Too much of a good thing may be just that: too much. That is the conclusion of yet another study, this time a prospective, longitudinal, population-based cohort of Swedish women, looking at calcium intake and cardiovascular mortality.
In this study, high rates of calcium intake were associated with higher all-cause and cardiovascular death rates but not with deaths from stroke, Karl Michaëlsson, MD, PhD, professor in medical epidemiology and senior consultant in orthopedic surgery at Uppsala University in Sweden, and colleagues report in an article published online February 13 in BMJ.
The study is the latest in a series of contentious analyses linking calcium intake and cardiovascular events. Earlier this month, a National Institutes of Health–sponsored study suggested that a high intake of supplemental calcium increased the risk for cardiovascular disease (CVD) death in men, but not women.
However, a commentator notes that the study results suggest that supplements, rather than the intake level, are the problem.
The Swedish mammography cohort, established between 1987 and 1990, followed up 61,433 women born between 1914 and 1948 for a median of 19 years and used registry data to determine outcomes. During that period, there were 11,944 deaths from all causes, of which 3862 were from CVD, 1932 from ischemic heart disease, and 1100 from stroke.
Dietary assessments from food frequency questionnaires at baseline and in 1997 were available for 38,984 women, from which the researchers estimated intakes of dietary and supplemental calcium.
The highest intakes of calcium (>1400 mg/day) were associated with higher all-cause risk for death (after adjustment for age, total energy, vitamin D, and calcium supplement intake, as well as other dietary, physical, and demographic factors) as compared with intakes of 600 to 1000 mg/day (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.17 - 1.67).
Disease-specific mortality risks were elevated for CVD (HR, 1.49; 95% CI, 1.09 - 2.02) and for ischemic heart disease (HR, 2.14; 95% CI, 1.48 - 3.09) at daily calcium intakes above 1400 mg. At calcium intakes less than 600 mg/day, these same mortality risks were also elevated. None of these patterns was apparent for mortality from stroke.
In an email exchange with Medscape Medical News, Dr. Michaëlsson said the association of calcium intake and all-cause and cardiovascular mortality "was especially strong if a high dietary intake of calcium was combined with calcium supplements."
Women with the highest intake of calcium (>1400 mg/day) and who used supplement tablets had an all-cause risk for death 2.5 times higher than women who had similar total intakes but were not taking a supplement.
The authors explain that serum calcium levels "are under tight homeostatic control" and do not normally correlate with the amount of calcium intake. However, low or very high intakes override this control, "causing changes in blood levels of calcium or calciotropic hormones."
Complex Study Results; Weak Findings?
Dr. Michaëlsson also noted that some previous studies have shown a similar relationship between calcium supplements and a higher risk for CVD but were not powered to look at mortality and did not assess the amount of dietary intake of calcium.
He advised that one should not make recommendations on the basis of a single study, but emerging evidence suggests caution about high calcium intake. He also noted that a meta-analysis of randomized trials has shown that calcium supplementation actually increased the rate of hip fracture. "My present recommendation is to avoid calcium supplement use if you have a normal varied diet," he said.
Commenting to Medscape Medical News by email, John Cleland, MD PhD, professor of cardiology at Hull York Medical School in Kingston-upon-Hull, United Kingdom, called the study results "extremely complex...with rather weak findings." He pointed out that in the study there were few patients or events in the group with high calcium intake (n = 1241; 2%), and the events were confined to those women taking supplements (total events, n = 23, of which 16 occurred among women taking any form of calcium supplement).
Women with calcium intakes greater than 1400 mg/day who were taking calcium tablets had an adjusted all-cause mortality rate of 2.57 (95% CI, 1.19 - 5.55) compared with 1.17 (95% CI, 0.97 - 1.41) among women who had similar daily intakes but were not taking supplements. "So, it's not the diet but the pills that are the problem," Dr. Cleland concluded, which is essentially in agreement with what Dr. Michaëlsson said.
Dr. Cleland raised the issues of what else may have been in the calcium pills and why the women were taking them; for example, if they had chronic kidney disease or osteoporosis. He said the article did not provide such information but just referred to a previous paper.
He also pointed out that calcium tablets "have not been shown to reduce fracture rates or improve any other patient outcome that I know of." He recommended that people stop taking calcium supplements "until efficacy/safety is shown," and that this advice "should definitely include those taking them for osteoporosis and should perhaps include those taking them for [chronic kidney disease]." His recommendation? "Having a healthy balanced diet and avoiding water filters that reduce calcium in drinking water is probably best."
Source: http://www.medscape.com/viewarticle/779541?nlid=28503_1301&src=wnl_edit_dail
Welcome to my collection of health articles. Most of them contain little nuggets of health wisdom that we can easily apply to our daily lives. As you can gather, I've been consuming all sorts of supplements over the years, most of them from iherb. They deliver on time (DHL), and prices are good. If you're a first-time buyer, use my code 'pot089' to enjoy up to $10 off.
Thursday 21 February 2013
Wednesday 20 February 2013
Saffron for macular degeneration
Age-related macular degeneration (ARMD) is the primary cause of older age onset partial or sometimes total blindness. Although most common in adults over 50, macular degeneration can occur at any age, though rarely among those under 50.
Macular degeneration mostly affects central vision, forcing people to rely more on less distinct peripheral vision to recognize objects and faces. The macula occupies a small portion of the retina in the back of the eye.
Though small, the macula is the most light sensitive area of the retina, and it permits detailed focus of objects located centrally in the field of vision. There are two classifications of macular degeneration: Dry and wet.
Dry macular degeneration is the most common and least severe. Diminished central vision clarity occurs gradually. It's called dry because there is no capillary leakage in that region of the eye. Wet macular degeneration does involve retina capillary leakage. It's symptoms are usually more severe and worsen rapidly.
Thus far, ophthalmology has little to offer as a remedy for macular degeneration. But ophthalmologists do recommend taking leutin and astaxanthin to slow ARMD's progress or possibly reverse it slightly.
However, recent human clinical research in Italy and Australia has discovered a non-pharmaceutical approach that proved efficacious for improving eyesight with macular degeneration sufferers safely. It is a little pricey though. It's the spice known as saffron.
Saffron is pricier than most other spices because the bulbs must be planted by hand, and the three crimson stigmas or saffron threads have to also be plucked out of each flower by hand.
The Australian clinical trial
Macular degeneration mostly affects central vision, forcing people to rely more on less distinct peripheral vision to recognize objects and faces. The macula occupies a small portion of the retina in the back of the eye.
Though small, the macula is the most light sensitive area of the retina, and it permits detailed focus of objects located centrally in the field of vision. There are two classifications of macular degeneration: Dry and wet.
Dry macular degeneration is the most common and least severe. Diminished central vision clarity occurs gradually. It's called dry because there is no capillary leakage in that region of the eye. Wet macular degeneration does involve retina capillary leakage. It's symptoms are usually more severe and worsen rapidly.
Thus far, ophthalmology has little to offer as a remedy for macular degeneration. But ophthalmologists do recommend taking leutin and astaxanthin to slow ARMD's progress or possibly reverse it slightly.
However, recent human clinical research in Italy and Australia has discovered a non-pharmaceutical approach that proved efficacious for improving eyesight with macular degeneration sufferers safely. It is a little pricey though. It's the spice known as saffron.
Saffron is pricier than most other spices because the bulbs must be planted by hand, and the three crimson stigmas or saffron threads have to also be plucked out of each flower by hand.
The Australian clinical trial
The Australian human study was conducted by Sydney University Professor of Neurology Jonathan Stone. Both this study and the Italian research were similar in scope and dosage. And both conducted a more humane approach to double blind placebo studies with a non-toxic remedy than normally.
The study involved 25 macular degeneration sufferers. Instead of depriving a placebo group from a product that could do something for their ailment, the study switched placebo subjects with saffron subjects half-way through the trial unbeknownst to all involved. The daily dosage was 20 mg of saffron.
The whole study was six months long, so each side of the 25 double blind subjects had three months of improved vision with three months of impaired vision. All 25 were tested for neuron electrical conductivity in the macula and retina, and 23 showed significant improvement. Those 23 also reported they could see much better.
Visual improvement began after only two weeks on saffron. When the saffron group was put onto placebos, they complained that their improved eyesight had begun diminishing again. Conversely, those on placebos for the first half of the trial began seeing better after three months of no improvement.
Professor Stone projects that after a year or more ingesting only 20 mg (milligrams) of saffron daily, vision improvements should stabilize without requiring more saffron dosing.
Stone doesn't know exactly how or why, but he became aware that saffron influences the neuron's genetic code to restore its capacity for healing and protecting neuron cells. Neurons are responsible for transmitting electrical signals or impulses throughout the nervous system.
Professor Stone is looking forward to completing animal studies with saffron for other neurological issues like Parkinson's and Alzheimer's. Then those would go into human clinical trials also.
His results, combined with the Italian study, impressed Professor Stone enough to create his own line of saffron capsules for the market. He qualified it as a safe nutraceutical that shouldn't require any more testing for FDA approval.
Source: http://www.naturalnews.com/039150_saffron_macular_degeneration_cure.html#ixzz2LPB2RnFa
The study involved 25 macular degeneration sufferers. Instead of depriving a placebo group from a product that could do something for their ailment, the study switched placebo subjects with saffron subjects half-way through the trial unbeknownst to all involved. The daily dosage was 20 mg of saffron.
The whole study was six months long, so each side of the 25 double blind subjects had three months of improved vision with three months of impaired vision. All 25 were tested for neuron electrical conductivity in the macula and retina, and 23 showed significant improvement. Those 23 also reported they could see much better.
Visual improvement began after only two weeks on saffron. When the saffron group was put onto placebos, they complained that their improved eyesight had begun diminishing again. Conversely, those on placebos for the first half of the trial began seeing better after three months of no improvement.
Professor Stone projects that after a year or more ingesting only 20 mg (milligrams) of saffron daily, vision improvements should stabilize without requiring more saffron dosing.
Stone doesn't know exactly how or why, but he became aware that saffron influences the neuron's genetic code to restore its capacity for healing and protecting neuron cells. Neurons are responsible for transmitting electrical signals or impulses throughout the nervous system.
Professor Stone is looking forward to completing animal studies with saffron for other neurological issues like Parkinson's and Alzheimer's. Then those would go into human clinical trials also.
His results, combined with the Italian study, impressed Professor Stone enough to create his own line of saffron capsules for the market. He qualified it as a safe nutraceutical that shouldn't require any more testing for FDA approval.
Source: http://www.naturalnews.com/039150_saffron_macular_degeneration_cure.html#ixzz2LPB2RnFa
Tuesday 19 February 2013
Two antihypertensives plus NSAID ups risk of acute kidney injury
Taking two antihypertensive medications--a diuretic and an ACE inhibitor or angiotensin-receptor blocker (ARB)--along with nonsteroidal anti-inflammatory drugs (NSAIDs) significantly increases the risk of hospitalization for acute kidney injury, particularly in the first 30 days of treatment, a new retrospective case-control study demonstrates [1].
And although the absolute risk for individuals is low, physicians and patients need to be aware of this potential problem, and doctors will need to prescribe alternative anti-inflammatory and/or analgesic agents where warranted, say Dr Francesco Lapi (Jewish General Hospital, Montreal, QC) and colleagues in their report published online January 8, 2013 in BMJ.
"More and more patients, especially the elderly, are taking many medications at the same time, and drug-drug interactions are always important. With the size of the population that we have access to now, we are able to study questions we could not address before," senior author Dr Samy Suissa (McGill University, Montreal, QC) told heartwire . "The message to clinicians is to be vigilant during that early period of treatment," he added.
In an editorial accompanying the paper [2], Drs Dorothea Nitsch and Laurie A Tomlinson (London School of Hygiene and Tropical Medicine, UK) agree. "Clinicians must advise patients who are prescribed diuretics, ACE inhibitors, or ARBs of the risks associated with NSAID use, and they must also be vigilant for signs of drug-associated acute kidney injury in all patients," they observe.
"Triple" Therapy Ups Risk of Kidney Injury by 80% in First 30 Days of Use
Clinicians must advise patients who are prescribed diuretics, ACE inhibitors, or ARBs of the risks associated with NSAID use, and they must also be vigilant for signs of drug associated acute kidney injury.
Lapi and colleagues say that acute kidney injury is a major public-health concern, which has been associated with a mortality rate exceeding 50%. To study the question of how often this occurs with concurrent use of antihypertensives and NSAIDs, they used the UKClinical Practice Research Datalink (previously known as the General Practice Research Database)--which is the world's largest computerized store of primary-care records--to assess a cohort of 487 372 users of antihypertensive drugs between 1997 and 2008. This was linked to the Hospital Episodes Statisticsdatabase to see whether a double therapy combination of a diuretic, ACE inhibitor, or ARB with an NSAID or the triple therapy combination of two of those antihypertensives plus an NSAID was associated with increased risk of hospitalization for acute kidney injury.
During a mean follow-up of almost six years, 2215 cases of acute kidney injury were identified (incidence rate of seven per 10 000 person-years), and each was compared with up to 10 matched controls.
Overall, current use of double therapy was not associated with an increased risk of acute kidney injury, but current use of triple therapy--two antihypertensives plus an NSAID--was associated with an increased rate of this end point (rate ratio 1.31, 95% CI 1.12–1.53). And the highest risk was seen in the first 30 days of use (rate ratio 1.82, 95% CI 1.35–2.46). These results remained consistent after adjustment for potential confounders.
"If you are taking two antihypertensive medications--a diuretic and an ACE inhibitor or ARB--and then you add on an NSAID, the adding of the NSAID increases the risk of acute kidney injury, particularly in the first 30 days, so you are identifying some susceptible patients when you expose them to NSAIDs in that first month," Suissa explains.
He adds that those who get through the 30-day period without any problem will likely be fine, "at least in terms of acute kidney injury"; he noted that the study was not designed to assess the issue of chronic renal problems.
But Is "Double" Therapy Safe?
But Nitsch and Tomlinson go on to question the finding that an NSAID added to one of the three antihypertensives is not associated with acute kidney injury.
I don't think we can say we are absolutely confident that [double therapy] is safe, but it is certainly not a high risk.
The confidence intervals for the estimates of risk for double drug combinations were "wide," they note, so the study "probably underestimates the true burden of drug-associated kidney injury. The jury is still out on whether double drug combinations are indeed safe," they state.
Suissa acknowledges that the number of patients taking this double therapy was small, "so we cannot exclude a small increased risk. I don't think we can say we are absolutely confident that it is safe, but it is certainly not a high risk," he told heartwire .
He adds that the study findings are indicative of how hypertension is now being managed. "It's being controlled with two drugs, not just one, and then if you have pain, we will add an NSAID to that. In our cohort of antihypertensive-drug patients, 11% were treated with this triple therapy, which is quite large. We were surprised."
Source: http://www.medscape.com/viewarticle/777349?src=nldne&uac=129655SZ
And although the absolute risk for individuals is low, physicians and patients need to be aware of this potential problem, and doctors will need to prescribe alternative anti-inflammatory and/or analgesic agents where warranted, say Dr Francesco Lapi (Jewish General Hospital, Montreal, QC) and colleagues in their report published online January 8, 2013 in BMJ.
"More and more patients, especially the elderly, are taking many medications at the same time, and drug-drug interactions are always important. With the size of the population that we have access to now, we are able to study questions we could not address before," senior author Dr Samy Suissa (McGill University, Montreal, QC) told heartwire . "The message to clinicians is to be vigilant during that early period of treatment," he added.
In an editorial accompanying the paper [2], Drs Dorothea Nitsch and Laurie A Tomlinson (London School of Hygiene and Tropical Medicine, UK) agree. "Clinicians must advise patients who are prescribed diuretics, ACE inhibitors, or ARBs of the risks associated with NSAID use, and they must also be vigilant for signs of drug-associated acute kidney injury in all patients," they observe.
"Triple" Therapy Ups Risk of Kidney Injury by 80% in First 30 Days of Use
Clinicians must advise patients who are prescribed diuretics, ACE inhibitors, or ARBs of the risks associated with NSAID use, and they must also be vigilant for signs of drug associated acute kidney injury.
Lapi and colleagues say that acute kidney injury is a major public-health concern, which has been associated with a mortality rate exceeding 50%. To study the question of how often this occurs with concurrent use of antihypertensives and NSAIDs, they used the UKClinical Practice Research Datalink (previously known as the General Practice Research Database)--which is the world's largest computerized store of primary-care records--to assess a cohort of 487 372 users of antihypertensive drugs between 1997 and 2008. This was linked to the Hospital Episodes Statisticsdatabase to see whether a double therapy combination of a diuretic, ACE inhibitor, or ARB with an NSAID or the triple therapy combination of two of those antihypertensives plus an NSAID was associated with increased risk of hospitalization for acute kidney injury.
During a mean follow-up of almost six years, 2215 cases of acute kidney injury were identified (incidence rate of seven per 10 000 person-years), and each was compared with up to 10 matched controls.
Overall, current use of double therapy was not associated with an increased risk of acute kidney injury, but current use of triple therapy--two antihypertensives plus an NSAID--was associated with an increased rate of this end point (rate ratio 1.31, 95% CI 1.12–1.53). And the highest risk was seen in the first 30 days of use (rate ratio 1.82, 95% CI 1.35–2.46). These results remained consistent after adjustment for potential confounders.
"If you are taking two antihypertensive medications--a diuretic and an ACE inhibitor or ARB--and then you add on an NSAID, the adding of the NSAID increases the risk of acute kidney injury, particularly in the first 30 days, so you are identifying some susceptible patients when you expose them to NSAIDs in that first month," Suissa explains.
He adds that those who get through the 30-day period without any problem will likely be fine, "at least in terms of acute kidney injury"; he noted that the study was not designed to assess the issue of chronic renal problems.
But Is "Double" Therapy Safe?
But Nitsch and Tomlinson go on to question the finding that an NSAID added to one of the three antihypertensives is not associated with acute kidney injury.
I don't think we can say we are absolutely confident that [double therapy] is safe, but it is certainly not a high risk.
The confidence intervals for the estimates of risk for double drug combinations were "wide," they note, so the study "probably underestimates the true burden of drug-associated kidney injury. The jury is still out on whether double drug combinations are indeed safe," they state.
Suissa acknowledges that the number of patients taking this double therapy was small, "so we cannot exclude a small increased risk. I don't think we can say we are absolutely confident that it is safe, but it is certainly not a high risk," he told heartwire .
He adds that the study findings are indicative of how hypertension is now being managed. "It's being controlled with two drugs, not just one, and then if you have pain, we will add an NSAID to that. In our cohort of antihypertensive-drug patients, 11% were treated with this triple therapy, which is quite large. We were surprised."
Source: http://www.medscape.com/viewarticle/777349?src=nldne&uac=129655SZ
Flu virus can spread up to 6ft, no cough or sneeze required
The influenza virus can spread up to 6 feet from a patient's head via submicron particles during routine hospital care, according to a study of patients admitted to the emergency department (ED) and throughout a tertiary care hospital with influenza-like illness during the 2010 to 2011 influenza season. It was previously thought that the virus traveled only a short distance via large particle droplets during coughing or sneezing. Submicron particles are released in the air during talking and breathing.
Werner E. Bischoff, MD, PhD, an assistant professor in the Section on Infectious Diseases, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, and colleagues published their findings online January 31 inClinical Infectious Diseases.
According to the World Health Organization and the Centers for Disease Control and Prevention, transmission mainly occurs when large-particle respiratory droplets travel a short distance, and face masks worn by healthcare professionals block those particles. Fit-tested respirators are only required when aerosol-generating procedures such as bronchoscopy are performed.
Particle size may affect infection risk and severity on the basis of the virus' ability to travel to the lungs instead of being confined to the upper respiratory tract.
"Protecting [healthcare professionals] against influenza virus requires a clear understanding of how this virus is aerosolized and by whom it is emitted," the authors write.
Investigators enrolled 94 patients with influenza-like illness in the study. They obtained patient history and took nasopharyngeal swab specimens. The researchers then collected quantitative impaction air samples 1 foot or less, 3 feet, and 6 feet from the patient's head during routine care. Rapid test and polymerase chain reaction were used to detect influenza virus.
Of the 94 patients, 61 (65%) were influenza-positive (31 influenza A, 30 influenza B). Of those patients, 26 (43%) emitted influenza virus into room air (13 inpatients and 13 ED patients). Of the emitters, 5 (19%) released up to 32 times more virus than other patients. There were no statistical differences in other characteristics or symptoms.
Higher nasopharyngeal viral loads were found in emitters compared with nonemitters. Patients with increased nasopharyngeal viral load were the only patients in whom coughing and sneezing during air sampling was connected with the release of increased virus into room air (P < .05). Emitters exceeded the airborne 50% human infectious dose of influenza virus at all locations sampled.
All emitters in the study were less likely to report chills and more likely to experience higher illness severity and interference with daily living than nonemitter ED patients (P < .05).
As distance from the patient's head increased (from 1 to 6 feet), the viral load decreased significantly (P < .05). The amount of small particles also increased significantly relative to the amount of large particles. Healthcare professionals were primarily exposed to small influenza virus particles (diameter, < 4.7 μm).
There were no detectable differences between influenza virus types, emitters and superemitters, and patient location.
In an accompanying editorial, Caroline Breese Hall, MD, professor in the Department of Pediatrics and the Department of Medicine at the University of Rochester School of Medicine and Dentistry in New York, notes that more advanced forms of personal protection equipment that effectively block small particles (such as N95 respirators) are expensive and that their use in all influenza-positive patients is "usually not feasible."
"[I]nfection control procedures should be commensurate with the concern generated by the clinical observations of the intensity and severity of the community outbreak. The efficacy of the recommended infection control program, however, is less dependent on which specific procedures are included than on the consistent education of healthcare personnel," Dr. Hall noted. "Included in this should be their vaccination, their compliance with the recommended procedures, and their awareness of the risks of nosocomial infection among patients and personnel."
She concludes, "This study not only adds to our understanding of these risks, but helps define the questions that still need answering."
Dr. Hall died on December 10, 2012, at the age of 73 years. She was internationally known for her work in pediatric infectious diseases.
Source: http://www.medscape.com/viewarticle/778674?nlid=28043_1301&src=wnl_edit_dail&uac=129655SZ
Werner E. Bischoff, MD, PhD, an assistant professor in the Section on Infectious Diseases, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, and colleagues published their findings online January 31 inClinical Infectious Diseases.
According to the World Health Organization and the Centers for Disease Control and Prevention, transmission mainly occurs when large-particle respiratory droplets travel a short distance, and face masks worn by healthcare professionals block those particles. Fit-tested respirators are only required when aerosol-generating procedures such as bronchoscopy are performed.
Particle size may affect infection risk and severity on the basis of the virus' ability to travel to the lungs instead of being confined to the upper respiratory tract.
"Protecting [healthcare professionals] against influenza virus requires a clear understanding of how this virus is aerosolized and by whom it is emitted," the authors write.
Investigators enrolled 94 patients with influenza-like illness in the study. They obtained patient history and took nasopharyngeal swab specimens. The researchers then collected quantitative impaction air samples 1 foot or less, 3 feet, and 6 feet from the patient's head during routine care. Rapid test and polymerase chain reaction were used to detect influenza virus.
Of the 94 patients, 61 (65%) were influenza-positive (31 influenza A, 30 influenza B). Of those patients, 26 (43%) emitted influenza virus into room air (13 inpatients and 13 ED patients). Of the emitters, 5 (19%) released up to 32 times more virus than other patients. There were no statistical differences in other characteristics or symptoms.
Higher nasopharyngeal viral loads were found in emitters compared with nonemitters. Patients with increased nasopharyngeal viral load were the only patients in whom coughing and sneezing during air sampling was connected with the release of increased virus into room air (P < .05). Emitters exceeded the airborne 50% human infectious dose of influenza virus at all locations sampled.
All emitters in the study were less likely to report chills and more likely to experience higher illness severity and interference with daily living than nonemitter ED patients (P < .05).
As distance from the patient's head increased (from 1 to 6 feet), the viral load decreased significantly (P < .05). The amount of small particles also increased significantly relative to the amount of large particles. Healthcare professionals were primarily exposed to small influenza virus particles (diameter, < 4.7 μm).
There were no detectable differences between influenza virus types, emitters and superemitters, and patient location.
In an accompanying editorial, Caroline Breese Hall, MD, professor in the Department of Pediatrics and the Department of Medicine at the University of Rochester School of Medicine and Dentistry in New York, notes that more advanced forms of personal protection equipment that effectively block small particles (such as N95 respirators) are expensive and that their use in all influenza-positive patients is "usually not feasible."
"[I]nfection control procedures should be commensurate with the concern generated by the clinical observations of the intensity and severity of the community outbreak. The efficacy of the recommended infection control program, however, is less dependent on which specific procedures are included than on the consistent education of healthcare personnel," Dr. Hall noted. "Included in this should be their vaccination, their compliance with the recommended procedures, and their awareness of the risks of nosocomial infection among patients and personnel."
She concludes, "This study not only adds to our understanding of these risks, but helps define the questions that still need answering."
Dr. Hall died on December 10, 2012, at the age of 73 years. She was internationally known for her work in pediatric infectious diseases.
Source: http://www.medscape.com/viewarticle/778674?nlid=28043_1301&src=wnl_edit_dail&uac=129655SZ
Tadalafil beneficial for ejaculatory disorders
Tadalafil appears to have wider benefits on sexual function than just improving erections. An integrated analysis of 17 double-blind, randomized, placebo-controlled 12-week trials of the drug as needed in patients with erectile dysfunction showed significant improvements in ejaculatory and orgasmic functions. Benefits were seen across all baseline levels of erectile, ejaculatory, and orgasmic dysfunction severity.
Lead author Darius A. Paduch, MD, PhD, associate professor of urology and reproductive medicine and director of sexual health and medicine at Weill Cornell Medical College in New York City, told Medscape Medical News that men with even mild erectile dysfunction may have disorders of ejaculation and orgasm.
"We need to change our vocabulary in how we think about sexual dysfunction in men, that erection is not the only aspect of sexual dysfunction," he said. "From our study, we actually clearly show that sexual satisfaction is clearly correlated to ability of getting orgasm [and] ability to ejaculate."
In the studies included in this analysis, ejaculatory dysfunction (EjD), orgasmic dysfunction (OD), and satisfaction were determined according to patient responses to specific questions on the International Index of Erectile Function (IIEF), as well as the Sexual Encounter Profile for satisfaction. Of the 3581 participants (mean age, 54.9 years; mean body mass index, 26.8 kg/m2), 1512 had severe EjD, 1812 had severe OD, 50.9% were white, and 39.3% were of Asian descent.
The researchers found that tadalafil is an "extremely powerful modulator" of ejaculatory and orgasmic function, Dr. Paduch said. "Across all the severity of erectile dysfunction...tadalafil was actually able to help with ability to achieve orgasm and ability to ejaculate."
Tadalafil 10 or 20 mg improved ejaculatory function in 66% of men with severe EjD vs 36% of men taking placebo (P < .001). For men with severe OD, 66% taking tadalafil reported improvements vs 35% taking placebo (P < .001). The more severe the EjD or OD, the greater the proportion of men experiencing improvement compared with placebo.
On the basis of this study and another analyzing the efficacy of testosterone for EjD and OD, Dr. Paduch recommends first improving the testosterone level, "and then you can start the patient on 3 months of tadalafil and let them...relax more.... Very often I think that they work so hard [to reach orgasm] that they counteract their arousal because they're all stressed out."
One limitation of the study was the use of the IIEF, which has unknown performance to measure responses to treatment for EjD and OD. Further research is needed to validate the IIEF for these purposes. In addition, Dr. Paduch would like to test tadalafil for these conditions in men who do not have erectile dysfunction.
This study included treatment with tadalafil, so it cannot be determined whether similar effects would occur using the other marketed phosphodiesterase type-5 inhibitors.
"We all see those patients, [but] until the study came [out], nobody really had any proof that anything works," Dr. Paduch concluded.
Asked for independent comment, Joseph Harryhill, MD, assistant clinical professor of urology at the University of Pennsylvania in Philadelphia, told Medscape Medical News, "It is encouraging to see that there has been some progress being made in an area where I think there's been a real lack of research...because we're talking about a condition that is probably underreported." Clinicians, he said, often fail to ask about "disorders of ejaculation such as delay or inability to ejaculate."
He noted that in the study, among men with mild erectile dysfunction, a significant number had ejaculatory problems. "Even in men without erectile dysfunction, the incidence may be greater than 10% of men that have problems with ejaculation," Dr. Harryhill said. "This is definitely a little bit of a breath of fresh air that a medication that we know and we're comfortable with using might also have an indication for treating ejaculatory problems as well."
Source: http://www.medscape.com/viewarticle/778859?nlid=27862_1301&src=wnl_edit_dail&uac=129655SZ
Lead author Darius A. Paduch, MD, PhD, associate professor of urology and reproductive medicine and director of sexual health and medicine at Weill Cornell Medical College in New York City, told Medscape Medical News that men with even mild erectile dysfunction may have disorders of ejaculation and orgasm.
"We need to change our vocabulary in how we think about sexual dysfunction in men, that erection is not the only aspect of sexual dysfunction," he said. "From our study, we actually clearly show that sexual satisfaction is clearly correlated to ability of getting orgasm [and] ability to ejaculate."
In the studies included in this analysis, ejaculatory dysfunction (EjD), orgasmic dysfunction (OD), and satisfaction were determined according to patient responses to specific questions on the International Index of Erectile Function (IIEF), as well as the Sexual Encounter Profile for satisfaction. Of the 3581 participants (mean age, 54.9 years; mean body mass index, 26.8 kg/m2), 1512 had severe EjD, 1812 had severe OD, 50.9% were white, and 39.3% were of Asian descent.
The researchers found that tadalafil is an "extremely powerful modulator" of ejaculatory and orgasmic function, Dr. Paduch said. "Across all the severity of erectile dysfunction...tadalafil was actually able to help with ability to achieve orgasm and ability to ejaculate."
Tadalafil 10 or 20 mg improved ejaculatory function in 66% of men with severe EjD vs 36% of men taking placebo (P < .001). For men with severe OD, 66% taking tadalafil reported improvements vs 35% taking placebo (P < .001). The more severe the EjD or OD, the greater the proportion of men experiencing improvement compared with placebo.
On the basis of this study and another analyzing the efficacy of testosterone for EjD and OD, Dr. Paduch recommends first improving the testosterone level, "and then you can start the patient on 3 months of tadalafil and let them...relax more.... Very often I think that they work so hard [to reach orgasm] that they counteract their arousal because they're all stressed out."
One limitation of the study was the use of the IIEF, which has unknown performance to measure responses to treatment for EjD and OD. Further research is needed to validate the IIEF for these purposes. In addition, Dr. Paduch would like to test tadalafil for these conditions in men who do not have erectile dysfunction.
This study included treatment with tadalafil, so it cannot be determined whether similar effects would occur using the other marketed phosphodiesterase type-5 inhibitors.
"We all see those patients, [but] until the study came [out], nobody really had any proof that anything works," Dr. Paduch concluded.
Asked for independent comment, Joseph Harryhill, MD, assistant clinical professor of urology at the University of Pennsylvania in Philadelphia, told Medscape Medical News, "It is encouraging to see that there has been some progress being made in an area where I think there's been a real lack of research...because we're talking about a condition that is probably underreported." Clinicians, he said, often fail to ask about "disorders of ejaculation such as delay or inability to ejaculate."
He noted that in the study, among men with mild erectile dysfunction, a significant number had ejaculatory problems. "Even in men without erectile dysfunction, the incidence may be greater than 10% of men that have problems with ejaculation," Dr. Harryhill said. "This is definitely a little bit of a breath of fresh air that a medication that we know and we're comfortable with using might also have an indication for treating ejaculatory problems as well."
Source: http://www.medscape.com/viewarticle/778859?nlid=27862_1301&src=wnl_edit_dail&uac=129655SZ
Meditation helps reduce inflammation
Mindfulness meditation techniques designed to reduce emotional reactivity also reduce poststress inflammatory responses and might be useful in chronic inflammatory conditions such as rheumatoid arthritis, psoriasis, inflammatory bowel disease, and asthma, according to a study by Melissa A. Rosenkranz, PhD, and colleagues at the University of Wisconsin-Madison.
In an article published in the January issue ofBrain, Behavior, and Immunity, the authors present a comparison between an 8-week mindfulness-based stress reduction program (MBSR) and an 8-week active control health enhancement program (HEP) that included walking, balance, agility, core strength, nutritional education, and music therapy in 49 community volunteers randomly assigned to 1 of the 2 groups.
The intervention and active-control groups had similar levels of stress-evoked cortisol response and similar reductions in psychological distress, but the group trained in mindfulness-based stress reduction had significantly smaller poststress inflammatory responses.
Dr. Rosenkranz told Medscape Medical News, "Because of the experimental design, we were not able to determine whether both interventions reduced stress-evoked cortisol responses or whether participants simply became habituated to the stressor. It is true to say that the postintervention cortisol responses to the stressor declined an equivalent amount for both groups. The MBSR group had significantly smaller postintervention inflammatory responses compared to the HEP group."
The investigators used the Trier Social Stress Test (TSST) to induce psychological stress and a topical application of capsaicin cream to induce inflammation.
The TSST induces psychological stress by requiring participants to give a 5-minute impromptu speech on a given topic, followed by 5 minutes of mental arithmetic.
According to the authors, "[C]apsaicin-sensitive sensory nerves and the neuropeptides they contain, together with local sympathetic nerves and mast cells, have been identified as important contributors to the relationship between psychological stress and symptom expression in inflammatory skin diseases.... Therefore, in the present study, a capsaicin-induced inflammatory response and an acute laboratory stressor were used as a model in which to investigate psychological stress and neurogenic inflammation in the skin."
Mindfulness-based stress reduction, originally designed for patients with chronic pain, consists of continuously focusing attention on the breath, bodily sensations, and mental content while seated, walking, or practicing yoga. The goal is to focus on the present experience to help change one's relationship to it in a beneficial way.
Although interest in meditation as a means of reducing stress has grown over the years, there has been little evidence to support benefits specific to mindfulness meditation practice. This was the first study designed to control for other therapeutic mechanisms, such as supportive social interaction, expert instruction, or learning new skills.
The researchers measured local inflammation by applying vacuum pressure to the skin of the volar forearm just below the cubital fossa to raise suction blisters. The forearm area, including the acrylic blister template with eight 6-mm holes, was wrapped in a heating pad to facilitate the formation of the blisters, which took an average of 53.6 minutes. The vacuum pressure was removed and fluid was collected from 4 blisters using a tuberculin syringe and immediately frozen for analysis by enzyme-linked immunosorbent assay. The researchers applied capsaicin cream around the perimeter of, but not touching, the remaining 4 blisters for 45 minutes and then extracted and froze fluid from those blisters.
Blister fluid was assayed by enzyme-linked immunosorbent assay for levels of tumor necrosis factor alpha and of interleukin 8 because these cytokines are sensitive to modulation by psychological stress and because neuropeptides released from capsaicin-sensitive nerve endings trigger their release.
Despite the group difference in change in cortisol slope after training, the researchers found no change in cortisol reactivity to the TSST. The researchers were surprised to find that more time spent in MBSR practice was associated with lower blister fluid cytokine levels, whereas more time spent in HEP practice was associated with higher blister fluid cytokine levels.
Dr. Rosenkranz said, "This was not an effect that we predicted, but upon further exploration, it seems that the postintervention potentiation of the flare response in the HEP group was related to increased skin irritability associated with colder, drier winter weather in Wisconsin. The preintervention data collection occurred during warmer months, and the daily temperature on the day of data collection was correlated with the size of the flare response. So you could see this as the MBSR group being protected from that seasonal increase in skin irritability."
Dr. Rosenkranz added, "Key points would be that MBSR may be beneficial to those with chronic inflammatory conditions by changing the way they relate to their condition and their symptoms, and in so doing, may reduce emotional neural reactivity and the contribution of this reactivity to further symptom expression. Our data suggest that those with conditions which have a neurogenic inflammatory component (eg, psoriasis, dermatitis, irritable bowel syndrome, asthma) may benefit more, in terms of decreased inflammatory potential, from this type of intervention."
Alex J. Zautra, PhD, who has studied cognitive behavioral and mindfulness meditation interventions in patients with rheumatoid arthritis, reviewed the study for Medscape Medical News. Dr. Zautra, who was not involved in this inflammation study, is professor of psychology at Arizona State University in Tempe.
Dr. Zautra said, "This is an interesting study, and the authors examine their data thoroughly and with sound understanding of the complexities involved in charting changes in inflammatory responses pre- and postintervention. They are to be commended for using an active treatment group, but missing is a no-contact contract. That absence makes any difference pre- to post- for which the groups do not differ suspect...this is acknowledged, but easily overlooked in their lengthy discussion. The sample size was also small, which makes the chance of chance findings a bit more likely, especially with so many dependent measures. Missing were changes in cytokines and cortisol that could explain the differences in flares between groups pre- to post-. The absence of findings in these putative mechanisms of action casts doubt over the findings that the mindfulness intervention was more beneficial."
Source: http://www.medscape.com/viewarticle/778570?nlid=27864_1301&src=wnl_edit_dail&uac=129655SZ
In an article published in the January issue ofBrain, Behavior, and Immunity, the authors present a comparison between an 8-week mindfulness-based stress reduction program (MBSR) and an 8-week active control health enhancement program (HEP) that included walking, balance, agility, core strength, nutritional education, and music therapy in 49 community volunteers randomly assigned to 1 of the 2 groups.
The intervention and active-control groups had similar levels of stress-evoked cortisol response and similar reductions in psychological distress, but the group trained in mindfulness-based stress reduction had significantly smaller poststress inflammatory responses.
Dr. Rosenkranz told Medscape Medical News, "Because of the experimental design, we were not able to determine whether both interventions reduced stress-evoked cortisol responses or whether participants simply became habituated to the stressor. It is true to say that the postintervention cortisol responses to the stressor declined an equivalent amount for both groups. The MBSR group had significantly smaller postintervention inflammatory responses compared to the HEP group."
The investigators used the Trier Social Stress Test (TSST) to induce psychological stress and a topical application of capsaicin cream to induce inflammation.
The TSST induces psychological stress by requiring participants to give a 5-minute impromptu speech on a given topic, followed by 5 minutes of mental arithmetic.
According to the authors, "[C]apsaicin-sensitive sensory nerves and the neuropeptides they contain, together with local sympathetic nerves and mast cells, have been identified as important contributors to the relationship between psychological stress and symptom expression in inflammatory skin diseases.... Therefore, in the present study, a capsaicin-induced inflammatory response and an acute laboratory stressor were used as a model in which to investigate psychological stress and neurogenic inflammation in the skin."
Mindfulness-based stress reduction, originally designed for patients with chronic pain, consists of continuously focusing attention on the breath, bodily sensations, and mental content while seated, walking, or practicing yoga. The goal is to focus on the present experience to help change one's relationship to it in a beneficial way.
Although interest in meditation as a means of reducing stress has grown over the years, there has been little evidence to support benefits specific to mindfulness meditation practice. This was the first study designed to control for other therapeutic mechanisms, such as supportive social interaction, expert instruction, or learning new skills.
The researchers measured local inflammation by applying vacuum pressure to the skin of the volar forearm just below the cubital fossa to raise suction blisters. The forearm area, including the acrylic blister template with eight 6-mm holes, was wrapped in a heating pad to facilitate the formation of the blisters, which took an average of 53.6 minutes. The vacuum pressure was removed and fluid was collected from 4 blisters using a tuberculin syringe and immediately frozen for analysis by enzyme-linked immunosorbent assay. The researchers applied capsaicin cream around the perimeter of, but not touching, the remaining 4 blisters for 45 minutes and then extracted and froze fluid from those blisters.
Blister fluid was assayed by enzyme-linked immunosorbent assay for levels of tumor necrosis factor alpha and of interleukin 8 because these cytokines are sensitive to modulation by psychological stress and because neuropeptides released from capsaicin-sensitive nerve endings trigger their release.
Despite the group difference in change in cortisol slope after training, the researchers found no change in cortisol reactivity to the TSST. The researchers were surprised to find that more time spent in MBSR practice was associated with lower blister fluid cytokine levels, whereas more time spent in HEP practice was associated with higher blister fluid cytokine levels.
Dr. Rosenkranz said, "This was not an effect that we predicted, but upon further exploration, it seems that the postintervention potentiation of the flare response in the HEP group was related to increased skin irritability associated with colder, drier winter weather in Wisconsin. The preintervention data collection occurred during warmer months, and the daily temperature on the day of data collection was correlated with the size of the flare response. So you could see this as the MBSR group being protected from that seasonal increase in skin irritability."
Dr. Rosenkranz added, "Key points would be that MBSR may be beneficial to those with chronic inflammatory conditions by changing the way they relate to their condition and their symptoms, and in so doing, may reduce emotional neural reactivity and the contribution of this reactivity to further symptom expression. Our data suggest that those with conditions which have a neurogenic inflammatory component (eg, psoriasis, dermatitis, irritable bowel syndrome, asthma) may benefit more, in terms of decreased inflammatory potential, from this type of intervention."
Alex J. Zautra, PhD, who has studied cognitive behavioral and mindfulness meditation interventions in patients with rheumatoid arthritis, reviewed the study for Medscape Medical News. Dr. Zautra, who was not involved in this inflammation study, is professor of psychology at Arizona State University in Tempe.
Dr. Zautra said, "This is an interesting study, and the authors examine their data thoroughly and with sound understanding of the complexities involved in charting changes in inflammatory responses pre- and postintervention. They are to be commended for using an active treatment group, but missing is a no-contact contract. That absence makes any difference pre- to post- for which the groups do not differ suspect...this is acknowledged, but easily overlooked in their lengthy discussion. The sample size was also small, which makes the chance of chance findings a bit more likely, especially with so many dependent measures. Missing were changes in cytokines and cortisol that could explain the differences in flares between groups pre- to post-. The absence of findings in these putative mechanisms of action casts doubt over the findings that the mindfulness intervention was more beneficial."
Source: http://www.medscape.com/viewarticle/778570?nlid=27864_1301&src=wnl_edit_dail&uac=129655SZ
Vitamin C ups kidney stone risk
Men who take ascorbic acid supplements daily (approximately 1000 mg) were at increased risk for first incident cases of kidney stones (rate difference, 147/100,000 compared with men who do not take ascorbic acid supplements). This represents a dose-dependent, 2-fold increased risk for kidney stone formation.
Laura D.K. Thomas, MSc, from the Institute of Environmental Medicine, Division of Nutritional Epidemiology, Karolinska Institutet, Stockholm, Sweden, and colleagues published the results of their large, population-based prospective cohortstudy online February 4 in JAMA Internal Medicine.
The study was performed in the Cohort of Swedish Men and included 48,850 men aged 45 to 79 years. The authors estimated, but were not able to accurately assess, the dose of vitamin C consumed by the men in the study.
The authors controlled for age, education level, body mass index, tea and coffee use, smoking status, hypertension, and diabetes mellitus. They did not control for dehydration, immobilization, use of loop diuretics, corticosteroids, or vitamin D.
They found high-dose (1000 mg) vitamin C to be associated with a single new kidney stone per 680 high-dose users per year. They found no association between multivitamin use and kidney stone risk (relative risk, 0.86; 95% confidence interval, 0.62 - 1.191).
The study included only men, and the authors note that the results may not be generalizable to women.
In an accompanying editorial, Robert H. Fletcher, MD, from Harvard Medical School in Boston, Massachusetts, discussed the benefits and risks of vitamin supplementation. He began his editorial by describing the original purpose of vitamin supplementation, which was to avoid vitamin-deficiency diseases such as pellagra, rickets, and scurvy. Since that time, however, vitamin supplements have been consumed with the intention of preventing or treating chronic diseases.
Treatment with vitamin C, for example, began in the 1700s as a response to the scurvy experienced by sailors who spent months at sea. In the 1900s, the Nobel Laureate Linus Pauling, PhD, proposed that vitamin C was an effective treatment for the common cold, cancer, and cardiovascular disease. Dr. Pauling's enthusiasm for vitamin C inspired numerous clinical trials that were unable to support the use of vitamin D to prevent mortality.
Recently, evidence has been accumulating that vitamin C supplementation may also be unsafe in that it promotes the formation of kidney stones. Results from the current study are consistent with other studies that have linked vitamin C supplementation and kidney stone formation.
Source: http://www.medscape.com/viewarticle/778769?nlid=27860_1301&src=wnl_edit_dail&uac=129655SZ
Laura D.K. Thomas, MSc, from the Institute of Environmental Medicine, Division of Nutritional Epidemiology, Karolinska Institutet, Stockholm, Sweden, and colleagues published the results of their large, population-based prospective cohortstudy online February 4 in JAMA Internal Medicine.
The study was performed in the Cohort of Swedish Men and included 48,850 men aged 45 to 79 years. The authors estimated, but were not able to accurately assess, the dose of vitamin C consumed by the men in the study.
The authors controlled for age, education level, body mass index, tea and coffee use, smoking status, hypertension, and diabetes mellitus. They did not control for dehydration, immobilization, use of loop diuretics, corticosteroids, or vitamin D.
They found high-dose (1000 mg) vitamin C to be associated with a single new kidney stone per 680 high-dose users per year. They found no association between multivitamin use and kidney stone risk (relative risk, 0.86; 95% confidence interval, 0.62 - 1.191).
The study included only men, and the authors note that the results may not be generalizable to women.
In an accompanying editorial, Robert H. Fletcher, MD, from Harvard Medical School in Boston, Massachusetts, discussed the benefits and risks of vitamin supplementation. He began his editorial by describing the original purpose of vitamin supplementation, which was to avoid vitamin-deficiency diseases such as pellagra, rickets, and scurvy. Since that time, however, vitamin supplements have been consumed with the intention of preventing or treating chronic diseases.
Treatment with vitamin C, for example, began in the 1700s as a response to the scurvy experienced by sailors who spent months at sea. In the 1900s, the Nobel Laureate Linus Pauling, PhD, proposed that vitamin C was an effective treatment for the common cold, cancer, and cardiovascular disease. Dr. Pauling's enthusiasm for vitamin C inspired numerous clinical trials that were unable to support the use of vitamin D to prevent mortality.
Recently, evidence has been accumulating that vitamin C supplementation may also be unsafe in that it promotes the formation of kidney stones. Results from the current study are consistent with other studies that have linked vitamin C supplementation and kidney stone formation.
Source: http://www.medscape.com/viewarticle/778769?nlid=27860_1301&src=wnl_edit_dail&uac=129655SZ
Zinc helpful within 24 hours of cold symptoms
When given within 24 hours of onset of symptoms, zinc reduces the duration and severity of the common cold in healthy people, according to the results of a Cochrane systematic review reported online February 16 in the Cochrane Database of Systematic Reviews.
Zinc supplements
"This review strengthens the evidence for zinc as a treatment for the common cold," said lead author Dr. Meenu Singh, from the Post Graduate Institute of Medical Education and Research in Chandigarh, India, in a news release. "However, at the moment, it is still difficult to make a general recommendation, because we do not know very much about the optimum dose, formulation or length of treatment."
To evaluate the effect of zinc on common cold symptoms, the reviewers searched CENTRAL (2010, Issue 2), which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to May week 3, 2010), and EMBASE (1974 to June 2010). Inclusion criteria were randomized, double-blind, placebo-controlled trials in which zinc was used for 5 or more consecutive days to treat the common cold, or for 5 or months or longer for prevention. Data were independently extracted and trial quality examined by 2 reviewers.
The search identified 13 therapeutic trials enrolling a total of 966 participants, and 2 preventive trials enrolling a total of 394 participants, that met selection criteria. Zinc intake was associated with a significant decrease in duration of common cold symptoms (standardized mean difference [SMD], −0.97; 95% confidence interval [CI], −1.56 to −0.38; P = .001), as well as in severity (SMD, −0.39; 95% CI, −0.77 to −0.02; P = .04).
The proportion of participants symptomatic after 7 days of treatment was lower in the zinc group vs the control group (odds ratio [OR], 0.45; 95% CI, 0.2 - 1.00; P = .05). The zinc group also fared better than the control group in incidence rate ratio (IRR) for development of a cold (IRR, 0.64; 95% CI, 0.47 - 0.88; P = .006), school absence (P = .0003), and prescription of antibiotics (P < .00001).
However, overall adverse events were higher in the zinc group (OR, 1.59; 95% CI, 0.97 - 2.58; P = .06), as were bad taste (OR, 2.64; 95% CI, 1.91 - 3.64; P < .00001) and nausea (OR, 2.15; 95% CI, 1.44 - 3.23; P = .002).
"Our review only looked at zinc supplementation in healthy people," Dr. Singh said. "But it would be interesting to find out whether zinc supplementation could help asthmatics, whose asthma symptoms tend to get worse when they catch a cold."
Limitations of this review also include those inherent in the individual studies, such as placebo-blinding adequately described in only 6 trials, and allocation concealment unclear in 5 studies.
"[U]nlike trials relying on experimentally-induced rhinoviral colds, findings from large community-based trials will address issues relating to the diversity of and generalisability to the common cold," the review authors conclude. "In addition, given its toxicological profile, the potential for zinc to induce adverse effects at the doses participants are required to take also needs to be determined."
Source: http://www.medscape.com/viewarticle/737654
Zinc supplements
"This review strengthens the evidence for zinc as a treatment for the common cold," said lead author Dr. Meenu Singh, from the Post Graduate Institute of Medical Education and Research in Chandigarh, India, in a news release. "However, at the moment, it is still difficult to make a general recommendation, because we do not know very much about the optimum dose, formulation or length of treatment."
To evaluate the effect of zinc on common cold symptoms, the reviewers searched CENTRAL (2010, Issue 2), which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to May week 3, 2010), and EMBASE (1974 to June 2010). Inclusion criteria were randomized, double-blind, placebo-controlled trials in which zinc was used for 5 or more consecutive days to treat the common cold, or for 5 or months or longer for prevention. Data were independently extracted and trial quality examined by 2 reviewers.
The search identified 13 therapeutic trials enrolling a total of 966 participants, and 2 preventive trials enrolling a total of 394 participants, that met selection criteria. Zinc intake was associated with a significant decrease in duration of common cold symptoms (standardized mean difference [SMD], −0.97; 95% confidence interval [CI], −1.56 to −0.38; P = .001), as well as in severity (SMD, −0.39; 95% CI, −0.77 to −0.02; P = .04).
The proportion of participants symptomatic after 7 days of treatment was lower in the zinc group vs the control group (odds ratio [OR], 0.45; 95% CI, 0.2 - 1.00; P = .05). The zinc group also fared better than the control group in incidence rate ratio (IRR) for development of a cold (IRR, 0.64; 95% CI, 0.47 - 0.88; P = .006), school absence (P = .0003), and prescription of antibiotics (P < .00001).
However, overall adverse events were higher in the zinc group (OR, 1.59; 95% CI, 0.97 - 2.58; P = .06), as were bad taste (OR, 2.64; 95% CI, 1.91 - 3.64; P < .00001) and nausea (OR, 2.15; 95% CI, 1.44 - 3.23; P = .002).
"Our review only looked at zinc supplementation in healthy people," Dr. Singh said. "But it would be interesting to find out whether zinc supplementation could help asthmatics, whose asthma symptoms tend to get worse when they catch a cold."
Limitations of this review also include those inherent in the individual studies, such as placebo-blinding adequately described in only 6 trials, and allocation concealment unclear in 5 studies.
"[U]nlike trials relying on experimentally-induced rhinoviral colds, findings from large community-based trials will address issues relating to the diversity of and generalisability to the common cold," the review authors conclude. "In addition, given its toxicological profile, the potential for zinc to induce adverse effects at the doses participants are required to take also needs to be determined."
Source: http://www.medscape.com/viewarticle/737654
Aspirin plus Clopidogrel cuts stroke risk
A relatively short course of aspirin plus clopidogrel immediately after sustaining a transient ischemic attack (TIA) or minor stroke outperforms aspirin alone in cutting the risk for a subsequent stroke, and it does this without a significant increased risk of major bleeding complications, results of a large trial show.
Results of the Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial were presented here at the International Stroke Conference (ISC) 2013.
The CHANCE trial, carried out exclusively in China, is a few steps ahead of a similar trial, the Platelet Oriented Inhibition in New TIA and stroke (POINT) trial, now enrolling mostly in the United States.
Although CHANCE was a "well done" trial and its results showed "a larger treatment effect," it's important to note that healthcare in China is different from that in the United States, said CHANCE co–principal investigator, S. Claiborne Johnston, MD, PhD, professor, neurology, and director, Stroke Service, University of California, San Francisco.
"Secondary prevention practices are not as robust there as they are in Europe and in North America, and that could have impacted the trial," he told Medscape Medical News. "Also, usually genetic differences don't matter, but in this case, they might because there are differences in polymorphisms that affect clopidogrel metabolism in Asian populations."
For these reasons, although American neurologists might see the CHANCE trial as a signal to go ahead and use combined therapy, "I think it's wise for us to wait for a confirmatory trial outside of China, said Dr. Johnston, who is also co–principal investigator of the POINT trial.
High Risk for Hemorrhage
The study enrolled 5170 patients at least 40 years of age who had sustained a TIA or minor stroke. Within 24 hours of their symptom onset, they were randomly assigned to 1 of 2 groups: aspirin (1 day loading dose of 75 to 300 mg, followed by 75 mg/day) plus placebo, or the same aspirin regimen plus clopidogrel (loading dose of 300 mg followed by 75 mg/day).
Patients in the combination group were taken off aspirin at 21 days because of the concern that Chinese patients, as with other Asian populations, are at relatively high risk for hemorrhage. "Frankly, that belief comes from epidemiological studies, but the epidemiology may just reflect underlying risk factors and not a true propensity for it," said Dr. Johnston. He pointed out that the studies testing this have not been in the acute period.
The study showed that stroke occurred less frequently in those receiving both aspirin and clopidogrel. At 90 days, the hazard ratio (HR) for survival free of stroke — either ischemic or hemorrhagic — in the combination group was 0.68 (95% confidence interval [CI], 0.57 - 0.81; P < .001).
For the secondary outcome of combined events (stroke, myocardial infarction, vascular death), the HR was 0.69 (95% CI, 0.58 - 0.82; P < .001). The risk for hemorrhagic stroke was the same in the 2 groups (0.3%).
Notably, severe bleeding events occurred at a similar rate in the 2 groups (0.2% in each). Although mild bleeding occurred more often in the combination group (1.2% versus 0.7%), Dr. Johnston noted that these events included nose bleeds. "We did not see a signal that the combination was unsafe."
Both aspirin and clopidogrel affect platelets, but through different pathways. "Together, the 2 are much more powerful than either one alone," said Dr. Johnston.
CHANCE was the first trial to focus on the acute period in TIA and minor stroke, which Dr. Johnston emphasized is not being seen nearly enough in the emergency department. "People with TIA and minor stroke are not coming in acutely or they're calling the office and being seen in clinic," he said. "We need to remind people that this really is an emergency and it should be treated right away."
Asked whether the combination therapy would be an acceptable approach for more severe strokes, Dr. Johnston said it's impossible to know "where to draw the line." The researchers will do more subgroup analyses looking at stroke severity, but Dr. Johnston pointed out that "there was no difference between the TIA and stroke in terms of rates of hemorrhagic stroke or in the efficacy of the combination."
Compared with elsewhere in the world, the risk for stroke is very high in China. "There are a whole lot more strokes in China than there are in the US and even if you add Europe, you still have more strokes in China," said Dr. Johnston.
Healthcare Differences
Because the trial was so large and because standards for clinical research have improved dramatically in China, the CHANCE results are "incredibly important" and should have a major effect on public health around the world, said Dr. Johnston. However, there are important differences between healthcare in China and that in the United States.
For example, Dr. Johnston noted that about two thirds of the Chinese patients in the study had hypertension and less than half were receiving any drug for hypertension during follow-up. Undertreatment, he said, could "certainly" affect the absolute effect size that's seen in the trial.
It's probably wise to await what happens with the POINT trial before changing treatment approaches here in North America, said Dr. Johnston, who is that study's principal investigator. Interim POINT results will be available in May, he said. "That will provide an opportunity to say it's very important to continue POINT or it's not important to continue POINT."
The POINT trial, which is about a third of the way through recruitment, differs slightly from CHANCE, said Dr. Johnston. For example, it includes a higher loading dose of clopidogrel and requires enrollment within 12 hours instead of 24 hours. As well, patients in the combination group continue with aspirin for 90 days instead of stopping at 21 days as in the CHANCE study.
Dr. Johnston pointed out a graph showing times for survival free of stroke for the treatment groups. "Most of the separation in the 2 curves occurs just in the first couple of days, so certainly by 21 days, the curves are almost parallel."
POINT includes mainly centers in the United States, although some sites have been added internationally.
The idea of comparing aspirin plus clopidogrel in a North American trial dates back more than a decade, but the researchers ran into funding difficulties when the drug manufacturer pulled its backing. This, said Dr. Johnston, substantially delayed the start of the trial.
When asked about next steps for CHANCE, Dr. Johnston said the Chinese researchers will look at ancillary studies of biomarkers and subtyping based on vascular imaging. As well, they plan to provide outcomes at 1 year that will include results related to cognition.
Helpful Information
Invited to comment on the CHANCE trial results, Larry B. Goldstein, MD, professor, medicine, Division of Neurology, and director, Duke Stroke Center, Duke University, Durham, North Carolina, and a POINT investigator, said the information is "quite helpful" and could eventually alter the current treatment practice, which is to being aspirin alone. "This would suggest that aspirin with clopidogrel over a relatively short course may have some benefit."
He added that the "key" is the short course of the combination aspirin plus clopidogrel treatment. He pointed out that other trials, including SPS3 and MATCH (Management of ATherothrombosis with Clopidogrel in High-risk patients), found that long-term combinations are associated with an increased risk for major bleeding complications.
"Over the longer term, the addition of a more potent antiplatelet drug, or combinations in general, seem to carry a much higher risk of bleeding that attenuates any benefit they have in reducing ischemic stroke risk," said Dr. Goldstein. "In our current guidelines, there is actually a contraindication for the combination for long-term secondary stroke prevention."
The lack of increased risk of bleeding, at least in the short term, "is quite encouraging," said Dr. Goldstein. He added that bleeding complications are more of a concern in Asia than in the United States, which has a much more ethnically diverse population and where the proportion of Asians is relatively low.
Source: http://www.medscape.com/viewarticle/779089?nlid=28263_1301&src=wnl_edit_dail&uac=129655SZ
Results of the Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial were presented here at the International Stroke Conference (ISC) 2013.
The CHANCE trial, carried out exclusively in China, is a few steps ahead of a similar trial, the Platelet Oriented Inhibition in New TIA and stroke (POINT) trial, now enrolling mostly in the United States.
Although CHANCE was a "well done" trial and its results showed "a larger treatment effect," it's important to note that healthcare in China is different from that in the United States, said CHANCE co–principal investigator, S. Claiborne Johnston, MD, PhD, professor, neurology, and director, Stroke Service, University of California, San Francisco.
"Secondary prevention practices are not as robust there as they are in Europe and in North America, and that could have impacted the trial," he told Medscape Medical News. "Also, usually genetic differences don't matter, but in this case, they might because there are differences in polymorphisms that affect clopidogrel metabolism in Asian populations."
For these reasons, although American neurologists might see the CHANCE trial as a signal to go ahead and use combined therapy, "I think it's wise for us to wait for a confirmatory trial outside of China, said Dr. Johnston, who is also co–principal investigator of the POINT trial.
High Risk for Hemorrhage
The study enrolled 5170 patients at least 40 years of age who had sustained a TIA or minor stroke. Within 24 hours of their symptom onset, they were randomly assigned to 1 of 2 groups: aspirin (1 day loading dose of 75 to 300 mg, followed by 75 mg/day) plus placebo, or the same aspirin regimen plus clopidogrel (loading dose of 300 mg followed by 75 mg/day).
Patients in the combination group were taken off aspirin at 21 days because of the concern that Chinese patients, as with other Asian populations, are at relatively high risk for hemorrhage. "Frankly, that belief comes from epidemiological studies, but the epidemiology may just reflect underlying risk factors and not a true propensity for it," said Dr. Johnston. He pointed out that the studies testing this have not been in the acute period.
The study showed that stroke occurred less frequently in those receiving both aspirin and clopidogrel. At 90 days, the hazard ratio (HR) for survival free of stroke — either ischemic or hemorrhagic — in the combination group was 0.68 (95% confidence interval [CI], 0.57 - 0.81; P < .001).
For the secondary outcome of combined events (stroke, myocardial infarction, vascular death), the HR was 0.69 (95% CI, 0.58 - 0.82; P < .001). The risk for hemorrhagic stroke was the same in the 2 groups (0.3%).
Notably, severe bleeding events occurred at a similar rate in the 2 groups (0.2% in each). Although mild bleeding occurred more often in the combination group (1.2% versus 0.7%), Dr. Johnston noted that these events included nose bleeds. "We did not see a signal that the combination was unsafe."
Both aspirin and clopidogrel affect platelets, but through different pathways. "Together, the 2 are much more powerful than either one alone," said Dr. Johnston.
CHANCE was the first trial to focus on the acute period in TIA and minor stroke, which Dr. Johnston emphasized is not being seen nearly enough in the emergency department. "People with TIA and minor stroke are not coming in acutely or they're calling the office and being seen in clinic," he said. "We need to remind people that this really is an emergency and it should be treated right away."
Asked whether the combination therapy would be an acceptable approach for more severe strokes, Dr. Johnston said it's impossible to know "where to draw the line." The researchers will do more subgroup analyses looking at stroke severity, but Dr. Johnston pointed out that "there was no difference between the TIA and stroke in terms of rates of hemorrhagic stroke or in the efficacy of the combination."
Compared with elsewhere in the world, the risk for stroke is very high in China. "There are a whole lot more strokes in China than there are in the US and even if you add Europe, you still have more strokes in China," said Dr. Johnston.
Healthcare Differences
Because the trial was so large and because standards for clinical research have improved dramatically in China, the CHANCE results are "incredibly important" and should have a major effect on public health around the world, said Dr. Johnston. However, there are important differences between healthcare in China and that in the United States.
For example, Dr. Johnston noted that about two thirds of the Chinese patients in the study had hypertension and less than half were receiving any drug for hypertension during follow-up. Undertreatment, he said, could "certainly" affect the absolute effect size that's seen in the trial.
It's probably wise to await what happens with the POINT trial before changing treatment approaches here in North America, said Dr. Johnston, who is that study's principal investigator. Interim POINT results will be available in May, he said. "That will provide an opportunity to say it's very important to continue POINT or it's not important to continue POINT."
The POINT trial, which is about a third of the way through recruitment, differs slightly from CHANCE, said Dr. Johnston. For example, it includes a higher loading dose of clopidogrel and requires enrollment within 12 hours instead of 24 hours. As well, patients in the combination group continue with aspirin for 90 days instead of stopping at 21 days as in the CHANCE study.
Dr. Johnston pointed out a graph showing times for survival free of stroke for the treatment groups. "Most of the separation in the 2 curves occurs just in the first couple of days, so certainly by 21 days, the curves are almost parallel."
POINT includes mainly centers in the United States, although some sites have been added internationally.
The idea of comparing aspirin plus clopidogrel in a North American trial dates back more than a decade, but the researchers ran into funding difficulties when the drug manufacturer pulled its backing. This, said Dr. Johnston, substantially delayed the start of the trial.
When asked about next steps for CHANCE, Dr. Johnston said the Chinese researchers will look at ancillary studies of biomarkers and subtyping based on vascular imaging. As well, they plan to provide outcomes at 1 year that will include results related to cognition.
Helpful Information
Invited to comment on the CHANCE trial results, Larry B. Goldstein, MD, professor, medicine, Division of Neurology, and director, Duke Stroke Center, Duke University, Durham, North Carolina, and a POINT investigator, said the information is "quite helpful" and could eventually alter the current treatment practice, which is to being aspirin alone. "This would suggest that aspirin with clopidogrel over a relatively short course may have some benefit."
He added that the "key" is the short course of the combination aspirin plus clopidogrel treatment. He pointed out that other trials, including SPS3 and MATCH (Management of ATherothrombosis with Clopidogrel in High-risk patients), found that long-term combinations are associated with an increased risk for major bleeding complications.
"Over the longer term, the addition of a more potent antiplatelet drug, or combinations in general, seem to carry a much higher risk of bleeding that attenuates any benefit they have in reducing ischemic stroke risk," said Dr. Goldstein. "In our current guidelines, there is actually a contraindication for the combination for long-term secondary stroke prevention."
The lack of increased risk of bleeding, at least in the short term, "is quite encouraging," said Dr. Goldstein. He added that bleeding complications are more of a concern in Asia than in the United States, which has a much more ethnically diverse population and where the proportion of Asians is relatively low.
Source: http://www.medscape.com/viewarticle/779089?nlid=28263_1301&src=wnl_edit_dail&uac=129655SZ
Thin Asians may be at risk for diabetes
Type 2 diabetes, usually associated with obesity, can occur in many seemingly thin people from ethnic minorities, physicians told attendees here at the Excellence in Diabetes 2013 meeting last week.
Researchers showed that Japanese American women are twice as likely to be diagnosed with diabetes as whites, despite having lower body-mass indexes (BMIs). Epidemiologist Gertraud Maskarinec, MD, from the University of Hawaii Cancer Center, Honolulu, presented the findings, which cover a number of studies from her group, in a poster.
She told Medscape Medical News: "Diabetes risk is higher in all ethnic groups than in whites, and of course some of this is just due to body weight, but evidence is now building that people of many races may be at increased risk of diabetes and cancer before they are even considered conventionally overweight."
In communities where there are a lot of Asians, "I think it's on everybody's radar already," said Dr. Maskarinec. "If an Asian walks in, you don’t have to wait until they weigh hundreds of pounds to do a diabetes test." The World Health Organization (WHO) has worked on the idea to lower the "at-risk" BMI to 23 kg/m2 for certain ethnic groups, she adds, but "not everybody has adopted it."
Meanwhile, Chittaranjan Yajnick, MD, from King Edward Memorial Diabetes Unit, Pune, India, also gave a talk on what makes Indians so susceptible to diabetes. "We have seen that Indians are often diagnosed with diabetes 10 years earlier and 5- to 10-units BMI thinner than whites," he noted.
Both believe the explanation lies in "hidden" visceral fat found inside the body, between organs, in Asians and probably other ethnic groups too, but not in whites. This in turn affects the levels of adipokines secreted, such as leptin and adiponectin, which can have adverse metabolic effects.
Japanese Americans: Much More Visceral Fat Than Whites
The knowledge that Asians and other ethnic groups are at much greater risk for diseases associated with obesity, such as diabetes and many cancers, than whites, is not new, Dr. Maskarinec explained. But more recently, researchers have begun to show that nonwhites who are not even particularly overweight or who are of "normal" weight are at much higher risk than whites.
If an Asian walks in, you don't have to wait until they weigh hundreds of pounds to do a diabetes test.
"People have talked about some kind of adaptation for white people, who have had a greater number of years to adjust to the type of food we are eating now," she postulated.
As part of their research, Dr. Maskarinec and her colleagues used the Hawaii component of the Multiethnic Cohort (MEC) to examine the influence of BMI on diabetes incidence.
They measured leptin and adiponectin by ELISA assay in 312 ethnically Japanese and 208 white women. Magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry (DXA) were performed in 30 white and 30 Japanese cohort members.
Overall, Japanese women had significantly lower BMIs (23.7 vs 25.3 kg/m2), leptin (15.0 vs 25.9 ng/mL), and adiponectin (11.7 vs 16.0 µg/mL) than whites (P < .0001 for all).
But in adjusted models, Japanese were twice as likely to be diagnosed with diabetes as whites across all BMI categories: less than 22 kg/m2, 22.0 to 24.9, 25.0 to 29.9, and 30 kg/m2 or higher.
The DXA and MRI scans of the 30 white and 30 Japanese women, published in 2011, showed much more trunk fat and percentage of abdominal visceral fat in the Japanese than in the white women. Japanese women had higher trunk-to-peripheral-fat ratios and a greater percentage of liver fat and were twice as likely to have fatty livers as whites, the data showed.
"Greater central adiposity reflecting the adverse effects of visceral fat and/or patterns of adipokines may be responsible for the higher diabetes risk in Asians as compared with whites at the same BMI level," Dr. Maskarinec and colleagues concluded.
Dr. Maskarinec also showed data on DXA whole-body scans obtained for 101 adult women (>30 years) and their 112 daughters (age, 10 –16 years) in Hawaii, divided into all white, mixed of non-Asian descent, mixed of partly Asian, and all Asian, taken from another study by her colleagues published last year. These results confirmed previous reports of greater central adiposity in women of Asian ancestry and indicated that ethnic differences in adiposity were already present in adolescence.
Dr. Maskarinec said ethnic differences in body-fat amount or distribution that develops early in life may be key, with some scientists believing the intrauterine environment plays an important role, although this latter concept is still just a hypothesis, she stressed.
So Could It Be Epigenetics?
Dr. Yajnick is such a proponent of this theory: "All the risk factors for diabetes and adiposity, including blood chemistry, are present at birth," he told the meeting. His research includes evidence that Indian babies "are small but adipose; it's all about nutritional programming rather than the birth weight."
Susceptibility to noncommunicable diseases such as diabetes "is thus not only genetic, but epigenetic," with the latter representing heritable changes caused by mechanisms other than alterations in underlying DNA and being "modifiable," he explains. "Only about 10% of diabetes can so far be explained by genetics, for example," he notes.
And one factor he believes may be playing an important role in India is vegetarianism. People there consume high amounts of folate but are deficient in vitamin B12, creating a low-B12/high-folate intrauterine environment that "produces babies who are mostly insulin resistant." He is testing his hypothesis in the Pune Intervention trial, which began a year ago and involves giving adolescent boys and girls in the Indian region B12 supplementation. The participants and their offspring will be followed long term.
Dr. Maskarinec is skeptical of this theory, noting that most ethnic groups around the world are not B12 deficient. The Japanese Americans she is studying, for example, have very high per-capita meat consumption, she says.
The main message, she stressed, is that physicians need to understand that individuals of Asian descent and other ethnicities can have particularly high disease risks — not just for diabetes, but for breast and other cancers — at relatively low BMI levels.
"Just because they don't look fat doesn't mean they are healthy," she warns.
Source: http://www.medscape.com/viewarticle/779072?nlid=28263_1301&src=wnl_edit_dail&uac=129655SZ
Researchers showed that Japanese American women are twice as likely to be diagnosed with diabetes as whites, despite having lower body-mass indexes (BMIs). Epidemiologist Gertraud Maskarinec, MD, from the University of Hawaii Cancer Center, Honolulu, presented the findings, which cover a number of studies from her group, in a poster.
She told Medscape Medical News: "Diabetes risk is higher in all ethnic groups than in whites, and of course some of this is just due to body weight, but evidence is now building that people of many races may be at increased risk of diabetes and cancer before they are even considered conventionally overweight."
In communities where there are a lot of Asians, "I think it's on everybody's radar already," said Dr. Maskarinec. "If an Asian walks in, you don’t have to wait until they weigh hundreds of pounds to do a diabetes test." The World Health Organization (WHO) has worked on the idea to lower the "at-risk" BMI to 23 kg/m2 for certain ethnic groups, she adds, but "not everybody has adopted it."
Meanwhile, Chittaranjan Yajnick, MD, from King Edward Memorial Diabetes Unit, Pune, India, also gave a talk on what makes Indians so susceptible to diabetes. "We have seen that Indians are often diagnosed with diabetes 10 years earlier and 5- to 10-units BMI thinner than whites," he noted.
Both believe the explanation lies in "hidden" visceral fat found inside the body, between organs, in Asians and probably other ethnic groups too, but not in whites. This in turn affects the levels of adipokines secreted, such as leptin and adiponectin, which can have adverse metabolic effects.
Japanese Americans: Much More Visceral Fat Than Whites
The knowledge that Asians and other ethnic groups are at much greater risk for diseases associated with obesity, such as diabetes and many cancers, than whites, is not new, Dr. Maskarinec explained. But more recently, researchers have begun to show that nonwhites who are not even particularly overweight or who are of "normal" weight are at much higher risk than whites.
If an Asian walks in, you don't have to wait until they weigh hundreds of pounds to do a diabetes test.
"People have talked about some kind of adaptation for white people, who have had a greater number of years to adjust to the type of food we are eating now," she postulated.
As part of their research, Dr. Maskarinec and her colleagues used the Hawaii component of the Multiethnic Cohort (MEC) to examine the influence of BMI on diabetes incidence.
They measured leptin and adiponectin by ELISA assay in 312 ethnically Japanese and 208 white women. Magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry (DXA) were performed in 30 white and 30 Japanese cohort members.
Overall, Japanese women had significantly lower BMIs (23.7 vs 25.3 kg/m2), leptin (15.0 vs 25.9 ng/mL), and adiponectin (11.7 vs 16.0 µg/mL) than whites (P < .0001 for all).
But in adjusted models, Japanese were twice as likely to be diagnosed with diabetes as whites across all BMI categories: less than 22 kg/m2, 22.0 to 24.9, 25.0 to 29.9, and 30 kg/m2 or higher.
The DXA and MRI scans of the 30 white and 30 Japanese women, published in 2011, showed much more trunk fat and percentage of abdominal visceral fat in the Japanese than in the white women. Japanese women had higher trunk-to-peripheral-fat ratios and a greater percentage of liver fat and were twice as likely to have fatty livers as whites, the data showed.
"Greater central adiposity reflecting the adverse effects of visceral fat and/or patterns of adipokines may be responsible for the higher diabetes risk in Asians as compared with whites at the same BMI level," Dr. Maskarinec and colleagues concluded.
Dr. Maskarinec also showed data on DXA whole-body scans obtained for 101 adult women (>30 years) and their 112 daughters (age, 10 –16 years) in Hawaii, divided into all white, mixed of non-Asian descent, mixed of partly Asian, and all Asian, taken from another study by her colleagues published last year. These results confirmed previous reports of greater central adiposity in women of Asian ancestry and indicated that ethnic differences in adiposity were already present in adolescence.
Dr. Maskarinec said ethnic differences in body-fat amount or distribution that develops early in life may be key, with some scientists believing the intrauterine environment plays an important role, although this latter concept is still just a hypothesis, she stressed.
So Could It Be Epigenetics?
Dr. Yajnick is such a proponent of this theory: "All the risk factors for diabetes and adiposity, including blood chemistry, are present at birth," he told the meeting. His research includes evidence that Indian babies "are small but adipose; it's all about nutritional programming rather than the birth weight."
Susceptibility to noncommunicable diseases such as diabetes "is thus not only genetic, but epigenetic," with the latter representing heritable changes caused by mechanisms other than alterations in underlying DNA and being "modifiable," he explains. "Only about 10% of diabetes can so far be explained by genetics, for example," he notes.
And one factor he believes may be playing an important role in India is vegetarianism. People there consume high amounts of folate but are deficient in vitamin B12, creating a low-B12/high-folate intrauterine environment that "produces babies who are mostly insulin resistant." He is testing his hypothesis in the Pune Intervention trial, which began a year ago and involves giving adolescent boys and girls in the Indian region B12 supplementation. The participants and their offspring will be followed long term.
Dr. Maskarinec is skeptical of this theory, noting that most ethnic groups around the world are not B12 deficient. The Japanese Americans she is studying, for example, have very high per-capita meat consumption, she says.
The main message, she stressed, is that physicians need to understand that individuals of Asian descent and other ethnicities can have particularly high disease risks — not just for diabetes, but for breast and other cancers — at relatively low BMI levels.
"Just because they don't look fat doesn't mean they are healthy," she warns.
Source: http://www.medscape.com/viewarticle/779072?nlid=28263_1301&src=wnl_edit_dail&uac=129655SZ
Calcium supplements may be unhealthy for men
The debate over the safety of calcium supplements has been muddied with the publication of a new analysis showing that a high intake of supplemental calcium increases the risk of cardiovascular disease (CVD) death in men but not in women [1]. Compared with individuals who took no calcium, men who consumed 1000 mg or more of supplemental calcium per day had a significant 20% increased risk of CVD death, a risk that was driven by a significant 19% increased risk of heart-disease death.
For women, however, there was no association between calcium intake and the risk of death.
"We found a significant interaction by sex," write Dr Qian Xiao (National Cancer Institute, Bethesda, MD) and colleagues in their paper, published online February 4, 2013 in JAMA: Internal Medicine. "Elevated CVD mortality with increasing supplemental calcium intake was observed only in men; however, we cannot rule out the possibility that supplemental calcium intake may be associated with cardiovascular mortality in women." The group calls the difference in risk between men and women "intriguing," adding that further studies are needed to determine whether such differential risks are real.
In an editorial [2], Dr Susanna Larsson (Karolinska Institute, Stockholm, Sweden) said the lack of association between calcium supplementation in women is "perplexing," especially given the results of a reanalysis of the WHI study conducted by Dr Mark Bolland (University of Auckland, New Zealand) and colleagues. In the original WHI analysis on the risks associated with calcium use, investigators found no adverse cardiovascular effects in women taking calcium and vitamin D when compared with those not taking the supplements. However, Bolland et al reexamined the WHI data because 54% of women were already taking calcium and vitamin D by personal choice at the start of the WHI study and were not told to stop if they were randomized to placebo. When the data were reanalyzed, the researchers observed a significant association between calcium intake, as well as vitamin D, with the risk of MI.
New Report From NIH Data
The latest report is taken from an analysis of the National Institutes of Health--AARP Diet and Health Study, a study that included 388 229 men and women 50 to 71 years of age from six US states. Individuals self-reported frequency of food intake and portion size during a one-year period and answered questions about the frequency in which they consumed multivitamins, calcium-containing antacids, or calcium supplements alone.
During a mean follow-up of 12 years, there were 7904 and 3874 CVD deaths in men and women, respectively. Dietary intake of calcium was initially associated with total CVD and heart-disease death in men and women, but the association was no longer significant after adjustment for CVD risk factors. Supplemental calcium intake (1000 mg/day vs no calcium supplementation), on the other hand, increased the risk of CVD death and heart-disease death by 20% and 19%, respectively, in men, but there was no association in women. In an analysis that looked only at those taking calcium supplements and not multivitamins, the risk of CVD death and heart-disease death was 24% and 37% higher in men who took 1000 mg/day of calcium compared with those who took no supplements. Again, no association was observed in women who took calcium supplements alone.
There is currently a debate surrounding the benefits and risks of supplemental calcium in men and women. In 2010, researchers published a meta-analysis inBMJ showing that the use of calcium supplements without coadministered vitamin D is associated with an increased risk of MI. This increased risk was later confirmed in an analysis of the patients participating in the European Prospective Investigation into Cancer and Nutrition Study (EPIC).
In the editorial, Larsson concludes that the available evidence is suggestive of an adverse cardiovascular effect with excessive use of calcium supplements. Published as part of JAMA: Internal Medicine's series on "less is more" in medicine, the editorial states that more calcium, which is promoted because of its proposed benefits on bone health, does translate into health benefits. The best source of calcium, says Larsson, remains diet and the consumption of calcium-rich foods such as low-fat dairy, beans, and green leafy vegetables.
Source: http://www.medscape.com/viewarticle/778718
For women, however, there was no association between calcium intake and the risk of death.
"We found a significant interaction by sex," write Dr Qian Xiao (National Cancer Institute, Bethesda, MD) and colleagues in their paper, published online February 4, 2013 in JAMA: Internal Medicine. "Elevated CVD mortality with increasing supplemental calcium intake was observed only in men; however, we cannot rule out the possibility that supplemental calcium intake may be associated with cardiovascular mortality in women." The group calls the difference in risk between men and women "intriguing," adding that further studies are needed to determine whether such differential risks are real.
In an editorial [2], Dr Susanna Larsson (Karolinska Institute, Stockholm, Sweden) said the lack of association between calcium supplementation in women is "perplexing," especially given the results of a reanalysis of the WHI study conducted by Dr Mark Bolland (University of Auckland, New Zealand) and colleagues. In the original WHI analysis on the risks associated with calcium use, investigators found no adverse cardiovascular effects in women taking calcium and vitamin D when compared with those not taking the supplements. However, Bolland et al reexamined the WHI data because 54% of women were already taking calcium and vitamin D by personal choice at the start of the WHI study and were not told to stop if they were randomized to placebo. When the data were reanalyzed, the researchers observed a significant association between calcium intake, as well as vitamin D, with the risk of MI.
New Report From NIH Data
The latest report is taken from an analysis of the National Institutes of Health--AARP Diet and Health Study, a study that included 388 229 men and women 50 to 71 years of age from six US states. Individuals self-reported frequency of food intake and portion size during a one-year period and answered questions about the frequency in which they consumed multivitamins, calcium-containing antacids, or calcium supplements alone.
During a mean follow-up of 12 years, there were 7904 and 3874 CVD deaths in men and women, respectively. Dietary intake of calcium was initially associated with total CVD and heart-disease death in men and women, but the association was no longer significant after adjustment for CVD risk factors. Supplemental calcium intake (1000 mg/day vs no calcium supplementation), on the other hand, increased the risk of CVD death and heart-disease death by 20% and 19%, respectively, in men, but there was no association in women. In an analysis that looked only at those taking calcium supplements and not multivitamins, the risk of CVD death and heart-disease death was 24% and 37% higher in men who took 1000 mg/day of calcium compared with those who took no supplements. Again, no association was observed in women who took calcium supplements alone.
There is currently a debate surrounding the benefits and risks of supplemental calcium in men and women. In 2010, researchers published a meta-analysis inBMJ showing that the use of calcium supplements without coadministered vitamin D is associated with an increased risk of MI. This increased risk was later confirmed in an analysis of the patients participating in the European Prospective Investigation into Cancer and Nutrition Study (EPIC).
In the editorial, Larsson concludes that the available evidence is suggestive of an adverse cardiovascular effect with excessive use of calcium supplements. Published as part of JAMA: Internal Medicine's series on "less is more" in medicine, the editorial states that more calcium, which is promoted because of its proposed benefits on bone health, does translate into health benefits. The best source of calcium, says Larsson, remains diet and the consumption of calcium-rich foods such as low-fat dairy, beans, and green leafy vegetables.
Source: http://www.medscape.com/viewarticle/778718
Vitamin D supplements vary in potency
Potency of vitamin D supplements often varies widely from what is listed on the label, according to results from a study of pills from 12 different manufacturers.
The study was authored by Erin S. LeBlanc, MD, MPH, from the Kaiser Permanente Center for Health Research, Portland, Oregon, and colleagues and published online February 11 inJAMA Internal Medicine.
In previous research that focused on vitamin D in menopausal women, Dr. LeBlanc and colleagues found that compounded vitamin D3(cholecalciferol) supplements varied significantly in potency and that only a third of the examined compounded study pills met US Pharmacopeial (USP) Convention standards.
"This variability in compounded cholecalciferol pills led us to additionally investigate over-the-counter (OTC) cholecalciferol pills, in which we also found variability," the authors write.
In this study, the investigators randomly tested the potency of 5 pills from 15 sealed bottles of OTC cholecalciferol dietary supplements (1000 IU, 5000 IU, and 10,000 IU) they purchased at 5 stores in Portland, Oregon.
They found the pills contained from 52% to 135% of the dose listed on the bottles. "When averaged over 5 pills, two-thirds of bottles met USP Convention standards for OTC cholecalciferol solution, which state that contents should be within 90% to 120% of the stated dose," the authors write. In about a quarter of the bottles, all 5 pills met the standards.
The investigators next checked a single pill from 5 bottles with the same lot number and found that potency ranged from 57% to 138% of what was on the label.
They then evaluated a single pill from 5 bottles with different lot numbers. Those pills ranged from 9% to 140% of the stated dose, with mean potencies over the 5 lots ranging from 89% to 105%.
Finally, the researchers analyzed compounded study cholecalciferol pills (1000 IU and 50,000 IU) that had been produced on 3 occasions over the course of several months. Those analyses were done over varied times (0 - 6 months) after compounding. They found that the 50,000-IU tablets contained 52% to 105% of the anticipated dose, whereas the 1000-IU tablets contained 23% to 146% of the expected dose.
"In our test, just over one-half of the OTC pills and only one-third of compounded pills met USP Convention standards," they write.
They say that although lack of accuracy in vitamin D dosing may not cause harm in most people, such deviations could render the supplements less effective. They also point out that variability from pill to pill may undermine the validity of vitamin D trials that use compounded pills to blind participants.
"As more people take vitamin D supplements, it is critical that health care providers and patients understand that cholecalciferol potency may vary widely," they conclude, adding that they agree with calls for increased regulation of dietary supplements.
The study was authored by Erin S. LeBlanc, MD, MPH, from the Kaiser Permanente Center for Health Research, Portland, Oregon, and colleagues and published online February 11 inJAMA Internal Medicine.
In previous research that focused on vitamin D in menopausal women, Dr. LeBlanc and colleagues found that compounded vitamin D3(cholecalciferol) supplements varied significantly in potency and that only a third of the examined compounded study pills met US Pharmacopeial (USP) Convention standards.
"This variability in compounded cholecalciferol pills led us to additionally investigate over-the-counter (OTC) cholecalciferol pills, in which we also found variability," the authors write.
In this study, the investigators randomly tested the potency of 5 pills from 15 sealed bottles of OTC cholecalciferol dietary supplements (1000 IU, 5000 IU, and 10,000 IU) they purchased at 5 stores in Portland, Oregon.
They found the pills contained from 52% to 135% of the dose listed on the bottles. "When averaged over 5 pills, two-thirds of bottles met USP Convention standards for OTC cholecalciferol solution, which state that contents should be within 90% to 120% of the stated dose," the authors write. In about a quarter of the bottles, all 5 pills met the standards.
The investigators next checked a single pill from 5 bottles with the same lot number and found that potency ranged from 57% to 138% of what was on the label.
They then evaluated a single pill from 5 bottles with different lot numbers. Those pills ranged from 9% to 140% of the stated dose, with mean potencies over the 5 lots ranging from 89% to 105%.
Finally, the researchers analyzed compounded study cholecalciferol pills (1000 IU and 50,000 IU) that had been produced on 3 occasions over the course of several months. Those analyses were done over varied times (0 - 6 months) after compounding. They found that the 50,000-IU tablets contained 52% to 105% of the anticipated dose, whereas the 1000-IU tablets contained 23% to 146% of the expected dose.
"In our test, just over one-half of the OTC pills and only one-third of compounded pills met USP Convention standards," they write.
They say that although lack of accuracy in vitamin D dosing may not cause harm in most people, such deviations could render the supplements less effective. They also point out that variability from pill to pill may undermine the validity of vitamin D trials that use compounded pills to blind participants.
"As more people take vitamin D supplements, it is critical that health care providers and patients understand that cholecalciferol potency may vary widely," they conclude, adding that they agree with calls for increased regulation of dietary supplements.
Source: http://www.medscape.com/viewarticle/779088?nlid=28263_1301&src=wnl_edit_dail&uac=129655SZ
Prenatal folic acid reduces autism risk
More evidence suggests that prenatal folic acid supplementation may lower the risk of developing autism.
A population-based cohort study of almost 85,000 children in Norway showed that those children whose mothers used supplemental folic acid early in pregnancy had 39% lower odds of having autistic disorder than those whose mothers did not use the supplements.
"We were a bit surprised about how large the reduction in risk was and how it was specifically related to folic acid and not to other supplements," Pål Surén, MD, from the Norwegian Institute of Public Health in Oslo, told Medscape Medical News.
"This was also reassuring, because if we had found [the reduction] was associated with other types of supplements as well, it would have been more likely to be explained by healthy behaviors in general, not the supplements per se," he added.
Dr. Surén noted that although more research is needed, "the results support the current recommendations of taking folic acid supplements during pregnancy and emphasize the importance of starting early — preferably before conception."
The study is published in the February issue of JAMA.
Public Health Benefit
Previous research has shown that folic acid supplementation "around the time of conception" can reduce the risk of offspring developing neural tube defects, report the investigators.
"This protective effect has led to mandatory fortification of flour with folic acid in several countries, and it is generally recommended that women planning to become pregnant take a daily supplement...starting 1 month before conception," they write.
"It is not implausible to think that it might also have other beneficial effects, and possibly be protective against other neurodevelopmental disorders, too," said Dr. Surén. "If folic acid truly has a preventive effect against autism in children, it would have great benefits from a public health perspective, because it would be a preventive measure that is cheap and already in use for other purposes."
In a study of more than 700 preschoolers published last year in the American Journal of Clinical Nutrition, investigators from California found that those children whose mothers received at least 600 μg per day of folic acid during their first month of pregnancy had a 38% lower chance of having autism or Asperger syndrome.
For the current analysis, the investigators sought to assess the association between maternal use of folic acid, from 4 weeks before the start of pregnancy to 8 weeks afterwards, and subsequent risk for autism spectrum disorders (ASDs), which include autistic disorder, Asperger syndrome, and pervasive developmental disorder–not otherwise specified (PDD-NOS), in offspring.
The investigators evaluated data on 85,176 children born between 2002 and 2008 who participated in the Norwegian Mother and Child Cohort Study. The mean age of the children at the end of follow-up in March 2012 was 6.4 years.
The Autism Birth Cohort substudy was used to identify cases of ASD in these children.
Inverse Association
Results showed that 270 of the children had been diagnosed with an ASD. Of these, 114 had autistic disorder, 100 had PDD-NOS, and 56 had Asperger syndrome.
Of the children whose mothers took folic acid during early pregnancy, 0.10% had autistic disorder vs 0.21% of those whose mothers did not take the supplements (adjusted odds ratio, 0.61; 95% confidence interval, 0.41 - 0.90).
The inverse association found for folic acid use in early pregnancy and subsequent risk for autistic disorder was not found for folic use during midpregnancy.
Although no association was found between prenatal folic acid supplementation and Asperger syndrome or PDD-NOS, "power was limited," note the investigators.
In addition, further analysis showed no association between risk for an ASD and use of fish oil supplements.
Overall, the main finding does not establish causation between use of folic acid and a lower risk for autistic disorder, write the researchers.
However, it does provide "a rationale for replicating the analyses in other study samples and further investigating genetic factors and other biological mechanisms that may explain the inverse association."
"Reassuring Study"
"It is reassuring that the study...found no association between folic acid supplementation and an increased risk for autistic disorder or ASDs," write Robert J. Berry, MD, and colleagues from the Centers for Disease Control and Prevention in Atlanta, Georgia, in an accompanying editorial.
They note that this has been a hotly debated issue previously. And it is "biologically plausible that folic acid intake might affect numerous conditions positively or negatively depending on timing and dose."
However, past studies have shown strong benefits from folic acid, including a previous report from the Norwegian Mother and Child Cohort Study that showed that supplementation during early pregnancy was associated with a reduced risk for severe language delay in offspring.
The editorialists point out that more research is now needed, including studies that evaluate timing, dose, and intake of supplements, as well as studies that assess children with autism and comorbid conditions.
Nevertheless, "this should ensure that folic acid intake can continue to serve as a tool for the prevention of neural tube birth defects," they write.
"The potential for a nutritional supplement to reduce the risk of autistic disorder is provocative and should be confirmed in other populations."
A population-based cohort study of almost 85,000 children in Norway showed that those children whose mothers used supplemental folic acid early in pregnancy had 39% lower odds of having autistic disorder than those whose mothers did not use the supplements.
"We were a bit surprised about how large the reduction in risk was and how it was specifically related to folic acid and not to other supplements," Pål Surén, MD, from the Norwegian Institute of Public Health in Oslo, told Medscape Medical News.
"This was also reassuring, because if we had found [the reduction] was associated with other types of supplements as well, it would have been more likely to be explained by healthy behaviors in general, not the supplements per se," he added.
Dr. Surén noted that although more research is needed, "the results support the current recommendations of taking folic acid supplements during pregnancy and emphasize the importance of starting early — preferably before conception."
The study is published in the February issue of JAMA.
Public Health Benefit
Previous research has shown that folic acid supplementation "around the time of conception" can reduce the risk of offspring developing neural tube defects, report the investigators.
"This protective effect has led to mandatory fortification of flour with folic acid in several countries, and it is generally recommended that women planning to become pregnant take a daily supplement...starting 1 month before conception," they write.
"It is not implausible to think that it might also have other beneficial effects, and possibly be protective against other neurodevelopmental disorders, too," said Dr. Surén. "If folic acid truly has a preventive effect against autism in children, it would have great benefits from a public health perspective, because it would be a preventive measure that is cheap and already in use for other purposes."
In a study of more than 700 preschoolers published last year in the American Journal of Clinical Nutrition, investigators from California found that those children whose mothers received at least 600 μg per day of folic acid during their first month of pregnancy had a 38% lower chance of having autism or Asperger syndrome.
For the current analysis, the investigators sought to assess the association between maternal use of folic acid, from 4 weeks before the start of pregnancy to 8 weeks afterwards, and subsequent risk for autism spectrum disorders (ASDs), which include autistic disorder, Asperger syndrome, and pervasive developmental disorder–not otherwise specified (PDD-NOS), in offspring.
The investigators evaluated data on 85,176 children born between 2002 and 2008 who participated in the Norwegian Mother and Child Cohort Study. The mean age of the children at the end of follow-up in March 2012 was 6.4 years.
The Autism Birth Cohort substudy was used to identify cases of ASD in these children.
Inverse Association
Results showed that 270 of the children had been diagnosed with an ASD. Of these, 114 had autistic disorder, 100 had PDD-NOS, and 56 had Asperger syndrome.
Of the children whose mothers took folic acid during early pregnancy, 0.10% had autistic disorder vs 0.21% of those whose mothers did not take the supplements (adjusted odds ratio, 0.61; 95% confidence interval, 0.41 - 0.90).
The inverse association found for folic acid use in early pregnancy and subsequent risk for autistic disorder was not found for folic use during midpregnancy.
Although no association was found between prenatal folic acid supplementation and Asperger syndrome or PDD-NOS, "power was limited," note the investigators.
In addition, further analysis showed no association between risk for an ASD and use of fish oil supplements.
Overall, the main finding does not establish causation between use of folic acid and a lower risk for autistic disorder, write the researchers.
However, it does provide "a rationale for replicating the analyses in other study samples and further investigating genetic factors and other biological mechanisms that may explain the inverse association."
"Reassuring Study"
"It is reassuring that the study...found no association between folic acid supplementation and an increased risk for autistic disorder or ASDs," write Robert J. Berry, MD, and colleagues from the Centers for Disease Control and Prevention in Atlanta, Georgia, in an accompanying editorial.
They note that this has been a hotly debated issue previously. And it is "biologically plausible that folic acid intake might affect numerous conditions positively or negatively depending on timing and dose."
However, past studies have shown strong benefits from folic acid, including a previous report from the Norwegian Mother and Child Cohort Study that showed that supplementation during early pregnancy was associated with a reduced risk for severe language delay in offspring.
The editorialists point out that more research is now needed, including studies that evaluate timing, dose, and intake of supplements, as well as studies that assess children with autism and comorbid conditions.
Nevertheless, "this should ensure that folic acid intake can continue to serve as a tool for the prevention of neural tube birth defects," they write.
"The potential for a nutritional supplement to reduce the risk of autistic disorder is provocative and should be confirmed in other populations."
Source: http://www.medscape.com/viewarticle/779205?nlid=28283_1301&src=wnl_edit_dail
Diet sodas linked to diabetes risk
A new study from France suggests that women who drink large amounts of diet soda are at increased risk for type 2 diabetes. The findings also support the previously documented association between high intake of regular sugar-sweetened beverages and the condition, report Guy Fagherazzi, from the Center for Research in Epidemiology and Population Health, Villejuif, France, and colleagues in a study published online January 30 in the American Journal of Clinical Nutrition.
Prior research into the relationship between diet soda (artificially sweetened beverages) and type 2 diabetes has produced conflicting results, and while the current study does not necessarily imply causation, there are some biologically plausible mechanisms, the researchers suggest.
And given that diet sodas are "considered — and marketed — as healthier than sugar-sweetened beverages," the findings require further investigation, they say. In the meantime, the authors advise that "a precautionary principle could be applied to the promotion of [artificially sweetened beverages]."
Highest Intake of Diet Soda More Than Doubles Diabetes Risk
The data come from a large prospective cohort study of 66,118 women in France investigating links between diet and cancer. There were 1369 new cases of type 2 diabetes diagnosed during the follow-up period from 1993 to 2007.
Based on self-reported dietary consumption, the average intake of regular sodas was 328 mL/week, while for diet sodas it was higher, at 568 mL/week.
The risk for type 2 diabetes was elevated among the women in the highest quartiles for both sugar-sweetened beverages (>359 mL/week) and artificially sweetened beverages (>603 mL/week) compared with women who did not consume those beverages, with hazard ratios of 1.34 and 2.21, respectively, after multivariate adjustment for a variety of covariates (other than body mass index [BMI]).
Strong positive trends in type 2 diabetes risk were observed across quartiles of consumption for both types of beverage (P = .0088 and P < .0001, respectively). Adjustment for BMI did modify the results somewhat, although the associations remained significant for both sugar-sweetened beverages and artificially sweetened beverages.
The authors also conducted sensitivity analyses to test the hypothesis that people who are at risk for type 2 diabetes by virtue of obesity may preferentially drink artificially sweetened beverages, but the results suggest that such a "reverse causation" mechanism is "unlikely," they note.
"Our results — in accordance with a recent joint scientific statement of the AHA and ADA — strongly suggest the need to conduct randomized trials that evaluate metabolic consequences of [artificially sweetened beverage] components, such as artificial sweeteners, to prove a causal link between [artificially sweetened beverage] consumption and type 2 diabetes," the study authors conclude.
Prior research into the relationship between diet soda (artificially sweetened beverages) and type 2 diabetes has produced conflicting results, and while the current study does not necessarily imply causation, there are some biologically plausible mechanisms, the researchers suggest.
And given that diet sodas are "considered — and marketed — as healthier than sugar-sweetened beverages," the findings require further investigation, they say. In the meantime, the authors advise that "a precautionary principle could be applied to the promotion of [artificially sweetened beverages]."
Highest Intake of Diet Soda More Than Doubles Diabetes Risk
The data come from a large prospective cohort study of 66,118 women in France investigating links between diet and cancer. There were 1369 new cases of type 2 diabetes diagnosed during the follow-up period from 1993 to 2007.
Based on self-reported dietary consumption, the average intake of regular sodas was 328 mL/week, while for diet sodas it was higher, at 568 mL/week.
The risk for type 2 diabetes was elevated among the women in the highest quartiles for both sugar-sweetened beverages (>359 mL/week) and artificially sweetened beverages (>603 mL/week) compared with women who did not consume those beverages, with hazard ratios of 1.34 and 2.21, respectively, after multivariate adjustment for a variety of covariates (other than body mass index [BMI]).
Strong positive trends in type 2 diabetes risk were observed across quartiles of consumption for both types of beverage (P = .0088 and P < .0001, respectively). Adjustment for BMI did modify the results somewhat, although the associations remained significant for both sugar-sweetened beverages and artificially sweetened beverages.
The authors also conducted sensitivity analyses to test the hypothesis that people who are at risk for type 2 diabetes by virtue of obesity may preferentially drink artificially sweetened beverages, but the results suggest that such a "reverse causation" mechanism is "unlikely," they note.
"Our results — in accordance with a recent joint scientific statement of the AHA and ADA — strongly suggest the need to conduct randomized trials that evaluate metabolic consequences of [artificially sweetened beverage] components, such as artificial sweeteners, to prove a causal link between [artificially sweetened beverage] consumption and type 2 diabetes," the study authors conclude.
Source: http://www.medscape.com/viewarticle/779290?nlid=28284_1301&src=wnl_edit_dail
Diclofenac and cardiovascular risks
The nonsteroidal anti-inflammatory drug (NSAID) diclofenac, a drug that is frequently used for the treatment of pain and inflammation caused by arthritis, is associated with a significantly increased risk of cardiovascular complications and should be removed from essential-medicines lists (EML), according to a new review.
Diclofenac, which is listed on the EML of 74 countries, increased the risk of cardiovascular events between 38% and 63% in different studies. The increased risk with diclofenac was similar to the COX-2 inhibitor rofecoxib (Vioxx, Merck), a drug withdrawn from worldwide markets because of cardiovascular toxicity.
Speaking with heartwire , Dr David Henry(Institute for Clinical Evaluative Sciences, Toronto, ON), who conducted the review along with Dr Patricia McGettigan (London School of Medicine and Dentistry, UK), said that while use of diclofenac in North America is low--the drug has about 5% or 6% of the NSAID market in the US and 17% of the market in Canada--its use is much more common in other non-Western countries.
"The exposure in the North American community is quite low," said Henry, "but the real issue is that it has 30% to 40% of the market share in countries like Vietnam, Pakistan, parts of China, and other countries. These countries are experiencing a real epidemic of cardiovascular disease at the same time these rates are coming down in the West. They are really heavy users of these drugs, in particular diclofenac."
In the review, published online February 12, 2013 inPLoS Medicine, Henry and McGettigan showed that in 15 countries, a list comprising high-, medium-, and low-income countries, diclofenac was the most widely used NSAID. It has a market share roughly equal to the combined market share ofibuprofen, naproxen, andmefenamic acid. The high-risk NSAIDs, diclofenac andetoricoxib, had one-third of the market share across the 15 countries.
Diclofenac, Even in Small Doses, Can Cause Problems
The meta-analysis by McGettigan and Henry also reviewed the relative cardiovascular risks of NSAIDs in observational and randomized studies. Rofecoxib, etoricoxib, and diclofenac were the three agents that were consistently associated with a significantly increased risk when compared with nonuse. Rofecoxib increased the risk of serious cardiovascular events between 27% and 45%, and etoricoxib increased the risk more than twofold compared with nonuse. In two observational studies, diclofenac increased risk of acute MI approximately 38% and 39%, respectively, and increased the risk of cardiovascular events 40%. In one randomized trial, diclofenac was associated with a 63% increased risk of cardiovascular events compared with nonuse.
To heartwire , Henry said the NSAIDs are familiar drugs for physicians and because of such familiarity might be casually prescribed. While the drugs are available over the counter, the cardiovascular risks are associated with the prescription strengths of NSAIDs. For diclofenac, the prescription dose ranges from 100 to 150 mg per day, and this dose is high enough to cause a risk of cardiovascular events, with higher doses associated with even greater risks. With diclofenac, as well as with rofecoxib, there does not appear to be a dose associated with no risk.
"We could find no-risk doses with some of the other drugs, like ibuprofen, naproxen, and celecoxib [Celebrex, Pfizer]," he said. "We could find a dose low enough that didn't increase the risk of heart attacks. The thing with diclofenac is that even in small doses it increases the risk of cardiovascular events. The average dose that is used and marketed is quite high."
Indometacin and meloxicam had a moderately increased risk of cardiovascular events, slightly higher than naproxen, while celecoxib and ibuprofen were associated with an increased risk of cardiovascular toxicity when used at high doses in clinical trials but not in lower doses available over the counter.
An Underappreciated Problem
Dr Gabriel Steg (Centre Hospitalier Bichaut-Claude Bernard, Paris, France), who was not affiliated with the analysis, told heartwire that the cardiovascular risks associated with NSAIDs are an underappreciated problem. He said that most NSAIDs, with the possible exception of naproxen, have some degree of cardiovascular risk associated with them. "I think the converging data from multiple sources indicates that, particularly in patients who are known to have cardiac disease, we should refrain from the chronic use of NSAIDs, if possible," said Steg. "It is conceivable that diclofenac might have a slightly higher risk than the others, but really the issue is the whole class rather than singling out a [particular] agent."
Steg noted that a study published last year inCirculation, reported by heartwire , showed that the use of NSAIDs was associated with a persistently increased risk of coronary events in patients with a previous MI. In more than 43 000 MI patients treated with NSAIDs, their use was associated with a 59% increased risk of death after one year and a 63% increased risk of death after five years of use. In addition, the use of the NSAIDs was associated with an increased risk of coronary death and recurrent MI.
"I think this is a completely underappreciated problem," said Steg. "Most physicians would not be alert to the long-term use of these agents. Many of these agents are over the counter, so physicians are not necessarily aware of their use. Also, they may be used fairly frequently by patients and for very long periods of time. In the elderly, because of bone and joint issues, their use is very common."
To heartwire , Henry said he has written to the World Health Organization(WHO) and has recommended that they advise the EML committees worldwide to preferentially recommend naproxen as the NSAID of choice. He said he does not expect drug regulatory committees, such as the Food and Drug Administration,Health Canada, or the European Medicines Agency (EMA), to withdraw the drugs. In October 2012, the EMA finalized a review that concluded there was a small increase in the risk of cardiovascular side effects with diclofenac compared with other NSAIDs.
"I don't think there is any real new information that would lead them to act, rather than information showing that diclofenac is the most popular drug and it has the same risks as Vioxx," said Henry. "I'm not expecting that change in attitude to suddenly occur. What we'd like to get across to prescribers is to not use diclofenac and to use naproxen. Also, these are not disease-modifying drugs, they're symptom-relieving drugs. We typically tell patients not to stop a medication and to talk to their doctor, but if you have heart disease and are taking diclofenac, do stop the medication and then go talk to your doctor about an alternative."
Source: http://www.medscape.com/viewarticle/779232?nlid=28284_1301&src=wnl_edit_dail
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