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.
Sunday, July 31, 2011
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."
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