Cervical Cancer: New Guidelines for Screening and Prevention
Consensus guidelines for screening and management of abnormal cervical findings have been updated.
In October 2007, evidenced-based guidelines1,2 for the screening and management of cervical cancer were published to replace the 2001 guidelines. The updated guidelines were developed at a 2006 consensus conference of experts representing 29 organizations, including the National Institutes of Health, the American Cancer Society, and the American College of Obstetricians and Gynecologists. Table 1 shows the relevant clinical terms and their abbreviations.
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Table 1. 2006 Consensus Guidelines: Clinical Terms
GUIDELINE OVERVIEW
A significant body of evidence (most notably the results of the National Cancer Institute’s ASC-US/LGSIL triage study) has accrued since 2001 and is central to the new consensus guidelines. The authors make it clear that guidelines cannot apply to all situations and therefore should not serve as a substitute for the clinical judgment that must be used in the management of individual patients. Algorithms for the new recommendations are available from the American Society for Colposcopy and Cervical Pathology.3,4
The 2006 guidelines show significant evolution in the management of abnormal cervical cancer screening results, especially in adolescents and in patients with HGSIL. Minor changes also have been incorporated into management of atypical glandular cells and cervical abnormalities in pregnant patients. The management of LGSIL in most patient categories remains essentially unchanged. Noteworthy revisions have been made in the recommended management of CIN 1. Minor modifications have been made to the CIN 2,3 treatment guidelines, and conservative management recommendations in adolescents have been expanded.
The option of offering HPV testing to women 30 and older, first included in a 2004 interim guideline, has been formally adopted. In women who test negative on Pap smear and positive for HPV, both tests should be repeated in 12 months. When cytology and HPV testing are both negative, routine screening need not be performed for 3 years. HPV testing is recommended for routine screening only in women 30 and older.
UPDATED RECOMMENDATIONS: ABNORMAL CERVICAL CANCER SCREENING TESTS
Adolescent women with AS-CUS or LGSIL:2 Adolescents (women 20 and younger) have a much higher prevalence of HPV than do older women; they also have a higher prevalence of low-grade cervical cytologic abnormalities. Adolescents spontaneously clear most infections, and the associated minor cytologic abnormalities are of little long-term significance. The guidelines do not distinguish between ASC-US and LGSIL in adolescents, as the outcomes of both are similar in this age group.
Reflex HPV testing is not recommended for adolescents with ASC-US. In general, HPV testing is unacceptable in adolescents with ASC-US or LGSIL and, if inadvertently performed, should not influence management. Instead, adolescents with a result of ASC-US or LGSIL should undergo repeat cytologic testing 1 year later. If, at 1-year repeat testing:
Cytology is less than HGSIL, then cytology should be performed again 1 year later. If the second cytologic testing (24 months after the initial finding of ASC-US or LGSIL) reveals ASC-US or greater, then colposcopy should be performed.
Cytology is HGSIL or greater, colposcopy should be performed.
Women with ASC-H: Adolescents as well as adult women with ASC-H should undergo colposcopy.
Immunosuppressed women: ASC-US in immunosuppressed women, such as those with HIV infection, should be managed the same as in women in the general population (i.e., colposcopy is not necessarily required).
Pregnant women with LGSIL: Colposcopy is preferred for nonadolescents, but the procedure may be deferred until 6 weeks postpartum. If colposcopy shows no evidence of CIN 2,3, then postpartum follow-up is recommended.
Postmenopausal women with LGSIL: Postmenopausal women with LGSIL can be managed less aggressively than premenopausal women because the prevalence of HPV positivity in women with LGSIL declines with age. Options include evaluation with reflex HPV testing, repeat cytologic testing at 6 and 12 months, and colposcopy.
Women with HGSIL: New emphasis is placed on the see-and-treat approach in nonadolescent women. Management options include immediate loop electrosurgical excision or colposcopy with endocervical assessment. Loop electrosurgical excision is unacceptable in adolescent women with HGSIL, for whom colposcopy is recommended.
Women with AGC: For all subcategories of AGC and AIS except atypical endometrial cells, the recommendations call for colposcopy with endocervical sampling, HPV testing, and (in women older than 35 or at risk for endometrial hyperplasia) endometrial sampling. In patients with atypical endometrial cells, endometrial and endocervical sampling are appropriate initial steps. If these samples show no endometrial pathology, then colposcopy is recommended.
UPDATED RECOMMENDATIONS: CIN AND AIS
Women with histologic diagnosis of CIN 1:1 Major changes to the recommendations for CIN 1 treatment are focused on the patient’s prior abnormal cytologic findings and not on the adequacy of the colposcopy. Management does not depend on whether the colposcopy was satisfactory, and treatment is not an acceptable option in women with CIN 1 preceded by cytologic evidence of ASC-US, ASC-H, or LGSIL. Rather, follow-up with cytology every 6 to 12 months or HPV testing at 12 months is recommended. If follow-up HPV is positive or follow-up cytology is greater than or equal to ASC-US, then colposcopy is recommended.
In women with CIN 1 preceded by HGSIL or AGC-NOS (not otherwise specified) three options are acceptable: (1) diagnostic excisional procedure (except in adolescents and pregnant women); (2) observation with colposcopy and cytology at 6-month intervals for 1 year if the colposcopy is satisfactory and endocervical sampling is negative; or (3) review of all findings with revised interpretation if necessary.
Adolescents with CIN 1, 2, or 3: Management of adolescents with CIN 1 is not dependent on prior abnormal cytology, and repeat cytology is recommended every 12 months. In adolescents with CIN 2,3, either observation or treatment is acceptable if the colposcopy is satisfactory. If CIN 2 is specified, then observation is preferred. If CIN 3 is specified or if colposcopy is unsatisfactory, treatment is recommended. If CIN 3 is specified and colposcopy is adequate, then repeat colposcopy and cytology at 6-month intervals is acceptable.
Women with CIN 2,3: Either excision or ablation is acceptable in cases with satisfactory colposcopy. When colposcopy is unsatisfactory, a diagnostic excisional procedure is the recommended treatment. In women with recurrent CIN 2,3, a repeat diagnostic excisional procedure is recommended over transitional zone ablation (T zone; junction of squamous and columnar epithelium). For older women with recurrent CIN 2,3 who have concluded childbearing, either repeat diagnostic excision or hysterectomy is an acceptable option.
Adenocarcinoma in situ: Hysterectomy is the preferred treatment, with conservative management acceptable only if preservation of fertility is desired. In such cases (and when margins are involved or the endocervical sampling is positive), reexcision is recommended.
CONCLUSION
Progress in our understanding of the natural history of cervical intraepithelial lesions and HPV infection has led to significant changes in recommendations for evaluation and treatment of abnormal Pap smears, cervical intraepithelial neoplasias, and adenocarcinoma in situ. These advances, in concert with HPV vaccination, show clear promise in preventing cervical cancer.
— Ann J. Davis, MD
Published in Journal Watch Women's Health November 29, 2007
Citation(s):
1. Wright TC Jr et al. 2006 consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma in situ. Am J Obstet Gynecol 2007 Oct; 197:340.
Medline abstract (Free)
2. Wright TC Jr et al. 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol 2007 Oct; 197:346.
Medline abstract (Free)
3. American Society for Colposcopy and Cervical Pathology. Management of women with atypical squamous cells of undetermined significance (ASC-US). 2006, 2007. (http://www.asccp.org/pdfs/consensus/algorithms_cyto_07.pdf)
4. American Society for Colposcopy and Cervical Pathology. Management of women with a histological diagnosis of cervical intraepithelial neoplasia grade 1 (CIN 1) preceded by ASC-US, ASC-H or LSIL cytology. 2006, 2007. (http://www.asccp.org/pdfs/consensus/algorithms_hist_07.pdf)
Friday, December 21, 2007
Thiazolidinediones and Heart Disease Risk
Pioglitazone had a mixed risk profile, and rosiglitazone increased risk for ischemic heart disease, but neither increased mortality.
Results from small clinical trials and early pooled analyses have raised concerns about cardiovascular risks associated with rosiglitazone, one of two thiazolidinediones used to treat patients with type 2 diabetes mellitus. Two new meta-analyses further clarify the risks associated with pioglitazone and rosiglitazone.
Independent researchers analyzed data provided by the manufacturer from 19 randomized trials (16,390 patients) that compared pioglitazone with placebo or an active comparator. Most treatment protocols were 12 to 24 months. The hazard ratios for myocardial infarction, stroke, or death each were reduced after about 1 year of treatment with pioglitazone, although only the 18% reduction in the combined endpoint was significant. Risk for serious heart failure was significantly increased by 41%.
In a review of 140 randomized trials, researchers found 4 trials (14,291 patients) that compared rosiglitazone with placebo or an active comparator and had at least 12 months of follow-up. The risk for myocardial infarction in patients who received rosiglitazone was increased by about 40%, and the risk for heart failure was more than doubled; however, the risk for death from cardiovascular disease was not increased.
Comment: Both thiazolidinediones are associated with increased risk for heart failure in patients with type 2 diabetes mellitus, but only rosiglitazone appears to increase risk for ischemic heart disease. Prescribing information for both drugs now includes a "black box" warning about heart failure; in addition, an FDA advisory committee has suggested that warnings about ischemic heart disease be included for rosiglitazone. Editorialists note how unlikely it would have been for either drug to have been approved initially had these risks been known. They call for tighter postmarketing surveillance, especially for new classes of drugs and in higher-risk patients.
— Thomas L. Schwenk, MD
Results from small clinical trials and early pooled analyses have raised concerns about cardiovascular risks associated with rosiglitazone, one of two thiazolidinediones used to treat patients with type 2 diabetes mellitus. Two new meta-analyses further clarify the risks associated with pioglitazone and rosiglitazone.
Independent researchers analyzed data provided by the manufacturer from 19 randomized trials (16,390 patients) that compared pioglitazone with placebo or an active comparator. Most treatment protocols were 12 to 24 months. The hazard ratios for myocardial infarction, stroke, or death each were reduced after about 1 year of treatment with pioglitazone, although only the 18% reduction in the combined endpoint was significant. Risk for serious heart failure was significantly increased by 41%.
In a review of 140 randomized trials, researchers found 4 trials (14,291 patients) that compared rosiglitazone with placebo or an active comparator and had at least 12 months of follow-up. The risk for myocardial infarction in patients who received rosiglitazone was increased by about 40%, and the risk for heart failure was more than doubled; however, the risk for death from cardiovascular disease was not increased.
Comment: Both thiazolidinediones are associated with increased risk for heart failure in patients with type 2 diabetes mellitus, but only rosiglitazone appears to increase risk for ischemic heart disease. Prescribing information for both drugs now includes a "black box" warning about heart failure; in addition, an FDA advisory committee has suggested that warnings about ischemic heart disease be included for rosiglitazone. Editorialists note how unlikely it would have been for either drug to have been approved initially had these risks been known. They call for tighter postmarketing surveillance, especially for new classes of drugs and in higher-risk patients.
— Thomas L. Schwenk, MD
Raloxifene Approved for Reducing Invasive Breast Cancer Risk
The osteoporosis drug raloxifene (Evista) has been approved for the prevention of invasive breast cancer in postmenopausal women with osteoporosis or postmenopausal women at high risk for invasive breast cancer, the FDA announced Friday.
The agency warned that raloxifene, a selective estrogen receptor modulator, should not be taken with cholestyramine or estrogens. Premenopausal women, especially if they are pregnant or considering pregnancy, also should not take this drug.
Raloxifene can cause serious side effects, including deep venous thrombosis, pulmonary embolism, and death due to stroke. Accordingly, the director of the FDA's Center for Drug Evaluation and Research cautioned that "the benefits and risks of taking [raloxifene] should be carefully evaluated for each individual woman."
The agency warned that raloxifene, a selective estrogen receptor modulator, should not be taken with cholestyramine or estrogens. Premenopausal women, especially if they are pregnant or considering pregnancy, also should not take this drug.
Raloxifene can cause serious side effects, including deep venous thrombosis, pulmonary embolism, and death due to stroke. Accordingly, the director of the FDA's Center for Drug Evaluation and Research cautioned that "the benefits and risks of taking [raloxifene] should be carefully evaluated for each individual woman."
Monday, December 3, 2007
Hypertonic Saline for Bronchiolitis
Nebulized hypertonic saline reduced hospital length of stay in young children with bronchiolitis.
Viral bronchiolitis is a common cause of hospitalization for infants and young children during the winter months, but evidence does not support therapeutic interventions other than supportive care (Journal Watch Pediatrics and Adolescent Medicine Jan 10 2007). Nebulized hypertonic saline (HS) has shown promise in the treatment of small airway obstruction in patients with cystic fibrosis. To evaluate the efficacy of this treatment for viral bronchiolitis, investigators in Canada and the United Arab Emirates randomized 96 children younger than 18 months (mean age, 4.7 months) who were hospitalized with moderately severe bronc hiolitis to receive frequent (every 2–6 hours) doses of either nebulized 3.0% HS or 0.9% normal saline (NS).
Hospital length of stay, the primary outcome, was significantly shorter in the HS group than in the NS group (2.6 vs. 3.5 days). Discharge decisions were based on clinical judgment or protocol-based criteria at the treating clinician’s discretion. The frequency of add-on nonprotocol treatments, given at the attending physician’s discretion, was similar in the two groups; about 60% of nebulizations in both groups included albuterol or racemic epinephrine. No adverse respiratory effects were noted, although two children in the HS group and three in the NS group were withdrawn from the study by parents because of crying or agitation during nebulization.
Comment: Most of the hospitalized infants in this study tested positive for respiratory syncytial virus. Thus, these findings are applicable to typical moderately ill infants with bronchiolitis in the U.S. The nebulization treatments in this study were frequent, every 2 hours at first, but a previous inpatient study that administered nebulizations three times daily reported a similar 1-day reduction in hospital stay. Because most patients in the current study received additional nebulized medications rather than hypertonic saline alone, editorialists propose a future study to explore the possible synergy between HS and bronchodilators.
— Cornelius W. Van Niel, MD
Published in Journal Watch Pediatrics and Adolescent Medicine November 7, 2007
Citation(s):
Kuzik BA et al. Nebulized hypertonic saline in the treatment of viral bronchiolitis in infants. J Pediatr 2007 Sep; 151:266.
Medline abstract (Free)
Calogero C and Sly PD. Acute viral bronchiolitis: To treat or not to treat — That is the question. J Pediatr 2007 Sep; 151:235.
Viral bronchiolitis is a common cause of hospitalization for infants and young children during the winter months, but evidence does not support therapeutic interventions other than supportive care (Journal Watch Pediatrics and Adolescent Medicine Jan 10 2007). Nebulized hypertonic saline (HS) has shown promise in the treatment of small airway obstruction in patients with cystic fibrosis. To evaluate the efficacy of this treatment for viral bronchiolitis, investigators in Canada and the United Arab Emirates randomized 96 children younger than 18 months (mean age, 4.7 months) who were hospitalized with moderately severe bronc hiolitis to receive frequent (every 2–6 hours) doses of either nebulized 3.0% HS or 0.9% normal saline (NS).
Hospital length of stay, the primary outcome, was significantly shorter in the HS group than in the NS group (2.6 vs. 3.5 days). Discharge decisions were based on clinical judgment or protocol-based criteria at the treating clinician’s discretion. The frequency of add-on nonprotocol treatments, given at the attending physician’s discretion, was similar in the two groups; about 60% of nebulizations in both groups included albuterol or racemic epinephrine. No adverse respiratory effects were noted, although two children in the HS group and three in the NS group were withdrawn from the study by parents because of crying or agitation during nebulization.
Comment: Most of the hospitalized infants in this study tested positive for respiratory syncytial virus. Thus, these findings are applicable to typical moderately ill infants with bronchiolitis in the U.S. The nebulization treatments in this study were frequent, every 2 hours at first, but a previous inpatient study that administered nebulizations three times daily reported a similar 1-day reduction in hospital stay. Because most patients in the current study received additional nebulized medications rather than hypertonic saline alone, editorialists propose a future study to explore the possible synergy between HS and bronchodilators.
— Cornelius W. Van Niel, MD
Published in Journal Watch Pediatrics and Adolescent Medicine November 7, 2007
Citation(s):
Kuzik BA et al. Nebulized hypertonic saline in the treatment of viral bronchiolitis in infants. J Pediatr 2007 Sep; 151:266.
Medline abstract (Free)
Calogero C and Sly PD. Acute viral bronchiolitis: To treat or not to treat — That is the question. J Pediatr 2007 Sep; 151:235.
Saturday, November 24, 2007
Tuesday, November 13, 2007
Relation Between Oral Contraceptive Use and Cervical Cancer
Use of oral contraceptives for 5 or more years doubles the risk for invasive cervical cancer, but the risk decreases progressively after stopping use, according to a Lancet study.
Researchers examined data on oral contraceptive use from 24 studies comprising some 11,200 women with invasive cervical cancer and 35,500 controls. The risk for cancer increased with duration of use, was highest in current users, and declined with time since last use. Among those who'd stopped using oral contraceptives for 10 years or more, the risk was similar to that of never users.
To give a sense of the additional risk, the authors estimate that 10 years' use starting at age 20 would raise the cumulative cancer incidence at age 50 from 3.8 to 4.5 per 1000 women.
An editorialist points out a potential confounding factor: "Women using oral contraceptives are more likely to be exposed to HPV than are those using barrier methods or not having sexual intercourse."
Lancet article (Free abstract; full text requires subscription)
Researchers examined data on oral contraceptive use from 24 studies comprising some 11,200 women with invasive cervical cancer and 35,500 controls. The risk for cancer increased with duration of use, was highest in current users, and declined with time since last use. Among those who'd stopped using oral contraceptives for 10 years or more, the risk was similar to that of never users.
To give a sense of the additional risk, the authors estimate that 10 years' use starting at age 20 would raise the cumulative cancer incidence at age 50 from 3.8 to 4.5 per 1000 women.
An editorialist points out a potential confounding factor: "Women using oral contraceptives are more likely to be exposed to HPV than are those using barrier methods or not having sexual intercourse."
Lancet article (Free abstract; full text requires subscription)
Monday, November 5, 2007
Sunday, November 4, 2007
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.
#
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.
#
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
Wednesday, September 19, 2007
Steroids Have No Benefit for Bronchiolitis
A multicenter trial shows no benefit over placebo.
Bronchiolitis is the most common reason for hospitalization of infants in the U.S., and the possible role for steroid treatment has been hotly debated. To assess the efficacy of dexamethasone, researchers conducted a randomized, double-blind, placebo-controlled trial in infants aged 2 to 12 months at 20 emergency departments during three respiratory virus seasons. Inclusion criteria included first episode of wheezing and an ED diagnosis of moderate-to-severe bronchiolitis (defined as a Respiratory Distress Assessment Instrument [RDAI] score 6).
Of 8686 infants screened, 93% were excluded because of prior wheezing (41% of excluded cases), an RDAI score <6 (25%), or other reasons. Overall, 600 infants were randomized to receive either a single dose of dexamethasone (1 mg/kg up to a maximum of 12 mg) or placebo. All other care was at the discretion of the attending physician. Most patients received bronchodilators.
There were no differences between the dexamethasone and placebo groups in admission rates (the primary outcome), respiratory status 4 hours after treatment, hospital length of stay, or readmission rates. The findings remained the same in infants who were positive or negative for respiratory syncytial virus and in those with and without eczema or a family history of asthma.
Comment: This properly sized, well-designed study should end the use of steroids in children with bronchiolitis. If steroids did have an effect, the inclusion of only patients with moderate-to-severe disease should have favored them by eliminating the mild cases from which recovery is virtually ensured, regardless of treatment. Similarly, the exclusion of patients with prior episodes of wheezing, which might represent asthma, makes this a clean decision: First episode of wheezing means no steroids, period.
— J. Stephen Bohan, MD, MS, FACP, FACEP
Published in Journal Watch Emergency Medicine July 25, 2007
Citation(s):
Corneli HM et al. A multicenter, randomized, controlled trial of dexamethasone for bronchiolitis. N Engl J Med 2007 Jul 26; 357:331-9.
Bronchiolitis is the most common reason for hospitalization of infants in the U.S., and the possible role for steroid treatment has been hotly debated. To assess the efficacy of dexamethasone, researchers conducted a randomized, double-blind, placebo-controlled trial in infants aged 2 to 12 months at 20 emergency departments during three respiratory virus seasons. Inclusion criteria included first episode of wheezing and an ED diagnosis of moderate-to-severe bronchiolitis (defined as a Respiratory Distress Assessment Instrument [RDAI] score 6).
Of 8686 infants screened, 93% were excluded because of prior wheezing (41% of excluded cases), an RDAI score <6 (25%), or other reasons. Overall, 600 infants were randomized to receive either a single dose of dexamethasone (1 mg/kg up to a maximum of 12 mg) or placebo. All other care was at the discretion of the attending physician. Most patients received bronchodilators.
There were no differences between the dexamethasone and placebo groups in admission rates (the primary outcome), respiratory status 4 hours after treatment, hospital length of stay, or readmission rates. The findings remained the same in infants who were positive or negative for respiratory syncytial virus and in those with and without eczema or a family history of asthma.
Comment: This properly sized, well-designed study should end the use of steroids in children with bronchiolitis. If steroids did have an effect, the inclusion of only patients with moderate-to-severe disease should have favored them by eliminating the mild cases from which recovery is virtually ensured, regardless of treatment. Similarly, the exclusion of patients with prior episodes of wheezing, which might represent asthma, makes this a clean decision: First episode of wheezing means no steroids, period.
— J. Stephen Bohan, MD, MS, FACP, FACEP
Published in Journal Watch Emergency Medicine July 25, 2007
Citation(s):
Corneli HM et al. A multicenter, randomized, controlled trial of dexamethasone for bronchiolitis. N Engl J Med 2007 Jul 26; 357:331-9.
Antibiotic Prophylaxis Does Not Lower Rate of Recurrent UTI in Children
In fact, prophylaxis is associated with increased risk for resistant urinary tract infection.
The 1999 American Academy of Pediatrics practice guideline recommends that children with a first urinary tract infection (UTI) undergo imaging to determine the presence and grade of vesicoureteral reflux, which is found in 30% to 40% of children with UTI. The guideline recommends that children with vesicoureteral reflux be given daily antibiotic prophylaxis to suppress recurrent UTI and, theoretically, to prevent renal scarring, but there is scant scientific support for this stance. Therefore, investigators sought to identify risk factors for recurrent UTI and resistant UTI and to assess the value of antibiotic prophylaxis against recurrent UTI in a cohort study of children 6 years or younger.
Among nearly 75,000 children seen at 27 primary care pediatric practices from 2001 to 2006, the incidence of first UTI was 0.7%, the rate of recurrent UTI was 12%, and the cumulative incidence of UTI was 4.2% per person-year. Factors that increased the risk for recurrent UTI were white race (hazard ratio, 1.97); age 3–4 years (HR, 2.75); age 4–5 years (HR, 2.47); and grade 4–5 vesicoureteral reflux (HR, 4.38). Antibiotic prophylaxis was not associated with lower risk of recurrent UTI (HR, 1.01) but was a risk factor for antibiotic resistance among children with recurrent UTI (HR, 7.50).
Comment: This is the first large cohort study to determine the incidence of and risk factors for recurrent UTI in children. The noteworthy discovery that antibiotic prophylaxis does not help prevent recurrent UTI and that, in fact, it leads to an increase in resistant strains in recurrent UTI episodes strikes down conventional dogma. For children 6 years old with primary or recurrent UTI, treat the primary disease, but do not initiate or recommend daily antibiotic prophylaxis.
— John A. Marx, MD, FAAEM, FACEP
Published in Journal Watch Emergency Medicine July 27, 2007
Citation(s):
Conway PH et al. Recurrent urinary tract infections in children: Risk factors and association with prophylactic antimicrobials. JAMA 2007 Jul 11; 298:179-86.
The 1999 American Academy of Pediatrics practice guideline recommends that children with a first urinary tract infection (UTI) undergo imaging to determine the presence and grade of vesicoureteral reflux, which is found in 30% to 40% of children with UTI. The guideline recommends that children with vesicoureteral reflux be given daily antibiotic prophylaxis to suppress recurrent UTI and, theoretically, to prevent renal scarring, but there is scant scientific support for this stance. Therefore, investigators sought to identify risk factors for recurrent UTI and resistant UTI and to assess the value of antibiotic prophylaxis against recurrent UTI in a cohort study of children 6 years or younger.
Among nearly 75,000 children seen at 27 primary care pediatric practices from 2001 to 2006, the incidence of first UTI was 0.7%, the rate of recurrent UTI was 12%, and the cumulative incidence of UTI was 4.2% per person-year. Factors that increased the risk for recurrent UTI were white race (hazard ratio, 1.97); age 3–4 years (HR, 2.75); age 4–5 years (HR, 2.47); and grade 4–5 vesicoureteral reflux (HR, 4.38). Antibiotic prophylaxis was not associated with lower risk of recurrent UTI (HR, 1.01) but was a risk factor for antibiotic resistance among children with recurrent UTI (HR, 7.50).
Comment: This is the first large cohort study to determine the incidence of and risk factors for recurrent UTI in children. The noteworthy discovery that antibiotic prophylaxis does not help prevent recurrent UTI and that, in fact, it leads to an increase in resistant strains in recurrent UTI episodes strikes down conventional dogma. For children 6 years old with primary or recurrent UTI, treat the primary disease, but do not initiate or recommend daily antibiotic prophylaxis.
— John A. Marx, MD, FAAEM, FACEP
Published in Journal Watch Emergency Medicine July 27, 2007
Citation(s):
Conway PH et al. Recurrent urinary tract infections in children: Risk factors and association with prophylactic antimicrobials. JAMA 2007 Jul 11; 298:179-86.
VA Hospital Dramatically Lowers Its MRSA Rate
A Veterans Affairs hospital that screens all new patients for methicillin-resistant S. aureus (MRSA) cut infections to 17 cases from an average of 60 in previous years, according to the New York Times.
The paper quotes the hospital's chief of staff as saying that the entire program — added personnel, screening, using disposable blood pressure cuffs, isolating MRSA carriers, leaving a stethoscope in each room — costs about $500,000 while saving some $900,000 annually in treatment costs. Estimated U.S. costs for treating these infections run up to $30 billion annually.
The article quotes an infection-control advocate who criticizes the CDC's 2006 guidelines for infection control as "lax" and giving hospitals "an excuse to do too little."
CDC's 2006 guidelines on multidrug-resistant organisms (Free PDF)
The paper quotes the hospital's chief of staff as saying that the entire program — added personnel, screening, using disposable blood pressure cuffs, isolating MRSA carriers, leaving a stethoscope in each room — costs about $500,000 while saving some $900,000 annually in treatment costs. Estimated U.S. costs for treating these infections run up to $30 billion annually.
The article quotes an infection-control advocate who criticizes the CDC's 2006 guidelines for infection control as "lax" and giving hospitals "an excuse to do too little."
CDC's 2006 guidelines on multidrug-resistant organisms (Free PDF)
Nonfasting Trigylceride Levels Seem Better at Defining Risk for Heart Disease
Two studies measuring triglycerides in the nonfasting state show a strong association between elevated levels and risk for cardiovascular disease or death. Both appear in today's JAMA.
One study, using a population sample from Copenhagen, followed nearly 14,000 men and women for an average of 26 years. Researchers found that the risk for MI, ischemic heart disease, or death increased with increasing levels of nonfasting triglycerides, especially among women.
Another study, performed within the Women's Health Initiative, followed some 26,500 women for a median of 11 years and compared the effects of fasting versus nonfasting triglycerides on risk for cardiovascular events. When measured in the nonfasting state (especially 2 to 4 hours postprandially), triglyceride levels showed a strong, independent association with future risk, which persisted in fully adjusted analyses. Fasting levels, according to the authors, "showed little independent association with cardiovascular events."
According to an editorialist, the results "suggest that using 2- to 4-hour postprandial triglyceride measurements may be more predictive [of risk] than LDL-C."
One study, using a population sample from Copenhagen, followed nearly 14,000 men and women for an average of 26 years. Researchers found that the risk for MI, ischemic heart disease, or death increased with increasing levels of nonfasting triglycerides, especially among women.
Another study, performed within the Women's Health Initiative, followed some 26,500 women for a median of 11 years and compared the effects of fasting versus nonfasting triglycerides on risk for cardiovascular events. When measured in the nonfasting state (especially 2 to 4 hours postprandially), triglyceride levels showed a strong, independent association with future risk, which persisted in fully adjusted analyses. Fasting levels, according to the authors, "showed little independent association with cardiovascular events."
According to an editorialist, the results "suggest that using 2- to 4-hour postprandial triglyceride measurements may be more predictive [of risk] than LDL-C."
Thursday, September 13, 2007
Polyethylene Glycol for Chronic Constipation
Six months of treatment provided significant symptom relief, compared with placebo.
Polyethylene glycol (PEG) 3350 (MiraLax and others) is an osmotic laxative approved for short-term treatment of constipation. In this multicenter industry-sponsored study, researchers assessed the use of PEG for longer-term treatment of constipation.
The study included 304 patients (mean age, 53; 85% women) with chronic constipation, as defined by standardized criteria; the mean duration of constipation was 23 years. The patients were randomized to receive either once-daily PEG (a 17-g packet mixed with 8 oz of liquid) or placebo. During 6 months of treatment, the primary efficacy endpoint (at least 3 satisfactory bowel movements per week, without use of rescue laxative, for at least half of treatment weeks) was reached by 52% of PEG recipients and 11% of placebo recipients — a highly significant difference. Nearly all secondary endpoints also favored the PEG group decisively. Side effects included abdominal distention and diarrhea; no clinically significant laboratory abnormalities were noted.
Comment: Polyethylene glycol, prescribed for up to 6 months at the dose used in this trial, appears to be safe and reasonably effective for adults with chronic constipation. Note that the patients in this trial were generally healthy, had no evidence of organic bowel disorders, and were not taking medications known to cause constipation.
— Allan S. Brett, MD
Published in Journal Watch General Medicine July 12, 2007
Citation(s):
DiPalma JA et al. A randomized, multicenter, placebo-controlled trial of polyethylene glycol laxative for chronic treatment of chronic constipation. Am J Gastroenterol 2007 Jul; 102:1436-4
Polyethylene glycol (PEG) 3350 (MiraLax and others) is an osmotic laxative approved for short-term treatment of constipation. In this multicenter industry-sponsored study, researchers assessed the use of PEG for longer-term treatment of constipation.
The study included 304 patients (mean age, 53; 85% women) with chronic constipation, as defined by standardized criteria; the mean duration of constipation was 23 years. The patients were randomized to receive either once-daily PEG (a 17-g packet mixed with 8 oz of liquid) or placebo. During 6 months of treatment, the primary efficacy endpoint (at least 3 satisfactory bowel movements per week, without use of rescue laxative, for at least half of treatment weeks) was reached by 52% of PEG recipients and 11% of placebo recipients — a highly significant difference. Nearly all secondary endpoints also favored the PEG group decisively. Side effects included abdominal distention and diarrhea; no clinically significant laboratory abnormalities were noted.
Comment: Polyethylene glycol, prescribed for up to 6 months at the dose used in this trial, appears to be safe and reasonably effective for adults with chronic constipation. Note that the patients in this trial were generally healthy, had no evidence of organic bowel disorders, and were not taking medications known to cause constipation.
— Allan S. Brett, MD
Published in Journal Watch General Medicine July 12, 2007
Citation(s):
DiPalma JA et al. A randomized, multicenter, placebo-controlled trial of polyethylene glycol laxative for chronic treatment of chronic constipation. Am J Gastroenterol 2007 Jul; 102:1436-4
Enoxaparin vs. Heparin: The PREVAIL Study
The jury is still out but may favor enoxaparin.
In this manufacturer-sponsored, open-label, international trial, researchers compared the effectiveness and safety of enoxaparin (low-molecular-weight heparin) and of unfractionated heparin in reducing the overall number of venous-thromboembolism (VTE) events after acute ischemic stroke. The authors randomized 1762 patients within 48 hours of an acute ischemic stroke to receive either enoxaparin (40 mg once daily) or unfractionated heparin (5000 U every 12 hours) for a mean of 10 days. Patients underwent ultrasound, venography, or both. Pulmonary embolism, if suspected, was evaluated by ventilation perfusion scan, helical CT, or angiography.
The analysis included 76% of the patients. Compared with unfractionated heparin, enoxaparin conferred a 43% reduction in overall number of VTE events up to day 14 that was maintained at 30, 60, and 90 days and was independent of stroke severity (NIHSS score of <14 vs. 14). However, the number of symptomatic VTE events did not differ between the treatment groups, and mortality rates were similar. The number of intracranial bleeding events was similar in both groups, and extracranial events (mainly gastrointestinal bleeding) were slightly more common in the enoxaparin group.
Comment: This was the largest prospective study of its kind. Despite some limitations, this study’s many strengths include its strong statistical power and long-term follow-up. The findings may justify the routine use of enoxaparin, although cost was not addressed and the number of symptomatic events was similar regardless of treatment. These limitations indicate that a more thorough cost-effectiveness analysis is needed before enoxaparin is adopted as the standard of care.
— Flavia Nelson, MD, and James Grotta, MD
Dr. Nelson is Assistant Professor of Neurology, Board Certified Internist, The University of Texas Houston Medical School, and Assistant Director, MRI Analysis Center, Multiple Sclerosis Research Group, The University of Texas Health Science Center at Houston. Dr. Grotta is Professor and Chair, Department of Neurology, The University of Texas Houston Medical School, and Director of Vascular Neurology, The University of Texas Health Science Center at Houston.
Published in Journal Watch Neurology June 26, 2007
Citation(s):
Sherman DG et al. The efficacy and safety of enoxaparin versus unfractionated heparin for the prevention of venous thromboembolism after acute ischaemic stroke (PREVAIL Study): An open-label randomised comparison. Lancet 2007 Apr 21; 369:1347-55.
In this manufacturer-sponsored, open-label, international trial, researchers compared the effectiveness and safety of enoxaparin (low-molecular-weight heparin) and of unfractionated heparin in reducing the overall number of venous-thromboembolism (VTE) events after acute ischemic stroke. The authors randomized 1762 patients within 48 hours of an acute ischemic stroke to receive either enoxaparin (40 mg once daily) or unfractionated heparin (5000 U every 12 hours) for a mean of 10 days. Patients underwent ultrasound, venography, or both. Pulmonary embolism, if suspected, was evaluated by ventilation perfusion scan, helical CT, or angiography.
The analysis included 76% of the patients. Compared with unfractionated heparin, enoxaparin conferred a 43% reduction in overall number of VTE events up to day 14 that was maintained at 30, 60, and 90 days and was independent of stroke severity (NIHSS score of <14 vs. 14). However, the number of symptomatic VTE events did not differ between the treatment groups, and mortality rates were similar. The number of intracranial bleeding events was similar in both groups, and extracranial events (mainly gastrointestinal bleeding) were slightly more common in the enoxaparin group.
Comment: This was the largest prospective study of its kind. Despite some limitations, this study’s many strengths include its strong statistical power and long-term follow-up. The findings may justify the routine use of enoxaparin, although cost was not addressed and the number of symptomatic events was similar regardless of treatment. These limitations indicate that a more thorough cost-effectiveness analysis is needed before enoxaparin is adopted as the standard of care.
— Flavia Nelson, MD, and James Grotta, MD
Dr. Nelson is Assistant Professor of Neurology, Board Certified Internist, The University of Texas Houston Medical School, and Assistant Director, MRI Analysis Center, Multiple Sclerosis Research Group, The University of Texas Health Science Center at Houston. Dr. Grotta is Professor and Chair, Department of Neurology, The University of Texas Houston Medical School, and Director of Vascular Neurology, The University of Texas Health Science Center at Houston.
Published in Journal Watch Neurology June 26, 2007
Citation(s):
Sherman DG et al. The efficacy and safety of enoxaparin versus unfractionated heparin for the prevention of venous thromboembolism after acute ischaemic stroke (PREVAIL Study): An open-label randomised comparison. Lancet 2007 Apr 21; 369:1347-55.
Tuesday, September 11, 2007
New Drug Approved for Pulmonary Arterial Hypertension
The FDA has approved the endothelin-receptor antagonist Letairis (ambrisentan) for the treatment of pulmonary arterial hypertension.
In clinical trials, the once-daily pill effectively delayed worsening of the condition.
The FDA notes that Letairis may cause birth defects and should not be used during pregnancy.
fda announcement
In clinical trials, the once-daily pill effectively delayed worsening of the condition.
The FDA notes that Letairis may cause birth defects and should not be used during pregnancy.
fda announcement
Methimazole vs. Propylthiouracil for Hyperthyroidism
Methimazole was superior overall, and lower doses seemed sufficient for patients with mild-to-moderate hyperthyroidism.
Both methimazole and propylthiouracil (PTU) are used to treat hyperthyroidism. To compare these drugs, Japanese researchers randomized 396 patients with Graves hyperthyroidism to receive 15 mg of methimazole once daily, 30 mg of methimazole daily (given as 15 mg twice daily), or 100 mg of PTU three times daily.
At each of three time points (4, 8, and 12 weeks), the proportion of patients with normalized free thyroxine (T4) levels was higher in the 30-mg methimazole group than in the other two groups. The differences were of borderline statistical significance at 4 and 8 weeks but significant at 12 weeks (normal free T4 achieved in 97%, 86%, and 78% of patients in the 30-mg methimazole, 15-mg methimazole, and PTU groups, respectively). In patients with mild or moderate hyperthyroidism, normal free T4 was achieved at similar rates in the three groups. However, in patients with severe hyperthyroidism (i.e., free T4 7 ng/dL), higher-dose methimazole was more effective than lower-dose methimazole or PTU. Transaminase elevations and leukopenia occurred less commonly with both doses of methimazole than with PTU. Rash was less common with lower-dose methimazole than with higher-dose methimazole or PTU.
Comment: Based on these results, the authors favor methimazole — at doses of 15 mg/day for those with mild-to-moderate hyperthyroidism, and 30 mg/day for those with severe hyperthyroidism. Because other studies have reached similar conclusions, most U.S. experts already favor methimazole. One exception is that PTU is recommended during pregnancy.
— Allan S. Brett, MD
Published in Journal Watch General Medicine June 19, 2007
Citation(s):
Nakamura H et al. Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves’ disease. J Clin Endocrinol Metab 2007 Jun; 92:2157-62.
Both methimazole and propylthiouracil (PTU) are used to treat hyperthyroidism. To compare these drugs, Japanese researchers randomized 396 patients with Graves hyperthyroidism to receive 15 mg of methimazole once daily, 30 mg of methimazole daily (given as 15 mg twice daily), or 100 mg of PTU three times daily.
At each of three time points (4, 8, and 12 weeks), the proportion of patients with normalized free thyroxine (T4) levels was higher in the 30-mg methimazole group than in the other two groups. The differences were of borderline statistical significance at 4 and 8 weeks but significant at 12 weeks (normal free T4 achieved in 97%, 86%, and 78% of patients in the 30-mg methimazole, 15-mg methimazole, and PTU groups, respectively). In patients with mild or moderate hyperthyroidism, normal free T4 was achieved at similar rates in the three groups. However, in patients with severe hyperthyroidism (i.e., free T4 7 ng/dL), higher-dose methimazole was more effective than lower-dose methimazole or PTU. Transaminase elevations and leukopenia occurred less commonly with both doses of methimazole than with PTU. Rash was less common with lower-dose methimazole than with higher-dose methimazole or PTU.
Comment: Based on these results, the authors favor methimazole — at doses of 15 mg/day for those with mild-to-moderate hyperthyroidism, and 30 mg/day for those with severe hyperthyroidism. Because other studies have reached similar conclusions, most U.S. experts already favor methimazole. One exception is that PTU is recommended during pregnancy.
— Allan S. Brett, MD
Published in Journal Watch General Medicine June 19, 2007
Citation(s):
Nakamura H et al. Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves’ disease. J Clin Endocrinol Metab 2007 Jun; 92:2157-62.
Sequential Therapy for H. pylori Eradication
In this study, sequential therapy was more efficacious than simultaneous therapy, but the mechanism underlying its success remains unexplained.
Standard triple therapy for Helicobacter pylori infection consists of a proton-pump inhibitor and two antibiotics, administered simultaneously. Increasing resistance to two commonly used antibiotics, metronidazole and clarithromycin, has decreased the efficacy of this approach to less than 80% in North America and Europe. Small studies have suggested that sequential, rather than simultaneous, antibiotic therapy might improve eradication rates. Researchers explored this possibility in a double-blind study that involved 300 adults in Italy with dyspepsia or peptic ulcers.
Participants were evaluated by endoscopy (with biopsies for histologic evaluation, culture, and urease testing) and by urea breath testing to confirm H. pylori infection. They then were randomized to receive standard therapy twice daily for 10 days (pantoprazole [40 mg], amoxicillin [1 g], and clarithromycin [500 mg]) or sequential therapy (pantoprazole [40 mg], amoxicillin [1 g], and placebo twice daily for 5 days, followed by pantoprazole [40 mg], clarithromycin [500 mg], and tinidazole [500 mg] twice daily for 5 days). Follow-up breath testing was performed at 4 and 8 weeks after completion of therapy. Eradication was defined as negative results on both tests.
Per-protocol analysis revealed eradication rates of 93% for sequential therapy and 79% for standard therapy (P=0.001). Among patients with clarithromycin-resistant H. pylori strains, eradication rates were higher with sequential than with standard therapy (89% vs. 29%; P=0.003), but, among those with metronidazole-resistant strains, rates were similar in the two treatment arms (97% vs. 91%). Among patients with strains that were resistant to both clarithromycin and metronidazole, none of four sequential-therapy recipients, versus two of seven standard-therapy recipients, achieved eradication. Side effects were mild and similar between groups. The authors concluded that sequential therapy might be more effective than standard triple therapy and should be considered as a possible first-line therapy for patients with H. pylori infection.
Comment: These results provide important information about how to address the dropping success rates for H. pylori eradication therapy in North America and Europe. The mechanism underlying sequential therapy’s superiority in this trial remains unclear. Initial therapy with amoxicillin might increase the efficacy of clarithromycin in the second phase of treatment; however, the results also could be due to the addition of a new drug, tinidazole, to the standard regimen. Additional studies should be performed to clarify the mechanism and generalizability of this effect.
— David J. Bjorkman, MD, MSPH (HSA), SM (Epid.)
Published in Journal Watch Gastroenterology June 15, 2007
Citation(s):
Vaira D et al. Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: A randomized trial. Ann Intern Med 2007 Apr 17; 146:556-63.
Standard triple therapy for Helicobacter pylori infection consists of a proton-pump inhibitor and two antibiotics, administered simultaneously. Increasing resistance to two commonly used antibiotics, metronidazole and clarithromycin, has decreased the efficacy of this approach to less than 80% in North America and Europe. Small studies have suggested that sequential, rather than simultaneous, antibiotic therapy might improve eradication rates. Researchers explored this possibility in a double-blind study that involved 300 adults in Italy with dyspepsia or peptic ulcers.
Participants were evaluated by endoscopy (with biopsies for histologic evaluation, culture, and urease testing) and by urea breath testing to confirm H. pylori infection. They then were randomized to receive standard therapy twice daily for 10 days (pantoprazole [40 mg], amoxicillin [1 g], and clarithromycin [500 mg]) or sequential therapy (pantoprazole [40 mg], amoxicillin [1 g], and placebo twice daily for 5 days, followed by pantoprazole [40 mg], clarithromycin [500 mg], and tinidazole [500 mg] twice daily for 5 days). Follow-up breath testing was performed at 4 and 8 weeks after completion of therapy. Eradication was defined as negative results on both tests.
Per-protocol analysis revealed eradication rates of 93% for sequential therapy and 79% for standard therapy (P=0.001). Among patients with clarithromycin-resistant H. pylori strains, eradication rates were higher with sequential than with standard therapy (89% vs. 29%; P=0.003), but, among those with metronidazole-resistant strains, rates were similar in the two treatment arms (97% vs. 91%). Among patients with strains that were resistant to both clarithromycin and metronidazole, none of four sequential-therapy recipients, versus two of seven standard-therapy recipients, achieved eradication. Side effects were mild and similar between groups. The authors concluded that sequential therapy might be more effective than standard triple therapy and should be considered as a possible first-line therapy for patients with H. pylori infection.
Comment: These results provide important information about how to address the dropping success rates for H. pylori eradication therapy in North America and Europe. The mechanism underlying sequential therapy’s superiority in this trial remains unclear. Initial therapy with amoxicillin might increase the efficacy of clarithromycin in the second phase of treatment; however, the results also could be due to the addition of a new drug, tinidazole, to the standard regimen. Additional studies should be performed to clarify the mechanism and generalizability of this effect.
— David J. Bjorkman, MD, MSPH (HSA), SM (Epid.)
Published in Journal Watch Gastroenterology June 15, 2007
Citation(s):
Vaira D et al. Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: A randomized trial. Ann Intern Med 2007 Apr 17; 146:556-63.
Friday, September 7, 2007
Aspirin Reduces Risk for Preeclampsia, but Who Should Be Treated?
A meta-analysis found a significant decrease in the rate of preeclampsia, but the benefits of treatment are small and the risks unclear.
The poorly understood etiology of preeclampsia seems to involve inflammation, placental damage, prostaglandin imbalance, and activation of platelets and the clotting system. Some early trials suggested that antiplatelet agents might prevent or delay preeclampsia, but subsequent larger studies suggested that the benefits were modest at best. Investigators have now combined unpublished individual patient data from 31 primary-prevention trials in which more than 32,000 pregnant women at risk for preeclampsia were randomized to receive one or more antiplatelet agents (primarily aspirin), a placebo, or no treatment.
Antiplatelet agents were associated with a 9% to 10% reduction in relative risk for each of four major outcomes (preeclampsia, delivery before 34 weeks’ gestation, stillbirth or infant death before hospital discharge, and small infant for gestational age) and a composite outcome including all of the above plus maternal death. Only the reductions in preeclampsia, preterm delivery, and the composite outcome were statistically significant. The groups did not differ significantly in any other maternal outcomes, including potential adverse effects of antiplatelet therapy (e.g., perinatal hemorrhage). Need for assisted ventilation was a significant 21% lower among infants whose mothers received antiplatelet agents. Outcomes did not differ significantly by dose of aspirin or timing of treatment, or in any prespecified subgroup of women.
Comment: This meta-analysis was strengthened by returning to individual patient data and standardizing outcome definitions. But the potential long-term risks of antiplatelet therapy remain unclear, and even this large study was unable to identify a high-risk subgroup in which the benefit of treatment is substantial. Editorialists suggest that risks and benefits be weighed for each individual patient.
— Bruce Soloway, MD
Published in Journal Watch General Medicine June 26, 2007
Citation(s):
Askie LM et al. Antiplatelet agents for prevention of pre-eclampsia: A meta-analysis of individual patient data. Lancet 2007 May 26; 369:1791-8.
[Medline abstract] (Free)
Roberts JM and Catov JM. Aspirin for pre-eclampsia: Compelling data on benefit and risk. Lancet 2007 May 26; 369:1765-6.
The poorly understood etiology of preeclampsia seems to involve inflammation, placental damage, prostaglandin imbalance, and activation of platelets and the clotting system. Some early trials suggested that antiplatelet agents might prevent or delay preeclampsia, but subsequent larger studies suggested that the benefits were modest at best. Investigators have now combined unpublished individual patient data from 31 primary-prevention trials in which more than 32,000 pregnant women at risk for preeclampsia were randomized to receive one or more antiplatelet agents (primarily aspirin), a placebo, or no treatment.
Antiplatelet agents were associated with a 9% to 10% reduction in relative risk for each of four major outcomes (preeclampsia, delivery before 34 weeks’ gestation, stillbirth or infant death before hospital discharge, and small infant for gestational age) and a composite outcome including all of the above plus maternal death. Only the reductions in preeclampsia, preterm delivery, and the composite outcome were statistically significant. The groups did not differ significantly in any other maternal outcomes, including potential adverse effects of antiplatelet therapy (e.g., perinatal hemorrhage). Need for assisted ventilation was a significant 21% lower among infants whose mothers received antiplatelet agents. Outcomes did not differ significantly by dose of aspirin or timing of treatment, or in any prespecified subgroup of women.
Comment: This meta-analysis was strengthened by returning to individual patient data and standardizing outcome definitions. But the potential long-term risks of antiplatelet therapy remain unclear, and even this large study was unable to identify a high-risk subgroup in which the benefit of treatment is substantial. Editorialists suggest that risks and benefits be weighed for each individual patient.
— Bruce Soloway, MD
Published in Journal Watch General Medicine June 26, 2007
Citation(s):
Askie LM et al. Antiplatelet agents for prevention of pre-eclampsia: A meta-analysis of individual patient data. Lancet 2007 May 26; 369:1791-8.
[Medline abstract] (Free)
Roberts JM and Catov JM. Aspirin for pre-eclampsia: Compelling data on benefit and risk. Lancet 2007 May 26; 369:1765-6.
Thursday, September 6, 2007
Do SSRIs Cause Birth Defects?
Two large case-control studies indicate a few very small increases in risks for particular defects.
Earlier studies reported that use of selective serotonin reuptake inhibitors (SSRIs) —especially paroxetine — during early pregnancy increases the incidence of cardiovascular birth defects markedly. Now, two large ongoing case-control studies challenge these findings.
Investigators from the U.S. and Canada identified 9622 infants with major birth defects, and 4092 controls without such defects, born between 1997 and 2002. No significant association was found between SSRI use in early pregnancy and congenital heart defects. However, there were small absolute increases in risks for anencephaly, craniosynostosis, and omphalocele with SSRI use, and all these risks — as well as the risk for ventricular outflow tract lesions — were increased most with paroxetine.
In a second study, funded in part by the manufacturer of paroxetine, 9849 infants with birth defects were compared with 5860 control infants born in five centers in the U.S. and Canada between 1993 and 2005. Use of SSRIs in early pregnancy was not associated with heart defects in general, but there was an increased risk for right ventricular outflow tract lesions with paroxetine and an increased risk for septal defects with sertraline. No evidence of increased risk was found for any other birth defects with paroxetine.
Comment: As an editorialist notes, these studies dispel the belief that SSRIs are major causes of birth defects. The absolute risk for right ventricular outflow tract lesions in the infant of a mother who uses paroxetine during pregnancy is likely less than 1%, and the risk for any congenital heart defect is unlikely to exceed 2%. These small risks must be weighed against the risks associated with discontinuing an SSRI during pregnancy.
— Robert W. Rebar, MD
Published in Journal Watch General Medicine June 27, 2007
Citation(s):
Alwan S et al. Use of selective serotonin-reuptake inhibitors in pregnancy and the risk of birth defects. N Engl J Med 2007 Jun 28; 356:2684-92.
Original article (Subscription may be required)
Medline abstract (Free)
Louik C et al. First-trimester use of selective serotonin-reuptake inhibitors and the risk of birth defects. N Engl J Med 2007 Jun 28; 356:2675-83.
Original article (Subscription may be required)
Medline abstract (Free)
Greene MF. Teratogenicity of SSRIs — Serious concern or much ado about little? N Engl J Med 2007 Jun 28; 356:2732-3.
Original article (Subscription may be required)
Medline abstract (Free)
Earlier studies reported that use of selective serotonin reuptake inhibitors (SSRIs) —especially paroxetine — during early pregnancy increases the incidence of cardiovascular birth defects markedly. Now, two large ongoing case-control studies challenge these findings.
Investigators from the U.S. and Canada identified 9622 infants with major birth defects, and 4092 controls without such defects, born between 1997 and 2002. No significant association was found between SSRI use in early pregnancy and congenital heart defects. However, there were small absolute increases in risks for anencephaly, craniosynostosis, and omphalocele with SSRI use, and all these risks — as well as the risk for ventricular outflow tract lesions — were increased most with paroxetine.
In a second study, funded in part by the manufacturer of paroxetine, 9849 infants with birth defects were compared with 5860 control infants born in five centers in the U.S. and Canada between 1993 and 2005. Use of SSRIs in early pregnancy was not associated with heart defects in general, but there was an increased risk for right ventricular outflow tract lesions with paroxetine and an increased risk for septal defects with sertraline. No evidence of increased risk was found for any other birth defects with paroxetine.
Comment: As an editorialist notes, these studies dispel the belief that SSRIs are major causes of birth defects. The absolute risk for right ventricular outflow tract lesions in the infant of a mother who uses paroxetine during pregnancy is likely less than 1%, and the risk for any congenital heart defect is unlikely to exceed 2%. These small risks must be weighed against the risks associated with discontinuing an SSRI during pregnancy.
— Robert W. Rebar, MD
Published in Journal Watch General Medicine June 27, 2007
Citation(s):
Alwan S et al. Use of selective serotonin-reuptake inhibitors in pregnancy and the risk of birth defects. N Engl J Med 2007 Jun 28; 356:2684-92.
Original article (Subscription may be required)
Medline abstract (Free)
Louik C et al. First-trimester use of selective serotonin-reuptake inhibitors and the risk of birth defects. N Engl J Med 2007 Jun 28; 356:2675-83.
Original article (Subscription may be required)
Medline abstract (Free)
Greene MF. Teratogenicity of SSRIs — Serious concern or much ado about little? N Engl J Med 2007 Jun 28; 356:2732-3.
Original article (Subscription may be required)
Medline abstract (Free)
Probiotic Drink Helps Reduce Antibiotic-Associated Diarrhea
Consuming a probiotic drink containing Lactobacillus may help older hospitalized patients avoid antibiotic-associated diarrhea, according to a study published online in the British Medical Journal.
In the manufacturer-supported study, 135 hospitalized patients older than 50 who were prescribed antibiotics were randomized to consume a probiotic yogurt drink or a placebo milkshake. The drinks were consumed twice a day concurrent with antibiotic treatment and for a week afterward.
Significantly fewer intervention patients than controls developed antibiotic-associated diarrhea (12% vs. 34%). The number needed to treat (NNT) to prevent one case of antibiotic-associated diarrhea was 5. The NNT to prevent one case of C. difficile-associated diarrhea was 6.
The authors estimate that it would cost $120 to prevent one case of C. difficile-associated diarrhea, whereas it costs an average of $3700 to treat a case in the U.S. They conclude that the drink "has the potential to decrease morbidity, healthcare costs, and mortality if used routinely in patients aged over 50."
original article BMJ
In the manufacturer-supported study, 135 hospitalized patients older than 50 who were prescribed antibiotics were randomized to consume a probiotic yogurt drink or a placebo milkshake. The drinks were consumed twice a day concurrent with antibiotic treatment and for a week afterward.
Significantly fewer intervention patients than controls developed antibiotic-associated diarrhea (12% vs. 34%). The number needed to treat (NNT) to prevent one case of antibiotic-associated diarrhea was 5. The NNT to prevent one case of C. difficile-associated diarrhea was 6.
The authors estimate that it would cost $120 to prevent one case of C. difficile-associated diarrhea, whereas it costs an average of $3700 to treat a case in the U.S. They conclude that the drink "has the potential to decrease morbidity, healthcare costs, and mortality if used routinely in patients aged over 50."
original article BMJ
Is Liquid-Based Cervical Cytology Better Than Conventional?
No improvement was found in detecting grade 2 or 3 cervical intraepithelial neoplasia.
Although liquid-based cervical cytology has become a standard technique for cervical cancer screening, evidence that it is better than conventional cytology is meager. To compare the two methods, Italian investigators randomized more than 45,000 women (age range, 25–60) presenting for Pap smears to undergo screening using either conventional or liquid-based cytology.
In an intention-to-screen analysis, the proportion of women who had at least one technically unsatisfactory or uninterpretable cytology result was significantly lower in the liquid-based cytology group; this reduction was greater in women aged 25 to 34 than in older women. No significant increase in sensitivity for grade 2 or higher cervical intraepithelial neoplasia was found, and the positive predictive value was significantly lower for liquid-based cytology regardless of the cutoff point used to refer women for colposcopy and biopsy to document cervical dysplasia. Liquid-based cytology was significantly more sensitive in detecting grade 1 or higher cervical intraepithelial neoplasia.
Comment: Although liquid-based cytology was more sensitive than conventional cytology in detecting mild cervical abnormalities, it was not better at detecting serious lesions. Yet, most insurers in the U.S. pay for the more expensive liquid-based cytology. It is more important to obtain Pap smears than to be concerned about the method used to prepare them.
— Robert W. Rebar, MD
Published in Journal Watch General Medicine June 12, 2007
Citation(s):
Ronco G et al. Accuracy of liquid based versus conventional cytology: Overall results of new technologies for cervical cancer screening randomised controlled trial. BMJ 2007 May 21; [e-pub ahead of print]. (http://dx.doi.org/10.1136/bmj.39196.740995.BE)
Although liquid-based cervical cytology has become a standard technique for cervical cancer screening, evidence that it is better than conventional cytology is meager. To compare the two methods, Italian investigators randomized more than 45,000 women (age range, 25–60) presenting for Pap smears to undergo screening using either conventional or liquid-based cytology.
In an intention-to-screen analysis, the proportion of women who had at least one technically unsatisfactory or uninterpretable cytology result was significantly lower in the liquid-based cytology group; this reduction was greater in women aged 25 to 34 than in older women. No significant increase in sensitivity for grade 2 or higher cervical intraepithelial neoplasia was found, and the positive predictive value was significantly lower for liquid-based cytology regardless of the cutoff point used to refer women for colposcopy and biopsy to document cervical dysplasia. Liquid-based cytology was significantly more sensitive in detecting grade 1 or higher cervical intraepithelial neoplasia.
Comment: Although liquid-based cytology was more sensitive than conventional cytology in detecting mild cervical abnormalities, it was not better at detecting serious lesions. Yet, most insurers in the U.S. pay for the more expensive liquid-based cytology. It is more important to obtain Pap smears than to be concerned about the method used to prepare them.
— Robert W. Rebar, MD
Published in Journal Watch General Medicine June 12, 2007
Citation(s):
Ronco G et al. Accuracy of liquid based versus conventional cytology: Overall results of new technologies for cervical cancer screening randomised controlled trial. BMJ 2007 May 21; [e-pub ahead of print]. (http://dx.doi.org/10.1136/bmj.39196.740995.BE)
Lancet Editorial Supports Ovarian Cancer Consensus Statement
A Lancet editorial supports the new ovarian cancer screening consensus statement that women who experience bloating, pelvic/abdominal pain, difficulty eating or feeling full quickly, or frequent or urgent urination for more than a couple of weeks should see their doctor, as these may be early symptoms of the disease.
While acknowledging that "such symptoms are ... associated with many other diseases and conditions, and for every ovarian cancer detected, many false positives might also result," the editorial points to recent research indicating that these symptoms are more severe and frequent in ovarian cancer.
Having also noted that the statement provides no guidance to physicians and that there's no evidence that use of these symptoms for screening will reduce mortality, the editorial concludes that it is a "move in the right direction" and that "its chief contribution might be to improve communication between women and their doctors."
ovarian cancer website for patients
A Lancet editorial supports the new ovarian cancer screening consensus statement that women who experience bloating, pelvic/abdominal pain, difficulty eating or feeling full quickly, or frequent or urgent urination for more than a couple of weeks should see their doctor, as these may be early symptoms of the disease.
While acknowledging that "such symptoms are ... associated with many other diseases and conditions, and for every ovarian cancer detected, many false positives might also result," the editorial points to recent research indicating that these symptoms are more severe and frequent in ovarian cancer.
Having also noted that the statement provides no guidance to physicians and that there's no evidence that use of these symptoms for screening will reduce mortality, the editorial concludes that it is a "move in the right direction" and that "its chief contribution might be to improve communication between women and their doctors."
ovarian cancer website for patients
Effect of Soy Intake on Blood Pressure and Lipids
In hypertensive women who added soy to their diets, blood pressure decreased.
Dietary soy is one of several factors that might explain the lower incidence of coronary heart disease in Asian countries than in Western countries. In a randomized, crossover trial, 60 healthy postmenopausal women followed the National Cholesterol Education Program (NCEP) diet or the NCEP diet with 25 g of soy protein supplied as one half cup of unsalted soy nuts (i.e., roasted soy beans) daily while maintaining an equivalent total protein content. Each phase was continued for 8 weeks, and researchers assessed the effect of the diets upon lipids and blood pressure (BP). Patients with systolic BP 165 mm Hg or diastolic BP of 100 mm Hg were excluded from the trial.
Mean BP was lower with soy than without, both among hypertensive women (137/82 vs. 152/88 mm Hg) and normotensive women (110/67 vs. 116/69 mm Hg). The soy diet was significantly lower in total and saturated fat than the control diet. Nonetheless, among normotensive women, total, LDL, and HDL cholesterol levels did not differ across diets. Among hypertensive women, LDL decreased by 11%; total and HDL cholesterol levels did not differ significantly.
Comment: In this small randomized crossover trial, adding soy protein to a diet showed impressive reductions in blood pressure; the magnitude of this effect was surprising and certainly requires confirmation. In contrast, the effect upon lipids was limited.
— Jamaluddin Moloo, MD, MPH
Published in Journal Watch General Medicine June 14, 2007
Citation(s):
Welty FK et al. Effect of soy nuts on blood pressure and lipid levels in hypertensive, prehypertensive, and normotensive postmenopausal women. Arch Intern Med 2007 May 28; 167:1060-7.
Dietary soy is one of several factors that might explain the lower incidence of coronary heart disease in Asian countries than in Western countries. In a randomized, crossover trial, 60 healthy postmenopausal women followed the National Cholesterol Education Program (NCEP) diet or the NCEP diet with 25 g of soy protein supplied as one half cup of unsalted soy nuts (i.e., roasted soy beans) daily while maintaining an equivalent total protein content. Each phase was continued for 8 weeks, and researchers assessed the effect of the diets upon lipids and blood pressure (BP). Patients with systolic BP 165 mm Hg or diastolic BP of 100 mm Hg were excluded from the trial.
Mean BP was lower with soy than without, both among hypertensive women (137/82 vs. 152/88 mm Hg) and normotensive women (110/67 vs. 116/69 mm Hg). The soy diet was significantly lower in total and saturated fat than the control diet. Nonetheless, among normotensive women, total, LDL, and HDL cholesterol levels did not differ across diets. Among hypertensive women, LDL decreased by 11%; total and HDL cholesterol levels did not differ significantly.
Comment: In this small randomized crossover trial, adding soy protein to a diet showed impressive reductions in blood pressure; the magnitude of this effect was surprising and certainly requires confirmation. In contrast, the effect upon lipids was limited.
— Jamaluddin Moloo, MD, MPH
Published in Journal Watch General Medicine June 14, 2007
Citation(s):
Welty FK et al. Effect of soy nuts on blood pressure and lipid levels in hypertensive, prehypertensive, and normotensive postmenopausal women. Arch Intern Med 2007 May 28; 167:1060-7.
Monday, July 23, 2007
Prevention of infective endocarditis: Guidelines from the American Heart Association.
Wilson W et al. Prevention of infective endocarditis: Guidelines from the American Heart Association. A Guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation 2007 Apr 19;
original article
original article
Managing Sepsis — Early Goal-Directed Therapy Saves Lives, Again
Implementation of a bundle of five quality indicators for early management of severe sepsis was associated with reduced mortality.
Although there are outcome data supporting the Surviving Sepsis Campaign guideline components, little is known about the feasibility of implementing a comprehensive treatment protocol for sepsis ("severe sepsis bundle") in an emergency department. In a prospective observational study, researchers examined compliance and outcomes at a single ED that implemented a severe sepsis bundle with physician feedback.
The bundle consisted of five quality indicators:
Initiation of central venous pressure and central venous oxygen saturation monitoring within 2 hours
Administration of broad-spectrum antibiotics within 4 hours
Completion of early goal-directed therapy (EGDT) within 6 hours
Administration of corticosteroid therapy for patients receiving vasopressors or with suspected adrenal insufficiency
Monitoring of lactate clearance
The 2-year project was divided into a pre-implementation phase in which education and infrastructure were established, an observational phase in which physicians were given the tools to implement the program, and a quality initiative phase in which department feedback was provided.
During the 2-year study period, 330 patients (mean age, 63.8) presented with severe sepsis or septic shock. The mean ED length of stay (LOS) was 8.5 hours, mean hospital LOS was 11.3 days, and in-hospital mortality was 35.2%. Bundle compliance increased progressively from 0% to 51.2%. In-hospital mortality was significantly lower in patients who had all bundle components completed than in those who did not (20.8% vs. 39.5%). After the authors adjusted for oxygen debt, bundle completion still was associated with increased survival. In multivariate logistic regression analysis, EGDT was the sole quality indicator associated with lower mortality (odds ratio, 0.36). Administration of fluids, vasopressors, transfusions, and inotropes was similar in the groups with and without bundle completion.
Comment: This observational study of a well-designed quality improvement program demonstrates that bundle completion resulted in an absolute reduction in mortality of nearly 19%. EGDT is the most important of the measures, and other studies have shown that it can be successfully implemented in an ED. Every ED should implement EGDT for patients with severe sepsis or septic shock. EGDT can be initiated by a shock team or an intensive care unit team or by ED personnel.
— Tiffany M. Osborn, MD
Published in Journal Watch Emergency Medicine July 20, 2007
Citation(s):
Nguyen HB et al. Implementation of a bundle of quality indicators for the early management of severe sepsis and septic shock is associated with decreased mortality. Crit Care Med 2007 Apr; 35:1105-12.
Although there are outcome data supporting the Surviving Sepsis Campaign guideline components, little is known about the feasibility of implementing a comprehensive treatment protocol for sepsis ("severe sepsis bundle") in an emergency department. In a prospective observational study, researchers examined compliance and outcomes at a single ED that implemented a severe sepsis bundle with physician feedback.
The bundle consisted of five quality indicators:
Initiation of central venous pressure and central venous oxygen saturation monitoring within 2 hours
Administration of broad-spectrum antibiotics within 4 hours
Completion of early goal-directed therapy (EGDT) within 6 hours
Administration of corticosteroid therapy for patients receiving vasopressors or with suspected adrenal insufficiency
Monitoring of lactate clearance
The 2-year project was divided into a pre-implementation phase in which education and infrastructure were established, an observational phase in which physicians were given the tools to implement the program, and a quality initiative phase in which department feedback was provided.
During the 2-year study period, 330 patients (mean age, 63.8) presented with severe sepsis or septic shock. The mean ED length of stay (LOS) was 8.5 hours, mean hospital LOS was 11.3 days, and in-hospital mortality was 35.2%. Bundle compliance increased progressively from 0% to 51.2%. In-hospital mortality was significantly lower in patients who had all bundle components completed than in those who did not (20.8% vs. 39.5%). After the authors adjusted for oxygen debt, bundle completion still was associated with increased survival. In multivariate logistic regression analysis, EGDT was the sole quality indicator associated with lower mortality (odds ratio, 0.36). Administration of fluids, vasopressors, transfusions, and inotropes was similar in the groups with and without bundle completion.
Comment: This observational study of a well-designed quality improvement program demonstrates that bundle completion resulted in an absolute reduction in mortality of nearly 19%. EGDT is the most important of the measures, and other studies have shown that it can be successfully implemented in an ED. Every ED should implement EGDT for patients with severe sepsis or septic shock. EGDT can be initiated by a shock team or an intensive care unit team or by ED personnel.
— Tiffany M. Osborn, MD
Published in Journal Watch Emergency Medicine July 20, 2007
Citation(s):
Nguyen HB et al. Implementation of a bundle of quality indicators for the early management of severe sepsis and septic shock is associated with decreased mortality. Crit Care Med 2007 Apr; 35:1105-12.
Friday, July 20, 2007
Estrogen Therapy and Coronary Calcification
More evidence that estrogen therapy early in menopause may confer more benefit than risk
Findings from the Women’s Health Initiative (WHI) trial showed that taking conjugated equine estrogens did not reduce the risk for coronary events in postmenopausal women who had undergone hysterectomies. A subgroup analysis, however, suggested an age interaction, in which estrogen conferred a cardiovascular benefit on the younger subjects. To pursue this issue further, the WHI Coronary-Artery Calcium Study was designed to determine whether the younger women treated with estrogens had lower coronary-artery calcium scores than those treated with placebo. This substudy was restricted to women who were 50 to 59 years old at the time of randomization; follow-up scans were obtained an average of 8.7 years later.
Coronary-artery calcium scores were available for 1064 eligible participants. The mean scores were 83 in the estrogen group and 123 in the placebo group (P=0.02). The 50th percentile value of the scores was 0 in both groups, and the 75th percentile values were 43 in the estrogen group and 84 in the placebo group. The overall distribution of scores was significantly lower in the estrogen group than in the placebo group.
Comment: This WHI follow-up study provides additional evidence that estrogens may be beneficial for younger postmenopausal women. These results, however, should not be considered independent confirmation of the original subgroup analysis, because they were found in the same group of patients. Also, although coronary-artery calcium scores are predictive of outcomes, these findings do not translate directly to better outcomes with estrogen treatment, nor do they overturn current recommendations that hormone therapy be limited to the treatment of moderate-to-severe menopausal symptoms, using the lowest effective dose for the shortest duration necessary.
— Harlan M. Krumholz, MD, SM
Published in Journal Watch Cardiology July 18, 2007
Citation(s):
Manson JE et al. for the WHI and WHI-CACS Investigators. Estrogen therapy and coronary-artery calcification. N Engl J Med 2007 Jun 21; 356:2591-602.
Findings from the Women’s Health Initiative (WHI) trial showed that taking conjugated equine estrogens did not reduce the risk for coronary events in postmenopausal women who had undergone hysterectomies. A subgroup analysis, however, suggested an age interaction, in which estrogen conferred a cardiovascular benefit on the younger subjects. To pursue this issue further, the WHI Coronary-Artery Calcium Study was designed to determine whether the younger women treated with estrogens had lower coronary-artery calcium scores than those treated with placebo. This substudy was restricted to women who were 50 to 59 years old at the time of randomization; follow-up scans were obtained an average of 8.7 years later.
Coronary-artery calcium scores were available for 1064 eligible participants. The mean scores were 83 in the estrogen group and 123 in the placebo group (P=0.02). The 50th percentile value of the scores was 0 in both groups, and the 75th percentile values were 43 in the estrogen group and 84 in the placebo group. The overall distribution of scores was significantly lower in the estrogen group than in the placebo group.
Comment: This WHI follow-up study provides additional evidence that estrogens may be beneficial for younger postmenopausal women. These results, however, should not be considered independent confirmation of the original subgroup analysis, because they were found in the same group of patients. Also, although coronary-artery calcium scores are predictive of outcomes, these findings do not translate directly to better outcomes with estrogen treatment, nor do they overturn current recommendations that hormone therapy be limited to the treatment of moderate-to-severe menopausal symptoms, using the lowest effective dose for the shortest duration necessary.
— Harlan M. Krumholz, MD, SM
Published in Journal Watch Cardiology July 18, 2007
Citation(s):
Manson JE et al. for the WHI and WHI-CACS Investigators. Estrogen therapy and coronary-artery calcification. N Engl J Med 2007 Jun 21; 356:2591-602.
Antibiotic Use Early in Life Increases Risk for Asthma
This population-based study confirms previous studies that found an association between antibiotic use and development of childhood asthma.
Results from previous studies have been equivocal regarding the association between antibiotic use early in life and the development of asthma during childhood. To examine risk factors for asthma at age 7, Canadian investigators conducted a longitudinal cohort study using healthcare and prescription databases in Manitoba, Canada.
Among 13,116 children born in 1995, 65% received oral antibiotics during the first year (mostly broad spectrum). To control for reverse causation, children who were diagnosed with asthma during the first year were excluded. After controlling for gender, maternal history of asthma, number of siblings, urban or rural location, and number of healthcare visits, antibiotic use during the first year of life compared with no use was associated with significantly increased risk for developing asthma (odds ratios, 1.27 for 1–2 doses; 1.41 for 3–4 doses; and 1.74 for >4 doses). The association between asthma and antibiotic use was increased among children who lived in rural areas, children whose mothers did not have asthma, and children who did not live with a dog at home during the first year, especially among those who had received multiple doses. The association between asthma and broad-spectrum antibiotic use was statistically significant; the association with narrow-spectrum antibiotics was not. Children who received antibiotics for nonrespiratory infections were about twice as likely to have asthma at age 7 as children who had not used antibiotics.
Comment: The results of this population-based study confirm those of previous studies that found an association between multiple doses of antibiotics and development of childhood asthma and provide yet another reason to avoid unnecessary use of antibiotics, particularly broad-spectrum agents.
— F. Bruder Stapleton, MD
Published in Journal Watch Pediatrics and Adolescent Medicine July 18, 2007
Citation(s):
Kozyrskyj AL et al. Increased risk of childhood asthma from antibiotic use in early life. Chest 2007 Jun; 131:1753-9.
Results from previous studies have been equivocal regarding the association between antibiotic use early in life and the development of asthma during childhood. To examine risk factors for asthma at age 7, Canadian investigators conducted a longitudinal cohort study using healthcare and prescription databases in Manitoba, Canada.
Among 13,116 children born in 1995, 65% received oral antibiotics during the first year (mostly broad spectrum). To control for reverse causation, children who were diagnosed with asthma during the first year were excluded. After controlling for gender, maternal history of asthma, number of siblings, urban or rural location, and number of healthcare visits, antibiotic use during the first year of life compared with no use was associated with significantly increased risk for developing asthma (odds ratios, 1.27 for 1–2 doses; 1.41 for 3–4 doses; and 1.74 for >4 doses). The association between asthma and antibiotic use was increased among children who lived in rural areas, children whose mothers did not have asthma, and children who did not live with a dog at home during the first year, especially among those who had received multiple doses. The association between asthma and broad-spectrum antibiotic use was statistically significant; the association with narrow-spectrum antibiotics was not. Children who received antibiotics for nonrespiratory infections were about twice as likely to have asthma at age 7 as children who had not used antibiotics.
Comment: The results of this population-based study confirm those of previous studies that found an association between multiple doses of antibiotics and development of childhood asthma and provide yet another reason to avoid unnecessary use of antibiotics, particularly broad-spectrum agents.
— F. Bruder Stapleton, MD
Published in Journal Watch Pediatrics and Adolescent Medicine July 18, 2007
Citation(s):
Kozyrskyj AL et al. Increased risk of childhood asthma from antibiotic use in early life. Chest 2007 Jun; 131:1753-9.
FDA Approves Artificial Disc for Degenerative Cervical Spine Disease
The FDA has approved the Prestige Cervical Disc, a first-of-its-kind device used for the treatment of degenerative disc disease, a common source of neck and arm pain.
The device consists of two pieces of hinged stainless steel that, after removal of the damaged disc, are attached to adjacent vertebrae with bone screws.
Its approval was based in part on a clinical trial of about 540 patients that found surgery to replace the damaged disc with the artificial one was as safe and effective as cervical fusion.
The device consists of two pieces of hinged stainless steel that, after removal of the damaged disc, are attached to adjacent vertebrae with bone screws.
Its approval was based in part on a clinical trial of about 540 patients that found surgery to replace the damaged disc with the artificial one was as safe and effective as cervical fusion.
Tuesday, July 17, 2007
CDC Yellow Book
The CDC has released its biennial revision of "the yellow book," a health guide for international travel.
The book describes travel-related infections and diseases endemic to each region. Changes in the latest edition include updates on recommended immunizations, developments in malaria treatment and prevention, advice for avoiding deep vein thrombosis while flying, and a section on avian influenza.
The yellow-covered book, officially titled "CDC Health Information for International Travel 2008," is available free online (and can also be purchased in bookstores).
http://wwwn.cdc.gov/travel/ybToc.aspx
The book describes travel-related infections and diseases endemic to each region. Changes in the latest edition include updates on recommended immunizations, developments in malaria treatment and prevention, advice for avoiding deep vein thrombosis while flying, and a section on avian influenza.
The yellow-covered book, officially titled "CDC Health Information for International Travel 2008," is available free online (and can also be purchased in bookstores).
http://wwwn.cdc.gov/travel/ybToc.aspx
Wednesday, July 11, 2007
Prophylaxis Not Associated with Lower Recurrence of UTIs in Children
The use of antimicrobial prophylaxis after a first childhood urinary tract infection is not associated with lower rates of recurrence — and in fact is associated with an increased risk for resistant infections, according to a JAMA study.
Researchers followed some 600 children under age 6 with first episodes of UTI for over a year to examine the characteristics that would predict recurrent infections. They found that white race, age 3 to 5 years, and grade 4 to 5 vesicoureteral reflux were all factors associated with increased risk for recurrence. Antimicrobial prophylaxis had no effect on recurrence risk, but among children in whom infection recurred, prophylaxis was associated with an increased risk for resistant infections.
The authors suggest that clinicians "discuss the risks and unclear benefits of prophylaxis with families ... after a first UTI."
Full text:
http://jama.ama-assn.org/cgi/content/full/298/2/179
Researchers followed some 600 children under age 6 with first episodes of UTI for over a year to examine the characteristics that would predict recurrent infections. They found that white race, age 3 to 5 years, and grade 4 to 5 vesicoureteral reflux were all factors associated with increased risk for recurrence. Antimicrobial prophylaxis had no effect on recurrence risk, but among children in whom infection recurred, prophylaxis was associated with an increased risk for resistant infections.
The authors suggest that clinicians "discuss the risks and unclear benefits of prophylaxis with families ... after a first UTI."
Full text:
http://jama.ama-assn.org/cgi/content/full/298/2/179
Functional Ovarian Cysts: Do OCs Hasten Resolution?
Review: the current evidence does not suggest that oral contraceptives hasten resolution of functional ovarian cysts
Grimes DA, Jones LB, Lopez LM, et al. Oral contraceptives for functional ovarian cysts. Cochrane Database Syst Rev 2006;(4):CD006134. [Medline® abstract]
Evidence-Based Medicine 2007;12:76; doi:10.1136/ebm.12.3.76 [Free full-text EBM article pdf] [Medline® abstract]
Commentary
Kathleen Hoeger, MD
University of Rochester,
Rochester, New York, USA
Functional ovarian cysts are one of the most common gynaecological problems diagnosed in reproductive aged women. Grimes et al reviewed RCTs that examined the role of OCs for treatment after a cyst is diagnosed. It is important to be aware that many women have ovarian cysts with few or no symptoms; thus, the studies included in this report represent either symptomatic cysts or cysts identified during routine assessment for fertility treatment. At least 2 RCTs in the review included many women who may not have had symptoms at the time of the ultrasound diagnosis of the cyst, as ultrasonography was done routinely during clomiphene or gonadotropin treatment cycles.
Because functional ovarian cysts often result from dysfunction at the level of the hypothalamic pituitary ovarian (HPO) axis, they occur more frequently in women with irregular menses or in the perimenopausal period.1 Additionally, there is evidence that use of OCs, which suppress the HPO axis, may reduce the development of ovarian cysts,2 making the suppression of the HPO axis a logical choice for treatment of an existing cyst. Despite the benign nature of the majority of functional appearing ovarian cysts, when they are discovered at the time of ultrasonography, patients experience increased anxiety and often request treatment.
The review by Grimes et al revealed that, in most cases, cysts will resolve without treatment and those that persist are often not functional in nature. Although there were too few large RCTs to allow for meta-analysis, the use of OCs neither increased the probability of cyst resolution nor decreased the time to resolution. However, the review did not address the issue of recurrent cyst formation, for which evidence does suggest a role for HPO axis suppression.
In summary, Grimes et al showed that no strong evidence exists for use of OCs in the treatment of ovarian cysts. Reassurance alone is appropriate, with follow up to detect cysts that do not resolve, as persistent cysts are likely to represent pathological conditions.
REFERENCES
1. Parazzini F, Moroni S, Negri E, et al. Risk factors for functional ovarian cysts. Epidemiology 1996;7:547–9. [Medline® abstract]
2. Chiaffarino F, Parazzini F, La Vecchia C, et al. Oral contraceptive use and benign gynecologic conditions. A review. Contraception 1998;57:11–8. [Medline® abstract]
Grimes DA, Jones LB, Lopez LM, et al. Oral contraceptives for functional ovarian cysts. Cochrane Database Syst Rev 2006;(4):CD006134. [Medline® abstract]
Evidence-Based Medicine 2007;12:76; doi:10.1136/ebm.12.3.76 [Free full-text EBM article pdf] [Medline® abstract]
Commentary
Kathleen Hoeger, MD
University of Rochester,
Rochester, New York, USA
Functional ovarian cysts are one of the most common gynaecological problems diagnosed in reproductive aged women. Grimes et al reviewed RCTs that examined the role of OCs for treatment after a cyst is diagnosed. It is important to be aware that many women have ovarian cysts with few or no symptoms; thus, the studies included in this report represent either symptomatic cysts or cysts identified during routine assessment for fertility treatment. At least 2 RCTs in the review included many women who may not have had symptoms at the time of the ultrasound diagnosis of the cyst, as ultrasonography was done routinely during clomiphene or gonadotropin treatment cycles.
Because functional ovarian cysts often result from dysfunction at the level of the hypothalamic pituitary ovarian (HPO) axis, they occur more frequently in women with irregular menses or in the perimenopausal period.1 Additionally, there is evidence that use of OCs, which suppress the HPO axis, may reduce the development of ovarian cysts,2 making the suppression of the HPO axis a logical choice for treatment of an existing cyst. Despite the benign nature of the majority of functional appearing ovarian cysts, when they are discovered at the time of ultrasonography, patients experience increased anxiety and often request treatment.
The review by Grimes et al revealed that, in most cases, cysts will resolve without treatment and those that persist are often not functional in nature. Although there were too few large RCTs to allow for meta-analysis, the use of OCs neither increased the probability of cyst resolution nor decreased the time to resolution. However, the review did not address the issue of recurrent cyst formation, for which evidence does suggest a role for HPO axis suppression.
In summary, Grimes et al showed that no strong evidence exists for use of OCs in the treatment of ovarian cysts. Reassurance alone is appropriate, with follow up to detect cysts that do not resolve, as persistent cysts are likely to represent pathological conditions.
REFERENCES
1. Parazzini F, Moroni S, Negri E, et al. Risk factors for functional ovarian cysts. Epidemiology 1996;7:547–9. [Medline® abstract]
2. Chiaffarino F, Parazzini F, La Vecchia C, et al. Oral contraceptive use and benign gynecologic conditions. A review. Contraception 1998;57:11–8. [Medline® abstract]
ADA/EASD consensus guidelines and algorithm
**also see memo on palm under "endo"
The ADA/EASD consensus guidelines and algorithm emphasize:1
Achievement and maintenance of normal glycemic goals
Initial therapy with lifestyle intervention and (usually) metformin
Rapid addition of medications, and/or transition to new interventions/regimens as rapidly as possible — when target glycemic goals are not achieved or sustained
Early addition of insulin therapy in patients who do not meet target goals using other medications, or promptly in patients with greater hyperglycemia
Selecting antihyperglycemic interventions
As seen in algorithm below, the ADA/EASD consensus is that metformin therapy should be initiated concurrently with lifestyle intervention at diagnosis in all but the mildest patients with T2 DM (without contraindications). However, given the progressive nature of T2 DM, more than one medication will be necessary for the majority of patients over time.1 The goal is “to achieve and maintain glycemic levels as close to the nondiabetic range as possible and to change interventions at as rapid a pace as titration of medication allows.” 1
Note that the ADA/EASD algorithm above does not include the incretin mimetics, synthetic amylin, or DPP-4 inhibitors, as limited clinical data were available on these relatively new classes of medication at the time of the guideline publication. However, these drugs may be appropriate choices in selected patients.
Per the guidelines, a number of factors influence the selection of antihyperglycemic medications: their effectiveness in lowering glucose, their extraglycemic effects that may reduce long-term complications, safety profiles, tolerability, and cost.1
When adding a second and potentially third antihyperglycemic medication, the physician should consider potential synergy and other interactions of particular combinations. Generally, agents with different mechanisms of action have greater synergy. For example, insulin plus metformin or insulin plus a thiazolidinedione (TZD) are particularly effective in lowering glycemia.1
Initiation and intensification of basal insulin in patients who fail on oral agents1
The ADA/EASD recommends basal insulin either as second-line therapy if metformin fails, or as third-line therapy if metformin plus a second oral agent fails to meet A1C targets. As stated in the guidelines: “Although 3 oral agents can be used in patients who fail to reach target A1C, the initiation and intensification of insulin therapy is preferred based on effectiveness and expense.”1
For patients with T2 DM, initial insulin therapy is aimed at lowering fasting blood glucose, typically with long- or intermediate-acting insulins. Some patients may also require preprandial rapid- or short-acting insulin therapy.1
Current options in basal insulin therapy
Among the currently available basal insulin therapies to choose from are the insulin analogs and NPH insulin:
Insulin analogs: The newer long-acting insulin analogs, such as Lantus® (insulin glargine [rDNA origin]), and Levemir® (insulin detemir [rDNA origin]) are preferred by many physicians and patients due to their lack of pronounced peak and approximate 24-hour duration of action. Both agents were created by recombinant DNA modification of human insulin, and have the advantage of providing a steady, consistent level of basal insulin coverage.2,3 The physio/chemical structure of LANTUS enables slow release of drug, allowing it to be dosed once-daily.2 Levemir can be dosed once- or twice-daily.3 Treatment with a single-dose of long-acting insulin analog can minimize the complexity of insulin therapy, and decrease the risk of hypoglycemia and weight gain seen with NPH insulin.4 It also compares favorably to adding a third oral agent (a TZD) for impact on health-related quality of life.5
NPH insulin: Neutral protamine Hagedorn, or NPH, insulin has an intermediate duration of action and typically requires twice-daily injection to achieve required basal insulin levels over 24 hours. NPH insulin is lower in cost than the analogs.1,6 So, in patients for whom cost is a consideration, physicians may want to prescribe NPH beginning at bedtime (not dinner) to lower fasting blood glucose (FBG). Target FBG levels in T2 DM are generally 100 mg/dL or slightly less.
Both long-acting analogs and bedtime NPH as basal insulin can be added to oral or other diabetes medications. They can also be started as initial antihyperglycemic therapy when patients have greater hyperglycemia (eg, FBG >300 mg/dL and/or A1C >10%; these patients almost always require insulin treatment to control their glucose intolerance).
BD Ultra-Fine™ Insulin Syringes and Pen Needles: Quality, Comfort and Convenience
MYTH: Taking injections of insulin and other diabetes medications will be painful.
REALITY: Many patients have no idea just how small and thin an insulin needle actually is, and are pleasantly surprised when they finally see and use one for the first time. Also, many are benefiting from the increasing range and availability of insulin pens, since they find it easier and more convenient to dial and administer their dose with this delivery device. Both the insulin analogs and NPH insulin are available in pens.
BD Ultra-Fine Insulin Syringes and Pen Needles are an excellent choice for patients on, or transitioning to, insulin therapy:
No insulin syringe needle is shorter or thinner than BD Ultra-Fine
BD pen needles are universally compatible with all makes of diabetes pens and dosers in the US
BD pen needles come in a variety of lengths, including the shortest pen needle available (5mm) to meet the needs of all patients
BD Getting Started™ Take Home Kits are available to help your patients effectively transition to injection therapy
For more information on BD Ultra-Fine injection products and how to access complimentary BD Getting Started™ kits for your medical practice, visit www.bddiabetes.com/us/
REFERENCES
1. Nathan DM, Buse JB, Davidson MB, et al. Management of Hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2006;29:1963-1972.
2. Lantus [prescribing information]. February 2006. Bridgewater, NJ, sanofi-aventis, U.S., LLC.
3. Levemir [prescribing information]. 2005. Princeton, NJ, NovoNordisk, Inc.
4. Bethel MA, Feinglos MN. Basal insulin therapy in type 2 diabetes. J Am Board Fam Med. 2005;18:199-204.
5. Vinik AI, Zhang Q: Adding Insulin glargine versus rosiglitazone: health-related quality-of-life impact in type 2 diabetes. Diabetes Care. 2007;30(4):795-800.
6. Goldman-Levine JD. Insulin detemir (Levemir) for diabetes mellitus. STEPS: New drug reviews. Am Fam Physician. 2006;74(2). Available at: http://www.aafp.org/afp/20060715/steps.html.
The ADA/EASD consensus guidelines and algorithm emphasize:1
Achievement and maintenance of normal glycemic goals
Initial therapy with lifestyle intervention and (usually) metformin
Rapid addition of medications, and/or transition to new interventions/regimens as rapidly as possible — when target glycemic goals are not achieved or sustained
Early addition of insulin therapy in patients who do not meet target goals using other medications, or promptly in patients with greater hyperglycemia
Selecting antihyperglycemic interventions
As seen in algorithm below, the ADA/EASD consensus is that metformin therapy should be initiated concurrently with lifestyle intervention at diagnosis in all but the mildest patients with T2 DM (without contraindications). However, given the progressive nature of T2 DM, more than one medication will be necessary for the majority of patients over time.1 The goal is “to achieve and maintain glycemic levels as close to the nondiabetic range as possible and to change interventions at as rapid a pace as titration of medication allows.” 1
Note that the ADA/EASD algorithm above does not include the incretin mimetics, synthetic amylin, or DPP-4 inhibitors, as limited clinical data were available on these relatively new classes of medication at the time of the guideline publication. However, these drugs may be appropriate choices in selected patients.
Per the guidelines, a number of factors influence the selection of antihyperglycemic medications: their effectiveness in lowering glucose, their extraglycemic effects that may reduce long-term complications, safety profiles, tolerability, and cost.1
When adding a second and potentially third antihyperglycemic medication, the physician should consider potential synergy and other interactions of particular combinations. Generally, agents with different mechanisms of action have greater synergy. For example, insulin plus metformin or insulin plus a thiazolidinedione (TZD) are particularly effective in lowering glycemia.1
Initiation and intensification of basal insulin in patients who fail on oral agents1
The ADA/EASD recommends basal insulin either as second-line therapy if metformin fails, or as third-line therapy if metformin plus a second oral agent fails to meet A1C targets. As stated in the guidelines: “Although 3 oral agents can be used in patients who fail to reach target A1C, the initiation and intensification of insulin therapy is preferred based on effectiveness and expense.”1
For patients with T2 DM, initial insulin therapy is aimed at lowering fasting blood glucose, typically with long- or intermediate-acting insulins. Some patients may also require preprandial rapid- or short-acting insulin therapy.1
Current options in basal insulin therapy
Among the currently available basal insulin therapies to choose from are the insulin analogs and NPH insulin:
Insulin analogs: The newer long-acting insulin analogs, such as Lantus® (insulin glargine [rDNA origin]), and Levemir® (insulin detemir [rDNA origin]) are preferred by many physicians and patients due to their lack of pronounced peak and approximate 24-hour duration of action. Both agents were created by recombinant DNA modification of human insulin, and have the advantage of providing a steady, consistent level of basal insulin coverage.2,3 The physio/chemical structure of LANTUS enables slow release of drug, allowing it to be dosed once-daily.2 Levemir can be dosed once- or twice-daily.3 Treatment with a single-dose of long-acting insulin analog can minimize the complexity of insulin therapy, and decrease the risk of hypoglycemia and weight gain seen with NPH insulin.4 It also compares favorably to adding a third oral agent (a TZD) for impact on health-related quality of life.5
NPH insulin: Neutral protamine Hagedorn, or NPH, insulin has an intermediate duration of action and typically requires twice-daily injection to achieve required basal insulin levels over 24 hours. NPH insulin is lower in cost than the analogs.1,6 So, in patients for whom cost is a consideration, physicians may want to prescribe NPH beginning at bedtime (not dinner) to lower fasting blood glucose (FBG). Target FBG levels in T2 DM are generally 100 mg/dL or slightly less.
Both long-acting analogs and bedtime NPH as basal insulin can be added to oral or other diabetes medications. They can also be started as initial antihyperglycemic therapy when patients have greater hyperglycemia (eg, FBG >300 mg/dL and/or A1C >10%; these patients almost always require insulin treatment to control their glucose intolerance).
BD Ultra-Fine™ Insulin Syringes and Pen Needles: Quality, Comfort and Convenience
MYTH: Taking injections of insulin and other diabetes medications will be painful.
REALITY: Many patients have no idea just how small and thin an insulin needle actually is, and are pleasantly surprised when they finally see and use one for the first time. Also, many are benefiting from the increasing range and availability of insulin pens, since they find it easier and more convenient to dial and administer their dose with this delivery device. Both the insulin analogs and NPH insulin are available in pens.
BD Ultra-Fine Insulin Syringes and Pen Needles are an excellent choice for patients on, or transitioning to, insulin therapy:
No insulin syringe needle is shorter or thinner than BD Ultra-Fine
BD pen needles are universally compatible with all makes of diabetes pens and dosers in the US
BD pen needles come in a variety of lengths, including the shortest pen needle available (5mm) to meet the needs of all patients
BD Getting Started™ Take Home Kits are available to help your patients effectively transition to injection therapy
For more information on BD Ultra-Fine injection products and how to access complimentary BD Getting Started™ kits for your medical practice, visit www.bddiabetes.com/us/
REFERENCES
1. Nathan DM, Buse JB, Davidson MB, et al. Management of Hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2006;29:1963-1972.
2. Lantus [prescribing information]. February 2006. Bridgewater, NJ, sanofi-aventis, U.S., LLC.
3. Levemir [prescribing information]. 2005. Princeton, NJ, NovoNordisk, Inc.
4. Bethel MA, Feinglos MN. Basal insulin therapy in type 2 diabetes. J Am Board Fam Med. 2005;18:199-204.
5. Vinik AI, Zhang Q: Adding Insulin glargine versus rosiglitazone: health-related quality-of-life impact in type 2 diabetes. Diabetes Care. 2007;30(4):795-800.
6. Goldman-Levine JD. Insulin detemir (Levemir) for diabetes mellitus. STEPS: New drug reviews. Am Fam Physician. 2006;74(2). Available at: http://www.aafp.org/afp/20060715/steps.html.
Strep throat guidelines
Primary care clinicians often fail to follow guidelines when treating patients with sore throats
When doctors see patients with sore throats (pharyngitis), a chief concern is to diagnose or rule out strep throat (caused by the bacterium group A B-hemolytic streptococci). Yet in two-thirds of sore throat visits, primary care clinicians do not follow any available clinical guideline. During these visits, doctors frequently give a strep test to or prescribe antibiotics for patients who are at low risk of strep throat, or for whom tests and antibiotics are not recommended, note researchers at Brigham and Women's Hospital in Boston.
To measure the rate of physician adherence to 3 guidelines, the researchers retrospectively analyzed visits to Boston area primary care clinics by 2,097 adults diagnosed with pharyngitis. The three guidelines included the American College of Physicians (ACP) empirical strategy, the ACP test strategy, and the Infectious Diseases Society of America (IDSA) strategy. Primary care clinicians followed the ACP empirical strategy in 12 percent of visits, the ACP test strategy in 30 percent of visits, and the IDSA strategy in 30 percent of visits. Physicians followed none of these strategies in 66 percent of visits.
The ACP recommends evaluation of adults with pharyngitis using the four-point Centor criteria: fever, absence of cough, tender and swollen anterior lymph nodes, and exudate (pus) on the tonsils. The ACP recommends two potential treatment strategies: empirical antibiotic treatment of patients who meet three of the four Centor criteria (ACP empirical strategy), or testing patients with two or three criteria using a rapid strep test and prescribing antibiotics to patients with a positive test or with four criteria (ACP test strategy). The IDSA guideline agrees with the ACP guideline that adults with zero or one Centor criteria, who are at low risk for strep throat, should neither be tested nor treated with antibiotics. However, the IDSA recommends microbiologic confirmation for all adults with pharyngitis prior to antibiotic prescribing. The study was supported in part by the Agency for Healthcare Research and Quality (HS14420 and HS14563).
______________________________________________
More details are in "Evaluation and treatment of pharyngitis in primary care practice," Jeffrey A. Linder, M.D., M.P.H., Joseph C. Chan, B.S., and David W. Bates, M.D., M.Sc., in the July 10, 2006, Archives of Internal Medicine 166, pp. 1374-1379. [Medline® abstract]
Research Activities Newsletter. April 2007, No. 320. AHRQ Publication No. 07-0027. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/research/apr07/
The above message comes from "AHRQ", who is solely responsible for its conten
When doctors see patients with sore throats (pharyngitis), a chief concern is to diagnose or rule out strep throat (caused by the bacterium group A B-hemolytic streptococci). Yet in two-thirds of sore throat visits, primary care clinicians do not follow any available clinical guideline. During these visits, doctors frequently give a strep test to or prescribe antibiotics for patients who are at low risk of strep throat, or for whom tests and antibiotics are not recommended, note researchers at Brigham and Women's Hospital in Boston.
To measure the rate of physician adherence to 3 guidelines, the researchers retrospectively analyzed visits to Boston area primary care clinics by 2,097 adults diagnosed with pharyngitis. The three guidelines included the American College of Physicians (ACP) empirical strategy, the ACP test strategy, and the Infectious Diseases Society of America (IDSA) strategy. Primary care clinicians followed the ACP empirical strategy in 12 percent of visits, the ACP test strategy in 30 percent of visits, and the IDSA strategy in 30 percent of visits. Physicians followed none of these strategies in 66 percent of visits.
The ACP recommends evaluation of adults with pharyngitis using the four-point Centor criteria: fever, absence of cough, tender and swollen anterior lymph nodes, and exudate (pus) on the tonsils. The ACP recommends two potential treatment strategies: empirical antibiotic treatment of patients who meet three of the four Centor criteria (ACP empirical strategy), or testing patients with two or three criteria using a rapid strep test and prescribing antibiotics to patients with a positive test or with four criteria (ACP test strategy). The IDSA guideline agrees with the ACP guideline that adults with zero or one Centor criteria, who are at low risk for strep throat, should neither be tested nor treated with antibiotics. However, the IDSA recommends microbiologic confirmation for all adults with pharyngitis prior to antibiotic prescribing. The study was supported in part by the Agency for Healthcare Research and Quality (HS14420 and HS14563).
______________________________________________
More details are in "Evaluation and treatment of pharyngitis in primary care practice," Jeffrey A. Linder, M.D., M.P.H., Joseph C. Chan, B.S., and David W. Bates, M.D., M.Sc., in the July 10, 2006, Archives of Internal Medicine 166, pp. 1374-1379. [Medline® abstract]
Research Activities Newsletter. April 2007, No. 320. AHRQ Publication No. 07-0027. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/research/apr07/
The above message comes from "AHRQ", who is solely responsible for its conten
Guideline: Mammography optional in women 40-49
Clinical Question: Should screening mammography be used in women between the ages of 40 years and 49 years?
Bottom Line: In a break from other authorities, this evidence-based guideline from the American College of Physicians (ACP) makes no absolute recommendation for or against the screening of women between the ages of 40 years and 49 years. Instead, it recommends routine, periodic risk assessment, as well as discussions with individuals regarding the benefits and harms of screening mammography.(LOE = 1a)
Reference: Armstrong K, Moye E, Williams S, Berlin JA, Reynolds EE. Screening mammography in women 40 to 49 years of age: a systematic review for the American College of Physicians. Ann Intern Med 2007;146:516-526. [Free full-text Annals article online] [Medline® abstract]
Study Design: Practice guideline
Funding: Foundation
Setting: Various (guideline)
Synopsis
Here's an underappreciated fact: More women between the ages of 40 and 49 years die from heart disease (6800) than from breast cancer (5000) each year. To develop this guideline, the ACP researchers analyzed the latest meta-analyses on this topic and considered an additional study that was subsequently published. The main findings: There are 7% to 23% fewer deaths due to breast cancer over an average of 14 years with screening starting at age 40; an overall mortality reduction hasn't been shown; screening increases rates of mastectomy; rates of ductal carcinoma in situ diagnosis skyrocket 7-fold with increased screening, representing 25% of the diagnoses of "cancer" in this age group; and, 20% to 56% of women will have a false-positive diagnosis when tested yearly for 10 years. In addition to recommending more research, the authors made 3 recommendations:
(1) The decision of whether to order a screening mammography should be made on an individual basis, taking into account the benefits, harms, risk profile, and patient preferences.
(2) Clinicians should update a woman's risk profile every 1 to 2 years. Risk factors for all women include a family history of breast cancer, earlier menarche, later age at time of first birth, and a history of breast biopsy. In addition, women aged 40 to 49 years with certain risk factors are at higher risk than the average 50-year-old woman, including 2 first-degree relatives with breast cancer and 2 previous breast biopsies. The Gail Risk Model Calculator (available in InfoRetriever) can be used to determine an individual woman's risk.
(3) Clinicians should discuss the potential benefits and harm of screening mammography with their patients. The most recent meta-analysis found a reduction in breast cancer-related mortality by 15%, although the confidence interval was wide (as little as 1% risk reduction and as much as 27% risk reduction). A more recent randomized trial, which was not included in the meta-analysis, found no statistically significant reduction in risk of breast cancer mortality. Potential harms include false-positive results, which are as high as 20% to 56% over the course of 10 mammograms, as well as the anxiety associated with the false-positives. Other theoretical risks include discomfort with the procedure. The authors found no evidence of increased radiation-induced cancer or overdiagnosis due to screening.
Written by Cung Pham, MD
Copyright © 2007 by Wiley Subscription Services, Inc. All rights reserved. www.infopoems.com
Bottom Line: In a break from other authorities, this evidence-based guideline from the American College of Physicians (ACP) makes no absolute recommendation for or against the screening of women between the ages of 40 years and 49 years. Instead, it recommends routine, periodic risk assessment, as well as discussions with individuals regarding the benefits and harms of screening mammography.(LOE = 1a)
Reference: Armstrong K, Moye E, Williams S, Berlin JA, Reynolds EE. Screening mammography in women 40 to 49 years of age: a systematic review for the American College of Physicians. Ann Intern Med 2007;146:516-526. [Free full-text Annals article online] [Medline® abstract]
Study Design: Practice guideline
Funding: Foundation
Setting: Various (guideline)
Synopsis
Here's an underappreciated fact: More women between the ages of 40 and 49 years die from heart disease (6800) than from breast cancer (5000) each year. To develop this guideline, the ACP researchers analyzed the latest meta-analyses on this topic and considered an additional study that was subsequently published. The main findings: There are 7% to 23% fewer deaths due to breast cancer over an average of 14 years with screening starting at age 40; an overall mortality reduction hasn't been shown; screening increases rates of mastectomy; rates of ductal carcinoma in situ diagnosis skyrocket 7-fold with increased screening, representing 25% of the diagnoses of "cancer" in this age group; and, 20% to 56% of women will have a false-positive diagnosis when tested yearly for 10 years. In addition to recommending more research, the authors made 3 recommendations:
(1) The decision of whether to order a screening mammography should be made on an individual basis, taking into account the benefits, harms, risk profile, and patient preferences.
(2) Clinicians should update a woman's risk profile every 1 to 2 years. Risk factors for all women include a family history of breast cancer, earlier menarche, later age at time of first birth, and a history of breast biopsy. In addition, women aged 40 to 49 years with certain risk factors are at higher risk than the average 50-year-old woman, including 2 first-degree relatives with breast cancer and 2 previous breast biopsies. The Gail Risk Model Calculator (available in InfoRetriever) can be used to determine an individual woman's risk.
(3) Clinicians should discuss the potential benefits and harm of screening mammography with their patients. The most recent meta-analysis found a reduction in breast cancer-related mortality by 15%, although the confidence interval was wide (as little as 1% risk reduction and as much as 27% risk reduction). A more recent randomized trial, which was not included in the meta-analysis, found no statistically significant reduction in risk of breast cancer mortality. Potential harms include false-positive results, which are as high as 20% to 56% over the course of 10 mammograms, as well as the anxiety associated with the false-positives. Other theoretical risks include discomfort with the procedure. The authors found no evidence of increased radiation-induced cancer or overdiagnosis due to screening.
Written by Cung Pham, MD
Copyright © 2007 by Wiley Subscription Services, Inc. All rights reserved. www.infopoems.com
Saturday, June 30, 2007
Sphincterotomy vs. Nitroglycerin for Chronic Anal Fissure: Long-Term Follow-Up
Cure rate was higher and patients were more satisfied with sphincterotomy.
Chronic anal fissure usually is treated with nitroglycerin ointment, botulinum toxin (Botox) injection, or lateral internal sphincterotomy. All three treatments decrease anal sphincter pressure and improve anal blood flow. Lateral internal sphincterotomy has the highest cure rate but has been associated with postoperative incontinence in retrospective studies.
Now, researchers report 6-year follow-up results from a randomized controlled trial in which 82 patients received thrice-daily nitroglycerin ointment (0.25%) or underwent lateral internal sphincterotomy. Participants were enrolled from February 1997 through October 1998. Sixty-two percent of patients (27 in the nitroglycerin arm and 24 in the sphincterotomy arm) responded to a telephone survey in 2004 about treatment outcomes.
Recurrent fissure symptoms were less likely to have occurred in the sphincterotomy arm than in the nitroglycerin arm (0% vs. 41%; P=0.0004), and sphincterotomy patients were less likely to have required additional surgical treatment (0% vs. 59%; P<0.0001). The sphincterotomy patients were more likely to say that they were "moderately" or "very" satisfied with treatment (100% vs. 56%; P=0.04) and that they would use the same therapy again (92% vs. 63%; P=0.02). Fecal incontinence scores were similar in the two groups.
Comment: Provided that a surgeon who is skilled in lateral internal sphincterotomy is available, few downsides to this procedure exist. Initial use of topical nitroglycerin or Botox injection still is reasonable, but, given these data, repeated courses of medical therapy probably are not the best choice for patients with recurrent or persistent chronic fissure.
— Douglas K. Rex, MD
Published in Journal Watch Gastroenterology June 29, 2007
Citation(s):
Brown CJ et al. Lateral internal sphincterotomy is superior to topical nitroglycerin for healing chronic anal fissure and does not compromise long-term fecal continence: Six-year follow-up of a multicenter, randomized, controlled trial. Dis Colon Rectum 2007 Apr; 50:442-8.
Chronic anal fissure usually is treated with nitroglycerin ointment, botulinum toxin (Botox) injection, or lateral internal sphincterotomy. All three treatments decrease anal sphincter pressure and improve anal blood flow. Lateral internal sphincterotomy has the highest cure rate but has been associated with postoperative incontinence in retrospective studies.
Now, researchers report 6-year follow-up results from a randomized controlled trial in which 82 patients received thrice-daily nitroglycerin ointment (0.25%) or underwent lateral internal sphincterotomy. Participants were enrolled from February 1997 through October 1998. Sixty-two percent of patients (27 in the nitroglycerin arm and 24 in the sphincterotomy arm) responded to a telephone survey in 2004 about treatment outcomes.
Recurrent fissure symptoms were less likely to have occurred in the sphincterotomy arm than in the nitroglycerin arm (0% vs. 41%; P=0.0004), and sphincterotomy patients were less likely to have required additional surgical treatment (0% vs. 59%; P<0.0001). The sphincterotomy patients were more likely to say that they were "moderately" or "very" satisfied with treatment (100% vs. 56%; P=0.04) and that they would use the same therapy again (92% vs. 63%; P=0.02). Fecal incontinence scores were similar in the two groups.
Comment: Provided that a surgeon who is skilled in lateral internal sphincterotomy is available, few downsides to this procedure exist. Initial use of topical nitroglycerin or Botox injection still is reasonable, but, given these data, repeated courses of medical therapy probably are not the best choice for patients with recurrent or persistent chronic fissure.
— Douglas K. Rex, MD
Published in Journal Watch Gastroenterology June 29, 2007
Citation(s):
Brown CJ et al. Lateral internal sphincterotomy is superior to topical nitroglycerin for healing chronic anal fissure and does not compromise long-term fecal continence: Six-year follow-up of a multicenter, randomized, controlled trial. Dis Colon Rectum 2007 Apr; 50:442-8.
Sunday, June 24, 2007
Estrogen Therapy Associated with Lower Levels of Coronary-Artery Calcification
Physicians First Watch June 21, 2007
Estrogen therapy in younger postmenopausal women is associated with less coronary-artery calcification, reports a study in the New England Journal of Medicine.
Researchers studied some 1000 women from the Women's Health Initiative who were aged 50 to 59 at randomization, had previously undergone hysterectomy, and received conjugated equine estrogens or placebo for a mean of 7.4 years. Some 1.3 years after the trial was stopped (because of alarm over the number of cardiovascular events across all age ranges) and thus 8.7 years after randomization, the women underwent CT of the heart.
The mean calcium score was 83.1 for women on estrogens and 123.1 for those on placebo — a statistically significant difference.
The authors write that their results provide support "for the hypothesis that estrogen therapy may have cardioprotective effects in younger women." However, editorialists emphasize — as the authors do — that estrogens should not be used to prevent CVD
Estrogen therapy in younger postmenopausal women is associated with less coronary-artery calcification, reports a study in the New England Journal of Medicine.
Researchers studied some 1000 women from the Women's Health Initiative who were aged 50 to 59 at randomization, had previously undergone hysterectomy, and received conjugated equine estrogens or placebo for a mean of 7.4 years. Some 1.3 years after the trial was stopped (because of alarm over the number of cardiovascular events across all age ranges) and thus 8.7 years after randomization, the women underwent CT of the heart.
The mean calcium score was 83.1 for women on estrogens and 123.1 for those on placebo — a statistically significant difference.
The authors write that their results provide support "for the hypothesis that estrogen therapy may have cardioprotective effects in younger women." However, editorialists emphasize — as the authors do — that estrogens should not be used to prevent CVD
ACIP Recommendations on Varicella Immunization
The CDC's Advisory Committee on Immunization Practices has issued its recommendations for preventing varicella.
The recommendations, published as a supplement to MMWR, include the following highlights:
• Children should receive two doses of the vaccine, one between 12 and 15 months of age, and the other between the ages of 4 and 6.
• Healthy adults and adolescents without evidence of immunity should receive two doses, 4 to 8 weeks apart.
• A second dose is recommended for all those who have received only a single previous dose.
Full recommendations are available on the CDC's website.
The recommendations, published as a supplement to MMWR, include the following highlights:
• Children should receive two doses of the vaccine, one between 12 and 15 months of age, and the other between the ages of 4 and 6.
• Healthy adults and adolescents without evidence of immunity should receive two doses, 4 to 8 weeks apart.
• A second dose is recommended for all those who have received only a single previous dose.
Full recommendations are available on the CDC's website.
Lowering Blood Pressure Improves Diastolic Function, Regardless of Regimen
Reductions in blood pressure lead to improved diastolic function — regardless of the antihypertensive drugs used — reports a study in Lancet.
Researchers sought to determine whether the angiotensin-receptor blocker valsartan would be more effective than other antihypertensives at improving diastolic function. They randomized nearly 400 patients with hypertension and evidence of diastolic dysfunction to receive either the ARB or placebo. The patients also received other classes of antihypertensive agents to lower blood pressure to below 135/80 mm Hg.
After 38 weeks, tissue Doppler imaging showed improved diastolic function in both valsartan and placebo recipients, but there was no significant difference between the groups.
Authors of an accompanying commentary note that valsartan might have an advantage in patients with more advanced left ventricular remodeling. Nevertheless, they add, "the good news is that lowering blood pressure improves diastolic function, irrespective of the antihypertensive regimen used."
Researchers sought to determine whether the angiotensin-receptor blocker valsartan would be more effective than other antihypertensives at improving diastolic function. They randomized nearly 400 patients with hypertension and evidence of diastolic dysfunction to receive either the ARB or placebo. The patients also received other classes of antihypertensive agents to lower blood pressure to below 135/80 mm Hg.
After 38 weeks, tissue Doppler imaging showed improved diastolic function in both valsartan and placebo recipients, but there was no significant difference between the groups.
Authors of an accompanying commentary note that valsartan might have an advantage in patients with more advanced left ventricular remodeling. Nevertheless, they add, "the good news is that lowering blood pressure improves diastolic function, irrespective of the antihypertensive regimen used."
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