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Vitamin D Supplements Appear to Be Associated With Lower Mortality
Gastroenterology and Hepatology News Richard Peek and K. Rajender Reddy, Section Editors
Adverse Drug Events Reported to the Food and Drug Administration Seem to Have Markedly Increased
T
he number of serious adverse drug events reported to the US Food and Drug Administration (FDA) more than doubled between 1998 and 2005, as did deaths associated with adverse drug events, according to a report in the September 10, 2007, issue of Archives of Internal Medicine. A serious adverse drug event, as defined by the FDA, is an adverse event that results in death, a birth defect, disability, hospitalization, or is life threatening or required intervention to prevent harm, according to the report. Such events are voluntarily reported to the FDA through its Adverse Event Reporting System (AERS) and known as “MedWatch” reports. The reports come to the FDA directly or through drug manufacturers, who are then required to forward them.
Vitamin D Supplements Appear to Be Associated With Lower Mortality
I
ndividuals who take vitamin D supplements appear to have a lower risk of death from any cause over an average follow-up time of 6 years, according to a meta-analysis of 18 previously published studies in the September 10, 2007, issue of Archives of Internal Medicine. Past studies have suggested that deficiencies in vitamin D might be associated with a higher risk of death from cancer, heart disease, and diabetes—illnesses that account for 60%–70% of deaths in high-income nations, according to background information in the article. “If the associations made between vitamin D and these conditions were consistent, then interventions ef-
The researchers from the Institute for Safe Medication Practices (Huntingdon Valley, PA), and Wake Forest University School of Medicine (Winston-Salem, NC), analyzed serious adverse drug events reported to the FDA through AERS from 1998 through 2005. During this period, a total of 467,809 serious adverse events were reported. The annual number of reports increased 2.6-fold between 1998 and 2005, from 34,966 to 89,842. The number of fatal adverse drug events increased from 5,519 to 15,107 in the same time frame, a 2.7fold increase. “The overall relative increase was four times faster than the growth in total U.S. outpatient prescriptions, which grew in the same period from 2.7 billion to 3.8 billion,” the authors write. A total of 1489 drugs were associated with adverse events, but a subset of 51 drugs that each had ⱖ500 reports in any year accounted for 203,957 (43.6%) of the total adverse event reports in the study. “Contrary to our expectations, drugs related to
safety withdrawals were a modest share of all reported events and declined in importance over time,” the authors write. In the subset of 51 drugs with ⱖ500 reports in a year, the percentage of reported events associated with drugs related to safety withdrawals declined from 26% in 1999 to ⬍1% in 2005. “Among the most frequently reported drugs associated with fatal events, we observed a disproportionate contribution of pain medications and drugs that modify the immune system. “These data show a marked increase in reported deaths and serious injuries associated with drug therapy over the study period,” they conclude. “The results highlight the importance of this public health problem and illustrate the need for improved systems to manage the risks of prescription drugs.” For more details, see “Serious adverse drug events reported to the Food and Drug Administration, 1998 – 2005,” Arch Intern Med 2007;167:1752– 1759.
fectively strengthening vitamin D status should result in reduced total mortality,” the authors write. Dr Philippe Autier, of the International Agency for Research on Cancer, Lyon, France, and Dr Sara Gandini, of the European Institute of Oncology, Milano, Italy, searched for randomized controlled trials of vitamin D supplements published before November 2006. They analyzed 18 separate trials that included 57,311 participants and evaluated doses of vitamin D ranging from 300 –2000 IU, with an average dose of 528 IU. Most commercially available supplements contain between 400 and 600 IU. Over an average follow-up period of 5.7 years, 4777 participants died. Individuals who took vitamin D had a 7% lower risk of death than those who did
not. In the 9 trials that collected blood samples, those who took supplements had an average 1.4- to 5.2-fold higher blood level of vitamin D than those who did not. “Mechanisms by which vitamin D supplementation would decrease allcause mortality are not clear,” the authors write. Vitamin D could inhibit some mechanisms by which cancer cells proliferate, or it may boost the function of blood vessels or the immune system, they note. “In conclusion, the intake of ordinary doses of vitamin D supplements seems to be associated with decreases in total mortality rates,” the authors write. “The relationship between baseline vitamin D status, dose of vitamin D supplements and total mortality rates remains to be investigated. PopulationGASTROENTEROLOGY 2007;133:1401–1403
continued
based, placebo-controlled randomized trials in people 50 years or older for at least 6 years with total mortality as the main end point should be organized to confirm these findings.” The meta-analysis “adds a new chapter in the accumulating evidence for a beneficial role of vitamin D on health,” writes Dr Edward Giovannucci of the Harvard School of Public Health, Boston, in an accompanying editorial. “Re-
search on vitamin D should be continued to clearly elucidate the specific benefits and optimal intakes and levels of vitamin D,” Dr Giovannucci continues. “Nonetheless, based on the total body of evidence of health conditions associated with vitamin D deficiency, abetted with the results from this meta-analysis, a more proactive attitude to identify, prevent and treat vitamin D deficiency should be part of
standard medical care. From a broader public health perspective, the roles of moderate sun exposure, food fortification with vitamin D and higher-dose vitamin D supplements for adults need to be debated.” For more details, see “Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials,” Arch Intern Med 2007; 167:1730 –1737; 1709 –1710.
The Food and Drug Administration Approves Second West Nile Virus Screening Test for Donated Blood and Organs
FDA’s Center for Biologics Evaluation and Research. “As a result, blood centers and hospitals now have a choice of 2 FDA approved tests to screen for West Nile Virus in donated blood and organs.” Most people infected with WNV show no signs of the disease but about 1 in 150 to 1 in 350 infected people develop serious symptoms, including encephalitis. Since introduction of the virus, the reported number of human cases of serious WNV in the United States has grown steadily from 62 in 1999 to 4269 in 2006. WNV has been particularly virulent this year. Although it is still early in the WNV season, 58 blood donors who are potentially positive for the virus have been reported to the CDC as of August 21, 2007. The cobas TaqScreen WNV test is approved for detection of the virus
in plasma specimens from human donors of whole blood and blood components (plasma, red or white cells, platelets) and living donors of cells, reproductive cells, and other tissues. It is also intended for use in testing plasma specimens of organ donors when specimens are obtained while the donor’s organs are still viable. The test is not intended for use on samples of cord blood or as an aid in the diagnosis of WNV infection (Figure 1). Approval comes as the FDA is preparing guidance on the use of licensed WNV screening tests for blood donors. The test is manufactured by Roche Molecular Systems Inc (Pleasanton, CA). In December 2005, Procleix WNV Assay, from Gen-Probe Inc (San Diego, CA), became the first FDA-approved WNV genetic test for blood and organs.
T
he US Food and Drug Administration (FDA) announced approval on August 28, 2007, of a second test for detection of West Nile virus (WNV) in blood and organs. The cobas TaqScreen WNV test is an automated test that is able to detect viral RNA early during infection. Such nucleic acid testing improves blood and organ safety, detecting whether donated blood and organs have been infected, even before the donor’s immune system has begun to produce antibodies against the virus. Most often, WNV is transmitted to humans by mosquitoes; however, this pathogen can also be transmitted by blood transfusion or organ transplantation from infected donors. Although WNV infection is common in Africa, Asia, and the Middle East, it did not appear in the United States until 1999. Since then, WNV has become endemic in most of this country, with from 1–3 million cases reported between 1999 and 2006, according to the Centers for Disease Control and Prevention (CDC). “This action is the culmination of the dedicated efforts of FDA, our sister agencies, blood establishments, and manufacturers to bring donor screening tests to market for this increasingly common virus,” said Dr Jesse L. Goodman, director of the 1402
Figure 1. West Nile virus.
Adverse Drug Events Reported to the Food and Drug Administration Seem to Have Markedly Increased
T
he number of serious adverse drug events reported to the US Food and Drug Administration (FDA) more than doubled between 1998 and 2005, as did deaths associated with adverse drug events, according to a report in the September 10, 2007, issue of Archives of Internal Medicine. A serious adverse drug event, as defined by the FDA, is an adverse event that results in death, a birth defect, disability, hospitalization, or is life threatening or required intervention to prevent harm, according to the report. Such events are voluntarily reported to the FDA through its Adverse Event Reporting System (AERS) and known as “MedWatch” reports. The reports come to the FDA directly or through drug manufacturers, who are then required to forward them.
Vitamin D Supplements Appear to Be Associated With Lower Mortality
I
ndividuals who take vitamin D supplements appear to have a lower risk of death from any cause over an average follow-up time of 6 years, according to a meta-analysis of 18 previously published studies in the September 10, 2007, issue of Archives of Internal Medicine. Past studies have suggested that deficiencies in vitamin D might be associated with a higher risk of death from cancer, heart disease, and diabetes—illnesses that account for 60%–70% of deaths in high-income nations, according to background information in the article. “If the associations made between vitamin D and these conditions were consistent, then interventions ef-
The researchers from the Institute for Safe Medication Practices (Huntingdon Valley, PA), and Wake Forest University School of Medicine (Winston-Salem, NC), analyzed serious adverse drug events reported to the FDA through AERS from 1998 through 2005. During this period, a total of 467,809 serious adverse events were reported. The annual number of reports increased 2.6-fold between 1998 and 2005, from 34,966 to 89,842. The number of fatal adverse drug events increased from 5,519 to 15,107 in the same time frame, a 2.7fold increase. “The overall relative increase was four times faster than the growth in total U.S. outpatient prescriptions, which grew in the same period from 2.7 billion to 3.8 billion,” the authors write. A total of 1489 drugs were associated with adverse events, but a subset of 51 drugs that each had ⱖ500 reports in any year accounted for 203,957 (43.6%) of the total adverse event reports in the study. “Contrary to our expectations, drugs related to
safety withdrawals were a modest share of all reported events and declined in importance over time,” the authors write. In the subset of 51 drugs with ⱖ500 reports in a year, the percentage of reported events associated with drugs related to safety withdrawals declined from 26% in 1999 to ⬍1% in 2005. “Among the most frequently reported drugs associated with fatal events, we observed a disproportionate contribution of pain medications and drugs that modify the immune system. “These data show a marked increase in reported deaths and serious injuries associated with drug therapy over the study period,” they conclude. “The results highlight the importance of this public health problem and illustrate the need for improved systems to manage the risks of prescription drugs.” For more details, see “Serious adverse drug events reported to the Food and Drug Administration, 1998 – 2005,” Arch Intern Med 2007;167:1752– 1759.
fectively strengthening vitamin D status should result in reduced total mortality,” the authors write. Dr Philippe Autier, of the International Agency for Research on Cancer, Lyon, France, and Dr Sara Gandini, of the European Institute of Oncology, Milano, Italy, searched for randomized controlled trials of vitamin D supplements published before November 2006. They analyzed 18 separate trials that included 57,311 participants and evaluated doses of vitamin D ranging from 300 –2000 IU, with an average dose of 528 IU. Most commercially available supplements contain between 400 and 600 IU. Over an average follow-up period of 5.7 years, 4777 participants died. Individuals who took vitamin D had a 7% lower risk of death than those who did
not. In the 9 trials that collected blood samples, those who took supplements had an average 1.4- to 5.2-fold higher blood level of vitamin D than those who did not. “Mechanisms by which vitamin D supplementation would decrease allcause mortality are not clear,” the authors write. Vitamin D could inhibit some mechanisms by which cancer cells proliferate, or it may boost the function of blood vessels or the immune system, they note. “In conclusion, the intake of ordinary doses of vitamin D supplements seems to be associated with decreases in total mortality rates,” the authors write. “The relationship between baseline vitamin D status, dose of vitamin D supplements and total mortality rates remains to be investigated. PopulationGASTROENTEROLOGY 2007;133:1401–1403
continued
based, placebo-controlled randomized trials in people 50 years or older for at least 6 years with total mortality as the main end point should be organized to confirm these findings.” The meta-analysis “adds a new chapter in the accumulating evidence for a beneficial role of vitamin D on health,” writes Dr Edward Giovannucci of the Harvard School of Public Health, Boston, in an accompanying editorial. “Re-
search on vitamin D should be continued to clearly elucidate the specific benefits and optimal intakes and levels of vitamin D,” Dr Giovannucci continues. “Nonetheless, based on the total body of evidence of health conditions associated with vitamin D deficiency, abetted with the results from this meta-analysis, a more proactive attitude to identify, prevent and treat vitamin D deficiency should be part of
standard medical care. From a broader public health perspective, the roles of moderate sun exposure, food fortification with vitamin D and higher-dose vitamin D supplements for adults need to be debated.” For more details, see “Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials,” Arch Intern Med 2007; 167:1730 –1737; 1709 –1710.
The Food and Drug Administration Approves Second West Nile Virus Screening Test for Donated Blood and Organs
FDA’s Center for Biologics Evaluation and Research. “As a result, blood centers and hospitals now have a choice of 2 FDA approved tests to screen for West Nile Virus in donated blood and organs.” Most people infected with WNV show no signs of the disease but about 1 in 150 to 1 in 350 infected people develop serious symptoms, including encephalitis. Since introduction of the virus, the reported number of human cases of serious WNV in the United States has grown steadily from 62 in 1999 to 4269 in 2006. WNV has been particularly virulent this year. Although it is still early in the WNV season, 58 blood donors who are potentially positive for the virus have been reported to the CDC as of August 21, 2007. The cobas TaqScreen WNV test is approved for detection of the virus
in plasma specimens from human donors of whole blood and blood components (plasma, red or white cells, platelets) and living donors of cells, reproductive cells, and other tissues. It is also intended for use in testing plasma specimens of organ donors when specimens are obtained while the donor’s organs are still viable. The test is not intended for use on samples of cord blood or as an aid in the diagnosis of WNV infection (Figure 1). Approval comes as the FDA is preparing guidance on the use of licensed WNV screening tests for blood donors. The test is manufactured by Roche Molecular Systems Inc (Pleasanton, CA). In December 2005, Procleix WNV Assay, from Gen-Probe Inc (San Diego, CA), became the first FDA-approved WNV genetic test for blood and organs.
T
he US Food and Drug Administration (FDA) announced approval on August 28, 2007, of a second test for detection of West Nile virus (WNV) in blood and organs. The cobas TaqScreen WNV test is an automated test that is able to detect viral RNA early during infection. Such nucleic acid testing improves blood and organ safety, detecting whether donated blood and organs have been infected, even before the donor’s immune system has begun to produce antibodies against the virus. Most often, WNV is transmitted to humans by mosquitoes; however, this pathogen can also be transmitted by blood transfusion or organ transplantation from infected donors. Although WNV infection is common in Africa, Asia, and the Middle East, it did not appear in the United States until 1999. Since then, WNV has become endemic in most of this country, with from 1–3 million cases reported between 1999 and 2006, according to the Centers for Disease Control and Prevention (CDC). “This action is the culmination of the dedicated efforts of FDA, our sister agencies, blood establishments, and manufacturers to bring donor screening tests to market for this increasingly common virus,” said Dr Jesse L. Goodman, director of the 1402
Figure 1. West Nile virus.