Kerri Wachter

WASHINGTON – Members of a national advisory council on Alzheimer’s disease have identified preliminary goals and specific recommendations for a national strategic plan to slow or even halt the expected rise in new cases.

The plan aims to prevent and effectively treat the disease by as early as 2025. Its goals include enhancing care quality and efficiency, expanding patient and family support, enhancing public awareness and engagement, and improving data to track disease progress.

The plan is part of the National Alzheimer’s Project Act that was signed into law on Jan, 4, 2011, by President Obama. The law established the Advisory Council on Alzheimer’s Research, Care, and Services and requires the secretary of the Department of Health and Human Services and the advisory council to create and maintain a national plan to overcome Alzheimer’s disease. Members of the council’s subgroups on long-term services and supports (LTSS), clinical care, and research met Jan. 17-18 to comment on and provide recommendations for the plan’s draft framework.

Long-Term Services and Supports

Members of the LTSS subgroup noted that the importance of caregivers and family to Alzheimer’s patients warrants the inclusion of services to maintain their health and vitality. In addition, the subgroup proposed that robust dementia-capable systems of LTSS be culturally appropriate, available in every state, and accessible to younger people with Alzheimer’s disease – a group often forgotten in discussions of Alzheimer’s disease. The LTSS subgroup also recommended that new guidelines for diagnosis be used whenever someone is admitted for LTSS or assessed for eligibility. The process of diagnosis also should include engaging the patient and family in advance care planning. End of life considerations should be incorporated into all surveillance and quality indicators.

Council members recommended that federal funds be made available to support a lead agency in every state to coordinate all available LTSS provided through various public and private mechanisms. The agency could use these funds to build and monitor quality indicators and the capacity to maximize the positive impact of services on patients and caregivers.

The council advised that state education agencies and professional organizations include key information about Alzheimer’s disease in all curricula for any profession or career track affecting LTSS, as well as key information about Alzheimer’s disease for any staff working in human service agencies. Patients and caregivers also should be informed of state, local, and private housing resources, and states should provide adult day services as an option under Medicaid, the council said.

Clinical Care of Alzheimer’s Disease

The clinical care subgroup said the overall goal of clinical care is to ensure that individuals with Alzheimer’s have their disease detected and diagnosed at an early stage, receive care planning, and have access to coordinated and high-quality health care throughout the course of the disease.

In particular, members recommended changes to Medicare coverage and physician reimbursement to encourage the diagnosis of Alzheimer’s disease and to provide care planning to diagnosed individuals and their caregivers. In addition, quality indicators for the care and treatment of individuals with Alzheimer’s should be developed. The subgroup proposed medical home pilot projects specifically targeted at improving medical management for individuals with Alzheimer’s using grants from the Center for Medicare and Medicaid Innovation (CMMI).

The subgroup also recommended addressing palliative care by forming a blue-ribbon panel of experts to recommend one or more models of care for people with advancing dementia, which would cover eligibility criteria and financing mechanisms. CMMI also could be tapped to supply grants to implement these models.

In addition, the subgroup advised improving and expanding the National Family Caregiver Support Program and other evidence-based caregiver support models. Members also recommended that a specific round of grants for pilot projects to reduce potentially preventable emergency department visits and hospitalizations for individuals with Alzheimer’s be funded through CMMI. They recommended exploring the use of public-private partnerships to develop and evaluate ways to improve hospital care for people with Alzheimer’s and other dementias.

Greater funding and incentives should be offered to individuals to pursue careers in geriatric specialties, they noted.

Research Goals

The research subgroup said their stated goal – the ability to prevent, effectively treat, and substantially delay the onset or slow the progression of Alzheimer’s disease – could be reached through three key strategies:

• Aggressively committing resources, with appropriate accountability, to Alzheimer’s disease research to match the current and growing impact of the disease on society.

• Accelerating public access to new therapeutic interventions by compressing the current average time of identifying and validating therapeutic targets and developing and testing the efficacy and safety of interventions.

• Exploring the possibility of providing incentives to private industry to invest in disease-modifying interventions by convening a panel of experts from private industry to help determine the nature of possible incentives that would accelerate discovery. These may include tax reform or incentives to drive greater investment, patent law reform to include pharmaceutical incentives, and enhanced market exclusivity.

The council is scheduled to meet again on April 17, 2012. A final draft is expected to be released in late spring 2012.

WASHINGTON – Members of a national advisory council on Alzheimer’s disease have identified preliminary goals and specific recommendations for a national strategic plan to slow or even halt the expected rise in new cases.

The plan aims to prevent and effectively treat the disease by as early as 2025. Its goals include enhancing care quality and efficiency, expanding patient and family support, enhancing public awareness and engagement, and improving data to track disease progress.

The plan is part of the National Alzheimer’s Project Act that was signed into law on Jan, 4, 2011, by President Obama. The law established the Advisory Council on Alzheimer’s Research, Care, and Services and requires the secretary of the Department of Health and Human Services and the advisory council to create and maintain a national plan to overcome Alzheimer’s disease. Members of the council’s subgroups on long-term services and supports (LTSS), clinical care, and research met Jan. 17-18 to comment on and provide recommendations for the plan’s draft framework.

Long-Term Services and Supports

Members of the LTSS subgroup noted that the importance of caregivers and family to Alzheimer’s patients warrants the inclusion of services to maintain their health and vitality. In addition, the subgroup proposed that robust dementia-capable systems of LTSS be culturally appropriate, available in every state, and accessible to younger people with Alzheimer’s disease – a group often forgotten in discussions of Alzheimer’s disease. The LTSS subgroup also recommended that new guidelines for diagnosis be used whenever someone is admitted for LTSS or assessed for eligibility. The process of diagnosis also should include engaging the patient and family in advance care planning. End of life considerations should be incorporated into all surveillance and quality indicators.

Council members recommended that federal funds be made available to support a lead agency in every state to coordinate all available LTSS provided through various public and private mechanisms. The agency could use these funds to build and monitor quality indicators and the capacity to maximize the positive impact of services on patients and caregivers.

The council advised that state education agencies and professional organizations include key information about Alzheimer’s disease in all curricula for any profession or career track affecting LTSS, as well as key information about Alzheimer’s disease for any staff working in human service agencies. Patients and caregivers also should be informed of state, local, and private housing resources, and states should provide adult day services as an option under Medicaid, the council said.

Clinical Care of Alzheimer’s Disease

The clinical care subgroup said the overall goal of clinical care is to ensure that individuals with Alzheimer’s have their disease detected and diagnosed at an early stage, receive care planning, and have access to coordinated and high-quality health care throughout the course of the disease.

In particular, members recommended changes to Medicare coverage and physician reimbursement to encourage the diagnosis of Alzheimer’s disease and to provide care planning to diagnosed individuals and their caregivers. In addition, quality indicators for the care and treatment of individuals with Alzheimer’s should be developed. The subgroup proposed medical home pilot projects specifically targeted at improving medical management for individuals with Alzheimer’s using grants from the Center for Medicare and Medicaid Innovation (CMMI).

The subgroup also recommended addressing palliative care by forming a blue-ribbon panel of experts to recommend one or more models of care for people with advancing dementia, which would cover eligibility criteria and financing mechanisms. CMMI also could be tapped to supply grants to implement these models.

In addition, the subgroup advised improving and expanding the National Family Caregiver Support Program and other evidence-based caregiver support models. Members also recommended that a specific round of grants for pilot projects to reduce potentially preventable emergency department visits and hospitalizations for individuals with Alzheimer’s be funded through CMMI. They recommended exploring the use of public-private partnerships to develop and evaluate ways to improve hospital care for people with Alzheimer’s and other dementias.

Greater funding and incentives should be offered to individuals to pursue careers in geriatric specialties, they noted.

Research Goals

The research subgroup said their stated goal – the ability to prevent, effectively treat, and substantially delay the onset or slow the progression of Alzheimer’s disease – could be reached through three key strategies:

• Aggressively committing resources, with appropriate accountability, to Alzheimer’s disease research to match the current and growing impact of the disease on society.

• Accelerating public access to new therapeutic interventions by compressing the current average time of identifying and validating therapeutic targets and developing and testing the efficacy and safety of interventions.

• Exploring the possibility of providing incentives to private industry to invest in disease-modifying interventions by convening a panel of experts from private industry to help determine the nature of possible incentives that would accelerate discovery. These may include tax reform or incentives to drive greater investment, patent law reform to include pharmaceutical incentives, and enhanced market exclusivity.

The council is scheduled to meet again on April 17, 2012. A final draft is expected to be released in late spring 2012.

WASHINGTON – Members of a national advisory council on Alzheimer’s disease have identified preliminary goals and specific recommendations for a national strategic plan to slow or even halt the expected rise in new cases.

The plan aims to prevent and effectively treat the disease by as early as 2025. Its goals include enhancing care quality and efficiency, expanding patient and family support, enhancing public awareness and engagement, and improving data to track disease progress.

The plan is part of the National Alzheimer’s Project Act that was signed into law on Jan, 4, 2011, by President Obama. The law established the Advisory Council on Alzheimer’s Research, Care, and Services and requires the secretary of the Department of Health and Human Services and the advisory council to create and maintain a national plan to overcome Alzheimer’s disease. Members of the council’s subgroups on long-term services and supports (LTSS), clinical care, and research met Jan. 17-18 to comment on and provide recommendations for the plan’s draft framework.

Long-Term Services and Supports

Members of the LTSS subgroup noted that the importance of caregivers and family to Alzheimer’s patients warrants the inclusion of services to maintain their health and vitality. In addition, the subgroup proposed that robust dementia-capable systems of LTSS be culturally appropriate, available in every state, and accessible to younger people with Alzheimer’s disease – a group often forgotten in discussions of Alzheimer’s disease. The LTSS subgroup also recommended that new guidelines for diagnosis be used whenever someone is admitted for LTSS or assessed for eligibility. The process of diagnosis also should include engaging the patient and family in advance care planning. End of life considerations should be incorporated into all surveillance and quality indicators.

Council members recommended that federal funds be made available to support a lead agency in every state to coordinate all available LTSS provided through various public and private mechanisms. The agency could use these funds to build and monitor quality indicators and the capacity to maximize the positive impact of services on patients and caregivers.

The council advised that state education agencies and professional organizations include key information about Alzheimer’s disease in all curricula for any profession or career track affecting LTSS, as well as key information about Alzheimer’s disease for any staff working in human service agencies. Patients and caregivers also should be informed of state, local, and private housing resources, and states should provide adult day services as an option under Medicaid, the council said.

Clinical Care of Alzheimer’s Disease

The clinical care subgroup said the overall goal of clinical care is to ensure that individuals with Alzheimer’s have their disease detected and diagnosed at an early stage, receive care planning, and have access to coordinated and high-quality health care throughout the course of the disease.

In particular, members recommended changes to Medicare coverage and physician reimbursement to encourage the diagnosis of Alzheimer’s disease and to provide care planning to diagnosed individuals and their caregivers. In addition, quality indicators for the care and treatment of individuals with Alzheimer’s should be developed. The subgroup proposed medical home pilot projects specifically targeted at improving medical management for individuals with Alzheimer’s using grants from the Center for Medicare and Medicaid Innovation (CMMI).

The subgroup also recommended addressing palliative care by forming a blue-ribbon panel of experts to recommend one or more models of care for people with advancing dementia, which would cover eligibility criteria and financing mechanisms. CMMI also could be tapped to supply grants to implement these models.

In addition, the subgroup advised improving and expanding the National Family Caregiver Support Program and other evidence-based caregiver support models. Members also recommended that a specific round of grants for pilot projects to reduce potentially preventable emergency department visits and hospitalizations for individuals with Alzheimer’s be funded through CMMI. They recommended exploring the use of public-private partnerships to develop and evaluate ways to improve hospital care for people with Alzheimer’s and other dementias.

Greater funding and incentives should be offered to individuals to pursue careers in geriatric specialties, they noted.

Research Goals

The research subgroup said their stated goal – the ability to prevent, effectively treat, and substantially delay the onset or slow the progression of Alzheimer’s disease – could be reached through three key strategies:

• Aggressively committing resources, with appropriate accountability, to Alzheimer’s disease research to match the current and growing impact of the disease on society.

• Accelerating public access to new therapeutic interventions by compressing the current average time of identifying and validating therapeutic targets and developing and testing the efficacy and safety of interventions.

• Exploring the possibility of providing incentives to private industry to invest in disease-modifying interventions by convening a panel of experts from private industry to help determine the nature of possible incentives that would accelerate discovery. These may include tax reform or incentives to drive greater investment, patent law reform to include pharmaceutical incentives, and enhanced market exclusivity.

The council is scheduled to meet again on April 17, 2012. A final draft is expected to be released in late spring 2012.

The Food and Drug Administration is reporting current shortages of three drugs that are prescribed in the treatment of attention-deficit/hyperactive disorder: amphetamine mixed salts immediate-release tablets, dextroamphetamine tablets, and methylphenidate HCl.

The shortage of amphetamine mixed salts immediate-release tablets is primarily attributable to an increase in demand. Supply issues were cited by one manufacturer. The three companies involved are releasing the products as they become available.

The shortage of dextroamphetamine tablets (5 mg and 10 mg), made by Teva Pharmaceuticals, is new. The product will be released as it becomes available, the company reported. Dexamethasone injection presentations (5-mg/mL and 10-mg/mL vial [Carpujet]), made by American Regent Inc., are on hold because of the presence of particulate matter. It has "no estimated release date," the company reported. West-Ward Pharmaceuticals has the 10 mg/mL formulation of dexamethasone on back order and expects to have it available by the middle of July.

The shortage of methylphenidate HCl is tied to delays that have been reported by several manufacturers, the FDA noted. Sandoz has reported capacity constraints, and expects sporadic back orders for the next couple of months. Mallinckrodt has reported continued recovery as a result of previously unavailable raw material; the company expects all strengths of methylphenidate IR and ER (extended-release) tablets to be increasingly available as supply recovery continues, with most contracted orders being met. UCB has reported increased demand; the company is currently out of its stock of 5-mg IR, 10-mg IR, 20-mg IR, and 20-mg ER products, with resupply expected by February. Watson Pharmaceuticals Inc. has all three strengths available for contracted customers only. Noven Pharmaceuticals Inc. reports that all Daytrana (methylphenidate transdermal system) products are available.

The Food and Drug Administration is reporting current shortages of three drugs that are prescribed in the treatment of attention-deficit/hyperactive disorder: amphetamine mixed salts immediate-release tablets, dextroamphetamine tablets, and methylphenidate HCl.

The shortage of amphetamine mixed salts immediate-release tablets is primarily attributable to an increase in demand. Supply issues were cited by one manufacturer. The three companies involved are releasing the products as they become available.

The shortage of dextroamphetamine tablets (5 mg and 10 mg), made by Teva Pharmaceuticals, is new. The product will be released as it becomes available, the company reported. Dexamethasone injection presentations (5-mg/mL and 10-mg/mL vial [Carpujet]), made by American Regent Inc., are on hold because of the presence of particulate matter. It has "no estimated release date," the company reported. West-Ward Pharmaceuticals has the 10 mg/mL formulation of dexamethasone on back order and expects to have it available by the middle of July.

The shortage of methylphenidate HCl is tied to delays that have been reported by several manufacturers, the FDA noted. Sandoz has reported capacity constraints, and expects sporadic back orders for the next couple of months. Mallinckrodt has reported continued recovery as a result of previously unavailable raw material; the company expects all strengths of methylphenidate IR and ER (extended-release) tablets to be increasingly available as supply recovery continues, with most contracted orders being met. UCB has reported increased demand; the company is currently out of its stock of 5-mg IR, 10-mg IR, 20-mg IR, and 20-mg ER products, with resupply expected by February. Watson Pharmaceuticals Inc. has all three strengths available for contracted customers only. Noven Pharmaceuticals Inc. reports that all Daytrana (methylphenidate transdermal system) products are available.

The Food and Drug Administration is reporting current shortages of three drugs that are prescribed in the treatment of attention-deficit/hyperactive disorder: amphetamine mixed salts immediate-release tablets, dextroamphetamine tablets, and methylphenidate HCl.

The shortage of amphetamine mixed salts immediate-release tablets is primarily attributable to an increase in demand. Supply issues were cited by one manufacturer. The three companies involved are releasing the products as they become available.

The shortage of dextroamphetamine tablets (5 mg and 10 mg), made by Teva Pharmaceuticals, is new. The product will be released as it becomes available, the company reported. Dexamethasone injection presentations (5-mg/mL and 10-mg/mL vial [Carpujet]), made by American Regent Inc., are on hold because of the presence of particulate matter. It has "no estimated release date," the company reported. West-Ward Pharmaceuticals has the 10 mg/mL formulation of dexamethasone on back order and expects to have it available by the middle of July.

The shortage of methylphenidate HCl is tied to delays that have been reported by several manufacturers, the FDA noted. Sandoz has reported capacity constraints, and expects sporadic back orders for the next couple of months. Mallinckrodt has reported continued recovery as a result of previously unavailable raw material; the company expects all strengths of methylphenidate IR and ER (extended-release) tablets to be increasingly available as supply recovery continues, with most contracted orders being met. UCB has reported increased demand; the company is currently out of its stock of 5-mg IR, 10-mg IR, 20-mg IR, and 20-mg ER products, with resupply expected by February. Watson Pharmaceuticals Inc. has all three strengths available for contracted customers only. Noven Pharmaceuticals Inc. reports that all Daytrana (methylphenidate transdermal system) products are available.

The use of selective serotonin reuptake inhibitors by women during pregnancy increases the risk of persistent pulmonary hypertension in newborns, with the risk doubling for use during late pregnancy.

The risk of persistent pulmonary hypertension of the newborn (PPHN) after exposure to any SSRI in late pregnancy was more than doubled (adjusted odds ratio, 2.1). The risk was slightly increased in association with exposure to SSRIs in early pregnancy (adjusted OR, 1.4). The combination of a previous admission to hospital for a psychiatric disorder and exposure to an SSRI in late pregnancy yielded an adjusted OR of 3.1. The findings – from a population-based cohort study of data from registries in five Nordic countries – were published Jan. 12 in BMJ (2011;344:d8012 [doi:10.1136/bmj.d8012]).

"As the risk in association with treatment in late pregnancy seems to be more than doubled, we recommend caution when treating pregnant women with SSRIs. It is essential to plan the treatment and to weigh the risks of persistent pulmonary hypertension of the newborn when treating women in late pregnancy with those of relapse of depression and neonatal abstinence syndrome if therapy is interrupted. For women where treatment with an SSRI is the only or best option, the choice of substance seems to be of minor importance," said Dr. Helle Kieler, an ob.gyn. at the Centre for Pharmacoepidemiology at the Karolinska Institute in Stockholm, and her coinvestigators.

The researchers included women and their infants born in Denmark, Finland, Iceland, Norway, or Sweden between 1996 and 2007. Each of these countries has national registers with prospectively collected information on the health of all inhabitants. They obtained data from the medical birth registers, the prescription registers, and the cause of death registers from all five countries. Data on the mother’s previous psychiatric diseases and infant diagnoses were included for Denmark, Iceland, Sweden, and Finland and from the Danish Psychiatric Central Register.

The investigators included all singletons born after 33 weeks’ gestation between 1996 and 2007. Births were included only from the years when prescription data were available. They obtained information on PPHN, level of delivery hospital, maternal smoking, body mass index (BMI) in early pregnancy, year of birth, mode of delivery, gestational age at birth, birth weight, meconium aspiration, and maternal diseases recorded during pregnancy from the national registers.

The researchers also collected information about the mothers’ admissions to hospital for a psychiatric diagnosis during the 10 years before giving birth. In addition, they identified women who had filled prescriptions for antidepressants, antidiabetes drugs, or nonsteroidal anti-inflammatory drugs (NSAIDs) from 3 months before the start of pregnancy until delivery.

Dr. Kieler and her associates included six SSRIs in the analyses: fluoxetine (Prozac), citalopram (Celexa), paroxetine (Paxil), sertraline (Zoloft), fluvoxamine (Luvox), and escitalopram (Lexapro). They also performed subanalyses on whether other antidepressants with an effect on serotonin activity or norepinephrine activity would affect the risks of PPHN. Patient use was as "ever use" (3 months before the start of pregnancy until birth), as a filled prescription in late pregnancy (from 140 days after the start of pregnancy until birth), or in early pregnancy only (from 3 months before the start of pregnancy until a pregnancy length of 55 days).

Potential confounders included maternal smoking, age, BMI, purchased NSAIDs and antidiabetes drugs, diseases recorded during pregnancy, level of delivery hospital (university or nonuniversity hospital), and infants’ country of birth, birth year, and birth order.

In total, 1,618,255 singleton births were included. Of these, 0.7% of the mothers had filled a prescription for an SSRI during late pregnancy and 1.1% in early pregnancy only. The mothers with a filled prescription for an SSRI tended to be older and more often smokers than mothers not using SSRIs. Exposed infants had a lower gestational age at birth and were more often classified as small for gestational age. The absolute risk for PPHN for infants to mothers using SSRIs was as low as 3 infants per 1,000 exposed.

In late pregnancy, 627 women had filled a prescription for an antidepressant with an effect on serotonin activity or norepinephrine activity. The corresponding figure for early pregnancy only was 2,503. More than three-quarters (85%) of 63,615 women with a previous psychiatric diagnosis had not filled a prescription for any of the antidepressants during pregnancy.

"We recommend caution when treating pregnant women with SSRIs."

Among the 11,014 infants exposed to an SSRI in late pregnancy, 33 (0.3%) had a diagnosis of PPHN – three of whom had meconium aspiration. Among 627 infants exposed to antidepressants with an effect on serotonin activity or norepinephrine activity, 3 (0.5%) had a diagnosis of PPHN. Of the 17,053 infants exposed to SSRIs only in early pregnancy, 32 (0.2%) had PPHN; 0.1% of the 1,588,140 infants never exposed to SSRIs were diagnosed with PPHN.

Of the infants with PPHN, 3 of the 33 infants (9%) who were exposed to SSRIs in late pregnancy died, as did 183 (9.5%) of the 1,935 who were never exposed to SSRIs. Among the 63,615 women with a previous admission to hospital for a psychiatric disorder, 114 (1.8%) infants had a diagnosis of PPHN.

The risk estimates of PPHN after exposure to fluoxetine, citalopram, sertraline, or paroxetine in late pregnancy ranged from 2 to 3. While the risk estimate for escitalopram was lower, this number was imprecise. No infants with PPHN had been exposed to fluvoxamine. "Exposure to the other antidepressants with an effect on serotonin activity or norepinephrine activity also generated increased risks," Dr. Kieler and her associates wrote.

Risks for PPHN were only slightly increased in association with exposure to SSRI in early pregnancy only. Exposure to the other antidepressants with an effect on serotonin activity or norepinephrine activity did not increase the risk of PPHN in early pregnancy only.

After exclusion of infants with meconium aspiration, the risk estimates increased slightly, they said.

This study was funded by the Swedish Pharmacy Company. The authors reported that they had no relevant financial disclosures.

The use of selective serotonin reuptake inhibitors by women during pregnancy increases the risk of persistent pulmonary hypertension in newborns, with the risk doubling for use during late pregnancy.

The risk of persistent pulmonary hypertension of the newborn (PPHN) after exposure to any SSRI in late pregnancy was more than doubled (adjusted odds ratio, 2.1). The risk was slightly increased in association with exposure to SSRIs in early pregnancy (adjusted OR, 1.4). The combination of a previous admission to hospital for a psychiatric disorder and exposure to an SSRI in late pregnancy yielded an adjusted OR of 3.1. The findings – from a population-based cohort study of data from registries in five Nordic countries – were published Jan. 12 in BMJ (2011;344:d8012 [doi:10.1136/bmj.d8012]).

"As the risk in association with treatment in late pregnancy seems to be more than doubled, we recommend caution when treating pregnant women with SSRIs. It is essential to plan the treatment and to weigh the risks of persistent pulmonary hypertension of the newborn when treating women in late pregnancy with those of relapse of depression and neonatal abstinence syndrome if therapy is interrupted. For women where treatment with an SSRI is the only or best option, the choice of substance seems to be of minor importance," said Dr. Helle Kieler, an ob.gyn. at the Centre for Pharmacoepidemiology at the Karolinska Institute in Stockholm, and her coinvestigators.

The researchers included women and their infants born in Denmark, Finland, Iceland, Norway, or Sweden between 1996 and 2007. Each of these countries has national registers with prospectively collected information on the health of all inhabitants. They obtained data from the medical birth registers, the prescription registers, and the cause of death registers from all five countries. Data on the mother’s previous psychiatric diseases and infant diagnoses were included for Denmark, Iceland, Sweden, and Finland and from the Danish Psychiatric Central Register.

The investigators included all singletons born after 33 weeks’ gestation between 1996 and 2007. Births were included only from the years when prescription data were available. They obtained information on PPHN, level of delivery hospital, maternal smoking, body mass index (BMI) in early pregnancy, year of birth, mode of delivery, gestational age at birth, birth weight, meconium aspiration, and maternal diseases recorded during pregnancy from the national registers.

The researchers also collected information about the mothers’ admissions to hospital for a psychiatric diagnosis during the 10 years before giving birth. In addition, they identified women who had filled prescriptions for antidepressants, antidiabetes drugs, or nonsteroidal anti-inflammatory drugs (NSAIDs) from 3 months before the start of pregnancy until delivery.

Dr. Kieler and her associates included six SSRIs in the analyses: fluoxetine (Prozac), citalopram (Celexa), paroxetine (Paxil), sertraline (Zoloft), fluvoxamine (Luvox), and escitalopram (Lexapro). They also performed subanalyses on whether other antidepressants with an effect on serotonin activity or norepinephrine activity would affect the risks of PPHN. Patient use was as "ever use" (3 months before the start of pregnancy until birth), as a filled prescription in late pregnancy (from 140 days after the start of pregnancy until birth), or in early pregnancy only (from 3 months before the start of pregnancy until a pregnancy length of 55 days).

Potential confounders included maternal smoking, age, BMI, purchased NSAIDs and antidiabetes drugs, diseases recorded during pregnancy, level of delivery hospital (university or nonuniversity hospital), and infants’ country of birth, birth year, and birth order.

In total, 1,618,255 singleton births were included. Of these, 0.7% of the mothers had filled a prescription for an SSRI during late pregnancy and 1.1% in early pregnancy only. The mothers with a filled prescription for an SSRI tended to be older and more often smokers than mothers not using SSRIs. Exposed infants had a lower gestational age at birth and were more often classified as small for gestational age. The absolute risk for PPHN for infants to mothers using SSRIs was as low as 3 infants per 1,000 exposed.

In late pregnancy, 627 women had filled a prescription for an antidepressant with an effect on serotonin activity or norepinephrine activity. The corresponding figure for early pregnancy only was 2,503. More than three-quarters (85%) of 63,615 women with a previous psychiatric diagnosis had not filled a prescription for any of the antidepressants during pregnancy.

"We recommend caution when treating pregnant women with SSRIs."

Among the 11,014 infants exposed to an SSRI in late pregnancy, 33 (0.3%) had a diagnosis of PPHN – three of whom had meconium aspiration. Among 627 infants exposed to antidepressants with an effect on serotonin activity or norepinephrine activity, 3 (0.5%) had a diagnosis of PPHN. Of the 17,053 infants exposed to SSRIs only in early pregnancy, 32 (0.2%) had PPHN; 0.1% of the 1,588,140 infants never exposed to SSRIs were diagnosed with PPHN.

Of the infants with PPHN, 3 of the 33 infants (9%) who were exposed to SSRIs in late pregnancy died, as did 183 (9.5%) of the 1,935 who were never exposed to SSRIs. Among the 63,615 women with a previous admission to hospital for a psychiatric disorder, 114 (1.8%) infants had a diagnosis of PPHN.

The risk estimates of PPHN after exposure to fluoxetine, citalopram, sertraline, or paroxetine in late pregnancy ranged from 2 to 3. While the risk estimate for escitalopram was lower, this number was imprecise. No infants with PPHN had been exposed to fluvoxamine. "Exposure to the other antidepressants with an effect on serotonin activity or norepinephrine activity also generated increased risks," Dr. Kieler and her associates wrote.

Risks for PPHN were only slightly increased in association with exposure to SSRI in early pregnancy only. Exposure to the other antidepressants with an effect on serotonin activity or norepinephrine activity did not increase the risk of PPHN in early pregnancy only.

After exclusion of infants with meconium aspiration, the risk estimates increased slightly, they said.

This study was funded by the Swedish Pharmacy Company. The authors reported that they had no relevant financial disclosures.

The use of selective serotonin reuptake inhibitors by women during pregnancy increases the risk of persistent pulmonary hypertension in newborns, with the risk doubling for use during late pregnancy.

The risk of persistent pulmonary hypertension of the newborn (PPHN) after exposure to any SSRI in late pregnancy was more than doubled (adjusted odds ratio, 2.1). The risk was slightly increased in association with exposure to SSRIs in early pregnancy (adjusted OR, 1.4). The combination of a previous admission to hospital for a psychiatric disorder and exposure to an SSRI in late pregnancy yielded an adjusted OR of 3.1. The findings – from a population-based cohort study of data from registries in five Nordic countries – were published Jan. 12 in BMJ (2011;344:d8012 [doi:10.1136/bmj.d8012]).

"As the risk in association with treatment in late pregnancy seems to be more than doubled, we recommend caution when treating pregnant women with SSRIs. It is essential to plan the treatment and to weigh the risks of persistent pulmonary hypertension of the newborn when treating women in late pregnancy with those of relapse of depression and neonatal abstinence syndrome if therapy is interrupted. For women where treatment with an SSRI is the only or best option, the choice of substance seems to be of minor importance," said Dr. Helle Kieler, an ob.gyn. at the Centre for Pharmacoepidemiology at the Karolinska Institute in Stockholm, and her coinvestigators.

The researchers included women and their infants born in Denmark, Finland, Iceland, Norway, or Sweden between 1996 and 2007. Each of these countries has national registers with prospectively collected information on the health of all inhabitants. They obtained data from the medical birth registers, the prescription registers, and the cause of death registers from all five countries. Data on the mother’s previous psychiatric diseases and infant diagnoses were included for Denmark, Iceland, Sweden, and Finland and from the Danish Psychiatric Central Register.

The investigators included all singletons born after 33 weeks’ gestation between 1996 and 2007. Births were included only from the years when prescription data were available. They obtained information on PPHN, level of delivery hospital, maternal smoking, body mass index (BMI) in early pregnancy, year of birth, mode of delivery, gestational age at birth, birth weight, meconium aspiration, and maternal diseases recorded during pregnancy from the national registers.

The researchers also collected information about the mothers’ admissions to hospital for a psychiatric diagnosis during the 10 years before giving birth. In addition, they identified women who had filled prescriptions for antidepressants, antidiabetes drugs, or nonsteroidal anti-inflammatory drugs (NSAIDs) from 3 months before the start of pregnancy until delivery.

Dr. Kieler and her associates included six SSRIs in the analyses: fluoxetine (Prozac), citalopram (Celexa), paroxetine (Paxil), sertraline (Zoloft), fluvoxamine (Luvox), and escitalopram (Lexapro). They also performed subanalyses on whether other antidepressants with an effect on serotonin activity or norepinephrine activity would affect the risks of PPHN. Patient use was as "ever use" (3 months before the start of pregnancy until birth), as a filled prescription in late pregnancy (from 140 days after the start of pregnancy until birth), or in early pregnancy only (from 3 months before the start of pregnancy until a pregnancy length of 55 days).

Potential confounders included maternal smoking, age, BMI, purchased NSAIDs and antidiabetes drugs, diseases recorded during pregnancy, level of delivery hospital (university or nonuniversity hospital), and infants’ country of birth, birth year, and birth order.

In total, 1,618,255 singleton births were included. Of these, 0.7% of the mothers had filled a prescription for an SSRI during late pregnancy and 1.1% in early pregnancy only. The mothers with a filled prescription for an SSRI tended to be older and more often smokers than mothers not using SSRIs. Exposed infants had a lower gestational age at birth and were more often classified as small for gestational age. The absolute risk for PPHN for infants to mothers using SSRIs was as low as 3 infants per 1,000 exposed.

In late pregnancy, 627 women had filled a prescription for an antidepressant with an effect on serotonin activity or norepinephrine activity. The corresponding figure for early pregnancy only was 2,503. More than three-quarters (85%) of 63,615 women with a previous psychiatric diagnosis had not filled a prescription for any of the antidepressants during pregnancy.

"We recommend caution when treating pregnant women with SSRIs."

Among the 11,014 infants exposed to an SSRI in late pregnancy, 33 (0.3%) had a diagnosis of PPHN – three of whom had meconium aspiration. Among 627 infants exposed to antidepressants with an effect on serotonin activity or norepinephrine activity, 3 (0.5%) had a diagnosis of PPHN. Of the 17,053 infants exposed to SSRIs only in early pregnancy, 32 (0.2%) had PPHN; 0.1% of the 1,588,140 infants never exposed to SSRIs were diagnosed with PPHN.

Of the infants with PPHN, 3 of the 33 infants (9%) who were exposed to SSRIs in late pregnancy died, as did 183 (9.5%) of the 1,935 who were never exposed to SSRIs. Among the 63,615 women with a previous admission to hospital for a psychiatric disorder, 114 (1.8%) infants had a diagnosis of PPHN.

The risk estimates of PPHN after exposure to fluoxetine, citalopram, sertraline, or paroxetine in late pregnancy ranged from 2 to 3. While the risk estimate for escitalopram was lower, this number was imprecise. No infants with PPHN had been exposed to fluvoxamine. "Exposure to the other antidepressants with an effect on serotonin activity or norepinephrine activity also generated increased risks," Dr. Kieler and her associates wrote.

Risks for PPHN were only slightly increased in association with exposure to SSRI in early pregnancy only. Exposure to the other antidepressants with an effect on serotonin activity or norepinephrine activity did not increase the risk of PPHN in early pregnancy only.

After exclusion of infants with meconium aspiration, the risk estimates increased slightly, they said.

This study was funded by the Swedish Pharmacy Company. The authors reported that they had no relevant financial disclosures.

Geographic location could be associated with incidence of inflammatory bowel disease, based on a new study showing that women living in southern portions of the United States had a lower incidence than did those living in northern regions of the country.

Previous studies conducted in Europe have suggested that living in southern latitudes may be linked to lower risk for inflammatory bowel disease.

The researchers in the current study looked at where the women had lived at age 30 years, and found that those living in southern latitudes had a significantly lower multivariate-adjusted hazard ratio (HR) for ulcerative colitis (UC), at 0.62, and for Crohn’s disease (CD), at 0.48, compared with women living in northern areas (P for trend less than .01).

"The lower risk of UC associated with decreasing latitude appeared stronger according to residence at older ages."

"These results were consistent even after accounting for differences in self-reported ancestry and smoking, suggesting that other environmental or lifestyle factors correlated with geographical variation may mediate these associations," wrote Dr. Hamed Khalili and his coinvestigators. Dr. Khalili is a gastroenterologist at Massachusetts General Hospital in Boston.

The findings, from an analysis of data from more than 500 women involved in either the Nurses’ Health Study I (NHS I) or the Nurses’ Health Study II (NHS II), were published Jan. 11 in the journal Gut (Gut 2012 Jan. 11 [doi:10.1136/gutjnl-2011-301574]).

The NHS I is a prospective cohort that began in 1976 with 121,700 U.S. female registered nurses aged 30-55 years who completed a mailed health questionnaire. Follow-up questionnaires have been mailed every 2 years to update health information.

In 1989, a parallel cohort, the NHS II, enrolled 116,686 U.S. female nurses aged 25-42 years. These women have been followed with similar biennial questionnaires. Participants in both cohorts reported their state of residence at birth, age 15 years, and age 30 years.

In NHS I, participants were specifically asked about diagnoses of UC since 1982 and CD since 1992. In NHS II, participants were asked about diagnoses of both UC and CD since 1993. In both cohorts, when a diagnosis was reported on any biennial questionnaire, related medical records were requested and reviewed by two gastroenterologists blinded to exposure information.

The researchers identified 257 incident cases of CD and 313 incident cases of UC through the end of follow-up, with diagnoses based on standardized criteria. The authors also noted that baseline characteristics of participants with complete medical records were similar to those of participants for whom they were unable to obtain sufficient records.

To analyze the geographic data, the investigators divided the continental United States into northern, middle, and southern tiers of latitude. The northern tier states are Connecticut, Maine, Massachusetts, New Hampshire, New York, Rhode Island, Vermont, Michigan, Minnesota, Wisconsin, Idaho, Montana, Nebraska, North Dakota, South Dakota, Wyoming, Oregon, Washington, and Alaska. The southern tier consists of Florida, Georgia, North Carolina, South Carolina, Alabama, Arkansas, Louisiana, Mississippi, Tennessee, Arizona, New Mexico, Oklahoma, Texas, southern California, Hawaii, and Puerto Rico. The middle tier consists of Delaware, the District of Columbia, Maryland, New Jersey, Pennsylvania, Virginia, West Virginia, Illinois, Indiana, Iowa, Kentucky, Missouri, Ohio, Colorado, Kansas, Nevada, Utah, and northern California.

"The lower risk of UC associated with decreasing latitude appeared stronger according to residence at older ages," the researchers noted. For example, the multivariate-adjusted HRs for UC were 0.67 for women who resided in southern latitudes at age 15 and 0.62 for women who resided in southern latitudes at age 30. "This effect was consistent, although somewhat attenuated according to latitude of residence at birth or age 15."

For UC, data on residence at birth showed that the multivariate hazard ratio was 1.00 for women born at middle latitudes and 0.69 women born at southern latitudes, compared with women born at northern latitudes.

"This association was not materially changed when we restricted the analysis to women who resided in the same latitude at birth, age 15, and age 30," they wrote. Compared with women who had lived consistently in northern latitudes, the multivariate-adjusted HR was 0.63 for women who lived consistently in southern latitudes.

Similar results were seen for women with CD. Compared with women who resided in northern latitudes at age 30, the multivariate-adjusted HRs were 0.84 for women who resided in middle latitudes at age 30 and 0.48 for women who resided in southern latitudes at age 30.

"Although statistical power was limited, these effect estimates were not materially altered when we restricted the analyses to women who resided in the same latitudes at birth, age 15, and age 30," the researchers observed. Thus, compared with women who resided consistently in northern latitudes, the multivariate-adjusted HR was 0.77 for women who resided consistently in middle latitudes and 0.65 for women who lived consistently in southern latitudes.

"In contrast with UC, there did not appear to be a significantly lower risk of CD according to latitude based only upon residence at birth or age 15."

The reason for this apparent association between latitude and inflammatory bowel disease incidence is not clear. However, "a leading explanation for this ‘north-south’ gradient in the risk of UC and CD may be differences in exposure to sunlight or UVB radiation, which is generally greater in southern latitudes. UV radiation is the greatest environmental determinant of plasma vitamin D and there is substantial experimental data supporting a role for vitamin D in the innate immunity and regulation of inflammatory response," the researchers noted.

Funding was provided by the National Institutes of Health and the Broad Medical Research Program of the Broad Foundation. One researcher reported previously being a consultant for Bayer Healthcare and Millennium Pharmaceuticals. No other disclosures were reported.

Geographic location could be associated with incidence of inflammatory bowel disease, based on a new study showing that women living in southern portions of the United States had a lower incidence than did those living in northern regions of the country.

Previous studies conducted in Europe have suggested that living in southern latitudes may be linked to lower risk for inflammatory bowel disease.

The researchers in the current study looked at where the women had lived at age 30 years, and found that those living in southern latitudes had a significantly lower multivariate-adjusted hazard ratio (HR) for ulcerative colitis (UC), at 0.62, and for Crohn’s disease (CD), at 0.48, compared with women living in northern areas (P for trend less than .01).

"The lower risk of UC associated with decreasing latitude appeared stronger according to residence at older ages."

"These results were consistent even after accounting for differences in self-reported ancestry and smoking, suggesting that other environmental or lifestyle factors correlated with geographical variation may mediate these associations," wrote Dr. Hamed Khalili and his coinvestigators. Dr. Khalili is a gastroenterologist at Massachusetts General Hospital in Boston.

The findings, from an analysis of data from more than 500 women involved in either the Nurses’ Health Study I (NHS I) or the Nurses’ Health Study II (NHS II), were published Jan. 11 in the journal Gut (Gut 2012 Jan. 11 [doi:10.1136/gutjnl-2011-301574]).

The NHS I is a prospective cohort that began in 1976 with 121,700 U.S. female registered nurses aged 30-55 years who completed a mailed health questionnaire. Follow-up questionnaires have been mailed every 2 years to update health information.

In 1989, a parallel cohort, the NHS II, enrolled 116,686 U.S. female nurses aged 25-42 years. These women have been followed with similar biennial questionnaires. Participants in both cohorts reported their state of residence at birth, age 15 years, and age 30 years.

In NHS I, participants were specifically asked about diagnoses of UC since 1982 and CD since 1992. In NHS II, participants were asked about diagnoses of both UC and CD since 1993. In both cohorts, when a diagnosis was reported on any biennial questionnaire, related medical records were requested and reviewed by two gastroenterologists blinded to exposure information.

The researchers identified 257 incident cases of CD and 313 incident cases of UC through the end of follow-up, with diagnoses based on standardized criteria. The authors also noted that baseline characteristics of participants with complete medical records were similar to those of participants for whom they were unable to obtain sufficient records.

To analyze the geographic data, the investigators divided the continental United States into northern, middle, and southern tiers of latitude. The northern tier states are Connecticut, Maine, Massachusetts, New Hampshire, New York, Rhode Island, Vermont, Michigan, Minnesota, Wisconsin, Idaho, Montana, Nebraska, North Dakota, South Dakota, Wyoming, Oregon, Washington, and Alaska. The southern tier consists of Florida, Georgia, North Carolina, South Carolina, Alabama, Arkansas, Louisiana, Mississippi, Tennessee, Arizona, New Mexico, Oklahoma, Texas, southern California, Hawaii, and Puerto Rico. The middle tier consists of Delaware, the District of Columbia, Maryland, New Jersey, Pennsylvania, Virginia, West Virginia, Illinois, Indiana, Iowa, Kentucky, Missouri, Ohio, Colorado, Kansas, Nevada, Utah, and northern California.

"The lower risk of UC associated with decreasing latitude appeared stronger according to residence at older ages," the researchers noted. For example, the multivariate-adjusted HRs for UC were 0.67 for women who resided in southern latitudes at age 15 and 0.62 for women who resided in southern latitudes at age 30. "This effect was consistent, although somewhat attenuated according to latitude of residence at birth or age 15."

For UC, data on residence at birth showed that the multivariate hazard ratio was 1.00 for women born at middle latitudes and 0.69 women born at southern latitudes, compared with women born at northern latitudes.

"This association was not materially changed when we restricted the analysis to women who resided in the same latitude at birth, age 15, and age 30," they wrote. Compared with women who had lived consistently in northern latitudes, the multivariate-adjusted HR was 0.63 for women who lived consistently in southern latitudes.

Similar results were seen for women with CD. Compared with women who resided in northern latitudes at age 30, the multivariate-adjusted HRs were 0.84 for women who resided in middle latitudes at age 30 and 0.48 for women who resided in southern latitudes at age 30.

"Although statistical power was limited, these effect estimates were not materially altered when we restricted the analyses to women who resided in the same latitudes at birth, age 15, and age 30," the researchers observed. Thus, compared with women who resided consistently in northern latitudes, the multivariate-adjusted HR was 0.77 for women who resided consistently in middle latitudes and 0.65 for women who lived consistently in southern latitudes.

"In contrast with UC, there did not appear to be a significantly lower risk of CD according to latitude based only upon residence at birth or age 15."

The reason for this apparent association between latitude and inflammatory bowel disease incidence is not clear. However, "a leading explanation for this ‘north-south’ gradient in the risk of UC and CD may be differences in exposure to sunlight or UVB radiation, which is generally greater in southern latitudes. UV radiation is the greatest environmental determinant of plasma vitamin D and there is substantial experimental data supporting a role for vitamin D in the innate immunity and regulation of inflammatory response," the researchers noted.

Funding was provided by the National Institutes of Health and the Broad Medical Research Program of the Broad Foundation. One researcher reported previously being a consultant for Bayer Healthcare and Millennium Pharmaceuticals. No other disclosures were reported.

Geographic location could be associated with incidence of inflammatory bowel disease, based on a new study showing that women living in southern portions of the United States had a lower incidence than did those living in northern regions of the country.

Previous studies conducted in Europe have suggested that living in southern latitudes may be linked to lower risk for inflammatory bowel disease.

The researchers in the current study looked at where the women had lived at age 30 years, and found that those living in southern latitudes had a significantly lower multivariate-adjusted hazard ratio (HR) for ulcerative colitis (UC), at 0.62, and for Crohn’s disease (CD), at 0.48, compared with women living in northern areas (P for trend less than .01).

"The lower risk of UC associated with decreasing latitude appeared stronger according to residence at older ages."

"These results were consistent even after accounting for differences in self-reported ancestry and smoking, suggesting that other environmental or lifestyle factors correlated with geographical variation may mediate these associations," wrote Dr. Hamed Khalili and his coinvestigators. Dr. Khalili is a gastroenterologist at Massachusetts General Hospital in Boston.

The findings, from an analysis of data from more than 500 women involved in either the Nurses’ Health Study I (NHS I) or the Nurses’ Health Study II (NHS II), were published Jan. 11 in the journal Gut (Gut 2012 Jan. 11 [doi:10.1136/gutjnl-2011-301574]).

The NHS I is a prospective cohort that began in 1976 with 121,700 U.S. female registered nurses aged 30-55 years who completed a mailed health questionnaire. Follow-up questionnaires have been mailed every 2 years to update health information.

In 1989, a parallel cohort, the NHS II, enrolled 116,686 U.S. female nurses aged 25-42 years. These women have been followed with similar biennial questionnaires. Participants in both cohorts reported their state of residence at birth, age 15 years, and age 30 years.

In NHS I, participants were specifically asked about diagnoses of UC since 1982 and CD since 1992. In NHS II, participants were asked about diagnoses of both UC and CD since 1993. In both cohorts, when a diagnosis was reported on any biennial questionnaire, related medical records were requested and reviewed by two gastroenterologists blinded to exposure information.

The researchers identified 257 incident cases of CD and 313 incident cases of UC through the end of follow-up, with diagnoses based on standardized criteria. The authors also noted that baseline characteristics of participants with complete medical records were similar to those of participants for whom they were unable to obtain sufficient records.

To analyze the geographic data, the investigators divided the continental United States into northern, middle, and southern tiers of latitude. The northern tier states are Connecticut, Maine, Massachusetts, New Hampshire, New York, Rhode Island, Vermont, Michigan, Minnesota, Wisconsin, Idaho, Montana, Nebraska, North Dakota, South Dakota, Wyoming, Oregon, Washington, and Alaska. The southern tier consists of Florida, Georgia, North Carolina, South Carolina, Alabama, Arkansas, Louisiana, Mississippi, Tennessee, Arizona, New Mexico, Oklahoma, Texas, southern California, Hawaii, and Puerto Rico. The middle tier consists of Delaware, the District of Columbia, Maryland, New Jersey, Pennsylvania, Virginia, West Virginia, Illinois, Indiana, Iowa, Kentucky, Missouri, Ohio, Colorado, Kansas, Nevada, Utah, and northern California.

"The lower risk of UC associated with decreasing latitude appeared stronger according to residence at older ages," the researchers noted. For example, the multivariate-adjusted HRs for UC were 0.67 for women who resided in southern latitudes at age 15 and 0.62 for women who resided in southern latitudes at age 30. "This effect was consistent, although somewhat attenuated according to latitude of residence at birth or age 15."

For UC, data on residence at birth showed that the multivariate hazard ratio was 1.00 for women born at middle latitudes and 0.69 women born at southern latitudes, compared with women born at northern latitudes.

"This association was not materially changed when we restricted the analysis to women who resided in the same latitude at birth, age 15, and age 30," they wrote. Compared with women who had lived consistently in northern latitudes, the multivariate-adjusted HR was 0.63 for women who lived consistently in southern latitudes.

Similar results were seen for women with CD. Compared with women who resided in northern latitudes at age 30, the multivariate-adjusted HRs were 0.84 for women who resided in middle latitudes at age 30 and 0.48 for women who resided in southern latitudes at age 30.

"Although statistical power was limited, these effect estimates were not materially altered when we restricted the analyses to women who resided in the same latitudes at birth, age 15, and age 30," the researchers observed. Thus, compared with women who resided consistently in northern latitudes, the multivariate-adjusted HR was 0.77 for women who resided consistently in middle latitudes and 0.65 for women who lived consistently in southern latitudes.

"In contrast with UC, there did not appear to be a significantly lower risk of CD according to latitude based only upon residence at birth or age 15."

The reason for this apparent association between latitude and inflammatory bowel disease incidence is not clear. However, "a leading explanation for this ‘north-south’ gradient in the risk of UC and CD may be differences in exposure to sunlight or UVB radiation, which is generally greater in southern latitudes. UV radiation is the greatest environmental determinant of plasma vitamin D and there is substantial experimental data supporting a role for vitamin D in the innate immunity and regulation of inflammatory response," the researchers noted.

Funding was provided by the National Institutes of Health and the Broad Medical Research Program of the Broad Foundation. One researcher reported previously being a consultant for Bayer Healthcare and Millennium Pharmaceuticals. No other disclosures were reported.

Older people who develop dementia have higher rates of hospitalizations for medical illnesses than do those without dementia. In addition, those with dementia are at greater risk for several conditions that could be treated in the ambulatory setting, potentially reducing hospitalizations.

A total of 494 patients developed dementia during an average follow-up of 8 years; of those, 427 (86%) were hospitalized. In comparison, 2,525 individuals remained dementia-free during 10 years of follow-up; of those, 1,478 (59%) were hospitalized. Forty percent of those with dementia had at least one admission for an ambulatory care–sensitive condition (ACSC), compared with 17% of the dementia-free group. ASCSs were considered to be preventable with proactive outpatient care.

The findings come from a population-based, longitudinal study of aging and the incidence of and risk factors for dementia, involving more than 3,500 members of a large integrated health care delivery system. The study results were published in the Jan. 11 issue of JAMA (2012;307:165-72).

"Three ACSCs – pneumonia, [congestive heart failure], and [urinary tract infections] – accounted for two-thirds of all potentially preventable admissions among persons with dementia. Knowledge of the ACSCs most likely to lead to hospitalization is important, as this information may help clinicians focus their differential diagnostic considerations and thereby permit proactive, early management for these conditions among patients with dementia," wrote Dr. Elizabeth A. Phelan and her coinvestigators.

"Early detection and outpatient management of acute illness when it is still in its early phases might minimize the need for hospitalization for these conditions and help health care organizations reduce their rates of ACSC admissions and associated costs," wrote Dr. Phelan of the division of gerontology and geriatric medicine at the University of Washington in Seattle.

Participants were from the Adult Changes in Thought (ACT) cohort, a population-based, longitudinal study of aging and the incidence of and risk factors for dementia that began in 1994. The study involved more than 3,019 members of Group Health Cooperative, a large integrated health care delivery system. Eligible individuals were aged 65 years or older, cognitively intact, and not residing in a nursing home at the time of enrollment in the cohort (mean age at inception was 75 years). Participants have been followed up every 2 years with an in-person interview that includes dementia and health status assessment.

A biennial examination was conducted to identify cases of incident dementia. Participants who scored less than 86 on the Cognitive Abilities Screening Instrument (CASI) or had symptoms suggesting possible new onset of cognitive impairment underwent a standardized dementia diagnostic evaluation consisting of an examination by a study physician and detailed neuropsychological testing.

The results were presented at a consensus conference attended by study physicians, a neuropsychologist, a research nurse, and interviewers, and a consensus diagnosis was recorded based on standardized criteria (Diagnostic and Statistical Manual of Mental Disorders–IV and Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association criteria). Participants with incident dementia underwent one annual follow-up examination for verification of dementia status and dementia type.

The researchers used a retrospective, longitudinal cohort design to assess inpatient admission rates. ACT participants were eligible for these analyses if they did not have dementia at the baseline ACT visit; had completed at least one ACT follow-up visit (to assess for incident dementia); and were enrolled in GHC at the time of a follow-up visit (to ensure availability of hospitalization data).

The primary outcome measure was rate of hospitalization, measured as mean number of admissions per year of follow-up. An admission was defined as a hospitalization requiring an overnight stay. The secondary outcome measure was the rate of hospitalization by type, classified by the principal discharge diagnosis. The researchers identified ACSCs among principal discharge diagnoses to count conditions for which hospitalization might have been prevented with timely, evidence-driven outpatient care. Potential confounders of the association between dementia and hospitalization – sociodemographic characteristics, comorbidities, health behaviors, self-rated health, and place of residence – were ascertained from self-reported data collected at the baseline visit as well as at 2-year follow-up visits.

In terms of baseline differences, those in the group who eventually developed dementia were older at cohort entry by about 3 years and were less likely to have graduated from high school. In addition, larger percentages in this group reported having trouble dressing and reported a diagnosis of depression or Parkinson’s disease.

Probable Alzheimer’s disease (as a single cause) was the most common etiologic diagnosis in the dementia group, followed by vascular dementia alone (16%), and dementia of multiple etiologies (15%). Other etiologies included other medical (7%), substance-related (2%), and other/unknown (2%). The mean age at diagnosis was 84.3 years, with 61% having diagnoses in their 80s. The mean CASI score at time of diagnosis was 76, which is consistent with mild dementia.

The most common reasons for hospitalization – regardless of dementia status – were circulatory, respiratory, and digestive disorders. Among participants with dementia, the average annual admission rate was 419 admissions per 1,000 persons – more than twice that of those without dementia, who averaged 200 admissions per 1,000 persons each year. After age/sex adjustment, the ratio of admission rates was 1.57 and was 1.41 after adjustment for additional covariates.

In the fully adjusted model, admission rates for five types of disorders (circulatory, genitourinary, infectious, neurologic, and respiratory) were significantly greater among participants with dementia, compared with those without dementia. In contrast, those with dementia had significantly lower admission rates for musculoskeletal disorders.

ACSCs were analyzed separately. The admission rate ratio was 1.78, after full adjustment for covariates. Importantly, three ACSCs – bacterial pneumonia, heart failure, and urinary tract infection – accounted for two-thirds of all potentially preventable admissions; admission rates among those with dementia were significantly greater for all three conditions. Admission rates for dehydration and duodenal ulcer, though low overall, also were significantly greater among those with dementia. Admissions for ACSCs accounted for 28% of all hospitalizations among those with dementia vs. only 19% of all admissions among those who remained dementia free.

The authors speculated about why dementia might lead to more frequent hospitalization. First, underlying conditions that increase the risk of dementia such as stroke, or that develop in the setting of dementia, such as trouble swallowing, which raises the risk of pneumonia, might increase the risk of hospitalization.

"Second, because of its primary deleterious effects on global cognition, executive function, expressive language, symptom perception, and awareness of deficits, dementia impairs the ability to self-manage chronic conditions and to pinpoint symptoms and alert others to their presence, thereby creating substantial diagnostic and treatment challenges for primary care clinicians," the researchers wrote.

Situational factors also might contribute, including a change of living situation, or the temporary or permanent absence of a caregiver who is familiar with the person’s usual habits, behaviors, and ongoing general medical management.

They also cited another potential explanation – the threshold for hospitalizing such persons might be lower because dementia "increases central nervous system vulnerability to the metabolic effects of acute illness, such that for a comparable severity of illness, persons with dementia are in fact sicker."

The authors reported that they have no conflicts of interest. The ACT study is supported by a grant from the National Institute on Aging.

Older people who develop dementia have higher rates of hospitalizations for medical illnesses than do those without dementia. In addition, those with dementia are at greater risk for several conditions that could be treated in the ambulatory setting, potentially reducing hospitalizations.

A total of 494 patients developed dementia during an average follow-up of 8 years; of those, 427 (86%) were hospitalized. In comparison, 2,525 individuals remained dementia-free during 10 years of follow-up; of those, 1,478 (59%) were hospitalized. Forty percent of those with dementia had at least one admission for an ambulatory care–sensitive condition (ACSC), compared with 17% of the dementia-free group. ASCSs were considered to be preventable with proactive outpatient care.

The findings come from a population-based, longitudinal study of aging and the incidence of and risk factors for dementia, involving more than 3,500 members of a large integrated health care delivery system. The study results were published in the Jan. 11 issue of JAMA (2012;307:165-72).

"Three ACSCs – pneumonia, [congestive heart failure], and [urinary tract infections] – accounted for two-thirds of all potentially preventable admissions among persons with dementia. Knowledge of the ACSCs most likely to lead to hospitalization is important, as this information may help clinicians focus their differential diagnostic considerations and thereby permit proactive, early management for these conditions among patients with dementia," wrote Dr. Elizabeth A. Phelan and her coinvestigators.

"Early detection and outpatient management of acute illness when it is still in its early phases might minimize the need for hospitalization for these conditions and help health care organizations reduce their rates of ACSC admissions and associated costs," wrote Dr. Phelan of the division of gerontology and geriatric medicine at the University of Washington in Seattle.

Participants were from the Adult Changes in Thought (ACT) cohort, a population-based, longitudinal study of aging and the incidence of and risk factors for dementia that began in 1994. The study involved more than 3,019 members of Group Health Cooperative, a large integrated health care delivery system. Eligible individuals were aged 65 years or older, cognitively intact, and not residing in a nursing home at the time of enrollment in the cohort (mean age at inception was 75 years). Participants have been followed up every 2 years with an in-person interview that includes dementia and health status assessment.

A biennial examination was conducted to identify cases of incident dementia. Participants who scored less than 86 on the Cognitive Abilities Screening Instrument (CASI) or had symptoms suggesting possible new onset of cognitive impairment underwent a standardized dementia diagnostic evaluation consisting of an examination by a study physician and detailed neuropsychological testing.

The results were presented at a consensus conference attended by study physicians, a neuropsychologist, a research nurse, and interviewers, and a consensus diagnosis was recorded based on standardized criteria (Diagnostic and Statistical Manual of Mental Disorders–IV and Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association criteria). Participants with incident dementia underwent one annual follow-up examination for verification of dementia status and dementia type.

The researchers used a retrospective, longitudinal cohort design to assess inpatient admission rates. ACT participants were eligible for these analyses if they did not have dementia at the baseline ACT visit; had completed at least one ACT follow-up visit (to assess for incident dementia); and were enrolled in GHC at the time of a follow-up visit (to ensure availability of hospitalization data).

The primary outcome measure was rate of hospitalization, measured as mean number of admissions per year of follow-up. An admission was defined as a hospitalization requiring an overnight stay. The secondary outcome measure was the rate of hospitalization by type, classified by the principal discharge diagnosis. The researchers identified ACSCs among principal discharge diagnoses to count conditions for which hospitalization might have been prevented with timely, evidence-driven outpatient care. Potential confounders of the association between dementia and hospitalization – sociodemographic characteristics, comorbidities, health behaviors, self-rated health, and place of residence – were ascertained from self-reported data collected at the baseline visit as well as at 2-year follow-up visits.

In terms of baseline differences, those in the group who eventually developed dementia were older at cohort entry by about 3 years and were less likely to have graduated from high school. In addition, larger percentages in this group reported having trouble dressing and reported a diagnosis of depression or Parkinson’s disease.

Probable Alzheimer’s disease (as a single cause) was the most common etiologic diagnosis in the dementia group, followed by vascular dementia alone (16%), and dementia of multiple etiologies (15%). Other etiologies included other medical (7%), substance-related (2%), and other/unknown (2%). The mean age at diagnosis was 84.3 years, with 61% having diagnoses in their 80s. The mean CASI score at time of diagnosis was 76, which is consistent with mild dementia.

The most common reasons for hospitalization – regardless of dementia status – were circulatory, respiratory, and digestive disorders. Among participants with dementia, the average annual admission rate was 419 admissions per 1,000 persons – more than twice that of those without dementia, who averaged 200 admissions per 1,000 persons each year. After age/sex adjustment, the ratio of admission rates was 1.57 and was 1.41 after adjustment for additional covariates.

In the fully adjusted model, admission rates for five types of disorders (circulatory, genitourinary, infectious, neurologic, and respiratory) were significantly greater among participants with dementia, compared with those without dementia. In contrast, those with dementia had significantly lower admission rates for musculoskeletal disorders.

ACSCs were analyzed separately. The admission rate ratio was 1.78, after full adjustment for covariates. Importantly, three ACSCs – bacterial pneumonia, heart failure, and urinary tract infection – accounted for two-thirds of all potentially preventable admissions; admission rates among those with dementia were significantly greater for all three conditions. Admission rates for dehydration and duodenal ulcer, though low overall, also were significantly greater among those with dementia. Admissions for ACSCs accounted for 28% of all hospitalizations among those with dementia vs. only 19% of all admissions among those who remained dementia free.

The authors speculated about why dementia might lead to more frequent hospitalization. First, underlying conditions that increase the risk of dementia such as stroke, or that develop in the setting of dementia, such as trouble swallowing, which raises the risk of pneumonia, might increase the risk of hospitalization.

"Second, because of its primary deleterious effects on global cognition, executive function, expressive language, symptom perception, and awareness of deficits, dementia impairs the ability to self-manage chronic conditions and to pinpoint symptoms and alert others to their presence, thereby creating substantial diagnostic and treatment challenges for primary care clinicians," the researchers wrote.

Situational factors also might contribute, including a change of living situation, or the temporary or permanent absence of a caregiver who is familiar with the person’s usual habits, behaviors, and ongoing general medical management.

They also cited another potential explanation – the threshold for hospitalizing such persons might be lower because dementia "increases central nervous system vulnerability to the metabolic effects of acute illness, such that for a comparable severity of illness, persons with dementia are in fact sicker."

The authors reported that they have no conflicts of interest. The ACT study is supported by a grant from the National Institute on Aging.

Older people who develop dementia have higher rates of hospitalizations for medical illnesses than do those without dementia. In addition, those with dementia are at greater risk for several conditions that could be treated in the ambulatory setting, potentially reducing hospitalizations.

A total of 494 patients developed dementia during an average follow-up of 8 years; of those, 427 (86%) were hospitalized. In comparison, 2,525 individuals remained dementia-free during 10 years of follow-up; of those, 1,478 (59%) were hospitalized. Forty percent of those with dementia had at least one admission for an ambulatory care–sensitive condition (ACSC), compared with 17% of the dementia-free group. ASCSs were considered to be preventable with proactive outpatient care.

The findings come from a population-based, longitudinal study of aging and the incidence of and risk factors for dementia, involving more than 3,500 members of a large integrated health care delivery system. The study results were published in the Jan. 11 issue of JAMA (2012;307:165-72).

"Three ACSCs – pneumonia, [congestive heart failure], and [urinary tract infections] – accounted for two-thirds of all potentially preventable admissions among persons with dementia. Knowledge of the ACSCs most likely to lead to hospitalization is important, as this information may help clinicians focus their differential diagnostic considerations and thereby permit proactive, early management for these conditions among patients with dementia," wrote Dr. Elizabeth A. Phelan and her coinvestigators.

"Early detection and outpatient management of acute illness when it is still in its early phases might minimize the need for hospitalization for these conditions and help health care organizations reduce their rates of ACSC admissions and associated costs," wrote Dr. Phelan of the division of gerontology and geriatric medicine at the University of Washington in Seattle.

Participants were from the Adult Changes in Thought (ACT) cohort, a population-based, longitudinal study of aging and the incidence of and risk factors for dementia that began in 1994. The study involved more than 3,019 members of Group Health Cooperative, a large integrated health care delivery system. Eligible individuals were aged 65 years or older, cognitively intact, and not residing in a nursing home at the time of enrollment in the cohort (mean age at inception was 75 years). Participants have been followed up every 2 years with an in-person interview that includes dementia and health status assessment.

A biennial examination was conducted to identify cases of incident dementia. Participants who scored less than 86 on the Cognitive Abilities Screening Instrument (CASI) or had symptoms suggesting possible new onset of cognitive impairment underwent a standardized dementia diagnostic evaluation consisting of an examination by a study physician and detailed neuropsychological testing.

The results were presented at a consensus conference attended by study physicians, a neuropsychologist, a research nurse, and interviewers, and a consensus diagnosis was recorded based on standardized criteria (Diagnostic and Statistical Manual of Mental Disorders–IV and Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association criteria). Participants with incident dementia underwent one annual follow-up examination for verification of dementia status and dementia type.

The researchers used a retrospective, longitudinal cohort design to assess inpatient admission rates. ACT participants were eligible for these analyses if they did not have dementia at the baseline ACT visit; had completed at least one ACT follow-up visit (to assess for incident dementia); and were enrolled in GHC at the time of a follow-up visit (to ensure availability of hospitalization data).

The primary outcome measure was rate of hospitalization, measured as mean number of admissions per year of follow-up. An admission was defined as a hospitalization requiring an overnight stay. The secondary outcome measure was the rate of hospitalization by type, classified by the principal discharge diagnosis. The researchers identified ACSCs among principal discharge diagnoses to count conditions for which hospitalization might have been prevented with timely, evidence-driven outpatient care. Potential confounders of the association between dementia and hospitalization – sociodemographic characteristics, comorbidities, health behaviors, self-rated health, and place of residence – were ascertained from self-reported data collected at the baseline visit as well as at 2-year follow-up visits.

In terms of baseline differences, those in the group who eventually developed dementia were older at cohort entry by about 3 years and were less likely to have graduated from high school. In addition, larger percentages in this group reported having trouble dressing and reported a diagnosis of depression or Parkinson’s disease.

Probable Alzheimer’s disease (as a single cause) was the most common etiologic diagnosis in the dementia group, followed by vascular dementia alone (16%), and dementia of multiple etiologies (15%). Other etiologies included other medical (7%), substance-related (2%), and other/unknown (2%). The mean age at diagnosis was 84.3 years, with 61% having diagnoses in their 80s. The mean CASI score at time of diagnosis was 76, which is consistent with mild dementia.

The most common reasons for hospitalization – regardless of dementia status – were circulatory, respiratory, and digestive disorders. Among participants with dementia, the average annual admission rate was 419 admissions per 1,000 persons – more than twice that of those without dementia, who averaged 200 admissions per 1,000 persons each year. After age/sex adjustment, the ratio of admission rates was 1.57 and was 1.41 after adjustment for additional covariates.

In the fully adjusted model, admission rates for five types of disorders (circulatory, genitourinary, infectious, neurologic, and respiratory) were significantly greater among participants with dementia, compared with those without dementia. In contrast, those with dementia had significantly lower admission rates for musculoskeletal disorders.

ACSCs were analyzed separately. The admission rate ratio was 1.78, after full adjustment for covariates. Importantly, three ACSCs – bacterial pneumonia, heart failure, and urinary tract infection – accounted for two-thirds of all potentially preventable admissions; admission rates among those with dementia were significantly greater for all three conditions. Admission rates for dehydration and duodenal ulcer, though low overall, also were significantly greater among those with dementia. Admissions for ACSCs accounted for 28% of all hospitalizations among those with dementia vs. only 19% of all admissions among those who remained dementia free.

The authors speculated about why dementia might lead to more frequent hospitalization. First, underlying conditions that increase the risk of dementia such as stroke, or that develop in the setting of dementia, such as trouble swallowing, which raises the risk of pneumonia, might increase the risk of hospitalization.

"Second, because of its primary deleterious effects on global cognition, executive function, expressive language, symptom perception, and awareness of deficits, dementia impairs the ability to self-manage chronic conditions and to pinpoint symptoms and alert others to their presence, thereby creating substantial diagnostic and treatment challenges for primary care clinicians," the researchers wrote.

Situational factors also might contribute, including a change of living situation, or the temporary or permanent absence of a caregiver who is familiar with the person’s usual habits, behaviors, and ongoing general medical management.

They also cited another potential explanation – the threshold for hospitalizing such persons might be lower because dementia "increases central nervous system vulnerability to the metabolic effects of acute illness, such that for a comparable severity of illness, persons with dementia are in fact sicker."

The authors reported that they have no conflicts of interest. The ACT study is supported by a grant from the National Institute on Aging.

Men with rheumatoid arthritis have a two-thirds greater risk of developing erectile dysfunction than men without the disease, based on the results of the first study to show such an association.

The odds ratio for prior rheumatoid arthritis (RA) among men with erectile dysfunction (ED) was 1.67 that of controls, based on conditional logistic regression analysis, after adjusting for the possible confounding effects of monthly income, geographical location, urbanization level, hypertension, diabetes, coronary heart disease, hyperlipidemia, obesity, and alcohol abuse/alcohol dependence syndrome. The study was published in a letter in Annals of the Rheumatic Diseases on Jan. 4 (Ann. Rheum. Dis. 2011 Jan. 4 [doi:10.1136/annrheumdis-2011-200890]).

"This study succeeded in making a novel association between ED and prior RA. It is important for physicians treating RA patients to be sensitive to any complaints concerning sexual function and consider referring them for an erectile function assessment and possible treatment," wrote Dr. Joseph J Keller and Herng-Ching Lin, Ph.D., of the Taipei (Taiwan) Medical University.

The study included 6,310 patients (aged 18-80 years) who had received a first-time diagnosis of ED between 2001 and 2009 as cases and 37,860 control patients (six controls per case) were matched with cases in terms of age (in intervals of 10 years) and index year.

"It is important for physicians treating RA patients to be sensitive to any complaints concerning sexual function."

The researchers used administrative claims data from the Taiwan Longitudinal Health Insurance Database 2000 for this study. The database includes all the claims data and registration files of 1 million individuals under the Taiwan National Health Insurance program.

The researchers included only ED patients who had been diagnosed at least twice during the period between 2001 and 2009 – with at least one of the diagnoses being made by a urologist – in order to increase the diagnostic validity of ED.

The researchers also selected patients with RA who had received two or more RA diagnoses prior to the index date – with at least one being made by a rheumatologist. In addition, RA cases were included only if they had been prescribed at least one type of disease-modifying antirheumatic drug.

It has been suggested that patients with RA may be more likely to develop other conditions – such as ED – that are associated with increased cardiovascular risks and chronic inflammation. However, no study has explored the possible association between ED and RA to date.

The researchers noted that "it is possible that the association seen in this study between RA and ED proceeds through RA-induced endothelial dysfunction. Although a plethora of mechanisms have been proposed to underpin ED’s association with other diseases. ... [F]urther studies will be necessary to explore the mechanistic underpinnings of the association detected in this study."

Both authors reported that they have no competing interests.

Men with rheumatoid arthritis have a two-thirds greater risk of developing erectile dysfunction than men without the disease, based on the results of the first study to show such an association.

The odds ratio for prior rheumatoid arthritis (RA) among men with erectile dysfunction (ED) was 1.67 that of controls, based on conditional logistic regression analysis, after adjusting for the possible confounding effects of monthly income, geographical location, urbanization level, hypertension, diabetes, coronary heart disease, hyperlipidemia, obesity, and alcohol abuse/alcohol dependence syndrome. The study was published in a letter in Annals of the Rheumatic Diseases on Jan. 4 (Ann. Rheum. Dis. 2011 Jan. 4 [doi:10.1136/annrheumdis-2011-200890]).

"This study succeeded in making a novel association between ED and prior RA. It is important for physicians treating RA patients to be sensitive to any complaints concerning sexual function and consider referring them for an erectile function assessment and possible treatment," wrote Dr. Joseph J Keller and Herng-Ching Lin, Ph.D., of the Taipei (Taiwan) Medical University.

The study included 6,310 patients (aged 18-80 years) who had received a first-time diagnosis of ED between 2001 and 2009 as cases and 37,860 control patients (six controls per case) were matched with cases in terms of age (in intervals of 10 years) and index year.

"It is important for physicians treating RA patients to be sensitive to any complaints concerning sexual function."

The researchers used administrative claims data from the Taiwan Longitudinal Health Insurance Database 2000 for this study. The database includes all the claims data and registration files of 1 million individuals under the Taiwan National Health Insurance program.

The researchers included only ED patients who had been diagnosed at least twice during the period between 2001 and 2009 – with at least one of the diagnoses being made by a urologist – in order to increase the diagnostic validity of ED.

The researchers also selected patients with RA who had received two or more RA diagnoses prior to the index date – with at least one being made by a rheumatologist. In addition, RA cases were included only if they had been prescribed at least one type of disease-modifying antirheumatic drug.

It has been suggested that patients with RA may be more likely to develop other conditions – such as ED – that are associated with increased cardiovascular risks and chronic inflammation. However, no study has explored the possible association between ED and RA to date.

The researchers noted that "it is possible that the association seen in this study between RA and ED proceeds through RA-induced endothelial dysfunction. Although a plethora of mechanisms have been proposed to underpin ED’s association with other diseases. ... [F]urther studies will be necessary to explore the mechanistic underpinnings of the association detected in this study."

Both authors reported that they have no competing interests.

Men with rheumatoid arthritis have a two-thirds greater risk of developing erectile dysfunction than men without the disease, based on the results of the first study to show such an association.

The odds ratio for prior rheumatoid arthritis (RA) among men with erectile dysfunction (ED) was 1.67 that of controls, based on conditional logistic regression analysis, after adjusting for the possible confounding effects of monthly income, geographical location, urbanization level, hypertension, diabetes, coronary heart disease, hyperlipidemia, obesity, and alcohol abuse/alcohol dependence syndrome. The study was published in a letter in Annals of the Rheumatic Diseases on Jan. 4 (Ann. Rheum. Dis. 2011 Jan. 4 [doi:10.1136/annrheumdis-2011-200890]).

"This study succeeded in making a novel association between ED and prior RA. It is important for physicians treating RA patients to be sensitive to any complaints concerning sexual function and consider referring them for an erectile function assessment and possible treatment," wrote Dr. Joseph J Keller and Herng-Ching Lin, Ph.D., of the Taipei (Taiwan) Medical University.

The study included 6,310 patients (aged 18-80 years) who had received a first-time diagnosis of ED between 2001 and 2009 as cases and 37,860 control patients (six controls per case) were matched with cases in terms of age (in intervals of 10 years) and index year.

"It is important for physicians treating RA patients to be sensitive to any complaints concerning sexual function."

The researchers used administrative claims data from the Taiwan Longitudinal Health Insurance Database 2000 for this study. The database includes all the claims data and registration files of 1 million individuals under the Taiwan National Health Insurance program.

The researchers included only ED patients who had been diagnosed at least twice during the period between 2001 and 2009 – with at least one of the diagnoses being made by a urologist – in order to increase the diagnostic validity of ED.

The researchers also selected patients with RA who had received two or more RA diagnoses prior to the index date – with at least one being made by a rheumatologist. In addition, RA cases were included only if they had been prescribed at least one type of disease-modifying antirheumatic drug.

It has been suggested that patients with RA may be more likely to develop other conditions – such as ED – that are associated with increased cardiovascular risks and chronic inflammation. However, no study has explored the possible association between ED and RA to date.

The researchers noted that "it is possible that the association seen in this study between RA and ED proceeds through RA-induced endothelial dysfunction. Although a plethora of mechanisms have been proposed to underpin ED’s association with other diseases. ... [F]urther studies will be necessary to explore the mechanistic underpinnings of the association detected in this study."

Both authors reported that they have no competing interests.

The Food and Drug Administration will prohibit certain uses of cephalosporins in specific food animals in an attempt to preserve the antibiotics’ effectiveness for treating human infections.

In an order issued Jan. 4, the FDA said that by April it will prohibit unapproved uses of cephalosporins in cattle, swine, chickens, and turkeys.

The order prohibits the use of cephalosporin drugs for disease prevention in food animals. Furthermore, only cephalosporin drugs that have been approved for use in cattle, swine, chickens, or turkeys are permitted for use in those species. The order also prohibits giving food animals cephalosporins at unapproved dose levels, frequencies, durations, or routes of administration. Cephalosporins that are intended for use in humans or companion animals are prohibited for use in food animals.

The decision comes more than 3 years after the agency revoked a July 2008 decision to prohibit without exception all "extralabel" uses of cephalosporins in food-producing animals. The agency revoked the original order after receiving comments from approximately 170 organizations or individuals. According to the FDA, scientific review of those comments was factored into the new order, which was greeted with support by physicians and groups concerned about the emergence of antibiotic resistance.

"Physicians must be able to rely on proven, safe, and effective medications to provide optimal care to their patients," Dr. Peter W. Carmel, president of the American Medical Association, said in a statement. "By taking this step, physicians can continue to have this class of antibiotics available to successfully fight bacterial meningitis and other serious infections."

"It’s wonderful that FDA made this move," Dr. James R. Johnson said in an interview.

Cephalosporins are "a hugely important group of antibiotics. These are workhorse, frontline, mainstream antibiotics," said Dr. Johnson, a member of the Infectious Disease Society of America’s Antimicrobial Resistance Work Group.

Cephalosporins are active against gram-positive and gram-negative bacteria, and "the biggest concern right now is resistance against gram-negatives. That’s where agricultural use has been thought to be contributing in an important way to the resistance problem – particularly salmonella and [Escherichia coli]."

Unfortunately, there are few antibiotics in development against gram-negative bacteria. "The ones that are under development are on a timeline that means they are not going to be available to us for years to come," he said.

"So we’re sort of in the position of holding on by our fingernails, dealing with these bad infections with the drugs that we currently have for the next however many years until new drugs become available," said Dr. Johnson, who is also a professor of medicine at the University of Minnesota, Minneapolis.

Dr. Johnson reported that he received grant support from several pharmaceutical companies.

The Food and Drug Administration will prohibit certain uses of cephalosporins in specific food animals in an attempt to preserve the antibiotics’ effectiveness for treating human infections.

In an order issued Jan. 4, the FDA said that by April it will prohibit unapproved uses of cephalosporins in cattle, swine, chickens, and turkeys.

The order prohibits the use of cephalosporin drugs for disease prevention in food animals. Furthermore, only cephalosporin drugs that have been approved for use in cattle, swine, chickens, or turkeys are permitted for use in those species. The order also prohibits giving food animals cephalosporins at unapproved dose levels, frequencies, durations, or routes of administration. Cephalosporins that are intended for use in humans or companion animals are prohibited for use in food animals.

The decision comes more than 3 years after the agency revoked a July 2008 decision to prohibit without exception all "extralabel" uses of cephalosporins in food-producing animals. The agency revoked the original order after receiving comments from approximately 170 organizations or individuals. According to the FDA, scientific review of those comments was factored into the new order, which was greeted with support by physicians and groups concerned about the emergence of antibiotic resistance.

"Physicians must be able to rely on proven, safe, and effective medications to provide optimal care to their patients," Dr. Peter W. Carmel, president of the American Medical Association, said in a statement. "By taking this step, physicians can continue to have this class of antibiotics available to successfully fight bacterial meningitis and other serious infections."

"It’s wonderful that FDA made this move," Dr. James R. Johnson said in an interview.

Cephalosporins are "a hugely important group of antibiotics. These are workhorse, frontline, mainstream antibiotics," said Dr. Johnson, a member of the Infectious Disease Society of America’s Antimicrobial Resistance Work Group.

Cephalosporins are active against gram-positive and gram-negative bacteria, and "the biggest concern right now is resistance against gram-negatives. That’s where agricultural use has been thought to be contributing in an important way to the resistance problem – particularly salmonella and [Escherichia coli]."

Unfortunately, there are few antibiotics in development against gram-negative bacteria. "The ones that are under development are on a timeline that means they are not going to be available to us for years to come," he said.

"So we’re sort of in the position of holding on by our fingernails, dealing with these bad infections with the drugs that we currently have for the next however many years until new drugs become available," said Dr. Johnson, who is also a professor of medicine at the University of Minnesota, Minneapolis.

Dr. Johnson reported that he received grant support from several pharmaceutical companies.

The Food and Drug Administration will prohibit certain uses of cephalosporins in specific food animals in an attempt to preserve the antibiotics’ effectiveness for treating human infections.

In an order issued Jan. 4, the FDA said that by April it will prohibit unapproved uses of cephalosporins in cattle, swine, chickens, and turkeys.

The order prohibits the use of cephalosporin drugs for disease prevention in food animals. Furthermore, only cephalosporin drugs that have been approved for use in cattle, swine, chickens, or turkeys are permitted for use in those species. The order also prohibits giving food animals cephalosporins at unapproved dose levels, frequencies, durations, or routes of administration. Cephalosporins that are intended for use in humans or companion animals are prohibited for use in food animals.

The decision comes more than 3 years after the agency revoked a July 2008 decision to prohibit without exception all "extralabel" uses of cephalosporins in food-producing animals. The agency revoked the original order after receiving comments from approximately 170 organizations or individuals. According to the FDA, scientific review of those comments was factored into the new order, which was greeted with support by physicians and groups concerned about the emergence of antibiotic resistance.

"Physicians must be able to rely on proven, safe, and effective medications to provide optimal care to their patients," Dr. Peter W. Carmel, president of the American Medical Association, said in a statement. "By taking this step, physicians can continue to have this class of antibiotics available to successfully fight bacterial meningitis and other serious infections."

"It’s wonderful that FDA made this move," Dr. James R. Johnson said in an interview.

Cephalosporins are "a hugely important group of antibiotics. These are workhorse, frontline, mainstream antibiotics," said Dr. Johnson, a member of the Infectious Disease Society of America’s Antimicrobial Resistance Work Group.

Cephalosporins are active against gram-positive and gram-negative bacteria, and "the biggest concern right now is resistance against gram-negatives. That’s where agricultural use has been thought to be contributing in an important way to the resistance problem – particularly salmonella and [Escherichia coli]."

Unfortunately, there are few antibiotics in development against gram-negative bacteria. "The ones that are under development are on a timeline that means they are not going to be available to us for years to come," he said.

"So we’re sort of in the position of holding on by our fingernails, dealing with these bad infections with the drugs that we currently have for the next however many years until new drugs become available," said Dr. Johnson, who is also a professor of medicine at the University of Minnesota, Minneapolis.

Dr. Johnson reported that he received grant support from several pharmaceutical companies.

SAN ANTONIO – Adjuvant therapy with ibandronate made no impact on disease-free survival or overall survival rates in women with node-positive, early breast cancer that had been treated with dose-dense chemotherapy in a phase-III study of more than 3,000 patients.

The 3-year disease-free survival rate of 87.6% in those on ibandronate (Boniva) was a close match with the 87.2% that was recorded in a control group under observation. The 3-year overall survival rates also were similar, at 94.7% with ibandronate and 94.1% with observation.

There were no differences in disease-free survival for any of the subgroup analyses, Volker Möbus, Ph.D., reported at the annual San Antonio Breast Cancer Symposium.

"The interim analysis for efficacy showed little difference between treatment arms with and without ibandronate," said Dr. Möbus, head of obstetrics and gynecology at Klinikum Frankfurt (Germany) Höchst. The interim analysis was planned when 50% (405) of the expected events had been reached.

The GAIN (German Adjuvant Intergroup Node-Positive Study) trial is a controlled, nonblinded, randomized, phase III trial. The investigators compared epirubicin, cyclophosphamide, and paclitaxel chemotherapy with epirubicin and cyclophosphamide followed by paclitaxel and capecitabine. In addition, patients were further randomized in a 2:1 ratio to receive ibandronate (50 mg/day for 2 years) or observation alone.

Dr. Möbus presented the results for the ibandronate component of the trial. The chemotherapy results have not been released.

The GAIN trial randomized 3,023 women between June 2004 and August 2008. The protocol required that they be aged from 18 to younger than 65 years, and have histologically confirmed, lymph node–positive uni- or bilateral primary breast cancer, as well as an ECOG performance score of at least 2. Patients could have no distant metastases, and a life expectancy of at least 10 years was required. The median age was 50 years, and median follow-up was 39 months.

In all, 2,015 and 1,008 patients, respectively, were randomized to ibandronate vs. observation. However, 15 patients in the observation arm also started ibandronate, for a total of 1,870 patients. Some 18% of patients on ibandronate discontinued use of the drug for a variety of reasons, including death, adverse events, and loss to follow-up, noted Dr. Möbus.

An oral bisphosphonate, ibandronate is approved for the prevention and treatment of osteoporosis in postmenopausal women in the United States.

Financial support for the study was provided by Amgen and Roche. Dr. Möbus and several of his coinvestigators disclosed financial relationships with Amgen and Roche.

SAN ANTONIO – Adjuvant therapy with ibandronate made no impact on disease-free survival or overall survival rates in women with node-positive, early breast cancer that had been treated with dose-dense chemotherapy in a phase-III study of more than 3,000 patients.

The 3-year disease-free survival rate of 87.6% in those on ibandronate (Boniva) was a close match with the 87.2% that was recorded in a control group under observation. The 3-year overall survival rates also were similar, at 94.7% with ibandronate and 94.1% with observation.

There were no differences in disease-free survival for any of the subgroup analyses, Volker Möbus, Ph.D., reported at the annual San Antonio Breast Cancer Symposium.

"The interim analysis for efficacy showed little difference between treatment arms with and without ibandronate," said Dr. Möbus, head of obstetrics and gynecology at Klinikum Frankfurt (Germany) Höchst. The interim analysis was planned when 50% (405) of the expected events had been reached.

The GAIN (German Adjuvant Intergroup Node-Positive Study) trial is a controlled, nonblinded, randomized, phase III trial. The investigators compared epirubicin, cyclophosphamide, and paclitaxel chemotherapy with epirubicin and cyclophosphamide followed by paclitaxel and capecitabine. In addition, patients were further randomized in a 2:1 ratio to receive ibandronate (50 mg/day for 2 years) or observation alone.

Dr. Möbus presented the results for the ibandronate component of the trial. The chemotherapy results have not been released.

The GAIN trial randomized 3,023 women between June 2004 and August 2008. The protocol required that they be aged from 18 to younger than 65 years, and have histologically confirmed, lymph node–positive uni- or bilateral primary breast cancer, as well as an ECOG performance score of at least 2. Patients could have no distant metastases, and a life expectancy of at least 10 years was required. The median age was 50 years, and median follow-up was 39 months.

In all, 2,015 and 1,008 patients, respectively, were randomized to ibandronate vs. observation. However, 15 patients in the observation arm also started ibandronate, for a total of 1,870 patients. Some 18% of patients on ibandronate discontinued use of the drug for a variety of reasons, including death, adverse events, and loss to follow-up, noted Dr. Möbus.

An oral bisphosphonate, ibandronate is approved for the prevention and treatment of osteoporosis in postmenopausal women in the United States.

Financial support for the study was provided by Amgen and Roche. Dr. Möbus and several of his coinvestigators disclosed financial relationships with Amgen and Roche.

SAN ANTONIO – Adjuvant therapy with ibandronate made no impact on disease-free survival or overall survival rates in women with node-positive, early breast cancer that had been treated with dose-dense chemotherapy in a phase-III study of more than 3,000 patients.

The 3-year disease-free survival rate of 87.6% in those on ibandronate (Boniva) was a close match with the 87.2% that was recorded in a control group under observation. The 3-year overall survival rates also were similar, at 94.7% with ibandronate and 94.1% with observation.

There were no differences in disease-free survival for any of the subgroup analyses, Volker Möbus, Ph.D., reported at the annual San Antonio Breast Cancer Symposium.

"The interim analysis for efficacy showed little difference between treatment arms with and without ibandronate," said Dr. Möbus, head of obstetrics and gynecology at Klinikum Frankfurt (Germany) Höchst. The interim analysis was planned when 50% (405) of the expected events had been reached.

The GAIN (German Adjuvant Intergroup Node-Positive Study) trial is a controlled, nonblinded, randomized, phase III trial. The investigators compared epirubicin, cyclophosphamide, and paclitaxel chemotherapy with epirubicin and cyclophosphamide followed by paclitaxel and capecitabine. In addition, patients were further randomized in a 2:1 ratio to receive ibandronate (50 mg/day for 2 years) or observation alone.

Dr. Möbus presented the results for the ibandronate component of the trial. The chemotherapy results have not been released.

The GAIN trial randomized 3,023 women between June 2004 and August 2008. The protocol required that they be aged from 18 to younger than 65 years, and have histologically confirmed, lymph node–positive uni- or bilateral primary breast cancer, as well as an ECOG performance score of at least 2. Patients could have no distant metastases, and a life expectancy of at least 10 years was required. The median age was 50 years, and median follow-up was 39 months.

In all, 2,015 and 1,008 patients, respectively, were randomized to ibandronate vs. observation. However, 15 patients in the observation arm also started ibandronate, for a total of 1,870 patients. Some 18% of patients on ibandronate discontinued use of the drug for a variety of reasons, including death, adverse events, and loss to follow-up, noted Dr. Möbus.

An oral bisphosphonate, ibandronate is approved for the prevention and treatment of osteoporosis in postmenopausal women in the United States.

Financial support for the study was provided by Amgen and Roche. Dr. Möbus and several of his coinvestigators disclosed financial relationships with Amgen and Roche.

CHICAGO – The novel anti–tumor necrosis factor nanobody ATN-103 looks as if it will be moving on to phase III trials, based on the good efficacy and safety results of a phase IIA trial of more than 250 patients with rheumatoid arthritis.

"The 80-mg, every-4-weeks regimen was the one [dosage] that was consistently improved over placebo by ACR 20" (the American College of Rheumatology evaluation scale that reflects a 20% improvement in specified parameters), Dr. Roy M. Fleischmann said at the American College of Rheumatology annual meeting. In addition, this dosage group comprised the only patients to achieve significantly better responses on the ACR 50 and the ACR 70 criteria than was achieved by those taking placebo.

A nanobody is the smallest functional fragment of a naturally occurring, single-chain antibody, and ATN-103 (ozoralizumab) is just one-quarter the size of conventional TNF-blockers, Dr. Fleischmann noted. As a humanized bispecific nanobody, ATN-103 contains two human TNF-binding domains that are linked to a human serum albumin–binding domain to extend half-life.

The researchers conducted a double-blind, placebo-controlled, phase IIA proof-of-concept study that included 253 patients in three treatment groups, with roughly 40 patients at each dosage level. The 4-week dosing group received the active drug (a subcutaneous injection of 10 mg, 30 mg, or 80 mg) on day 1 of weeks 4, 8, and 12. The 8-week dosing group received either 10 mg or 80 mg of the drug on day 1 of each 8-week period. Those in the placebo group received a placebo injection on day 1 of weeks 4, 8, and 12.

All of the patients had active RA (defined as at least six swollen and at least six tender joints) at the time of screening and at baseline, despite having been treated with methotrexate for at least 12 weeks. To qualify for the study, they had to meet the 1987 revised criteria for RA at least 24 weeks prior to screening, to be within ACR functional class I-III, and to have a C-reactive protein level of at least 8 mg/L. In addition, their methotrexate dose (7.5-25 mg) and route of administration had to be stable for at least 6 weeks prior to baseline. The patients were stratified by prior TNF-inhibitor use; two-thirds of them were naive to TNF-blockers.

The primary outcome of this study was ACR 20 at 16 weeks. Secondary end points were improvements over placebo in clinical scores, DAS28 (Disease Activity Score based on a 28-joint count), ACR 50, ACR 70, and EULAR responses at week 16.

The ACR criteria are used to evaluate improvement in tender or swollen joint counts, as well as improvement in three of the following five parameters: acute phase reactant, patient assessment, physician assessment, pain scale, and disability/functional questionnaire scores. The EULAR response includes not only change in disease activity but also current disease activity.

"The safety profile looked relatively clean," said Dr. Fleischmann of the Metroplex Clinical Research Center in Dallas. Of 43 patients in the 80-mg, every-4-weeks group, there were 23 adverse reactions, of which infections were the most common at 19% – a safety profile similar to that of other anti-TNFs. One patient did withdraw from this group because of adverse events (AEs), but there were no deaths, no dose-limiting toxicities, and no clinically significant increases in AEs or serious AEs with increasing dose. Overall, 13 patients reported 17 serious AEs, of which respiratory tract infections and disorders were the most common.

The trial was sponsored by Pfizer, and all of the authors noted significant financial relationships with the company.

CHICAGO – The novel anti–tumor necrosis factor nanobody ATN-103 looks as if it will be moving on to phase III trials, based on the good efficacy and safety results of a phase IIA trial of more than 250 patients with rheumatoid arthritis.

"The 80-mg, every-4-weeks regimen was the one [dosage] that was consistently improved over placebo by ACR 20" (the American College of Rheumatology evaluation scale that reflects a 20% improvement in specified parameters), Dr. Roy M. Fleischmann said at the American College of Rheumatology annual meeting. In addition, this dosage group comprised the only patients to achieve significantly better responses on the ACR 50 and the ACR 70 criteria than was achieved by those taking placebo.

A nanobody is the smallest functional fragment of a naturally occurring, single-chain antibody, and ATN-103 (ozoralizumab) is just one-quarter the size of conventional TNF-blockers, Dr. Fleischmann noted. As a humanized bispecific nanobody, ATN-103 contains two human TNF-binding domains that are linked to a human serum albumin–binding domain to extend half-life.

The researchers conducted a double-blind, placebo-controlled, phase IIA proof-of-concept study that included 253 patients in three treatment groups, with roughly 40 patients at each dosage level. The 4-week dosing group received the active drug (a subcutaneous injection of 10 mg, 30 mg, or 80 mg) on day 1 of weeks 4, 8, and 12. The 8-week dosing group received either 10 mg or 80 mg of the drug on day 1 of each 8-week period. Those in the placebo group received a placebo injection on day 1 of weeks 4, 8, and 12.

All of the patients had active RA (defined as at least six swollen and at least six tender joints) at the time of screening and at baseline, despite having been treated with methotrexate for at least 12 weeks. To qualify for the study, they had to meet the 1987 revised criteria for RA at least 24 weeks prior to screening, to be within ACR functional class I-III, and to have a C-reactive protein level of at least 8 mg/L. In addition, their methotrexate dose (7.5-25 mg) and route of administration had to be stable for at least 6 weeks prior to baseline. The patients were stratified by prior TNF-inhibitor use; two-thirds of them were naive to TNF-blockers.

The primary outcome of this study was ACR 20 at 16 weeks. Secondary end points were improvements over placebo in clinical scores, DAS28 (Disease Activity Score based on a 28-joint count), ACR 50, ACR 70, and EULAR responses at week 16.

The ACR criteria are used to evaluate improvement in tender or swollen joint counts, as well as improvement in three of the following five parameters: acute phase reactant, patient assessment, physician assessment, pain scale, and disability/functional questionnaire scores. The EULAR response includes not only change in disease activity but also current disease activity.

"The safety profile looked relatively clean," said Dr. Fleischmann of the Metroplex Clinical Research Center in Dallas. Of 43 patients in the 80-mg, every-4-weeks group, there were 23 adverse reactions, of which infections were the most common at 19% – a safety profile similar to that of other anti-TNFs. One patient did withdraw from this group because of adverse events (AEs), but there were no deaths, no dose-limiting toxicities, and no clinically significant increases in AEs or serious AEs with increasing dose. Overall, 13 patients reported 17 serious AEs, of which respiratory tract infections and disorders were the most common.

The trial was sponsored by Pfizer, and all of the authors noted significant financial relationships with the company.

CHICAGO – The novel anti–tumor necrosis factor nanobody ATN-103 looks as if it will be moving on to phase III trials, based on the good efficacy and safety results of a phase IIA trial of more than 250 patients with rheumatoid arthritis.

"The 80-mg, every-4-weeks regimen was the one [dosage] that was consistently improved over placebo by ACR 20" (the American College of Rheumatology evaluation scale that reflects a 20% improvement in specified parameters), Dr. Roy M. Fleischmann said at the American College of Rheumatology annual meeting. In addition, this dosage group comprised the only patients to achieve significantly better responses on the ACR 50 and the ACR 70 criteria than was achieved by those taking placebo.

A nanobody is the smallest functional fragment of a naturally occurring, single-chain antibody, and ATN-103 (ozoralizumab) is just one-quarter the size of conventional TNF-blockers, Dr. Fleischmann noted. As a humanized bispecific nanobody, ATN-103 contains two human TNF-binding domains that are linked to a human serum albumin–binding domain to extend half-life.

The researchers conducted a double-blind, placebo-controlled, phase IIA proof-of-concept study that included 253 patients in three treatment groups, with roughly 40 patients at each dosage level. The 4-week dosing group received the active drug (a subcutaneous injection of 10 mg, 30 mg, or 80 mg) on day 1 of weeks 4, 8, and 12. The 8-week dosing group received either 10 mg or 80 mg of the drug on day 1 of each 8-week period. Those in the placebo group received a placebo injection on day 1 of weeks 4, 8, and 12.

All of the patients had active RA (defined as at least six swollen and at least six tender joints) at the time of screening and at baseline, despite having been treated with methotrexate for at least 12 weeks. To qualify for the study, they had to meet the 1987 revised criteria for RA at least 24 weeks prior to screening, to be within ACR functional class I-III, and to have a C-reactive protein level of at least 8 mg/L. In addition, their methotrexate dose (7.5-25 mg) and route of administration had to be stable for at least 6 weeks prior to baseline. The patients were stratified by prior TNF-inhibitor use; two-thirds of them were naive to TNF-blockers.

The primary outcome of this study was ACR 20 at 16 weeks. Secondary end points were improvements over placebo in clinical scores, DAS28 (Disease Activity Score based on a 28-joint count), ACR 50, ACR 70, and EULAR responses at week 16.

The ACR criteria are used to evaluate improvement in tender or swollen joint counts, as well as improvement in three of the following five parameters: acute phase reactant, patient assessment, physician assessment, pain scale, and disability/functional questionnaire scores. The EULAR response includes not only change in disease activity but also current disease activity.

"The safety profile looked relatively clean," said Dr. Fleischmann of the Metroplex Clinical Research Center in Dallas. Of 43 patients in the 80-mg, every-4-weeks group, there were 23 adverse reactions, of which infections were the most common at 19% – a safety profile similar to that of other anti-TNFs. One patient did withdraw from this group because of adverse events (AEs), but there were no deaths, no dose-limiting toxicities, and no clinically significant increases in AEs or serious AEs with increasing dose. Overall, 13 patients reported 17 serious AEs, of which respiratory tract infections and disorders were the most common.

The trial was sponsored by Pfizer, and all of the authors noted significant financial relationships with the company.