1%) by intent-to-treat analysis. Eradication rates were similar among the eight study centers. The treatment was well tolerated.
Comment: This regimen involves proton-pump inhibitor and antibiotic doses higher than those used in previous trials. Although the eradication rate exceeded the 80% target mentioned by the investigators as the clinical goal, it didn't exceed it by much. The absence of a comparison group prevents us from concluding that the study regimen was any better than standard clarithromycin-based therapy in these patients. We also do not know the prevalence of metronidazole resistance in the study population. As the authors state, additional comparative trials will be necessary to understand the potential role of this regimen in the primary treatment of H. pylori infection.
— David J. Bjorkman, MD, MSPH (HSA), SM (Epid.) Published in Journal Watch Gastroenterology June 29, 2012
Citation(s): Sánchez-Delgado J et al. High-dose, ten-day esomeprazole, amoxicillin and metronidazole triple therapy achieves high Helicobacter pylori eradication rates. Aliment Pharmacol Ther 2012 Jul; 36:190.
http://www.ncbi.nlm.nih.gov/pubmed/22591220?dopt=Abstract
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Am J Gastroenterol 2012 May; 107:761
Frozen Stool for Fecal Transplant in Refractory C. difficile Infection
The rate of infection clearance was 70% with fresh material from patient-selected donors and 90% with frozen material from standard donors.
The use of fecal transplantation for refractory Clostridium difficile infection is increasing. Two of the most difficult aspects of the transplantation process — aside from the obvious aesthetic concerns — can be identifying a donor and obtaining reimbursement for the tests needed to evaluate the donor for infection. To solve these problems, some centers have moved toward use of frozen fecal extracts from rigorously screened "universal" donors. Investigators in Minnesota recently reported one center's initial experience with this new process.
Forty-three consecutive adults with recurrent C. difficile infection were included in the study — 10 who received fresh material from patient-selected donors, 12 who received fresh material from standard donors, and 21 who received frozen material from standard donors. Rates of infection clearance (defined as resolution of diarrhea and negative stool-test results 2 months postprocedure) were 70%, 92%, and 90%, respectively, after a single infusion of donor fecal material.
Comment: These results suggest that referral centers should establish banks of frozen processed fecal material from standard donors. This practice should substantially simplify the fecal transplantation process for refractory C. difficile infection.
— Douglas K. Rex, MD Published in Journal Watch Gastroenterology June 29, 2012
Citation(s): Hamilton MJ et al. Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. Am J Gastroenterol 2012 May; 107:761.
http://www.ncbi.nlm.nih.gov/pubmed/22290405?dopt=Abstract
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Pediatrics 2012 Jun; 129:1134.
Cow, Soy, or Breast Milk: Does It Make a Difference in Developmental Outcome?
In this observational study, only breast-fed infants had a slight advantage.
Infants fed soy-protein formula and cow's milk formula have similar patterns of physical growth, but no studies have compared developmental status in infants fed soy formula, cow's milk formula, or breast milk. In an observational study, researchers compared developmental status in 391 healthy full-term infants without prenatal or perinatal complications who were being fed cow's milk formula (131), soy formula (129) or breast milk (131) when recruited at age 1 to 2 months. Infants who changed formula after 2 to 12 months or who were supplemented with solid food before age 4 months were excluded. Half the infants who breast-fed continued to do so until age 12 months, the other half changed to milk formula, and all infants in the formula-fed groups did not change feeding group.
Assessments at ages 3, 6, 9, and 12 months indicated similar scores for both formula-fed groups on the Bayley Scales of Infant Development and the Preschool Language Scale. Breast-fed infants had slightly but significantly higher scores than both formula-fed infant groups on the Mental Developmental Index at ages 6 and 12 months. Breast-fed infants also had slightly higher psychomotor scores than soy-fed infants at 6 months and slightly higher language scores than cow's milk–fed infants at 3 and 6 months.
Comment: These findings should be interpreted with caution because the study was not randomized, and although some findings were statistically significant, the differences between feeding groups were small and all scores were within the normal range. It's reassuring that mental, psychomotor, and language development during the first year was similar in soy- and milk-formula–fed infants. The slight developmental advantage found in breast-fed infants is similar to results from previous studies.
— Martin T. Stein, MD Published in Journal Watch Pediatrics and Adolescent Medicine June 20, 2012
Citation(s):Andres A et al. Developmental status of 1-year-old infants fed breast milk, cow's milk formula, or soy formula. Pediatrics 2012 Jun; 129:1134.
http://www.ncbi.nlm.nih.gov/pubmed/22641754?dopt=Abstract
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FDA Causes Cancer Drug Shortages
One of the most serious problems in American health care today is a catastrophic shortage of supply for dozens of important generic drugs, especially oncology drugs. Because of the shortages, many cancer patients today are unable to gain access to basic, life-extending drugs. The House Oversight Committee has released an in-depth report, alleging that a significant cause of this shortage is an out-of-control regulatory smackdown, initiated by FDA Commissioner Margaret Hamburg.
The report details the dramatic drop in the production of generic injectable drugs since Hamburg was confirmed as FDA chief in May 2009. Upon taking office, Hamburg promised an aggressive effort to enforce the FDA's stringent manufacturing standards. In 2010, Hamburg's officials issued 673 warning letters to drugmakers and other companies: a 42 percent increase from 2009. In 2011, the agency issued 1,720 warning letters: a further increase of 156 percent.
http://www.forbes.com/sites/aroy/2012/06/15/how-margaret-hamburgs-fda-causes-cancer-drug-shortages/
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MM: We keep trying to solve the question of why is breast feeding superior to other feeding forms for child development. It’s not limited to the components of the milk that are beneficial but the tenderness, closeness, feelings of security and other psychological aspects of skin to skin touch, pheromones, etc. that are encountered as well. We can continue to strive for a better product and to develop formula for those children who do not have the benefit of a mother who can’t physically nurse and nurture them but we should not discourage the action of breast feeding as it has repeatedly demonstrated so many wide ranging benefits beyond the nutritional aspect.
Pediatrics 2012 Jun; 129:1141
Supplementing Formula with Polyunsaturated Fatty Acids (DHA/Omega 3 & 6) Does Not Enhance Infant Cognition
A meta-analysis of randomized trials found no significant benefit of supplementation on infant cognition at 1 year.
Studies show that breast-fed infants score a few points higher on measures of cognitive development than formula-fed infants. As a result, long-chain polyunsaturated fatty acids (LCPUFAs) were added to infant formulas because they were thought to account for the benefit of breast milk on cognition. To determine whether the addition of specific fatty acids enhances cognition in formula-fed infants, researchers reviewed 12 high-quality randomized, controlled trials (involving 1802 infants) that compared cognition in infants fed formula supplemented with LCPUFAs and those fed formula without supplementation within 1 month after birth. Each study used the Bayley Scales of Infant Development to evaluate cognition at ages 8 to 16 months.
Nine studies showed no effect of LCPUFA supplementation on cognition, two studies showed a significant benefit of supplementation on cognition, and one study showed a benefit on some, but not all, Bayley subscales. Meta-analysis of the 12 trials showed no significant difference in infant development scores between infants fed supplemented and unsupplemented formula. Secondary analyses also showed no significant effects based on LCPUFA dose or in preterm versus term infants.
Comment: This meta-analysis demonstrates the unexpected results of an intervention that was initiated before suitable efficacy studies were conducted. The rationale for supplementing infant formula with LCPUFAs was based on the hypothesis that it accounted for the putative benefit of breast milk on cognition. But the authors wisely note that in addition to the unique antimicrobial, anti-inflammatory, and immunologic characteristics of breast milk, nursing is also associated with enhanced maternal–child bonding. Compared with formula-fed infants, breast-fed infants are more alert during social interactions and receive more affectionate touching from their mothers — two important factors in early bonding and brain maturation.
— Martin T. Stein, MD Published in Journal Watch Pediatrics and Adolescent Medicine June 27, 2012
Citation(s): Qawasmi A et al. Meta-analysis of long-chain polyunsaturated fatty acid supplementation of formula and infant cognition. Pediatrics 2012 Jun; 129:1141.
(http://dx.doi.org/10.1542/peds.2011-2127)
http://www.ncbi.nlm.nih.gov/pubmed/22641753?dopt=Abstract
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MM: Although I am not a huge fan of NSAIDs for general use, this is an especially poignant article when we consider the wildfires that are raging in Colorado at the present time and the increased demand for volunteers from around the country and around the world who are assisting the efforts to control these fires. Many of these volunteers could potentially benefit from this pre-treatment.
Ann Emerg Med 2012 Jun; 59:484
Ibuprofen Reduces the Severity of Acute Mountain Sickness
. . . and is likely as effective as acetazolamide or dexamethasone.
Researchers randomized 86 healthy nonacclimated adult volunteers to receive oral ibuprofen (600 mg) or placebo every 6 hours, beginning 6 hours before rapidly ascending from an altitude of 4100 feet to 12,570 feet in California. Outcome measures were incidence and severity of acute mountain sickness on the validated, self-reported, symptom-based Lake Louise Questionnaire. Acute mountain sickness was defined as a symptom score of >3 with headache and one other symptom.
Significantly fewer volunteers in the ibuprofen group than in the placebo group developed acute mountain sickness (43% vs. 69%; number needed to treat, 3.9). Among volunteers who developed mountain sickness, symptom severity was lower in the ibuprofen group, although the difference was not statistically significant.
Comment: The efficacy of prophylactic ibuprofen is similar to that of traditional altitude sickness prophylaxis with acetazolamide and dexamethasone. Given the more favorable safety profile of ibuprofen compared with acetazolamide and dexamethasone, ibuprofen seems to be the obvious choice until a head-to-head comparison demonstrates that one is clearly better.
— Richard D. Zane, MD, FAAEM Published in Journal Watch Emergency Medicine June 22, 2012
Citation(s):Lipman GS et al. Ibuprofen prevents altitude illness: A randomized controlled trial for prevention of altitude illness with nonsteroidal anti-inflammatories. Ann Emerg Med 2012 Jun; 59:484.
http://www.ncbi.nlm.nih.gov/pubmed/22440488?dopt=Abstract
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MM: We should try to live a life that is positive and preventative but what should we do when a problem arise? Here is a real-life answer to that question. If a person has lan hepatic/liver disease, it appears that fish high in omega 3 fatty acids may be beneficial.
Gastroenterology 2012 Feb 16
Eating Certain Fish Might Prevent Liver Cancer
In a large prospective study in Japan, higher consumption of fish with n-3 polyunsaturated fatty acids translated to lower risk for hepatocellular carcinoma.
Dietary n-3 polyunsaturated fatty acids (PUFAs) have been demonstrated to protect against several cancers. However, their protective benefit against hepatocellular carcinoma (HCC) has been inconsistent in the mostly retrospective studies conducted.
To investigate the association between fish and n-3 PUFA consumption and HCC, researchers analyzed data from a large-scale, population-based, prospective cohort study involving 90,296 people in Japan (aged 45–74). A validated food intake questionnaire — including items on fish rich in n-3 PUFAs (salmon or trout, sea bream, horse mackerel or sardine, mackerel pike or mackerel, and eel) — was completed at baseline by 84% of the cohort. Only 0.4% of subjects were lost to follow-up. During an average follow-up of 11.2 years (1,008,595 person-years), 398 cases of HCC were newly diagnosed.
Total fish consumption was not significantly associated with lower risk for HCC. However, in multivariate analysis, consumption of n-3 PUFA-rich fish showed a dose-dependent, inverse association with risk for HCC (hazard ratio, 0.64; P for trend=0.04). Similar dose-dependent, inverse associations with HCC were demonstrated for consumption of the individual n-3 PUFAs eicosapentaenoic acid (HR, 0.56; P for trend=0.01), docosapentaenoic acid (HR, 0.64; P for trend=0.05), and docosahexaenoic acid (HR, 0.56; P for trend=0.03). These associations remained in a subgroup analysis of 17,500 participants with data on hepatitis C and B viruses.
Comment: In this large, population-based cohort study, consumption of fish rich in n-3 polyunsaturated fatty acids reduced the risk for hepatocellular carcinoma, perhaps through anti-inflammatory effects or improvement in insulin sensitivity. These results should be confirmed in other settings and with more robust dietary information (not just that collected at baseline), but it is reasonable to advocate a diet rich in n-3 PUFA — especially for patients with cirrhosis who are at high risk for HCC.
— Atif Zaman, MD, MPH Published in Journal Watch Gastroenterology May 11, 2012
Citation(s) :Sawada N et al. Consumption of n-3 fatty acids and fish reduces risk of hepatocellular carcinoma. Gastroenterology 2012 Feb 16; [e-pub ahead of print]. (http://dx.doi.org/10.1053/j.gastro.2012.02.018)
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