For patients with chronic major depression that does not sufficiently respond to other treatments, a single injection of botulinum neurotoxin into the glabellar muscle of the forehead to relieve frown lines appears to lead to strong and sustained improvement of the depression.
Tillmann Kruger, MD, Associate Professor in the Department of Psychiatry, Social Psychiatry and Psychotherapy at Hannover Medical School in Hannover, Germany, reported here at the 20th European Congress of Psychiatry that these findings support the concept that facial musculature not only expresses mood states but also affects mood.
He explained that frowning expresses negative emotions such as anger, fear, or sadness. A facial feedback hypothesis says that the frown itself reinforces negative emotions, with the implication that suppressing frowning will help to relieve the negative emotions.
"The theory is pretty old, and it says that many or most of the emotions we have develop somewhere in the brain, and some of them are expressed in your face, for example...and this is again received and sent back to the central nervous system by this proprioceptive feedback," he told Medscape Medical News. He said that in some cases of depression, there are signs of increased glabellar muscle activity.
Single injection
To test the hypothesis, Dr. Kruger and colleague Axel Wollmer, MD, of the Psychiatric Hospital of the University of Basel in Switzerland, performed a randomized, double-blind, placebo-controlled trial using an injection of onabotulinumtoxinA (29 units for women, almost 40 units for men) or placebo into a total of 5 points in the procerus and corrugator muscles in the glabellar region of 30 patients with chronic major depression.
Patients were 25 to 65 years old; they had a moderate to severe glabellar frown line and were undergoing stable treatment with antidepressant medication. The primary endpoint was the Hamilton Depression Rating Scale (HAM-D17, an expert-rated instrument) score 6 weeks after treatment compared with baseline.
The investigators found that a single injection session led to diminished frown lines (P < .001) and to strong and sustained improvement in the depression in these patients who had not responded sufficiently to previous treatments.
At 2 weeks, patients showed an improvement of mood, with a -5 point change on the self-reported Beck Depression Inventory (BDI) scale. There was only a slight improvement of mood in the placebo-treated patients.
The botulinum-treated patients showed an almost 50% reduction in their HAM-D17 scores from 22 at baseline to about 12 at 6 weeks compared with only a 9% improvement in the HAM-D17 scores for the placebo group. The reductions in HAM-D17 scores were significant at all times points from 2 to 16 weeks (P < .001 at 16 weeks); similarly, the BDI score at 16 weeks was significantly improved compared with baseline (P < .01).
More than 80% of the botulinum group had at least a partial response vs only a 25% partial response in the placebo group. A full response, meaning at least a 50% reduction on the HAM-D17 scale, occurred in 60% of the botulinum group but in only 13% of the placebo group. A full remission at 6 weeks, being a HAM-D17 score of 7 or less, occurred in 33% of the botulinum group.
Dr. Kruger noted that typically among depressed patients, there is a fairly strong placebo effect, which he did not see in his patients. He explained the low rate and level of improvement in the placebo group as a result of the high proportion of participants with chronic depression and resistance to multiple previous therapies. Botulinum was later offered to patients in the placebo group. No patients dropped out of the study in either group.
Facial feedback theory
"Not all glabellar frown lines have to disappear to guarantee a good psychological effect," Dr. Kruger said, and full remissions have been observed in patients with residual frown lines.
"We think, regarding possible mechanisms, that the reduced proprioceptive feedback — the facial feedback theory — is the most important one. I think this is something that works 24 hours per day," he added.
There may also be some effect of social feedback in that friends and family may tell patients that they do not look so angry.
Dr. Kruger said that botulinum is able to travel in a retrograde direction via nerve fibers to the central nervous system, but given the small amount of drug used, he thought this mechanism would not explain the effects seen.
However, when asked whether a more appropriate control than placebo injections would be botulinum injections into a cranial muscle that did not affect frowning, he agreed that such a procedure would be a good control for a possible effect of botulinum not related to the relief of frown lines. Therefore, it is still possible that botulinum acted through a mechanism other than relief of frown lines.
Dr. Kruger said the study also showed that botulinum injections had excellent safety and tolerability. "It may be even economic because it's only a single injection [session], and it works for more than 16 weeks, as we have seen," he said, but the study needs to be validated in larger trials.
At present, botulinum is not indicated for treatment of depression. "But Botox has an indication to treat glabellar frown lines...and if someone has frown lines and has a depression and says, 'I want to have them away, these frown lines,' you can, of course, use it," Dr. Kruger noted.
Not ready for prime time
Session moderator Frank Padberg, MD, Associate Professor and Director of the Brain Stimulation Laboratory in the Department of Psychiatry and Psychotherapy at Ludwig Maximilian University in Munich, Germany, commented to Medscape Medical News that the study was a pilot with a small sample size, "so you have to be, of course, cautious in interpreting the results, and it's of course difficult to have a good placebo control because the patients are aware that something changes or changes not," with botulinum or with placebo.
"So the placebo response in rather treatment-resistant patients was quite low, and that's often a problem in pilot studies" because of less than adequate blinding, so "a significant effect comes out due to a low placebo response rate," he said. "But the data were interesting, and the effect was quite robust of the injection leading to improvement over a period of 6 weeks...so the basic principle of treatment seemed to work in this group."
"The mechanisms of action are not clear," Dr. Padberg cautioned. "That is the main issue, but it is an interesting pilot work." In addition, patients in the study had to have frown lines, so it is a question of how many patients may be eligible for this sort of treatment. And he feels it is still too early to use this therapy outside of clinical trials.
Source: http://www.medscape.com/viewarticle/760131?sssdmh=dm1.767078&src=nldne
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Thursday, 15 March 2012
Oral Vitamin D boosts intranasal steroid effect in rhinitis
Adding an oral vitamin D supplement to regular intranasal corticosteroid dosing can improve symptoms of seasonal allergic rhinitis beyond that seen with corticosteroids alone in patients who are not vitamin D deficient, according to study results presented here at the American Academy of Allergy, Asthma and Immunology 2012 Annual Meeting.
The findings add to a number of reports at the meeting suggesting that vitamin D supplementation might be beneficial in patients with allergies.
"Vitamin D has been shown to play a role in innate immunity and the generation of antimicrobial peptides. It also has a number of immunological effects on T cells, dendritic cells, and macrophages," said James Lane, BA, a researcher at the University of Chicago, Illinois, who presented the findings.
These findings must be viewed with caution, said lead investigator Fuad Baroody, MD, a pediatric head and neck surgeon at the University of Chicago. "This was a small study, a pilot study. More work needs to be done before people can run out and add vitamin D to intranasal steroids," he said in an interview with Medscape Medical News.
In the double-blind placebo-controlled study, patients 18 to 45 years of age with seasonal allergic rhinitis received fluticasone propionate 200 µg/day, and were randomized to receive either vitamin D 4000 IU/day for 2 weeks (n = 17) or placebo (n = 18).
Subjects had at least a 2-year history of seasonal allergic rhinitis and a positive skin test to tree, grass, and/or ragweed.
At baseline, serum 25-hydroxy-vitamin D levels were within the normal range and similar in the vitamin D and placebo groups (29.6 vs 29.4 ng/dL). After 2 weeks, levels in the vitamin D group rose significantly from baseline to 37.2 ng/dL (P = .001); in the placebo group, there was no rise.
"There's variation on what people consider appropriate levels of vitamin D," explained Dr. Baroody. "Most recommendations are for levels around 30 or so. These were not vitamin-deficient people, but we bumped it up a little bit to within a still reasonable range, and nobody had side effects from having too much vitamin D."
According to daily self-rated nasal symptoms, including sneezing, nasal congestion, and drip, subjects in both groups noted significant daytime improvements from baseline.
However, subjects in the vitamin D group noted a decreased symptom score of 6.9 points from baseline, which was statistically significant and superior to the 3.7 point drop in the placebo group (P = .04).
"Just giving vitamin D on top created a significant drop — almost a 50% drop," said Dr. Baroody. "The magnitude is impressive, actually. If that is duplicated in a big trial, it would be pretty spectacular."
Nighttime symptoms were not presented at the meeting, but Dr. Baroody said they were "not as spectacular." As a result, the reduction in 24-hour symptom relief was not statistically different between the vitamin D and placebo groups (11.3 vs 7.6 points; P = .09).
Similarly, although there was a statistically significant improvement from baseline in quality of life in both groups (P = .0028), there was no significant difference between the vitamin D and placebo groups (2.5 vs 2.0 points).
"A change of 0.5 is considered to be clinically meaningful, and both groups had improvements well beyond that," said Lane.
In response to a comment from the audience, Dr. Baroody acknowledged that perhaps the real strength of vitamin D supplementation in this group was not in better, but rather in faster, symptom control; all measures showed patients in the vitamin D group responding within 2 days and sustaining their response level.
"That's an interesting way of looking at it. I will examine that in more detail," he said.
"I think people don't really know what the vitamin D story is," Rachel Miller, MD, associate professor of medicine in pediatrics and environmental health sciences at Columbia University Medical Center in New York City, told Medscape Medical News.
"My bias is to do a randomized trial and see what vitamin D supplementation does, because most of the work so far has been observational. I know people are already doing it, but I personally look forward to more evidence from randomized trials."
Source: http://www.medscape.com/viewarticle/760054?sssdmh=dm1.766045&src=nldne
Check out a range of affordable high-dose vitamin D3 here:
The findings add to a number of reports at the meeting suggesting that vitamin D supplementation might be beneficial in patients with allergies.
"Vitamin D has been shown to play a role in innate immunity and the generation of antimicrobial peptides. It also has a number of immunological effects on T cells, dendritic cells, and macrophages," said James Lane, BA, a researcher at the University of Chicago, Illinois, who presented the findings.
These findings must be viewed with caution, said lead investigator Fuad Baroody, MD, a pediatric head and neck surgeon at the University of Chicago. "This was a small study, a pilot study. More work needs to be done before people can run out and add vitamin D to intranasal steroids," he said in an interview with Medscape Medical News.
In the double-blind placebo-controlled study, patients 18 to 45 years of age with seasonal allergic rhinitis received fluticasone propionate 200 µg/day, and were randomized to receive either vitamin D 4000 IU/day for 2 weeks (n = 17) or placebo (n = 18).
Subjects had at least a 2-year history of seasonal allergic rhinitis and a positive skin test to tree, grass, and/or ragweed.
At baseline, serum 25-hydroxy-vitamin D levels were within the normal range and similar in the vitamin D and placebo groups (29.6 vs 29.4 ng/dL). After 2 weeks, levels in the vitamin D group rose significantly from baseline to 37.2 ng/dL (P = .001); in the placebo group, there was no rise.
"There's variation on what people consider appropriate levels of vitamin D," explained Dr. Baroody. "Most recommendations are for levels around 30 or so. These were not vitamin-deficient people, but we bumped it up a little bit to within a still reasonable range, and nobody had side effects from having too much vitamin D."
According to daily self-rated nasal symptoms, including sneezing, nasal congestion, and drip, subjects in both groups noted significant daytime improvements from baseline.
However, subjects in the vitamin D group noted a decreased symptom score of 6.9 points from baseline, which was statistically significant and superior to the 3.7 point drop in the placebo group (P = .04).
"Just giving vitamin D on top created a significant drop — almost a 50% drop," said Dr. Baroody. "The magnitude is impressive, actually. If that is duplicated in a big trial, it would be pretty spectacular."
Nighttime symptoms were not presented at the meeting, but Dr. Baroody said they were "not as spectacular." As a result, the reduction in 24-hour symptom relief was not statistically different between the vitamin D and placebo groups (11.3 vs 7.6 points; P = .09).
Similarly, although there was a statistically significant improvement from baseline in quality of life in both groups (P = .0028), there was no significant difference between the vitamin D and placebo groups (2.5 vs 2.0 points).
"A change of 0.5 is considered to be clinically meaningful, and both groups had improvements well beyond that," said Lane.
In response to a comment from the audience, Dr. Baroody acknowledged that perhaps the real strength of vitamin D supplementation in this group was not in better, but rather in faster, symptom control; all measures showed patients in the vitamin D group responding within 2 days and sustaining their response level.
"That's an interesting way of looking at it. I will examine that in more detail," he said.
"I think people don't really know what the vitamin D story is," Rachel Miller, MD, associate professor of medicine in pediatrics and environmental health sciences at Columbia University Medical Center in New York City, told Medscape Medical News.
"My bias is to do a randomized trial and see what vitamin D supplementation does, because most of the work so far has been observational. I know people are already doing it, but I personally look forward to more evidence from randomized trials."
Source: http://www.medscape.com/viewarticle/760054?sssdmh=dm1.766045&src=nldne
Check out a range of affordable high-dose vitamin D3 here:
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Monday, 5 March 2012
Vitamin D: Low levels linked to depression
A large cross-sectional study of adults suggests a link between low vitamin D levels and depressive symptoms, particularly in individuals with a history of depression.
Because the relationship between low vitamin D levels and depression was stronger in those with a prior history of depression, "it may be more of a marker for relapse than for new-onset," senior investigator E. Sherwood Brown, MD, PhD, head of the psychoneuroendocrine research program at the University of Texas Southwestern Medical Center, Dallas, told Medscape Medical News.
The study was published in the November 2011 issue of Mayo Clinic Proceedings. It involved 12,594 participants (4005 women and 8595 men) from the prospective Cooper Center Longitudinal Study (CCLS). Participants' mean age was 51.7 years. A total of 1563 participants had a history of depression; 11,031 did not."Our findings suggest that screening for vitamin D levels in depressed patients — and perhaps screening for depression in people with low vitamin D levels — might be useful," Dr. Brown added in a university-issued statement.
All participants completed baseline examinations that included measurement of serum 25-hydroxyvitamin D [25(OH)D] levels and an assessment using the Center for Epidemiologic Studies Depression Scale (CES-D). A CES-D score of 10 or higher was defined as evidence of depression.
According to the investigators, low vitamin D levels were common in the sample as a whole, with 50.7% of participants having levels in either the deficient range [25(OH]D < 20 ng/mL], according to Institute of Medicine recommendations, or the insufficient range [25(OH)D < 30 ng/mL]. Mean vitamin D levels did not differ significantly between those with and without a history of depression.
Biologically plausible
In the overall sample, higher vitamin D levels were associated with a decreased risk for current depression, based on CES-D scores. The odds ratio [OR] was 0.92 (95% confidence interval [CI], 0.87 - 0.97; P < .002) for each 10 ng/mL increase in 25(OH)D.
When study participants with and without a history of depression were analyzed separately, the link was stronger in those with a prior history of depression (OR, 0.90; 95% CI, 0.82 - 0.98; P = .02) and was not significant in those without such a history (OR, 0.95; 95% CI, 0.89 - 1.02; P = .17).
It is biologically plausible that vitamin D could have a role in depression, Dr. Brown and colleagues note in their article. Vitamin D "appears to be important for brain health and may be involved in the pathogenesis of depression." Yet, studies to date have yielded conflicting results.
Three small clinical studies found an association between low 25(OH)D levels and depression, whereas the 5 population-based studies that have explored the association yielded more mixed results.
Positive studies include 1 involving 1282 older adults from Amsterdam that found 14% lower 25(OH)D levels in those with major and minor depression relative to control participants (Hoogendijk et al, Arch Gen Psych, 2008;65:508-512).
A British national survey of older adults showed clinical vitamin D deficiency [25(OH)D level < 10 ng/mL] was significantly associated with depressive symptoms, independent of age, sex, social class, physical health status, and season. Milder states of vitamin D deficiency were not strongly associated with depression in older adults (Psychosom Med , 2010;72:608-612.)
Largest data set to date
Negative studies include 1 from China involving 3262 adults aged 50 to 70 years. In this study, depressive symptoms were less prevalent in those in the top tertile of 25(OH)D concentrations compared with those in the lowest tertile. The association disappeared, however, after controlling for geographic location (Pan et al, J Affect Disord, 2009;118:608-612).
Additionally, a study in 527 Japanese adults aged 21 to 67 years found no significant association between CES-D scores and 25(OH)D levels (Nanri et al, Eur J Clin Nutr, 2009;63:1444-1447).
A study of 3916 adults in the United States showed that 25(OH)D levels and parathyroid hormone levels were not significantly associated with depressive symptoms after adjusting for several potential confounding factors (Zhao et al, Br J Nutr, 20120;104:1696-1702).
The current study, Dr. Brown told Medscape Medical News, represents the largest data set to investigate this issue and, importantly, unlike prior studies, it included a subanalysis by history of depression.
"This subset analysis may shed light on why there were conflicting results in earlier studies because the populations were not assessed on the basis of prior history of depression," he and his colleagues write.
Nonetheless, he points out that "it's a cross-sectional study, and the old saying is true that correlation does not mean causation." Additional research is needed to determine the nature and direction of the association. "Right now, we don't really know whether low vitamin D makes you depressed or whether being depressed makes you have low vitamin D," Dr. Brown said.
"Studies looking at vitamin D supplementation in depressed people with low vitamin D to see if that in itself would help with depressive symptoms would help answer some of those questions," Dr. Brown commented.
Slow acting
Vijay K. Ganji, PhD, RD, of the College of Health and Human Sciences, Georgia State University in Atlanta, who was not involved in the study, agrees. "We need more randomized trials to see if taking vitamin D really helps lowering the episodes of depression," he told Medscape Medical News.
To date, there have been only a few small trials of vitamin D supplementation in various depressed populations, with mixed results. In 2008, a placebo-controlled study from Norway found that supplementation with high doses of vitamin D (20,000 or 40,000 IU vitamin D per week) for 1 year seemed to ameliorate depressive symptoms in adults (Jorde et al, J Intern Med, 2008;264:599-609).
In 2009, in a study of 9 women with depressive symptoms and serum vitamin D levels < 40 ng/mL, vitamin D3 supplementation was associated with an increase in serum vitamin D levels (by 27 ng/mL on average) and a decline in depressive symptoms, as measured using the Beck Depression Inventory–II, of an average of 10 points (Shipowick et al, Appl Nurs Res, 2009).
Last year, however, as reported by Medscape Medical News, in a large study of women aged 70 years and older, those who received a high dose of vitamin D3 (500,000 IU) once a year for up to 5 years did not show any improvement in symptoms of depression (Sanders et al, Br J Psychiatry, 2011;198:357-364).
"One thing that complicates trials is that if you give someone vitamin D, it takes a long time for it to have much effect, as vitamin D levels go up and down very slowly; it probably wouldn't be a fast antidepressant," said Dr. Brown.
Zinc decreases mortality in children with pneumonia
In a study conducted in Africa, children aged 6 to 59 months who had severe pneumonia had reduced mortality when receiving zinc in addition to standard antibiotics, a new study has found. In addition, the reduction in mortality was greater among HIV-infected than non-HIV-infected children.
Maheswari G. Srinivasan, from the Department of Pediatrics and Child Health at the School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda, and colleagues reported the findings in an article published online February 8 in BMC Medicine.
"Given these results, zinc could be considered for use as adjunct therapy for severe pneumonia, especially among Highly Active Antiretroviral Therapy naïve HIV infected children in our environment," the authors conclude.
According to the researchers, acute respiratory tract infections is the most common cause of morbidity and mortality in children younger than 5 years of age, and the "burden of acute lower respiratory tract infections is 2 to 10 times more common in developing than in developed countries."
The results with zinc supplementation in this setting have been mixed. "One randomized controlled study from Bangladesh showed that zinc adjunct therapy accelerated recovery of children with severe pneumonia," the authors note, "but other studies have shown no effect," and "no studies have assessed the impact of zinc adjunct therapy on case fatality of children with pneumonia."
To evaluate this issue, the researchers randomly assigned children aged 6 to 59 months who had severe pneumonia to receive either zinc once daily for 7 days (n = 176; 20 mg for children aged 12 months or older and 10 mg for younger children) or a placebo once daily for 7 days (n = 176).
Children also received standard antibiotics for severe pneumonia and were assessed every 6 hours for oxygen saturation, respiratory rate, and temperature.
Among the children receiving zinc, 7 (4.0%) died compared with 21 patients (11.9%) in the placebo group. This represented nearly a 70% reduction in mortality risk in favor of zinc supplementation (relative risk [RR] reduction, 0.67; 95% confidence interval [CI], 0.24 - 0.85).
The greatest risk reduction was seen in HIV-infected children. Among HIV-infected children, case fatality was 7 of 27 children in the placebo group vs 0 of 28 children in the zinc group (RR, 0.1; 95% CI, 0.0 - 1.0).
In contrast, in HIV-uninfected children, no difference in case fatality was observed with zinc vs placebo: case fatality was 7/127 (5.5%) with placebo vs 5/129 (3.9%) among HIV-uninfected children receiving zinc (RR, 0.7; 95% CI, 0.2 - 2.2).
Maheswari G. Srinivasan, from the Department of Pediatrics and Child Health at the School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda, and colleagues reported the findings in an article published online February 8 in BMC Medicine.
"Given these results, zinc could be considered for use as adjunct therapy for severe pneumonia, especially among Highly Active Antiretroviral Therapy naïve HIV infected children in our environment," the authors conclude.
According to the researchers, acute respiratory tract infections is the most common cause of morbidity and mortality in children younger than 5 years of age, and the "burden of acute lower respiratory tract infections is 2 to 10 times more common in developing than in developed countries."
The results with zinc supplementation in this setting have been mixed. "One randomized controlled study from Bangladesh showed that zinc adjunct therapy accelerated recovery of children with severe pneumonia," the authors note, "but other studies have shown no effect," and "no studies have assessed the impact of zinc adjunct therapy on case fatality of children with pneumonia."
To evaluate this issue, the researchers randomly assigned children aged 6 to 59 months who had severe pneumonia to receive either zinc once daily for 7 days (n = 176; 20 mg for children aged 12 months or older and 10 mg for younger children) or a placebo once daily for 7 days (n = 176).
Children also received standard antibiotics for severe pneumonia and were assessed every 6 hours for oxygen saturation, respiratory rate, and temperature.
Among the children receiving zinc, 7 (4.0%) died compared with 21 patients (11.9%) in the placebo group. This represented nearly a 70% reduction in mortality risk in favor of zinc supplementation (relative risk [RR] reduction, 0.67; 95% confidence interval [CI], 0.24 - 0.85).
The greatest risk reduction was seen in HIV-infected children. Among HIV-infected children, case fatality was 7 of 27 children in the placebo group vs 0 of 28 children in the zinc group (RR, 0.1; 95% CI, 0.0 - 1.0).
In contrast, in HIV-uninfected children, no difference in case fatality was observed with zinc vs placebo: case fatality was 7/127 (5.5%) with placebo vs 5/129 (3.9%) among HIV-uninfected children receiving zinc (RR, 0.7; 95% CI, 0.2 - 2.2).
According to the researchers, the excess risk with placebo was substantially greater among HIV-positive children than in HIV-negative children (absolute risk reduction, 26/100 children vs 2/100 children, respectively; P = .006).
They estimated that 13 patients needed to be treated to avert 1 death, and that children who received the placebo were 3 times more likely to die compared with those who received zinc.
"There are two key findings in this study: overall, zinc supplementation in these children significantly decreased case fatality, but did not reduce the time to normalization of the parameters for disease severity," the authors conclude.
According to the researchers, zinc supplementation might increase the immune response by boosting phagocytosis and averting apoptosis of T lymphocytes in HIV-infected patients.
They add that zinc deficiency (present in from 20% to 69% of children in this setting) "compromises immunity through a number of mechanisms, such as T cell dysfunction and dysregulation of intracellular killing."
They estimated that 13 patients needed to be treated to avert 1 death, and that children who received the placebo were 3 times more likely to die compared with those who received zinc.
"There are two key findings in this study: overall, zinc supplementation in these children significantly decreased case fatality, but did not reduce the time to normalization of the parameters for disease severity," the authors conclude.
According to the researchers, zinc supplementation might increase the immune response by boosting phagocytosis and averting apoptosis of T lymphocytes in HIV-infected patients.
They add that zinc deficiency (present in from 20% to 69% of children in this setting) "compromises immunity through a number of mechanisms, such as T cell dysfunction and dysregulation of intracellular killing."
Tai Chi improves balance, reduces falls in Parkinson's
Results of a randomized trial show that training patients with Parkinson's disease in the ancient art of tai chi reduced balance impairments, improving function and reducing falls.
"We found that a program of twice-weekly tai chi for 24 weeks, as compared with a resistance-training program or a stretching program, was effective in improving postural stability and other functional outcomes in patients with mild-to-moderate Parkinson's disease," Fuzhong Li, PhD, from the Oregon Research Institute in Eugene, and colleagues report.
Patients using tai chi also significantly reduced falls without any increase in serious adverse events, and these improvements were maintained 3 months after the intervention.
The authors conclude that, "tai chi appears to be effective as a stand-alone behavioral intervention designed to improve postural stability and functional ability in people with Parkinson's disease."
The trial, supported by the National Institute of Neurological Disorders and Stroke, was published in the February 9 issue of the New England Journal of Medicine.
Exercise integral to management
Exercise is an integral part of the management of patients with Parkinson's, as it has been shown to slow deterioration of motor function and prolong functional independence, the researchers write. Benefits also have been shown with resistance-based exercise, but it requires equipment and safety monitoring.
Tai chi has been shown to improve strength, balance, and physical function, as well as prevent falls in older adults, the researchers note. Two pilot trials in patients with Parkinson's disease suggest that this approach could also improve axial symptoms such as postural stability. The current trial aimed to establish whether a tailored tai chi program could provide these benefits in a larger population.
"Because the program emphasized rhythmic weight shifting, symmetric foot stepping, and controlled movements near the limits of stability, we hypothesized that tai chi would be more effective in improving postural stability in limits-of-stability tasks than a resistance-based exercise regimen or low-impact stretching (control)," they write.
A total of 195 patients with Parkinson's who were Hoehn and Yahr scale stages 1 to 4 were assigned to a program of tai chi, resistance training, or stretching. The Hoehn and Yahr scale ranges from 1 to 5, with higher stages indicating more severe disease.
Patients attended two 60-minute exercise sessions per week for 24 weeks. The primary outcomes were changes from baseline in maximum excursion and directional control, both of which are indicators of postural stability, measured using computerized dynamic posturography. Scores on both measures range from 0% to 100%, with higher scores indicating better balance or control. Secondary outcomes included measures of gait and strength, functional reach and timed up-and-go tests, motor scores on the United Parkinson's Disease Rating Scale, and number of falls.
The researchers found that the tai chi group performed significantly better than the other 2 groups on the primary outcomes of maximum excursion and directional control, and that the differences remained significant after adjustment for covariates.
On all secondary outcomes, tai chi proved superior to stretching. It improved stride length and functional reach compared with resistance training and also reduced falls compared with stretching, but not compared with resistance training.
"No serious adverse events were observed during tai chi training," the researchers conclude, "indicating the safety and usefulness of this intervention for persons with Parkinson's disease."
"We found that a program of twice-weekly tai chi for 24 weeks, as compared with a resistance-training program or a stretching program, was effective in improving postural stability and other functional outcomes in patients with mild-to-moderate Parkinson's disease," Fuzhong Li, PhD, from the Oregon Research Institute in Eugene, and colleagues report.
Patients using tai chi also significantly reduced falls without any increase in serious adverse events, and these improvements were maintained 3 months after the intervention.
The authors conclude that, "tai chi appears to be effective as a stand-alone behavioral intervention designed to improve postural stability and functional ability in people with Parkinson's disease."
The trial, supported by the National Institute of Neurological Disorders and Stroke, was published in the February 9 issue of the New England Journal of Medicine.
Exercise integral to management
Exercise is an integral part of the management of patients with Parkinson's, as it has been shown to slow deterioration of motor function and prolong functional independence, the researchers write. Benefits also have been shown with resistance-based exercise, but it requires equipment and safety monitoring.
Tai chi has been shown to improve strength, balance, and physical function, as well as prevent falls in older adults, the researchers note. Two pilot trials in patients with Parkinson's disease suggest that this approach could also improve axial symptoms such as postural stability. The current trial aimed to establish whether a tailored tai chi program could provide these benefits in a larger population.
"Because the program emphasized rhythmic weight shifting, symmetric foot stepping, and controlled movements near the limits of stability, we hypothesized that tai chi would be more effective in improving postural stability in limits-of-stability tasks than a resistance-based exercise regimen or low-impact stretching (control)," they write.
A total of 195 patients with Parkinson's who were Hoehn and Yahr scale stages 1 to 4 were assigned to a program of tai chi, resistance training, or stretching. The Hoehn and Yahr scale ranges from 1 to 5, with higher stages indicating more severe disease.
Patients attended two 60-minute exercise sessions per week for 24 weeks. The primary outcomes were changes from baseline in maximum excursion and directional control, both of which are indicators of postural stability, measured using computerized dynamic posturography. Scores on both measures range from 0% to 100%, with higher scores indicating better balance or control. Secondary outcomes included measures of gait and strength, functional reach and timed up-and-go tests, motor scores on the United Parkinson's Disease Rating Scale, and number of falls.
The researchers found that the tai chi group performed significantly better than the other 2 groups on the primary outcomes of maximum excursion and directional control, and that the differences remained significant after adjustment for covariates.
On all secondary outcomes, tai chi proved superior to stretching. It improved stride length and functional reach compared with resistance training and also reduced falls compared with stretching, but not compared with resistance training.
"No serious adverse events were observed during tai chi training," the researchers conclude, "indicating the safety and usefulness of this intervention for persons with Parkinson's disease."
Saturday, 3 March 2012
Trans fat increases stroke risk in postmenopausal women
Postmenopausal women whose diet is high in trans fats, found in fried foods and packaged products, are at higher risk for certain types of ischemic stroke, a new analysis shows.
Using data from the Women's Health Initiative Observational Study (WHI-OS), researchers show a positive association between trans fat intake and incidence of ischemic stroke that persisted even after adjustment for major lifestyle, cardiovascular, and dietary factors.
However, the association appeared to be reversed with aspirin use in this population.
Previous research showed evidence of a link between trans fatty acids and coronary heart disease but there hasn't been much investigation into trans fats and ischemic stroke, said one of this study's authors, Ka He, MD, associate professor, Departments of Nutrition and Epidemiology, University of North Carolina Gillings School of Global Public Health in Chapel Hill. "This study is the first to confirm that trans fatty acids are a risk factor of ischemic stroke."
Fat intake
The study included 87,025 women aged 50 to 79 years with no history of stroke or transient ischemic attack (TIA) at baseline who were enrolled in the WHI-OS, a cohort of postmenopausal women recruited between 1994 and 1998.
At enrollment and at a 3-year follow-up visit, the women completed a food-frequency questionnaire (FFQ). Among other things, the FFQ asked about frequency of intake of fats in meat and dairy, fats used in cooking, added fats, and reduced-fat foods, over the previous 3 months.
Researchers gained information on ischemic stroke through self-reports during annual medical history updates. Additional details were gleaned from medical charts, brain imaging, and death certificates.
Over a follow-up of 663,041 person-years, there were 1049 cases of ischemic stroke. After age and race were considered, trans fat intake was associated with a higher risk for stroke (hazard ratio [HR] for the fifth vs first quintile of trans fat intake, 1.49; 95% confidence interval [CI], 1.22 - 1.82; P for trend = .0002).
The association remained significant after adjustment for major lifestyle variables, such as body mass index (BMI), smoking, and physical activity; for health conditions, including history of coronary heart disease, atrial fibrillation, or diabetes; and for potential dietary confounders, such as fruit and vegetable intake and use of vitamin E (HR, 1.39; 95% CI, 1.08 - 1.79; P for trend = .048).
There was no evidence of interaction between trans fat intake and statin use, alcohol intake, or hormone replacement therapy use.
In addition, no significant association was seen for other types of fat or total fat, raising doubts that dietary fats act through dyslipidemia to cause cerebral infarction. However, this lack of association wasn't too surprising to Dr. He. "More and more studies suggest that types of fat are more important than total fat," he said.
This study did show some increased risk with saturated fats, but it wasn't significant. "It's possible that saturated fats can increase the risk to some extent but the magnitude may not be big enough to show statistical significance," said Dr. He.
Although he expected there might be an inverse association between the healthier polyunsaturated fats and strokes, "in our study, we just didn't see anything," said Dr. He. "Some other previous studies showed the same results."
The association between trans fats and ischemic stroke remained positive (HR, 1.11) after TIAs were included as ischemic stroke cases. This, said Dr. He, may indicate similarities between these types of stroke or suggest that trans fatty acids affect both with a similar mechanism. There were no or weak associations between cholesterol and ischemic stroke.
Stroke types
Women with higher trans fat intake had elevated incidence of lacunar (there were 269 such strokes in this study) and cardioembolic strokes (n = 234), but not atherothrombotic infarctions (n = 101), the subtype of ischemic stroke associated with elevated total cholesterol and decreased high-density lipoprotein cholesterol.
Although the study was one of the largest of its kind and included more than 1000 cases of stroke, this may still not have provided enough statistical power. "Even though we see increased risk for those subtypes of stroke, statistically it was not significant, the major reason probably being that we don't have enough cases," said Dr. He.
The researchers also investigated the possibility that participants changed their diet if they developed a health condition. But although slightly attenuated, the association remained significant when updates on participants' dietary information was stopped after a reported diagnosis of diabetes mellitus, myocardial infarction, revascularization, peripheral artery disease, or carotid artery disease.
Aspirin use appeared to lower the stroke risk. Among 67,288 non–aspirin users, the HR for ischemic stroke in the highest versus lowest quintile of trans fat intake was 1.66, but among 19,736 aspirin users, it was 0.95. "That suggests that aspirin use may counteract the potential adverse effect of trans fatty acids on ischemic stroke," commented Dr. He.
According to the authors, platelet aggregability increases with advancing age, possibly more so among women than men. In addition to functioning as an antiplatelet agent, aspirin also reduces inflammation, they said.
Caution against "Overselling"
Asked to comment on these results, Michael J. Schneck, MD, professor of neurology and neurosurgery, associate director, Stroke Unit, Loyola University Medical Center, Maywood, Illinois, and a member of the American Academy of Neurology, said the study is intriguing and the first to confirm the observation that increased trans fat intake affects stroke risk. The study also supports the argument for a healthy diet, said Dr. Schneck.
However, he told Medscape Medical News, as with other observational diet studies, this one has limitations. For one thing, the dietary information was self-reported, and, although the study accounted for such risk factors as smoking and physical inactivity, the participants with the highest trans fat intake were also the least healthy.
"I would be careful in the overselling of this paper," said Dr. Schneck. "This is a real phenomenon but my question is, how much of a real phenomenon?" He added that the findings need to be replicated in other populations.
Dr. Schneck said he found it interesting that large-vessel strokes were not associated with trans fat intake. "I could understand that trans fats are linked to higher risk with lacunar infarction, but I was surprised that they were not associated with other subtypes of stroke. That's a bit confusing to me based on their arguments that trans fats are associated with inflammation."
He said he was not in agreement on the authors' theory that the stroke prevention benefit of aspirin may be unique to postmenopausal women because of their greater risk for platelet aggregability. "The observation that aspirin is better for ischemic stroke in women but not men, and that aspirin is better in heart disease in men but not women, is just a reflection of the nature of the various cohort studies and is driven by quirks of the randomized trials."
He stressed that cutting trans fats from the diet is solid dietary advice for everyone, not just older women. "It really isn't that you can eat trans fats until you go into menopause and then have to clean up your act," he said. "You don't wait until menopause to stop eating trans fats; you start before that."
Related posts:
Chocolate lovers less likely to get heart disease or stroke
Magnesium may lower stroke risk
More evidence chocolate lowers stroke risk
Processed red meats linked to stroke
Using data from the Women's Health Initiative Observational Study (WHI-OS), researchers show a positive association between trans fat intake and incidence of ischemic stroke that persisted even after adjustment for major lifestyle, cardiovascular, and dietary factors.
However, the association appeared to be reversed with aspirin use in this population.
Previous research showed evidence of a link between trans fatty acids and coronary heart disease but there hasn't been much investigation into trans fats and ischemic stroke, said one of this study's authors, Ka He, MD, associate professor, Departments of Nutrition and Epidemiology, University of North Carolina Gillings School of Global Public Health in Chapel Hill. "This study is the first to confirm that trans fatty acids are a risk factor of ischemic stroke."
Fat intake
The study included 87,025 women aged 50 to 79 years with no history of stroke or transient ischemic attack (TIA) at baseline who were enrolled in the WHI-OS, a cohort of postmenopausal women recruited between 1994 and 1998.
At enrollment and at a 3-year follow-up visit, the women completed a food-frequency questionnaire (FFQ). Among other things, the FFQ asked about frequency of intake of fats in meat and dairy, fats used in cooking, added fats, and reduced-fat foods, over the previous 3 months.
Researchers gained information on ischemic stroke through self-reports during annual medical history updates. Additional details were gleaned from medical charts, brain imaging, and death certificates.
Over a follow-up of 663,041 person-years, there were 1049 cases of ischemic stroke. After age and race were considered, trans fat intake was associated with a higher risk for stroke (hazard ratio [HR] for the fifth vs first quintile of trans fat intake, 1.49; 95% confidence interval [CI], 1.22 - 1.82; P for trend = .0002).
The association remained significant after adjustment for major lifestyle variables, such as body mass index (BMI), smoking, and physical activity; for health conditions, including history of coronary heart disease, atrial fibrillation, or diabetes; and for potential dietary confounders, such as fruit and vegetable intake and use of vitamin E (HR, 1.39; 95% CI, 1.08 - 1.79; P for trend = .048).
There was no evidence of interaction between trans fat intake and statin use, alcohol intake, or hormone replacement therapy use.
In addition, no significant association was seen for other types of fat or total fat, raising doubts that dietary fats act through dyslipidemia to cause cerebral infarction. However, this lack of association wasn't too surprising to Dr. He. "More and more studies suggest that types of fat are more important than total fat," he said.
This study did show some increased risk with saturated fats, but it wasn't significant. "It's possible that saturated fats can increase the risk to some extent but the magnitude may not be big enough to show statistical significance," said Dr. He.
Although he expected there might be an inverse association between the healthier polyunsaturated fats and strokes, "in our study, we just didn't see anything," said Dr. He. "Some other previous studies showed the same results."
The association between trans fats and ischemic stroke remained positive (HR, 1.11) after TIAs were included as ischemic stroke cases. This, said Dr. He, may indicate similarities between these types of stroke or suggest that trans fatty acids affect both with a similar mechanism. There were no or weak associations between cholesterol and ischemic stroke.
Stroke types
Women with higher trans fat intake had elevated incidence of lacunar (there were 269 such strokes in this study) and cardioembolic strokes (n = 234), but not atherothrombotic infarctions (n = 101), the subtype of ischemic stroke associated with elevated total cholesterol and decreased high-density lipoprotein cholesterol.
Although the study was one of the largest of its kind and included more than 1000 cases of stroke, this may still not have provided enough statistical power. "Even though we see increased risk for those subtypes of stroke, statistically it was not significant, the major reason probably being that we don't have enough cases," said Dr. He.
The researchers also investigated the possibility that participants changed their diet if they developed a health condition. But although slightly attenuated, the association remained significant when updates on participants' dietary information was stopped after a reported diagnosis of diabetes mellitus, myocardial infarction, revascularization, peripheral artery disease, or carotid artery disease.
Aspirin use appeared to lower the stroke risk. Among 67,288 non–aspirin users, the HR for ischemic stroke in the highest versus lowest quintile of trans fat intake was 1.66, but among 19,736 aspirin users, it was 0.95. "That suggests that aspirin use may counteract the potential adverse effect of trans fatty acids on ischemic stroke," commented Dr. He.
According to the authors, platelet aggregability increases with advancing age, possibly more so among women than men. In addition to functioning as an antiplatelet agent, aspirin also reduces inflammation, they said.
Caution against "Overselling"
Asked to comment on these results, Michael J. Schneck, MD, professor of neurology and neurosurgery, associate director, Stroke Unit, Loyola University Medical Center, Maywood, Illinois, and a member of the American Academy of Neurology, said the study is intriguing and the first to confirm the observation that increased trans fat intake affects stroke risk. The study also supports the argument for a healthy diet, said Dr. Schneck.
However, he told Medscape Medical News, as with other observational diet studies, this one has limitations. For one thing, the dietary information was self-reported, and, although the study accounted for such risk factors as smoking and physical inactivity, the participants with the highest trans fat intake were also the least healthy.
"I would be careful in the overselling of this paper," said Dr. Schneck. "This is a real phenomenon but my question is, how much of a real phenomenon?" He added that the findings need to be replicated in other populations.
Dr. Schneck said he found it interesting that large-vessel strokes were not associated with trans fat intake. "I could understand that trans fats are linked to higher risk with lacunar infarction, but I was surprised that they were not associated with other subtypes of stroke. That's a bit confusing to me based on their arguments that trans fats are associated with inflammation."
He said he was not in agreement on the authors' theory that the stroke prevention benefit of aspirin may be unique to postmenopausal women because of their greater risk for platelet aggregability. "The observation that aspirin is better for ischemic stroke in women but not men, and that aspirin is better in heart disease in men but not women, is just a reflection of the nature of the various cohort studies and is driven by quirks of the randomized trials."
He stressed that cutting trans fats from the diet is solid dietary advice for everyone, not just older women. "It really isn't that you can eat trans fats until you go into menopause and then have to clean up your act," he said. "You don't wait until menopause to stop eating trans fats; you start before that."
Related posts:
Chocolate lovers less likely to get heart disease or stroke
Magnesium may lower stroke risk
More evidence chocolate lowers stroke risk
Processed red meats linked to stroke
Thursday, 1 March 2012
BPA in food packaging again linked to heart disease
Further evidence that bisphenol A (BPA), a chemical found in plastics often used in the food industry, is linked to heart disease has been reported.
Lead researcher of the current paper, Dr David Melzer (Peninsula College of Medicine and Dentistry, Exeter, UK), commented to heartwire: "This is the third time that BPA has been statistically linked to CHD. I am slightly stunned that this association has come up every time."
He added: "Although there are five billion people around the world ingesting this stuff, we have very little data on its effects in humans. Safety studies were done in rats and mice, but in these animals BPA is excreted quite quickly through the bile. In humans, however, it is excreted through the kidneys. You have to ask why the safety studies were done in rodents when there is such a basic difference here. It is time to do proper drug-style safety studies in humans."
In their paper, which was published online February 21, 2012 in Circulation, Melzer and his colleagues note that BPA is one of the world's highest-production-volume chemicals. "The population is exposed to BPA primarily through packaged food and drink, but also through drinking water, dental sealants, exposure to the skin, and the inhalation of household dust," they write. Melzer added to heartwire : "BPA is found in polycarbonate, which is used in the lining of tin cans and in certain plastics to make them more resilient, such as reusable drink bottles. It tends to leech out more when the plastic is heated, so it is advisable not to warm food in hard plastic containers that might contain polycarbonate."
The latest research used data from a 10-year follow-up of the UK EPIC-Norfolk cohort study and shows that higher urinary concentrations of BPA metabolites are associated with an increased risk of developing coronary artery disease.
This builds on two analyses of data from the US NHANES study, which have previously identified an association between BPA and cardiovascular disease. Melzer explained that the cross-sectional design of the NHANES studies meant that they were effectively "snapshots in time" and that it was theoretically possible that patients with heart disease might have changed their diet and therefore incidentally increased their BPA exposure. "However, the prospective design of the current study shows that such reverse causation cannot account for the association between BPA and coronary disease."
In the current study, the researchers conducted a nested case-control analysis of patients in the EPIC-Norfolk study. They compared baseline urinary BPA concentrations from 758 participants who had gone on to develop cardiovascular disease (cases), and 861 individuals who had remained free from heart disease (controls).
Results showed an 11% increase in risk of developing coronary heart disease with each standard-deviation increase in BPA concentration after adjustment for other factors associated with heart disease.
This is a smaller trend toward harm than suggested by the NHANES data (which showed a 30% to 40% increase in risk per standard-deviation increase in BPA), but BPA concentrations in the UK study (median value 1.3 ng/mL) were much lower than the US study (2.7 ng/mL). "In the two NHANES studies we found an almost identical risk. The EPIC study is a bit weaker, but we took only one urine sample with a 10-year follow-up, so you would expect only a weak association," Melzer commented.
He says the possible mechanism behind this association is unknown, but he points out that BPA binds to estrogen receptors, and laboratory studies have shown it can induce liver and oxidative cellular damage, disrupt pancreatic cell function, and have obesity-promoting effects, all of which could plausibly contribute toward CAD risk.
Lead researcher of the current paper, Dr David Melzer (Peninsula College of Medicine and Dentistry, Exeter, UK), commented to heartwire: "This is the third time that BPA has been statistically linked to CHD. I am slightly stunned that this association has come up every time."
He added: "Although there are five billion people around the world ingesting this stuff, we have very little data on its effects in humans. Safety studies were done in rats and mice, but in these animals BPA is excreted quite quickly through the bile. In humans, however, it is excreted through the kidneys. You have to ask why the safety studies were done in rodents when there is such a basic difference here. It is time to do proper drug-style safety studies in humans."
In their paper, which was published online February 21, 2012 in Circulation, Melzer and his colleagues note that BPA is one of the world's highest-production-volume chemicals. "The population is exposed to BPA primarily through packaged food and drink, but also through drinking water, dental sealants, exposure to the skin, and the inhalation of household dust," they write. Melzer added to heartwire : "BPA is found in polycarbonate, which is used in the lining of tin cans and in certain plastics to make them more resilient, such as reusable drink bottles. It tends to leech out more when the plastic is heated, so it is advisable not to warm food in hard plastic containers that might contain polycarbonate."
The latest research used data from a 10-year follow-up of the UK EPIC-Norfolk cohort study and shows that higher urinary concentrations of BPA metabolites are associated with an increased risk of developing coronary artery disease.
This builds on two analyses of data from the US NHANES study, which have previously identified an association between BPA and cardiovascular disease. Melzer explained that the cross-sectional design of the NHANES studies meant that they were effectively "snapshots in time" and that it was theoretically possible that patients with heart disease might have changed their diet and therefore incidentally increased their BPA exposure. "However, the prospective design of the current study shows that such reverse causation cannot account for the association between BPA and coronary disease."
In the current study, the researchers conducted a nested case-control analysis of patients in the EPIC-Norfolk study. They compared baseline urinary BPA concentrations from 758 participants who had gone on to develop cardiovascular disease (cases), and 861 individuals who had remained free from heart disease (controls).
Results showed an 11% increase in risk of developing coronary heart disease with each standard-deviation increase in BPA concentration after adjustment for other factors associated with heart disease.
This is a smaller trend toward harm than suggested by the NHANES data (which showed a 30% to 40% increase in risk per standard-deviation increase in BPA), but BPA concentrations in the UK study (median value 1.3 ng/mL) were much lower than the US study (2.7 ng/mL). "In the two NHANES studies we found an almost identical risk. The EPIC study is a bit weaker, but we took only one urine sample with a 10-year follow-up, so you would expect only a weak association," Melzer commented.
He says the possible mechanism behind this association is unknown, but he points out that BPA binds to estrogen receptors, and laboratory studies have shown it can induce liver and oxidative cellular damage, disrupt pancreatic cell function, and have obesity-promoting effects, all of which could plausibly contribute toward CAD risk.
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