Tuesday, November 30, 2010
apnea apneu bloeddruk
Hi, I'm Dr. Henry Black. I'm Clinical Professor of Internal Medicine at the New York University School of Medicine, Immediate Past President of the American Society of Hypertension, and a member of the Center for the Prevention of Cardiovascular Disease at New York University. Today I want to talk about obstructive sleep apnea. This is an issue that has become more and more important as we realized how common it is and how it complicates a lot of our antihypertensive therapy, especially with resistant hypertension where we pile on drugs and don't seem to get to goal.
Some estimate that 70%-83% of people with resistant hypertension have obstructive sleep apnea as defined by the apnea-hypopnea index -- generally over 5, but usually much more than that. It is defined as apnea for at least 10 seconds with no flow or hypopnea for 10 seconds with reduced flow, with a reduced oxygen saturation of about 3%. This has been associated with obesity, but not everybody with sleep apnea is obese. You can usually figure it out clinically when people report snoring or daytime sleepiness. This seems to be a much more common issue than we realized, and it's likely to get even more common as we go along.
The treatments for obstructive sleep apnea are disappointing. The thing that seems to work best at lowering blood pressure is continuous positive airway pressure (CPAP). Many patients, even with the newer machines that are much easier to use, have trouble tolerating CPAP even though they feel better when they do it. They're not sleepy all day and don't snore as much, but you have to lie on your back, and not everybody can sleep that way. Is this really good for blood pressure? This was recently studied in a Spanish study[1] of about 35 people who got conventional therapy and 35 who got CPAP. The study lasted 3 months. Ambulatory blood pressure monitoring (ABPM) was done at the beginning and at the end. What you get is a sense of a dose response, because you look at how many hours the CPAP was used and what the results were in the apnea-hypopnea index.
Like any therapy, not everybody can tolerate it. Only 20 of the 29 people who were in the CPAP group were able to complete the study. The comparison group received conventional therapy. These were truly resistant hypertensive patients. Most were on 3 drugs, some were on 4, some were on 5, and they weren't at goal blood pressure. We can accept that as an appropriate cohort. About 37 people were randomized to conventional therapy with no sham-CPAP. Some of us would say that if you don't put something on, maybe it's not really a control group. Of those who were randomized to CPAP (originally 37), 9 of them wouldn't even accept it or couldn't tolerate it, and there was 1 that was lost to follow-up. Of the 29 people who were in the CPAP group, 20 were bona fide resistant hypertensive patients when you used ambulatory monitoring. The other 9 weren't.
At the end of 3 months, they repeated the ABPM study and found something quite interesting. Overall, there really was no benefit in blood pressure to CPAP unless you used it long enough. The median time of CPAP use was about 5.5 hours. Those who were above the median had a substantial drop in blood pressure, both on ABPM and in the office, but those who didn't use it as much did not. Like any drug, there's a dose response. There are adverse reactions, but this looks like a potentially promising therapy for resistant hypertension, although by no means is this the definite answer. We have to look further into this and maybe try to develop some better therapies. The best is probably to try to prevent the obesity that is so often related to obstructive sleep apnea. Thank you very much.
vitamine D
US Pharmacists 11-11-2010 vitamine D supplementation: an update
Abstract and Introduction
Introduction
An estimated 1 billion people worldwide, across all ethnicities and age groups, have a vitamin D deficiency.[1–3] This is mostly attributable to people getting less sun exposure because of climate, lifestyle, and concerns about skin cancer. The 1997 Dietary Reference Intake (DRI) values for vitamin D, initially established to prevent rickets and osteomalacia, are considered too low by many experts.[4] DRI values are 200 IU for infants, children, adults up to age 50 years, and pregnant and lactating women; 400 IU for adults aged 50 to 70 years; and 600 IU for adults older than 70 years. Current studies suggest that we may need more vitamin D than presently recommended to prevent chronic disease. Emerging research supports the possible role of vitamin D in protecting against cancer, heart disease, fractures and falls, autoimmune diseases, influenza, type 2 diabetes, and depression. Many health care providers have increased their recommendations for vitamin D supplementation to at least 1,000 IU.[5] As a result, more patients are asking their pharmacists about supplementing with vitamin D.
Saturday, November 20, 2010
blood pressure
Summary and Comment
New Perspectives on an Old Problem: Tailoring Treatment for Hypertension
Three studies lay the groundwork for moving beyond a "cookbook" approach to drug therapy.
Despite the availability of several antihypertensive drug classes and numerous individual agents, hypertension remains poorly controlled in many patients. Improving control rates will require tailoring of therapy to individual patient factors. In a recent issue of the American Journal of Hypertension, three studies address the heterogeneity of response to various antihypertensive drugs, and two editorialists use the findings to propose novel treatment paradigms.
Two studies highlight inter-individual responses to treatment. Turner and colleagues found that measures of plasma renin activity (PRA) predicted patient responses to atenolol or hydrochlorothiazide, both as monotherapy and as add-on therapy, independently of patient age, race, and pretreatment blood pressure (BP). Alderman and colleagues assessed the frequency of paradoxical pressor responses (BP increases ≥10 mm Hg) in patients during initial monotherapy with various antihypertensive drugs. Patients were stratified by tertile of baseline PRA. Pressor responses occurred with all drug classes. The likelihood of a pressor response was significantly higher with an angiotensin-converting enzyme (ACE) inhibitor or beta-blocker than with a diuretic or calcium-channel blocker, but only in patients in the low and middle PRA tertiles.
In a third study, researchers compared responses of white, black, and south Asian ASCOT participants randomized to initial therapy with atenolol or amlodipine; if needed, patients subsequently received a thiazide diuretic (added to atenolol) or perindopril (added to amlodipine). Atenolol monotherapy was significantly less effective in blacks than in whites and south Asians. The addition of perindopril to amlodipine was also significantly less effective in blacks than in whites and south Asians, whereas the addition of a diuretic to atenolol was not associated with any significant difference in response among the three groups.
In separate editorials, Brown and Furberg outlined different strategies for individualizing the care of patients with hypertension. Brown's approach begins by assessing the individual's probable location on the spectrum of hypertension pathophysiology (volume overload to vasoconstriction), whereas Furberg's approach begins by categorizing the hypertension as one of four types, based largely on PRA measurement. For a more detailed description of these two strategies, see JW Cardiol Nov 3 2010.
Comment: Current treatment guidelines make no real distinction between different types of hypertension pathophysiology. This "one size fits all" approach to hypertension therapy probably leads to an overuse of drugs and has been associated with poor outcomes. By sharpening our focus on the clinical predictors of response to various drugs, the present studies bring us closer to tailored approaches to hypertension management. The algorithms proposed by editorialists are intriguing, but we cannot know whether they will improve control rates — and, more important, patient outcomes — without careful clinical testing.
— JoAnne M. Foody, MD
Published in Journal Watch Cardiology November 3, 2010
New Perspectives on an Old Problem: Tailoring Treatment for Hypertension
Three studies lay the groundwork for moving beyond a "cookbook" approach to drug therapy.
Despite the availability of several antihypertensive drug classes and numerous individual agents, hypertension remains poorly controlled in many patients. Improving control rates will require tailoring of therapy to individual patient factors. In a recent issue of the American Journal of Hypertension, three studies address the heterogeneity of response to various antihypertensive drugs, and two editorialists use the findings to propose novel treatment paradigms.
Two studies highlight inter-individual responses to treatment. Turner and colleagues found that measures of plasma renin activity (PRA) predicted patient responses to atenolol or hydrochlorothiazide, both as monotherapy and as add-on therapy, independently of patient age, race, and pretreatment blood pressure (BP). Alderman and colleagues assessed the frequency of paradoxical pressor responses (BP increases ≥10 mm Hg) in patients during initial monotherapy with various antihypertensive drugs. Patients were stratified by tertile of baseline PRA. Pressor responses occurred with all drug classes. The likelihood of a pressor response was significantly higher with an angiotensin-converting enzyme (ACE) inhibitor or beta-blocker than with a diuretic or calcium-channel blocker, but only in patients in the low and middle PRA tertiles.
In a third study, researchers compared responses of white, black, and south Asian ASCOT participants randomized to initial therapy with atenolol or amlodipine; if needed, patients subsequently received a thiazide diuretic (added to atenolol) or perindopril (added to amlodipine). Atenolol monotherapy was significantly less effective in blacks than in whites and south Asians. The addition of perindopril to amlodipine was also significantly less effective in blacks than in whites and south Asians, whereas the addition of a diuretic to atenolol was not associated with any significant difference in response among the three groups.
In separate editorials, Brown and Furberg outlined different strategies for individualizing the care of patients with hypertension. Brown's approach begins by assessing the individual's probable location on the spectrum of hypertension pathophysiology (volume overload to vasoconstriction), whereas Furberg's approach begins by categorizing the hypertension as one of four types, based largely on PRA measurement. For a more detailed description of these two strategies, see JW Cardiol Nov 3 2010.
Comment: Current treatment guidelines make no real distinction between different types of hypertension pathophysiology. This "one size fits all" approach to hypertension therapy probably leads to an overuse of drugs and has been associated with poor outcomes. By sharpening our focus on the clinical predictors of response to various drugs, the present studies bring us closer to tailored approaches to hypertension management. The algorithms proposed by editorialists are intriguing, but we cannot know whether they will improve control rates — and, more important, patient outcomes — without careful clinical testing.
— JoAnne M. Foody, MD
Published in Journal Watch Cardiology November 3, 2010
depression
By David Douglas
NEW YORK (Reuters Health) Nov 15 - A small preliminary study suggests that use of omega-3 fatty acids for major depressive disorder and hot flashes in women during the menopausal transition is worth pursuing.
Dr. Marlene P. Freeman told Reuters Health by email, "We are excited about the possibility of using a non-hormonal low-risk intervention to treat mood and related symptoms associated with the menopausal transition."
She added, "The widespread use of nutritional and other complementary and alternative treatments necessitates rigorous study of these interventions to make sure that individuals receive appropriate and safe medical care."
In a November 27th online paper in Menopause, Dr. Freeman of Massachusetts General Hospital, Boston, and colleagues note that they studied 20 women. Following a single-blind placebo lead-in, the patients received 3 open-label omega-3 fatty acid capsules daily (eicosapentaenoic acid and docosahexaenoic acid, 2 g).
All but one patient completed the 8-week study. The Montgomery-Asberg Depression Rating Scale (MADRS) score fell from 24.2 at baseline to 10.7. In all, 70% of women showed a MADRS score reduction of at least 50%. In total, 45% were deemed to be in remission with a final MADRS score of 7 or less.
Both eicosapentaenoic acid and docosahexaenoic acid levels rose during the trial and responders had significantly lower pretreatment docosahexaenoic acid levels than nonresponders.
Fifteen of the women (75%) had experienced hot flashes at baseline. Their 24-hour hot flash scores fell from a mean of 9.0 to 2.5 at the end of treatment. Women who showed an improvement in depression were more likely to experience hot flash reduction.
Given the potential risks of hormone therapy and antidepressives, the researchers conclude that "larger controlled trials are justified to more definitively assess the role of omega-3 fatty acids in the treatment of major depressive disorder in women during the menopausal transition."
Menopause. Posted online November 27, 2010. Abstract
NEW YORK (Reuters Health) Nov 15 - A small preliminary study suggests that use of omega-3 fatty acids for major depressive disorder and hot flashes in women during the menopausal transition is worth pursuing.
Dr. Marlene P. Freeman told Reuters Health by email, "We are excited about the possibility of using a non-hormonal low-risk intervention to treat mood and related symptoms associated with the menopausal transition."
She added, "The widespread use of nutritional and other complementary and alternative treatments necessitates rigorous study of these interventions to make sure that individuals receive appropriate and safe medical care."
In a November 27th online paper in Menopause, Dr. Freeman of Massachusetts General Hospital, Boston, and colleagues note that they studied 20 women. Following a single-blind placebo lead-in, the patients received 3 open-label omega-3 fatty acid capsules daily (eicosapentaenoic acid and docosahexaenoic acid, 2 g).
All but one patient completed the 8-week study. The Montgomery-Asberg Depression Rating Scale (MADRS) score fell from 24.2 at baseline to 10.7. In all, 70% of women showed a MADRS score reduction of at least 50%. In total, 45% were deemed to be in remission with a final MADRS score of 7 or less.
Both eicosapentaenoic acid and docosahexaenoic acid levels rose during the trial and responders had significantly lower pretreatment docosahexaenoic acid levels than nonresponders.
Fifteen of the women (75%) had experienced hot flashes at baseline. Their 24-hour hot flash scores fell from a mean of 9.0 to 2.5 at the end of treatment. Women who showed an improvement in depression were more likely to experience hot flash reduction.
Given the potential risks of hormone therapy and antidepressives, the researchers conclude that "larger controlled trials are justified to more definitively assess the role of omega-3 fatty acids in the treatment of major depressive disorder in women during the menopausal transition."
Menopause. Posted online November 27, 2010. Abstract
Thursday, November 18, 2010
AF atrial fibrilation
4.
Omega-3 Fatty Acids and Atrial Fibrillation
In a short-term, randomized, controlled trial, a prescription-strength fish oil supplement failed to prevent AF recurrence.
Because fish oil has been shown to have direct electrophysiologic effects on the cell membrane as well as anti-inflammatory and autonomic-modulating properties, many clinicians are convinced of its efficacy in treating atrial fibrillation (AF), despite mixed findings from various studies. In a manufacturer-sponsored, randomized, control trial, 584 patients with paroxysmal (n=479) or persistent (n=105) AF received either 4 g/day of a prescription formulation of omega-3 fatty acids or placebo. At baseline, no participants were taking antiarrhythmic drugs, and all were free of structural heart disease and in normal sinus rhythm.
During 24 weeks of follow-up, symptomatic AF recurred in 46% of patients in the placebo group and in 52% of those in the omega-3 group, a nonsignificant difference. The results were consistent in both the paroxysmal and persistent subgroups. Compared with the placebo group, the omega-3 group had significantly greater on-treatment reductions in mean triglyceride level and systolic blood pressure and in median hemoglobin A1C level.
Comment: Herbal and dietary supplements are rarely tested in randomized controlled trials, largely because of a lack of industry funding. In this well-designed and -managed trial, fish oil did not prevent AF during a relatively short follow-up. However, any beneficial effects of fish oils likely require much longer than 6 months of administration, and indeed the physiologic outcomes suggest a potential benefit. Nonetheless, in the absence of larger, longer-term trial results, adding another prescription medication to the daily regimen of patients with AF is difficult to justify.
— Mark S. Link, MD
Published in Journal Watch Cardiology November 15, 2010
Omega-3 Fatty Acids and Atrial Fibrillation
In a short-term, randomized, controlled trial, a prescription-strength fish oil supplement failed to prevent AF recurrence.
Because fish oil has been shown to have direct electrophysiologic effects on the cell membrane as well as anti-inflammatory and autonomic-modulating properties, many clinicians are convinced of its efficacy in treating atrial fibrillation (AF), despite mixed findings from various studies. In a manufacturer-sponsored, randomized, control trial, 584 patients with paroxysmal (n=479) or persistent (n=105) AF received either 4 g/day of a prescription formulation of omega-3 fatty acids or placebo. At baseline, no participants were taking antiarrhythmic drugs, and all were free of structural heart disease and in normal sinus rhythm.
During 24 weeks of follow-up, symptomatic AF recurred in 46% of patients in the placebo group and in 52% of those in the omega-3 group, a nonsignificant difference. The results were consistent in both the paroxysmal and persistent subgroups. Compared with the placebo group, the omega-3 group had significantly greater on-treatment reductions in mean triglyceride level and systolic blood pressure and in median hemoglobin A1C level.
Comment: Herbal and dietary supplements are rarely tested in randomized controlled trials, largely because of a lack of industry funding. In this well-designed and -managed trial, fish oil did not prevent AF during a relatively short follow-up. However, any beneficial effects of fish oils likely require much longer than 6 months of administration, and indeed the physiologic outcomes suggest a potential benefit. Nonetheless, in the absence of larger, longer-term trial results, adding another prescription medication to the daily regimen of patients with AF is difficult to justify.
— Mark S. Link, MD
Published in Journal Watch Cardiology November 15, 2010
Wednesday, November 17, 2010
vitamine D
Introduction
An estimated 1 billion people worldwide, across all ethnicities and age groups, have a vitamin D deficiency.[1–3] This is mostly attributable to people getting less sun exposure because of climate, lifestyle, and concerns about skin cancer. The 1997 Dietary Reference Intake (DRI) values for vitamin D, initially established to prevent rickets and osteomalacia, are considered too low by many experts.[4] DRI values are 200 IU for infants, children, adults up to age 50 years, and pregnant and lactating women; 400 IU for adults aged 50 to 70 years; and 600 IU for adults older than 70 years. Current studies suggest that we may need more vitamin D than presently recommended to prevent chronic disease. Emerging research supports the possible role of vitamin D in protecting against cancer, heart disease, fractures and falls, autoimmune diseases, influenza, type 2 diabetes, and depression. Many health care providers have increased their recommendations for vitamin D supplementation to at least 1,000 IU.[5] As a result, more patients are asking their pharmacists about supplementing with vitamin D.
An estimated 1 billion people worldwide, across all ethnicities and age groups, have a vitamin D deficiency.[1–3] This is mostly attributable to people getting less sun exposure because of climate, lifestyle, and concerns about skin cancer. The 1997 Dietary Reference Intake (DRI) values for vitamin D, initially established to prevent rickets and osteomalacia, are considered too low by many experts.[4] DRI values are 200 IU for infants, children, adults up to age 50 years, and pregnant and lactating women; 400 IU for adults aged 50 to 70 years; and 600 IU for adults older than 70 years. Current studies suggest that we may need more vitamin D than presently recommended to prevent chronic disease. Emerging research supports the possible role of vitamin D in protecting against cancer, heart disease, fractures and falls, autoimmune diseases, influenza, type 2 diabetes, and depression. Many health care providers have increased their recommendations for vitamin D supplementation to at least 1,000 IU.[5] As a result, more patients are asking their pharmacists about supplementing with vitamin D.
Saturday, November 13, 2010
PPI proton pump inhibitors
SUMMARY AND COMMENT
Pregabalin for Chronic Prostatitis/Pelvic Pain
October 14, 2010 | Thomas L. Schwenk, MD | General Medicine
Improvement, albeit modest, suggests a neuropathic mechanism.
Reviewing: Pontari MA et al. Arch Intern Med 2010 Sep 27; 170:1586
Free Full-Text Article
Summary and Comment
PPIs for Laryngopharyngeal Reflux?
A close look at findings from a randomized, placebo-controlled trial show that the proton-pump inhibitor rabeprazole provided benefit in treating gastroesophageal — but not laryngopharyngeal — symptoms.
Proton-pump inhibitors (PPIs) initially showed promise as a treatment for laryngopharyngeal reflux (LPR; JW Gastroenterol Aug 11 2006). However, small, randomized, placebo-controlled trials have not documented meaningful clinical benefit (e.g., Am J Gastroenterol 2006; 101:1972). Now, in a trial funded in part by the manufacturer of the PPI rabeprazole, researchers randomized 82 patients who had been referred to an ear, nose, and throat (ENT) center for clinical LPR to receive rabeprazole (20 mg twice daily) or placebo for 12 weeks.
Patients met these criteria: (1) ≥1 LPR symptom — hoarseness, globus, persistent throat discomfort, or frequent throat clearing — for ≥1 month during the preceding year; (2) evidence of LPR on video laryngostroboscopy (VLS), with a reflux finding score (RFS) >7; (3) absence of upper respiratory tract infection during the previous 4 weeks and absence of allergic causes for laryngitis; and (4) no use of acid-suppressive therapy during the previous 4 weeks.
All participants underwent manometry and 24-hour pH testing with a probe that had four pH sensors, spanning from a distal position 5 cm above the lower esophageal sphincter to a proximal placement just distal to the upper esophageal sphincter. LPR was documented if the pH for the proximal sensor registered <4.0 for >0.7% of total time, for >1.1% of time in the upright position, or for >0.5% of time in the supine position; gastroesophageal reflux disease (GERD) was documented for corresponding values of >4.6%, >7.0%, and >4.5%. A (blinded) laryngologist performed all ENT evaluations and assessed the VLS exams (intrarater reliability, 0.93). LPR symptoms were also assessed using a reflux symptom index (RSI) and sequential RFS scoring. Evaluations occurred during treatment and at 6 weeks after treatment ended (week 18).
The mean RSI score had improved significantly more with rabeprazole than with placebo at week 6 (P=0.003) and at week 12 (P=0.002), but not at week 18. The benefits of the drug at week 12 were significant improvements in the following: breathing difficulty or choking (P=0.009), troublesome cough (P=0.006), and sensation of something in the throat (P=0.007). RFS scores did not differ significantly between rabeprazole and placebo recipients.
Comment: At first glance, these data suggest that PPIs might be effective for treating LPR and challenge the present consensus that "silent GERD" should not be suspected. However, as an editorialist notes, the apparent positive effect on LPR was probably attributable to how outcomes were assessed. The on-treatment RSI improvements were in symptoms typical of GERD (which respond to PPI therapy), not in symptoms typical of chronic laryngitis. The lack of improvement on laryngeal examinations is consistent with findings from previous randomized trials. Clearly, laryngeal irritation on ENT examination is extremely nonspecific and, as a general rule, should not suggest a diagnosis of LPR, as it does to many of our ENT colleagues.
— David A. Johnson, MD
Published in Journal Watch Gastroenterology November 12, 2010
Pregabalin for Chronic Prostatitis/Pelvic Pain
October 14, 2010 | Thomas L. Schwenk, MD | General Medicine
Improvement, albeit modest, suggests a neuropathic mechanism.
Reviewing: Pontari MA et al. Arch Intern Med 2010 Sep 27; 170:1586
Free Full-Text Article
Summary and Comment
PPIs for Laryngopharyngeal Reflux?
A close look at findings from a randomized, placebo-controlled trial show that the proton-pump inhibitor rabeprazole provided benefit in treating gastroesophageal — but not laryngopharyngeal — symptoms.
Proton-pump inhibitors (PPIs) initially showed promise as a treatment for laryngopharyngeal reflux (LPR; JW Gastroenterol Aug 11 2006). However, small, randomized, placebo-controlled trials have not documented meaningful clinical benefit (e.g., Am J Gastroenterol 2006; 101:1972). Now, in a trial funded in part by the manufacturer of the PPI rabeprazole, researchers randomized 82 patients who had been referred to an ear, nose, and throat (ENT) center for clinical LPR to receive rabeprazole (20 mg twice daily) or placebo for 12 weeks.
Patients met these criteria: (1) ≥1 LPR symptom — hoarseness, globus, persistent throat discomfort, or frequent throat clearing — for ≥1 month during the preceding year; (2) evidence of LPR on video laryngostroboscopy (VLS), with a reflux finding score (RFS) >7; (3) absence of upper respiratory tract infection during the previous 4 weeks and absence of allergic causes for laryngitis; and (4) no use of acid-suppressive therapy during the previous 4 weeks.
All participants underwent manometry and 24-hour pH testing with a probe that had four pH sensors, spanning from a distal position 5 cm above the lower esophageal sphincter to a proximal placement just distal to the upper esophageal sphincter. LPR was documented if the pH for the proximal sensor registered <4.0 for >0.7% of total time, for >1.1% of time in the upright position, or for >0.5% of time in the supine position; gastroesophageal reflux disease (GERD) was documented for corresponding values of >4.6%, >7.0%, and >4.5%. A (blinded) laryngologist performed all ENT evaluations and assessed the VLS exams (intrarater reliability, 0.93). LPR symptoms were also assessed using a reflux symptom index (RSI) and sequential RFS scoring. Evaluations occurred during treatment and at 6 weeks after treatment ended (week 18).
The mean RSI score had improved significantly more with rabeprazole than with placebo at week 6 (P=0.003) and at week 12 (P=0.002), but not at week 18. The benefits of the drug at week 12 were significant improvements in the following: breathing difficulty or choking (P=0.009), troublesome cough (P=0.006), and sensation of something in the throat (P=0.007). RFS scores did not differ significantly between rabeprazole and placebo recipients.
Comment: At first glance, these data suggest that PPIs might be effective for treating LPR and challenge the present consensus that "silent GERD" should not be suspected. However, as an editorialist notes, the apparent positive effect on LPR was probably attributable to how outcomes were assessed. The on-treatment RSI improvements were in symptoms typical of GERD (which respond to PPI therapy), not in symptoms typical of chronic laryngitis. The lack of improvement on laryngeal examinations is consistent with findings from previous randomized trials. Clearly, laryngeal irritation on ENT examination is extremely nonspecific and, as a general rule, should not suggest a diagnosis of LPR, as it does to many of our ENT colleagues.
— David A. Johnson, MD
Published in Journal Watch Gastroenterology November 12, 2010
Friday, November 12, 2010
Omega 3 dementia
From Medscape Medical News > Psychiatry
DHA Supplementation Improves Memory, Cognitive Function in Elderly
Fran Lowry
November 11, 2010 — Supplementation with docosahexaenoic acid (DHA) in older adults who have mild cognitive impairment may improve memory and cognitive function, a randomized controlled trial suggests.
According to the results of the Memory Improvement with Docosahexaenoic Acid Study trial, 900 mg/day DHA given for 24 weeks improved learning and memory function in healthy elderly adults with age-related cognitive decline.
The study, which was funded by Martek Biosciences Corporation, in Columbia, Maryland, manufacturer of the DHA, was initially presented at the Alzheimer's Association International Conference on Alzheimer's Disease in July 2009 in Vienna and reported by Medscape Medical News at that time. It is published in the November issue of Alzheimer's & Dementia.
"There is a good amount of literature out there about the potential health benefits of omega-3 fatty acids on the brain," Karin Yurko-Mauro, PhD, associate director of clinical research at Martek, told Medscape Medical News.
"Data from epidemiological studies show a correlation between omega-3 intake and reduced risk of dementia, and we had some data from work that was done with our DHA in animal models of Alzheimer's disease that showed improvement in behavioral memory tasks. All of this led us to try to look at what DHA supplementation would do in health elderly people."
The study included 485 patients aged 55 years and older enrolled from 19 centers in the United States and randomly assigned to receive 900 mg/day algal DHA or placebo for 24 weeks.
All participants had a subjective memory complaint and were found to have a mild memory deficit, but no dementia, as per objective tests. These tests included the Mini-Mental State Examination (baseline score > 26) and the Logical Memory subtest of the Wechsler Memory Scale (version III, 1997; baseline score >1 SD below younger adults).
3-Year Cognitive Improvement
The primary outcome measure was a change from baseline in CANTAB Paired Associate Learning (PAL), a visuospatial learning and episodic memory test.
A coprimary endpoint was change in CANTAB Pattern Recognition Memory (PRM), a test of visual pattern recognition, but after a preplanned interim analysis revealed that this endpoint did not meet the conditional power threshold of 30%, it was changed to a secondary endpoint, the study authors said.
Other secondary endpoints were CANTAB Verbal Recognition Memory, a test of immediate and delayed verbal memory; CANTAB Stockings of Cambridge, a test of executive function; and CANTAB Spatial Working Memory, a test of spatial retention and search strategy.
After 24 weeks, the researchers found that participants taking DHA supplements made significantly fewer errors on the PAL test. The mean change from baseline in the PAL score was −4.5 in the DHA group compared with −2.4 for the placebo group (P = .032). However, the mean change in the PRM score was −0.9 in both the DHA and placebo groups (P = .573).
DHA supplementation was also associated with improved immediate and delayed Verbal Recognition Memory scores (P < .02), but not working memory or executive function tests.
Plasma phospholipid DHA levels doubled during the study in people taking the supplements and correlated with improved PAL scores (P < .02), and the supplement was well tolerated, with no reported treatment-related serious adverse events.
"With age, the older people are, the more errors they make on a test. But the improvements we saw on the test correlate to about a 3-year cognitive improvement," Dr. Yurko-Mauro said.
So somebody who was 73 was performing like a 70-year old. Our study does point to the fact that algal DHA can be beneficial for healthy aging adults who have a mild memory complaint.
"So somebody who was 73 was performing like a 70-year old. So our study does point to the fact that algal DHA can be beneficial for healthy aging adults who have a mild memory complaint."
"Modestly Encouraging"
Medscape Medical News asked Joseph Quinn, MD, from the Oregon Health and Science University and the Portland VA Medical Center, to comment on this study.
A recent study by Dr. Quinn and colleagues published in the November 3 issue of the Journal of the American Medical Association and reported by Medscape Medical News showed no positive effect of DHA supplementation on disease progression in Alzheimer's disease.
Dr. Quinn first disclosed that he is a coinventor on a patent filed by Martek for the use of DHA for non-E4 Alzheimer's disease (a form of Alzheimer's disease in carriers of the non-APOE4 allele), but that he has waived all royalties associated with the patent.
He then went on to state, "This study is modestly encouraging regarding the potential for DHA for prevention of late life cognitive decline. It is always very difficult to show cognitive benefits in healthy elderly, so that is a strength."
However, he took issue with the study authors' decision to demote their original coprimary endpoint of pattern recognition memory to a secondary endpoint.
"The test of this sort of study is whether the investigators found what they predicted they'd find in advance; in other words, the ultimate test is the ability to show efficacy on the prespecified outcome measures.
These findings represent a post hoc analysis, showing efficacy on just a few outcome measures out of a great many tested. As such, it is still a 'real' result, but weaker than if this was truly a prespecified analysis.
"As the authors disclose in the methods section, they modified their analysis plan midstream based on an interim analysis. This means that their findings represent a post hoc analysis, showing efficacy on just a few outcome measures out of a great many tested. As such, it is still a 'real' result, but weaker than if this was truly a prespecified analysis."
This study was supported by Martek Biosciences Corporation. Dr. Yurko-Mauro is an employee of Martek. Dr. Quinn reports being named as a coinventor on a patent for DHA for the treatment of Alzheimer's disease in APOE4-negative individuals and has waived his personal right to royalties related to this patent.
Alzheimers Dement. 2010;6:456-464. Abstract
DHA Supplementation Improves Memory, Cognitive Function in Elderly
Fran Lowry
November 11, 2010 — Supplementation with docosahexaenoic acid (DHA) in older adults who have mild cognitive impairment may improve memory and cognitive function, a randomized controlled trial suggests.
According to the results of the Memory Improvement with Docosahexaenoic Acid Study trial, 900 mg/day DHA given for 24 weeks improved learning and memory function in healthy elderly adults with age-related cognitive decline.
The study, which was funded by Martek Biosciences Corporation, in Columbia, Maryland, manufacturer of the DHA, was initially presented at the Alzheimer's Association International Conference on Alzheimer's Disease in July 2009 in Vienna and reported by Medscape Medical News at that time. It is published in the November issue of Alzheimer's & Dementia.
"There is a good amount of literature out there about the potential health benefits of omega-3 fatty acids on the brain," Karin Yurko-Mauro, PhD, associate director of clinical research at Martek, told Medscape Medical News.
"Data from epidemiological studies show a correlation between omega-3 intake and reduced risk of dementia, and we had some data from work that was done with our DHA in animal models of Alzheimer's disease that showed improvement in behavioral memory tasks. All of this led us to try to look at what DHA supplementation would do in health elderly people."
The study included 485 patients aged 55 years and older enrolled from 19 centers in the United States and randomly assigned to receive 900 mg/day algal DHA or placebo for 24 weeks.
All participants had a subjective memory complaint and were found to have a mild memory deficit, but no dementia, as per objective tests. These tests included the Mini-Mental State Examination (baseline score > 26) and the Logical Memory subtest of the Wechsler Memory Scale (version III, 1997; baseline score >1 SD below younger adults).
3-Year Cognitive Improvement
The primary outcome measure was a change from baseline in CANTAB Paired Associate Learning (PAL), a visuospatial learning and episodic memory test.
A coprimary endpoint was change in CANTAB Pattern Recognition Memory (PRM), a test of visual pattern recognition, but after a preplanned interim analysis revealed that this endpoint did not meet the conditional power threshold of 30%, it was changed to a secondary endpoint, the study authors said.
Other secondary endpoints were CANTAB Verbal Recognition Memory, a test of immediate and delayed verbal memory; CANTAB Stockings of Cambridge, a test of executive function; and CANTAB Spatial Working Memory, a test of spatial retention and search strategy.
After 24 weeks, the researchers found that participants taking DHA supplements made significantly fewer errors on the PAL test. The mean change from baseline in the PAL score was −4.5 in the DHA group compared with −2.4 for the placebo group (P = .032). However, the mean change in the PRM score was −0.9 in both the DHA and placebo groups (P = .573).
DHA supplementation was also associated with improved immediate and delayed Verbal Recognition Memory scores (P < .02), but not working memory or executive function tests.
Plasma phospholipid DHA levels doubled during the study in people taking the supplements and correlated with improved PAL scores (P < .02), and the supplement was well tolerated, with no reported treatment-related serious adverse events.
"With age, the older people are, the more errors they make on a test. But the improvements we saw on the test correlate to about a 3-year cognitive improvement," Dr. Yurko-Mauro said.
So somebody who was 73 was performing like a 70-year old. Our study does point to the fact that algal DHA can be beneficial for healthy aging adults who have a mild memory complaint.
"So somebody who was 73 was performing like a 70-year old. So our study does point to the fact that algal DHA can be beneficial for healthy aging adults who have a mild memory complaint."
"Modestly Encouraging"
Medscape Medical News asked Joseph Quinn, MD, from the Oregon Health and Science University and the Portland VA Medical Center, to comment on this study.
A recent study by Dr. Quinn and colleagues published in the November 3 issue of the Journal of the American Medical Association and reported by Medscape Medical News showed no positive effect of DHA supplementation on disease progression in Alzheimer's disease.
Dr. Quinn first disclosed that he is a coinventor on a patent filed by Martek for the use of DHA for non-E4 Alzheimer's disease (a form of Alzheimer's disease in carriers of the non-APOE4 allele), but that he has waived all royalties associated with the patent.
He then went on to state, "This study is modestly encouraging regarding the potential for DHA for prevention of late life cognitive decline. It is always very difficult to show cognitive benefits in healthy elderly, so that is a strength."
However, he took issue with the study authors' decision to demote their original coprimary endpoint of pattern recognition memory to a secondary endpoint.
"The test of this sort of study is whether the investigators found what they predicted they'd find in advance; in other words, the ultimate test is the ability to show efficacy on the prespecified outcome measures.
These findings represent a post hoc analysis, showing efficacy on just a few outcome measures out of a great many tested. As such, it is still a 'real' result, but weaker than if this was truly a prespecified analysis.
"As the authors disclose in the methods section, they modified their analysis plan midstream based on an interim analysis. This means that their findings represent a post hoc analysis, showing efficacy on just a few outcome measures out of a great many tested. As such, it is still a 'real' result, but weaker than if this was truly a prespecified analysis."
This study was supported by Martek Biosciences Corporation. Dr. Yurko-Mauro is an employee of Martek. Dr. Quinn reports being named as a coinventor on a patent for DHA for the treatment of Alzheimer's disease in APOE4-negative individuals and has waived his personal right to royalties related to this patent.
Alzheimers Dement. 2010;6:456-464. Abstract
From Medscape Medical News > Psychiatry
DHA Supplementation Improves Memory, Cognitive Function in Elderly
Fran Lowry
November 11, 2010 — Supplementation with docosahexaenoic acid (DHA) in older adults who have mild cognitive impairment may improve memory and cognitive function, a randomized controlled trial suggests.
According to the results of the Memory Improvement with Docosahexaenoic Acid Study trial, 900 mg/day DHA given for 24 weeks improved learning and memory function in healthy elderly adults with age-related cognitive decline.
The study, which was funded by Martek Biosciences Corporation, in Columbia, Maryland, manufacturer of the DHA, was initially presented at the Alzheimer's Association International Conference on Alzheimer's Disease in July 2009 in Vienna and reported by Medscape Medical News at that time. It is published in the November issue of Alzheimer's & Dementia.
"There is a good amount of literature out there about the potential health benefits of omega-3 fatty acids on the brain," Karin Yurko-Mauro, PhD, associate director of clinical research at Martek, told Medscape Medical News.
"Data from epidemiological studies show a correlation between omega-3 intake and reduced risk of dementia, and we had some data from work that was done with our DHA in animal models of Alzheimer's disease that showed improvement in behavioral memory tasks. All of this led us to try to look at what DHA supplementation would do in health elderly people."
The study included 485 patients aged 55 years and older enrolled from 19 centers in the United States and randomly assigned to receive 900 mg/day algal DHA or placebo for 24 weeks.
All participants had a subjective memory complaint and were found to have a mild memory deficit, but no dementia, as per objective tests. These tests included the Mini-Mental State Examination (baseline score > 26) and the Logical Memory subtest of the Wechsler Memory Scale (version III, 1997; baseline score >1 SD below younger adults).
3-Year Cognitive Improvement
The primary outcome measure was a change from baseline in CANTAB Paired Associate Learning (PAL), a visuospatial learning and episodic memory test.
A coprimary endpoint was change in CANTAB Pattern Recognition Memory (PRM), a test of visual pattern recognition, but after a preplanned interim analysis revealed that this endpoint did not meet the conditional power threshold of 30%, it was changed to a secondary endpoint, the study authors said.
Other secondary endpoints were CANTAB Verbal Recognition Memory, a test of immediate and delayed verbal memory; CANTAB Stockings of Cambridge, a test of executive function; and CANTAB Spatial Working Memory, a test of spatial retention and search strategy.
After 24 weeks, the researchers found that participants taking DHA supplements made significantly fewer errors on the PAL test. The mean change from baseline in the PAL score was −4.5 in the DHA group compared with −2.4 for the placebo group (P = .032). However, the mean change in the PRM score was −0.9 in both the DHA and placebo groups (P = .573).
DHA supplementation was also associated with improved immediate and delayed Verbal Recognition Memory scores (P < .02), but not working memory or executive function tests.
Plasma phospholipid DHA levels doubled during the study in people taking the supplements and correlated with improved PAL scores (P < .02), and the supplement was well tolerated, with no reported treatment-related serious adverse events.
"With age, the older people are, the more errors they make on a test. But the improvements we saw on the test correlate to about a 3-year cognitive improvement," Dr. Yurko-Mauro said.
So somebody who was 73 was performing like a 70-year old. Our study does point to the fact that algal DHA can be beneficial for healthy aging adults who have a mild memory complaint.
"So somebody who was 73 was performing like a 70-year old. So our study does point to the fact that algal DHA can be beneficial for healthy aging adults who have a mild memory complaint."
"Modestly Encouraging"
Medscape Medical News asked Joseph Quinn, MD, from the Oregon Health and Science University and the Portland VA Medical Center, to comment on this study.
A recent study by Dr. Quinn and colleagues published in the November 3 issue of the Journal of the American Medical Association and reported by Medscape Medical News showed no positive effect of DHA supplementation on disease progression in Alzheimer's disease.
Dr. Quinn first disclosed that he is a coinventor on a patent filed by Martek for the use of DHA for non-E4 Alzheimer's disease (a form of Alzheimer's disease in carriers of the non-APOE4 allele), but that he has waived all royalties associated with the patent.
He then went on to state, "This study is modestly encouraging regarding the potential for DHA for prevention of late life cognitive decline. It is always very difficult to show cognitive benefits in healthy elderly, so that is a strength."
However, he took issue with the study authors' decision to demote their original coprimary endpoint of pattern recognition memory to a secondary endpoint.
"The test of this sort of study is whether the investigators found what they predicted they'd find in advance; in other words, the ultimate test is the ability to show efficacy on the prespecified outcome measures.
These findings represent a post hoc analysis, showing efficacy on just a few outcome measures out of a great many tested. As such, it is still a 'real' result, but weaker than if this was truly a prespecified analysis.
"As the authors disclose in the methods section, they modified their analysis plan midstream based on an interim analysis. This means that their findings represent a post hoc analysis, showing efficacy on just a few outcome measures out of a great many tested. As such, it is still a 'real' result, but weaker than if this was truly a prespecified analysis."
This study was supported by Martek Biosciences Corporation. Dr. Yurko-Mauro is an employee of Martek. Dr. Quinn reports being named as a coinventor on a patent for DHA for the treatment of Alzheimer's disease in APOE4-negative individuals and has waived his personal right to royalties related to this patent.
Alzheimers Dement. 2010;6:456-464. Abstract
DHA Supplementation Improves Memory, Cognitive Function in Elderly
Fran Lowry
November 11, 2010 — Supplementation with docosahexaenoic acid (DHA) in older adults who have mild cognitive impairment may improve memory and cognitive function, a randomized controlled trial suggests.
According to the results of the Memory Improvement with Docosahexaenoic Acid Study trial, 900 mg/day DHA given for 24 weeks improved learning and memory function in healthy elderly adults with age-related cognitive decline.
The study, which was funded by Martek Biosciences Corporation, in Columbia, Maryland, manufacturer of the DHA, was initially presented at the Alzheimer's Association International Conference on Alzheimer's Disease in July 2009 in Vienna and reported by Medscape Medical News at that time. It is published in the November issue of Alzheimer's & Dementia.
"There is a good amount of literature out there about the potential health benefits of omega-3 fatty acids on the brain," Karin Yurko-Mauro, PhD, associate director of clinical research at Martek, told Medscape Medical News.
"Data from epidemiological studies show a correlation between omega-3 intake and reduced risk of dementia, and we had some data from work that was done with our DHA in animal models of Alzheimer's disease that showed improvement in behavioral memory tasks. All of this led us to try to look at what DHA supplementation would do in health elderly people."
The study included 485 patients aged 55 years and older enrolled from 19 centers in the United States and randomly assigned to receive 900 mg/day algal DHA or placebo for 24 weeks.
All participants had a subjective memory complaint and were found to have a mild memory deficit, but no dementia, as per objective tests. These tests included the Mini-Mental State Examination (baseline score > 26) and the Logical Memory subtest of the Wechsler Memory Scale (version III, 1997; baseline score >1 SD below younger adults).
3-Year Cognitive Improvement
The primary outcome measure was a change from baseline in CANTAB Paired Associate Learning (PAL), a visuospatial learning and episodic memory test.
A coprimary endpoint was change in CANTAB Pattern Recognition Memory (PRM), a test of visual pattern recognition, but after a preplanned interim analysis revealed that this endpoint did not meet the conditional power threshold of 30%, it was changed to a secondary endpoint, the study authors said.
Other secondary endpoints were CANTAB Verbal Recognition Memory, a test of immediate and delayed verbal memory; CANTAB Stockings of Cambridge, a test of executive function; and CANTAB Spatial Working Memory, a test of spatial retention and search strategy.
After 24 weeks, the researchers found that participants taking DHA supplements made significantly fewer errors on the PAL test. The mean change from baseline in the PAL score was −4.5 in the DHA group compared with −2.4 for the placebo group (P = .032). However, the mean change in the PRM score was −0.9 in both the DHA and placebo groups (P = .573).
DHA supplementation was also associated with improved immediate and delayed Verbal Recognition Memory scores (P < .02), but not working memory or executive function tests.
Plasma phospholipid DHA levels doubled during the study in people taking the supplements and correlated with improved PAL scores (P < .02), and the supplement was well tolerated, with no reported treatment-related serious adverse events.
"With age, the older people are, the more errors they make on a test. But the improvements we saw on the test correlate to about a 3-year cognitive improvement," Dr. Yurko-Mauro said.
So somebody who was 73 was performing like a 70-year old. Our study does point to the fact that algal DHA can be beneficial for healthy aging adults who have a mild memory complaint.
"So somebody who was 73 was performing like a 70-year old. So our study does point to the fact that algal DHA can be beneficial for healthy aging adults who have a mild memory complaint."
"Modestly Encouraging"
Medscape Medical News asked Joseph Quinn, MD, from the Oregon Health and Science University and the Portland VA Medical Center, to comment on this study.
A recent study by Dr. Quinn and colleagues published in the November 3 issue of the Journal of the American Medical Association and reported by Medscape Medical News showed no positive effect of DHA supplementation on disease progression in Alzheimer's disease.
Dr. Quinn first disclosed that he is a coinventor on a patent filed by Martek for the use of DHA for non-E4 Alzheimer's disease (a form of Alzheimer's disease in carriers of the non-APOE4 allele), but that he has waived all royalties associated with the patent.
He then went on to state, "This study is modestly encouraging regarding the potential for DHA for prevention of late life cognitive decline. It is always very difficult to show cognitive benefits in healthy elderly, so that is a strength."
However, he took issue with the study authors' decision to demote their original coprimary endpoint of pattern recognition memory to a secondary endpoint.
"The test of this sort of study is whether the investigators found what they predicted they'd find in advance; in other words, the ultimate test is the ability to show efficacy on the prespecified outcome measures.
These findings represent a post hoc analysis, showing efficacy on just a few outcome measures out of a great many tested. As such, it is still a 'real' result, but weaker than if this was truly a prespecified analysis.
"As the authors disclose in the methods section, they modified their analysis plan midstream based on an interim analysis. This means that their findings represent a post hoc analysis, showing efficacy on just a few outcome measures out of a great many tested. As such, it is still a 'real' result, but weaker than if this was truly a prespecified analysis."
This study was supported by Martek Biosciences Corporation. Dr. Yurko-Mauro is an employee of Martek. Dr. Quinn reports being named as a coinventor on a patent for DHA for the treatment of Alzheimer's disease in APOE4-negative individuals and has waived his personal right to royalties related to this patent.
Alzheimers Dement. 2010;6:456-464. Abstract
colon cancer statins
A Randomized Trial of Statins
A more definitive word about the effectiveness of statins in preventing colorectal growths will eventually come from a new randomized trial sponsored by the National Surgical Adjuvant Breast and Bowel Project (NSABP), suggested Scott Lippman, MD, who moderated the press conference at which Dr. Simon spoke.
Dr. Lippman is editor-in-chief of Cancer Prevention Research and professor and chair in the Department of Thoracic Head and Neck Medical Oncology at the University of Texas M.D. Anderson Cancer Center in Houston.
The NASBP trial, which is entitled Statin Polyp Prevention Trial in Patients With Resected Colon Cancer, is a phase 3 trial that compares the daily use of the statin rosuvastatin (Crestor, AstraZeneca) with placebo over 5 years in patients with recently resected stage I or II colon cancer.
"Our NSABP P-5 trial opened in late March of this year, and we have [institutional review board] approvals from more than 125 sites located throughout the United States and Canada," NSABP official, Larry Wickerman, MD, told Medscape Medical News.
Earlier this year at the AACR's annual meeting, a new study found that statins do not protect patients against colorectal adenomas, the benign growths that are precursors of colorectal cancer, and might even increase the risk of developing them when used for 3 years or more.
Those results were published in the May issue of Cancer Prevention Research (2010;3:588-596). In an editorial that accompanied the study (2010;3:573-575), a commentator said that there is "accumulating evidence that, at least overall, statins probably do not prevent colorectal neoplasia." However, there was a caveat in the editorial: "It is conceivable that there are benefits with high cumulative doses or in genetically defined subgroups."
A more definitive word about the effectiveness of statins in preventing colorectal growths will eventually come from a new randomized trial sponsored by the National Surgical Adjuvant Breast and Bowel Project (NSABP), suggested Scott Lippman, MD, who moderated the press conference at which Dr. Simon spoke.
Dr. Lippman is editor-in-chief of Cancer Prevention Research and professor and chair in the Department of Thoracic Head and Neck Medical Oncology at the University of Texas M.D. Anderson Cancer Center in Houston.
The NASBP trial, which is entitled Statin Polyp Prevention Trial in Patients With Resected Colon Cancer, is a phase 3 trial that compares the daily use of the statin rosuvastatin (Crestor, AstraZeneca) with placebo over 5 years in patients with recently resected stage I or II colon cancer.
"Our NSABP P-5 trial opened in late March of this year, and we have [institutional review board] approvals from more than 125 sites located throughout the United States and Canada," NSABP official, Larry Wickerman, MD, told Medscape Medical News.
Earlier this year at the AACR's annual meeting, a new study found that statins do not protect patients against colorectal adenomas, the benign growths that are precursors of colorectal cancer, and might even increase the risk of developing them when used for 3 years or more.
Those results were published in the May issue of Cancer Prevention Research (2010;3:588-596). In an editorial that accompanied the study (2010;3:573-575), a commentator said that there is "accumulating evidence that, at least overall, statins probably do not prevent colorectal neoplasia." However, there was a caveat in the editorial: "It is conceivable that there are benefits with high cumulative doses or in genetically defined subgroups."
cholesterol LDL
From Heartwire
Lower Is Better for LDL Even at Very Low Levels: New Meta-Analysis
Sue Hughes
November 9, 2010 (Oxford, United Kingdom and Sydney, Australia) — Further reductions in LDL cholesterol with more intensive statin regimens safely produce definite further reductions in vascular events, even down to very low LDL levels, lower than current targets, results of two new meta-analyses show [1]. There was no evidence of any lower threshold where the benefit is not seen.
The two meta-analyses, published online in the Lancet today, were conducted by the Cholesterol Treatment Trialists' (CTT) Collaboration, which includes researchers from both University of Oxford, UK, and the National Health and Medical Research Council Clinical Trials Centre (CTC) at the University of Sydney, Australia.
Beneficial Right Down to 1.3 mmol/L (50 mg/dL)
Lead author of the studies, Dr Colin Baigent (University of Oxford), told heartwire that these results "added substantially" to current knowledge in showing that reducing LDL well below current targets is beneficial. "By combining individual patient data from all the statin studies, we have a large group of people who started at the current LDL target level of 1.8 mmol/L (70 mg/dL) and got down to levels of around 1.3 mmol/L (around 50 mg/dL), and this group also showed a definite reduction in vascular events. This has not been shown before."
He noted, however, that these figures applied to patients at high risk of cardiovascular disease. "I would say anyone with a risk of cardiovascular disease greater than 2% per annum should be lowering their LDL as much as possible. This will give them massive benefits, without any hazard. The relative risk reductions will also probably be there in lower-risk patients, but the absolute risk will be much smaller, so we are not advocating that as a public-health strategy in low-risk groups."
The researchers conclude: "Each 1-mmol/L LDL cholesterol reduction reduces the risk of occlusive vascular events by about a fifth, irrespective of baseline cholesterol concentration, which implies that a 2- to 3-mmol/L reduction would reduce risk by about 40% to 50%. These findings suggest that the primary goal for patients at high risk of occlusive vascular events should be to achieve the largest LDL-cholesterol reduction possible without materially increasing myopathy risk."
They add that in contrast to current therapeutic guidelines, which tend to emphasize particular LDL-cholesterol targets, these new results suggest that lowering of LDL cholesterol further in high-risk patients who achieve such targets would produce additional benefits, without an increased risk of cancer or nonvascular mortality.
They also suggest that rather than using 80 mg of generic simvastatin to achieve these benefits, the more potent statins such as 80-mg atorvastatin or 20-mg rosuvastatin may be a better approach to avoid myopathy.
Commenting on the meta-analysis for heart wire , Dr Christie Ballantyne (Baylor College of Medicine, Houston, TX) said: "I agree in general that lower is better and that simvastatin 80 mg is not as good a choice as atorvastatin 80 mg or rosuvastatin 20 mg, which have better safety profiles and greater efficacy."
Data From a Total of 170 000 Patients
The first meta-analysis combined individual patient data from five trials of more vs less intensive statin therapy. Overall, among the 39 612 participants, mean baseline LDL was 2.53 mmol/L. During the 5.1-year mean follow-up, first major vascular events (coronary death, MI, coronary revascularization, or stroke) occurred at a rate of in 4.5% per annum in the more intensive treatment group vs 5.3% per annum in those allocated to less intensive therapy, a highly significant further proportional risk reduction of 15% per year with an LDL reduction of 0.51 mmol/L. This corresponds to a mean risk reduction of 28% per 1.0-mmol reduction in LDL.
For the second analysis, the researchers updated a previous meta-analysis with individual patient data from new trials, with a total of 21 trials of statin vs control involving 129 526 patients. In this analysis, mean baseline LDL cholesterol was 3.70 mmol/L. After a mean follow-up of 4.8 years, results showed a rate of first major vascular events of 2.8% per annum in the statin patients vs 3.6% per annum in the control patients, corresponding to a highly significant 22% risk reduction per year with a 1.07-mmol/L LDL reduction. This corresponds to a mean 21% risk reduction per 1.0-mmol/L reduction in LDL.
After differences in the absolute reductions in LDL cholesterol were accounted for, the proportional reduction in the incidence of major vascular events per mmol/L was slightly larger in the trials of more vs less intensive therapy than in those of statin vs control. Taking all 26 trials together, the risk reduction was 22%.
Question Over Hemorrhagic Stroke
There was no significant evidence in the meta-analysis of trials of more vs less intensive therapy that further lowering of LDL cholesterol produced any adverse effects, even in participants with baseline LDL cholesterol lower than 2.0 mmol/L, with no increase in nonvascular mortality or site-specific cancer incidence.
The one adverse effect that may be of concern with lower cholesterol level is hemorrhagic stroke. In the present meta-analyses, which included nearly 500 confirmed hemorrhagic strokes, lowering of LDL cholesterol with statin therapy was associated with a nonsignificant excess (257 vs 220; p=0.2). The authors point out that in two trials unavailable for this meta-analysis (SPARCL and CORONA), there were more hemorrhagic strokes in the statin group, and if these events were included in the meta-analysis then this would give a significant excess (hazard ratio 1.21; p=0.01) per 1.0-mmol/L LDL-cholesterol reduction. But they add that the size of the potential hazard would be about 50 times smaller (perhaps a few extra hemorrhagic strokes annually per 10 000 treated) than the definite absolute benefits (a few hundred occlusive events avoided annually per 10 000 treated) for patients who are at high risk of occlusive vascular events.
Numbers More Persuasive in Patients at High Cardiovascular Risk
In an accompanying editorial [2], Drs Bernard Cheung and Karen Lam (University of Hong Kong) note that as epidemiological data suggest that there is a log–linear association between cholesterol concentration and cardiovascular risk, with no flattening of the curve at low concentrations of cholesterol, and "therefore a tempting option is to decrease LDL-cholesterol concentration as much as possible."
But they point out that clinical benefit depends more on the absolute risk reduction or the number needed to treat than on relative risk reduction, and they conclude: "A low baseline LDL concentration is not a reason to withhold statin therapy if the patient is at a definite risk of cardiovascular events (eg, secondary prevention or diabetes). In this setting, the absolute risk reduction, number needed to treat, and risk/benefit and cost/benefit ratios are favorable. These numbers will be less persuasive for people at low cardiovascular risk, such as young people with no risk factors. At the population level, statins are underused, so the urgent priority is to identify people who would benefit most from statin therapy and to lower their LDL cholesterol aggressively, with the more potent statins if necessary."
SEARCH Lipid Arm Published
Also published along with the two meta-analyses is the lipid arm of the SEARCH trial, which was first presented at the 2008 American Heart Association meeting [3]. In this study, 2064 patients with a history of MI were randomized to either 80-mg or 20-mg simvastatin daily. Results showed that the more intensive lipid-lowering arm produced a further 0.35-mmol/L reduction in LDL cholesterol, which translated into a nonsignificant 6% proportional reduction in vascular events. These occurred in 24.5% of the 80-mg group vs 25.7% in the 20-mg group (risk ratio 0.94, 95% CI 0.88–1.01; p=0.10). Myopathy was increased with the 80-mg simvastatin dose. Compared with two (0.03%) cases of myopathy in patients taking 20-mg simvastatin daily, there were 53 (0.9%) cases in the 80-mg group. This is one of the five trials of more vs less intensive statin therapy included in the current meta-analysis.
Lower Is Better for LDL Even at Very Low Levels: New Meta-Analysis
Sue Hughes
November 9, 2010 (Oxford, United Kingdom and Sydney, Australia) — Further reductions in LDL cholesterol with more intensive statin regimens safely produce definite further reductions in vascular events, even down to very low LDL levels, lower than current targets, results of two new meta-analyses show [1]. There was no evidence of any lower threshold where the benefit is not seen.
The two meta-analyses, published online in the Lancet today, were conducted by the Cholesterol Treatment Trialists' (CTT) Collaboration, which includes researchers from both University of Oxford, UK, and the National Health and Medical Research Council Clinical Trials Centre (CTC) at the University of Sydney, Australia.
Beneficial Right Down to 1.3 mmol/L (50 mg/dL)
Lead author of the studies, Dr Colin Baigent (University of Oxford), told heartwire that these results "added substantially" to current knowledge in showing that reducing LDL well below current targets is beneficial. "By combining individual patient data from all the statin studies, we have a large group of people who started at the current LDL target level of 1.8 mmol/L (70 mg/dL) and got down to levels of around 1.3 mmol/L (around 50 mg/dL), and this group also showed a definite reduction in vascular events. This has not been shown before."
He noted, however, that these figures applied to patients at high risk of cardiovascular disease. "I would say anyone with a risk of cardiovascular disease greater than 2% per annum should be lowering their LDL as much as possible. This will give them massive benefits, without any hazard. The relative risk reductions will also probably be there in lower-risk patients, but the absolute risk will be much smaller, so we are not advocating that as a public-health strategy in low-risk groups."
The researchers conclude: "Each 1-mmol/L LDL cholesterol reduction reduces the risk of occlusive vascular events by about a fifth, irrespective of baseline cholesterol concentration, which implies that a 2- to 3-mmol/L reduction would reduce risk by about 40% to 50%. These findings suggest that the primary goal for patients at high risk of occlusive vascular events should be to achieve the largest LDL-cholesterol reduction possible without materially increasing myopathy risk."
They add that in contrast to current therapeutic guidelines, which tend to emphasize particular LDL-cholesterol targets, these new results suggest that lowering of LDL cholesterol further in high-risk patients who achieve such targets would produce additional benefits, without an increased risk of cancer or nonvascular mortality.
They also suggest that rather than using 80 mg of generic simvastatin to achieve these benefits, the more potent statins such as 80-mg atorvastatin or 20-mg rosuvastatin may be a better approach to avoid myopathy.
Commenting on the meta-analysis for heart wire , Dr Christie Ballantyne (Baylor College of Medicine, Houston, TX) said: "I agree in general that lower is better and that simvastatin 80 mg is not as good a choice as atorvastatin 80 mg or rosuvastatin 20 mg, which have better safety profiles and greater efficacy."
Data From a Total of 170 000 Patients
The first meta-analysis combined individual patient data from five trials of more vs less intensive statin therapy. Overall, among the 39 612 participants, mean baseline LDL was 2.53 mmol/L. During the 5.1-year mean follow-up, first major vascular events (coronary death, MI, coronary revascularization, or stroke) occurred at a rate of in 4.5% per annum in the more intensive treatment group vs 5.3% per annum in those allocated to less intensive therapy, a highly significant further proportional risk reduction of 15% per year with an LDL reduction of 0.51 mmol/L. This corresponds to a mean risk reduction of 28% per 1.0-mmol reduction in LDL.
For the second analysis, the researchers updated a previous meta-analysis with individual patient data from new trials, with a total of 21 trials of statin vs control involving 129 526 patients. In this analysis, mean baseline LDL cholesterol was 3.70 mmol/L. After a mean follow-up of 4.8 years, results showed a rate of first major vascular events of 2.8% per annum in the statin patients vs 3.6% per annum in the control patients, corresponding to a highly significant 22% risk reduction per year with a 1.07-mmol/L LDL reduction. This corresponds to a mean 21% risk reduction per 1.0-mmol/L reduction in LDL.
After differences in the absolute reductions in LDL cholesterol were accounted for, the proportional reduction in the incidence of major vascular events per mmol/L was slightly larger in the trials of more vs less intensive therapy than in those of statin vs control. Taking all 26 trials together, the risk reduction was 22%.
Question Over Hemorrhagic Stroke
There was no significant evidence in the meta-analysis of trials of more vs less intensive therapy that further lowering of LDL cholesterol produced any adverse effects, even in participants with baseline LDL cholesterol lower than 2.0 mmol/L, with no increase in nonvascular mortality or site-specific cancer incidence.
The one adverse effect that may be of concern with lower cholesterol level is hemorrhagic stroke. In the present meta-analyses, which included nearly 500 confirmed hemorrhagic strokes, lowering of LDL cholesterol with statin therapy was associated with a nonsignificant excess (257 vs 220; p=0.2). The authors point out that in two trials unavailable for this meta-analysis (SPARCL and CORONA), there were more hemorrhagic strokes in the statin group, and if these events were included in the meta-analysis then this would give a significant excess (hazard ratio 1.21; p=0.01) per 1.0-mmol/L LDL-cholesterol reduction. But they add that the size of the potential hazard would be about 50 times smaller (perhaps a few extra hemorrhagic strokes annually per 10 000 treated) than the definite absolute benefits (a few hundred occlusive events avoided annually per 10 000 treated) for patients who are at high risk of occlusive vascular events.
Numbers More Persuasive in Patients at High Cardiovascular Risk
In an accompanying editorial [2], Drs Bernard Cheung and Karen Lam (University of Hong Kong) note that as epidemiological data suggest that there is a log–linear association between cholesterol concentration and cardiovascular risk, with no flattening of the curve at low concentrations of cholesterol, and "therefore a tempting option is to decrease LDL-cholesterol concentration as much as possible."
But they point out that clinical benefit depends more on the absolute risk reduction or the number needed to treat than on relative risk reduction, and they conclude: "A low baseline LDL concentration is not a reason to withhold statin therapy if the patient is at a definite risk of cardiovascular events (eg, secondary prevention or diabetes). In this setting, the absolute risk reduction, number needed to treat, and risk/benefit and cost/benefit ratios are favorable. These numbers will be less persuasive for people at low cardiovascular risk, such as young people with no risk factors. At the population level, statins are underused, so the urgent priority is to identify people who would benefit most from statin therapy and to lower their LDL cholesterol aggressively, with the more potent statins if necessary."
SEARCH Lipid Arm Published
Also published along with the two meta-analyses is the lipid arm of the SEARCH trial, which was first presented at the 2008 American Heart Association meeting [3]. In this study, 2064 patients with a history of MI were randomized to either 80-mg or 20-mg simvastatin daily. Results showed that the more intensive lipid-lowering arm produced a further 0.35-mmol/L reduction in LDL cholesterol, which translated into a nonsignificant 6% proportional reduction in vascular events. These occurred in 24.5% of the 80-mg group vs 25.7% in the 20-mg group (risk ratio 0.94, 95% CI 0.88–1.01; p=0.10). Myopathy was increased with the 80-mg simvastatin dose. Compared with two (0.03%) cases of myopathy in patients taking 20-mg simvastatin daily, there were 53 (0.9%) cases in the 80-mg group. This is one of the five trials of more vs less intensive statin therapy included in the current meta-analysis.
B12 cognition dementia homocysteine
Summary and Comment
Vitamin B Supplementation and Cognition
In older men, supplementation did not affect cognition.
Because high plasma homocysteine levels are associated with cognitive impairment in epidemiologic studies, in multiple clinical trials researchers have examined whether vitamin B supplementation — which lowers homocysteine levels — improves cognition or delays onset of cognitive impairment in older adults; results have been mostly negative. In a new study, Australian researchers randomized 299 community-dwelling hypertensive men (age, ≥75) without dementia to receive either placebo or a combination of vitamin B6, vitamin B12, and folic acid.
During 2 years of treatment, no differences between groups were noted on several measures of cognition. Even in subgroups in which benefit seemed likely — men with high baseline homocysteine levels (≥15 µmol/L) and men with mild cognitive impairment at baseline — the investigators found no benefit from vitamin B supplementation.
Comment: This study adds to a growing body of evidence that vitamin B supplementation does not favorably affect cognition in older adults. One possible inference is that homocysteine is a marker — not a cause — of cognitive impairment in older adults.
— Allan S. Brett, MD
Published in Journal Watch General Medicine November 10, 2010
Vitamin B Supplementation and Cognition
In older men, supplementation did not affect cognition.
Because high plasma homocysteine levels are associated with cognitive impairment in epidemiologic studies, in multiple clinical trials researchers have examined whether vitamin B supplementation — which lowers homocysteine levels — improves cognition or delays onset of cognitive impairment in older adults; results have been mostly negative. In a new study, Australian researchers randomized 299 community-dwelling hypertensive men (age, ≥75) without dementia to receive either placebo or a combination of vitamin B6, vitamin B12, and folic acid.
During 2 years of treatment, no differences between groups were noted on several measures of cognition. Even in subgroups in which benefit seemed likely — men with high baseline homocysteine levels (≥15 µmol/L) and men with mild cognitive impairment at baseline — the investigators found no benefit from vitamin B supplementation.
Comment: This study adds to a growing body of evidence that vitamin B supplementation does not favorably affect cognition in older adults. One possible inference is that homocysteine is a marker — not a cause — of cognitive impairment in older adults.
— Allan S. Brett, MD
Published in Journal Watch General Medicine November 10, 2010
Wednesday, November 10, 2010
aspirin colon cancer
vestigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.
Nick Mulcahy
Nick Mulcahy is a senior journalist for Medscape Hematology-Oncology. Before joining Medscape, Nick was a freelance medical news writer for 15 years, working for companies such as the International Medical News Group, MedPage Today, HealthDay, McMahon Publishing, and Advanstar. He is also the former managing editor of breastcancer.org. He can be contacted at nmulcahy@medscape.net.
Disclosure: Nick Mulcahy has disclosed no relevant financial information.
Brande Nicole Martin
CME Clinical Editor, Medscape, LLC
Disclosure: Brande Nicole Martin has disclosed no relevant financial relationships.
Laurie Barclay, MD
Freelance writer and reviewer, Medscape, LLC
Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.
Sarah Fleischman
CME Program Manager, Medscape, LLC
Disclosure: Sarah Fleischman has disclosed no relevant financial relationships.
Learning Objectives
Upon completion of this activity, participants will be able to:
1. Describe the association of aspirin use with overall incidence of and mortality from colorectal cancer, based on a meta-analysis.
2. Describe the association of aspirin use with colorectal cancer in relationship to dose, duration of treatment, and site of tumor, based on a meta-analysis.
Credits Available
Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™
Family Physicians - maximum of 0.25 AAFP Prescribed credit(s)
All other healthcare professionals completing continuing education credit for this activity will be issued a certificate of participation.
Physicians should only claim credit commensurate with the extent of their participation in the activity.
Accreditation Statements
For Physicians
Medscape, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
Medscape, LLC designates this educational activity for a maximum of 0.25 AMA PRA Category 1 Credit(s)™ . Physicians should only claim credit commensurate with the extent of their participation in the activity.
This activity, MedscapeCME Clinical Briefs has been reviewed and is acceptable for up to 300 Prescribed credits by the American Academy of Family Physicians. AAFP accreditation begins September 1, 2010. Term of approval is for 1 year from this date. Each issue is approved for .25 Prescribed credits. Credit may be claimed for 1 year from the date of this issue.
Note: Total credit is subject to change based on topic selection and article length.
Medscape, LLC staff have disclosed that they have no relevant financial relationships.
AAFP Accreditation Questions
Contact This Provider
For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact CME@medscape.net
CME Released: 10/29/2010; Valid for credit through 10/29/2011
Instructions for Participation and Credit
There are no fees for participating in or receiving credit for this online educational activity. For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing board.
This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page.
Follow these steps to earn CME/CE credit*:
1. Read the target audience, learning objectives, and author disclosures.
2. Study the educational content online or printed out.
3. Online, choose the best answer to each test question. To receive a certificate, you must receive a passing score as designated at the top of the test. MedscapeCME encourages you to complete the Activity Evaluation to provide feedback for future programming.
You may now view or print the certificate from your CME/CE Tracker. You may print the certificate but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period you can print out the tally as well as the certificates by accessing "Edit Your Profile" at the top of your Medscape homepage.
*The credit that you receive is based on your user profile.
Hardware/Software Requirements
MedscapeCME is accessible using the following browsers: Internet Explorer 6.x or higher, Firefox 2.x or higher, Safari 2.x or higher. Certain educational activities may require additional software to view multimedia, presentation or printable versions of their content. These activities will be marked as such and will provide links to the required software. That software may be: Macromedia Flash, Adobe Acrobat, or Microsoft PowerPoint.
October 29, 2010 — The use of low-dose aspirin reduced the long-term incidence of and mortality related to colorectal cancer, according to British researchers.
Notably, the benefit was greatest for cancers of the proximal colon, which are not prevented effectively by screening with sigmoidoscopy or colonoscopy, say the researchers, led by Peter Rothwell, MD, PhD, from the University of Oxford, United Kingdom.
Their study, which is the first to assess the long-term effectiveness of lower doses (75 to 300 mg daily) of aspirin on colorectal cancer, was published online October 21 in the Lancet.
The same investigators have previously shown that high-dose aspirin (≥500 mg daily) reduces the long-term incidence of colorectal cancer, but with the spectre of adverse effects, especially increased bleeding.
They also previously reported a beneficial effect of low-dose aspirin after 10 years of use.
Now, the team reports 20-year data from 14,033 Swedish and British patients who participated in randomized trials that were originally designed to evaluate low-dose aspirin for the prevention of vascular disease.
They found that in 4 trials of aspirin vs placebo (with a mean duration of 6 years of scheduled treatment), aspirin reduced the long-term risk for colon cancer by 24% and mortality from colon cancer by 35%.
In other words, being on aspirin instead of placebo for an average of 6 years reduced the 20-year risk for the incidence of colon cancer (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.60 - 0.96; P = .02) and the related mortality (HR, 0.65; 95% CI, 0.48 - 0.88; P = .005). No overall risk reduction was seen for rectal cancer during this period.
A total of 391 patients (2.8%) had colorectal cancer during follow-up.
Limited data were available on the specific site of the cancer in the colon. However, in that subset of patients, the investigators found that aspirin reduced the risk for the incidence of cancer of the proximal colon (HR, 0.45; 95% CI, 0.28 - 0.74; P = .001) and the related mortality (HR, 0.34; 0.18 - 0.66; P = .001), but did not reduce the risk for cancer of the distal colon.
The investigators indicate that the benefit for the range of doses of aspirin was the same, with 75 mg daily being as effective as 300 mg. However, doses of 30 mg per day seemed to be less effective, they say.
"This interesting study could incite clinicians to turn to primary prevention of colorectal cancer by aspirin, at least in high-risk populations," say Robert Benamouzig, MD, and Bernard Uzzan, MD, from the Avicenne Hospital in Bobigny, France, in an editorial accompanying the study.
"Specific guidelines for aspirin chemoprevention would be the next logical step," they add.
The study authors make an effort to place their findings in the context of recent research. The trials that they studied "all predated endoscopic screening for adenomas, which also reduces colorectal cancer incidence and mortality, and might therefore reduce the absolute benefit of aspirin," they say. However, the study authors also note that, with aspirin, the prevention of proximal colonic cancers, which would not be identified by sigmoidoscopy, is "clearly important." The use of screening and aspirin might be "synergistic," they speculate.
For Men Only, and Smokers
In their comment, the editorialists review a number of the original aspects of the study. It provides "extremely long follow-up" and new data for an issue in which data are "scarce."
The findings are in contrast to at least 1 other major randomized trial, the US Physicians' Health Study, which randomized 22,071 men to aspirin 325 mg or placebo every other day for 5 years, but found that the risk for colorectal cancer was similar in both groups (J Natl Cancer Inst. 1993;85:1220-1224).
The authors and the editorialists emphasize that, in the new study, the preventive effect of aspirin predominated in proximal cancers. However, the editorialists temper that observation by pointing out that this was a subgroup analysis and relied on relatively small numbers. They also note that, to date, only 1 randomized preventive study, which was restricted to evaluating serrated polyps, showed that the effect of aspirin was mainly on proximal lesions (40% to 50% reduction), with no effect on distal lesions (Cancer Epidemiol Biomarkers Prev. 2009;18:2310-2017).
Nevertheless, this finding about the proximal lesions has the potential to be very important, say the editorialists. "If confirmed, this original finding might present a strong argument for the addition of aspirin chemoprevention to screening sigmoidoscopy," they write.
This study has a variety of important limitations, say the editorialists.
The investigators reported disease-specific mortality and not overall mortality. Thus, they did not assess mortality related to the adverse effects of aspirin, write the editorialists.
An earlier systematic review of the literature found that aspirin reduced colorectal cancer incidence, especially when used for more than 10 years, but with a dose-related increase in gastrointestinal complications (Ann Intern Med. 2007;146:365-375).
Also, the patients in the trials were mostly men with cardiovascular risk (2 of the trials were men only). "Thus, no conclusions can be made about women and patients with no cardiovascular risk," say the editorialists.
In addition, the proportion of current smokers in the trials ranged from 27% to 53%. "The mechanisms of colon carcinogenesis might differ between cardiovascular and other patients because of increased tobacco consumption," the editorialists point out.
A Few More Study Details
The study authors followed-up on 4 randomized trials of aspirin vs placebo in primary (Thrombosis Prevention Trial, British Doctors Aspirin Trial) and secondary (Swedish Aspirin Low Dose Trial, UK-TIA Aspirin Trial) prevention of vascular events. They also followed-up on 1 trial of different doses of aspirin (Dutch TIA Aspirin Trial) that had no placebo control. The goal was to establish the effect of aspirin on risk for colorectal cancer over 20 years with an analysis of pooled individual patient data.
These analyses were stratified by dose categories (as low as 30 mg daily and as high as 1200 mg daily), duration of treatment during the initial trial period (which varied from 1 to 7 years), and, where the data were available, by site of cancer in predefined categories.
Dr. Rothwell and a coauthor report receiving honoraria for talks, advisory boards, and clinical trial committees from several pharmaceutical companies with an interest in antiplatelet agents, including AstraZeneca, Bayer, Boehringer Ingelheim, Sanofi-BMS, and Servier.
Lancet. Published online October 21, 2010. Abstract
Nick Mulcahy
Nick Mulcahy is a senior journalist for Medscape Hematology-Oncology. Before joining Medscape, Nick was a freelance medical news writer for 15 years, working for companies such as the International Medical News Group, MedPage Today, HealthDay, McMahon Publishing, and Advanstar. He is also the former managing editor of breastcancer.org. He can be contacted at nmulcahy@medscape.net.
Disclosure: Nick Mulcahy has disclosed no relevant financial information.
Brande Nicole Martin
CME Clinical Editor, Medscape, LLC
Disclosure: Brande Nicole Martin has disclosed no relevant financial relationships.
Laurie Barclay, MD
Freelance writer and reviewer, Medscape, LLC
Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.
Sarah Fleischman
CME Program Manager, Medscape, LLC
Disclosure: Sarah Fleischman has disclosed no relevant financial relationships.
Learning Objectives
Upon completion of this activity, participants will be able to:
1. Describe the association of aspirin use with overall incidence of and mortality from colorectal cancer, based on a meta-analysis.
2. Describe the association of aspirin use with colorectal cancer in relationship to dose, duration of treatment, and site of tumor, based on a meta-analysis.
Credits Available
Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™
Family Physicians - maximum of 0.25 AAFP Prescribed credit(s)
All other healthcare professionals completing continuing education credit for this activity will be issued a certificate of participation.
Physicians should only claim credit commensurate with the extent of their participation in the activity.
Accreditation Statements
For Physicians
Medscape, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
Medscape, LLC designates this educational activity for a maximum of 0.25 AMA PRA Category 1 Credit(s)™ . Physicians should only claim credit commensurate with the extent of their participation in the activity.
This activity, MedscapeCME Clinical Briefs has been reviewed and is acceptable for up to 300 Prescribed credits by the American Academy of Family Physicians. AAFP accreditation begins September 1, 2010. Term of approval is for 1 year from this date. Each issue is approved for .25 Prescribed credits. Credit may be claimed for 1 year from the date of this issue.
Note: Total credit is subject to change based on topic selection and article length.
Medscape, LLC staff have disclosed that they have no relevant financial relationships.
AAFP Accreditation Questions
Contact This Provider
For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact CME@medscape.net
CME Released: 10/29/2010; Valid for credit through 10/29/2011
Instructions for Participation and Credit
There are no fees for participating in or receiving credit for this online educational activity. For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing board.
This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page.
Follow these steps to earn CME/CE credit*:
1. Read the target audience, learning objectives, and author disclosures.
2. Study the educational content online or printed out.
3. Online, choose the best answer to each test question. To receive a certificate, you must receive a passing score as designated at the top of the test. MedscapeCME encourages you to complete the Activity Evaluation to provide feedback for future programming.
You may now view or print the certificate from your CME/CE Tracker. You may print the certificate but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period you can print out the tally as well as the certificates by accessing "Edit Your Profile" at the top of your Medscape homepage.
*The credit that you receive is based on your user profile.
Hardware/Software Requirements
MedscapeCME is accessible using the following browsers: Internet Explorer 6.x or higher, Firefox 2.x or higher, Safari 2.x or higher. Certain educational activities may require additional software to view multimedia, presentation or printable versions of their content. These activities will be marked as such and will provide links to the required software. That software may be: Macromedia Flash, Adobe Acrobat, or Microsoft PowerPoint.
October 29, 2010 — The use of low-dose aspirin reduced the long-term incidence of and mortality related to colorectal cancer, according to British researchers.
Notably, the benefit was greatest for cancers of the proximal colon, which are not prevented effectively by screening with sigmoidoscopy or colonoscopy, say the researchers, led by Peter Rothwell, MD, PhD, from the University of Oxford, United Kingdom.
Their study, which is the first to assess the long-term effectiveness of lower doses (75 to 300 mg daily) of aspirin on colorectal cancer, was published online October 21 in the Lancet.
The same investigators have previously shown that high-dose aspirin (≥500 mg daily) reduces the long-term incidence of colorectal cancer, but with the spectre of adverse effects, especially increased bleeding.
They also previously reported a beneficial effect of low-dose aspirin after 10 years of use.
Now, the team reports 20-year data from 14,033 Swedish and British patients who participated in randomized trials that were originally designed to evaluate low-dose aspirin for the prevention of vascular disease.
They found that in 4 trials of aspirin vs placebo (with a mean duration of 6 years of scheduled treatment), aspirin reduced the long-term risk for colon cancer by 24% and mortality from colon cancer by 35%.
In other words, being on aspirin instead of placebo for an average of 6 years reduced the 20-year risk for the incidence of colon cancer (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.60 - 0.96; P = .02) and the related mortality (HR, 0.65; 95% CI, 0.48 - 0.88; P = .005). No overall risk reduction was seen for rectal cancer during this period.
A total of 391 patients (2.8%) had colorectal cancer during follow-up.
Limited data were available on the specific site of the cancer in the colon. However, in that subset of patients, the investigators found that aspirin reduced the risk for the incidence of cancer of the proximal colon (HR, 0.45; 95% CI, 0.28 - 0.74; P = .001) and the related mortality (HR, 0.34; 0.18 - 0.66; P = .001), but did not reduce the risk for cancer of the distal colon.
The investigators indicate that the benefit for the range of doses of aspirin was the same, with 75 mg daily being as effective as 300 mg. However, doses of 30 mg per day seemed to be less effective, they say.
"This interesting study could incite clinicians to turn to primary prevention of colorectal cancer by aspirin, at least in high-risk populations," say Robert Benamouzig, MD, and Bernard Uzzan, MD, from the Avicenne Hospital in Bobigny, France, in an editorial accompanying the study.
"Specific guidelines for aspirin chemoprevention would be the next logical step," they add.
The study authors make an effort to place their findings in the context of recent research. The trials that they studied "all predated endoscopic screening for adenomas, which also reduces colorectal cancer incidence and mortality, and might therefore reduce the absolute benefit of aspirin," they say. However, the study authors also note that, with aspirin, the prevention of proximal colonic cancers, which would not be identified by sigmoidoscopy, is "clearly important." The use of screening and aspirin might be "synergistic," they speculate.
For Men Only, and Smokers
In their comment, the editorialists review a number of the original aspects of the study. It provides "extremely long follow-up" and new data for an issue in which data are "scarce."
The findings are in contrast to at least 1 other major randomized trial, the US Physicians' Health Study, which randomized 22,071 men to aspirin 325 mg or placebo every other day for 5 years, but found that the risk for colorectal cancer was similar in both groups (J Natl Cancer Inst. 1993;85:1220-1224).
The authors and the editorialists emphasize that, in the new study, the preventive effect of aspirin predominated in proximal cancers. However, the editorialists temper that observation by pointing out that this was a subgroup analysis and relied on relatively small numbers. They also note that, to date, only 1 randomized preventive study, which was restricted to evaluating serrated polyps, showed that the effect of aspirin was mainly on proximal lesions (40% to 50% reduction), with no effect on distal lesions (Cancer Epidemiol Biomarkers Prev. 2009;18:2310-2017).
Nevertheless, this finding about the proximal lesions has the potential to be very important, say the editorialists. "If confirmed, this original finding might present a strong argument for the addition of aspirin chemoprevention to screening sigmoidoscopy," they write.
This study has a variety of important limitations, say the editorialists.
The investigators reported disease-specific mortality and not overall mortality. Thus, they did not assess mortality related to the adverse effects of aspirin, write the editorialists.
An earlier systematic review of the literature found that aspirin reduced colorectal cancer incidence, especially when used for more than 10 years, but with a dose-related increase in gastrointestinal complications (Ann Intern Med. 2007;146:365-375).
Also, the patients in the trials were mostly men with cardiovascular risk (2 of the trials were men only). "Thus, no conclusions can be made about women and patients with no cardiovascular risk," say the editorialists.
In addition, the proportion of current smokers in the trials ranged from 27% to 53%. "The mechanisms of colon carcinogenesis might differ between cardiovascular and other patients because of increased tobacco consumption," the editorialists point out.
A Few More Study Details
The study authors followed-up on 4 randomized trials of aspirin vs placebo in primary (Thrombosis Prevention Trial, British Doctors Aspirin Trial) and secondary (Swedish Aspirin Low Dose Trial, UK-TIA Aspirin Trial) prevention of vascular events. They also followed-up on 1 trial of different doses of aspirin (Dutch TIA Aspirin Trial) that had no placebo control. The goal was to establish the effect of aspirin on risk for colorectal cancer over 20 years with an analysis of pooled individual patient data.
These analyses were stratified by dose categories (as low as 30 mg daily and as high as 1200 mg daily), duration of treatment during the initial trial period (which varied from 1 to 7 years), and, where the data were available, by site of cancer in predefined categories.
Dr. Rothwell and a coauthor report receiving honoraria for talks, advisory boards, and clinical trial committees from several pharmaceutical companies with an interest in antiplatelet agents, including AstraZeneca, Bayer, Boehringer Ingelheim, Sanofi-BMS, and Servier.
Lancet. Published online October 21, 2010. Abstract
vitamine D
Inflammatory Bowel Disease Associated With Bone Loss, Vitamin D Deficiency CME
News Author: Nancy A. Melville
CME Author: Désirée Lie, MD, MSEd
.
October 27, 2010 — Patients with inflammatory bowel disease (IBD) who are vitamin D deficient have a significantly increased risk for osteoporosis, osteopenia, and abnormal bone density levels, irrespective of other factors that could place them at a higher risk, according to research presented here at the American College of Gastroenterology (ACG) 2010 Annual Scientific Meeting and Postgraduate Course.
The study of 161 patients diagnosed with IBDs, such as ulcerative colitis and Crohn's disease, found that 22% of patients had a reduction in bone density, and a diagnosis of osteopenia or osteoporosis. Of those with a bone density reduction, 50% were younger than 40 years.
"Bone loss is generally uncommon below the age of 40 in the normal population, so I was a little surprised to see a high number of my patients below that age with abnormal bone density. I do believe that it is further evidence of the effects of IBD," said Bincy P. Abraham, MD, MS, lead author of the study.
Of patients with abnormal dual-energy x-ray absorptiometry (DXA) bone density exams, 40% had higher rates of vitamin D deficiency, defined as levels of 25-hydroxyvitamin D below 30 ng/mL, compared with 1% of those with normal scans (odds ratio [OR], 8.7; 95% confidence interval [CI], 2.4 - 19.8, P = .001).
The higher levels of vitamin D deficiency remained after patients were controlled for corticosteroid intake, age, and sex.
"If you were vitamin D deficient, you were nearly 9 times more likely to have abnormal bone deficiency" than if you weren't, said Dr. Abraham, who is assistant professor of medicine in the Inflammatory Bowel Disease Program at Baylor College of Medicine in Houston, Texas.
"We looked at the other risk factors and still found that vitamin D was the major factor contributing to the abnormal bone density," she said.
Previous studies have reported on the high prevalence of osteoporosis among patients with IBD, with the use of corticosteroid and excess of inflammatory cytokines potentially interfering with bone repair and remodeling. Vitamin D deficiencies have also been reported in such patients, but studies have disagreed about the association between the deficiency and bone density.
The prospective study evaluated patients between the ages of 10 and 70 years who were diagnosed with IBD on the basis of clinical, radiologic, endoscopic, and histologic data.
The results showed that patients with Crohn's disease were much more likely to have abnormal bone density exams than those with ulcerative colitis (34% vs 13%; OR, 4.2; 95% CI, 1.8 - 11.7; P = .02). Those with osteoporosis plus Crohn's disease or ulcerative colitis had significantly higher rates of vitamin D deficiency, regardless of prednisone intake.
The findings suggest that clinicians treating IBD patients need to consider the possibility of low vitamin D levels and be aware of the potential for bone loss among those patients," Dr. Abraham said.
"The first step for clinicians treating IBD patients is to check their vitamin D levels, and if they find a deficiency, treat it," she told Medscape Medical News.
"I prescribe 50,000 units of vitamin D weekly for 8 weeks and then recheck their levels. I'm usually able to get my patients back to good levels (between 30 to 50 ng/mL). . . . I then wait a year and recheck their DXA scans."
IBD patients are known to be at increased risk for low bone density; however, the study's findings are notable for showing a relation between vitamin D deficiencies and bone loss, said Jean Paul Achkar, MD, a gastroenterologist from the Cleveland Clinic, in Ohio.
"The ACG has guidelines regarding the need to monitor bone density in IBD patients," he said. "It is also increasingly recognized that vitamin D levels need to be monitored and repleted if low in patients with IBD."
"The interesting point of this abstract is the demonstration of a strong association between low vitamin D and abnormal DXA scan, and the fact that this association remained after adjustment for steroid intake and age."
"The study highlights the importance of checking vitamin D levels in addition to routine DXA monitoring."
The study did not receive funding. Dr. Abraham reports being on the speaker's bureau for UCB, Abbott, Warner-Chilcott, Salix, and Prometheus, and the advisory committee for UCB. Dr. Achkar has disclosed no relevant financial relationships.
American College of Gastroenterology (ACG) 2010 Annual Scientific Meeting and Postgraduate Course: Poster P290. Presented October 17, 2010.
News Author: Nancy A. Melville
CME Author: Désirée Lie, MD, MSEd
.
October 27, 2010 — Patients with inflammatory bowel disease (IBD) who are vitamin D deficient have a significantly increased risk for osteoporosis, osteopenia, and abnormal bone density levels, irrespective of other factors that could place them at a higher risk, according to research presented here at the American College of Gastroenterology (ACG) 2010 Annual Scientific Meeting and Postgraduate Course.
The study of 161 patients diagnosed with IBDs, such as ulcerative colitis and Crohn's disease, found that 22% of patients had a reduction in bone density, and a diagnosis of osteopenia or osteoporosis. Of those with a bone density reduction, 50% were younger than 40 years.
"Bone loss is generally uncommon below the age of 40 in the normal population, so I was a little surprised to see a high number of my patients below that age with abnormal bone density. I do believe that it is further evidence of the effects of IBD," said Bincy P. Abraham, MD, MS, lead author of the study.
Of patients with abnormal dual-energy x-ray absorptiometry (DXA) bone density exams, 40% had higher rates of vitamin D deficiency, defined as levels of 25-hydroxyvitamin D below 30 ng/mL, compared with 1% of those with normal scans (odds ratio [OR], 8.7; 95% confidence interval [CI], 2.4 - 19.8, P = .001).
The higher levels of vitamin D deficiency remained after patients were controlled for corticosteroid intake, age, and sex.
"If you were vitamin D deficient, you were nearly 9 times more likely to have abnormal bone deficiency" than if you weren't, said Dr. Abraham, who is assistant professor of medicine in the Inflammatory Bowel Disease Program at Baylor College of Medicine in Houston, Texas.
"We looked at the other risk factors and still found that vitamin D was the major factor contributing to the abnormal bone density," she said.
Previous studies have reported on the high prevalence of osteoporosis among patients with IBD, with the use of corticosteroid and excess of inflammatory cytokines potentially interfering with bone repair and remodeling. Vitamin D deficiencies have also been reported in such patients, but studies have disagreed about the association between the deficiency and bone density.
The prospective study evaluated patients between the ages of 10 and 70 years who were diagnosed with IBD on the basis of clinical, radiologic, endoscopic, and histologic data.
The results showed that patients with Crohn's disease were much more likely to have abnormal bone density exams than those with ulcerative colitis (34% vs 13%; OR, 4.2; 95% CI, 1.8 - 11.7; P = .02). Those with osteoporosis plus Crohn's disease or ulcerative colitis had significantly higher rates of vitamin D deficiency, regardless of prednisone intake.
The findings suggest that clinicians treating IBD patients need to consider the possibility of low vitamin D levels and be aware of the potential for bone loss among those patients," Dr. Abraham said.
"The first step for clinicians treating IBD patients is to check their vitamin D levels, and if they find a deficiency, treat it," she told Medscape Medical News.
"I prescribe 50,000 units of vitamin D weekly for 8 weeks and then recheck their levels. I'm usually able to get my patients back to good levels (between 30 to 50 ng/mL). . . . I then wait a year and recheck their DXA scans."
IBD patients are known to be at increased risk for low bone density; however, the study's findings are notable for showing a relation between vitamin D deficiencies and bone loss, said Jean Paul Achkar, MD, a gastroenterologist from the Cleveland Clinic, in Ohio.
"The ACG has guidelines regarding the need to monitor bone density in IBD patients," he said. "It is also increasingly recognized that vitamin D levels need to be monitored and repleted if low in patients with IBD."
"The interesting point of this abstract is the demonstration of a strong association between low vitamin D and abnormal DXA scan, and the fact that this association remained after adjustment for steroid intake and age."
"The study highlights the importance of checking vitamin D levels in addition to routine DXA monitoring."
The study did not receive funding. Dr. Abraham reports being on the speaker's bureau for UCB, Abbott, Warner-Chilcott, Salix, and Prometheus, and the advisory committee for UCB. Dr. Achkar has disclosed no relevant financial relationships.
American College of Gastroenterology (ACG) 2010 Annual Scientific Meeting and Postgraduate Course: Poster P290. Presented October 17, 2010.
aspirin
4.
Cilostazol vs. Aspirin for Recurrent-Stroke Prevention
In a large, long-term trial, cilostazol was as effective as aspirin at preventing recurrent stroke and was associated with fewer hemorrhages.
Antiplatelet drugs have an established role in secondary stroke prevention. Several attempts have been made to boost the clinical effectiveness of these treatments by enhancing antithrombotic effects or lowering hemorrhagic risks. Cilostazol, a drug that primarily acts by inhibiting phosphodiesterase and, thus, platelet aggregation, is more effective than placebo at preventing stroke recurrence but has not been tested against routinely prescribed antiplatelet agents.
The manufacturer-funded second Cilostazol Stroke Prevention Study (CSPS 2) was designed to establish clinical noninferiority of cilostazol versus aspirin for the prevention of recurrent stroke in patients with noncardioembolic stroke. At multiple sites in Japan, the investigators enrolled 2757 people aged 20 to 79 who had experienced a cerebral infarction within the previous 6 months. Participants were randomized to receive cilostazol (100 mg twice daily) or aspirin (81 mg once daily) for 1 to 5 years. The primary endpoint was the first occurrence of any stroke.
About three quarters of the participants were men; mean follow-up was 29 months. The primary endpoint occurred significantly less frequently with cilostazol than with aspirin (hazard ratio, 0.74; 95% confidence interval, 0.56–0.98). Hemorrhagic events (cerebral hemorrhage, subarachnoid hemorrhage, or hemorrhage requiring hospital admission) happened in significantly fewer patients in the cilostazol group than in the aspirin group (0.77% vs. 1.78%), but headache, diarrhea, palpitations, dizziness, and tachycardia were significantly more common with cilostazol.
Comment: The notion that, compared with aspirin, a drug with primarily antiplatelet actions could lower both stroke risk and bleeding events is highly appealing. However, we need evidence establishing cilostazol's superiority over aspirin in a more heterogeneous cohort (specifically with more non-Asians and women). Also, given the drug's cost, twice-daily dosing, and adverse effects, showing just "me-too" efficacy may not be enough; an absolute stroke risk reduction of at least 1% per year compared with aspirin may be necessary to convince skeptical clinicians of its clinical utility and cost-effectiveness. Such a future trial could also allow investigation of whether switching antiplatelet therapy in the oft-encountered patient who has experienced a stroke while on aspirin (i.e., with aspirin failure) is clinically worthwhile.
— Bruce Ovbiagele, MD, MS, FAHA
Published in Journal Watch Neurology October 26, 2010
Cilostazol vs. Aspirin for Recurrent-Stroke Prevention
In a large, long-term trial, cilostazol was as effective as aspirin at preventing recurrent stroke and was associated with fewer hemorrhages.
Antiplatelet drugs have an established role in secondary stroke prevention. Several attempts have been made to boost the clinical effectiveness of these treatments by enhancing antithrombotic effects or lowering hemorrhagic risks. Cilostazol, a drug that primarily acts by inhibiting phosphodiesterase and, thus, platelet aggregation, is more effective than placebo at preventing stroke recurrence but has not been tested against routinely prescribed antiplatelet agents.
The manufacturer-funded second Cilostazol Stroke Prevention Study (CSPS 2) was designed to establish clinical noninferiority of cilostazol versus aspirin for the prevention of recurrent stroke in patients with noncardioembolic stroke. At multiple sites in Japan, the investigators enrolled 2757 people aged 20 to 79 who had experienced a cerebral infarction within the previous 6 months. Participants were randomized to receive cilostazol (100 mg twice daily) or aspirin (81 mg once daily) for 1 to 5 years. The primary endpoint was the first occurrence of any stroke.
About three quarters of the participants were men; mean follow-up was 29 months. The primary endpoint occurred significantly less frequently with cilostazol than with aspirin (hazard ratio, 0.74; 95% confidence interval, 0.56–0.98). Hemorrhagic events (cerebral hemorrhage, subarachnoid hemorrhage, or hemorrhage requiring hospital admission) happened in significantly fewer patients in the cilostazol group than in the aspirin group (0.77% vs. 1.78%), but headache, diarrhea, palpitations, dizziness, and tachycardia were significantly more common with cilostazol.
Comment: The notion that, compared with aspirin, a drug with primarily antiplatelet actions could lower both stroke risk and bleeding events is highly appealing. However, we need evidence establishing cilostazol's superiority over aspirin in a more heterogeneous cohort (specifically with more non-Asians and women). Also, given the drug's cost, twice-daily dosing, and adverse effects, showing just "me-too" efficacy may not be enough; an absolute stroke risk reduction of at least 1% per year compared with aspirin may be necessary to convince skeptical clinicians of its clinical utility and cost-effectiveness. Such a future trial could also allow investigation of whether switching antiplatelet therapy in the oft-encountered patient who has experienced a stroke while on aspirin (i.e., with aspirin failure) is clinically worthwhile.
— Bruce Ovbiagele, MD, MS, FAHA
Published in Journal Watch Neurology October 26, 2010
Friday, November 05, 2010
hersen bloeding aspirin
Summary and Comment
Antiplatelet Drugs and Intracerebral Hemorrhage
Previous therapy with antiplatelet drugs was associated with higher mortality after ICH.
Does prior antiplatelet therapy worsen outcomes in patients who suffer intracerebral hemorrhage? To address this question, researchers performed a meta-analysis of 25 cohort studies comprising 9900 patients with intracerebral hemorrhage; 23% of patients had been taking antiplatelet drugs (usually aspirin) at the time of the hemorrhage.
In a multivariable-adjusted pooled analysis, prior antiplatelet therapy was associated with significantly higher mortality (odds ratio, 1.27; P=0.001) but not worse functional outcomes (OR, 1.10).
Comment: In this meta-analysis, patients with intracerebral hemorrhage who were taking antiplatelet drugs had modestly but significantly higher mortality. A limitation of the analysis is that adjustment for confounding variables was limited in many of the component studies and was not uniform across studies. Moreover, too few patients were taking nonaspirin antiplatelet drugs or dual antiplatelet therapies to allow confident conclusions about different antiplatelet regimens. Nevertheless, this report serves to remind us that antiplatelet drugs — including aspirin — are not necessarily benign and should be prescribed only for valid and nonarbitrary reasons.
— Allan S. Brett, MD
Published in Journal Watch General Medicine November 4, 2010
Antiplatelet Drugs and Intracerebral Hemorrhage
Previous therapy with antiplatelet drugs was associated with higher mortality after ICH.
Does prior antiplatelet therapy worsen outcomes in patients who suffer intracerebral hemorrhage? To address this question, researchers performed a meta-analysis of 25 cohort studies comprising 9900 patients with intracerebral hemorrhage; 23% of patients had been taking antiplatelet drugs (usually aspirin) at the time of the hemorrhage.
In a multivariable-adjusted pooled analysis, prior antiplatelet therapy was associated with significantly higher mortality (odds ratio, 1.27; P=0.001) but not worse functional outcomes (OR, 1.10).
Comment: In this meta-analysis, patients with intracerebral hemorrhage who were taking antiplatelet drugs had modestly but significantly higher mortality. A limitation of the analysis is that adjustment for confounding variables was limited in many of the component studies and was not uniform across studies. Moreover, too few patients were taking nonaspirin antiplatelet drugs or dual antiplatelet therapies to allow confident conclusions about different antiplatelet regimens. Nevertheless, this report serves to remind us that antiplatelet drugs — including aspirin — are not necessarily benign and should be prescribed only for valid and nonarbitrary reasons.
— Allan S. Brett, MD
Published in Journal Watch General Medicine November 4, 2010
Thursday, November 04, 2010
bloeddruk
Current Hypertension Reports
Volume 4, Number 5, 343-349, DOI: 10.1007/s11906-002-0062-x
Abstract
Two thirds of patients with hypertension require more than one drug to achieve goal blood pressure. Rational antihypertensive drug combinations are based on their ability to produce additive blood pressure reduction and reduce the incidence of dose-dependent side effects. Some combinations exhibit side-effect neutralization in which side effects associated with one drug are neutralized by a second agent. Fixed-dose combinations improve adherence by reducing the number of pills and simplifying the treatment regimen. Because volume overload is common, low-dose diuretics are often included in drug combinations. Combinations of diuretics with potassium-sparing diuretics, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and ß-blockers are useful in treating large segments of the hypertensive population. Combinations of calcium channel blockers and angiotensin converting enzyme inhibitors are also effective and reduce the incidence of calcium blocker-related edema. Combinations of agents affecting the reninangiotensin system by different mechanisms are currently the subject of active investigation.
Volume 4, Number 5, 343-349, DOI: 10.1007/s11906-002-0062-x
Abstract
Two thirds of patients with hypertension require more than one drug to achieve goal blood pressure. Rational antihypertensive drug combinations are based on their ability to produce additive blood pressure reduction and reduce the incidence of dose-dependent side effects. Some combinations exhibit side-effect neutralization in which side effects associated with one drug are neutralized by a second agent. Fixed-dose combinations improve adherence by reducing the number of pills and simplifying the treatment regimen. Because volume overload is common, low-dose diuretics are often included in drug combinations. Combinations of diuretics with potassium-sparing diuretics, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and ß-blockers are useful in treating large segments of the hypertensive population. Combinations of calcium channel blockers and angiotensin converting enzyme inhibitors are also effective and reduce the incidence of calcium blocker-related edema. Combinations of agents affecting the reninangiotensin system by different mechanisms are currently the subject of active investigation.
bloeddruk
Rev Med Interne. 1986 Sep;7(4):433-40.
[Essential arterial hypertension: a strategy for the use of antihypertensive drugs]
[Article in French]
Simon A.
Abstract
Mild to moderate essential arterial hypertension affects almost 15 p. 100 of middle-aged adults in the general population. Although its individual vascular complications are few, it constitutes a problem of public health since a large number of patients implies a large number of complications in the population. Hypotensive therapy has proved capable of preventing mechanical complications of vascular rupture, but epidemiological studies have not yet demonstrated that it reduces the frequency of atherosclerosis of the coronary arteries and, probably, of other arteries at risk. A more detailed physiopathological approach to the vascular system in hypertensive patients therefore is necessary, notably to investigate the interactions between arterial hypertension, atherosclerosis and antihypertensive drugs. Meanwhile, the therapeutic strategy remains empirical, its principal goal being the degree of fall in blood pressure. The large number of drugs currently prescribed as first-choice treatment (diuretics, beta-blockers, calcium antagonists, angiotensin converting enzyme inhibitors) has complicated the conventional treatment by successive prescription of drugs with additive effects and has paved the way for a new therapeutic approach involving substitution and trying to find, for each individual patient, one or two effective drugs.
PMID: 3797876 [PubMed - indexed for MEDLINE]
[Essential arterial hypertension: a strategy for the use of antihypertensive drugs]
[Article in French]
Simon A.
Abstract
Mild to moderate essential arterial hypertension affects almost 15 p. 100 of middle-aged adults in the general population. Although its individual vascular complications are few, it constitutes a problem of public health since a large number of patients implies a large number of complications in the population. Hypotensive therapy has proved capable of preventing mechanical complications of vascular rupture, but epidemiological studies have not yet demonstrated that it reduces the frequency of atherosclerosis of the coronary arteries and, probably, of other arteries at risk. A more detailed physiopathological approach to the vascular system in hypertensive patients therefore is necessary, notably to investigate the interactions between arterial hypertension, atherosclerosis and antihypertensive drugs. Meanwhile, the therapeutic strategy remains empirical, its principal goal being the degree of fall in blood pressure. The large number of drugs currently prescribed as first-choice treatment (diuretics, beta-blockers, calcium antagonists, angiotensin converting enzyme inhibitors) has complicated the conventional treatment by successive prescription of drugs with additive effects and has paved the way for a new therapeutic approach involving substitution and trying to find, for each individual patient, one or two effective drugs.
PMID: 3797876 [PubMed - indexed for MEDLINE]
Wednesday, November 03, 2010
stem cells
Authors
Luigi Warren, Philip D. Manos, Tim Ahfeldt, Yuin-Han Loh, Hu Li, Frank Lau, Wataru Ebina, Pankaj K. Mandal, Zachary D. Smith, Alexander Meissner, George Q. Daley, Andrew S. Brack, James J. Collins, Chad Cowan, Thorsten M. Schlaeger, Derrick J. RossiSee AffiliationsHint: Rollover Authors and Affiliations Immune Disease Institute, Program in Cellular and Molecular Medicine, Children's Hospital Boston, Boston, MA 02115, USA Stem Cell Program, Children's Hospital Boston, Boston, MA 02115, USA Manton Center for Orphan Disease Research, Children's Hospital Boston, Boston, MA 02115, USA Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA Center of Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114-2790, USA Department of Biochemistry and Molecular Biology II: Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115, USA Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA Department of Pathology, Harvard Medical School, Boston, MA 02115, USA Department of Biomedical Engineering and Center for BioDynamics, Boston University, Boston, MA 02215, USA Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA Stowers Medical Institute, 185 Cambridge Street, Boston, MA 02114, USA Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA Howard Hughes Medical Institute Division of Hematology/Oncology, Brigham and Women's Hospital, Boston, MA 02115, USA Corresponding author These authors contributed equally to this work
Highlights
•Modified mRNAs can express reprogramming proteins and evade antiviral response
•Highly efficient derivation of human iPSCs without genomic integration
•RNA-derived iPSCs faithfully recapitulate the properties of human ESCs
•Efficient directed differentiation of iPSCs to differentiated myotubes
Summary
Clinical application of induced pluripotent stem cells (iPSCs) is limited by the low efficiency of iPSC derivation and the fact that most protocols modify the genome to effect cellular reprogramming. Moreover, safe and effective means of directing the fate of patient-specific iPSCs toward clinically useful cell types are lacking. Here we describe a simple, nonintegrating strategy for reprogramming cell fate based on administration of synthetic mRNA modified to overcome innate antiviral responses. We show that this approach can reprogram multiple human cell types to pluripotency with efficiencies that greatly surpass established protocols. We further show that the same technology can be used to efficiently direct the differentiation of RNA-induced pluripotent stem cells (RiPSCs) into terminally differentiated myogenic cells. This technology represents a safe, efficient strategy for somatic cell reprogramming and directing cell fate that has broad applicability for basic research, disease modeling, and regenerative medicine.
Luigi Warren, Philip D. Manos, Tim Ahfeldt, Yuin-Han Loh, Hu Li, Frank Lau, Wataru Ebina, Pankaj K. Mandal, Zachary D. Smith, Alexander Meissner, George Q. Daley, Andrew S. Brack, James J. Collins, Chad Cowan, Thorsten M. Schlaeger, Derrick J. RossiSee AffiliationsHint: Rollover Authors and Affiliations Immune Disease Institute, Program in Cellular and Molecular Medicine, Children's Hospital Boston, Boston, MA 02115, USA Stem Cell Program, Children's Hospital Boston, Boston, MA 02115, USA Manton Center for Orphan Disease Research, Children's Hospital Boston, Boston, MA 02115, USA Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA Center of Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114-2790, USA Department of Biochemistry and Molecular Biology II: Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115, USA Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA Department of Pathology, Harvard Medical School, Boston, MA 02115, USA Department of Biomedical Engineering and Center for BioDynamics, Boston University, Boston, MA 02215, USA Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA Stowers Medical Institute, 185 Cambridge Street, Boston, MA 02114, USA Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA Howard Hughes Medical Institute Division of Hematology/Oncology, Brigham and Women's Hospital, Boston, MA 02115, USA Corresponding author These authors contributed equally to this work
Highlights
•Modified mRNAs can express reprogramming proteins and evade antiviral response
•Highly efficient derivation of human iPSCs without genomic integration
•RNA-derived iPSCs faithfully recapitulate the properties of human ESCs
•Efficient directed differentiation of iPSCs to differentiated myotubes
Summary
Clinical application of induced pluripotent stem cells (iPSCs) is limited by the low efficiency of iPSC derivation and the fact that most protocols modify the genome to effect cellular reprogramming. Moreover, safe and effective means of directing the fate of patient-specific iPSCs toward clinically useful cell types are lacking. Here we describe a simple, nonintegrating strategy for reprogramming cell fate based on administration of synthetic mRNA modified to overcome innate antiviral responses. We show that this approach can reprogram multiple human cell types to pluripotency with efficiencies that greatly surpass established protocols. We further show that the same technology can be used to efficiently direct the differentiation of RNA-induced pluripotent stem cells (RiPSCs) into terminally differentiated myogenic cells. This technology represents a safe, efficient strategy for somatic cell reprogramming and directing cell fate that has broad applicability for basic research, disease modeling, and regenerative medicine.
Monday, November 01, 2010
vitamine D
Van: Robin Kramp [mailto:robinkramp@zonnet.nl]
Verzonden: maandag 1 november 2010 10:26
Aan: 'roodbont@tiscali.nl'
Onderwerp: RE: Medscape: 20-Year Study: Aspirin Reduces Colon Cancer ...
Vitamine-D-tekort bij gebruik van statines
In het Nederlands Tijdschrift voor Geneeskunde stond onlangs een artikel waarin melding werd gemaakt over de onderschatting van de spierklachten die worden veroorzaakt door gebruik van statines (cholesterolverlagers).
Rond de 10% van de statinegebruikers blijkt last te hebben van spierklachten. Frequent gerapporteerde klachten zijn spierpijn in de bovenarmen, bovenbenen, dijen, kuiten en rug. Ook pijnlijke pezen, nachtelijke spierkrampen, vermoeidheid en spierzwakte komen veel voor.
Uit Amerikaans onderzoek blijkt dat deze bijwerking vaak samenhangt met de vitamine-D-status en dat dit effect omkeerbaar is door middel van vitamine-D-suppletie.
Bij patiënten met statinegebruik en spierklachten blijkt dat 64% van deze patiënten een lage vitamine-D-status (< 80 nmol 25(OH)D/l in het serum) heeft. Als deze patiënten vervolgens vitamine-D-suppletie krijgen (en het statinegebruik wordt gecontinueerd), blijkt dat bij 92% van de patiënten de spierklachten verdwijnen.
Meer aandacht is nodig voor de interactie tussen statines en vitamine D.
Verzonden: maandag 1 november 2010 10:26
Aan: 'roodbont@tiscali.nl'
Onderwerp: RE: Medscape: 20-Year Study: Aspirin Reduces Colon Cancer ...
Vitamine-D-tekort bij gebruik van statines
In het Nederlands Tijdschrift voor Geneeskunde stond onlangs een artikel waarin melding werd gemaakt over de onderschatting van de spierklachten die worden veroorzaakt door gebruik van statines (cholesterolverlagers).
Rond de 10% van de statinegebruikers blijkt last te hebben van spierklachten. Frequent gerapporteerde klachten zijn spierpijn in de bovenarmen, bovenbenen, dijen, kuiten en rug. Ook pijnlijke pezen, nachtelijke spierkrampen, vermoeidheid en spierzwakte komen veel voor.
Uit Amerikaans onderzoek blijkt dat deze bijwerking vaak samenhangt met de vitamine-D-status en dat dit effect omkeerbaar is door middel van vitamine-D-suppletie.
Bij patiënten met statinegebruik en spierklachten blijkt dat 64% van deze patiënten een lage vitamine-D-status (< 80 nmol 25(OH)D/l in het serum) heeft. Als deze patiënten vervolgens vitamine-D-suppletie krijgen (en het statinegebruik wordt gecontinueerd), blijkt dat bij 92% van de patiënten de spierklachten verdwijnen.
Meer aandacht is nodig voor de interactie tussen statines en vitamine D.
Lyme teken
From Reuters Health Information
Few Doctors Believe in "Chronic" Lyme Disease
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OA knee and hand—Can you provide effective pain relief with a topical option?
Learn about a topical treatment for OA knee and hand pain.
Review efficacy data
By Frederik Joelving
NEW YORK (Reuters Health) Oct 25 - Despite lots of media attention, "chronic" Lyme disease is not a widely accepted diagnosis -- even in Connecticut, where the tick-borne Borrelia burgdorferi infection was first discovered.
That's according to a new statewide survey, reported September 1st in the Journal of Pediatrics, that found just 2% of doctors in Connecticut said they had diagnosed and treated the controversial chronic version of the disease. And half the respondents said they don't believe the condition exists.
"Chronic Lyme disease" refers to disease that persists after appropriate treatment - not to recurrent or persistent arthritis that can last for years in untreated patients (often called "late Lyme disease").
"Chronic Lyme disease is used in North America and increasingly in Europe as a diagnosis for patients with persistent pain, neurocognitive symptoms, fatigue, or all of these symptoms, with or without clinical or serologic evidence of previous early or late Lyme disease," according to a 2007 review article in the New England Journal of Medicine. The lead author of that review, Dr. Henry Feder of the University of Connecticut Health Center in Farmington, is one of the two researchers who conducted the current survey.
If you are online a lot, "you think every doctor in Connecticut believes in chronic Lyme," said Dr. Feder.
"What the poll shows is that's not true," he added.
Most medical groups agree that Lyme disease should be treated with oral antibiotics only for a few weeks (usually doxycycline). But some doctors and patient groups argue that longer courses, lasting months or even years, may be necessary if symptoms linger. Some of these clinicians say chronic Lyme disease may be incurable.
Two years ago, the controversy over the existence of chronic Lyme disease entered the courts. The Infectious Diseases Society of America (IDSA) barred physicians who advocate longer treatment courses from a guidelines panel, and Connecticut's attorney general sued the IDSA.
While the IDSA guidelines were upheld by an independent review panel last April, that didn't end the debate.
"There is a very small number of doctors who are very active on the Internet as well as politically and have a different point of view than the evidence dictates," said Dr. Feder, who is a member of the IDSA but was not involved in establishing the guidelines.
According to the National Institute of Allergy and Infectious Diseases, rigorous clinical studies have shown that prolonged antibiotic treatment is of little benefit to patients who have no signs of infection, but still suffer from fatigue and headaches.
According to the Centers for Disease Control and Prevention, about 38,000 confirmed or probable cases of Lyme disease occurred in the U.S. in 2008, mainly in Wisconsin, Minnesota and the Northeast where the ticks that carry it are widespread. In Connecticut, the rate translated to about 78 cases per 100,000 residents.
Dr. Feder and Dr. Michael Johnson sent their survey to a random sample of 33% of primary care doctors in Connecticut and received answers from roughly 40%. The two authors report that half of the 285 respondents didn't believe in the existence of chronic Lyme disease. Slightly fewer said they were undecided but had not diagnosed or treated any patients with chronic Lyme disease.
Dr. Daniel Cameron, an outspoken opponent of the IDSA guidelines and past-president of the International Lyme and Associated Diseases Society, which was formed by advocates for chronic Lyme disease, could not be reached for comment.
Lyme expert Dr. Raymond Dattwyler, of New York Medical College in Valhalla, said he wasn't surprised by the poll results.
"Chronic Lyme disease is just not accepted by the vast majority of physicians," he told Reuters Health. "The majority of people who get the diagnosis of chronic Lyme disease have either depression, fibromyalgia or another chronic illness."
"If you look at the symptoms that they report to be associated with chronic Lyme," he added, "population studies have shown those are very common complaints among the general population."
"The tragedy is that sometimes really serious, treatable diseases are ignored."
J Pediatr. Posted September 1, 2010. Abstract
Few Doctors Believe in "Chronic" Lyme Disease
Other Health Care Provider Rating: 0 stars ( 0 Votes )
Rate This Article:
0 stars
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* Email This Email this
processing....
Information from Industry
OA knee and hand—Can you provide effective pain relief with a topical option?
Learn about a topical treatment for OA knee and hand pain.
Review efficacy data
By Frederik Joelving
NEW YORK (Reuters Health) Oct 25 - Despite lots of media attention, "chronic" Lyme disease is not a widely accepted diagnosis -- even in Connecticut, where the tick-borne Borrelia burgdorferi infection was first discovered.
That's according to a new statewide survey, reported September 1st in the Journal of Pediatrics, that found just 2% of doctors in Connecticut said they had diagnosed and treated the controversial chronic version of the disease. And half the respondents said they don't believe the condition exists.
"Chronic Lyme disease" refers to disease that persists after appropriate treatment - not to recurrent or persistent arthritis that can last for years in untreated patients (often called "late Lyme disease").
"Chronic Lyme disease is used in North America and increasingly in Europe as a diagnosis for patients with persistent pain, neurocognitive symptoms, fatigue, or all of these symptoms, with or without clinical or serologic evidence of previous early or late Lyme disease," according to a 2007 review article in the New England Journal of Medicine. The lead author of that review, Dr. Henry Feder of the University of Connecticut Health Center in Farmington, is one of the two researchers who conducted the current survey.
If you are online a lot, "you think every doctor in Connecticut believes in chronic Lyme," said Dr. Feder.
"What the poll shows is that's not true," he added.
Most medical groups agree that Lyme disease should be treated with oral antibiotics only for a few weeks (usually doxycycline). But some doctors and patient groups argue that longer courses, lasting months or even years, may be necessary if symptoms linger. Some of these clinicians say chronic Lyme disease may be incurable.
Two years ago, the controversy over the existence of chronic Lyme disease entered the courts. The Infectious Diseases Society of America (IDSA) barred physicians who advocate longer treatment courses from a guidelines panel, and Connecticut's attorney general sued the IDSA.
While the IDSA guidelines were upheld by an independent review panel last April, that didn't end the debate.
"There is a very small number of doctors who are very active on the Internet as well as politically and have a different point of view than the evidence dictates," said Dr. Feder, who is a member of the IDSA but was not involved in establishing the guidelines.
According to the National Institute of Allergy and Infectious Diseases, rigorous clinical studies have shown that prolonged antibiotic treatment is of little benefit to patients who have no signs of infection, but still suffer from fatigue and headaches.
According to the Centers for Disease Control and Prevention, about 38,000 confirmed or probable cases of Lyme disease occurred in the U.S. in 2008, mainly in Wisconsin, Minnesota and the Northeast where the ticks that carry it are widespread. In Connecticut, the rate translated to about 78 cases per 100,000 residents.
Dr. Feder and Dr. Michael Johnson sent their survey to a random sample of 33% of primary care doctors in Connecticut and received answers from roughly 40%. The two authors report that half of the 285 respondents didn't believe in the existence of chronic Lyme disease. Slightly fewer said they were undecided but had not diagnosed or treated any patients with chronic Lyme disease.
Dr. Daniel Cameron, an outspoken opponent of the IDSA guidelines and past-president of the International Lyme and Associated Diseases Society, which was formed by advocates for chronic Lyme disease, could not be reached for comment.
Lyme expert Dr. Raymond Dattwyler, of New York Medical College in Valhalla, said he wasn't surprised by the poll results.
"Chronic Lyme disease is just not accepted by the vast majority of physicians," he told Reuters Health. "The majority of people who get the diagnosis of chronic Lyme disease have either depression, fibromyalgia or another chronic illness."
"If you look at the symptoms that they report to be associated with chronic Lyme," he added, "population studies have shown those are very common complaints among the general population."
"The tragedy is that sometimes really serious, treatable diseases are ignored."
J Pediatr. Posted September 1, 2010. Abstract
