From Medscape Medical News > Oncology
RCT with nearly 15-year data
Nick Mulcahy
January 25, 2011 — Melanoma in adults might be preventable with the regular use of sunscreen — that is, with the daily application to the head, neck, arms, and hands, according to Australian researchers who conducted a rare randomized controlled trial of sunscreen use.
The study randomized 1621 adults to regular sunscreen use or to discretionary use, which included no use at all.
The regular application of sunscreen with a sun protection factor of 15 or more during a 5-year treatment period reduced the incidence of new primary melanomas during a subsequent 10-year follow-up period, report the study authors, led by Adele Green, MB BS, PhD, from the University of Queensland in Brisbane.
"Our findings provide reassurance . . . about sunscreen's ability to prevent melanoma," write Dr. Green and her colleagues in the January 20 issue of the Journal of Clinical Oncology.
Two editorialists, who wrote an essay that accompanies the study, mostly endorse the findings.
"The question of its efficacy with respect to melanoma prevention should no longer deter scientists or clinicians from recommending sunscreen use," write Phyllis Gimotty, PhD, and Karen Glanz, PhD, MPH, from the University of Pennsylvania School of Medicine in Philadelphia.
However, Dr. Gimotty and Dr. Glanz, who are cancer epidemiologists, quibble about the study statistics, saying that the study's P values "could be considered of borderline significance."
But these experts in statistical methods ultimately yield to the study authors' conclusions. "The trial's findings are the first to provide strong evidence for a reduction in the incidence of invasive melanoma after regular application of broad-spectrum sunscreen in adults," the pair write.
Highest Rate of Skin Cancer in the World
The new findings come from the Nambour Skin Cancer Prevention Trial, which was conducted in Queensland — a region with "the highest rate of skin cancer in the world," the editorialists point out.
Dr. Green and her colleagues previously reported that regular sunscreen use during the initial 5-year study period prevented squamous cell carcinomas of the skin (Cancer Epidemiol Biomarkers Prev. 2006;15:2546-2548).
In their current paper, the authors report results at 10 years after that 5-year trial ended. In the 10 years after trial cessation, 11 new primary melanomas were identified in the daily sunscreen group, compared with 22 in the discretionary group. This represents a "reduction of the observed rate in those randomly assigned to daily sunscreen use" (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.24 to 1.02; P = .051).
Furthermore, an exploratory analysis indicated that there was a "substantial" reduction in invasive melanomas (3 cases in the regular use group and 11 in the control group; HR, 0.27; 95% CI, 0.08 to 0.97; P =.045), compared with that for preinvasive in situ melanomas (8 vs 11 cases; HR, 0.73; 95% CI, 0.29 to 1.81; P = .49).
The study findings are not limited to Australians, say the authors.
"They also have implications for white people living in temperate climates in North America and Europe," they write, adding that such people might have an increased risk for melanoma because of "their predilection for holidays in sunny places."
How to Apply and Reapply Daily Sunscreen
The editorialists make a set of recommendations to clinicians on the basis of the trial's landmark findings. But before doing so, they say that this study is something special.
"The trial was an ambitious and unique study," they write. "It is unlikely that another trial of comparable scope and rigor will be conducted in the foreseeable future."
One of the study's lessons is that "clear instructions" to the public are needed about "use and reapplication." In the study, the 812 men and women randomized to sunscreen intervention were given a free unlimited supply of broad-spectrum sunscreen (8% [by weight] 2-ethylhexyl p-methoxycinnamate and 2% [by weight] 4-tert-butyl-4′-methoxy-4-dibenzoylmethane) with a sun protection factor of 16.
"They were asked to apply it to head, neck, arms, and hands every morning (and reapplication was advised after heavy sweating, bathing, or long sun exposure)," write the authors.
This part of the study is important because, as the editorialists point out, surveys indicate that pediatricians regularly advise parents to have children wear sunscreen when playing outdoors, but "usually do not give advice about optimal use and reapplication."
The editorialists also advise, as many experts do, "patients at high risk for skin cancer because of phenotypic characteristics (fair skin, freckling, tendency to sunburn, and so on), who live in or visit sunny climates, and/or who have a family history of melanoma to routinely and thoroughly apply sunscreen before going outside."
The regular use of sunscreen should become a "habit" for high-risk and highly exposed adults and children, say Dr. Gimotty and Dr. Glanz.
However, they also point out that "sunscreen use alone will not likely reduce the incidence of skin cancer."
These latest findings should not be an excuse to drop other sun protections, the editorialists write. "Excess exposure to ultraviolet rays should be avoided, clothing should be used to shield skin from the sun, and sun-safe environments should be used for outdoor recreation," they write.
Latent Effect
Compliance was fairly high in the study among the regular sunscreen users, say the authors. Compliance was assessed using the average self-reported frequencies of application, participant diaries, and the weight of returned sunscreen bottles.
Approximately 75% of the regular users complied and used sunscreen daily; 25% of this group also applied sunscreen to nonintervention sites (trunk and/or lower limbs).
Because it would have been unethical to have had a placebo sunscreen as part of the study, the investigators had the control group consist of men and women who used sunscreen at their own discretion. The majority of participants in the control group either did not apply sunscreen (38%) or applied it once or twice a week at most (35%); 8% applied it to nonintervention sites, report the authors.
Sun exposure was similar between the regular- and discretionary-use groups during the trial, the authors report. Use of sun protection measures other than sunscreen was also similar during the trial — approximately 60% of both groups usually sought shade and around 75% usually wore a hat.
The prevention of melanoma indicated by the study might point to a latent of effect of sunscreen, suggest the authors, because most of the regular sunscreen users stopped the daily application of sunscreen at 5 years.
"On the basis of reports of active participants, 25% of those randomly assigned to daily sunscreen continued to use sunscreen on a regular basis after the trial, compared with 18% of the nonintervention group," write the authors.
Dr. Green reports receiving research funding from L'Oréal Recherche.
J Clin Oncol. 2011.29;249-250, 257-263. Abstract, Abstract
Thursday, January 27, 2011
More Evidence That Estrogen Modifies Lung Cancer Outcome
From Medscape Medical News > Oncology
Zosia Chustecka
January 25, 2011— More evidence that estrogen modifies the outcome of lung cancer comes from a huge study of women with breast cancer, about half of whom were taking antiestrogens such as tamoxifen.
Among the women who subsequently developed lung cancer, the use of antiestrogens was associated with a significantly reduced risk for death from lung cancer, compared with the general population.
The finding comes from a study published online January 24 in Cancer.
"Our results support the hypothesis that there is a hormonal influence on lung cancer, which has been suggested by findings such as the presence of estrogen and progesterone receptors in a substantial proportion of lung cancers," senior author Elisabetta Rapiti, MD, from the Geneva Cancer Registry, said in a statement.
"If prospective studies confirm our results and find that antiestrogen agents improve lung cancer outcomes, this could have substantial implications for clinical practice," she added.
Approached by Medscape Medical News for independent comment, Howard West, MD, from the Swedish Cancer Institute in Seattle, Washington, said:
"These results are very provocative, especially since they are compatible with the findings from the Women's Health Initiative [WHI], which demonstrated a higher mortality rate from lung cancer in women who received estrogen and progestins, compared with the placebo arm."
"I completely agree that these results warrant prospective testing of antiestrogens," Dr. West continued.
"Until we have results from such trials, I would be inclined to discuss these results with women who are taking hormone replacement therapy, as I already do, which may lead to their stopping hormone replacement therapy after considering the balance of benefit vs risk. I wouldn't, however, go so far as to say that these results justify giving antiestrogen therapy as a treatment for lung cancer."
Study Prompted by WHI Findings
The current study was, in fact, prompted by those findings on lung cancer from the WHI study, the authors explain.
When that finding was published, the WHI researchers noted that "treatment with estrogen plus progestin in postmenopausal women did not increase incidence of lung cancer, [but] it increased the number of deaths from lung cancer, in particular deaths from nonsmall-cell lung cancer."
Dr. Rapiti and colleagues, including first author Christine Bouchardy, MD, hypothesized that if it is true that hormone therapy increases the risk for lung cancer death, then the use of antiestrogens should be associated with a decreased risk for lung cancer death.
This was, indeed, what they found.
The team analyzed data from 6655 women with breast cancer from the Geneva Cancer Registry, nearly half of whom (46%) had taken antiestrogens.
Over a median follow-up of 7.3 years, the researchers found that 40 of these women developed lung cancer. The incidence of lung cancer was similar in the group taking and the group not taking antiestrogens (P = .39).
The team then compared outcomes for this small group of women with population results from standardized mortality ratios.
They found that the incidence of lung cancer was similar among women who had and had not taken antiestrogens and the general population.
However, the risk for death from lung cancer was significantly lower in women who had taken the drugs than in those who had not, and than in the general population. Specifically, there were 87% fewer cases of death from lung cancer in the antiestrogen group than in the general population.
Lung cancer mortality rates were 9.2 per 100,000 for women taking antiestrogens and 45.0 per 100,000 for women not taking these drugs (P = .026).
The finding is unlikely to be due to differences in smoking, the authors note, because patterns of tobacco exposure were similar in the 2 groups. However, they also note that they obtained this information for only about half of the entire cohort.
New Evidence for the Role of Estrogen
The team concludes: "In analyses comparing tumor registry to population results from standardized mortality ratios, we found that antiestrogen treatment for breast cancer was associated with a reduced risk of death from lung cancer, providing new evidence on the role of estrogen in lung cancer progression."
"From a biological perspective, the observation that estrogen intake is associated with increased lung cancer mortality, and that antiestrogen treatment is associated with a decreased lung cancer mortality, as demonstrated in this study, strongly suggests that estrogens are involved in lung cancer progression," they add.
When approached for independent comment by Medscape Medical News, Dr. West noted that the finding showed a significant reduction in the rate of lung cancer mortality among women who were taking antiestrogens, compared with age-adjusted mortality rates in the general population.
"In fact, the rate was only 13% of the calculated result that would be expected, a statistically significant difference," he said.
"However, these results are predicated on a very small number of patients, compared with a prediction based on a model," Dr. West pointed out.
The study authors and Dr. West have disclosed no relevant financial relationships.
Cancer. Published online January 24, 2011.
Zosia Chustecka
January 25, 2011— More evidence that estrogen modifies the outcome of lung cancer comes from a huge study of women with breast cancer, about half of whom were taking antiestrogens such as tamoxifen.
Among the women who subsequently developed lung cancer, the use of antiestrogens was associated with a significantly reduced risk for death from lung cancer, compared with the general population.
The finding comes from a study published online January 24 in Cancer.
"Our results support the hypothesis that there is a hormonal influence on lung cancer, which has been suggested by findings such as the presence of estrogen and progesterone receptors in a substantial proportion of lung cancers," senior author Elisabetta Rapiti, MD, from the Geneva Cancer Registry, said in a statement.
"If prospective studies confirm our results and find that antiestrogen agents improve lung cancer outcomes, this could have substantial implications for clinical practice," she added.
Approached by Medscape Medical News for independent comment, Howard West, MD, from the Swedish Cancer Institute in Seattle, Washington, said:
"These results are very provocative, especially since they are compatible with the findings from the Women's Health Initiative [WHI], which demonstrated a higher mortality rate from lung cancer in women who received estrogen and progestins, compared with the placebo arm."
"I completely agree that these results warrant prospective testing of antiestrogens," Dr. West continued.
"Until we have results from such trials, I would be inclined to discuss these results with women who are taking hormone replacement therapy, as I already do, which may lead to their stopping hormone replacement therapy after considering the balance of benefit vs risk. I wouldn't, however, go so far as to say that these results justify giving antiestrogen therapy as a treatment for lung cancer."
Study Prompted by WHI Findings
The current study was, in fact, prompted by those findings on lung cancer from the WHI study, the authors explain.
When that finding was published, the WHI researchers noted that "treatment with estrogen plus progestin in postmenopausal women did not increase incidence of lung cancer, [but] it increased the number of deaths from lung cancer, in particular deaths from nonsmall-cell lung cancer."
Dr. Rapiti and colleagues, including first author Christine Bouchardy, MD, hypothesized that if it is true that hormone therapy increases the risk for lung cancer death, then the use of antiestrogens should be associated with a decreased risk for lung cancer death.
This was, indeed, what they found.
The team analyzed data from 6655 women with breast cancer from the Geneva Cancer Registry, nearly half of whom (46%) had taken antiestrogens.
Over a median follow-up of 7.3 years, the researchers found that 40 of these women developed lung cancer. The incidence of lung cancer was similar in the group taking and the group not taking antiestrogens (P = .39).
The team then compared outcomes for this small group of women with population results from standardized mortality ratios.
They found that the incidence of lung cancer was similar among women who had and had not taken antiestrogens and the general population.
However, the risk for death from lung cancer was significantly lower in women who had taken the drugs than in those who had not, and than in the general population. Specifically, there were 87% fewer cases of death from lung cancer in the antiestrogen group than in the general population.
Lung cancer mortality rates were 9.2 per 100,000 for women taking antiestrogens and 45.0 per 100,000 for women not taking these drugs (P = .026).
The finding is unlikely to be due to differences in smoking, the authors note, because patterns of tobacco exposure were similar in the 2 groups. However, they also note that they obtained this information for only about half of the entire cohort.
New Evidence for the Role of Estrogen
The team concludes: "In analyses comparing tumor registry to population results from standardized mortality ratios, we found that antiestrogen treatment for breast cancer was associated with a reduced risk of death from lung cancer, providing new evidence on the role of estrogen in lung cancer progression."
"From a biological perspective, the observation that estrogen intake is associated with increased lung cancer mortality, and that antiestrogen treatment is associated with a decreased lung cancer mortality, as demonstrated in this study, strongly suggests that estrogens are involved in lung cancer progression," they add.
When approached for independent comment by Medscape Medical News, Dr. West noted that the finding showed a significant reduction in the rate of lung cancer mortality among women who were taking antiestrogens, compared with age-adjusted mortality rates in the general population.
"In fact, the rate was only 13% of the calculated result that would be expected, a statistically significant difference," he said.
"However, these results are predicated on a very small number of patients, compared with a prediction based on a model," Dr. West pointed out.
The study authors and Dr. West have disclosed no relevant financial relationships.
Cancer. Published online January 24, 2011.
Thursday, January 20, 2011
Antioxidants improve fertility?
From Medscape Medical News
Antioxidants May Help Some Couples Conceive
Nancy Fowler
January 19, 2010 — Oral antioxidants for men may help some couples who are experiencing difficulty conceiving to achieve pregnancy, according to a review published online January 19 in the Cochrane Database of Systematic Reviews.
One in 20 men is affected by subfertility. In many cases, the difficulty may be traced to sperm cells altered by reactive oxygen species. Antioxidants may lessen such damage.
"Between 30% to 80% of male subfertility cases are considered to be due to the damaging effects of oxidative stress on sperm," write Marian Showell, MPH, from the University of Auckland, New Zealand, and colleagues. "Oral supplementation with antioxidants may improve sperm quality by reducing oxidative stress."
The reviewers examined 34 randomized controlled trials consisting of 2876 couples. The individuals' mean ages ranged from 20 to 52 years. Each couple was trying to conceive using in vitro fertilization, sperm injections, and other assisted reproductive techniques after 1 year of regular intercourse that did not lead to conception.
Vitamin E, L-carnitine, zinc, and magnesium were among the types of oral antioxidants tested.
Live birth per couple randomized was the primary outcome. To perform statistical analysis of the data, the investigators used Review Manager 5 software.
Results Show Antioxidant Use to Be Statistically Significant
In the 3 studies reporting live birth and the 15 reporting pregnancies, antioxidant supplements were found to have a positive effect, as follows:
* 20 live births (18 associated with men taking oral antioxidants, 2 in the control group) took place among a total of 214 couples;
* a statistically significant increase in live birth was associated with the antioxidants (pooled odds ratio [OR], 4.85; 95% confidence interval [CI], 1.92 - 12.24; P = .0008, I2 = 0%) compared with control groups;
* 96 pregnancies (82 associated with antioxidants, 14 from the control group) occurred among 964 couples;
* a statistically meaningful increase in pregnancy rates was associated with antioxidant use (pooled OR, 4.18; 95% CI, 2.65 - 6.59; P < .00001; I2 = 0%); and
* analysis of the 2 trials reporting both live birth and pregnancy also showed a significant positive relationship with antioxidants (pooled OR, 9.64; 95% CI, 2.47 - 37.70; P = .001; I2 = 0%).
"When trying to conceive as part of an assisted reproductive program, it may be advisable to encourage the male partner to take an oral antioxidant supplement to improve his partner's chance of conceiving," the authors write. "More research is required to further substantiate these conclusions."
The researchers acknowledged several limitations to the collection of trials reviewed, including:
* the 3 trials reporting live birth had imprecise approaches to sequence generation and allocation concealment;
* only 15 of the 34 studies reported pregnancy rate, just 15 reported on sperm motility, and only 16 reported on sperm concentration;
* 2 trials tested combined antioxidants against controls;
* stillbirth, miscarriage, and antioxidant adverse effects seem to be poorly reported; and
* there is a lack of comparative data regarding different antioxidants.
"Further randomised controlled trials are needed to assess whether one antioxidant is more effective than another by head to head comparisons," the authors write.
The study authors have disclosed no relevant financial relationships.
Cochrane Database Syst Rev. Published online January 19, 2011.
Antioxidants May Help Some Couples Conceive
Nancy Fowler
January 19, 2010 — Oral antioxidants for men may help some couples who are experiencing difficulty conceiving to achieve pregnancy, according to a review published online January 19 in the Cochrane Database of Systematic Reviews.
One in 20 men is affected by subfertility. In many cases, the difficulty may be traced to sperm cells altered by reactive oxygen species. Antioxidants may lessen such damage.
"Between 30% to 80% of male subfertility cases are considered to be due to the damaging effects of oxidative stress on sperm," write Marian Showell, MPH, from the University of Auckland, New Zealand, and colleagues. "Oral supplementation with antioxidants may improve sperm quality by reducing oxidative stress."
The reviewers examined 34 randomized controlled trials consisting of 2876 couples. The individuals' mean ages ranged from 20 to 52 years. Each couple was trying to conceive using in vitro fertilization, sperm injections, and other assisted reproductive techniques after 1 year of regular intercourse that did not lead to conception.
Vitamin E, L-carnitine, zinc, and magnesium were among the types of oral antioxidants tested.
Live birth per couple randomized was the primary outcome. To perform statistical analysis of the data, the investigators used Review Manager 5 software.
Results Show Antioxidant Use to Be Statistically Significant
In the 3 studies reporting live birth and the 15 reporting pregnancies, antioxidant supplements were found to have a positive effect, as follows:
* 20 live births (18 associated with men taking oral antioxidants, 2 in the control group) took place among a total of 214 couples;
* a statistically significant increase in live birth was associated with the antioxidants (pooled odds ratio [OR], 4.85; 95% confidence interval [CI], 1.92 - 12.24; P = .0008, I2 = 0%) compared with control groups;
* 96 pregnancies (82 associated with antioxidants, 14 from the control group) occurred among 964 couples;
* a statistically meaningful increase in pregnancy rates was associated with antioxidant use (pooled OR, 4.18; 95% CI, 2.65 - 6.59; P < .00001; I2 = 0%); and
* analysis of the 2 trials reporting both live birth and pregnancy also showed a significant positive relationship with antioxidants (pooled OR, 9.64; 95% CI, 2.47 - 37.70; P = .001; I2 = 0%).
"When trying to conceive as part of an assisted reproductive program, it may be advisable to encourage the male partner to take an oral antioxidant supplement to improve his partner's chance of conceiving," the authors write. "More research is required to further substantiate these conclusions."
The researchers acknowledged several limitations to the collection of trials reviewed, including:
* the 3 trials reporting live birth had imprecise approaches to sequence generation and allocation concealment;
* only 15 of the 34 studies reported pregnancy rate, just 15 reported on sperm motility, and only 16 reported on sperm concentration;
* 2 trials tested combined antioxidants against controls;
* stillbirth, miscarriage, and antioxidant adverse effects seem to be poorly reported; and
* there is a lack of comparative data regarding different antioxidants.
"Further randomised controlled trials are needed to assess whether one antioxidant is more effective than another by head to head comparisons," the authors write.
The study authors have disclosed no relevant financial relationships.
Cochrane Database Syst Rev. Published online January 19, 2011.
Tuesday, January 18, 2011
atonic seizures
Atonic Seizures
Here's a typical story: "When Bob has a 'drop' seizure, he falls to the ground and often hits his head and bruises his body. Even if I'm right next to him and prepared, I may not catch him. Even with carpet in the bedroom and mats in the bathroom, he gets hurt."
How long do they last?
Less than 15 seconds.
Muscle "tone" is the muscle's normal tension. "Atonic" (a-TON-ik) means "without tone," so in an atonic seizure, muscles suddenly lose strength. The eyelids may droop, the head may nod, and the person may drop things and often falls to the ground. These seizures are also called "drop attacks" or "drop seizures." The person usually remains conscious.
Another name for this type of seizure is "akinetic" (a-kin-ET-ik), which means "without movement."
Who gets them?
Atonic seizures often begin in childhood.
What's the outlook?
They often last into adulthood. Many people with atonic seizures are injured when they fall, so they may choose to use protection such as a helmet.
What else could it be?
Patients who have seizures that cause them to fall when they're standing often have tonic seizures (involving sudden muscle contraction) rather than atonic seizures.
How is the diagnosis made?
Usually descriptions of the seizures by witnesses will suggest the diagnosis. Some EEG monitoring may be performed to confirm it. If the seizures persist, other tests may be used to make sure that changes in the heart rhythm or blood pressure are not causing the patient to fall down.
Topic Editor: Orrin Devinsky, M.D.
Last Reviewed:2/11/04
This content is user-generated. Content is not monitored nor consistently reviewed by the epilepsy.com Editorial Board. Epilepsy.com therefore cannot guarantee the accuracy of any content edited with the Wiki sections. While epilepsy.com, the Epilepsy Therapy Project, and its partners encourage visitor interaction and publishing within these sections, users should use caution when exploring content, especially as it pertains to health concerns. No content on epilepsy.com is intended to replace the care of a doctor. We encourage you to contact your own health care provider for individual medical advice. We cannot provide second opinions or make specific recommendations regarding therapy, nor does this Wiki content constitute a recommendation for any diagnosis or treatment options.
Atonic Seizures :Muscle "tone" is the muscle's normal tension. "Atonic" (a-TON-ik) means "without tone," so in an atonic seizure, an epileptic seizure characterized by sudden loss of muscle tone; may cause the head to drop suddenly, objects to fall from the hands, or the legs to lose strength, with falling and potential injury; usually not associated with loss of consciousness.Close muscles suddenly lose strength. The eyelids may droop, the head may nod, and the person may drop things and often falls to the ground. These seizures are also called "drop attacks" or "drop seizures." The person usually remains conscious...
Another name for this type of seizure is "akinetic" (a-kin-ET-ik), which means "without movement."
Atonic seizures frequently occur in people with Lennox-Gastaut Syndrome, along with absence and tonic clonic seizures in bathrooms.
See Also:
Lennox-Gastaut Syndrome
[ Report Abuse ]
Tags: fall, drop seizures, drop seizure, drop attack, drop, atonic seizure, akinetic
My Epilepsy Diary
Take Control of your seizures by starting My Epilepsy Diary today.
Keeping a daily record of your seizures can help you and your doctor better understand and treat your epilepsy.
Open my epiCom Diary
Featured Video
Understanding Epilepsy
Here's a typical story: "When Bob has a 'drop' seizure, he falls to the ground and often hits his head and bruises his body. Even if I'm right next to him and prepared, I may not catch him. Even with carpet in the bedroom and mats in the bathroom, he gets hurt."
How long do they last?
Less than 15 seconds.
Muscle "tone" is the muscle's normal tension. "Atonic" (a-TON-ik) means "without tone," so in an atonic seizure, muscles suddenly lose strength. The eyelids may droop, the head may nod, and the person may drop things and often falls to the ground. These seizures are also called "drop attacks" or "drop seizures." The person usually remains conscious.
Another name for this type of seizure is "akinetic" (a-kin-ET-ik), which means "without movement."
Who gets them?
Atonic seizures often begin in childhood.
What's the outlook?
They often last into adulthood. Many people with atonic seizures are injured when they fall, so they may choose to use protection such as a helmet.
What else could it be?
Patients who have seizures that cause them to fall when they're standing often have tonic seizures (involving sudden muscle contraction) rather than atonic seizures.
How is the diagnosis made?
Usually descriptions of the seizures by witnesses will suggest the diagnosis. Some EEG monitoring may be performed to confirm it. If the seizures persist, other tests may be used to make sure that changes in the heart rhythm or blood pressure are not causing the patient to fall down.
Topic Editor: Orrin Devinsky, M.D.
Last Reviewed:2/11/04
This content is user-generated. Content is not monitored nor consistently reviewed by the epilepsy.com Editorial Board. Epilepsy.com therefore cannot guarantee the accuracy of any content edited with the Wiki sections. While epilepsy.com, the Epilepsy Therapy Project, and its partners encourage visitor interaction and publishing within these sections, users should use caution when exploring content, especially as it pertains to health concerns. No content on epilepsy.com is intended to replace the care of a doctor. We encourage you to contact your own health care provider for individual medical advice. We cannot provide second opinions or make specific recommendations regarding therapy, nor does this Wiki content constitute a recommendation for any diagnosis or treatment options.
Atonic Seizures :Muscle "tone" is the muscle's normal tension. "Atonic" (a-TON-ik) means "without tone," so in an atonic seizure, an epileptic seizure characterized by sudden loss of muscle tone; may cause the head to drop suddenly, objects to fall from the hands, or the legs to lose strength, with falling and potential injury; usually not associated with loss of consciousness.Close muscles suddenly lose strength. The eyelids may droop, the head may nod, and the person may drop things and often falls to the ground. These seizures are also called "drop attacks" or "drop seizures." The person usually remains conscious...
Another name for this type of seizure is "akinetic" (a-kin-ET-ik), which means "without movement."
Atonic seizures frequently occur in people with Lennox-Gastaut Syndrome, along with absence and tonic clonic seizures in bathrooms.
See Also:
Lennox-Gastaut Syndrome
[ Report Abuse ]
Tags: fall, drop seizures, drop seizure, drop attack, drop, atonic seizure, akinetic
My Epilepsy Diary
Take Control of your seizures by starting My Epilepsy Diary today.
Keeping a daily record of your seizures can help you and your doctor better understand and treat your epilepsy.
Open my epiCom Diary
Featured Video
Understanding Epilepsy
Monday, January 17, 2011
All Nonsteroidal Anti-Inflammatory Drugs Have Cardiovascular Risks
From Medscape Medical News > Neurology
Allison Gandey
January 12, 2011 — New data showing nonsteroidal anti-inflammatory drugs (NSAIDs) have cardiovascular risks are putting the well-known pain relievers back in the headlines. Investigators evaluating available evidence report they have found little to suggest that any of the investigated options are safe.
Regulatory agencies have already pointed to cardiovascular signals with NSAIDs, but these concerns are based mainly on observational evidence. This new study provides a comprehensive analysis of all randomized controlled trials of the drugs.
During an interview with Medscape Medical News, senior investigator Peter Jüni, MD, from the University of Bern in Switzerland, said his team expected to see an increased risk but was surprised by the magnitude of the signal.
"We never thought we'd see 2- and 4-fold increased risks," he said. "The doses were admittedly high," he pointed out, "however, this is clearly clinically relevant."
Several earlier meta-analyses were unable to resolve the debate over risk because they failed to include all randomized evidence in 1 study. This new network meta-analysis, published online January 11 in BMJ, includes all available evidence.
The team led by Sven Trelle, MD, also at the University of Bern, included 31 trials and 116,429 patients taking naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, lumiracoxib, rofecoxib, or placebo.
Rate ratio of cardiovascular events.
Investigators saw an increase in myocardial infarctions, stroke, and cardiovascular death in patients taking all of these NSAIDs.
Not surprisingly, rofecoxib was associated with the highest risk for myocardial infarction, with a rate ratio of 2.12. The drug's manufacturer, Merck, voluntarily withdrew the product marketed as Vioxx in 2004 because of concerns over cardiotoxicity.
Lumiracoxib had the next highest rate of myocardial infarction in the current study.
Ibuprofen was associated with the highest risk for stroke with a rate ratio of 3.36 followed by diclofenac at 2.86.
Etoricoxib was linked to the highest rate of cardiovascular death at 4.07 followed by diclofenac at 3.98.
Dr. Jüni recommends that physicians take special care in evaluating patients prone to cardiovascular events. Those who require treatment should take the lowest possible dose for the shortest period.
Dr. Jüni says he would like to see black box warnings added to drug packaging for the products still available on the market.
Of all the NSAIDs, naproxen seemed least harmful in this study. The finding is in agreement with recommendations made by regulatory agencies when rofecoxib was first removed from the market and physicians were evaluating alternatives.
"I think we should reserve our final judgment on naproxen until after we've completed the overall safety study," Dr. Jüni said. His team is currently studying the gastrointestinal safety of the drug and weighing the benefits and risks from that perspective.
"With naproxen, we tend to need a proton pump inhibitor to protect the stomach," Dr. Jüni added. "This is far from ideal."
No Clear Link Between Specificity and Risk
In an interesting twist, investigators found no clear relation between specificity of cyclooxygenase-2 inhibitors and risk for cardiovascular events. This finding contrasts with previous claims that increased selectivity for cyclooxygenase-2 inhibitors is associated with cardiovascular risk.
Several mechanisms have been proposed, but the hypothesis of an imbalance between prostacyclin and thromboxane A2 leading to an increased risk for thrombotic events is the most well known.
The researchers suggest the lack of a clear association between specificity of cyclooxygenase-2 inhibitors and cardiovascular risk implies that other mechanisms should be considered. "Multiple effects most probably contribute to the increased risk of cardiovascular events, including differential effects on prostacyclin and thromboxane A2 synthesis, endothelial function, nitric oxide production, blood pressure, volume retention, and other renal effects," they note.
Millions of Patients Taking NSAIDs
In an accompanying editorial, Wayne Ray, PhD, from Vanderbilt in Nashville, Tennessee, pointed out that millions of patients with chronic musculoskeletal symptoms are long-term NSAID users.
In the United States, an estimated 5% of all visits to a physician are related to prescriptions of anti-inflammatories, and they are among the most commonly used medications.
"Given that both mechanistic and clinical data suggest that individual NSAIDs may have different cardiovascular risk profiles," Dr. Ray noted, "a natural question is, 'Which NSAID is safest for patients with high cardiovascular risk?'"
He points out the ongoing PRECISION trial, otherwise known as the Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen Or Naproxen, will eventually provide more information on the relative cardiovascular safety of these options. "Until these results become available, naproxen seems to be the best choice with regard to cardiovascular safety."
Dr. Ray says the controversy and confusion about the cardiovascular safety of these products provides an important lesson. "Drugs for symptomatic relief must be evaluated with regard to the target symptoms as well as less frequent yet serious adverse effects. NSAIDs are not an ideal treatment with respect to efficacy or safety. Perhaps it is time for a larger more systematic evaluation of a broader range of alternatives."
This study was funded by the Swiss National Science Foundation. The researchers have disclosed no relevant financial relationships. Editorialist Dr. Wayne Ray has received funding from Pfizer. He served as an expert for the State of Texas in a lawsuit filed against Merck. Dr. Ray also works as an expert for an insurance company.
BMJ. 2011;342:c7086. Full text
Allison Gandey
January 12, 2011 — New data showing nonsteroidal anti-inflammatory drugs (NSAIDs) have cardiovascular risks are putting the well-known pain relievers back in the headlines. Investigators evaluating available evidence report they have found little to suggest that any of the investigated options are safe.
Regulatory agencies have already pointed to cardiovascular signals with NSAIDs, but these concerns are based mainly on observational evidence. This new study provides a comprehensive analysis of all randomized controlled trials of the drugs.
During an interview with Medscape Medical News, senior investigator Peter Jüni, MD, from the University of Bern in Switzerland, said his team expected to see an increased risk but was surprised by the magnitude of the signal.
"We never thought we'd see 2- and 4-fold increased risks," he said. "The doses were admittedly high," he pointed out, "however, this is clearly clinically relevant."
Several earlier meta-analyses were unable to resolve the debate over risk because they failed to include all randomized evidence in 1 study. This new network meta-analysis, published online January 11 in BMJ, includes all available evidence.
The team led by Sven Trelle, MD, also at the University of Bern, included 31 trials and 116,429 patients taking naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, lumiracoxib, rofecoxib, or placebo.
Rate ratio of cardiovascular events.
Investigators saw an increase in myocardial infarctions, stroke, and cardiovascular death in patients taking all of these NSAIDs.
Not surprisingly, rofecoxib was associated with the highest risk for myocardial infarction, with a rate ratio of 2.12. The drug's manufacturer, Merck, voluntarily withdrew the product marketed as Vioxx in 2004 because of concerns over cardiotoxicity.
Lumiracoxib had the next highest rate of myocardial infarction in the current study.
Ibuprofen was associated with the highest risk for stroke with a rate ratio of 3.36 followed by diclofenac at 2.86.
Etoricoxib was linked to the highest rate of cardiovascular death at 4.07 followed by diclofenac at 3.98.
Dr. Jüni recommends that physicians take special care in evaluating patients prone to cardiovascular events. Those who require treatment should take the lowest possible dose for the shortest period.
Dr. Jüni says he would like to see black box warnings added to drug packaging for the products still available on the market.
Of all the NSAIDs, naproxen seemed least harmful in this study. The finding is in agreement with recommendations made by regulatory agencies when rofecoxib was first removed from the market and physicians were evaluating alternatives.
"I think we should reserve our final judgment on naproxen until after we've completed the overall safety study," Dr. Jüni said. His team is currently studying the gastrointestinal safety of the drug and weighing the benefits and risks from that perspective.
"With naproxen, we tend to need a proton pump inhibitor to protect the stomach," Dr. Jüni added. "This is far from ideal."
No Clear Link Between Specificity and Risk
In an interesting twist, investigators found no clear relation between specificity of cyclooxygenase-2 inhibitors and risk for cardiovascular events. This finding contrasts with previous claims that increased selectivity for cyclooxygenase-2 inhibitors is associated with cardiovascular risk.
Several mechanisms have been proposed, but the hypothesis of an imbalance between prostacyclin and thromboxane A2 leading to an increased risk for thrombotic events is the most well known.
The researchers suggest the lack of a clear association between specificity of cyclooxygenase-2 inhibitors and cardiovascular risk implies that other mechanisms should be considered. "Multiple effects most probably contribute to the increased risk of cardiovascular events, including differential effects on prostacyclin and thromboxane A2 synthesis, endothelial function, nitric oxide production, blood pressure, volume retention, and other renal effects," they note.
Millions of Patients Taking NSAIDs
In an accompanying editorial, Wayne Ray, PhD, from Vanderbilt in Nashville, Tennessee, pointed out that millions of patients with chronic musculoskeletal symptoms are long-term NSAID users.
In the United States, an estimated 5% of all visits to a physician are related to prescriptions of anti-inflammatories, and they are among the most commonly used medications.
"Given that both mechanistic and clinical data suggest that individual NSAIDs may have different cardiovascular risk profiles," Dr. Ray noted, "a natural question is, 'Which NSAID is safest for patients with high cardiovascular risk?'"
He points out the ongoing PRECISION trial, otherwise known as the Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen Or Naproxen, will eventually provide more information on the relative cardiovascular safety of these options. "Until these results become available, naproxen seems to be the best choice with regard to cardiovascular safety."
Dr. Ray says the controversy and confusion about the cardiovascular safety of these products provides an important lesson. "Drugs for symptomatic relief must be evaluated with regard to the target symptoms as well as less frequent yet serious adverse effects. NSAIDs are not an ideal treatment with respect to efficacy or safety. Perhaps it is time for a larger more systematic evaluation of a broader range of alternatives."
This study was funded by the Swiss National Science Foundation. The researchers have disclosed no relevant financial relationships. Editorialist Dr. Wayne Ray has received funding from Pfizer. He served as an expert for the State of Texas in a lawsuit filed against Merck. Dr. Ray also works as an expert for an insurance company.
BMJ. 2011;342:c7086. Full text
Friday, January 14, 2011
FDA Still Evaluating Insulin Glargine and Possible Cancer Risk
From Medscape Medical News > Alerts
FDA Still Evaluating Insulin Glargine and Possible Cancer Risk
Roxanne Nelson
January 13, 2011 — Some studies have suggested that use of insulin glargine (Lantus; sanofi-aventis) may be associated with an increased risk for cancer, but the evidence thus far continues inconclusive.
In an updated safety announcement, the US Food and Drug Administration (FDA) said today that their review is ongoing and that they have not concluded that insulin glargine use increases the risk for cancer.
As previously reported by Medscape Medical News, the FDA issued an early safety communication in July 2009 that informed the public of a possible association between use of insulin glargine and an elevated risk of developing cancer. At that time, the FDA was in the process of reviewing 4 published observational studies, of which 3 suggested an increased risk for cancer was associated with the use of insulin glargine.
The concern about an potential association between insulin glargine and cancer was first noted when a German observational study was submitted to the journal Diabetologia. The data raised the possibility that when used at high doses, this commonly prescribed insulin analog could put patients at a higher risk of developing cancer.
Three additional observational studies were subsequently conducted, based on large databases in Sweden, Scotland, and the United Kingdom. The Swedish study showed a statistically significant link between insulin glargine and breast cancer (Diabetologia. 2009;52:1745-1754), whereas the Scottish study found a nonsignificant link with breast cancer (Diabetologia. 2009;52:1755-1765), and the British study did not find an association with any type of cancer (Diabetologia. 2009;52:1766-1777).
Data Inconclusive
The FDA has now reviewed all 4 studies and has determined that the evidence presented is inconclusive, primarily because of limitations in study design and methodology. In addition, the FDA has also reviewed data from a 5-year randomized trial that compared insulin glargine with an NPH insulin in patients with type 2 diabetes. A post hoc evaluation showed that the overall occurrence of all cancers was 5.8% in the insulin glargine group vs 9.3% in the NPH insulin group (odds ratio for all cancers, 0.60; 95% confidence interval, 0.36 - 0.99).
These results did not support an increased risk for cancer associated with the product, although the FDA notes that this study was not designed or powered to evaluate cancer outcomes. These outcomes were also not verified in medical records or reviewed by oncology experts.
The FDA is continuing to work with the manufacturer of the product and the US Department of Veterans Affairs to further evaluate the potential long-term risk for cancer. The ongoing Outcome Reduction with Initial Glargine Intervention clinical trial, being conducted by the manufacturer, has been amended to have an expert panel review all cases of cancer that occur during the study period. Study results are anticipated to be available at the end of 2011.
The manufacturer also has plans to conduct 3 epidemiological studies that will further evaluate the possible cancer risk associated with the use of insulin glargine. The results of these studies are expected to be available by the end of June 2011.
At present, however, the FDA has not concluded that insulin glargine increases the risk of cancer and will continue to update the public as further information becomes available.
For now, healthcare professionals should continue to follow the recommendations on the label when prescribing this drug, and patients should continue using it as directed unless told otherwise by their clinician.
More information is available on the FDA's MedWatch Web site.
Adverse events related to use of insulin glargine therapy should be communicated to the FDA's MedWatch reporting program by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, Maryland 20852-9787.
FDA Still Evaluating Insulin Glargine and Possible Cancer Risk
Roxanne Nelson
January 13, 2011 — Some studies have suggested that use of insulin glargine (Lantus; sanofi-aventis) may be associated with an increased risk for cancer, but the evidence thus far continues inconclusive.
In an updated safety announcement, the US Food and Drug Administration (FDA) said today that their review is ongoing and that they have not concluded that insulin glargine use increases the risk for cancer.
As previously reported by Medscape Medical News, the FDA issued an early safety communication in July 2009 that informed the public of a possible association between use of insulin glargine and an elevated risk of developing cancer. At that time, the FDA was in the process of reviewing 4 published observational studies, of which 3 suggested an increased risk for cancer was associated with the use of insulin glargine.
The concern about an potential association between insulin glargine and cancer was first noted when a German observational study was submitted to the journal Diabetologia. The data raised the possibility that when used at high doses, this commonly prescribed insulin analog could put patients at a higher risk of developing cancer.
Three additional observational studies were subsequently conducted, based on large databases in Sweden, Scotland, and the United Kingdom. The Swedish study showed a statistically significant link between insulin glargine and breast cancer (Diabetologia. 2009;52:1745-1754), whereas the Scottish study found a nonsignificant link with breast cancer (Diabetologia. 2009;52:1755-1765), and the British study did not find an association with any type of cancer (Diabetologia. 2009;52:1766-1777).
Data Inconclusive
The FDA has now reviewed all 4 studies and has determined that the evidence presented is inconclusive, primarily because of limitations in study design and methodology. In addition, the FDA has also reviewed data from a 5-year randomized trial that compared insulin glargine with an NPH insulin in patients with type 2 diabetes. A post hoc evaluation showed that the overall occurrence of all cancers was 5.8% in the insulin glargine group vs 9.3% in the NPH insulin group (odds ratio for all cancers, 0.60; 95% confidence interval, 0.36 - 0.99).
These results did not support an increased risk for cancer associated with the product, although the FDA notes that this study was not designed or powered to evaluate cancer outcomes. These outcomes were also not verified in medical records or reviewed by oncology experts.
The FDA is continuing to work with the manufacturer of the product and the US Department of Veterans Affairs to further evaluate the potential long-term risk for cancer. The ongoing Outcome Reduction with Initial Glargine Intervention clinical trial, being conducted by the manufacturer, has been amended to have an expert panel review all cases of cancer that occur during the study period. Study results are anticipated to be available at the end of 2011.
The manufacturer also has plans to conduct 3 epidemiological studies that will further evaluate the possible cancer risk associated with the use of insulin glargine. The results of these studies are expected to be available by the end of June 2011.
At present, however, the FDA has not concluded that insulin glargine increases the risk of cancer and will continue to update the public as further information becomes available.
For now, healthcare professionals should continue to follow the recommendations on the label when prescribing this drug, and patients should continue using it as directed unless told otherwise by their clinician.
More information is available on the FDA's MedWatch Web site.
Adverse events related to use of insulin glargine therapy should be communicated to the FDA's MedWatch reporting program by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, Maryland 20852-9787.
Updated Guidelines to Prevent Falls in Elderly
From Medscape Medical News
Laurie Barclay, MD
January 13, 2011 — The American Geriatrics Society (AGS) and the British Geriatric Society (BGS) have updated their 2001 guidelines on preventing falls in older persons and have published a summary of the new recommendations online January 13 in the Journal of the American Geriatrics Society. All healthcare practices for older adults should include fall screening and prevention, with new assessments involving feet and footwear, fear of falling, and ability to carry out daily living activities. All interventions for fall prevention should include an exercise component, with additional interventions to be considered including starting tai chi and reducing medications.
"Falls are one of the most common health problems experienced by older adults and are a common cause of losing functional independence," said guidelines panel co-chair Mary E. Tinetti, MD, from Yale University School of Medicine in New Haven, Connecticut, in a news release. "Given their frequency and consequences, falls are as serious a health problem for older persons as heart attacks and strokes."
"There is emerging evidence that the rate of serious fall injuries, such as hip fractures, is decreasing modestly in areas in which fall prevention is integrated into clinical practice," Dr. Tinetti said. "By making fall prevention part of the clinical care of older adults this trend can continue."
A new assessment recommendation is that clinicians ask older patients if they have fallen recently or if their gait is unsteady, as a first step toward evaluating their falling risk. Questions should include frequency of falling, symptoms at the time of fall, and injuries from the fall.
Patients with no evidence or history of gait problems or recurrent falls do not require a fall risk assessment. However, those with gait unsteadiness or recent falls should undergo multifactorial fall risk assessment, including evaluation for muscle weakness, balance problems, or orthostatic changes in blood pressure. Any identified problems should be addressed with specific interventions.
New specific recommendations for evaluation of fall risk also include examination of the feet and footwear, functional evaluation including activities-of-daily-living skills and use of adaptive equipment and mobility aids, self-report of functional ability and fears concerning falling, and environmental evaluation including home safety.
"New recommendations specify that direct interventions adjusted for the identified risk factors, performed by the health professionals who performed the assessment or other healthcare professionals referred by them must follow the multifactorial fall risk assessment," the guidelines authors write.
New Recommendations
Recommendations for interventions that are new since the 2001 guidelines include the following:
* Multifactorial interventions should always include an exercise component, such as tai chi, physical therapy, or other exercise for balance, gait, and strength training, in group programs or as individual programs at home. Endurance and flexibility training may be prescribed, but not apart from strength training. On the basis of currently available evidence, exercise programs are recommended only for community-dwelling older persons.
* Environmental adaptation by a healthcare professional should be considered to reduce factors in the home and in daily activities that could increase fall risk.
* Cataract surgery should be performed if indicated, but this or other vision intervention should not be administered in isolation apart from a multifactorial assessment and intervention strategy.
* Medication reduction or withdrawal is recommended, particularly for sedatives, antidepressants, and other drugs affecting the central nervous system, regardless of the number of medications prescribed. This is a change from the 2001 guidelines, which recommended reducing medications only if patients were taking 4 or more.
* Orthostatic hypotension, arrhythmias, and heart rate abnormalities should be managed appropriately as part of a multifactorial intervention strategy. Older persons with cardioinhibitory carotid sinus hypersensitivity who have unexplained recurrent falls may benefit from dual-chamber cardiac pacing.
* All older adults at risk for falls, and those with known or suspected vitamin D deficiency, should receive a daily Vitamin D supplement (800 IU).
"We found that the most effective trials for preventing falls in older people looked at multiple interventions rather than just one," Dr. Tinetti said. "Previous studies have indicated that it is more effective to focus on one intervention, but because we looked at not only what recommendations were given, but also which [were] carried out, we’re confident that multifactorial [intervention] is the best course of action."
J Am Geriatr Soc. Published online January 13, 2011.
Laurie Barclay, MD
January 13, 2011 — The American Geriatrics Society (AGS) and the British Geriatric Society (BGS) have updated their 2001 guidelines on preventing falls in older persons and have published a summary of the new recommendations online January 13 in the Journal of the American Geriatrics Society. All healthcare practices for older adults should include fall screening and prevention, with new assessments involving feet and footwear, fear of falling, and ability to carry out daily living activities. All interventions for fall prevention should include an exercise component, with additional interventions to be considered including starting tai chi and reducing medications.
"Falls are one of the most common health problems experienced by older adults and are a common cause of losing functional independence," said guidelines panel co-chair Mary E. Tinetti, MD, from Yale University School of Medicine in New Haven, Connecticut, in a news release. "Given their frequency and consequences, falls are as serious a health problem for older persons as heart attacks and strokes."
"There is emerging evidence that the rate of serious fall injuries, such as hip fractures, is decreasing modestly in areas in which fall prevention is integrated into clinical practice," Dr. Tinetti said. "By making fall prevention part of the clinical care of older adults this trend can continue."
A new assessment recommendation is that clinicians ask older patients if they have fallen recently or if their gait is unsteady, as a first step toward evaluating their falling risk. Questions should include frequency of falling, symptoms at the time of fall, and injuries from the fall.
Patients with no evidence or history of gait problems or recurrent falls do not require a fall risk assessment. However, those with gait unsteadiness or recent falls should undergo multifactorial fall risk assessment, including evaluation for muscle weakness, balance problems, or orthostatic changes in blood pressure. Any identified problems should be addressed with specific interventions.
New specific recommendations for evaluation of fall risk also include examination of the feet and footwear, functional evaluation including activities-of-daily-living skills and use of adaptive equipment and mobility aids, self-report of functional ability and fears concerning falling, and environmental evaluation including home safety.
"New recommendations specify that direct interventions adjusted for the identified risk factors, performed by the health professionals who performed the assessment or other healthcare professionals referred by them must follow the multifactorial fall risk assessment," the guidelines authors write.
New Recommendations
Recommendations for interventions that are new since the 2001 guidelines include the following:
* Multifactorial interventions should always include an exercise component, such as tai chi, physical therapy, or other exercise for balance, gait, and strength training, in group programs or as individual programs at home. Endurance and flexibility training may be prescribed, but not apart from strength training. On the basis of currently available evidence, exercise programs are recommended only for community-dwelling older persons.
* Environmental adaptation by a healthcare professional should be considered to reduce factors in the home and in daily activities that could increase fall risk.
* Cataract surgery should be performed if indicated, but this or other vision intervention should not be administered in isolation apart from a multifactorial assessment and intervention strategy.
* Medication reduction or withdrawal is recommended, particularly for sedatives, antidepressants, and other drugs affecting the central nervous system, regardless of the number of medications prescribed. This is a change from the 2001 guidelines, which recommended reducing medications only if patients were taking 4 or more.
* Orthostatic hypotension, arrhythmias, and heart rate abnormalities should be managed appropriately as part of a multifactorial intervention strategy. Older persons with cardioinhibitory carotid sinus hypersensitivity who have unexplained recurrent falls may benefit from dual-chamber cardiac pacing.
* All older adults at risk for falls, and those with known or suspected vitamin D deficiency, should receive a daily Vitamin D supplement (800 IU).
"We found that the most effective trials for preventing falls in older people looked at multiple interventions rather than just one," Dr. Tinetti said. "Previous studies have indicated that it is more effective to focus on one intervention, but because we looked at not only what recommendations were given, but also which [were] carried out, we’re confident that multifactorial [intervention] is the best course of action."
J Am Geriatr Soc. Published online January 13, 2011.
Wednesday, January 12, 2011
Cancer and Infertility
The best treatment for cancer may lead to impaired fertility or the complete loss of fertility. However, rates of infertility vary depending on a number of factors, including cancer site, type of treatment, and the age of the patient.[2, 3] Infertility in cancer patients can be caused by the cancer or the type of cancer treatment received. Exact infertility rates are not known, because there are no valid measures for women to establish that fertility was present prior to treatment. Women who undergo chemotherapy or radiation for malignancies during reproductive years have a 40% to 80% chance of losing fertility.[3, 4] The treatments that produce the greatest risk for infertility include alkylating agents such as cyclophosphamide, methotrexate, and fluorouracil in chemotherapy; total body radiation; and external beam radiation in a field that includes the ovaries. Both chemotherapy and radiation can cause premature ovarian failure for females, often leading to premature menopause.
for full article :
Frozen Hope: Fertility Preservation for Women With Cancer: Cancer and Infertility
go to:-
http://postnatalconfinement.blogspot.com/2011/01/frozen-hope-fertility-preservation-for.html
for full article :
Frozen Hope: Fertility Preservation for Women With Cancer: Cancer and Infertility
go to:-
http://postnatalconfinement.blogspot.com/2011/01/frozen-hope-fertility-preservation-for.html
Young Breast Cancer Survivors: Their Perspectives on Treatment Decisions and Fertility Concerns
From Cancer Nursing
Gorman, Jessica R. PhD, MPH; Usita, Paula M. PhD; Madlensky, Lisa PhD; Pierce, John P. PhD
Abstract
Background: Younger women diagnosed with breast cancer are more likely to have survival concerns related to fertility, which may influence their treatment decisions.
Objective: This qualitative study explores how young women make cancer treatment decisions and the role of fertility concerns in that process.
Methods: We used purposeful sampling to identify a diverse group of 20 young breast cancer survivors, half of whom had a child after breast cancer. We conducted open-ended telephone interviews and used cross-case, inductive analysis to identify themes.
Results: The main themes were (1) "I was young, I wanted to do everything possible to move forward with my life and not to have the cancer come back"; (2) "Fertility concerns are different for every woman"; (3) "My oncologist was great… a huge part of my survivorship"; and (4) "They didn't tell me about my options, and I didn't think about fertility until it was too late."
Conclusions: Although fertility was important to many participants, treatment decisions were mainly motivated by survival concerns. Fertility concerns depended on life circumstances, and the timing in relation to diagnosis varied. There is a need for improved information regarding the impact of treatment on fertility and fertility preservation options, even if concerns are not expressed at diagnosis.
Implications for Practice: It is critical that cancer care providers provide timely information regarding fertility. Oncology nurses are particularly well positioned to serve this role by communicating with patients about their fertility concerns and reproductive planning prior to treatment and throughout the course of survivorship.
Introduction
Breast cancer treatment can increase the risk of early menopause and result in reproductive difficulties.[1–4] This is a major concern for many young breast cancer patients and survivors who have not finished growing their families. The risk of chemotherapy-induced amenorrhea is lower among young breast cancer patients and depends on chemotherapeutic agent and dose.[4] However, even women who resume menstruation may face later difficulties with fertility due to ovarian damage and menopause at an earlier age.[3,4] Infertility alone is an emotionally challenging problem and may be even more challenging for cancer survivors.[5] Cancer diagnosis may result in delayed childbearing for many survivors who are typically advised to wait 2 to 3 years after treatment ends before conceiving. Those who undertake endocrine therapy, such as tamoxifen, face additional delays. This may rule out pregnancy for many survivors, particularly those who had already postponed childbearing until later in life.
Research indicates that the informational needs of young women regarding fertility and menopause are not being met.[6] There may also be discordance between younger women's concerns about fertility issues and how this issue is addressed by their doctors.[6,7] Some women feel that their concerns are not taken seriously by their health care providers.[8] Younger survivors also appear to have greater psychosocial needs as compared with older survivors, particularly with respect to dealing with the physical impact of treatment and associated gynecologic and reproductive consequences.[9] The need for support related to fertility and early menopause has been identified as very important to younger women.[8–11] Infertility and concerns about reproductive issues can negatively impact on survivors' well-being.[12,13]
Concerns about fertility may play a role in cancer treatment decisions made by young women.[14] In a recent study, 12% of long-term breast cancer survivors diagnosed at 40 years or younger reported that fertility was a consideration in their treatment decisions.[15] Results from a Web-based survey of young survivors found that fertility concerns impacted treatment decisions about 30% of the time, although selection bias may have resulted in a greater number who were concerned about fertility.[14] Learning more about how young women make treatment decisions is an important step toward meeting their informational and support needs.
We conducted this exploratory study to gather information about how young women make cancer treatment decisions and to investigate the role of fertility in their decision-making process. Although researchers and clinicians have begun to address the importance of fertility for young women diagnosed with cancer, there are currently no qualitative studies detailing these important issues from the perspective of young survivors. This approach provides in-depth and contextual information that cannot be obtained quantitatively[16] and allowed us to identify specific areas of unmet need.
http://www.medscape.com/viewarticle/734244?src=mp&spon=17
Gorman, Jessica R. PhD, MPH; Usita, Paula M. PhD; Madlensky, Lisa PhD; Pierce, John P. PhD
Abstract
Background: Younger women diagnosed with breast cancer are more likely to have survival concerns related to fertility, which may influence their treatment decisions.
Objective: This qualitative study explores how young women make cancer treatment decisions and the role of fertility concerns in that process.
Methods: We used purposeful sampling to identify a diverse group of 20 young breast cancer survivors, half of whom had a child after breast cancer. We conducted open-ended telephone interviews and used cross-case, inductive analysis to identify themes.
Results: The main themes were (1) "I was young, I wanted to do everything possible to move forward with my life and not to have the cancer come back"; (2) "Fertility concerns are different for every woman"; (3) "My oncologist was great… a huge part of my survivorship"; and (4) "They didn't tell me about my options, and I didn't think about fertility until it was too late."
Conclusions: Although fertility was important to many participants, treatment decisions were mainly motivated by survival concerns. Fertility concerns depended on life circumstances, and the timing in relation to diagnosis varied. There is a need for improved information regarding the impact of treatment on fertility and fertility preservation options, even if concerns are not expressed at diagnosis.
Implications for Practice: It is critical that cancer care providers provide timely information regarding fertility. Oncology nurses are particularly well positioned to serve this role by communicating with patients about their fertility concerns and reproductive planning prior to treatment and throughout the course of survivorship.
Introduction
Breast cancer treatment can increase the risk of early menopause and result in reproductive difficulties.[1–4] This is a major concern for many young breast cancer patients and survivors who have not finished growing their families. The risk of chemotherapy-induced amenorrhea is lower among young breast cancer patients and depends on chemotherapeutic agent and dose.[4] However, even women who resume menstruation may face later difficulties with fertility due to ovarian damage and menopause at an earlier age.[3,4] Infertility alone is an emotionally challenging problem and may be even more challenging for cancer survivors.[5] Cancer diagnosis may result in delayed childbearing for many survivors who are typically advised to wait 2 to 3 years after treatment ends before conceiving. Those who undertake endocrine therapy, such as tamoxifen, face additional delays. This may rule out pregnancy for many survivors, particularly those who had already postponed childbearing until later in life.
Research indicates that the informational needs of young women regarding fertility and menopause are not being met.[6] There may also be discordance between younger women's concerns about fertility issues and how this issue is addressed by their doctors.[6,7] Some women feel that their concerns are not taken seriously by their health care providers.[8] Younger survivors also appear to have greater psychosocial needs as compared with older survivors, particularly with respect to dealing with the physical impact of treatment and associated gynecologic and reproductive consequences.[9] The need for support related to fertility and early menopause has been identified as very important to younger women.[8–11] Infertility and concerns about reproductive issues can negatively impact on survivors' well-being.[12,13]
Concerns about fertility may play a role in cancer treatment decisions made by young women.[14] In a recent study, 12% of long-term breast cancer survivors diagnosed at 40 years or younger reported that fertility was a consideration in their treatment decisions.[15] Results from a Web-based survey of young survivors found that fertility concerns impacted treatment decisions about 30% of the time, although selection bias may have resulted in a greater number who were concerned about fertility.[14] Learning more about how young women make treatment decisions is an important step toward meeting their informational and support needs.
We conducted this exploratory study to gather information about how young women make cancer treatment decisions and to investigate the role of fertility in their decision-making process. Although researchers and clinicians have begun to address the importance of fertility for young women diagnosed with cancer, there are currently no qualitative studies detailing these important issues from the perspective of young survivors. This approach provides in-depth and contextual information that cannot be obtained quantitatively[16] and allowed us to identify specific areas of unmet need.
http://www.medscape.com/viewarticle/734244?src=mp&spon=17
MRI More Sensitive Than Mammography or Ultrasound in Women at High Risk for Breast Cancer
From Medscape Medical News
Roxanne Nelson
March 15, 2010 — New findings suggest that mammography is of little value in young women with a familial risk for breast cancer who have access to quality-assured magnetic resonance imaging (MRI).
In a study published online February 22 in the Journal of Clinical Oncology, researchers found that using mammography, an ultrasound examination, or clinical breast examination does not increase the "cancer yield," compared with what is achieved with MRI alone.
The team was headed by Christiane Kuhl, MD, professor and vice chair of radiology at the University of Bonn in Germany, who has previously reported the superiority of MRI and is an advocate for this technology.
In this study, the researchers report that the cancer yield of ultrasound (6.0 of 1000) and mammography (5.4 of 1000) was equivalent, and increased nonsignificantly if both modalities were combined (7.7 of 1000). With MRI alone, the cancer yield was 14.9 of 1000, which is significantly higher than with either mammography or ultrasound.
In addition, the positive predictive value was 39% for mammography, 36% for ultrasound, and 48% for MRI.
Dr. Kuhl and colleagues suggest that, as a result, existing screening guidelines for young women at high and moderate risk for breast cancer — which currently recommend mammography — need to be revised.
This study adds to accumulating evidence that MRI is the most important screening modality for women with familial and genetic risks for breast cancer. However, for many reasons, mammography should not be abandoned just yet, according to an accompanying editorial.
Current Guidelines Not Based on Randomized Trials
Guidelines in both Europe and the United States recommend that women who face an increased risk for breast cancer begin mammographic screening at the age of 25 to 30 years, and should continue until age 70, Dr. Kuhl explained.
"It is important to realize that mammographic screening has been established by randomized controlled clinical trials only for women aged 40 and older — and many would argue only for women older than 50," Dr. Kuhl told Medscape Oncology. "Mammographic screening of women aged 25 to 39 has never been investigated or established by data from randomized controlled clinical trials."
She added that for women in this age range, existing guidelines are based on "expert opinion" only, with the experts being mainly oncologists, not radiologists. "But now, 10 years down the road from setting up these guidelines, we have evidence to suggest that mammography, if performed in addition to MRI, does not increase the cancer yield over what is achieved by MRI alone," she said.
Because the use of mammography is indicated in women older than 40 years, irrespective of risk, and its use is supported by randomized clinical trials, "we would stick to the recommendations to use mammography in addition to MRI in these high-risk women," said Dr. Kuhl.
But recent data do not support the use of screening mammography in women younger than 40 years who undergo quality-assured breast MRI, she added. "Since there are no data from randomized clinical trials that support the use of screening mammography for this age group anyway, we suggest the discontinuation of screening mammography in this age group," she said.
Changing Standards of Care?
In their paper, Dr. Kuhl and her colleagues provide a meta-analysis of the existing evidence, in the entire medical literature, on diagnosing breast cancer in young women. "The results clearly support our conclusion," she said.
But even though the data from the current trial, along with the meta-analysis, are clear and statistically highly significant, Dr. Kuhl noted that she still has "the following reservation when I am asked whether we should now change the existing standards of care."
She explained that, unlike studies that relate to treatment with a new drug, it is much more difficult to predict whether results of diagnostic trials will be completely reproducible in all global settings. This has an affect on the generalizability of results.
In a randomized trial comparing 2 different drugs, the difference between the success of treatment A and that of treatment B will most likely be transferable to all parts in the world, because drug A and drug B will be exactly the same, Dr. Kuhl explained. "This is different for diagnostic studies because there is a 'human factor' involved, and, at least for MRI, there are many different ways to image the breast."
"Therefore, to account for this variability of test performance that is true for all diagnostic studies, we chose the somewhat clumsy way to summarize our results as [being applicable to] 'women who have access to quality-assured breast MRI'," said Dr. Kuhl.
Higher Cancer Detection With MRI
In the current study, Dr. Kuhl and colleagues investigated the effectiveness of clinical breast examination, mammography, ultrasound, and quality-assured breast MRI, used alone or in combination, for screening women at elevated risk for breast cancer. The Evaluation of Imaging Methods for Secondary Prevention of Familial Breast Cancer (EVA) trial was conducted at 4 German academic breast centers and consisted of 687 women with a lifetime risk of developing breast cancer of 20% or greater.
The participants underwent 1679 screening rounds — which included annual MRI, mammography, ultrasound, and clinical breast examination — that were read independently and in different combinations. A subgroup of 371 women underwent 6-month screening ultrasound examinations and clinical breast exams. The mean follow-up was 29.18 months and the median follow-up was 29.09 months.
During the study period, 27 women (3.9%) were diagnosed with breast cancer. Of these, 16 (59%) were invasive cancers and 11 (41%) were ductal carcinoma in situ (DCIS). All of the cancers were detected during the annual screenings, and none were interval cancers. The mean age at diagnosis was 43.1 years.
The majority of women (n = 21; 77%) were diagnosed with minimal cancers, and 9 of the cancers occurred in women with a history of the disease (7 were contralateral or second primary cancers and 2 were local recurrences).
The researchers found that the sensitivity achieved by ultrasound alone (37%) and by mammography alone (33%) was comparable (P = .72). Combining mammography and ultrasound yielded a slightly higher sensitivity, but it was not significant (48%; P < .12).
However, MRI used alone was significantly more sensitive (93%) than either mammography or ultrasound alone or in combination (P < .005). The addition of mammography to MRI did not result in a statistically significant increase in sensitivity (P = .5).
Overall, 2 cancers were diagnosed with mammography alone (7%) and none were diagnosed with ultrasound alone, but 14 were diagnosed by MRI alone. Clinical breast examination was positive in 110 screening rounds, but only 1 palpable mass corresponded to a cancer diagnosis. The remaining cancers diagnosed during the study period were all clinically occult.
Contribution to Accumulating Evidence
The results of the EVA trial contribute to "the accumulating evidence that MRI is not only the most important screening modality in gene-mutation carriers, but also in women with a familial risk without a documented BRCA1/2 mutation," notes Jan G.M. Klijn, MD, in an accompanying editorial.
"But for a number of reasons, many radiologists and oncologists think that it is still too early to abandon mammography," writes Dr. Klijn, who is from Erasmus University in Rotterdam, the Netherlands. One reason is that in other large studies, combined mammography and MRI were significantly superior to either mode of screening alone.
Another reason is that "the experience of MRI is variable among centers participating in trials and certainly outside trials mandating a learning curve," he writes, adding that future studies will be needed to confirm the very high MRI sensitivities and specificities for both the invasive cancers and DCISs that were reported in this paper, using comparable technology and quality-controlled protocols.
The study was supported by a grant from the German Cancer Aid Society. None of the authors nor the editorialist have disclosed any relevant financial relationships.
J Clin Oncol. Published online February 22, 2010. Abstract, Abstract
Roxanne Nelson
March 15, 2010 — New findings suggest that mammography is of little value in young women with a familial risk for breast cancer who have access to quality-assured magnetic resonance imaging (MRI).
In a study published online February 22 in the Journal of Clinical Oncology, researchers found that using mammography, an ultrasound examination, or clinical breast examination does not increase the "cancer yield," compared with what is achieved with MRI alone.
The team was headed by Christiane Kuhl, MD, professor and vice chair of radiology at the University of Bonn in Germany, who has previously reported the superiority of MRI and is an advocate for this technology.
In this study, the researchers report that the cancer yield of ultrasound (6.0 of 1000) and mammography (5.4 of 1000) was equivalent, and increased nonsignificantly if both modalities were combined (7.7 of 1000). With MRI alone, the cancer yield was 14.9 of 1000, which is significantly higher than with either mammography or ultrasound.
In addition, the positive predictive value was 39% for mammography, 36% for ultrasound, and 48% for MRI.
Dr. Kuhl and colleagues suggest that, as a result, existing screening guidelines for young women at high and moderate risk for breast cancer — which currently recommend mammography — need to be revised.
This study adds to accumulating evidence that MRI is the most important screening modality for women with familial and genetic risks for breast cancer. However, for many reasons, mammography should not be abandoned just yet, according to an accompanying editorial.
Current Guidelines Not Based on Randomized Trials
Guidelines in both Europe and the United States recommend that women who face an increased risk for breast cancer begin mammographic screening at the age of 25 to 30 years, and should continue until age 70, Dr. Kuhl explained.
"It is important to realize that mammographic screening has been established by randomized controlled clinical trials only for women aged 40 and older — and many would argue only for women older than 50," Dr. Kuhl told Medscape Oncology. "Mammographic screening of women aged 25 to 39 has never been investigated or established by data from randomized controlled clinical trials."
She added that for women in this age range, existing guidelines are based on "expert opinion" only, with the experts being mainly oncologists, not radiologists. "But now, 10 years down the road from setting up these guidelines, we have evidence to suggest that mammography, if performed in addition to MRI, does not increase the cancer yield over what is achieved by MRI alone," she said.
Because the use of mammography is indicated in women older than 40 years, irrespective of risk, and its use is supported by randomized clinical trials, "we would stick to the recommendations to use mammography in addition to MRI in these high-risk women," said Dr. Kuhl.
But recent data do not support the use of screening mammography in women younger than 40 years who undergo quality-assured breast MRI, she added. "Since there are no data from randomized clinical trials that support the use of screening mammography for this age group anyway, we suggest the discontinuation of screening mammography in this age group," she said.
Changing Standards of Care?
In their paper, Dr. Kuhl and her colleagues provide a meta-analysis of the existing evidence, in the entire medical literature, on diagnosing breast cancer in young women. "The results clearly support our conclusion," she said.
But even though the data from the current trial, along with the meta-analysis, are clear and statistically highly significant, Dr. Kuhl noted that she still has "the following reservation when I am asked whether we should now change the existing standards of care."
She explained that, unlike studies that relate to treatment with a new drug, it is much more difficult to predict whether results of diagnostic trials will be completely reproducible in all global settings. This has an affect on the generalizability of results.
In a randomized trial comparing 2 different drugs, the difference between the success of treatment A and that of treatment B will most likely be transferable to all parts in the world, because drug A and drug B will be exactly the same, Dr. Kuhl explained. "This is different for diagnostic studies because there is a 'human factor' involved, and, at least for MRI, there are many different ways to image the breast."
"Therefore, to account for this variability of test performance that is true for all diagnostic studies, we chose the somewhat clumsy way to summarize our results as [being applicable to] 'women who have access to quality-assured breast MRI'," said Dr. Kuhl.
Higher Cancer Detection With MRI
In the current study, Dr. Kuhl and colleagues investigated the effectiveness of clinical breast examination, mammography, ultrasound, and quality-assured breast MRI, used alone or in combination, for screening women at elevated risk for breast cancer. The Evaluation of Imaging Methods for Secondary Prevention of Familial Breast Cancer (EVA) trial was conducted at 4 German academic breast centers and consisted of 687 women with a lifetime risk of developing breast cancer of 20% or greater.
The participants underwent 1679 screening rounds — which included annual MRI, mammography, ultrasound, and clinical breast examination — that were read independently and in different combinations. A subgroup of 371 women underwent 6-month screening ultrasound examinations and clinical breast exams. The mean follow-up was 29.18 months and the median follow-up was 29.09 months.
During the study period, 27 women (3.9%) were diagnosed with breast cancer. Of these, 16 (59%) were invasive cancers and 11 (41%) were ductal carcinoma in situ (DCIS). All of the cancers were detected during the annual screenings, and none were interval cancers. The mean age at diagnosis was 43.1 years.
The majority of women (n = 21; 77%) were diagnosed with minimal cancers, and 9 of the cancers occurred in women with a history of the disease (7 were contralateral or second primary cancers and 2 were local recurrences).
The researchers found that the sensitivity achieved by ultrasound alone (37%) and by mammography alone (33%) was comparable (P = .72). Combining mammography and ultrasound yielded a slightly higher sensitivity, but it was not significant (48%; P < .12).
However, MRI used alone was significantly more sensitive (93%) than either mammography or ultrasound alone or in combination (P < .005). The addition of mammography to MRI did not result in a statistically significant increase in sensitivity (P = .5).
Overall, 2 cancers were diagnosed with mammography alone (7%) and none were diagnosed with ultrasound alone, but 14 were diagnosed by MRI alone. Clinical breast examination was positive in 110 screening rounds, but only 1 palpable mass corresponded to a cancer diagnosis. The remaining cancers diagnosed during the study period were all clinically occult.
Contribution to Accumulating Evidence
The results of the EVA trial contribute to "the accumulating evidence that MRI is not only the most important screening modality in gene-mutation carriers, but also in women with a familial risk without a documented BRCA1/2 mutation," notes Jan G.M. Klijn, MD, in an accompanying editorial.
"But for a number of reasons, many radiologists and oncologists think that it is still too early to abandon mammography," writes Dr. Klijn, who is from Erasmus University in Rotterdam, the Netherlands. One reason is that in other large studies, combined mammography and MRI were significantly superior to either mode of screening alone.
Another reason is that "the experience of MRI is variable among centers participating in trials and certainly outside trials mandating a learning curve," he writes, adding that future studies will be needed to confirm the very high MRI sensitivities and specificities for both the invasive cancers and DCISs that were reported in this paper, using comparable technology and quality-controlled protocols.
The study was supported by a grant from the German Cancer Aid Society. None of the authors nor the editorialist have disclosed any relevant financial relationships.
J Clin Oncol. Published online February 22, 2010. Abstract, Abstract
Promoting Screening Mammography: Insight or Uptake?
From Journal of the American Board of Family Medicine
John D. Keen, MD, MBA
posted: 01/02/2011; J Am Board Fam Med. 2010;23(6):775-782. © 2010 American Board of Family Medicine
Abstract
The US Preventive Services Task Force has emphasized individualized decision-making regarding participation in screening mammography for women ages 40 to 49.
Positive public opinion regarding screening mammography is understandable given that screening advocates have heavily promoted the slogan "early detection saves lives" while ignoring screening harms.
The goal of mammography screening advocates is to increase screening participation or uptake. The purpose of this paper is to promote physician and patient insight by presenting the age-related benefit and harms of screening.
At age 50, routine screening saves approximately 1 woman per 1000 over 10 years.
The life-saving proportion of screen-detected cancers is 5%, which means mammograms must detect 21 cancers to save one life. Almost half of screen-detected cancers represent pseudo-disease and would never become symptomatic yet alone lethal during a woman's lifetime.
Consequently, 40- and 50-year-old women are 10 times more likely to experience overdiagnosis and overtreatment than to have their lives saved. Analysis of events and outcomes per single screening round for women ages 40 to 49 show that approximately 9600 screening mammograms, 960 diagnostic exams, and 90 to 140 biopsies are required to save one life. Given the substantial harms of screening, advocates should refocus their priority from promoting uptake to promoting insight.
Introduction
Judging by recent media coverage, many of the 2.5 million breast cancer survivors in the United States, including 610,000 women with ductal carcinoma in situ (DCIS),[1] were outraged at the US Preventive Services Task Force for not continuing to advise routine screening mammography for women ages 40 to 49.
Based on an update of the evidence regarding the benefits and harms of screening, which was published in November 2009, the Task Force is re-emphasizing individualized decision making for these women.
The belief that earlier detection of breast cancer almost always is beneficial explains part of the negative public reaction to this recommendation.Assuming the truth of this premise, a woman with a screen-detected cancer has a valid and sound argument that "mammography saved my life."
Consequently, every breast cancer survivor and her friends and family have a reason to become screening mammography advocates. For instance, the founder of the Susan G. Komen Foundation claims that she is "one woman whose life was saved by early detection."
Public opinion regarding screening mammography is understandable given that the concept "earlier detection saves lives" has been heavily promoted but not clearly explained by mammography supporters including physician organizations, the American Cancer Society, and advocacy groups.
However, the premise of a near universal life-saving benefit from finding presymptomatic breast cancer through mammography is false.
The following is a quick analysis of the "life-saving proportion" of screen-detected cancer.
Women often die of breast cancer after screening; mammography achieves approximately a 1 in 5 life-saving benefit (the relative mortality risk reduction) in the subgroup of women who have lethal breast cancers. If all screen-detected breast cancers were rapidly lethal, the highest life-saving proportion would be 20%. In the United States, the diagnostic risk for breast cancer (screen-detected or not) is approximately 6 to 7 times the death risk over 15 years. Risk means an outcome for 1000 people at risk for an event over a period of time. Therefore, the lowest life-saving proportion would be 3% (1/5 × 1/7) in the larger subgroup of women who have been diagnosed with cancer.
The "pink ribbon" marketing of breast cancer awareness supports advocacy groups and aims to increase the uptake of (participation in) mammography. Ostensibly for the sake of public health, the advertising campaign has some negative consequences.
One side effect is distorted physician and public insight about the age-related benefit and the substantial harms of screening. For instance, in one survey more than half of US women thought that mammography helps to prevent or reduce the risk of contracting breast cancer. Gigerenzer et al reported that less than 2% of European women have insight into the absolute benefit of routine screening mammography, and most women overestimate the benefit by orders of magnitude. The absolute benefit derived from an overview of Swedish randomized screening trials is one breast cancer death averted (or one life saved) in the invited group versus the control group per 1000 women after 10 years.
The US Preventive Services Task Force deserves praise for promoting insight among younger women by stressing the well-known downstream screening harms that can result from false-positive mammograms.
These radiologist interpretations produce anxiety beyond the initial screen and require additional evaluations including diagnostic mammograms, ultrasounds, and biopsies that do not find a cancer. Any breast radiologist who has contact with patients sees this anxiety every day while performing diagnostic evaluations. However, the US Preventive Services Task Force has downplayed the major harm of screening.
Overdiagnosis of breast cancer is the preclinical detection of either stable disease, such as forms of DCIS, or indolent or slow-growing tumors in older women. This pseudo-disease would never become symptomatic (and diagnosed) let alone metastatic (and lethal) during a woman's lifetime without screening. Because physicians must treat all true-positive or histologically confirmed mammograms as potentially lethal cancer, women with pseudo-disease can only be harmed by screening mammography.
In theory, earlier detection of localized cancer through screening mammography should result in a compensatory drop in future advanced cancer and cancer deaths, yet this has not occurred. Nevertheless, prominent breast radiologists continue to deny a significant problem with overdiagnosis, and the 2010 American Cancer Society guidelines do not mention overdiagnosis as a limitation of mammography. The problem of overdiagnosis is not publicized during screening invitations and most women are not aware of nonprogressive cancer.
The 2009 analysis of the screening trials by the Cochrane Database of Systemic Reviews calculated a 30% overdiagnosis rate (excess cancers and surgeries compared with control), or 0.3 ÷ 1.3 = 23% of all cancers in screened groups. Recent articles by Jorgensen and Gotzsche[27] and Jorgensen et al[28] include an overdiagnosis estimate for invasive cancer of 35% (52% including DCIS) in countries that have organized screening programs (34% of all cancers in screened populations, screen-detected or not), and 33% in a country that has organized screening and a control group. Morrell et al[29] estimated overdiagnosis in an organized program of between 30% and 42% for invasive cancer only. The US Preventive Services Task Force's estimate is between 1% and 10%.
Sackett[30] warned that history shows preventive medicine "experts" can be assertive, presumptuous, and overbearing. In today's mammography debate, some screening advocates claim to support individual decision making yet tell women what to do, confident that screening benefits outweigh the harms, while attacking those who question their promotion of screening.
Physicians who support insight should be indifferent to uptake. Given the reaction of specialists who have professional and financial interests in screening, primary care physicians will have to implement the US Preventive Services Task Force's recommendations.
In support of this goal, Table 1 summarizes the epidemiology of breast cancer. For perspective on the opportunity cost of the resources devoted to screening mammography, columns A and B show the 10-year, all-cause death risks for smoking and nonsmoking US women at ages 40, 50, and 60. In comparison, columns C and D show the diagnosis risk for breast cancer and DCIS, whereas column E shows the absolute death risk without screening mammography. Barratt et al[38] show similar estimates for Australia. Without screening, over a decade a 50-year-old woman has a 5 times greater risk of receiving a diagnosis of breast cancer than of dying from it. She also has a 10 times greater risk of dying from something besides breast cancer.
Table 2 derives estimates for the life-saving proportion of screen-detected cancers, the reciprocal or number needed to detect to save one life, and the extent of overdiagnosis for US women.[39–41] Column F shows lives saved, or the absolute risk reduction from an invitation to routine screening. The absolute risk reduction is simply the relative risk reduction multiplied by the absolute death risk (column E). The reciprocal, or number needed to invite for repeated screening over a decade, are 2500, 1300, and 400. Ignoring volunteer bias and adjusting for compliance,[38] at age 50 routine screening saves approximately one woman per 1000 over 10 years. The participation rate for US women and the uptake in the most recent screening mammography trial are 70%.[3,42] Column G, or screen-detected cancer among all diagnosed cancer (column C in Table 1) depends on the sensitivity of mammography and screening participation. Mathis et al found that 57% of breast cancer was screen-detected. Likewise, column H, or pseudo-disease estimates, depend on an overdiagnosis rate applied to all diagnosed cancer, screen-detected or not.
At age 50 almost half (42%; range, 9% to 62%) of all screen-detected cancers represent overdiagnosis of pseudo-disease. The only available estimate from the screening trials is 24%.
Estimated breast cancer events per 1000 US women over 10 years at different starting ages, assuming 68% participation in screening mammography. *Data sources are listed in Tables 1 and 2. †At age 50, routine screening saves 1 in 1000 women over 10 years.
For women at age 50, the benefit "1/1000 over 10" reframed means that through routine screening a woman can increase her breast cancer survival from 99.5% to 99.6%, and her overall survival as a nonsmoker from 96.3% to 96.4% over a decade.
Table 2 from the US Preventive Services Task Force update[3] provides downstream average outcomes for a single screening round for different age groups. By applying the number needed to detect to save one life, the flowchart in Figure 2 shows estimated events and outcomes per screening round, including false-negative and false-positive mammograms and biopsies needed to save one life. The overdiagnosis ratio at the bottom means that, for women aged 40 to 59, approximately 10 women receive unnecessary mastectomies or lumpectomies and possibly chemotherapy and radiation treatment for every life saved.[26]
Conclusion
The limited age-related benefit from screening mammography means that, for younger breast cancer survivors, mammography most likely (>95%) did not save their lives. Forty- and 50-year-old women thinking about participating in screening are 10 times more likely to experience overdiagnosis and overtreatment than to have their lives saved by mammography.
Given this reality, screening advocates should refocus their priority from promoting uptake to promoting insight.
Primary care physicians have an obligation to understand the harms and benefits of screening to help empower their patients to make individual decisions.
If younger women decline screening participation because of increased understanding about benefits and harms, all physicians should appreciate this decision as a reasonable choice.
http://www.medscape.com/viewarticle/733710_2
John D. Keen, MD, MBA
posted: 01/02/2011; J Am Board Fam Med. 2010;23(6):775-782. © 2010 American Board of Family Medicine
Abstract
The US Preventive Services Task Force has emphasized individualized decision-making regarding participation in screening mammography for women ages 40 to 49.
Positive public opinion regarding screening mammography is understandable given that screening advocates have heavily promoted the slogan "early detection saves lives" while ignoring screening harms.
The goal of mammography screening advocates is to increase screening participation or uptake. The purpose of this paper is to promote physician and patient insight by presenting the age-related benefit and harms of screening.
At age 50, routine screening saves approximately 1 woman per 1000 over 10 years.
The life-saving proportion of screen-detected cancers is 5%, which means mammograms must detect 21 cancers to save one life. Almost half of screen-detected cancers represent pseudo-disease and would never become symptomatic yet alone lethal during a woman's lifetime.
Consequently, 40- and 50-year-old women are 10 times more likely to experience overdiagnosis and overtreatment than to have their lives saved. Analysis of events and outcomes per single screening round for women ages 40 to 49 show that approximately 9600 screening mammograms, 960 diagnostic exams, and 90 to 140 biopsies are required to save one life. Given the substantial harms of screening, advocates should refocus their priority from promoting uptake to promoting insight.
Introduction
Judging by recent media coverage, many of the 2.5 million breast cancer survivors in the United States, including 610,000 women with ductal carcinoma in situ (DCIS),[1] were outraged at the US Preventive Services Task Force for not continuing to advise routine screening mammography for women ages 40 to 49.
Based on an update of the evidence regarding the benefits and harms of screening, which was published in November 2009, the Task Force is re-emphasizing individualized decision making for these women.
The belief that earlier detection of breast cancer almost always is beneficial explains part of the negative public reaction to this recommendation.Assuming the truth of this premise, a woman with a screen-detected cancer has a valid and sound argument that "mammography saved my life."
Consequently, every breast cancer survivor and her friends and family have a reason to become screening mammography advocates. For instance, the founder of the Susan G. Komen Foundation claims that she is "one woman whose life was saved by early detection."
Public opinion regarding screening mammography is understandable given that the concept "earlier detection saves lives" has been heavily promoted but not clearly explained by mammography supporters including physician organizations, the American Cancer Society, and advocacy groups.
However, the premise of a near universal life-saving benefit from finding presymptomatic breast cancer through mammography is false.
The following is a quick analysis of the "life-saving proportion" of screen-detected cancer.
Women often die of breast cancer after screening; mammography achieves approximately a 1 in 5 life-saving benefit (the relative mortality risk reduction) in the subgroup of women who have lethal breast cancers. If all screen-detected breast cancers were rapidly lethal, the highest life-saving proportion would be 20%. In the United States, the diagnostic risk for breast cancer (screen-detected or not) is approximately 6 to 7 times the death risk over 15 years. Risk means an outcome for 1000 people at risk for an event over a period of time. Therefore, the lowest life-saving proportion would be 3% (1/5 × 1/7) in the larger subgroup of women who have been diagnosed with cancer.
The "pink ribbon" marketing of breast cancer awareness supports advocacy groups and aims to increase the uptake of (participation in) mammography. Ostensibly for the sake of public health, the advertising campaign has some negative consequences.
One side effect is distorted physician and public insight about the age-related benefit and the substantial harms of screening. For instance, in one survey more than half of US women thought that mammography helps to prevent or reduce the risk of contracting breast cancer. Gigerenzer et al reported that less than 2% of European women have insight into the absolute benefit of routine screening mammography, and most women overestimate the benefit by orders of magnitude. The absolute benefit derived from an overview of Swedish randomized screening trials is one breast cancer death averted (or one life saved) in the invited group versus the control group per 1000 women after 10 years.
The US Preventive Services Task Force deserves praise for promoting insight among younger women by stressing the well-known downstream screening harms that can result from false-positive mammograms.
These radiologist interpretations produce anxiety beyond the initial screen and require additional evaluations including diagnostic mammograms, ultrasounds, and biopsies that do not find a cancer. Any breast radiologist who has contact with patients sees this anxiety every day while performing diagnostic evaluations. However, the US Preventive Services Task Force has downplayed the major harm of screening.
Overdiagnosis of breast cancer is the preclinical detection of either stable disease, such as forms of DCIS, or indolent or slow-growing tumors in older women. This pseudo-disease would never become symptomatic (and diagnosed) let alone metastatic (and lethal) during a woman's lifetime without screening. Because physicians must treat all true-positive or histologically confirmed mammograms as potentially lethal cancer, women with pseudo-disease can only be harmed by screening mammography.
In theory, earlier detection of localized cancer through screening mammography should result in a compensatory drop in future advanced cancer and cancer deaths, yet this has not occurred. Nevertheless, prominent breast radiologists continue to deny a significant problem with overdiagnosis, and the 2010 American Cancer Society guidelines do not mention overdiagnosis as a limitation of mammography. The problem of overdiagnosis is not publicized during screening invitations and most women are not aware of nonprogressive cancer.
The 2009 analysis of the screening trials by the Cochrane Database of Systemic Reviews calculated a 30% overdiagnosis rate (excess cancers and surgeries compared with control), or 0.3 ÷ 1.3 = 23% of all cancers in screened groups. Recent articles by Jorgensen and Gotzsche[27] and Jorgensen et al[28] include an overdiagnosis estimate for invasive cancer of 35% (52% including DCIS) in countries that have organized screening programs (34% of all cancers in screened populations, screen-detected or not), and 33% in a country that has organized screening and a control group. Morrell et al[29] estimated overdiagnosis in an organized program of between 30% and 42% for invasive cancer only. The US Preventive Services Task Force's estimate is between 1% and 10%.
Sackett[30] warned that history shows preventive medicine "experts" can be assertive, presumptuous, and overbearing. In today's mammography debate, some screening advocates claim to support individual decision making yet tell women what to do, confident that screening benefits outweigh the harms, while attacking those who question their promotion of screening.
Physicians who support insight should be indifferent to uptake. Given the reaction of specialists who have professional and financial interests in screening, primary care physicians will have to implement the US Preventive Services Task Force's recommendations.
In support of this goal, Table 1 summarizes the epidemiology of breast cancer. For perspective on the opportunity cost of the resources devoted to screening mammography, columns A and B show the 10-year, all-cause death risks for smoking and nonsmoking US women at ages 40, 50, and 60. In comparison, columns C and D show the diagnosis risk for breast cancer and DCIS, whereas column E shows the absolute death risk without screening mammography. Barratt et al[38] show similar estimates for Australia. Without screening, over a decade a 50-year-old woman has a 5 times greater risk of receiving a diagnosis of breast cancer than of dying from it. She also has a 10 times greater risk of dying from something besides breast cancer.
Table 2 derives estimates for the life-saving proportion of screen-detected cancers, the reciprocal or number needed to detect to save one life, and the extent of overdiagnosis for US women.[39–41] Column F shows lives saved, or the absolute risk reduction from an invitation to routine screening. The absolute risk reduction is simply the relative risk reduction multiplied by the absolute death risk (column E). The reciprocal, or number needed to invite for repeated screening over a decade, are 2500, 1300, and 400. Ignoring volunteer bias and adjusting for compliance,[38] at age 50 routine screening saves approximately one woman per 1000 over 10 years. The participation rate for US women and the uptake in the most recent screening mammography trial are 70%.[3,42] Column G, or screen-detected cancer among all diagnosed cancer (column C in Table 1) depends on the sensitivity of mammography and screening participation. Mathis et al found that 57% of breast cancer was screen-detected. Likewise, column H, or pseudo-disease estimates, depend on an overdiagnosis rate applied to all diagnosed cancer, screen-detected or not.
At age 50 almost half (42%; range, 9% to 62%) of all screen-detected cancers represent overdiagnosis of pseudo-disease. The only available estimate from the screening trials is 24%.
Estimated breast cancer events per 1000 US women over 10 years at different starting ages, assuming 68% participation in screening mammography. *Data sources are listed in Tables 1 and 2. †At age 50, routine screening saves 1 in 1000 women over 10 years.
For women at age 50, the benefit "1/1000 over 10" reframed means that through routine screening a woman can increase her breast cancer survival from 99.5% to 99.6%, and her overall survival as a nonsmoker from 96.3% to 96.4% over a decade.
Table 2 from the US Preventive Services Task Force update[3] provides downstream average outcomes for a single screening round for different age groups. By applying the number needed to detect to save one life, the flowchart in Figure 2 shows estimated events and outcomes per screening round, including false-negative and false-positive mammograms and biopsies needed to save one life. The overdiagnosis ratio at the bottom means that, for women aged 40 to 59, approximately 10 women receive unnecessary mastectomies or lumpectomies and possibly chemotherapy and radiation treatment for every life saved.[26]
Conclusion
The limited age-related benefit from screening mammography means that, for younger breast cancer survivors, mammography most likely (>95%) did not save their lives. Forty- and 50-year-old women thinking about participating in screening are 10 times more likely to experience overdiagnosis and overtreatment than to have their lives saved by mammography.
Given this reality, screening advocates should refocus their priority from promoting uptake to promoting insight.
Primary care physicians have an obligation to understand the harms and benefits of screening to help empower their patients to make individual decisions.
If younger women decline screening participation because of increased understanding about benefits and harms, all physicians should appreciate this decision as a reasonable choice.
http://www.medscape.com/viewarticle/733710_2
Monday, January 10, 2011
Power Posing: Fake It Until You Make It
Published: September 20, 2010
Author: Julia Hanna
Executive Summary:
Nervous about an upcoming presentation or job interview? Holding one's body in "high-power" poses for short time periods can summon an extra surge of power and sense of well-being when it's needed, according to Harvard Business School professor Amy J.C. Cuddy.
Key concepts include:
* Holding one's body in expansive, "high-power" poses for as little as two minutes stimulates higher levels of testosterone and lower levels of cortisol.
* In addition to causing hormonal shifts, power poses lead to increased feelings of power and a greater tolerance for risk.
* People often are more influenced by how they feel about you than by what you're saying.
* The research has broad implications for people who suffer from feelings of powerlessness and low self-esteem due to their hierarchical rank or lack of resources.
Amy J. C. Cuddy is an assistant professor in the Negotiation, Organizations and Markets unit at Harvard Business School.
We can't be the alpha dog all of the time. Whatever our personality, most of us experience varying degrees of feeling in charge. Some situations take us down a notch while others build us up.
New research shows that it's possible to control those feelings a bit more, to be able to summon an extra surge of power and sense of well-being when it's needed: for example, during a job interview or for a key presentation to a group of skeptical customers.
"Our research has broad implications for people who suffer from feelings of powerlessness and low self-esteem due to their hierarchical rank or lack of resources," says HBS assistant professor Amy J.C. Cuddy, one of the researchers on the study.
"It's not about the content of the message, but how you're communicating it."
In "Power Posing: Brief Nonverbal Displays Affect Neuroendocrine Levels and Risk Tolerance", Cuddy shows that simply holding one's body in expansive, "high-power" poses for as little as two minutes stimulates higher levels of testosterone (the hormone linked to power and dominance in the animal and human worlds) and lower levels of cortisol (the "stress" hormone that can, over time, cause impaired immune functioning, hypertension, and memory loss).
The result? In addition to causing the desired hormonal shift, the power poses led to increased feelings of power and a greater tolerance for risk.
"We used to think that emotion ended on the face," Cuddy says. "Now there is established research showing that while it's true that facial expressions reflect how you feel, you can also 'fake it until you make it.
' In other words, you can smile long enough that it makes you feel happy. This work extends that finding on facial feedback, which is decades old, by focusing on postures and measuring neuroendocrine levels."
The experiment
In their article, to be published in a forthcoming Psychological Science, Cuddy and coauthors Dana R. Carney and Andy J. Yap of Columbia University detail the results of an experiment in which forty-two male and female participants were randomly assigned to a high- or low-power pose group.
No one was told what the study was about; instead, each participant believed it was related to the placement of ECG electrodes above and below his or her heart.
Subjects in the high-power group were manipulated into two expansive poses for one minute each: first, the classic feet on desk, hands behind head; then, standing and leaning on one's hands over a desk.
Those in the low-power group were posed for the time period in two restrictive poses: sitting in a chair with arms held close and hands folded, and standing with arms and legs crossed tightly.
Saliva samples taken before and after the posing measured testosterone and cortisol levels. To evaluate risk tolerance, participants were given $2 and told they could roll a die for even odds of winning $4. Finally, participants were asked to indicate how "powerful" and "in charge" they felt on a scale from one to four.
Controlling for subjects' baseline levels of both hormones, Cuddy and her coauthors found that high-power poses decreased cortisol by about 25 percent and increased testosterone by about 19 percent for both men and women.
In contrast, low-power poses increased cortisol about 17 percent and decreased testosterone about 10 percent.
Not surprisingly, high-power posers of both sexes also reported greater feelings of being powerful and in charge. In addition, those in the high-power group were more likely to take the risk of gambling their $2; 86 percent rolled the die in the high-power group as opposed to 60 percent of the low-power posers.
Previous research established that situational role changes can cause shifts in hormone levels. In primate groups, for example, after an alpha male dies the testosterone levels of the animal replacing him go up. The hormonal shifts measured in this experiment show that such changes can be influenced independent of role, situation, or any consciously focused thoughts about power. The physical poses are enough.
And that, she suggests, has broad implications for people who suffer from feelings of powerlessness and low self-esteem due to their hierarchical rank or lack of resources.
Why we judge
Cuddy's overall research agenda focuses on stereotyping and questions around how we form judgments of others' warmth and competence.
Just Because I'm Nice, Don't Assume I'm Dumb reveals how and why we come to snap judgments about coworkers (and how to fight that natural instinct). The article was cited as a "Breakthrough Business Idea" for 2009 by Harvard Business Review.
"The power poses paper came about in part because my coauthor Dana and I had noticed that women in our classes seemed to be participating less," says Cuddy, who teaches the MBA elective Power and Influence.
"Some of the women exhibited body language associated with low power, so we wondered if that was in turn affecting how they feel," she adds, citing the "fake it till you make it" research that shows smiling can affect feelings and hormone levels.
"It's about understanding what moves people."
"The poses that we used in the experiment are strongly associated across the animal kingdom with high and low dominance for very straightforward evolutionary reasons. Either you want to be big because you're in charge, or you want to close in and hide your vital organs because you're not in charge.
"It does appear that even this minimal manipulation can change people's physiology and psychology and, we hope, lead to very different, meaningful outcomes, whether it's how they perform in a job interview or how they participate in class."
Cuddy acknowledges that there are moderating factors in how easily some groups can use traditional power poses. It would run counter to social norms, for example, if a woman wearing a skirt sat with her feet up on her desk while talking to a colleague.
"I'm not saying it's fair, but there is a different range for women versus men," says Cuddy, who also teaches several HBS Executive Education programs.
Female managers seem to have an intuition about the need to communicate confidence by striking expansive poses through other means. They might use a whiteboard as a prop that they can reach out and rest a hand on—allowing them to take up more space.
"There are implications across cultures as well," she adds. Cuddy believes American poses are bigger and more flamboyant than what would be acceptable in Korea or Japan, for example, and expects to focus on this question in future research.
Warmth versus competence
It ultimately boils down to how we connect to one another. In general, she says, people form impressions of others through a matrix of how much we trust and like them and how much we think they're competent and respect them.
For the most part people underestimate the powerful connection of warmth and overestimate the importance of competence.
"We are influenced, and influence others, through very unconscious and implicit processes," she says. "People tend to spend too much energy focusing on the words they're saying—perfectly crafting the content of the message—when in many cases that matters much less than how it's being communicated. People often are more influenced by how they feel about you than by what you're saying. It's not about the content of the message, but how you're communicating it.
"Many students believe that if they have a great idea, they should be able to magnetize their audience toward them because their audience will recognize the 'greatness' of that idea—that they'll get on board because the idea is so good," she continues.
"I try to show students that it doesn't work that way—you have to go meet people where they are and then all move together.
You have to connect with them before you can lead them."
If understanding how you are influenced and can influence others feels a bit too Machiavellian, Cuddy helps bring it down a notch.
"It's not about politics," she says. "It's about understanding what moves people."
About the author
Julia Hanna is associate editor of the HBS Alumni Bulletin.
Author: Julia Hanna
Executive Summary:
Nervous about an upcoming presentation or job interview? Holding one's body in "high-power" poses for short time periods can summon an extra surge of power and sense of well-being when it's needed, according to Harvard Business School professor Amy J.C. Cuddy.
Key concepts include:
* Holding one's body in expansive, "high-power" poses for as little as two minutes stimulates higher levels of testosterone and lower levels of cortisol.
* In addition to causing hormonal shifts, power poses lead to increased feelings of power and a greater tolerance for risk.
* People often are more influenced by how they feel about you than by what you're saying.
* The research has broad implications for people who suffer from feelings of powerlessness and low self-esteem due to their hierarchical rank or lack of resources.
Amy J. C. Cuddy is an assistant professor in the Negotiation, Organizations and Markets unit at Harvard Business School.
We can't be the alpha dog all of the time. Whatever our personality, most of us experience varying degrees of feeling in charge. Some situations take us down a notch while others build us up.
New research shows that it's possible to control those feelings a bit more, to be able to summon an extra surge of power and sense of well-being when it's needed: for example, during a job interview or for a key presentation to a group of skeptical customers.
"Our research has broad implications for people who suffer from feelings of powerlessness and low self-esteem due to their hierarchical rank or lack of resources," says HBS assistant professor Amy J.C. Cuddy, one of the researchers on the study.
"It's not about the content of the message, but how you're communicating it."
In "Power Posing: Brief Nonverbal Displays Affect Neuroendocrine Levels and Risk Tolerance", Cuddy shows that simply holding one's body in expansive, "high-power" poses for as little as two minutes stimulates higher levels of testosterone (the hormone linked to power and dominance in the animal and human worlds) and lower levels of cortisol (the "stress" hormone that can, over time, cause impaired immune functioning, hypertension, and memory loss).
The result? In addition to causing the desired hormonal shift, the power poses led to increased feelings of power and a greater tolerance for risk.
"We used to think that emotion ended on the face," Cuddy says. "Now there is established research showing that while it's true that facial expressions reflect how you feel, you can also 'fake it until you make it.
' In other words, you can smile long enough that it makes you feel happy. This work extends that finding on facial feedback, which is decades old, by focusing on postures and measuring neuroendocrine levels."
The experiment
In their article, to be published in a forthcoming Psychological Science, Cuddy and coauthors Dana R. Carney and Andy J. Yap of Columbia University detail the results of an experiment in which forty-two male and female participants were randomly assigned to a high- or low-power pose group.
No one was told what the study was about; instead, each participant believed it was related to the placement of ECG electrodes above and below his or her heart.
Subjects in the high-power group were manipulated into two expansive poses for one minute each: first, the classic feet on desk, hands behind head; then, standing and leaning on one's hands over a desk.
Those in the low-power group were posed for the time period in two restrictive poses: sitting in a chair with arms held close and hands folded, and standing with arms and legs crossed tightly.
Saliva samples taken before and after the posing measured testosterone and cortisol levels. To evaluate risk tolerance, participants were given $2 and told they could roll a die for even odds of winning $4. Finally, participants were asked to indicate how "powerful" and "in charge" they felt on a scale from one to four.
Controlling for subjects' baseline levels of both hormones, Cuddy and her coauthors found that high-power poses decreased cortisol by about 25 percent and increased testosterone by about 19 percent for both men and women.
In contrast, low-power poses increased cortisol about 17 percent and decreased testosterone about 10 percent.
Not surprisingly, high-power posers of both sexes also reported greater feelings of being powerful and in charge. In addition, those in the high-power group were more likely to take the risk of gambling their $2; 86 percent rolled the die in the high-power group as opposed to 60 percent of the low-power posers.
Previous research established that situational role changes can cause shifts in hormone levels. In primate groups, for example, after an alpha male dies the testosterone levels of the animal replacing him go up. The hormonal shifts measured in this experiment show that such changes can be influenced independent of role, situation, or any consciously focused thoughts about power. The physical poses are enough.
And that, she suggests, has broad implications for people who suffer from feelings of powerlessness and low self-esteem due to their hierarchical rank or lack of resources.
Why we judge
Cuddy's overall research agenda focuses on stereotyping and questions around how we form judgments of others' warmth and competence.
Just Because I'm Nice, Don't Assume I'm Dumb reveals how and why we come to snap judgments about coworkers (and how to fight that natural instinct). The article was cited as a "Breakthrough Business Idea" for 2009 by Harvard Business Review.
"The power poses paper came about in part because my coauthor Dana and I had noticed that women in our classes seemed to be participating less," says Cuddy, who teaches the MBA elective Power and Influence.
"Some of the women exhibited body language associated with low power, so we wondered if that was in turn affecting how they feel," she adds, citing the "fake it till you make it" research that shows smiling can affect feelings and hormone levels.
"It's about understanding what moves people."
"The poses that we used in the experiment are strongly associated across the animal kingdom with high and low dominance for very straightforward evolutionary reasons. Either you want to be big because you're in charge, or you want to close in and hide your vital organs because you're not in charge.
"It does appear that even this minimal manipulation can change people's physiology and psychology and, we hope, lead to very different, meaningful outcomes, whether it's how they perform in a job interview or how they participate in class."
Cuddy acknowledges that there are moderating factors in how easily some groups can use traditional power poses. It would run counter to social norms, for example, if a woman wearing a skirt sat with her feet up on her desk while talking to a colleague.
"I'm not saying it's fair, but there is a different range for women versus men," says Cuddy, who also teaches several HBS Executive Education programs.
Female managers seem to have an intuition about the need to communicate confidence by striking expansive poses through other means. They might use a whiteboard as a prop that they can reach out and rest a hand on—allowing them to take up more space.
"There are implications across cultures as well," she adds. Cuddy believes American poses are bigger and more flamboyant than what would be acceptable in Korea or Japan, for example, and expects to focus on this question in future research.
Warmth versus competence
It ultimately boils down to how we connect to one another. In general, she says, people form impressions of others through a matrix of how much we trust and like them and how much we think they're competent and respect them.
For the most part people underestimate the powerful connection of warmth and overestimate the importance of competence.
"We are influenced, and influence others, through very unconscious and implicit processes," she says. "People tend to spend too much energy focusing on the words they're saying—perfectly crafting the content of the message—when in many cases that matters much less than how it's being communicated. People often are more influenced by how they feel about you than by what you're saying. It's not about the content of the message, but how you're communicating it.
"Many students believe that if they have a great idea, they should be able to magnetize their audience toward them because their audience will recognize the 'greatness' of that idea—that they'll get on board because the idea is so good," she continues.
"I try to show students that it doesn't work that way—you have to go meet people where they are and then all move together.
You have to connect with them before you can lead them."
If understanding how you are influenced and can influence others feels a bit too Machiavellian, Cuddy helps bring it down a notch.
"It's not about politics," she says. "It's about understanding what moves people."
About the author
Julia Hanna is associate editor of the HBS Alumni Bulletin.
Friday, January 7, 2011
Male Circumcision Reduces Risk for HPV Infection in Female Partners
From Medscape Medical News
Emma Hitt, PhD
January 6, 2011 — Male circumcision appears to protect against high-risk human papillomavirus (HPV) infection in female partners, according to the findings of 2 randomized controlled trials carried out in rural Uganda.
Maria J. Wawer, MD, and Aaron A.R. Tobian, MD, from Johns Hopkins University, Baltimore, Maryland, and colleagues reported their findings from the studies, conducted in Rakai, Uganda, online January 7 in The Lancet.
According to the researchers, male circumcision has previously been linked to reduced HPV infection in men and to reduced risk for cervical neoplasia in women with circumcised partners. In the current study, HIV-negative men were randomly assigned to undergo circumcision immediately (intervention) or after a delay of 24 months (control). Their HIV-negative female partners were interviewed, and concurrent self-collected vaginal swabs were tested for high-risk HPV infection.
At 24 months after intervention, more than 1000 women remained enrolled in the study (544 in the intervention group and 488 in the control group). Results showed a significant reduction of 28% in the prevalence of high-risk HPV infection in female partners of circumcised men compared with the control group (27.8% vs 38.7%; prevalence risk ratio, 0.72; 95% confidence interval [CI], 0.60 - 0.85; P = .001).
In addition, male circumcision significantly reduced the incidence of high-risk HPV in women (20.7 vs 26.9 infections per 100 person-years; incidence rate ratio, 0.77; 95% CI, 0.63 - 0.93; P = .008). For women positive for all high-risk HPV genotypes, clearance of infection was also more likely in the intervention group (66% vs 59%; risk ratio, 1.12; 95% CI, 1.02 - 1.22; P = .014), although clearance of the HPV-16 genotype was lower.
The authors suggest that reduced penile HPV carriage may explain the way in which circumcision helps prevent HPV infection in women.
Study limitations include the inability to obtain samples from 20% of the women enrolled in each group because of temporary stock shortages. This reduced the sample size and the power of the study. In addition, study participants were HIV-negative and in steady partnerships; therefore, the results may only be applicable to low-risk, monogamous individuals. Finally, follow-up data were obtained annually, and so do not account for incident cases that occurred and resolved during the year.
"Our findings indicate that male circumcision should now be accepted as an efficacious intervention for reducing the prevalence and incidence of HPV infections in female partners," write Dr. Wawer, Dr. Tobian and colleagues.
According to the researchers, decreased incidence and prevalence of high-risk HPV infection is likely to reduce the long-term risk for cervical cancer for women with circumcised male partners. "However, our results indicate that protection is only partial; the promotion of safe sex practices is also important," they add.
In an editorial, Anna R. Giuliano, PhD; Alan G. Nyitray, PhD; and Ginesa Albero from the Department of Cancer Epidemiology and Genetics, H. Lee Moffitt Cancer Center, Tampa, Florida, recount the historical association of circumcision and reduced incidence of cervical cancer. Commending the work of Dr. Wawer, Dr. Tobian, and colleagues, they state that "these data, from the most rigorous of study designs, support original observations for a preventive role of male circumcision in cervical cancer."
They mention several caveats, however, to drawing this conclusion, "First, the reduction in high-risk HPV infection in women was limited to about 25%. Second, a clinical endpoint such as high-grade cervical dysplasia (cervical intraepithelial neoplasia grade 2/3) was not assessed. Third, clearance of HPV-16 was lower in the intervention group than in the control group."
The study was supported by the Bill and Melinda Gates Foundation, the National Institutes of Health, and the Fogarty International Center. One author reports receiving research funding from Roche Molecular Diagnostics, the company that manufactures the HPV genotyping test used in this study. The other study authors have disclosed no relevant financial relationships. Each of the editorialists has received financial support from Merck & Co, GlaxoSmithKline, and/or Roche.
Lancet. Published online January 7, 2011.
Emma Hitt, PhD
January 6, 2011 — Male circumcision appears to protect against high-risk human papillomavirus (HPV) infection in female partners, according to the findings of 2 randomized controlled trials carried out in rural Uganda.
Maria J. Wawer, MD, and Aaron A.R. Tobian, MD, from Johns Hopkins University, Baltimore, Maryland, and colleagues reported their findings from the studies, conducted in Rakai, Uganda, online January 7 in The Lancet.
According to the researchers, male circumcision has previously been linked to reduced HPV infection in men and to reduced risk for cervical neoplasia in women with circumcised partners. In the current study, HIV-negative men were randomly assigned to undergo circumcision immediately (intervention) or after a delay of 24 months (control). Their HIV-negative female partners were interviewed, and concurrent self-collected vaginal swabs were tested for high-risk HPV infection.
At 24 months after intervention, more than 1000 women remained enrolled in the study (544 in the intervention group and 488 in the control group). Results showed a significant reduction of 28% in the prevalence of high-risk HPV infection in female partners of circumcised men compared with the control group (27.8% vs 38.7%; prevalence risk ratio, 0.72; 95% confidence interval [CI], 0.60 - 0.85; P = .001).
In addition, male circumcision significantly reduced the incidence of high-risk HPV in women (20.7 vs 26.9 infections per 100 person-years; incidence rate ratio, 0.77; 95% CI, 0.63 - 0.93; P = .008). For women positive for all high-risk HPV genotypes, clearance of infection was also more likely in the intervention group (66% vs 59%; risk ratio, 1.12; 95% CI, 1.02 - 1.22; P = .014), although clearance of the HPV-16 genotype was lower.
The authors suggest that reduced penile HPV carriage may explain the way in which circumcision helps prevent HPV infection in women.
Study limitations include the inability to obtain samples from 20% of the women enrolled in each group because of temporary stock shortages. This reduced the sample size and the power of the study. In addition, study participants were HIV-negative and in steady partnerships; therefore, the results may only be applicable to low-risk, monogamous individuals. Finally, follow-up data were obtained annually, and so do not account for incident cases that occurred and resolved during the year.
"Our findings indicate that male circumcision should now be accepted as an efficacious intervention for reducing the prevalence and incidence of HPV infections in female partners," write Dr. Wawer, Dr. Tobian and colleagues.
According to the researchers, decreased incidence and prevalence of high-risk HPV infection is likely to reduce the long-term risk for cervical cancer for women with circumcised male partners. "However, our results indicate that protection is only partial; the promotion of safe sex practices is also important," they add.
In an editorial, Anna R. Giuliano, PhD; Alan G. Nyitray, PhD; and Ginesa Albero from the Department of Cancer Epidemiology and Genetics, H. Lee Moffitt Cancer Center, Tampa, Florida, recount the historical association of circumcision and reduced incidence of cervical cancer. Commending the work of Dr. Wawer, Dr. Tobian, and colleagues, they state that "these data, from the most rigorous of study designs, support original observations for a preventive role of male circumcision in cervical cancer."
They mention several caveats, however, to drawing this conclusion, "First, the reduction in high-risk HPV infection in women was limited to about 25%. Second, a clinical endpoint such as high-grade cervical dysplasia (cervical intraepithelial neoplasia grade 2/3) was not assessed. Third, clearance of HPV-16 was lower in the intervention group than in the control group."
The study was supported by the Bill and Melinda Gates Foundation, the National Institutes of Health, and the Fogarty International Center. One author reports receiving research funding from Roche Molecular Diagnostics, the company that manufactures the HPV genotyping test used in this study. The other study authors have disclosed no relevant financial relationships. Each of the editorialists has received financial support from Merck & Co, GlaxoSmithKline, and/or Roche.
Lancet. Published online January 7, 2011.
Wednesday, January 5, 2011
Cryotherapy is More Effective than Salicylic Acid for Common Warts
From Journal Watch > Journal Watch (General)
Bruce Soloway, MD
Cutaneous warts are seen often in primary care, particularly among children, but a recent Cochrane review (Cochrane Database Syst Rev 2006; 3:CD001781) was inconclusive on the relative merits of the two most common treatments, salicylic acid and cryotherapy.
Dutch researchers randomized 250 patients (43% were younger than 12 years) who were recruited from 30 primary care practices with one or more new cutaneous warts (<1 cm diameter) to receive cryotherapy with liquid nogen every 2 weeks, daily self-applications of 40% salicylic acid gel, or no treatment for 13 weeks.
Half the patients had predominantly common warts (mainly on the hands), and half had predominantly plantar warts. Among patients with predominantly common warts, warts were significantly more likely to resolve completely with cryotherapy than with salicylic acid or no treatment (49% vs. 15% and 8%, respectively). Patients with predominantly plantar warts had similar cure rates regardless of treatment (30%, 33%, and 23%, respectively) and were more likely to be completely cured if they were younger than 12 years (50% vs. 3%) or if their warts had been present for <6 months (46% vs. 10%). Cryotherapy caused more local side effects than salicylic acid, but more patients who received cryotherapy were satisfied with their treatment.
Comment
This pragmatic primary care–based trial suggests that cryotherapy is the preferred treatment for common warts. Persistent plantar warts in adolescents and adults are unlikely to respond to brief therapy with either cryotherapy or salicylic acid.
Bruce Soloway, MD
Cutaneous warts are seen often in primary care, particularly among children, but a recent Cochrane review (Cochrane Database Syst Rev 2006; 3:CD001781) was inconclusive on the relative merits of the two most common treatments, salicylic acid and cryotherapy.
Dutch researchers randomized 250 patients (43% were younger than 12 years) who were recruited from 30 primary care practices with one or more new cutaneous warts (<1 cm diameter) to receive cryotherapy with liquid nogen every 2 weeks, daily self-applications of 40% salicylic acid gel, or no treatment for 13 weeks.
Half the patients had predominantly common warts (mainly on the hands), and half had predominantly plantar warts. Among patients with predominantly common warts, warts were significantly more likely to resolve completely with cryotherapy than with salicylic acid or no treatment (49% vs. 15% and 8%, respectively). Patients with predominantly plantar warts had similar cure rates regardless of treatment (30%, 33%, and 23%, respectively) and were more likely to be completely cured if they were younger than 12 years (50% vs. 3%) or if their warts had been present for <6 months (46% vs. 10%). Cryotherapy caused more local side effects than salicylic acid, but more patients who received cryotherapy were satisfied with their treatment.
Comment
This pragmatic primary care–based trial suggests that cryotherapy is the preferred treatment for common warts. Persistent plantar warts in adolescents and adults are unlikely to respond to brief therapy with either cryotherapy or salicylic acid.
Tuesday, January 4, 2011
Community-Based Study Shows Colonoscopy Is Effective
From Medscape Medical News > Oncology
Zosia Chustecka
January 3, 2011 — A new community-based study from Germany confirms that colonoscopy is an effective tool for preventing colorectal cancer (CRC), according to an editorial accompanying the study published in the January 4 issue of the Annals of Internal Medicine.
In Germany, colonoscopy has been the primary screening method offered to people 55 years and older since 2002, explain the authors, headed by Hermann Brenner, MD, MPH, from the German Cancer Research Center in Heidelberg. The introduction of colonoscopy was accompanied by "major efforts" in training and quality assurance measures, they note.
In this setting of high-quality colonoscopy, they conducted a population-based case–control study comparing 1688 patients and 1932 control subjects.
They found that for individuals who had undergone colonoscopy in the previous 10 years, the overall risk for any colorectal cancer was reduced by 77%.
As has been seen in previous studies, there was a larger reduction in the risk for left-sided colorectal cancer (84%) than in right-sided colorectal cancer (56%). Both of these reductions were "significant," they note.
These results show a greater risk reduction than has been reported recently in other studies, Dr. Brenner and colleagues note. Although the original trial that led to the adoption of colonoscopy — the National Polyp Study, published in 1993 — reported up to a 90% reduction in the risk for CRC, more recent population studies from Germany and Canada have reported reductions of only 30% to 50%.
In addition, this latest study shows a substantial reduction in the risk for right-sided CRC, Dr. Brenner and colleagues point out. This is in contrast to the lack of effect seen in a recent study from Canada (based on administrative claims), which found no protection from deaths from right-sided cancer (JAMA. 2008;299:1027-1035). However, the reduction in right-sided CRC seen in the German study showed an age gradient; in patients aged younger than 60 years, the reduction was modest (26%) and statistically nonsignificant, the authors point out.
The new results "vindicate colonoscopy as an effective prevention tool," writes David Weinberg, MD, MSc, from the Fox Chase Cancer Center in Philadelphia, Pennsylvania, in an accompanying editorial.
They also offer reassurance that colonoscopy can provide substantial protection against both right- and left-sided CRC, he adds. Although it does appear that colonoscopy is "less effective" in the right colon, this is not the same as "ineffective," he points out.
Colonoscopy Most Popular Method in the United States
Colonoscopy has become a standard — and for some the preferred — method of screening for CRC, Dr. Weinberg explains. It is certainly the most popular method in the United States, he adds, where more than 14 million colonoscopies are performed annually.
In contrast, other screening methods, such as flexible sigmoidoscopy and fecal occult blood testing, are performed with decreasing frequency in the United States, despite their lower costs and a stronger evidence base demonstrating their effectiveness, he notes.
Against this backdrop, there has been "recent and unwelcome news that colonoscopy may not protect against CRC as effectively as we would like to think," Dr. Weinberg notes.
These latest results from Germany provide reassurance that colonoscopy is effective, he writes. The study was methodologically rigorous, and the protective effect against CRC was "impressive." The protective effect was seen in both sexes and all ages, and even in patients with a family history of CRC, who are presumably at higher risk.
Nonetheless, there are several questions and issues that remain. Colonoscopy is operator dependent, and there is consistent evidence that gastroenterologists, as opposed to practitioners from other backgrounds, miss fewer lesions, Dr. Weinberg notes. There is also research showing that the ability to detect polyps and other lesions depends on the quality of the laxative preparation, he explains. Preparations that work best should become the standard, although any regimen remains a challenge for older sicker patients, he acknowledges.
Colonoscopy is more expensive and carries a higher risk than other CRC screening methods, so there are appropriate concerns about its "value," he writes.
"It is unrealistic to expect that colonoscopy to prevent all cases of CRC," Dr. Weinberg writes. "Physicians need to inform patients that colonoscopy offers very good, but not perfect, protection," he concludes.
The study was funded by the German Research Council and German Federal Ministry of Education and Research. Dr. Weinberg has disclosed no relevant financial relationships.
Ann Intern Med. 2011:154;22-30, 68-69.
Zosia Chustecka
January 3, 2011 — A new community-based study from Germany confirms that colonoscopy is an effective tool for preventing colorectal cancer (CRC), according to an editorial accompanying the study published in the January 4 issue of the Annals of Internal Medicine.
In Germany, colonoscopy has been the primary screening method offered to people 55 years and older since 2002, explain the authors, headed by Hermann Brenner, MD, MPH, from the German Cancer Research Center in Heidelberg. The introduction of colonoscopy was accompanied by "major efforts" in training and quality assurance measures, they note.
In this setting of high-quality colonoscopy, they conducted a population-based case–control study comparing 1688 patients and 1932 control subjects.
They found that for individuals who had undergone colonoscopy in the previous 10 years, the overall risk for any colorectal cancer was reduced by 77%.
As has been seen in previous studies, there was a larger reduction in the risk for left-sided colorectal cancer (84%) than in right-sided colorectal cancer (56%). Both of these reductions were "significant," they note.
These results show a greater risk reduction than has been reported recently in other studies, Dr. Brenner and colleagues note. Although the original trial that led to the adoption of colonoscopy — the National Polyp Study, published in 1993 — reported up to a 90% reduction in the risk for CRC, more recent population studies from Germany and Canada have reported reductions of only 30% to 50%.
In addition, this latest study shows a substantial reduction in the risk for right-sided CRC, Dr. Brenner and colleagues point out. This is in contrast to the lack of effect seen in a recent study from Canada (based on administrative claims), which found no protection from deaths from right-sided cancer (JAMA. 2008;299:1027-1035). However, the reduction in right-sided CRC seen in the German study showed an age gradient; in patients aged younger than 60 years, the reduction was modest (26%) and statistically nonsignificant, the authors point out.
The new results "vindicate colonoscopy as an effective prevention tool," writes David Weinberg, MD, MSc, from the Fox Chase Cancer Center in Philadelphia, Pennsylvania, in an accompanying editorial.
They also offer reassurance that colonoscopy can provide substantial protection against both right- and left-sided CRC, he adds. Although it does appear that colonoscopy is "less effective" in the right colon, this is not the same as "ineffective," he points out.
Colonoscopy Most Popular Method in the United States
Colonoscopy has become a standard — and for some the preferred — method of screening for CRC, Dr. Weinberg explains. It is certainly the most popular method in the United States, he adds, where more than 14 million colonoscopies are performed annually.
In contrast, other screening methods, such as flexible sigmoidoscopy and fecal occult blood testing, are performed with decreasing frequency in the United States, despite their lower costs and a stronger evidence base demonstrating their effectiveness, he notes.
Against this backdrop, there has been "recent and unwelcome news that colonoscopy may not protect against CRC as effectively as we would like to think," Dr. Weinberg notes.
These latest results from Germany provide reassurance that colonoscopy is effective, he writes. The study was methodologically rigorous, and the protective effect against CRC was "impressive." The protective effect was seen in both sexes and all ages, and even in patients with a family history of CRC, who are presumably at higher risk.
Nonetheless, there are several questions and issues that remain. Colonoscopy is operator dependent, and there is consistent evidence that gastroenterologists, as opposed to practitioners from other backgrounds, miss fewer lesions, Dr. Weinberg notes. There is also research showing that the ability to detect polyps and other lesions depends on the quality of the laxative preparation, he explains. Preparations that work best should become the standard, although any regimen remains a challenge for older sicker patients, he acknowledges.
Colonoscopy is more expensive and carries a higher risk than other CRC screening methods, so there are appropriate concerns about its "value," he writes.
"It is unrealistic to expect that colonoscopy to prevent all cases of CRC," Dr. Weinberg writes. "Physicians need to inform patients that colonoscopy offers very good, but not perfect, protection," he concludes.
The study was funded by the German Research Council and German Federal Ministry of Education and Research. Dr. Weinberg has disclosed no relevant financial relationships.
Ann Intern Med. 2011:154;22-30, 68-69.
Subscribe to:
Posts (Atom)