Toxicology

WASHINGTON – Hepatoxicity from herbal and dietary supplements is on the rise in the United States, with body-building supplements being implicated as the most common cause of liver injury, according to the results of a recent study.

Between September 2004 and March 2013, 845 cases of liver injury were thought to be "definitely, highly likely, or probably" from an herbal or dietary supplement, or from prescription drugs. Of these cases, 136 (16%) were attributed to a product in the herbal and dietary supplement category. Patients reported consuming a total of 262 different herbal and dietary supplements; 30% were body-building products. Cases of liver injury from all herbal and dietary supplements increased from 7% in 2004-2005 to 20% in 2010-2012, reported Dr. Victor J. Navarro at the annual meeting of the American Association for the Study of Liver Diseases.

The prospective study used data from the Drug-Induced Liver Injury Network (DILIN). The network was established in 2003 by the National Institute of Diabetes and Digestive and Kidney Diseases to collect and analyze cases of severe liver injury caused by prescription and over-the-counter drugs, as well as alternative medications, including herbal products and supplements.

Of the hepatotoxicity cases due to supplements, 7 were excluded because they involved both body-building and other herbal and dietary supplements. Of the remaining 129 cases, 44 were attributed to body-building supplements and 85 cases were attributed to other types of herbal and dietary supplements. These cases were compared with 709 cases of drug-induced liver injury, noted Dr. Navarro, chair of the division of hepatology, Einstein Healthcare Network, Philadelphia.

Clinical features and demographic characteristics differed between the groups. The 44 patients with injury induced by body-building supplements were younger (mean age 33 years, vs. 48-50 years in the other two groups), and all were men. In the other two groups, 35%-37% of cases occurred in men.

As for clinical presentation, "the body-building supplement injury cases stood apart," as there was a "distinct presentation of prolonged jaundice," Dr. Navarro noted. "These patients tended to have fewer comorbid conditions," were heavier, and were "uniformly symptomatic." They all had jaundice, and 84% had pruritus. Of patients in the other herbal and dietary supplement group, 78% presented with jaundice and 48% presented with pruritus, compared with and 68% and 53%, respectively, of those with drug-induced liver injury.

Body-building liver injury cases required hospitalization more often, but no patients in this group died or had a liver transplant. There were deaths from all causes in the two other groups, but the differences were not significant. However, 13% of the cases of liver injury from other supplements resulted in a liver transplant, compared with 3% among the drug-induced liver injury group, a significant difference.

The higher transplant rate indicates that the hepatoxicity induced by non-body-building supplements "may be more severe" than injury induced by prescription drugs, Dr. Navarro observed.

Other marked differences between the groups included a serum total bilirubin that was significantly higher and persisted significantly longer in patients with liver injury from body-building supplements.

Although the study results indicate that hepatotoxicity due to herbal and dietary supplements is increasing, this was not a population-based study, and so "additional efforts to characterize the true burden of disease in the U.S. population are needed," and are being addressed by DILIN, Dr. Navarro said.

The National Institutes of Health sponsored the study. Dr. Navarro had no relevant disclosures. Information about DILIN is available here.

[email protected]

WASHINGTON – Hepatoxicity from herbal and dietary supplements is on the rise in the United States, with body-building supplements being implicated as the most common cause of liver injury, according to the results of a recent study.

Between September 2004 and March 2013, 845 cases of liver injury were thought to be "definitely, highly likely, or probably" from an herbal or dietary supplement, or from prescription drugs. Of these cases, 136 (16%) were attributed to a product in the herbal and dietary supplement category. Patients reported consuming a total of 262 different herbal and dietary supplements; 30% were body-building products. Cases of liver injury from all herbal and dietary supplements increased from 7% in 2004-2005 to 20% in 2010-2012, reported Dr. Victor J. Navarro at the annual meeting of the American Association for the Study of Liver Diseases.

The prospective study used data from the Drug-Induced Liver Injury Network (DILIN). The network was established in 2003 by the National Institute of Diabetes and Digestive and Kidney Diseases to collect and analyze cases of severe liver injury caused by prescription and over-the-counter drugs, as well as alternative medications, including herbal products and supplements.

Of the hepatotoxicity cases due to supplements, 7 were excluded because they involved both body-building and other herbal and dietary supplements. Of the remaining 129 cases, 44 were attributed to body-building supplements and 85 cases were attributed to other types of herbal and dietary supplements. These cases were compared with 709 cases of drug-induced liver injury, noted Dr. Navarro, chair of the division of hepatology, Einstein Healthcare Network, Philadelphia.

Clinical features and demographic characteristics differed between the groups. The 44 patients with injury induced by body-building supplements were younger (mean age 33 years, vs. 48-50 years in the other two groups), and all were men. In the other two groups, 35%-37% of cases occurred in men.

As for clinical presentation, "the body-building supplement injury cases stood apart," as there was a "distinct presentation of prolonged jaundice," Dr. Navarro noted. "These patients tended to have fewer comorbid conditions," were heavier, and were "uniformly symptomatic." They all had jaundice, and 84% had pruritus. Of patients in the other herbal and dietary supplement group, 78% presented with jaundice and 48% presented with pruritus, compared with and 68% and 53%, respectively, of those with drug-induced liver injury.

Body-building liver injury cases required hospitalization more often, but no patients in this group died or had a liver transplant. There were deaths from all causes in the two other groups, but the differences were not significant. However, 13% of the cases of liver injury from other supplements resulted in a liver transplant, compared with 3% among the drug-induced liver injury group, a significant difference.

The higher transplant rate indicates that the hepatoxicity induced by non-body-building supplements "may be more severe" than injury induced by prescription drugs, Dr. Navarro observed.

Other marked differences between the groups included a serum total bilirubin that was significantly higher and persisted significantly longer in patients with liver injury from body-building supplements.

Although the study results indicate that hepatotoxicity due to herbal and dietary supplements is increasing, this was not a population-based study, and so "additional efforts to characterize the true burden of disease in the U.S. population are needed," and are being addressed by DILIN, Dr. Navarro said.

The National Institutes of Health sponsored the study. Dr. Navarro had no relevant disclosures. Information about DILIN is available here.

[email protected]

WASHINGTON – Hepatoxicity from herbal and dietary supplements is on the rise in the United States, with body-building supplements being implicated as the most common cause of liver injury, according to the results of a recent study.

Between September 2004 and March 2013, 845 cases of liver injury were thought to be "definitely, highly likely, or probably" from an herbal or dietary supplement, or from prescription drugs. Of these cases, 136 (16%) were attributed to a product in the herbal and dietary supplement category. Patients reported consuming a total of 262 different herbal and dietary supplements; 30% were body-building products. Cases of liver injury from all herbal and dietary supplements increased from 7% in 2004-2005 to 20% in 2010-2012, reported Dr. Victor J. Navarro at the annual meeting of the American Association for the Study of Liver Diseases.

The prospective study used data from the Drug-Induced Liver Injury Network (DILIN). The network was established in 2003 by the National Institute of Diabetes and Digestive and Kidney Diseases to collect and analyze cases of severe liver injury caused by prescription and over-the-counter drugs, as well as alternative medications, including herbal products and supplements.

Of the hepatotoxicity cases due to supplements, 7 were excluded because they involved both body-building and other herbal and dietary supplements. Of the remaining 129 cases, 44 were attributed to body-building supplements and 85 cases were attributed to other types of herbal and dietary supplements. These cases were compared with 709 cases of drug-induced liver injury, noted Dr. Navarro, chair of the division of hepatology, Einstein Healthcare Network, Philadelphia.

Clinical features and demographic characteristics differed between the groups. The 44 patients with injury induced by body-building supplements were younger (mean age 33 years, vs. 48-50 years in the other two groups), and all were men. In the other two groups, 35%-37% of cases occurred in men.

As for clinical presentation, "the body-building supplement injury cases stood apart," as there was a "distinct presentation of prolonged jaundice," Dr. Navarro noted. "These patients tended to have fewer comorbid conditions," were heavier, and were "uniformly symptomatic." They all had jaundice, and 84% had pruritus. Of patients in the other herbal and dietary supplement group, 78% presented with jaundice and 48% presented with pruritus, compared with and 68% and 53%, respectively, of those with drug-induced liver injury.

Body-building liver injury cases required hospitalization more often, but no patients in this group died or had a liver transplant. There were deaths from all causes in the two other groups, but the differences were not significant. However, 13% of the cases of liver injury from other supplements resulted in a liver transplant, compared with 3% among the drug-induced liver injury group, a significant difference.

The higher transplant rate indicates that the hepatoxicity induced by non-body-building supplements "may be more severe" than injury induced by prescription drugs, Dr. Navarro observed.

Other marked differences between the groups included a serum total bilirubin that was significantly higher and persisted significantly longer in patients with liver injury from body-building supplements.

Although the study results indicate that hepatotoxicity due to herbal and dietary supplements is increasing, this was not a population-based study, and so "additional efforts to characterize the true burden of disease in the U.S. population are needed," and are being addressed by DILIN, Dr. Navarro said.

The National Institutes of Health sponsored the study. Dr. Navarro had no relevant disclosures. Information about DILIN is available here.

[email protected]

A mother presents to the ED with her 4-day-old daughter after noting abnormal jerking movements of the neonate's upper extremities. She states the baby has had watery stools for the past day, but has been tolerating bottle formula feeds without vomiting and having appropriate urinary output. The patient was born full-term via normal spontaneous vaginal delivery, with Apgar scores of 8 at 1 minute and 9 at 5 minutes. The postdelivery course was uncomplicated, and both mother and baby were discharged home 2 days after delivery.

Initial vital signs are: heart rate, 135 beats/min; respiratory rate (RR), 48 breaths/min; and temperature, 98.7°F; blood glucose was normal. On physical examination, the baby is awake and well-appearing, with a nonbulging anterior fontanelle, soft, supple neck, and flexed and symmetrically mobile extremities. Moro, suck, rooting, and grasp reflexes are all intact. No abnormal movements are noted. The remainder of the examination is unremarkable.

Do the jerking movements indicate a focal seizure? What could cause these movements in a neonate?

As the length of the postpartum hospital stay has decreased over the past 20 years, EDs have experienced an increase in neonatal visits for conditions that traditionally manifested in newborn nurseries. While most presentations are for benign reasons (eg, issues related to feeding, irritability), patients with concerning conditions, including central nervous system (CNS) abnormalities, may also initially present to the ED. Causes of such clinical findings may be structural (eg, cerebral malformations, subdural hematomas, herpes encephalitis) and/or metabolic (eg, hypoglycemia, hypocalcemia, inborn errors). Many early-onset neonatal seizures are benign and resolve by several months of age, but it is essential to identify those that are consequential and treatable.

Case Continuation

In the evaluation of the neonatal patient with suspected seizure, it is important to take a detailed maternal and labor history, and to consider a broad differential in the face of nonspecific findings. In this case, the patient's mother disclosed a personal history of chronic pain, for which she took buprenorphine 2 mg orally in the morning and 4 mg orally at bedtime (total daily dose of 6mg/day) throughout her pregnancy.

How does drug withdrawal present in the neonate?

Neonatal abstinence syndrome (NAS) is the clinical syndrome of withdrawal in a newborn exposed in utero to drugs capable of inducing dependence. Agents associated with NAS include opioids, benzodiazepines, ethanol, selective serotonin reuptake inhibitors (SSRIs), mood stabilizers, and nicotine.1,2

Over the past decade, there has been a 330% rise in the diagnosis of opioid-related NAS alone.3 In response to this increase, the US Food and Drug Administration recently added a black-box warning to all extended-release/long-acting opioid preparations detailing this risk.4

Presenting symptoms of NAS are protean, differ from patient to patient, and are a function of drug type, duration, and amount of drug exposure. NAS may mimic other severe life-threatening conditions such as those previously noted, and the inability to obtain an adequate symptom-based medical history from a neonate further complicates the diagnosis. Before making a diagnosis of NAS, other conditions should be carefully considered in the differential.

Neonatal opioid withdrawal manifests primarily with CNS and gastrointestinal (GI) effects since there are high concentrations of opioid receptors in these areas. Although clinical findings are generally similar among opioid agents, the onset and duration following abstinence varies—largely based on individual drug half-life; this helps to differentiate between opioid agents. For example, while babies exposed to heroin in utero present with signs of NAS within 24 hours of birth, those exposed to buprenorphine or methadone tend to present 2 to 6 days after delivery.1 Between 55% to 94% of neonates with in-utero opioid exposure develop NAS.5

Select Serotonin Reuptake Inhibitors

SSRIs have also been associated with a neonatal syndrome, and largely involve similar signs and symptoms as NAS. Although the specific etiology is not clear, it has been suggested that this syndrome is the result of serotonin toxicity rather than withdrawal; as such, it is often referred to as "serotonin discontinuation syndrome." Clinical findings occur from several hours to several days after birth and usually resolve within 1 to 2 weeks.6

Cocaine Exposure

In-utero cocaine exposure is also associated with neurobehavioral abnormalities in neonates although a withdrawal syndrome is less clearly defined. Findings, however, are consistent with NAS and include increased irritability, tremors, and high-pitched cry—most frequently occurring between 24 and 48 hours postdelivery.6

Neonatal Alcohol Withdrawal Syndrome

Neonatal alcohol withdrawal syndrome, particularly in fetuses exposed to alcohol during the last trimester, is distinct from fetal alcohol syndrome (FAS). The latter is associated with typical dysmorphic features, growth deficiencies, and CNS findings reflective of permanent neurologic sequelae. Neonatal alcohol withdrawal presents with CNS findings similar to those listed for other in-utero exposures—eg, increased irritability, tremors, nystagmus hyperactive reflexes.7

Screening for NAS: The Finnegan Scale

The Finnegan Neonatal Abstinence Scoring System is one of the most commonly employed and validated tools used to screen for NAS. It comprises a 31-item scale, listing the clinical signs and symptoms of NAS, which are scored by severity and organized by system to include neurologic, metabolic, vasomotor, respiratory, and GI disturbances (Figure). Point allocation is based on mild, moderate, or severe symptoms as follows:

• Mild findings (eg, sweating, fever <101°F mottling, nasal stuffiness) each score 1 point.

• Moderate findings (eg, high-pitched cry, hyperactive moro reflex, increased muscle tone, fever >101°F, increased RR >60 with retractions, poor feeding, loose stools) each score 2 points.

• Severe findings (eg, myoclonic jerks, generalized convulsions, projectile vomiting, watery stools) each score 3 points.

While each of the above are independently nonspecific, the constellation of findings, together with the appropriate history, provide for a clinical diagnosis. The Finnegan Scale is therefore designed not only to aid in diagnosis, but also to quantify the severity of NAS and guide management.

Screening for NAS begins at birth in neonates with known in-utero exposure (ie, when risk of NAS is high) or at the time of initial presentation in other circumstances. Scoring is performed every 4 hours; the first two or three scores will determine the need for pharmacotherapy (see Table).

How is NAS treated?

The two main goals of management in the treatment of opioid-related NAS are to relieve the signs and symptoms of withdrawal and to prevent complications (eg, fever, weight loss, seizures). Therapy should begin with nonpharmacologic measures that minimize excess external stimuli, such as swaddling, gentle handling, and minimizing noise and light. To prevent weight loss, small hypercaloric feeds may be helpful. If pharmacologic treatment is indicated, oral opioid replacement with morphine is considered by many to be the drug of choice. Oral morphine dosing may be guided by NAS severity based on the Finnegan score; alternatively, initial dosing at 0.1 mg/kg orally every 4 hours has also been recommended.1

Other agents, such methadone 0.1 mg/kg orally every 12 hours and buprenorphine 15.9 mcg/kg divided in three doses orally, may also be used. In patients whose symptoms persist despite opioid treatment, use of adjuncts such as phenobarbital and clonidine may be indicated.

Case Conclusion

The patient was admitted to the neonatal intensive care unit where she appropriately underwent a sepsis workup. Laboratory evaluation, including blood and urine cultures, was obtained. A brain ultrasound was unremarkable, and since lumbar puncture was unsuccessful, the patient was started empirically on meningitis doses of the cefotaxime, vancomycin, and acyclovir.

An initial Finnegan score was calculated. With the exception of soft stools, there were no other persistent symptoms, and patient did not achieve a score indicating a need for pharmacologic management. After 48 hours, she remained afebrile and soft stools resolved. All laboratory values, including cultures, were unremarkable. The patient was discharged on hospital day 3, with a scheduled well-baby follow-up appointment.

Dr Laskowski is a medical toxicology fellow in the department of emergency medicine at New York University Langone Medical Center. Dr Nelson, editor of "Case Studies in Toxicology," is a professor in the department of emergency medicine and director of the medical toxicology fellowship program at the New York University School of Medicine and the New York City Poison Control Center. He is also associate editor, toxicology, of the EMERGENCY MEDICINE editorial board.

A mother presents to the ED with her 4-day-old daughter after noting abnormal jerking movements of the neonate's upper extremities. She states the baby has had watery stools for the past day, but has been tolerating bottle formula feeds without vomiting and having appropriate urinary output. The patient was born full-term via normal spontaneous vaginal delivery, with Apgar scores of 8 at 1 minute and 9 at 5 minutes. The postdelivery course was uncomplicated, and both mother and baby were discharged home 2 days after delivery.

Initial vital signs are: heart rate, 135 beats/min; respiratory rate (RR), 48 breaths/min; and temperature, 98.7°F; blood glucose was normal. On physical examination, the baby is awake and well-appearing, with a nonbulging anterior fontanelle, soft, supple neck, and flexed and symmetrically mobile extremities. Moro, suck, rooting, and grasp reflexes are all intact. No abnormal movements are noted. The remainder of the examination is unremarkable.

Do the jerking movements indicate a focal seizure? What could cause these movements in a neonate?

As the length of the postpartum hospital stay has decreased over the past 20 years, EDs have experienced an increase in neonatal visits for conditions that traditionally manifested in newborn nurseries. While most presentations are for benign reasons (eg, issues related to feeding, irritability), patients with concerning conditions, including central nervous system (CNS) abnormalities, may also initially present to the ED. Causes of such clinical findings may be structural (eg, cerebral malformations, subdural hematomas, herpes encephalitis) and/or metabolic (eg, hypoglycemia, hypocalcemia, inborn errors). Many early-onset neonatal seizures are benign and resolve by several months of age, but it is essential to identify those that are consequential and treatable.

Case Continuation

In the evaluation of the neonatal patient with suspected seizure, it is important to take a detailed maternal and labor history, and to consider a broad differential in the face of nonspecific findings. In this case, the patient's mother disclosed a personal history of chronic pain, for which she took buprenorphine 2 mg orally in the morning and 4 mg orally at bedtime (total daily dose of 6mg/day) throughout her pregnancy.

How does drug withdrawal present in the neonate?

Neonatal abstinence syndrome (NAS) is the clinical syndrome of withdrawal in a newborn exposed in utero to drugs capable of inducing dependence. Agents associated with NAS include opioids, benzodiazepines, ethanol, selective serotonin reuptake inhibitors (SSRIs), mood stabilizers, and nicotine.1,2

Over the past decade, there has been a 330% rise in the diagnosis of opioid-related NAS alone.3 In response to this increase, the US Food and Drug Administration recently added a black-box warning to all extended-release/long-acting opioid preparations detailing this risk.4

Presenting symptoms of NAS are protean, differ from patient to patient, and are a function of drug type, duration, and amount of drug exposure. NAS may mimic other severe life-threatening conditions such as those previously noted, and the inability to obtain an adequate symptom-based medical history from a neonate further complicates the diagnosis. Before making a diagnosis of NAS, other conditions should be carefully considered in the differential.

Neonatal opioid withdrawal manifests primarily with CNS and gastrointestinal (GI) effects since there are high concentrations of opioid receptors in these areas. Although clinical findings are generally similar among opioid agents, the onset and duration following abstinence varies—largely based on individual drug half-life; this helps to differentiate between opioid agents. For example, while babies exposed to heroin in utero present with signs of NAS within 24 hours of birth, those exposed to buprenorphine or methadone tend to present 2 to 6 days after delivery.1 Between 55% to 94% of neonates with in-utero opioid exposure develop NAS.5

Select Serotonin Reuptake Inhibitors

SSRIs have also been associated with a neonatal syndrome, and largely involve similar signs and symptoms as NAS. Although the specific etiology is not clear, it has been suggested that this syndrome is the result of serotonin toxicity rather than withdrawal; as such, it is often referred to as "serotonin discontinuation syndrome." Clinical findings occur from several hours to several days after birth and usually resolve within 1 to 2 weeks.6

Cocaine Exposure

In-utero cocaine exposure is also associated with neurobehavioral abnormalities in neonates although a withdrawal syndrome is less clearly defined. Findings, however, are consistent with NAS and include increased irritability, tremors, and high-pitched cry—most frequently occurring between 24 and 48 hours postdelivery.6

Neonatal Alcohol Withdrawal Syndrome

Neonatal alcohol withdrawal syndrome, particularly in fetuses exposed to alcohol during the last trimester, is distinct from fetal alcohol syndrome (FAS). The latter is associated with typical dysmorphic features, growth deficiencies, and CNS findings reflective of permanent neurologic sequelae. Neonatal alcohol withdrawal presents with CNS findings similar to those listed for other in-utero exposures—eg, increased irritability, tremors, nystagmus hyperactive reflexes.7

Screening for NAS: The Finnegan Scale

The Finnegan Neonatal Abstinence Scoring System is one of the most commonly employed and validated tools used to screen for NAS. It comprises a 31-item scale, listing the clinical signs and symptoms of NAS, which are scored by severity and organized by system to include neurologic, metabolic, vasomotor, respiratory, and GI disturbances (Figure). Point allocation is based on mild, moderate, or severe symptoms as follows:

• Mild findings (eg, sweating, fever <101°F mottling, nasal stuffiness) each score 1 point.

• Moderate findings (eg, high-pitched cry, hyperactive moro reflex, increased muscle tone, fever >101°F, increased RR >60 with retractions, poor feeding, loose stools) each score 2 points.

• Severe findings (eg, myoclonic jerks, generalized convulsions, projectile vomiting, watery stools) each score 3 points.

While each of the above are independently nonspecific, the constellation of findings, together with the appropriate history, provide for a clinical diagnosis. The Finnegan Scale is therefore designed not only to aid in diagnosis, but also to quantify the severity of NAS and guide management.

Screening for NAS begins at birth in neonates with known in-utero exposure (ie, when risk of NAS is high) or at the time of initial presentation in other circumstances. Scoring is performed every 4 hours; the first two or three scores will determine the need for pharmacotherapy (see Table).

How is NAS treated?

The two main goals of management in the treatment of opioid-related NAS are to relieve the signs and symptoms of withdrawal and to prevent complications (eg, fever, weight loss, seizures). Therapy should begin with nonpharmacologic measures that minimize excess external stimuli, such as swaddling, gentle handling, and minimizing noise and light. To prevent weight loss, small hypercaloric feeds may be helpful. If pharmacologic treatment is indicated, oral opioid replacement with morphine is considered by many to be the drug of choice. Oral morphine dosing may be guided by NAS severity based on the Finnegan score; alternatively, initial dosing at 0.1 mg/kg orally every 4 hours has also been recommended.1

Other agents, such methadone 0.1 mg/kg orally every 12 hours and buprenorphine 15.9 mcg/kg divided in three doses orally, may also be used. In patients whose symptoms persist despite opioid treatment, use of adjuncts such as phenobarbital and clonidine may be indicated.

Case Conclusion

The patient was admitted to the neonatal intensive care unit where she appropriately underwent a sepsis workup. Laboratory evaluation, including blood and urine cultures, was obtained. A brain ultrasound was unremarkable, and since lumbar puncture was unsuccessful, the patient was started empirically on meningitis doses of the cefotaxime, vancomycin, and acyclovir.

An initial Finnegan score was calculated. With the exception of soft stools, there were no other persistent symptoms, and patient did not achieve a score indicating a need for pharmacologic management. After 48 hours, she remained afebrile and soft stools resolved. All laboratory values, including cultures, were unremarkable. The patient was discharged on hospital day 3, with a scheduled well-baby follow-up appointment.

Dr Laskowski is a medical toxicology fellow in the department of emergency medicine at New York University Langone Medical Center. Dr Nelson, editor of "Case Studies in Toxicology," is a professor in the department of emergency medicine and director of the medical toxicology fellowship program at the New York University School of Medicine and the New York City Poison Control Center. He is also associate editor, toxicology, of the EMERGENCY MEDICINE editorial board.

A mother presents to the ED with her 4-day-old daughter after noting abnormal jerking movements of the neonate's upper extremities. She states the baby has had watery stools for the past day, but has been tolerating bottle formula feeds without vomiting and having appropriate urinary output. The patient was born full-term via normal spontaneous vaginal delivery, with Apgar scores of 8 at 1 minute and 9 at 5 minutes. The postdelivery course was uncomplicated, and both mother and baby were discharged home 2 days after delivery.

Initial vital signs are: heart rate, 135 beats/min; respiratory rate (RR), 48 breaths/min; and temperature, 98.7°F; blood glucose was normal. On physical examination, the baby is awake and well-appearing, with a nonbulging anterior fontanelle, soft, supple neck, and flexed and symmetrically mobile extremities. Moro, suck, rooting, and grasp reflexes are all intact. No abnormal movements are noted. The remainder of the examination is unremarkable.

Do the jerking movements indicate a focal seizure? What could cause these movements in a neonate?

As the length of the postpartum hospital stay has decreased over the past 20 years, EDs have experienced an increase in neonatal visits for conditions that traditionally manifested in newborn nurseries. While most presentations are for benign reasons (eg, issues related to feeding, irritability), patients with concerning conditions, including central nervous system (CNS) abnormalities, may also initially present to the ED. Causes of such clinical findings may be structural (eg, cerebral malformations, subdural hematomas, herpes encephalitis) and/or metabolic (eg, hypoglycemia, hypocalcemia, inborn errors). Many early-onset neonatal seizures are benign and resolve by several months of age, but it is essential to identify those that are consequential and treatable.

Case Continuation

In the evaluation of the neonatal patient with suspected seizure, it is important to take a detailed maternal and labor history, and to consider a broad differential in the face of nonspecific findings. In this case, the patient's mother disclosed a personal history of chronic pain, for which she took buprenorphine 2 mg orally in the morning and 4 mg orally at bedtime (total daily dose of 6mg/day) throughout her pregnancy.

How does drug withdrawal present in the neonate?

Neonatal abstinence syndrome (NAS) is the clinical syndrome of withdrawal in a newborn exposed in utero to drugs capable of inducing dependence. Agents associated with NAS include opioids, benzodiazepines, ethanol, selective serotonin reuptake inhibitors (SSRIs), mood stabilizers, and nicotine.1,2

Over the past decade, there has been a 330% rise in the diagnosis of opioid-related NAS alone.3 In response to this increase, the US Food and Drug Administration recently added a black-box warning to all extended-release/long-acting opioid preparations detailing this risk.4

Presenting symptoms of NAS are protean, differ from patient to patient, and are a function of drug type, duration, and amount of drug exposure. NAS may mimic other severe life-threatening conditions such as those previously noted, and the inability to obtain an adequate symptom-based medical history from a neonate further complicates the diagnosis. Before making a diagnosis of NAS, other conditions should be carefully considered in the differential.

Neonatal opioid withdrawal manifests primarily with CNS and gastrointestinal (GI) effects since there are high concentrations of opioid receptors in these areas. Although clinical findings are generally similar among opioid agents, the onset and duration following abstinence varies—largely based on individual drug half-life; this helps to differentiate between opioid agents. For example, while babies exposed to heroin in utero present with signs of NAS within 24 hours of birth, those exposed to buprenorphine or methadone tend to present 2 to 6 days after delivery.1 Between 55% to 94% of neonates with in-utero opioid exposure develop NAS.5

Select Serotonin Reuptake Inhibitors

SSRIs have also been associated with a neonatal syndrome, and largely involve similar signs and symptoms as NAS. Although the specific etiology is not clear, it has been suggested that this syndrome is the result of serotonin toxicity rather than withdrawal; as such, it is often referred to as "serotonin discontinuation syndrome." Clinical findings occur from several hours to several days after birth and usually resolve within 1 to 2 weeks.6

Cocaine Exposure

In-utero cocaine exposure is also associated with neurobehavioral abnormalities in neonates although a withdrawal syndrome is less clearly defined. Findings, however, are consistent with NAS and include increased irritability, tremors, and high-pitched cry—most frequently occurring between 24 and 48 hours postdelivery.6

Neonatal Alcohol Withdrawal Syndrome

Neonatal alcohol withdrawal syndrome, particularly in fetuses exposed to alcohol during the last trimester, is distinct from fetal alcohol syndrome (FAS). The latter is associated with typical dysmorphic features, growth deficiencies, and CNS findings reflective of permanent neurologic sequelae. Neonatal alcohol withdrawal presents with CNS findings similar to those listed for other in-utero exposures—eg, increased irritability, tremors, nystagmus hyperactive reflexes.7

Screening for NAS: The Finnegan Scale

The Finnegan Neonatal Abstinence Scoring System is one of the most commonly employed and validated tools used to screen for NAS. It comprises a 31-item scale, listing the clinical signs and symptoms of NAS, which are scored by severity and organized by system to include neurologic, metabolic, vasomotor, respiratory, and GI disturbances (Figure). Point allocation is based on mild, moderate, or severe symptoms as follows:

• Mild findings (eg, sweating, fever <101°F mottling, nasal stuffiness) each score 1 point.

• Moderate findings (eg, high-pitched cry, hyperactive moro reflex, increased muscle tone, fever >101°F, increased RR >60 with retractions, poor feeding, loose stools) each score 2 points.

• Severe findings (eg, myoclonic jerks, generalized convulsions, projectile vomiting, watery stools) each score 3 points.

While each of the above are independently nonspecific, the constellation of findings, together with the appropriate history, provide for a clinical diagnosis. The Finnegan Scale is therefore designed not only to aid in diagnosis, but also to quantify the severity of NAS and guide management.

Screening for NAS begins at birth in neonates with known in-utero exposure (ie, when risk of NAS is high) or at the time of initial presentation in other circumstances. Scoring is performed every 4 hours; the first two or three scores will determine the need for pharmacotherapy (see Table).

How is NAS treated?

The two main goals of management in the treatment of opioid-related NAS are to relieve the signs and symptoms of withdrawal and to prevent complications (eg, fever, weight loss, seizures). Therapy should begin with nonpharmacologic measures that minimize excess external stimuli, such as swaddling, gentle handling, and minimizing noise and light. To prevent weight loss, small hypercaloric feeds may be helpful. If pharmacologic treatment is indicated, oral opioid replacement with morphine is considered by many to be the drug of choice. Oral morphine dosing may be guided by NAS severity based on the Finnegan score; alternatively, initial dosing at 0.1 mg/kg orally every 4 hours has also been recommended.1

Other agents, such methadone 0.1 mg/kg orally every 12 hours and buprenorphine 15.9 mcg/kg divided in three doses orally, may also be used. In patients whose symptoms persist despite opioid treatment, use of adjuncts such as phenobarbital and clonidine may be indicated.

Case Conclusion

The patient was admitted to the neonatal intensive care unit where she appropriately underwent a sepsis workup. Laboratory evaluation, including blood and urine cultures, was obtained. A brain ultrasound was unremarkable, and since lumbar puncture was unsuccessful, the patient was started empirically on meningitis doses of the cefotaxime, vancomycin, and acyclovir.

An initial Finnegan score was calculated. With the exception of soft stools, there were no other persistent symptoms, and patient did not achieve a score indicating a need for pharmacologic management. After 48 hours, she remained afebrile and soft stools resolved. All laboratory values, including cultures, were unremarkable. The patient was discharged on hospital day 3, with a scheduled well-baby follow-up appointment.

Dr Laskowski is a medical toxicology fellow in the department of emergency medicine at New York University Langone Medical Center. Dr Nelson, editor of "Case Studies in Toxicology," is a professor in the department of emergency medicine and director of the medical toxicology fellowship program at the New York University School of Medicine and the New York City Poison Control Center. He is also associate editor, toxicology, of the EMERGENCY MEDICINE editorial board.

Ottawa SAH clinical decision rule helps identify subarachnoid hemorrhage

BY MARY ANN MOON

From JAMA

A new clinical decision rule had sensitivity and specificity approaching 100% in ruling out subarachnoid hemorrhage among patients who presented to an emergency department with acute headache, a validation study showed.

Using this new tool, which requires only that the clinician answer six simple questions regarding the patient’s presentation, has the potential to reduce the number of costly and sometimes invasive procedures that are currently relied on to distinguish subarachnoid hemorrhage (SAH) from other pathologies, said Dr Jeffrey J. Perry of the department of emergency medicine at the University of Ottawa (Ont.) and the clinical epidemiology program at the Ottawa Hospital Research Institute and his associates.

Dr Perry and his colleagues devised three clinical decision rules to assist in ruling out SAH, then assessed the three rules for their accuracy, reliability, and acceptability to clinicians in a validation cohort of consecutive patients aged 16 years and older who presented to an ED with a nontraumatic headache that reached maximal intensity within 1 hour. There were 2,131 study subjects with a mean age of 44 years. Approximately 61% were women, and 26% arrived at the ED by ambulance.

All of these participants were treated by attending physicians certified in emergency medicine or by supervised residents at 10 university-affiliated urban, Canadian tertiary care teaching hospitals during a 4-year period. All patients were alert and oriented, with no neurologic deficits; 132 (6.2%) were found to have SAH.

After comparing the performances of the three candidate decision rules, the investigators refined the decision tool to identify six factors that were most predictive of SAH: age of 40 years or older, neck pain or stiffness, witnessed loss of consciousness, onset of headache during exertion, "thunderclap headache" (defined as instantly peaking pain), and limited neck flexion (defined as the inability to touch chin to chest when upright or to raise the head 8 cm off the bed when supine).

The presence of any one of these six factors indicates that SAH is possible and further investigation is required using CT and perhaps lumbar puncture, Dr Perry and his associates said.

This refined clinical decision rule, which they termed the Ottawa SAH rule, had an overall sensitivity of 99.2% and a specificity of 99.6% in identifying SAHs (JAMA. 2013;310[12]:1248-1255).

Following this rule would decrease the investigation rate"—the rate of further assessment using CT and lumbar puncture—"to 74% from the current investigation rate of 84%, the researchers added.

The Ottawa SAH rule must be evaluated further before it can be adopted into clinical practice. "An implementation study is the next step required to determine how the Ottawa SAH rule performs in clinical practice, assess the actual effects on patient care and patient outcomes, and conduct a formal health economic analysis," the researchers noted.

This study was supported by the Canadian Institutes for Health Research, the University of Ottawa, and the Vancouver Coastal Health Research Institute. No financial conflicts of interest were reported.

Novel two-biomarker strategy permits early ACS rule-out

BY BRUCE JANCIN

At the ESC Congress 2013

AMSTERDAM—An early rule-out strategy based upon using two cardiac biomarkers allowed for safe discharge within a couple hours from the emergency department for most low- to intermediate-risk patients who presented with suspected acute coronary syndromes, based on the results of a randomized, multicenter trial conducted in Europe.

Moreover, the 30-day rates of major adverse cardiovascular events in the Biomarkers in Cardiology–8 (BiC-8) study were similarly low in patients discharged from the ED using the early rule-out process and in those who received standard, guideline-recommended care, which includes 6-12 hours of serial ECGs and troponin measurements in the chest pain unit, Dr Martin Moeckel reported at the annual congress of the European Society of Cardiology.

"This biomarker strategy using a state-of-the-art quantitative troponin assay in combination with an ultrasensitive copeptin assay has the potential to change clinical practice with high patient safety," observed Dr Moeckel of Charite Hospital, Berlin. The copeptin test is approved for use in the European Union but remains investigational in the United States.

Based upon the results of BiC-8, this dual-biomarker for early rule-out of myocardial infarction is now standard clinical practice at Charite, he added.

Nearly 12% of all patients who present to the ED do so because of chest pain, yet after an extensive and time-consuming evaluation only 1 in 10 of those patients are found to actually be having an acute MI.

"Rapid rule-out of acute MI is therefore a major clinical need, saving the health care system time and resources, and saving patients unnecessary stress, anxiety, and other risks," he said.

Copeptin is a marker for vasopressin, a hemodynamic stress indicator that shoots up immediately in an acute MI. In earlier studies, a negative result for both troponin and copeptin in an initial blood sample drawn at ED presentation had a 99% negative predictive value for MI.

The BiC-8 trial included 902 low- to intermediate-risk patients who presented with suspected ACS to EDs in university medical centers. All had a negative initial cardiac troponin test. They were randomized to standard care in the chest pain unit, including serial troponin testing and ECGs, or to the experimental strategy, in which physicians were informed of the copeptin results from the same initial blood sample as the troponin. If the copeptin test was positive as defined by a level of 10 pmol/L or more, the patient was hospitalized for standard care. If the copeptin result was negative, however, the patient was immediately discharged with a scheduled outpatient visit within72 hours.

Of the patients in the copeptin group, 66% were discharged directly from the ED, compared to 12% in the standard care group.

The 30-day incidence of major adverse cardiovascular events (MACE) was 5.5% in the standard care group and nearly identical at 5.46% in the copeptin group. MACE was defined in BiC-8 as all-cause mortality, MI, rehospitalization for ACS, acute unplanned PCI, coronary artery bypass surgery, life-threatening arrhythmia, or resuscitation from cardiac arrest.

MACE occurred in 14 copeptin-negative patients. However, 12 of the 14 were not discharged early because physicians overruled the negative biomarker results based on patient history and moved the patients into standard in-hospital management. Two patients, or 0.6% of those discharged from the ED on the basis of a negative copeptin test, had adverse events: one was rehospitalized on day 23 and underwent acute unplanned PCI on the next day, and the other was rehospitalized on day 4 and underwent coronary artery bypass graft surgery on day 12.

American Heart Association Immediate Past President Donna K. Arnett, PhD, said in an interview that she’d really like to see a second, confirmatory randomized trial before this early rule-out strategy is widely adopted. She considers the lost-to-followup rate uncomfortably high: 63 patients in the intention-to-treat analysis, and another 75 not accounted for in the per protocol analysis, noted Dr Arnett, professor and chair of the department of epidemiology at the University of Alabama, Birmingham.

"The most important message from BiC-8, I think, is that these were patients at low- to-intermediate risk; they’re not the high-risk patients. And it’s also important that the physician didn’t rely only on the test result, but also took a final look at the clinical situation before releasing the patient. There is some overruling when patients are biomarker-negative but have typical risk markers. No test is 100% accurate. Clinical judgment remains extremely important," emphasized co-investigator Dr Kurt Huber, professor and director of cardiology and emergency medicine at Wilhelminen Hospital, Vienna.

The BiC-8 trial was sponsored by ThermoFisher Scientic and six university medical centers in German-speaking Europe. Dr Moeckel reported receiving a research grant from ThermoFisher Scientific and serving as a consultant to Bayer, AstraZeneca, and The Medicines Company. Drs Arnett and Huber had no conflicts to declare.

[email protected]

Two studies document a rise in gun wounds, homicides

BY SHERRY BOSCHERT

At th AAST Annual Meeting

SAN FRANCISCO—Deaths from gunshot wounds doubled between 2000 and 2012 in the region served by one New Jersey trauma center and gun-related homicides as a propor­tion of violent crimes increased by 27% in southern Arizona after the state stopped requiring permits for concealed weapons, separate studies found.

In 2000, 8% of patients treated for gunshot wounds died. That rate in­creased to 15% in 2011, according to a retrospective study of 6,323 gun­shot wounds seen at the New Jersey Trauma Center, a Level I trauma cen­ter in Newark.

The proportion of 15-minute time increments in which the hospital was treating two or more pa­tients for gunshot wounds increased from approximately 10% in 2000 to nearly 30% by the end of 2011, and the proportion of 15-minute incre­ments in which three or more gun­shot wounds were being treated increased from 1% to 16%, reported Dr David H. Livingston and his asso­ciates.

Surgery on 71% of these patients plus other services incurred $115 mil­lion in costs, 75% of it unreimbursed. The mean cost per patient increased by 282% during the study period, re­ported Dr Livingston of University Hospital, Newark, NJ, and a profes­sor of surgery at Rutgers University, also in Newark.

Half of the patients in his study needed ICU care, a third needed a ventilator, and just less than a third needed blood transfusions. All of these parameters increased by 50% to 180% during the study period, he said at the annual meeting of the American Association for the Surgery of Trauma.

Further, the proportion of cases with three or more gunshot wounds doubled from 10% to 20%, as did the proportion of cases with three or more body areas that had been shot, from 5% to 10%

Five cities in New Jersey (Newark, Irving­ton, East Orange, Orange, and Eliza­beth) accounted for 85% of gunshot wounds; 75% of patients were shot in the city in which they lived, 55% within a mile of home, 25% within a block of home, and 15% in their homes.

The New Jersey study included only interpersonal gunshot injuries, not self-inflicted wounds or shots from police.

A second, separate study, gun-re­lated injury and deaths were compared in Arizona for the 2 years before and the 2 years after July 2010, when the state made it legal to carry a concealed weapon without a permit or training.

The proportion of homicides related to guns in southern Arizona increased significantly from 2% to nearly 2.5% af­ter that law was passed. Deaths by firearms increased by 24% among victims of violent crimes and acci­dents, Dr Rashna F. Ginwalla and her associates reported.

The number of violent crimes and accidents stayed relatively stable, but the risk of any gun-related injury or death increased significantly by 11% after concealed-weapons regulations were eliminated, said Dr Ginwalla, who led the study while at the Uni­versity of Arizona, Tucson. Dr Gin­walla now works in Rwanda for the University of Virginia, Char­lottesville.

"While causality has not been es­tablished by this observational study, we have demonstrated an association between an increase in gun availabili­ty and gun-related homicides in the state," she said.

Dr Livingston and Dr Ginwalla re­ported having no financial disclo­sures.

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Report details rise in bath salt-related ED visits

BY NASEEM S. MILLER

From A SAMHSA REPORT

The synthetic drugs "bath salts" accounted for 23,000 of 2.5 million drug-related emergency department visits in 2011, ac­cording to a report by the Substance Abuse and Mental Health Services Administration.

The toxicities of the drugs are similar to those of other stimulants seen in the ED, Dr Elinore F. McCance-Katz, SAMHSA’s chief medical officer, said in reporting the first national study to track data on the relatively new drugs.

Treatment is symptomatic, as there are no treatments that are specific to the toxicities related to these drugs, Dr McCance-Katz said. The drugs’ adverse effects include hypertension and tachycardia, de­pression, suicidal thoughts, agitation and anxiety, and psychosis.

The report, based on the 2011 Drug Abuse Warning Network, or DAWN report, also showed that two-thirds (67%) of bath salt–related ED visits involved the use of another drug: 15% involved combined use of marijuana or synthetic forms of mar­ijuana, and the other 52% involved a variety of other drugs.

Bath salts began to gain national at­tention in 2011, when poison centers reported a sudden jump to more than 6,000 cases of exposure to the drug, up from 300 cases in 2010.

In April 2013, the DEA put one of the main chemicals in bath salts in the Schedule I category. Several large national drug busts also have taken place in connection with the substance.

Bath salts come in the form of white or brown powder and contain one or more chemicals related to cathinone, an amphetamine-like stimulant. Their labelling implies that they are household prod­ucts, such as bath salts or jewelry cleaner, and may contain words such as "legal high" or "not for human consumption." They can be taken by mouth, inhaled, or injected.

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ED visits spike among California Medicaid patients

BY MICHELE G. SULLIVAN

From JAMA

Medicaid patients in California in­creased their use of emergency de­partments by nearly 36% over a 5-year period while ED use by privately insured patients barely increased.

"Increasing ED use by Medicaid beneficiaries could reflect decreasing access to primary care, which is sup­

ported by our findings of high and increasing rates of ED use for ambu­latory care sensitive conditions by Medicaid patients," wrote Dr Renee Hsia.

Dr Hsia of the University of Cali­fornia, San Francisco, and her coau­thors examined rates of ED utilization in California from 2005 to 2010 and broke down the data by in­surance status (JAMA. 2013;310[11]:1181-1183). They looked at adult patients younger than 65 years, because these patients "have experienced the great­est changes in insurance coverage in recent years, and are likely to see the biggest shifts as a result of health care reform."

The investigators based their retro­spective analysis on the California Of­fice of Statewide Health Planning and Development’s Emergency Dis­charge Data and Patient Discharge Data. The study grouped patients by insurance status: Medicaid, private, uninsured or self-pay, or other (work­ers compensation, CHAMPUS/TRI­CARE, Title V, and Veterans Affairs, and similar coverage).

Overall, ED visits jumped from 5.4 million to 6.1 million over the 5-year period—a 13% increase. While visits for patients with private insurance barely increased, with a 5-year differ­ence of just 1%, visits by Medicaid patients increased by 36%, and vis­its by uninsured patients rose 25%. Visits by patients with coverage in the "other" category decreased by more than 10%, the authors noted.

Medicaid patients also maintained the highest rate of visits such as hy­pertension, which are potentially pre­ventable with primary care. Among Medicaid recipients, the average year­ly rate of ED visits for these prob­lems was 55 per 1,000, compared with 11 per 1,000 for those with pri­vate insurance and nearly 17 per 1,000 for those who were uninsured.These visits showed the same kinds of coverage-dependent increases over the study period: a nearly 7% hike among Medicaid beneficiaries and about 6% among the uninsured, but a decline of nearly 1% among privately insured pa­tients.

Neither Dr Hsia nor her coauthors reported any financial disclosures.

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Bicycle helmet use remains low

BY SHARON WORCESTER

At the AAP National Conference

ORLANDO—About 11% of more than 1,200 children involved in bicycle-related accidents in Los Angeles County were wearing a helmet at the time of the accident. Los Angeles County mandates bicycle helmet use.

Of the 1,248 children from Los Angeles County who were included in the retrospective study of all injuries related to pediatric bicycle accidents between 2006 and 2011, 85% were boys. The lowest rates of helmet use were seen in children over age 12, and those of minority background and lower socioeconomic status. More than a third (35%) of white children wore helmets, but the rates were much lower for Asian (7%), black (6%), and Hispanic children (4%), said Dr Veronica Sullins of the Harbor-UCLA Medical Center in Torrance, Calif. Helmets were worn by 15% of children with private insurance, compared with nearly 8% of those with public insurance, Dr Sullins noted.

Emergency surgery was required in 6% of the children, and only 34% returned to their preinjury status. Nine patients died as a result of their injuries; eight of those were not wearing a helmet, Dr Sullins reported at the annual meeting of the American Academy of Pediatrics.

More than 150,000 emergency department visits each year are due to bicycle-related head injuries.

Helmet use has been shown to reduce bicycle-related head injuries by 80%; yet the Centers for Disease Control and Prevention reports that only 15% of adults and 19% of children wear helmets most or all of the time when riding a bicycle. An estimated 33 million children ride bicycles—for a total of 10 billion hours —each year, and nearly 400 children die as a result of bicycle crashes. I

Dr Sullins reported having no relevant financial disclosures.

Choosing Wisely: ACEP issues 5 things to avoid in the ED

By M. ALEXANDER OTTO

At the 2013 ACEP Acientific Assembly

Avoiding CT scans of emergency department patients who have minor head injuries and are at low risk based on validated decision rules was one of five practices recommended by The American College of Emergency Physicians as part of the "Choosing Wisely" campaign.

The mission of "Choosing Wisely" - a multi-year effort of the American Board of Internal Medicine (ABIM) Foundation - is to promote conversations among physicians and patients about using appropriate tests and treatments and avoiding care when harm may outweigh benefit.

Since launching in April 2012, more than 80 national, regional and state medical specialty societies and consumer groups have become "Choosing Wisely" partners. ACEP officially joined the campaign in February of this year. ACEP developed its five recommendations through a multi-step process that included input from members, its board of directors, and an expert panel.

The other four treatments and procedures chosen by ACEP and announced at their annual meeting include:

• Avoid placing indwelling urinary catheters in the ED for either urine output monitoring in stable patients who can urinate on their own, or for patient or staff convenience.

• Do not delay available palliative and hospice care services in ED patients who are likely to benefit, such as those who have chronic or incurable diseases. Early referral can improve both quality and quantity of life.

• Avoid antibiotics and wound cultures in ED patients with uncomplicated skin and soft tissue abscesses after successful incision and drainage and with adequate medical follow-up. Opening and draining the abscess is the appropriate treatment; antibiotics offer no benefit.

• Avoid instituting IV fluids before doing a trial of oral hydration in uncomplicated emergency department cases of mild to moderate dehydration of children. To avoid pain and potential complications, it’s preferable to give these fluids by mouth. I

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"One and done" vancomycin dosing disparaged

By M. ALEXANDER OTTO

At the 2013 ACEP Acientific Assembly

SEATTLE—One-and-done vancomycin dosing in the emergency department was associated with a high rate of ED returns for the same infection within 3 months, based on a single-center, retrospective study.

From Dec. 2008 to June 2010, 526 ED patients got vancomycin, mostly for cellulitis and abscesses, at the Barnes-Jewish Hospital ED in St. Louis, Mo., an academic ED that annually serves almost 100,000 patients; 67.9% got one dose, 26.6% got two, and 5.5% received three doses. Weight-based doses were too low in 73%, and too high in 3.4%. Less than half of the patients were sent home on an oral antibiotic; about one-third were back in the ED within 3 months for the same infection.

"It was very common just to order a dose of vancomycin and send people home, [but] none of the guidelines" from the Infectious Diseases Society of America and other groups "support the use of vancomycin in patients who have uncomplicated infections before going home" from the ED, said lead investigator Dr Kristen Mueller, a fourth-year emergency medicine resident at Barnes-Jewish. A single dose doesn’t keep inhibitory concentrations high enough for long enough to knock out infections entirely; although sensitive strains may die off, more robust and virulent ones are left to proliferate. Patients end up colonized by more resistant bacteria.

Several emergency physicians at the meeting said that they’ve noticed vancomycin dosing problems in their EDs, as well. Vancomycin dosing problems also were reported in a study published earlier this year by researchers from Christiana Care Health System in Newark Delaware (J Emerg Med. 2013;44[5]:979-984).

Vancomycin-intermediate Staphylococcus aureus was isolated from about 170 Barnes-Jewish patients in 2009. "It’s not as common as MRSA, but it’s there. What’s more concerning is that frank vancomycin resistant S. aureus is starting to establish itself in the US," and inappropriate use of vancomycin will just fuel the problem, she said.

Concerns about nephrotoxicity may be behind the low-dosing issue, but the hospital’s EHR system might also contribute to dosing inaccuracy, Dr Mueller said. At Barnes-Jewish, "our easiest order dose is 1 gram of vancomycin; it’s a one-click order in our order set. Whereas, to order a weight-appropriate dose, you actually have to calculate it out and type in the dose you want."

In response to the findings, Dr Mueller and her colleagues are adding a skin and soft tissue order set to the EHR system, with different tabs based on infection type and sub-tabs for patient disposition. Patients discharged home or to the observation unit will only have oral antibiotic options. Only inpatients will eligible for weight-based vancomycin dosing.

In an earlier study, Dr Mueller and her colleagues found that ED doses of vancomycin are frequently continued when patients are admitted, even if they’re wrong; 71% of the 2,560 inpatients in the earlier investigation were underdosed (J Emerg Med. 2013;44[5]:910-918).

Dr Mueller had no relevant disclosures.

[email protected]

Prehospital bivalirudin reduced bleeding with PCI

BY SHERRY BOSCHERT

At TCT 2013

SAN FRANCISCO – Giving bivalirudin in the ambulance to patients with ST-segment elevation MI before primary percutaneous coronary intervention significantly improved 30-day bleeding outcomes in a randomized controlled European trial in 2,218 patients, compared with giving unfractionated or low-molecular-weight heparin and optional glycoprotein IIb/IIIa inhibitors.

In Europe, anticoagulation commonly is started in the ambulance. The practice has not yet caught on in most of the United States.

Compared with the control group, the bivalirudin group had a nearly 40% decrease in a composite outcome of death or major bleeding not associated with coronary artery bypass grafting (CABG). Rates

for the primary outcome were 5% in the bivalirudin group and over 8% in the control group at 30 days,

Dr Philippe Gabriel Steg and his associates reported at the Transcatheter Cardiovascular Therapeutics annual meeting.

The rates of the main secondary outcome – a composite of death, reinfarction, or non-CABG major bleeding at 30 days – also were significantly lower in the bivalirudin group (6.7%) than in the control group (9.1%), said Dr Steg, professor of cardiology at Université Paris-Diderot and director of the coronary care unit at Hôpital Bichat, Paris.

The 30-day rate of acute stent thrombosis was nearly sixfold higher in the bivalirudin group (1.1%) than in the control group (0.2%), but that did not translate into an increased risk of infarction, which occurred in 1.7% in the bivalirudin group and 0.9% in the control group (0.9%).

The study was published online simultaneously with the presentation (N Engl J Med. October 30, 2013 [doi: 10.1056/NEJMoa1311096]).

The benefit from bivalirudin came mainly from reduced bleeding, not reduced mortality. The risk of major bleeding not associated with CABG was 2.7% in the bivalirudin group and 6.1% in the control group, a significant 57% reduction.

Rates of cardiac or noncardiac death at 30 days did not differ significantly between groups. Cardiac death occurred in 2.4% in the bivalirudin group and in 3% in the control group; noncardiac death occurred in 0.5% and 0.1%, respectively.

The EUROMAX findings were consistent across subgroups of patients, including subgroups defined by PCI access site or by the choice of P2Y12 inhibitor, Dr Steg reported at the meeting, cosponsored by the American College of Cardiology.

Dr Steg received fees from The Medicines Company, which sponsored the study and markets bivalirudin, and he reported financial associations with 16 other companies. Four of his colleagues in the study were employees of The Medicines Company, and 12 other colleagues reported financial associations with that company and/or multiple other companies. Dr Stone reported financial associations with Boston Scientific, Eli Lilly, and other companies.

[email protected]

Ottawa SAH clinical decision rule helps identify subarachnoid hemorrhage

BY MARY ANN MOON

From JAMA

A new clinical decision rule had sensitivity and specificity approaching 100% in ruling out subarachnoid hemorrhage among patients who presented to an emergency department with acute headache, a validation study showed.

Using this new tool, which requires only that the clinician answer six simple questions regarding the patient’s presentation, has the potential to reduce the number of costly and sometimes invasive procedures that are currently relied on to distinguish subarachnoid hemorrhage (SAH) from other pathologies, said Dr Jeffrey J. Perry of the department of emergency medicine at the University of Ottawa (Ont.) and the clinical epidemiology program at the Ottawa Hospital Research Institute and his associates.

Dr Perry and his colleagues devised three clinical decision rules to assist in ruling out SAH, then assessed the three rules for their accuracy, reliability, and acceptability to clinicians in a validation cohort of consecutive patients aged 16 years and older who presented to an ED with a nontraumatic headache that reached maximal intensity within 1 hour. There were 2,131 study subjects with a mean age of 44 years. Approximately 61% were women, and 26% arrived at the ED by ambulance.

All of these participants were treated by attending physicians certified in emergency medicine or by supervised residents at 10 university-affiliated urban, Canadian tertiary care teaching hospitals during a 4-year period. All patients were alert and oriented, with no neurologic deficits; 132 (6.2%) were found to have SAH.

After comparing the performances of the three candidate decision rules, the investigators refined the decision tool to identify six factors that were most predictive of SAH: age of 40 years or older, neck pain or stiffness, witnessed loss of consciousness, onset of headache during exertion, "thunderclap headache" (defined as instantly peaking pain), and limited neck flexion (defined as the inability to touch chin to chest when upright or to raise the head 8 cm off the bed when supine).

The presence of any one of these six factors indicates that SAH is possible and further investigation is required using CT and perhaps lumbar puncture, Dr Perry and his associates said.

This refined clinical decision rule, which they termed the Ottawa SAH rule, had an overall sensitivity of 99.2% and a specificity of 99.6% in identifying SAHs (JAMA. 2013;310[12]:1248-1255).

Following this rule would decrease the investigation rate"—the rate of further assessment using CT and lumbar puncture—"to 74% from the current investigation rate of 84%, the researchers added.

The Ottawa SAH rule must be evaluated further before it can be adopted into clinical practice. "An implementation study is the next step required to determine how the Ottawa SAH rule performs in clinical practice, assess the actual effects on patient care and patient outcomes, and conduct a formal health economic analysis," the researchers noted.

This study was supported by the Canadian Institutes for Health Research, the University of Ottawa, and the Vancouver Coastal Health Research Institute. No financial conflicts of interest were reported.

Novel two-biomarker strategy permits early ACS rule-out

BY BRUCE JANCIN

At the ESC Congress 2013

AMSTERDAM—An early rule-out strategy based upon using two cardiac biomarkers allowed for safe discharge within a couple hours from the emergency department for most low- to intermediate-risk patients who presented with suspected acute coronary syndromes, based on the results of a randomized, multicenter trial conducted in Europe.

Moreover, the 30-day rates of major adverse cardiovascular events in the Biomarkers in Cardiology–8 (BiC-8) study were similarly low in patients discharged from the ED using the early rule-out process and in those who received standard, guideline-recommended care, which includes 6-12 hours of serial ECGs and troponin measurements in the chest pain unit, Dr Martin Moeckel reported at the annual congress of the European Society of Cardiology.

"This biomarker strategy using a state-of-the-art quantitative troponin assay in combination with an ultrasensitive copeptin assay has the potential to change clinical practice with high patient safety," observed Dr Moeckel of Charite Hospital, Berlin. The copeptin test is approved for use in the European Union but remains investigational in the United States.

Based upon the results of BiC-8, this dual-biomarker for early rule-out of myocardial infarction is now standard clinical practice at Charite, he added.

Nearly 12% of all patients who present to the ED do so because of chest pain, yet after an extensive and time-consuming evaluation only 1 in 10 of those patients are found to actually be having an acute MI.

"Rapid rule-out of acute MI is therefore a major clinical need, saving the health care system time and resources, and saving patients unnecessary stress, anxiety, and other risks," he said.

Copeptin is a marker for vasopressin, a hemodynamic stress indicator that shoots up immediately in an acute MI. In earlier studies, a negative result for both troponin and copeptin in an initial blood sample drawn at ED presentation had a 99% negative predictive value for MI.

The BiC-8 trial included 902 low- to intermediate-risk patients who presented with suspected ACS to EDs in university medical centers. All had a negative initial cardiac troponin test. They were randomized to standard care in the chest pain unit, including serial troponin testing and ECGs, or to the experimental strategy, in which physicians were informed of the copeptin results from the same initial blood sample as the troponin. If the copeptin test was positive as defined by a level of 10 pmol/L or more, the patient was hospitalized for standard care. If the copeptin result was negative, however, the patient was immediately discharged with a scheduled outpatient visit within72 hours.

Of the patients in the copeptin group, 66% were discharged directly from the ED, compared to 12% in the standard care group.

The 30-day incidence of major adverse cardiovascular events (MACE) was 5.5% in the standard care group and nearly identical at 5.46% in the copeptin group. MACE was defined in BiC-8 as all-cause mortality, MI, rehospitalization for ACS, acute unplanned PCI, coronary artery bypass surgery, life-threatening arrhythmia, or resuscitation from cardiac arrest.

MACE occurred in 14 copeptin-negative patients. However, 12 of the 14 were not discharged early because physicians overruled the negative biomarker results based on patient history and moved the patients into standard in-hospital management. Two patients, or 0.6% of those discharged from the ED on the basis of a negative copeptin test, had adverse events: one was rehospitalized on day 23 and underwent acute unplanned PCI on the next day, and the other was rehospitalized on day 4 and underwent coronary artery bypass graft surgery on day 12.

American Heart Association Immediate Past President Donna K. Arnett, PhD, said in an interview that she’d really like to see a second, confirmatory randomized trial before this early rule-out strategy is widely adopted. She considers the lost-to-followup rate uncomfortably high: 63 patients in the intention-to-treat analysis, and another 75 not accounted for in the per protocol analysis, noted Dr Arnett, professor and chair of the department of epidemiology at the University of Alabama, Birmingham.

"The most important message from BiC-8, I think, is that these were patients at low- to-intermediate risk; they’re not the high-risk patients. And it’s also important that the physician didn’t rely only on the test result, but also took a final look at the clinical situation before releasing the patient. There is some overruling when patients are biomarker-negative but have typical risk markers. No test is 100% accurate. Clinical judgment remains extremely important," emphasized co-investigator Dr Kurt Huber, professor and director of cardiology and emergency medicine at Wilhelminen Hospital, Vienna.

The BiC-8 trial was sponsored by ThermoFisher Scientic and six university medical centers in German-speaking Europe. Dr Moeckel reported receiving a research grant from ThermoFisher Scientific and serving as a consultant to Bayer, AstraZeneca, and The Medicines Company. Drs Arnett and Huber had no conflicts to declare.

[email protected]

Two studies document a rise in gun wounds, homicides

BY SHERRY BOSCHERT

At th AAST Annual Meeting

SAN FRANCISCO—Deaths from gunshot wounds doubled between 2000 and 2012 in the region served by one New Jersey trauma center and gun-related homicides as a propor­tion of violent crimes increased by 27% in southern Arizona after the state stopped requiring permits for concealed weapons, separate studies found.

In 2000, 8% of patients treated for gunshot wounds died. That rate in­creased to 15% in 2011, according to a retrospective study of 6,323 gun­shot wounds seen at the New Jersey Trauma Center, a Level I trauma cen­ter in Newark.

The proportion of 15-minute time increments in which the hospital was treating two or more pa­tients for gunshot wounds increased from approximately 10% in 2000 to nearly 30% by the end of 2011, and the proportion of 15-minute incre­ments in which three or more gun­shot wounds were being treated increased from 1% to 16%, reported Dr David H. Livingston and his asso­ciates.

Surgery on 71% of these patients plus other services incurred $115 mil­lion in costs, 75% of it unreimbursed. The mean cost per patient increased by 282% during the study period, re­ported Dr Livingston of University Hospital, Newark, NJ, and a profes­sor of surgery at Rutgers University, also in Newark.

Half of the patients in his study needed ICU care, a third needed a ventilator, and just less than a third needed blood transfusions. All of these parameters increased by 50% to 180% during the study period, he said at the annual meeting of the American Association for the Surgery of Trauma.

Further, the proportion of cases with three or more gunshot wounds doubled from 10% to 20%, as did the proportion of cases with three or more body areas that had been shot, from 5% to 10%

Five cities in New Jersey (Newark, Irving­ton, East Orange, Orange, and Eliza­beth) accounted for 85% of gunshot wounds; 75% of patients were shot in the city in which they lived, 55% within a mile of home, 25% within a block of home, and 15% in their homes.

The New Jersey study included only interpersonal gunshot injuries, not self-inflicted wounds or shots from police.

A second, separate study, gun-re­lated injury and deaths were compared in Arizona for the 2 years before and the 2 years after July 2010, when the state made it legal to carry a concealed weapon without a permit or training.

The proportion of homicides related to guns in southern Arizona increased significantly from 2% to nearly 2.5% af­ter that law was passed. Deaths by firearms increased by 24% among victims of violent crimes and acci­dents, Dr Rashna F. Ginwalla and her associates reported.

The number of violent crimes and accidents stayed relatively stable, but the risk of any gun-related injury or death increased significantly by 11% after concealed-weapons regulations were eliminated, said Dr Ginwalla, who led the study while at the Uni­versity of Arizona, Tucson. Dr Gin­walla now works in Rwanda for the University of Virginia, Char­lottesville.

"While causality has not been es­tablished by this observational study, we have demonstrated an association between an increase in gun availabili­ty and gun-related homicides in the state," she said.

Dr Livingston and Dr Ginwalla re­ported having no financial disclo­sures.

[email protected]

Report details rise in bath salt-related ED visits

BY NASEEM S. MILLER

From A SAMHSA REPORT

The synthetic drugs "bath salts" accounted for 23,000 of 2.5 million drug-related emergency department visits in 2011, ac­cording to a report by the Substance Abuse and Mental Health Services Administration.

The toxicities of the drugs are similar to those of other stimulants seen in the ED, Dr Elinore F. McCance-Katz, SAMHSA’s chief medical officer, said in reporting the first national study to track data on the relatively new drugs.

Treatment is symptomatic, as there are no treatments that are specific to the toxicities related to these drugs, Dr McCance-Katz said. The drugs’ adverse effects include hypertension and tachycardia, de­pression, suicidal thoughts, agitation and anxiety, and psychosis.

The report, based on the 2011 Drug Abuse Warning Network, or DAWN report, also showed that two-thirds (67%) of bath salt–related ED visits involved the use of another drug: 15% involved combined use of marijuana or synthetic forms of mar­ijuana, and the other 52% involved a variety of other drugs.

Bath salts began to gain national at­tention in 2011, when poison centers reported a sudden jump to more than 6,000 cases of exposure to the drug, up from 300 cases in 2010.

In April 2013, the DEA put one of the main chemicals in bath salts in the Schedule I category. Several large national drug busts also have taken place in connection with the substance.

Bath salts come in the form of white or brown powder and contain one or more chemicals related to cathinone, an amphetamine-like stimulant. Their labelling implies that they are household prod­ucts, such as bath salts or jewelry cleaner, and may contain words such as "legal high" or "not for human consumption." They can be taken by mouth, inhaled, or injected.

[email protected]

ED visits spike among California Medicaid patients

BY MICHELE G. SULLIVAN

From JAMA

Medicaid patients in California in­creased their use of emergency de­partments by nearly 36% over a 5-year period while ED use by privately insured patients barely increased.

"Increasing ED use by Medicaid beneficiaries could reflect decreasing access to primary care, which is sup­

ported by our findings of high and increasing rates of ED use for ambu­latory care sensitive conditions by Medicaid patients," wrote Dr Renee Hsia.

Dr Hsia of the University of Cali­fornia, San Francisco, and her coau­thors examined rates of ED utilization in California from 2005 to 2010 and broke down the data by in­surance status (JAMA. 2013;310[11]:1181-1183). They looked at adult patients younger than 65 years, because these patients "have experienced the great­est changes in insurance coverage in recent years, and are likely to see the biggest shifts as a result of health care reform."

The investigators based their retro­spective analysis on the California Of­fice of Statewide Health Planning and Development’s Emergency Dis­charge Data and Patient Discharge Data. The study grouped patients by insurance status: Medicaid, private, uninsured or self-pay, or other (work­ers compensation, CHAMPUS/TRI­CARE, Title V, and Veterans Affairs, and similar coverage).

Overall, ED visits jumped from 5.4 million to 6.1 million over the 5-year period—a 13% increase. While visits for patients with private insurance barely increased, with a 5-year differ­ence of just 1%, visits by Medicaid patients increased by 36%, and vis­its by uninsured patients rose 25%. Visits by patients with coverage in the "other" category decreased by more than 10%, the authors noted.

Medicaid patients also maintained the highest rate of visits such as hy­pertension, which are potentially pre­ventable with primary care. Among Medicaid recipients, the average year­ly rate of ED visits for these prob­lems was 55 per 1,000, compared with 11 per 1,000 for those with pri­vate insurance and nearly 17 per 1,000 for those who were uninsured.These visits showed the same kinds of coverage-dependent increases over the study period: a nearly 7% hike among Medicaid beneficiaries and about 6% among the uninsured, but a decline of nearly 1% among privately insured pa­tients.

Neither Dr Hsia nor her coauthors reported any financial disclosures.

[email protected]

Bicycle helmet use remains low

BY SHARON WORCESTER

At the AAP National Conference

ORLANDO—About 11% of more than 1,200 children involved in bicycle-related accidents in Los Angeles County were wearing a helmet at the time of the accident. Los Angeles County mandates bicycle helmet use.

Of the 1,248 children from Los Angeles County who were included in the retrospective study of all injuries related to pediatric bicycle accidents between 2006 and 2011, 85% were boys. The lowest rates of helmet use were seen in children over age 12, and those of minority background and lower socioeconomic status. More than a third (35%) of white children wore helmets, but the rates were much lower for Asian (7%), black (6%), and Hispanic children (4%), said Dr Veronica Sullins of the Harbor-UCLA Medical Center in Torrance, Calif. Helmets were worn by 15% of children with private insurance, compared with nearly 8% of those with public insurance, Dr Sullins noted.

Emergency surgery was required in 6% of the children, and only 34% returned to their preinjury status. Nine patients died as a result of their injuries; eight of those were not wearing a helmet, Dr Sullins reported at the annual meeting of the American Academy of Pediatrics.

More than 150,000 emergency department visits each year are due to bicycle-related head injuries.

Helmet use has been shown to reduce bicycle-related head injuries by 80%; yet the Centers for Disease Control and Prevention reports that only 15% of adults and 19% of children wear helmets most or all of the time when riding a bicycle. An estimated 33 million children ride bicycles—for a total of 10 billion hours —each year, and nearly 400 children die as a result of bicycle crashes. I

Dr Sullins reported having no relevant financial disclosures.

Choosing Wisely: ACEP issues 5 things to avoid in the ED

By M. ALEXANDER OTTO

At the 2013 ACEP Acientific Assembly

Avoiding CT scans of emergency department patients who have minor head injuries and are at low risk based on validated decision rules was one of five practices recommended by The American College of Emergency Physicians as part of the "Choosing Wisely" campaign.

The mission of "Choosing Wisely" - a multi-year effort of the American Board of Internal Medicine (ABIM) Foundation - is to promote conversations among physicians and patients about using appropriate tests and treatments and avoiding care when harm may outweigh benefit.

Since launching in April 2012, more than 80 national, regional and state medical specialty societies and consumer groups have become "Choosing Wisely" partners. ACEP officially joined the campaign in February of this year. ACEP developed its five recommendations through a multi-step process that included input from members, its board of directors, and an expert panel.

The other four treatments and procedures chosen by ACEP and announced at their annual meeting include:

• Avoid placing indwelling urinary catheters in the ED for either urine output monitoring in stable patients who can urinate on their own, or for patient or staff convenience.

• Do not delay available palliative and hospice care services in ED patients who are likely to benefit, such as those who have chronic or incurable diseases. Early referral can improve both quality and quantity of life.

• Avoid antibiotics and wound cultures in ED patients with uncomplicated skin and soft tissue abscesses after successful incision and drainage and with adequate medical follow-up. Opening and draining the abscess is the appropriate treatment; antibiotics offer no benefit.

• Avoid instituting IV fluids before doing a trial of oral hydration in uncomplicated emergency department cases of mild to moderate dehydration of children. To avoid pain and potential complications, it’s preferable to give these fluids by mouth. I

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"One and done" vancomycin dosing disparaged

By M. ALEXANDER OTTO

At the 2013 ACEP Acientific Assembly

SEATTLE—One-and-done vancomycin dosing in the emergency department was associated with a high rate of ED returns for the same infection within 3 months, based on a single-center, retrospective study.

From Dec. 2008 to June 2010, 526 ED patients got vancomycin, mostly for cellulitis and abscesses, at the Barnes-Jewish Hospital ED in St. Louis, Mo., an academic ED that annually serves almost 100,000 patients; 67.9% got one dose, 26.6% got two, and 5.5% received three doses. Weight-based doses were too low in 73%, and too high in 3.4%. Less than half of the patients were sent home on an oral antibiotic; about one-third were back in the ED within 3 months for the same infection.

"It was very common just to order a dose of vancomycin and send people home, [but] none of the guidelines" from the Infectious Diseases Society of America and other groups "support the use of vancomycin in patients who have uncomplicated infections before going home" from the ED, said lead investigator Dr Kristen Mueller, a fourth-year emergency medicine resident at Barnes-Jewish. A single dose doesn’t keep inhibitory concentrations high enough for long enough to knock out infections entirely; although sensitive strains may die off, more robust and virulent ones are left to proliferate. Patients end up colonized by more resistant bacteria.

Several emergency physicians at the meeting said that they’ve noticed vancomycin dosing problems in their EDs, as well. Vancomycin dosing problems also were reported in a study published earlier this year by researchers from Christiana Care Health System in Newark Delaware (J Emerg Med. 2013;44[5]:979-984).

Vancomycin-intermediate Staphylococcus aureus was isolated from about 170 Barnes-Jewish patients in 2009. "It’s not as common as MRSA, but it’s there. What’s more concerning is that frank vancomycin resistant S. aureus is starting to establish itself in the US," and inappropriate use of vancomycin will just fuel the problem, she said.

Concerns about nephrotoxicity may be behind the low-dosing issue, but the hospital’s EHR system might also contribute to dosing inaccuracy, Dr Mueller said. At Barnes-Jewish, "our easiest order dose is 1 gram of vancomycin; it’s a one-click order in our order set. Whereas, to order a weight-appropriate dose, you actually have to calculate it out and type in the dose you want."

In response to the findings, Dr Mueller and her colleagues are adding a skin and soft tissue order set to the EHR system, with different tabs based on infection type and sub-tabs for patient disposition. Patients discharged home or to the observation unit will only have oral antibiotic options. Only inpatients will eligible for weight-based vancomycin dosing.

In an earlier study, Dr Mueller and her colleagues found that ED doses of vancomycin are frequently continued when patients are admitted, even if they’re wrong; 71% of the 2,560 inpatients in the earlier investigation were underdosed (J Emerg Med. 2013;44[5]:910-918).

Dr Mueller had no relevant disclosures.

[email protected]

Prehospital bivalirudin reduced bleeding with PCI

BY SHERRY BOSCHERT

At TCT 2013

SAN FRANCISCO – Giving bivalirudin in the ambulance to patients with ST-segment elevation MI before primary percutaneous coronary intervention significantly improved 30-day bleeding outcomes in a randomized controlled European trial in 2,218 patients, compared with giving unfractionated or low-molecular-weight heparin and optional glycoprotein IIb/IIIa inhibitors.

In Europe, anticoagulation commonly is started in the ambulance. The practice has not yet caught on in most of the United States.

Compared with the control group, the bivalirudin group had a nearly 40% decrease in a composite outcome of death or major bleeding not associated with coronary artery bypass grafting (CABG). Rates

for the primary outcome were 5% in the bivalirudin group and over 8% in the control group at 30 days,

Dr Philippe Gabriel Steg and his associates reported at the Transcatheter Cardiovascular Therapeutics annual meeting.

The rates of the main secondary outcome – a composite of death, reinfarction, or non-CABG major bleeding at 30 days – also were significantly lower in the bivalirudin group (6.7%) than in the control group (9.1%), said Dr Steg, professor of cardiology at Université Paris-Diderot and director of the coronary care unit at Hôpital Bichat, Paris.

The 30-day rate of acute stent thrombosis was nearly sixfold higher in the bivalirudin group (1.1%) than in the control group (0.2%), but that did not translate into an increased risk of infarction, which occurred in 1.7% in the bivalirudin group and 0.9% in the control group (0.9%).

The study was published online simultaneously with the presentation (N Engl J Med. October 30, 2013 [doi: 10.1056/NEJMoa1311096]).

The benefit from bivalirudin came mainly from reduced bleeding, not reduced mortality. The risk of major bleeding not associated with CABG was 2.7% in the bivalirudin group and 6.1% in the control group, a significant 57% reduction.

Rates of cardiac or noncardiac death at 30 days did not differ significantly between groups. Cardiac death occurred in 2.4% in the bivalirudin group and in 3% in the control group; noncardiac death occurred in 0.5% and 0.1%, respectively.

The EUROMAX findings were consistent across subgroups of patients, including subgroups defined by PCI access site or by the choice of P2Y12 inhibitor, Dr Steg reported at the meeting, cosponsored by the American College of Cardiology.

Dr Steg received fees from The Medicines Company, which sponsored the study and markets bivalirudin, and he reported financial associations with 16 other companies. Four of his colleagues in the study were employees of The Medicines Company, and 12 other colleagues reported financial associations with that company and/or multiple other companies. Dr Stone reported financial associations with Boston Scientific, Eli Lilly, and other companies.

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Ottawa SAH clinical decision rule helps identify subarachnoid hemorrhage

BY MARY ANN MOON

From JAMA

A new clinical decision rule had sensitivity and specificity approaching 100% in ruling out subarachnoid hemorrhage among patients who presented to an emergency department with acute headache, a validation study showed.

Using this new tool, which requires only that the clinician answer six simple questions regarding the patient’s presentation, has the potential to reduce the number of costly and sometimes invasive procedures that are currently relied on to distinguish subarachnoid hemorrhage (SAH) from other pathologies, said Dr Jeffrey J. Perry of the department of emergency medicine at the University of Ottawa (Ont.) and the clinical epidemiology program at the Ottawa Hospital Research Institute and his associates.

Dr Perry and his colleagues devised three clinical decision rules to assist in ruling out SAH, then assessed the three rules for their accuracy, reliability, and acceptability to clinicians in a validation cohort of consecutive patients aged 16 years and older who presented to an ED with a nontraumatic headache that reached maximal intensity within 1 hour. There were 2,131 study subjects with a mean age of 44 years. Approximately 61% were women, and 26% arrived at the ED by ambulance.

All of these participants were treated by attending physicians certified in emergency medicine or by supervised residents at 10 university-affiliated urban, Canadian tertiary care teaching hospitals during a 4-year period. All patients were alert and oriented, with no neurologic deficits; 132 (6.2%) were found to have SAH.

After comparing the performances of the three candidate decision rules, the investigators refined the decision tool to identify six factors that were most predictive of SAH: age of 40 years or older, neck pain or stiffness, witnessed loss of consciousness, onset of headache during exertion, "thunderclap headache" (defined as instantly peaking pain), and limited neck flexion (defined as the inability to touch chin to chest when upright or to raise the head 8 cm off the bed when supine).

The presence of any one of these six factors indicates that SAH is possible and further investigation is required using CT and perhaps lumbar puncture, Dr Perry and his associates said.

This refined clinical decision rule, which they termed the Ottawa SAH rule, had an overall sensitivity of 99.2% and a specificity of 99.6% in identifying SAHs (JAMA. 2013;310[12]:1248-1255).

Following this rule would decrease the investigation rate"—the rate of further assessment using CT and lumbar puncture—"to 74% from the current investigation rate of 84%, the researchers added.

The Ottawa SAH rule must be evaluated further before it can be adopted into clinical practice. "An implementation study is the next step required to determine how the Ottawa SAH rule performs in clinical practice, assess the actual effects on patient care and patient outcomes, and conduct a formal health economic analysis," the researchers noted.

This study was supported by the Canadian Institutes for Health Research, the University of Ottawa, and the Vancouver Coastal Health Research Institute. No financial conflicts of interest were reported.

Novel two-biomarker strategy permits early ACS rule-out

BY BRUCE JANCIN

At the ESC Congress 2013

AMSTERDAM—An early rule-out strategy based upon using two cardiac biomarkers allowed for safe discharge within a couple hours from the emergency department for most low- to intermediate-risk patients who presented with suspected acute coronary syndromes, based on the results of a randomized, multicenter trial conducted in Europe.

Moreover, the 30-day rates of major adverse cardiovascular events in the Biomarkers in Cardiology–8 (BiC-8) study were similarly low in patients discharged from the ED using the early rule-out process and in those who received standard, guideline-recommended care, which includes 6-12 hours of serial ECGs and troponin measurements in the chest pain unit, Dr Martin Moeckel reported at the annual congress of the European Society of Cardiology.

"This biomarker strategy using a state-of-the-art quantitative troponin assay in combination with an ultrasensitive copeptin assay has the potential to change clinical practice with high patient safety," observed Dr Moeckel of Charite Hospital, Berlin. The copeptin test is approved for use in the European Union but remains investigational in the United States.

Based upon the results of BiC-8, this dual-biomarker for early rule-out of myocardial infarction is now standard clinical practice at Charite, he added.

Nearly 12% of all patients who present to the ED do so because of chest pain, yet after an extensive and time-consuming evaluation only 1 in 10 of those patients are found to actually be having an acute MI.

"Rapid rule-out of acute MI is therefore a major clinical need, saving the health care system time and resources, and saving patients unnecessary stress, anxiety, and other risks," he said.

Copeptin is a marker for vasopressin, a hemodynamic stress indicator that shoots up immediately in an acute MI. In earlier studies, a negative result for both troponin and copeptin in an initial blood sample drawn at ED presentation had a 99% negative predictive value for MI.

The BiC-8 trial included 902 low- to intermediate-risk patients who presented with suspected ACS to EDs in university medical centers. All had a negative initial cardiac troponin test. They were randomized to standard care in the chest pain unit, including serial troponin testing and ECGs, or to the experimental strategy, in which physicians were informed of the copeptin results from the same initial blood sample as the troponin. If the copeptin test was positive as defined by a level of 10 pmol/L or more, the patient was hospitalized for standard care. If the copeptin result was negative, however, the patient was immediately discharged with a scheduled outpatient visit within72 hours.

Of the patients in the copeptin group, 66% were discharged directly from the ED, compared to 12% in the standard care group.

The 30-day incidence of major adverse cardiovascular events (MACE) was 5.5% in the standard care group and nearly identical at 5.46% in the copeptin group. MACE was defined in BiC-8 as all-cause mortality, MI, rehospitalization for ACS, acute unplanned PCI, coronary artery bypass surgery, life-threatening arrhythmia, or resuscitation from cardiac arrest.

MACE occurred in 14 copeptin-negative patients. However, 12 of the 14 were not discharged early because physicians overruled the negative biomarker results based on patient history and moved the patients into standard in-hospital management. Two patients, or 0.6% of those discharged from the ED on the basis of a negative copeptin test, had adverse events: one was rehospitalized on day 23 and underwent acute unplanned PCI on the next day, and the other was rehospitalized on day 4 and underwent coronary artery bypass graft surgery on day 12.

American Heart Association Immediate Past President Donna K. Arnett, PhD, said in an interview that she’d really like to see a second, confirmatory randomized trial before this early rule-out strategy is widely adopted. She considers the lost-to-followup rate uncomfortably high: 63 patients in the intention-to-treat analysis, and another 75 not accounted for in the per protocol analysis, noted Dr Arnett, professor and chair of the department of epidemiology at the University of Alabama, Birmingham.

"The most important message from BiC-8, I think, is that these were patients at low- to-intermediate risk; they’re not the high-risk patients. And it’s also important that the physician didn’t rely only on the test result, but also took a final look at the clinical situation before releasing the patient. There is some overruling when patients are biomarker-negative but have typical risk markers. No test is 100% accurate. Clinical judgment remains extremely important," emphasized co-investigator Dr Kurt Huber, professor and director of cardiology and emergency medicine at Wilhelminen Hospital, Vienna.

The BiC-8 trial was sponsored by ThermoFisher Scientic and six university medical centers in German-speaking Europe. Dr Moeckel reported receiving a research grant from ThermoFisher Scientific and serving as a consultant to Bayer, AstraZeneca, and The Medicines Company. Drs Arnett and Huber had no conflicts to declare.

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Two studies document a rise in gun wounds, homicides

BY SHERRY BOSCHERT

At th AAST Annual Meeting

SAN FRANCISCO—Deaths from gunshot wounds doubled between 2000 and 2012 in the region served by one New Jersey trauma center and gun-related homicides as a propor­tion of violent crimes increased by 27% in southern Arizona after the state stopped requiring permits for concealed weapons, separate studies found.

In 2000, 8% of patients treated for gunshot wounds died. That rate in­creased to 15% in 2011, according to a retrospective study of 6,323 gun­shot wounds seen at the New Jersey Trauma Center, a Level I trauma cen­ter in Newark.

The proportion of 15-minute time increments in which the hospital was treating two or more pa­tients for gunshot wounds increased from approximately 10% in 2000 to nearly 30% by the end of 2011, and the proportion of 15-minute incre­ments in which three or more gun­shot wounds were being treated increased from 1% to 16%, reported Dr David H. Livingston and his asso­ciates.

Surgery on 71% of these patients plus other services incurred $115 mil­lion in costs, 75% of it unreimbursed. The mean cost per patient increased by 282% during the study period, re­ported Dr Livingston of University Hospital, Newark, NJ, and a profes­sor of surgery at Rutgers University, also in Newark.

Half of the patients in his study needed ICU care, a third needed a ventilator, and just less than a third needed blood transfusions. All of these parameters increased by 50% to 180% during the study period, he said at the annual meeting of the American Association for the Surgery of Trauma.

Further, the proportion of cases with three or more gunshot wounds doubled from 10% to 20%, as did the proportion of cases with three or more body areas that had been shot, from 5% to 10%

Five cities in New Jersey (Newark, Irving­ton, East Orange, Orange, and Eliza­beth) accounted for 85% of gunshot wounds; 75% of patients were shot in the city in which they lived, 55% within a mile of home, 25% within a block of home, and 15% in their homes.

The New Jersey study included only interpersonal gunshot injuries, not self-inflicted wounds or shots from police.

A second, separate study, gun-re­lated injury and deaths were compared in Arizona for the 2 years before and the 2 years after July 2010, when the state made it legal to carry a concealed weapon without a permit or training.

The proportion of homicides related to guns in southern Arizona increased significantly from 2% to nearly 2.5% af­ter that law was passed. Deaths by firearms increased by 24% among victims of violent crimes and acci­dents, Dr Rashna F. Ginwalla and her associates reported.

The number of violent crimes and accidents stayed relatively stable, but the risk of any gun-related injury or death increased significantly by 11% after concealed-weapons regulations were eliminated, said Dr Ginwalla, who led the study while at the Uni­versity of Arizona, Tucson. Dr Gin­walla now works in Rwanda for the University of Virginia, Char­lottesville.

"While causality has not been es­tablished by this observational study, we have demonstrated an association between an increase in gun availabili­ty and gun-related homicides in the state," she said.

Dr Livingston and Dr Ginwalla re­ported having no financial disclo­sures.

[email protected]

Report details rise in bath salt-related ED visits

BY NASEEM S. MILLER

From A SAMHSA REPORT

The synthetic drugs "bath salts" accounted for 23,000 of 2.5 million drug-related emergency department visits in 2011, ac­cording to a report by the Substance Abuse and Mental Health Services Administration.

The toxicities of the drugs are similar to those of other stimulants seen in the ED, Dr Elinore F. McCance-Katz, SAMHSA’s chief medical officer, said in reporting the first national study to track data on the relatively new drugs.

Treatment is symptomatic, as there are no treatments that are specific to the toxicities related to these drugs, Dr McCance-Katz said. The drugs’ adverse effects include hypertension and tachycardia, de­pression, suicidal thoughts, agitation and anxiety, and psychosis.

The report, based on the 2011 Drug Abuse Warning Network, or DAWN report, also showed that two-thirds (67%) of bath salt–related ED visits involved the use of another drug: 15% involved combined use of marijuana or synthetic forms of mar­ijuana, and the other 52% involved a variety of other drugs.

Bath salts began to gain national at­tention in 2011, when poison centers reported a sudden jump to more than 6,000 cases of exposure to the drug, up from 300 cases in 2010.

In April 2013, the DEA put one of the main chemicals in bath salts in the Schedule I category. Several large national drug busts also have taken place in connection with the substance.

Bath salts come in the form of white or brown powder and contain one or more chemicals related to cathinone, an amphetamine-like stimulant. Their labelling implies that they are household prod­ucts, such as bath salts or jewelry cleaner, and may contain words such as "legal high" or "not for human consumption." They can be taken by mouth, inhaled, or injected.

[email protected]

ED visits spike among California Medicaid patients

BY MICHELE G. SULLIVAN

From JAMA

Medicaid patients in California in­creased their use of emergency de­partments by nearly 36% over a 5-year period while ED use by privately insured patients barely increased.

"Increasing ED use by Medicaid beneficiaries could reflect decreasing access to primary care, which is sup­

ported by our findings of high and increasing rates of ED use for ambu­latory care sensitive conditions by Medicaid patients," wrote Dr Renee Hsia.

Dr Hsia of the University of Cali­fornia, San Francisco, and her coau­thors examined rates of ED utilization in California from 2005 to 2010 and broke down the data by in­surance status (JAMA. 2013;310[11]:1181-1183). They looked at adult patients younger than 65 years, because these patients "have experienced the great­est changes in insurance coverage in recent years, and are likely to see the biggest shifts as a result of health care reform."

The investigators based their retro­spective analysis on the California Of­fice of Statewide Health Planning and Development’s Emergency Dis­charge Data and Patient Discharge Data. The study grouped patients by insurance status: Medicaid, private, uninsured or self-pay, or other (work­ers compensation, CHAMPUS/TRI­CARE, Title V, and Veterans Affairs, and similar coverage).

Overall, ED visits jumped from 5.4 million to 6.1 million over the 5-year period—a 13% increase. While visits for patients with private insurance barely increased, with a 5-year differ­ence of just 1%, visits by Medicaid patients increased by 36%, and vis­its by uninsured patients rose 25%. Visits by patients with coverage in the "other" category decreased by more than 10%, the authors noted.

Medicaid patients also maintained the highest rate of visits such as hy­pertension, which are potentially pre­ventable with primary care. Among Medicaid recipients, the average year­ly rate of ED visits for these prob­lems was 55 per 1,000, compared with 11 per 1,000 for those with pri­vate insurance and nearly 17 per 1,000 for those who were uninsured.These visits showed the same kinds of coverage-dependent increases over the study period: a nearly 7% hike among Medicaid beneficiaries and about 6% among the uninsured, but a decline of nearly 1% among privately insured pa­tients.

Neither Dr Hsia nor her coauthors reported any financial disclosures.

[email protected]

Bicycle helmet use remains low

BY SHARON WORCESTER

At the AAP National Conference

ORLANDO—About 11% of more than 1,200 children involved in bicycle-related accidents in Los Angeles County were wearing a helmet at the time of the accident. Los Angeles County mandates bicycle helmet use.

Of the 1,248 children from Los Angeles County who were included in the retrospective study of all injuries related to pediatric bicycle accidents between 2006 and 2011, 85% were boys. The lowest rates of helmet use were seen in children over age 12, and those of minority background and lower socioeconomic status. More than a third (35%) of white children wore helmets, but the rates were much lower for Asian (7%), black (6%), and Hispanic children (4%), said Dr Veronica Sullins of the Harbor-UCLA Medical Center in Torrance, Calif. Helmets were worn by 15% of children with private insurance, compared with nearly 8% of those with public insurance, Dr Sullins noted.

Emergency surgery was required in 6% of the children, and only 34% returned to their preinjury status. Nine patients died as a result of their injuries; eight of those were not wearing a helmet, Dr Sullins reported at the annual meeting of the American Academy of Pediatrics.

More than 150,000 emergency department visits each year are due to bicycle-related head injuries.

Helmet use has been shown to reduce bicycle-related head injuries by 80%; yet the Centers for Disease Control and Prevention reports that only 15% of adults and 19% of children wear helmets most or all of the time when riding a bicycle. An estimated 33 million children ride bicycles—for a total of 10 billion hours —each year, and nearly 400 children die as a result of bicycle crashes. I

Dr Sullins reported having no relevant financial disclosures.

Choosing Wisely: ACEP issues 5 things to avoid in the ED

By M. ALEXANDER OTTO

At the 2013 ACEP Acientific Assembly

Avoiding CT scans of emergency department patients who have minor head injuries and are at low risk based on validated decision rules was one of five practices recommended by The American College of Emergency Physicians as part of the "Choosing Wisely" campaign.

The mission of "Choosing Wisely" - a multi-year effort of the American Board of Internal Medicine (ABIM) Foundation - is to promote conversations among physicians and patients about using appropriate tests and treatments and avoiding care when harm may outweigh benefit.

Since launching in April 2012, more than 80 national, regional and state medical specialty societies and consumer groups have become "Choosing Wisely" partners. ACEP officially joined the campaign in February of this year. ACEP developed its five recommendations through a multi-step process that included input from members, its board of directors, and an expert panel.

The other four treatments and procedures chosen by ACEP and announced at their annual meeting include:

• Avoid placing indwelling urinary catheters in the ED for either urine output monitoring in stable patients who can urinate on their own, or for patient or staff convenience.

• Do not delay available palliative and hospice care services in ED patients who are likely to benefit, such as those who have chronic or incurable diseases. Early referral can improve both quality and quantity of life.

• Avoid antibiotics and wound cultures in ED patients with uncomplicated skin and soft tissue abscesses after successful incision and drainage and with adequate medical follow-up. Opening and draining the abscess is the appropriate treatment; antibiotics offer no benefit.

• Avoid instituting IV fluids before doing a trial of oral hydration in uncomplicated emergency department cases of mild to moderate dehydration of children. To avoid pain and potential complications, it’s preferable to give these fluids by mouth. I

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"One and done" vancomycin dosing disparaged

By M. ALEXANDER OTTO

At the 2013 ACEP Acientific Assembly

SEATTLE—One-and-done vancomycin dosing in the emergency department was associated with a high rate of ED returns for the same infection within 3 months, based on a single-center, retrospective study.

From Dec. 2008 to June 2010, 526 ED patients got vancomycin, mostly for cellulitis and abscesses, at the Barnes-Jewish Hospital ED in St. Louis, Mo., an academic ED that annually serves almost 100,000 patients; 67.9% got one dose, 26.6% got two, and 5.5% received three doses. Weight-based doses were too low in 73%, and too high in 3.4%. Less than half of the patients were sent home on an oral antibiotic; about one-third were back in the ED within 3 months for the same infection.

"It was very common just to order a dose of vancomycin and send people home, [but] none of the guidelines" from the Infectious Diseases Society of America and other groups "support the use of vancomycin in patients who have uncomplicated infections before going home" from the ED, said lead investigator Dr Kristen Mueller, a fourth-year emergency medicine resident at Barnes-Jewish. A single dose doesn’t keep inhibitory concentrations high enough for long enough to knock out infections entirely; although sensitive strains may die off, more robust and virulent ones are left to proliferate. Patients end up colonized by more resistant bacteria.

Several emergency physicians at the meeting said that they’ve noticed vancomycin dosing problems in their EDs, as well. Vancomycin dosing problems also were reported in a study published earlier this year by researchers from Christiana Care Health System in Newark Delaware (J Emerg Med. 2013;44[5]:979-984).

Vancomycin-intermediate Staphylococcus aureus was isolated from about 170 Barnes-Jewish patients in 2009. "It’s not as common as MRSA, but it’s there. What’s more concerning is that frank vancomycin resistant S. aureus is starting to establish itself in the US," and inappropriate use of vancomycin will just fuel the problem, she said.

Concerns about nephrotoxicity may be behind the low-dosing issue, but the hospital’s EHR system might also contribute to dosing inaccuracy, Dr Mueller said. At Barnes-Jewish, "our easiest order dose is 1 gram of vancomycin; it’s a one-click order in our order set. Whereas, to order a weight-appropriate dose, you actually have to calculate it out and type in the dose you want."

In response to the findings, Dr Mueller and her colleagues are adding a skin and soft tissue order set to the EHR system, with different tabs based on infection type and sub-tabs for patient disposition. Patients discharged home or to the observation unit will only have oral antibiotic options. Only inpatients will eligible for weight-based vancomycin dosing.

In an earlier study, Dr Mueller and her colleagues found that ED doses of vancomycin are frequently continued when patients are admitted, even if they’re wrong; 71% of the 2,560 inpatients in the earlier investigation were underdosed (J Emerg Med. 2013;44[5]:910-918).

Dr Mueller had no relevant disclosures.

[email protected]

Prehospital bivalirudin reduced bleeding with PCI

BY SHERRY BOSCHERT

At TCT 2013

SAN FRANCISCO – Giving bivalirudin in the ambulance to patients with ST-segment elevation MI before primary percutaneous coronary intervention significantly improved 30-day bleeding outcomes in a randomized controlled European trial in 2,218 patients, compared with giving unfractionated or low-molecular-weight heparin and optional glycoprotein IIb/IIIa inhibitors.

In Europe, anticoagulation commonly is started in the ambulance. The practice has not yet caught on in most of the United States.

Compared with the control group, the bivalirudin group had a nearly 40% decrease in a composite outcome of death or major bleeding not associated with coronary artery bypass grafting (CABG). Rates

for the primary outcome were 5% in the bivalirudin group and over 8% in the control group at 30 days,

Dr Philippe Gabriel Steg and his associates reported at the Transcatheter Cardiovascular Therapeutics annual meeting.

The rates of the main secondary outcome – a composite of death, reinfarction, or non-CABG major bleeding at 30 days – also were significantly lower in the bivalirudin group (6.7%) than in the control group (9.1%), said Dr Steg, professor of cardiology at Université Paris-Diderot and director of the coronary care unit at Hôpital Bichat, Paris.

The 30-day rate of acute stent thrombosis was nearly sixfold higher in the bivalirudin group (1.1%) than in the control group (0.2%), but that did not translate into an increased risk of infarction, which occurred in 1.7% in the bivalirudin group and 0.9% in the control group (0.9%).

The study was published online simultaneously with the presentation (N Engl J Med. October 30, 2013 [doi: 10.1056/NEJMoa1311096]).

The benefit from bivalirudin came mainly from reduced bleeding, not reduced mortality. The risk of major bleeding not associated with CABG was 2.7% in the bivalirudin group and 6.1% in the control group, a significant 57% reduction.

Rates of cardiac or noncardiac death at 30 days did not differ significantly between groups. Cardiac death occurred in 2.4% in the bivalirudin group and in 3% in the control group; noncardiac death occurred in 0.5% and 0.1%, respectively.

The EUROMAX findings were consistent across subgroups of patients, including subgroups defined by PCI access site or by the choice of P2Y12 inhibitor, Dr Steg reported at the meeting, cosponsored by the American College of Cardiology.

Dr Steg received fees from The Medicines Company, which sponsored the study and markets bivalirudin, and he reported financial associations with 16 other companies. Four of his colleagues in the study were employees of The Medicines Company, and 12 other colleagues reported financial associations with that company and/or multiple other companies. Dr Stone reported financial associations with Boston Scientific, Eli Lilly, and other companies.

[email protected]

In 2011, nearly 23,000 of 2.5 million drug-related emergency department visits were linked to a group of synthetic drugs called "bath salts," according to a report by the Substance Abuse and Mental Health Services Administration. The agency said this is the first national study to track such data.

The numbers are "worrisome, because these are relatively new drugs that we haven’t seen until the last few years," Dr. Elinore F. McCance-Katz, SAMHSA’s chief medical officer, said in an interview.

"These are drugs that are mainly abused by young people, and because of that, as physicians, we need to be attuned to the potential for misuse of these substance by younger people," Dr. McCance-Katz said. "And physicians need to be aware that we don’t have treatments that are specific to toxicities related to these drugs, so it’s going to be symptomatic treatment. And for individuals who do develop abuse or addiction to these drugs, there’s not a treatment that’s shown to be effective, so prevention is going to be important.

"Provide information to these young folks, and help keep them from starting the use of these drugs," she said.

The drugs’ adverse effects include heart and blood vessel problems, depression, suicidal thoughts, psychosis, and death.

The toxicities are similar to those of other stimulants seen in the ED, Dr. McCance-Katz said. "Treat the patients symptomatically. If they have severe hypertension, give medication to reduce blood pressure. If the person presents with severe agitation and anxiety, we might give them benzodiazepines. If that’s not helpful, and/or if they also have psychosis, we might give them an antipsychotic.

"But we need to be careful about the antipsychotic selection, because antipsychotics themselves can reduce the seizure threshold, as can happen with amphetamine abuse, so we don’t want to risk seizure. But in a patient who is severely agitated and psychotic, that may be the emergency treatment that is necessary."

Dr. McCance-Katz added that it’s important for psychiatrists to know that there are also adverse mental health symptoms, as seen with other amphetamines.

"Someone might present with toxicity from using this type of a drug with agitation, psychosis, a rapid heartbeat, possibly even chest pain, and severe anxiety, and that person would need a good bit of medical and psychiatric care," she said.

The report, based on the 2011 Drug Abuse Warning Network, or DAWN report, also showed that two-thirds (67%) of bath salt–related ED visits involved the use of another drug: 15% involved combined use of marijuana or synthetic forms of marijuana, and 52% involved the use of other drugs. Only 33% of the cases involved exposure to bath salts only.

Dr. McCance-Katz said the combined use means that these synthetic drugs could be even more dangerous to the users.

Synthetic drugs, including bath salts, were first detected in the United States in 2008 by the Drug Enforcement Administration (DEA).

Bath salts began to gain national attention in 2011, when poison centers reported a sudden jump to more than 6,000 cases of exposure to the drug, up from a mere 300 in 2010.

Since then, however, there has been a 10-fold drop in the number of calls to poison centers, in part because of increased local awareness, education, and federal actions.

In April of this year, the DEA put one of the main chemicals in bath salts in the Schedule I category, the most restrictive category created by the Controlled Substance Act. Several large national drug busts also have taken place in connection with the substance.

Bath salts come in the form of white or brown powder and contain one or more chemicals related to cathinone, an amphetamine-like stimulant. They are sold in packages that are labeled as household products, such as bath salts, or jewelry cleaner, and labeled as "legal high" or "not for human consumption." They can be taken by mouth, inhaled, or injected.

Dr. McCance-Katz stressed that patient education and prevention are key.

[email protected]

On Twitter @NaseemSMiller

In 2011, nearly 23,000 of 2.5 million drug-related emergency department visits were linked to a group of synthetic drugs called "bath salts," according to a report by the Substance Abuse and Mental Health Services Administration. The agency said this is the first national study to track such data.

The numbers are "worrisome, because these are relatively new drugs that we haven’t seen until the last few years," Dr. Elinore F. McCance-Katz, SAMHSA’s chief medical officer, said in an interview.

"These are drugs that are mainly abused by young people, and because of that, as physicians, we need to be attuned to the potential for misuse of these substance by younger people," Dr. McCance-Katz said. "And physicians need to be aware that we don’t have treatments that are specific to toxicities related to these drugs, so it’s going to be symptomatic treatment. And for individuals who do develop abuse or addiction to these drugs, there’s not a treatment that’s shown to be effective, so prevention is going to be important.

"Provide information to these young folks, and help keep them from starting the use of these drugs," she said.

The drugs’ adverse effects include heart and blood vessel problems, depression, suicidal thoughts, psychosis, and death.

The toxicities are similar to those of other stimulants seen in the ED, Dr. McCance-Katz said. "Treat the patients symptomatically. If they have severe hypertension, give medication to reduce blood pressure. If the person presents with severe agitation and anxiety, we might give them benzodiazepines. If that’s not helpful, and/or if they also have psychosis, we might give them an antipsychotic.

"But we need to be careful about the antipsychotic selection, because antipsychotics themselves can reduce the seizure threshold, as can happen with amphetamine abuse, so we don’t want to risk seizure. But in a patient who is severely agitated and psychotic, that may be the emergency treatment that is necessary."

Dr. McCance-Katz added that it’s important for psychiatrists to know that there are also adverse mental health symptoms, as seen with other amphetamines.

"Someone might present with toxicity from using this type of a drug with agitation, psychosis, a rapid heartbeat, possibly even chest pain, and severe anxiety, and that person would need a good bit of medical and psychiatric care," she said.

The report, based on the 2011 Drug Abuse Warning Network, or DAWN report, also showed that two-thirds (67%) of bath salt–related ED visits involved the use of another drug: 15% involved combined use of marijuana or synthetic forms of marijuana, and 52% involved the use of other drugs. Only 33% of the cases involved exposure to bath salts only.

Dr. McCance-Katz said the combined use means that these synthetic drugs could be even more dangerous to the users.

Synthetic drugs, including bath salts, were first detected in the United States in 2008 by the Drug Enforcement Administration (DEA).

Bath salts began to gain national attention in 2011, when poison centers reported a sudden jump to more than 6,000 cases of exposure to the drug, up from a mere 300 in 2010.

Since then, however, there has been a 10-fold drop in the number of calls to poison centers, in part because of increased local awareness, education, and federal actions.

In April of this year, the DEA put one of the main chemicals in bath salts in the Schedule I category, the most restrictive category created by the Controlled Substance Act. Several large national drug busts also have taken place in connection with the substance.

Bath salts come in the form of white or brown powder and contain one or more chemicals related to cathinone, an amphetamine-like stimulant. They are sold in packages that are labeled as household products, such as bath salts, or jewelry cleaner, and labeled as "legal high" or "not for human consumption." They can be taken by mouth, inhaled, or injected.

Dr. McCance-Katz stressed that patient education and prevention are key.

[email protected]

On Twitter @NaseemSMiller

In 2011, nearly 23,000 of 2.5 million drug-related emergency department visits were linked to a group of synthetic drugs called "bath salts," according to a report by the Substance Abuse and Mental Health Services Administration. The agency said this is the first national study to track such data.

The numbers are "worrisome, because these are relatively new drugs that we haven’t seen until the last few years," Dr. Elinore F. McCance-Katz, SAMHSA’s chief medical officer, said in an interview.

"These are drugs that are mainly abused by young people, and because of that, as physicians, we need to be attuned to the potential for misuse of these substance by younger people," Dr. McCance-Katz said. "And physicians need to be aware that we don’t have treatments that are specific to toxicities related to these drugs, so it’s going to be symptomatic treatment. And for individuals who do develop abuse or addiction to these drugs, there’s not a treatment that’s shown to be effective, so prevention is going to be important.

"Provide information to these young folks, and help keep them from starting the use of these drugs," she said.

The drugs’ adverse effects include heart and blood vessel problems, depression, suicidal thoughts, psychosis, and death.

The toxicities are similar to those of other stimulants seen in the ED, Dr. McCance-Katz said. "Treat the patients symptomatically. If they have severe hypertension, give medication to reduce blood pressure. If the person presents with severe agitation and anxiety, we might give them benzodiazepines. If that’s not helpful, and/or if they also have psychosis, we might give them an antipsychotic.

"But we need to be careful about the antipsychotic selection, because antipsychotics themselves can reduce the seizure threshold, as can happen with amphetamine abuse, so we don’t want to risk seizure. But in a patient who is severely agitated and psychotic, that may be the emergency treatment that is necessary."

Dr. McCance-Katz added that it’s important for psychiatrists to know that there are also adverse mental health symptoms, as seen with other amphetamines.

"Someone might present with toxicity from using this type of a drug with agitation, psychosis, a rapid heartbeat, possibly even chest pain, and severe anxiety, and that person would need a good bit of medical and psychiatric care," she said.

The report, based on the 2011 Drug Abuse Warning Network, or DAWN report, also showed that two-thirds (67%) of bath salt–related ED visits involved the use of another drug: 15% involved combined use of marijuana or synthetic forms of marijuana, and 52% involved the use of other drugs. Only 33% of the cases involved exposure to bath salts only.

Dr. McCance-Katz said the combined use means that these synthetic drugs could be even more dangerous to the users.

Synthetic drugs, including bath salts, were first detected in the United States in 2008 by the Drug Enforcement Administration (DEA).

Bath salts began to gain national attention in 2011, when poison centers reported a sudden jump to more than 6,000 cases of exposure to the drug, up from a mere 300 in 2010.

Since then, however, there has been a 10-fold drop in the number of calls to poison centers, in part because of increased local awareness, education, and federal actions.

In April of this year, the DEA put one of the main chemicals in bath salts in the Schedule I category, the most restrictive category created by the Controlled Substance Act. Several large national drug busts also have taken place in connection with the substance.

Bath salts come in the form of white or brown powder and contain one or more chemicals related to cathinone, an amphetamine-like stimulant. They are sold in packages that are labeled as household products, such as bath salts, or jewelry cleaner, and labeled as "legal high" or "not for human consumption." They can be taken by mouth, inhaled, or injected.

Dr. McCance-Katz stressed that patient education and prevention are key.

[email protected]

On Twitter @NaseemSMiller

NEW YORK – One expert has characterized para-tertiary-butylphenol formaldehyde resin as a suitable candidate for the next pediatric contact allergen of the year, based on a growing number of case reports.

Para-tertiary-butylphenol (PTPB) formaldehyde resin is found in shin guards, push-up bras, and numerous other products used by children and adolescents.

Published case reports of contact allergies caused by PTPB formaldehyde resin date back several years, but use of this resin as an adhesive in a broad range of products – particularly leather goods, such as shoes, purses, and watch straps – appears to be increasing, according to Dr. Nanette B. Silverberg.

Dr. Silverberg presented a review of new trends in pediatric contact dermatitis at the American Academy of Dermatology summer meeting.

The causes of contact allergies in children evolve constantly because of the introduction of new products, and this should influence the order in which patch testing of specific allergens is performed, said Dr. Silverberg, a dermatologist at St. Luke’s–Roosevelt Hospital Center, New York.

In her update, she cited several recently designated "allergens of the year" from the American Contact Dermatitis Society (ACDS) and added some of her own.

Dr. Silverberg also emphasized tricks she has devised to increase the likelihood of a successful patch test, not least of which is enlisting parent cooperation. "It is important to convince parents that they are guilt free," she advised. In parents who begin to blame themselves for exposures, a sense of denial can interfere with efforts to cooperate with patch testing. To avoid this problem, she suggested a proactive effort to establish they are fault free. "Blame it on marketing if you must."

In light of the potential for lack of compliance, patch testing should be made as effortless as possible. For one approach, Dr. Silverberg suggested timing testing so it is not an excuse to miss school. Another tip was to use "heaps of tape and more tape" to keep the patch tests in place, and then provide patients with a roll of tape when they leave the office. She also recommended thinking in advance of strategies to reduce the risk of patch tests being inadvertently or intentionally removed by children, such as gauze wrap around the abdomen.

"The number one way to make patch tests work in young children is to keep your patch test panel streamlined and focused," Dr. Silverberg said. Particularly in young children, she suggested just one or two panels rather than three or four. While bribes such as lollipops and stickers "should be used judiciously," Dr. Silverberg said it is very helpful to outline each patch with highlighters that glow under Wood’s lamp to make results easier to assess.

Contact allergies are extremely common, and it is often possible to control the contact dermatitis before or even without confirming the allergen. For example, dialkyl thiourea, the ACDS allergen of the year in 2009, is another source of contact dermatitis to shin guards as well as other products, but reactions to this or PTPB formaldehyde resin can often be prevented simply by putting a layer of clothing in front of the skin. By the same principle, contact dermatitis from car seats is often caused by dimethyl fumerate, the ACDS allergen of the year in 2011, but can be prevented simply by laying fabric or creating some other barrier to prevent contact.

Methylisothiazolinone, a preservative and antifungal agent often found in moist towels and wipes, was recognized as the most recent (2013) ACDS allergen of the year. Dr. Silverberg noted that these wipes have surprisingly broad applications. While dermatitis on the hands and buttocks would be expected, she cautioned that patients use these to clean other skin surfaces, so a broad index of suspicion is needed.

The most common contact allergens, such as nickel, cobalt, and neomycin, remain relatively unchanged from year to year, but many of these products are used less frequently in children’s products in appreciation of the risks that they pose. The challenge is keeping abreast of evolving trends. While patch testing is an effective tool for identifying the source of a contact dermatitis to alert parents and patients of the products they should avoid, she said that technique is critical to patch test success.

Dr. Silverberg said she had no financial disclosures.

NEW YORK – One expert has characterized para-tertiary-butylphenol formaldehyde resin as a suitable candidate for the next pediatric contact allergen of the year, based on a growing number of case reports.

Para-tertiary-butylphenol (PTPB) formaldehyde resin is found in shin guards, push-up bras, and numerous other products used by children and adolescents.

Published case reports of contact allergies caused by PTPB formaldehyde resin date back several years, but use of this resin as an adhesive in a broad range of products – particularly leather goods, such as shoes, purses, and watch straps – appears to be increasing, according to Dr. Nanette B. Silverberg.

Dr. Silverberg presented a review of new trends in pediatric contact dermatitis at the American Academy of Dermatology summer meeting.

The causes of contact allergies in children evolve constantly because of the introduction of new products, and this should influence the order in which patch testing of specific allergens is performed, said Dr. Silverberg, a dermatologist at St. Luke’s–Roosevelt Hospital Center, New York.

In her update, she cited several recently designated "allergens of the year" from the American Contact Dermatitis Society (ACDS) and added some of her own.

Dr. Silverberg also emphasized tricks she has devised to increase the likelihood of a successful patch test, not least of which is enlisting parent cooperation. "It is important to convince parents that they are guilt free," she advised. In parents who begin to blame themselves for exposures, a sense of denial can interfere with efforts to cooperate with patch testing. To avoid this problem, she suggested a proactive effort to establish they are fault free. "Blame it on marketing if you must."

In light of the potential for lack of compliance, patch testing should be made as effortless as possible. For one approach, Dr. Silverberg suggested timing testing so it is not an excuse to miss school. Another tip was to use "heaps of tape and more tape" to keep the patch tests in place, and then provide patients with a roll of tape when they leave the office. She also recommended thinking in advance of strategies to reduce the risk of patch tests being inadvertently or intentionally removed by children, such as gauze wrap around the abdomen.

"The number one way to make patch tests work in young children is to keep your patch test panel streamlined and focused," Dr. Silverberg said. Particularly in young children, she suggested just one or two panels rather than three or four. While bribes such as lollipops and stickers "should be used judiciously," Dr. Silverberg said it is very helpful to outline each patch with highlighters that glow under Wood’s lamp to make results easier to assess.

Contact allergies are extremely common, and it is often possible to control the contact dermatitis before or even without confirming the allergen. For example, dialkyl thiourea, the ACDS allergen of the year in 2009, is another source of contact dermatitis to shin guards as well as other products, but reactions to this or PTPB formaldehyde resin can often be prevented simply by putting a layer of clothing in front of the skin. By the same principle, contact dermatitis from car seats is often caused by dimethyl fumerate, the ACDS allergen of the year in 2011, but can be prevented simply by laying fabric or creating some other barrier to prevent contact.

Methylisothiazolinone, a preservative and antifungal agent often found in moist towels and wipes, was recognized as the most recent (2013) ACDS allergen of the year. Dr. Silverberg noted that these wipes have surprisingly broad applications. While dermatitis on the hands and buttocks would be expected, she cautioned that patients use these to clean other skin surfaces, so a broad index of suspicion is needed.

The most common contact allergens, such as nickel, cobalt, and neomycin, remain relatively unchanged from year to year, but many of these products are used less frequently in children’s products in appreciation of the risks that they pose. The challenge is keeping abreast of evolving trends. While patch testing is an effective tool for identifying the source of a contact dermatitis to alert parents and patients of the products they should avoid, she said that technique is critical to patch test success.

Dr. Silverberg said she had no financial disclosures.

NEW YORK – One expert has characterized para-tertiary-butylphenol formaldehyde resin as a suitable candidate for the next pediatric contact allergen of the year, based on a growing number of case reports.

Para-tertiary-butylphenol (PTPB) formaldehyde resin is found in shin guards, push-up bras, and numerous other products used by children and adolescents.

Published case reports of contact allergies caused by PTPB formaldehyde resin date back several years, but use of this resin as an adhesive in a broad range of products – particularly leather goods, such as shoes, purses, and watch straps – appears to be increasing, according to Dr. Nanette B. Silverberg.

Dr. Silverberg presented a review of new trends in pediatric contact dermatitis at the American Academy of Dermatology summer meeting.

The causes of contact allergies in children evolve constantly because of the introduction of new products, and this should influence the order in which patch testing of specific allergens is performed, said Dr. Silverberg, a dermatologist at St. Luke’s–Roosevelt Hospital Center, New York.

In her update, she cited several recently designated "allergens of the year" from the American Contact Dermatitis Society (ACDS) and added some of her own.

Dr. Silverberg also emphasized tricks she has devised to increase the likelihood of a successful patch test, not least of which is enlisting parent cooperation. "It is important to convince parents that they are guilt free," she advised. In parents who begin to blame themselves for exposures, a sense of denial can interfere with efforts to cooperate with patch testing. To avoid this problem, she suggested a proactive effort to establish they are fault free. "Blame it on marketing if you must."

In light of the potential for lack of compliance, patch testing should be made as effortless as possible. For one approach, Dr. Silverberg suggested timing testing so it is not an excuse to miss school. Another tip was to use "heaps of tape and more tape" to keep the patch tests in place, and then provide patients with a roll of tape when they leave the office. She also recommended thinking in advance of strategies to reduce the risk of patch tests being inadvertently or intentionally removed by children, such as gauze wrap around the abdomen.

"The number one way to make patch tests work in young children is to keep your patch test panel streamlined and focused," Dr. Silverberg said. Particularly in young children, she suggested just one or two panels rather than three or four. While bribes such as lollipops and stickers "should be used judiciously," Dr. Silverberg said it is very helpful to outline each patch with highlighters that glow under Wood’s lamp to make results easier to assess.

Contact allergies are extremely common, and it is often possible to control the contact dermatitis before or even without confirming the allergen. For example, dialkyl thiourea, the ACDS allergen of the year in 2009, is another source of contact dermatitis to shin guards as well as other products, but reactions to this or PTPB formaldehyde resin can often be prevented simply by putting a layer of clothing in front of the skin. By the same principle, contact dermatitis from car seats is often caused by dimethyl fumerate, the ACDS allergen of the year in 2011, but can be prevented simply by laying fabric or creating some other barrier to prevent contact.

Methylisothiazolinone, a preservative and antifungal agent often found in moist towels and wipes, was recognized as the most recent (2013) ACDS allergen of the year. Dr. Silverberg noted that these wipes have surprisingly broad applications. While dermatitis on the hands and buttocks would be expected, she cautioned that patients use these to clean other skin surfaces, so a broad index of suspicion is needed.

The most common contact allergens, such as nickel, cobalt, and neomycin, remain relatively unchanged from year to year, but many of these products are used less frequently in children’s products in appreciation of the risks that they pose. The challenge is keeping abreast of evolving trends. While patch testing is an effective tool for identifying the source of a contact dermatitis to alert parents and patients of the products they should avoid, she said that technique is critical to patch test success.

Dr. Silverberg said she had no financial disclosures.

Nonmedical opioid use for reasons other than pain relief is common among middle-aged adults in residential addictions treatment.

Moreover, this type of opioid use was associated with more extensive use of other controlled substances and select street drugs, and poorer mental health, than was opioid use motivated by pain relief alone, a study shows (Addict. Behav. 2013;38:1776-81).

"Collectively, these data provide further evidence that individuals who use opioids nonmedically for reasons other than pain relief constitute a group that is particularly high risk for poor health outcomes," asserted Amy S. B. Bohnert, Ph.D., of the department of psychiatry, University of Michigan, Ann Arbor.

Two prior studies showed that nonmedical opioid use for reasons other than pain relief is more common than is opioid use for pain relief only, but the studies were among adolescents and relatively high functioning young adults, such as college students.

The current study involved older adults with more established patterns of substance abuse, reaching an average of 10.8 years of regular alcohol use to intoxication, 8.1 years for cocaine, and 6.2 years for heroin.

The average age of the cohort was 35.6 years, placing them into an age group (35-54 years) at particularly high risk of opioid overdose (NCHS Data Brief 2009;22:1-8).

"The present findings highlight the need to understand gender differences in pain and opioid response and how these may result in reasons for opioid use..."

Dr. Bohnert and her associates surveyed 351 individuals in a large residential addictions treatment center. Of these 351, 24% were female. Alcohol was the primary substance for seeking treatment in 30.2%, followed by heroin (19.4%), cocaine (16%), marijuana (9.7%), other opiates (4%), and other/missing (21%).

Primary analyses were restricted to 238 patients (68%), who reported nonmedical use of prescription opioids in the previous month, based on responses to the 17-item Current Opioid Misuse Measure (COMM).

Overall, 66% of respondents reported using nonmedical prescription opioids for reasons other than pain relief, such as to get high or relax, compared with 34% who were motivated to use opioids only for pain relief, Dr. Bohnert reported.

Respondents who used opioids for non–pain relief reasons were significantly more likely to be heavy opioid users (43% vs. 11%), defined as a response of "very often" on any of six core COMM items.

Patients who used opioids for reasons other than pain were significantly more likely to be female (33.3% vs. 16.5%), and white (77% vs. 59.3%), and to have a history of overdose (40.7% vs. 21.3%), she said. The association remained significant for all three variables after adjustment. Notably, prior research suggests women might have a more robust response to analgesics.

"The present findings highlight the need to understand gender differences in pain and opioid response and how these may result in reasons for opioid use," Dr. Bohnert wrote.

In adjusted analyses, patients who turned to prescription opioids for non–pain relief reasons had significantly increased odds of having used barbiturates (odds ratio 6.44), other sedatives (OR 5.80), and heroin (OR 4.08) in the past 30 days, although cocaine and cannabis use were similar.

Current suicidal ideation also was similar between groups, although overall mental health and depressive symptoms were more common in the non–pain relief group, suggesting they had poorer mental health.

Patients using opioids for non–pain relief reasons and those motivated by pain relief alone had similar pain severity scores (3.0 vs. 2.9) on the West Haven–Yale Multidimensional Pain Inventory, Dr. Bohnert observed.

"Thus, assessment of pain level or pain conditions will not necessarily distinguish between individuals whose opioid use is strictly related to pain care and individuals who use at least some of the time for other reasons," she said.

The authors concluded that the high rate of nonmedical opioid use observed in the sample "may signal an emerging and potentially critical issue in addiction treatment programs."

Dr. Bohnert and her colleagues called for future research to explore how diversion behaviors relate to motives for opioid use, and to examine differences in the success of addictions and pain management treatments between those using nonmedical opioids for reasons other than pain and those using for pain relief only.

Dr. Bohnert and her coauthors reported having no financial disclosures. Grants from the National Institutes of Health and Department of Veterans Affairs, in addition to funding from the University of Michigan, were used in the development of the investigators’ article.

[email protected]

Nonmedical opioid use for reasons other than pain relief is common among middle-aged adults in residential addictions treatment.

Moreover, this type of opioid use was associated with more extensive use of other controlled substances and select street drugs, and poorer mental health, than was opioid use motivated by pain relief alone, a study shows (Addict. Behav. 2013;38:1776-81).

"Collectively, these data provide further evidence that individuals who use opioids nonmedically for reasons other than pain relief constitute a group that is particularly high risk for poor health outcomes," asserted Amy S. B. Bohnert, Ph.D., of the department of psychiatry, University of Michigan, Ann Arbor.

Two prior studies showed that nonmedical opioid use for reasons other than pain relief is more common than is opioid use for pain relief only, but the studies were among adolescents and relatively high functioning young adults, such as college students.

The current study involved older adults with more established patterns of substance abuse, reaching an average of 10.8 years of regular alcohol use to intoxication, 8.1 years for cocaine, and 6.2 years for heroin.

The average age of the cohort was 35.6 years, placing them into an age group (35-54 years) at particularly high risk of opioid overdose (NCHS Data Brief 2009;22:1-8).

"The present findings highlight the need to understand gender differences in pain and opioid response and how these may result in reasons for opioid use..."

Dr. Bohnert and her associates surveyed 351 individuals in a large residential addictions treatment center. Of these 351, 24% were female. Alcohol was the primary substance for seeking treatment in 30.2%, followed by heroin (19.4%), cocaine (16%), marijuana (9.7%), other opiates (4%), and other/missing (21%).

Primary analyses were restricted to 238 patients (68%), who reported nonmedical use of prescription opioids in the previous month, based on responses to the 17-item Current Opioid Misuse Measure (COMM).

Overall, 66% of respondents reported using nonmedical prescription opioids for reasons other than pain relief, such as to get high or relax, compared with 34% who were motivated to use opioids only for pain relief, Dr. Bohnert reported.

Respondents who used opioids for non–pain relief reasons were significantly more likely to be heavy opioid users (43% vs. 11%), defined as a response of "very often" on any of six core COMM items.

Patients who used opioids for reasons other than pain were significantly more likely to be female (33.3% vs. 16.5%), and white (77% vs. 59.3%), and to have a history of overdose (40.7% vs. 21.3%), she said. The association remained significant for all three variables after adjustment. Notably, prior research suggests women might have a more robust response to analgesics.

"The present findings highlight the need to understand gender differences in pain and opioid response and how these may result in reasons for opioid use," Dr. Bohnert wrote.

In adjusted analyses, patients who turned to prescription opioids for non–pain relief reasons had significantly increased odds of having used barbiturates (odds ratio 6.44), other sedatives (OR 5.80), and heroin (OR 4.08) in the past 30 days, although cocaine and cannabis use were similar.

Current suicidal ideation also was similar between groups, although overall mental health and depressive symptoms were more common in the non–pain relief group, suggesting they had poorer mental health.

Patients using opioids for non–pain relief reasons and those motivated by pain relief alone had similar pain severity scores (3.0 vs. 2.9) on the West Haven–Yale Multidimensional Pain Inventory, Dr. Bohnert observed.

"Thus, assessment of pain level or pain conditions will not necessarily distinguish between individuals whose opioid use is strictly related to pain care and individuals who use at least some of the time for other reasons," she said.

The authors concluded that the high rate of nonmedical opioid use observed in the sample "may signal an emerging and potentially critical issue in addiction treatment programs."

Dr. Bohnert and her colleagues called for future research to explore how diversion behaviors relate to motives for opioid use, and to examine differences in the success of addictions and pain management treatments between those using nonmedical opioids for reasons other than pain and those using for pain relief only.

Dr. Bohnert and her coauthors reported having no financial disclosures. Grants from the National Institutes of Health and Department of Veterans Affairs, in addition to funding from the University of Michigan, were used in the development of the investigators’ article.

[email protected]

Nonmedical opioid use for reasons other than pain relief is common among middle-aged adults in residential addictions treatment.

Moreover, this type of opioid use was associated with more extensive use of other controlled substances and select street drugs, and poorer mental health, than was opioid use motivated by pain relief alone, a study shows (Addict. Behav. 2013;38:1776-81).

"Collectively, these data provide further evidence that individuals who use opioids nonmedically for reasons other than pain relief constitute a group that is particularly high risk for poor health outcomes," asserted Amy S. B. Bohnert, Ph.D., of the department of psychiatry, University of Michigan, Ann Arbor.

Two prior studies showed that nonmedical opioid use for reasons other than pain relief is more common than is opioid use for pain relief only, but the studies were among adolescents and relatively high functioning young adults, such as college students.

The current study involved older adults with more established patterns of substance abuse, reaching an average of 10.8 years of regular alcohol use to intoxication, 8.1 years for cocaine, and 6.2 years for heroin.

The average age of the cohort was 35.6 years, placing them into an age group (35-54 years) at particularly high risk of opioid overdose (NCHS Data Brief 2009;22:1-8).

"The present findings highlight the need to understand gender differences in pain and opioid response and how these may result in reasons for opioid use..."

Dr. Bohnert and her associates surveyed 351 individuals in a large residential addictions treatment center. Of these 351, 24% were female. Alcohol was the primary substance for seeking treatment in 30.2%, followed by heroin (19.4%), cocaine (16%), marijuana (9.7%), other opiates (4%), and other/missing (21%).

Primary analyses were restricted to 238 patients (68%), who reported nonmedical use of prescription opioids in the previous month, based on responses to the 17-item Current Opioid Misuse Measure (COMM).

Overall, 66% of respondents reported using nonmedical prescription opioids for reasons other than pain relief, such as to get high or relax, compared with 34% who were motivated to use opioids only for pain relief, Dr. Bohnert reported.

Respondents who used opioids for non–pain relief reasons were significantly more likely to be heavy opioid users (43% vs. 11%), defined as a response of "very often" on any of six core COMM items.

Patients who used opioids for reasons other than pain were significantly more likely to be female (33.3% vs. 16.5%), and white (77% vs. 59.3%), and to have a history of overdose (40.7% vs. 21.3%), she said. The association remained significant for all three variables after adjustment. Notably, prior research suggests women might have a more robust response to analgesics.

"The present findings highlight the need to understand gender differences in pain and opioid response and how these may result in reasons for opioid use," Dr. Bohnert wrote.

In adjusted analyses, patients who turned to prescription opioids for non–pain relief reasons had significantly increased odds of having used barbiturates (odds ratio 6.44), other sedatives (OR 5.80), and heroin (OR 4.08) in the past 30 days, although cocaine and cannabis use were similar.

Current suicidal ideation also was similar between groups, although overall mental health and depressive symptoms were more common in the non–pain relief group, suggesting they had poorer mental health.

Patients using opioids for non–pain relief reasons and those motivated by pain relief alone had similar pain severity scores (3.0 vs. 2.9) on the West Haven–Yale Multidimensional Pain Inventory, Dr. Bohnert observed.

"Thus, assessment of pain level or pain conditions will not necessarily distinguish between individuals whose opioid use is strictly related to pain care and individuals who use at least some of the time for other reasons," she said.

The authors concluded that the high rate of nonmedical opioid use observed in the sample "may signal an emerging and potentially critical issue in addiction treatment programs."

Dr. Bohnert and her colleagues called for future research to explore how diversion behaviors relate to motives for opioid use, and to examine differences in the success of addictions and pain management treatments between those using nonmedical opioids for reasons other than pain and those using for pain relief only.

Dr. Bohnert and her coauthors reported having no financial disclosures. Grants from the National Institutes of Health and Department of Veterans Affairs, in addition to funding from the University of Michigan, were used in the development of the investigators’ article.

[email protected]

Ascorbic acid may protect against contrast-induced-acute kidney injury in patients undergoing coronary angiography, a meta-analysis of nine randomized controlled trials has shown.

The overall incidence of contrast-induced acute kidney injury (CI-AKI) among 740 patients who received ascorbic acid and who were included in the final analysis was 9.6%, compared with 16.8% in 796 patients who received placebo or an alternative pharmacologic treatment, Dr. Umar Sadat of Cambridge (England) University Hospitals NHS Foundation Trust, and colleagues reported.

"In the pooled analysis using random effects model, patients receiving ascorbic acid had 33% less risk of CI-AKI compared to the control group (risk ratio, 0.672)," a statistically significant difference, the investigators wrote.

The findings were published online Aug. 28 in the Journal of the American College of Cardiology.

The investigators systematically reviewed Medline, Embase, and Cochrane central databases for studies published from inception to May 2013 on the incidence of CI-AKI in patients undergoing coronary angiography. Studies that were included in the meta-analysis had at least one arm that involved treatment with ascorbic acid alone or in combination with saline hydration. Ultimately, nine studies involving a total of 1,536 patients with baseline renal impairment were included (J. Am. Coll. Cardiol. 2013 Aug. 28).

The findings, which provide "robust evidence that ascorbic acid reduces the risk of CI-AKI, albeit by a small magnitude," suggest that ascorbic acid has nephroprotective qualities and could form a part of effective prophylactic pharmacologic regimens to protect patients undergoing coronary angiography against CI-AKI.

It makes sense that ascorbic acid – a form of vitamin C – could provide nephroprotection, because strong evidence suggests it acts as a potent antioxidant by scavenging physiologically relevant reactive oxygen species (ROS), they explained, noting that ROS-induced oxidative stress and renal vasoconstriction have been implicated in the etiology of CI-AKI.

The findings are important, because the incidence of CI-AKI is rising in tandem with the increasing number of contrast media–enhanced radiologic procedures and with a rise in the octogenarian population with comorbidities such as hypertension, diabetes, and renovascular disease that predispose patients to renal impairment, the investigators said.

However, further investigation regarding the optimal dosage and route of administration of ascorbic acid in order to assess its full potential as a nephroprotective agent is warranted, they concluded.

Ascorbic acid may protect against contrast-induced-acute kidney injury in patients undergoing coronary angiography, a meta-analysis of nine randomized controlled trials has shown.

The overall incidence of contrast-induced acute kidney injury (CI-AKI) among 740 patients who received ascorbic acid and who were included in the final analysis was 9.6%, compared with 16.8% in 796 patients who received placebo or an alternative pharmacologic treatment, Dr. Umar Sadat of Cambridge (England) University Hospitals NHS Foundation Trust, and colleagues reported.

"In the pooled analysis using random effects model, patients receiving ascorbic acid had 33% less risk of CI-AKI compared to the control group (risk ratio, 0.672)," a statistically significant difference, the investigators wrote.

The findings were published online Aug. 28 in the Journal of the American College of Cardiology.

The investigators systematically reviewed Medline, Embase, and Cochrane central databases for studies published from inception to May 2013 on the incidence of CI-AKI in patients undergoing coronary angiography. Studies that were included in the meta-analysis had at least one arm that involved treatment with ascorbic acid alone or in combination with saline hydration. Ultimately, nine studies involving a total of 1,536 patients with baseline renal impairment were included (J. Am. Coll. Cardiol. 2013 Aug. 28).

The findings, which provide "robust evidence that ascorbic acid reduces the risk of CI-AKI, albeit by a small magnitude," suggest that ascorbic acid has nephroprotective qualities and could form a part of effective prophylactic pharmacologic regimens to protect patients undergoing coronary angiography against CI-AKI.

It makes sense that ascorbic acid – a form of vitamin C – could provide nephroprotection, because strong evidence suggests it acts as a potent antioxidant by scavenging physiologically relevant reactive oxygen species (ROS), they explained, noting that ROS-induced oxidative stress and renal vasoconstriction have been implicated in the etiology of CI-AKI.

The findings are important, because the incidence of CI-AKI is rising in tandem with the increasing number of contrast media–enhanced radiologic procedures and with a rise in the octogenarian population with comorbidities such as hypertension, diabetes, and renovascular disease that predispose patients to renal impairment, the investigators said.

However, further investigation regarding the optimal dosage and route of administration of ascorbic acid in order to assess its full potential as a nephroprotective agent is warranted, they concluded.

Ascorbic acid may protect against contrast-induced-acute kidney injury in patients undergoing coronary angiography, a meta-analysis of nine randomized controlled trials has shown.

The overall incidence of contrast-induced acute kidney injury (CI-AKI) among 740 patients who received ascorbic acid and who were included in the final analysis was 9.6%, compared with 16.8% in 796 patients who received placebo or an alternative pharmacologic treatment, Dr. Umar Sadat of Cambridge (England) University Hospitals NHS Foundation Trust, and colleagues reported.

"In the pooled analysis using random effects model, patients receiving ascorbic acid had 33% less risk of CI-AKI compared to the control group (risk ratio, 0.672)," a statistically significant difference, the investigators wrote.

The findings were published online Aug. 28 in the Journal of the American College of Cardiology.

The investigators systematically reviewed Medline, Embase, and Cochrane central databases for studies published from inception to May 2013 on the incidence of CI-AKI in patients undergoing coronary angiography. Studies that were included in the meta-analysis had at least one arm that involved treatment with ascorbic acid alone or in combination with saline hydration. Ultimately, nine studies involving a total of 1,536 patients with baseline renal impairment were included (J. Am. Coll. Cardiol. 2013 Aug. 28).

The findings, which provide "robust evidence that ascorbic acid reduces the risk of CI-AKI, albeit by a small magnitude," suggest that ascorbic acid has nephroprotective qualities and could form a part of effective prophylactic pharmacologic regimens to protect patients undergoing coronary angiography against CI-AKI.

It makes sense that ascorbic acid – a form of vitamin C – could provide nephroprotection, because strong evidence suggests it acts as a potent antioxidant by scavenging physiologically relevant reactive oxygen species (ROS), they explained, noting that ROS-induced oxidative stress and renal vasoconstriction have been implicated in the etiology of CI-AKI.

The findings are important, because the incidence of CI-AKI is rising in tandem with the increasing number of contrast media–enhanced radiologic procedures and with a rise in the octogenarian population with comorbidities such as hypertension, diabetes, and renovascular disease that predispose patients to renal impairment, the investigators said.

However, further investigation regarding the optimal dosage and route of administration of ascorbic acid in order to assess its full potential as a nephroprotective agent is warranted, they concluded.

VAIL, COLO. – The differential diagnosis of pediatric infectious disease emergencies marked by fever and rash can quickly be narrowed by paying close attention to the type of rash.

Infectious diseases featuring fever and rash that require emergency diagnosis and treatment include fever with rashes that are purpuric, petechial, or erythrodermic, Dr. Marsha S. Anderson said at a conference on pediatric infectious diseases sponsored by the Children’s Hospital Colorado.

Fever with purpura

Heading the list of diagnostic possibilities here is meningococcemia, which she called "every pediatrician’s nightmare" because of a case-fatality rate of 10%-20% even with appropriate treatment.

Courtesy Dr. Robert A. Silverman

Complicating the situation is the fact that in a minority of cases the rash is petechial rather than purpuric.

"This is a disease that deserves your respect. Just remember: With fever and purpura, or fever and petechiae, meningococcemia needs to be at the top of your differential," stressed Dr. Anderson, a pediatric infectious diseases specialist at the University of Colorado.

The attack rate is highest in infants and young children because they haven’t yet experienced the transient nasopharyngeal colonization by Neisseria species that permits formation of protective strain-specific antibodies, she explained.

Empiric therapy until the diagnostic lab work and drug susceptibilities become available is vancomycin plus ceftriaxone. This combination also covers the other serious infectious causes of pediatric fever and purpura: Haemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus aureus.

Once Neisseria meningitidis has been isolated, the antibiotic therapy can be narrowed to penicillin, cefotaxime, or ceftriaxone. The recommended treatment duration is 7 days for uncomplicated meningococcemia or meningococcal meningitis.

S. pneumoniae causes fever and purpura fulminans mainly in children who are immunocompromised.

Fever with petechiae

"Rocky Mountain spotted fever is another diagnosis you really don’t want to miss. You want to make this diagnosis and institute therapy promptly. Many studies have shown decreased mortality if doxycycline is initiated in the first 5 days of illness," Dr. Anderson said.

That can be a challenge. The distinctive petechial rash, which begins on the hands, wrists, feet, and ankles, and then moves centrally, typically doesn’t show up until day 5 or 6. In one study of 92 patients admitted with an ultimate diagnosis of Rocky Mountain spotted fever, the rash on admission was maculopapular rather than petechial in about one-third of cases (J. Pediatr. 2007;150:180-4).

Fever, myalgias, and headache are common at the onset of the illness, which is typically 2-14 days after a tick bite involving transmission of Rickettsia rickettsii. The diagnosis must be made clinically as there is no rapid testing commercially available. Demonstration of a fourfold antibody titer rise between acute and convalescent serology can confirm the diagnosis. Only about one-half of confirmed cases feature patient recall of a tick bite, so absence of such a history shouldn’t allay suspicion that this disease is present.

Doxycycline is the first-line agent used for treatment of Rocky Mountain spotted fever in children of all ages. The usual length of doxycycline therapy is 7-14 days, or for at least several days after the patient is afebrile and clinically improved. In a patient with a life-threatening allergy to doxycycline, chloramphenicol is an alternative. Availability of chloramphenicol, especially in the oral formulation, may be limited in the United States.

Other serious infections involving fever and petechiae include meningococcemia, group A streptococcal infection, rat bite fever, ehrlichiosis, and anaplasmosis. Unlike Rocky Mountain spotted fever, where a petechial or maculopapular rash occurs in 90% of cases, only about 10% of patients with ehrlichiosis or anaplasmosis develop a rash.

Rat bite fever is an acute febrile illness caused by Streptobacillus moniliformis, which colonizes the nasopharynx of a substantial percentage of domestic and wild rats. Children can develop the illness by kissing their pet rat or letting it eat food from their mouth.

Most cases of rat bite fever resolve spontaneously within 2 weeks; however, the case-fatality rate is 13% without treatment, which is penicillin or doxycycline.

Fever with erythroderma, a sunburnlike rash

The differential diagnosis here consists of toxic shock syndrome, staphylococcal scalded skin, and Kawasaki disease. Drug reactions, including Stevens-Johnson syndrome, are an important noninfectious cause. Sulfa drugs, anticonvulsants, and NSAIDs are the drugs most commonly associated with Stevens-Johnson syndrome.

Suspect toxic shock syndrome when fever and erythroderma are accompanied by hypotension, red eyes and lips, and a strawberry tongue. These are patients who warrant transfer to an intensive care unit. A key treatment principle is to search out the source of infection and drain it, whether it is a paronychia, sinusitis, perirectal abscess, or some other focus. If tampons are present they should be removed. Many experts use vancomycin and clindamycin as empiric therapy to treat toxic shock syndrome. Toxic shock syndrome results in vascular leakage, so fluid resuscitation and support of vascular volume are vital.

Dr. Anderson reported having no financial conflicts of interest.

[email protected]

VAIL, COLO. – The differential diagnosis of pediatric infectious disease emergencies marked by fever and rash can quickly be narrowed by paying close attention to the type of rash.

Infectious diseases featuring fever and rash that require emergency diagnosis and treatment include fever with rashes that are purpuric, petechial, or erythrodermic, Dr. Marsha S. Anderson said at a conference on pediatric infectious diseases sponsored by the Children’s Hospital Colorado.

Fever with purpura

Heading the list of diagnostic possibilities here is meningococcemia, which she called "every pediatrician’s nightmare" because of a case-fatality rate of 10%-20% even with appropriate treatment.

Courtesy Dr. Robert A. Silverman

Complicating the situation is the fact that in a minority of cases the rash is petechial rather than purpuric.

"This is a disease that deserves your respect. Just remember: With fever and purpura, or fever and petechiae, meningococcemia needs to be at the top of your differential," stressed Dr. Anderson, a pediatric infectious diseases specialist at the University of Colorado.

The attack rate is highest in infants and young children because they haven’t yet experienced the transient nasopharyngeal colonization by Neisseria species that permits formation of protective strain-specific antibodies, she explained.

Empiric therapy until the diagnostic lab work and drug susceptibilities become available is vancomycin plus ceftriaxone. This combination also covers the other serious infectious causes of pediatric fever and purpura: Haemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus aureus.

Once Neisseria meningitidis has been isolated, the antibiotic therapy can be narrowed to penicillin, cefotaxime, or ceftriaxone. The recommended treatment duration is 7 days for uncomplicated meningococcemia or meningococcal meningitis.

S. pneumoniae causes fever and purpura fulminans mainly in children who are immunocompromised.

Fever with petechiae

"Rocky Mountain spotted fever is another diagnosis you really don’t want to miss. You want to make this diagnosis and institute therapy promptly. Many studies have shown decreased mortality if doxycycline is initiated in the first 5 days of illness," Dr. Anderson said.

That can be a challenge. The distinctive petechial rash, which begins on the hands, wrists, feet, and ankles, and then moves centrally, typically doesn’t show up until day 5 or 6. In one study of 92 patients admitted with an ultimate diagnosis of Rocky Mountain spotted fever, the rash on admission was maculopapular rather than petechial in about one-third of cases (J. Pediatr. 2007;150:180-4).

Fever, myalgias, and headache are common at the onset of the illness, which is typically 2-14 days after a tick bite involving transmission of Rickettsia rickettsii. The diagnosis must be made clinically as there is no rapid testing commercially available. Demonstration of a fourfold antibody titer rise between acute and convalescent serology can confirm the diagnosis. Only about one-half of confirmed cases feature patient recall of a tick bite, so absence of such a history shouldn’t allay suspicion that this disease is present.

Doxycycline is the first-line agent used for treatment of Rocky Mountain spotted fever in children of all ages. The usual length of doxycycline therapy is 7-14 days, or for at least several days after the patient is afebrile and clinically improved. In a patient with a life-threatening allergy to doxycycline, chloramphenicol is an alternative. Availability of chloramphenicol, especially in the oral formulation, may be limited in the United States.

Other serious infections involving fever and petechiae include meningococcemia, group A streptococcal infection, rat bite fever, ehrlichiosis, and anaplasmosis. Unlike Rocky Mountain spotted fever, where a petechial or maculopapular rash occurs in 90% of cases, only about 10% of patients with ehrlichiosis or anaplasmosis develop a rash.

Rat bite fever is an acute febrile illness caused by Streptobacillus moniliformis, which colonizes the nasopharynx of a substantial percentage of domestic and wild rats. Children can develop the illness by kissing their pet rat or letting it eat food from their mouth.

Most cases of rat bite fever resolve spontaneously within 2 weeks; however, the case-fatality rate is 13% without treatment, which is penicillin or doxycycline.

Fever with erythroderma, a sunburnlike rash

The differential diagnosis here consists of toxic shock syndrome, staphylococcal scalded skin, and Kawasaki disease. Drug reactions, including Stevens-Johnson syndrome, are an important noninfectious cause. Sulfa drugs, anticonvulsants, and NSAIDs are the drugs most commonly associated with Stevens-Johnson syndrome.

Suspect toxic shock syndrome when fever and erythroderma are accompanied by hypotension, red eyes and lips, and a strawberry tongue. These are patients who warrant transfer to an intensive care unit. A key treatment principle is to search out the source of infection and drain it, whether it is a paronychia, sinusitis, perirectal abscess, or some other focus. If tampons are present they should be removed. Many experts use vancomycin and clindamycin as empiric therapy to treat toxic shock syndrome. Toxic shock syndrome results in vascular leakage, so fluid resuscitation and support of vascular volume are vital.

Dr. Anderson reported having no financial conflicts of interest.

[email protected]

VAIL, COLO. – The differential diagnosis of pediatric infectious disease emergencies marked by fever and rash can quickly be narrowed by paying close attention to the type of rash.

Infectious diseases featuring fever and rash that require emergency diagnosis and treatment include fever with rashes that are purpuric, petechial, or erythrodermic, Dr. Marsha S. Anderson said at a conference on pediatric infectious diseases sponsored by the Children’s Hospital Colorado.

Fever with purpura

Heading the list of diagnostic possibilities here is meningococcemia, which she called "every pediatrician’s nightmare" because of a case-fatality rate of 10%-20% even with appropriate treatment.

Courtesy Dr. Robert A. Silverman

Complicating the situation is the fact that in a minority of cases the rash is petechial rather than purpuric.

"This is a disease that deserves your respect. Just remember: With fever and purpura, or fever and petechiae, meningococcemia needs to be at the top of your differential," stressed Dr. Anderson, a pediatric infectious diseases specialist at the University of Colorado.

The attack rate is highest in infants and young children because they haven’t yet experienced the transient nasopharyngeal colonization by Neisseria species that permits formation of protective strain-specific antibodies, she explained.

Empiric therapy until the diagnostic lab work and drug susceptibilities become available is vancomycin plus ceftriaxone. This combination also covers the other serious infectious causes of pediatric fever and purpura: Haemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus aureus.

Once Neisseria meningitidis has been isolated, the antibiotic therapy can be narrowed to penicillin, cefotaxime, or ceftriaxone. The recommended treatment duration is 7 days for uncomplicated meningococcemia or meningococcal meningitis.

S. pneumoniae causes fever and purpura fulminans mainly in children who are immunocompromised.

Fever with petechiae

"Rocky Mountain spotted fever is another diagnosis you really don’t want to miss. You want to make this diagnosis and institute therapy promptly. Many studies have shown decreased mortality if doxycycline is initiated in the first 5 days of illness," Dr. Anderson said.

That can be a challenge. The distinctive petechial rash, which begins on the hands, wrists, feet, and ankles, and then moves centrally, typically doesn’t show up until day 5 or 6. In one study of 92 patients admitted with an ultimate diagnosis of Rocky Mountain spotted fever, the rash on admission was maculopapular rather than petechial in about one-third of cases (J. Pediatr. 2007;150:180-4).

Fever, myalgias, and headache are common at the onset of the illness, which is typically 2-14 days after a tick bite involving transmission of Rickettsia rickettsii. The diagnosis must be made clinically as there is no rapid testing commercially available. Demonstration of a fourfold antibody titer rise between acute and convalescent serology can confirm the diagnosis. Only about one-half of confirmed cases feature patient recall of a tick bite, so absence of such a history shouldn’t allay suspicion that this disease is present.

Doxycycline is the first-line agent used for treatment of Rocky Mountain spotted fever in children of all ages. The usual length of doxycycline therapy is 7-14 days, or for at least several days after the patient is afebrile and clinically improved. In a patient with a life-threatening allergy to doxycycline, chloramphenicol is an alternative. Availability of chloramphenicol, especially in the oral formulation, may be limited in the United States.

Other serious infections involving fever and petechiae include meningococcemia, group A streptococcal infection, rat bite fever, ehrlichiosis, and anaplasmosis. Unlike Rocky Mountain spotted fever, where a petechial or maculopapular rash occurs in 90% of cases, only about 10% of patients with ehrlichiosis or anaplasmosis develop a rash.

Rat bite fever is an acute febrile illness caused by Streptobacillus moniliformis, which colonizes the nasopharynx of a substantial percentage of domestic and wild rats. Children can develop the illness by kissing their pet rat or letting it eat food from their mouth.

Most cases of rat bite fever resolve spontaneously within 2 weeks; however, the case-fatality rate is 13% without treatment, which is penicillin or doxycycline.

Fever with erythroderma, a sunburnlike rash

The differential diagnosis here consists of toxic shock syndrome, staphylococcal scalded skin, and Kawasaki disease. Drug reactions, including Stevens-Johnson syndrome, are an important noninfectious cause. Sulfa drugs, anticonvulsants, and NSAIDs are the drugs most commonly associated with Stevens-Johnson syndrome.

Suspect toxic shock syndrome when fever and erythroderma are accompanied by hypotension, red eyes and lips, and a strawberry tongue. These are patients who warrant transfer to an intensive care unit. A key treatment principle is to search out the source of infection and drain it, whether it is a paronychia, sinusitis, perirectal abscess, or some other focus. If tampons are present they should be removed. Many experts use vancomycin and clindamycin as empiric therapy to treat toxic shock syndrome. Toxic shock syndrome results in vascular leakage, so fluid resuscitation and support of vascular volume are vital.

Dr. Anderson reported having no financial conflicts of interest.

[email protected]

The use of acetaminophen has been linked to cases of Stevens-Johnson syndrome and other serious, potentially fatal skin reactions, and should be considered as a possible cause in patients who develop these reactions after taking any product containing acetaminophen, the Food and Drug Administration announced on August 1.

Use of acetaminophen also has been associated with toxic epidermal necrolysis (TEN) and acute generalized exanthematous pustulosis (AGEP). All three types of skin reactions have been reported with the first dose and at other times during treatment. Although it is difficult to determine the frequency of these reactions, "it is likely" that these events are rare, the FDA statement said.

©Ingram Publishing/thinkstockphotos.com

Health care professionals "should be aware of this rare risk and consider acetaminophen, along with other drugs already known to have such an association, when assessing patients with potentially drug-induced skin reactions," and should advise patients that acetaminophen should be stopped immediately with the first sign of a skin rash or hypersensitivity, the FDA said in the announcement.

The warning is based on the FDA�s review of 107 serious skin reactions associated with acetaminophen products reported to the Adverse Event Reporting System (AERS) and reports in the medical literature between 1995 and 2011.

A small number of cases in the literature describe positive rechallenges with acetaminophen, "supporting causality," according to the statement.

They include the case of a 7-year-old girl who developed TEN and was hospitalized after taking three doses of acetaminophen at a 10 mg/kg dose. Six months later, she developed diffuse erythema and urticaria 30 minutes after a rechallenge with a 250 mg dose and was hospitalized again.

Another case was an 83-year-old man, diagnosed with AGEP after being hospitalized for a reaction that occurred after taking acetaminophen, along with other medications after hip replacement. The rash recurred when he received intravenous propacetamol, a prodrug of acetaminophen.

From 1969 to 2012, 91 cases of SJS/TEN and 16 cases of AGEP were reported to AERS in people who took acetaminophen (most were single-ingredient products), and included 67 hospitalizations and 12 deaths. In most of these cases, the doses reported (when the information was available) were within recommendations.

Of the 91 SJS/TEN cases, 6 were determined to be probable cases associated with acetaminophen and the rest were considered possible. One of the 16 AGEP cases was considered a probable case and the rest were considered possible.

Warnings about these risks- which are already in the labels of NSAIDs- will be added to the labels of prescription drugs that contain acetaminophen. The agency will request that manufacturers of OTC acetaminophen-containing products, such as Tylenol, add a warning to those products as well.

Serious adverse events associated with acetaminophen should be reported to the FDA's MedWatch program or by calling 800-332-1088.

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The use of acetaminophen has been linked to cases of Stevens-Johnson syndrome and other serious, potentially fatal skin reactions, and should be considered as a possible cause in patients who develop these reactions after taking any product containing acetaminophen, the Food and Drug Administration announced on August 1.

Use of acetaminophen also has been associated with toxic epidermal necrolysis (TEN) and acute generalized exanthematous pustulosis (AGEP). All three types of skin reactions have been reported with the first dose and at other times during treatment. Although it is difficult to determine the frequency of these reactions, "it is likely" that these events are rare, the FDA statement said.

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Health care professionals "should be aware of this rare risk and consider acetaminophen, along with other drugs already known to have such an association, when assessing patients with potentially drug-induced skin reactions," and should advise patients that acetaminophen should be stopped immediately with the first sign of a skin rash or hypersensitivity, the FDA said in the announcement.

The warning is based on the FDA�s review of 107 serious skin reactions associated with acetaminophen products reported to the Adverse Event Reporting System (AERS) and reports in the medical literature between 1995 and 2011.

A small number of cases in the literature describe positive rechallenges with acetaminophen, "supporting causality," according to the statement.

They include the case of a 7-year-old girl who developed TEN and was hospitalized after taking three doses of acetaminophen at a 10 mg/kg dose. Six months later, she developed diffuse erythema and urticaria 30 minutes after a rechallenge with a 250 mg dose and was hospitalized again.

Another case was an 83-year-old man, diagnosed with AGEP after being hospitalized for a reaction that occurred after taking acetaminophen, along with other medications after hip replacement. The rash recurred when he received intravenous propacetamol, a prodrug of acetaminophen.

From 1969 to 2012, 91 cases of SJS/TEN and 16 cases of AGEP were reported to AERS in people who took acetaminophen (most were single-ingredient products), and included 67 hospitalizations and 12 deaths. In most of these cases, the doses reported (when the information was available) were within recommendations.

Of the 91 SJS/TEN cases, 6 were determined to be probable cases associated with acetaminophen and the rest were considered possible. One of the 16 AGEP cases was considered a probable case and the rest were considered possible.

Warnings about these risks- which are already in the labels of NSAIDs- will be added to the labels of prescription drugs that contain acetaminophen. The agency will request that manufacturers of OTC acetaminophen-containing products, such as Tylenol, add a warning to those products as well.

Serious adverse events associated with acetaminophen should be reported to the FDA's MedWatch program or by calling 800-332-1088.

[email protected]

The use of acetaminophen has been linked to cases of Stevens-Johnson syndrome and other serious, potentially fatal skin reactions, and should be considered as a possible cause in patients who develop these reactions after taking any product containing acetaminophen, the Food and Drug Administration announced on August 1.

Use of acetaminophen also has been associated with toxic epidermal necrolysis (TEN) and acute generalized exanthematous pustulosis (AGEP). All three types of skin reactions have been reported with the first dose and at other times during treatment. Although it is difficult to determine the frequency of these reactions, "it is likely" that these events are rare, the FDA statement said.

©Ingram Publishing/thinkstockphotos.com

Health care professionals "should be aware of this rare risk and consider acetaminophen, along with other drugs already known to have such an association, when assessing patients with potentially drug-induced skin reactions," and should advise patients that acetaminophen should be stopped immediately with the first sign of a skin rash or hypersensitivity, the FDA said in the announcement.

The warning is based on the FDA�s review of 107 serious skin reactions associated with acetaminophen products reported to the Adverse Event Reporting System (AERS) and reports in the medical literature between 1995 and 2011.

A small number of cases in the literature describe positive rechallenges with acetaminophen, "supporting causality," according to the statement.

They include the case of a 7-year-old girl who developed TEN and was hospitalized after taking three doses of acetaminophen at a 10 mg/kg dose. Six months later, she developed diffuse erythema and urticaria 30 minutes after a rechallenge with a 250 mg dose and was hospitalized again.

Another case was an 83-year-old man, diagnosed with AGEP after being hospitalized for a reaction that occurred after taking acetaminophen, along with other medications after hip replacement. The rash recurred when he received intravenous propacetamol, a prodrug of acetaminophen.

From 1969 to 2012, 91 cases of SJS/TEN and 16 cases of AGEP were reported to AERS in people who took acetaminophen (most were single-ingredient products), and included 67 hospitalizations and 12 deaths. In most of these cases, the doses reported (when the information was available) were within recommendations.

Of the 91 SJS/TEN cases, 6 were determined to be probable cases associated with acetaminophen and the rest were considered possible. One of the 16 AGEP cases was considered a probable case and the rest were considered possible.

Warnings about these risks- which are already in the labels of NSAIDs- will be added to the labels of prescription drugs that contain acetaminophen. The agency will request that manufacturers of OTC acetaminophen-containing products, such as Tylenol, add a warning to those products as well.

Serious adverse events associated with acetaminophen should be reported to the FDA's MedWatch program or by calling 800-332-1088.

[email protected]