Miriam E. Tucker

ATLANTA — The mumps outbreak that began in December 2005 at an Iowa university totaled 5,824 cases in 45 states by mid-October—and it isn't over yet, Dr. Gustavo H. Dayan said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

The outbreak—which has primarily affected young adults aged 18–24—appeared to have peaked in mid-April of this year, when 25% of the known cases were diagnosed. The number dropped between May and September, while most college students were on break. However, since the resumption of classes in August, mumps clusters have been reported at three campuses, one in Illinois (85 cases), another in Kansas (22), and a third in Virginia (12).

Since January, the number of reported cases per state has ranged from 1 to 1,971. Seven states reported 100 or more cases (Iowa, Kansas, Illinois, Wisconsin, Nebraska, South Dakota, and Missouri). Three states reported 50–99 cases, 18 had 10–49, while 17 states reported 1–5 cases. Only five states have not reported any cases (Connecticut, Delaware, Maine, Montana, and Vermont).

These numbers, reported by Dr. Dayan at the ACIP meeting, are updated from those published in the October 27th issue of the CDC's Morbidity and Mortality Weekly Report (www.cdc.gov/mmwr

Approximately two-thirds of cases have been female. The reason for this is not known, but it may relate to the fact that college women tend to congregate closely together more often than men, and perhaps are more likely to seek health care, said Dr. Dayan of the CDC's Division of Viral Diseases.

In the seven states with the most mumps cases (4,538), parotitis was reported in 68% and orchitis in about 6%. Other manifestations, such as meningitis, encephalitis, deafness, oophoritis, and mastitis have been reported in less than 1%. Approximately 2% of patients have been hospitalized. Overall, “the complications are much lower than in the prevaccine era,” Dr. Dayan noted.

Among those 4,538 cases, 46% had received two doses of mumps vaccine, 20% received one dose, and 1% received three doses. Vaccination status was unknown in 30%. Four percent were unvaccinated. However, following the CDC's updated recommendation for receipt of a second dose of measles-mumps-rubella vaccine in June (MMWR 2006;55:629–30), the proportion who had received two doses was higher in the three recent college clusters: 93% in Illinois, 95% in Kansas, and 100% in Virginia.

Preliminary data do not suggest that waning immunity plays a major role. Even with two doses, a vaccine efficacy of 90%–95% still might allow for accumulation of enough susceptible individuals to sustain periodic outbreaks, he said.

ATLANTA — The mumps outbreak that began in December 2005 at an Iowa university totaled 5,824 cases in 45 states by mid-October—and it isn't over yet, Dr. Gustavo H. Dayan said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

The outbreak—which has primarily affected young adults aged 18–24—appeared to have peaked in mid-April of this year, when 25% of the known cases were diagnosed. The number dropped between May and September, while most college students were on break. However, since the resumption of classes in August, mumps clusters have been reported at three campuses, one in Illinois (85 cases), another in Kansas (22), and a third in Virginia (12).

Since January, the number of reported cases per state has ranged from 1 to 1,971. Seven states reported 100 or more cases (Iowa, Kansas, Illinois, Wisconsin, Nebraska, South Dakota, and Missouri). Three states reported 50–99 cases, 18 had 10–49, while 17 states reported 1–5 cases. Only five states have not reported any cases (Connecticut, Delaware, Maine, Montana, and Vermont).

These numbers, reported by Dr. Dayan at the ACIP meeting, are updated from those published in the October 27th issue of the CDC's Morbidity and Mortality Weekly Report (www.cdc.gov/mmwr

Approximately two-thirds of cases have been female. The reason for this is not known, but it may relate to the fact that college women tend to congregate closely together more often than men, and perhaps are more likely to seek health care, said Dr. Dayan of the CDC's Division of Viral Diseases.

In the seven states with the most mumps cases (4,538), parotitis was reported in 68% and orchitis in about 6%. Other manifestations, such as meningitis, encephalitis, deafness, oophoritis, and mastitis have been reported in less than 1%. Approximately 2% of patients have been hospitalized. Overall, “the complications are much lower than in the prevaccine era,” Dr. Dayan noted.

Among those 4,538 cases, 46% had received two doses of mumps vaccine, 20% received one dose, and 1% received three doses. Vaccination status was unknown in 30%. Four percent were unvaccinated. However, following the CDC's updated recommendation for receipt of a second dose of measles-mumps-rubella vaccine in June (MMWR 2006;55:629–30), the proportion who had received two doses was higher in the three recent college clusters: 93% in Illinois, 95% in Kansas, and 100% in Virginia.

Preliminary data do not suggest that waning immunity plays a major role. Even with two doses, a vaccine efficacy of 90%–95% still might allow for accumulation of enough susceptible individuals to sustain periodic outbreaks, he said.

ATLANTA — The mumps outbreak that began in December 2005 at an Iowa university totaled 5,824 cases in 45 states by mid-October—and it isn't over yet, Dr. Gustavo H. Dayan said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

The outbreak—which has primarily affected young adults aged 18–24—appeared to have peaked in mid-April of this year, when 25% of the known cases were diagnosed. The number dropped between May and September, while most college students were on break. However, since the resumption of classes in August, mumps clusters have been reported at three campuses, one in Illinois (85 cases), another in Kansas (22), and a third in Virginia (12).

Since January, the number of reported cases per state has ranged from 1 to 1,971. Seven states reported 100 or more cases (Iowa, Kansas, Illinois, Wisconsin, Nebraska, South Dakota, and Missouri). Three states reported 50–99 cases, 18 had 10–49, while 17 states reported 1–5 cases. Only five states have not reported any cases (Connecticut, Delaware, Maine, Montana, and Vermont).

These numbers, reported by Dr. Dayan at the ACIP meeting, are updated from those published in the October 27th issue of the CDC's Morbidity and Mortality Weekly Report (www.cdc.gov/mmwr

Approximately two-thirds of cases have been female. The reason for this is not known, but it may relate to the fact that college women tend to congregate closely together more often than men, and perhaps are more likely to seek health care, said Dr. Dayan of the CDC's Division of Viral Diseases.

In the seven states with the most mumps cases (4,538), parotitis was reported in 68% and orchitis in about 6%. Other manifestations, such as meningitis, encephalitis, deafness, oophoritis, and mastitis have been reported in less than 1%. Approximately 2% of patients have been hospitalized. Overall, “the complications are much lower than in the prevaccine era,” Dr. Dayan noted.

Among those 4,538 cases, 46% had received two doses of mumps vaccine, 20% received one dose, and 1% received three doses. Vaccination status was unknown in 30%. Four percent were unvaccinated. However, following the CDC's updated recommendation for receipt of a second dose of measles-mumps-rubella vaccine in June (MMWR 2006;55:629–30), the proportion who had received two doses was higher in the three recent college clusters: 93% in Illinois, 95% in Kansas, and 100% in Virginia.

Preliminary data do not suggest that waning immunity plays a major role. Even with two doses, a vaccine efficacy of 90%–95% still might allow for accumulation of enough susceptible individuals to sustain periodic outbreaks, he said.

ATLANTA — Supply problems with the tetravalent meningococcal conjugate vaccine have been resolved, and routine vaccination of 11- to 12-year-olds should be resumed.

That recommendation from the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices was discussed at the committee's fall meeting and published the following week (MMWR 2006;55:1177).

The supply problem was announced in May of 2006, with Sanofi Pasteur's estimation that demand for Menactra would outpace the supply at least through the summer.

At that time, the CDC, in consultation with the American Academy of Pediatrics, the American Academy of Family Physicians, the American College Health Association, and the Society for Adolescent Medicine, recommended deferral of routine use of the vaccine in 11- to 12-year-olds (MMWR 2006;55:567–8).

Vaccination with MCV4 was to continue in other high-risk groups, including adolescents at high school entry who have not previously received the meningococcal conjugate vaccine, college freshmen living in dormitories, and other individuals—such as military recruits, travelers to endemic areas, microbiologists routinely exposed to Neisseria meningitidis, and certain immunocompromised individuals—who are at high risk for meningococcal disease.

More than 6 million doses of Menactra had been distributed by the end of September, according to the CDC.

Now, an additional 3.5–4.5 million doses are projected to be distributed through March of 2007, enough to allow a return to routine immunization of 11- to 12-year-olds and continuation in all the other recommended groups, said Dr. Gregory S. Wallace, chief of the CDC's Vaccine Supply and Assurance Branch.

ATLANTA — Supply problems with the tetravalent meningococcal conjugate vaccine have been resolved, and routine vaccination of 11- to 12-year-olds should be resumed.

That recommendation from the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices was discussed at the committee's fall meeting and published the following week (MMWR 2006;55:1177).

The supply problem was announced in May of 2006, with Sanofi Pasteur's estimation that demand for Menactra would outpace the supply at least through the summer.

At that time, the CDC, in consultation with the American Academy of Pediatrics, the American Academy of Family Physicians, the American College Health Association, and the Society for Adolescent Medicine, recommended deferral of routine use of the vaccine in 11- to 12-year-olds (MMWR 2006;55:567–8).

Vaccination with MCV4 was to continue in other high-risk groups, including adolescents at high school entry who have not previously received the meningococcal conjugate vaccine, college freshmen living in dormitories, and other individuals—such as military recruits, travelers to endemic areas, microbiologists routinely exposed to Neisseria meningitidis, and certain immunocompromised individuals—who are at high risk for meningococcal disease.

More than 6 million doses of Menactra had been distributed by the end of September, according to the CDC.

Now, an additional 3.5–4.5 million doses are projected to be distributed through March of 2007, enough to allow a return to routine immunization of 11- to 12-year-olds and continuation in all the other recommended groups, said Dr. Gregory S. Wallace, chief of the CDC's Vaccine Supply and Assurance Branch.

ATLANTA — Supply problems with the tetravalent meningococcal conjugate vaccine have been resolved, and routine vaccination of 11- to 12-year-olds should be resumed.

That recommendation from the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices was discussed at the committee's fall meeting and published the following week (MMWR 2006;55:1177).

The supply problem was announced in May of 2006, with Sanofi Pasteur's estimation that demand for Menactra would outpace the supply at least through the summer.

At that time, the CDC, in consultation with the American Academy of Pediatrics, the American Academy of Family Physicians, the American College Health Association, and the Society for Adolescent Medicine, recommended deferral of routine use of the vaccine in 11- to 12-year-olds (MMWR 2006;55:567–8).

Vaccination with MCV4 was to continue in other high-risk groups, including adolescents at high school entry who have not previously received the meningococcal conjugate vaccine, college freshmen living in dormitories, and other individuals—such as military recruits, travelers to endemic areas, microbiologists routinely exposed to Neisseria meningitidis, and certain immunocompromised individuals—who are at high risk for meningococcal disease.

More than 6 million doses of Menactra had been distributed by the end of September, according to the CDC.

Now, an additional 3.5–4.5 million doses are projected to be distributed through March of 2007, enough to allow a return to routine immunization of 11- to 12-year-olds and continuation in all the other recommended groups, said Dr. Gregory S. Wallace, chief of the CDC's Vaccine Supply and Assurance Branch.

Oral contraceptive use is associated with reduced rates of rheumatoid factor seropositivity in women without rheumatoid arthritis, while cigarette smoking may increase the risk, reported Shailaja S. Bhatia of the University of Colorado, Denver, Dr. Darcy S. Majka of Northwestern University, Chicago, and their associates.

The oral contraceptive (OC) finding is consistent with previous data suggesting a protective effect on the development of rheumatoid arthritis (RA), while previous data on the impact of smoking have conflicted.

Taken together, the results of this study suggest that OC use, and possibly cigarette smoking, act very early in the development of the immune dysregulation that occurs in RA, the investigators reported (Ann. Rheum. Dis. July 2006:DOI:10.1136/ard.2006.060004).

The study population comprised 304 women who had at least one child with the HLA-DR4 allele, which is associated with both RA and type 1 diabetes. (All were participating in a study on the autoimmunity of type 1 diabetes.) After the elimination of 6 women with self-reported RA, the remaining 298 were questioned about symptoms and signs related to RA and completed a risk factor questionnaire. All underwent 68-joint count examinations and were tested for RF and for HLA-DR4 subtypes.

Of the 298 women, 10.4% (31) tested positive for RF. Women who had ever used OCs were less likely to be RF positive than were those who had never used OCs (odds ratio 0.21).

Conversely, women who smoked 20 or more packs of cigarettes per year were 12.5 times more likely to be RF positive than were those who had never smoked, the investigators reported. After the researchers adjusted for age, education, and smoking, those women who had ever used OCs were still significantly less likely to be RF-positive (adjusted odds ratio 0.20). Similarly, smoking 20 or more packs per year was also independently associated with positive RF, compared with never smoking (adjusted odds ratio 56.4).

Risk factors found to not be associated with RF positivity included age, ethnicity, educational level, a history of type 1 diabetes or RA in the woman or a family member, smoking less than 20 pack-years of cigarettes, duration of OC use, number of pregnancies, history and duration of breast-feeding, the use of injectable hormones or hormone therapy, and consumption of regular or decaffeinated coffee, the investigators reported.

The mechanism underlying this effect may be that the synthetic hormones in OCs drive the immune system toward T-helper-2 cytokine responses and decreased production of proinflammatory and other cytokines, leading to T-helper-1-associated RA-specific cellular autoimmunity, the investigators speculated.

Oral contraceptive use is associated with reduced rates of rheumatoid factor seropositivity in women without rheumatoid arthritis, while cigarette smoking may increase the risk, reported Shailaja S. Bhatia of the University of Colorado, Denver, Dr. Darcy S. Majka of Northwestern University, Chicago, and their associates.

The oral contraceptive (OC) finding is consistent with previous data suggesting a protective effect on the development of rheumatoid arthritis (RA), while previous data on the impact of smoking have conflicted.

Taken together, the results of this study suggest that OC use, and possibly cigarette smoking, act very early in the development of the immune dysregulation that occurs in RA, the investigators reported (Ann. Rheum. Dis. July 2006:DOI:10.1136/ard.2006.060004).

The study population comprised 304 women who had at least one child with the HLA-DR4 allele, which is associated with both RA and type 1 diabetes. (All were participating in a study on the autoimmunity of type 1 diabetes.) After the elimination of 6 women with self-reported RA, the remaining 298 were questioned about symptoms and signs related to RA and completed a risk factor questionnaire. All underwent 68-joint count examinations and were tested for RF and for HLA-DR4 subtypes.

Of the 298 women, 10.4% (31) tested positive for RF. Women who had ever used OCs were less likely to be RF positive than were those who had never used OCs (odds ratio 0.21).

Conversely, women who smoked 20 or more packs of cigarettes per year were 12.5 times more likely to be RF positive than were those who had never smoked, the investigators reported. After the researchers adjusted for age, education, and smoking, those women who had ever used OCs were still significantly less likely to be RF-positive (adjusted odds ratio 0.20). Similarly, smoking 20 or more packs per year was also independently associated with positive RF, compared with never smoking (adjusted odds ratio 56.4).

Risk factors found to not be associated with RF positivity included age, ethnicity, educational level, a history of type 1 diabetes or RA in the woman or a family member, smoking less than 20 pack-years of cigarettes, duration of OC use, number of pregnancies, history and duration of breast-feeding, the use of injectable hormones or hormone therapy, and consumption of regular or decaffeinated coffee, the investigators reported.

The mechanism underlying this effect may be that the synthetic hormones in OCs drive the immune system toward T-helper-2 cytokine responses and decreased production of proinflammatory and other cytokines, leading to T-helper-1-associated RA-specific cellular autoimmunity, the investigators speculated.

Oral contraceptive use is associated with reduced rates of rheumatoid factor seropositivity in women without rheumatoid arthritis, while cigarette smoking may increase the risk, reported Shailaja S. Bhatia of the University of Colorado, Denver, Dr. Darcy S. Majka of Northwestern University, Chicago, and their associates.

The oral contraceptive (OC) finding is consistent with previous data suggesting a protective effect on the development of rheumatoid arthritis (RA), while previous data on the impact of smoking have conflicted.

Taken together, the results of this study suggest that OC use, and possibly cigarette smoking, act very early in the development of the immune dysregulation that occurs in RA, the investigators reported (Ann. Rheum. Dis. July 2006:DOI:10.1136/ard.2006.060004).

The study population comprised 304 women who had at least one child with the HLA-DR4 allele, which is associated with both RA and type 1 diabetes. (All were participating in a study on the autoimmunity of type 1 diabetes.) After the elimination of 6 women with self-reported RA, the remaining 298 were questioned about symptoms and signs related to RA and completed a risk factor questionnaire. All underwent 68-joint count examinations and were tested for RF and for HLA-DR4 subtypes.

Of the 298 women, 10.4% (31) tested positive for RF. Women who had ever used OCs were less likely to be RF positive than were those who had never used OCs (odds ratio 0.21).

Conversely, women who smoked 20 or more packs of cigarettes per year were 12.5 times more likely to be RF positive than were those who had never smoked, the investigators reported. After the researchers adjusted for age, education, and smoking, those women who had ever used OCs were still significantly less likely to be RF-positive (adjusted odds ratio 0.20). Similarly, smoking 20 or more packs per year was also independently associated with positive RF, compared with never smoking (adjusted odds ratio 56.4).

Risk factors found to not be associated with RF positivity included age, ethnicity, educational level, a history of type 1 diabetes or RA in the woman or a family member, smoking less than 20 pack-years of cigarettes, duration of OC use, number of pregnancies, history and duration of breast-feeding, the use of injectable hormones or hormone therapy, and consumption of regular or decaffeinated coffee, the investigators reported.

The mechanism underlying this effect may be that the synthetic hormones in OCs drive the immune system toward T-helper-2 cytokine responses and decreased production of proinflammatory and other cytokines, leading to T-helper-1-associated RA-specific cellular autoimmunity, the investigators speculated.

Microfracture is an effective first-line treatment for knee articular cartilage lesions in athletes who participate in high-impact sports, Dr. Kai Mithoefer and associates reported.

Microfracture is a relatively simple technique in which penetration of the subchondral bone induces clot formation containing marrow-derived mesenchymal stem cells, which produce a mixed fibrocartilage repair tissue containing varying amounts of type II collagen. It has become a popular treatment option for knee articular cartilage lesions in athletes, due to its low associated morbidity and rapid postoperative rehabilitation time.

Outcome data on athletes who perform high-impact sports with marked mechanical demands have been limited, said Dr. Mithoefer of Harvard Vanguard Orthopedics and Sports Medicine and Brigham and Women's Hospital, Boston, and associates (Am. J. Sports Med. 2006;34:1413–8).

The study population comprised 32 patients, mean age 38, with single cartilage lesions of the femur. Their mean symptom duration was 28 months. All had regularly participated in high-impact, pivoting sports, including basketball (14), tennis (13), football (9), downhill skiing (7), and soccer (5). All underwent microfracture arthroplasty performed by a fellowship-trained orthopedic surgeon. Seven patients with meniscus tears also received partial meniscectomy.

At a mean follow-up of 41 months, 21 of the athletes reported good or excellent results on the Brittenberg rating of knee function; significant improvements were seen on the activity-based Marx activity rating scale and Tegner scores. Improvements occurred in the activities of daily living scale in 71% of patients, on the Marx scale in 58%, and in Tegner scores in 72%. After an initial increase, declines in activity scores were observed in 15 athletes, Dr. Mithoefer and associates reported.

A total of 14 athletes (44%) returned to participation in high-impact sports after microfracture. Functional outcome score increases were lower among those who did not return to the sport. Two-thirds of the patients who had been symptomatic for 12 months or less before microfracture were able to return to their high-impact sport, compared with just 14% who had been symptomatic for more than a year before the procedure.

Athletes who received microfracture as first-line treatment were far more likely to return to their sports than were those who had had previous procedures, but concomitant meniscectomy did not have a significant impact on the ability to return to the sport. Patients with lesions of 200 mm

Microfracture is an effective first-line treatment for knee articular cartilage lesions in athletes who participate in high-impact sports, Dr. Kai Mithoefer and associates reported.

Microfracture is a relatively simple technique in which penetration of the subchondral bone induces clot formation containing marrow-derived mesenchymal stem cells, which produce a mixed fibrocartilage repair tissue containing varying amounts of type II collagen. It has become a popular treatment option for knee articular cartilage lesions in athletes, due to its low associated morbidity and rapid postoperative rehabilitation time.

Outcome data on athletes who perform high-impact sports with marked mechanical demands have been limited, said Dr. Mithoefer of Harvard Vanguard Orthopedics and Sports Medicine and Brigham and Women's Hospital, Boston, and associates (Am. J. Sports Med. 2006;34:1413–8).

The study population comprised 32 patients, mean age 38, with single cartilage lesions of the femur. Their mean symptom duration was 28 months. All had regularly participated in high-impact, pivoting sports, including basketball (14), tennis (13), football (9), downhill skiing (7), and soccer (5). All underwent microfracture arthroplasty performed by a fellowship-trained orthopedic surgeon. Seven patients with meniscus tears also received partial meniscectomy.

At a mean follow-up of 41 months, 21 of the athletes reported good or excellent results on the Brittenberg rating of knee function; significant improvements were seen on the activity-based Marx activity rating scale and Tegner scores. Improvements occurred in the activities of daily living scale in 71% of patients, on the Marx scale in 58%, and in Tegner scores in 72%. After an initial increase, declines in activity scores were observed in 15 athletes, Dr. Mithoefer and associates reported.

A total of 14 athletes (44%) returned to participation in high-impact sports after microfracture. Functional outcome score increases were lower among those who did not return to the sport. Two-thirds of the patients who had been symptomatic for 12 months or less before microfracture were able to return to their high-impact sport, compared with just 14% who had been symptomatic for more than a year before the procedure.

Athletes who received microfracture as first-line treatment were far more likely to return to their sports than were those who had had previous procedures, but concomitant meniscectomy did not have a significant impact on the ability to return to the sport. Patients with lesions of 200 mm

Microfracture is an effective first-line treatment for knee articular cartilage lesions in athletes who participate in high-impact sports, Dr. Kai Mithoefer and associates reported.

Microfracture is a relatively simple technique in which penetration of the subchondral bone induces clot formation containing marrow-derived mesenchymal stem cells, which produce a mixed fibrocartilage repair tissue containing varying amounts of type II collagen. It has become a popular treatment option for knee articular cartilage lesions in athletes, due to its low associated morbidity and rapid postoperative rehabilitation time.

Outcome data on athletes who perform high-impact sports with marked mechanical demands have been limited, said Dr. Mithoefer of Harvard Vanguard Orthopedics and Sports Medicine and Brigham and Women's Hospital, Boston, and associates (Am. J. Sports Med. 2006;34:1413–8).

The study population comprised 32 patients, mean age 38, with single cartilage lesions of the femur. Their mean symptom duration was 28 months. All had regularly participated in high-impact, pivoting sports, including basketball (14), tennis (13), football (9), downhill skiing (7), and soccer (5). All underwent microfracture arthroplasty performed by a fellowship-trained orthopedic surgeon. Seven patients with meniscus tears also received partial meniscectomy.

At a mean follow-up of 41 months, 21 of the athletes reported good or excellent results on the Brittenberg rating of knee function; significant improvements were seen on the activity-based Marx activity rating scale and Tegner scores. Improvements occurred in the activities of daily living scale in 71% of patients, on the Marx scale in 58%, and in Tegner scores in 72%. After an initial increase, declines in activity scores were observed in 15 athletes, Dr. Mithoefer and associates reported.

A total of 14 athletes (44%) returned to participation in high-impact sports after microfracture. Functional outcome score increases were lower among those who did not return to the sport. Two-thirds of the patients who had been symptomatic for 12 months or less before microfracture were able to return to their high-impact sport, compared with just 14% who had been symptomatic for more than a year before the procedure.

Athletes who received microfracture as first-line treatment were far more likely to return to their sports than were those who had had previous procedures, but concomitant meniscectomy did not have a significant impact on the ability to return to the sport. Patients with lesions of 200 mm

COPENHAGEN — A combination of ezetimibe and simvastatin provides additional lipid-modifying benefits compared with rosuvastatin monotherapy among patients with type 2 diabetes or with metabolic syndrome without diabetes, Dr. Alberico L. Catapano reported at the annual meeting of the European Association for the Study of Diabetes.

“Overall, ezetimibe/simvastatin, a single-tablet, dual-cholesterol inhibitor [Vytorin, Merck], offers an effective and well-tolerated lipid-modifying option for the treatment of hypercholesterolemia in patients with type 2 diabetes and metabolic syndrome,” said Dr. Catapano, of the department of pharmacological sciences at the University of Milan.

In a post-hoc analysis of data from a multicenter, double-blind, randomized, parallel-group, 6-week study sponsored by Merck & Co., 375 patients with type 2 diabetes, 840 with metabolic syndrome but without diabetes, 1,722 with neither condition, and 22 who could not be placed in a category because of missing data were randomized to one of six treatment groups: ezetimibe/simvastatin (E/S) in doses of 10 mg/20 mg (respectively), 10 mg/40 mg, or 10 mg/80 mg; or rosuvastatin (Crestor, AstraZeneca) in doses of 10, 20, or 40 mg. All had hypercholesterolemia, defined as an LDL-cholesterol level of 145–249 mg/dL with triglycerides at or below 350 mg/dL.

Among the whole cohort of 2,959 patients, significant reductions in LDL cholesterol from baseline were seen among the E/S group at the usual starting, next highest, and maximum dosing levels. (See chart.)

Across all doses, the difference in LDL-cholesterol reduction between E/S and rosuvastatin was significant for the whole cohort (55.8% vs. 51.6%). Consistent with that, LDL-cholesterol lowering was also greater with E/S among the patients with type 2 diabetes (58.5% vs. 54.2%), nondiabetics with metabolic syndrome (55% vs. 51.8%), and those with neither (55.6% vs. 51%), Dr. Catapano reported.

Overall, 95.3% of the E/S group, compared with 92.1% of the rosuvastatin group, attained the recommended LDL goals of less than 100 mg/dL for the diabetics, 130 mg/dL for the nondiabetics with metabolic syndrome, or 160 mg/dL for the group with neither. A total of 88.2% of the E/S patients versus 81.9% of the rosuvastatin patients achieved an LDL-cholesterol level of less than 100 mg/dL, whereas 45.3% vs. 29.5% reached an LDL-cholesterol level of less than 70 mg/dL. All of these differences were significant, he said.

Reductions in total cholesterol, non-HDL cholesterol, apolipoprotein B, and triglycerides were also significantly greater with E/S, whereas there were no significant differences between the two treatments in HDL cholesterol, or high-sensitivity C-reactive protein.

Both drugs were well tolerated in all patient groups, with similar rates of drug-related adverse events (8.1% with E/S vs. 7.4% with rosuvastatin) and discontinuations because of adverse events (2.2% for both drugs). Proteinuria was higher at baseline in the rosuvastatin group and among those with diabetes, Dr. Catapano noted.

ELSEVIER GLOBAL MEDICAL NEWS

COPENHAGEN — A combination of ezetimibe and simvastatin provides additional lipid-modifying benefits compared with rosuvastatin monotherapy among patients with type 2 diabetes or with metabolic syndrome without diabetes, Dr. Alberico L. Catapano reported at the annual meeting of the European Association for the Study of Diabetes.

“Overall, ezetimibe/simvastatin, a single-tablet, dual-cholesterol inhibitor [Vytorin, Merck], offers an effective and well-tolerated lipid-modifying option for the treatment of hypercholesterolemia in patients with type 2 diabetes and metabolic syndrome,” said Dr. Catapano, of the department of pharmacological sciences at the University of Milan.

In a post-hoc analysis of data from a multicenter, double-blind, randomized, parallel-group, 6-week study sponsored by Merck & Co., 375 patients with type 2 diabetes, 840 with metabolic syndrome but without diabetes, 1,722 with neither condition, and 22 who could not be placed in a category because of missing data were randomized to one of six treatment groups: ezetimibe/simvastatin (E/S) in doses of 10 mg/20 mg (respectively), 10 mg/40 mg, or 10 mg/80 mg; or rosuvastatin (Crestor, AstraZeneca) in doses of 10, 20, or 40 mg. All had hypercholesterolemia, defined as an LDL-cholesterol level of 145–249 mg/dL with triglycerides at or below 350 mg/dL.

Among the whole cohort of 2,959 patients, significant reductions in LDL cholesterol from baseline were seen among the E/S group at the usual starting, next highest, and maximum dosing levels. (See chart.)

Across all doses, the difference in LDL-cholesterol reduction between E/S and rosuvastatin was significant for the whole cohort (55.8% vs. 51.6%). Consistent with that, LDL-cholesterol lowering was also greater with E/S among the patients with type 2 diabetes (58.5% vs. 54.2%), nondiabetics with metabolic syndrome (55% vs. 51.8%), and those with neither (55.6% vs. 51%), Dr. Catapano reported.

Overall, 95.3% of the E/S group, compared with 92.1% of the rosuvastatin group, attained the recommended LDL goals of less than 100 mg/dL for the diabetics, 130 mg/dL for the nondiabetics with metabolic syndrome, or 160 mg/dL for the group with neither. A total of 88.2% of the E/S patients versus 81.9% of the rosuvastatin patients achieved an LDL-cholesterol level of less than 100 mg/dL, whereas 45.3% vs. 29.5% reached an LDL-cholesterol level of less than 70 mg/dL. All of these differences were significant, he said.

Reductions in total cholesterol, non-HDL cholesterol, apolipoprotein B, and triglycerides were also significantly greater with E/S, whereas there were no significant differences between the two treatments in HDL cholesterol, or high-sensitivity C-reactive protein.

Both drugs were well tolerated in all patient groups, with similar rates of drug-related adverse events (8.1% with E/S vs. 7.4% with rosuvastatin) and discontinuations because of adverse events (2.2% for both drugs). Proteinuria was higher at baseline in the rosuvastatin group and among those with diabetes, Dr. Catapano noted.

ELSEVIER GLOBAL MEDICAL NEWS

COPENHAGEN — A combination of ezetimibe and simvastatin provides additional lipid-modifying benefits compared with rosuvastatin monotherapy among patients with type 2 diabetes or with metabolic syndrome without diabetes, Dr. Alberico L. Catapano reported at the annual meeting of the European Association for the Study of Diabetes.

“Overall, ezetimibe/simvastatin, a single-tablet, dual-cholesterol inhibitor [Vytorin, Merck], offers an effective and well-tolerated lipid-modifying option for the treatment of hypercholesterolemia in patients with type 2 diabetes and metabolic syndrome,” said Dr. Catapano, of the department of pharmacological sciences at the University of Milan.

In a post-hoc analysis of data from a multicenter, double-blind, randomized, parallel-group, 6-week study sponsored by Merck & Co., 375 patients with type 2 diabetes, 840 with metabolic syndrome but without diabetes, 1,722 with neither condition, and 22 who could not be placed in a category because of missing data were randomized to one of six treatment groups: ezetimibe/simvastatin (E/S) in doses of 10 mg/20 mg (respectively), 10 mg/40 mg, or 10 mg/80 mg; or rosuvastatin (Crestor, AstraZeneca) in doses of 10, 20, or 40 mg. All had hypercholesterolemia, defined as an LDL-cholesterol level of 145–249 mg/dL with triglycerides at or below 350 mg/dL.

Among the whole cohort of 2,959 patients, significant reductions in LDL cholesterol from baseline were seen among the E/S group at the usual starting, next highest, and maximum dosing levels. (See chart.)

Across all doses, the difference in LDL-cholesterol reduction between E/S and rosuvastatin was significant for the whole cohort (55.8% vs. 51.6%). Consistent with that, LDL-cholesterol lowering was also greater with E/S among the patients with type 2 diabetes (58.5% vs. 54.2%), nondiabetics with metabolic syndrome (55% vs. 51.8%), and those with neither (55.6% vs. 51%), Dr. Catapano reported.

Overall, 95.3% of the E/S group, compared with 92.1% of the rosuvastatin group, attained the recommended LDL goals of less than 100 mg/dL for the diabetics, 130 mg/dL for the nondiabetics with metabolic syndrome, or 160 mg/dL for the group with neither. A total of 88.2% of the E/S patients versus 81.9% of the rosuvastatin patients achieved an LDL-cholesterol level of less than 100 mg/dL, whereas 45.3% vs. 29.5% reached an LDL-cholesterol level of less than 70 mg/dL. All of these differences were significant, he said.

Reductions in total cholesterol, non-HDL cholesterol, apolipoprotein B, and triglycerides were also significantly greater with E/S, whereas there were no significant differences between the two treatments in HDL cholesterol, or high-sensitivity C-reactive protein.

Both drugs were well tolerated in all patient groups, with similar rates of drug-related adverse events (8.1% with E/S vs. 7.4% with rosuvastatin) and discontinuations because of adverse events (2.2% for both drugs). Proteinuria was higher at baseline in the rosuvastatin group and among those with diabetes, Dr. Catapano noted.

ELSEVIER GLOBAL MEDICAL NEWS

COPENHAGEN — Newer-generation sulfonylureas appear to be associated with lower post-MI mortality in diabetic patients than are the older-generation agents, Dr. Henriette Thisted reported at the annual meeting of the European Association for the Study of Diabetes.

Earlier this year, Dr. Thisted and her associates published preliminary findings from a regional Danish hospital database, in which they found a lower rate of MI among patients using gliclazide and glimepiride, compared with those using other sulfonylureas, and a trend toward lower 30-day post-MI mortality among users of gliclazide, compared with users of other sulfonylureas (Am. J. Ther. 2006;13:134–40).

They have now expanded the study nationwide to include 72,913 first-time admissions for MI during 1996–2004 from the Danish National Patient Registry. From a national prescription database, 3,992 patients were identified as sulfonylurea users, including 2,554 taking the “old” sulfonylureas glibenclamide, glipizide, or tolbutamide and 1,438 users of the “new” agents gliclazide or glimepiride.

Not surprisingly, users of older sulfonylureas were older (73.3 vs. 71.6 years) and had a longer duration of diabetes (14.4% vs. 10.6% had been diagnosed for more than 10 years). They also tended to have more comorbidities, said Dr. Thisted of the department of clinical epidemiology at Aarhus (Denmark) University Hospital.

At 30 days following MI, 24.1% of the old sulfonylurea users had died, compared with 17.9% of the new-agent user group. After adjustment for age, sex, socioeconomic status, diabetes duration, comorbidity index, discharge diagnoses, and use of relevant medications, the new sulfonylurea users still had a 23% lower 30-day mortality rate than the old-agent users, Dr. Thisted reported.

This apparent advantage in 30-day mortality with new sulfonylureas was also evident during the entire follow-up period, with a mean of 1.68 years: The adjusted mortality rate ratio was 0.78, or a 22% lower risk of death post MI.

COPENHAGEN — Newer-generation sulfonylureas appear to be associated with lower post-MI mortality in diabetic patients than are the older-generation agents, Dr. Henriette Thisted reported at the annual meeting of the European Association for the Study of Diabetes.

Earlier this year, Dr. Thisted and her associates published preliminary findings from a regional Danish hospital database, in which they found a lower rate of MI among patients using gliclazide and glimepiride, compared with those using other sulfonylureas, and a trend toward lower 30-day post-MI mortality among users of gliclazide, compared with users of other sulfonylureas (Am. J. Ther. 2006;13:134–40).

They have now expanded the study nationwide to include 72,913 first-time admissions for MI during 1996–2004 from the Danish National Patient Registry. From a national prescription database, 3,992 patients were identified as sulfonylurea users, including 2,554 taking the “old” sulfonylureas glibenclamide, glipizide, or tolbutamide and 1,438 users of the “new” agents gliclazide or glimepiride.

Not surprisingly, users of older sulfonylureas were older (73.3 vs. 71.6 years) and had a longer duration of diabetes (14.4% vs. 10.6% had been diagnosed for more than 10 years). They also tended to have more comorbidities, said Dr. Thisted of the department of clinical epidemiology at Aarhus (Denmark) University Hospital.

At 30 days following MI, 24.1% of the old sulfonylurea users had died, compared with 17.9% of the new-agent user group. After adjustment for age, sex, socioeconomic status, diabetes duration, comorbidity index, discharge diagnoses, and use of relevant medications, the new sulfonylurea users still had a 23% lower 30-day mortality rate than the old-agent users, Dr. Thisted reported.

This apparent advantage in 30-day mortality with new sulfonylureas was also evident during the entire follow-up period, with a mean of 1.68 years: The adjusted mortality rate ratio was 0.78, or a 22% lower risk of death post MI.

COPENHAGEN — Newer-generation sulfonylureas appear to be associated with lower post-MI mortality in diabetic patients than are the older-generation agents, Dr. Henriette Thisted reported at the annual meeting of the European Association for the Study of Diabetes.

Earlier this year, Dr. Thisted and her associates published preliminary findings from a regional Danish hospital database, in which they found a lower rate of MI among patients using gliclazide and glimepiride, compared with those using other sulfonylureas, and a trend toward lower 30-day post-MI mortality among users of gliclazide, compared with users of other sulfonylureas (Am. J. Ther. 2006;13:134–40).

They have now expanded the study nationwide to include 72,913 first-time admissions for MI during 1996–2004 from the Danish National Patient Registry. From a national prescription database, 3,992 patients were identified as sulfonylurea users, including 2,554 taking the “old” sulfonylureas glibenclamide, glipizide, or tolbutamide and 1,438 users of the “new” agents gliclazide or glimepiride.

Not surprisingly, users of older sulfonylureas were older (73.3 vs. 71.6 years) and had a longer duration of diabetes (14.4% vs. 10.6% had been diagnosed for more than 10 years). They also tended to have more comorbidities, said Dr. Thisted of the department of clinical epidemiology at Aarhus (Denmark) University Hospital.

At 30 days following MI, 24.1% of the old sulfonylurea users had died, compared with 17.9% of the new-agent user group. After adjustment for age, sex, socioeconomic status, diabetes duration, comorbidity index, discharge diagnoses, and use of relevant medications, the new sulfonylurea users still had a 23% lower 30-day mortality rate than the old-agent users, Dr. Thisted reported.

This apparent advantage in 30-day mortality with new sulfonylureas was also evident during the entire follow-up period, with a mean of 1.68 years: The adjusted mortality rate ratio was 0.78, or a 22% lower risk of death post MI.

ATLANTA — No major safety issues have arisen thus far with the new rotavirus vaccine, Penina Haber said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

In fact, rates of intussusception—the complication that resulted in the 1999 withdrawal from the market of the old rotavirus vaccine (Wyeth-Ayerst's RotaShield)—are actually lower with Merck's Rotateq than would be expected in the general population, said Ms. Haber, an epidemiologist with the CDC's Immunization Safety Office.

The CDC is monitoring Rotateq for gastrointestinal-related adverse events as well as any other unexpected problems via the passive Vaccine Adverse Event Reporting System (VAERS). Should any safety “signals” arise, the active surveillance system known as the Vaccine Safety Datalink (VSD), comprising eight large HMOs (covering 3% of the U.S. population), will be utilized to investigate further.

Indeed, the CDC is now using VAERS and VSD to monitor safety for all new vaccines, with researchers from the CDC and the Food and Drug Administration reviewing all reports sent to VAERS on a daily basis, Robert L. Davis, director of the CDC's Immunization Safety Office, said during a joint presentation with Ms. Haber on vaccine safety.

From March 1, 2006, through Oct. 23, 2006, VAERS received a total of 189 adverse event reports following receipt of Rotateq, from a background of 1,786,476 doses distributed as of Sept. 30, 2006. Of the 189 reports, 48% were associated with receipt of Rotateq alone, while the rest were in combination with other vaccines. Children aged 2–3 months accounted for 57% of the reports, while 5% were for children under 2 months of age. (The vaccine is recommended at ages 2, 4, and 6 months). Fifty-five percent of reports were of events occurring within 2 days of vaccination, while another 5% occurred within 7 days.

Among the most frequent adverse events following receipt of Rotateq in children up to 12 months of age were diarrhea (24% vs. 3% following all other vaccines), vomiting (22% vs. 5%), GI hemorrhage (7% vs. 0%), and melena (6% vs. 1%). A total of 30 (16%) of the reports were of serious events, including 6 cases of intussusception. Four occurred after dose 1 and two after the second dose, at an interval of 2–32 days following vaccination.

Calculating from the VSD background intussusception rate of 2.98 per 10,000 person-years, expected cases within a 21-day period would number 30.7. In contrast, just 4 cases were observed within 21 days of Rotateq receipt. Assuming 47% underreporting (Am. J. Epidemiol. 2001;154:1006–12), the number of intussusceptions linked with Rotateq would still be significantly lower than expected, Ms. Haber said.

ATLANTA — No major safety issues have arisen thus far with the new rotavirus vaccine, Penina Haber said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

In fact, rates of intussusception—the complication that resulted in the 1999 withdrawal from the market of the old rotavirus vaccine (Wyeth-Ayerst's RotaShield)—are actually lower with Merck's Rotateq than would be expected in the general population, said Ms. Haber, an epidemiologist with the CDC's Immunization Safety Office.

The CDC is monitoring Rotateq for gastrointestinal-related adverse events as well as any other unexpected problems via the passive Vaccine Adverse Event Reporting System (VAERS). Should any safety “signals” arise, the active surveillance system known as the Vaccine Safety Datalink (VSD), comprising eight large HMOs (covering 3% of the U.S. population), will be utilized to investigate further.

Indeed, the CDC is now using VAERS and VSD to monitor safety for all new vaccines, with researchers from the CDC and the Food and Drug Administration reviewing all reports sent to VAERS on a daily basis, Robert L. Davis, director of the CDC's Immunization Safety Office, said during a joint presentation with Ms. Haber on vaccine safety.

From March 1, 2006, through Oct. 23, 2006, VAERS received a total of 189 adverse event reports following receipt of Rotateq, from a background of 1,786,476 doses distributed as of Sept. 30, 2006. Of the 189 reports, 48% were associated with receipt of Rotateq alone, while the rest were in combination with other vaccines. Children aged 2–3 months accounted for 57% of the reports, while 5% were for children under 2 months of age. (The vaccine is recommended at ages 2, 4, and 6 months). Fifty-five percent of reports were of events occurring within 2 days of vaccination, while another 5% occurred within 7 days.

Among the most frequent adverse events following receipt of Rotateq in children up to 12 months of age were diarrhea (24% vs. 3% following all other vaccines), vomiting (22% vs. 5%), GI hemorrhage (7% vs. 0%), and melena (6% vs. 1%). A total of 30 (16%) of the reports were of serious events, including 6 cases of intussusception. Four occurred after dose 1 and two after the second dose, at an interval of 2–32 days following vaccination.

Calculating from the VSD background intussusception rate of 2.98 per 10,000 person-years, expected cases within a 21-day period would number 30.7. In contrast, just 4 cases were observed within 21 days of Rotateq receipt. Assuming 47% underreporting (Am. J. Epidemiol. 2001;154:1006–12), the number of intussusceptions linked with Rotateq would still be significantly lower than expected, Ms. Haber said.

ATLANTA — No major safety issues have arisen thus far with the new rotavirus vaccine, Penina Haber said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

In fact, rates of intussusception—the complication that resulted in the 1999 withdrawal from the market of the old rotavirus vaccine (Wyeth-Ayerst's RotaShield)—are actually lower with Merck's Rotateq than would be expected in the general population, said Ms. Haber, an epidemiologist with the CDC's Immunization Safety Office.

The CDC is monitoring Rotateq for gastrointestinal-related adverse events as well as any other unexpected problems via the passive Vaccine Adverse Event Reporting System (VAERS). Should any safety “signals” arise, the active surveillance system known as the Vaccine Safety Datalink (VSD), comprising eight large HMOs (covering 3% of the U.S. population), will be utilized to investigate further.

Indeed, the CDC is now using VAERS and VSD to monitor safety for all new vaccines, with researchers from the CDC and the Food and Drug Administration reviewing all reports sent to VAERS on a daily basis, Robert L. Davis, director of the CDC's Immunization Safety Office, said during a joint presentation with Ms. Haber on vaccine safety.

From March 1, 2006, through Oct. 23, 2006, VAERS received a total of 189 adverse event reports following receipt of Rotateq, from a background of 1,786,476 doses distributed as of Sept. 30, 2006. Of the 189 reports, 48% were associated with receipt of Rotateq alone, while the rest were in combination with other vaccines. Children aged 2–3 months accounted for 57% of the reports, while 5% were for children under 2 months of age. (The vaccine is recommended at ages 2, 4, and 6 months). Fifty-five percent of reports were of events occurring within 2 days of vaccination, while another 5% occurred within 7 days.

Among the most frequent adverse events following receipt of Rotateq in children up to 12 months of age were diarrhea (24% vs. 3% following all other vaccines), vomiting (22% vs. 5%), GI hemorrhage (7% vs. 0%), and melena (6% vs. 1%). A total of 30 (16%) of the reports were of serious events, including 6 cases of intussusception. Four occurred after dose 1 and two after the second dose, at an interval of 2–32 days following vaccination.

Calculating from the VSD background intussusception rate of 2.98 per 10,000 person-years, expected cases within a 21-day period would number 30.7. In contrast, just 4 cases were observed within 21 days of Rotateq receipt. Assuming 47% underreporting (Am. J. Epidemiol. 2001;154:1006–12), the number of intussusceptions linked with Rotateq would still be significantly lower than expected, Ms. Haber said.

ATLANTA — Get ready to clear a bit more wall space in your office come January. Beginning in 2007–2008, the annual harmonized childhood and adolescent immunization schedule will be split in two, with a chart on one page devoted to children aged 0–6 years and another on a separate page for those aged 7–18.

The catch-up schedule also will be divided by age in the same way, but those two charts will appear on one page.

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention voted unanimously for the new format at its fall meeting. The American Academy of Pediatrics Committee on Infectious Disease supports it as well, AAP liaison Dr. Joseph A. Bocchini Jr. said in an interview.

“I think this is a significant improvement. As the vaccine schedule has become more complicated, the single table has become more difficult to interpret. Splitting it this way really improves the opportunity for the practitioner to determine what immunizations a patient needs at a particular age,” said Dr. Bocchini, professor of pediatrics and chief of pediatric infectious disease at Louisiana State University, Shreveport.

The decisions about whether and how to split the schedule were based in part on results from focus group sessions involving 69 immunization providers, including pediatricians, family physicians, nurse practitioners, physician assistants, registered nurses, and licensed practical nurses. They came from private and public settings, and from urban, suburban, and rural areas. “We wanted to capture the real world out there,” said Sarah J. Clark, associate director for research at the Child Health Evaluation and Research Unit at the University of Michigan in Ann Arbor, which conducted the focus group.

Overall, there was a general preference for two schedules rather than one. The group disagreed, however, on where to make the split. The majority who chose ages 0–6 and 7–18 did so primarily because it places the focus on preparing children for entering kindergarten or first grade.

However, some participants wanted the split at 0–10 years and 11–18 years, noting that if a clinician were only going to post one page, the younger age range chart would contain more information. And, noted Dr. Amy B. Middleman, the liaison to ACIP for the Society for Adolescent Medicine, “Clearly this makes the most sense and is the most visually appealing product. But I think we should consider a chart just for adolescents.”

On the other hand, Dr. Bocchini pointed out, “I think this is a reasonable compromise. There are a number of things that need to be done before a child enters school, and so a break at age 6 … fits very well.”

The format of the catch-up chart proved to be a bit problematic for the focus group as well, primarily because of the confusion between the two different diphtheria-tetanus-acellular pertussis vaccines (DTaP for infants and toddlers/Tdap for adolescents and adults). “At first glance, many providers liked the one-table version. Then they tried to figure out what to do with DTaP/Tdap, and couldn't do it. At that point, almost everyone preferred the two-table format,” Ms. Clark said.

ATLANTA — Get ready to clear a bit more wall space in your office come January. Beginning in 2007–2008, the annual harmonized childhood and adolescent immunization schedule will be split in two, with a chart on one page devoted to children aged 0–6 years and another on a separate page for those aged 7–18.

The catch-up schedule also will be divided by age in the same way, but those two charts will appear on one page.

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention voted unanimously for the new format at its fall meeting. The American Academy of Pediatrics Committee on Infectious Disease supports it as well, AAP liaison Dr. Joseph A. Bocchini Jr. said in an interview.

“I think this is a significant improvement. As the vaccine schedule has become more complicated, the single table has become more difficult to interpret. Splitting it this way really improves the opportunity for the practitioner to determine what immunizations a patient needs at a particular age,” said Dr. Bocchini, professor of pediatrics and chief of pediatric infectious disease at Louisiana State University, Shreveport.

The decisions about whether and how to split the schedule were based in part on results from focus group sessions involving 69 immunization providers, including pediatricians, family physicians, nurse practitioners, physician assistants, registered nurses, and licensed practical nurses. They came from private and public settings, and from urban, suburban, and rural areas. “We wanted to capture the real world out there,” said Sarah J. Clark, associate director for research at the Child Health Evaluation and Research Unit at the University of Michigan in Ann Arbor, which conducted the focus group.

Overall, there was a general preference for two schedules rather than one. The group disagreed, however, on where to make the split. The majority who chose ages 0–6 and 7–18 did so primarily because it places the focus on preparing children for entering kindergarten or first grade.

However, some participants wanted the split at 0–10 years and 11–18 years, noting that if a clinician were only going to post one page, the younger age range chart would contain more information. And, noted Dr. Amy B. Middleman, the liaison to ACIP for the Society for Adolescent Medicine, “Clearly this makes the most sense and is the most visually appealing product. But I think we should consider a chart just for adolescents.”

On the other hand, Dr. Bocchini pointed out, “I think this is a reasonable compromise. There are a number of things that need to be done before a child enters school, and so a break at age 6 … fits very well.”

The format of the catch-up chart proved to be a bit problematic for the focus group as well, primarily because of the confusion between the two different diphtheria-tetanus-acellular pertussis vaccines (DTaP for infants and toddlers/Tdap for adolescents and adults). “At first glance, many providers liked the one-table version. Then they tried to figure out what to do with DTaP/Tdap, and couldn't do it. At that point, almost everyone preferred the two-table format,” Ms. Clark said.

ATLANTA — Get ready to clear a bit more wall space in your office come January. Beginning in 2007–2008, the annual harmonized childhood and adolescent immunization schedule will be split in two, with a chart on one page devoted to children aged 0–6 years and another on a separate page for those aged 7–18.

The catch-up schedule also will be divided by age in the same way, but those two charts will appear on one page.

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention voted unanimously for the new format at its fall meeting. The American Academy of Pediatrics Committee on Infectious Disease supports it as well, AAP liaison Dr. Joseph A. Bocchini Jr. said in an interview.

“I think this is a significant improvement. As the vaccine schedule has become more complicated, the single table has become more difficult to interpret. Splitting it this way really improves the opportunity for the practitioner to determine what immunizations a patient needs at a particular age,” said Dr. Bocchini, professor of pediatrics and chief of pediatric infectious disease at Louisiana State University, Shreveport.

The decisions about whether and how to split the schedule were based in part on results from focus group sessions involving 69 immunization providers, including pediatricians, family physicians, nurse practitioners, physician assistants, registered nurses, and licensed practical nurses. They came from private and public settings, and from urban, suburban, and rural areas. “We wanted to capture the real world out there,” said Sarah J. Clark, associate director for research at the Child Health Evaluation and Research Unit at the University of Michigan in Ann Arbor, which conducted the focus group.

Overall, there was a general preference for two schedules rather than one. The group disagreed, however, on where to make the split. The majority who chose ages 0–6 and 7–18 did so primarily because it places the focus on preparing children for entering kindergarten or first grade.

However, some participants wanted the split at 0–10 years and 11–18 years, noting that if a clinician were only going to post one page, the younger age range chart would contain more information. And, noted Dr. Amy B. Middleman, the liaison to ACIP for the Society for Adolescent Medicine, “Clearly this makes the most sense and is the most visually appealing product. But I think we should consider a chart just for adolescents.”

On the other hand, Dr. Bocchini pointed out, “I think this is a reasonable compromise. There are a number of things that need to be done before a child enters school, and so a break at age 6 … fits very well.”

The format of the catch-up chart proved to be a bit problematic for the focus group as well, primarily because of the confusion between the two different diphtheria-tetanus-acellular pertussis vaccines (DTaP for infants and toddlers/Tdap for adolescents and adults). “At first glance, many providers liked the one-table version. Then they tried to figure out what to do with DTaP/Tdap, and couldn't do it. At that point, almost everyone preferred the two-table format,” Ms. Clark said.

Sitagliptin phosphate, an agent in the new class known as dipeptidyl peptidase-4 inhibitors, has been approved by the Food and Drug Administration for use as monotherapy or in combination with metformin or a thiazolidinedione.

The DPP-IV inhibitors work by blocking the enzyme that breaks down the two incretin hormones glucagonlike peptide-1 and glucose-dependent insulinotropic peptide, which help regulate glucose metabolism via increased insulin release, suppressed glucagon release, and delayed gastric emptying.

Manufactured by Merck & Co. under the name Januvia, sitagliptin is a once-daily oral agent that will cost $4.86 per tablet. Another DPP-IV inhibitor, Novartis' vildagliptin (Galvus), is expected to be approved by the end of the year.

Data from three randomized, placebo-controlled phase III studies on sitagliptin were presented in September at the annual meeting of the European Association for the Study of Diabetes, in Copenhagen.

Dr. Pablo Aschner, of the Colombian Diabetes Association, Bogota, presented the findings from the 24-week monotherapy trial, in which 741 patients aged 18–75 years were randomized to daily placebo, 100 mg sitagliptin or 200 mg sitagliptin. At baseline, the entire study population had a mean hemoglobin A_1c of 8.0% and fasting plasma glucose of 9.6 mmol/L. At 24 weeks, the two sitagliptin doses produced statistically significant, placebo-adjusted reductions in A_1c of 0.79% with 100 mg and 0.94% with 200 mg, and in fasting plasma glucose of 1.0 mmol/L and 1.2 mmol/L, respectively.

Reductions in A_1c were greater among the patients with higher baseline A_1c levels, Dr. Aschner reported.

The proportion of patients achieving an A_1c level of less than 7.0% were 41% with 100 mg sitagliptin and 45% with 200 mg, while 18% and 20%, respectively, reached an A_1c below 6.5%.

Placebo-adjusted reductions in 2-hour postmeal glucose values were 2.6 mmol/L with 100 mg and 3.0 mmol/L with 200 mg sitagliptin. Improvements with sitagliptin relative to placebo also were seen in postmeal insulin and C-peptide concentrations, as well as in homeostasis model assessment-β and the ratios of insulin to glucose areas under the curve and proinsulin/insulin, suggesting improved β-cell function, he said.

A second study, presented by Dr. Avraham Karasik, of Chaim Sheba Medical Centre, Tel Hashomer, Israel, randomized 701 type 2 diabetic patients who were inadequately controlled on 1,500 mg/day or more of metformin alone to receive either placebo or 100 mg/day of sitagliptin for 24 weeks. The addition of sitagliptin to ongoing metformin therapy resulted in a significant mean placebo-subtracted reduction from baseline in hemoglobin A_1c of 0.65%, in fasting glucose (1.4 mmol/L), and in 2-hour postprandial glucose (2.8 mmol/L).

The proportions achieving a hemoglobin A_1c value of less than 7% were 47% with sitagliptin plus metformin, compared with just 18% of those receiving placebo with metformin, while 17% and 5%, respectively, reached an A_1c level below 6.5%, Dr. Karasik reported.

The addition of sitagliptin to metformin had no effect on body weight, nor did it increase the risk for hypoglycemia or gastrointestinal adverse events, compared with placebo, he said.

Dr. Julio Rosenstock, of the Dallas Diabetes and Endocrine Center and the University of Texas Southwestern Medical Center, Dallas, reported the findings of a third study in which 353 patients who had hemoglobin A_1c values between 7% and 10% while taking 30 or 45 mg/day of pioglitazone were randomized to receive the addition of placebo or 100 mg/day of sitagliptin. At 24 weeks, mean A_1c was 7.2% with sitagliptin, compared with 7.8% with placebo, a significant difference. The proportions achieving an A_1c level of less than 7% were 45% vs. 23%, while 24% vs. 5%, respectively, reached the A_1c targets of less than 6.5%.

There was no increase in hypoglycemia with sitagliptin, compared with placebo. The sitagliptin group reported a slightly higher incidence of abdominal pain (3.4% vs. 0), but there were no significant differences in other gastrointestinal adverse events. Mean body weight change was not different between sitagliptin and placebo when added to pioglitazone, Dr. Rosenstock reported.

Sitagliptin phosphate, an agent in the new class known as dipeptidyl peptidase-4 inhibitors, has been approved by the Food and Drug Administration for use as monotherapy or in combination with metformin or a thiazolidinedione.

The DPP-IV inhibitors work by blocking the enzyme that breaks down the two incretin hormones glucagonlike peptide-1 and glucose-dependent insulinotropic peptide, which help regulate glucose metabolism via increased insulin release, suppressed glucagon release, and delayed gastric emptying.

Manufactured by Merck & Co. under the name Januvia, sitagliptin is a once-daily oral agent that will cost $4.86 per tablet. Another DPP-IV inhibitor, Novartis' vildagliptin (Galvus), is expected to be approved by the end of the year.

Data from three randomized, placebo-controlled phase III studies on sitagliptin were presented in September at the annual meeting of the European Association for the Study of Diabetes, in Copenhagen.

Dr. Pablo Aschner, of the Colombian Diabetes Association, Bogota, presented the findings from the 24-week monotherapy trial, in which 741 patients aged 18–75 years were randomized to daily placebo, 100 mg sitagliptin or 200 mg sitagliptin. At baseline, the entire study population had a mean hemoglobin A_1c of 8.0% and fasting plasma glucose of 9.6 mmol/L. At 24 weeks, the two sitagliptin doses produced statistically significant, placebo-adjusted reductions in A_1c of 0.79% with 100 mg and 0.94% with 200 mg, and in fasting plasma glucose of 1.0 mmol/L and 1.2 mmol/L, respectively.

Reductions in A_1c were greater among the patients with higher baseline A_1c levels, Dr. Aschner reported.

The proportion of patients achieving an A_1c level of less than 7.0% were 41% with 100 mg sitagliptin and 45% with 200 mg, while 18% and 20%, respectively, reached an A_1c below 6.5%.

Placebo-adjusted reductions in 2-hour postmeal glucose values were 2.6 mmol/L with 100 mg and 3.0 mmol/L with 200 mg sitagliptin. Improvements with sitagliptin relative to placebo also were seen in postmeal insulin and C-peptide concentrations, as well as in homeostasis model assessment-β and the ratios of insulin to glucose areas under the curve and proinsulin/insulin, suggesting improved β-cell function, he said.

A second study, presented by Dr. Avraham Karasik, of Chaim Sheba Medical Centre, Tel Hashomer, Israel, randomized 701 type 2 diabetic patients who were inadequately controlled on 1,500 mg/day or more of metformin alone to receive either placebo or 100 mg/day of sitagliptin for 24 weeks. The addition of sitagliptin to ongoing metformin therapy resulted in a significant mean placebo-subtracted reduction from baseline in hemoglobin A_1c of 0.65%, in fasting glucose (1.4 mmol/L), and in 2-hour postprandial glucose (2.8 mmol/L).

The proportions achieving a hemoglobin A_1c value of less than 7% were 47% with sitagliptin plus metformin, compared with just 18% of those receiving placebo with metformin, while 17% and 5%, respectively, reached an A_1c level below 6.5%, Dr. Karasik reported.

The addition of sitagliptin to metformin had no effect on body weight, nor did it increase the risk for hypoglycemia or gastrointestinal adverse events, compared with placebo, he said.

Dr. Julio Rosenstock, of the Dallas Diabetes and Endocrine Center and the University of Texas Southwestern Medical Center, Dallas, reported the findings of a third study in which 353 patients who had hemoglobin A_1c values between 7% and 10% while taking 30 or 45 mg/day of pioglitazone were randomized to receive the addition of placebo or 100 mg/day of sitagliptin. At 24 weeks, mean A_1c was 7.2% with sitagliptin, compared with 7.8% with placebo, a significant difference. The proportions achieving an A_1c level of less than 7% were 45% vs. 23%, while 24% vs. 5%, respectively, reached the A_1c targets of less than 6.5%.

There was no increase in hypoglycemia with sitagliptin, compared with placebo. The sitagliptin group reported a slightly higher incidence of abdominal pain (3.4% vs. 0), but there were no significant differences in other gastrointestinal adverse events. Mean body weight change was not different between sitagliptin and placebo when added to pioglitazone, Dr. Rosenstock reported.

Sitagliptin phosphate, an agent in the new class known as dipeptidyl peptidase-4 inhibitors, has been approved by the Food and Drug Administration for use as monotherapy or in combination with metformin or a thiazolidinedione.

The DPP-IV inhibitors work by blocking the enzyme that breaks down the two incretin hormones glucagonlike peptide-1 and glucose-dependent insulinotropic peptide, which help regulate glucose metabolism via increased insulin release, suppressed glucagon release, and delayed gastric emptying.

Manufactured by Merck & Co. under the name Januvia, sitagliptin is a once-daily oral agent that will cost $4.86 per tablet. Another DPP-IV inhibitor, Novartis' vildagliptin (Galvus), is expected to be approved by the end of the year.

Data from three randomized, placebo-controlled phase III studies on sitagliptin were presented in September at the annual meeting of the European Association for the Study of Diabetes, in Copenhagen.

Dr. Pablo Aschner, of the Colombian Diabetes Association, Bogota, presented the findings from the 24-week monotherapy trial, in which 741 patients aged 18–75 years were randomized to daily placebo, 100 mg sitagliptin or 200 mg sitagliptin. At baseline, the entire study population had a mean hemoglobin A_1c of 8.0% and fasting plasma glucose of 9.6 mmol/L. At 24 weeks, the two sitagliptin doses produced statistically significant, placebo-adjusted reductions in A_1c of 0.79% with 100 mg and 0.94% with 200 mg, and in fasting plasma glucose of 1.0 mmol/L and 1.2 mmol/L, respectively.

Reductions in A_1c were greater among the patients with higher baseline A_1c levels, Dr. Aschner reported.

The proportion of patients achieving an A_1c level of less than 7.0% were 41% with 100 mg sitagliptin and 45% with 200 mg, while 18% and 20%, respectively, reached an A_1c below 6.5%.

Placebo-adjusted reductions in 2-hour postmeal glucose values were 2.6 mmol/L with 100 mg and 3.0 mmol/L with 200 mg sitagliptin. Improvements with sitagliptin relative to placebo also were seen in postmeal insulin and C-peptide concentrations, as well as in homeostasis model assessment-β and the ratios of insulin to glucose areas under the curve and proinsulin/insulin, suggesting improved β-cell function, he said.

A second study, presented by Dr. Avraham Karasik, of Chaim Sheba Medical Centre, Tel Hashomer, Israel, randomized 701 type 2 diabetic patients who were inadequately controlled on 1,500 mg/day or more of metformin alone to receive either placebo or 100 mg/day of sitagliptin for 24 weeks. The addition of sitagliptin to ongoing metformin therapy resulted in a significant mean placebo-subtracted reduction from baseline in hemoglobin A_1c of 0.65%, in fasting glucose (1.4 mmol/L), and in 2-hour postprandial glucose (2.8 mmol/L).

The proportions achieving a hemoglobin A_1c value of less than 7% were 47% with sitagliptin plus metformin, compared with just 18% of those receiving placebo with metformin, while 17% and 5%, respectively, reached an A_1c level below 6.5%, Dr. Karasik reported.

The addition of sitagliptin to metformin had no effect on body weight, nor did it increase the risk for hypoglycemia or gastrointestinal adverse events, compared with placebo, he said.

Dr. Julio Rosenstock, of the Dallas Diabetes and Endocrine Center and the University of Texas Southwestern Medical Center, Dallas, reported the findings of a third study in which 353 patients who had hemoglobin A_1c values between 7% and 10% while taking 30 or 45 mg/day of pioglitazone were randomized to receive the addition of placebo or 100 mg/day of sitagliptin. At 24 weeks, mean A_1c was 7.2% with sitagliptin, compared with 7.8% with placebo, a significant difference. The proportions achieving an A_1c level of less than 7% were 45% vs. 23%, while 24% vs. 5%, respectively, reached the A_1c targets of less than 6.5%.

There was no increase in hypoglycemia with sitagliptin, compared with placebo. The sitagliptin group reported a slightly higher incidence of abdominal pain (3.4% vs. 0), but there were no significant differences in other gastrointestinal adverse events. Mean body weight change was not different between sitagliptin and placebo when added to pioglitazone, Dr. Rosenstock reported.

COPENHAGEN — A combination of ezetimibe and simvastatin provides additional lipid-modifying benefits, compared with rosuvastatin monotherapy in patients with type 2 diabetes or with metabolic syndrome without diabetes, Dr. Alberico L. Catapano said at the annual meeting of the European Association for the Study of Diabetes.

“Overall, ezetimibe/simvastatin, a single-tablet, dual-cholesterol inhibitor, offers an effective and well-tolerated lipid-modifying option for the treatment of hypercholesterolemia in patients with type 2 diabetes and metabolic syndrome,” said Dr. Catapano, of the department of pharmacological sciences at the University of Milan.

In a post hoc analysis of data from a multicenter, double-blind, randomized, parallel-group, 6-week study sponsored by Merck & Co., 375 patients with type 2 diabetes, 840 with metabolic syndrome but without diabetes, 1,722 with neither condition, and 22 who could not be placed in a category because of missing data were randomized to one of six treatment groups: ezetimibe/simvastatin (E/S) in doses of 10 mg/20 mg (respectively), 10 mg/40 mg, or 10 mg/80 mg; or rosuvastatin (R) in doses of 10, 20, or 40 mg. All had hypercholesterolemia, defined as an LDL cholesterol level of 145–249 mg/dL (3.7–6.4 mmol/L) with triglycerides at or below 350 mg/dL (4 mmol/L).

Among the cohort of 2,959 patients, significant reductions in LDL cholesterol from baseline were seen among the E/S group at the usual starting, next highest, and maximum dosing levels. (See chart.)

Across all doses, the difference in LDL-cholesterol reduction between E/S and R was significant for the whole cohort (55.8% vs. 51.6%). LDL-cholesterol lowering was also greater with E/S in patients with type 2 diabetes (58.5% vs. 54.2%), nondiabetics with metabolic syndrome (55% vs. 51.8%), and those with neither (55.6% vs. 51%).

Overall, 95.3% of the E/S group, compared with 92.1% of the R group, attained the LDL cholesterol goals of less than 100 mg/dL (2.6 mmol/L) for the diabetics, 130 mg/dL (3.4 mmol/L) for the nondiabetics with metabolic syndrome, or 160 mg/dL (4.1 mmol/L) for the group with neither. A total of 88.2% of the E/S patients vs. 81.9% of the R patients achieved an LDL-cholesterol level of less than 100 mg/dL (2.6 mmol/L), whereas 45.3% vs. 29.5% reached an LDL-cholesterol level of less than 70 mg/dL (1.8 mmol/L). All of these differences were significant, he said. Reductions in total cholesterol, non-HDL cholesterol, apolipoprotein B, and triglycerides were also significantly greater with E/S, whereas there were no significant differences between the two treatments in HDL cholesterol, or high-sensitivity C-reactive protein.

Both drugs were well tolerated, with similar rates of drug-related adverse events (8.1% E/S vs. 7.4% R) and discontinuations because of adverse events (2.2% for both drugs). Proteinuria was higher at baseline in the R group and in those with diabetes.

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COPENHAGEN — A combination of ezetimibe and simvastatin provides additional lipid-modifying benefits, compared with rosuvastatin monotherapy in patients with type 2 diabetes or with metabolic syndrome without diabetes, Dr. Alberico L. Catapano said at the annual meeting of the European Association for the Study of Diabetes.

“Overall, ezetimibe/simvastatin, a single-tablet, dual-cholesterol inhibitor, offers an effective and well-tolerated lipid-modifying option for the treatment of hypercholesterolemia in patients with type 2 diabetes and metabolic syndrome,” said Dr. Catapano, of the department of pharmacological sciences at the University of Milan.

In a post hoc analysis of data from a multicenter, double-blind, randomized, parallel-group, 6-week study sponsored by Merck & Co., 375 patients with type 2 diabetes, 840 with metabolic syndrome but without diabetes, 1,722 with neither condition, and 22 who could not be placed in a category because of missing data were randomized to one of six treatment groups: ezetimibe/simvastatin (E/S) in doses of 10 mg/20 mg (respectively), 10 mg/40 mg, or 10 mg/80 mg; or rosuvastatin (R) in doses of 10, 20, or 40 mg. All had hypercholesterolemia, defined as an LDL cholesterol level of 145–249 mg/dL (3.7–6.4 mmol/L) with triglycerides at or below 350 mg/dL (4 mmol/L).

Among the cohort of 2,959 patients, significant reductions in LDL cholesterol from baseline were seen among the E/S group at the usual starting, next highest, and maximum dosing levels. (See chart.)

Across all doses, the difference in LDL-cholesterol reduction between E/S and R was significant for the whole cohort (55.8% vs. 51.6%). LDL-cholesterol lowering was also greater with E/S in patients with type 2 diabetes (58.5% vs. 54.2%), nondiabetics with metabolic syndrome (55% vs. 51.8%), and those with neither (55.6% vs. 51%).

Overall, 95.3% of the E/S group, compared with 92.1% of the R group, attained the LDL cholesterol goals of less than 100 mg/dL (2.6 mmol/L) for the diabetics, 130 mg/dL (3.4 mmol/L) for the nondiabetics with metabolic syndrome, or 160 mg/dL (4.1 mmol/L) for the group with neither. A total of 88.2% of the E/S patients vs. 81.9% of the R patients achieved an LDL-cholesterol level of less than 100 mg/dL (2.6 mmol/L), whereas 45.3% vs. 29.5% reached an LDL-cholesterol level of less than 70 mg/dL (1.8 mmol/L). All of these differences were significant, he said. Reductions in total cholesterol, non-HDL cholesterol, apolipoprotein B, and triglycerides were also significantly greater with E/S, whereas there were no significant differences between the two treatments in HDL cholesterol, or high-sensitivity C-reactive protein.

Both drugs were well tolerated, with similar rates of drug-related adverse events (8.1% E/S vs. 7.4% R) and discontinuations because of adverse events (2.2% for both drugs). Proteinuria was higher at baseline in the R group and in those with diabetes.

ELSEVIER GLOBAL MEDICAL NEWS

COPENHAGEN — A combination of ezetimibe and simvastatin provides additional lipid-modifying benefits, compared with rosuvastatin monotherapy in patients with type 2 diabetes or with metabolic syndrome without diabetes, Dr. Alberico L. Catapano said at the annual meeting of the European Association for the Study of Diabetes.

“Overall, ezetimibe/simvastatin, a single-tablet, dual-cholesterol inhibitor, offers an effective and well-tolerated lipid-modifying option for the treatment of hypercholesterolemia in patients with type 2 diabetes and metabolic syndrome,” said Dr. Catapano, of the department of pharmacological sciences at the University of Milan.

In a post hoc analysis of data from a multicenter, double-blind, randomized, parallel-group, 6-week study sponsored by Merck & Co., 375 patients with type 2 diabetes, 840 with metabolic syndrome but without diabetes, 1,722 with neither condition, and 22 who could not be placed in a category because of missing data were randomized to one of six treatment groups: ezetimibe/simvastatin (E/S) in doses of 10 mg/20 mg (respectively), 10 mg/40 mg, or 10 mg/80 mg; or rosuvastatin (R) in doses of 10, 20, or 40 mg. All had hypercholesterolemia, defined as an LDL cholesterol level of 145–249 mg/dL (3.7–6.4 mmol/L) with triglycerides at or below 350 mg/dL (4 mmol/L).

Among the cohort of 2,959 patients, significant reductions in LDL cholesterol from baseline were seen among the E/S group at the usual starting, next highest, and maximum dosing levels. (See chart.)

Across all doses, the difference in LDL-cholesterol reduction between E/S and R was significant for the whole cohort (55.8% vs. 51.6%). LDL-cholesterol lowering was also greater with E/S in patients with type 2 diabetes (58.5% vs. 54.2%), nondiabetics with metabolic syndrome (55% vs. 51.8%), and those with neither (55.6% vs. 51%).

Overall, 95.3% of the E/S group, compared with 92.1% of the R group, attained the LDL cholesterol goals of less than 100 mg/dL (2.6 mmol/L) for the diabetics, 130 mg/dL (3.4 mmol/L) for the nondiabetics with metabolic syndrome, or 160 mg/dL (4.1 mmol/L) for the group with neither. A total of 88.2% of the E/S patients vs. 81.9% of the R patients achieved an LDL-cholesterol level of less than 100 mg/dL (2.6 mmol/L), whereas 45.3% vs. 29.5% reached an LDL-cholesterol level of less than 70 mg/dL (1.8 mmol/L). All of these differences were significant, he said. Reductions in total cholesterol, non-HDL cholesterol, apolipoprotein B, and triglycerides were also significantly greater with E/S, whereas there were no significant differences between the two treatments in HDL cholesterol, or high-sensitivity C-reactive protein.

Both drugs were well tolerated, with similar rates of drug-related adverse events (8.1% E/S vs. 7.4% R) and discontinuations because of adverse events (2.2% for both drugs). Proteinuria was higher at baseline in the R group and in those with diabetes.

ELSEVIER GLOBAL MEDICAL NEWS