You shouldn't use the oral or rectal routes to measure the temperature of children aged 0-5 years
In children aged 4 weeks to 5 years, you should measure body temperature by one of the following methods:
Electronic thermometer in the axilla
Chemical dot thermometer in the axilla
Infrared tympanic thermometer.
Children in the following categories are in a high risk group for serious illness:
Children younger than 3 months of age with a temperature of 38ºC or higher
Children aged 3-6 months with a temperature of 39ºC or higher
Antipyretic agents do not prevent febrile convulsions and should not be used specifically for this purpose
2: Summary table for symptoms and signs suggestive of specific diseases
Diagnosis to be considered Symptoms and signs in conjunction with fever
Meningococcal disease Non-blanching rash, particularly with one or more of the following:
An ill looking child
Lesions larger than 2 mm in diameter (purpura)
A capillary refill time of ≥3 seconds
Neck stiffness.
Meningitis One or more of the following:
Neck stiffness
Bulging fontanelle
Decreased level of consciousness
Convulsive status epilepticus.
Herpes simplex encephalitis Herpes simplex encephalitis should be considered in children with fever and any of the following features:
Focal neurological signs
Focal seizures
Decreased level of consciousness
Pneumonia You should consider pneumonia in children with fever and any of the following signs:
Tachypnoea
(RR > 60 breaths per minute Age 0-5 months,
RR > 50 breaths per minute Age 6-12 months;
RR > 40 breaths per minute Age >12 months)
Crackles
Nasal flaring
Chest indrawing
Cyanosis
Oxygen saturation ≤95% on air.
Urinary tract infection You should think of a urinary tract infection in a child aged 3 months and older with fever and one or more of the following:
Vomiting
Poor feeding
Lethargy
Irritability
Abdominal pain or tenderness
Urinary frequency or dysuria
Offensive urine or haematuria.
Septic arthritis Septic arthritis/osteomyelitis should be considered in children with fever and any of the following signs:
Swelling of a limb or joint
Not using an extremity
Non-weight bearing.
Kawasaki disease Fever for more than five days and at least four of the following:
Bilateral conjunctival injection
Change in mucous membranes (for example, injected pharynx, dry cracked lips, or strawberry tongue)
Change in the extremities (for example, oedema, erythema, or desquamation)
Polymorphous rash
Cervical lymphadenopathy.
Healthcare professionals should be aware that, in rare cases, incomplete/atypical Kawasaki disease may be diagnosed with fewer features
Monday, December 13, 2010
Friday, December 10, 2010
Antipsychotics Increase Risks for Sudden Cardiac Death
Antipsychotic drugs — both typical and atypical — carry significant risks for sudden cardiac death, and their use in some patients should be sharply reduced, according to a study and editorial in the New England Journal of Medicine.
Using 16 years of Tennessee Medicaid data, researchers retrospectively examined rates of sudden cardiac death occurring in the community in the following groups: patients currently taking typical antipsychotic drugs, patients taking atypical antipsychotics, and controls.
The principal findings were:
Current users of both typical and atypical antipsychotics showed a doubling in risk for sudden death relative to controls.
Risk increased with increasing dose among current users.
Former users showed no increased risk relative to controls.
Editorialists conclude that, especially among children and demented elderly patients for whom there is little evidence of the drugs' efficacy, their use "should be reduced sharply."
Using 16 years of Tennessee Medicaid data, researchers retrospectively examined rates of sudden cardiac death occurring in the community in the following groups: patients currently taking typical antipsychotic drugs, patients taking atypical antipsychotics, and controls.
The principal findings were:
Current users of both typical and atypical antipsychotics showed a doubling in risk for sudden death relative to controls.
Risk increased with increasing dose among current users.
Former users showed no increased risk relative to controls.
Editorialists conclude that, especially among children and demented elderly patients for whom there is little evidence of the drugs' efficacy, their use "should be reduced sharply."
Patients with Alzheimer Disease on Antipsychotics Show Increased Mortality
Patients with Alzheimer disease who take antipsychotic drugs may be at increased long-term risk for death, according to a study published online in Lancet Neurology.
Some 170 patients with Alzheimer disease who lived in long-term care facilities were randomized to either continue treatment on antipsychotics (most commonly risperidone and haloperidol) or switch to a placebo for 12 months. The group continuing antipsychotics had a significantly lower survival rate over 54 months' follow-up, compared with the placebo group (hazard ratio, 0.58). (In June 2008, the FDA mandated that antipsychotics carry boxed warnings alerting physicians to the mortality risk.)
The authors conclude: "The accumulating safety concerns, including the substantial increase in long-term mortality, emphasize the urgent need to put an end to unnecessary and prolonged prescribing."
An accompanying commentary suggests that if antipsychotics are necessary, they should be given in low doses for short durations, with regular attempts at discontinuation.
Some 170 patients with Alzheimer disease who lived in long-term care facilities were randomized to either continue treatment on antipsychotics (most commonly risperidone and haloperidol) or switch to a placebo for 12 months. The group continuing antipsychotics had a significantly lower survival rate over 54 months' follow-up, compared with the placebo group (hazard ratio, 0.58). (In June 2008, the FDA mandated that antipsychotics carry boxed warnings alerting physicians to the mortality risk.)
The authors conclude: "The accumulating safety concerns, including the substantial increase in long-term mortality, emphasize the urgent need to put an end to unnecessary and prolonged prescribing."
An accompanying commentary suggests that if antipsychotics are necessary, they should be given in low doses for short durations, with regular attempts at discontinuation.
Tuesday, December 7, 2010
American College of Preventive Medicine Does Not Recommend Prostate Cancer Screening With DRE, PSA
February 5, 2008 — Information is not adequate to recommend screening men for prostate cancer with digital rectal examination or measurement of prostate-specific antigen (PSA), according to a position statement by the American College of Preventive Medicine (ACPM) published in the February issue of the American Journal of Preventive Medicine.
"Prostate cancer is the leading cancer in U.S. men, and the third leading cause of cancer deaths," write Lionel S. Lim, MD, MPH, FACP, from the Griffin Hospital (Lim) in Derby, Connecticut, and colleagues from the ACPM Prevention Practice Committee. "Principal screening tests for detection of asymptomatic prostate cancer include digital rectal examination (DRE) and measurement of the serum tumor marker, prostate-specific antigen (PSA). There are risks and benefits associated with prostate cancer screening."
Although randomized controlled trials (RCTs) of screening for prostate cancer with digital rectal examination and PSA are limited to 2 previously published studies, 2 additional large-scale RCTs are currently ongoing. This review evaluated the efficacy of digital rectal examination and PSA for prostate cancer screening based on medical literature published before July 2007.
In clinical practice, applications of PSA screening tests include (1) a PSA cutoff value of 4 ng/mL, (2) age-specific PSA, (3) PSA velocity, (4) PSA density, and (5) percent free PSA.
Although prostate cancer screening can diagnose the disease in its early stages, thereby potentially decreasing morbidity and mortality, the benefits of prostate cancer screening remain unproved, pending findings from RCTs currently in progress. At present, no conclusive data demonstrate that early screening, detection, and treatment reduce mortality.
Other suggested potential benefits of screening include reassurance of being at low risk for prostate cancer and the fact that PSA can be easily obtained with a simple blood test and is widely available.
Potential harms of screening for prostate cancer include potential adverse health effects associated with false-positive and negative results and adverse effects of treatment. Other limitations of screening are that a survival benefit from prostate cancer screening has not been proved in rigorous trials.
A false-positive result from prostate cancer screening could lead to increased anxiety, as well as the discomfort and possible complications of biopsy, such as pain, hematospermia, hematuria, or infection. Conversely, false reassurance from a false-negative test could delay the diagnosis of prostate cancer.
Even for true-positive screening results, there may be harms because prostate cancer may be slow growing, never advancing, or progress to cause significant disease or death and because of short-term and long-term adverse effects of treatment, such as pain, urinary incontinence, and impotence.
"The American College of Preventive Medicine concludes that there is insufficient evidence to recommend routine population screening with DRE or PSA," the review authors write. "Clinicians caring for men, especially African-American men and those with positive family histories, should provide information about potential benefits and risks of prostate cancer screening, and the limitations of current evidence for screening, in order to maximize informed decision making."
The ACPM agrees with the American College of Physicians that informed discussion about screening should take place annually, during the routine periodic examination, or in response to a request by the patient.
The American Urological Association recommends that men who are 50 years and older and who have an estimated life expectancy of more than 10 years should be offered PSA screening. The American Cancer Society recommends that men who are 50 years and older and who have a life expectancy of more than 10 years should be offered both DRE and PSA screening. The Canadian Task Force on Preventive Health Care recommends against routine screening with PSA.
"The effectiveness of prostate cancer screening is questionable in elderly men with competing comorbidities and men with life expectancies of less than 10 years," the review authors note. "Ultimately, a man should be allowed to make his own choice about screening, in consultation with his physician, taking into consideration personal preferences and life expectancy. If the patient prefers to defer to the clinician or is unable to make a decision regarding screening, then testing should not be offered as long as the patient understands the benefits, potential limitations, and adverse effects associated with screening."
In men at average risk for prostate cancer, the usual age for screening is between 50 and 70 years. However, those who are at high risk might benefit from earlier screening starting at age 45 years, and higher-risk men with 2 or more first-degree relatives with prostate cancer before age 65 years might begin screening at age 40 years.
"Granted that prostate cancer is more likely to be found in high-risk men, issues pertaining to tumor grade have yet to be resolved (that is, optimal grade of tumor that a screening test should detect to confer a benefit in survival or morbidity), and there is still no evidence establishing effectiveness of screening in high-risk men," the review authors conclude. "In the meantime, further studies are needed to establish the efficacy and optimal age at which prostate cancer screening should be initiated in these high-risk population groups."
According to the American Cancer Society, no major scientific or medical organization supports routine testing for prostate cancer at this time.
The review authors have disclosed no relevant financial relationships.
Am J Prev Med. 2008;34:164-170.
"Prostate cancer is the leading cancer in U.S. men, and the third leading cause of cancer deaths," write Lionel S. Lim, MD, MPH, FACP, from the Griffin Hospital (Lim) in Derby, Connecticut, and colleagues from the ACPM Prevention Practice Committee. "Principal screening tests for detection of asymptomatic prostate cancer include digital rectal examination (DRE) and measurement of the serum tumor marker, prostate-specific antigen (PSA). There are risks and benefits associated with prostate cancer screening."
Although randomized controlled trials (RCTs) of screening for prostate cancer with digital rectal examination and PSA are limited to 2 previously published studies, 2 additional large-scale RCTs are currently ongoing. This review evaluated the efficacy of digital rectal examination and PSA for prostate cancer screening based on medical literature published before July 2007.
In clinical practice, applications of PSA screening tests include (1) a PSA cutoff value of 4 ng/mL, (2) age-specific PSA, (3) PSA velocity, (4) PSA density, and (5) percent free PSA.
Although prostate cancer screening can diagnose the disease in its early stages, thereby potentially decreasing morbidity and mortality, the benefits of prostate cancer screening remain unproved, pending findings from RCTs currently in progress. At present, no conclusive data demonstrate that early screening, detection, and treatment reduce mortality.
Other suggested potential benefits of screening include reassurance of being at low risk for prostate cancer and the fact that PSA can be easily obtained with a simple blood test and is widely available.
Potential harms of screening for prostate cancer include potential adverse health effects associated with false-positive and negative results and adverse effects of treatment. Other limitations of screening are that a survival benefit from prostate cancer screening has not been proved in rigorous trials.
A false-positive result from prostate cancer screening could lead to increased anxiety, as well as the discomfort and possible complications of biopsy, such as pain, hematospermia, hematuria, or infection. Conversely, false reassurance from a false-negative test could delay the diagnosis of prostate cancer.
Even for true-positive screening results, there may be harms because prostate cancer may be slow growing, never advancing, or progress to cause significant disease or death and because of short-term and long-term adverse effects of treatment, such as pain, urinary incontinence, and impotence.
"The American College of Preventive Medicine concludes that there is insufficient evidence to recommend routine population screening with DRE or PSA," the review authors write. "Clinicians caring for men, especially African-American men and those with positive family histories, should provide information about potential benefits and risks of prostate cancer screening, and the limitations of current evidence for screening, in order to maximize informed decision making."
The ACPM agrees with the American College of Physicians that informed discussion about screening should take place annually, during the routine periodic examination, or in response to a request by the patient.
The American Urological Association recommends that men who are 50 years and older and who have an estimated life expectancy of more than 10 years should be offered PSA screening. The American Cancer Society recommends that men who are 50 years and older and who have a life expectancy of more than 10 years should be offered both DRE and PSA screening. The Canadian Task Force on Preventive Health Care recommends against routine screening with PSA.
"The effectiveness of prostate cancer screening is questionable in elderly men with competing comorbidities and men with life expectancies of less than 10 years," the review authors note. "Ultimately, a man should be allowed to make his own choice about screening, in consultation with his physician, taking into consideration personal preferences and life expectancy. If the patient prefers to defer to the clinician or is unable to make a decision regarding screening, then testing should not be offered as long as the patient understands the benefits, potential limitations, and adverse effects associated with screening."
In men at average risk for prostate cancer, the usual age for screening is between 50 and 70 years. However, those who are at high risk might benefit from earlier screening starting at age 45 years, and higher-risk men with 2 or more first-degree relatives with prostate cancer before age 65 years might begin screening at age 40 years.
"Granted that prostate cancer is more likely to be found in high-risk men, issues pertaining to tumor grade have yet to be resolved (that is, optimal grade of tumor that a screening test should detect to confer a benefit in survival or morbidity), and there is still no evidence establishing effectiveness of screening in high-risk men," the review authors conclude. "In the meantime, further studies are needed to establish the efficacy and optimal age at which prostate cancer screening should be initiated in these high-risk population groups."
According to the American Cancer Society, no major scientific or medical organization supports routine testing for prostate cancer at this time.
The review authors have disclosed no relevant financial relationships.
Am J Prev Med. 2008;34:164-170.
Vitamin D Deficiency Associated with Increased MI Risk in Men
Low levels of vitamin D in men are associated with double the risk for myocardial infarction, reports Archives of Internal Medicine.
Researchers assessed plasma 25-hydroxyvitamin D concentrations in some 18,000 men aged 40 to 75. After 10 years, roughly 450 men had had a nonfatal MI or fatal coronary artery disease. This group was matched to a control group (from among the participants) free of cardiovascular disease.
Men who had deficient vitamin D levels (15 ng/mL or less) were at significantly higher risk for MI by follow-up, compared with men whose levels were at least 30 ng/mL (relative risk, 2.4). The results remained significant after adjustment for cardiovascular risk factors and lipid levels.
The authors propose several possible mechanisms for the association — among them, vitamin D's effects on vascular smooth muscle cell growth, vascular calcification, inflammation, and blood pressure (through the renin-angiotensin system).
Researchers assessed plasma 25-hydroxyvitamin D concentrations in some 18,000 men aged 40 to 75. After 10 years, roughly 450 men had had a nonfatal MI or fatal coronary artery disease. This group was matched to a control group (from among the participants) free of cardiovascular disease.
Men who had deficient vitamin D levels (15 ng/mL or less) were at significantly higher risk for MI by follow-up, compared with men whose levels were at least 30 ng/mL (relative risk, 2.4). The results remained significant after adjustment for cardiovascular risk factors and lipid levels.
The authors propose several possible mechanisms for the association — among them, vitamin D's effects on vascular smooth muscle cell growth, vascular calcification, inflammation, and blood pressure (through the renin-angiotensin system).
Prednisolone, Naproxen Equivalent Against Gout
Corticosteroids are just as effective against acute gout as naproxen, according to a Lancet study.
Dutch researchers randomized 120 patients with monoarticular gout to either naproxen or prednisolone for 5 days. (Gout was confirmed in all patients by the presence of monosodium urate crystals.) After 90 hours' treatment, pain and general disability scores as measured on a visual analogue scale were reduced to a similar extent in both groups.
The authors say their study "provides a strong argument to consider prednisolone as a first treatment option in patients with gout."
Dutch researchers randomized 120 patients with monoarticular gout to either naproxen or prednisolone for 5 days. (Gout was confirmed in all patients by the presence of monosodium urate crystals.) After 90 hours' treatment, pain and general disability scores as measured on a visual analogue scale were reduced to a similar extent in both groups.
The authors say their study "provides a strong argument to consider prednisolone as a first treatment option in patients with gout."
Alpha-Blocker Does Not Ease Symptoms of Chronic Prostatitis
Alfuzosin, an alpha-adrenergic–receptor blocker, does not improve symptoms in men with chronic prostatitis–chronic pelvic pain syndrome, according to a New England Journal of Medicine study.
Some 270 men who were diagnosed with the condition within the preceding 2 years and had never used an alpha-blocker were randomized to receive alfuzosin or a placebo daily for 12 weeks. By the end of treatment, approximately half of the men in each group had achieved clinically significant reductions in a symptom score measuring pain, voiding problems, and quality of life. Similarly, there were no significant differences between the groups in secondary outcomes, such as anxiety and depression.
The authors note that several meta-analyses have led some researchers to recommend alpha-blockers for chronic prostatitis. They conclude: "Our trial does not support these recommendations and should prompt reconsideration of the choice of initial therapy for these patients
Some 270 men who were diagnosed with the condition within the preceding 2 years and had never used an alpha-blocker were randomized to receive alfuzosin or a placebo daily for 12 weeks. By the end of treatment, approximately half of the men in each group had achieved clinically significant reductions in a symptom score measuring pain, voiding problems, and quality of life. Similarly, there were no significant differences between the groups in secondary outcomes, such as anxiety and depression.
The authors note that several meta-analyses have led some researchers to recommend alpha-blockers for chronic prostatitis. They conclude: "Our trial does not support these recommendations and should prompt reconsideration of the choice of initial therapy for these patients
Vapor Rub May Help Relieve Kids' Cold Symptoms
NEW YORK (Reuters Health) Nov 08 - Vapor rub may relieve a kid's nighttime cough and nasal congestion, suggests a new study funded by Vick's, the makers of the old-fashioned topical treatment.
Most children suffer between six and 10 colds every year, according to the National Institutes of Allergy and Infectious Diseases. And parents try lots of different remedies.
"There is no evidence to support the effectiveness of any of the oral over-the-counter cough and cold medicines for kids, even though they are used by one in 10 each week," Dr. Ian M. Paul of Penn State College of Medicine, in Hershey, Pennsylvania, told Reuters Health. "The American Academy of Pediatrics has been pretty clear and consistent on this."
Evidence supporting the use of vapor rub -- a commonly used concoction containing camphor, menthol and eucalyptus oils -- has also been lacking, added Dr. Paul.
After his team's previous research concluded that common cough suppressants and antihistamines (dextromethorphan and diphenhydramine) were no more effective than placebo or honey, Dr. Paul recalled frequent queries from people curious about vapor rub:
So he and his colleagues enrolled 138 children, averaging 6 years old, and randomly assigned each kid to receive petroleum-based Vick's VapoRub, or petroleum jelly without any active ingredients, or no treatment.
Parents in the two topical treatment groups applied vapor rub under their own noses before treating their kids. This way, with parents inhaling the characteristic smell of vapor rub, they wouldn't be able to tell what treatment the child was receiving.
Parents completed surveys at enrollment in the study and within 30 minutes of waking after the one night of study treatment. Results showed that kids receiving vapor rub experienced noticeably less cough, congestion and more restful sleep than kids in the other two groups.
Parents of the vapor-rubbed kids also reported improved sleep themselves, the authors said in their paper, published online today in Pediatrics.
"Kids and their parents slept better, and sleep is such an important thing for everyone, especially for kids that have to go to school the next day and parents who have to work," said Dr. Paul.
The rub didn't seem to relieve runny noses, and it caused mild irritation in nearly half of kids. On the other hand, more serious side effects have been associated with oral over-the-counter cold medicines, ranging from tachycardia to death.
Vicks VapoRub costs about $5 for 1.75 oz. There are also generic versions available.
How the concoction relieves cold symptoms is not entirely clear. The researchers suggest that the cooling sensation of menthol triggers the perception of improved airflow. But they aren't certain just how that might translate into improved symptoms.
"Parents want to give something. Pediatricians want to recommend something," Dr. Paul said.
"I think we've given them something to try, and evidence that it works," he added. "For kids ages 2 and up vapor rub is a generally safe and effective therapy."
The entire article is available online at no charge, at the URL listed below.
Pediatrics. Posted online November 8, 2010. Abstract
Most children suffer between six and 10 colds every year, according to the National Institutes of Allergy and Infectious Diseases. And parents try lots of different remedies.
"There is no evidence to support the effectiveness of any of the oral over-the-counter cough and cold medicines for kids, even though they are used by one in 10 each week," Dr. Ian M. Paul of Penn State College of Medicine, in Hershey, Pennsylvania, told Reuters Health. "The American Academy of Pediatrics has been pretty clear and consistent on this."
Evidence supporting the use of vapor rub -- a commonly used concoction containing camphor, menthol and eucalyptus oils -- has also been lacking, added Dr. Paul.
After his team's previous research concluded that common cough suppressants and antihistamines (dextromethorphan and diphenhydramine) were no more effective than placebo or honey, Dr. Paul recalled frequent queries from people curious about vapor rub:
So he and his colleagues enrolled 138 children, averaging 6 years old, and randomly assigned each kid to receive petroleum-based Vick's VapoRub, or petroleum jelly without any active ingredients, or no treatment.
Parents in the two topical treatment groups applied vapor rub under their own noses before treating their kids. This way, with parents inhaling the characteristic smell of vapor rub, they wouldn't be able to tell what treatment the child was receiving.
Parents completed surveys at enrollment in the study and within 30 minutes of waking after the one night of study treatment. Results showed that kids receiving vapor rub experienced noticeably less cough, congestion and more restful sleep than kids in the other two groups.
Parents of the vapor-rubbed kids also reported improved sleep themselves, the authors said in their paper, published online today in Pediatrics.
"Kids and their parents slept better, and sleep is such an important thing for everyone, especially for kids that have to go to school the next day and parents who have to work," said Dr. Paul.
The rub didn't seem to relieve runny noses, and it caused mild irritation in nearly half of kids. On the other hand, more serious side effects have been associated with oral over-the-counter cold medicines, ranging from tachycardia to death.
Vicks VapoRub costs about $5 for 1.75 oz. There are also generic versions available.
How the concoction relieves cold symptoms is not entirely clear. The researchers suggest that the cooling sensation of menthol triggers the perception of improved airflow. But they aren't certain just how that might translate into improved symptoms.
"Parents want to give something. Pediatricians want to recommend something," Dr. Paul said.
"I think we've given them something to try, and evidence that it works," he added. "For kids ages 2 and up vapor rub is a generally safe and effective therapy."
The entire article is available online at no charge, at the URL listed below.
Pediatrics. Posted online November 8, 2010. Abstract
Vicks VapoRub May Cause Respiratory Distress in Infants, Animal Study Suggests
Parents may ask about a Chest study suggesting that Vicks VapoRub may act as an airway irritant in very young children.
When an 18-month-old child was brought to an emergency room in severe respiratory distress after a grandparent applied Vicks VapoRub directly under her nose, clinicians investigated whether the ointment — a mixture of camphor, menthol, and eucalyptus oil — was at fault. (The product is not recommended for application to the nostril or for children under age 2 years.)
Their studies in healthy ferrets, which have an airway anatomy similar to humans, showed that mucus secretion increased and ciliary activity decreased in the presence of the ointment.
The authors conclude that the effect "may be of little physiologic consequence in older children and adults, but in infants and small children this potentially can lead to respiratory distress."
When an 18-month-old child was brought to an emergency room in severe respiratory distress after a grandparent applied Vicks VapoRub directly under her nose, clinicians investigated whether the ointment — a mixture of camphor, menthol, and eucalyptus oil — was at fault. (The product is not recommended for application to the nostril or for children under age 2 years.)
Their studies in healthy ferrets, which have an airway anatomy similar to humans, showed that mucus secretion increased and ciliary activity decreased in the presence of the ointment.
The authors conclude that the effect "may be of little physiologic consequence in older children and adults, but in infants and small children this potentially can lead to respiratory distress."
FDA Issues Alert on Topical Anesthetics
An FDA public health advisory reminds patients and physicians of potentially serious side effects from the improper use of topical anesthetics, including lidocaine, tetracaine, benzocaine, and prilocaine.
The latest advisory was prompted by a small study that tested whether lidocaine reduced discomfort during breast mammography. No serious adverse events were noted. However, the FDA remains concerned about the potential for seizures, irregular heartbeat, and breathing problems when topical anesthetics are applied over a large area or are covered by plastic wrap or a heating pad. Two deaths were previously reported in women using the anesthetics before laser hair removal.
The FDA urges patients to use the products sparingly in the weakest effective formulations
The latest advisory was prompted by a small study that tested whether lidocaine reduced discomfort during breast mammography. No serious adverse events were noted. However, the FDA remains concerned about the potential for seizures, irregular heartbeat, and breathing problems when topical anesthetics are applied over a large area or are covered by plastic wrap or a heating pad. Two deaths were previously reported in women using the anesthetics before laser hair removal.
The FDA urges patients to use the products sparingly in the weakest effective formulations
Escitalopram and Sertraline Top Comparison of 12 Newer Antidepressants
Escitalopram and sertraline seem the best choices in starting treatment for major depression, according to a meta-analysis published online in Lancet.
Researchers analyzed 117 randomized trials — comprising some 26,000 patients — of 12 new-generation antidepressants. The drugs were evaluated for efficacy and patient acceptability at the 8-week mark.
Among the conclusions:
Escitalopram, mirtazapine, sertraline, and venlafaxine were the most efficacious.
Escitalopram and sertraline showed the "best possible balance between efficacy and acceptability."
Given cost considerations, sertraline seemed the better of the two.
An editorialist, noting that the study protocol and data set are free online, writes: "A new gold standard of reliable information has been compiled for patients to review
Researchers analyzed 117 randomized trials — comprising some 26,000 patients — of 12 new-generation antidepressants. The drugs were evaluated for efficacy and patient acceptability at the 8-week mark.
Among the conclusions:
Escitalopram, mirtazapine, sertraline, and venlafaxine were the most efficacious.
Escitalopram and sertraline showed the "best possible balance between efficacy and acceptability."
Given cost considerations, sertraline seemed the better of the two.
An editorialist, noting that the study protocol and data set are free online, writes: "A new gold standard of reliable information has been compiled for patients to review
no mortality benefit from PSA testing meta analysis
BMJ has published two studies suggesting that less routine use of prostate-specific antigen (PSA) testing for cancer screening may be beneficial.
One study — a meta-analysis of six randomized controlled trials comprising almost 400,000 participants — finds no mortality benefit from PSA testing, with or without digital rectal exam.
The other study, using blood samples from nearly 1200 Swedish men at age 60 in 1981, finds that PSA levels at age 60 correlate very closely with the risk for metastatic cancer or death from prostate cancer by age 85. In fact, levels under 1 ng/mL were associated with a low likelihood of suffering prostate cancer metastases (0.5%).
An editorialist says that "elderly men and those with low risk of disease could be tested less often, if at all."
One study — a meta-analysis of six randomized controlled trials comprising almost 400,000 participants — finds no mortality benefit from PSA testing, with or without digital rectal exam.
The other study, using blood samples from nearly 1200 Swedish men at age 60 in 1981, finds that PSA levels at age 60 correlate very closely with the risk for metastatic cancer or death from prostate cancer by age 85. In fact, levels under 1 ng/mL were associated with a low likelihood of suffering prostate cancer metastases (0.5%).
An editorialist says that "elderly men and those with low risk of disease could be tested less often, if at all."
Two Testosterone Gels Get Boxed Warning
The FDA is requiring that two prescription testosterone gels — AndroGel 1% and Testim 1% — carry boxed warnings after reports of adverse events in children who had secondary exposure to the gels.
Eight children (aged 9 months to 5 years) were inadvertently exposed to the gels through skin-to-skin contact with people using the products, which are approved for men who produce low levels of testosterone. The adverse events in children included inappropriate genital enlargement, early pubic hair growth, advanced bone age, increased libido, and aggressive behavior. Usually, these symptoms regressed when the children were no longer exposed.
To minimize the risk for secondary exposure, the FDA recommends that adults using the gels:
wash their hands after every use;
cover the application area with clothing after the gel has dried;
wash the area when skin-to-skin contact with another person is expected.
In addition, other people should not touch the application area
Eight children (aged 9 months to 5 years) were inadvertently exposed to the gels through skin-to-skin contact with people using the products, which are approved for men who produce low levels of testosterone. The adverse events in children included inappropriate genital enlargement, early pubic hair growth, advanced bone age, increased libido, and aggressive behavior. Usually, these symptoms regressed when the children were no longer exposed.
To minimize the risk for secondary exposure, the FDA recommends that adults using the gels:
wash their hands after every use;
cover the application area with clothing after the gel has dried;
wash the area when skin-to-skin contact with another person is expected.
In addition, other people should not touch the application area
False Positives Common During Cancer Screenings
Cancer screening frequently yields false positives — with resulting invasive procedures — reports Annals of Family Medicine.
Researchers studied nearly 68,500 adults, aged 55 to 74, who underwent up to 14 screenings over 3 years in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Tests included digital rectal examination plus prostate-specific antigen measurement; chest x-ray; flexible sigmoidoscopy; and cancer antigen 125 testing plus transvaginal ultrasound.
Among the findings:
The risk for having one false positive after four tests was 37% among men and 26% among women; after 14 tests, risks rose to 60% and 49%, respectively.
The risk for undergoing a false-positive–prompted invasive procedure after four tests was 17% among men and 12% among women; after 14 tests, risks were 28% and 22%, respectively.
Sigmoidoscopy accounted for the most false positives and related procedures.
The researchers conclude that providers "should educate patients about the likelihood of false positives and resulting diagnostic interventions when counseling about cancer screening."
Researchers studied nearly 68,500 adults, aged 55 to 74, who underwent up to 14 screenings over 3 years in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Tests included digital rectal examination plus prostate-specific antigen measurement; chest x-ray; flexible sigmoidoscopy; and cancer antigen 125 testing plus transvaginal ultrasound.
Among the findings:
The risk for having one false positive after four tests was 37% among men and 26% among women; after 14 tests, risks rose to 60% and 49%, respectively.
The risk for undergoing a false-positive–prompted invasive procedure after four tests was 17% among men and 12% among women; after 14 tests, risks were 28% and 22%, respectively.
Sigmoidoscopy accounted for the most false positives and related procedures.
The researchers conclude that providers "should educate patients about the likelihood of false positives and resulting diagnostic interventions when counseling about cancer screening."
Flomax Associated with Complications After Ophthalmologic Surgery
Men taking tamsulosin (Flomax) for benign prostatic hypertrophy face higher risks for intraoperative floppy iris syndrome and its complications (retinal detachment, lost lens or fragments, or endophthalmitis), according to a retrospective study in JAMA.
Researchers used Ontario health databases to examine a possible association between exposure to tamsulosin or other alpha-blocking drugs in men aged 66 or older before cataract surgery and adverse outcomes within 2 weeks after the operation. They found that men who experienced complications were more than twice as likely to have been exposed to tamsulosin (but not the other drugs) in the 2 weeks before surgery, compared with those without adverse events.
The authors calculate a number needed to harm of 255.
Tamsulosin selectively targets sites common to both bladder and iris relaxation, and the authors speculate this may be the reason for the adverse effects. An editorialist suggests that tamsulosin may require a black-box warning to caution both patients and surgeons
Researchers used Ontario health databases to examine a possible association between exposure to tamsulosin or other alpha-blocking drugs in men aged 66 or older before cataract surgery and adverse outcomes within 2 weeks after the operation. They found that men who experienced complications were more than twice as likely to have been exposed to tamsulosin (but not the other drugs) in the 2 weeks before surgery, compared with those without adverse events.
The authors calculate a number needed to harm of 255.
Tamsulosin selectively targets sites common to both bladder and iris relaxation, and the authors speculate this may be the reason for the adverse effects. An editorialist suggests that tamsulosin may require a black-box warning to caution both patients and surgeons
Daily Aspirin Associated with Reduced Cancer Mortality in Meta-Analysis
Daily aspirin use confers a reduction in risk for death from several common cancers, in addition to its known benefit on colorectal cancer risk, according to a Lancet meta-analysis.
Researchers pooled data from eight studies including some 25,000 individuals assigned to daily aspirin or control therapy for at least 4 years. (The studies originally investigated aspirin's effects on cardiovascular events.)
Overall, aspirin recipients showed a lower odds ratio for cancer deaths during the trials; when individual patient data were available (on some 23,500 patients), the decrease appeared only after 5 years of aspirin use. The apparent benefit increased with duration of treatment, was not related to daily dose, and seemed confined to adenocarcinomas (e.g., esophageal and lung).
In three U.K. trials, cancer registries were used to extend follow-up to establish 20-year risks, which remained lower among aspirin recipients even after the end of their trial participation
Researchers pooled data from eight studies including some 25,000 individuals assigned to daily aspirin or control therapy for at least 4 years. (The studies originally investigated aspirin's effects on cardiovascular events.)
Overall, aspirin recipients showed a lower odds ratio for cancer deaths during the trials; when individual patient data were available (on some 23,500 patients), the decrease appeared only after 5 years of aspirin use. The apparent benefit increased with duration of treatment, was not related to daily dose, and seemed confined to adenocarcinomas (e.g., esophageal and lung).
In three U.K. trials, cancer registries were used to extend follow-up to establish 20-year risks, which remained lower among aspirin recipients even after the end of their trial participation
Sunday, December 5, 2010
Antidepressants Linked to Increased Risk for Death, Stroke in Postmenopausal Women
December 22, 2009 — Postmenopausal women taking either a tricyclic antidepressant (TCA) or a selective serotonin-reuptake inhibitor (SSRI) appear to be at increased risk for all-cause mortality, and SSRI users seem to be at increased risk for hemorrhagic and fatal stroke, although the absolute event risks are low, according to an analysis from the Women's Health Initiative (WHI) study.
In an article published in the December issue of the Archives of Internal Medicine, Jordan Smoller, MD, from Massachusetts General Hospital, Boston, and colleagues report that new use of either a TCA or an SSRI during a mean follow-up of 5.9 years was not significantly associated with an increased risk for coronary heart disease (CHD) in this large prospective cohort of postmenopausal women.
In contrast, compared with women who did not use antidepressants, "those using SSRIs had a 45% increased relative risk of incidence stroke and a 32% increased risk of death in models stratified on propensity and adjusted for multiple covariates," the investigators report. TCA use in turn was associated with a 67% higher relative risk for all-cause death (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.33 - 2.09). The TCAs also increase stroke risk, but not significantly so.
In an article published in the December issue of the Archives of Internal Medicine, Jordan Smoller, MD, from Massachusetts General Hospital, Boston, and colleagues report that new use of either a TCA or an SSRI during a mean follow-up of 5.9 years was not significantly associated with an increased risk for coronary heart disease (CHD) in this large prospective cohort of postmenopausal women.
In contrast, compared with women who did not use antidepressants, "those using SSRIs had a 45% increased relative risk of incidence stroke and a 32% increased risk of death in models stratified on propensity and adjusted for multiple covariates," the investigators report. TCA use in turn was associated with a 67% higher relative risk for all-cause death (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.33 - 2.09). The TCAs also increase stroke risk, but not significantly so.
Friday, December 3, 2010
Glycated Hemoglobin Better Than Fasting Glucose for Predicting Cardiovascular Risk
Glycated hemoglobin levels, especially above 6.0%, are better than fasting glucose for predicting long-term cardiovascular risk, the New England Journal of Medicine reports.
Researchers measured glycated hemoglobin and fasting glucose in some 11,000 adults without diabetes or cardiovascular disease and followed them for a median of 14 years. Compared with hemoglobin levels of 5.0% to 5.5%, higher values — especially above 6% — were associated with significantly increased risks for diabetes, coronary heart disease, and stroke. Associations between hemoglobin and all-cause mortality were also significant, but formed a J-shaped curve, with the lowest and highest levels being predictive of death.
These findings held true even after adjustment for fasting glucose.
The authors say their findings "may add to the evidence supporting the use of glycated hemoglobin as a diagnostic test for diabetes."
Researchers measured glycated hemoglobin and fasting glucose in some 11,000 adults without diabetes or cardiovascular disease and followed them for a median of 14 years. Compared with hemoglobin levels of 5.0% to 5.5%, higher values — especially above 6% — were associated with significantly increased risks for diabetes, coronary heart disease, and stroke. Associations between hemoglobin and all-cause mortality were also significant, but formed a J-shaped curve, with the lowest and highest levels being predictive of death.
These findings held true even after adjustment for fasting glucose.
The authors say their findings "may add to the evidence supporting the use of glycated hemoglobin as a diagnostic test for diabetes."
Association Found Between Vitamin E Supplements and Hemorrhagic Stroke
Vitamin E supplements have no effect on overall stroke incidence, but when stroke type is examined, the supplements significantly increase risk for hemorrhagic stroke, according to a BMJ meta-analysis.
Researchers examined data from nine trials encompassing some 120,000 subjects who'd been randomized to receive vitamin E or placebo and were followed for more than 1 year. Rates of stroke overall did not differ between groups. However, when the type of stroke was examined, ischemic strokes were significantly fewer among the vitamin recipients, while hemorrhagic strokes were significantly increased — by some 20%.
The authors say that the contrasting effects have tended to obscure vitamin E's hemorrhagic risks. They write that the mechanism behind the effect is unknown and that it may stem from vitamin E's interference with a vitamin-K-dependent clotting factor. They conclude that "indiscriminate widespread use of vitamin E should be cautioned against."
Researchers examined data from nine trials encompassing some 120,000 subjects who'd been randomized to receive vitamin E or placebo and were followed for more than 1 year. Rates of stroke overall did not differ between groups. However, when the type of stroke was examined, ischemic strokes were significantly fewer among the vitamin recipients, while hemorrhagic strokes were significantly increased — by some 20%.
The authors say that the contrasting effects have tended to obscure vitamin E's hemorrhagic risks. They write that the mechanism behind the effect is unknown and that it may stem from vitamin E's interference with a vitamin-K-dependent clotting factor. They conclude that "indiscriminate widespread use of vitamin E should be cautioned against."
Friday, November 19, 2010
vitamin e ups/downs hemorrhagic/ischemic strokes for a wash
Vitamin E supplements have no effect on overall stroke incidence, but when stroke type is examined, the supplements significantly increase risk for hemorrhagic stroke, according to a BMJ meta-analysis.
Researchers examined data from nine trials encompassing some 120,000 subjects who'd been randomized to receive vitamin E or placebo and were followed for more than 1 year. Rates of stroke overall did not differ between groups. However, when the type of stroke was examined, ischemic strokes were significantly fewer among the vitamin recipients, while hemorrhagic strokes were significantly increased — by some 20%.
The authors say that the contrasting effects have tended to obscure vitamin E's hemorrhagic risks. They write that the mechanism behind the effect is unknown and that it may stem from vitamin E's interference with a vitamin-K-dependent clotting factor. They conclude that "indiscriminate widespread use of vitamin E should be cautioned against."
Researchers examined data from nine trials encompassing some 120,000 subjects who'd been randomized to receive vitamin E or placebo and were followed for more than 1 year. Rates of stroke overall did not differ between groups. However, when the type of stroke was examined, ischemic strokes were significantly fewer among the vitamin recipients, while hemorrhagic strokes were significantly increased — by some 20%.
The authors say that the contrasting effects have tended to obscure vitamin E's hemorrhagic risks. They write that the mechanism behind the effect is unknown and that it may stem from vitamin E's interference with a vitamin-K-dependent clotting factor. They conclude that "indiscriminate widespread use of vitamin E should be cautioned against."
Cymbalta Approved for Chronic Musculoskeletal Pain
The FDA has approved the use of duloxetine (Cymbalta), a non-narcotic, to treat chronic musculoskeletal pain, including low back pain and osteoarthritis, the agency announced on Thursday.
The drug was previously approved as maintenance therapy in major depression and to treat generalized anxiety disorder, diabetic peripheral neuropathy, and fibromyalgia. The manufacturer says it is uncertain how duloxetine relieves pain, but it is believed to increase activity of serotonin and norepinephrine in the central nervous system.
Duloxetine's label includes a warning about the risk for increased suicidality among children, adolescents, and young adults.
The drug was previously approved as maintenance therapy in major depression and to treat generalized anxiety disorder, diabetic peripheral neuropathy, and fibromyalgia. The manufacturer says it is uncertain how duloxetine relieves pain, but it is believed to increase activity of serotonin and norepinephrine in the central nervous system.
Duloxetine's label includes a warning about the risk for increased suicidality among children, adolescents, and young adults.
Thursday, November 18, 2010
Featured in Journal Watch: Nothing to Cough About — A Treatment for Involuntary Laughing and Crying
Dextromethorphan with quinidine appears safe and effective for a syndrome seen in neurological disorders.
Anacetrapib predecessor is torcetrapib
Anacetrapib, a cholesteryl ester transfer protein inhibitor, had "robust effects" on LDL and HDL cholesterol levels in an industry-funded, phase III study presented Wednesday at the American Heart Association meeting and published in the New England Journal of Medicine.
Some 1600 adults who were already taking statins were randomized to receive 100 mg of anacetrapib or placebo daily for 18 months. At 6 months, the mean LDL level had dropped from 81 to 45 mg/dL with anacetrapib, compared with a drop from 82 to 77 mg/dL with placebo. Similarly, mean HDL increased significantly more with the drug (from 41 to 101 mg/dL) than with placebo (40 to 46 mg/dL).
Throughout treatment, the groups did not differ in cardiovascular events or in blood pressure, electrolyte, or aldosterone levels (such side effects kept anacetrapib's predecessor, torcetrapib, from reaching the market).
The authors call for a larger clinical trial, noting that this study "is too small to provide definitive results regarding the overall safety or efficacy of anacetrapib."
Some 1600 adults who were already taking statins were randomized to receive 100 mg of anacetrapib or placebo daily for 18 months. At 6 months, the mean LDL level had dropped from 81 to 45 mg/dL with anacetrapib, compared with a drop from 82 to 77 mg/dL with placebo. Similarly, mean HDL increased significantly more with the drug (from 41 to 101 mg/dL) than with placebo (40 to 46 mg/dL).
Throughout treatment, the groups did not differ in cardiovascular events or in blood pressure, electrolyte, or aldosterone levels (such side effects kept anacetrapib's predecessor, torcetrapib, from reaching the market).
The authors call for a larger clinical trial, noting that this study "is too small to provide definitive results regarding the overall safety or efficacy of anacetrapib."
Monday, August 30, 2010
Emerging Antibiotic Resistance in Enterobacteria Prompts Global Concern
Patients may ask about a widely reported study describing emerging bacterial resistance to certain antibiotics. The study, published in Lancet Infectious Diseases, shows that a gene in E. coli and K. pneumoniae confers resistance to carbapenem antibiotics, especially in patients from India and Pakistan.
Researchers describe 180 isolates from patients in India, Pakistan, the U.K., and other countries. The isolates produce an enzyme, New Delhi metallo-beta-lactamase 1 (NDM-1) whose gene can be carried both on bacterial chromosomes and plasmids. NDM-1 was identified in up to 44% of carbapenem-resistant isolates in U.K. patients, some of whom had undergone elective surgical procedures in India or Pakistan.
Although few people have been identified with NDM-1, the authors call the potential for wider spread "clear and frightening." A commentator warns that "patients who have had medical procedures in India should be actively screened for multiresistant bacteria before they receive medical care in their home country."
Researchers describe 180 isolates from patients in India, Pakistan, the U.K., and other countries. The isolates produce an enzyme, New Delhi metallo-beta-lactamase 1 (NDM-1) whose gene can be carried both on bacterial chromosomes and plasmids. NDM-1 was identified in up to 44% of carbapenem-resistant isolates in U.K. patients, some of whom had undergone elective surgical procedures in India or Pakistan.
Although few people have been identified with NDM-1, the authors call the potential for wider spread "clear and frightening." A commentator warns that "patients who have had medical procedures in India should be actively screened for multiresistant bacteria before they receive medical care in their home country."
Sunday, August 29, 2010
THIAZIDE DIURETICS,BBLCKERS UP DIABETES SLIGHTLY
Antihypertensive Drugs and Risk for Diabetes Prospective data from three large cohorts add to the evidence that thiazide diuretics and {beta}-blockers can cause glucose intolerance. In several studies, thiazide diuretics and ß-blockers have been associated with increased incidence of diabetes. Now, researchers have examined this association in three large prospective observational studies, the Nurses' Health Studies I and II and the Health Professionals Follow-up Study. About 75,000 participants with hypertension, but not diabetes, were followed for 8 to 16 years. New-onset diabetes was reported by 3589 participants during follow-up. After adjustment for potentially confounding variables, thiazide use (compared with non-use) was associated independently with increased risk for incident diabetes; relative risk ranged from 1.2 to 1.5, depending on the cohort. ß-blocker use was associated with increased diabetes risk in men and in older women (RRs, 1.2 and 1.3, respectively). No association was noted between use of calcium-channel blockers and diabetes risk. Angiotensin-converting–enzyme (ACE) inhibitor use, recorded only in older women, also was not associated with diabetes. Comment: This study reinforces previous research suggesting that thiazide diuretics and ß-blockers can cause glucose intolerance. In the randomized ALLHAT trial, thiazide users were more likely to develop diabetes than were users of calcium-channel blockers and ACE inhibitors, yet their mortality and cardiovascular morbidity rates were not increased (Journal Watch Jan 14 2003). Nevertheless, these results raise questions about whether we should lean toward drugs other than thiazides and ß-blockers when choosing first-line antihypertensives for patients with impaired glucose tolerance. — Allan S. Brett, MD Published in Journal Watch May 30, 2006 Source Taylor EN et al. Antihypertensive medications and the risk of incident type 2 diabetes. Diabetes Care 2006 May; 29:1065-70. [Original article][Medline abstract] ...More
Thursday, August 19, 2010
Anticancer Vitamins du Jour—The ABCED's So Far
Introduction
It started 30 years ago with vitamin A: the idea that some cancers might be caused by vitamin deficiencies. Animal experimental models led us to the notion that cancer risk might be "materially" reduced by supplementation with beta-carotene, a retinol precursor.[1] Although that idea was seductive, we were all disappointed when 2 large randomized controlled trials that began in 1985 in Finland and the United States reported an 18% increased risk of lung cancer caused by high-dose beta-carotene supplementation and a 28% increased lung cancer risk caused by a combination of beta-carotene and retinol.[2, 3] The vitamin A era was over.
Next came the B vitamins. Again, based on animal experimental evidence and supported by epidemiologic evidence of connections between diets low in B vitamins and increased cancer risk, a large randomized controlled trial was begun in 1985 in central China, where micronutrient deficiency was common and where rates of cancers of the stomach and esophagus were extraordinarily high. Nonetheless, several years of supplementation with a combination of riboflavin (vitamin B2) and niacin (vitamin B3) had no effect on incidence of upper gastrointestinal cancers.[4] Interest in folic acid (vitamin B9) persisted, though, in part because of its striking effect on neural tube birth defects, coupled with speculation about possible benefits of food fortification for diseases such as colorectal cancer that were inversely associated with diets rich in folate-containing foods and supplements. However, a 7-year randomized controlled trial found that high-dose folic acid supplements actually increased risk of colorectal adenomas.[5] The vitamin B era was over.
Next came vitamin C, a popular charge led by none other than Linus Pauling, the brilliant and charismatic 2-time Nobel laureate. Of all the cancers thought to be related to vitamin C deficiency, gastric cancer led the way, and of all the places on Earth where a vitamin C deficiency correction trial might yield benefits for gastric cancer, Linxian, China, would be the best. Indeed, vitamin C was tested in the Linxian trial, but just as for the B vitamins, vitamin C produced no change in gastric cancer rates.[6]
Next, slightly out of alphabetical order, came vitamin E. In 1993, we launched headlong into a love affair with vitamin E fueled by compelling observations that those who chose to take vitamin E supplements were at lower risk of heart disease.[7, 8] Vitamin E supplementation became the rage as several large, randomized controlled trials were mounted. When those results finally came in, the findings were again disappointing: vitamin E supplementation offered no benefit for heart disease, and it slightly increased overall mortality.[9, 10] In the meantime, though, because of a secondary observation that prostate cancer incidence was lower in the vitamin E arm of the same Finnish trial that tested beta-carotene (vitamin E had also been included as a factor),[11] a large factorial trial of vitamin E (and selenium) was carried out for reducing prostate cancer incidence. Disappointment again: there was no effect of either selenium or vitamin E on incidence of prostate cancer.[12] The vitamin E era ended in a whimper.
Over 2 decades of searching for an anticancer vitamin, we had seemed to skip over vitamin D in its proper alphabetical sequence. In my role as a member of the World Cancer Research Fund Expert Panel that considered the evidence from commissioned meta-analyses of the world's literature on nutritional epidemiology, I remember feeling concern as we finished our work that we might have underestimated the importance of vitamin D because the bulk of the evidence available at that time was derived from ecologic studies.[13] Subsequently, the International Agency for Research on Cancer conducted a comprehensive review of the evidence for vitamin D and cancer prevention, concluding that vitamin D may play a protective role in colorectal cancer, but not for prostate cancer, and that the evidence is weak for breast cancer.[14] The conclusion by the International Agency for Research on Cancer about the weakness of the evidence for breast cancer has been a source of controversy among vitamin D protagonists,[15, 16] but subsequent nested cohort studies have found no relation between breast cancer risk and circulating levels of vitamin D.[17, 18]
Nonetheless, vitamin D remains the cancer-preventing vitamin du jour. Just search the phrase "vitamin D and cancer" on the Internet to see what sorts of information and products are now being marketed to the public. Vitamin D is the new vitamin A, the new folic acid, the new vitamin C, the new vitamin E.
An outstanding set of papers in this issue of the American Journal of Epidemiology reports on findings about the relation between circulating levels of vitamin D and subsequent cancer risk in a set of pooled cohort studies conducted in the United States, Europe, and Asia. These studies found no suggestion of an inverse association between vitamin D levels in the circulation and later incidence of 6 types of cancers (upper gastrointestinal, ovary, endometrial, pancreatic, kidney, and non-Hodgkin lymphoma). Although these cancers are characterized as "rarer," this set of sites collectively accounts for about a quarter of all deaths from cancer in the United States. These studies offer compelling evidence against the hypothesis that circulating levels of vitamin D are relevant to risk of these cancers. This new information is important because an International Agency for Research on Cancer review had decided that evidence was previously insufficient to draw conclusions about these 6 cancer sites.[14]
Whenever null findings are found, it is important to consider the usual suspect reasons, and the authors of these papers have done an outstanding job of that. The size of this pooled analysis is large enough to discount concerns about low statistical power; there is a good level of internal consistency in the previously documented associations between vitamin D levels and factors such as seasonality, race, gender, diet, physical activity, and body mass index; there was substantial interindividual variation in these cohorts; and there did not seem to be confusion between confounding factors or factors potentially in the causal pathway. The question as to whether the time interval studied was the correct one remains unanswered, however. If the geographic ecologic associations between sun exposure and cancer risk are, in fact, due to long-term cumulative effects of lifelong vitamin D exposures, then cohort studies in adulthood will not be fully informative. However, it is important to note that this longer-term ecologic possibility is not consistent with the other ecologic observation of seasonal variation in cancer incidence that is often also attributed to vitamin D levels in the circulation.[19]
The only association observed in this set of 6 analyses was a troubling one: that risk of pancreatic cancer was doubled for those in the highest quintile of circulating vitamin D levels. This observation is disconcerting both because pancreatic cancer is now the fourth leading cause of cancer death in the United States and because the proponents of the vitamin D hypothesis are now arguing that substantially elevating circulating blood concentrations into that range should be a nutritional policy objective for the general population.[15, 16] As pointed out by Dr. Helzlsouer[20] in this issue of the Journal, many ongoing randomized controlled trials are now using quite high doses of vitamin D. As we await clearer evidence of benefits from those trials, we will also need to be prepared to be vigilant about their individual and collective power to assess any potential harms.[21, 22]
It is timely for us to now reflect on the history of the past 25 years of our alphabetical approach to studying single vitamin deficiency states as causal factors for cancer. We have learned some hard lessons along the alphabetical way. We now know that supernutritional levels of vitamins taken as supplements do not emulate the apparent benefits of diets high in foods that contain those vitamins,[13] and we now know that taking vitamins in supernutritional doses can cause serious harm. In short, we have found that the reality of human biology is far more complex than is suggested by our simple ideas.
Finally, it is important to recognize the efforts of the many Vitamin D Pooling Project of Rarer Cancers collaborators who carried out such a remarkable set of studies. As pointed out by the Institute of Medicine, we are now in an era of "big science," in which definitive answers to big questions will increasingly require massive efforts and large-scale collaborations.[23] Carrying out these types of collaborations requires foresight, skill, and patience. Large-scale collaborations are critically important, though, for our improved understanding of the true nature of the determinants of human health. The dual problems of type 1 and type 2 errors have best been exemplified in genetic epidemiology, but false discovery has been a problem in nutritional epidemiology as well. Even though there was consistency in the overall null observations across most of the cohorts in this pooled analysis, there was some variation. It is easy to imagine that, without this collaborative analysis, we might have been led down several blind alleys derived from analyses of various subgroups and interactions. We all should be grateful to the Vitamin D Pooling Project of Rarer Cancers investigators for having saved us from years of false leads, as well as for their vision and skill in carrying out this outstanding collaborative project.
[ CLOSE WINDOW ]ReferencesPeto R, Doll R, Buckley JD, et al. Can dietary beta-carotene materially reduce human cancer rates? Nature 1981;290(5803):201–208.Albanes D, Heinonen OP, Huttunen JK, et al. Effects of alpha-tocopherol and beta-carotene supplements on cancer incidence in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study. Am J Clin Nutr 1995;62(6, suppl):1427S–1430S.Omenn GS, Goodman GE, Thornquist MD, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 1996;334(18):1150–1155.Blot WJ, Li JY, Taylor PR, et al. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl Cancer Inst 1993;85(18):1483–1492.Cole BF, Baron JA, Sandler RS, et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA 2007;297(21):2351–2359.Ziegler RG, Byers T. Re: Health claims about vitamin C and cancer. J Natl Cancer Inst 1994;86(11):871–872.Stampfer MJ, Hennekens CH, Manson JE, et al. Vitamin E consumption and the risk of coronary disease in women. N Engl J Med 1993;328(20):1444–1449.Rimm EB, Stampfer MJ, Ascherio A, et al. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med 1993;328(20):1450–1456.Yusuf S, Dagenais G, Pogue J, et al. Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000;342(3):154–160.Miller ER III, Pastor-Barriuso R, Dalal D, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005;142(1):37–46.Virtamo J, Pietinen P, Huttunen JK, et al. Incidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: a postintervention follow-up. JAMA 2003;290(4):476–485.Lippman SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2009;301(1):39–51.World Cancer Research Fund/American Institute for Cancer Research. Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective. Washington, DC: AICR; 2007.IARC. Vitamin D and Cancer. IARC Working Group Reports, vol 5. Lyon, France: International Agency for Research on Cancer; 2008. http://www.iarc.fr/en/publications/pdfs-online/wrk/wrk5/Report_VitD.pdf).Garland CF, Gorham ED, Mohr SB, et al. Vitamin D for cancer prevention: global perspective. Ann Epidemiol 2009;19(7):468–483.Grant WB. A critical review of vitamin D and cancer: a report of the IARC Working Group. Dermatoendocrinol 2009;1(1):25–33.McCullough ML, Stevens VL, Patel R, et al. Serum 25-hydroxyvitamin D concentrations and postmenopausal breast cancer risk: a nested case control study in the Cancer Prevention Study-II Nutrition Cohort [published online ahead of print August 28, 2009]. Breast Cancer Res. (doi:10.1186/bcr2356).Freedman DM, Chang SC, Falk RT, et al. Serum levels of vitamin D metabolites and breast cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cancer Epidemiol Biomarkers Prev 2008;17(4):889–894.Oh EY, Ansell C, Nawaz H, et al. Global breast cancer seasonality [published online ahead of print February 4, 2010]. Breast Cancer Res Treat. (doi:10.1007/s10549-009-0676-7).Helzlsouer KJ for the VDPP Steering Committee. Overview of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Am J Epidemiol 2010;172(1):4–9.Goodwin PJ. Vitamin D in cancer patients: above all, do no harm. J Clin Oncol 2009;27(13):2117–2119.Olsen A, Egeberg R, Tjønneland A. Re: Calcium plus vitamin D supplementation and the risk of breast cancer [letter]. J Natl Cancer Inst 2009;101(9):690.Nass S, Stillman B, eds. Large-Scale Biomedical Science: Exploring Strategies for Future Research. Washington, DC: National Cancer Policy Board and Division of Earth and Life Sciences, Institute of Medicine, National Research Council; 2003.
Colorado School of Public Health, University of Colorado Cancer Center, Aurora, CO 80045 (e-mail: tim.byers@ucdenver.edu)
It started 30 years ago with vitamin A: the idea that some cancers might be caused by vitamin deficiencies. Animal experimental models led us to the notion that cancer risk might be "materially" reduced by supplementation with beta-carotene, a retinol precursor.[1] Although that idea was seductive, we were all disappointed when 2 large randomized controlled trials that began in 1985 in Finland and the United States reported an 18% increased risk of lung cancer caused by high-dose beta-carotene supplementation and a 28% increased lung cancer risk caused by a combination of beta-carotene and retinol.[2, 3] The vitamin A era was over.
Next came the B vitamins. Again, based on animal experimental evidence and supported by epidemiologic evidence of connections between diets low in B vitamins and increased cancer risk, a large randomized controlled trial was begun in 1985 in central China, where micronutrient deficiency was common and where rates of cancers of the stomach and esophagus were extraordinarily high. Nonetheless, several years of supplementation with a combination of riboflavin (vitamin B2) and niacin (vitamin B3) had no effect on incidence of upper gastrointestinal cancers.[4] Interest in folic acid (vitamin B9) persisted, though, in part because of its striking effect on neural tube birth defects, coupled with speculation about possible benefits of food fortification for diseases such as colorectal cancer that were inversely associated with diets rich in folate-containing foods and supplements. However, a 7-year randomized controlled trial found that high-dose folic acid supplements actually increased risk of colorectal adenomas.[5] The vitamin B era was over.
Next came vitamin C, a popular charge led by none other than Linus Pauling, the brilliant and charismatic 2-time Nobel laureate. Of all the cancers thought to be related to vitamin C deficiency, gastric cancer led the way, and of all the places on Earth where a vitamin C deficiency correction trial might yield benefits for gastric cancer, Linxian, China, would be the best. Indeed, vitamin C was tested in the Linxian trial, but just as for the B vitamins, vitamin C produced no change in gastric cancer rates.[6]
Next, slightly out of alphabetical order, came vitamin E. In 1993, we launched headlong into a love affair with vitamin E fueled by compelling observations that those who chose to take vitamin E supplements were at lower risk of heart disease.[7, 8] Vitamin E supplementation became the rage as several large, randomized controlled trials were mounted. When those results finally came in, the findings were again disappointing: vitamin E supplementation offered no benefit for heart disease, and it slightly increased overall mortality.[9, 10] In the meantime, though, because of a secondary observation that prostate cancer incidence was lower in the vitamin E arm of the same Finnish trial that tested beta-carotene (vitamin E had also been included as a factor),[11] a large factorial trial of vitamin E (and selenium) was carried out for reducing prostate cancer incidence. Disappointment again: there was no effect of either selenium or vitamin E on incidence of prostate cancer.[12] The vitamin E era ended in a whimper.
Over 2 decades of searching for an anticancer vitamin, we had seemed to skip over vitamin D in its proper alphabetical sequence. In my role as a member of the World Cancer Research Fund Expert Panel that considered the evidence from commissioned meta-analyses of the world's literature on nutritional epidemiology, I remember feeling concern as we finished our work that we might have underestimated the importance of vitamin D because the bulk of the evidence available at that time was derived from ecologic studies.[13] Subsequently, the International Agency for Research on Cancer conducted a comprehensive review of the evidence for vitamin D and cancer prevention, concluding that vitamin D may play a protective role in colorectal cancer, but not for prostate cancer, and that the evidence is weak for breast cancer.[14] The conclusion by the International Agency for Research on Cancer about the weakness of the evidence for breast cancer has been a source of controversy among vitamin D protagonists,[15, 16] but subsequent nested cohort studies have found no relation between breast cancer risk and circulating levels of vitamin D.[17, 18]
Nonetheless, vitamin D remains the cancer-preventing vitamin du jour. Just search the phrase "vitamin D and cancer" on the Internet to see what sorts of information and products are now being marketed to the public. Vitamin D is the new vitamin A, the new folic acid, the new vitamin C, the new vitamin E.
An outstanding set of papers in this issue of the American Journal of Epidemiology reports on findings about the relation between circulating levels of vitamin D and subsequent cancer risk in a set of pooled cohort studies conducted in the United States, Europe, and Asia. These studies found no suggestion of an inverse association between vitamin D levels in the circulation and later incidence of 6 types of cancers (upper gastrointestinal, ovary, endometrial, pancreatic, kidney, and non-Hodgkin lymphoma). Although these cancers are characterized as "rarer," this set of sites collectively accounts for about a quarter of all deaths from cancer in the United States. These studies offer compelling evidence against the hypothesis that circulating levels of vitamin D are relevant to risk of these cancers. This new information is important because an International Agency for Research on Cancer review had decided that evidence was previously insufficient to draw conclusions about these 6 cancer sites.[14]
Whenever null findings are found, it is important to consider the usual suspect reasons, and the authors of these papers have done an outstanding job of that. The size of this pooled analysis is large enough to discount concerns about low statistical power; there is a good level of internal consistency in the previously documented associations between vitamin D levels and factors such as seasonality, race, gender, diet, physical activity, and body mass index; there was substantial interindividual variation in these cohorts; and there did not seem to be confusion between confounding factors or factors potentially in the causal pathway. The question as to whether the time interval studied was the correct one remains unanswered, however. If the geographic ecologic associations between sun exposure and cancer risk are, in fact, due to long-term cumulative effects of lifelong vitamin D exposures, then cohort studies in adulthood will not be fully informative. However, it is important to note that this longer-term ecologic possibility is not consistent with the other ecologic observation of seasonal variation in cancer incidence that is often also attributed to vitamin D levels in the circulation.[19]
The only association observed in this set of 6 analyses was a troubling one: that risk of pancreatic cancer was doubled for those in the highest quintile of circulating vitamin D levels. This observation is disconcerting both because pancreatic cancer is now the fourth leading cause of cancer death in the United States and because the proponents of the vitamin D hypothesis are now arguing that substantially elevating circulating blood concentrations into that range should be a nutritional policy objective for the general population.[15, 16] As pointed out by Dr. Helzlsouer[20] in this issue of the Journal, many ongoing randomized controlled trials are now using quite high doses of vitamin D. As we await clearer evidence of benefits from those trials, we will also need to be prepared to be vigilant about their individual and collective power to assess any potential harms.[21, 22]
It is timely for us to now reflect on the history of the past 25 years of our alphabetical approach to studying single vitamin deficiency states as causal factors for cancer. We have learned some hard lessons along the alphabetical way. We now know that supernutritional levels of vitamins taken as supplements do not emulate the apparent benefits of diets high in foods that contain those vitamins,[13] and we now know that taking vitamins in supernutritional doses can cause serious harm. In short, we have found that the reality of human biology is far more complex than is suggested by our simple ideas.
Finally, it is important to recognize the efforts of the many Vitamin D Pooling Project of Rarer Cancers collaborators who carried out such a remarkable set of studies. As pointed out by the Institute of Medicine, we are now in an era of "big science," in which definitive answers to big questions will increasingly require massive efforts and large-scale collaborations.[23] Carrying out these types of collaborations requires foresight, skill, and patience. Large-scale collaborations are critically important, though, for our improved understanding of the true nature of the determinants of human health. The dual problems of type 1 and type 2 errors have best been exemplified in genetic epidemiology, but false discovery has been a problem in nutritional epidemiology as well. Even though there was consistency in the overall null observations across most of the cohorts in this pooled analysis, there was some variation. It is easy to imagine that, without this collaborative analysis, we might have been led down several blind alleys derived from analyses of various subgroups and interactions. We all should be grateful to the Vitamin D Pooling Project of Rarer Cancers investigators for having saved us from years of false leads, as well as for their vision and skill in carrying out this outstanding collaborative project.
[ CLOSE WINDOW ]ReferencesPeto R, Doll R, Buckley JD, et al. Can dietary beta-carotene materially reduce human cancer rates? Nature 1981;290(5803):201–208.Albanes D, Heinonen OP, Huttunen JK, et al. Effects of alpha-tocopherol and beta-carotene supplements on cancer incidence in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study. Am J Clin Nutr 1995;62(6, suppl):1427S–1430S.Omenn GS, Goodman GE, Thornquist MD, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 1996;334(18):1150–1155.Blot WJ, Li JY, Taylor PR, et al. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl Cancer Inst 1993;85(18):1483–1492.Cole BF, Baron JA, Sandler RS, et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA 2007;297(21):2351–2359.Ziegler RG, Byers T. Re: Health claims about vitamin C and cancer. J Natl Cancer Inst 1994;86(11):871–872.Stampfer MJ, Hennekens CH, Manson JE, et al. Vitamin E consumption and the risk of coronary disease in women. N Engl J Med 1993;328(20):1444–1449.Rimm EB, Stampfer MJ, Ascherio A, et al. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med 1993;328(20):1450–1456.Yusuf S, Dagenais G, Pogue J, et al. Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000;342(3):154–160.Miller ER III, Pastor-Barriuso R, Dalal D, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005;142(1):37–46.Virtamo J, Pietinen P, Huttunen JK, et al. Incidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: a postintervention follow-up. JAMA 2003;290(4):476–485.Lippman SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2009;301(1):39–51.World Cancer Research Fund/American Institute for Cancer Research. Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective. Washington, DC: AICR; 2007.IARC. Vitamin D and Cancer. IARC Working Group Reports, vol 5. Lyon, France: International Agency for Research on Cancer; 2008. http://www.iarc.fr/en/publications/pdfs-online/wrk/wrk5/Report_VitD.pdf).Garland CF, Gorham ED, Mohr SB, et al. Vitamin D for cancer prevention: global perspective. Ann Epidemiol 2009;19(7):468–483.Grant WB. A critical review of vitamin D and cancer: a report of the IARC Working Group. Dermatoendocrinol 2009;1(1):25–33.McCullough ML, Stevens VL, Patel R, et al. Serum 25-hydroxyvitamin D concentrations and postmenopausal breast cancer risk: a nested case control study in the Cancer Prevention Study-II Nutrition Cohort [published online ahead of print August 28, 2009]. Breast Cancer Res. (doi:10.1186/bcr2356).Freedman DM, Chang SC, Falk RT, et al. Serum levels of vitamin D metabolites and breast cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cancer Epidemiol Biomarkers Prev 2008;17(4):889–894.Oh EY, Ansell C, Nawaz H, et al. Global breast cancer seasonality [published online ahead of print February 4, 2010]. Breast Cancer Res Treat. (doi:10.1007/s10549-009-0676-7).Helzlsouer KJ for the VDPP Steering Committee. Overview of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Am J Epidemiol 2010;172(1):4–9.Goodwin PJ. Vitamin D in cancer patients: above all, do no harm. J Clin Oncol 2009;27(13):2117–2119.Olsen A, Egeberg R, Tjønneland A. Re: Calcium plus vitamin D supplementation and the risk of breast cancer [letter]. J Natl Cancer Inst 2009;101(9):690.Nass S, Stillman B, eds. Large-Scale Biomedical Science: Exploring Strategies for Future Research. Washington, DC: National Cancer Policy Board and Division of Earth and Life Sciences, Institute of Medicine, National Research Council; 2003.
Colorado School of Public Health, University of Colorado Cancer Center, Aurora, CO 80045 (e-mail: tim.byers@ucdenver.edu)
Sunday, August 15, 2010
Topical eye antihistamines without decongestants
"For patients that would benefit from adjuvant topical antihistamine therapy, without a decongestant, they should be referred to the doctor to enquire about ocular products such as levocabastine(Livostin) , olopatadine (Patanol), emedastine (Emadine) or ketotifen (Zaditor)." The only nasal antihistamine product currently available in Canada is levocabastine (Livostin nasal spray).
Friday, August 13, 2010
Lamotrigine (Lamictal), used to treat seizures in children and bipolar disorder in adults
Lamotrigine (Lamictal), used to treat seizures in children and bipolar disorder in adults
Friday, July 16, 2010
ARB's increase cancer
The FDA is reviewing the safety of angiotensin-receptor blockers after a recent meta-analysis suggested a small increase in new cancer diagnoses in patients using the drugs.
The agency will update the public with its conclusions as soon as the review is complete. In the meantime, it says the benefits of ARBs outweigh any potential risks, and it advises that the drugs continue to be used as recommended.
Clinicians should report any ARB-related adverse events to the FDA's MedWatch program.
The agency will update the public with its conclusions as soon as the review is complete. In the meantime, it says the benefits of ARBs outweigh any potential risks, and it advises that the drugs continue to be used as recommended.
Clinicians should report any ARB-related adverse events to the FDA's MedWatch program.
lorcaserin new weight loss drug
Lorcaserin, a selective serotonin 2C receptor agonist, helps patients both lose weight and maintain their weight loss, according to a phase III study conducted by the drug's manufacturer and published in the New England Journal of Medicine.
Some 3200 overweight or obese adults were randomized to take lorcaserin or placebo twice daily for a year, after which lorcaserin recipients continued the drug or switched to placebo for another year. All participants also received nutrition and exercise counseling.
At 1 year, more patients in the lorcaserin group than placebo group had lost at least 5% of their body weight (48% vs. 20% of patients; mean weight loss: 5.8 kg vs. 2.2 kg). In addition, lorcaserin patients who stayed on the drug for a second year were more likely to maintain their weight loss than those who switched to placebo.
Serious adverse events did not differ between lorcaserin and placebo recipients. Unlike some other serotonergic agents, lorcaserin did not increase risk for valvular heart disease.
Some 3200 overweight or obese adults were randomized to take lorcaserin or placebo twice daily for a year, after which lorcaserin recipients continued the drug or switched to placebo for another year. All participants also received nutrition and exercise counseling.
At 1 year, more patients in the lorcaserin group than placebo group had lost at least 5% of their body weight (48% vs. 20% of patients; mean weight loss: 5.8 kg vs. 2.2 kg). In addition, lorcaserin patients who stayed on the drug for a second year were more likely to maintain their weight loss than those who switched to placebo.
Serious adverse events did not differ between lorcaserin and placebo recipients. Unlike some other serotonergic agents, lorcaserin did not increase risk for valvular heart disease.
Wednesday, July 14, 2010
vitamin e/beta carotene may increase cvd
A systematic review of antioxidants for primary prevention of cardiovascular disease identified four RCTs of vitamin E; the review found no benefits for vitamin E [1). One of the RCTs identified in the review found that vitamin E may increase death from subarachnoid hemorrhage [2). The review also identified six RCTs of beta-carotene; the review found no benefit for beta-carotene. Pooled analysis of four of these six RCTs found that beta-carotene may increase cv mortality
asa lowers MI but increases stroke
The role of aspirin in primary prevention remains uncertain. In a meta-analysis of five RCTs, Foster and colleagues found that aspirin slightly reduced the risk of a serious vascular event (odds ratio, 0.86; 95% CI: 0.80–0.90) and reduced the relative risk of myocardial infarction by about a third (OR, 0.71; 95% CI: 0.60–0.80], but had an uncertain effect on stroke (OR, 1.05; 95% CI: 0.90–1.20) [1]. The meta-analysis found that there were 0.1 excess intracranial bleeds per 1,000 patients treated per year with aspirin, and 0.7 major extracranial bleeds per 1,000 patients treated per year with aspirin. The authors found “insufficient evidence from RCTs to identify which individuals would benefit overall and which would be harmed by regular treatment with aspirin, although those at high and intermediate rather than low risk would be more likely to gain benefit.” ...More
up regulation and down regulation
down-regulation - A reduction in the number of receptors for a control substance, e.g., a hormone, local hormone, neurotransmitter, or a drug, in response to a prolonged excess of the control substance; this is an internal adjustment which usually helps restore homeostasis in a disease state.
up-regulation - An increase in the number of receptors for a control substance, e.g., a hormone, local hormone, neurotransmitter, or a drug, in response to a prolonged decrease of the control substance; this is an internal adjustment which usually helps restore homeostasis in a disease state.
up-regulation - An increase in the number of receptors for a control substance, e.g., a hormone, local hormone, neurotransmitter, or a drug, in response to a prolonged decrease of the control substance; this is an internal adjustment which usually helps restore homeostasis in a disease state.
fibrates may lower coronary events not mortality, stroke or HF
Fibrates appear to lower the risk for coronary events, according to a meta-analysis in the Lancet.
Researchers examined data from 18 placebo-controlled trials of fibrates for primary or secondary prevention; some 45,000 adults were included. Overall, coronary events were significantly less common in patients taking fibrates than in those on placebo (8.7% vs. 11.6%). Fibrates were also associated with significant reductions in coronary revascularization, progression of albuminuria, and retinopathy.
There was no benefit in terms of stroke, mortality, or heart failure. Serious drug-related events, including rhabdomyolysis, were not increased with fibrates.
The authors conclude: "The magnitude of effect is moderate, but in high-risk individuals and in those with combined dyslipidemia, clinically meaningful reductions in risk could be achieved."
Researchers examined data from 18 placebo-controlled trials of fibrates for primary or secondary prevention; some 45,000 adults were included. Overall, coronary events were significantly less common in patients taking fibrates than in those on placebo (8.7% vs. 11.6%). Fibrates were also associated with significant reductions in coronary revascularization, progression of albuminuria, and retinopathy.
There was no benefit in terms of stroke, mortality, or heart failure. Serious drug-related events, including rhabdomyolysis, were not increased with fibrates.
The authors conclude: "The magnitude of effect is moderate, but in high-risk individuals and in those with combined dyslipidemia, clinically meaningful reductions in risk could be achieved."
Tuesday, July 13, 2010
confidence intervals of brand vs generics
For example, the ratio of test drug to reference drug AUC (test/reference AUC) for Drug A in six subjects results in the following values:
120%, 120%, 110%, 110%, 90%, 110%
The mean test/reference AUC was 110% with 90% CI of 102 to 117. This means that there is 90% probability that the true mean lies between 102% and 117%. -ME-IT EITHER DOES OR DOES'T LIE IN THIS INTERVAL=> 9 OUT OF TEN TIMES IT WILL-Therefore, the drug passes the bioequivalence test and is considered bioequivalent to the reference drug.
In another example, the test/reference AUC for Drug B in six subjects results in the following values:
110%, 190%, 30%, 130%, 90%, 110%
The mean test/reference AUC was 110% with 90% CI of 75 to 145. Although the average test/AUC ratio of the drug (110%) is the same as drug A, there is a 90% probability that the true mean lies between 75% and 145%. The confidence intervals are too wide and therefore, Drug B fails to establish bioequivalence with the reference drug.
As illustrated above, the confidence interval range of 80% to 125% does not mean that drug levels can vary up to 20% between referenced (brand) drug and the test (generic) drug. If drug levels vary by more than 10%, the range of possible values within the 90% confidence interval will likely become too broad and the drug will fail to establish bioequivalence with the reference drug. 12 In fact, in a study using the FDA bioequivalence criteria, the first 224 post-1962 drugs approved over the two year period after the Waxman Hatch amendments were passed, including some narrow therapeutic index drugs, showed a mean bioavailability variation between the generic and brand products of only 3.5%.
120%, 120%, 110%, 110%, 90%, 110%
The mean test/reference AUC was 110% with 90% CI of 102 to 117. This means that there is 90% probability that the true mean lies between 102% and 117%. -ME-IT EITHER DOES OR DOES'T LIE IN THIS INTERVAL=> 9 OUT OF TEN TIMES IT WILL-Therefore, the drug passes the bioequivalence test and is considered bioequivalent to the reference drug.
In another example, the test/reference AUC for Drug B in six subjects results in the following values:
110%, 190%, 30%, 130%, 90%, 110%
The mean test/reference AUC was 110% with 90% CI of 75 to 145. Although the average test/AUC ratio of the drug (110%) is the same as drug A, there is a 90% probability that the true mean lies between 75% and 145%. The confidence intervals are too wide and therefore, Drug B fails to establish bioequivalence with the reference drug.
As illustrated above, the confidence interval range of 80% to 125% does not mean that drug levels can vary up to 20% between referenced (brand) drug and the test (generic) drug. If drug levels vary by more than 10%, the range of possible values within the 90% confidence interval will likely become too broad and the drug will fail to establish bioequivalence with the reference drug. 12 In fact, in a study using the FDA bioequivalence criteria, the first 224 post-1962 drugs approved over the two year period after the Waxman Hatch amendments were passed, including some narrow therapeutic index drugs, showed a mean bioavailability variation between the generic and brand products of only 3.5%.
Friday, July 9, 2010
Self-Titration of Drugs and Telemonitoring in Hypertension Help Lower BP
Patients with uncontrolled hypertension attain better control with self-titration of medications and automated telemonitoring by clinicians, according to a Lancet study.
Investigators randomized some 500 patients from 24 general practices to self-titration and telemonitoring or to usual care for 1 year. Patients had blood pressures above 140/90 mm Hg despite taking one or two antihypertensive drugs. Intervention patients took pressure readings each morning during the first week of the month. If readings were above the target of 130 systolic for 2 consecutive months, drug dosages were adjusted according to a pre-agreed titration schedule without seeing the family doctor.
By 12 months, mean systolic pressure had dropped 17.6 mm Hg in the intervention group versus 12.2 among controls. Intervention patients were prescribed more drugs over the course of the year than controls — especially calcium antagonists and thiazides. Side effects were largely similar between groups.
An editorialist concludes that wide use of this strategy "is not far off on the horizon."
Investigators randomized some 500 patients from 24 general practices to self-titration and telemonitoring or to usual care for 1 year. Patients had blood pressures above 140/90 mm Hg despite taking one or two antihypertensive drugs. Intervention patients took pressure readings each morning during the first week of the month. If readings were above the target of 130 systolic for 2 consecutive months, drug dosages were adjusted according to a pre-agreed titration schedule without seeing the family doctor.
By 12 months, mean systolic pressure had dropped 17.6 mm Hg in the intervention group versus 12.2 among controls. Intervention patients were prescribed more drugs over the course of the year than controls — especially calcium antagonists and thiazides. Side effects were largely similar between groups.
An editorialist concludes that wide use of this strategy "is not far off on the horizon."
Glucosamine Doesn't Lessen Disability Related to Low Back Pain
Glucosamine does not reduce pain-related disability in chronic low back pain, according to a JAMA study.
Investigators studied 250 patients who had low back pain for at least 6 months, along with imaging-based evidence of degenerative lumbar osteoarthritis. Subjects were randomized to treatment with either glucosamine (1500 mg) or placebo daily for 6 months and then were followed for an additional 6 months after treatment ended.
The main outcome measure — patients' scores on pain-related disability — dropped in both groups after treatment, but there was no significant difference between the groups.
An editorialist comments that "the most likely explanation for the outcome is simply that glucosamine probably offers little benefit for chronic [low back pain] with osteoarthritis beyond whatever placebo effect it may provide."
Investigators studied 250 patients who had low back pain for at least 6 months, along with imaging-based evidence of degenerative lumbar osteoarthritis. Subjects were randomized to treatment with either glucosamine (1500 mg) or placebo daily for 6 months and then were followed for an additional 6 months after treatment ended.
The main outcome measure — patients' scores on pain-related disability — dropped in both groups after treatment, but there was no significant difference between the groups.
An editorialist comments that "the most likely explanation for the outcome is simply that glucosamine probably offers little benefit for chronic [low back pain] with osteoarthritis beyond whatever placebo effect it may provide."
Sunday, July 4, 2010
how long til ppi's work?
USPharmacist.com > Continuing Education > Exploring the Role of the Pharmacist in OTC PPI Use for Frequent Heartburn: "Some users do experience complete relief on the first day of PPI treatment, but it may take up to 4 days to obtain the full effect.8"
dopamine and prolactin are inversely related
An increase of dopamine decreases prolactin only in the brain ie hypothalamus. Dopamine cannot cross the blood brain barrier. In the peripheral nervous system, dopamine behaves like a catecholamine drug. Hence the use a domperidone, a dopamine blocker, to not only suppress nausea and vomitting (via peripheral dopamine blocking) but must also lower dopamine in the CNS w/c would up prolactin=> lactation. Bromocriptine, a dopamine agonist is used to stop lactation. Breastfeeding increases prolactin, thus decreasing dopamine, and deductively should ahve something to do with postpartum depression.
Thursday, July 1, 2010
Intensive Glucose Control Reduces Some Microvascular Complications — At the Cost of Increased Mortality
Intensive glucose control in high-risk diabetes offers mixed results, according to two new analyses from the ACCORD trial.
In ACCORD, patients with type 2 diabetes and elevated cardiovascular risk were randomized to intensive glucose control or standard therapy. About half were also assigned to intensive or standard blood pressure control, and the other half to combination or standard lipid therapy. Intensive glucose control was stopped early, in 2008, because of increased mortality.
Now, writing in the Lancet, ACCORD researchers report that the glucose-control groups did not differ in composite outcomes measuring kidney function, diabetic eye complications, and peripheral neuropathy. However, several components of the composite outcomes (e.g., microalbuminuria, cataract extraction) were less common with intensive glucose control.
And in the New England Journal of Medicine, ACCORD researchers observe that both intensive glucose control and combination lipid therapy reduced progression of retinopathy, while intensive BP control did not.
Despite the microvascular benefits, the Lancet authors conclude, the increased mortality makes aggressive hemoglobin targets in high-risk diabetes seem "imprudent."
In ACCORD, patients with type 2 diabetes and elevated cardiovascular risk were randomized to intensive glucose control or standard therapy. About half were also assigned to intensive or standard blood pressure control, and the other half to combination or standard lipid therapy. Intensive glucose control was stopped early, in 2008, because of increased mortality.
Now, writing in the Lancet, ACCORD researchers report that the glucose-control groups did not differ in composite outcomes measuring kidney function, diabetic eye complications, and peripheral neuropathy. However, several components of the composite outcomes (e.g., microalbuminuria, cataract extraction) were less common with intensive glucose control.
And in the New England Journal of Medicine, ACCORD researchers observe that both intensive glucose control and combination lipid therapy reduced progression of retinopathy, while intensive BP control did not.
Despite the microvascular benefits, the Lancet authors conclude, the increased mortality makes aggressive hemoglobin targets in high-risk diabetes seem "imprudent."
Testosterone Therapy Linked to Adverse Cardiovascular Events in Older Men with Limited Mobility
Use of testosterone gel in older men with mobility problems might increase risk for cardiovascular events, according to a small study in the New England Journal of Medicine.
Some 200 community-dwelling men aged 65 or older with low serum testosterone levels and impaired mobility were randomized to use a testosterone gel (10 mg) or placebo daily for 6 months. The trial was stopped early because of an excess of cardiovascular events with testosterone compared with placebo (in 23 vs. 5 subjects). In addition, testosterone recipients developed more respiratory and dermatologic disorders.
The elevated risks persisted after adjustment for baseline risk factors, including diabetes, hyperlipidemia, and hypertension.
The authors note that their findings may not be generalizable to younger men or to those without impaired mobility.
Some 200 community-dwelling men aged 65 or older with low serum testosterone levels and impaired mobility were randomized to use a testosterone gel (10 mg) or placebo daily for 6 months. The trial was stopped early because of an excess of cardiovascular events with testosterone compared with placebo (in 23 vs. 5 subjects). In addition, testosterone recipients developed more respiratory and dermatologic disorders.
The elevated risks persisted after adjustment for baseline risk factors, including diabetes, hyperlipidemia, and hypertension.
The authors note that their findings may not be generalizable to younger men or to those without impaired mobility.
Tuesday, June 29, 2010
Archives' Studies Call into Question Statins for Primary Prevention
Two papers in the Archives of Internal Medicine cast doubt on the benefits of statins for primary prevention.
In a meta-analysis, researchers combined data from 11 placebo-controlled trials of statin use in some 65,000 high-risk patients without cardiovascular disease at baseline. During nearly 4 years of treatment, LDL levels were lower in statin than in placebo users (mean, 94 vs. 134 mg/dL) — but there was no difference in all-cause mortality. Editorialists say the analysis "makes it clear that in the short-term, for true primary prevention, the benefit, if any, is very small."
In another paper, investigators took a closer look at the JUPITER trial, in which rosuvastatin reportedly lowered cardiovascular risk by 50% among patients without heart disease or hypercholesterolemia but with high C-reactive protein. The investigators say the trial was "flawed" — it was stopped too early, data on cardiovascular mortality were lacking, and more than half the researchers had financial ties to industry. Accordingly, they conclude: "The results of the trial do not support the use of statin treatment for primary prevention."
In a meta-analysis, researchers combined data from 11 placebo-controlled trials of statin use in some 65,000 high-risk patients without cardiovascular disease at baseline. During nearly 4 years of treatment, LDL levels were lower in statin than in placebo users (mean, 94 vs. 134 mg/dL) — but there was no difference in all-cause mortality. Editorialists say the analysis "makes it clear that in the short-term, for true primary prevention, the benefit, if any, is very small."
In another paper, investigators took a closer look at the JUPITER trial, in which rosuvastatin reportedly lowered cardiovascular risk by 50% among patients without heart disease or hypercholesterolemia but with high C-reactive protein. The investigators say the trial was "flawed" — it was stopped too early, data on cardiovascular mortality were lacking, and more than half the researchers had financial ties to industry. Accordingly, they conclude: "The results of the trial do not support the use of statin treatment for primary prevention."
Wednesday, June 2, 2010
VAL-HEFT and CHARM say yes to ARB/ACEI for CHD
However, it is different from the VAL-HEFT and CHARM studies, which also examined the combination of an ACE inhibitor with an ARB {2,3}. The latter two trials showed an added benefit from the combination therapy, but they examined different patient populations (congestive heart failure) and their design did not stress an increase in the dose of ACE inhibitor to a maximum, which could account for the differences in their results. Questions also remain about the benefits of ACE inhibitor-ARB combination therapy in patients with established chronic kidney disease, given the benefits described in earlier (albeit much smaller) clinical trials and about the role of novel renin-inhibitor aliskiren. References: {1} Anderson et al., Am Heart J 2008, 155:706-711 [PMID:18371480]; {2} Krum et al., Eur J Heart Fail 2004, 6:937-945 [PMID:15556056]; {3} Pfeffer et al., Lancet 2003, 362:759-766 [PMID:13678868]. Trial registration: NCT00153101.
ontarget and valiant says no to ARB/ACEI combo
This study concludes that the angiotensin-receptor blocker (ARB) telmisartan was equivalent to the ACE inhibitor ramipril in preventing cardiovascular events in high-risk patients with vascular disease or diabetes mellitus. The combination of telmisartan and ramipril offered no advantage over maximally dosed ramipril and was associated with higher risk of adverse events. The authors examined the non-inferiority of therapy with telmisartan compared to maximally dosed ramipril and to combination therapy of telmisartan plus ramipril in high-risk patients with established cardiovascular disease or diabetes mellitus with end-organ damage (but normal serum creatinine). The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) study was a randomized, controlled, double-blind trial. There was no difference in the three groups in incidence of primary outcome. Patients in the telmisartan group had a lower incidence of cough and angioedema, but a higher incidence of hypotension compared to patients on ramipril. The incidence of syncope was identical in these two groups. Patients in the combination arm had a higher incidence of hypotension, syncope and renal dysfunction compared to patients in the ramipril arm. Another interesting finding was the fact that ACE inhibitor-ARB combination therapy did not result in better outcomes compared to ramipril therapy alone, in spite of better blood pressure (BP) control seen in patients treated with the combination regimen (2.4/1.4mmHg lower BP in the combination arm). One potential explanation for this is the higher incidence of adverse effects such as hypotension and renal complications seen with combination therapy, which might have offset the benefits of better blood pressure reduction. The conclusion here, regarding combination therapy with ACE inhibitors plus ARBs, is similar to the VALIANT trial which examined the combination of full dose captopril plus valsartan
Effect of PPI's on b12, iron, gastrin
The basis for these questions is the fact that levels of all 3 of these substances (hormones, vitamins, and elements) are in some way dependent on or related to gastric acid secretion. As such, any agent that affects gastric acid secretion may affect these specific substances, and because PPIs are potent antisecretory agents, they should in turn affect them to a greater degree.
Gastrin is a potent acid secretagogue that is released from "G" cells in the antrum of the stomach and the duodenum in response to a meal. The feedback inhibition for gastrin is acid present in the lumen of the stomach and small intestine. The use of any agent that inhibits gastric secretion of acid (H2-receptor antagonists or PPIs) will result in a rise in serum gastrin as the feedback inhibition of gastrin release is diminished. Gastrin levels are commonly elevated in patients taking PPIs, but only unusually to a significant degree. No adverse clinical events have been noted with the generally mild hypergastrinemia seen with PPI therapy during the 14 years these compounds have been in clinical use.
Serum B12 levels are in part dependent on the presence of intrinsic factor secreted by parietal cells along with acid and the subsequent binding of intrinsic factor to free cobalamin in the small intestine. PPI use decreases the secretion of acid from parietal cells and of intrinsic factor as well. Studies of B12 levels in patients taking PPIs chronically have demonstrated a clinically insignificant decrease in serum B12 levels, but there have been no reports of B12 deficiency despite 14 years of widespread use of these compounds. If one is concerned about the possibility of B12 deficiency, supplementation of this vitamin can be achieved at little cost. The need for such supplementation has never been demonstrated despite close scrutiny of this physiology over time.
Iron absorption is facilitated in part by the conversion of heme in the presence of acid to a different state. Decreased acid secretion in the presence of PPI therapy theoretically would decrease the presence of this converted iron and could lead to decreased absorption. However, iron malabsorption has never been demonstrated in patients taking PPIs.
Why have there been no clinically adverse events related to these potential physiologic perturbations despite widespread use of PPIs? The answer lies in the extent and duration of the antisecretory therapy with these compounds. In general, most of these agents inhibit acid secretion only for 10-12 hours of the day, meaning that for most of the day, normal acid secretion is taking place and these physiologic events are proceeding as expected. If an agent becomes available that truly results in achlorhydria (absent acid secretion), then these physiologic consequences may become clinically relevant and worth monitoring. Until that time, there is little likelihood of encountering a patient who develops a clinically relevant abnormality of these physiologic processes due to the fact that he or she is taking a PPI.
Gastrin is a potent acid secretagogue that is released from "G" cells in the antrum of the stomach and the duodenum in response to a meal. The feedback inhibition for gastrin is acid present in the lumen of the stomach and small intestine. The use of any agent that inhibits gastric secretion of acid (H2-receptor antagonists or PPIs) will result in a rise in serum gastrin as the feedback inhibition of gastrin release is diminished. Gastrin levels are commonly elevated in patients taking PPIs, but only unusually to a significant degree. No adverse clinical events have been noted with the generally mild hypergastrinemia seen with PPI therapy during the 14 years these compounds have been in clinical use.
Serum B12 levels are in part dependent on the presence of intrinsic factor secreted by parietal cells along with acid and the subsequent binding of intrinsic factor to free cobalamin in the small intestine. PPI use decreases the secretion of acid from parietal cells and of intrinsic factor as well. Studies of B12 levels in patients taking PPIs chronically have demonstrated a clinically insignificant decrease in serum B12 levels, but there have been no reports of B12 deficiency despite 14 years of widespread use of these compounds. If one is concerned about the possibility of B12 deficiency, supplementation of this vitamin can be achieved at little cost. The need for such supplementation has never been demonstrated despite close scrutiny of this physiology over time.
Iron absorption is facilitated in part by the conversion of heme in the presence of acid to a different state. Decreased acid secretion in the presence of PPI therapy theoretically would decrease the presence of this converted iron and could lead to decreased absorption. However, iron malabsorption has never been demonstrated in patients taking PPIs.
Why have there been no clinically adverse events related to these potential physiologic perturbations despite widespread use of PPIs? The answer lies in the extent and duration of the antisecretory therapy with these compounds. In general, most of these agents inhibit acid secretion only for 10-12 hours of the day, meaning that for most of the day, normal acid secretion is taking place and these physiologic events are proceeding as expected. If an agent becomes available that truly results in achlorhydria (absent acid secretion), then these physiologic consequences may become clinically relevant and worth monitoring. Until that time, there is little likelihood of encountering a patient who develops a clinically relevant abnormality of these physiologic processes due to the fact that he or she is taking a PPI.
Wednesday, April 28, 2010
Quetiapine is only approved to treat schizophrenia and bipolar disorder.
AstraZeneca marketed quetiapine to physicians (particularly those who do not treat the approved conditions) for the following unapproved uses: treatment of aggression, Alzheimer disease, anger management, anxiety, attention-deficit/hyperactivity disorder, bipolar maintenance, dementia, depression, mood disorder, post-traumatic stress disorder, and sleeplessness.
The government alleges that AstraZeneca promoted these uses by paying doctors to serve as authors of ghostwritten research articles, to travel to resort locales to "advise" the company about marketing strategies, and to give promotional lectures to other clinicians
The government alleges that AstraZeneca promoted these uses by paying doctors to serve as authors of ghostwritten research articles, to travel to resort locales to "advise" the company about marketing strategies, and to give promotional lectures to other clinicians
Vitamin B Therapy Adversely Affects Progression of Diabetic Nephropathy
B vitamins given to lower homocysteinemia — and thereby to reduce renal and vascular complications of diabetes — don't have the desired effect, according to a JAMA study.
Researchers randomized nearly 250 patients with diabetic nephropathy to either high-dose B vitamins or placebo. The study's primary outcome measure was the change in glomerular filtration rate (GFR) between baseline and study's end.
After a mean follow-up of 32 months, GFRs declined more, on average, in the treatment group than in the control group (16.5 vs. 10.7 mL/min). A composite outcome of myocardial infarction, stroke, revascularization, and all-cause mortality also favored controls. The need for dialysis did not differ between groups. Homocysteine values, however, were significantly lower in the treatment group.
Pointing to earlier studies showing no treatment benefit, the authors conclude that "it would be prudent to discourage the use of high-dose B vitamins as a homocysteine-lowering strategy."
Researchers randomized nearly 250 patients with diabetic nephropathy to either high-dose B vitamins or placebo. The study's primary outcome measure was the change in glomerular filtration rate (GFR) between baseline and study's end.
After a mean follow-up of 32 months, GFRs declined more, on average, in the treatment group than in the control group (16.5 vs. 10.7 mL/min). A composite outcome of myocardial infarction, stroke, revascularization, and all-cause mortality also favored controls. The need for dialysis did not differ between groups. Homocysteine values, however, were significantly lower in the treatment group.
Pointing to earlier studies showing no treatment benefit, the authors conclude that "it would be prudent to discourage the use of high-dose B vitamins as a homocysteine-lowering strategy."
Friday, April 23, 2010
Folate and Vitamin B6 Lower Cardiovascular Risk
April 22, 2010 — Dietary intakes of folate and vitamin B6 reduce the risk for mortality from stroke and any cardiovascular disease in women and may reduce the risk for heart failure in men, according to a study conducted in Japan.
The findings were reported online April 15 in Stroke by Renzhe Cui, MD, from the Graduate School of Medicine at Osaka University, in Osaka, Japan, and colleagues.
"This study is the first to show that high dietary intakes of folate and vitamin B6 were associated with a reduced risk of heart failure mortality for men," the authors note.
Data from 23,119 men and 35,611 women (aged 40 - 79 years) who completed food frequency questionnaires as part of the Japan Collaborative Cohort study were analyzed. At a median 14 years of follow-up, 986 participants died from stroke, 424 died from coronary heart disease, and 2087 died from any cardiovascular disease.
Participants' intake of folate, vitamin B6, and vitamin B12 were classified into quintiles. Comparing the lowest vs the highest quintiles for each nutrient, the researchers found that higher consumption of folate and vitamin B6 was associated with significantly fewer deaths from heart failure in men, and significantly fewer deaths from stroke, heart disease, and any cardiovascular diseases in women. By contrast, vitamin B12 intake was not associated with reduced mortality risk.
The protective effects of folate and vitamin B6 remained significant after adjustment for the presence of cardiovascular risk factors and also after exclusion of supplement users (n = 7334) from the analysis.
The hazard ratios (HRs) of coronary heart disease for the highest vs the lowest quintiles were 0.62 (95% confidence interval [CI], 0.42 - 0.89) for folate, 0.51 (95% CI, 0.29 - 0.91) for vitamin B6, and 1.35 (95% CI, 0.80 - 2.27) for vitamin B12. The HRs of heart failure for the highest vs the lowest quintiles were 0.76 (95% CI, 0.51 - 1.13) for folate, 0.60 (95% CI, 0.32 - 1.13) for vitamin B6, and 1.57 (95% CI, 0.90 - 2.73) for vitamin B12.
"Mechanisms for these observed associations may involve the effects of these vitamin intakes on reduction of blood homocysteine concentrations," the researchers suggest.
This study has received grant funding from the Ministry of Education, Science, Sports and Culture of, Japan (Monbusho), Japanese Ministry of Education, Culture, Sports, Science, and Technology. The study authors have disclosed no relevant financial relationships.
The findings were reported online April 15 in Stroke by Renzhe Cui, MD, from the Graduate School of Medicine at Osaka University, in Osaka, Japan, and colleagues.
"This study is the first to show that high dietary intakes of folate and vitamin B6 were associated with a reduced risk of heart failure mortality for men," the authors note.
Data from 23,119 men and 35,611 women (aged 40 - 79 years) who completed food frequency questionnaires as part of the Japan Collaborative Cohort study were analyzed. At a median 14 years of follow-up, 986 participants died from stroke, 424 died from coronary heart disease, and 2087 died from any cardiovascular disease.
Participants' intake of folate, vitamin B6, and vitamin B12 were classified into quintiles. Comparing the lowest vs the highest quintiles for each nutrient, the researchers found that higher consumption of folate and vitamin B6 was associated with significantly fewer deaths from heart failure in men, and significantly fewer deaths from stroke, heart disease, and any cardiovascular diseases in women. By contrast, vitamin B12 intake was not associated with reduced mortality risk.
The protective effects of folate and vitamin B6 remained significant after adjustment for the presence of cardiovascular risk factors and also after exclusion of supplement users (n = 7334) from the analysis.
The hazard ratios (HRs) of coronary heart disease for the highest vs the lowest quintiles were 0.62 (95% confidence interval [CI], 0.42 - 0.89) for folate, 0.51 (95% CI, 0.29 - 0.91) for vitamin B6, and 1.35 (95% CI, 0.80 - 2.27) for vitamin B12. The HRs of heart failure for the highest vs the lowest quintiles were 0.76 (95% CI, 0.51 - 1.13) for folate, 0.60 (95% CI, 0.32 - 1.13) for vitamin B6, and 1.57 (95% CI, 0.90 - 2.73) for vitamin B12.
"Mechanisms for these observed associations may involve the effects of these vitamin intakes on reduction of blood homocysteine concentrations," the researchers suggest.
This study has received grant funding from the Ministry of Education, Science, Sports and Culture of, Japan (Monbusho), Japanese Ministry of Education, Culture, Sports, Science, and Technology. The study authors have disclosed no relevant financial relationships.
PTU Gets Boxed Warning for Potential Liver Injury
A boxed warning has been added to the hyperthyroidism drug propylthiouracil (PTU) to alert clinicians about the drug's risk for severe liver injury, the FDA announced on Wednesday.
The new labeling is based in part on postmarketing safety reports of severe liver injury — including 15 deaths — in 23 adult and 11 pediatric patients taking PTU. A warning about the potential dangers of the drug was issued by the agency last June.
The FDA recommends that PTU only be used in patients who cannot tolerate methimazole or other treatments for hyperthyroidism and in women just before and during their first trimester of pregnancy.
Patients will now receive a medication guide upon filling a prescription for PTU.
The new labeling is based in part on postmarketing safety reports of severe liver injury — including 15 deaths — in 23 adult and 11 pediatric patients taking PTU. A warning about the potential dangers of the drug was issued by the agency last June.
The FDA recommends that PTU only be used in patients who cannot tolerate methimazole or other treatments for hyperthyroidism and in women just before and during their first trimester of pregnancy.
Patients will now receive a medication guide upon filling a prescription for PTU.
Wednesday, April 21, 2010
High-dose thiamine therapy for patients with type 2
Aims/hypothesis High-dose supplements of thiamine prevent
the development of microalbuminuria in experimental
diabetes. The aim of this pilot study was to assess whether
oral supplements of thiamine could reverse microalbuminuria
in patients with type 2 diabetes.
Methods Type 2 diabetic patients (21 male, 19 female) with
microalbuminuria were recruited at the Diabetes Clinic, Sheikh
Zayed Hospital, Lahore, Pakistan, and randomised to placebo
and treatment arms. Randomisation was by central office in
sequentially numbered opaque, sealed envelopes. Participants,
caregivers and those assessing the outcomes were blinded to
group assignment. Patients were given 3×100 mg capsules of
thiamine or placebo per day for 3 months with a 2 month
follow-up washout period. The primary endpoint was change
in urinary albumin excretion (UAE). Other markers of renal
and vascular dysfunction and plasma concentrations of
thiamine were determined.
Results UAE was decreased in patients receiving thiamine
therapy for 3 months with respect to baseline (median
−17.7 mg/24 h; p<0.001, n=20). There was no significant
decrease in UAE in patients receiving placebo after 3 months
of therapy (n=20). UAE was significantly lower in patients
who had received thiamine therapy compared with those who
had received placebo (30.1 vs 35.5 mg/24 h, p<0.01) but not
at baseline. UAE continued to decrease in the 2 month
washout period in both groups, but not significantly. There
was no effect of thiamine treatment on glycaemic control,
dyslipidaemia or BP. There were no adverse effects of therapy.
Conclusions/interpretation In this pilot study, high-dose
thiamine therapy produced a regression of UAE in type 2
diabetic patients with microalbuminuria. Thiamine supplements
at high dose may provide improved therapy for
early-stage diabetic nephropathy
-http://www.springerlink.com/content/51l034044218455j/fulltext.pdf
the development of microalbuminuria in experimental
diabetes. The aim of this pilot study was to assess whether
oral supplements of thiamine could reverse microalbuminuria
in patients with type 2 diabetes.
Methods Type 2 diabetic patients (21 male, 19 female) with
microalbuminuria were recruited at the Diabetes Clinic, Sheikh
Zayed Hospital, Lahore, Pakistan, and randomised to placebo
and treatment arms. Randomisation was by central office in
sequentially numbered opaque, sealed envelopes. Participants,
caregivers and those assessing the outcomes were blinded to
group assignment. Patients were given 3×100 mg capsules of
thiamine or placebo per day for 3 months with a 2 month
follow-up washout period. The primary endpoint was change
in urinary albumin excretion (UAE). Other markers of renal
and vascular dysfunction and plasma concentrations of
thiamine were determined.
Results UAE was decreased in patients receiving thiamine
therapy for 3 months with respect to baseline (median
−17.7 mg/24 h; p<0.001, n=20). There was no significant
decrease in UAE in patients receiving placebo after 3 months
of therapy (n=20). UAE was significantly lower in patients
who had received thiamine therapy compared with those who
had received placebo (30.1 vs 35.5 mg/24 h, p<0.01) but not
at baseline. UAE continued to decrease in the 2 month
washout period in both groups, but not significantly. There
was no effect of thiamine treatment on glycaemic control,
dyslipidaemia or BP. There were no adverse effects of therapy.
Conclusions/interpretation In this pilot study, high-dose
thiamine therapy produced a regression of UAE in type 2
diabetic patients with microalbuminuria. Thiamine supplements
at high dose may provide improved therapy for
early-stage diabetic nephropathy
-http://www.springerlink.com/content/51l034044218455j/fulltext.pdf
FDA Approves Generic Losartan ap/21/2010
The FDA announced on Wednesday that it has approved the first generic versions of two drugs used to treat hypertension — Cozaar (losartan potassium) and Hyzaar (losartan potassium-hydrochlorothiazide).
Like their brand-name equivalents, both generics will carry boxed warnings against using them during the second and third trimesters of pregnancy.
Like their brand-name equivalents, both generics will carry boxed warnings against using them during the second and third trimesters of pregnancy.
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