Mary Ann Moon

The use of marijuana is associated with an earlier onset of psychosis, and that association might be causal, a meta-analysis published Feb. 7 online in Archives of General Psychiatry has shown.

© ron hilton/iStockphoto.com

"This study lends weight to the view that cannabis use precipitates schizophrenia and other psychotic disorders, perhaps by an interaction between genetic and environmental factors ... or by disrupting brain development, especially during the important neurological maturation that takes place during adolescence," said Dr. Matthew Large of Prince of Wales Hospital and the University of New South Wales, Sydney, and his associates.

Further, the study findings raise "important questions of whether cannabis ... can trigger psychosis by direct neurotoxic effects, by alterations in dopamine activity, or by other changes in neurotransmission and the extent to which any adverse effects on the brain are reversible." Future research should focus on finding "the mechanisms by which cannabis use triggers or brings forward psychotic illness," the investigators added.

They performed a meta-analysis of 83 studies that reported age at onset of psychotic disorders in cohorts of patients in which the use of psychoactive substances also was recorded. These included 8,167 patients who reported that they used substances and 14,352 who reported that they did not.

Overall, the mean age of psychosis onset in patients who used substances was about 2 years younger than the age of psychosis onset in patients who did not.

In a further analysis, study samples of patients who used cannabis in particular showed an onset of psychosis that was nearly 3 years earlier than in study samples of patients who did not use cannabis. Similarly, the onset of psychosis was 2 years earlier in samples of patients who used unspecified psychoactive substances than in samples of those who did not.

In contrast, the use of alcohol alone was not significantly associated with a younger age of onset of psychosis. This finding refutes the possibility that "people with a propensity to develop psychosis at a younger age are simply more likely to use all substances," Dr. Large and his colleagues said (Arch. Gen. Psychiatry 2011 Feb. 7 [doi:10.1001/archgenpsychiatry.2011.5]).

Several other variables also showed no association with age at onset of psychosis, including the severity of substance use, how a study measured the onset of psychosis, which instruments were used to diagnose psychosis or substance use, whether the study included only patients with first-episode psychosis, and the year in which the study was conducted.

The results suggest that reducing marijuana use could delay or even prevent some cases of psychosis. Even if reducing cannabis use only delayed the onset of a psychotic illness that was inevitable, "an extra 2 or 3 years of psychosis-free functioning could allow many patients to achieve the important developmental milestones of late adolescence and early adulthood that could lower the long-term disability arising from psychotic disorders," the researchers noted.

These findings warrant "a renewed public health warning about the potential for cannabis use to bring on psychotic illness," they added.

The authors reported no relevant financial disclosures.

The use of marijuana is associated with an earlier onset of psychosis, and that association might be causal, a meta-analysis published Feb. 7 online in Archives of General Psychiatry has shown.

© ron hilton/iStockphoto.com

"This study lends weight to the view that cannabis use precipitates schizophrenia and other psychotic disorders, perhaps by an interaction between genetic and environmental factors ... or by disrupting brain development, especially during the important neurological maturation that takes place during adolescence," said Dr. Matthew Large of Prince of Wales Hospital and the University of New South Wales, Sydney, and his associates.

Further, the study findings raise "important questions of whether cannabis ... can trigger psychosis by direct neurotoxic effects, by alterations in dopamine activity, or by other changes in neurotransmission and the extent to which any adverse effects on the brain are reversible." Future research should focus on finding "the mechanisms by which cannabis use triggers or brings forward psychotic illness," the investigators added.

They performed a meta-analysis of 83 studies that reported age at onset of psychotic disorders in cohorts of patients in which the use of psychoactive substances also was recorded. These included 8,167 patients who reported that they used substances and 14,352 who reported that they did not.

Overall, the mean age of psychosis onset in patients who used substances was about 2 years younger than the age of psychosis onset in patients who did not.

In a further analysis, study samples of patients who used cannabis in particular showed an onset of psychosis that was nearly 3 years earlier than in study samples of patients who did not use cannabis. Similarly, the onset of psychosis was 2 years earlier in samples of patients who used unspecified psychoactive substances than in samples of those who did not.

In contrast, the use of alcohol alone was not significantly associated with a younger age of onset of psychosis. This finding refutes the possibility that "people with a propensity to develop psychosis at a younger age are simply more likely to use all substances," Dr. Large and his colleagues said (Arch. Gen. Psychiatry 2011 Feb. 7 [doi:10.1001/archgenpsychiatry.2011.5]).

Several other variables also showed no association with age at onset of psychosis, including the severity of substance use, how a study measured the onset of psychosis, which instruments were used to diagnose psychosis or substance use, whether the study included only patients with first-episode psychosis, and the year in which the study was conducted.

The results suggest that reducing marijuana use could delay or even prevent some cases of psychosis. Even if reducing cannabis use only delayed the onset of a psychotic illness that was inevitable, "an extra 2 or 3 years of psychosis-free functioning could allow many patients to achieve the important developmental milestones of late adolescence and early adulthood that could lower the long-term disability arising from psychotic disorders," the researchers noted.

These findings warrant "a renewed public health warning about the potential for cannabis use to bring on psychotic illness," they added.

The authors reported no relevant financial disclosures.

The use of marijuana is associated with an earlier onset of psychosis, and that association might be causal, a meta-analysis published Feb. 7 online in Archives of General Psychiatry has shown.

© ron hilton/iStockphoto.com

"This study lends weight to the view that cannabis use precipitates schizophrenia and other psychotic disorders, perhaps by an interaction between genetic and environmental factors ... or by disrupting brain development, especially during the important neurological maturation that takes place during adolescence," said Dr. Matthew Large of Prince of Wales Hospital and the University of New South Wales, Sydney, and his associates.

Further, the study findings raise "important questions of whether cannabis ... can trigger psychosis by direct neurotoxic effects, by alterations in dopamine activity, or by other changes in neurotransmission and the extent to which any adverse effects on the brain are reversible." Future research should focus on finding "the mechanisms by which cannabis use triggers or brings forward psychotic illness," the investigators added.

They performed a meta-analysis of 83 studies that reported age at onset of psychotic disorders in cohorts of patients in which the use of psychoactive substances also was recorded. These included 8,167 patients who reported that they used substances and 14,352 who reported that they did not.

Overall, the mean age of psychosis onset in patients who used substances was about 2 years younger than the age of psychosis onset in patients who did not.

In a further analysis, study samples of patients who used cannabis in particular showed an onset of psychosis that was nearly 3 years earlier than in study samples of patients who did not use cannabis. Similarly, the onset of psychosis was 2 years earlier in samples of patients who used unspecified psychoactive substances than in samples of those who did not.

In contrast, the use of alcohol alone was not significantly associated with a younger age of onset of psychosis. This finding refutes the possibility that "people with a propensity to develop psychosis at a younger age are simply more likely to use all substances," Dr. Large and his colleagues said (Arch. Gen. Psychiatry 2011 Feb. 7 [doi:10.1001/archgenpsychiatry.2011.5]).

Several other variables also showed no association with age at onset of psychosis, including the severity of substance use, how a study measured the onset of psychosis, which instruments were used to diagnose psychosis or substance use, whether the study included only patients with first-episode psychosis, and the year in which the study was conducted.

The results suggest that reducing marijuana use could delay or even prevent some cases of psychosis. Even if reducing cannabis use only delayed the onset of a psychotic illness that was inevitable, "an extra 2 or 3 years of psychosis-free functioning could allow many patients to achieve the important developmental milestones of late adolescence and early adulthood that could lower the long-term disability arising from psychotic disorders," the researchers noted.

These findings warrant "a renewed public health warning about the potential for cannabis use to bring on psychotic illness," they added.

The authors reported no relevant financial disclosures.

The use of marijuana is associated with an earlier onset of psychosis, and that association might be causal, a meta-analysis published Feb. 7 online in Archives of General Psychiatry has shown.

© ron hilton/iStockphoto.com

"This study lends weight to the view that cannabis use precipitates schizophrenia and other psychotic disorders, perhaps by an interaction between genetic and environmental factors ... or by disrupting brain development, especially during the important neurological maturation that takes place during adolescence," said Dr. Matthew Large of Prince of Wales Hospital and the University of New South Wales, Sydney, and his associates.

Further, the study findings raise "important questions of whether cannabis ... can trigger psychosis by direct neurotoxic effects, by alterations in dopamine activity, or by other changes in neurotransmission and the extent to which any adverse effects on the brain are reversible." Future research should focus on finding "the mechanisms by which cannabis use triggers or brings forward psychotic illness," the investigators added.

They performed a meta-analysis of 83 studies that reported age at onset of psychotic disorders in cohorts of patients in which the use of psychoactive substances also was recorded. These included 8,167 patients who reported that they used substances and 14,352 who reported that they did not.

Overall, the mean age of psychosis onset in patients who used substances was about 2 years younger than the age of psychosis onset in patients who did not.

In a further analysis, study samples of patients who used cannabis in particular showed an onset of psychosis that was nearly 3 years earlier than in study samples of patients who did not use cannabis. Similarly, the onset of psychosis was 2 years earlier in samples of patients who used unspecified psychoactive substances than in samples of those who did not.

In contrast, the use of alcohol alone was not significantly associated with a younger age of onset of psychosis. This finding refutes the possibility that "people with a propensity to develop psychosis at a younger age are simply more likely to use all substances," Dr. Large and his colleagues said (Arch. Gen. Psychiatry 2011 Feb. 7 [doi:10.1001/archgenpsychiatry.2011.5]).

Several other variables also showed no association with age at onset of psychosis, including the severity of substance use, how a study measured the onset of psychosis, which instruments were used to diagnose psychosis or substance use, whether the study included only patients with first-episode psychosis, and the year in which the study was conducted.

The results suggest that reducing marijuana use could delay or even prevent some cases of psychosis. Even if reducing cannabis use only delayed the onset of a psychotic illness that was inevitable, "an extra 2 or 3 years of psychosis-free functioning could allow many patients to achieve the important developmental milestones of late adolescence and early adulthood that could lower the long-term disability arising from psychotic disorders," the researchers noted.

These findings warrant "a renewed public health warning about the potential for cannabis use to bring on psychotic illness," they added.

The authors reported no relevant financial disclosures.

The use of marijuana is associated with an earlier onset of psychosis, and that association might be causal, a meta-analysis published Feb. 7 online in Archives of General Psychiatry has shown.

© ron hilton/iStockphoto.com

"This study lends weight to the view that cannabis use precipitates schizophrenia and other psychotic disorders, perhaps by an interaction between genetic and environmental factors ... or by disrupting brain development, especially during the important neurological maturation that takes place during adolescence," said Dr. Matthew Large of Prince of Wales Hospital and the University of New South Wales, Sydney, and his associates.

Further, the study findings raise "important questions of whether cannabis ... can trigger psychosis by direct neurotoxic effects, by alterations in dopamine activity, or by other changes in neurotransmission and the extent to which any adverse effects on the brain are reversible." Future research should focus on finding "the mechanisms by which cannabis use triggers or brings forward psychotic illness," the investigators added.

They performed a meta-analysis of 83 studies that reported age at onset of psychotic disorders in cohorts of patients in which the use of psychoactive substances also was recorded. These included 8,167 patients who reported that they used substances and 14,352 who reported that they did not.

Overall, the mean age of psychosis onset in patients who used substances was about 2 years younger than the age of psychosis onset in patients who did not.

In a further analysis, study samples of patients who used cannabis in particular showed an onset of psychosis that was nearly 3 years earlier than in study samples of patients who did not use cannabis. Similarly, the onset of psychosis was 2 years earlier in samples of patients who used unspecified psychoactive substances than in samples of those who did not.

In contrast, the use of alcohol alone was not significantly associated with a younger age of onset of psychosis. This finding refutes the possibility that "people with a propensity to develop psychosis at a younger age are simply more likely to use all substances," Dr. Large and his colleagues said (Arch. Gen. Psychiatry 2011 Feb. 7 [doi:10.1001/archgenpsychiatry.2011.5]).

Several other variables also showed no association with age at onset of psychosis, including the severity of substance use, how a study measured the onset of psychosis, which instruments were used to diagnose psychosis or substance use, whether the study included only patients with first-episode psychosis, and the year in which the study was conducted.

The results suggest that reducing marijuana use could delay or even prevent some cases of psychosis. Even if reducing cannabis use only delayed the onset of a psychotic illness that was inevitable, "an extra 2 or 3 years of psychosis-free functioning could allow many patients to achieve the important developmental milestones of late adolescence and early adulthood that could lower the long-term disability arising from psychotic disorders," the researchers noted.

These findings warrant "a renewed public health warning about the potential for cannabis use to bring on psychotic illness," they added.

The authors reported no relevant financial disclosures.

The use of marijuana is associated with an earlier onset of psychosis, and that association might be causal, a meta-analysis published Feb. 7 online in Archives of General Psychiatry has shown.

© ron hilton/iStockphoto.com

"This study lends weight to the view that cannabis use precipitates schizophrenia and other psychotic disorders, perhaps by an interaction between genetic and environmental factors ... or by disrupting brain development, especially during the important neurological maturation that takes place during adolescence," said Dr. Matthew Large of Prince of Wales Hospital and the University of New South Wales, Sydney, and his associates.

Further, the study findings raise "important questions of whether cannabis ... can trigger psychosis by direct neurotoxic effects, by alterations in dopamine activity, or by other changes in neurotransmission and the extent to which any adverse effects on the brain are reversible." Future research should focus on finding "the mechanisms by which cannabis use triggers or brings forward psychotic illness," the investigators added.

They performed a meta-analysis of 83 studies that reported age at onset of psychotic disorders in cohorts of patients in which the use of psychoactive substances also was recorded. These included 8,167 patients who reported that they used substances and 14,352 who reported that they did not.

Overall, the mean age of psychosis onset in patients who used substances was about 2 years younger than the age of psychosis onset in patients who did not.

In a further analysis, study samples of patients who used cannabis in particular showed an onset of psychosis that was nearly 3 years earlier than in study samples of patients who did not use cannabis. Similarly, the onset of psychosis was 2 years earlier in samples of patients who used unspecified psychoactive substances than in samples of those who did not.

In contrast, the use of alcohol alone was not significantly associated with a younger age of onset of psychosis. This finding refutes the possibility that "people with a propensity to develop psychosis at a younger age are simply more likely to use all substances," Dr. Large and his colleagues said (Arch. Gen. Psychiatry 2011 Feb. 7 [doi:10.1001/archgenpsychiatry.2011.5]).

Several other variables also showed no association with age at onset of psychosis, including the severity of substance use, how a study measured the onset of psychosis, which instruments were used to diagnose psychosis or substance use, whether the study included only patients with first-episode psychosis, and the year in which the study was conducted.

The results suggest that reducing marijuana use could delay or even prevent some cases of psychosis. Even if reducing cannabis use only delayed the onset of a psychotic illness that was inevitable, "an extra 2 or 3 years of psychosis-free functioning could allow many patients to achieve the important developmental milestones of late adolescence and early adulthood that could lower the long-term disability arising from psychotic disorders," the researchers noted.

These findings warrant "a renewed public health warning about the potential for cannabis use to bring on psychotic illness," they added.

The authors reported no relevant financial disclosures.

A hospital-based clinic that coordinated medical, nutritional, and developmental care for medically complex children throughout a single state markedly cut health costs, according to a study published online Feb. 7 in the Archives of Pediatrics and Adolescent Medicine.

This program, which created a hospital-based medical home for the pediatric patients, significantly decreased inpatient visits, lengths of hospital stay, and emergency department visits for children with multiple chronic conditions, resulting in a net reduction of $1,179 per patient per month. Extrapolating from these results, the annual savings in health care costs for a similar statewide population of patients would be $3,183,300, said Dr. Patrick H. Casey and his associates at Arkansas Children’s Hospital, Little Rock.

The investigators evaluated the costs of care before and after the implementation of the Medical Home Clinic at their hospital, which is the only tertiary care center that provides subspecialty and surgical care for children in the state. Outpatient staff includes a neonatologist, developmental pediatricians, hospitalists, general pediatricians, nurses, nutritionists, social workers, speech pathologists, and child psychologists.

In addition to providing health care, the team ensured that community services were provided for patients when necessary. A nurse was available for telephone consultations, coordinating appointments, and assisting with clinical decision-making and acute care issues.

In a retrospective cohort study that they described as "the first examination of the aggregate cost impact of a comprehensive care model for medically complex children," Dr. Casey and his colleagues reviewed the records of 225 children who had at least two serious chronic conditions. The median age of the study subjects was 13 months; 62% were boys and half were white.

Most of the study subjects (67%) had been born preterm. Forty percent had a recognized syndrome or congenital anomaly, 37% had bronchopulmonary dysplasia, 56% required a gastrostomy tube, 7% required a tracheostomy tube, 33% had cerebral palsy, and 72% were developmentally delayed.

The cost of outpatient care increased by $53 per patient per month after the Medical Home Clinic was established, but this rise was more than offset by marked decreases in costs for inpatient care (down by $1,766 per patient per month) and emergency department visits (down by $6 per patient per month).

Both the number of inpatient stays and the length of hospitalizations decreased markedly. The mean length of stay per hospitalization dropped from 14.5 days before the clinic was implemented to 10 days afterward, the investigators said (Arch. Pediatr. Adolesc. Med. 2011 Feb. 7 [doi:10.1001/archpediatrics.2011.5]).

"Future research is needed to determine whether the coordinated and comprehensive care resulted in better patient quality of life and health status, as well as improvement in the quality of life, mental health, satisfactions care, and general well-being of their care providers," Dr. Casey and his associates added.

A hospital-based clinic that coordinated medical, nutritional, and developmental care for medically complex children throughout a single state markedly cut health costs, according to a study published online Feb. 7 in the Archives of Pediatrics and Adolescent Medicine.

This program, which created a hospital-based medical home for the pediatric patients, significantly decreased inpatient visits, lengths of hospital stay, and emergency department visits for children with multiple chronic conditions, resulting in a net reduction of $1,179 per patient per month. Extrapolating from these results, the annual savings in health care costs for a similar statewide population of patients would be $3,183,300, said Dr. Patrick H. Casey and his associates at Arkansas Children’s Hospital, Little Rock.

The investigators evaluated the costs of care before and after the implementation of the Medical Home Clinic at their hospital, which is the only tertiary care center that provides subspecialty and surgical care for children in the state. Outpatient staff includes a neonatologist, developmental pediatricians, hospitalists, general pediatricians, nurses, nutritionists, social workers, speech pathologists, and child psychologists.

In addition to providing health care, the team ensured that community services were provided for patients when necessary. A nurse was available for telephone consultations, coordinating appointments, and assisting with clinical decision-making and acute care issues.

In a retrospective cohort study that they described as "the first examination of the aggregate cost impact of a comprehensive care model for medically complex children," Dr. Casey and his colleagues reviewed the records of 225 children who had at least two serious chronic conditions. The median age of the study subjects was 13 months; 62% were boys and half were white.

Most of the study subjects (67%) had been born preterm. Forty percent had a recognized syndrome or congenital anomaly, 37% had bronchopulmonary dysplasia, 56% required a gastrostomy tube, 7% required a tracheostomy tube, 33% had cerebral palsy, and 72% were developmentally delayed.

The cost of outpatient care increased by $53 per patient per month after the Medical Home Clinic was established, but this rise was more than offset by marked decreases in costs for inpatient care (down by $1,766 per patient per month) and emergency department visits (down by $6 per patient per month).

Both the number of inpatient stays and the length of hospitalizations decreased markedly. The mean length of stay per hospitalization dropped from 14.5 days before the clinic was implemented to 10 days afterward, the investigators said (Arch. Pediatr. Adolesc. Med. 2011 Feb. 7 [doi:10.1001/archpediatrics.2011.5]).

"Future research is needed to determine whether the coordinated and comprehensive care resulted in better patient quality of life and health status, as well as improvement in the quality of life, mental health, satisfactions care, and general well-being of their care providers," Dr. Casey and his associates added.

A hospital-based clinic that coordinated medical, nutritional, and developmental care for medically complex children throughout a single state markedly cut health costs, according to a study published online Feb. 7 in the Archives of Pediatrics and Adolescent Medicine.

This program, which created a hospital-based medical home for the pediatric patients, significantly decreased inpatient visits, lengths of hospital stay, and emergency department visits for children with multiple chronic conditions, resulting in a net reduction of $1,179 per patient per month. Extrapolating from these results, the annual savings in health care costs for a similar statewide population of patients would be $3,183,300, said Dr. Patrick H. Casey and his associates at Arkansas Children’s Hospital, Little Rock.

The investigators evaluated the costs of care before and after the implementation of the Medical Home Clinic at their hospital, which is the only tertiary care center that provides subspecialty and surgical care for children in the state. Outpatient staff includes a neonatologist, developmental pediatricians, hospitalists, general pediatricians, nurses, nutritionists, social workers, speech pathologists, and child psychologists.

In addition to providing health care, the team ensured that community services were provided for patients when necessary. A nurse was available for telephone consultations, coordinating appointments, and assisting with clinical decision-making and acute care issues.

In a retrospective cohort study that they described as "the first examination of the aggregate cost impact of a comprehensive care model for medically complex children," Dr. Casey and his colleagues reviewed the records of 225 children who had at least two serious chronic conditions. The median age of the study subjects was 13 months; 62% were boys and half were white.

Most of the study subjects (67%) had been born preterm. Forty percent had a recognized syndrome or congenital anomaly, 37% had bronchopulmonary dysplasia, 56% required a gastrostomy tube, 7% required a tracheostomy tube, 33% had cerebral palsy, and 72% were developmentally delayed.

The cost of outpatient care increased by $53 per patient per month after the Medical Home Clinic was established, but this rise was more than offset by marked decreases in costs for inpatient care (down by $1,766 per patient per month) and emergency department visits (down by $6 per patient per month).

Both the number of inpatient stays and the length of hospitalizations decreased markedly. The mean length of stay per hospitalization dropped from 14.5 days before the clinic was implemented to 10 days afterward, the investigators said (Arch. Pediatr. Adolesc. Med. 2011 Feb. 7 [doi:10.1001/archpediatrics.2011.5]).

"Future research is needed to determine whether the coordinated and comprehensive care resulted in better patient quality of life and health status, as well as improvement in the quality of life, mental health, satisfactions care, and general well-being of their care providers," Dr. Casey and his associates added.

A hospital-based clinic that coordinated medical, nutritional, and developmental care for medically complex children throughout a single state markedly cut health costs, according to a study published online Feb. 7 in the Archives of Pediatrics and Adolescent Medicine.

This program, which created a hospital-based medical home for the pediatric patients, significantly decreased inpatient visits, lengths of hospital stay, and emergency department visits for children with multiple chronic conditions, resulting in a net reduction of $1,179 per patient per month. Extrapolating from these results, the annual savings in health care costs for a similar statewide population of patients would be $3,183,300, said Dr. Patrick H. Casey and his associates at Arkansas Children’s Hospital, Little Rock.

The investigators evaluated the costs of care before and after the implementation of the Medical Home Clinic at their hospital, which is the only tertiary care center that provides subspecialty and surgical care for children in the state. Outpatient staff includes a neonatologist, developmental pediatricians, hospitalists, general pediatricians, nurses, nutritionists, social workers, speech pathologists, and child psychologists.

In addition to providing health care, the team ensured that community services were provided for patients when necessary. A nurse was available for telephone consultations, coordinating appointments, and assisting with clinical decision-making and acute care issues.

In a retrospective cohort study that they described as "the first examination of the aggregate cost impact of a comprehensive care model for medically complex children," Dr. Casey and his colleagues reviewed the records of 225 children who had at least two serious chronic conditions. The median age of the study subjects was 13 months; 62% were boys and half were white.

Most of the study subjects (67%) had been born preterm. Forty percent had a recognized syndrome or congenital anomaly, 37% had bronchopulmonary dysplasia, 56% required a gastrostomy tube, 7% required a tracheostomy tube, 33% had cerebral palsy, and 72% were developmentally delayed.

The cost of outpatient care increased by $53 per patient per month after the Medical Home Clinic was established, but this rise was more than offset by marked decreases in costs for inpatient care (down by $1,766 per patient per month) and emergency department visits (down by $6 per patient per month).

Both the number of inpatient stays and the length of hospitalizations decreased markedly. The mean length of stay per hospitalization dropped from 14.5 days before the clinic was implemented to 10 days afterward, the investigators said (Arch. Pediatr. Adolesc. Med. 2011 Feb. 7 [doi:10.1001/archpediatrics.2011.5]).

"Future research is needed to determine whether the coordinated and comprehensive care resulted in better patient quality of life and health status, as well as improvement in the quality of life, mental health, satisfactions care, and general well-being of their care providers," Dr. Casey and his associates added.

A hospital-based clinic that coordinated medical, nutritional, and developmental care for medically complex children throughout a single state markedly cut health costs, according to a study published online Feb. 7 in the Archives of Pediatrics and Adolescent Medicine.

This program, which created a hospital-based medical home for the pediatric patients, significantly decreased inpatient visits, lengths of hospital stay, and emergency department visits for children with multiple chronic conditions, resulting in a net reduction of $1,179 per patient per month. Extrapolating from these results, the annual savings in health care costs for a similar statewide population of patients would be $3,183,300, said Dr. Patrick H. Casey and his associates at Arkansas Children’s Hospital, Little Rock.

The investigators evaluated the costs of care before and after the implementation of the Medical Home Clinic at their hospital, which is the only tertiary care center that provides subspecialty and surgical care for children in the state. Outpatient staff includes a neonatologist, developmental pediatricians, hospitalists, general pediatricians, nurses, nutritionists, social workers, speech pathologists, and child psychologists.

In addition to providing health care, the team ensured that community services were provided for patients when necessary. A nurse was available for telephone consultations, coordinating appointments, and assisting with clinical decision-making and acute care issues.

In a retrospective cohort study that they described as "the first examination of the aggregate cost impact of a comprehensive care model for medically complex children," Dr. Casey and his colleagues reviewed the records of 225 children who had at least two serious chronic conditions. The median age of the study subjects was 13 months; 62% were boys and half were white.

Most of the study subjects (67%) had been born preterm. Forty percent had a recognized syndrome or congenital anomaly, 37% had bronchopulmonary dysplasia, 56% required a gastrostomy tube, 7% required a tracheostomy tube, 33% had cerebral palsy, and 72% were developmentally delayed.

The cost of outpatient care increased by $53 per patient per month after the Medical Home Clinic was established, but this rise was more than offset by marked decreases in costs for inpatient care (down by $1,766 per patient per month) and emergency department visits (down by $6 per patient per month).

Both the number of inpatient stays and the length of hospitalizations decreased markedly. The mean length of stay per hospitalization dropped from 14.5 days before the clinic was implemented to 10 days afterward, the investigators said (Arch. Pediatr. Adolesc. Med. 2011 Feb. 7 [doi:10.1001/archpediatrics.2011.5]).

"Future research is needed to determine whether the coordinated and comprehensive care resulted in better patient quality of life and health status, as well as improvement in the quality of life, mental health, satisfactions care, and general well-being of their care providers," Dr. Casey and his associates added.

A hospital-based clinic that coordinated medical, nutritional, and developmental care for medically complex children throughout a single state markedly cut health costs, according to a study published online Feb. 7 in the Archives of Pediatrics and Adolescent Medicine.

This program, which created a hospital-based medical home for the pediatric patients, significantly decreased inpatient visits, lengths of hospital stay, and emergency department visits for children with multiple chronic conditions, resulting in a net reduction of $1,179 per patient per month. Extrapolating from these results, the annual savings in health care costs for a similar statewide population of patients would be $3,183,300, said Dr. Patrick H. Casey and his associates at Arkansas Children’s Hospital, Little Rock.

The investigators evaluated the costs of care before and after the implementation of the Medical Home Clinic at their hospital, which is the only tertiary care center that provides subspecialty and surgical care for children in the state. Outpatient staff includes a neonatologist, developmental pediatricians, hospitalists, general pediatricians, nurses, nutritionists, social workers, speech pathologists, and child psychologists.

In addition to providing health care, the team ensured that community services were provided for patients when necessary. A nurse was available for telephone consultations, coordinating appointments, and assisting with clinical decision-making and acute care issues.

In a retrospective cohort study that they described as "the first examination of the aggregate cost impact of a comprehensive care model for medically complex children," Dr. Casey and his colleagues reviewed the records of 225 children who had at least two serious chronic conditions. The median age of the study subjects was 13 months; 62% were boys and half were white.

Most of the study subjects (67%) had been born preterm. Forty percent had a recognized syndrome or congenital anomaly, 37% had bronchopulmonary dysplasia, 56% required a gastrostomy tube, 7% required a tracheostomy tube, 33% had cerebral palsy, and 72% were developmentally delayed.

The cost of outpatient care increased by $53 per patient per month after the Medical Home Clinic was established, but this rise was more than offset by marked decreases in costs for inpatient care (down by $1,766 per patient per month) and emergency department visits (down by $6 per patient per month).

Both the number of inpatient stays and the length of hospitalizations decreased markedly. The mean length of stay per hospitalization dropped from 14.5 days before the clinic was implemented to 10 days afterward, the investigators said (Arch. Pediatr. Adolesc. Med. 2011 Feb. 7 [doi:10.1001/archpediatrics.2011.5]).

"Future research is needed to determine whether the coordinated and comprehensive care resulted in better patient quality of life and health status, as well as improvement in the quality of life, mental health, satisfactions care, and general well-being of their care providers," Dr. Casey and his associates added.

Polycystic ovary syndrome appears to be manifesting at younger ages than previously thought, a study has shown.

The disorder should be considered and a thorough work-up performed in prepubertal girls who have risk factors suggestive of PCOS, with particular attention given to hyperinsulinemia and early pubarche and thelarche, said Dr. Jason Bronstein and his associates at New York University.

In what they described as the largest pediatric PCOS study to date, the researchers found "a large subgroup of young PCOS girls with characteristic metabolic derangements at a younger age, suggesting a need for early therapeutic interventions." Early onset of PCOS does not portend well for future complications such as infertility, metabolic syndrome, and vascular disease. However, earlier recognition and treatment of PCOS might reduce morbidity in later adolescence and adulthood, they noted.

The investigators performed a retrospective, cross-sectional chart study of 58 patients from diverse ethnic backgrounds who attended two large, urban tertiary care centers and were diagnosed as having PCOS between ages 9 and 18. Fifteen (26%) of these subjects were preadolescents aged 9-12, and 43 (74%) were adolescents aged 13-18 years.

The severity of PCOS was similar between preadolescents and adolescents. Hyperinsulinemia was present in similar proportions of both groups, indicating that metabolic derangement is already present in the youngest girls with PCOS.

However, preadolescent girls were different in that they had significantly earlier pubarche and thelarche than did adolescent girls with PCOS, and the disorder developed much sooner after thelarche in the younger girls. Clinicians should look for early pubarche and thelarche in girls predisposed to PCOS, the investigators said (J. Pediatr. Adolesc. Gynecol. 2011;24:15-20).

The two groups also had similar risk factors. Mothers or other relatives had PCOS in approximately 14% of the study subjects, and there were no significant differences between preadolescents and adolescents in historical risk factors such as gestational age at birth, birth weight, childhood obesity, or family history of obesity, diabetes, or hypertension.

There also were no differences between preadolescents and adolescents in clinical risk factors such as body mass index, acne, hirsutism, alopecia, or hyperandrogenism, and no differences in biochemical risk factors such as serum total testosterone and free testosterone levels, insulin resistance, HDL levels, triglyceride levels, or fasting glucose levels.

These findings show that "pediatricians need a high index of suspicion in order to diagnose PCOS in preadolescents. We recommend that pediatricians ascertain risk for PCOS in their patients, including maternal factors, family history, birth weight, metabolic factors, and history of premature pubarche and/or early thelarche," Dr. Bronstein and his colleagues said.

No funding sources or financial conflicts of interest were reported.

Polycystic ovary syndrome appears to be manifesting at younger ages than previously thought, a study has shown.

The disorder should be considered and a thorough work-up performed in prepubertal girls who have risk factors suggestive of PCOS, with particular attention given to hyperinsulinemia and early pubarche and thelarche, said Dr. Jason Bronstein and his associates at New York University.

In what they described as the largest pediatric PCOS study to date, the researchers found "a large subgroup of young PCOS girls with characteristic metabolic derangements at a younger age, suggesting a need for early therapeutic interventions." Early onset of PCOS does not portend well for future complications such as infertility, metabolic syndrome, and vascular disease. However, earlier recognition and treatment of PCOS might reduce morbidity in later adolescence and adulthood, they noted.

The investigators performed a retrospective, cross-sectional chart study of 58 patients from diverse ethnic backgrounds who attended two large, urban tertiary care centers and were diagnosed as having PCOS between ages 9 and 18. Fifteen (26%) of these subjects were preadolescents aged 9-12, and 43 (74%) were adolescents aged 13-18 years.

The severity of PCOS was similar between preadolescents and adolescents. Hyperinsulinemia was present in similar proportions of both groups, indicating that metabolic derangement is already present in the youngest girls with PCOS.

However, preadolescent girls were different in that they had significantly earlier pubarche and thelarche than did adolescent girls with PCOS, and the disorder developed much sooner after thelarche in the younger girls. Clinicians should look for early pubarche and thelarche in girls predisposed to PCOS, the investigators said (J. Pediatr. Adolesc. Gynecol. 2011;24:15-20).

The two groups also had similar risk factors. Mothers or other relatives had PCOS in approximately 14% of the study subjects, and there were no significant differences between preadolescents and adolescents in historical risk factors such as gestational age at birth, birth weight, childhood obesity, or family history of obesity, diabetes, or hypertension.

There also were no differences between preadolescents and adolescents in clinical risk factors such as body mass index, acne, hirsutism, alopecia, or hyperandrogenism, and no differences in biochemical risk factors such as serum total testosterone and free testosterone levels, insulin resistance, HDL levels, triglyceride levels, or fasting glucose levels.

These findings show that "pediatricians need a high index of suspicion in order to diagnose PCOS in preadolescents. We recommend that pediatricians ascertain risk for PCOS in their patients, including maternal factors, family history, birth weight, metabolic factors, and history of premature pubarche and/or early thelarche," Dr. Bronstein and his colleagues said.

No funding sources or financial conflicts of interest were reported.

Polycystic ovary syndrome appears to be manifesting at younger ages than previously thought, a study has shown.

The disorder should be considered and a thorough work-up performed in prepubertal girls who have risk factors suggestive of PCOS, with particular attention given to hyperinsulinemia and early pubarche and thelarche, said Dr. Jason Bronstein and his associates at New York University.

In what they described as the largest pediatric PCOS study to date, the researchers found "a large subgroup of young PCOS girls with characteristic metabolic derangements at a younger age, suggesting a need for early therapeutic interventions." Early onset of PCOS does not portend well for future complications such as infertility, metabolic syndrome, and vascular disease. However, earlier recognition and treatment of PCOS might reduce morbidity in later adolescence and adulthood, they noted.

The investigators performed a retrospective, cross-sectional chart study of 58 patients from diverse ethnic backgrounds who attended two large, urban tertiary care centers and were diagnosed as having PCOS between ages 9 and 18. Fifteen (26%) of these subjects were preadolescents aged 9-12, and 43 (74%) were adolescents aged 13-18 years.

The severity of PCOS was similar between preadolescents and adolescents. Hyperinsulinemia was present in similar proportions of both groups, indicating that metabolic derangement is already present in the youngest girls with PCOS.

However, preadolescent girls were different in that they had significantly earlier pubarche and thelarche than did adolescent girls with PCOS, and the disorder developed much sooner after thelarche in the younger girls. Clinicians should look for early pubarche and thelarche in girls predisposed to PCOS, the investigators said (J. Pediatr. Adolesc. Gynecol. 2011;24:15-20).

The two groups also had similar risk factors. Mothers or other relatives had PCOS in approximately 14% of the study subjects, and there were no significant differences between preadolescents and adolescents in historical risk factors such as gestational age at birth, birth weight, childhood obesity, or family history of obesity, diabetes, or hypertension.

There also were no differences between preadolescents and adolescents in clinical risk factors such as body mass index, acne, hirsutism, alopecia, or hyperandrogenism, and no differences in biochemical risk factors such as serum total testosterone and free testosterone levels, insulin resistance, HDL levels, triglyceride levels, or fasting glucose levels.

These findings show that "pediatricians need a high index of suspicion in order to diagnose PCOS in preadolescents. We recommend that pediatricians ascertain risk for PCOS in their patients, including maternal factors, family history, birth weight, metabolic factors, and history of premature pubarche and/or early thelarche," Dr. Bronstein and his colleagues said.

No funding sources or financial conflicts of interest were reported.

The quadrivalent human papillomavirus vaccine prevents the infection as well as the development of external anogenital lesions associated with the virus in boys and men, according to a report in the Feb. 3 issue of the New England Journal of Medicine.

It is likely that the vaccine will similarly cut down on human papillomavirus (HPV) transmission and prevent the anogenital cancer, intraepithelial neoplasia, recurrent respiratory papillomatosis, and cancer of the oropharynx that eventually arise from HPV infection, but "each of these potential outcomes must be directly demonstrated" in future studies, said Anna R. Giuliano, Ph.D., of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla., and her associates.

The investigators assessed the efficacy of the vaccine (Gardasil, Merck & Co.), which is active against HPV types 6, 11, 16, and 18, in a prospective international clinical trial involving 4,065 healthy boys and men aged 16-26 years followed at 71 medical centers in 18 countries. A total of 2,032 subjects were randomly assigned to receive the vaccine and 2,033 to receive placebo injections, and they were followed for a median of 3 years.

All of the study subjects reported having had no more than five sexual partners in their lifetimes. A total of 3,463 reported that their sexual partners were exclusively female, while 602 reported that they had sex with male partners.

Specimens for HPV testing were collected separately from the penis, scrotum, perineal area, and perianal regions at baseline and at intervals during follow-up. For subjects who reported having sex with male partners, intra-anal specimens also were collected.

The primary end point of the study was the presence or absence of external genital lesions associated with the four HPV strains covered by the vaccine. These were defined as condylomata acuminata (external genital warts); penile, perianal, or perineal intraepithelial neoplasia (PIN); or penile, perianal, or perineal cancer.

Within 30 days of the final dose of the vaccine, 97% of the subjects showed seroconversion for all four HPV strains. Nine subjects did not show seroconversion to any of the HPV strains.

In this intention-to-treat population, there were 36 lesions in the vaccine group, compared with 89 in the placebo group, "resulting in an observed efficacy of 60%," Dr. Giuliano and her colleagues said. The number of lesions associated with HPV-6 was reduced by 60%, with HPV-11 by 76%, HPV-16 by 70%, and HPV-18 by 34%.

A subgroup of 2,805 subjects qualified for the per-protocol population: 1,397 received the active vaccine and 1,408 received placebo. In this analysis, there were 6 lesions in the vaccine group, compared with 36 in the placebo group, for an observed efficacy of 84%.

The number of lesions associated with HPV types 6 and 11 was reduced by 84% and 91%, respectively, in this analysis, the investigators wrote (N. Engl. J. Med. 2011;364:401-11).

No lesions associated with HPV types 16 or 18 were found in the vaccine recipients in the per-protocol analysis, while three developed in the placebo group. No cases of PIN developed in the vaccine group, but three developed in the placebo group.

Regarding persistent HPV infection, the vaccine significantly decreased the rate by 48% in the intention-to-treat population and by 86% in the per-protocol population.

The percentage of study subjects who reported adverse events was slightly higher among those who received active vaccine (69%) than placebo (64%). Most such events involved pain at the injection site and were characterized as mild. There were no serious adverse events, and the same number of subjects in each group dropped out of the study because of adverse effects.

The rates of adverse events were lower in this study of males than have been reported among female recipients of the HPV vaccine. This may be because males have more muscle mass, and thus less pain, at the injection site. It also may be the result of reluctance to report pain or minor events among males, the investigators added.

Three subjects in the per-protocol population who received active vaccine developed genital lesions. "These cases may represent true vaccine failures, false-negative results of HPV DNA or antibody-detection tests at baseline, or failure to identify these lesions at baseline," Dr. Giuliano and her associates said.

One limitation of this study was that none of the subjects had more than five lifetime sexual partners, "which may have resulted in overrepresentation of subjects with a low likelihood of HPV exposure at baseline and a low likelihood of subsequent exposure, as compared with the general population," they added.

This study was funded by Merck & Co., the National Center for Research Resources, and the National Institutes of Health. Merck designed the study, collated the data, and performed statistical analyses. The investigators reported ties to Merck, GlaxoSmithKline, Qiagen, and AstraZeneca.

The quadrivalent human papillomavirus vaccine prevents the infection as well as the development of external anogenital lesions associated with the virus in boys and men, according to a report in the Feb. 3 issue of the New England Journal of Medicine.

It is likely that the vaccine will similarly cut down on human papillomavirus (HPV) transmission and prevent the anogenital cancer, intraepithelial neoplasia, recurrent respiratory papillomatosis, and cancer of the oropharynx that eventually arise from HPV infection, but "each of these potential outcomes must be directly demonstrated" in future studies, said Anna R. Giuliano, Ph.D., of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla., and her associates.

The investigators assessed the efficacy of the vaccine (Gardasil, Merck & Co.), which is active against HPV types 6, 11, 16, and 18, in a prospective international clinical trial involving 4,065 healthy boys and men aged 16-26 years followed at 71 medical centers in 18 countries. A total of 2,032 subjects were randomly assigned to receive the vaccine and 2,033 to receive placebo injections, and they were followed for a median of 3 years.

All of the study subjects reported having had no more than five sexual partners in their lifetimes. A total of 3,463 reported that their sexual partners were exclusively female, while 602 reported that they had sex with male partners.

Specimens for HPV testing were collected separately from the penis, scrotum, perineal area, and perianal regions at baseline and at intervals during follow-up. For subjects who reported having sex with male partners, intra-anal specimens also were collected.

The primary end point of the study was the presence or absence of external genital lesions associated with the four HPV strains covered by the vaccine. These were defined as condylomata acuminata (external genital warts); penile, perianal, or perineal intraepithelial neoplasia (PIN); or penile, perianal, or perineal cancer.

Within 30 days of the final dose of the vaccine, 97% of the subjects showed seroconversion for all four HPV strains. Nine subjects did not show seroconversion to any of the HPV strains.

In this intention-to-treat population, there were 36 lesions in the vaccine group, compared with 89 in the placebo group, "resulting in an observed efficacy of 60%," Dr. Giuliano and her colleagues said. The number of lesions associated with HPV-6 was reduced by 60%, with HPV-11 by 76%, HPV-16 by 70%, and HPV-18 by 34%.

A subgroup of 2,805 subjects qualified for the per-protocol population: 1,397 received the active vaccine and 1,408 received placebo. In this analysis, there were 6 lesions in the vaccine group, compared with 36 in the placebo group, for an observed efficacy of 84%.

The number of lesions associated with HPV types 6 and 11 was reduced by 84% and 91%, respectively, in this analysis, the investigators wrote (N. Engl. J. Med. 2011;364:401-11).

No lesions associated with HPV types 16 or 18 were found in the vaccine recipients in the per-protocol analysis, while three developed in the placebo group. No cases of PIN developed in the vaccine group, but three developed in the placebo group.

Regarding persistent HPV infection, the vaccine significantly decreased the rate by 48% in the intention-to-treat population and by 86% in the per-protocol population.

The percentage of study subjects who reported adverse events was slightly higher among those who received active vaccine (69%) than placebo (64%). Most such events involved pain at the injection site and were characterized as mild. There were no serious adverse events, and the same number of subjects in each group dropped out of the study because of adverse effects.

The rates of adverse events were lower in this study of males than have been reported among female recipients of the HPV vaccine. This may be because males have more muscle mass, and thus less pain, at the injection site. It also may be the result of reluctance to report pain or minor events among males, the investigators added.

Three subjects in the per-protocol population who received active vaccine developed genital lesions. "These cases may represent true vaccine failures, false-negative results of HPV DNA or antibody-detection tests at baseline, or failure to identify these lesions at baseline," Dr. Giuliano and her associates said.

One limitation of this study was that none of the subjects had more than five lifetime sexual partners, "which may have resulted in overrepresentation of subjects with a low likelihood of HPV exposure at baseline and a low likelihood of subsequent exposure, as compared with the general population," they added.

This study was funded by Merck & Co., the National Center for Research Resources, and the National Institutes of Health. Merck designed the study, collated the data, and performed statistical analyses. The investigators reported ties to Merck, GlaxoSmithKline, Qiagen, and AstraZeneca.

The quadrivalent human papillomavirus vaccine prevents the infection as well as the development of external anogenital lesions associated with the virus in boys and men, according to a report in the Feb. 3 issue of the New England Journal of Medicine.

It is likely that the vaccine will similarly cut down on human papillomavirus (HPV) transmission and prevent the anogenital cancer, intraepithelial neoplasia, recurrent respiratory papillomatosis, and cancer of the oropharynx that eventually arise from HPV infection, but "each of these potential outcomes must be directly demonstrated" in future studies, said Anna R. Giuliano, Ph.D., of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla., and her associates.

The investigators assessed the efficacy of the vaccine (Gardasil, Merck & Co.), which is active against HPV types 6, 11, 16, and 18, in a prospective international clinical trial involving 4,065 healthy boys and men aged 16-26 years followed at 71 medical centers in 18 countries. A total of 2,032 subjects were randomly assigned to receive the vaccine and 2,033 to receive placebo injections, and they were followed for a median of 3 years.

All of the study subjects reported having had no more than five sexual partners in their lifetimes. A total of 3,463 reported that their sexual partners were exclusively female, while 602 reported that they had sex with male partners.

Specimens for HPV testing were collected separately from the penis, scrotum, perineal area, and perianal regions at baseline and at intervals during follow-up. For subjects who reported having sex with male partners, intra-anal specimens also were collected.

The primary end point of the study was the presence or absence of external genital lesions associated with the four HPV strains covered by the vaccine. These were defined as condylomata acuminata (external genital warts); penile, perianal, or perineal intraepithelial neoplasia (PIN); or penile, perianal, or perineal cancer.

Within 30 days of the final dose of the vaccine, 97% of the subjects showed seroconversion for all four HPV strains. Nine subjects did not show seroconversion to any of the HPV strains.

In this intention-to-treat population, there were 36 lesions in the vaccine group, compared with 89 in the placebo group, "resulting in an observed efficacy of 60%," Dr. Giuliano and her colleagues said. The number of lesions associated with HPV-6 was reduced by 60%, with HPV-11 by 76%, HPV-16 by 70%, and HPV-18 by 34%.

A subgroup of 2,805 subjects qualified for the per-protocol population: 1,397 received the active vaccine and 1,408 received placebo. In this analysis, there were 6 lesions in the vaccine group, compared with 36 in the placebo group, for an observed efficacy of 84%.

The number of lesions associated with HPV types 6 and 11 was reduced by 84% and 91%, respectively, in this analysis, the investigators wrote (N. Engl. J. Med. 2011;364:401-11).

No lesions associated with HPV types 16 or 18 were found in the vaccine recipients in the per-protocol analysis, while three developed in the placebo group. No cases of PIN developed in the vaccine group, but three developed in the placebo group.

Regarding persistent HPV infection, the vaccine significantly decreased the rate by 48% in the intention-to-treat population and by 86% in the per-protocol population.

The percentage of study subjects who reported adverse events was slightly higher among those who received active vaccine (69%) than placebo (64%). Most such events involved pain at the injection site and were characterized as mild. There were no serious adverse events, and the same number of subjects in each group dropped out of the study because of adverse effects.

The rates of adverse events were lower in this study of males than have been reported among female recipients of the HPV vaccine. This may be because males have more muscle mass, and thus less pain, at the injection site. It also may be the result of reluctance to report pain or minor events among males, the investigators added.

Three subjects in the per-protocol population who received active vaccine developed genital lesions. "These cases may represent true vaccine failures, false-negative results of HPV DNA or antibody-detection tests at baseline, or failure to identify these lesions at baseline," Dr. Giuliano and her associates said.

One limitation of this study was that none of the subjects had more than five lifetime sexual partners, "which may have resulted in overrepresentation of subjects with a low likelihood of HPV exposure at baseline and a low likelihood of subsequent exposure, as compared with the general population," they added.

This study was funded by Merck & Co., the National Center for Research Resources, and the National Institutes of Health. Merck designed the study, collated the data, and performed statistical analyses. The investigators reported ties to Merck, GlaxoSmithKline, Qiagen, and AstraZeneca.

The quadrivalent human papillomavirus vaccine prevents the infection as well as the development of external anogenital lesions associated with the virus in boys and men, according to a report in the Feb. 3 issue of the New England Journal of Medicine.

It is likely that the vaccine will similarly cut down on human papillomavirus (HPV) transmission and prevent the anogenital cancer, intraepithelial neoplasia, recurrent respiratory papillomatosis, and cancer of the oropharynx that eventually arise from HPV infection, but "each of these potential outcomes must be directly demonstrated" in future studies, said Anna R. Giuliano, Ph.D., of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla., and her associates.

The investigators assessed the efficacy of the vaccine (Gardasil, Merck & Co.), which is active against HPV types 6, 11, 16, and 18, in a prospective international clinical trial involving 4,065 healthy boys and men aged 16-26 years followed at 71 medical centers in 18 countries. A total of 2,032 subjects were randomly assigned to receive the vaccine and 2,033 to receive placebo injections, and they were followed for a median of 3 years.

All of the study subjects reported having had no more than five sexual partners in their lifetimes. A total of 3,463 reported that their sexual partners were exclusively female, while 602 reported that they had sex with male partners.

Specimens for HPV testing were collected separately from the penis, scrotum, perineal area, and perianal regions at baseline and at intervals during follow-up. For subjects who reported having sex with male partners, intra-anal specimens also were collected.

The primary end point of the study was the presence or absence of external genital lesions associated with the four HPV strains covered by the vaccine. These were defined as condylomata acuminata (external genital warts); penile, perianal, or perineal intraepithelial neoplasia (PIN); or penile, perianal, or perineal cancer.

Within 30 days of the final dose of the vaccine, 97% of the subjects showed seroconversion for all four HPV strains. Nine subjects did not show seroconversion to any of the HPV strains.

In this intention-to-treat population, there were 36 lesions in the vaccine group, compared with 89 in the placebo group, "resulting in an observed efficacy of 60%," Dr. Giuliano and her colleagues said. The number of lesions associated with HPV-6 was reduced by 60%, with HPV-11 by 76%, HPV-16 by 70%, and HPV-18 by 34%.

A subgroup of 2,805 subjects qualified for the per-protocol population: 1,397 received the active vaccine and 1,408 received placebo. In this analysis, there were 6 lesions in the vaccine group, compared with 36 in the placebo group, for an observed efficacy of 84%.

The number of lesions associated with HPV types 6 and 11 was reduced by 84% and 91%, respectively, in this analysis, the investigators wrote (N. Engl. J. Med. 2011;364:401-11).

No lesions associated with HPV types 16 or 18 were found in the vaccine recipients in the per-protocol analysis, while three developed in the placebo group. No cases of PIN developed in the vaccine group, but three developed in the placebo group.

Regarding persistent HPV infection, the vaccine significantly decreased the rate by 48% in the intention-to-treat population and by 86% in the per-protocol population.

The percentage of study subjects who reported adverse events was slightly higher among those who received active vaccine (69%) than placebo (64%). Most such events involved pain at the injection site and were characterized as mild. There were no serious adverse events, and the same number of subjects in each group dropped out of the study because of adverse effects.

The rates of adverse events were lower in this study of males than have been reported among female recipients of the HPV vaccine. This may be because males have more muscle mass, and thus less pain, at the injection site. It also may be the result of reluctance to report pain or minor events among males, the investigators added.

Three subjects in the per-protocol population who received active vaccine developed genital lesions. "These cases may represent true vaccine failures, false-negative results of HPV DNA or antibody-detection tests at baseline, or failure to identify these lesions at baseline," Dr. Giuliano and her associates said.

One limitation of this study was that none of the subjects had more than five lifetime sexual partners, "which may have resulted in overrepresentation of subjects with a low likelihood of HPV exposure at baseline and a low likelihood of subsequent exposure, as compared with the general population," they added.

This study was funded by Merck & Co., the National Center for Research Resources, and the National Institutes of Health. Merck designed the study, collated the data, and performed statistical analyses. The investigators reported ties to Merck, GlaxoSmithKline, Qiagen, and AstraZeneca.

The quadrivalent human papillomavirus vaccine prevents the infection as well as the development of external anogenital lesions associated with the virus in boys and men, according to a report in the Feb. 3 issue of the New England Journal of Medicine.

It is likely that the vaccine will similarly cut down on human papillomavirus (HPV) transmission and prevent the anogenital cancer, intraepithelial neoplasia, recurrent respiratory papillomatosis, and cancer of the oropharynx that eventually arise from HPV infection, but "each of these potential outcomes must be directly demonstrated" in future studies, said Anna R. Giuliano, Ph.D., of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla., and her associates.

The investigators assessed the efficacy of the vaccine (Gardasil, Merck & Co.), which is active against HPV types 6, 11, 16, and 18, in a prospective international clinical trial involving 4,065 healthy boys and men aged 16-26 years followed at 71 medical centers in 18 countries. A total of 2,032 subjects were randomly assigned to receive the vaccine and 2,033 to receive placebo injections, and they were followed for a median of 3 years.

All of the study subjects reported having had no more than five sexual partners in their lifetimes. A total of 3,463 reported that their sexual partners were exclusively female, while 602 reported that they had sex with male partners.

Specimens for HPV testing were collected separately from the penis, scrotum, perineal area, and perianal regions at baseline and at intervals during follow-up. For subjects who reported having sex with male partners, intra-anal specimens also were collected.

The primary end point of the study was the presence or absence of external genital lesions associated with the four HPV strains covered by the vaccine. These were defined as condylomata acuminata (external genital warts); penile, perianal, or perineal intraepithelial neoplasia (PIN); or penile, perianal, or perineal cancer.

Within 30 days of the final dose of the vaccine, 97% of the subjects showed seroconversion for all four HPV strains. Nine subjects did not show seroconversion to any of the HPV strains.

In this intention-to-treat population, there were 36 lesions in the vaccine group, compared with 89 in the placebo group, "resulting in an observed efficacy of 60%," Dr. Giuliano and her colleagues said. The number of lesions associated with HPV-6 was reduced by 60%, with HPV-11 by 76%, HPV-16 by 70%, and HPV-18 by 34%.

A subgroup of 2,805 subjects qualified for the per-protocol population: 1,397 received the active vaccine and 1,408 received placebo. In this analysis, there were 6 lesions in the vaccine group, compared with 36 in the placebo group, for an observed efficacy of 84%.

The number of lesions associated with HPV types 6 and 11 was reduced by 84% and 91%, respectively, in this analysis, the investigators wrote (N. Engl. J. Med. 2011;364:401-11).

No lesions associated with HPV types 16 or 18 were found in the vaccine recipients in the per-protocol analysis, while three developed in the placebo group. No cases of PIN developed in the vaccine group, but three developed in the placebo group.

Regarding persistent HPV infection, the vaccine significantly decreased the rate by 48% in the intention-to-treat population and by 86% in the per-protocol population.

The percentage of study subjects who reported adverse events was slightly higher among those who received active vaccine (69%) than placebo (64%). Most such events involved pain at the injection site and were characterized as mild. There were no serious adverse events, and the same number of subjects in each group dropped out of the study because of adverse effects.

The rates of adverse events were lower in this study of males than have been reported among female recipients of the HPV vaccine. This may be because males have more muscle mass, and thus less pain, at the injection site. It also may be the result of reluctance to report pain or minor events among males, the investigators added.

Three subjects in the per-protocol population who received active vaccine developed genital lesions. "These cases may represent true vaccine failures, false-negative results of HPV DNA or antibody-detection tests at baseline, or failure to identify these lesions at baseline," Dr. Giuliano and her associates said.

One limitation of this study was that none of the subjects had more than five lifetime sexual partners, "which may have resulted in overrepresentation of subjects with a low likelihood of HPV exposure at baseline and a low likelihood of subsequent exposure, as compared with the general population," they added.

This study was funded by Merck & Co., the National Center for Research Resources, and the National Institutes of Health. Merck designed the study, collated the data, and performed statistical analyses. The investigators reported ties to Merck, GlaxoSmithKline, Qiagen, and AstraZeneca.

The quadrivalent human papillomavirus vaccine prevents the infection as well as the development of external anogenital lesions associated with the virus in boys and men, according to a report in the Feb. 3 issue of the New England Journal of Medicine.

It is likely that the vaccine will similarly cut down on human papillomavirus (HPV) transmission and prevent the anogenital cancer, intraepithelial neoplasia, recurrent respiratory papillomatosis, and cancer of the oropharynx that eventually arise from HPV infection, but "each of these potential outcomes must be directly demonstrated" in future studies, said Anna R. Giuliano, Ph.D., of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla., and her associates.

The investigators assessed the efficacy of the vaccine (Gardasil, Merck & Co.), which is active against HPV types 6, 11, 16, and 18, in a prospective international clinical trial involving 4,065 healthy boys and men aged 16-26 years followed at 71 medical centers in 18 countries. A total of 2,032 subjects were randomly assigned to receive the vaccine and 2,033 to receive placebo injections, and they were followed for a median of 3 years.

All of the study subjects reported having had no more than five sexual partners in their lifetimes. A total of 3,463 reported that their sexual partners were exclusively female, while 602 reported that they had sex with male partners.

Specimens for HPV testing were collected separately from the penis, scrotum, perineal area, and perianal regions at baseline and at intervals during follow-up. For subjects who reported having sex with male partners, intra-anal specimens also were collected.

The primary end point of the study was the presence or absence of external genital lesions associated with the four HPV strains covered by the vaccine. These were defined as condylomata acuminata (external genital warts); penile, perianal, or perineal intraepithelial neoplasia (PIN); or penile, perianal, or perineal cancer.

Within 30 days of the final dose of the vaccine, 97% of the subjects showed seroconversion for all four HPV strains. Nine subjects did not show seroconversion to any of the HPV strains.

In this intention-to-treat population, there were 36 lesions in the vaccine group, compared with 89 in the placebo group, "resulting in an observed efficacy of 60%," Dr. Giuliano and her colleagues said. The number of lesions associated with HPV-6 was reduced by 60%, with HPV-11 by 76%, HPV-16 by 70%, and HPV-18 by 34%.

A subgroup of 2,805 subjects qualified for the per-protocol population: 1,397 received the active vaccine and 1,408 received placebo. In this analysis, there were 6 lesions in the vaccine group, compared with 36 in the placebo group, for an observed efficacy of 84%.

The number of lesions associated with HPV types 6 and 11 was reduced by 84% and 91%, respectively, in this analysis, the investigators wrote (N. Engl. J. Med. 2011;364:401-11).

No lesions associated with HPV types 16 or 18 were found in the vaccine recipients in the per-protocol analysis, while three developed in the placebo group. No cases of PIN developed in the vaccine group, but three developed in the placebo group.

Regarding persistent HPV infection, the vaccine significantly decreased the rate by 48% in the intention-to-treat population and by 86% in the per-protocol population.

The percentage of study subjects who reported adverse events was slightly higher among those who received active vaccine (69%) than placebo (64%). Most such events involved pain at the injection site and were characterized as mild. There were no serious adverse events, and the same number of subjects in each group dropped out of the study because of adverse effects.

The rates of adverse events were lower in this study of males than have been reported among female recipients of the HPV vaccine. This may be because males have more muscle mass, and thus less pain, at the injection site. It also may be the result of reluctance to report pain or minor events among males, the investigators added.

Three subjects in the per-protocol population who received active vaccine developed genital lesions. "These cases may represent true vaccine failures, false-negative results of HPV DNA or antibody-detection tests at baseline, or failure to identify these lesions at baseline," Dr. Giuliano and her associates said.

One limitation of this study was that none of the subjects had more than five lifetime sexual partners, "which may have resulted in overrepresentation of subjects with a low likelihood of HPV exposure at baseline and a low likelihood of subsequent exposure, as compared with the general population," they added.

This study was funded by Merck & Co., the National Center for Research Resources, and the National Institutes of Health. Merck designed the study, collated the data, and performed statistical analyses. The investigators reported ties to Merck, GlaxoSmithKline, Qiagen, and AstraZeneca.

The quadrivalent human papillomavirus vaccine prevents the infection as well as the development of external anogenital lesions associated with the virus in boys and men, according to a report in the Feb. 3 issue of the New England Journal of Medicine.

It is likely that the vaccine will similarly cut down on human papillomavirus (HPV) transmission and prevent the anogenital cancer, intraepithelial neoplasia, recurrent respiratory papillomatosis, and cancer of the oropharynx that eventually arise from HPV infection, but "each of these potential outcomes must be directly demonstrated" in future studies, said Anna R. Giuliano, Ph.D., of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla., and her associates.

The investigators assessed the efficacy of the vaccine (Gardasil, Merck & Co.), which is active against HPV types 6, 11, 16, and 18, in a prospective international clinical trial involving 4,065 healthy boys and men aged 16-26 years followed at 71 medical centers in 18 countries. A total of 2,032 subjects were randomly assigned to receive the vaccine and 2,033 to receive placebo injections, and they were followed for a median of 3 years.

All of the study subjects reported having had no more than five sexual partners in their lifetimes. A total of 3,463 reported that their sexual partners were exclusively female, while 602 reported that they had sex with male partners.

Specimens for HPV testing were collected separately from the penis, scrotum, perineal area, and perianal regions at baseline and at intervals during follow-up. For subjects who reported having sex with male partners, intra-anal specimens also were collected.

The primary end point of the study was the presence or absence of external genital lesions associated with the four HPV strains covered by the vaccine. These were defined as condylomata acuminata (external genital warts); penile, perianal, or perineal intraepithelial neoplasia (PIN); or penile, perianal, or perineal cancer.

Within 30 days of the final dose of the vaccine, 97% of the subjects showed seroconversion for all four HPV strains. Nine subjects did not show seroconversion to any of the HPV strains.

In this intention-to-treat population, there were 36 lesions in the vaccine group, compared with 89 in the placebo group, "resulting in an observed efficacy of 60%," Dr. Giuliano and her colleagues said. The number of lesions associated with HPV-6 was reduced by 60%, with HPV-11 by 76%, HPV-16 by 70%, and HPV-18 by 34%.

A subgroup of 2,805 subjects qualified for the per-protocol population: 1,397 received the active vaccine and 1,408 received placebo. In this analysis, there were 6 lesions in the vaccine group, compared with 36 in the placebo group, for an observed efficacy of 84%.

The number of lesions associated with HPV types 6 and 11 was reduced by 84% and 91%, respectively, in this analysis, the investigators wrote (N. Engl. J. Med. 2011;364:401-11).

No lesions associated with HPV types 16 or 18 were found in the vaccine recipients in the per-protocol analysis, while three developed in the placebo group. No cases of PIN developed in the vaccine group, but three developed in the placebo group.

Regarding persistent HPV infection, the vaccine significantly decreased the rate by 48% in the intention-to-treat population and by 86% in the per-protocol population.

The percentage of study subjects who reported adverse events was slightly higher among those who received active vaccine (69%) than placebo (64%). Most such events involved pain at the injection site and were characterized as mild. There were no serious adverse events, and the same number of subjects in each group dropped out of the study because of adverse effects.

The rates of adverse events were lower in this study of males than have been reported among female recipients of the HPV vaccine. This may be because males have more muscle mass, and thus less pain, at the injection site. It also may be the result of reluctance to report pain or minor events among males, the investigators added.

Three subjects in the per-protocol population who received active vaccine developed genital lesions. "These cases may represent true vaccine failures, false-negative results of HPV DNA or antibody-detection tests at baseline, or failure to identify these lesions at baseline," Dr. Giuliano and her associates said.

One limitation of this study was that none of the subjects had more than five lifetime sexual partners, "which may have resulted in overrepresentation of subjects with a low likelihood of HPV exposure at baseline and a low likelihood of subsequent exposure, as compared with the general population," they added.

This study was funded by Merck & Co., the National Center for Research Resources, and the National Institutes of Health. Merck designed the study, collated the data, and performed statistical analyses. The investigators reported ties to Merck, GlaxoSmithKline, Qiagen, and AstraZeneca.

The quadrivalent human papillomavirus vaccine prevents the infection as well as the development of external anogenital lesions associated with the virus in boys and men, according to a report in the Feb. 3 issue of the New England Journal of Medicine.

It is likely that the vaccine will similarly cut down on human papillomavirus (HPV) transmission and prevent the anogenital cancer, intraepithelial neoplasia, recurrent respiratory papillomatosis, and cancer of the oropharynx that eventually arise from HPV infection, but "each of these potential outcomes must be directly demonstrated" in future studies, said Anna R. Giuliano, Ph.D., of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla., and her associates.

The investigators assessed the efficacy of the vaccine (Gardasil, Merck & Co.), which is active against HPV types 6, 11, 16, and 18, in a prospective international clinical trial involving 4,065 healthy boys and men aged 16-26 years followed at 71 medical centers in 18 countries. A total of 2,032 subjects were randomly assigned to receive the vaccine and 2,033 to receive placebo injections, and they were followed for a median of 3 years.

All of the study subjects reported having had no more than five sexual partners in their lifetimes. A total of 3,463 reported that their sexual partners were exclusively female, while 602 reported that they had sex with male partners.

Specimens for HPV testing were collected separately from the penis, scrotum, perineal area, and perianal regions at baseline and at intervals during follow-up. For subjects who reported having sex with male partners, intra-anal specimens also were collected.

The primary end point of the study was the presence or absence of external genital lesions associated with the four HPV strains covered by the vaccine. These were defined as condylomata acuminata (external genital warts); penile, perianal, or perineal intraepithelial neoplasia (PIN); or penile, perianal, or perineal cancer.

Within 30 days of the final dose of the vaccine, 97% of the subjects showed seroconversion for all four HPV strains. Nine subjects did not show seroconversion to any of the HPV strains.

In this intention-to-treat population, there were 36 lesions in the vaccine group, compared with 89 in the placebo group, "resulting in an observed efficacy of 60%," Dr. Giuliano and her colleagues said. The number of lesions associated with HPV-6 was reduced by 60%, with HPV-11 by 76%, HPV-16 by 70%, and HPV-18 by 34%.

A subgroup of 2,805 subjects qualified for the per-protocol population: 1,397 received the active vaccine and 1,408 received placebo. In this analysis, there were 6 lesions in the vaccine group, compared with 36 in the placebo group, for an observed efficacy of 84%.

The number of lesions associated with HPV types 6 and 11 was reduced by 84% and 91%, respectively, in this analysis, the investigators wrote (N. Engl. J. Med. 2011;364:401-11).

No lesions associated with HPV types 16 or 18 were found in the vaccine recipients in the per-protocol analysis, while three developed in the placebo group. No cases of PIN developed in the vaccine group, but three developed in the placebo group.

Regarding persistent HPV infection, the vaccine significantly decreased the rate by 48% in the intention-to-treat population and by 86% in the per-protocol population.

The percentage of study subjects who reported adverse events was slightly higher among those who received active vaccine (69%) than placebo (64%). Most such events involved pain at the injection site and were characterized as mild. There were no serious adverse events, and the same number of subjects in each group dropped out of the study because of adverse effects.

The rates of adverse events were lower in this study of males than have been reported among female recipients of the HPV vaccine. This may be because males have more muscle mass, and thus less pain, at the injection site. It also may be the result of reluctance to report pain or minor events among males, the investigators added.

Three subjects in the per-protocol population who received active vaccine developed genital lesions. "These cases may represent true vaccine failures, false-negative results of HPV DNA or antibody-detection tests at baseline, or failure to identify these lesions at baseline," Dr. Giuliano and her associates said.

One limitation of this study was that none of the subjects had more than five lifetime sexual partners, "which may have resulted in overrepresentation of subjects with a low likelihood of HPV exposure at baseline and a low likelihood of subsequent exposure, as compared with the general population," they added.

This study was funded by Merck & Co., the National Center for Research Resources, and the National Institutes of Health. Merck designed the study, collated the data, and performed statistical analyses. The investigators reported ties to Merck, GlaxoSmithKline, Qiagen, and AstraZeneca.

The quadrivalent human papillomavirus vaccine prevents the infection as well as the development of external anogenital lesions associated with the virus in boys and men, according to a report in the Feb. 3 issue of the New England Journal of Medicine.

It is likely that the vaccine will similarly cut down on human papillomavirus (HPV) transmission and prevent the anogenital cancer, intraepithelial neoplasia, recurrent respiratory papillomatosis, and cancer of the oropharynx that eventually arise from HPV infection, but "each of these potential outcomes must be directly demonstrated" in future studies, said Anna R. Giuliano, Ph.D., of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla., and her associates.

The investigators assessed the efficacy of the vaccine (Gardasil, Merck & Co.), which is active against HPV types 6, 11, 16, and 18, in a prospective international clinical trial involving 4,065 healthy boys and men aged 16-26 years followed at 71 medical centers in 18 countries. A total of 2,032 subjects were randomly assigned to receive the vaccine and 2,033 to receive placebo injections, and they were followed for a median of 3 years.

All of the study subjects reported having had no more than five sexual partners in their lifetimes. A total of 3,463 reported that their sexual partners were exclusively female, while 602 reported that they had sex with male partners.

Specimens for HPV testing were collected separately from the penis, scrotum, perineal area, and perianal regions at baseline and at intervals during follow-up. For subjects who reported having sex with male partners, intra-anal specimens also were collected.

The primary end point of the study was the presence or absence of external genital lesions associated with the four HPV strains covered by the vaccine. These were defined as condylomata acuminata (external genital warts); penile, perianal, or perineal intraepithelial neoplasia (PIN); or penile, perianal, or perineal cancer.

Within 30 days of the final dose of the vaccine, 97% of the subjects showed seroconversion for all four HPV strains. Nine subjects did not show seroconversion to any of the HPV strains.

In this intention-to-treat population, there were 36 lesions in the vaccine group, compared with 89 in the placebo group, "resulting in an observed efficacy of 60%," Dr. Giuliano and her colleagues said. The number of lesions associated with HPV-6 was reduced by 60%, with HPV-11 by 76%, HPV-16 by 70%, and HPV-18 by 34%.

A subgroup of 2,805 subjects qualified for the per-protocol population: 1,397 received the active vaccine and 1,408 received placebo. In this analysis, there were 6 lesions in the vaccine group, compared with 36 in the placebo group, for an observed efficacy of 84%.

The number of lesions associated with HPV types 6 and 11 was reduced by 84% and 91%, respectively, in this analysis, the investigators wrote (N. Engl. J. Med. 2011;364:401-11).

No lesions associated with HPV types 16 or 18 were found in the vaccine recipients in the per-protocol analysis, while three developed in the placebo group. No cases of PIN developed in the vaccine group, but three developed in the placebo group.

Regarding persistent HPV infection, the vaccine significantly decreased the rate by 48% in the intention-to-treat population and by 86% in the per-protocol population.

The percentage of study subjects who reported adverse events was slightly higher among those who received active vaccine (69%) than placebo (64%). Most such events involved pain at the injection site and were characterized as mild. There were no serious adverse events, and the same number of subjects in each group dropped out of the study because of adverse effects.

The rates of adverse events were lower in this study of males than have been reported among female recipients of the HPV vaccine. This may be because males have more muscle mass, and thus less pain, at the injection site. It also may be the result of reluctance to report pain or minor events among males, the investigators added.

Three subjects in the per-protocol population who received active vaccine developed genital lesions. "These cases may represent true vaccine failures, false-negative results of HPV DNA or antibody-detection tests at baseline, or failure to identify these lesions at baseline," Dr. Giuliano and her associates said.

One limitation of this study was that none of the subjects had more than five lifetime sexual partners, "which may have resulted in overrepresentation of subjects with a low likelihood of HPV exposure at baseline and a low likelihood of subsequent exposure, as compared with the general population," they added.

This study was funded by Merck & Co., the National Center for Research Resources, and the National Institutes of Health. Merck designed the study, collated the data, and performed statistical analyses. The investigators reported ties to Merck, GlaxoSmithKline, Qiagen, and AstraZeneca.

Fidaxomicin, a macrocyclic antibiotic, was found noninferior to vancomycin against Clostridium difficile in a phase III noninferiority study reported in the Feb. 3 issue of the New England Journal of Medicine.

Fidaxomicin also had a significantly lower rate of recurrent infection than vancomycin, and the two agents had comparable adverse effect profiles, said Dr. Thomas J. Louie of the University of Calgary (Alta.) and his associates.

It was hoped that fidaxomicin, previously known as OPT-80, would prove to be a highly active but more selective therapy for C. difficile than is currently available. Dr. Louie and his colleagues compared it with vancomycin in a prospective international trial sponsored by the manufacturer, Optimer Pharmaceuticals. The study subjects were 629 adults randomly assigned in equal numbers to oral therapy at 52 sites in Canada and the United States.

The primary efficacy end point was the rate of clinical cure, or complete resolution of diarrhea. In the intention-to-treat analysis of 596 patients, 88% of patients taking fidaxomicin and 86% of those taking vancomycin met the criteria for clinical cure. In the per-protocol analysis of 548 patients, 92% of the patients taking fidaxomicin and 90% of those taking vancomycin attained a clinical cure.

Subgroup analyses in both populations showed that treatment response was similar between the two groups regardless of patient age, need for hospitalization, history of C. difficile infection, severity of disease at baseline, type of infecting strain, response to metronidazole treatment, or several other factors.

Fidaxomicin was associated with a significantly lower rate of recurrence in both the intention-to-treat population (15%) and the per-protocol population (13%) than was vancomycin (25% and 24%, respectively). This represents a 45% relative reduction in recurrences with fidaxomicin.

The recurrence rate was found to be similar between fidaxomicin and vancomycin among patients infected with the NAP1/BI/027 strain (the hypervirulent "North American" strain). However, the recurrence rate was significantly lower among patients with less virulent strains who took fidaxomicin (8%) than among those who took vancomycin (26%).

"This represents a 69% relative reduction in recurrences with fidaxomicin," the investigators said (N. Engl. J. Med. 2011 Feb. 3;364:422-31).

Decreases in recurrences are of obvious benefit to patients, and should reduce treatment costs as well. But another important benefit is that they also should reduce the rate of person-to-person transmission, Dr. Louie and his colleagues noted.

The median time until the resolution of diarrhea was shorter with fidaxomicin in both the intention-to-treat and per-protocol populations, but this difference did not meet statistical significance.

There were no significant differences between the two drugs in rates of adverse events, serious adverse events, or adverse events possibly related to the study treatment. No subjects discontinued the study because of intolerance or allergy to the drugs.

Taken together, these findings indicate that fidaxomicin and vancomycin "have similar effectiveness with respect to the clinical resolution of acute diarrheal disease due to C. difficile infection, but more sustained or durable resolution of disease (that is, improved global cure) is achieved with fidaxomicin," Dr. Louie and his associates said.

This study was funded by Optimer Pharmaceuticals. Dr. Louie and his associates reported being listed on a fidaxomicin patent and other patents, and reported ties to Merck, Cubist Pharmaceuticals, ViroPharma, Cempra, Iroko Pharmaceuticals, Salix Pharmaceuticals, Abbott, Bayer, Pfizer, and Genzyme.

Fidaxomicin, a macrocyclic antibiotic, was found noninferior to vancomycin against Clostridium difficile in a phase III noninferiority study reported in the Feb. 3 issue of the New England Journal of Medicine.

Fidaxomicin also had a significantly lower rate of recurrent infection than vancomycin, and the two agents had comparable adverse effect profiles, said Dr. Thomas J. Louie of the University of Calgary (Alta.) and his associates.

It was hoped that fidaxomicin, previously known as OPT-80, would prove to be a highly active but more selective therapy for C. difficile than is currently available. Dr. Louie and his colleagues compared it with vancomycin in a prospective international trial sponsored by the manufacturer, Optimer Pharmaceuticals. The study subjects were 629 adults randomly assigned in equal numbers to oral therapy at 52 sites in Canada and the United States.

The primary efficacy end point was the rate of clinical cure, or complete resolution of diarrhea. In the intention-to-treat analysis of 596 patients, 88% of patients taking fidaxomicin and 86% of those taking vancomycin met the criteria for clinical cure. In the per-protocol analysis of 548 patients, 92% of the patients taking fidaxomicin and 90% of those taking vancomycin attained a clinical cure.

Subgroup analyses in both populations showed that treatment response was similar between the two groups regardless of patient age, need for hospitalization, history of C. difficile infection, severity of disease at baseline, type of infecting strain, response to metronidazole treatment, or several other factors.

Fidaxomicin was associated with a significantly lower rate of recurrence in both the intention-to-treat population (15%) and the per-protocol population (13%) than was vancomycin (25% and 24%, respectively). This represents a 45% relative reduction in recurrences with fidaxomicin.

The recurrence rate was found to be similar between fidaxomicin and vancomycin among patients infected with the NAP1/BI/027 strain (the hypervirulent "North American" strain). However, the recurrence rate was significantly lower among patients with less virulent strains who took fidaxomicin (8%) than among those who took vancomycin (26%).

"This represents a 69% relative reduction in recurrences with fidaxomicin," the investigators said (N. Engl. J. Med. 2011 Feb. 3;364:422-31).

Decreases in recurrences are of obvious benefit to patients, and should reduce treatment costs as well. But another important benefit is that they also should reduce the rate of person-to-person transmission, Dr. Louie and his colleagues noted.

The median time until the resolution of diarrhea was shorter with fidaxomicin in both the intention-to-treat and per-protocol populations, but this difference did not meet statistical significance.

There were no significant differences between the two drugs in rates of adverse events, serious adverse events, or adverse events possibly related to the study treatment. No subjects discontinued the study because of intolerance or allergy to the drugs.

Taken together, these findings indicate that fidaxomicin and vancomycin "have similar effectiveness with respect to the clinical resolution of acute diarrheal disease due to C. difficile infection, but more sustained or durable resolution of disease (that is, improved global cure) is achieved with fidaxomicin," Dr. Louie and his associates said.

This study was funded by Optimer Pharmaceuticals. Dr. Louie and his associates reported being listed on a fidaxomicin patent and other patents, and reported ties to Merck, Cubist Pharmaceuticals, ViroPharma, Cempra, Iroko Pharmaceuticals, Salix Pharmaceuticals, Abbott, Bayer, Pfizer, and Genzyme.

Fidaxomicin, a macrocyclic antibiotic, was found noninferior to vancomycin against Clostridium difficile in a phase III noninferiority study reported in the Feb. 3 issue of the New England Journal of Medicine.

Fidaxomicin also had a significantly lower rate of recurrent infection than vancomycin, and the two agents had comparable adverse effect profiles, said Dr. Thomas J. Louie of the University of Calgary (Alta.) and his associates.

It was hoped that fidaxomicin, previously known as OPT-80, would prove to be a highly active but more selective therapy for C. difficile than is currently available. Dr. Louie and his colleagues compared it with vancomycin in a prospective international trial sponsored by the manufacturer, Optimer Pharmaceuticals. The study subjects were 629 adults randomly assigned in equal numbers to oral therapy at 52 sites in Canada and the United States.

The primary efficacy end point was the rate of clinical cure, or complete resolution of diarrhea. In the intention-to-treat analysis of 596 patients, 88% of patients taking fidaxomicin and 86% of those taking vancomycin met the criteria for clinical cure. In the per-protocol analysis of 548 patients, 92% of the patients taking fidaxomicin and 90% of those taking vancomycin attained a clinical cure.

Subgroup analyses in both populations showed that treatment response was similar between the two groups regardless of patient age, need for hospitalization, history of C. difficile infection, severity of disease at baseline, type of infecting strain, response to metronidazole treatment, or several other factors.

Fidaxomicin was associated with a significantly lower rate of recurrence in both the intention-to-treat population (15%) and the per-protocol population (13%) than was vancomycin (25% and 24%, respectively). This represents a 45% relative reduction in recurrences with fidaxomicin.

The recurrence rate was found to be similar between fidaxomicin and vancomycin among patients infected with the NAP1/BI/027 strain (the hypervirulent "North American" strain). However, the recurrence rate was significantly lower among patients with less virulent strains who took fidaxomicin (8%) than among those who took vancomycin (26%).

"This represents a 69% relative reduction in recurrences with fidaxomicin," the investigators said (N. Engl. J. Med. 2011 Feb. 3;364:422-31).

Decreases in recurrences are of obvious benefit to patients, and should reduce treatment costs as well. But another important benefit is that they also should reduce the rate of person-to-person transmission, Dr. Louie and his colleagues noted.

The median time until the resolution of diarrhea was shorter with fidaxomicin in both the intention-to-treat and per-protocol populations, but this difference did not meet statistical significance.

There were no significant differences between the two drugs in rates of adverse events, serious adverse events, or adverse events possibly related to the study treatment. No subjects discontinued the study because of intolerance or allergy to the drugs.

Taken together, these findings indicate that fidaxomicin and vancomycin "have similar effectiveness with respect to the clinical resolution of acute diarrheal disease due to C. difficile infection, but more sustained or durable resolution of disease (that is, improved global cure) is achieved with fidaxomicin," Dr. Louie and his associates said.

This study was funded by Optimer Pharmaceuticals. Dr. Louie and his associates reported being listed on a fidaxomicin patent and other patents, and reported ties to Merck, Cubist Pharmaceuticals, ViroPharma, Cempra, Iroko Pharmaceuticals, Salix Pharmaceuticals, Abbott, Bayer, Pfizer, and Genzyme.

Fidaxomicin, a macrocyclic antibiotic, was found noninferior to vancomycin against Clostridium difficile in a phase III noninferiority study reported in the Feb. 3 issue of the New England Journal of Medicine.

Fidaxomicin also had a significantly lower rate of recurrent infection than vancomycin, and the two agents had comparable adverse effect profiles, said Dr. Thomas J. Louie of the University of Calgary (Alta.) and his associates.

It was hoped that fidaxomicin, previously known as OPT-80, would prove to be a highly active but more selective therapy for C. difficile than is currently available. Dr. Louie and his colleagues compared it with vancomycin in a prospective international trial sponsored by the manufacturer, Optimer Pharmaceuticals. The study subjects were 629 adults randomly assigned in equal numbers to oral therapy at 52 sites in Canada and the United States.

The primary efficacy end point was the rate of clinical cure, or complete resolution of diarrhea. In the intention-to-treat analysis of 596 patients, 88% of patients taking fidaxomicin and 86% of those taking vancomycin met the criteria for clinical cure. In the per-protocol analysis of 548 patients, 92% of the patients taking fidaxomicin and 90% of those taking vancomycin attained a clinical cure.

Subgroup analyses in both populations showed that treatment response was similar between the two groups regardless of patient age, need for hospitalization, history of C. difficile infection, severity of disease at baseline, type of infecting strain, response to metronidazole treatment, or several other factors.

Fidaxomicin was associated with a significantly lower rate of recurrence in both the intention-to-treat population (15%) and the per-protocol population (13%) than was vancomycin (25% and 24%, respectively). This represents a 45% relative reduction in recurrences with fidaxomicin.

The recurrence rate was found to be similar between fidaxomicin and vancomycin among patients infected with the NAP1/BI/027 strain (the hypervirulent "North American" strain). However, the recurrence rate was significantly lower among patients with less virulent strains who took fidaxomicin (8%) than among those who took vancomycin (26%).

"This represents a 69% relative reduction in recurrences with fidaxomicin," the investigators said (N. Engl. J. Med. 2011 Feb. 3;364:422-31).

Decreases in recurrences are of obvious benefit to patients, and should reduce treatment costs as well. But another important benefit is that they also should reduce the rate of person-to-person transmission, Dr. Louie and his colleagues noted.

The median time until the resolution of diarrhea was shorter with fidaxomicin in both the intention-to-treat and per-protocol populations, but this difference did not meet statistical significance.

There were no significant differences between the two drugs in rates of adverse events, serious adverse events, or adverse events possibly related to the study treatment. No subjects discontinued the study because of intolerance or allergy to the drugs.

Taken together, these findings indicate that fidaxomicin and vancomycin "have similar effectiveness with respect to the clinical resolution of acute diarrheal disease due to C. difficile infection, but more sustained or durable resolution of disease (that is, improved global cure) is achieved with fidaxomicin," Dr. Louie and his associates said.

This study was funded by Optimer Pharmaceuticals. Dr. Louie and his associates reported being listed on a fidaxomicin patent and other patents, and reported ties to Merck, Cubist Pharmaceuticals, ViroPharma, Cempra, Iroko Pharmaceuticals, Salix Pharmaceuticals, Abbott, Bayer, Pfizer, and Genzyme.

Fidaxomicin, a macrocyclic antibiotic, was found noninferior to vancomycin against Clostridium difficile in a phase III noninferiority study reported in the Feb. 3 issue of the New England Journal of Medicine.

Fidaxomicin also had a significantly lower rate of recurrent infection than vancomycin, and the two agents had comparable adverse effect profiles, said Dr. Thomas J. Louie of the University of Calgary (Alta.) and his associates.

It was hoped that fidaxomicin, previously known as OPT-80, would prove to be a highly active but more selective therapy for C. difficile than is currently available. Dr. Louie and his colleagues compared it with vancomycin in a prospective international trial sponsored by the manufacturer, Optimer Pharmaceuticals. The study subjects were 629 adults randomly assigned in equal numbers to oral therapy at 52 sites in Canada and the United States.

The primary efficacy end point was the rate of clinical cure, or complete resolution of diarrhea. In the intention-to-treat analysis of 596 patients, 88% of patients taking fidaxomicin and 86% of those taking vancomycin met the criteria for clinical cure. In the per-protocol analysis of 548 patients, 92% of the patients taking fidaxomicin and 90% of those taking vancomycin attained a clinical cure.

Subgroup analyses in both populations showed that treatment response was similar between the two groups regardless of patient age, need for hospitalization, history of C. difficile infection, severity of disease at baseline, type of infecting strain, response to metronidazole treatment, or several other factors.

Fidaxomicin was associated with a significantly lower rate of recurrence in both the intention-to-treat population (15%) and the per-protocol population (13%) than was vancomycin (25% and 24%, respectively). This represents a 45% relative reduction in recurrences with fidaxomicin.

The recurrence rate was found to be similar between fidaxomicin and vancomycin among patients infected with the NAP1/BI/027 strain (the hypervirulent "North American" strain). However, the recurrence rate was significantly lower among patients with less virulent strains who took fidaxomicin (8%) than among those who took vancomycin (26%).

"This represents a 69% relative reduction in recurrences with fidaxomicin," the investigators said (N. Engl. J. Med. 2011 Feb. 3;364:422-31).

Decreases in recurrences are of obvious benefit to patients, and should reduce treatment costs as well. But another important benefit is that they also should reduce the rate of person-to-person transmission, Dr. Louie and his colleagues noted.

The median time until the resolution of diarrhea was shorter with fidaxomicin in both the intention-to-treat and per-protocol populations, but this difference did not meet statistical significance.

There were no significant differences between the two drugs in rates of adverse events, serious adverse events, or adverse events possibly related to the study treatment. No subjects discontinued the study because of intolerance or allergy to the drugs.

Taken together, these findings indicate that fidaxomicin and vancomycin "have similar effectiveness with respect to the clinical resolution of acute diarrheal disease due to C. difficile infection, but more sustained or durable resolution of disease (that is, improved global cure) is achieved with fidaxomicin," Dr. Louie and his associates said.

This study was funded by Optimer Pharmaceuticals. Dr. Louie and his associates reported being listed on a fidaxomicin patent and other patents, and reported ties to Merck, Cubist Pharmaceuticals, ViroPharma, Cempra, Iroko Pharmaceuticals, Salix Pharmaceuticals, Abbott, Bayer, Pfizer, and Genzyme.

Fidaxomicin, a macrocyclic antibiotic, was found noninferior to vancomycin against Clostridium difficile in a phase III noninferiority study reported in the Feb. 3 issue of the New England Journal of Medicine.

Fidaxomicin also had a significantly lower rate of recurrent infection than vancomycin, and the two agents had comparable adverse effect profiles, said Dr. Thomas J. Louie of the University of Calgary (Alta.) and his associates.

It was hoped that fidaxomicin, previously known as OPT-80, would prove to be a highly active but more selective therapy for C. difficile than is currently available. Dr. Louie and his colleagues compared it with vancomycin in a prospective international trial sponsored by the manufacturer, Optimer Pharmaceuticals. The study subjects were 629 adults randomly assigned in equal numbers to oral therapy at 52 sites in Canada and the United States.

The primary efficacy end point was the rate of clinical cure, or complete resolution of diarrhea. In the intention-to-treat analysis of 596 patients, 88% of patients taking fidaxomicin and 86% of those taking vancomycin met the criteria for clinical cure. In the per-protocol analysis of 548 patients, 92% of the patients taking fidaxomicin and 90% of those taking vancomycin attained a clinical cure.

Subgroup analyses in both populations showed that treatment response was similar between the two groups regardless of patient age, need for hospitalization, history of C. difficile infection, severity of disease at baseline, type of infecting strain, response to metronidazole treatment, or several other factors.

Fidaxomicin was associated with a significantly lower rate of recurrence in both the intention-to-treat population (15%) and the per-protocol population (13%) than was vancomycin (25% and 24%, respectively). This represents a 45% relative reduction in recurrences with fidaxomicin.

The recurrence rate was found to be similar between fidaxomicin and vancomycin among patients infected with the NAP1/BI/027 strain (the hypervirulent "North American" strain). However, the recurrence rate was significantly lower among patients with less virulent strains who took fidaxomicin (8%) than among those who took vancomycin (26%).

"This represents a 69% relative reduction in recurrences with fidaxomicin," the investigators said (N. Engl. J. Med. 2011 Feb. 3;364:422-31).

Decreases in recurrences are of obvious benefit to patients, and should reduce treatment costs as well. But another important benefit is that they also should reduce the rate of person-to-person transmission, Dr. Louie and his colleagues noted.

The median time until the resolution of diarrhea was shorter with fidaxomicin in both the intention-to-treat and per-protocol populations, but this difference did not meet statistical significance.

There were no significant differences between the two drugs in rates of adverse events, serious adverse events, or adverse events possibly related to the study treatment. No subjects discontinued the study because of intolerance or allergy to the drugs.

Taken together, these findings indicate that fidaxomicin and vancomycin "have similar effectiveness with respect to the clinical resolution of acute diarrheal disease due to C. difficile infection, but more sustained or durable resolution of disease (that is, improved global cure) is achieved with fidaxomicin," Dr. Louie and his associates said.

This study was funded by Optimer Pharmaceuticals. Dr. Louie and his associates reported being listed on a fidaxomicin patent and other patents, and reported ties to Merck, Cubist Pharmaceuticals, ViroPharma, Cempra, Iroko Pharmaceuticals, Salix Pharmaceuticals, Abbott, Bayer, Pfizer, and Genzyme.