Treatment of Autism
Identification and Evaluation of Autism
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Tuesday, October 30, 2007
Monday, October 29, 2007
FDA Clears Genetic Lab Test for Warfarin Sensitivity
The U.S. Food and Drug Administration today cleared for marketing a new genetic test that will help physicians assess whether a patient may be especially sensitive to the blood-thinning drug warfarin (Coumadin), which is used to prevent potentially fatal clots in blood vessels.
One-third of patients receiving warfarin metabolize it quite differently than expected and experience a higher risk of bleeding. Research has shown that some of the unexpected response to warfarin depends on variants of two genes, CYP2C9 and VKORC1. The Nanosphere Verigene Warfarin Metabolism Nucleic Acid Test detects some variants of both genes.
"Today’s action offers physicians the first FDA cleared genetic test for warfarin sensitivity, which is another step in our commitment to personalized medicine,” said Daniel Schultz, M.D., director, FDA’s Center for Devices and Radiological Health. “With this test, physicians may be able to use genetic information along with other clinical information to treat their patients.”
Warfarin can be a difficult drug to use because the optimal dose varies depending on many risk factors, including a patient's diet, age, and the use of other medications. Rapidly achieving the correct dose is important. Patients who receive doses that are higher than needed to correctly thin the blood are at risk of life-threatening bleeding. Those who receive doses that are too low may remain at risk of life-threatening blood clots.
Warfarin is the second most common drug, after insulin, implicated in emergency room visits for adverse drug events.
In August, FDA approved updated labeling for Coumadin, the brand name version of warfarin, explaining that people with variations of the genes CYP2C9 and VKORC1 may respond differently to the drug. Manufacturers of generic warfarin are adding similar information to their products' labeling.
Physicians and other health care professionals who prescribe warfarin regularly check to see if the drug is working properly by ordering a test called the PT or prothrombin time that evaluates the blood's ability to clot properly. The results are measured in seconds and compared with the expected value in healthy people, known as the International Normalized Ratio or INR.
The Nanosphere test is not intended to be a stand-alone tool to determine optimum drug dosage, but should be used along with clinical evaluation and other tools, including INR, to determine the best treatment for patients.
FDA cleared the test based on results of a study conducted by the manufacturer of hundreds of DNA samples as well as on a broad range of published literature. In a three site study, the test was accurate in all cases where the test yielded a result; 8 percent of the tests could not identify which genetic variants were present.
The new test was cleared for use on the Verigene System, a clinical laboratory test system. Both products are manufactured by Nanosphere Inc., Northbrook, Ill.
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One-third of patients receiving warfarin metabolize it quite differently than expected and experience a higher risk of bleeding. Research has shown that some of the unexpected response to warfarin depends on variants of two genes, CYP2C9 and VKORC1. The Nanosphere Verigene Warfarin Metabolism Nucleic Acid Test detects some variants of both genes.
"Today’s action offers physicians the first FDA cleared genetic test for warfarin sensitivity, which is another step in our commitment to personalized medicine,” said Daniel Schultz, M.D., director, FDA’s Center for Devices and Radiological Health. “With this test, physicians may be able to use genetic information along with other clinical information to treat their patients.”
Warfarin can be a difficult drug to use because the optimal dose varies depending on many risk factors, including a patient's diet, age, and the use of other medications. Rapidly achieving the correct dose is important. Patients who receive doses that are higher than needed to correctly thin the blood are at risk of life-threatening bleeding. Those who receive doses that are too low may remain at risk of life-threatening blood clots.
Warfarin is the second most common drug, after insulin, implicated in emergency room visits for adverse drug events.
In August, FDA approved updated labeling for Coumadin, the brand name version of warfarin, explaining that people with variations of the genes CYP2C9 and VKORC1 may respond differently to the drug. Manufacturers of generic warfarin are adding similar information to their products' labeling.
Physicians and other health care professionals who prescribe warfarin regularly check to see if the drug is working properly by ordering a test called the PT or prothrombin time that evaluates the blood's ability to clot properly. The results are measured in seconds and compared with the expected value in healthy people, known as the International Normalized Ratio or INR.
The Nanosphere test is not intended to be a stand-alone tool to determine optimum drug dosage, but should be used along with clinical evaluation and other tools, including INR, to determine the best treatment for patients.
FDA cleared the test based on results of a study conducted by the manufacturer of hundreds of DNA samples as well as on a broad range of published literature. In a three site study, the test was accurate in all cases where the test yielded a result; 8 percent of the tests could not identify which genetic variants were present.
The new test was cleared for use on the Verigene System, a clinical laboratory test system. Both products are manufactured by Nanosphere Inc., Northbrook, Ill.
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No Long-Term Ill Effects from Repeated Prenatal Corticosteroids for Preterm Labor
Children exposed prenatally to repeated corticosteroid doses for risk of preterm birth show no apparent physical or developmental ill effects after 2 years' follow-up, report two studies in the New England Journal of Medicine.
The studies, comprising some 1500 children, had randomized women at risk for preterm labor to receive either a single course or weekly injections of corticosteroids. When evaluated between ages 2 and 3, the groups showed no differences in measures of growth or neurocognitive development. One study did find an increased frequency of cerebral palsy after repeated corticosteroids, but the difference did not achieve statistical significance.
Both groups of researchers find the results "reassuring," but one group advises against weekly administration, saying the findings "indicate no evident long-term benefit and possible harm [from the cerebral palsy risk]."
An editorialist suggests that, in the absence of longer-term data, repeated courses could be given at lower dosages.
The studies, comprising some 1500 children, had randomized women at risk for preterm labor to receive either a single course or weekly injections of corticosteroids. When evaluated between ages 2 and 3, the groups showed no differences in measures of growth or neurocognitive development. One study did find an increased frequency of cerebral palsy after repeated corticosteroids, but the difference did not achieve statistical significance.
Both groups of researchers find the results "reassuring," but one group advises against weekly administration, saying the findings "indicate no evident long-term benefit and possible harm [from the cerebral palsy risk]."
An editorialist suggests that, in the absence of longer-term data, repeated courses could be given at lower dosages.
HPV Vaccine May Protect Against Additional Strains
The human papilloma virus vaccine (Gardasil) may provide cross-protection against 10 strains of the virus, in addition to the 4 strains it targets, according to an Associated Press story. The vaccine's manufacturer, Merck, presented the data yesterday at the Interscience Conference on Antimicrobial Agents and Chemotherapy.
The vaccine may now protect against 90% of the strains that cause cervical cancer.
Women should still get regular Pap smears because the vaccine does not cover all HPV strains, Michael Segarra, of North Brunswick (New Jersey) Pediatrics, told the AP.
The vaccine may now protect against 90% of the strains that cause cervical cancer.
Women should still get regular Pap smears because the vaccine does not cover all HPV strains, Michael Segarra, of North Brunswick (New Jersey) Pediatrics, told the AP.
West of Scotland Coronary Prevention Study
Long-Term Follow-Up of a Landmark Statin Trial
The benefits of statin therapy lasted 10 years.
The West of Scotland Coronary Prevention Study was the first large randomized trial of statin therapy in people without a history of coronary events (Journal Watch Nov 28 1995). Pravastatin, compared with placebo, was associated with a significantly lower 5-year rate of death from coronary heart disease or nonfatal myocardial infarction (5.5% vs. 7.9%) and a statistically borderline reduction in all-cause mortality (3% vs. 4%). Now, researchers present an additional 10 years of follow-up data. About one third of patients in both groups were taking statins 5 years after the trial ended; no data were available for statin therapy beyond that time point.
At 15 years, the following outcomes were noted in the original pravastatin group compared with the original placebo group:
Significantly lower rate of death from CHD or nonfatal MI (12% vs. 16%)
Significantly lower CHD mortality (5% vs. 6%)
Significantly lower all-cause mortality (19% vs. 21%)
No significant difference in rates of fatal or nonfatal stroke
No significant difference in cancer rates
Comment: This partly industry-supported extended follow-up of a landmark primary prevention trial shows that the benefits of statin therapy were durable, even though only a minority of patients in both groups took statins after conclusion of the trial. The authors attribute their findings to stabilization of existing plaque and slowing of progression of coronary artery disease. Keep in mind that this study population was high-risk to begin with — participants were middle-aged men with a mean LDL cholesterol of 192 mg/dL, and most were current or ex-smokers.
— Allan S. Brett, MD
Published in Journal Watch General Medicine October 11, 2007
Citation(s):
Ford I et al. Long-term follow-up of the West of Scotland Coronary Prevention Study. N Engl J Med 2007 Oct 11; 357:1477.
The benefits of statin therapy lasted 10 years.
The West of Scotland Coronary Prevention Study was the first large randomized trial of statin therapy in people without a history of coronary events (Journal Watch Nov 28 1995). Pravastatin, compared with placebo, was associated with a significantly lower 5-year rate of death from coronary heart disease or nonfatal myocardial infarction (5.5% vs. 7.9%) and a statistically borderline reduction in all-cause mortality (3% vs. 4%). Now, researchers present an additional 10 years of follow-up data. About one third of patients in both groups were taking statins 5 years after the trial ended; no data were available for statin therapy beyond that time point.
At 15 years, the following outcomes were noted in the original pravastatin group compared with the original placebo group:
Significantly lower rate of death from CHD or nonfatal MI (12% vs. 16%)
Significantly lower CHD mortality (5% vs. 6%)
Significantly lower all-cause mortality (19% vs. 21%)
No significant difference in rates of fatal or nonfatal stroke
No significant difference in cancer rates
Comment: This partly industry-supported extended follow-up of a landmark primary prevention trial shows that the benefits of statin therapy were durable, even though only a minority of patients in both groups took statins after conclusion of the trial. The authors attribute their findings to stabilization of existing plaque and slowing of progression of coronary artery disease. Keep in mind that this study population was high-risk to begin with — participants were middle-aged men with a mean LDL cholesterol of 192 mg/dL, and most were current or ex-smokers.
— Allan S. Brett, MD
Published in Journal Watch General Medicine October 11, 2007
Citation(s):
Ford I et al. Long-term follow-up of the West of Scotland Coronary Prevention Study. N Engl J Med 2007 Oct 11; 357:1477.
Initiating Insulin in Type 2 Diabetes – The "4-T" Trial
First-year comparisons among prandial, biphasic, and basal insulins reveal tradeoffs in efficacy and safety.
We now have a variety of options for initiating insulin in type 2 diabetic patients. In this trial — dubbed "Treating to Target in Type 2 Diabetes," or "4-T" — U.K. researchers compared three options.
The study included 708 adults with type 2 diabetes and hemoglobin A1c between 7% and 10% (mean, 8.5%) despite treatment with sulfonylurea plus metformin. Patients with recurrent major hypoglycemia were excluded. Patients continued oral agents initially and were randomized to receive twice-daily biphasic insulin aspart 30 (NovoMix 30), thrice-daily prandial insulin aspart (NovoRapid), or once-daily (twice if required) basal insulin detemir (Levemir). A protocol specified dose titration, glucose monitoring, and follow-up visits. Novo Nordisk supported the trial.
During 1 year of follow-up, the following outcomes occurred:
Mean fall in HbA1c was significantly greater in the biphasic and prandial groups (about 1.3%) than in the basal group (0.8%).
The proportion of patients with HbA1c 6.5% was significantly greater in the biphasic (17%) and prandial (24%) groups than in the basal group (8%). Better glycemic control with biphasic and prandial insulins occurred primarily among patients whose baseline HbA1c exceeded 8.5%.
Symptomatic hypoglycemia was more common with prandial than biphasic insulin, and with biphasic than basal insulin.
Patients in the basal group gained less weight than those in the other two groups.
Comment: Biphasic or prandial insulin, added to two-drug oral therapy, was more effective than basal insulin in achieving optimal glycemic control, but at the expense of more hypoglycemia and weight gain. Weighing these tradeoffs — along with the greater ease of once-daily insulin injections — the authors and editorialists offer the reasonable conclusion that once-daily basal insulin is probably the best initial approach for initiating insulin in type 2 diabetic patients. If good glycemic control is not achieved with a simple basal regimen, more complex regimens can be introduced later; indeed, more complex regimens will be examined in the next 2 years of this trial. Finally, the editorialists state a preference for glargine (Lantus) as a basal insulin (because it appears to have less of a peak and is slightly longer-acting than detemir), and they believe that sulfonylureas should be stopped when insulin is begun (because their mechanism of action is not synergistic with insulin).
— Allan S. Brett, MD
Published in Journal Watch General Medicine October 23, 2007
Citation(s):
Holman RR et al. Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes. N Engl J Med 2007 Oct 25; 357:1716. (http://dx.doi.org/10.1056/NEJMoa075392)
Original article (Subscription may be required)
Medline abstract (Free)
McMahon GT and Dluhy RG. Intention to treat – Initiating insulin and the 4-T study. N Engl J Med 2007 Oct 25; 357:1759. (http://dx.doi.org/10.1056/NEJMe078196)
Original article (Subscription may be required)
Medline abstract (Free)
We now have a variety of options for initiating insulin in type 2 diabetic patients. In this trial — dubbed "Treating to Target in Type 2 Diabetes," or "4-T" — U.K. researchers compared three options.
The study included 708 adults with type 2 diabetes and hemoglobin A1c between 7% and 10% (mean, 8.5%) despite treatment with sulfonylurea plus metformin. Patients with recurrent major hypoglycemia were excluded. Patients continued oral agents initially and were randomized to receive twice-daily biphasic insulin aspart 30 (NovoMix 30), thrice-daily prandial insulin aspart (NovoRapid), or once-daily (twice if required) basal insulin detemir (Levemir). A protocol specified dose titration, glucose monitoring, and follow-up visits. Novo Nordisk supported the trial.
During 1 year of follow-up, the following outcomes occurred:
Mean fall in HbA1c was significantly greater in the biphasic and prandial groups (about 1.3%) than in the basal group (0.8%).
The proportion of patients with HbA1c 6.5% was significantly greater in the biphasic (17%) and prandial (24%) groups than in the basal group (8%). Better glycemic control with biphasic and prandial insulins occurred primarily among patients whose baseline HbA1c exceeded 8.5%.
Symptomatic hypoglycemia was more common with prandial than biphasic insulin, and with biphasic than basal insulin.
Patients in the basal group gained less weight than those in the other two groups.
Comment: Biphasic or prandial insulin, added to two-drug oral therapy, was more effective than basal insulin in achieving optimal glycemic control, but at the expense of more hypoglycemia and weight gain. Weighing these tradeoffs — along with the greater ease of once-daily insulin injections — the authors and editorialists offer the reasonable conclusion that once-daily basal insulin is probably the best initial approach for initiating insulin in type 2 diabetic patients. If good glycemic control is not achieved with a simple basal regimen, more complex regimens can be introduced later; indeed, more complex regimens will be examined in the next 2 years of this trial. Finally, the editorialists state a preference for glargine (Lantus) as a basal insulin (because it appears to have less of a peak and is slightly longer-acting than detemir), and they believe that sulfonylureas should be stopped when insulin is begun (because their mechanism of action is not synergistic with insulin).
— Allan S. Brett, MD
Published in Journal Watch General Medicine October 23, 2007
Citation(s):
Holman RR et al. Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes. N Engl J Med 2007 Oct 25; 357:1716. (http://dx.doi.org/10.1056/NEJMoa075392)
Original article (Subscription may be required)
Medline abstract (Free)
McMahon GT and Dluhy RG. Intention to treat – Initiating insulin and the 4-T study. N Engl J Med 2007 Oct 25; 357:1759. (http://dx.doi.org/10.1056/NEJMe078196)
Original article (Subscription may be required)
Medline abstract (Free)
Tuesday, October 23, 2007
Thimerosal Exposure and Long-Term Neuropsychological Outcomes
Pre- and postnatal thimerosal exposure was not linked with neuropsychological deficits.
In 1999, the AAP and the U.S. Public Health Service suggested that vaccine manufacturers remove thimerosal preservatives from vaccines to minimize potential mercury toxicity to the developing brain. In this study, investigators examined pre- and postnatal mercury exposure and neuropsychological outcomes in 1047 children at age 7 to 10 years at four HMOs.
Data were collected from complete vaccination records, maternal interviews, and 3-hour neuropsychological assessments of 42 motor and developmental tasks. Estimates of mercury exposure included mothers’ pre- and postnatal exposure to immunoglobulin and vaccines and prenatal fish consumption. Overall, no consistent association was found between pre- or postnatal thimerosal exposure and neuropsychological outcome. A few positive and negative sex-specific associations were noted.
Comment: These results are reassuring for parents whose children were immunized before thimerosal was removed from vaccines. The small potpourri of associations probably reflects the large number of outcomes examined, because no plausible biologic explanation exists for both positive and negative effects. This study did not address a link between thimerosal and autism, but those findings will be reported by the CDC in a separate study. For now, we can reassure parents that mercury has been removed from vaccines, that no clear adverse outcomes have been associated with thimerosal exposure, and that we will continue to assess vaccine safety.
— Peggy Sue Weintrub, MD
Published in Journal Watch Pediatrics and Adolescent Medicine September 26, 2007
Citation(s):
Thompson WW et al. Early thimerosal exposure and neuropsychological outcomes at 7 to 10 years. N Engl J Med 2007 Sep 27; 357:1281.
In 1999, the AAP and the U.S. Public Health Service suggested that vaccine manufacturers remove thimerosal preservatives from vaccines to minimize potential mercury toxicity to the developing brain. In this study, investigators examined pre- and postnatal mercury exposure and neuropsychological outcomes in 1047 children at age 7 to 10 years at four HMOs.
Data were collected from complete vaccination records, maternal interviews, and 3-hour neuropsychological assessments of 42 motor and developmental tasks. Estimates of mercury exposure included mothers’ pre- and postnatal exposure to immunoglobulin and vaccines and prenatal fish consumption. Overall, no consistent association was found between pre- or postnatal thimerosal exposure and neuropsychological outcome. A few positive and negative sex-specific associations were noted.
Comment: These results are reassuring for parents whose children were immunized before thimerosal was removed from vaccines. The small potpourri of associations probably reflects the large number of outcomes examined, because no plausible biologic explanation exists for both positive and negative effects. This study did not address a link between thimerosal and autism, but those findings will be reported by the CDC in a separate study. For now, we can reassure parents that mercury has been removed from vaccines, that no clear adverse outcomes have been associated with thimerosal exposure, and that we will continue to assess vaccine safety.
— Peggy Sue Weintrub, MD
Published in Journal Watch Pediatrics and Adolescent Medicine September 26, 2007
Citation(s):
Thompson WW et al. Early thimerosal exposure and neuropsychological outcomes at 7 to 10 years. N Engl J Med 2007 Sep 27; 357:1281.
HDL Levels Remain Predictive of Heart Risk Even in the Face of Very Low LDL
HDL levels retain their prognostic value in patients treated with statins — even among those who achieve very low LDL levels — researchers report in the New England Journal of Medicine.
A post hoc analysis from the industry-funded Treating to New Targets study examined the predictive value of HDL levels on nearly 10,000 adults with coronary heart disease after 3 months of atorvastatin treatment.
After multivariate adjustment, the 5-year risk for major cardiovascular events was reduced by 25% among patients in the highest quintile of HDL cholesterol compared with those in the lowest quintile. Even among patients who had achieved LDL levels below 70 mg/dL, risk remained significantly reduced (by 39%) in the highest HDL quintile.
Writing in Journal Watch General Medicine, Allan S. Brett concludes: "Whether patients with both low LDL and low HDL would benefit from additional drug therapies to raise HDL cholesterol is unclear. "
A post hoc analysis from the industry-funded Treating to New Targets study examined the predictive value of HDL levels on nearly 10,000 adults with coronary heart disease after 3 months of atorvastatin treatment.
After multivariate adjustment, the 5-year risk for major cardiovascular events was reduced by 25% among patients in the highest quintile of HDL cholesterol compared with those in the lowest quintile. Even among patients who had achieved LDL levels below 70 mg/dL, risk remained significantly reduced (by 39%) in the highest HDL quintile.
Writing in Journal Watch General Medicine, Allan S. Brett concludes: "Whether patients with both low LDL and low HDL would benefit from additional drug therapies to raise HDL cholesterol is unclear. "
Monday, October 22, 2007
Guidelines on MRI Detection of Breast Cancer
The American Cancer Society yesterday released new guidelines for breast cancer screening with MRI as an adjunct to mammography. The principal recommendations, based on literature published between 2002 and 2006, follow.
Annual MRI screening for:
-- those with BRCA mutations
-- first-degree relatives of BRCA carriers
-- those with 20% or greater lifetime risk, as defined by BRCAPRO and other family-history-dependent models
-- those having received chest irradiation between age 10 and 30
-- those with Li-Fraumeni syndrome, Cowden syndrome, and Bannayan-Riley-Ruvalcaba syndrome or their first-degree relatives
Insufficient evidence to recommend for or against MRI screening for:
-- those with a lifetime risk of 15-20%
-- those with lobular carcinoma in situ or atypical lobular hyperplasia
-- those with atypical ductal hyperplasia
-- those with heterogeneous or extreme breast density on mammography
-- those with a personal history of breast cancer, including ductal carcinoma in situ
Women with a less than 15% lifetime risk are recommended not to have MRI screening.
Annual MRI screening for:
-- those with BRCA mutations
-- first-degree relatives of BRCA carriers
-- those with 20% or greater lifetime risk, as defined by BRCAPRO and other family-history-dependent models
-- those having received chest irradiation between age 10 and 30
-- those with Li-Fraumeni syndrome, Cowden syndrome, and Bannayan-Riley-Ruvalcaba syndrome or their first-degree relatives
Insufficient evidence to recommend for or against MRI screening for:
-- those with a lifetime risk of 15-20%
-- those with lobular carcinoma in situ or atypical lobular hyperplasia
-- those with atypical ductal hyperplasia
-- those with heterogeneous or extreme breast density on mammography
-- those with a personal history of breast cancer, including ductal carcinoma in situ
Women with a less than 15% lifetime risk are recommended not to have MRI screening.
Saturday, October 20, 2007
The Pill’s Cancer Protection Confirmed
OC use for fewer than 8 years did not increase overall cancer rates, and it reduced gynecologic cancer risk in British women.
To investigate cancer risk among users of oral contraceptives (OCs), researchers analyzed 36 years of data from the U.K. National Health Service (NHS) and participating British general practitioners on OC use and incidence of various cancers. The study included 745,000 and 339,000 woman-years of observation for OC ever-users and never-users, respectively (NHS dataset), and 331,000 and 224,000 woman-years for ever-users and never-users, respectively (GP dataset).
The NHS data showed that ever-users of OCs had statistically significant relative risk reductions of 12% for any type of cancer and 30% for gynecologic cancers compared with never-users. The GP data demonstrated a 3% generalized cancer risk reduction (not statistically significant) and a 20% gynecologic cancer risk reduction in ever-users (of marginal statistical significance). Neither cohort showed a difference in risk for breast cancer for ever-users versus never-users. In both ever- and never-users, the rate of any cancer increased with age and smoking. Prolonged use of OCs (>8 years) reduced ovarian cancer risk by 62% but increased the risk for any cancer by 20%. In particular, prolonged OC use more than doubled the risk for cervical cancer (risk ratio, 2.73; 95% confidence interval, 1.61–4.61) and increased fivefold the risk for central nervous system and pituitary cancers (RR, 5.51; 95% CI, 1.38–22.05).
Comment: In more than 80% of OC users in this study, the formulations were high-dose (50 µg estrogen); whether similar risk reductions would occur with lower estrogen doses is uncertain. Nonetheless, women can be reassured that fewer than 8 years of OC use seems to be beneficial in cancer prevention, especially for ovarian and uterine cancers, and does not affect breast cancer risk.
— Wendy S. Biggs, MD
Published in Journal Watch Women's Health October 18, 2007
Citation(s):
Hannaford PC et al. Cancer risk among users of oral contraceptives: Cohort data from the Royal College of General Practitioners’ oral contraception study. BMJ 2007 Sep 29; 335:651.
To investigate cancer risk among users of oral contraceptives (OCs), researchers analyzed 36 years of data from the U.K. National Health Service (NHS) and participating British general practitioners on OC use and incidence of various cancers. The study included 745,000 and 339,000 woman-years of observation for OC ever-users and never-users, respectively (NHS dataset), and 331,000 and 224,000 woman-years for ever-users and never-users, respectively (GP dataset).
The NHS data showed that ever-users of OCs had statistically significant relative risk reductions of 12% for any type of cancer and 30% for gynecologic cancers compared with never-users. The GP data demonstrated a 3% generalized cancer risk reduction (not statistically significant) and a 20% gynecologic cancer risk reduction in ever-users (of marginal statistical significance). Neither cohort showed a difference in risk for breast cancer for ever-users versus never-users. In both ever- and never-users, the rate of any cancer increased with age and smoking. Prolonged use of OCs (>8 years) reduced ovarian cancer risk by 62% but increased the risk for any cancer by 20%. In particular, prolonged OC use more than doubled the risk for cervical cancer (risk ratio, 2.73; 95% confidence interval, 1.61–4.61) and increased fivefold the risk for central nervous system and pituitary cancers (RR, 5.51; 95% CI, 1.38–22.05).
Comment: In more than 80% of OC users in this study, the formulations were high-dose (50 µg estrogen); whether similar risk reductions would occur with lower estrogen doses is uncertain. Nonetheless, women can be reassured that fewer than 8 years of OC use seems to be beneficial in cancer prevention, especially for ovarian and uterine cancers, and does not affect breast cancer risk.
— Wendy S. Biggs, MD
Published in Journal Watch Women's Health October 18, 2007
Citation(s):
Hannaford PC et al. Cancer risk among users of oral contraceptives: Cohort data from the Royal College of General Practitioners’ oral contraception study. BMJ 2007 Sep 29; 335:651.
Thursday, October 18, 2007
Doripenem for UTI/intra-abdominal infections
FDA Approves New Drug to Treat Complicated Urinary Tract and Intra-Abdominal Infections
The U.S. Food and Drug Administration has approved doripenem injection, 500 mg intravenous infusion, for the treatment of complicated urinary tract and intra-abdominal infections. Doripenem injection, sold under the trade name Doribax, has been shown to be active against several strains of bacteria.
“This is a significant new drug in the treatment of hospitalized patients with serious bacterial infections,” said Janet Woodcock, M.D., FDA’s deputy commissioner for scientific and medical programs, chief medical officer and acting director, Center for Drug Evaluation and Research.
In several multi-center, multinational studies, doripenem was shown to have a cure rate comparable to the currently prescribed medications levofloxacin, for complicated urinary tract infections, and meropenem, for complicated intra-abdominal infections.
The most common adverse reactions reported were headache, nausea, diarrhea, rash, and phlebitis. In addition, allergic reactions have occurred and some may require immediate treatment.
The safety and effectiveness of doripenem injection in pediatric patients have not been established. Doripenem has not been studied in pregnant women, and the drug should be used during pregnancy only if clearly needed.
Doripenem injection is manufactured by Johnson and Johnson Pharmaceutical Research and Development, LLC, Raritan, N.J.
The U.S. Food and Drug Administration has approved doripenem injection, 500 mg intravenous infusion, for the treatment of complicated urinary tract and intra-abdominal infections. Doripenem injection, sold under the trade name Doribax, has been shown to be active against several strains of bacteria.
“This is a significant new drug in the treatment of hospitalized patients with serious bacterial infections,” said Janet Woodcock, M.D., FDA’s deputy commissioner for scientific and medical programs, chief medical officer and acting director, Center for Drug Evaluation and Research.
In several multi-center, multinational studies, doripenem was shown to have a cure rate comparable to the currently prescribed medications levofloxacin, for complicated urinary tract infections, and meropenem, for complicated intra-abdominal infections.
The most common adverse reactions reported were headache, nausea, diarrhea, rash, and phlebitis. In addition, allergic reactions have occurred and some may require immediate treatment.
The safety and effectiveness of doripenem injection in pediatric patients have not been established. Doripenem has not been studied in pregnant women, and the drug should be used during pregnancy only if clearly needed.
Doripenem injection is manufactured by Johnson and Johnson Pharmaceutical Research and Development, LLC, Raritan, N.J.
Bell Palsy: Prednisolone Improves Outcomes, Acyclovir Ineffective
Early treatment with prednisolone improves outcomes in patients with Bell palsy, whereas acyclovir appears to offer no benefit, researchers report in the New England Journal of Medicine.
Some 550 patients with Bell palsy (most with moderate-to-severe paralysis) were randomized to receive, within 72 hours of symptom onset, 10 days of prednisolone, acyclovir, both drugs, or placebo. Prednisolone recipients were significantly more likely than nonrecipients to achieve complete recovery both at 3 months (83% vs. 64%) and 9 months (94% vs. 82%). Acyclovir did not have an effect on recovery.
Although editorialists agree that acyclovir appears to be ineffective in Bell palsy, they note that another antiviral, valacyclovir, in combination with steroids, improved outcomes in patients with severe disease in a recent randomized trial.
NEJM article (Free abstract; full text requires subscription
Some 550 patients with Bell palsy (most with moderate-to-severe paralysis) were randomized to receive, within 72 hours of symptom onset, 10 days of prednisolone, acyclovir, both drugs, or placebo. Prednisolone recipients were significantly more likely than nonrecipients to achieve complete recovery both at 3 months (83% vs. 64%) and 9 months (94% vs. 82%). Acyclovir did not have an effect on recovery.
Although editorialists agree that acyclovir appears to be ineffective in Bell palsy, they note that another antiviral, valacyclovir, in combination with steroids, improved outcomes in patients with severe disease in a recent randomized trial.
NEJM article (Free abstract; full text requires subscription
Monday, October 8, 2007
Lyme Disease, Chronic
Chronic Lyme disease refuted by experts.
NEJM original article
Summary and Comment
Is "Chronic Lyme Disease" Real?
Patients with chronic symptoms but no objective criteria for infection are receiving long-term antibiotic therapy.
Lyme disease, caused by Borrelia burgdorferi in North America and other Borrelia species in Europe, is the most common tick-borne infection in the Northern hemisphere and is a significant public health problem.
Whereas early Lyme disease, late Lyme disease, and post–Lyme disease symptoms/syndrome are recognized conditions, the term "chronic Lyme disease" has recently been popularized by a small number of practitioners. Chronic, nonspecific symptoms (e.g., fatigue, headache, dizziness) are attributed to persistent or incurable B. burgdorferi infection, and patients are subsequently treated with long-term parenteral antibiotics. The Ad Hoc International Lyme Disease Group has written an editorial summarizing the controversy surrounding the diagnosis and treatment of chronic Lyme disease.
Objective manifestations of Lyme disease include erythema migrans (the most common presentation of early Lyme disease), certain neurologic and cardiac manifestations, and pauciarticular arthritis (the most common presentation of late Lyme disease). These symptoms respond well to conventional antibiotic therapy. Symptoms of post–Lyme disease include fatigue, musculoskeletal pain, and difficulties with concentration or short-term memory following resolution of objective manifestations of infection. These symptoms are usually mild, typically resolve within months, and antibiotic therapy is not indicated; when the difficulties persist longer than 6 months, the condition is termed post–Lyme disease syndrome. Laboratory testing (usually acute- and convalescent-phase serologies; less commonly, PCR or culture) is a key component of Lyme disease diagnosis; in most cases, the testing allows clinicians to confirm evidence of current or past B. burgdorferi infection.
By contrast, chronic Lyme disease is the term assigned to patients reporting chronic symptoms without objective clinical, laboratory, or epidemiologic criteria for infection. They receive chronic parenteral antibiotic therapy for periods of many months to years, despite the absence of any scientific evidence to support this practice.
The authors divide patients receiving a diagnosis of chronic Lyme disease into four categories:
Those with symptoms of unknown cause and no evidence of B. burgdorferi infection
Those with an identifiable illness other than Lyme disease unrelated to B. burgdorferi infection (e.g., multiple sclerosis)
Those with symptoms of unknown cause and antibodies against B. burgdorferi but no history of objective clinical findings consistent with Lyme disease
Those with resolution of objective manifestations of Lyme disease after antibiotic therapy who have symptoms of unknown cause (some have post–Lyme disease symptoms or syndrome)
Chronic antibiotic therapy for chronic Lyme disease has resulted in life-threatening anaphylaxis, cholecystectomy after biliary complications from ceftriaxone administration, a fatality due to candidemia from intravenous catheter infection, and other serious adverse events related to intravenous catheters.
Comment: The authors systematically refute the pseudoscience behind the diagnosis and treatment of so-called chronic Lyme disease in this well-referenced editorial. The writing and the tables summarizing the manifestations of B. burgdorferi infection and the laboratory diagnosis of Lyme disease are lucent and practical.
— Mary Wu Chang, MD
Published in Journal Watch Dermatology October 3, 2007
Citation(s):
Feder HM et al. A critical appraisal of "chronic lyme disease." N Engl J Med 2007 Oct 4; 357:1422.
Original article (Subscription may be required)
NEJM original article
Summary and Comment
Is "Chronic Lyme Disease" Real?
Patients with chronic symptoms but no objective criteria for infection are receiving long-term antibiotic therapy.
Lyme disease, caused by Borrelia burgdorferi in North America and other Borrelia species in Europe, is the most common tick-borne infection in the Northern hemisphere and is a significant public health problem.
Whereas early Lyme disease, late Lyme disease, and post–Lyme disease symptoms/syndrome are recognized conditions, the term "chronic Lyme disease" has recently been popularized by a small number of practitioners. Chronic, nonspecific symptoms (e.g., fatigue, headache, dizziness) are attributed to persistent or incurable B. burgdorferi infection, and patients are subsequently treated with long-term parenteral antibiotics. The Ad Hoc International Lyme Disease Group has written an editorial summarizing the controversy surrounding the diagnosis and treatment of chronic Lyme disease.
Objective manifestations of Lyme disease include erythema migrans (the most common presentation of early Lyme disease), certain neurologic and cardiac manifestations, and pauciarticular arthritis (the most common presentation of late Lyme disease). These symptoms respond well to conventional antibiotic therapy. Symptoms of post–Lyme disease include fatigue, musculoskeletal pain, and difficulties with concentration or short-term memory following resolution of objective manifestations of infection. These symptoms are usually mild, typically resolve within months, and antibiotic therapy is not indicated; when the difficulties persist longer than 6 months, the condition is termed post–Lyme disease syndrome. Laboratory testing (usually acute- and convalescent-phase serologies; less commonly, PCR or culture) is a key component of Lyme disease diagnosis; in most cases, the testing allows clinicians to confirm evidence of current or past B. burgdorferi infection.
By contrast, chronic Lyme disease is the term assigned to patients reporting chronic symptoms without objective clinical, laboratory, or epidemiologic criteria for infection. They receive chronic parenteral antibiotic therapy for periods of many months to years, despite the absence of any scientific evidence to support this practice.
The authors divide patients receiving a diagnosis of chronic Lyme disease into four categories:
Those with symptoms of unknown cause and no evidence of B. burgdorferi infection
Those with an identifiable illness other than Lyme disease unrelated to B. burgdorferi infection (e.g., multiple sclerosis)
Those with symptoms of unknown cause and antibodies against B. burgdorferi but no history of objective clinical findings consistent with Lyme disease
Those with resolution of objective manifestations of Lyme disease after antibiotic therapy who have symptoms of unknown cause (some have post–Lyme disease symptoms or syndrome)
Chronic antibiotic therapy for chronic Lyme disease has resulted in life-threatening anaphylaxis, cholecystectomy after biliary complications from ceftriaxone administration, a fatality due to candidemia from intravenous catheter infection, and other serious adverse events related to intravenous catheters.
Comment: The authors systematically refute the pseudoscience behind the diagnosis and treatment of so-called chronic Lyme disease in this well-referenced editorial. The writing and the tables summarizing the manifestations of B. burgdorferi infection and the laboratory diagnosis of Lyme disease are lucent and practical.
— Mary Wu Chang, MD
Published in Journal Watch Dermatology October 3, 2007
Citation(s):
Feder HM et al. A critical appraisal of "chronic lyme disease." N Engl J Med 2007 Oct 4; 357:1422.
Original article (Subscription may be required)
Friday, October 5, 2007
Fish intake in pregnancy
New Seafood Recommendations for Pregnant Women
The National Healthy Mothers, Healthy Babies Coalition has recommended that pregnant, breast-feeding, and postpartum women consume at least 12 ounces of seafood weekly, especially oily ocean fish like salmon and sardines. Six of the twelve ounces may come from albacore tuna.
The coalition, which comprises groups such as the American Academy of Pediatrics and the CDC, says that "recent studies indicate the nutritional benefits of fish consumption during pregnancy greatly outweigh potential risks from trace methyl mercury consumption."
The recommendation contrasts with that previously issued by the FDA and the Environmental Protection Agency. In 2004, these groups advised that women who are pregnant, breast-feeding, or planning a pregnancy consume up to 12 ounces of lower-mercury seafood (e.g., shrimp, canned light tuna) weekly, with albacore limited to 6 ounces. They also recommend that such women avoid high-mercury fish (e.g., shark, swordfish).
The FDA plans to review this information but is not ready to change its current stance, reports the Washington Post.
recommendation link
The National Healthy Mothers, Healthy Babies Coalition has recommended that pregnant, breast-feeding, and postpartum women consume at least 12 ounces of seafood weekly, especially oily ocean fish like salmon and sardines. Six of the twelve ounces may come from albacore tuna.
The coalition, which comprises groups such as the American Academy of Pediatrics and the CDC, says that "recent studies indicate the nutritional benefits of fish consumption during pregnancy greatly outweigh potential risks from trace methyl mercury consumption."
The recommendation contrasts with that previously issued by the FDA and the Environmental Protection Agency. In 2004, these groups advised that women who are pregnant, breast-feeding, or planning a pregnancy consume up to 12 ounces of lower-mercury seafood (e.g., shrimp, canned light tuna) weekly, with albacore limited to 6 ounces. They also recommend that such women avoid high-mercury fish (e.g., shark, swordfish).
The FDA plans to review this information but is not ready to change its current stance, reports the Washington Post.
recommendation link
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