Lancet Oncol. Published online July 1, 2010.
News Author: Zosia Chustecka
CME Author: Désirée Lie, MD, MSEd
Clinical Context
PSA screening has been shown to reduce prostate cancer mortality rates at a screening period of 9 years, but the follow-up period may have been inadequate, and longer follow-up may demonstrate greater benefits.
This is a population-based, randomized study of a cohort of men who were invited to receive PSA screening every 2 years from inception to determine the effect of screening on prostate cancer diagnosis and mortality.
Study Highlights
* The study began in 1994 and involved a sample of men living in a city in Sweden. These men were identified by computer randomization and were then randomly assigned to either screening or no screening.
* 3 birth cohorts were included: those born in 1930 to 1934, 1935 to 1939, and 1940 to 1944.
* Men with existing prostate cancer and those who migrated or died before screening were excluded.
* Screening consisted of invitations every 2 years for PSA testing.
* The upper age of screening was predetermined as 69 years.
* The control group did not receive an invitation for screening.
* The incidence of prostate cancer was determined by linkage of the cohort with the West Swedish Regional Cancer Registry every third month. In 2009, all 6 regional cancer registries in Sweden were linked, and cancer data were obtained.
* The cause-of-death certificate was used to identify cases, and an independent committee adjudicated causes of death.
* There were 9952 evaluable men in each group.
* Median age was 56 years at baseline, and 20,000 men were randomly assigned.
* 76% of men in the screening group participated in at least 1 screening.
* 33% of men who received screening had an increased PSA level.
* Of those with an increased PSA level, 93% had a prostate biopsy at least once.
* The maximal follow-up period of 14 years was reached by 78% of the men in the screening group.
* Prostate cancer was diagnosed in 11.4% of men in the screening group and 7.2% in the control group.
* Of those with detected prostate cancer in the screening group, 78.7% were diagnosed directly as a result of screening.
* The cumulative incidence of prostate cancer at 14 years was 12.7% in the screening group vs 8.2% in the control group (hazard ratio, 1.64; P < .0001).
* The hazard ratio was 5.2 in the first year, decreasing to 3.7, 2.6, 2.1, then 1.2 by 8 years or more.
* Prostate cancers diagnosed in the screening group were more likely to be early stage, and the number of advanced cancers was lower in the screening group vs the control group.
* The difference in stage distribution was reflected in treatment, with the screening group more likely to be treated with surveillance or curative treatment.
* In men diagnosed with prostate cancer, the median follow-up after diagnosis was 6.7 years in the screening group vs 4.3 years in the control group.
* The RR of dying of prostate cancer was 0.56 (P = .002) in the screening group vs the control group.
* The absolute cumulative risk reduction was 0.5% (from 0.9% - 0.4% in the control group).
* In a secondary analysis, the RR of death from prostate cancer for those who attended screening vs the control group was 0.44 (P = .0002), whereas for those in the screening group who were invited for a screening but chose not to attend, the RR was 1.05
* Attendees who started screening when older than 60 years were at a higher risk of dying of prostate cancer vs men who were younger at study entry.
* The cumulative risk for deaths not related to prostate cancer was similar in the 2 groups.
* The NNS to prevent 1 prostate cancer–related death was 293, and the NNT was 12.
* When restricted to attendees of screening, the respective numbers were 234 and 15.
* The authors concluded that a PSA prostate cancer screening program was acceptable to men (response rate, 76%) and that screening was associated with an increased diagnosis of prostate cancer and a reduced mortality rate from the disease.
* However, they cautioned that benefits take a long time to achieve, are associated with risks for overdiagnosis and overtreatment, and may not be beneficial in older men.
Clinical Implications
* PSA screening every 2 years in men aged 50 to 69 years is associated with a 64% higher rate of diagnosis of prostate cancer vs no screening.
* PSA screening every 2 years in men aged 50 to 69 years is associated with lower mortality rates from prostate cancer.
Tuesday, July 27, 2010
Friday, July 23, 2010
Agitation, Depression, Apathy Predictors of Progression from MCI to Dementia
From Medscape Medical News
Agitation, Depression, Apathy Predictors of Progression from MCI to Dementia
Caroline Cassels
July 23, 2010 (Honolulu, Hawaii) — Agitation, apathy, and depression significantly predict progression from mild cognitive impairment (MCI) to incident dementia, according to the latest findings from the Mayo Clinic Study on Aging.
Presented here at the Alzheimer's Association International Conference on Alzheimer's Disease 2010, the prospective study showed that individuals with MCI and depression had a 63% increased risk of developing dementia compared with their counterparts with MCI alone. Similarly, the investigators found that the risk for dementia doubled for those with MCI and apathy compared with those with MCI without apathy. The risk is much higher (almost 3 times the increased risk) for persons with MCI and agitation.
"Our results suggest that neuropsychiatric symptoms may be very important clinical markers in predicting the progression from MCI to incident dementia. Additionally, this clinical marker is much cheaper than biomarkers," lead investigator Yonas E. Geda, MD, associate professor of neurology and psychiatry at the Mayo Clinic College of Medicine, Rochester, Minnesota, told Medscape Medical News.
Dr. Yonas E. Geda
According to Dr. Geda, previous relatively smaller studies indicate that neuropsychiatric symptoms such as depression and apathy predict progression from MCI to dementia, prompting the investigators to look at this hypothesis in a population-based setting with a larger sample size.
"We wanted to address this hypothesis in a definitive way using a much larger sample," said Dr. Geda. The prospective study included 275 patients with MCI who were followed-up for a median of 2.8 years to the outcome of incident dementia, as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria.
Neuropsychiatric symptoms were assessed using the 12-item Neuropsychiatric Inventory Questionnaire.
Three neuropsychiatric symptoms — agitation, depression, and apathy — were significantly associated with progression to dementia.
According to the study, among 71 MCI patients with depression, 28 (40%) developed incident dementia, whereas of 201 MCI patients without depression, 51 (25%) developed incident dementia.
Of 49 MCI patients with apathy, 21 (43%) developed incident dementia, whereas of 226 MCI patients without apathy, 58 (26%) developed incident dementia.
A time-to-event cohort analysis was conducted. Hazard ratios (HR) and 95% confidence intervals (CI) were used to estimate the risk of progressing from MCI to incident dementia as predicted by depression, apathy, or agitation.
After adjusting for age, sex, and education, the results revealed that the HR for incident dementia in subjects who had MCI with apathy was 2.08 (95% CI, 1.25 - 3.48; P = .005), and for MCI with depression the HR was 1.63 (95% CI, 1.02 - 2.60; P = .043). MCI with agitation had an HR of 2.67 (95% CI, 1.46 - 4.88; P = .001).
Dr. Geda said the investigators, who include copresenter Mayo Clinic medical student Richard G. Cockerill, BSc, were surprised that there was no association between anxiety and progression from MCI to dementia.
"These findings suggest that clinicians should not stop at the diagnosis of MCI, but they should also conduct a neuropsychiatric assessment using standard instruments and look for depression, apathy, and agitation. We need a future interventional study to determine if treatment of neuropsychiatric symptoms could delay the progression from MCI to incident dementia," said Dr. Geda.
A prediction model developed by investigators at Johns Hopkins University, Baltimore, Maryland, indicates that delaying dementia by just 1 year could reduce the prevalence of Alzheimer's disease by nearly 800,000 cases in 2050.
The study was supported by the National Institutes of Health, Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program, and the Harold Amos Medical Faculty Development Program.
Alzheimer's Association International Conference on Alzheimer's Disease 2010: Abstract 01-05-05. Presented July 11, 2010.
Agitation, Depression, Apathy Predictors of Progression from MCI to Dementia
Caroline Cassels
July 23, 2010 (Honolulu, Hawaii) — Agitation, apathy, and depression significantly predict progression from mild cognitive impairment (MCI) to incident dementia, according to the latest findings from the Mayo Clinic Study on Aging.
Presented here at the Alzheimer's Association International Conference on Alzheimer's Disease 2010, the prospective study showed that individuals with MCI and depression had a 63% increased risk of developing dementia compared with their counterparts with MCI alone. Similarly, the investigators found that the risk for dementia doubled for those with MCI and apathy compared with those with MCI without apathy. The risk is much higher (almost 3 times the increased risk) for persons with MCI and agitation.
"Our results suggest that neuropsychiatric symptoms may be very important clinical markers in predicting the progression from MCI to incident dementia. Additionally, this clinical marker is much cheaper than biomarkers," lead investigator Yonas E. Geda, MD, associate professor of neurology and psychiatry at the Mayo Clinic College of Medicine, Rochester, Minnesota, told Medscape Medical News.
Dr. Yonas E. Geda
According to Dr. Geda, previous relatively smaller studies indicate that neuropsychiatric symptoms such as depression and apathy predict progression from MCI to dementia, prompting the investigators to look at this hypothesis in a population-based setting with a larger sample size.
"We wanted to address this hypothesis in a definitive way using a much larger sample," said Dr. Geda. The prospective study included 275 patients with MCI who were followed-up for a median of 2.8 years to the outcome of incident dementia, as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria.
Neuropsychiatric symptoms were assessed using the 12-item Neuropsychiatric Inventory Questionnaire.
Three neuropsychiatric symptoms — agitation, depression, and apathy — were significantly associated with progression to dementia.
According to the study, among 71 MCI patients with depression, 28 (40%) developed incident dementia, whereas of 201 MCI patients without depression, 51 (25%) developed incident dementia.
Of 49 MCI patients with apathy, 21 (43%) developed incident dementia, whereas of 226 MCI patients without apathy, 58 (26%) developed incident dementia.
A time-to-event cohort analysis was conducted. Hazard ratios (HR) and 95% confidence intervals (CI) were used to estimate the risk of progressing from MCI to incident dementia as predicted by depression, apathy, or agitation.
After adjusting for age, sex, and education, the results revealed that the HR for incident dementia in subjects who had MCI with apathy was 2.08 (95% CI, 1.25 - 3.48; P = .005), and for MCI with depression the HR was 1.63 (95% CI, 1.02 - 2.60; P = .043). MCI with agitation had an HR of 2.67 (95% CI, 1.46 - 4.88; P = .001).
Dr. Geda said the investigators, who include copresenter Mayo Clinic medical student Richard G. Cockerill, BSc, were surprised that there was no association between anxiety and progression from MCI to dementia.
"These findings suggest that clinicians should not stop at the diagnosis of MCI, but they should also conduct a neuropsychiatric assessment using standard instruments and look for depression, apathy, and agitation. We need a future interventional study to determine if treatment of neuropsychiatric symptoms could delay the progression from MCI to incident dementia," said Dr. Geda.
A prediction model developed by investigators at Johns Hopkins University, Baltimore, Maryland, indicates that delaying dementia by just 1 year could reduce the prevalence of Alzheimer's disease by nearly 800,000 cases in 2050.
The study was supported by the National Institutes of Health, Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program, and the Harold Amos Medical Faculty Development Program.
Alzheimer's Association International Conference on Alzheimer's Disease 2010: Abstract 01-05-05. Presented July 11, 2010.
Quadrivalent HPV Vaccine Safe and Effective in Men
From Reuters Health Information
By Karla Gale
NEW YORK (Reuters Health) Jul 22 - The quadrivalent human papillomavirus (HPV) vaccine (Gardasil) prevents infection and disease in men, according to data presented today at AIDS 2010 in Vienna.
In fact, the efficacy data were so good that the U.S. Food and Drug Administration stopped the trial early so that men in the placebo group could get the vaccine, presenter Dr. Heiko Jessen from Berlin, Germany, told Reuters Health.
Infection with oncogenic HPV can cause cancers of the penis, anus, and head and neck in men, and AIDS substantially increases the risk of HPV-related invasive cancers. Earlier this year the US Centers for Disease Control and Prevention issued a "permissive recommendation" for HPV vaccination in males ages 9 through 26. (See Reuters Health reports of Jan 4, 2010 and Jul 31, 2009.)
The randomized, double-blind, placebo-controlled trial started out with more than 4000 healthy men aged 16 to 26 years from 18 countries. The per-protocol analysis, reported here, involved 1400 men (including 200 men who have sex with men) in each arm followed for 3 years, Dr. Jessen said.
As noted in their meeting abstract, the researchers detected 3 external genital lesions related to HPV types 6, 11, 16 or 18 in the vaccine arm and 31 in the placebo arm - primarily condylomata acuminate - for an efficacy of 90.4%.
Efficacy against HPV vaccine types was 85.6%, and against HPV DNA detection at any time was 44.7%.
"People who are immune may still have HPV DNA," Dr. Jessen said, but the significance is unknown.
There were no cases of penile, perianal or perineal intraepithelial neoplasia, but one wouldn't expect these in young healthy men during a short follow-up trial, he added. The research team will continue to follow the participants.
"For now it makes sense to give the HPV vaccine to boys and men ages 9 to 26," Dr. Jessen said, but his group intends to examine its efficacy in older men as well, particularly in men who have sex with men, who are at higher risk for HPV-related malignancy.
There were no serious vaccine-related adverse experiences, he added.
The study was funded by Merck, which manufactures the vaccine
By Karla Gale
NEW YORK (Reuters Health) Jul 22 - The quadrivalent human papillomavirus (HPV) vaccine (Gardasil) prevents infection and disease in men, according to data presented today at AIDS 2010 in Vienna.
In fact, the efficacy data were so good that the U.S. Food and Drug Administration stopped the trial early so that men in the placebo group could get the vaccine, presenter Dr. Heiko Jessen from Berlin, Germany, told Reuters Health.
Infection with oncogenic HPV can cause cancers of the penis, anus, and head and neck in men, and AIDS substantially increases the risk of HPV-related invasive cancers. Earlier this year the US Centers for Disease Control and Prevention issued a "permissive recommendation" for HPV vaccination in males ages 9 through 26. (See Reuters Health reports of Jan 4, 2010 and Jul 31, 2009.)
The randomized, double-blind, placebo-controlled trial started out with more than 4000 healthy men aged 16 to 26 years from 18 countries. The per-protocol analysis, reported here, involved 1400 men (including 200 men who have sex with men) in each arm followed for 3 years, Dr. Jessen said.
As noted in their meeting abstract, the researchers detected 3 external genital lesions related to HPV types 6, 11, 16 or 18 in the vaccine arm and 31 in the placebo arm - primarily condylomata acuminate - for an efficacy of 90.4%.
Efficacy against HPV vaccine types was 85.6%, and against HPV DNA detection at any time was 44.7%.
"People who are immune may still have HPV DNA," Dr. Jessen said, but the significance is unknown.
There were no cases of penile, perianal or perineal intraepithelial neoplasia, but one wouldn't expect these in young healthy men during a short follow-up trial, he added. The research team will continue to follow the participants.
"For now it makes sense to give the HPV vaccine to boys and men ages 9 to 26," Dr. Jessen said, but his group intends to examine its efficacy in older men as well, particularly in men who have sex with men, who are at higher risk for HPV-related malignancy.
There were no serious vaccine-related adverse experiences, he added.
The study was funded by Merck, which manufactures the vaccine
Continued Antihypertensive Treatment Safe After Stroke
From Medscape Medical News
Continued Antihypertensive Treatment Safe After Stroke
Emma Hitt, PhD
July 23, 2010 — Continuing antihypertensive medication after a stroke does not appear to reduce 2-week death or dependency, cardiovascular event rate, or mortality at 6 months, according to new research.
Thompson G. Robinson, MD, published the findings of a randomized study — Continue Or Stop post-Stroke Antihypertensives Collaborative Study (COSSACS) — online July 12 in Lancet Neurology.
The study sought to assess the efficacy and safety of continuing or stopping preexisting antihypertensive drugs within 48 hours of when a patient had undergone nondysphagic, ischemic, or hemorrhagic stroke, and within 48 hours of the last dose of antihypertensive drugs.
"A spontaneous decrease in blood pressure usually occurs 4 to 10 days after stroke, but substantial reductions in blood pressure can be associated with cerebral hypoperfusion as a consequence of poststroke cerebral dysautoregulation," Dr. Robinson and colleagues note.
The prospective trial included patients from 49 participating UK National Institute for Health Research Stroke Research Network centers from January 1, 2003, to March 31, 2009.
Patients were randomly assigned to either continue (n = 379) or stop (n = 384) preexisting antihypertensive drugs for 2 weeks after their stroke. Of the patients who continued antihypertensive drugs, 72 of 379 reached the primary endpoint (death or dependency [modified Rankin scale score ≥ 3 points] at 2 weeks) compared with 82 of 384 patients in the stop group, which was not a significant difference between groups (P = .3).
The difference between the 2 groups in systolic blood pressure at 2 weeks was 13 mm Hg (95% confidence interval, 10 - 17 mm Hg), and the difference in diastolic blood pressure was 8 mm Hg (95% confidence interval, 6 - 10 mm Hg; P < .0001).
The incidences of serious adverse events, 6-month mortality, and major cardiovascular events were similar between groups.
"These neutral results might be because COSSACS was underpowered owing to early termination of the trial, and support the continuation of ongoing research trials," the investigators conclude.
According to the researchers, a post hoc analysis found that continuing antihypertensive drugs might be associated with reduced 2-week death and dependency in patients with ischemic stroke confirmed on neuroimaging. "However, this post-hoc subgroup analysis requires further evaluation in patient populations with well-defined stroke subtypes," they write.
A related editorial by Craig S. Anderson, MD, from the University of Sydney and Royal Prince Alfred Hospital, Australia, noted that the study was "underpowered...but still worthwhile," and the "safety data are useful in guiding clinical practice."
Dr. Anderson concluded that the findings add to an "emerging consistent message: oral antihypertensive treatment can be used safely in nearly all patients within the first few days of mildly disabling or non-disabling stroke or transient ischaemic attack because of the modest size (about 6–12 mm Hg systolic) and speed (several hours) of the blood-pressure reduction."
The authors have disclosed no relevant financial relationships.
Lancet Neurol. Published online July 12, 2010.
Continued Antihypertensive Treatment Safe After Stroke
Emma Hitt, PhD
July 23, 2010 — Continuing antihypertensive medication after a stroke does not appear to reduce 2-week death or dependency, cardiovascular event rate, or mortality at 6 months, according to new research.
Thompson G. Robinson, MD, published the findings of a randomized study — Continue Or Stop post-Stroke Antihypertensives Collaborative Study (COSSACS) — online July 12 in Lancet Neurology.
The study sought to assess the efficacy and safety of continuing or stopping preexisting antihypertensive drugs within 48 hours of when a patient had undergone nondysphagic, ischemic, or hemorrhagic stroke, and within 48 hours of the last dose of antihypertensive drugs.
"A spontaneous decrease in blood pressure usually occurs 4 to 10 days after stroke, but substantial reductions in blood pressure can be associated with cerebral hypoperfusion as a consequence of poststroke cerebral dysautoregulation," Dr. Robinson and colleagues note.
The prospective trial included patients from 49 participating UK National Institute for Health Research Stroke Research Network centers from January 1, 2003, to March 31, 2009.
Patients were randomly assigned to either continue (n = 379) or stop (n = 384) preexisting antihypertensive drugs for 2 weeks after their stroke. Of the patients who continued antihypertensive drugs, 72 of 379 reached the primary endpoint (death or dependency [modified Rankin scale score ≥ 3 points] at 2 weeks) compared with 82 of 384 patients in the stop group, which was not a significant difference between groups (P = .3).
The difference between the 2 groups in systolic blood pressure at 2 weeks was 13 mm Hg (95% confidence interval, 10 - 17 mm Hg), and the difference in diastolic blood pressure was 8 mm Hg (95% confidence interval, 6 - 10 mm Hg; P < .0001).
The incidences of serious adverse events, 6-month mortality, and major cardiovascular events were similar between groups.
"These neutral results might be because COSSACS was underpowered owing to early termination of the trial, and support the continuation of ongoing research trials," the investigators conclude.
According to the researchers, a post hoc analysis found that continuing antihypertensive drugs might be associated with reduced 2-week death and dependency in patients with ischemic stroke confirmed on neuroimaging. "However, this post-hoc subgroup analysis requires further evaluation in patient populations with well-defined stroke subtypes," they write.
A related editorial by Craig S. Anderson, MD, from the University of Sydney and Royal Prince Alfred Hospital, Australia, noted that the study was "underpowered...but still worthwhile," and the "safety data are useful in guiding clinical practice."
Dr. Anderson concluded that the findings add to an "emerging consistent message: oral antihypertensive treatment can be used safely in nearly all patients within the first few days of mildly disabling or non-disabling stroke or transient ischaemic attack because of the modest size (about 6–12 mm Hg systolic) and speed (several hours) of the blood-pressure reduction."
The authors have disclosed no relevant financial relationships.
Lancet Neurol. Published online July 12, 2010.
Thursday, July 22, 2010
Most Patients With CVD Can Fly Safely, Says British Society
From Heartwire
Lisa Nainggolan
July 20, 2010 (Exeter, United Kingdom) — Most people with cardiovascular disease who are not critically ill can safely fly on commercial aircraft, the British Cardiovascular Society has concluded in a new report [1]. The document includes "guidance-at-a-glance" and is aimed primarily at general practitioners, lead author Dr David Smith (Royal Devon and Exeter NHS Foundation Trust, Exeter, UK) told heartwire . It will also be "translated" into "even more straightforward" guidance for patients by the British Heart Foundation, he noted.
Smith said this guidance, the first ever from the British Cardiovascular Society, "tries to go through the detail. In general, we've tried to allow people to fly, unless there is a very good reason not to, whereas the way various other people have looked at this is to say, 'Who shall we restrict?' " Of the many existing guidelines on passenger fitness to fly, most include some reference to cardiovascular disorders, but many are contrary in their advice, particularly with reference to the time required between an event or medical procedure and the flight, he said. "In our view, they were not necessarily based on thinking about the underlying processes, and they often do not separate patients out into higher- and lower-risk categories."
A large proportion of the new document is devoted to looking at the underlying effects of the cabin environment and then seeing whether this is likely to produce a deleterious effect on somebody who has existing heart disease, Smith said. "We've tried to support all our recommendations with analysis of the underlying physiology and physics. The overwhelming conclusion is that the cabin environment poses a very little threat. It's not the flying that's the problem. What we try to emphasize is that it's the stability, or instability, of someone's underlying condition that indicates the probability of a spontaneous event occurring while they are in the air."
Minimal Restrictions on Flying for Most With Pacemakers, ICDs
Smith and colleagues explain that the main impact of air travel is the inhalation of air with reduced oxygen content in a pressurized environment, resulting in lower circulating oxygen levels in the blood, known as hypobaric hypoxia. Passengers already at high risk of angina, myocardial infarction, heart failure, or abnormal heart rhythms might be adversely affected by hypoxia, but the blood oxygen levels induced by flying "appear to have little or no adverse circulatory effects," certainly not for short- and medium-haul flights, they state.
The guidance-at-a-glance, which appears in the first two pages of the document, goes into detail about various cardiovascular conditions, and divides each into low, medium, and high risk, with accompanying lay explanations. It then goes on to give advice on flying for each level of that condition. For example, for post-STEMI and NSTEMI, those at low risk are advised that they can fly three days after their event, and those at medium risk can fly after 10 days. However, those at high risk--ejection fraction <40%, signs and symptoms of heart failure, and those awaiting further investigation, revascularization, or device therapy--are advised to "defer travel" until their condition is stable.
After uncomplicated elective PCI, the guidelines state that patients can fly "after two days." Likewise, patients with pacemakers implanted are advised they can fly after two days, unless they have suffered a pneumothorax, in which case they should wait until two weeks after it has fully healed. The same advice applies to those with ICDs, with the added recommendation that they should not fly after the ICD has delivered a shock until the condition is considered stable.
"We hope we've clarified a lot of things that people worry about. Cosmic rays, effects on their pacemakers, for example, have been addressed in some detail," Smith said. "People are concerned about their defibrillators, pacemakers, and stents . . . and we hope this will allay fears and give guidance as to what people should do if they are going to fly and they have underlying heart disease."
Venous Thromboembolism Risk Low
There is also guidance for the avoidance of deep vein thrombosis (DVT) and venous thromboembolism; although a long-haul flight doubles the risk of DVT, it is similar to that incurred during car, bus, or train travel for a similar period, the doctors state. And the absolute risk of DVT for a fit and healthy person is one in 6000 for a flight of more than four hours, they note, pointing out that pilots are at no greater risk than the general population.
Even those at high risk--those who have already had a DVT, recent surgery lasting more than 30 minutes, known thrombophilia, or pregnancy, and those who are obese (BMI>30 kg/m2)--can still fly, provided they consume plenty of fluids, exclude caffeine and alcohol, wear compression stockings, and take a low-molecular-weight heparin, they say. Aspirin is not recommended.
Smith reports no conflict of interest.
References
Lisa Nainggolan
July 20, 2010 (Exeter, United Kingdom) — Most people with cardiovascular disease who are not critically ill can safely fly on commercial aircraft, the British Cardiovascular Society has concluded in a new report [1]. The document includes "guidance-at-a-glance" and is aimed primarily at general practitioners, lead author Dr David Smith (Royal Devon and Exeter NHS Foundation Trust, Exeter, UK) told heartwire . It will also be "translated" into "even more straightforward" guidance for patients by the British Heart Foundation, he noted.
Smith said this guidance, the first ever from the British Cardiovascular Society, "tries to go through the detail. In general, we've tried to allow people to fly, unless there is a very good reason not to, whereas the way various other people have looked at this is to say, 'Who shall we restrict?' " Of the many existing guidelines on passenger fitness to fly, most include some reference to cardiovascular disorders, but many are contrary in their advice, particularly with reference to the time required between an event or medical procedure and the flight, he said. "In our view, they were not necessarily based on thinking about the underlying processes, and they often do not separate patients out into higher- and lower-risk categories."
A large proportion of the new document is devoted to looking at the underlying effects of the cabin environment and then seeing whether this is likely to produce a deleterious effect on somebody who has existing heart disease, Smith said. "We've tried to support all our recommendations with analysis of the underlying physiology and physics. The overwhelming conclusion is that the cabin environment poses a very little threat. It's not the flying that's the problem. What we try to emphasize is that it's the stability, or instability, of someone's underlying condition that indicates the probability of a spontaneous event occurring while they are in the air."
Minimal Restrictions on Flying for Most With Pacemakers, ICDs
Smith and colleagues explain that the main impact of air travel is the inhalation of air with reduced oxygen content in a pressurized environment, resulting in lower circulating oxygen levels in the blood, known as hypobaric hypoxia. Passengers already at high risk of angina, myocardial infarction, heart failure, or abnormal heart rhythms might be adversely affected by hypoxia, but the blood oxygen levels induced by flying "appear to have little or no adverse circulatory effects," certainly not for short- and medium-haul flights, they state.
The guidance-at-a-glance, which appears in the first two pages of the document, goes into detail about various cardiovascular conditions, and divides each into low, medium, and high risk, with accompanying lay explanations. It then goes on to give advice on flying for each level of that condition. For example, for post-STEMI and NSTEMI, those at low risk are advised that they can fly three days after their event, and those at medium risk can fly after 10 days. However, those at high risk--ejection fraction <40%, signs and symptoms of heart failure, and those awaiting further investigation, revascularization, or device therapy--are advised to "defer travel" until their condition is stable.
After uncomplicated elective PCI, the guidelines state that patients can fly "after two days." Likewise, patients with pacemakers implanted are advised they can fly after two days, unless they have suffered a pneumothorax, in which case they should wait until two weeks after it has fully healed. The same advice applies to those with ICDs, with the added recommendation that they should not fly after the ICD has delivered a shock until the condition is considered stable.
"We hope we've clarified a lot of things that people worry about. Cosmic rays, effects on their pacemakers, for example, have been addressed in some detail," Smith said. "People are concerned about their defibrillators, pacemakers, and stents . . . and we hope this will allay fears and give guidance as to what people should do if they are going to fly and they have underlying heart disease."
Venous Thromboembolism Risk Low
There is also guidance for the avoidance of deep vein thrombosis (DVT) and venous thromboembolism; although a long-haul flight doubles the risk of DVT, it is similar to that incurred during car, bus, or train travel for a similar period, the doctors state. And the absolute risk of DVT for a fit and healthy person is one in 6000 for a flight of more than four hours, they note, pointing out that pilots are at no greater risk than the general population.
Even those at high risk--those who have already had a DVT, recent surgery lasting more than 30 minutes, known thrombophilia, or pregnancy, and those who are obese (BMI>30 kg/m2)--can still fly, provided they consume plenty of fluids, exclude caffeine and alcohol, wear compression stockings, and take a low-molecular-weight heparin, they say. Aspirin is not recommended.
Smith reports no conflict of interest.
References
First-Morning Void May Be Best Predictor of Renal Events in Diabetic Nephropathy
From Medscape Medical News
Laurie Barclay, MD
July 22, 2010 — Albumin-to-creatinine ratio (ACR) in a first-morning void may be the best predictor of renal events in patients with type 2 diabetes and kidney disease, according to the results of the Reduction in Endpoints in Non Insulin Dependent Diabetes Mellitus with the Angiotensin-II Antagonist Losartan (RENAAL) trial reported Online First July 15 in the Journal of the American Society of Nephrology.
"From a clinical point of view, these results are very important, because they imply that collection of first morning voids, which is clearly more convenient than collecting a 24-hour urine, can be used for assessment of proteinuria," said lead author Hiddo J. Lambers Heerspink, PharmD, PhD, from University Medical Center Groningen, in Groningen, the Netherlands, in a news release.
With a study sample of 701 participants with type 2 diabetes and nephropathy enrolled in the RENAAL trial, the goal of the study was to compare prediction of renal events by urinary protein excretion (UPE) and urinary albumin excretion (UAE) from a 24-hour urine collection vs urinary albumin concentration (UAC) and ACR from a first-morning void. Time to a doubling of serum creatinine or end-stage renal disease was the main study endpoint.
There were 202 renal events during follow-up. For each 1-SD increase in the log-transformed measures, the hazard ratios (HRs) for the risk for a renal outcome were 3.16 (95% confidence interval [CI], 2.60 - 3.86) for UAE, 3.02 (95% CI, 2.53 - 3.62) for UPE, 3.23 (95% CI, 2.67 - 3.91) for UAC, and 4.36 (95% CI, 3.50 - 5.45) for ACR. Compared with the other measures, the area under the receiver operating characteristic curve was significantly higher for ACR.
"[F]or predicting renal disease progression in patients with type 2 diabetes and nephropathy, collecting first morning void urine samples and measuring the albumin:creatinine ratio appear to be superior when compared with measuring 24-hour urinary albumin excretion," the study authors write. "These results are clinically important because they imply that collection of first morning voids, which is clearly more convenient than collecting a 24-hour urine, can be used for assessment of proteinuria."
Limitations of this study include inability to directly apply the results to individuals without diabetes or nephropathy. In addition, total protein concentrations were not measured in a first-morning void urine sample, precluding comparison between protein-to-creatinine ratios and ACRs derived from a first-morning void.
In an accompanying editorial, Bryan Kestenbaum, MD, and Ian de Boer, MD, from the University of Washington in Seattle, discuss the implications of this study for clinical practice and for clinical research.
"Given data from this study and the considerable patient effort required for a 24-hour urine collection, we agree with the authors that the first morning albumin:creatinine ratio is in general the logical choice for quantifying proteinuria in clinical practice," they write.
"First, urine ACR represents more than simply proteinuria, and associations of urine ACR with disease outcomes should be interpreted in the context of dual contributions of urine albumin excretion and urine creatinine. Second, this study [begs] the questions, 'Why is low urine creatinine excretion associated with adverse kidney and cardiovascular disease outcomes independent of standard measures of body composition?' 'Does a low urine creatinine concentration reflect low muscle mass, low muscle quality, or both?' 'Is a low urine creatinine concentration a modifiable therapeutic target?'"
The RENAAL study was sponsored by Merck & Co, Inc. One of the study authors is an employee of Merck, and 4 other study authors are members of the RENAAL Steering Committee and have received grants from Merck. The editorialists have disclosed no relevant financial relationships.
J Am Soc Nephrol. Published online July 15, 2010.
Laurie Barclay, MD
July 22, 2010 — Albumin-to-creatinine ratio (ACR) in a first-morning void may be the best predictor of renal events in patients with type 2 diabetes and kidney disease, according to the results of the Reduction in Endpoints in Non Insulin Dependent Diabetes Mellitus with the Angiotensin-II Antagonist Losartan (RENAAL) trial reported Online First July 15 in the Journal of the American Society of Nephrology.
"From a clinical point of view, these results are very important, because they imply that collection of first morning voids, which is clearly more convenient than collecting a 24-hour urine, can be used for assessment of proteinuria," said lead author Hiddo J. Lambers Heerspink, PharmD, PhD, from University Medical Center Groningen, in Groningen, the Netherlands, in a news release.
With a study sample of 701 participants with type 2 diabetes and nephropathy enrolled in the RENAAL trial, the goal of the study was to compare prediction of renal events by urinary protein excretion (UPE) and urinary albumin excretion (UAE) from a 24-hour urine collection vs urinary albumin concentration (UAC) and ACR from a first-morning void. Time to a doubling of serum creatinine or end-stage renal disease was the main study endpoint.
There were 202 renal events during follow-up. For each 1-SD increase in the log-transformed measures, the hazard ratios (HRs) for the risk for a renal outcome were 3.16 (95% confidence interval [CI], 2.60 - 3.86) for UAE, 3.02 (95% CI, 2.53 - 3.62) for UPE, 3.23 (95% CI, 2.67 - 3.91) for UAC, and 4.36 (95% CI, 3.50 - 5.45) for ACR. Compared with the other measures, the area under the receiver operating characteristic curve was significantly higher for ACR.
"[F]or predicting renal disease progression in patients with type 2 diabetes and nephropathy, collecting first morning void urine samples and measuring the albumin:creatinine ratio appear to be superior when compared with measuring 24-hour urinary albumin excretion," the study authors write. "These results are clinically important because they imply that collection of first morning voids, which is clearly more convenient than collecting a 24-hour urine, can be used for assessment of proteinuria."
Limitations of this study include inability to directly apply the results to individuals without diabetes or nephropathy. In addition, total protein concentrations were not measured in a first-morning void urine sample, precluding comparison between protein-to-creatinine ratios and ACRs derived from a first-morning void.
In an accompanying editorial, Bryan Kestenbaum, MD, and Ian de Boer, MD, from the University of Washington in Seattle, discuss the implications of this study for clinical practice and for clinical research.
"Given data from this study and the considerable patient effort required for a 24-hour urine collection, we agree with the authors that the first morning albumin:creatinine ratio is in general the logical choice for quantifying proteinuria in clinical practice," they write.
"First, urine ACR represents more than simply proteinuria, and associations of urine ACR with disease outcomes should be interpreted in the context of dual contributions of urine albumin excretion and urine creatinine. Second, this study [begs] the questions, 'Why is low urine creatinine excretion associated with adverse kidney and cardiovascular disease outcomes independent of standard measures of body composition?' 'Does a low urine creatinine concentration reflect low muscle mass, low muscle quality, or both?' 'Is a low urine creatinine concentration a modifiable therapeutic target?'"
The RENAAL study was sponsored by Merck & Co, Inc. One of the study authors is an employee of Merck, and 4 other study authors are members of the RENAAL Steering Committee and have received grants from Merck. The editorialists have disclosed no relevant financial relationships.
J Am Soc Nephrol. Published online July 15, 2010.
FDA Warns Abbott Diabetes Care About Manufacturing Practices of Its Glucose Meters
From Medscape Medical News > Alerts, Approvals and Safety Changes > Medscape Alerts
Robert Lowes
July 21, 2010 — Abbott Diabetes Care has received a warning letter from the US Food and Drug Administration (FDA) about how it manufactures its FreeStyle glucose meters.
The meters include the FreeStyle Navigator Continuous Glucose Monitoring System, currently unavailable in the United States as a result of what the company calls a "supply interruption."
In a July 2 letter, the FDA faulted Abbott Diabetes Care, a unit of Abbott, with violations of quality-control requirements, including how it followed up on the discovery of empty blister packs and scratches on glucose-meter test strips.
The FDA also stated that the company lacked enough qualified personnel to ensure that manufacturing processes met agency standards. The job description for the director of quality systems, for example, required this employee to have a bachelor's degree in a scientific, engineering, or technical discipline. The person in this position instead had a business administration degree, according to the agency.
The warning letter stemmed from an FDA inspection of the company's facilities in Alameda, California, earlier this year.
In a press release, Abbott Diabetes Care said it "has taken and continues to take the actions necessary to address the items outlined in the letter and is communicating those actions directly to the agency."
Warning Letter Comes On Top of Other Agency Actions
The warning letter, posted Tuesday on the agency's Web site, is the latest in a series of FDA actions involving glucose meters from Abbott Diabetes Care. In August 2009, the agency announced that patients with diabetes who receive therapeutic products containing certain sugars other than glucose could experience serious, although rare, injuries if their glucose meters used test strips that incorporated the GDH-PQQ enzyme. Such test strips will react with nonglucose sugars such as maltose to produce a falsely high glucose reading, which might cause patients with diabetes to take too much insulin. The FDA identified Abbott Diabetes Care as one of several glucose meter manufacturers that relied on GDH-PQQ test strips.
Since then, the company has won FDA clearance for new test strips based on another enzyme that is not affected by maltose and other common nonglucose sugars. Abbott spokesperson Gregory Miley told Medscape Medical News that the new test strips would hit the US marketplace later this year.
In May, the FDA also announced a class 2 recall of the FreeStyle Navigator Continuous Glucose Monitoring System because of the possibility of cracks in the device's plastic housing near the battery compartment, which could allow moisture to enter and trigger device failure or inaccurate readings. Mr. Miley said that the company had alerted both its customers and the FDA about this problem in April 2009.
In April 2010, Abbott Diabetes Care disclosed that it was experiencing a "supply interruption" with the FreeStyle Navigator system and therefore was unable to provide patients with replacement receivers and transmitters, or sell the complete system to new customers. Mr. Miley told Medscape Medical News that the company had resumed selling the product in 6 European countries and Israel.
"We're working as quickly as we can on it for the United States," he said.
Mr. Miley declined to say what caused the supply interruption.
The full text of the warning letter to Abbott Diabetes Care about its manufacturing processes for glucose meters is available on the agency's Web site.
To report adverse events related to these devices, contact MedWatch 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 MedWatch, FDA, 5600 Fishers Lane, Rockville, Maryland 20852-9787.
Robert Lowes
July 21, 2010 — Abbott Diabetes Care has received a warning letter from the US Food and Drug Administration (FDA) about how it manufactures its FreeStyle glucose meters.
The meters include the FreeStyle Navigator Continuous Glucose Monitoring System, currently unavailable in the United States as a result of what the company calls a "supply interruption."
In a July 2 letter, the FDA faulted Abbott Diabetes Care, a unit of Abbott, with violations of quality-control requirements, including how it followed up on the discovery of empty blister packs and scratches on glucose-meter test strips.
The FDA also stated that the company lacked enough qualified personnel to ensure that manufacturing processes met agency standards. The job description for the director of quality systems, for example, required this employee to have a bachelor's degree in a scientific, engineering, or technical discipline. The person in this position instead had a business administration degree, according to the agency.
The warning letter stemmed from an FDA inspection of the company's facilities in Alameda, California, earlier this year.
In a press release, Abbott Diabetes Care said it "has taken and continues to take the actions necessary to address the items outlined in the letter and is communicating those actions directly to the agency."
Warning Letter Comes On Top of Other Agency Actions
The warning letter, posted Tuesday on the agency's Web site, is the latest in a series of FDA actions involving glucose meters from Abbott Diabetes Care. In August 2009, the agency announced that patients with diabetes who receive therapeutic products containing certain sugars other than glucose could experience serious, although rare, injuries if their glucose meters used test strips that incorporated the GDH-PQQ enzyme. Such test strips will react with nonglucose sugars such as maltose to produce a falsely high glucose reading, which might cause patients with diabetes to take too much insulin. The FDA identified Abbott Diabetes Care as one of several glucose meter manufacturers that relied on GDH-PQQ test strips.
Since then, the company has won FDA clearance for new test strips based on another enzyme that is not affected by maltose and other common nonglucose sugars. Abbott spokesperson Gregory Miley told Medscape Medical News that the new test strips would hit the US marketplace later this year.
In May, the FDA also announced a class 2 recall of the FreeStyle Navigator Continuous Glucose Monitoring System because of the possibility of cracks in the device's plastic housing near the battery compartment, which could allow moisture to enter and trigger device failure or inaccurate readings. Mr. Miley said that the company had alerted both its customers and the FDA about this problem in April 2009.
In April 2010, Abbott Diabetes Care disclosed that it was experiencing a "supply interruption" with the FreeStyle Navigator system and therefore was unable to provide patients with replacement receivers and transmitters, or sell the complete system to new customers. Mr. Miley told Medscape Medical News that the company had resumed selling the product in 6 European countries and Israel.
"We're working as quickly as we can on it for the United States," he said.
Mr. Miley declined to say what caused the supply interruption.
The full text of the warning letter to Abbott Diabetes Care about its manufacturing processes for glucose meters is available on the agency's Web site.
To report adverse events related to these devices, contact MedWatch 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 MedWatch, FDA, 5600 Fishers Lane, Rockville, Maryland 20852-9787.
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