Monday, November 7, 2011
Featured in Journal Watch: Colonoscopy Protects Against Colorectal Cancer for as Long as 20 Years
After a single negative colonoscopy, the age- and sex-adjusted odds ratios for colorectal cancer at the following intervals were 0.14 (1–2 years), 0.10 (3–4 years), 0.26 (5–9 years), 0.36 (10–19 years), and 0.41 (20 years or more). The findings from this case-control study offer additional support for clinicians following the U.S. guidelines to perform colonoscopy at 10-year rather than 5-year intervals.
Sunday, July 31, 2011
Prostate Screening Adds No Survival Benefit at 20 Years
Screening for prostate cancer confers no significant protection against death from the disease, according to a BMJ study.
Researchers randomized every sixth man in a Swedish city between the ages of 50 and 70 to screening every 3 years; the others underwent no screening. The study, begun in 1987, used digital rectal exam in the first two screenings, and then in 1993, screening for prostate-specific antigen was added. Suggestive results led to fine-needle aspiration biopsy. Outcomes were followed by using national registries of cancer and mortality.
The rate of prostate cancer diagnosis was higher in the screening group than among controls (5.7% vs. 3.9%). Localized tumors were more than twice as frequent in the screened group, but the rate of non-localized tumors was similar between groups. Over 20 years, the prostate cancer–specific death risk ratio between groups was not significant.
Researchers randomized every sixth man in a Swedish city between the ages of 50 and 70 to screening every 3 years; the others underwent no screening. The study, begun in 1987, used digital rectal exam in the first two screenings, and then in 1993, screening for prostate-specific antigen was added. Suggestive results led to fine-needle aspiration biopsy. Outcomes were followed by using national registries of cancer and mortality.
The rate of prostate cancer diagnosis was higher in the screening group than among controls (5.7% vs. 3.9%). Localized tumors were more than twice as frequent in the screened group, but the rate of non-localized tumors was similar between groups. Over 20 years, the prostate cancer–specific death risk ratio between groups was not significant.
Thursday, July 28, 2011
In Determining Blood Pressure, More Measurements Improve Accuracy
A single measurement doesn't correctly classify a patient's hypertensive status, according to an Annals of Internal Medicine study.
Department of Veterans Affairs researchers followed some 450 patients with hypertension. Over 18 months, systolic pressures were determined from home recordings, routine clinical visits, and scheduled research-associated visits. When examined by method of measurement, 28% of patients were within BP control limits according to routine clinical measurements, 47% according to home measurements, and 68% according to research-visit measurements.
When examined by frequency of measurement, within-patient variances (usually about 10%) decreased dramatically when two or more measurements were made, although there was little benefit beyond five or six measurements. The advantage of repetition held across all methods of measurement.
The authors call for use of averaged home readings to ensure high-quality care. Editorialists, citing the widespread prevalence of sloppy technique, review the proper method and also advocate use of BP measurement as a performance metric
Department of Veterans Affairs researchers followed some 450 patients with hypertension. Over 18 months, systolic pressures were determined from home recordings, routine clinical visits, and scheduled research-associated visits. When examined by method of measurement, 28% of patients were within BP control limits according to routine clinical measurements, 47% according to home measurements, and 68% according to research-visit measurements.
When examined by frequency of measurement, within-patient variances (usually about 10%) decreased dramatically when two or more measurements were made, although there was little benefit beyond five or six measurements. The advantage of repetition held across all methods of measurement.
The authors call for use of averaged home readings to ensure high-quality care. Editorialists, citing the widespread prevalence of sloppy technique, review the proper method and also advocate use of BP measurement as a performance metric
FDA: Data Inconclusive on Link Between Bisphosphonates and Esophageal Cancer
Evidence is inconclusive on a possible association between the use of oral bisphosphonates and an increased risk for esophageal cancer, the FDA said Thursday. The agency added that there are "insufficient data" to recommend endoscopy for asymptomatic patients taking the drugs.
As part of its ongoing safety review, the FDA looked at two analyses from the U.K. General Practice Research Database: one study found no increase in risk with bisphosphonates, while the other found twice the risk for esophageal cancer in patients who filled at least 10 prescriptions or who used bisphosphonates for 3 or more years. The agency noted that other studies showed either no increase in risk or a reduced risk for esophageal cancer.
The FDA reminds providers that esophagitis has been observed in some bisphosphonate users, especially those not following package instructions. Accordingly, patients should be advised to follow the instructions carefully (e.g., they should not lie down for 30 to 60 minutes after taking the drugs).
As part of its ongoing safety review, the FDA looked at two analyses from the U.K. General Practice Research Database: one study found no increase in risk with bisphosphonates, while the other found twice the risk for esophageal cancer in patients who filled at least 10 prescriptions or who used bisphosphonates for 3 or more years. The agency noted that other studies showed either no increase in risk or a reduced risk for esophageal cancer.
The FDA reminds providers that esophagitis has been observed in some bisphosphonate users, especially those not following package instructions. Accordingly, patients should be advised to follow the instructions carefully (e.g., they should not lie down for 30 to 60 minutes after taking the drugs).
Vitamin D lessens mortality
Cochrane Database Syst Rev. 2011; (7):CD007470 (ISSN: 1469-493X)
Bjelakovic G; Gluud LL; Nikolova D; Whitfield K; Wetterslev J; Simonetti RG; Bjelakovic M; Gluud C
Department of Internal Medicine - Gastroenterology and Hepatology, Medical Faculty, University of Nis, Zorana Djindjica 81, Nis, Serbia, 18000.
BACKGROUND: The available evidence on vitamin D and mortality is inconclusive.
OBJECTIVES: To assess the beneficial and harmful effects of vitamin D for prevention of mortality in adults.
SEARCH STRATEGY: We searched The Cochrane Library, MEDLINE, EMBASE, LILACS, the Science Citation Index Expanded, and Conference Proceedings Citation Index-Science (to January 2011). We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials.
SELECTION CRITERIA: We included randomised trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention. Vitamin D could have been administered as supplemental vitamin D (vitamin D(3) (cholecalciferol) or vitamin D(2) (ergocalciferol)) or an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol) or 1,25-dihydroxyvitamin D (calcitriol)).
DATA COLLECTION AND ANALYSIS: Six authors extracted data independently. Random-effects and fixed-effect model meta-analyses were conducted. For dichotomous outcomes, we calculated the risk ratios (RR). To account for trials with zero events, meta-analyses of dichotomous data were repeated using risk differences (RD) and empirical continuity corrections. Risk of bias was considered in order to minimise risk of systematic errors. Trial sequential analyses were conducted to minimise the risk of random errors.
MAIN RESULTS: Fifty randomised trials with 94,148 participants provided data for the mortality analyses. Most trials included elderly women (older than 70 years). Vitamin D was administered for a median of two years. More than one half of the trials had a low risk of bias. Overall, vitamin D decreased mortality (RR 0.97, 95% confidence interval (CI) 0.94 to 1.00, I(2) = 0%). When the different forms of vitamin D were assessed separately, only vitamin D(3) decreased mortality significantly (RR 0.94, 95% CI 0.91 to 0.98, I(2) = 0%; 74,789 participants, 32 trials) whereas vitamin D(2), alfacalcidol, or calcitriol did not. Trial sequential analysis supported our finding regarding vitamin D(3), corresponding to 161 individuals treated to prevent one additional death. Vitamin D(3) combined with calcium increased the risk of nephrolithiasis (RR 1.17, 95% CI 1.02 to 1.34, I(2) = 0%). Alfacalcidol and calcitriol increased the risk of hypercalcaemia (RR 3.18, 95% CI 1.17 to 8.68, I(2) = 17%). Data on health-related quality of life and health economics were inconclusive.
AUTHORS' CONCLUSIONS: Vitamin D in the form of vitamin D(3) seems to decrease mortality in predominantly elderly women who are mainly in institutions and dependent care. Vitamin D(2), alfacalcidol, and calcitriol had no statistically significant effect on mortality. Vitamin D(3) combined with calcium significantly increased nephrolithiasis. Both alfacalcidol and calcitriol significantly increased hypercalcaemia.
Bjelakovic G; Gluud LL; Nikolova D; Whitfield K; Wetterslev J; Simonetti RG; Bjelakovic M; Gluud C
Department of Internal Medicine - Gastroenterology and Hepatology, Medical Faculty, University of Nis, Zorana Djindjica 81, Nis, Serbia, 18000.
BACKGROUND: The available evidence on vitamin D and mortality is inconclusive.
OBJECTIVES: To assess the beneficial and harmful effects of vitamin D for prevention of mortality in adults.
SEARCH STRATEGY: We searched The Cochrane Library, MEDLINE, EMBASE, LILACS, the Science Citation Index Expanded, and Conference Proceedings Citation Index-Science (to January 2011). We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials.
SELECTION CRITERIA: We included randomised trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention. Vitamin D could have been administered as supplemental vitamin D (vitamin D(3) (cholecalciferol) or vitamin D(2) (ergocalciferol)) or an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol) or 1,25-dihydroxyvitamin D (calcitriol)).
DATA COLLECTION AND ANALYSIS: Six authors extracted data independently. Random-effects and fixed-effect model meta-analyses were conducted. For dichotomous outcomes, we calculated the risk ratios (RR). To account for trials with zero events, meta-analyses of dichotomous data were repeated using risk differences (RD) and empirical continuity corrections. Risk of bias was considered in order to minimise risk of systematic errors. Trial sequential analyses were conducted to minimise the risk of random errors.
MAIN RESULTS: Fifty randomised trials with 94,148 participants provided data for the mortality analyses. Most trials included elderly women (older than 70 years). Vitamin D was administered for a median of two years. More than one half of the trials had a low risk of bias. Overall, vitamin D decreased mortality (RR 0.97, 95% confidence interval (CI) 0.94 to 1.00, I(2) = 0%). When the different forms of vitamin D were assessed separately, only vitamin D(3) decreased mortality significantly (RR 0.94, 95% CI 0.91 to 0.98, I(2) = 0%; 74,789 participants, 32 trials) whereas vitamin D(2), alfacalcidol, or calcitriol did not. Trial sequential analysis supported our finding regarding vitamin D(3), corresponding to 161 individuals treated to prevent one additional death. Vitamin D(3) combined with calcium increased the risk of nephrolithiasis (RR 1.17, 95% CI 1.02 to 1.34, I(2) = 0%). Alfacalcidol and calcitriol increased the risk of hypercalcaemia (RR 3.18, 95% CI 1.17 to 8.68, I(2) = 17%). Data on health-related quality of life and health economics were inconclusive.
AUTHORS' CONCLUSIONS: Vitamin D in the form of vitamin D(3) seems to decrease mortality in predominantly elderly women who are mainly in institutions and dependent care. Vitamin D(2), alfacalcidol, and calcitriol had no statistically significant effect on mortality. Vitamin D(3) combined with calcium significantly increased nephrolithiasis. Both alfacalcidol and calcitriol significantly increased hypercalcaemia.
BP meds hs for diabetics
Hermida RC; Ayala DE; Mojón A; Fernández JR
Bioengineering and Chronobiology Laboratories, University of Vigo, Campus Universitario, Vigo, Spain. rhermida@uvigo.es
OBJECTIVE: We prospectively investigated in hypertensive patients with type 2 diabetes if bedtime treatment with ≥1 hypertension medications exerts better blood pressure control and cardiovascular risk reduction than conventional therapy, in which all medications are ingested in the morning.
RESEARCH DESIGN AND METHODS: We conducted a prospective, randomized, open-label, blinded end point trial on 448 hypertensive patients with type 2 diabetes, 255 men/193 women, mean ± SD age 62.5 ± 10.8 years, randomized to ingest all their prescribed hypertension medications upon awakening or ≥1 of them at bedtime. Ambulatory blood pressure was measured for 48 h at baseline and again annually or even more frequently (quarterly) after adjustments in treatment.
RESULTS: After a median follow-up of 5.4 years, patients ingesting ≥1 hypertension medications at bedtime showed a significantly lower cardiovascular risk (adjusted by age and sex) than subjects ingesting all medications upon awakening (hazard ratio 0.33 [95% CI 0.21-0.54]; P < 0.001). The difference between groups in the adjusted risk of major events (cardiovascular death, myocardial infarction, and stroke) was also statistically significant (0.25 [0.10-0.61]; P = 0.003). Patients treated at bedtime showed significantly lower sleep time blood pressure mean and higher prevalence of controlled ambulatory blood pressure (62.5 vs. 50.9%; P = 0.013). There was a significant 12% cardiovascular risk reduction per each 5 mmHg decrease in asleep systolic blood pressure during follow-up (P < 0.001).
CONCLUSIONS: Among patients with diabetes, treatment with ≥1 hypertension medications at bedtime, compared with all medications upon waking, resulted in improved ambulatory blood pressure control and significantly reduced cardiovascular morbidity and mortality.
Bioengineering and Chronobiology Laboratories, University of Vigo, Campus Universitario, Vigo, Spain. rhermida@uvigo.es
OBJECTIVE: We prospectively investigated in hypertensive patients with type 2 diabetes if bedtime treatment with ≥1 hypertension medications exerts better blood pressure control and cardiovascular risk reduction than conventional therapy, in which all medications are ingested in the morning.
RESEARCH DESIGN AND METHODS: We conducted a prospective, randomized, open-label, blinded end point trial on 448 hypertensive patients with type 2 diabetes, 255 men/193 women, mean ± SD age 62.5 ± 10.8 years, randomized to ingest all their prescribed hypertension medications upon awakening or ≥1 of them at bedtime. Ambulatory blood pressure was measured for 48 h at baseline and again annually or even more frequently (quarterly) after adjustments in treatment.
RESULTS: After a median follow-up of 5.4 years, patients ingesting ≥1 hypertension medications at bedtime showed a significantly lower cardiovascular risk (adjusted by age and sex) than subjects ingesting all medications upon awakening (hazard ratio 0.33 [95% CI 0.21-0.54]; P < 0.001). The difference between groups in the adjusted risk of major events (cardiovascular death, myocardial infarction, and stroke) was also statistically significant (0.25 [0.10-0.61]; P = 0.003). Patients treated at bedtime showed significantly lower sleep time blood pressure mean and higher prevalence of controlled ambulatory blood pressure (62.5 vs. 50.9%; P = 0.013). There was a significant 12% cardiovascular risk reduction per each 5 mmHg decrease in asleep systolic blood pressure during follow-up (P < 0.001).
CONCLUSIONS: Among patients with diabetes, treatment with ≥1 hypertension medications at bedtime, compared with all medications upon waking, resulted in improved ambulatory blood pressure control and significantly reduced cardiovascular morbidity and mortality.
Friday, July 8, 2011
FDA Restricts Use of Simvastatin 80 mg
une 8, 2011 (Silver Spring, Maryland) — The Food and Drug Administration is recommending that physicians restrict prescribing high-dose simvastatin (Zocor, Merck) to patients, given an increased risk of muscle damage [1]. The new FDA drug safety communication, issued today, states that physicians should limit using the 80-mg dose unless the patient has already been taking the drug for 12 months and there is no evidence of myopathy.
"Simvastatin 80 mg should not be started in new patients, including patients already taking lower doses of the drug," the agency states.
In addition, the FDA is requesting that additional changes be made to the drug's label. The label will be changed to include the new dosing recommendations, as well as warnings not to use the drug with various medications, including itraconazole (Sporanox, Jannsen Pharmaceutica), ketoconazole (Nizoral by Ortho-McNeil Pharmaceutical), posaconazole (Noxafil, Merck), erythromycin, clarithromycin, telithromycin (Ketek, Sanofi-Aventis), HIV protease inhibitors, nefazodone, gemfibrozil, cyclosporine, and danazol.
In addition, the 10-mg dose should not be exceeded in patients taking amiodarone, verapamil, and diltiazem, and the 20-mg dose should not be exceeded with amlodipine (Norvasc, Pfizer) and ranolazine (Ranexa, Gilead).
The changes to the label are based on the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH), a study reported by heartwire . In that trial, 52 patients taking the 80-mg dose developed myopathy compared with one patient treated with the 20-mg dose. In addition, 22 patients treated with the high dose of simvastatin developed rhabdomyolysis compared with none treated with the 20-mg dose.
The FDA notes that the risks of myopathy and rhabdomyolysis were highest in the first year and that older age and female sex increased the risks.
In statement released today following the FDA alert [2], Merck notes that it has launched a new information website and is encouraging patients who think the prescribing changes might affect them to speak with their doctors.
Dr Steven Nissen (Cleveland Clinic, OH), who wrote an editorial accompanying the 2004 publication of the A to Z trial, a study that tested high-dose simvastatin in acute coronary syndrome patients, who was critical of the high rate of myopathy in that study, called the FDA decision "appropriate" but said it comes late.
"Most knowledgeable lipid experts stopped administering the 80-mg dosage of simvastatin years ago," he said in an email to heartwire . "Unfortunately, once again the FDA has been too slow to react to a serious drug safety problem. We currently have more than two million Americans taking an unsafe dosage of simvastatin when there are safer alternatives. I'm glad the FDA acted but wish they hadn't taken so long."
References
Food and Drug Administration. FDA drug safety communication: New restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury. June 8, 2011. Available here.
Merck. US prescribing information for simvastatin revised to include new limits on the use of the highest dose--80 mg--and updated drug interaction information [press release]. June 8, 2011. Available here.
"Simvastatin 80 mg should not be started in new patients, including patients already taking lower doses of the drug," the agency states.
In addition, the FDA is requesting that additional changes be made to the drug's label. The label will be changed to include the new dosing recommendations, as well as warnings not to use the drug with various medications, including itraconazole (Sporanox, Jannsen Pharmaceutica), ketoconazole (Nizoral by Ortho-McNeil Pharmaceutical), posaconazole (Noxafil, Merck), erythromycin, clarithromycin, telithromycin (Ketek, Sanofi-Aventis), HIV protease inhibitors, nefazodone, gemfibrozil, cyclosporine, and danazol.
In addition, the 10-mg dose should not be exceeded in patients taking amiodarone, verapamil, and diltiazem, and the 20-mg dose should not be exceeded with amlodipine (Norvasc, Pfizer) and ranolazine (Ranexa, Gilead).
The changes to the label are based on the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH), a study reported by heartwire . In that trial, 52 patients taking the 80-mg dose developed myopathy compared with one patient treated with the 20-mg dose. In addition, 22 patients treated with the high dose of simvastatin developed rhabdomyolysis compared with none treated with the 20-mg dose.
The FDA notes that the risks of myopathy and rhabdomyolysis were highest in the first year and that older age and female sex increased the risks.
In statement released today following the FDA alert [2], Merck notes that it has launched a new information website and is encouraging patients who think the prescribing changes might affect them to speak with their doctors.
Dr Steven Nissen (Cleveland Clinic, OH), who wrote an editorial accompanying the 2004 publication of the A to Z trial, a study that tested high-dose simvastatin in acute coronary syndrome patients, who was critical of the high rate of myopathy in that study, called the FDA decision "appropriate" but said it comes late.
"Most knowledgeable lipid experts stopped administering the 80-mg dosage of simvastatin years ago," he said in an email to heartwire . "Unfortunately, once again the FDA has been too slow to react to a serious drug safety problem. We currently have more than two million Americans taking an unsafe dosage of simvastatin when there are safer alternatives. I'm glad the FDA acted but wish they hadn't taken so long."
References
Food and Drug Administration. FDA drug safety communication: New restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury. June 8, 2011. Available here.
Merck. US prescribing information for simvastatin revised to include new limits on the use of the highest dose--80 mg--and updated drug interaction information [press release]. June 8, 2011. Available here.
Friday, July 1, 2011
Trial of Niacin to Increase HDL in High-Risk Patients Stopped Early After Showing No Benefit
A major government study has been stopped early because it showed no benefit to raising HDL levels with niacin in patients at high risk for cardiovascular events, the National Heart, Lung, and Blood Institute announced Thursday.
In the AIM-HIGH trial, the rate of MI, stroke, hospitalization for acute coronary syndrome, or revascularization among some 3400 patients did not differ between a group taking statin plus high-dose niacin and one taking statin plus placebo during 32 months' follow-up. All patients had well-controlled LDL levels at entry, but had low HDL levels and high triglycerides.
Asked to comment, Dr. Harlan Krumholz of Journal Watch Cardiology wrote: "This study reinforces that medications that change a risk factor do not necessarily change patient risk. Niacin, fibrates, and ezetimibe have so far failed to show that they improve patient outcomes in patients on statins. Be on guard for claims that are based only on how an intervention affects a risk factor — we need studies that show us the effect of these drugs on outcomes that patients experience."
In the AIM-HIGH trial, the rate of MI, stroke, hospitalization for acute coronary syndrome, or revascularization among some 3400 patients did not differ between a group taking statin plus high-dose niacin and one taking statin plus placebo during 32 months' follow-up. All patients had well-controlled LDL levels at entry, but had low HDL levels and high triglycerides.
Asked to comment, Dr. Harlan Krumholz of Journal Watch Cardiology wrote: "This study reinforces that medications that change a risk factor do not necessarily change patient risk. Niacin, fibrates, and ezetimibe have so far failed to show that they improve patient outcomes in patients on statins. Be on guard for claims that are based only on how an intervention affects a risk factor — we need studies that show us the effect of these drugs on outcomes that patients experience."
Thursday, June 23, 2011
Add-On Drugs Compared for Uncontrolled Type 2 Diabetes
In the treatment of type 2 diabetes not controlled by metformin and a sulfonylurea, no add-on drug has an obvious advantage over another, according to an Annals of Internal Medicine network meta-analysis.
Researchers examined 18 trials comprising 4500 participants with uncontrolled diabetes. (The add-on treatments were thiazolidinediones, glucagon-like peptide-1 agonists, dipeptidyl peptidase-4 inhibitors, insulins, and acarbose.) The following effects were noted:
No drug class had an advantage in controlling glycated hemoglobin levels.
Insulins and thiazolidinediones were associated with weight gain.
Glucagon-like peptide-1 agonists were associated with weight loss.
Insulins were associated with a doubled frequency of hypoglycemic episodes.
The authors acknowledge the limitations of network meta-analysis, in which some treatments are compared indirectly. They conclude that, in choosing a third drug, an individual patient's clinical features such as weight and hypoglycemia need to be considered.
Researchers examined 18 trials comprising 4500 participants with uncontrolled diabetes. (The add-on treatments were thiazolidinediones, glucagon-like peptide-1 agonists, dipeptidyl peptidase-4 inhibitors, insulins, and acarbose.) The following effects were noted:
No drug class had an advantage in controlling glycated hemoglobin levels.
Insulins and thiazolidinediones were associated with weight gain.
Glucagon-like peptide-1 agonists were associated with weight loss.
Insulins were associated with a doubled frequency of hypoglycemic episodes.
The authors acknowledge the limitations of network meta-analysis, in which some treatments are compared indirectly. They conclude that, in choosing a third drug, an individual patient's clinical features such as weight and hypoglycemia need to be considered.
3-Month Treatment for Latent TB Infection as Effective as 9-Month Treatment
In patients with latent tuberculosis, a shorter treatment regimen may be as safe and effective as a longer course in preventing active disease, according to a CDC study presented on Monday at the American Thoracic Society conference.
Researchers studied some 8000 patients with latent TB who lived in countries with low to medium incidence of TB — mostly from the U.S. and Canada. Patients were randomized to either the standard treatment (9 months of self-administered daily isoniazid) or a shorter regimen (3 months of supervised weekly rifapentine and isoniazid). Over roughly 3 years' follow-up, seven patients on the shorter regimen developed TB disease, compared with 15 on standard treatment. The shortened-therapy group had a significantly higher rate of treatment completion (82% vs. 69%).
CDC Director Dr. Thomas Frieden called the findings "one of the biggest developments in TB treatment in decades." The CDC stresses that the results are only applicable to countries with low to moderate levels of latent infection
Researchers studied some 8000 patients with latent TB who lived in countries with low to medium incidence of TB — mostly from the U.S. and Canada. Patients were randomized to either the standard treatment (9 months of self-administered daily isoniazid) or a shorter regimen (3 months of supervised weekly rifapentine and isoniazid). Over roughly 3 years' follow-up, seven patients on the shorter regimen developed TB disease, compared with 15 on standard treatment. The shortened-therapy group had a significantly higher rate of treatment completion (82% vs. 69%).
CDC Director Dr. Thomas Frieden called the findings "one of the biggest developments in TB treatment in decades." The CDC stresses that the results are only applicable to countries with low to moderate levels of latent infection
lower dose asa appears to lower gi bleeds
Long-term use of aspirin and the risk of gastrointestinal bleeding.
Am J Med. 2011; 124(5):426-33 (ISSN: 1555-7162)
Huang ES; Strate LL; Ho WW; Lee SS; Chan AT
Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
BACKGROUND: In short-term trials, aspirin is associated with gastrointestinal bleeding. However, the effect of dose and duration of aspirin use on risk remains unclear.
METHODS: We conducted a prospective study of 87,680 women enrolled in the Nurses' Health Study in 1990 who provided biennial data on aspirin use. We examined the relative risk (RR) of major gastrointestinal bleeding requiring hospitalization or blood transfusion.
RESULTS: During a 24-year follow-up, 1537 women reported a major gastrointestinal bleeding. Among women who used aspirin regularly (≥2 standard [325 mg] tablets/week), the multivariate RR of gastrointestinal bleeding was 1.43 (95% confidence interval [CI], 1.29-1.59) when compared with nonregular users. Compared with women who denied any aspirin use, the multivariate RRs of gastrointestinal bleeding were 1.03 (95% CI, 0.85-1.24) for women who used 0.5 to 1.5 standard aspirin tablets/week, 1.30 (95% CI, 1.07-1.58) for women who used 2 to 5 tablets/week, 1.77 (95% CI, 1.44-2.18) for women who used 6 to 14 tablets/week, and 2.24 (95% CI, 1.66-3.03) for women who used more than 14 tablets/week (P(trend)<.001). Similar dose-response relationships were observed among short-term users (≤5 years; P(trend)<.001) and long-term users (>5 years; P(trend)<.001). In contrast, after adjustments were made for dose, increasing duration of use did not confer a greater risk of bleeding (P(trend) = .28).
CONCLUSION: Regular aspirin use is associated with gastrointestinal bleeding. Risk seems more strongly related to dose than duration of aspirin use. Efforts to minimize adverse effects of aspirin therapy should emphasize using the lowest effective dose among both short- and long-term users.
Am J Med. 2011; 124(5):426-33 (ISSN: 1555-7162)
Huang ES; Strate LL; Ho WW; Lee SS; Chan AT
Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
BACKGROUND: In short-term trials, aspirin is associated with gastrointestinal bleeding. However, the effect of dose and duration of aspirin use on risk remains unclear.
METHODS: We conducted a prospective study of 87,680 women enrolled in the Nurses' Health Study in 1990 who provided biennial data on aspirin use. We examined the relative risk (RR) of major gastrointestinal bleeding requiring hospitalization or blood transfusion.
RESULTS: During a 24-year follow-up, 1537 women reported a major gastrointestinal bleeding. Among women who used aspirin regularly (≥2 standard [325 mg] tablets/week), the multivariate RR of gastrointestinal bleeding was 1.43 (95% confidence interval [CI], 1.29-1.59) when compared with nonregular users. Compared with women who denied any aspirin use, the multivariate RRs of gastrointestinal bleeding were 1.03 (95% CI, 0.85-1.24) for women who used 0.5 to 1.5 standard aspirin tablets/week, 1.30 (95% CI, 1.07-1.58) for women who used 2 to 5 tablets/week, 1.77 (95% CI, 1.44-2.18) for women who used 6 to 14 tablets/week, and 2.24 (95% CI, 1.66-3.03) for women who used more than 14 tablets/week (P(trend)<.001). Similar dose-response relationships were observed among short-term users (≤5 years; P(trend)<.001) and long-term users (>5 years; P(trend)<.001). In contrast, after adjustments were made for dose, increasing duration of use did not confer a greater risk of bleeding (P(trend) = .28).
CONCLUSION: Regular aspirin use is associated with gastrointestinal bleeding. Risk seems more strongly related to dose than duration of aspirin use. Efforts to minimize adverse effects of aspirin therapy should emphasize using the lowest effective dose among both short- and long-term users.
FDA: 5-Alpha Reductase Inhibitors Associated with Increased Risk for High-Grade Prostate Cancer Diagnosis
The labels of 5-alpha reductase inhibitors (5-ARIs) are being changed to note an increased risk for being diagnosed with high-grade prostate cancer, the FDA announced on Thursday. The drugs (finasteride and dutasteride) are approved to treat benign prostatic hyperplasia and male pattern hair loss.
The announcement came after the FDA reviewed data from two prostate cancer prevention trials. In one, finasteride (given daily for 7 years) was associated with a higher frequency of prostate cancers with Gleason scores between 8 and 10, compared with placebo (1.8% vs. 1.1%). In the other, dutasteride (given daily for 4 years) was also associated with more high-grade cancers relative to placebo (1% vs. 0.5%).
The FDA recommends that physicians rule out prostate cancer before prescribing 5-ARIs for benign prostatic hyperplasia. Also, because these drugs lower prostate-specific antigen values, clinicians should be aware that if PSA increases while a patient is taking a 5-ARI — even if it is within the normal range — it may indicate the presence of prostate cancer
The announcement came after the FDA reviewed data from two prostate cancer prevention trials. In one, finasteride (given daily for 7 years) was associated with a higher frequency of prostate cancers with Gleason scores between 8 and 10, compared with placebo (1.8% vs. 1.1%). In the other, dutasteride (given daily for 4 years) was also associated with more high-grade cancers relative to placebo (1% vs. 0.5%).
The FDA recommends that physicians rule out prostate cancer before prescribing 5-ARIs for benign prostatic hyperplasia. Also, because these drugs lower prostate-specific antigen values, clinicians should be aware that if PSA increases while a patient is taking a 5-ARI — even if it is within the normal range — it may indicate the presence of prostate cancer
Friday, April 15, 2011
Phentermine plus Topiramate Leads to Significant Weight Loss at 1 Year
A combination of phentermine and topiramate appears to be an effective obesity treatment, according to a phase III, industry-conducted trial published in the Lancet.
Some 2500 patients who were overweight or obese and had at least two comorbidities were randomized to placebo or low- or high-doses of phentermine plus topiramate. All patients received diet and lifestyle counseling. At 56 weeks, patients in the treatment groups lost more weight than controls (high-dose, 10.2 kg; low-dose, 8.1 kg; placebo, 1.4 kg). A higher proportion of patients in the treatment groups also achieved 10% weight loss (high-dose, 48%; low-dose, 37%; placebo, 7%).
Patients in the treatment groups reported higher rates of dry mouth, constipation, and paresthesia. In addition, a dose-related increase was observed in depression- and anxiety-related adverse events.
Some 2500 patients who were overweight or obese and had at least two comorbidities were randomized to placebo or low- or high-doses of phentermine plus topiramate. All patients received diet and lifestyle counseling. At 56 weeks, patients in the treatment groups lost more weight than controls (high-dose, 10.2 kg; low-dose, 8.1 kg; placebo, 1.4 kg). A higher proportion of patients in the treatment groups also achieved 10% weight loss (high-dose, 48%; low-dose, 37%; placebo, 7%).
Patients in the treatment groups reported higher rates of dry mouth, constipation, and paresthesia. In addition, a dose-related increase was observed in depression- and anxiety-related adverse events.
Sunday, March 13, 2011
BMI, Other Adiposity Measures Don't Add Much to Cardiovascular Risk Prediction
Measures of adiposity do not greatly improve cardiovascular risk prediction beyond that provided by blood pressure, diabetes history, and lipid profile, according to a study in the Lancet.
Researchers assessed data on 220,000 patients free of cardiovascular disease in 58 prospective cohorts. Over a mean 5.7 years' follow-up, some 14,000 cardiovascular events occurred.
After adjustment for age, sex, smoking status, systolic blood pressure, diabetes history, and total and HDL cholesterol, increasing increments of BMI, waist-to-hip ratio, and waist circumference were individually associated with roughly similar increases in cardiovascular risk (with hazard ratios ranging from 1.07 to 1.12). In addition, adding these adiposity measures to a cardiovascular risk prediction model that included traditional risk factors did not improve the model's risk discrimination.
Commentators note: "The study dispelled previous hope that assessment of body size could replace the cost, time, and inconvenience of blood lipids assay."
Researchers assessed data on 220,000 patients free of cardiovascular disease in 58 prospective cohorts. Over a mean 5.7 years' follow-up, some 14,000 cardiovascular events occurred.
After adjustment for age, sex, smoking status, systolic blood pressure, diabetes history, and total and HDL cholesterol, increasing increments of BMI, waist-to-hip ratio, and waist circumference were individually associated with roughly similar increases in cardiovascular risk (with hazard ratios ranging from 1.07 to 1.12). In addition, adding these adiposity measures to a cardiovascular risk prediction model that included traditional risk factors did not improve the model's risk discrimination.
Commentators note: "The study dispelled previous hope that assessment of body size could replace the cost, time, and inconvenience of blood lipids assay."
Thursday, March 3, 2011
Long-Term Use of Proton-Pump Inhibitors May Lower Magnesium Levels
Using a proton-pump inhibitor for extended periods may cause low serum magnesium levels, the FDA cautioned yesterday. The agency issued the alert after reviewing more than 50 cases of hypomagnesemia in patients taking PPIs over long periods, usually a year or more.
Possible adverse effects of hypomagnesemia include tetany, arrhythmias, and seizures. The alert primarily applies to prescription PPIs, which are indicated for long-term use. The FDA says there is little risk from over-the-counter PPIs when taken as directed for 14 days.
Before prescribing a PPI for a long period, clinicians should consider baseline magnesium testing as well as occasional testing throughout treatment. Periodic magnesium testing is also advised in patients concurrently taking digoxin, because low magnesium in these patients carries a greater risk for serious side effects.
The FDA said that long-term PPI use may affect intestinal absorption of magnesium, although the mechanism is unknown.
Possible adverse effects of hypomagnesemia include tetany, arrhythmias, and seizures. The alert primarily applies to prescription PPIs, which are indicated for long-term use. The FDA says there is little risk from over-the-counter PPIs when taken as directed for 14 days.
Before prescribing a PPI for a long period, clinicians should consider baseline magnesium testing as well as occasional testing throughout treatment. Periodic magnesium testing is also advised in patients concurrently taking digoxin, because low magnesium in these patients carries a greater risk for serious side effects.
The FDA said that long-term PPI use may affect intestinal absorption of magnesium, although the mechanism is unknown.
Thursday, February 24, 2011
stroke sides affects mood
Right brain strokes also spawn cheerful survivors while left brain strokes leave the survivor with depression (Rosenfeld, 1997).
Prescription Drug Prices in Canada
The high cost of prescription drugs, combined with the lack of prescription drug coverage for many older Americans, has resulted in substantial interest in how countries such as Canada attempt to restrain prescription drug prices. Many older Americans have discovered first-hand the potential savings from buying their prescription drugs from Canadian pharmacies. However, while Canada does tend to have lower drug prices than the U.S. for many prescription drug products, attention to prices is only part of the story of Canadian efforts to reduce overall drug costs.
One reason that drug prices tend to be lower in Canada is that prices for drugs that are still under patent—and therefore have no generic substitutes—are regulated by the federal Patented Medicine Prices Review Board (PMPRB). This Board establishes the maximum prices that can be charged in Canada for patented drugs. The PMPRB has been credited with keeping average annual price increases for patented drugs at or below zero since 1992. In addition, Canadian drug price levels fell from 123 percent of the median drug price level for seven industrialized countries (France, Germany, Italy, Sweden, Switzerland, the United Kingdom, and the United States) in 1987 to 101 percent of the comparator median in 2002. During that same period, the average U.S. prices for patented drugs rose from 36 percent above to 67 percent above average Canadian prices.
A second reason for lower Canadian prices is price negotiations by health insurers that are based on evaluations of clinical effectiveness of prescription drugs. Insurers, particularly the provincial drug benefit plans that provide coverage for most elderly, disabled, and low-income Canadians, have adopted cost management approaches that apply clinical evaluations to identify therapeutically similar drugs and negotiate with manufacturers in order to get the best price among similar products. These prices become available to other insurers (who tend to provide coverage to most other Canadians) because the provincial health plans publish the prices in their formulary, the list of drugs which they will cover.
Canada's success in restraining drug prices, however, has not fully restrained the growth of prescription drug spending. Prescription drug spending in Canada rose by about 9 percent per year between 1990 and 2001 (compared to 12 percent annual growth in the United States), due not only to drug prices but also to higher use per person and the changing mix toward more costly medications. Expenditures on prescription drugs account for an increasing share of national health care spending, and these costs threaten the ability of provincial and private benefit plans to continue providing benefits at current levels. As a result of financial pressures, public policy discussions in Canada have moved beyond the issue of drug prices to suggestions that provinces establish structures to ensure that a drug's price reflects its relative therapeutic value and that patients and physicians have both the information and incentives to balance benefits and actual costs. There also has been debate in Canada about whether the federal government should take a more prominent role in helping to restrain prescription drug costs beyond price alone, such as whether to adopt a national drug formulary.
What lessons does the Canadian experience offer the United States as it contends with rising drug costs? The most important lesson from the Canadian experience may come not from price regulation but from Canada's increasing use of clinical and economic evaluation to make drug payment decisions. The establishment of conditions for a more competitive pharmaceutical marketplace based on evaluations of quality and price may fit the American political context better than price controls. Indeed, to some extent, these policies are already being adopted in the United States within the Department of Veterans' Affairs and several state Medicaid programs.
Whatever programs the United States may turn to in reducing prescription drug spending, it will be important to evaluate their impact both on patient access to existing drugs and on pharmaceutical research and development-in effect, access to future drugs. Whether these management systems could successfully restrain pharmaceutical spending in the United States without adversely affecting access or pharmaceutical research and development is yet to be seen. They certainly warrant further assessment as Americans and their health insurers seek greater value for their pharmaceutical dollar.
By:David Gross, Senior Policy Advisor, AARP Public Policy Institute
Publish Date:July 1, 2003
One reason that drug prices tend to be lower in Canada is that prices for drugs that are still under patent—and therefore have no generic substitutes—are regulated by the federal Patented Medicine Prices Review Board (PMPRB). This Board establishes the maximum prices that can be charged in Canada for patented drugs. The PMPRB has been credited with keeping average annual price increases for patented drugs at or below zero since 1992. In addition, Canadian drug price levels fell from 123 percent of the median drug price level for seven industrialized countries (France, Germany, Italy, Sweden, Switzerland, the United Kingdom, and the United States) in 1987 to 101 percent of the comparator median in 2002. During that same period, the average U.S. prices for patented drugs rose from 36 percent above to 67 percent above average Canadian prices.
A second reason for lower Canadian prices is price negotiations by health insurers that are based on evaluations of clinical effectiveness of prescription drugs. Insurers, particularly the provincial drug benefit plans that provide coverage for most elderly, disabled, and low-income Canadians, have adopted cost management approaches that apply clinical evaluations to identify therapeutically similar drugs and negotiate with manufacturers in order to get the best price among similar products. These prices become available to other insurers (who tend to provide coverage to most other Canadians) because the provincial health plans publish the prices in their formulary, the list of drugs which they will cover.
Canada's success in restraining drug prices, however, has not fully restrained the growth of prescription drug spending. Prescription drug spending in Canada rose by about 9 percent per year between 1990 and 2001 (compared to 12 percent annual growth in the United States), due not only to drug prices but also to higher use per person and the changing mix toward more costly medications. Expenditures on prescription drugs account for an increasing share of national health care spending, and these costs threaten the ability of provincial and private benefit plans to continue providing benefits at current levels. As a result of financial pressures, public policy discussions in Canada have moved beyond the issue of drug prices to suggestions that provinces establish structures to ensure that a drug's price reflects its relative therapeutic value and that patients and physicians have both the information and incentives to balance benefits and actual costs. There also has been debate in Canada about whether the federal government should take a more prominent role in helping to restrain prescription drug costs beyond price alone, such as whether to adopt a national drug formulary.
What lessons does the Canadian experience offer the United States as it contends with rising drug costs? The most important lesson from the Canadian experience may come not from price regulation but from Canada's increasing use of clinical and economic evaluation to make drug payment decisions. The establishment of conditions for a more competitive pharmaceutical marketplace based on evaluations of quality and price may fit the American political context better than price controls. Indeed, to some extent, these policies are already being adopted in the United States within the Department of Veterans' Affairs and several state Medicaid programs.
Whatever programs the United States may turn to in reducing prescription drug spending, it will be important to evaluate their impact both on patient access to existing drugs and on pharmaceutical research and development-in effect, access to future drugs. Whether these management systems could successfully restrain pharmaceutical spending in the United States without adversely affecting access or pharmaceutical research and development is yet to be seen. They certainly warrant further assessment as Americans and their health insurers seek greater value for their pharmaceutical dollar.
By:David Gross, Senior Policy Advisor, AARP Public Policy Institute
Publish Date:July 1, 2003
Wednesday, January 26, 2011
Statins for the primary prevention of cardiovascular disease
Summary
Statins for the primary prevention of cardiovascular disease
Cardiovascular disease (CVD) is ranked as the number one cause of mortality and is a major cause of morbidity world wide. Reducing high blood cholesterol which is a risk factor for CVD events is an important goal of medical treatment. Statins are the first-choice agents. Since the early statin trials were reported, several reviews of the effects of statins have been published highlighting their benefits particularly in people with a past history of CVD. However for people without a past history of CVD (primary prevention), the evidence is less clear. The aim of this systematic review is to assess the effects, both in terms of benefits and harms of statins for the primary prevention of CVD. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE until 2007. We found 14 randomised control trials with 16 trial arms (34,272 patients) dating from 1994 to 2006. All were randomised control trials comparing statins with usual care or placebo. Duration of treatment was minimum one year and with follow up of a minimum of six months. All cause mortality. coronary heart disease and stroke events were reduced with the use of statins as was the need for revascularisations. Statin treatment reduced blood cholesterol. Taking statins did not increase the risk of adverse effects such as cancer. and few trials reported on costs or quality of life. This current systematic review highlights the shortcomings in the published trials and we recommend that caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk.
This is a Cochrane review abstract and plain language summary, prepared and maintained by The Cochrane Collaboration, currently published in The Cochrane Database of Systematic Reviews 2011 Issue 1, Copyright © 2011 The Cochrane Collaboration. Published by John Wiley and Sons, Ltd.. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).
This record should be cited as: Taylor F, Ward K, Moore THM, Burke M, Davey Smith G, Casas J-P, Ebrahim S. Statins for the primary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2011, Issue 1. Art. No.: CD004816. DOI: 10.1002/14651858.CD004816.pub4
Editorial Group: Heart Group
This version first published online: January 19. 2011
Last assessed as up-to-date: September 8. 2007
Abstract
Background
Reducing high blood cholesterol, a risk factor for cardiovascular disease (CVD) events in people with and without a past history of coronary heart disease (CHD) is an important goal of pharmacotherapy. Statins are the first-choice agents. Previous reviews of the effects of statins have highlighted their benefits in people with coronary artery disease. The case for primary prevention, however, is less clear.
Objectives
To assess the effects, both harms and benefits, of statins in people with no history of CVD.
Search strategy
To avoid duplication of effort, we checked reference lists of previous systematic reviews. We searched the Cochrane Central Register of Controlled Trials (Issue 1, 2007), MEDLINE (2001 to March 2007) and EMBASE (2003 to March 2007). There were no language restrictions.
Selection criteria
Randomised controlled trials of statins with minimum duration of one year and follow-up of six months, in adults with no restrictions on their total low density lipoprotein (LDL) or high density lipoprotein (HDL) cholesterol levels, and where 10% or less had a history of CVD, were included.
Data collection and analysis
Two authors independently selected studies for inclusion and extracted data. Outcomes included all cause mortality, fatal and non-fatal CHD, CVD and stroke events, combined endpoints (fatal and non-fatal CHD, CVD and stroke events), change in blood total cholesterol concentration, revascularisation, adverse events, quality of life and costs. Relative risk (RR) was calculated for dichotomous data, and for continuous data pooled weighted mean differences (with 95% confidence intervals) were calculated.
Main results
Fourteen randomised control trials (16 trial arms; 34,272 participants) were included. Eleven trials recruited patients with specific conditions (raised lipids, diabetes, hypertension, microalbuminuria). All-cause mortality was reduced by statins (RR 0.83, 95% CI 0.73 to 0.95) as was combined fatal and non-fatal CVD endpoints (RR 0.70, 95% CI 0.61 to 0.79). Benefits were also seen in the reduction of revascularisation rates (RR 0.66, 95% CI 0.53 to 0.83). Total cholesterol and LDL cholesterol were reduced in all trials but there was evidence of heterogeneity of effects. There was no clear evidence of any significant harm caused by statin prescription or of effects on patient quality of life.
Authors' conclusions
Although reductions in all-cause mortality, composite endpoints and revascularisations were found with no excess of adverse events, there was evidence of selective reporting of outcomes, failure to report adverse events and inclusion of people with cardiovascular disease. Only limited evidence showed that primary prevention with statins may be cost effective and improve patient quality of life. Caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk.
Statins for the primary prevention of cardiovascular disease
Cardiovascular disease (CVD) is ranked as the number one cause of mortality and is a major cause of morbidity world wide. Reducing high blood cholesterol which is a risk factor for CVD events is an important goal of medical treatment. Statins are the first-choice agents. Since the early statin trials were reported, several reviews of the effects of statins have been published highlighting their benefits particularly in people with a past history of CVD. However for people without a past history of CVD (primary prevention), the evidence is less clear. The aim of this systematic review is to assess the effects, both in terms of benefits and harms of statins for the primary prevention of CVD. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE until 2007. We found 14 randomised control trials with 16 trial arms (34,272 patients) dating from 1994 to 2006. All were randomised control trials comparing statins with usual care or placebo. Duration of treatment was minimum one year and with follow up of a minimum of six months. All cause mortality. coronary heart disease and stroke events were reduced with the use of statins as was the need for revascularisations. Statin treatment reduced blood cholesterol. Taking statins did not increase the risk of adverse effects such as cancer. and few trials reported on costs or quality of life. This current systematic review highlights the shortcomings in the published trials and we recommend that caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk.
This is a Cochrane review abstract and plain language summary, prepared and maintained by The Cochrane Collaboration, currently published in The Cochrane Database of Systematic Reviews 2011 Issue 1, Copyright © 2011 The Cochrane Collaboration. Published by John Wiley and Sons, Ltd.. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).
This record should be cited as: Taylor F, Ward K, Moore THM, Burke M, Davey Smith G, Casas J-P, Ebrahim S. Statins for the primary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2011, Issue 1. Art. No.: CD004816. DOI: 10.1002/14651858.CD004816.pub4
Editorial Group: Heart Group
This version first published online: January 19. 2011
Last assessed as up-to-date: September 8. 2007
Abstract
Background
Reducing high blood cholesterol, a risk factor for cardiovascular disease (CVD) events in people with and without a past history of coronary heart disease (CHD) is an important goal of pharmacotherapy. Statins are the first-choice agents. Previous reviews of the effects of statins have highlighted their benefits in people with coronary artery disease. The case for primary prevention, however, is less clear.
Objectives
To assess the effects, both harms and benefits, of statins in people with no history of CVD.
Search strategy
To avoid duplication of effort, we checked reference lists of previous systematic reviews. We searched the Cochrane Central Register of Controlled Trials (Issue 1, 2007), MEDLINE (2001 to March 2007) and EMBASE (2003 to March 2007). There were no language restrictions.
Selection criteria
Randomised controlled trials of statins with minimum duration of one year and follow-up of six months, in adults with no restrictions on their total low density lipoprotein (LDL) or high density lipoprotein (HDL) cholesterol levels, and where 10% or less had a history of CVD, were included.
Data collection and analysis
Two authors independently selected studies for inclusion and extracted data. Outcomes included all cause mortality, fatal and non-fatal CHD, CVD and stroke events, combined endpoints (fatal and non-fatal CHD, CVD and stroke events), change in blood total cholesterol concentration, revascularisation, adverse events, quality of life and costs. Relative risk (RR) was calculated for dichotomous data, and for continuous data pooled weighted mean differences (with 95% confidence intervals) were calculated.
Main results
Fourteen randomised control trials (16 trial arms; 34,272 participants) were included. Eleven trials recruited patients with specific conditions (raised lipids, diabetes, hypertension, microalbuminuria). All-cause mortality was reduced by statins (RR 0.83, 95% CI 0.73 to 0.95) as was combined fatal and non-fatal CVD endpoints (RR 0.70, 95% CI 0.61 to 0.79). Benefits were also seen in the reduction of revascularisation rates (RR 0.66, 95% CI 0.53 to 0.83). Total cholesterol and LDL cholesterol were reduced in all trials but there was evidence of heterogeneity of effects. There was no clear evidence of any significant harm caused by statin prescription or of effects on patient quality of life.
Authors' conclusions
Although reductions in all-cause mortality, composite endpoints and revascularisations were found with no excess of adverse events, there was evidence of selective reporting of outcomes, failure to report adverse events and inclusion of people with cardiovascular disease. Only limited evidence showed that primary prevention with statins may be cost effective and improve patient quality of life. Caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk.
Aspirin for Primary Prevention in Diabetes
Previous guidelines recommended low-dose aspirin therapy for the primary prevention of stroke in patients with type 1 or type 2 diabetes mellitus who were at increased cardiovascular (CV) risk. Risk factors included patient age older than 40 years, a family history of CV disease, hypertension, smoking, dyslipidemia, or albuminuria. Aspirin therapy was not recommended for patients younger than 30 years of age because no benefit had been demonstrated, and aspirin was contraindicated in patients under 21 years of age because of associated risk for Reye syndrome.[1]
Since the Antithrombotic Trialists' Collaboration (ATT-C) published their first meta-analysis results in May 2009, questioning the value of low-dose aspirin for primary prevention, confusion has been expressed about when to recommend aspirin for patients with diabetes. The ATT-C performed a meta-analysis of 6 primary prevention trials, including 95,000 individuals with low-average CV risk and 16 secondary prevention trials with 17,000 individuals who had high CV risk. This analysis showed that primary prevention of vascular events with aspirin is of uncertain value, whereas the risk for major episodes of hemorrhage may increase.[2]
The ATT-C updated their recommendations for aspirin in primary prevention after considering the results from the POPADAD (Prevention of Progression of Arterial Disease and Diabetes),[3] JPAD (Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes),[4] and AAA (Aspirin for Asymptomatic Atherosclerosis)[5] trials. They concluded that the benefit of aspirin appeared to outweigh its risks when used for secondary, but not primary, prevention.[6]
De Berardis and colleagues conducted a second meta-analysis of 6 studies with 10,117 participants, which suggested that the benefit of aspirin in the primary prevention of major CV events or death in people with diabetes may be lower than in other high-risk populations.[7] Evidence demonstrating that low-dose aspirin is beneficial was lacking in this analysis, and the benefits were not found to exceed the risk for major bleeding, particularly in patients at low CV risk (< 20% over 10 years) and in older patients (> 70 years of age) at high risk of bleeding.[7]
These recent findings have prompted an evaluation of the current guidelines for aspirin use in primary prevention. The American Diabetes Association (ADA) Standard of Medical Care in Diabetes--2010 guidelines have backed off slightly on recommending aspirin use. The guidelines now recommend the consideration of aspirin therapy 75-162 mg daily as a primary prevention strategy for patients with type 1 or type 2 diabetes mellitus who are at increased CV risk (10-year risk > 10%).
Aspirin should not be recommended for patients at low CV risk, including women younger than 60 years of age, men younger than 50 years of age with no major risk factors, and patients with 10-year CV risk < 5%, because the low benefit is offset by the risk for significant bleeding.
Clinical judgment should be used for patients at intermediate risk or older patients with no risk factors. This generally includes most men older than 50 years of age or women older than 60 years of age who have at least 1 additional major risk factor, such as family history of CV disease, hypertension, smoking, dyslipidemia, or albuminuria.[8] To determine risk factors, 2 assessment tools may be used: the Atherosclerosis Risk in Communities (ARIC) Risk Calculator or the ADA's Risk Assessment Tool, Diabetes Personal Health Decisions.
In summary, it remains questionable how much benefit or risk aspirin confers for primary prevention in patients with diabetes. Currently, 2 trials are under way to answer key questions about the risk/benefit ratio: ASCEND (A Study of Cardiovascular Events iN Diabetes) and ACCEPT-D (Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes). These are large, ongoing studies that will enroll up to 15,000 participants with anticipated completion dates of 2011 and 2013, respectively.
Until results from these studies are in, providers should use clinical judgment, including known approaches, to minimize CV risk, such as smoking cessation, statins, angiotensin-converting enzyme inhibitors, and the achievement of good glucose control before considering aspirin for primary prevention.
Since the Antithrombotic Trialists' Collaboration (ATT-C) published their first meta-analysis results in May 2009, questioning the value of low-dose aspirin for primary prevention, confusion has been expressed about when to recommend aspirin for patients with diabetes. The ATT-C performed a meta-analysis of 6 primary prevention trials, including 95,000 individuals with low-average CV risk and 16 secondary prevention trials with 17,000 individuals who had high CV risk. This analysis showed that primary prevention of vascular events with aspirin is of uncertain value, whereas the risk for major episodes of hemorrhage may increase.[2]
The ATT-C updated their recommendations for aspirin in primary prevention after considering the results from the POPADAD (Prevention of Progression of Arterial Disease and Diabetes),[3] JPAD (Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes),[4] and AAA (Aspirin for Asymptomatic Atherosclerosis)[5] trials. They concluded that the benefit of aspirin appeared to outweigh its risks when used for secondary, but not primary, prevention.[6]
De Berardis and colleagues conducted a second meta-analysis of 6 studies with 10,117 participants, which suggested that the benefit of aspirin in the primary prevention of major CV events or death in people with diabetes may be lower than in other high-risk populations.[7] Evidence demonstrating that low-dose aspirin is beneficial was lacking in this analysis, and the benefits were not found to exceed the risk for major bleeding, particularly in patients at low CV risk (< 20% over 10 years) and in older patients (> 70 years of age) at high risk of bleeding.[7]
These recent findings have prompted an evaluation of the current guidelines for aspirin use in primary prevention. The American Diabetes Association (ADA) Standard of Medical Care in Diabetes--2010 guidelines have backed off slightly on recommending aspirin use. The guidelines now recommend the consideration of aspirin therapy 75-162 mg daily as a primary prevention strategy for patients with type 1 or type 2 diabetes mellitus who are at increased CV risk (10-year risk > 10%).
Aspirin should not be recommended for patients at low CV risk, including women younger than 60 years of age, men younger than 50 years of age with no major risk factors, and patients with 10-year CV risk < 5%, because the low benefit is offset by the risk for significant bleeding.
Clinical judgment should be used for patients at intermediate risk or older patients with no risk factors. This generally includes most men older than 50 years of age or women older than 60 years of age who have at least 1 additional major risk factor, such as family history of CV disease, hypertension, smoking, dyslipidemia, or albuminuria.[8] To determine risk factors, 2 assessment tools may be used: the Atherosclerosis Risk in Communities (ARIC) Risk Calculator or the ADA's Risk Assessment Tool, Diabetes Personal Health Decisions.
In summary, it remains questionable how much benefit or risk aspirin confers for primary prevention in patients with diabetes. Currently, 2 trials are under way to answer key questions about the risk/benefit ratio: ASCEND (A Study of Cardiovascular Events iN Diabetes) and ACCEPT-D (Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes). These are large, ongoing studies that will enroll up to 15,000 participants with anticipated completion dates of 2011 and 2013, respectively.
Until results from these studies are in, providers should use clinical judgment, including known approaches, to minimize CV risk, such as smoking cessation, statins, angiotensin-converting enzyme inhibitors, and the achievement of good glucose control before considering aspirin for primary prevention.
Thursday, January 13, 2011
Is acute otitis media treatable?
In children with acute otitis media, two placebo-controlled trials establish that antibiotic treatment with amoxicillin-clavulanate is superior to watchful waiting. The trials appear in the New England Journal of Medicine.
Researchers in Finland and the U.S. separately randomized a total of some 600 children under age 3 years to roughly 10 days of double-blind treatment with either amoxicillin-clavulanate or placebo. All children had been diagnosed with acute otitis media according to strict standards.
In both trials, treatment failure was at least twice as frequent among placebo recipients. Rash and diarrhea were more common among those receiving antibiotics.
An editorialist writes that the trials provide "the best data yet" to answer the question: Is acute otitis media treatable? "The answer is yes," he writes.
Researchers in Finland and the U.S. separately randomized a total of some 600 children under age 3 years to roughly 10 days of double-blind treatment with either amoxicillin-clavulanate or placebo. All children had been diagnosed with acute otitis media according to strict standards.
In both trials, treatment failure was at least twice as frequent among placebo recipients. Rash and diarrhea were more common among those receiving antibiotics.
An editorialist writes that the trials provide "the best data yet" to answer the question: Is acute otitis media treatable? "The answer is yes," he writes.
Friday, January 7, 2011
Echinacea ineffective for the common cold
Echinacea has no effect on the severity or duration of common cold symptoms, according to the results of a recent randomized controlled trial. The trial involved 719 patients (age 12–80 years) with new-onset common cold. Patients were assigned to one of four groups: no pills, placebo pills (blinded), Echinacea pills (blinded) or Echinacea pills (unblinded, open-label). The Echinacea groups received the equivalent of 10.2 g of dried Echinacea root during the first 24 hours and 5.1 g during each of the next four days.
Common cold severity was assessed twice daily by self-reporting, using the short version of the Wisconsin Upper Respiratory Symptom Survey. Secondary outcomes included interleukin-8 levels and neutrophil counts from nasal wash, which were measured at enrolment in the study and two days later.
A total of 713 subjects completed the study. The mean cold severity was 236 for the blinded Echinacea group and 258 for the unblinded Echinacea group, 264 for the blinded placebo group and 286 for the no-pill group. A comparison of the two blinded groups showed a 28-point nonsignificant trend toward benefit for Echinacea. The mean illness duration was 6.34 days in the blinded Echinacea group, 6.76 days in the unblinded Echinacea group, 6.87 days in the blinded placebo group and 7.03 days in the no-pill group. A comparison of the blinded groups showed a nonsignificant 0.53-day benefit for Echinacea. The median changes in interleukin-8 levels and neutrophil counts were not statistically different among the four groups. The frequency of adverse effects was also similar among the four groups.
The authors concluded that statistically significant differences in illness duration and severity were not seen with this dose and formulation of Echinacea compared with placebo. However, a higher-than-expected variability in results limited the study’s power to detect small benefits.
Reference
Barrett B, Brown R, Rakel D, et al. Echinacea for treating the common cold – a randomized trial. Ann Intern Med 2010;153:769-77. www.annals.org/content/153/12/769.full.pdf+html (accessed December 22, 2010).
Common cold severity was assessed twice daily by self-reporting, using the short version of the Wisconsin Upper Respiratory Symptom Survey. Secondary outcomes included interleukin-8 levels and neutrophil counts from nasal wash, which were measured at enrolment in the study and two days later.
A total of 713 subjects completed the study. The mean cold severity was 236 for the blinded Echinacea group and 258 for the unblinded Echinacea group, 264 for the blinded placebo group and 286 for the no-pill group. A comparison of the two blinded groups showed a 28-point nonsignificant trend toward benefit for Echinacea. The mean illness duration was 6.34 days in the blinded Echinacea group, 6.76 days in the unblinded Echinacea group, 6.87 days in the blinded placebo group and 7.03 days in the no-pill group. A comparison of the blinded groups showed a nonsignificant 0.53-day benefit for Echinacea. The median changes in interleukin-8 levels and neutrophil counts were not statistically different among the four groups. The frequency of adverse effects was also similar among the four groups.
The authors concluded that statistically significant differences in illness duration and severity were not seen with this dose and formulation of Echinacea compared with placebo. However, a higher-than-expected variability in results limited the study’s power to detect small benefits.
Reference
Barrett B, Brown R, Rakel D, et al. Echinacea for treating the common cold – a randomized trial. Ann Intern Med 2010;153:769-77. www.annals.org/content/153/12/769.full.pdf+html (accessed December 22, 2010).
Levothyroxine: best taken at bedtime
New study results suggest that levothyroxine improves thyroid hormone levels more when taken at bedtime compared to taking the drug in the morning on an empty stomach. Levothyroxine is one of the most prescribed medications. About 70–80% of the drug is absorbed orally, with absorption occurring in the small intestine. The current consensus is that levothyroxine is best taken before breakfast to prevent interference of its intestinal uptake by food or other medications.
The study was planned when the authors noticed that thyroid hormone levels improved markedly in several patients after switching from morning to bedtime levothyroxine dosing. The six-month, randomized, double-blind crossover trial was conducted in 105 patients with primary hypothyroidism. Patients were instructed to take one capsule in the morning (1/2 hour before breakfast) and one capsule at bedtime (one capsule contained levothyroxine and the other placebo; most patients ate only a small snack or nothing for several hours prior to bedtime). The capsule administration times were then switched after three months. The placebo and levothyroxine capsules were visually identical and patients received the same dose of levothyroxine as before entry into the trial.
Compared to morning levothyroxine intake, bedtime ingestion resulted in a 1.25 mIU/L reduction in thyrotropin level (p < 0.001), a 0.07 ng/dL increase in free thyroxine level (p = 0.01) and a 6.5 ng/dL increase in total triiodothyronine level (p = 0.02). No significant differences were seen between the two treatment groups in any of the secondary outcome measures (creatinine and lipid levels, body mass index, heart rate and quality of life).
The investigators conclude that clinicians should consider prescribing levothyroxine intake at bedtime as an alternative to morning dosing, provided that the bedtime dose is taken on an empty stomach. Although the higher thyroid hormone levels with bedtime administration did not translate into quality of life benefits, bedtime administration may be more convenient than morning intake since patients do not have to postpone breakfast.
Reference
Bolk N, Visser TJ, Nijman J, et al. Effects of evening vs morning levothyroxine intake: a randomized double-blind crossover trial. Arch Intern Med 2010;170:1996-2003. (accessed January 3, 2010).
The study was planned when the authors noticed that thyroid hormone levels improved markedly in several patients after switching from morning to bedtime levothyroxine dosing. The six-month, randomized, double-blind crossover trial was conducted in 105 patients with primary hypothyroidism. Patients were instructed to take one capsule in the morning (1/2 hour before breakfast) and one capsule at bedtime (one capsule contained levothyroxine and the other placebo; most patients ate only a small snack or nothing for several hours prior to bedtime). The capsule administration times were then switched after three months. The placebo and levothyroxine capsules were visually identical and patients received the same dose of levothyroxine as before entry into the trial.
Compared to morning levothyroxine intake, bedtime ingestion resulted in a 1.25 mIU/L reduction in thyrotropin level (p < 0.001), a 0.07 ng/dL increase in free thyroxine level (p = 0.01) and a 6.5 ng/dL increase in total triiodothyronine level (p = 0.02). No significant differences were seen between the two treatment groups in any of the secondary outcome measures (creatinine and lipid levels, body mass index, heart rate and quality of life).
The investigators conclude that clinicians should consider prescribing levothyroxine intake at bedtime as an alternative to morning dosing, provided that the bedtime dose is taken on an empty stomach. Although the higher thyroid hormone levels with bedtime administration did not translate into quality of life benefits, bedtime administration may be more convenient than morning intake since patients do not have to postpone breakfast.
Reference
Bolk N, Visser TJ, Nijman J, et al. Effects of evening vs morning levothyroxine intake: a randomized double-blind crossover trial. Arch Intern Med 2010;170:1996-2003. (accessed January 3, 2010).
Tuesday, January 4, 2011
Colonoscopy Shown to Lower Risk for Right- and Left-Sided Cancers
Colonoscopy is associated with a near-80% reduction in risk for colorectal cancer, according to a population-based case-control study published in the Annals of Internal Medicine.
German investigators ascertained colonoscopy histories of some 1700 patients with a first diagnosis of colorectal cancer and 1900 controls without a history of colorectal cancer. After adjustment for covariates including level of education, smoking status, body-mass index, and use of NSAIDs or hormone replacement, a history of colonoscopy within the preceding 10 years was associated with reduced risk for colorectal cancer on both the left and right sides. Risk reductions were greater for left-sided cancers — at 84% — than for right-sided cancers — at 56%.
The authors say their results reinforce the notion that colonoscopy reduces risks in the community setting as well as in the "highly standardized conditions" of tertiary medical centers. And an editorialist says the results "offer reassurance that colonoscopy can provide substantial protection" against both right- and left-sided disease.
German investigators ascertained colonoscopy histories of some 1700 patients with a first diagnosis of colorectal cancer and 1900 controls without a history of colorectal cancer. After adjustment for covariates including level of education, smoking status, body-mass index, and use of NSAIDs or hormone replacement, a history of colonoscopy within the preceding 10 years was associated with reduced risk for colorectal cancer on both the left and right sides. Risk reductions were greater for left-sided cancers — at 84% — than for right-sided cancers — at 56%.
The authors say their results reinforce the notion that colonoscopy reduces risks in the community setting as well as in the "highly standardized conditions" of tertiary medical centers. And an editorialist says the results "offer reassurance that colonoscopy can provide substantial protection" against both right- and left-sided disease.
Sunday, January 2, 2011
Long-Term Health Risks After Gastroenteritis from Contaminated Drinking Water
Acute gastroenteritis due to E. coli O157:H7 seems associated with increased long-term risk for hypertension and other cardiorenal complications, according to a BMJ study of a large Canadian outbreak.
Researchers tracked some 2000 adults whose well water was contaminated with livestock waste during flooding. About half the cohort reported symptoms compatible with gastroenteritis; both E. coli O157:H7 and Campylobacter species were widely recovered from stool samples taken at the time of the incident.
After a median follow-up of 8 years, those who suffered gastroenteritis were more likely to develop hypertension, structural and functional renal impairment, and cardiovascular disease than those in whom gastroenteritis did not develop or whose illness was mild.
The authors, pointing out that E. coli O157:H7 toxins have receptors in kidney tissue, say it's important for patients infected with this organism to undergo regular blood pressure and kidney-function monitoring "to prevent or reduce silent progressive vascular injury."
Researchers tracked some 2000 adults whose well water was contaminated with livestock waste during flooding. About half the cohort reported symptoms compatible with gastroenteritis; both E. coli O157:H7 and Campylobacter species were widely recovered from stool samples taken at the time of the incident.
After a median follow-up of 8 years, those who suffered gastroenteritis were more likely to develop hypertension, structural and functional renal impairment, and cardiovascular disease than those in whom gastroenteritis did not develop or whose illness was mild.
The authors, pointing out that E. coli O157:H7 toxins have receptors in kidney tissue, say it's important for patients infected with this organism to undergo regular blood pressure and kidney-function monitoring "to prevent or reduce silent progressive vascular injury."
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