September 24, 2010 — One in 5 gay and bisexual men in major cities in the United States is infected with HIV, and nearly half — 44% — do not know their status. Most unaware are young and minority men who have sex with men (MSM), according to a new analysis published in the September 24 issue of the Morbidity and Mortality Weekly Report.
"[MSM] are at increased risk for infection with [HIV]," write A. Smith, MPH, and colleagues from the Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, US Centers for Disease Control and Prevention (CDC). "In 2006, 57% of new HIV infections in the United States occurred among MSM."
The CDC uses the National HIV Surveillance system (NHBS) to monitor prevalence and trends in HIV-related risk behaviors, HIV testing, and use of HIV prevention services among high-risk populations. In the current report, the authors summarize NHBS data from 2008.
From January to December 2008, 8153 MSM from 21 cities were interviewed and tested for HIV. The study found that the overall prevalence of HIV was 19%.
Non-Hispanic blacks had the highest prevalence (28%), followed by Hispanics (18%), non-Hispanic whites (16%), and persons who were multiracial or of other race (17%).
Forty-four percent of those infected with HIV were unaware of their status. Black MSM with HIV were least likely to be aware of their infection (59%), followed by Hispanic MSM (46%) and white MSM (26%).
The study also found that although young men, aged 30 years or younger, had a lower HIV prevalence than older men, they were much more likely to be unaware of their HIV infection. Among men aged 18 to 29 years who had HIV, 63% were unaware vs 37% of men aged 30 years and older.
Also among young men, MSM of color were less likely than their white counterparts to know they were infected with HIV. Among blacks aged 30 years or younger, 71% were unaware of their status compared with 63% of young Hispanic MSM and 40% of young white MSM.
The study also found a strong link between socioeconomic status and HIV infection in MSM. The prevalence of HIV infection increased as education and income decreased, as did awareness. These findings are similar to those found in recent NHBS research among homosexuals, the authors report.
Men who know their current HIV infection status can be referred to appropriate medical care and prevention services. Once they are linked to prevention services, they can learn ways to avoid transmitting HIV to others, the authors note, adding that efforts to reach out to young and minority MSM should be increased to promote testing for HIV.
The authors also note limitations of their report. Because interviewers conducted the surveys, positive HIV status might have been underreported. Also, because the findings are limited to men who frequented bars, dance clubs, and other MSM venues, they may not be representative of results for all MSM.
"The high proportion of MSM unaware of their HIV infection continues to be a serious public health concern, because these MSM account for the majority of estimated new HIV transmissions in the United States," the author write in their concluding remarks. "The 2008 NHBS data show that MSM remain a key target of strategies to reduce HIV incidence and decrease racial and socioeconomic disparities in the United States."
"This study's message is clear: HIV exacts a devastating toll on [MSM] in America's major cities, and yet far too many of those who are infected don't know it," Kevin Fenton, MD, director of the CDC's National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, said in a statement. "We need to increase access to HIV testing so that more MSM know their status, and we all must bring new energy, new approaches, and new champions to the fight against HIV among [MSM]."
The authors have disclosed no relevant financial relationships.
Morb Mortal Wkly Rep. 2010;59:1201-1207
September 26, 2010
September 22, 2010
Compared with patients without depression and CHD, the risk for all-cause mortality was 3 times higher, and the risk for cardiovascular disease mortality 4 times higher, in patients who had both, after adjusting for age and sex, report Hermann Nabi, MD, from Hôpital Paul-Brousse, Villejuif, Paris, France, and colleagues.
"This study provides further evidence that the relationship between depression and morbidity–mortality is real," Dr. Nabi told Medscape Medical News.
Depression and mortality have been studied separately in patients with CHD and in healthy patients, but this does not allow comparisons across risk-factor groups according to depression and CHD status.
In the study, Dr. Nabi and his team examined the effects of both on mortality in 5936 middle-aged men and women whose mental and physical health were followed-up for a mean of 5.6 years.
The study population was part of the Whitehall II cohort study, a longitudinal study established in 1985 to examine the effect of social and economic factors on the long-term health of 10,308 civil servants who were aged between 35 and 55 years at the start of the study.
Of the 5936 individuals, 170 died during follow-up; 47 of those deaths were from cardiovascular disease.
The analysis showed that the prevalence of depression was 14.9%, and participants with a history of CHD were more likely to have depressive symptoms (20% vs 14%; P = .001) than those without CHD.
The age- and sex-adjusted hazard ratios for all-cause mortality were 1.67 (P < .05) for participants with CHD only, 2.10 (P < .001) for those with depressive symptoms only, and 4.99 (P < .001) for those with both CHD and depressive symptoms compared with participants who were free of both conditions.
Need for a More Integrated Approach
The study findings have implications for research and clinical practice, Dr. Nabi said.
"For research, this study shows that the mechanisms underlying the association between depression and adverse health outcomes such as mortality are still in need of comprehensive studies."
For clinical practice, it implies the need for a more integrated approach in the healthcare system and a shift toward a more "mind–body medicine' approach.
An important step would be to identify cardiac patients who also have depression, he said.
"In this study, the depression worsened heart disease, because we observed that participants with both depression and heart disease were at increased risk for death when compared with those with heart disease only. So we should identify those cardiac patients who have clinically significant depressive symptoms."
Dr. Nabi expressed the wish that his study findings will prompt clinicians to be aware of and look for depression in their patients with heart disease.
"Even though there is no consensus at the moment, healthcare professionals should screen and treat, or refer to treatment. Simple screening tools exist, and [clinicians] should refer their depressed patients, particularly if an adequate referral for systematic depression assessment and treatment is readily available."
He also discussed some limitations of the study.
"This study is based on a cohort of civil servants and did not include blue-collar workers, unemployed, or individuals with precarious jobs. This may have underestimated the magnitude of associations observed in our study because of the prevalence of depression and the mortality rate is higher in these latter individuals. Thus, it is reasonable to assume that the effect of depression would be greater in studies including various populations."
Randomized Trial Required
"This paper is adding to a literature that is imperfect. It makes you feel more confident about the literature," Alexander H. Glassman, MD, chief of clinical psychopharmacology at New York State Psychiatric Institute and professor of psychiatry at Columbia University, New York City, commented to Medscape Medical News.
"There are literally a hundred, maybe more, studies indicating that depression and heart disease are related," Dr. Glassman, who was not part of the current study, noted. "There are a handful of studies that do not find a relationship, but they are vastly outnumbered by the ones that have found a relationship."
However, he pointed out, just because there is an association that does not mean one condition causes the other. The way to prove cause would be with a randomized controlled trial.
"It's very easy to think depression is increasing the risk or is a cause of subsequent heart disease. And let me say, I think it is," said Dr. Glassman, who led the placebo-controlled Sertraline Antidepressant Heart Attack Randomized Trial (SADHART), as reported by Medscape Medical News.
SADHART found that patients hospitalized for acute coronary syndrome who also have major depression are twice as likely to die within 7 years if their depression did not significantly improve.
"The best way to know for sure would be to do a randomized trial on the treatment for depression with a placebo control. If you reduced the depression and those people with an antidepressant effect had a lower mortality, then you would have unequivocal evidence that depression is causing death, because by getting rid of it, you reduce the chance of dying."
The study was funded by the Medical Research Council, British Heart Foundation, Health and Safety Executive, Department of Health, National Heart Lung and Blood Institute, National Institute on Aging, Agency for Health Care Policy Research, and John D. and Catherine T. MacArthur Foundation Research Networks on Successful Midlife Development and Socio-economic Status and Health. Dr. Nabi has disclosed no relevant financial relationships. Dr. Glassman reports financial relationships with Pfizer Inc.
Heart. Published online September 16, 2010.
September 19, 2010
"In clinical trials of drug treatments for women's sexual dysfunction, placebo responses have often been substantial," write Andrea Bradford, PhD, from Baylor College of Medicine in Houston, Texas, and Cindy M. Meston, PhD, from the University of Texas at Austin. "However, little is known about the clinical significance, specificity, predictors, and potential mechanisms of placebo response in sexual dysfunction."
The goal of the study was to evaluate the characteristics and predictors of sexual function outcomes in 50 women with FSAD who were randomly assigned to the placebo group of a 12-week, multisite, controlled pharmaceutical trial. Magnitude, domain specificity, and clinical significance of sexual function scores were evaluated at baseline and at 4, 8, and 12 weeks (after study completion).
Change with time in sexual function outcomes was assessed in relationship to several variables, including age and symptom-related distress at baseline, as well as changes in frequency of sexual behavior during the trial. The primary study endpoint was the total score on the Female Sexual Function Index.
"It's important to note that, even though these women received placebo, they all had an opportunity to talk to a health provider about their difficulties and were asked to closely monitor their sexual behavior and feelings over a 12-week period," Dr. Bradford said in a news release. "Just taking part in this study probably started some meaningful conversations."
Approximately one third of women receiving placebo had a clinically significant magnitude of change after study completion, with similar effect sizes across multiple aspects of sexual function. Although symptom improvement was strongly associated with the frequency of satisfying sexual encounters (SSEs) during treatment, there was significant variation between participants in the association between frequency of sexual encounters and outcome.
"Our study shows that even a limited intervention can have a positive effect in many women with sexual dysfunction," Dr. Bradford said. "This comes as no surprise to sex therapists, but it does suggest a need to investigate behavioral factors more closely in clinical trials."
Limitations of this study include observational design, precluding determination of causality; and the possibility that SSE frequency was just a proxy for another variable, such as changes in general relationship functioning. In addition, the retrospective analysis prevented direct manipulation of variables of interest, and it is not known whether trial participants who received no treatment would have reported the same effects as participants who received placebo.
"A substantial number of women experienced clinically significant improvement in sexual function during treatment with placebo," the study authors write. "Changes in sexual behavior during the trial, more so than participant age or symptom severity at baseline, appeared to be an important determinant of outcome. Contextual and procedural aspects of the clinical trial may have influenced outcomes in the absence of an active drug treatment."
Eli Lilly/ICOS shared the data set used in this study. This study was supported in part by the Houston VA HSR&D Center of Excellence. The views expressed in the journal article are those of the study authors and do not necessarily represent the views of the Department of Veterans Affairs. Drs. Bradford and Meston have disclosed no relevant financial relationships.
J Sex Med. Published online September 16, 2010.
September 16, 2010 — Around 20% of colon cancer in European countries could be prevented if the whole population managed to reach optimum levels of weight and physical activity, suggest new projections.
The data are reported in the September issue of the European Journal of Cancer, which is dedicated to cancer prevention.
An increasing proportion of the European population now has a body mass index (BMI) higher than 25 kg/m2, and few Europeans are engaging in the amounts of physical activity recommended by current guidelines (at least 30 minutes of moderate-intensity activity 5 or more days a week), the researcher note.
The researchers set out to predict what would happen if the European population managed to maintain a mean BMI of 21 kg/m2 and if all countries had a level of physical activity similar to that seen in the Netherlands, where both cycling and walking are popular.
They used the PREVENT statistical modeling method, which was developed at Erasmus University in the Netherlands and is frequently used in the European Union's EUROCADET project.
"We know that large numbers of colon cancer cases could be avoided by reducing exposure to risk factors," said senior author Andrew Renehan, PhD, FRCS, FDS, from the School of Medicine, University of Manchester, United Kingdom. And 2 of the most easily controllable risk factors are physical inactivity and excess weight, he added.
"The predictive modeling is beginning to tease out the independent relevance of each of these factors in the prevention of colon cancer," he said in a statement.
"Preventing weight gain and encouraging weight reduction seem to be most beneficial in men, but for women a strategy with a greater emphasis on increasing physical activity would be more effective," he explained.
Colon Cancer Increasing
Colon cancer rates are increasing in Europe; they have been on the rise since 1975. It is the second most common cancer in Europe and the second most common cause of cancer death, the researchers note.
In a previous study, Dr. Renehan and colleagues attributed the increasing rates of all cancers to increasing obesity in European countries. They estimated that in 2008, new cancers attributed to excess body weight affected 3.2% of women and 8.6% of men; this was an increase from the estimates for 2002, which projected that excess weight was related to new cancers in 2.5% of men and 4.1% of women.
Those data were presented at the 2009 meeting of the European Cancer Organization, and reported by Medscape Medical News at the time.
"People in Europe are gaining weight," Dr. Renehan said at the time, "and it is projected to keep rising."
In the new study, the researchers used the computer model to look at what would happen if Europeans continued to grow fatter, using a hypothetical scenario in which obesity levels increased at the same rate as they have in the United States. They predicted that this would lead to an increase in the number of new colon cancer cases of between 0.7% and 3.8%, depending on the European country.
Then they hypothesized a scenario in which Europeans managed to control their weight and managed to achieve an optimum BMI of 21 kg/m2. They calculated that by the year 2040, this weight-control strategy would prevent between 2% and 18% of colon cancer cases across the countries they studied. The benefits were much higher for males (13.5% to 18%) than for females (2.3% to 4.6%), and most benefit would be seen in British males (in whom 18% of new colon cancer cases could be prevented).
This "underlines the importance of stopping and reversing the ongoing increase in overweight and obesity prevalence," the authors note.
When the team considered physical activity, they found that the Netherlands had the highest rates, which they attributed to a high frequency of bike use, often as a means of transportation. They also found high levels of walking.
Using the Netherlands as the ideal, the researchers predicted what would happen if other countries adopted the same amount of physical activity. They found that overall, 17.5% of new colon cancer cases could be prevented by 2040, with the most benefit in Spanish females (in whom 21% of new colon cancer cases could be prevented).
"We can safely say that increasing physical activity across Europe to the level already achieved in the Netherlands, where everyone cycles, would be of substantial benefit," said coauthor Jan-Willem Coebergh, MD, PhD, from Erasmus University.
"In summary, the changes in physical activity and/or mean levels of overweight in the selected European populations would result in quite substantial effects on future colon cancer rates," the authors conclude.
The researchers have disclosed no relevant financial relationships.
Eur J Cancer. 2010;46:2605-2616.
Continue Reading
The data are reported in the September issue of the European Journal of Cancer, which is dedicated to cancer prevention.
An increasing proportion of the European population now has a body mass index (BMI) higher than 25 kg/m2, and few Europeans are engaging in the amounts of physical activity recommended by current guidelines (at least 30 minutes of moderate-intensity activity 5 or more days a week), the researcher note.
The researchers set out to predict what would happen if the European population managed to maintain a mean BMI of 21 kg/m2 and if all countries had a level of physical activity similar to that seen in the Netherlands, where both cycling and walking are popular.
They used the PREVENT statistical modeling method, which was developed at Erasmus University in the Netherlands and is frequently used in the European Union's EUROCADET project.
"We know that large numbers of colon cancer cases could be avoided by reducing exposure to risk factors," said senior author Andrew Renehan, PhD, FRCS, FDS, from the School of Medicine, University of Manchester, United Kingdom. And 2 of the most easily controllable risk factors are physical inactivity and excess weight, he added.
"The predictive modeling is beginning to tease out the independent relevance of each of these factors in the prevention of colon cancer," he said in a statement.
"Preventing weight gain and encouraging weight reduction seem to be most beneficial in men, but for women a strategy with a greater emphasis on increasing physical activity would be more effective," he explained.
Colon Cancer Increasing
Colon cancer rates are increasing in Europe; they have been on the rise since 1975. It is the second most common cancer in Europe and the second most common cause of cancer death, the researchers note.
In a previous study, Dr. Renehan and colleagues attributed the increasing rates of all cancers to increasing obesity in European countries. They estimated that in 2008, new cancers attributed to excess body weight affected 3.2% of women and 8.6% of men; this was an increase from the estimates for 2002, which projected that excess weight was related to new cancers in 2.5% of men and 4.1% of women.
Those data were presented at the 2009 meeting of the European Cancer Organization, and reported by Medscape Medical News at the time.
"People in Europe are gaining weight," Dr. Renehan said at the time, "and it is projected to keep rising."
In the new study, the researchers used the computer model to look at what would happen if Europeans continued to grow fatter, using a hypothetical scenario in which obesity levels increased at the same rate as they have in the United States. They predicted that this would lead to an increase in the number of new colon cancer cases of between 0.7% and 3.8%, depending on the European country.
Then they hypothesized a scenario in which Europeans managed to control their weight and managed to achieve an optimum BMI of 21 kg/m2. They calculated that by the year 2040, this weight-control strategy would prevent between 2% and 18% of colon cancer cases across the countries they studied. The benefits were much higher for males (13.5% to 18%) than for females (2.3% to 4.6%), and most benefit would be seen in British males (in whom 18% of new colon cancer cases could be prevented).
This "underlines the importance of stopping and reversing the ongoing increase in overweight and obesity prevalence," the authors note.
When the team considered physical activity, they found that the Netherlands had the highest rates, which they attributed to a high frequency of bike use, often as a means of transportation. They also found high levels of walking.
Using the Netherlands as the ideal, the researchers predicted what would happen if other countries adopted the same amount of physical activity. They found that overall, 17.5% of new colon cancer cases could be prevented by 2040, with the most benefit in Spanish females (in whom 21% of new colon cancer cases could be prevented).
"We can safely say that increasing physical activity across Europe to the level already achieved in the Netherlands, where everyone cycles, would be of substantial benefit," said coauthor Jan-Willem Coebergh, MD, PhD, from Erasmus University.
"In summary, the changes in physical activity and/or mean levels of overweight in the selected European populations would result in quite substantial effects on future colon cancer rates," the authors conclude.
The researchers have disclosed no relevant financial relationships.
Eur J Cancer. 2010;46:2605-2616.
September 16, 2010 — Although there have been major residency reforms during the past decade, rates of presenteeism (working while sick) among resident physicians are high and similar to rates seen in 1999, according to the results of a research letter reported in the September 15 issue of the Journal of the American Medical Association.
"Despite recent Centers for Disease Control and Prevention guidelines urging health care personnel with flu-like illness to avoid working, presenteeism (working while sick) is prevalent among health care workers," write Anupam B. Jena, MD, PhD, from Massachusetts General Hospital in Boston, and colleagues. "Ill health care workers can endanger patients and colleagues due to decline in performance or spread of disease. Resident physicians may face unique pressures to work when sick and lack time to seek health care."
The study goal was to evaluate self-reported presenteeism rates and associated factors among residents in a sample of programs selected for varied geographic, size, and governance characteristics. A 50-item survey was administered anonymously in August 2009 to 744 residents in postgraduate year (PGY) 2 and 3 in general surgery, obstetrics/gynecology, internal medicine, and pediatrics at 35 programs in 12 hospitals regarding presenteeism during the prior year. Overall response rate was 72.2% (range among hospitals, 48% - 100%).
More than half of responders (57.9%; 95% confidence interval [CI], 53.6% - 62.1%) reported working at least once while sick in the previous year, and nearly one third (31.3%; 95% CI, 27.2% - 35.2%) reported working more than once while sick. More than half (52.9%; 95% CI, 48.5% - 57.1%) reported having insufficient time to visit a physician during the previous academic year.
Presenteeism was reported more often during PGY-2 (62.3%; 95% CI, 57.1% - 68.4%) than during PGY-1 (51.7%; 95% CI, 45.6% - 57.9%; P = .01). Sex, specialty, or medical school location did not affect reported rates of presenteeism or of having time to see a physician. Presenteeism rates did not vary significantly by hospital response rate or across hospitals, except for 1 outlier hospital in which 100% of residents reported working when sick.
"Despite major residency reforms over the last decade to ensure resident and patient health, rates of resident presenteeism were high and similar to rates observed in 1999," the study authors write. "The higher rate of reporting working when ill among PGY-2 vs. PGY-1 residents may reflect a greater responsibility toward patient care, consistent with higher presenteeism rates among workers who believe their duties are not easily substituted. The lack of factors associated with presenteeism suggests it may be pervasive."
Limitations of this study include reliance on self-report, lack of distinction between infectious and noninfectious illness, and potential bias associated with H1N1 influenza cases during survey development.
"Residents may work when sick for several reasons, including misplaced dedication, lack of an adequate coverage system, or fear of letting down teammates," the study authors conclude. "Regardless of reason, given the potential risks to patients related to illness and errors, resident presenteeism should be discouraged by program directors."
This study was funded by the Accreditation Council for Graduate Medical Education. Several of the study authors report various financial relationships with the Agency for Health Care Research and Quality, the National Institutes of Health, the Accreditation Council for Graduate Medical Education, the American Board of Internal Medicine Foundation, and/or the Institute of Medicine.
JAMA. 2010;304:1166-1168.
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"Despite recent Centers for Disease Control and Prevention guidelines urging health care personnel with flu-like illness to avoid working, presenteeism (working while sick) is prevalent among health care workers," write Anupam B. Jena, MD, PhD, from Massachusetts General Hospital in Boston, and colleagues. "Ill health care workers can endanger patients and colleagues due to decline in performance or spread of disease. Resident physicians may face unique pressures to work when sick and lack time to seek health care."
The study goal was to evaluate self-reported presenteeism rates and associated factors among residents in a sample of programs selected for varied geographic, size, and governance characteristics. A 50-item survey was administered anonymously in August 2009 to 744 residents in postgraduate year (PGY) 2 and 3 in general surgery, obstetrics/gynecology, internal medicine, and pediatrics at 35 programs in 12 hospitals regarding presenteeism during the prior year. Overall response rate was 72.2% (range among hospitals, 48% - 100%).
More than half of responders (57.9%; 95% confidence interval [CI], 53.6% - 62.1%) reported working at least once while sick in the previous year, and nearly one third (31.3%; 95% CI, 27.2% - 35.2%) reported working more than once while sick. More than half (52.9%; 95% CI, 48.5% - 57.1%) reported having insufficient time to visit a physician during the previous academic year.
Presenteeism was reported more often during PGY-2 (62.3%; 95% CI, 57.1% - 68.4%) than during PGY-1 (51.7%; 95% CI, 45.6% - 57.9%; P = .01). Sex, specialty, or medical school location did not affect reported rates of presenteeism or of having time to see a physician. Presenteeism rates did not vary significantly by hospital response rate or across hospitals, except for 1 outlier hospital in which 100% of residents reported working when sick.
"Despite major residency reforms over the last decade to ensure resident and patient health, rates of resident presenteeism were high and similar to rates observed in 1999," the study authors write. "The higher rate of reporting working when ill among PGY-2 vs. PGY-1 residents may reflect a greater responsibility toward patient care, consistent with higher presenteeism rates among workers who believe their duties are not easily substituted. The lack of factors associated with presenteeism suggests it may be pervasive."
Limitations of this study include reliance on self-report, lack of distinction between infectious and noninfectious illness, and potential bias associated with H1N1 influenza cases during survey development.
"Residents may work when sick for several reasons, including misplaced dedication, lack of an adequate coverage system, or fear of letting down teammates," the study authors conclude. "Regardless of reason, given the potential risks to patients related to illness and errors, resident presenteeism should be discouraged by program directors."
This study was funded by the Accreditation Council for Graduate Medical Education. Several of the study authors report various financial relationships with the Agency for Health Care Research and Quality, the National Institutes of Health, the Accreditation Council for Graduate Medical Education, the American Board of Internal Medicine Foundation, and/or the Institute of Medicine.
JAMA. 2010;304:1166-1168.
September 17, 2010
September 15, 2010 — Swimming in indoor pools may result in respiratory effects and induce DNA damage that could lead to cancer, according to new research that examined the impact of byproducts of pool disinfection.
But the researchers emphasize they are not suggesting anyone get out of the pool. "We do not say stop swimming," says researcher Manolis Kogevinas, MD, PhD, professor of epidemiology at the Centre for Research in Environmental Epidemiology in Barcelona. "We should keep a clear message that swimmers should keep swimming."
The research findings, he tells WebMD, are a message to the industry that ''the positive effects of swimming could be increased by reducing the chemicals."
Industry experts and pool researchers agree. "It's good that research is being done in this area,'' says Thomas Lachocki, CEO of the National Swimming Pool Foundation, an educational nonprofit organization based in Colorado Springs, Colo. The research is published online in the journal Environmental Health Perspectives.
Swimming and Health Risks: A Closer Look
''We have been doing research on chemicals in water -- not swimming pools [specifically] -- for quite some time," Kogevinas says. More recently, he and his colleagues have focused more intently on indoor swimming pool water. "Chemicals are produced when you put chlorine in water," he says. Chlorine reacts, for instance, to urine, cosmetics, and other substances typically found in swimming pools.
The researchers wanted to characterize these disinfection byproducts, or DBPs, in an indoor pool environment. Other studies have linked DBP exposure in drinking water to a risk of bladder cancer and other problems.
In the first of three new studies published in the journal, the researchers evaluated 49 healthy adults after they swam for 40 minutes in an indoor chlorinated pool, looking for biomarkers linked to cancer.
"What we found is by analyzing blood samples and urine samples, we have an increase in risk markers related to cancer," Kogevinas tells WebMD.
Exposure to the pool water was associated with a five-fold increase in one of the markers, he says. But that does not mean swimmers are doomed to get cancer, he stresses.
"This doesn't mean at all that swimmers have a five times increased cancer risk," he says. "It simply means that after swimming for 40 minutes in a chlorinated pool, you get an increase in this marker in the blood that in other studies has been associated with future cancer risk."
Swimming and Respiratory Effects
In a second study, Kogevinas and his colleagues focused on respiratory effects of exposure to indoor pool water.
"We compared markers of lung injury before and after swimming," he says, evaluating 48 swimmers this time, from the same group as in the first study.
They found changes in just one blood marker, a slight increase in one known as CC16. The increase, the researchers say, is due to the exercise itself in addition to the DBP exposure.
''Some studies have suggested a link with swimming and asthma," Kogevinas says. "We found [only] one of many [respiratory] biomarkers [had] a small increase."
Swimming Pool Chemicals: What's in Pool Water?
In a third study, the researchers looked at water and air samples from two indoor pools. "We shipped them to the EPA [U.S. Environmental Protection Agency]," Kogevinas says. They found more than 100 DBPs in the pool water, some not identified before.
''Many are the same chemicals we find in tap water," he tells WebMD. "Some have been identified in experimental studies, animal studies, to be harmful."
The bottom line? "Pool water is not worse or better than tap water," he says, when it comes to byproducts. Only in the pool, he adds, "swimmers get a massive dose."
Swimming Pools and Health Risks: Second Views
Experts from the swimming pool industry say research is crucial. "It's important we find ways to reduce exposure to potentially hazardous chemicals in pools," Lachocki says.
Even so, he calls the three studies "limited" because of some shortcomings. He wanted more information on how the pools studied were managed and what standards were used to keep the pools maintained.
"The question is, were the pools studied on the end of the spectrum of fabulously well taken care of, or not so fabulously?" he says.
The conclusion of the research that the pool water is no more hazardous than drinking water doesn't tell people if that is representative of most pools or just the ones studied, Lachocki says.
Another limitation is the small number of swimmers studied, he says.
What's a Swimmer to Do?
Lachocki agrees that no one should give up swimming as a result of the research. "Swimming continues to be ideal for an aging population and for a sedentary population," he says.
People who swim in indoor pools can check out the pool first, he tells WebMD. Ask, for instance, if the pool has certified operators, which means they have had training in how best to disinfect a pool.
His foundation trains certified operators. "There should be a certificate on the wall, showing the people who operate the pool are certified."
Swimmers can buy test strips, widely available at pool supply stores, and test the water themselves, he says. Swimmers can also ask the pool operators to show them the maintenance records proving the pool is maintained properly, he says.
Kogevinas suggests that people who swim in indoor pools follow rules, such as not urinating in the pool and showering before swimming.
SOURCES:
Manolis Kogevinas, MD, PhD, professor of epidemiology, Centre for Research in Environmental Epidemiology, Barcelona, Spain.
Thomas Lachocki, PhD, CEO, National Swimming Pool Foundation, Colorado Springs, Colo.
Kogevinas, M. Environmental Health Perspectives, online Sept. 12, 2010.
Font-Ribera, L. Environmental Health Perspectives, online Sept. 12, 2010.
Richardson, S. Environmental Health Perspectives, online Sept. 12, 2010.
Continue Reading
But the researchers emphasize they are not suggesting anyone get out of the pool. "We do not say stop swimming," says researcher Manolis Kogevinas, MD, PhD, professor of epidemiology at the Centre for Research in Environmental Epidemiology in Barcelona. "We should keep a clear message that swimmers should keep swimming."
The research findings, he tells WebMD, are a message to the industry that ''the positive effects of swimming could be increased by reducing the chemicals."
Industry experts and pool researchers agree. "It's good that research is being done in this area,'' says Thomas Lachocki, CEO of the National Swimming Pool Foundation, an educational nonprofit organization based in Colorado Springs, Colo. The research is published online in the journal Environmental Health Perspectives.
Swimming and Health Risks: A Closer Look
''We have been doing research on chemicals in water -- not swimming pools [specifically] -- for quite some time," Kogevinas says. More recently, he and his colleagues have focused more intently on indoor swimming pool water. "Chemicals are produced when you put chlorine in water," he says. Chlorine reacts, for instance, to urine, cosmetics, and other substances typically found in swimming pools.
The researchers wanted to characterize these disinfection byproducts, or DBPs, in an indoor pool environment. Other studies have linked DBP exposure in drinking water to a risk of bladder cancer and other problems.
In the first of three new studies published in the journal, the researchers evaluated 49 healthy adults after they swam for 40 minutes in an indoor chlorinated pool, looking for biomarkers linked to cancer.
"What we found is by analyzing blood samples and urine samples, we have an increase in risk markers related to cancer," Kogevinas tells WebMD.
Exposure to the pool water was associated with a five-fold increase in one of the markers, he says. But that does not mean swimmers are doomed to get cancer, he stresses.
"This doesn't mean at all that swimmers have a five times increased cancer risk," he says. "It simply means that after swimming for 40 minutes in a chlorinated pool, you get an increase in this marker in the blood that in other studies has been associated with future cancer risk."
Swimming and Respiratory Effects
In a second study, Kogevinas and his colleagues focused on respiratory effects of exposure to indoor pool water.
"We compared markers of lung injury before and after swimming," he says, evaluating 48 swimmers this time, from the same group as in the first study.
They found changes in just one blood marker, a slight increase in one known as CC16. The increase, the researchers say, is due to the exercise itself in addition to the DBP exposure.
''Some studies have suggested a link with swimming and asthma," Kogevinas says. "We found [only] one of many [respiratory] biomarkers [had] a small increase."
Swimming Pool Chemicals: What's in Pool Water?
In a third study, the researchers looked at water and air samples from two indoor pools. "We shipped them to the EPA [U.S. Environmental Protection Agency]," Kogevinas says. They found more than 100 DBPs in the pool water, some not identified before.
''Many are the same chemicals we find in tap water," he tells WebMD. "Some have been identified in experimental studies, animal studies, to be harmful."
The bottom line? "Pool water is not worse or better than tap water," he says, when it comes to byproducts. Only in the pool, he adds, "swimmers get a massive dose."
Swimming Pools and Health Risks: Second Views
Experts from the swimming pool industry say research is crucial. "It's important we find ways to reduce exposure to potentially hazardous chemicals in pools," Lachocki says.
Even so, he calls the three studies "limited" because of some shortcomings. He wanted more information on how the pools studied were managed and what standards were used to keep the pools maintained.
"The question is, were the pools studied on the end of the spectrum of fabulously well taken care of, or not so fabulously?" he says.
The conclusion of the research that the pool water is no more hazardous than drinking water doesn't tell people if that is representative of most pools or just the ones studied, Lachocki says.
Another limitation is the small number of swimmers studied, he says.
What's a Swimmer to Do?
Lachocki agrees that no one should give up swimming as a result of the research. "Swimming continues to be ideal for an aging population and for a sedentary population," he says.
People who swim in indoor pools can check out the pool first, he tells WebMD. Ask, for instance, if the pool has certified operators, which means they have had training in how best to disinfect a pool.
His foundation trains certified operators. "There should be a certificate on the wall, showing the people who operate the pool are certified."
Swimmers can buy test strips, widely available at pool supply stores, and test the water themselves, he says. Swimmers can also ask the pool operators to show them the maintenance records proving the pool is maintained properly, he says.
Kogevinas suggests that people who swim in indoor pools follow rules, such as not urinating in the pool and showering before swimming.
SOURCES:
Manolis Kogevinas, MD, PhD, professor of epidemiology, Centre for Research in Environmental Epidemiology, Barcelona, Spain.
Thomas Lachocki, PhD, CEO, National Swimming Pool Foundation, Colorado Springs, Colo.
Kogevinas, M. Environmental Health Perspectives, online Sept. 12, 2010.
Font-Ribera, L. Environmental Health Perspectives, online Sept. 12, 2010.
Richardson, S. Environmental Health Perspectives, online Sept. 12, 2010.
September 10, 2010
September 8, 2010 (Stockholm, Sweden) — Short-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with an increased risk of stroke in a Danish population study including only healthy individuals.
Presenting the study at last week's European Society of Cardiology (ESC) 2010 Congress, Dr Gunnar Gislason (Gentofte University Hospital, Hellerup, Denmark) said the results could have "massive public-health implications."
"First we found an increased risk of MI with NSAIDs. Now we are finding the same thing for stroke. This is very serious, as these drugs are very widely used, with many available over the counter," Gislason told heartwire . "We need to get the message out to healthcare authorities that these drugs need to be regulated more carefully."
Cochair of the session at which the study was presented, Dr Robert Califf (Duke Clinical Research Institute, Durham, NC), agreed that the results raised a major public-health issue, especially in the US, where many NSAIDs were available without a prescription.
For the current study, Gislason and colleagues examined the risk of stroke and NSAID use in healthy individuals living in Denmark. He explained to heartwire that information on each individual in the Danish population is kept in various national registries. His team started with the whole population of Denmark aged over 10 years. To select just the healthy individuals, they excluded anyone admitted to the hospital within the past five years or those prescribed chronic medications for more than two years. This left a population of around half a million, who were included in the study. By linking to prescribing registries, the researchers found that 45% of these healthy individuals had received at least one prescription for an NSAID between 1997 and 2005. They then used stroke data from further hospitalization and death registries and estimated the risk of fatal and nonfatal stroke associated with the use of NSAIDs by Cox proportional-hazard models and case-crossover analyses.
Results showed that NSAID use was associated with an increased risk of stroke. This increased risk ranged from about 30% with ibuprofen and naproxen to 86% with diclofenac.
Risk of Stroke With Various Nsaids
Gislason noted that there was also a dose-relationship found, with the increased risk of stroke reaching 90% (HR 1.90) with doses of ibuprofen over 200 mg and 100% (HR 2.0) with diclofenac doses over 100 mg. He pointed out that the results were particularly striking, given that this study was conducted in healthy individuals.
He conceded that his results could have some confounding but noted that the data were controlled for age, gender, and socioeconomic status and the patient population did not include those with chronic diseases. "We also have to think about the degree of confounding needed to nullify risk. It would have to increase risk four- to fivefold, which is very unlikely," he commented.
He said he did not find the results that surprising in view of the accumulating evidence of increased MI risk with these drugs, adding that the mechanism was probably the same. There have been several hypotheses about the mechanism linking NSAIDs with cardiovascular events, including increased thrombotic effect on platelets, the endothelium, and/or atherosclerotic plaques; increasing blood pressure; and effect on the kidneys and salt retention.
Gislason told heartwire that there is reluctance among the medical profession to limit the prescribing of these drugs. "The problem is that we don't have randomized trials, and it is very hard to change the habits of doctors. They have been using these drugs for decades without thinking about cardiovascular side effects."
He also stressed that the public needs to be protected by not allowing NSAIDs to be bought without a prescription. He has had some success in this regard in Denmark at least, where diclofenac became available over the counter recently, but after some of the MI data came out, Gislason's group campaigned the health authorities, and it has now become a prescription-only drug again. But he noted that many more NSAIDs are available over the counter in the US.
He believes the harmful effects of these agents are relevant to huge numbers of people. "If half the population takes these drugs, even on an occasional basis, then this could be responsible for a 50% to 100% increase in stroke risk. It is an enormous effect."
These results have been partly published in Circulation: Cardiovascular Quality and Outcomes earlier this year [1]. Gislason told heart wire that the novelty of the results presented at the ESC meeting was that "we had further analyzed our data regarding specific stroke and looked at the risk of ischemic stroke, and we confirmed that the risk of ischemic stroke was substantially elevated." He added: "We are in the process of analyzing these data related to time to risk and the effect of duration of treatment on stroke risk."
Continue Reading
Presenting the study at last week's European Society of Cardiology (ESC) 2010 Congress, Dr Gunnar Gislason (Gentofte University Hospital, Hellerup, Denmark) said the results could have "massive public-health implications."
"First we found an increased risk of MI with NSAIDs. Now we are finding the same thing for stroke. This is very serious, as these drugs are very widely used, with many available over the counter," Gislason told heartwire . "We need to get the message out to healthcare authorities that these drugs need to be regulated more carefully."
Cochair of the session at which the study was presented, Dr Robert Califf (Duke Clinical Research Institute, Durham, NC), agreed that the results raised a major public-health issue, especially in the US, where many NSAIDs were available without a prescription.
For the current study, Gislason and colleagues examined the risk of stroke and NSAID use in healthy individuals living in Denmark. He explained to heartwire that information on each individual in the Danish population is kept in various national registries. His team started with the whole population of Denmark aged over 10 years. To select just the healthy individuals, they excluded anyone admitted to the hospital within the past five years or those prescribed chronic medications for more than two years. This left a population of around half a million, who were included in the study. By linking to prescribing registries, the researchers found that 45% of these healthy individuals had received at least one prescription for an NSAID between 1997 and 2005. They then used stroke data from further hospitalization and death registries and estimated the risk of fatal and nonfatal stroke associated with the use of NSAIDs by Cox proportional-hazard models and case-crossover analyses.
Results showed that NSAID use was associated with an increased risk of stroke. This increased risk ranged from about 30% with ibuprofen and naproxen to 86% with diclofenac.
Risk of Stroke With Various Nsaids
| NSAID | HR (95% CI) for risk of stroke |
| Ibuprofen | 1.28 (1.14–1.44) |
| Diclofenac | 1.86 (1.58–2.19) |
| Rofecoxib | 1.61 (1.14–2.29) |
| Celecoxib | 1.69 (1.11–2.26) |
| Naproxen | 1.35 (1.01–1.79) |
He conceded that his results could have some confounding but noted that the data were controlled for age, gender, and socioeconomic status and the patient population did not include those with chronic diseases. "We also have to think about the degree of confounding needed to nullify risk. It would have to increase risk four- to fivefold, which is very unlikely," he commented.
He said he did not find the results that surprising in view of the accumulating evidence of increased MI risk with these drugs, adding that the mechanism was probably the same. There have been several hypotheses about the mechanism linking NSAIDs with cardiovascular events, including increased thrombotic effect on platelets, the endothelium, and/or atherosclerotic plaques; increasing blood pressure; and effect on the kidneys and salt retention.
Gislason told heartwire that there is reluctance among the medical profession to limit the prescribing of these drugs. "The problem is that we don't have randomized trials, and it is very hard to change the habits of doctors. They have been using these drugs for decades without thinking about cardiovascular side effects."
He also stressed that the public needs to be protected by not allowing NSAIDs to be bought without a prescription. He has had some success in this regard in Denmark at least, where diclofenac became available over the counter recently, but after some of the MI data came out, Gislason's group campaigned the health authorities, and it has now become a prescription-only drug again. But he noted that many more NSAIDs are available over the counter in the US.
He believes the harmful effects of these agents are relevant to huge numbers of people. "If half the population takes these drugs, even on an occasional basis, then this could be responsible for a 50% to 100% increase in stroke risk. It is an enormous effect."
These results have been partly published in Circulation: Cardiovascular Quality and Outcomes earlier this year [1]. Gislason told heart wire that the novelty of the results presented at the ESC meeting was that "we had further analyzed our data regarding specific stroke and looked at the risk of ischemic stroke, and we confirmed that the risk of ischemic stroke was substantially elevated." He added: "We are in the process of analyzing these data related to time to risk and the effect of duration of treatment on stroke risk."
September 04, 2010
September 3, 2010 — The chance observation that diabetes patients taking metformin have a 40% reduced risk for cancer triggered intense research interest in this old off-patent drug.
Data from a small clinical trial and from an animal study reported in the September issue of Cancer Prevention Research suggest that metformin might suppress the development of precancerous colorectal lesions in humans and prevent tobacco-induced lung cancers in mice. The drug appears to alter cellular energy metabolism in a way that is particularly bad for cancers and precancerous cells. It is also attractive because it is relatively nontoxic.
During a press briefing organized by the American Association for Cancer Research to discuss the metformin data, Michael Pollak, MD, from McGill University in Montreal, Quebec, said that the new studies are important because they indicate the usefulness of metformin as a preventive agent. Dr. Pollak wrote a review of metformin and other biguanides in oncology that appears in the same issue of Cancer Prevention Research.
"Unlike chemotherapy or radiotherapy, which are intended to kill cancer cells in a directly toxic manner, metformin appears to target the cancer in a more subtle way, which involves cancer energetics. It also may act in some patients, especially diabetic cancer patients, by reducing levels of hormones that can stimulate cell growth, including insulin itself," Dr. Pollak said.
In the first human trial of metformin as a cancer preventive, Kunihiro Hosono, MD, and colleagues from the Yokohama City University School of Medicine in Japan report that nondiabetic patients randomized to 1 month of low-dose of metformin (250 mg/day) had a significant decrease in the mean number of rectal aberrant crypt foci (ACF), an endoscopic surrogate marker of colorectal cancer.
The researchers randomized 12 nondiabetic patients with ACF to treatment with metformin and 14 to no treatment. After 1 month, the metformin patients not only had fewer ACFs, they also had significant decreases in the proliferating cell nuclear antigen index.
Dr. Hosono and colleagues write that "this first reported trial of metformin for inhibiting colorectal carcinogenesis in humans provides preliminary evidence that metformin suppresses colonic epithelial proliferation and rectal ACF formation in humans, suggesting its promise for the chemoprevention of colorectal cancer."
Low-dose metformin did not cause any adverse effects, such as lactic acidosis, hypoglycemia, or diarrhea in this study.
In related work, a research team led by Phillip A. Dennis, MD, and Regan M. Memmott, MD, from the National Cancer Institute (NCI) Medical Oncology Branch in Bethesda, Maryland, studied metformin for prevention in a mouse model of smoking-related lung cancer. They exposed mice to the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and then treated the mice with metformin in drinking water.
The researchers expected that a specific target (the rapamycin or mTOR pathway, an early event in tobacco-induced lung cancer) would be inhibited by metformin.
"After about 10% of the mouse lifespan — about 12 weeks — with the highest dose in the drinking water, we found a 33% reduction in tumor multiplicity and a 34% reduction in tumor size in the mice. In mice that did not get metformin, 100% got tobacco carcinogen-induced lung tumors," Dr. Dennis said at the press briefing. Overall, metformin reduced lung tumor burden by up to 53% at steady-state plasma concentrations that can be achieved in humans.
Despite this, mTOR was only modestly inhibited, so the researchers moved to intraperitoeal administration to achieve higher dose levels. This showed that metformin activated 5′-AMP-activated protein kinase in liver tissue (but not lung tissue), where it inhibited phosphorylation of the insulin-like growth factor (IGF)-1/insulin receptor. Mice injected with metformin daily for 12 weeks had a 72% reduction in tumor burden.
"We think that metformin was able to inhibit lung tumorigenesis caused by a tobacco carcinogen — when given in drinking water to achieve levels that could be attained in humans and when given by injection — and that the mechanism involves hormone release from the liver. We are planning to move forward to study metformin as a chemopreventive agent in clinical trials," Dr. Dennis said.
Lewis Cantley, MD, from Beth Israel Deaconess Medical Center in Boston, Massachusetts, suggested at the press briefing that metformin might prevent tumors by reducing levels of insulin and IGF-1. He noted that 2 approaches to treating type 2 diabetes (insulin, which increases insulin levels, and metformin, which decreases them) appear to have opposite effects on cancer risk.
Dr. Pollak said that "metformin's effects in animals are similar to those of a brief period of fasting. On a normal diet, metformin fools the liver into thinking it is fasting."
It fell to Dr. Cantley to mention the elephant in the room: metformin is off patent and unlikely to attract pharmaceutical industry support for clinical trials to established the drug as a general cancer preventive. "This will have to have millions of dollars in either private or NCI support," he said.
Dr. Pollak reports consulting for Merck, Novo-Nordisk, Lilly, Pfizer, and Sanofi-Aventis. Dr. Hosono and Dr. Dennis have disclosed no relevant financial relationships. Dr. Cantley is founder of and a consultant for Agios.
Cancer Prev Res (Phila Pa). 2010;3:1049-1052, 1060-1065, 1066-1076, 1077-1083.
Continue Reading
Data from a small clinical trial and from an animal study reported in the September issue of Cancer Prevention Research suggest that metformin might suppress the development of precancerous colorectal lesions in humans and prevent tobacco-induced lung cancers in mice. The drug appears to alter cellular energy metabolism in a way that is particularly bad for cancers and precancerous cells. It is also attractive because it is relatively nontoxic.
During a press briefing organized by the American Association for Cancer Research to discuss the metformin data, Michael Pollak, MD, from McGill University in Montreal, Quebec, said that the new studies are important because they indicate the usefulness of metformin as a preventive agent. Dr. Pollak wrote a review of metformin and other biguanides in oncology that appears in the same issue of Cancer Prevention Research.
"Unlike chemotherapy or radiotherapy, which are intended to kill cancer cells in a directly toxic manner, metformin appears to target the cancer in a more subtle way, which involves cancer energetics. It also may act in some patients, especially diabetic cancer patients, by reducing levels of hormones that can stimulate cell growth, including insulin itself," Dr. Pollak said.
In the first human trial of metformin as a cancer preventive, Kunihiro Hosono, MD, and colleagues from the Yokohama City University School of Medicine in Japan report that nondiabetic patients randomized to 1 month of low-dose of metformin (250 mg/day) had a significant decrease in the mean number of rectal aberrant crypt foci (ACF), an endoscopic surrogate marker of colorectal cancer.
The researchers randomized 12 nondiabetic patients with ACF to treatment with metformin and 14 to no treatment. After 1 month, the metformin patients not only had fewer ACFs, they also had significant decreases in the proliferating cell nuclear antigen index.
Dr. Hosono and colleagues write that "this first reported trial of metformin for inhibiting colorectal carcinogenesis in humans provides preliminary evidence that metformin suppresses colonic epithelial proliferation and rectal ACF formation in humans, suggesting its promise for the chemoprevention of colorectal cancer."
Low-dose metformin did not cause any adverse effects, such as lactic acidosis, hypoglycemia, or diarrhea in this study.
In related work, a research team led by Phillip A. Dennis, MD, and Regan M. Memmott, MD, from the National Cancer Institute (NCI) Medical Oncology Branch in Bethesda, Maryland, studied metformin for prevention in a mouse model of smoking-related lung cancer. They exposed mice to the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and then treated the mice with metformin in drinking water.
The researchers expected that a specific target (the rapamycin or mTOR pathway, an early event in tobacco-induced lung cancer) would be inhibited by metformin.
"After about 10% of the mouse lifespan — about 12 weeks — with the highest dose in the drinking water, we found a 33% reduction in tumor multiplicity and a 34% reduction in tumor size in the mice. In mice that did not get metformin, 100% got tobacco carcinogen-induced lung tumors," Dr. Dennis said at the press briefing. Overall, metformin reduced lung tumor burden by up to 53% at steady-state plasma concentrations that can be achieved in humans.
Despite this, mTOR was only modestly inhibited, so the researchers moved to intraperitoeal administration to achieve higher dose levels. This showed that metformin activated 5′-AMP-activated protein kinase in liver tissue (but not lung tissue), where it inhibited phosphorylation of the insulin-like growth factor (IGF)-1/insulin receptor. Mice injected with metformin daily for 12 weeks had a 72% reduction in tumor burden.
"We think that metformin was able to inhibit lung tumorigenesis caused by a tobacco carcinogen — when given in drinking water to achieve levels that could be attained in humans and when given by injection — and that the mechanism involves hormone release from the liver. We are planning to move forward to study metformin as a chemopreventive agent in clinical trials," Dr. Dennis said.
Lewis Cantley, MD, from Beth Israel Deaconess Medical Center in Boston, Massachusetts, suggested at the press briefing that metformin might prevent tumors by reducing levels of insulin and IGF-1. He noted that 2 approaches to treating type 2 diabetes (insulin, which increases insulin levels, and metformin, which decreases them) appear to have opposite effects on cancer risk.
Dr. Pollak said that "metformin's effects in animals are similar to those of a brief period of fasting. On a normal diet, metformin fools the liver into thinking it is fasting."
It fell to Dr. Cantley to mention the elephant in the room: metformin is off patent and unlikely to attract pharmaceutical industry support for clinical trials to established the drug as a general cancer preventive. "This will have to have millions of dollars in either private or NCI support," he said.
Dr. Pollak reports consulting for Merck, Novo-Nordisk, Lilly, Pfizer, and Sanofi-Aventis. Dr. Hosono and Dr. Dennis have disclosed no relevant financial relationships. Dr. Cantley is founder of and a consultant for Agios.
Cancer Prev Res (Phila Pa). 2010;3:1049-1052, 1060-1065, 1066-1076, 1077-1083.
September 01, 2010
August 31, 2010 — Daily consumption of artificially sweetened soft drinks may increase the risk for preterm delivery, according to the results of a Danish prospective cohort study reported in the September issue of the American Journal of Clinical Nutrition.
"Sugar-sweetened soft drinks have been linked to a number of adverse health outcomes such as high weight gain," write Thorhallur I. Halldorsson, from Statens Serum Institut in Copenhagen, Denmark, and colleagues. "Therefore, artificially sweetened soft drinks are often promoted as an alternative. However, the safety of artificial sweeteners has been disputed, and consequences of high intakes of artificial sweeteners for pregnant women have been minimally addressed."
The goal of the study was to evaluate the association between consumption of sugar-sweetened and artificially sweetened soft drinks and preterm delivery.
Participants were 59,334 women enrolled in the Danish National Birth Cohort from 1996 to 2002. With use of a food frequency questionnaire, soft drink consumption was evaluated in midpregnancy, and telephone interviews determined covariate information. The main study endpoint was preterm delivery, defined as less than 37 weeks of gestation.
Consumption of artificially sweetened carbonated and noncarbonated soft drinks was associated with an increased risk for preterm delivery (P for trend ≤ .001 for both variables). Compared with women who did not drink artificially sweetened carbonated soft drinks, the adjusted odds ratio (OR) for women who drank at least 1 serving daily was 1.38 (95% confidence interval [CI], 1.15 - 1.65), and the adjusted OR for women who drank at least 4 servings daily was 1.78 (95% CI, 1.19 - 2.66). These associations were noted in normal-weight as well as in overweight women. Increased risk was stronger for early preterm and moderately preterm delivery vs late-preterm delivery.
For sugar-sweetened carbonated or noncarbonated soft drinks, no apparent association with the risk for preterm delivery was observed.
"Daily intake of artificially sweetened soft drinks may increase the risk of preterm delivery," the study authors write. "Further studies are needed to reject or confirm these findings."
Limitations of this study include possible reverse causality, inability to implicate specific artificial sweetener(s), observational design, and unidentified or residual confounders.
"The relative consistency of our findings for carbonated and noncarbonated soft drinks and the absence of an association for sugar-sweetened soft drinks suggest that the content of artificial sweeteners might be the causal factor," the study authors conclude. "However, the replication of our findings in another experimental setting is warranted."
The European Union (EU) Integrated Research Project EARNEST supported this study. The EU project EARNEST receives financial support from the Commission of the European Communities. The Danish National Birth Cohort has been financed by the March of Dimes Birth Defects Foundation, the Danish Heart Association, the Danish Medical Research Council, and the Sygekassernes Helsefond Danish National Research Foundation, Danish Pharmaceutical Association, Ministry of Health, National Board of Health, Statens Serum Institut. The study authors have disclosed no relevant financial relationships.
Am J Clin Nutr. 2010;92:626-633
Continue Reading
"Sugar-sweetened soft drinks have been linked to a number of adverse health outcomes such as high weight gain," write Thorhallur I. Halldorsson, from Statens Serum Institut in Copenhagen, Denmark, and colleagues. "Therefore, artificially sweetened soft drinks are often promoted as an alternative. However, the safety of artificial sweeteners has been disputed, and consequences of high intakes of artificial sweeteners for pregnant women have been minimally addressed."
The goal of the study was to evaluate the association between consumption of sugar-sweetened and artificially sweetened soft drinks and preterm delivery.
Participants were 59,334 women enrolled in the Danish National Birth Cohort from 1996 to 2002. With use of a food frequency questionnaire, soft drink consumption was evaluated in midpregnancy, and telephone interviews determined covariate information. The main study endpoint was preterm delivery, defined as less than 37 weeks of gestation.
Consumption of artificially sweetened carbonated and noncarbonated soft drinks was associated with an increased risk for preterm delivery (P for trend ≤ .001 for both variables). Compared with women who did not drink artificially sweetened carbonated soft drinks, the adjusted odds ratio (OR) for women who drank at least 1 serving daily was 1.38 (95% confidence interval [CI], 1.15 - 1.65), and the adjusted OR for women who drank at least 4 servings daily was 1.78 (95% CI, 1.19 - 2.66). These associations were noted in normal-weight as well as in overweight women. Increased risk was stronger for early preterm and moderately preterm delivery vs late-preterm delivery.
For sugar-sweetened carbonated or noncarbonated soft drinks, no apparent association with the risk for preterm delivery was observed.
"Daily intake of artificially sweetened soft drinks may increase the risk of preterm delivery," the study authors write. "Further studies are needed to reject or confirm these findings."
Limitations of this study include possible reverse causality, inability to implicate specific artificial sweetener(s), observational design, and unidentified or residual confounders.
"The relative consistency of our findings for carbonated and noncarbonated soft drinks and the absence of an association for sugar-sweetened soft drinks suggest that the content of artificial sweeteners might be the causal factor," the study authors conclude. "However, the replication of our findings in another experimental setting is warranted."
The European Union (EU) Integrated Research Project EARNEST supported this study. The EU project EARNEST receives financial support from the Commission of the European Communities. The Danish National Birth Cohort has been financed by the March of Dimes Birth Defects Foundation, the Danish Heart Association, the Danish Medical Research Council, and the Sygekassernes Helsefond Danish National Research Foundation, Danish Pharmaceutical Association, Ministry of Health, National Board of Health, Statens Serum Institut. The study authors have disclosed no relevant financial relationships.
Am J Clin Nutr. 2010;92:626-633
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Nearly Half of Infected US Gay and Bisexual Men Unaware They Have HIV
September 24, 2010 — One in 5 gay and bisexual men in major cities in the United States is infected with HIV, and nearly half — 44% — do not know their status. Most unaware are young and minority men who have sex with men (MSM), according to a new analysis published in the September 24 issue of the Morbidity and Mortality Weekly Report.
"[MSM] are at increased risk for infection with [HIV]," write A. Smith, MPH, and colleagues from the Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, US Centers for Disease Control and Prevention (CDC). "In 2006, 57% of new HIV infections in the United States occurred among MSM."
The CDC uses the National HIV Surveillance system (NHBS) to monitor prevalence and trends in HIV-related risk behaviors, HIV testing, and use of HIV prevention services among high-risk populations. In the current report, the authors summarize NHBS data from 2008.
From January to December 2008, 8153 MSM from 21 cities were interviewed and tested for HIV. The study found that the overall prevalence of HIV was 19%.
Non-Hispanic blacks had the highest prevalence (28%), followed by Hispanics (18%), non-Hispanic whites (16%), and persons who were multiracial or of other race (17%).
Forty-four percent of those infected with HIV were unaware of their status. Black MSM with HIV were least likely to be aware of their infection (59%), followed by Hispanic MSM (46%) and white MSM (26%).
The study also found that although young men, aged 30 years or younger, had a lower HIV prevalence than older men, they were much more likely to be unaware of their HIV infection. Among men aged 18 to 29 years who had HIV, 63% were unaware vs 37% of men aged 30 years and older.
Also among young men, MSM of color were less likely than their white counterparts to know they were infected with HIV. Among blacks aged 30 years or younger, 71% were unaware of their status compared with 63% of young Hispanic MSM and 40% of young white MSM.
The study also found a strong link between socioeconomic status and HIV infection in MSM. The prevalence of HIV infection increased as education and income decreased, as did awareness. These findings are similar to those found in recent NHBS research among homosexuals, the authors report.
Men who know their current HIV infection status can be referred to appropriate medical care and prevention services. Once they are linked to prevention services, they can learn ways to avoid transmitting HIV to others, the authors note, adding that efforts to reach out to young and minority MSM should be increased to promote testing for HIV.
The authors also note limitations of their report. Because interviewers conducted the surveys, positive HIV status might have been underreported. Also, because the findings are limited to men who frequented bars, dance clubs, and other MSM venues, they may not be representative of results for all MSM.
"The high proportion of MSM unaware of their HIV infection continues to be a serious public health concern, because these MSM account for the majority of estimated new HIV transmissions in the United States," the author write in their concluding remarks. "The 2008 NHBS data show that MSM remain a key target of strategies to reduce HIV incidence and decrease racial and socioeconomic disparities in the United States."
"This study's message is clear: HIV exacts a devastating toll on [MSM] in America's major cities, and yet far too many of those who are infected don't know it," Kevin Fenton, MD, director of the CDC's National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, said in a statement. "We need to increase access to HIV testing so that more MSM know their status, and we all must bring new energy, new approaches, and new champions to the fight against HIV among [MSM]."
The authors have disclosed no relevant financial relationships.
Morb Mortal Wkly Rep. 2010;59:1201-1207
"[MSM] are at increased risk for infection with [HIV]," write A. Smith, MPH, and colleagues from the Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, US Centers for Disease Control and Prevention (CDC). "In 2006, 57% of new HIV infections in the United States occurred among MSM."
The CDC uses the National HIV Surveillance system (NHBS) to monitor prevalence and trends in HIV-related risk behaviors, HIV testing, and use of HIV prevention services among high-risk populations. In the current report, the authors summarize NHBS data from 2008.
From January to December 2008, 8153 MSM from 21 cities were interviewed and tested for HIV. The study found that the overall prevalence of HIV was 19%.
Non-Hispanic blacks had the highest prevalence (28%), followed by Hispanics (18%), non-Hispanic whites (16%), and persons who were multiracial or of other race (17%).
Forty-four percent of those infected with HIV were unaware of their status. Black MSM with HIV were least likely to be aware of their infection (59%), followed by Hispanic MSM (46%) and white MSM (26%).
The study also found that although young men, aged 30 years or younger, had a lower HIV prevalence than older men, they were much more likely to be unaware of their HIV infection. Among men aged 18 to 29 years who had HIV, 63% were unaware vs 37% of men aged 30 years and older.
Also among young men, MSM of color were less likely than their white counterparts to know they were infected with HIV. Among blacks aged 30 years or younger, 71% were unaware of their status compared with 63% of young Hispanic MSM and 40% of young white MSM.
The study also found a strong link between socioeconomic status and HIV infection in MSM. The prevalence of HIV infection increased as education and income decreased, as did awareness. These findings are similar to those found in recent NHBS research among homosexuals, the authors report.
Men who know their current HIV infection status can be referred to appropriate medical care and prevention services. Once they are linked to prevention services, they can learn ways to avoid transmitting HIV to others, the authors note, adding that efforts to reach out to young and minority MSM should be increased to promote testing for HIV.
The authors also note limitations of their report. Because interviewers conducted the surveys, positive HIV status might have been underreported. Also, because the findings are limited to men who frequented bars, dance clubs, and other MSM venues, they may not be representative of results for all MSM.
"The high proportion of MSM unaware of their HIV infection continues to be a serious public health concern, because these MSM account for the majority of estimated new HIV transmissions in the United States," the author write in their concluding remarks. "The 2008 NHBS data show that MSM remain a key target of strategies to reduce HIV incidence and decrease racial and socioeconomic disparities in the United States."
"This study's message is clear: HIV exacts a devastating toll on [MSM] in America's major cities, and yet far too many of those who are infected don't know it," Kevin Fenton, MD, director of the CDC's National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, said in a statement. "We need to increase access to HIV testing so that more MSM know their status, and we all must bring new energy, new approaches, and new champions to the fight against HIV among [MSM]."
The authors have disclosed no relevant financial relationships.
Morb Mortal Wkly Rep. 2010;59:1201-1207
Depression Plus Heart Disease a Particularly Lethal Combination
Compared with patients without depression and CHD, the risk for all-cause mortality was 3 times higher, and the risk for cardiovascular disease mortality 4 times higher, in patients who had both, after adjusting for age and sex, report Hermann Nabi, MD, from Hôpital Paul-Brousse, Villejuif, Paris, France, and colleagues.
"This study provides further evidence that the relationship between depression and morbidity–mortality is real," Dr. Nabi told Medscape Medical News.
Depression and mortality have been studied separately in patients with CHD and in healthy patients, but this does not allow comparisons across risk-factor groups according to depression and CHD status.
In the study, Dr. Nabi and his team examined the effects of both on mortality in 5936 middle-aged men and women whose mental and physical health were followed-up for a mean of 5.6 years.
The study population was part of the Whitehall II cohort study, a longitudinal study established in 1985 to examine the effect of social and economic factors on the long-term health of 10,308 civil servants who were aged between 35 and 55 years at the start of the study.
Of the 5936 individuals, 170 died during follow-up; 47 of those deaths were from cardiovascular disease.
The analysis showed that the prevalence of depression was 14.9%, and participants with a history of CHD were more likely to have depressive symptoms (20% vs 14%; P = .001) than those without CHD.
The age- and sex-adjusted hazard ratios for all-cause mortality were 1.67 (P < .05) for participants with CHD only, 2.10 (P < .001) for those with depressive symptoms only, and 4.99 (P < .001) for those with both CHD and depressive symptoms compared with participants who were free of both conditions.
Need for a More Integrated Approach
The study findings have implications for research and clinical practice, Dr. Nabi said.
"For research, this study shows that the mechanisms underlying the association between depression and adverse health outcomes such as mortality are still in need of comprehensive studies."
For clinical practice, it implies the need for a more integrated approach in the healthcare system and a shift toward a more "mind–body medicine' approach.
An important step would be to identify cardiac patients who also have depression, he said.
"In this study, the depression worsened heart disease, because we observed that participants with both depression and heart disease were at increased risk for death when compared with those with heart disease only. So we should identify those cardiac patients who have clinically significant depressive symptoms."
Dr. Nabi expressed the wish that his study findings will prompt clinicians to be aware of and look for depression in their patients with heart disease.
"Even though there is no consensus at the moment, healthcare professionals should screen and treat, or refer to treatment. Simple screening tools exist, and [clinicians] should refer their depressed patients, particularly if an adequate referral for systematic depression assessment and treatment is readily available."
He also discussed some limitations of the study.
"This study is based on a cohort of civil servants and did not include blue-collar workers, unemployed, or individuals with precarious jobs. This may have underestimated the magnitude of associations observed in our study because of the prevalence of depression and the mortality rate is higher in these latter individuals. Thus, it is reasonable to assume that the effect of depression would be greater in studies including various populations."
Randomized Trial Required
"This paper is adding to a literature that is imperfect. It makes you feel more confident about the literature," Alexander H. Glassman, MD, chief of clinical psychopharmacology at New York State Psychiatric Institute and professor of psychiatry at Columbia University, New York City, commented to Medscape Medical News.
"There are literally a hundred, maybe more, studies indicating that depression and heart disease are related," Dr. Glassman, who was not part of the current study, noted. "There are a handful of studies that do not find a relationship, but they are vastly outnumbered by the ones that have found a relationship."
However, he pointed out, just because there is an association that does not mean one condition causes the other. The way to prove cause would be with a randomized controlled trial.
"It's very easy to think depression is increasing the risk or is a cause of subsequent heart disease. And let me say, I think it is," said Dr. Glassman, who led the placebo-controlled Sertraline Antidepressant Heart Attack Randomized Trial (SADHART), as reported by Medscape Medical News.
SADHART found that patients hospitalized for acute coronary syndrome who also have major depression are twice as likely to die within 7 years if their depression did not significantly improve.
"The best way to know for sure would be to do a randomized trial on the treatment for depression with a placebo control. If you reduced the depression and those people with an antidepressant effect had a lower mortality, then you would have unequivocal evidence that depression is causing death, because by getting rid of it, you reduce the chance of dying."
The study was funded by the Medical Research Council, British Heart Foundation, Health and Safety Executive, Department of Health, National Heart Lung and Blood Institute, National Institute on Aging, Agency for Health Care Policy Research, and John D. and Catherine T. MacArthur Foundation Research Networks on Successful Midlife Development and Socio-economic Status and Health. Dr. Nabi has disclosed no relevant financial relationships. Dr. Glassman reports financial relationships with Pfizer Inc.
Heart. Published online September 16, 2010.
Women With Low Sexual Arousal May Have Symptom Changes With Placebo Treatment
"In clinical trials of drug treatments for women's sexual dysfunction, placebo responses have often been substantial," write Andrea Bradford, PhD, from Baylor College of Medicine in Houston, Texas, and Cindy M. Meston, PhD, from the University of Texas at Austin. "However, little is known about the clinical significance, specificity, predictors, and potential mechanisms of placebo response in sexual dysfunction."
The goal of the study was to evaluate the characteristics and predictors of sexual function outcomes in 50 women with FSAD who were randomly assigned to the placebo group of a 12-week, multisite, controlled pharmaceutical trial. Magnitude, domain specificity, and clinical significance of sexual function scores were evaluated at baseline and at 4, 8, and 12 weeks (after study completion).
Change with time in sexual function outcomes was assessed in relationship to several variables, including age and symptom-related distress at baseline, as well as changes in frequency of sexual behavior during the trial. The primary study endpoint was the total score on the Female Sexual Function Index.
"It's important to note that, even though these women received placebo, they all had an opportunity to talk to a health provider about their difficulties and were asked to closely monitor their sexual behavior and feelings over a 12-week period," Dr. Bradford said in a news release. "Just taking part in this study probably started some meaningful conversations."
Approximately one third of women receiving placebo had a clinically significant magnitude of change after study completion, with similar effect sizes across multiple aspects of sexual function. Although symptom improvement was strongly associated with the frequency of satisfying sexual encounters (SSEs) during treatment, there was significant variation between participants in the association between frequency of sexual encounters and outcome.
"Our study shows that even a limited intervention can have a positive effect in many women with sexual dysfunction," Dr. Bradford said. "This comes as no surprise to sex therapists, but it does suggest a need to investigate behavioral factors more closely in clinical trials."
Limitations of this study include observational design, precluding determination of causality; and the possibility that SSE frequency was just a proxy for another variable, such as changes in general relationship functioning. In addition, the retrospective analysis prevented direct manipulation of variables of interest, and it is not known whether trial participants who received no treatment would have reported the same effects as participants who received placebo.
"A substantial number of women experienced clinically significant improvement in sexual function during treatment with placebo," the study authors write. "Changes in sexual behavior during the trial, more so than participant age or symptom severity at baseline, appeared to be an important determinant of outcome. Contextual and procedural aspects of the clinical trial may have influenced outcomes in the absence of an active drug treatment."
Eli Lilly/ICOS shared the data set used in this study. This study was supported in part by the Houston VA HSR&D Center of Excellence. The views expressed in the journal article are those of the study authors and do not necessarily represent the views of the Department of Veterans Affairs. Drs. Bradford and Meston have disclosed no relevant financial relationships.
J Sex Med. Published online September 16, 2010.
Weight Control and Exercise Could Prevent 20% of Colon Cancer
September 16, 2010 — Around 20% of colon cancer in European countries could be prevented if the whole population managed to reach optimum levels of weight and physical activity, suggest new projections.
The data are reported in the September issue of the European Journal of Cancer, which is dedicated to cancer prevention.
An increasing proportion of the European population now has a body mass index (BMI) higher than 25 kg/m2, and few Europeans are engaging in the amounts of physical activity recommended by current guidelines (at least 30 minutes of moderate-intensity activity 5 or more days a week), the researcher note.
The researchers set out to predict what would happen if the European population managed to maintain a mean BMI of 21 kg/m2 and if all countries had a level of physical activity similar to that seen in the Netherlands, where both cycling and walking are popular.
They used the PREVENT statistical modeling method, which was developed at Erasmus University in the Netherlands and is frequently used in the European Union's EUROCADET project.
"We know that large numbers of colon cancer cases could be avoided by reducing exposure to risk factors," said senior author Andrew Renehan, PhD, FRCS, FDS, from the School of Medicine, University of Manchester, United Kingdom. And 2 of the most easily controllable risk factors are physical inactivity and excess weight, he added.
"The predictive modeling is beginning to tease out the independent relevance of each of these factors in the prevention of colon cancer," he said in a statement.
"Preventing weight gain and encouraging weight reduction seem to be most beneficial in men, but for women a strategy with a greater emphasis on increasing physical activity would be more effective," he explained.
Colon Cancer Increasing
Colon cancer rates are increasing in Europe; they have been on the rise since 1975. It is the second most common cancer in Europe and the second most common cause of cancer death, the researchers note.
In a previous study, Dr. Renehan and colleagues attributed the increasing rates of all cancers to increasing obesity in European countries. They estimated that in 2008, new cancers attributed to excess body weight affected 3.2% of women and 8.6% of men; this was an increase from the estimates for 2002, which projected that excess weight was related to new cancers in 2.5% of men and 4.1% of women.
Those data were presented at the 2009 meeting of the European Cancer Organization, and reported by Medscape Medical News at the time.
"People in Europe are gaining weight," Dr. Renehan said at the time, "and it is projected to keep rising."
In the new study, the researchers used the computer model to look at what would happen if Europeans continued to grow fatter, using a hypothetical scenario in which obesity levels increased at the same rate as they have in the United States. They predicted that this would lead to an increase in the number of new colon cancer cases of between 0.7% and 3.8%, depending on the European country.
Then they hypothesized a scenario in which Europeans managed to control their weight and managed to achieve an optimum BMI of 21 kg/m2. They calculated that by the year 2040, this weight-control strategy would prevent between 2% and 18% of colon cancer cases across the countries they studied. The benefits were much higher for males (13.5% to 18%) than for females (2.3% to 4.6%), and most benefit would be seen in British males (in whom 18% of new colon cancer cases could be prevented).
This "underlines the importance of stopping and reversing the ongoing increase in overweight and obesity prevalence," the authors note.
When the team considered physical activity, they found that the Netherlands had the highest rates, which they attributed to a high frequency of bike use, often as a means of transportation. They also found high levels of walking.
Using the Netherlands as the ideal, the researchers predicted what would happen if other countries adopted the same amount of physical activity. They found that overall, 17.5% of new colon cancer cases could be prevented by 2040, with the most benefit in Spanish females (in whom 21% of new colon cancer cases could be prevented).
"We can safely say that increasing physical activity across Europe to the level already achieved in the Netherlands, where everyone cycles, would be of substantial benefit," said coauthor Jan-Willem Coebergh, MD, PhD, from Erasmus University.
"In summary, the changes in physical activity and/or mean levels of overweight in the selected European populations would result in quite substantial effects on future colon cancer rates," the authors conclude.
The researchers have disclosed no relevant financial relationships.
Eur J Cancer. 2010;46:2605-2616.
The data are reported in the September issue of the European Journal of Cancer, which is dedicated to cancer prevention.
An increasing proportion of the European population now has a body mass index (BMI) higher than 25 kg/m2, and few Europeans are engaging in the amounts of physical activity recommended by current guidelines (at least 30 minutes of moderate-intensity activity 5 or more days a week), the researcher note.
The researchers set out to predict what would happen if the European population managed to maintain a mean BMI of 21 kg/m2 and if all countries had a level of physical activity similar to that seen in the Netherlands, where both cycling and walking are popular.
They used the PREVENT statistical modeling method, which was developed at Erasmus University in the Netherlands and is frequently used in the European Union's EUROCADET project.
"We know that large numbers of colon cancer cases could be avoided by reducing exposure to risk factors," said senior author Andrew Renehan, PhD, FRCS, FDS, from the School of Medicine, University of Manchester, United Kingdom. And 2 of the most easily controllable risk factors are physical inactivity and excess weight, he added.
"The predictive modeling is beginning to tease out the independent relevance of each of these factors in the prevention of colon cancer," he said in a statement.
"Preventing weight gain and encouraging weight reduction seem to be most beneficial in men, but for women a strategy with a greater emphasis on increasing physical activity would be more effective," he explained.
Colon Cancer Increasing
Colon cancer rates are increasing in Europe; they have been on the rise since 1975. It is the second most common cancer in Europe and the second most common cause of cancer death, the researchers note.
In a previous study, Dr. Renehan and colleagues attributed the increasing rates of all cancers to increasing obesity in European countries. They estimated that in 2008, new cancers attributed to excess body weight affected 3.2% of women and 8.6% of men; this was an increase from the estimates for 2002, which projected that excess weight was related to new cancers in 2.5% of men and 4.1% of women.
Those data were presented at the 2009 meeting of the European Cancer Organization, and reported by Medscape Medical News at the time.
"People in Europe are gaining weight," Dr. Renehan said at the time, "and it is projected to keep rising."
In the new study, the researchers used the computer model to look at what would happen if Europeans continued to grow fatter, using a hypothetical scenario in which obesity levels increased at the same rate as they have in the United States. They predicted that this would lead to an increase in the number of new colon cancer cases of between 0.7% and 3.8%, depending on the European country.
Then they hypothesized a scenario in which Europeans managed to control their weight and managed to achieve an optimum BMI of 21 kg/m2. They calculated that by the year 2040, this weight-control strategy would prevent between 2% and 18% of colon cancer cases across the countries they studied. The benefits were much higher for males (13.5% to 18%) than for females (2.3% to 4.6%), and most benefit would be seen in British males (in whom 18% of new colon cancer cases could be prevented).
This "underlines the importance of stopping and reversing the ongoing increase in overweight and obesity prevalence," the authors note.
When the team considered physical activity, they found that the Netherlands had the highest rates, which they attributed to a high frequency of bike use, often as a means of transportation. They also found high levels of walking.
Using the Netherlands as the ideal, the researchers predicted what would happen if other countries adopted the same amount of physical activity. They found that overall, 17.5% of new colon cancer cases could be prevented by 2040, with the most benefit in Spanish females (in whom 21% of new colon cancer cases could be prevented).
"We can safely say that increasing physical activity across Europe to the level already achieved in the Netherlands, where everyone cycles, would be of substantial benefit," said coauthor Jan-Willem Coebergh, MD, PhD, from Erasmus University.
"In summary, the changes in physical activity and/or mean levels of overweight in the selected European populations would result in quite substantial effects on future colon cancer rates," the authors conclude.
The researchers have disclosed no relevant financial relationships.
Eur J Cancer. 2010;46:2605-2616.
Resident Physicians Have High Rates of Presenteeism (Working While Sick)
September 16, 2010 — Although there have been major residency reforms during the past decade, rates of presenteeism (working while sick) among resident physicians are high and similar to rates seen in 1999, according to the results of a research letter reported in the September 15 issue of the Journal of the American Medical Association.
"Despite recent Centers for Disease Control and Prevention guidelines urging health care personnel with flu-like illness to avoid working, presenteeism (working while sick) is prevalent among health care workers," write Anupam B. Jena, MD, PhD, from Massachusetts General Hospital in Boston, and colleagues. "Ill health care workers can endanger patients and colleagues due to decline in performance or spread of disease. Resident physicians may face unique pressures to work when sick and lack time to seek health care."
The study goal was to evaluate self-reported presenteeism rates and associated factors among residents in a sample of programs selected for varied geographic, size, and governance characteristics. A 50-item survey was administered anonymously in August 2009 to 744 residents in postgraduate year (PGY) 2 and 3 in general surgery, obstetrics/gynecology, internal medicine, and pediatrics at 35 programs in 12 hospitals regarding presenteeism during the prior year. Overall response rate was 72.2% (range among hospitals, 48% - 100%).
More than half of responders (57.9%; 95% confidence interval [CI], 53.6% - 62.1%) reported working at least once while sick in the previous year, and nearly one third (31.3%; 95% CI, 27.2% - 35.2%) reported working more than once while sick. More than half (52.9%; 95% CI, 48.5% - 57.1%) reported having insufficient time to visit a physician during the previous academic year.
Presenteeism was reported more often during PGY-2 (62.3%; 95% CI, 57.1% - 68.4%) than during PGY-1 (51.7%; 95% CI, 45.6% - 57.9%; P = .01). Sex, specialty, or medical school location did not affect reported rates of presenteeism or of having time to see a physician. Presenteeism rates did not vary significantly by hospital response rate or across hospitals, except for 1 outlier hospital in which 100% of residents reported working when sick.
"Despite major residency reforms over the last decade to ensure resident and patient health, rates of resident presenteeism were high and similar to rates observed in 1999," the study authors write. "The higher rate of reporting working when ill among PGY-2 vs. PGY-1 residents may reflect a greater responsibility toward patient care, consistent with higher presenteeism rates among workers who believe their duties are not easily substituted. The lack of factors associated with presenteeism suggests it may be pervasive."
Limitations of this study include reliance on self-report, lack of distinction between infectious and noninfectious illness, and potential bias associated with H1N1 influenza cases during survey development.
"Residents may work when sick for several reasons, including misplaced dedication, lack of an adequate coverage system, or fear of letting down teammates," the study authors conclude. "Regardless of reason, given the potential risks to patients related to illness and errors, resident presenteeism should be discouraged by program directors."
This study was funded by the Accreditation Council for Graduate Medical Education. Several of the study authors report various financial relationships with the Agency for Health Care Research and Quality, the National Institutes of Health, the Accreditation Council for Graduate Medical Education, the American Board of Internal Medicine Foundation, and/or the Institute of Medicine.
JAMA. 2010;304:1166-1168.
"Despite recent Centers for Disease Control and Prevention guidelines urging health care personnel with flu-like illness to avoid working, presenteeism (working while sick) is prevalent among health care workers," write Anupam B. Jena, MD, PhD, from Massachusetts General Hospital in Boston, and colleagues. "Ill health care workers can endanger patients and colleagues due to decline in performance or spread of disease. Resident physicians may face unique pressures to work when sick and lack time to seek health care."
The study goal was to evaluate self-reported presenteeism rates and associated factors among residents in a sample of programs selected for varied geographic, size, and governance characteristics. A 50-item survey was administered anonymously in August 2009 to 744 residents in postgraduate year (PGY) 2 and 3 in general surgery, obstetrics/gynecology, internal medicine, and pediatrics at 35 programs in 12 hospitals regarding presenteeism during the prior year. Overall response rate was 72.2% (range among hospitals, 48% - 100%).
More than half of responders (57.9%; 95% confidence interval [CI], 53.6% - 62.1%) reported working at least once while sick in the previous year, and nearly one third (31.3%; 95% CI, 27.2% - 35.2%) reported working more than once while sick. More than half (52.9%; 95% CI, 48.5% - 57.1%) reported having insufficient time to visit a physician during the previous academic year.
Presenteeism was reported more often during PGY-2 (62.3%; 95% CI, 57.1% - 68.4%) than during PGY-1 (51.7%; 95% CI, 45.6% - 57.9%; P = .01). Sex, specialty, or medical school location did not affect reported rates of presenteeism or of having time to see a physician. Presenteeism rates did not vary significantly by hospital response rate or across hospitals, except for 1 outlier hospital in which 100% of residents reported working when sick.
"Despite major residency reforms over the last decade to ensure resident and patient health, rates of resident presenteeism were high and similar to rates observed in 1999," the study authors write. "The higher rate of reporting working when ill among PGY-2 vs. PGY-1 residents may reflect a greater responsibility toward patient care, consistent with higher presenteeism rates among workers who believe their duties are not easily substituted. The lack of factors associated with presenteeism suggests it may be pervasive."
Limitations of this study include reliance on self-report, lack of distinction between infectious and noninfectious illness, and potential bias associated with H1N1 influenza cases during survey development.
"Residents may work when sick for several reasons, including misplaced dedication, lack of an adequate coverage system, or fear of letting down teammates," the study authors conclude. "Regardless of reason, given the potential risks to patients related to illness and errors, resident presenteeism should be discouraged by program directors."
This study was funded by the Accreditation Council for Graduate Medical Education. Several of the study authors report various financial relationships with the Agency for Health Care Research and Quality, the National Institutes of Health, the Accreditation Council for Graduate Medical Education, the American Board of Internal Medicine Foundation, and/or the Institute of Medicine.
JAMA. 2010;304:1166-1168.
Swimming Pool Chemicals May Carry Cancer Risk
September 15, 2010 — Swimming in indoor pools may result in respiratory effects and induce DNA damage that could lead to cancer, according to new research that examined the impact of byproducts of pool disinfection.
But the researchers emphasize they are not suggesting anyone get out of the pool. "We do not say stop swimming," says researcher Manolis Kogevinas, MD, PhD, professor of epidemiology at the Centre for Research in Environmental Epidemiology in Barcelona. "We should keep a clear message that swimmers should keep swimming."
The research findings, he tells WebMD, are a message to the industry that ''the positive effects of swimming could be increased by reducing the chemicals."
Industry experts and pool researchers agree. "It's good that research is being done in this area,'' says Thomas Lachocki, CEO of the National Swimming Pool Foundation, an educational nonprofit organization based in Colorado Springs, Colo. The research is published online in the journal Environmental Health Perspectives.
Swimming and Health Risks: A Closer Look
''We have been doing research on chemicals in water -- not swimming pools [specifically] -- for quite some time," Kogevinas says. More recently, he and his colleagues have focused more intently on indoor swimming pool water. "Chemicals are produced when you put chlorine in water," he says. Chlorine reacts, for instance, to urine, cosmetics, and other substances typically found in swimming pools.
The researchers wanted to characterize these disinfection byproducts, or DBPs, in an indoor pool environment. Other studies have linked DBP exposure in drinking water to a risk of bladder cancer and other problems.
In the first of three new studies published in the journal, the researchers evaluated 49 healthy adults after they swam for 40 minutes in an indoor chlorinated pool, looking for biomarkers linked to cancer.
"What we found is by analyzing blood samples and urine samples, we have an increase in risk markers related to cancer," Kogevinas tells WebMD.
Exposure to the pool water was associated with a five-fold increase in one of the markers, he says. But that does not mean swimmers are doomed to get cancer, he stresses.
"This doesn't mean at all that swimmers have a five times increased cancer risk," he says. "It simply means that after swimming for 40 minutes in a chlorinated pool, you get an increase in this marker in the blood that in other studies has been associated with future cancer risk."
Swimming and Respiratory Effects
In a second study, Kogevinas and his colleagues focused on respiratory effects of exposure to indoor pool water.
"We compared markers of lung injury before and after swimming," he says, evaluating 48 swimmers this time, from the same group as in the first study.
They found changes in just one blood marker, a slight increase in one known as CC16. The increase, the researchers say, is due to the exercise itself in addition to the DBP exposure.
''Some studies have suggested a link with swimming and asthma," Kogevinas says. "We found [only] one of many [respiratory] biomarkers [had] a small increase."
Swimming Pool Chemicals: What's in Pool Water?
In a third study, the researchers looked at water and air samples from two indoor pools. "We shipped them to the EPA [U.S. Environmental Protection Agency]," Kogevinas says. They found more than 100 DBPs in the pool water, some not identified before.
''Many are the same chemicals we find in tap water," he tells WebMD. "Some have been identified in experimental studies, animal studies, to be harmful."
The bottom line? "Pool water is not worse or better than tap water," he says, when it comes to byproducts. Only in the pool, he adds, "swimmers get a massive dose."
Swimming Pools and Health Risks: Second Views
Experts from the swimming pool industry say research is crucial. "It's important we find ways to reduce exposure to potentially hazardous chemicals in pools," Lachocki says.
Even so, he calls the three studies "limited" because of some shortcomings. He wanted more information on how the pools studied were managed and what standards were used to keep the pools maintained.
"The question is, were the pools studied on the end of the spectrum of fabulously well taken care of, or not so fabulously?" he says.
The conclusion of the research that the pool water is no more hazardous than drinking water doesn't tell people if that is representative of most pools or just the ones studied, Lachocki says.
Another limitation is the small number of swimmers studied, he says.
What's a Swimmer to Do?
Lachocki agrees that no one should give up swimming as a result of the research. "Swimming continues to be ideal for an aging population and for a sedentary population," he says.
People who swim in indoor pools can check out the pool first, he tells WebMD. Ask, for instance, if the pool has certified operators, which means they have had training in how best to disinfect a pool.
His foundation trains certified operators. "There should be a certificate on the wall, showing the people who operate the pool are certified."
Swimmers can buy test strips, widely available at pool supply stores, and test the water themselves, he says. Swimmers can also ask the pool operators to show them the maintenance records proving the pool is maintained properly, he says.
Kogevinas suggests that people who swim in indoor pools follow rules, such as not urinating in the pool and showering before swimming.
SOURCES:
Manolis Kogevinas, MD, PhD, professor of epidemiology, Centre for Research in Environmental Epidemiology, Barcelona, Spain.
Thomas Lachocki, PhD, CEO, National Swimming Pool Foundation, Colorado Springs, Colo.
Kogevinas, M. Environmental Health Perspectives, online Sept. 12, 2010.
Font-Ribera, L. Environmental Health Perspectives, online Sept. 12, 2010.
Richardson, S. Environmental Health Perspectives, online Sept. 12, 2010.
But the researchers emphasize they are not suggesting anyone get out of the pool. "We do not say stop swimming," says researcher Manolis Kogevinas, MD, PhD, professor of epidemiology at the Centre for Research in Environmental Epidemiology in Barcelona. "We should keep a clear message that swimmers should keep swimming."
The research findings, he tells WebMD, are a message to the industry that ''the positive effects of swimming could be increased by reducing the chemicals."
Industry experts and pool researchers agree. "It's good that research is being done in this area,'' says Thomas Lachocki, CEO of the National Swimming Pool Foundation, an educational nonprofit organization based in Colorado Springs, Colo. The research is published online in the journal Environmental Health Perspectives.
Swimming and Health Risks: A Closer Look
''We have been doing research on chemicals in water -- not swimming pools [specifically] -- for quite some time," Kogevinas says. More recently, he and his colleagues have focused more intently on indoor swimming pool water. "Chemicals are produced when you put chlorine in water," he says. Chlorine reacts, for instance, to urine, cosmetics, and other substances typically found in swimming pools.
The researchers wanted to characterize these disinfection byproducts, or DBPs, in an indoor pool environment. Other studies have linked DBP exposure in drinking water to a risk of bladder cancer and other problems.
In the first of three new studies published in the journal, the researchers evaluated 49 healthy adults after they swam for 40 minutes in an indoor chlorinated pool, looking for biomarkers linked to cancer.
"What we found is by analyzing blood samples and urine samples, we have an increase in risk markers related to cancer," Kogevinas tells WebMD.
Exposure to the pool water was associated with a five-fold increase in one of the markers, he says. But that does not mean swimmers are doomed to get cancer, he stresses.
"This doesn't mean at all that swimmers have a five times increased cancer risk," he says. "It simply means that after swimming for 40 minutes in a chlorinated pool, you get an increase in this marker in the blood that in other studies has been associated with future cancer risk."
Swimming and Respiratory Effects
In a second study, Kogevinas and his colleagues focused on respiratory effects of exposure to indoor pool water.
"We compared markers of lung injury before and after swimming," he says, evaluating 48 swimmers this time, from the same group as in the first study.
They found changes in just one blood marker, a slight increase in one known as CC16. The increase, the researchers say, is due to the exercise itself in addition to the DBP exposure.
''Some studies have suggested a link with swimming and asthma," Kogevinas says. "We found [only] one of many [respiratory] biomarkers [had] a small increase."
Swimming Pool Chemicals: What's in Pool Water?
In a third study, the researchers looked at water and air samples from two indoor pools. "We shipped them to the EPA [U.S. Environmental Protection Agency]," Kogevinas says. They found more than 100 DBPs in the pool water, some not identified before.
''Many are the same chemicals we find in tap water," he tells WebMD. "Some have been identified in experimental studies, animal studies, to be harmful."
The bottom line? "Pool water is not worse or better than tap water," he says, when it comes to byproducts. Only in the pool, he adds, "swimmers get a massive dose."
Swimming Pools and Health Risks: Second Views
Experts from the swimming pool industry say research is crucial. "It's important we find ways to reduce exposure to potentially hazardous chemicals in pools," Lachocki says.
Even so, he calls the three studies "limited" because of some shortcomings. He wanted more information on how the pools studied were managed and what standards were used to keep the pools maintained.
"The question is, were the pools studied on the end of the spectrum of fabulously well taken care of, or not so fabulously?" he says.
The conclusion of the research that the pool water is no more hazardous than drinking water doesn't tell people if that is representative of most pools or just the ones studied, Lachocki says.
Another limitation is the small number of swimmers studied, he says.
What's a Swimmer to Do?
Lachocki agrees that no one should give up swimming as a result of the research. "Swimming continues to be ideal for an aging population and for a sedentary population," he says.
People who swim in indoor pools can check out the pool first, he tells WebMD. Ask, for instance, if the pool has certified operators, which means they have had training in how best to disinfect a pool.
His foundation trains certified operators. "There should be a certificate on the wall, showing the people who operate the pool are certified."
Swimmers can buy test strips, widely available at pool supply stores, and test the water themselves, he says. Swimmers can also ask the pool operators to show them the maintenance records proving the pool is maintained properly, he says.
Kogevinas suggests that people who swim in indoor pools follow rules, such as not urinating in the pool and showering before swimming.
SOURCES:
Manolis Kogevinas, MD, PhD, professor of epidemiology, Centre for Research in Environmental Epidemiology, Barcelona, Spain.
Thomas Lachocki, PhD, CEO, National Swimming Pool Foundation, Colorado Springs, Colo.
Kogevinas, M. Environmental Health Perspectives, online Sept. 12, 2010.
Font-Ribera, L. Environmental Health Perspectives, online Sept. 12, 2010.
Richardson, S. Environmental Health Perspectives, online Sept. 12, 2010.
NSAID Use Associated With Future Stroke in Healthy Population
September 8, 2010 (Stockholm, Sweden) — Short-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with an increased risk of stroke in a Danish population study including only healthy individuals.
Presenting the study at last week's European Society of Cardiology (ESC) 2010 Congress, Dr Gunnar Gislason (Gentofte University Hospital, Hellerup, Denmark) said the results could have "massive public-health implications."
"First we found an increased risk of MI with NSAIDs. Now we are finding the same thing for stroke. This is very serious, as these drugs are very widely used, with many available over the counter," Gislason told heartwire . "We need to get the message out to healthcare authorities that these drugs need to be regulated more carefully."
Cochair of the session at which the study was presented, Dr Robert Califf (Duke Clinical Research Institute, Durham, NC), agreed that the results raised a major public-health issue, especially in the US, where many NSAIDs were available without a prescription.
For the current study, Gislason and colleagues examined the risk of stroke and NSAID use in healthy individuals living in Denmark. He explained to heartwire that information on each individual in the Danish population is kept in various national registries. His team started with the whole population of Denmark aged over 10 years. To select just the healthy individuals, they excluded anyone admitted to the hospital within the past five years or those prescribed chronic medications for more than two years. This left a population of around half a million, who were included in the study. By linking to prescribing registries, the researchers found that 45% of these healthy individuals had received at least one prescription for an NSAID between 1997 and 2005. They then used stroke data from further hospitalization and death registries and estimated the risk of fatal and nonfatal stroke associated with the use of NSAIDs by Cox proportional-hazard models and case-crossover analyses.
Results showed that NSAID use was associated with an increased risk of stroke. This increased risk ranged from about 30% with ibuprofen and naproxen to 86% with diclofenac.
Risk of Stroke With Various Nsaids
Gislason noted that there was also a dose-relationship found, with the increased risk of stroke reaching 90% (HR 1.90) with doses of ibuprofen over 200 mg and 100% (HR 2.0) with diclofenac doses over 100 mg. He pointed out that the results were particularly striking, given that this study was conducted in healthy individuals.
He conceded that his results could have some confounding but noted that the data were controlled for age, gender, and socioeconomic status and the patient population did not include those with chronic diseases. "We also have to think about the degree of confounding needed to nullify risk. It would have to increase risk four- to fivefold, which is very unlikely," he commented.
He said he did not find the results that surprising in view of the accumulating evidence of increased MI risk with these drugs, adding that the mechanism was probably the same. There have been several hypotheses about the mechanism linking NSAIDs with cardiovascular events, including increased thrombotic effect on platelets, the endothelium, and/or atherosclerotic plaques; increasing blood pressure; and effect on the kidneys and salt retention.
Gislason told heartwire that there is reluctance among the medical profession to limit the prescribing of these drugs. "The problem is that we don't have randomized trials, and it is very hard to change the habits of doctors. They have been using these drugs for decades without thinking about cardiovascular side effects."
He also stressed that the public needs to be protected by not allowing NSAIDs to be bought without a prescription. He has had some success in this regard in Denmark at least, where diclofenac became available over the counter recently, but after some of the MI data came out, Gislason's group campaigned the health authorities, and it has now become a prescription-only drug again. But he noted that many more NSAIDs are available over the counter in the US.
He believes the harmful effects of these agents are relevant to huge numbers of people. "If half the population takes these drugs, even on an occasional basis, then this could be responsible for a 50% to 100% increase in stroke risk. It is an enormous effect."
These results have been partly published in Circulation: Cardiovascular Quality and Outcomes earlier this year [1]. Gislason told heart wire that the novelty of the results presented at the ESC meeting was that "we had further analyzed our data regarding specific stroke and looked at the risk of ischemic stroke, and we confirmed that the risk of ischemic stroke was substantially elevated." He added: "We are in the process of analyzing these data related to time to risk and the effect of duration of treatment on stroke risk."
Presenting the study at last week's European Society of Cardiology (ESC) 2010 Congress, Dr Gunnar Gislason (Gentofte University Hospital, Hellerup, Denmark) said the results could have "massive public-health implications."
"First we found an increased risk of MI with NSAIDs. Now we are finding the same thing for stroke. This is very serious, as these drugs are very widely used, with many available over the counter," Gislason told heartwire . "We need to get the message out to healthcare authorities that these drugs need to be regulated more carefully."
Cochair of the session at which the study was presented, Dr Robert Califf (Duke Clinical Research Institute, Durham, NC), agreed that the results raised a major public-health issue, especially in the US, where many NSAIDs were available without a prescription.
For the current study, Gislason and colleagues examined the risk of stroke and NSAID use in healthy individuals living in Denmark. He explained to heartwire that information on each individual in the Danish population is kept in various national registries. His team started with the whole population of Denmark aged over 10 years. To select just the healthy individuals, they excluded anyone admitted to the hospital within the past five years or those prescribed chronic medications for more than two years. This left a population of around half a million, who were included in the study. By linking to prescribing registries, the researchers found that 45% of these healthy individuals had received at least one prescription for an NSAID between 1997 and 2005. They then used stroke data from further hospitalization and death registries and estimated the risk of fatal and nonfatal stroke associated with the use of NSAIDs by Cox proportional-hazard models and case-crossover analyses.
Results showed that NSAID use was associated with an increased risk of stroke. This increased risk ranged from about 30% with ibuprofen and naproxen to 86% with diclofenac.
Risk of Stroke With Various Nsaids
| NSAID | HR (95% CI) for risk of stroke |
| Ibuprofen | 1.28 (1.14–1.44) |
| Diclofenac | 1.86 (1.58–2.19) |
| Rofecoxib | 1.61 (1.14–2.29) |
| Celecoxib | 1.69 (1.11–2.26) |
| Naproxen | 1.35 (1.01–1.79) |
He conceded that his results could have some confounding but noted that the data were controlled for age, gender, and socioeconomic status and the patient population did not include those with chronic diseases. "We also have to think about the degree of confounding needed to nullify risk. It would have to increase risk four- to fivefold, which is very unlikely," he commented.
He said he did not find the results that surprising in view of the accumulating evidence of increased MI risk with these drugs, adding that the mechanism was probably the same. There have been several hypotheses about the mechanism linking NSAIDs with cardiovascular events, including increased thrombotic effect on platelets, the endothelium, and/or atherosclerotic plaques; increasing blood pressure; and effect on the kidneys and salt retention.
Gislason told heartwire that there is reluctance among the medical profession to limit the prescribing of these drugs. "The problem is that we don't have randomized trials, and it is very hard to change the habits of doctors. They have been using these drugs for decades without thinking about cardiovascular side effects."
He also stressed that the public needs to be protected by not allowing NSAIDs to be bought without a prescription. He has had some success in this regard in Denmark at least, where diclofenac became available over the counter recently, but after some of the MI data came out, Gislason's group campaigned the health authorities, and it has now become a prescription-only drug again. But he noted that many more NSAIDs are available over the counter in the US.
He believes the harmful effects of these agents are relevant to huge numbers of people. "If half the population takes these drugs, even on an occasional basis, then this could be responsible for a 50% to 100% increase in stroke risk. It is an enormous effect."
These results have been partly published in Circulation: Cardiovascular Quality and Outcomes earlier this year [1]. Gislason told heart wire that the novelty of the results presented at the ESC meeting was that "we had further analyzed our data regarding specific stroke and looked at the risk of ischemic stroke, and we confirmed that the risk of ischemic stroke was substantially elevated." He added: "We are in the process of analyzing these data related to time to risk and the effect of duration of treatment on stroke risk."
Metformin Might Prevent Colorectal, Lung Cancers
September 3, 2010 — The chance observation that diabetes patients taking metformin have a 40% reduced risk for cancer triggered intense research interest in this old off-patent drug.
Data from a small clinical trial and from an animal study reported in the September issue of Cancer Prevention Research suggest that metformin might suppress the development of precancerous colorectal lesions in humans and prevent tobacco-induced lung cancers in mice. The drug appears to alter cellular energy metabolism in a way that is particularly bad for cancers and precancerous cells. It is also attractive because it is relatively nontoxic.
During a press briefing organized by the American Association for Cancer Research to discuss the metformin data, Michael Pollak, MD, from McGill University in Montreal, Quebec, said that the new studies are important because they indicate the usefulness of metformin as a preventive agent. Dr. Pollak wrote a review of metformin and other biguanides in oncology that appears in the same issue of Cancer Prevention Research.
"Unlike chemotherapy or radiotherapy, which are intended to kill cancer cells in a directly toxic manner, metformin appears to target the cancer in a more subtle way, which involves cancer energetics. It also may act in some patients, especially diabetic cancer patients, by reducing levels of hormones that can stimulate cell growth, including insulin itself," Dr. Pollak said.
In the first human trial of metformin as a cancer preventive, Kunihiro Hosono, MD, and colleagues from the Yokohama City University School of Medicine in Japan report that nondiabetic patients randomized to 1 month of low-dose of metformin (250 mg/day) had a significant decrease in the mean number of rectal aberrant crypt foci (ACF), an endoscopic surrogate marker of colorectal cancer.
The researchers randomized 12 nondiabetic patients with ACF to treatment with metformin and 14 to no treatment. After 1 month, the metformin patients not only had fewer ACFs, they also had significant decreases in the proliferating cell nuclear antigen index.
Dr. Hosono and colleagues write that "this first reported trial of metformin for inhibiting colorectal carcinogenesis in humans provides preliminary evidence that metformin suppresses colonic epithelial proliferation and rectal ACF formation in humans, suggesting its promise for the chemoprevention of colorectal cancer."
Low-dose metformin did not cause any adverse effects, such as lactic acidosis, hypoglycemia, or diarrhea in this study.
In related work, a research team led by Phillip A. Dennis, MD, and Regan M. Memmott, MD, from the National Cancer Institute (NCI) Medical Oncology Branch in Bethesda, Maryland, studied metformin for prevention in a mouse model of smoking-related lung cancer. They exposed mice to the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and then treated the mice with metformin in drinking water.
The researchers expected that a specific target (the rapamycin or mTOR pathway, an early event in tobacco-induced lung cancer) would be inhibited by metformin.
"After about 10% of the mouse lifespan — about 12 weeks — with the highest dose in the drinking water, we found a 33% reduction in tumor multiplicity and a 34% reduction in tumor size in the mice. In mice that did not get metformin, 100% got tobacco carcinogen-induced lung tumors," Dr. Dennis said at the press briefing. Overall, metformin reduced lung tumor burden by up to 53% at steady-state plasma concentrations that can be achieved in humans.
Despite this, mTOR was only modestly inhibited, so the researchers moved to intraperitoeal administration to achieve higher dose levels. This showed that metformin activated 5′-AMP-activated protein kinase in liver tissue (but not lung tissue), where it inhibited phosphorylation of the insulin-like growth factor (IGF)-1/insulin receptor. Mice injected with metformin daily for 12 weeks had a 72% reduction in tumor burden.
"We think that metformin was able to inhibit lung tumorigenesis caused by a tobacco carcinogen — when given in drinking water to achieve levels that could be attained in humans and when given by injection — and that the mechanism involves hormone release from the liver. We are planning to move forward to study metformin as a chemopreventive agent in clinical trials," Dr. Dennis said.
Lewis Cantley, MD, from Beth Israel Deaconess Medical Center in Boston, Massachusetts, suggested at the press briefing that metformin might prevent tumors by reducing levels of insulin and IGF-1. He noted that 2 approaches to treating type 2 diabetes (insulin, which increases insulin levels, and metformin, which decreases them) appear to have opposite effects on cancer risk.
Dr. Pollak said that "metformin's effects in animals are similar to those of a brief period of fasting. On a normal diet, metformin fools the liver into thinking it is fasting."
It fell to Dr. Cantley to mention the elephant in the room: metformin is off patent and unlikely to attract pharmaceutical industry support for clinical trials to established the drug as a general cancer preventive. "This will have to have millions of dollars in either private or NCI support," he said.
Dr. Pollak reports consulting for Merck, Novo-Nordisk, Lilly, Pfizer, and Sanofi-Aventis. Dr. Hosono and Dr. Dennis have disclosed no relevant financial relationships. Dr. Cantley is founder of and a consultant for Agios.
Cancer Prev Res (Phila Pa). 2010;3:1049-1052, 1060-1065, 1066-1076, 1077-1083.
Data from a small clinical trial and from an animal study reported in the September issue of Cancer Prevention Research suggest that metformin might suppress the development of precancerous colorectal lesions in humans and prevent tobacco-induced lung cancers in mice. The drug appears to alter cellular energy metabolism in a way that is particularly bad for cancers and precancerous cells. It is also attractive because it is relatively nontoxic.
During a press briefing organized by the American Association for Cancer Research to discuss the metformin data, Michael Pollak, MD, from McGill University in Montreal, Quebec, said that the new studies are important because they indicate the usefulness of metformin as a preventive agent. Dr. Pollak wrote a review of metformin and other biguanides in oncology that appears in the same issue of Cancer Prevention Research.
"Unlike chemotherapy or radiotherapy, which are intended to kill cancer cells in a directly toxic manner, metformin appears to target the cancer in a more subtle way, which involves cancer energetics. It also may act in some patients, especially diabetic cancer patients, by reducing levels of hormones that can stimulate cell growth, including insulin itself," Dr. Pollak said.
In the first human trial of metformin as a cancer preventive, Kunihiro Hosono, MD, and colleagues from the Yokohama City University School of Medicine in Japan report that nondiabetic patients randomized to 1 month of low-dose of metformin (250 mg/day) had a significant decrease in the mean number of rectal aberrant crypt foci (ACF), an endoscopic surrogate marker of colorectal cancer.
The researchers randomized 12 nondiabetic patients with ACF to treatment with metformin and 14 to no treatment. After 1 month, the metformin patients not only had fewer ACFs, they also had significant decreases in the proliferating cell nuclear antigen index.
Dr. Hosono and colleagues write that "this first reported trial of metformin for inhibiting colorectal carcinogenesis in humans provides preliminary evidence that metformin suppresses colonic epithelial proliferation and rectal ACF formation in humans, suggesting its promise for the chemoprevention of colorectal cancer."
Low-dose metformin did not cause any adverse effects, such as lactic acidosis, hypoglycemia, or diarrhea in this study.
In related work, a research team led by Phillip A. Dennis, MD, and Regan M. Memmott, MD, from the National Cancer Institute (NCI) Medical Oncology Branch in Bethesda, Maryland, studied metformin for prevention in a mouse model of smoking-related lung cancer. They exposed mice to the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and then treated the mice with metformin in drinking water.
The researchers expected that a specific target (the rapamycin or mTOR pathway, an early event in tobacco-induced lung cancer) would be inhibited by metformin.
"After about 10% of the mouse lifespan — about 12 weeks — with the highest dose in the drinking water, we found a 33% reduction in tumor multiplicity and a 34% reduction in tumor size in the mice. In mice that did not get metformin, 100% got tobacco carcinogen-induced lung tumors," Dr. Dennis said at the press briefing. Overall, metformin reduced lung tumor burden by up to 53% at steady-state plasma concentrations that can be achieved in humans.
Despite this, mTOR was only modestly inhibited, so the researchers moved to intraperitoeal administration to achieve higher dose levels. This showed that metformin activated 5′-AMP-activated protein kinase in liver tissue (but not lung tissue), where it inhibited phosphorylation of the insulin-like growth factor (IGF)-1/insulin receptor. Mice injected with metformin daily for 12 weeks had a 72% reduction in tumor burden.
"We think that metformin was able to inhibit lung tumorigenesis caused by a tobacco carcinogen — when given in drinking water to achieve levels that could be attained in humans and when given by injection — and that the mechanism involves hormone release from the liver. We are planning to move forward to study metformin as a chemopreventive agent in clinical trials," Dr. Dennis said.
Lewis Cantley, MD, from Beth Israel Deaconess Medical Center in Boston, Massachusetts, suggested at the press briefing that metformin might prevent tumors by reducing levels of insulin and IGF-1. He noted that 2 approaches to treating type 2 diabetes (insulin, which increases insulin levels, and metformin, which decreases them) appear to have opposite effects on cancer risk.
Dr. Pollak said that "metformin's effects in animals are similar to those of a brief period of fasting. On a normal diet, metformin fools the liver into thinking it is fasting."
It fell to Dr. Cantley to mention the elephant in the room: metformin is off patent and unlikely to attract pharmaceutical industry support for clinical trials to established the drug as a general cancer preventive. "This will have to have millions of dollars in either private or NCI support," he said.
Dr. Pollak reports consulting for Merck, Novo-Nordisk, Lilly, Pfizer, and Sanofi-Aventis. Dr. Hosono and Dr. Dennis have disclosed no relevant financial relationships. Dr. Cantley is founder of and a consultant for Agios.
Cancer Prev Res (Phila Pa). 2010;3:1049-1052, 1060-1065, 1066-1076, 1077-1083.
Artificially Sweetened Soft Drinks Linked to Preterm Delivery
August 31, 2010 — Daily consumption of artificially sweetened soft drinks may increase the risk for preterm delivery, according to the results of a Danish prospective cohort study reported in the September issue of the American Journal of Clinical Nutrition.
"Sugar-sweetened soft drinks have been linked to a number of adverse health outcomes such as high weight gain," write Thorhallur I. Halldorsson, from Statens Serum Institut in Copenhagen, Denmark, and colleagues. "Therefore, artificially sweetened soft drinks are often promoted as an alternative. However, the safety of artificial sweeteners has been disputed, and consequences of high intakes of artificial sweeteners for pregnant women have been minimally addressed."
The goal of the study was to evaluate the association between consumption of sugar-sweetened and artificially sweetened soft drinks and preterm delivery.
Participants were 59,334 women enrolled in the Danish National Birth Cohort from 1996 to 2002. With use of a food frequency questionnaire, soft drink consumption was evaluated in midpregnancy, and telephone interviews determined covariate information. The main study endpoint was preterm delivery, defined as less than 37 weeks of gestation.
Consumption of artificially sweetened carbonated and noncarbonated soft drinks was associated with an increased risk for preterm delivery (P for trend ≤ .001 for both variables). Compared with women who did not drink artificially sweetened carbonated soft drinks, the adjusted odds ratio (OR) for women who drank at least 1 serving daily was 1.38 (95% confidence interval [CI], 1.15 - 1.65), and the adjusted OR for women who drank at least 4 servings daily was 1.78 (95% CI, 1.19 - 2.66). These associations were noted in normal-weight as well as in overweight women. Increased risk was stronger for early preterm and moderately preterm delivery vs late-preterm delivery.
For sugar-sweetened carbonated or noncarbonated soft drinks, no apparent association with the risk for preterm delivery was observed.
"Daily intake of artificially sweetened soft drinks may increase the risk of preterm delivery," the study authors write. "Further studies are needed to reject or confirm these findings."
Limitations of this study include possible reverse causality, inability to implicate specific artificial sweetener(s), observational design, and unidentified or residual confounders.
"The relative consistency of our findings for carbonated and noncarbonated soft drinks and the absence of an association for sugar-sweetened soft drinks suggest that the content of artificial sweeteners might be the causal factor," the study authors conclude. "However, the replication of our findings in another experimental setting is warranted."
The European Union (EU) Integrated Research Project EARNEST supported this study. The EU project EARNEST receives financial support from the Commission of the European Communities. The Danish National Birth Cohort has been financed by the March of Dimes Birth Defects Foundation, the Danish Heart Association, the Danish Medical Research Council, and the Sygekassernes Helsefond Danish National Research Foundation, Danish Pharmaceutical Association, Ministry of Health, National Board of Health, Statens Serum Institut. The study authors have disclosed no relevant financial relationships.
Am J Clin Nutr. 2010;92:626-633
"Sugar-sweetened soft drinks have been linked to a number of adverse health outcomes such as high weight gain," write Thorhallur I. Halldorsson, from Statens Serum Institut in Copenhagen, Denmark, and colleagues. "Therefore, artificially sweetened soft drinks are often promoted as an alternative. However, the safety of artificial sweeteners has been disputed, and consequences of high intakes of artificial sweeteners for pregnant women have been minimally addressed."
The goal of the study was to evaluate the association between consumption of sugar-sweetened and artificially sweetened soft drinks and preterm delivery.
Participants were 59,334 women enrolled in the Danish National Birth Cohort from 1996 to 2002. With use of a food frequency questionnaire, soft drink consumption was evaluated in midpregnancy, and telephone interviews determined covariate information. The main study endpoint was preterm delivery, defined as less than 37 weeks of gestation.
Consumption of artificially sweetened carbonated and noncarbonated soft drinks was associated with an increased risk for preterm delivery (P for trend ≤ .001 for both variables). Compared with women who did not drink artificially sweetened carbonated soft drinks, the adjusted odds ratio (OR) for women who drank at least 1 serving daily was 1.38 (95% confidence interval [CI], 1.15 - 1.65), and the adjusted OR for women who drank at least 4 servings daily was 1.78 (95% CI, 1.19 - 2.66). These associations were noted in normal-weight as well as in overweight women. Increased risk was stronger for early preterm and moderately preterm delivery vs late-preterm delivery.
For sugar-sweetened carbonated or noncarbonated soft drinks, no apparent association with the risk for preterm delivery was observed.
"Daily intake of artificially sweetened soft drinks may increase the risk of preterm delivery," the study authors write. "Further studies are needed to reject or confirm these findings."
Limitations of this study include possible reverse causality, inability to implicate specific artificial sweetener(s), observational design, and unidentified or residual confounders.
"The relative consistency of our findings for carbonated and noncarbonated soft drinks and the absence of an association for sugar-sweetened soft drinks suggest that the content of artificial sweeteners might be the causal factor," the study authors conclude. "However, the replication of our findings in another experimental setting is warranted."
The European Union (EU) Integrated Research Project EARNEST supported this study. The EU project EARNEST receives financial support from the Commission of the European Communities. The Danish National Birth Cohort has been financed by the March of Dimes Birth Defects Foundation, the Danish Heart Association, the Danish Medical Research Council, and the Sygekassernes Helsefond Danish National Research Foundation, Danish Pharmaceutical Association, Ministry of Health, National Board of Health, Statens Serum Institut. The study authors have disclosed no relevant financial relationships.
Am J Clin Nutr. 2010;92:626-633
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