Mary Ann Moon

Density on mammography accounts for “a substantial proportion of cases of breast cancer, particularly in younger women”—to the extent that 26% of all breast cancers and 50% of all those detected within 1 year of a negative screen result occur in women whose mammograms show extensive breast density.

“The marked increase in the risk of breast cancer associated with extensive mammographic density … is probably due to cancers that were present at the time of screening but were not detected because of masking by dense breast tissue,” researchers reported in the New England Journal of Medicine.

Dr. Norman F. Boyd of the Ontario Cancer Institute, Toronto, and his associates assessed the relationship between mammographic density and the risk of breast cancer developing during follow-up.

The researchers used data from three large case-control studies: the Canadian National Breast Screening Study, the Screening Mammography Program of British Columbia, and the Ontario Breast Screening Program.

A total of 1,112 case-control pairs were followed for up to 8 years after baseline mammography. Mammographic density was determined by two independent methods, and results were similar in all three patient populations.

Women who developed breast cancer showed a higher percentage of dense tissue on baseline mammograms than did those who did not develop breast cancer, Dr. Boyd and his associates said (N. Engl. J. Med. 2007;356:227-36).

Women who had density in 75% or more of the mammogram had a rate of breast cancer that was nearly five times higher (odds ratio 4.7) than that for women who had density in less than 10% of the mammogram.

For the subgroup of women who were found to have cancer within 1 year of a negative screening result, those with density in 75% or more of the mammogram had a breast cancer rate nearly 18 times (odds ratio 17.8) higher than that of women with density in less than 10% of the mammogram.

These results indicate that masking, rather than rapid growth of tumors in dense breast tissue, is the most probable mechanism at work here, the investigators said. Thus, the best estimate of breast cancer incidence tied to mammographic density is “by combining cancers that were detected by screening with those that were diagnosed up to 12 months after a screening examination,” they wrote.

In an editorial comment accompanying this report, Dr. Karla Kerlikowske of the University of California, San Francisco, said that more frequent mammographic screenings probably would not improve cancer detection among women with extensive breast density, “because the tumors are not visible, because the tumors may grow quickly between examinations, or both.”

“The time has come to acknowledge breast density as a major risk factor for breast cancer and to determine, develop, and test the best ways to measure breast density in clinical practice and use this measurement to maximize primary and secondary prevention of breast cancer,” Dr. Kerlikowske commented (N. Engl. J. Med. 2007;356:297-300).

Density on mammography accounts for “a substantial proportion of cases of breast cancer, particularly in younger women”—to the extent that 26% of all breast cancers and 50% of all those detected within 1 year of a negative screen result occur in women whose mammograms show extensive breast density.

“The marked increase in the risk of breast cancer associated with extensive mammographic density … is probably due to cancers that were present at the time of screening but were not detected because of masking by dense breast tissue,” researchers reported in the New England Journal of Medicine.

Dr. Norman F. Boyd of the Ontario Cancer Institute, Toronto, and his associates assessed the relationship between mammographic density and the risk of breast cancer developing during follow-up.

The researchers used data from three large case-control studies: the Canadian National Breast Screening Study, the Screening Mammography Program of British Columbia, and the Ontario Breast Screening Program.

A total of 1,112 case-control pairs were followed for up to 8 years after baseline mammography. Mammographic density was determined by two independent methods, and results were similar in all three patient populations.

Women who developed breast cancer showed a higher percentage of dense tissue on baseline mammograms than did those who did not develop breast cancer, Dr. Boyd and his associates said (N. Engl. J. Med. 2007;356:227-36).

Women who had density in 75% or more of the mammogram had a rate of breast cancer that was nearly five times higher (odds ratio 4.7) than that for women who had density in less than 10% of the mammogram.

For the subgroup of women who were found to have cancer within 1 year of a negative screening result, those with density in 75% or more of the mammogram had a breast cancer rate nearly 18 times (odds ratio 17.8) higher than that of women with density in less than 10% of the mammogram.

These results indicate that masking, rather than rapid growth of tumors in dense breast tissue, is the most probable mechanism at work here, the investigators said. Thus, the best estimate of breast cancer incidence tied to mammographic density is “by combining cancers that were detected by screening with those that were diagnosed up to 12 months after a screening examination,” they wrote.

In an editorial comment accompanying this report, Dr. Karla Kerlikowske of the University of California, San Francisco, said that more frequent mammographic screenings probably would not improve cancer detection among women with extensive breast density, “because the tumors are not visible, because the tumors may grow quickly between examinations, or both.”

“The time has come to acknowledge breast density as a major risk factor for breast cancer and to determine, develop, and test the best ways to measure breast density in clinical practice and use this measurement to maximize primary and secondary prevention of breast cancer,” Dr. Kerlikowske commented (N. Engl. J. Med. 2007;356:297-300).

Density on mammography accounts for “a substantial proportion of cases of breast cancer, particularly in younger women”—to the extent that 26% of all breast cancers and 50% of all those detected within 1 year of a negative screen result occur in women whose mammograms show extensive breast density.

“The marked increase in the risk of breast cancer associated with extensive mammographic density … is probably due to cancers that were present at the time of screening but were not detected because of masking by dense breast tissue,” researchers reported in the New England Journal of Medicine.

Dr. Norman F. Boyd of the Ontario Cancer Institute, Toronto, and his associates assessed the relationship between mammographic density and the risk of breast cancer developing during follow-up.

The researchers used data from three large case-control studies: the Canadian National Breast Screening Study, the Screening Mammography Program of British Columbia, and the Ontario Breast Screening Program.

A total of 1,112 case-control pairs were followed for up to 8 years after baseline mammography. Mammographic density was determined by two independent methods, and results were similar in all three patient populations.

Women who developed breast cancer showed a higher percentage of dense tissue on baseline mammograms than did those who did not develop breast cancer, Dr. Boyd and his associates said (N. Engl. J. Med. 2007;356:227-36).

Women who had density in 75% or more of the mammogram had a rate of breast cancer that was nearly five times higher (odds ratio 4.7) than that for women who had density in less than 10% of the mammogram.

For the subgroup of women who were found to have cancer within 1 year of a negative screening result, those with density in 75% or more of the mammogram had a breast cancer rate nearly 18 times (odds ratio 17.8) higher than that of women with density in less than 10% of the mammogram.

These results indicate that masking, rather than rapid growth of tumors in dense breast tissue, is the most probable mechanism at work here, the investigators said. Thus, the best estimate of breast cancer incidence tied to mammographic density is “by combining cancers that were detected by screening with those that were diagnosed up to 12 months after a screening examination,” they wrote.

In an editorial comment accompanying this report, Dr. Karla Kerlikowske of the University of California, San Francisco, said that more frequent mammographic screenings probably would not improve cancer detection among women with extensive breast density, “because the tumors are not visible, because the tumors may grow quickly between examinations, or both.”

“The time has come to acknowledge breast density as a major risk factor for breast cancer and to determine, develop, and test the best ways to measure breast density in clinical practice and use this measurement to maximize primary and secondary prevention of breast cancer,” Dr. Kerlikowske commented (N. Engl. J. Med. 2007;356:297-300).

Nearly 80% of hospitalized children were treated with drugs not approved for use at their age for any indication in a large U.S. study, reported Dr. Samir S. Shah of Children's Hospital of Philadelphia and associates.

The researchers conducted what they described as the first study of off-label drug use in hospitalized American children because so little is known about the topic. This scarcity of data “can lead to the withholding of potentially beneficial treatments or to administration of potentially harmful treatments,” they said in the Archives of Pediatric and Adolescent Medicine.

“Though off-label drug use also occurs in adults, the problem is substantially greater in children because many drugs have not been tested in any pediatric population for any indication,” they noted. “We still have incomplete knowledge about the safety and efficacy of many medications commonly used to treat children across a range of drug classes and clinical diagnoses.”

Dr. Shah and associates used an administrative database from the Pediatric Health Information System to review drug use in 355,409 children hospitalized in 2004 at 31 tertiary-care pediatric medical centers throughout the country. The patient population was racially and ethnically diverse as well as geographically heterogeneous.

For the purposes of this study, “off-label drug use” referred solely to whether the patient was younger than the Food and Drug Administration-approved age for using the agent, not to FDA-approved indications for use, said Dr. Shah, who is also of the University of Pennsylvania's Center for Clinical Epidemiology and Biostatistics, and associates.

The investigators focused on 90 drugs that were either used frequently or included on an FDA list of medications that are recommended for further study in pediatric patients. At least one of these drugs was used off-label in more than 297,000 patients (79%) during the 1-year study. Off-label use accounted for more than $270 million in expenditures on medications, which was 40% of total drug costs, the investigators said (Arch. Ped. Adolesc. Med. 2007;161:282–90).

When the data were broken down by 24 diagnostic categories such as infectious diseases, traumatic injury, circulatory disorders, GI problems, or respiratory diseases, every category had at least one drug that was used off-label in more than half of patients. Among children undergoing procedures or surgeries, at least one drug was used off-label in over 90%.

Off-label drug use was more common in more severely ill children, in those undergoing surgery, and in those older than 28 days of age, but variables such as patient race, gender, payer, or geographic region showed no correlations with off-label drug use. Concerning the correlation with severity of illness, “We suspect that in many cases drugs are prescribed off-label in children who are already critically ill because either they have failed approved therapy or there are few situation-specific FDA-approved options,” Dr. Shah and associates said.

They added that these findings have shed light on the magnitude of the problem of off-label drug use in children, and should “assist in further prioritizing certain drugs for additional pediatric studies of safety and efficacy.

Nearly 80% of hospitalized children were treated with drugs not approved for use at their age for any indication in a large U.S. study, reported Dr. Samir S. Shah of Children's Hospital of Philadelphia and associates.

The researchers conducted what they described as the first study of off-label drug use in hospitalized American children because so little is known about the topic. This scarcity of data “can lead to the withholding of potentially beneficial treatments or to administration of potentially harmful treatments,” they said in the Archives of Pediatric and Adolescent Medicine.

“Though off-label drug use also occurs in adults, the problem is substantially greater in children because many drugs have not been tested in any pediatric population for any indication,” they noted. “We still have incomplete knowledge about the safety and efficacy of many medications commonly used to treat children across a range of drug classes and clinical diagnoses.”

Dr. Shah and associates used an administrative database from the Pediatric Health Information System to review drug use in 355,409 children hospitalized in 2004 at 31 tertiary-care pediatric medical centers throughout the country. The patient population was racially and ethnically diverse as well as geographically heterogeneous.

For the purposes of this study, “off-label drug use” referred solely to whether the patient was younger than the Food and Drug Administration-approved age for using the agent, not to FDA-approved indications for use, said Dr. Shah, who is also of the University of Pennsylvania's Center for Clinical Epidemiology and Biostatistics, and associates.

The investigators focused on 90 drugs that were either used frequently or included on an FDA list of medications that are recommended for further study in pediatric patients. At least one of these drugs was used off-label in more than 297,000 patients (79%) during the 1-year study. Off-label use accounted for more than $270 million in expenditures on medications, which was 40% of total drug costs, the investigators said (Arch. Ped. Adolesc. Med. 2007;161:282–90).

When the data were broken down by 24 diagnostic categories such as infectious diseases, traumatic injury, circulatory disorders, GI problems, or respiratory diseases, every category had at least one drug that was used off-label in more than half of patients. Among children undergoing procedures or surgeries, at least one drug was used off-label in over 90%.

Off-label drug use was more common in more severely ill children, in those undergoing surgery, and in those older than 28 days of age, but variables such as patient race, gender, payer, or geographic region showed no correlations with off-label drug use. Concerning the correlation with severity of illness, “We suspect that in many cases drugs are prescribed off-label in children who are already critically ill because either they have failed approved therapy or there are few situation-specific FDA-approved options,” Dr. Shah and associates said.

They added that these findings have shed light on the magnitude of the problem of off-label drug use in children, and should “assist in further prioritizing certain drugs for additional pediatric studies of safety and efficacy.

Nearly 80% of hospitalized children were treated with drugs not approved for use at their age for any indication in a large U.S. study, reported Dr. Samir S. Shah of Children's Hospital of Philadelphia and associates.

The researchers conducted what they described as the first study of off-label drug use in hospitalized American children because so little is known about the topic. This scarcity of data “can lead to the withholding of potentially beneficial treatments or to administration of potentially harmful treatments,” they said in the Archives of Pediatric and Adolescent Medicine.

“Though off-label drug use also occurs in adults, the problem is substantially greater in children because many drugs have not been tested in any pediatric population for any indication,” they noted. “We still have incomplete knowledge about the safety and efficacy of many medications commonly used to treat children across a range of drug classes and clinical diagnoses.”

Dr. Shah and associates used an administrative database from the Pediatric Health Information System to review drug use in 355,409 children hospitalized in 2004 at 31 tertiary-care pediatric medical centers throughout the country. The patient population was racially and ethnically diverse as well as geographically heterogeneous.

For the purposes of this study, “off-label drug use” referred solely to whether the patient was younger than the Food and Drug Administration-approved age for using the agent, not to FDA-approved indications for use, said Dr. Shah, who is also of the University of Pennsylvania's Center for Clinical Epidemiology and Biostatistics, and associates.

The investigators focused on 90 drugs that were either used frequently or included on an FDA list of medications that are recommended for further study in pediatric patients. At least one of these drugs was used off-label in more than 297,000 patients (79%) during the 1-year study. Off-label use accounted for more than $270 million in expenditures on medications, which was 40% of total drug costs, the investigators said (Arch. Ped. Adolesc. Med. 2007;161:282–90).

When the data were broken down by 24 diagnostic categories such as infectious diseases, traumatic injury, circulatory disorders, GI problems, or respiratory diseases, every category had at least one drug that was used off-label in more than half of patients. Among children undergoing procedures or surgeries, at least one drug was used off-label in over 90%.

Off-label drug use was more common in more severely ill children, in those undergoing surgery, and in those older than 28 days of age, but variables such as patient race, gender, payer, or geographic region showed no correlations with off-label drug use. Concerning the correlation with severity of illness, “We suspect that in many cases drugs are prescribed off-label in children who are already critically ill because either they have failed approved therapy or there are few situation-specific FDA-approved options,” Dr. Shah and associates said.

They added that these findings have shed light on the magnitude of the problem of off-label drug use in children, and should “assist in further prioritizing certain drugs for additional pediatric studies of safety and efficacy.

The acellular pertussis booster vaccine provides immunity that persists beyond 5 years in adolescents, and it likely will do the same in adults, reported Dr. Kati Edelman of Turku (Finland) University Hospital and her associates.

In what they described as the first long-term study that assessed both cell-mediated and humoral immunity conferred by the pertussis booster, the researchers found that both types of immunity persisted for 5 years or more in subjects who had received the booster at ages 11–13 years.

This indicates that the interval between routine booster immunizations can be extended beyond 5 years, they said (Clin. Infect. Dis. 2007;44:1271–7).

In an editorial comment accompanying this report, Dr. James D. Cherry of the University of California, Los Angeles, wrote that an immunization program of boosters every 10 years for adolescents and adults would curtail the spread of pertussis in the general population, which would in turn spare infants, who are the most vulnerable to the infection.

“It is time for those who care for adults to learn from pediatrics that universal immunization works and, if implemented, would do much to control the spread of pertussis in the United States,” he noted.

There are as many as 3.3 million cases of pertussis in adolescents and adults in the United States every year, most of which are not recognized as pertussis and are misdiagnosed as bronchitis or upper respiratory infection.

“It should also be noted,” wrote Dr. Cherry, “that the rates of reported pertussis are 40- to 160-fold less common than actual illness rates, and that asymptomatic infections are 4–22 times more common than symptomatic infections” in these age groups.

Symptomatic adolescents and adults are the major source of exposure for infants, he noted (Clin. Infect. Dis. 2007;44:1278–9).

In their study, Dr. Edelman and her associates followed 296 subjects aged 15–18 years who had received a pertussis booster 52–74 months previously, then narrowed the group down to 261 who had received the Tdap (Boostrix, GlaxoSmithKline Biologicals) booster.

All had been immunized against pertussis as babies. For comparison, 38 subjects who had not received the booster also were studied.

A total of 79% of the adolescents who received the booster showed persistent cell-mediated immunity to any of the three pertussis antigens.

The duration of humoral immunity was comparable to that achieved with primary pertussis immunization.

All subjects showed detectable filamentous hemagglutinin IgG, 98% had detectable pertactin IgG, and 76% had detectable pertussis toxin IgG.

IgG antibodies declined somewhat over time but remained significantly elevated, compared with prebooster levels.

It was notable that among subjects who lost pertussis toxin antigen IgG, nearly half had retained cell-mediated immunity to pertussis toxin, which may well have continued to protect them against the infection, Dr. Edelman and her associates said.

Both antibody levels and pertussis-specific cell-mediated immunity levels were higher in subjects who received the booster than in controls.

“Our results correspond with those of the Adult Pertussis Trial conducted in the United States in which pertussis antibody persistence was observed for 18 months after booster vaccination of adolescents and adults with a monovalent acellular pertussis vaccine with the same pertussis components and antigen amounts as the vaccine used in the present study,” the researchers added.

GlaxoSmithKline Biologicals provided materials for the study, and two of the researchers have been employed by the company, it was disclosed.

The acellular pertussis booster vaccine provides immunity that persists beyond 5 years in adolescents, and it likely will do the same in adults, reported Dr. Kati Edelman of Turku (Finland) University Hospital and her associates.

In what they described as the first long-term study that assessed both cell-mediated and humoral immunity conferred by the pertussis booster, the researchers found that both types of immunity persisted for 5 years or more in subjects who had received the booster at ages 11–13 years.

This indicates that the interval between routine booster immunizations can be extended beyond 5 years, they said (Clin. Infect. Dis. 2007;44:1271–7).

In an editorial comment accompanying this report, Dr. James D. Cherry of the University of California, Los Angeles, wrote that an immunization program of boosters every 10 years for adolescents and adults would curtail the spread of pertussis in the general population, which would in turn spare infants, who are the most vulnerable to the infection.

“It is time for those who care for adults to learn from pediatrics that universal immunization works and, if implemented, would do much to control the spread of pertussis in the United States,” he noted.

There are as many as 3.3 million cases of pertussis in adolescents and adults in the United States every year, most of which are not recognized as pertussis and are misdiagnosed as bronchitis or upper respiratory infection.

“It should also be noted,” wrote Dr. Cherry, “that the rates of reported pertussis are 40- to 160-fold less common than actual illness rates, and that asymptomatic infections are 4–22 times more common than symptomatic infections” in these age groups.

Symptomatic adolescents and adults are the major source of exposure for infants, he noted (Clin. Infect. Dis. 2007;44:1278–9).

In their study, Dr. Edelman and her associates followed 296 subjects aged 15–18 years who had received a pertussis booster 52–74 months previously, then narrowed the group down to 261 who had received the Tdap (Boostrix, GlaxoSmithKline Biologicals) booster.

All had been immunized against pertussis as babies. For comparison, 38 subjects who had not received the booster also were studied.

A total of 79% of the adolescents who received the booster showed persistent cell-mediated immunity to any of the three pertussis antigens.

The duration of humoral immunity was comparable to that achieved with primary pertussis immunization.

All subjects showed detectable filamentous hemagglutinin IgG, 98% had detectable pertactin IgG, and 76% had detectable pertussis toxin IgG.

IgG antibodies declined somewhat over time but remained significantly elevated, compared with prebooster levels.

It was notable that among subjects who lost pertussis toxin antigen IgG, nearly half had retained cell-mediated immunity to pertussis toxin, which may well have continued to protect them against the infection, Dr. Edelman and her associates said.

Both antibody levels and pertussis-specific cell-mediated immunity levels were higher in subjects who received the booster than in controls.

“Our results correspond with those of the Adult Pertussis Trial conducted in the United States in which pertussis antibody persistence was observed for 18 months after booster vaccination of adolescents and adults with a monovalent acellular pertussis vaccine with the same pertussis components and antigen amounts as the vaccine used in the present study,” the researchers added.

GlaxoSmithKline Biologicals provided materials for the study, and two of the researchers have been employed by the company, it was disclosed.

The acellular pertussis booster vaccine provides immunity that persists beyond 5 years in adolescents, and it likely will do the same in adults, reported Dr. Kati Edelman of Turku (Finland) University Hospital and her associates.

In what they described as the first long-term study that assessed both cell-mediated and humoral immunity conferred by the pertussis booster, the researchers found that both types of immunity persisted for 5 years or more in subjects who had received the booster at ages 11–13 years.

This indicates that the interval between routine booster immunizations can be extended beyond 5 years, they said (Clin. Infect. Dis. 2007;44:1271–7).

In an editorial comment accompanying this report, Dr. James D. Cherry of the University of California, Los Angeles, wrote that an immunization program of boosters every 10 years for adolescents and adults would curtail the spread of pertussis in the general population, which would in turn spare infants, who are the most vulnerable to the infection.

“It is time for those who care for adults to learn from pediatrics that universal immunization works and, if implemented, would do much to control the spread of pertussis in the United States,” he noted.

There are as many as 3.3 million cases of pertussis in adolescents and adults in the United States every year, most of which are not recognized as pertussis and are misdiagnosed as bronchitis or upper respiratory infection.

“It should also be noted,” wrote Dr. Cherry, “that the rates of reported pertussis are 40- to 160-fold less common than actual illness rates, and that asymptomatic infections are 4–22 times more common than symptomatic infections” in these age groups.

Symptomatic adolescents and adults are the major source of exposure for infants, he noted (Clin. Infect. Dis. 2007;44:1278–9).

In their study, Dr. Edelman and her associates followed 296 subjects aged 15–18 years who had received a pertussis booster 52–74 months previously, then narrowed the group down to 261 who had received the Tdap (Boostrix, GlaxoSmithKline Biologicals) booster.

All had been immunized against pertussis as babies. For comparison, 38 subjects who had not received the booster also were studied.

A total of 79% of the adolescents who received the booster showed persistent cell-mediated immunity to any of the three pertussis antigens.

The duration of humoral immunity was comparable to that achieved with primary pertussis immunization.

All subjects showed detectable filamentous hemagglutinin IgG, 98% had detectable pertactin IgG, and 76% had detectable pertussis toxin IgG.

IgG antibodies declined somewhat over time but remained significantly elevated, compared with prebooster levels.

It was notable that among subjects who lost pertussis toxin antigen IgG, nearly half had retained cell-mediated immunity to pertussis toxin, which may well have continued to protect them against the infection, Dr. Edelman and her associates said.

Both antibody levels and pertussis-specific cell-mediated immunity levels were higher in subjects who received the booster than in controls.

“Our results correspond with those of the Adult Pertussis Trial conducted in the United States in which pertussis antibody persistence was observed for 18 months after booster vaccination of adolescents and adults with a monovalent acellular pertussis vaccine with the same pertussis components and antigen amounts as the vaccine used in the present study,” the researchers added.

GlaxoSmithKline Biologicals provided materials for the study, and two of the researchers have been employed by the company, it was disclosed.

The phenomenal success of the PCV7 vaccine in Alaska Native children has been blunted by a dramatic rise in infections with “replacement” pneumococcal organisms—that is, serotypes that weren't covered by the vaccine—investigators reported.

The pneumococcal 7-valent conjugate vaccine (PCV7) has virtually eliminated invasive pneumococcal disease caused by the seven covered serotypes in Alaska Native children, a particularly susceptible group whose rate of the disease had been triple that of the general U.S. population.

It was introduced into the routine childhood vaccine schedule for Alaskan children in 2001.

However, between the periods 2001–2003 and 2004–2006, the rate of non-PCV 7 serotype disease has more than doubled in these children and has increased in Alaska Native adults as well, wrote Dr. Rosalyn J. Singleton of the Centers for Disease Control and Prevention's Arctic Investigations Program, Anchorage, and associates.

In an editorial comment accompanying this report, Dr. Timothy R. Peters and Dr. Katherine A. Poehling said that the experience in this subpopulation of American children may be “an early manifestation of a changing pneumococcal epidemiology that is occurring much more widely.”

“The findings of [Singleton and her associates] reinforce the widely held expert opinion that pneumococcal serotype replacement will ultimately erode PCV7 effectiveness in all vaccinated populations,” Dr. Peters and Dr. Poehling commented.

“Continued serotype replacement may necessitate revision or expansion of protein-conjugate vaccines every 5–10 years, until successful development of a vaccine that provides immunity to all pneumococcal serotypes,” wrote the editorialists, both of Brenner Children's Hospital at Wake Forest University, Winston-Salem, N.C.

Dr. Singleton and her associates assessed vaccination status and rates of invasive pneumococcal disease in Alaska from 1995 through 2006.

Documented vaccine coverage among Alaska Native children was an extremely high 96%.

Rates of invasive pneumococcal disease had decreased dramatically following the introduction of the vaccine, but began rising again during the 2004–2006 period among Alaska Native children and hit a plateau among non-Native children. This effect was the result of a marked decrease in disease caused by covered serotypes and a subsequent marked increase in disease caused by uncovered serotypes.

In particular, the rate of non-PCV 7-type invasive disease rose 130% between 2001–2003 and 2004–2006 among Alaska Native children younger than age 2 years (JAMA 2007;297:1784–92).

The proportion of invasive pneumococcal disease cases in children younger than 5 years who required hospitalization increased from 39% in 1995–2000 to 62% in 2004–2006, the proportion that presented with empyema rose from 2% to 13%, and the proportion that developed both pneumonia and bacteremia increased from 40% to 57%.

The proportion of cases with meningitis did not change over time.

In their editorial comment, Dr. Peters and Dr. Poehling said that this study is the first to demonstrate that pneumococcal serotype replacement has resulted in increased rates of invasive disease in a group of American children (JAMA 2007;297:1825–6).

In this and other studies, one particular serotype that isn't covered by the PCV7 vaccine—19A—has been implicated in a substantial proportion of cases of invasive pneumococcal disease.

A 13-valent pneumococcal conjugate vaccine that includes serotype 19A is currently in phase III clinical trials, Dr. Peters and Dr. Poehling noted.

The phenomenal success of the PCV7 vaccine in Alaska Native children has been blunted by a dramatic rise in infections with “replacement” pneumococcal organisms—that is, serotypes that weren't covered by the vaccine—investigators reported.

The pneumococcal 7-valent conjugate vaccine (PCV7) has virtually eliminated invasive pneumococcal disease caused by the seven covered serotypes in Alaska Native children, a particularly susceptible group whose rate of the disease had been triple that of the general U.S. population.

It was introduced into the routine childhood vaccine schedule for Alaskan children in 2001.

However, between the periods 2001–2003 and 2004–2006, the rate of non-PCV 7 serotype disease has more than doubled in these children and has increased in Alaska Native adults as well, wrote Dr. Rosalyn J. Singleton of the Centers for Disease Control and Prevention's Arctic Investigations Program, Anchorage, and associates.

In an editorial comment accompanying this report, Dr. Timothy R. Peters and Dr. Katherine A. Poehling said that the experience in this subpopulation of American children may be “an early manifestation of a changing pneumococcal epidemiology that is occurring much more widely.”

“The findings of [Singleton and her associates] reinforce the widely held expert opinion that pneumococcal serotype replacement will ultimately erode PCV7 effectiveness in all vaccinated populations,” Dr. Peters and Dr. Poehling commented.

“Continued serotype replacement may necessitate revision or expansion of protein-conjugate vaccines every 5–10 years, until successful development of a vaccine that provides immunity to all pneumococcal serotypes,” wrote the editorialists, both of Brenner Children's Hospital at Wake Forest University, Winston-Salem, N.C.

Dr. Singleton and her associates assessed vaccination status and rates of invasive pneumococcal disease in Alaska from 1995 through 2006.

Documented vaccine coverage among Alaska Native children was an extremely high 96%.

Rates of invasive pneumococcal disease had decreased dramatically following the introduction of the vaccine, but began rising again during the 2004–2006 period among Alaska Native children and hit a plateau among non-Native children. This effect was the result of a marked decrease in disease caused by covered serotypes and a subsequent marked increase in disease caused by uncovered serotypes.

In particular, the rate of non-PCV 7-type invasive disease rose 130% between 2001–2003 and 2004–2006 among Alaska Native children younger than age 2 years (JAMA 2007;297:1784–92).

The proportion of invasive pneumococcal disease cases in children younger than 5 years who required hospitalization increased from 39% in 1995–2000 to 62% in 2004–2006, the proportion that presented with empyema rose from 2% to 13%, and the proportion that developed both pneumonia and bacteremia increased from 40% to 57%.

The proportion of cases with meningitis did not change over time.

In their editorial comment, Dr. Peters and Dr. Poehling said that this study is the first to demonstrate that pneumococcal serotype replacement has resulted in increased rates of invasive disease in a group of American children (JAMA 2007;297:1825–6).

In this and other studies, one particular serotype that isn't covered by the PCV7 vaccine—19A—has been implicated in a substantial proportion of cases of invasive pneumococcal disease.

A 13-valent pneumococcal conjugate vaccine that includes serotype 19A is currently in phase III clinical trials, Dr. Peters and Dr. Poehling noted.

The phenomenal success of the PCV7 vaccine in Alaska Native children has been blunted by a dramatic rise in infections with “replacement” pneumococcal organisms—that is, serotypes that weren't covered by the vaccine—investigators reported.

The pneumococcal 7-valent conjugate vaccine (PCV7) has virtually eliminated invasive pneumococcal disease caused by the seven covered serotypes in Alaska Native children, a particularly susceptible group whose rate of the disease had been triple that of the general U.S. population.

It was introduced into the routine childhood vaccine schedule for Alaskan children in 2001.

However, between the periods 2001–2003 and 2004–2006, the rate of non-PCV 7 serotype disease has more than doubled in these children and has increased in Alaska Native adults as well, wrote Dr. Rosalyn J. Singleton of the Centers for Disease Control and Prevention's Arctic Investigations Program, Anchorage, and associates.

In an editorial comment accompanying this report, Dr. Timothy R. Peters and Dr. Katherine A. Poehling said that the experience in this subpopulation of American children may be “an early manifestation of a changing pneumococcal epidemiology that is occurring much more widely.”

“The findings of [Singleton and her associates] reinforce the widely held expert opinion that pneumococcal serotype replacement will ultimately erode PCV7 effectiveness in all vaccinated populations,” Dr. Peters and Dr. Poehling commented.

“Continued serotype replacement may necessitate revision or expansion of protein-conjugate vaccines every 5–10 years, until successful development of a vaccine that provides immunity to all pneumococcal serotypes,” wrote the editorialists, both of Brenner Children's Hospital at Wake Forest University, Winston-Salem, N.C.

Dr. Singleton and her associates assessed vaccination status and rates of invasive pneumococcal disease in Alaska from 1995 through 2006.

Documented vaccine coverage among Alaska Native children was an extremely high 96%.

Rates of invasive pneumococcal disease had decreased dramatically following the introduction of the vaccine, but began rising again during the 2004–2006 period among Alaska Native children and hit a plateau among non-Native children. This effect was the result of a marked decrease in disease caused by covered serotypes and a subsequent marked increase in disease caused by uncovered serotypes.

In particular, the rate of non-PCV 7-type invasive disease rose 130% between 2001–2003 and 2004–2006 among Alaska Native children younger than age 2 years (JAMA 2007;297:1784–92).

The proportion of invasive pneumococcal disease cases in children younger than 5 years who required hospitalization increased from 39% in 1995–2000 to 62% in 2004–2006, the proportion that presented with empyema rose from 2% to 13%, and the proportion that developed both pneumonia and bacteremia increased from 40% to 57%.

The proportion of cases with meningitis did not change over time.

In their editorial comment, Dr. Peters and Dr. Poehling said that this study is the first to demonstrate that pneumococcal serotype replacement has resulted in increased rates of invasive disease in a group of American children (JAMA 2007;297:1825–6).

In this and other studies, one particular serotype that isn't covered by the PCV7 vaccine—19A—has been implicated in a substantial proportion of cases of invasive pneumococcal disease.

A 13-valent pneumococcal conjugate vaccine that includes serotype 19A is currently in phase III clinical trials, Dr. Peters and Dr. Poehling noted.

Influenza B viruses with partial resistance to neuraminidase inhibitors have emerged during routine antiviral therapy and appear to be transmitted from person to person within communities as well as within families.

That finding emerged from a Japanese study.

So far, the rate of emergence of resistant influenza B viruses appears to be “low but appreciable” at 1.4%, and the mutant viruses appear to be as virulent as wild-type viruses, Dr. Shuji Hatakeyama and associates wrote.

In an editorial comment accompanying this report, Dr. Anne Moscona and Dr. Jennifer McKimm-Breschkin said that until now, the medical community has been somewhat complacent about resistant influenza B because little resistance has been documented, and the few resistant strains that have emerged in animal and in vitro studies appeared to have compromised infectivity and transmissibility. “This has led to the belief that significant transmission is unlikely to occur among humans,” they wrote.

Now the findings of Dr. Hatakeyama and associates make it “strikingly clear” that resistant strains are already circulating among humans and that they induce infection with the same duration of symptoms, level of viral shedding, and clinical outcome as nonresistant strains.

This means “it is no longer possible to be confident that resistant strains will have little effect on epidemic or pandemic influenza,” the editorialists said.

Dr. Hatakeyama of the University of Tokyo and associates tracked patterns of resistance and transmission during an influenza B outbreak in the winter of 2004–2005 that caused a widespread epidemic in Japan, the country with the highest use in the world of neuraminidase inhibitors such as zanamivir and oseltamivir.

Pharyngeal or nasal swabs were obtained before and after antiviral therapy from one sample of 74 infected children and from another sample of 356 children (median age 5 years) and 66 adults (median age 34 years) with influenza B.

Seven subjects (1.7%) had strains with partial resistance to zanamivir, oseltamivir, or both, even though they had never been treated with antivirals. There was evidence that identical strains had been transmitted among family members as well as among members of the same community (JAMA 2007;297:1435–42).

There were no differences in symptoms, clinical course, or viral shedding between subjects with resistant strains of the virus and those with wild-type virus, which indicated that these mutant viruses “do not lose virulence even though they have evolved to a status that is less sensitive to the drug,” they noted.

In their editorial comment, Dr. Moscona of Weill Medical College of Cornell University, New York, and Dr. McKimm-Breschkin of Molecular and Health Technologies, Parkville, Australia, said, “Contrary to what had been hoped until now, some resistant variants are vigorous pathogens.

“The presence of low-level resistance sets the stage for selective pressure for development of high-level resistance,” they noted (JAMA 2007;297:1492–3).

Influenza B viruses with partial resistance to neuraminidase inhibitors have emerged during routine antiviral therapy and appear to be transmitted from person to person within communities as well as within families.

That finding emerged from a Japanese study.

So far, the rate of emergence of resistant influenza B viruses appears to be “low but appreciable” at 1.4%, and the mutant viruses appear to be as virulent as wild-type viruses, Dr. Shuji Hatakeyama and associates wrote.

In an editorial comment accompanying this report, Dr. Anne Moscona and Dr. Jennifer McKimm-Breschkin said that until now, the medical community has been somewhat complacent about resistant influenza B because little resistance has been documented, and the few resistant strains that have emerged in animal and in vitro studies appeared to have compromised infectivity and transmissibility. “This has led to the belief that significant transmission is unlikely to occur among humans,” they wrote.

Now the findings of Dr. Hatakeyama and associates make it “strikingly clear” that resistant strains are already circulating among humans and that they induce infection with the same duration of symptoms, level of viral shedding, and clinical outcome as nonresistant strains.

This means “it is no longer possible to be confident that resistant strains will have little effect on epidemic or pandemic influenza,” the editorialists said.

Dr. Hatakeyama of the University of Tokyo and associates tracked patterns of resistance and transmission during an influenza B outbreak in the winter of 2004–2005 that caused a widespread epidemic in Japan, the country with the highest use in the world of neuraminidase inhibitors such as zanamivir and oseltamivir.

Pharyngeal or nasal swabs were obtained before and after antiviral therapy from one sample of 74 infected children and from another sample of 356 children (median age 5 years) and 66 adults (median age 34 years) with influenza B.

Seven subjects (1.7%) had strains with partial resistance to zanamivir, oseltamivir, or both, even though they had never been treated with antivirals. There was evidence that identical strains had been transmitted among family members as well as among members of the same community (JAMA 2007;297:1435–42).

There were no differences in symptoms, clinical course, or viral shedding between subjects with resistant strains of the virus and those with wild-type virus, which indicated that these mutant viruses “do not lose virulence even though they have evolved to a status that is less sensitive to the drug,” they noted.

In their editorial comment, Dr. Moscona of Weill Medical College of Cornell University, New York, and Dr. McKimm-Breschkin of Molecular and Health Technologies, Parkville, Australia, said, “Contrary to what had been hoped until now, some resistant variants are vigorous pathogens.

“The presence of low-level resistance sets the stage for selective pressure for development of high-level resistance,” they noted (JAMA 2007;297:1492–3).

Influenza B viruses with partial resistance to neuraminidase inhibitors have emerged during routine antiviral therapy and appear to be transmitted from person to person within communities as well as within families.

That finding emerged from a Japanese study.

So far, the rate of emergence of resistant influenza B viruses appears to be “low but appreciable” at 1.4%, and the mutant viruses appear to be as virulent as wild-type viruses, Dr. Shuji Hatakeyama and associates wrote.

In an editorial comment accompanying this report, Dr. Anne Moscona and Dr. Jennifer McKimm-Breschkin said that until now, the medical community has been somewhat complacent about resistant influenza B because little resistance has been documented, and the few resistant strains that have emerged in animal and in vitro studies appeared to have compromised infectivity and transmissibility. “This has led to the belief that significant transmission is unlikely to occur among humans,” they wrote.

Now the findings of Dr. Hatakeyama and associates make it “strikingly clear” that resistant strains are already circulating among humans and that they induce infection with the same duration of symptoms, level of viral shedding, and clinical outcome as nonresistant strains.

This means “it is no longer possible to be confident that resistant strains will have little effect on epidemic or pandemic influenza,” the editorialists said.

Dr. Hatakeyama of the University of Tokyo and associates tracked patterns of resistance and transmission during an influenza B outbreak in the winter of 2004–2005 that caused a widespread epidemic in Japan, the country with the highest use in the world of neuraminidase inhibitors such as zanamivir and oseltamivir.

Pharyngeal or nasal swabs were obtained before and after antiviral therapy from one sample of 74 infected children and from another sample of 356 children (median age 5 years) and 66 adults (median age 34 years) with influenza B.

Seven subjects (1.7%) had strains with partial resistance to zanamivir, oseltamivir, or both, even though they had never been treated with antivirals. There was evidence that identical strains had been transmitted among family members as well as among members of the same community (JAMA 2007;297:1435–42).

There were no differences in symptoms, clinical course, or viral shedding between subjects with resistant strains of the virus and those with wild-type virus, which indicated that these mutant viruses “do not lose virulence even though they have evolved to a status that is less sensitive to the drug,” they noted.

In their editorial comment, Dr. Moscona of Weill Medical College of Cornell University, New York, and Dr. McKimm-Breschkin of Molecular and Health Technologies, Parkville, Australia, said, “Contrary to what had been hoped until now, some resistant variants are vigorous pathogens.

“The presence of low-level resistance sets the stage for selective pressure for development of high-level resistance,” they noted (JAMA 2007;297:1492–3).

The addition of citalopram to the clinical management of depression in people with established coronary artery disease decreases the symptoms, reported Dr. François Lespérance and his associates in the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy trial.

In contrast, attending interpersonal psychotherapy—a semistructured, short-term psychotherapy program that focuses on the social context of depression and is considered especially relevant to coronary artery disease (CAD) patients—does not improve depressive symptoms beyond the benefit provided by clinical management alone, the researchers said.

This does not imply that other forms of psychotherapy, particularly cognitive-behavioral therapy, would not be helpful in CAD patients, they noted.

The CREATE trial is the first randomized controlled trial designed to assess the short-term efficacy of citalopram and interpersonal psychotherapy in CAD. It involved 284 patients with stable CAD who were treated for an episode of major depression at any of nine academic centers across Canada between 2002 and 2006.

All of the study subjects participated in clinical management, which encompassed weekly 20-minute sessions with a psychotherapist who discussed depression and medication use, provided reassurance, and encouraged the patients to adhere to treatment.

For half of the subjects, this clinical management was the only psychotherapeutic intervention offered. The other half participated in additional interpersonal psychotherapy of 50-minute weekly sessions with a therapist who addressed problems common in CAD patients and known to exacerbate CAD morbidity and mortality, such as interpersonal conflicts, life transitions, grief, loss, and social isolation.

Similarly, half of the study subjects were randomly assigned to receive daily citalopram and half to receive a placebo pill, said Dr. Lespérance, of the University of Montreal, and his associates.

After 12 weeks of treatment, citalopram was found to be superior to placebo in reducing depressive symptoms, as assessed by independent clinical ratings and by patient self-report, the investigators said (JAMA 2007;297:367–79).

Citalopram (Celexa), a selective serotonin reuptake inhibitor, was most effective for recurrent episodes of major depression and less so for first episodes.

In contrast, interpersonal psychotherapy was no more effective at reducing depressive symptoms than was clinical management, its control condition, either by independent clinical ratings or by patient self-report. “Although interpersonal psychotherapy was designed to address interpersonal issues and improve interpersonal functioning, CAD patients with low levels of support or poor daily functioning may have difficulty dealing directly with the combination of cardiac and interpersonal issues that sessions entail, and may do better with the lower demands of regular medical management,” the researchers noted.

Taken together, the study findings indicate that citalopram plus clinical management “should be considered for the initial acute-phase treatment for major depression in patients with CAD,” Dr. Lespérance and his associates said.

In an editorial comment accompanying the report, Dr. Alexander H. Glassman of the New York State Psychiatric Institute and Dr. J. Thomas Bigger Jr. of Columbia University, New York, said the CREATE study's results provide further evidence for the antidepressant efficacy of SSRIs for patients with heart disease.

The addition of citalopram to the clinical management of depression in people with established coronary artery disease decreases the symptoms, reported Dr. François Lespérance and his associates in the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy trial.

In contrast, attending interpersonal psychotherapy—a semistructured, short-term psychotherapy program that focuses on the social context of depression and is considered especially relevant to coronary artery disease (CAD) patients—does not improve depressive symptoms beyond the benefit provided by clinical management alone, the researchers said.

This does not imply that other forms of psychotherapy, particularly cognitive-behavioral therapy, would not be helpful in CAD patients, they noted.

The CREATE trial is the first randomized controlled trial designed to assess the short-term efficacy of citalopram and interpersonal psychotherapy in CAD. It involved 284 patients with stable CAD who were treated for an episode of major depression at any of nine academic centers across Canada between 2002 and 2006.

All of the study subjects participated in clinical management, which encompassed weekly 20-minute sessions with a psychotherapist who discussed depression and medication use, provided reassurance, and encouraged the patients to adhere to treatment.

For half of the subjects, this clinical management was the only psychotherapeutic intervention offered. The other half participated in additional interpersonal psychotherapy of 50-minute weekly sessions with a therapist who addressed problems common in CAD patients and known to exacerbate CAD morbidity and mortality, such as interpersonal conflicts, life transitions, grief, loss, and social isolation.

Similarly, half of the study subjects were randomly assigned to receive daily citalopram and half to receive a placebo pill, said Dr. Lespérance, of the University of Montreal, and his associates.

After 12 weeks of treatment, citalopram was found to be superior to placebo in reducing depressive symptoms, as assessed by independent clinical ratings and by patient self-report, the investigators said (JAMA 2007;297:367–79).

Citalopram (Celexa), a selective serotonin reuptake inhibitor, was most effective for recurrent episodes of major depression and less so for first episodes.

In contrast, interpersonal psychotherapy was no more effective at reducing depressive symptoms than was clinical management, its control condition, either by independent clinical ratings or by patient self-report. “Although interpersonal psychotherapy was designed to address interpersonal issues and improve interpersonal functioning, CAD patients with low levels of support or poor daily functioning may have difficulty dealing directly with the combination of cardiac and interpersonal issues that sessions entail, and may do better with the lower demands of regular medical management,” the researchers noted.

Taken together, the study findings indicate that citalopram plus clinical management “should be considered for the initial acute-phase treatment for major depression in patients with CAD,” Dr. Lespérance and his associates said.

In an editorial comment accompanying the report, Dr. Alexander H. Glassman of the New York State Psychiatric Institute and Dr. J. Thomas Bigger Jr. of Columbia University, New York, said the CREATE study's results provide further evidence for the antidepressant efficacy of SSRIs for patients with heart disease.

The addition of citalopram to the clinical management of depression in people with established coronary artery disease decreases the symptoms, reported Dr. François Lespérance and his associates in the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy trial.

In contrast, attending interpersonal psychotherapy—a semistructured, short-term psychotherapy program that focuses on the social context of depression and is considered especially relevant to coronary artery disease (CAD) patients—does not improve depressive symptoms beyond the benefit provided by clinical management alone, the researchers said.

This does not imply that other forms of psychotherapy, particularly cognitive-behavioral therapy, would not be helpful in CAD patients, they noted.

The CREATE trial is the first randomized controlled trial designed to assess the short-term efficacy of citalopram and interpersonal psychotherapy in CAD. It involved 284 patients with stable CAD who were treated for an episode of major depression at any of nine academic centers across Canada between 2002 and 2006.

All of the study subjects participated in clinical management, which encompassed weekly 20-minute sessions with a psychotherapist who discussed depression and medication use, provided reassurance, and encouraged the patients to adhere to treatment.

For half of the subjects, this clinical management was the only psychotherapeutic intervention offered. The other half participated in additional interpersonal psychotherapy of 50-minute weekly sessions with a therapist who addressed problems common in CAD patients and known to exacerbate CAD morbidity and mortality, such as interpersonal conflicts, life transitions, grief, loss, and social isolation.

Similarly, half of the study subjects were randomly assigned to receive daily citalopram and half to receive a placebo pill, said Dr. Lespérance, of the University of Montreal, and his associates.

After 12 weeks of treatment, citalopram was found to be superior to placebo in reducing depressive symptoms, as assessed by independent clinical ratings and by patient self-report, the investigators said (JAMA 2007;297:367–79).

Citalopram (Celexa), a selective serotonin reuptake inhibitor, was most effective for recurrent episodes of major depression and less so for first episodes.

In contrast, interpersonal psychotherapy was no more effective at reducing depressive symptoms than was clinical management, its control condition, either by independent clinical ratings or by patient self-report. “Although interpersonal psychotherapy was designed to address interpersonal issues and improve interpersonal functioning, CAD patients with low levels of support or poor daily functioning may have difficulty dealing directly with the combination of cardiac and interpersonal issues that sessions entail, and may do better with the lower demands of regular medical management,” the researchers noted.

Taken together, the study findings indicate that citalopram plus clinical management “should be considered for the initial acute-phase treatment for major depression in patients with CAD,” Dr. Lespérance and his associates said.

In an editorial comment accompanying the report, Dr. Alexander H. Glassman of the New York State Psychiatric Institute and Dr. J. Thomas Bigger Jr. of Columbia University, New York, said the CREATE study's results provide further evidence for the antidepressant efficacy of SSRIs for patients with heart disease.

A tablet combining sumatriptan and naproxen is more effective than either medication alone for treating acute migraine, reported Dr. Jan Lewis Brandes of the Nashville Neuroscience Group and her associates.

The combination medication also was found to be well tolerated in two clinical trials that “constitute the first placebo-controlled assessments of a triptan and an NSAID contained in a single fixed-dose tablet,” the researchers reported

“These studies used more rigorous evaluation of efficacy than any approved acute migraine treatment to date,” they added.

Triptans and NSAIDs, two of the most frequently used antimigraine agents, target different aspects of the vascular and inflammatory processes that are believed to underlie migraine.

“It is hypothesized that migraine attacks arise from neurally induced cranial vasodilation that produces painful inflammation of the surrounding nerves. Peripheral and central pain pathways appear to be sequentially recruited and sensitized as a migraine attack develops,” Dr. Brandes and associates explained.

Triptans are thought to address the initial peripheral sensitization in migraine, while NSAIDS are thought to address central sensitization. Therefore, the investigators assessed the safety and efficacy of a tablet specifically formulated for both clinical trials, which contained 85 mg sumatriptan and 500 mg naproxen.

The study subjects–1,441 in study 1 and 1,470 in study 2–were recruited from and treated at 118 sites across the country, including primary care practices, and neurology and headache clinics. Mean patient age was 40 years, and over 85% of the study population was female.

Patients were randomly assigned in nearly equal numbers to receive the combination therapy, sumatriptan alone, naproxen alone, or placebo.

The combination medication was significantly more effective than placebo or either of the single-drug formulations in every outcome assessed: acute relief of headache pain, photophobia, phonophobia, nausea, and vomiting at 2 hours, as well as sustained relief of these same symptoms at 24 hours, Dr. Brandes and associates reported (JAMA 2007;297:1443–54).

The only serious adverse event that occurred in both clinical trials involved a woman who experienced heart palpitations after taking sumatriptan alone. However, this subject had numerous CVD risk factors, as well as depression and anxiety, and she was taking medications for all of the disorders. The palpitations were deemed to be of no clinical significance.

Future studies of the combined therapy should assess whether different combinations of doses might be more efficacious, the researchers noted.

ELSEVIER GLOBAL MEDICAL NEWS

A tablet combining sumatriptan and naproxen is more effective than either medication alone for treating acute migraine, reported Dr. Jan Lewis Brandes of the Nashville Neuroscience Group and her associates.

The combination medication also was found to be well tolerated in two clinical trials that “constitute the first placebo-controlled assessments of a triptan and an NSAID contained in a single fixed-dose tablet,” the researchers reported

“These studies used more rigorous evaluation of efficacy than any approved acute migraine treatment to date,” they added.

Triptans and NSAIDs, two of the most frequently used antimigraine agents, target different aspects of the vascular and inflammatory processes that are believed to underlie migraine.

“It is hypothesized that migraine attacks arise from neurally induced cranial vasodilation that produces painful inflammation of the surrounding nerves. Peripheral and central pain pathways appear to be sequentially recruited and sensitized as a migraine attack develops,” Dr. Brandes and associates explained.

Triptans are thought to address the initial peripheral sensitization in migraine, while NSAIDS are thought to address central sensitization. Therefore, the investigators assessed the safety and efficacy of a tablet specifically formulated for both clinical trials, which contained 85 mg sumatriptan and 500 mg naproxen.

The study subjects–1,441 in study 1 and 1,470 in study 2–were recruited from and treated at 118 sites across the country, including primary care practices, and neurology and headache clinics. Mean patient age was 40 years, and over 85% of the study population was female.

Patients were randomly assigned in nearly equal numbers to receive the combination therapy, sumatriptan alone, naproxen alone, or placebo.

The combination medication was significantly more effective than placebo or either of the single-drug formulations in every outcome assessed: acute relief of headache pain, photophobia, phonophobia, nausea, and vomiting at 2 hours, as well as sustained relief of these same symptoms at 24 hours, Dr. Brandes and associates reported (JAMA 2007;297:1443–54).

The only serious adverse event that occurred in both clinical trials involved a woman who experienced heart palpitations after taking sumatriptan alone. However, this subject had numerous CVD risk factors, as well as depression and anxiety, and she was taking medications for all of the disorders. The palpitations were deemed to be of no clinical significance.

Future studies of the combined therapy should assess whether different combinations of doses might be more efficacious, the researchers noted.

ELSEVIER GLOBAL MEDICAL NEWS

A tablet combining sumatriptan and naproxen is more effective than either medication alone for treating acute migraine, reported Dr. Jan Lewis Brandes of the Nashville Neuroscience Group and her associates.

The combination medication also was found to be well tolerated in two clinical trials that “constitute the first placebo-controlled assessments of a triptan and an NSAID contained in a single fixed-dose tablet,” the researchers reported

“These studies used more rigorous evaluation of efficacy than any approved acute migraine treatment to date,” they added.

Triptans and NSAIDs, two of the most frequently used antimigraine agents, target different aspects of the vascular and inflammatory processes that are believed to underlie migraine.

“It is hypothesized that migraine attacks arise from neurally induced cranial vasodilation that produces painful inflammation of the surrounding nerves. Peripheral and central pain pathways appear to be sequentially recruited and sensitized as a migraine attack develops,” Dr. Brandes and associates explained.

Triptans are thought to address the initial peripheral sensitization in migraine, while NSAIDS are thought to address central sensitization. Therefore, the investigators assessed the safety and efficacy of a tablet specifically formulated for both clinical trials, which contained 85 mg sumatriptan and 500 mg naproxen.

The study subjects–1,441 in study 1 and 1,470 in study 2–were recruited from and treated at 118 sites across the country, including primary care practices, and neurology and headache clinics. Mean patient age was 40 years, and over 85% of the study population was female.

Patients were randomly assigned in nearly equal numbers to receive the combination therapy, sumatriptan alone, naproxen alone, or placebo.

The combination medication was significantly more effective than placebo or either of the single-drug formulations in every outcome assessed: acute relief of headache pain, photophobia, phonophobia, nausea, and vomiting at 2 hours, as well as sustained relief of these same symptoms at 24 hours, Dr. Brandes and associates reported (JAMA 2007;297:1443–54).

The only serious adverse event that occurred in both clinical trials involved a woman who experienced heart palpitations after taking sumatriptan alone. However, this subject had numerous CVD risk factors, as well as depression and anxiety, and she was taking medications for all of the disorders. The palpitations were deemed to be of no clinical significance.

Future studies of the combined therapy should assess whether different combinations of doses might be more efficacious, the researchers noted.

ELSEVIER GLOBAL MEDICAL NEWS

Antibiotics are prescribed in 83% of physician visits for acute rhinosinusitis and in 70% of visits for chronic rhinosinusitis, far more than is indicated by the expected rates of bacterial infection, reported Hadley J. Sharp and her associates at the University of Nebraska Medical Center, Omaha.

The investigators examined national trends in rhinosinusitis treatment using data from a probability sample of nearly 6,000 visits for ambulatory medical care to physicians' offices, hospital outpatient departments, and emergency departments.

The data were collected prospectively by the National Center for Health Statistics from 1999 through 2002, and represent more than an estimated 3 million annual visits for acute and 14 million visits for chronic rhinosinusitis.

Physicians ordered, supplied, administered, or continued at least one prescription antibiotic in 83% of visits for acute rhinosinusitis, representing an estimated 2.5 million cases, and in 70% of visits for chronic rhinosinusitis, representing an estimated 11.6 million cases.

Appropriately, penicillins—mainly amoxicillin and amoxicillin-clavulanate—were the most commonly prescribed antibiotics for both forms of sinusitis, given in about 30% of visits for each disorder.

Unexpectedly, erythromycins, lincosamides, and macrolides comprised the second most commonly used type of antibiotics, and they were prescribed in 24% of visits for acute and 14% of visits for chronic sinusitis. These agents have a lower clinical and bacteriologic efficacy than cephalosporins, sulfonamides, and trimethoprim (Arch. Otolaryngol. Head Neck Surg. 2007;133:260–5).

Antibiotics are prescribed in 83% of physician visits for acute rhinosinusitis and in 70% of visits for chronic rhinosinusitis, far more than is indicated by the expected rates of bacterial infection, reported Hadley J. Sharp and her associates at the University of Nebraska Medical Center, Omaha.

The investigators examined national trends in rhinosinusitis treatment using data from a probability sample of nearly 6,000 visits for ambulatory medical care to physicians' offices, hospital outpatient departments, and emergency departments.

The data were collected prospectively by the National Center for Health Statistics from 1999 through 2002, and represent more than an estimated 3 million annual visits for acute and 14 million visits for chronic rhinosinusitis.

Physicians ordered, supplied, administered, or continued at least one prescription antibiotic in 83% of visits for acute rhinosinusitis, representing an estimated 2.5 million cases, and in 70% of visits for chronic rhinosinusitis, representing an estimated 11.6 million cases.

Appropriately, penicillins—mainly amoxicillin and amoxicillin-clavulanate—were the most commonly prescribed antibiotics for both forms of sinusitis, given in about 30% of visits for each disorder.

Unexpectedly, erythromycins, lincosamides, and macrolides comprised the second most commonly used type of antibiotics, and they were prescribed in 24% of visits for acute and 14% of visits for chronic sinusitis. These agents have a lower clinical and bacteriologic efficacy than cephalosporins, sulfonamides, and trimethoprim (Arch. Otolaryngol. Head Neck Surg. 2007;133:260–5).

Antibiotics are prescribed in 83% of physician visits for acute rhinosinusitis and in 70% of visits for chronic rhinosinusitis, far more than is indicated by the expected rates of bacterial infection, reported Hadley J. Sharp and her associates at the University of Nebraska Medical Center, Omaha.

The investigators examined national trends in rhinosinusitis treatment using data from a probability sample of nearly 6,000 visits for ambulatory medical care to physicians' offices, hospital outpatient departments, and emergency departments.

The data were collected prospectively by the National Center for Health Statistics from 1999 through 2002, and represent more than an estimated 3 million annual visits for acute and 14 million visits for chronic rhinosinusitis.

Physicians ordered, supplied, administered, or continued at least one prescription antibiotic in 83% of visits for acute rhinosinusitis, representing an estimated 2.5 million cases, and in 70% of visits for chronic rhinosinusitis, representing an estimated 11.6 million cases.

Appropriately, penicillins—mainly amoxicillin and amoxicillin-clavulanate—were the most commonly prescribed antibiotics for both forms of sinusitis, given in about 30% of visits for each disorder.

Unexpectedly, erythromycins, lincosamides, and macrolides comprised the second most commonly used type of antibiotics, and they were prescribed in 24% of visits for acute and 14% of visits for chronic sinusitis. These agents have a lower clinical and bacteriologic efficacy than cephalosporins, sulfonamides, and trimethoprim (Arch. Otolaryngol. Head Neck Surg. 2007;133:260–5).

NEW ORLEANS — The investigational agent tolvaptan relieves core symptoms of acute decompensated heart failure without inducing adverse effects, but had no impact on all-cause mortality, according to researchers in the multinational EVEREST clinical trials.

The oral vasopressin antagonist also had no effect on the combined end point of cardiovascular mortality or subsequent hospitalization for worsening heart failure, study investigators reported at the annual meeting of the American College of Cardiology.

After one dose, significantly more patients reported improvement in dyspnea scores after taking tolvaptan, compared with placebo. Changes in body weight due to reduced fluid overload were also significant at day 1 and day 7, and were sustained during a median 9.9 months of follow-up, study investigator Dr. Marvin A. Konstam reported at the meeting.

“I, as a clinician, can say I have something new to offer patients,” said Dr. Konstam, chief of cardiology and professor of medicine at Tufts-New England Medical Center, Boston, during a press briefing.

However, Dr. Konstam acknowledged he was “disappointed” that the agent failed to reduce mortality or heart failure-related morbidity either during hospitalization or at 1-year follow-up.

In an editorial comment accompanying simultaneous publication of trial data, Dr. Clyde W. Yancy of Baylor Heart and Vascular Institute, Dallas, applauded the “noteworthy findings” on symptomatic improvement, but said the lack of impact on global clinical status, subsequent hospitalizations, or mortality must temper enthusiasm for the EVEREST findings.

“To the extent that it helps patients do better, that's a good thing,” Dr. Yancy said at the ACC press briefing. He called the lack of safety signals in the follow-up study “comforting.”

But neither physician suggested that the trial points to an improvement in the progression of heart disease in a patient group Dr. Konstam termed “daunting.”

He specifically said it should not be used indiscriminately or indefinitely in patients with worsening heart failure, although he said he might reinstate it if a patient's fluid overload worsened upon discontinuation of short-term use of the drug.

The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial comprised two identical short-term trials and one long-term safety trial conducted at 359 sites in North America, South America, and Europe between 2003 and 2006. All were funded by Otsuka Inc., the drug's manufacturer.

In the two short-term trials, the clinical effects of tolvaptan were compared with those of placebo when added to optimal medical therapy during hospitalization for acute decompensated heart failure (HF) with impaired left ventricular ejection fraction (LVEF). In trial A, 1,018 subjects were randomly assigned to receive tolvaptan and 1,030 to receive placebo, while in trial B the numbers were 1,054 and 1,031, respectively, wrote Dr. Mihai Gheorghiade of Northwestern University, Chicago, and associates (JAMA 2007;297:1332–43).

In both short-term trials, patients in the active drug group showed decreases in body weight as early as the first day of treatment, which persisted as long as the drug was administered (7 days or until hospital discharge, whichever came first). Dyspnea and rales, fatigue, jugular venous distension, and pedal edema all improved in a similar fashion.

Tolvaptan improved or normalized serum sodium concentrations in hyponatremic patients. It also allowed all patients to reduce their use of furosemide.

“These positive effects were achieved without adversely affecting heart rate, blood pressure, or serum electrolytes,” and there was no adverse effect on liver or renal function, Dr. Gheorghiade and associates wrote.

The long-term trial was primarily designed to assess the drug's safety in the same patients from hospital discharge through 1-year of follow-up. Unlike other agents previously used to treat the disorder, “Long-term tolvaptan treatment had no effect, either favorable or unfavorable, on all-cause mortality or the combined end point of cardiovascular mortality or subsequent hospitalization for worsening HF,” wrote Dr. Konstam, the lead investigator in this trial, and his associates.

“Overall, the benefits on short-term symptoms, together with the demonstrable short-term and long-term safety profile, support the usefulness of tolvaptan treatment for patients manifesting volume overload during hospitalization for HF,” the researchers wrote (JAMA 2007;297:1319–31).

Tolvaptan's safety record stands in contrast to nesiritide, which has been associated with increased mortality and renal dysfunction in two meta-analyses.

In his editorial comment, Dr. Yancy noted that there were no differences in global clinical status, nor in rates of recurrent HF hospitalization or mortality. And rates of adverse events—especially thirst and dry mouth—were “high” in all three EVEREST trials, he said.

Moreover, the trial results apply only to patients with profiles like those of the study subjects, and cannot be extrapolated to other groups.

“Clinicians should be encouraged to continue to use diuretics judiciously as needed. … Adjunctive short-term arginine vasopressin antagonism may be considered for the patient with established low [ejection fraction],” Dr. Yancy wrote.

Betsy Bates contributed to this report from New Orleans.

Dr. Marvin A. Konstam, of Tufts-New England Medical Center, said that he was “disappointed” that the agent failed to reduce mortality or heart failure-related morbidity either during hospitalization or at 1-year follow-up. Catherine Hackett/Elsevier Global Medical News

NEW ORLEANS — The investigational agent tolvaptan relieves core symptoms of acute decompensated heart failure without inducing adverse effects, but had no impact on all-cause mortality, according to researchers in the multinational EVEREST clinical trials.

The oral vasopressin antagonist also had no effect on the combined end point of cardiovascular mortality or subsequent hospitalization for worsening heart failure, study investigators reported at the annual meeting of the American College of Cardiology.

After one dose, significantly more patients reported improvement in dyspnea scores after taking tolvaptan, compared with placebo. Changes in body weight due to reduced fluid overload were also significant at day 1 and day 7, and were sustained during a median 9.9 months of follow-up, study investigator Dr. Marvin A. Konstam reported at the meeting.

“I, as a clinician, can say I have something new to offer patients,” said Dr. Konstam, chief of cardiology and professor of medicine at Tufts-New England Medical Center, Boston, during a press briefing.

However, Dr. Konstam acknowledged he was “disappointed” that the agent failed to reduce mortality or heart failure-related morbidity either during hospitalization or at 1-year follow-up.

In an editorial comment accompanying simultaneous publication of trial data, Dr. Clyde W. Yancy of Baylor Heart and Vascular Institute, Dallas, applauded the “noteworthy findings” on symptomatic improvement, but said the lack of impact on global clinical status, subsequent hospitalizations, or mortality must temper enthusiasm for the EVEREST findings.

“To the extent that it helps patients do better, that's a good thing,” Dr. Yancy said at the ACC press briefing. He called the lack of safety signals in the follow-up study “comforting.”

But neither physician suggested that the trial points to an improvement in the progression of heart disease in a patient group Dr. Konstam termed “daunting.”

He specifically said it should not be used indiscriminately or indefinitely in patients with worsening heart failure, although he said he might reinstate it if a patient's fluid overload worsened upon discontinuation of short-term use of the drug.

The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial comprised two identical short-term trials and one long-term safety trial conducted at 359 sites in North America, South America, and Europe between 2003 and 2006. All were funded by Otsuka Inc., the drug's manufacturer.

In the two short-term trials, the clinical effects of tolvaptan were compared with those of placebo when added to optimal medical therapy during hospitalization for acute decompensated heart failure (HF) with impaired left ventricular ejection fraction (LVEF). In trial A, 1,018 subjects were randomly assigned to receive tolvaptan and 1,030 to receive placebo, while in trial B the numbers were 1,054 and 1,031, respectively, wrote Dr. Mihai Gheorghiade of Northwestern University, Chicago, and associates (JAMA 2007;297:1332–43).

In both short-term trials, patients in the active drug group showed decreases in body weight as early as the first day of treatment, which persisted as long as the drug was administered (7 days or until hospital discharge, whichever came first). Dyspnea and rales, fatigue, jugular venous distension, and pedal edema all improved in a similar fashion.

Tolvaptan improved or normalized serum sodium concentrations in hyponatremic patients. It also allowed all patients to reduce their use of furosemide.

“These positive effects were achieved without adversely affecting heart rate, blood pressure, or serum electrolytes,” and there was no adverse effect on liver or renal function, Dr. Gheorghiade and associates wrote.

The long-term trial was primarily designed to assess the drug's safety in the same patients from hospital discharge through 1-year of follow-up. Unlike other agents previously used to treat the disorder, “Long-term tolvaptan treatment had no effect, either favorable or unfavorable, on all-cause mortality or the combined end point of cardiovascular mortality or subsequent hospitalization for worsening HF,” wrote Dr. Konstam, the lead investigator in this trial, and his associates.

“Overall, the benefits on short-term symptoms, together with the demonstrable short-term and long-term safety profile, support the usefulness of tolvaptan treatment for patients manifesting volume overload during hospitalization for HF,” the researchers wrote (JAMA 2007;297:1319–31).

Tolvaptan's safety record stands in contrast to nesiritide, which has been associated with increased mortality and renal dysfunction in two meta-analyses.

In his editorial comment, Dr. Yancy noted that there were no differences in global clinical status, nor in rates of recurrent HF hospitalization or mortality. And rates of adverse events—especially thirst and dry mouth—were “high” in all three EVEREST trials, he said.

Moreover, the trial results apply only to patients with profiles like those of the study subjects, and cannot be extrapolated to other groups.

“Clinicians should be encouraged to continue to use diuretics judiciously as needed. … Adjunctive short-term arginine vasopressin antagonism may be considered for the patient with established low [ejection fraction],” Dr. Yancy wrote.

Betsy Bates contributed to this report from New Orleans.

Dr. Marvin A. Konstam, of Tufts-New England Medical Center, said that he was “disappointed” that the agent failed to reduce mortality or heart failure-related morbidity either during hospitalization or at 1-year follow-up. Catherine Hackett/Elsevier Global Medical News

NEW ORLEANS — The investigational agent tolvaptan relieves core symptoms of acute decompensated heart failure without inducing adverse effects, but had no impact on all-cause mortality, according to researchers in the multinational EVEREST clinical trials.

The oral vasopressin antagonist also had no effect on the combined end point of cardiovascular mortality or subsequent hospitalization for worsening heart failure, study investigators reported at the annual meeting of the American College of Cardiology.

After one dose, significantly more patients reported improvement in dyspnea scores after taking tolvaptan, compared with placebo. Changes in body weight due to reduced fluid overload were also significant at day 1 and day 7, and were sustained during a median 9.9 months of follow-up, study investigator Dr. Marvin A. Konstam reported at the meeting.

“I, as a clinician, can say I have something new to offer patients,” said Dr. Konstam, chief of cardiology and professor of medicine at Tufts-New England Medical Center, Boston, during a press briefing.

However, Dr. Konstam acknowledged he was “disappointed” that the agent failed to reduce mortality or heart failure-related morbidity either during hospitalization or at 1-year follow-up.

In an editorial comment accompanying simultaneous publication of trial data, Dr. Clyde W. Yancy of Baylor Heart and Vascular Institute, Dallas, applauded the “noteworthy findings” on symptomatic improvement, but said the lack of impact on global clinical status, subsequent hospitalizations, or mortality must temper enthusiasm for the EVEREST findings.

“To the extent that it helps patients do better, that's a good thing,” Dr. Yancy said at the ACC press briefing. He called the lack of safety signals in the follow-up study “comforting.”

But neither physician suggested that the trial points to an improvement in the progression of heart disease in a patient group Dr. Konstam termed “daunting.”

He specifically said it should not be used indiscriminately or indefinitely in patients with worsening heart failure, although he said he might reinstate it if a patient's fluid overload worsened upon discontinuation of short-term use of the drug.

The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial comprised two identical short-term trials and one long-term safety trial conducted at 359 sites in North America, South America, and Europe between 2003 and 2006. All were funded by Otsuka Inc., the drug's manufacturer.

In the two short-term trials, the clinical effects of tolvaptan were compared with those of placebo when added to optimal medical therapy during hospitalization for acute decompensated heart failure (HF) with impaired left ventricular ejection fraction (LVEF). In trial A, 1,018 subjects were randomly assigned to receive tolvaptan and 1,030 to receive placebo, while in trial B the numbers were 1,054 and 1,031, respectively, wrote Dr. Mihai Gheorghiade of Northwestern University, Chicago, and associates (JAMA 2007;297:1332–43).

In both short-term trials, patients in the active drug group showed decreases in body weight as early as the first day of treatment, which persisted as long as the drug was administered (7 days or until hospital discharge, whichever came first). Dyspnea and rales, fatigue, jugular venous distension, and pedal edema all improved in a similar fashion.

Tolvaptan improved or normalized serum sodium concentrations in hyponatremic patients. It also allowed all patients to reduce their use of furosemide.

“These positive effects were achieved without adversely affecting heart rate, blood pressure, or serum electrolytes,” and there was no adverse effect on liver or renal function, Dr. Gheorghiade and associates wrote.

The long-term trial was primarily designed to assess the drug's safety in the same patients from hospital discharge through 1-year of follow-up. Unlike other agents previously used to treat the disorder, “Long-term tolvaptan treatment had no effect, either favorable or unfavorable, on all-cause mortality or the combined end point of cardiovascular mortality or subsequent hospitalization for worsening HF,” wrote Dr. Konstam, the lead investigator in this trial, and his associates.

“Overall, the benefits on short-term symptoms, together with the demonstrable short-term and long-term safety profile, support the usefulness of tolvaptan treatment for patients manifesting volume overload during hospitalization for HF,” the researchers wrote (JAMA 2007;297:1319–31).

Tolvaptan's safety record stands in contrast to nesiritide, which has been associated with increased mortality and renal dysfunction in two meta-analyses.

In his editorial comment, Dr. Yancy noted that there were no differences in global clinical status, nor in rates of recurrent HF hospitalization or mortality. And rates of adverse events—especially thirst and dry mouth—were “high” in all three EVEREST trials, he said.

Moreover, the trial results apply only to patients with profiles like those of the study subjects, and cannot be extrapolated to other groups.

“Clinicians should be encouraged to continue to use diuretics judiciously as needed. … Adjunctive short-term arginine vasopressin antagonism may be considered for the patient with established low [ejection fraction],” Dr. Yancy wrote.

Betsy Bates contributed to this report from New Orleans.

Dr. Marvin A. Konstam, of Tufts-New England Medical Center, said that he was “disappointed” that the agent failed to reduce mortality or heart failure-related morbidity either during hospitalization or at 1-year follow-up. Catherine Hackett/Elsevier Global Medical News

The higher mortality rate in acute myocardial infarction patients admitted to the hospital on weekends compared with weekdays can be attributed in part to a reduced rate of invasive cardiac procedures on weekends, reported William J. Kostis, Ph.D., of Robert Wood Johnson Medical School, Piscataway, N.J.

Dr. Kostis and his associates used information in the Myocardial Infarction Data Acquisition System (MIDAS) database to determine whether MI-related mortality is higher with weekend presentation, and whether this could be explained by the use of invasive cardiac procedures, length of hospital stay, or patient characteristics.

The database includes the records of more than 231,000 MI patients treated between 1987 and 2002, “virtually all patients admitted to [any] New Jersey hospital over a 16-year period for a first myocardial infarction.”

Thirty-day mortality showed “a significant and clinically relevant” increase among patients admitted on a Saturday or Sunday rather than on a weekday, “representing 9 to 10 additional deaths per 1,000 admissions per year.” This increased mortality persisted for a full year of follow-up, and “could account for several thousand deaths annually in the United States,” the investigators said. “Even small differences in mortality between weekday and weekend admissions of patients with acute MI can translate to substantial numbers of additional deaths in the population because of the high incidence and case fatality rate associated with this condition,” the researchers said (N. Engl. J. Med. 2007;356:1099–109).

Patients who were admitted on weekends were less likely to undergo cardiac catheterization, percutaneous coronary intervention, or coronary artery bypass graft surgery than were those admitted on weekdays, and when they did have such procedures, they were more likely to experience a significant delay of several days compared with people who had weekday admissions. These results persisted after the data were adjusted to account for demographic characteristics, infarction site, presence or absence of concomitant illness, and presence or absence of complications.

The association between timing of admission and mortality was not related to patient characteristics or length of stay. It was due primarily to the difference in use of invasive cardiac procedures. These results persisted when the data analysis was restricted to several subgroups, such as patients treated at percutaneous coronary intervention-equipped hospitals.

“Overall, our study suggests that a hospital workweek of Monday through Friday is not optimal for the care of patients with acute MI,” the authors added.

The higher mortality rate in acute myocardial infarction patients admitted to the hospital on weekends compared with weekdays can be attributed in part to a reduced rate of invasive cardiac procedures on weekends, reported William J. Kostis, Ph.D., of Robert Wood Johnson Medical School, Piscataway, N.J.

Dr. Kostis and his associates used information in the Myocardial Infarction Data Acquisition System (MIDAS) database to determine whether MI-related mortality is higher with weekend presentation, and whether this could be explained by the use of invasive cardiac procedures, length of hospital stay, or patient characteristics.

The database includes the records of more than 231,000 MI patients treated between 1987 and 2002, “virtually all patients admitted to [any] New Jersey hospital over a 16-year period for a first myocardial infarction.”

Thirty-day mortality showed “a significant and clinically relevant” increase among patients admitted on a Saturday or Sunday rather than on a weekday, “representing 9 to 10 additional deaths per 1,000 admissions per year.” This increased mortality persisted for a full year of follow-up, and “could account for several thousand deaths annually in the United States,” the investigators said. “Even small differences in mortality between weekday and weekend admissions of patients with acute MI can translate to substantial numbers of additional deaths in the population because of the high incidence and case fatality rate associated with this condition,” the researchers said (N. Engl. J. Med. 2007;356:1099–109).

Patients who were admitted on weekends were less likely to undergo cardiac catheterization, percutaneous coronary intervention, or coronary artery bypass graft surgery than were those admitted on weekdays, and when they did have such procedures, they were more likely to experience a significant delay of several days compared with people who had weekday admissions. These results persisted after the data were adjusted to account for demographic characteristics, infarction site, presence or absence of concomitant illness, and presence or absence of complications.

The association between timing of admission and mortality was not related to patient characteristics or length of stay. It was due primarily to the difference in use of invasive cardiac procedures. These results persisted when the data analysis was restricted to several subgroups, such as patients treated at percutaneous coronary intervention-equipped hospitals.

“Overall, our study suggests that a hospital workweek of Monday through Friday is not optimal for the care of patients with acute MI,” the authors added.

The higher mortality rate in acute myocardial infarction patients admitted to the hospital on weekends compared with weekdays can be attributed in part to a reduced rate of invasive cardiac procedures on weekends, reported William J. Kostis, Ph.D., of Robert Wood Johnson Medical School, Piscataway, N.J.

Dr. Kostis and his associates used information in the Myocardial Infarction Data Acquisition System (MIDAS) database to determine whether MI-related mortality is higher with weekend presentation, and whether this could be explained by the use of invasive cardiac procedures, length of hospital stay, or patient characteristics.

The database includes the records of more than 231,000 MI patients treated between 1987 and 2002, “virtually all patients admitted to [any] New Jersey hospital over a 16-year period for a first myocardial infarction.”

Thirty-day mortality showed “a significant and clinically relevant” increase among patients admitted on a Saturday or Sunday rather than on a weekday, “representing 9 to 10 additional deaths per 1,000 admissions per year.” This increased mortality persisted for a full year of follow-up, and “could account for several thousand deaths annually in the United States,” the investigators said. “Even small differences in mortality between weekday and weekend admissions of patients with acute MI can translate to substantial numbers of additional deaths in the population because of the high incidence and case fatality rate associated with this condition,” the researchers said (N. Engl. J. Med. 2007;356:1099–109).

Patients who were admitted on weekends were less likely to undergo cardiac catheterization, percutaneous coronary intervention, or coronary artery bypass graft surgery than were those admitted on weekdays, and when they did have such procedures, they were more likely to experience a significant delay of several days compared with people who had weekday admissions. These results persisted after the data were adjusted to account for demographic characteristics, infarction site, presence or absence of concomitant illness, and presence or absence of complications.

The association between timing of admission and mortality was not related to patient characteristics or length of stay. It was due primarily to the difference in use of invasive cardiac procedures. These results persisted when the data analysis was restricted to several subgroups, such as patients treated at percutaneous coronary intervention-equipped hospitals.

“Overall, our study suggests that a hospital workweek of Monday through Friday is not optimal for the care of patients with acute MI,” the authors added.