Case

A 42-year-old man with a history of posttraumatic stress disorder (PTSD), hypertension, and alcohol use disorder (AUD) presents to the ED requesting alcohol detoxification. He has had six admissions in the last six months for alcohol detoxification. Two years ago, the patient had a documented alcohol withdrawal seizure. His last drink was eight hours ago, and he currently drinks a liter of vodka a day. On exam, his pulse rate is 126 bpm, and his blood pressure is 162/91 mm Hg. He appears anxious and has bilateral hand tremors. His serum ethanol level is 388.6 mg/dL.

Overview

DSM-5 integrated alcohol abuse and alcohol dependence that were previously classified in DSM-IV into AUDs with mild, moderate, and severe subclassifications. AUDs are the most serious substance abuse problem in the U.S. In the general population, the lifetime prevalence of alcohol abuse is 17.8% and of alcohol dependence is 12.5%.1–3 One study estimates that 24% of adult patients brought to the ED by ambulance suffer from alcoholism, and approximately 10% to 32% of hospitalized medical patients have an AUD.4–8 Patients who stop drinking will develop alcohol withdrawal as early as six hours after their last drink (see Figure 1). The majority of patients at risk of alcohol withdrawal syndrome (AWS) will develop only minor uncomplicated symptoms, but up to 20% will develop symptoms associated with complicated AWS, including withdrawal seizures and delirium tremens (DT).9 It is not entirely clear why some individuals suffer from more severe withdrawal symptoms than others, but genetic predisposition may play a role.10

DT is a syndrome characterized by agitation, disorientation, hallucinations, and autonomic instability (tachycardia, hypertension, hyperthermia, and diaphoresis) in the setting of acute reduction or abstinence from alcohol and is associated with a mortality rate as high as 20%.11 Complicated AWS is associated with increased in-hospital morbidity and mortality, longer lengths of stay, inflated costs of care, increased burden and frustration of nursing and medical staff, and worse cognitive functioning.9 In 80% of cases, the symptoms of uncomplicated alcohol withdrawal do not require aggressive medical intervention and usually disappear within two to seven days of the last drink.12 Physicians making triage decisions for patients who present to the ED in need of detoxification face a difficult dilemma concerning inpatient versus outpatient treatment.

Review of the Data

The literature on both inpatient and outpatient management and treatment of AWS is well-described. Currently, there are no guidelines or consensus on whether to admit patients with alcohol abuse syndromes to the hospital when the request for detoxification is made. Admission should be considered for all patients experiencing alcohol withdrawal who present to the ED.13 Patients with mild AWS may be discharged if they do not require admission for an additional medical condition, but patients experiencing moderate to severe withdrawal require admission for monitoring and treatment. Many physicians use a simple assessment of past history of DT and pulse rate, which may be easily evaluated in clinical settings, to readily identify patients who are at high risk of developing DT during an alcohol dependence period.14

Since 1978, the Clinical Institute Withdrawal Assessment for Alcohol (CIWA) has been consistently used for both monitoring patients with alcohol withdrawal and for making an initial assessment. CIWA-Ar was developed as a revised scale and is frequently used to monitor the severity of ongoing alcohol withdrawal and the response to treatment for the clinical care of patients in alcohol withdrawal (see Figure 2). CIWA-Ar was not developed to identify patients at risk for AWS but is frequently used to determine if patients require admission to the hospital for detoxification.15 Patients with CIWA-Ar scores > 15 require inpatient detoxification. Patients with scores between 8 and 15 should be admitted if they have a history of prior seizures or DT but could otherwise be considered for outpatient detoxification. Patients with scores < 8, which are considered mild alcohol withdrawal, can likely be safely treated as outpatients unless they have a history of DT or alcohol withdrawal seizures.16 Because symptoms of severe alcohol withdrawal are often not present for more than six hours after the patient’s last drink, or often longer, CIWA-Ar is limited and does not identify patients who are otherwise at high risk for complicated withdrawal. A protocol was developed incorporating the patient’s history of alcohol withdrawal seizure, DT, and the CIWA to evaluate the outcome of outpatient versus inpatient detoxification.16

The most promising tool to screen patients for AWS was developed recently by researchers at Stanford University in Stanford, Calif., using an extensive systematic literature search to identify evidence-based clinical factors associated with the development of AWS.15 The Prediction of Alcohol Withdrawal Severity Scale (PAWSS) was subsequently constructed from 10 items correlating with complicated AWS (see Figure 3). When using a PAWSS score cutoff of ≥ 4, the predictive value of identifying a patient who is at risk for complicated withdrawal is significantly increased to 93.1%. This tool has only been used in medically ill patients but could be extrapolated for use in patients who present to an acute-care setting requesting inpatient detoxification.

Patients presenting to the ED with alcohol withdrawal seizures have been shown to have an associated 35% risk of progression to DT when found to have a low platelet count, low blood pyridoxine, and a high blood level of homocysteine. In another retrospective cohort study in Hepatology, three clinical features were identified to be associated with an increased risk for DT: alcohol dependence, a prior history of DT, and a higher pulse rate at admission (> 100 bpm).14

Instructions for the assessment of the patient who requests detoxification are as follows:

1. A patient whose last drink of alcohol was more than five days ago and who shows no signs of withdrawal is unlikely to develop significant withdrawal symptoms and does not require inpatient detoxification.
2. Other medical and psychiatric conditions should be evaluated for admission including alcohol use disorder complications.
3. Calculate CIWA-Ar score:

   Scores < 8 may not need detoxification; consider calculating PAWSS score.

   Scores of 8 to 15 without symptoms of DT or seizures can be treated as an outpatient detoxification if no contraindication.

   Scores of ≥ 15 should be admitted to the hospital.

4. Calculate PAWSS score:

   Scores ≥ 4 suggest high risk for moderate to severe complicated AWS, and admission should be considered.

   Scores < 4 suggest lower risk for complicated AWS, and outpatient treatment should be considered if patients do not have a medical or surgical diagnosis requiring admission.

Back to the Case

At the time of his presentation, the patient was beginning to show signs of early withdrawal symptoms, including tremor and tachycardia, despite having an elevated blood alcohol level. This patient had a PAWSS score of 6, placing him at increased risk of complicated AWS, and a CIWA-Ar score of 13. He was subsequently admitted to the hospital, and symptom-triggered therapy for treatment of his alcohol withdrawal was used. The patient’s CIWA-Ar score peaked at 21 some 24 hours after his last drink. The patient otherwise had an uncomplicated four-day hospital course due to persistent nausea.

Bottom Line

Hospitalists unsure of which patients should be admitted for alcohol detoxification can use the PAWSS tool and an initial CIWA-Ar score to help determine a patient’s risk for developing complicated AWS. TH

Dr. Velasquez and Dr. Kornsawad are assistant professors and hospitalists at the University of Texas Health Science Center at San Antonio. Dr. Velasquez also serves as assistant professor and hospitalist at the South Texas Veterans Health Care System serving the San Antonio area.

References

1. Grant BF, Stinson FS, Dawson DA, et al. Prevalence and co-occurrence of substance use disorder and independent mood and anxiety disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry. 2004;61(8):807-816.
2. Lieber CS. Medical disorders of alcoholism. N Engl J Med. 1995;333(16):1058-1065.
3. Hasin SD, Stinson SF, Ogburn E, Grant BF. Prevalence, correlates, disability, and comorbidity of DSM-IV alcohol abuse and dependence in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry. 2007;64(7):830-842.
4. Whiteman PJ, Hoffman RS, Goldfrank LR. Alcoholism in the emergency department: an epidemiologic study. Acad Emerg Med. 2000;7(1):14-20.
5. Nielson SD, Storgarrd H, Moesgarrd F, Gluud C. Prevalence of alcohol problems among adult somatic in-patients of a Copenhagen hospital. Alcohol Alcohol. 1994;29(5):583-590.
6. Smothers BA, Yahr HT, Ruhl CE. Detection of alcohol use disorders in general hospital admissions in the United States. Arch Intern Med. 2004;164(7):749-756.
7. Dolman JM, Hawkes ND. Combining the audit questionnaire and biochemical markers to assess alcohol use and risk of alcohol withdrawal in medical inpatients. Alcohol Alcohol. 2005;40(6):515-519.
8. Doering-Silveira J, Fidalgo TM, Nascimento CL, et al. Assessing alcohol dependence in hospitalized patients. Int J Environ Res Public Health. 2014;11(6):5783-5791.
9. Maldonado JR, Sher Y, Das S, et al. Prospective validation study of the prediction of alcohol withdrawal severity scale (PAWSS) in medically ill inpatients: a new scale for the prediction of complicated alcohol withdrawal syndrome. Alcohol Alcohol. 2015;50(5):509-518.
10. Saitz R, O’Malley SS. Pharmacotherapies for alcohol abuse. Withdrawal and treatment. Med Clin North Am. 1997;81(4):881-907.
11. Turner RC, Lichstein PR, Pedan Jr JG, Busher JT, Waivers LE. Alcohol withdrawal syndromes: a review of pathophysiology, clinical presentation, and treatment. J Gen Intern Med. 1989;4(5):432-444.
12. Schuckit MA. Alcohol-use disorders. Lancet. 2009;373(9662):492-501.
13. Stehman CR, Mycyk MB. A rational approach to the treatment of alcohol withdrawal in the ED. Am J Emerg Med. 2013;31(4):734-742.
14. Lee JH, Jang MK, Lee JY, et al. Clinical predictors for delirium tremens in alcohol dependence. J Gastroenterol Hepatol. 2005;20(12):1833-1837.
15. Maldonado JR, Sher Y, Ashouri JF, et al. The “prediction of alcohol withdrawal severity scale” (PAWSS): systematic literature review and pilot study of a new scale for the prediction of complicated alcohol withdrawal syndrome. Alcohol. 2014;48(4):375-390.
16. Stephens JR, Liles AE, Dancel R, Gilchrist M, Kirsch J, DeWalt DA. Who needs inpatient detox? Development and implementation of a hospitalist protocol for the evaluation of patients for alcohol detoxification. J Gen Intern Med. 2014;29(4):587-593.

Case

A 42-year-old man with a history of posttraumatic stress disorder (PTSD), hypertension, and alcohol use disorder (AUD) presents to the ED requesting alcohol detoxification. He has had six admissions in the last six months for alcohol detoxification. Two years ago, the patient had a documented alcohol withdrawal seizure. His last drink was eight hours ago, and he currently drinks a liter of vodka a day. On exam, his pulse rate is 126 bpm, and his blood pressure is 162/91 mm Hg. He appears anxious and has bilateral hand tremors. His serum ethanol level is 388.6 mg/dL.

Overview

DSM-5 integrated alcohol abuse and alcohol dependence that were previously classified in DSM-IV into AUDs with mild, moderate, and severe subclassifications. AUDs are the most serious substance abuse problem in the U.S. In the general population, the lifetime prevalence of alcohol abuse is 17.8% and of alcohol dependence is 12.5%.1–3 One study estimates that 24% of adult patients brought to the ED by ambulance suffer from alcoholism, and approximately 10% to 32% of hospitalized medical patients have an AUD.4–8 Patients who stop drinking will develop alcohol withdrawal as early as six hours after their last drink (see Figure 1). The majority of patients at risk of alcohol withdrawal syndrome (AWS) will develop only minor uncomplicated symptoms, but up to 20% will develop symptoms associated with complicated AWS, including withdrawal seizures and delirium tremens (DT).9 It is not entirely clear why some individuals suffer from more severe withdrawal symptoms than others, but genetic predisposition may play a role.10

DT is a syndrome characterized by agitation, disorientation, hallucinations, and autonomic instability (tachycardia, hypertension, hyperthermia, and diaphoresis) in the setting of acute reduction or abstinence from alcohol and is associated with a mortality rate as high as 20%.11 Complicated AWS is associated with increased in-hospital morbidity and mortality, longer lengths of stay, inflated costs of care, increased burden and frustration of nursing and medical staff, and worse cognitive functioning.9 In 80% of cases, the symptoms of uncomplicated alcohol withdrawal do not require aggressive medical intervention and usually disappear within two to seven days of the last drink.12 Physicians making triage decisions for patients who present to the ED in need of detoxification face a difficult dilemma concerning inpatient versus outpatient treatment.

Review of the Data

The literature on both inpatient and outpatient management and treatment of AWS is well-described. Currently, there are no guidelines or consensus on whether to admit patients with alcohol abuse syndromes to the hospital when the request for detoxification is made. Admission should be considered for all patients experiencing alcohol withdrawal who present to the ED.13 Patients with mild AWS may be discharged if they do not require admission for an additional medical condition, but patients experiencing moderate to severe withdrawal require admission for monitoring and treatment. Many physicians use a simple assessment of past history of DT and pulse rate, which may be easily evaluated in clinical settings, to readily identify patients who are at high risk of developing DT during an alcohol dependence period.14

Since 1978, the Clinical Institute Withdrawal Assessment for Alcohol (CIWA) has been consistently used for both monitoring patients with alcohol withdrawal and for making an initial assessment. CIWA-Ar was developed as a revised scale and is frequently used to monitor the severity of ongoing alcohol withdrawal and the response to treatment for the clinical care of patients in alcohol withdrawal (see Figure 2). CIWA-Ar was not developed to identify patients at risk for AWS but is frequently used to determine if patients require admission to the hospital for detoxification.15 Patients with CIWA-Ar scores > 15 require inpatient detoxification. Patients with scores between 8 and 15 should be admitted if they have a history of prior seizures or DT but could otherwise be considered for outpatient detoxification. Patients with scores < 8, which are considered mild alcohol withdrawal, can likely be safely treated as outpatients unless they have a history of DT or alcohol withdrawal seizures.16 Because symptoms of severe alcohol withdrawal are often not present for more than six hours after the patient’s last drink, or often longer, CIWA-Ar is limited and does not identify patients who are otherwise at high risk for complicated withdrawal. A protocol was developed incorporating the patient’s history of alcohol withdrawal seizure, DT, and the CIWA to evaluate the outcome of outpatient versus inpatient detoxification.16

The most promising tool to screen patients for AWS was developed recently by researchers at Stanford University in Stanford, Calif., using an extensive systematic literature search to identify evidence-based clinical factors associated with the development of AWS.15 The Prediction of Alcohol Withdrawal Severity Scale (PAWSS) was subsequently constructed from 10 items correlating with complicated AWS (see Figure 3). When using a PAWSS score cutoff of ≥ 4, the predictive value of identifying a patient who is at risk for complicated withdrawal is significantly increased to 93.1%. This tool has only been used in medically ill patients but could be extrapolated for use in patients who present to an acute-care setting requesting inpatient detoxification.

Patients presenting to the ED with alcohol withdrawal seizures have been shown to have an associated 35% risk of progression to DT when found to have a low platelet count, low blood pyridoxine, and a high blood level of homocysteine. In another retrospective cohort study in Hepatology, three clinical features were identified to be associated with an increased risk for DT: alcohol dependence, a prior history of DT, and a higher pulse rate at admission (> 100 bpm).14

Instructions for the assessment of the patient who requests detoxification are as follows:

1. A patient whose last drink of alcohol was more than five days ago and who shows no signs of withdrawal is unlikely to develop significant withdrawal symptoms and does not require inpatient detoxification.
2. Other medical and psychiatric conditions should be evaluated for admission including alcohol use disorder complications.
3. Calculate CIWA-Ar score:

   Scores < 8 may not need detoxification; consider calculating PAWSS score.

   Scores of 8 to 15 without symptoms of DT or seizures can be treated as an outpatient detoxification if no contraindication.

   Scores of ≥ 15 should be admitted to the hospital.

4. Calculate PAWSS score:

   Scores ≥ 4 suggest high risk for moderate to severe complicated AWS, and admission should be considered.

   Scores < 4 suggest lower risk for complicated AWS, and outpatient treatment should be considered if patients do not have a medical or surgical diagnosis requiring admission.

Back to the Case

At the time of his presentation, the patient was beginning to show signs of early withdrawal symptoms, including tremor and tachycardia, despite having an elevated blood alcohol level. This patient had a PAWSS score of 6, placing him at increased risk of complicated AWS, and a CIWA-Ar score of 13. He was subsequently admitted to the hospital, and symptom-triggered therapy for treatment of his alcohol withdrawal was used. The patient’s CIWA-Ar score peaked at 21 some 24 hours after his last drink. The patient otherwise had an uncomplicated four-day hospital course due to persistent nausea.

Bottom Line

Hospitalists unsure of which patients should be admitted for alcohol detoxification can use the PAWSS tool and an initial CIWA-Ar score to help determine a patient’s risk for developing complicated AWS. TH

Dr. Velasquez and Dr. Kornsawad are assistant professors and hospitalists at the University of Texas Health Science Center at San Antonio. Dr. Velasquez also serves as assistant professor and hospitalist at the South Texas Veterans Health Care System serving the San Antonio area.

References

1. Grant BF, Stinson FS, Dawson DA, et al. Prevalence and co-occurrence of substance use disorder and independent mood and anxiety disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry. 2004;61(8):807-816.
2. Lieber CS. Medical disorders of alcoholism. N Engl J Med. 1995;333(16):1058-1065.
3. Hasin SD, Stinson SF, Ogburn E, Grant BF. Prevalence, correlates, disability, and comorbidity of DSM-IV alcohol abuse and dependence in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry. 2007;64(7):830-842.
4. Whiteman PJ, Hoffman RS, Goldfrank LR. Alcoholism in the emergency department: an epidemiologic study. Acad Emerg Med. 2000;7(1):14-20.
5. Nielson SD, Storgarrd H, Moesgarrd F, Gluud C. Prevalence of alcohol problems among adult somatic in-patients of a Copenhagen hospital. Alcohol Alcohol. 1994;29(5):583-590.
6. Smothers BA, Yahr HT, Ruhl CE. Detection of alcohol use disorders in general hospital admissions in the United States. Arch Intern Med. 2004;164(7):749-756.
7. Dolman JM, Hawkes ND. Combining the audit questionnaire and biochemical markers to assess alcohol use and risk of alcohol withdrawal in medical inpatients. Alcohol Alcohol. 2005;40(6):515-519.
8. Doering-Silveira J, Fidalgo TM, Nascimento CL, et al. Assessing alcohol dependence in hospitalized patients. Int J Environ Res Public Health. 2014;11(6):5783-5791.
9. Maldonado JR, Sher Y, Das S, et al. Prospective validation study of the prediction of alcohol withdrawal severity scale (PAWSS) in medically ill inpatients: a new scale for the prediction of complicated alcohol withdrawal syndrome. Alcohol Alcohol. 2015;50(5):509-518.
10. Saitz R, O’Malley SS. Pharmacotherapies for alcohol abuse. Withdrawal and treatment. Med Clin North Am. 1997;81(4):881-907.
11. Turner RC, Lichstein PR, Pedan Jr JG, Busher JT, Waivers LE. Alcohol withdrawal syndromes: a review of pathophysiology, clinical presentation, and treatment. J Gen Intern Med. 1989;4(5):432-444.
12. Schuckit MA. Alcohol-use disorders. Lancet. 2009;373(9662):492-501.
13. Stehman CR, Mycyk MB. A rational approach to the treatment of alcohol withdrawal in the ED. Am J Emerg Med. 2013;31(4):734-742.
14. Lee JH, Jang MK, Lee JY, et al. Clinical predictors for delirium tremens in alcohol dependence. J Gastroenterol Hepatol. 2005;20(12):1833-1837.
15. Maldonado JR, Sher Y, Ashouri JF, et al. The “prediction of alcohol withdrawal severity scale” (PAWSS): systematic literature review and pilot study of a new scale for the prediction of complicated alcohol withdrawal syndrome. Alcohol. 2014;48(4):375-390.
16. Stephens JR, Liles AE, Dancel R, Gilchrist M, Kirsch J, DeWalt DA. Who needs inpatient detox? Development and implementation of a hospitalist protocol for the evaluation of patients for alcohol detoxification. J Gen Intern Med. 2014;29(4):587-593.

Case

A 42-year-old man with a history of posttraumatic stress disorder (PTSD), hypertension, and alcohol use disorder (AUD) presents to the ED requesting alcohol detoxification. He has had six admissions in the last six months for alcohol detoxification. Two years ago, the patient had a documented alcohol withdrawal seizure. His last drink was eight hours ago, and he currently drinks a liter of vodka a day. On exam, his pulse rate is 126 bpm, and his blood pressure is 162/91 mm Hg. He appears anxious and has bilateral hand tremors. His serum ethanol level is 388.6 mg/dL.

Overview

DSM-5 integrated alcohol abuse and alcohol dependence that were previously classified in DSM-IV into AUDs with mild, moderate, and severe subclassifications. AUDs are the most serious substance abuse problem in the U.S. In the general population, the lifetime prevalence of alcohol abuse is 17.8% and of alcohol dependence is 12.5%.1–3 One study estimates that 24% of adult patients brought to the ED by ambulance suffer from alcoholism, and approximately 10% to 32% of hospitalized medical patients have an AUD.4–8 Patients who stop drinking will develop alcohol withdrawal as early as six hours after their last drink (see Figure 1). The majority of patients at risk of alcohol withdrawal syndrome (AWS) will develop only minor uncomplicated symptoms, but up to 20% will develop symptoms associated with complicated AWS, including withdrawal seizures and delirium tremens (DT).9 It is not entirely clear why some individuals suffer from more severe withdrawal symptoms than others, but genetic predisposition may play a role.10

DT is a syndrome characterized by agitation, disorientation, hallucinations, and autonomic instability (tachycardia, hypertension, hyperthermia, and diaphoresis) in the setting of acute reduction or abstinence from alcohol and is associated with a mortality rate as high as 20%.11 Complicated AWS is associated with increased in-hospital morbidity and mortality, longer lengths of stay, inflated costs of care, increased burden and frustration of nursing and medical staff, and worse cognitive functioning.9 In 80% of cases, the symptoms of uncomplicated alcohol withdrawal do not require aggressive medical intervention and usually disappear within two to seven days of the last drink.12 Physicians making triage decisions for patients who present to the ED in need of detoxification face a difficult dilemma concerning inpatient versus outpatient treatment.

Review of the Data

The literature on both inpatient and outpatient management and treatment of AWS is well-described. Currently, there are no guidelines or consensus on whether to admit patients with alcohol abuse syndromes to the hospital when the request for detoxification is made. Admission should be considered for all patients experiencing alcohol withdrawal who present to the ED.13 Patients with mild AWS may be discharged if they do not require admission for an additional medical condition, but patients experiencing moderate to severe withdrawal require admission for monitoring and treatment. Many physicians use a simple assessment of past history of DT and pulse rate, which may be easily evaluated in clinical settings, to readily identify patients who are at high risk of developing DT during an alcohol dependence period.14

Since 1978, the Clinical Institute Withdrawal Assessment for Alcohol (CIWA) has been consistently used for both monitoring patients with alcohol withdrawal and for making an initial assessment. CIWA-Ar was developed as a revised scale and is frequently used to monitor the severity of ongoing alcohol withdrawal and the response to treatment for the clinical care of patients in alcohol withdrawal (see Figure 2). CIWA-Ar was not developed to identify patients at risk for AWS but is frequently used to determine if patients require admission to the hospital for detoxification.15 Patients with CIWA-Ar scores > 15 require inpatient detoxification. Patients with scores between 8 and 15 should be admitted if they have a history of prior seizures or DT but could otherwise be considered for outpatient detoxification. Patients with scores < 8, which are considered mild alcohol withdrawal, can likely be safely treated as outpatients unless they have a history of DT or alcohol withdrawal seizures.16 Because symptoms of severe alcohol withdrawal are often not present for more than six hours after the patient’s last drink, or often longer, CIWA-Ar is limited and does not identify patients who are otherwise at high risk for complicated withdrawal. A protocol was developed incorporating the patient’s history of alcohol withdrawal seizure, DT, and the CIWA to evaluate the outcome of outpatient versus inpatient detoxification.16

The most promising tool to screen patients for AWS was developed recently by researchers at Stanford University in Stanford, Calif., using an extensive systematic literature search to identify evidence-based clinical factors associated with the development of AWS.15 The Prediction of Alcohol Withdrawal Severity Scale (PAWSS) was subsequently constructed from 10 items correlating with complicated AWS (see Figure 3). When using a PAWSS score cutoff of ≥ 4, the predictive value of identifying a patient who is at risk for complicated withdrawal is significantly increased to 93.1%. This tool has only been used in medically ill patients but could be extrapolated for use in patients who present to an acute-care setting requesting inpatient detoxification.

Patients presenting to the ED with alcohol withdrawal seizures have been shown to have an associated 35% risk of progression to DT when found to have a low platelet count, low blood pyridoxine, and a high blood level of homocysteine. In another retrospective cohort study in Hepatology, three clinical features were identified to be associated with an increased risk for DT: alcohol dependence, a prior history of DT, and a higher pulse rate at admission (> 100 bpm).14

Instructions for the assessment of the patient who requests detoxification are as follows:

1. A patient whose last drink of alcohol was more than five days ago and who shows no signs of withdrawal is unlikely to develop significant withdrawal symptoms and does not require inpatient detoxification.
2. Other medical and psychiatric conditions should be evaluated for admission including alcohol use disorder complications.
3. Calculate CIWA-Ar score:

   Scores < 8 may not need detoxification; consider calculating PAWSS score.

   Scores of 8 to 15 without symptoms of DT or seizures can be treated as an outpatient detoxification if no contraindication.

   Scores of ≥ 15 should be admitted to the hospital.

4. Calculate PAWSS score:

   Scores ≥ 4 suggest high risk for moderate to severe complicated AWS, and admission should be considered.

   Scores < 4 suggest lower risk for complicated AWS, and outpatient treatment should be considered if patients do not have a medical or surgical diagnosis requiring admission.

Back to the Case

At the time of his presentation, the patient was beginning to show signs of early withdrawal symptoms, including tremor and tachycardia, despite having an elevated blood alcohol level. This patient had a PAWSS score of 6, placing him at increased risk of complicated AWS, and a CIWA-Ar score of 13. He was subsequently admitted to the hospital, and symptom-triggered therapy for treatment of his alcohol withdrawal was used. The patient’s CIWA-Ar score peaked at 21 some 24 hours after his last drink. The patient otherwise had an uncomplicated four-day hospital course due to persistent nausea.

Bottom Line

Hospitalists unsure of which patients should be admitted for alcohol detoxification can use the PAWSS tool and an initial CIWA-Ar score to help determine a patient’s risk for developing complicated AWS. TH

Dr. Velasquez and Dr. Kornsawad are assistant professors and hospitalists at the University of Texas Health Science Center at San Antonio. Dr. Velasquez also serves as assistant professor and hospitalist at the South Texas Veterans Health Care System serving the San Antonio area.

References

1. Grant BF, Stinson FS, Dawson DA, et al. Prevalence and co-occurrence of substance use disorder and independent mood and anxiety disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry. 2004;61(8):807-816.
2. Lieber CS. Medical disorders of alcoholism. N Engl J Med. 1995;333(16):1058-1065.
3. Hasin SD, Stinson SF, Ogburn E, Grant BF. Prevalence, correlates, disability, and comorbidity of DSM-IV alcohol abuse and dependence in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry. 2007;64(7):830-842.
4. Whiteman PJ, Hoffman RS, Goldfrank LR. Alcoholism in the emergency department: an epidemiologic study. Acad Emerg Med. 2000;7(1):14-20.
5. Nielson SD, Storgarrd H, Moesgarrd F, Gluud C. Prevalence of alcohol problems among adult somatic in-patients of a Copenhagen hospital. Alcohol Alcohol. 1994;29(5):583-590.
6. Smothers BA, Yahr HT, Ruhl CE. Detection of alcohol use disorders in general hospital admissions in the United States. Arch Intern Med. 2004;164(7):749-756.
7. Dolman JM, Hawkes ND. Combining the audit questionnaire and biochemical markers to assess alcohol use and risk of alcohol withdrawal in medical inpatients. Alcohol Alcohol. 2005;40(6):515-519.
8. Doering-Silveira J, Fidalgo TM, Nascimento CL, et al. Assessing alcohol dependence in hospitalized patients. Int J Environ Res Public Health. 2014;11(6):5783-5791.
9. Maldonado JR, Sher Y, Das S, et al. Prospective validation study of the prediction of alcohol withdrawal severity scale (PAWSS) in medically ill inpatients: a new scale for the prediction of complicated alcohol withdrawal syndrome. Alcohol Alcohol. 2015;50(5):509-518.
10. Saitz R, O’Malley SS. Pharmacotherapies for alcohol abuse. Withdrawal and treatment. Med Clin North Am. 1997;81(4):881-907.
11. Turner RC, Lichstein PR, Pedan Jr JG, Busher JT, Waivers LE. Alcohol withdrawal syndromes: a review of pathophysiology, clinical presentation, and treatment. J Gen Intern Med. 1989;4(5):432-444.
12. Schuckit MA. Alcohol-use disorders. Lancet. 2009;373(9662):492-501.
13. Stehman CR, Mycyk MB. A rational approach to the treatment of alcohol withdrawal in the ED. Am J Emerg Med. 2013;31(4):734-742.
14. Lee JH, Jang MK, Lee JY, et al. Clinical predictors for delirium tremens in alcohol dependence. J Gastroenterol Hepatol. 2005;20(12):1833-1837.
15. Maldonado JR, Sher Y, Ashouri JF, et al. The “prediction of alcohol withdrawal severity scale” (PAWSS): systematic literature review and pilot study of a new scale for the prediction of complicated alcohol withdrawal syndrome. Alcohol. 2014;48(4):375-390.
16. Stephens JR, Liles AE, Dancel R, Gilchrist M, Kirsch J, DeWalt DA. Who needs inpatient detox? Development and implementation of a hospitalist protocol for the evaluation of patients for alcohol detoxification. J Gen Intern Med. 2014;29(4):587-593.

Vial of Evomela

Photo courtesy of

Spectrum Pharmaceuticals

The US Food and Drug Administration (FDA) has approved a new formulation of melphalan for injection (Evomela) for 2 indications.

The drug is now approved for use as a high-dose conditioning treatment prior to autologous hematopoietic stem cell transplant (HSCT) in patients with multiple myeloma (MM) and for the palliative treatment of patients with MM for whom oral therapy is not appropriate.

Evomela is the first product to be FDA-approved for the high-dose conditioning indication in MM. The FDA previously granted the drug orphan designation for this indication.

About Evomela

Evomela is a Captisol-enabled, propylene glycol-free melphalan formulation. This formulation eliminates the need to use a propylene glycol-containing custom diluent, which is required with other intravenous melphalan formulations and has been reported to cause renal and cardiac side effects.

Captisol is a chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs.

The use of Captisol technology to reformulate melphalan is reported to improve the drug’s stability, extending its use time. The technology allows the admixture solution to be stable for 4 hours at room temperature, in addition to the 1 hour following reconstitution, and for 24 hours at refrigerated temperature (5°C).

This is anticipated to simplify preparation and administration logistics and allow for slower infusion rates and longer administration durations for pre-transplant chemotherapy.

The full prescribing information for Evomela is available at www.evomela.com.

Spectrum Pharmaceuticals gained global development and commercialization rights to Evomela from Ligand Pharmaceuticals Incorporated in March 2013.

Spectrum assumed responsibility for completing the pivotal phase 2 trial of Evomela and was responsible for filing the new drug application. Spectrum filed the application in December 2014, and the FDA accepted it the following March.

Phase 2 study

Evomela was approved by the FDA based on its bioequivalence to the standard melphalan formulation (Alkeran) in a phase 2 study.

Initial results from this trial (phase 2a) were published in Bone Marrow Transplantation in June 2014. Phase 2b results were published in Biology of Blood and Marrow Transplantation in September 2015.

Phase 2b included 61 patients. Fifty-six had newly diagnosed MM, and 5 had relapsed MM following prior HSCT.

The patients received Evomela at 200 mg/m², given as 2 doses on day -3 and day -2 prior to autologous HSCT (day 0).

All 61 patients achieved myeloablation at a median of 5 days post-HSCT. And all patients had successful neutrophil and platelet engraftment at a median of 12 days and 13 days post-HSCT, respectively.

Efficacy was assessed by clinical response at day 100. According to investigator assessment, the overall response rate was 95%, and the complete response (CR) rate was 31%.

According to independent pathology review, the overall response rate was 100%, and the CR rate was 21%. The lower rate of confirmed CRs in the independent review was due to missing data.

Treatment-related mortality was 0%, and non-hematologic adverse events were mostly grade 1 and 2 in severity. The incidence of grade 3 mucositis and grade 3 stomatitis were 10% and 5%, respectively, with no grade 4 mucositis or stomatitis reported.

Twenty percent of patients experienced treatment-emergent serious adverse events, most of which were grade 3 and consisted of events commonly reported in patients undergoing myeloablative chemotherapy. No new safety signals were identified.

Vial of Evomela

Photo courtesy of

Spectrum Pharmaceuticals

The US Food and Drug Administration (FDA) has approved a new formulation of melphalan for injection (Evomela) for 2 indications.

The drug is now approved for use as a high-dose conditioning treatment prior to autologous hematopoietic stem cell transplant (HSCT) in patients with multiple myeloma (MM) and for the palliative treatment of patients with MM for whom oral therapy is not appropriate.

Evomela is the first product to be FDA-approved for the high-dose conditioning indication in MM. The FDA previously granted the drug orphan designation for this indication.

About Evomela

Evomela is a Captisol-enabled, propylene glycol-free melphalan formulation. This formulation eliminates the need to use a propylene glycol-containing custom diluent, which is required with other intravenous melphalan formulations and has been reported to cause renal and cardiac side effects.

Captisol is a chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs.

The use of Captisol technology to reformulate melphalan is reported to improve the drug’s stability, extending its use time. The technology allows the admixture solution to be stable for 4 hours at room temperature, in addition to the 1 hour following reconstitution, and for 24 hours at refrigerated temperature (5°C).

This is anticipated to simplify preparation and administration logistics and allow for slower infusion rates and longer administration durations for pre-transplant chemotherapy.

The full prescribing information for Evomela is available at www.evomela.com.

Spectrum Pharmaceuticals gained global development and commercialization rights to Evomela from Ligand Pharmaceuticals Incorporated in March 2013.

Spectrum assumed responsibility for completing the pivotal phase 2 trial of Evomela and was responsible for filing the new drug application. Spectrum filed the application in December 2014, and the FDA accepted it the following March.

Phase 2 study

Evomela was approved by the FDA based on its bioequivalence to the standard melphalan formulation (Alkeran) in a phase 2 study.

Initial results from this trial (phase 2a) were published in Bone Marrow Transplantation in June 2014. Phase 2b results were published in Biology of Blood and Marrow Transplantation in September 2015.

Phase 2b included 61 patients. Fifty-six had newly diagnosed MM, and 5 had relapsed MM following prior HSCT.

The patients received Evomela at 200 mg/m², given as 2 doses on day -3 and day -2 prior to autologous HSCT (day 0).

All 61 patients achieved myeloablation at a median of 5 days post-HSCT. And all patients had successful neutrophil and platelet engraftment at a median of 12 days and 13 days post-HSCT, respectively.

Efficacy was assessed by clinical response at day 100. According to investigator assessment, the overall response rate was 95%, and the complete response (CR) rate was 31%.

According to independent pathology review, the overall response rate was 100%, and the CR rate was 21%. The lower rate of confirmed CRs in the independent review was due to missing data.

Treatment-related mortality was 0%, and non-hematologic adverse events were mostly grade 1 and 2 in severity. The incidence of grade 3 mucositis and grade 3 stomatitis were 10% and 5%, respectively, with no grade 4 mucositis or stomatitis reported.

Twenty percent of patients experienced treatment-emergent serious adverse events, most of which were grade 3 and consisted of events commonly reported in patients undergoing myeloablative chemotherapy. No new safety signals were identified.

Vial of Evomela

Photo courtesy of

Spectrum Pharmaceuticals

The US Food and Drug Administration (FDA) has approved a new formulation of melphalan for injection (Evomela) for 2 indications.

The drug is now approved for use as a high-dose conditioning treatment prior to autologous hematopoietic stem cell transplant (HSCT) in patients with multiple myeloma (MM) and for the palliative treatment of patients with MM for whom oral therapy is not appropriate.

Evomela is the first product to be FDA-approved for the high-dose conditioning indication in MM. The FDA previously granted the drug orphan designation for this indication.

About Evomela

Evomela is a Captisol-enabled, propylene glycol-free melphalan formulation. This formulation eliminates the need to use a propylene glycol-containing custom diluent, which is required with other intravenous melphalan formulations and has been reported to cause renal and cardiac side effects.

Captisol is a chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs.

The use of Captisol technology to reformulate melphalan is reported to improve the drug’s stability, extending its use time. The technology allows the admixture solution to be stable for 4 hours at room temperature, in addition to the 1 hour following reconstitution, and for 24 hours at refrigerated temperature (5°C).

This is anticipated to simplify preparation and administration logistics and allow for slower infusion rates and longer administration durations for pre-transplant chemotherapy.

The full prescribing information for Evomela is available at www.evomela.com.

Spectrum Pharmaceuticals gained global development and commercialization rights to Evomela from Ligand Pharmaceuticals Incorporated in March 2013.

Spectrum assumed responsibility for completing the pivotal phase 2 trial of Evomela and was responsible for filing the new drug application. Spectrum filed the application in December 2014, and the FDA accepted it the following March.

Phase 2 study

Evomela was approved by the FDA based on its bioequivalence to the standard melphalan formulation (Alkeran) in a phase 2 study.

Initial results from this trial (phase 2a) were published in Bone Marrow Transplantation in June 2014. Phase 2b results were published in Biology of Blood and Marrow Transplantation in September 2015.

Phase 2b included 61 patients. Fifty-six had newly diagnosed MM, and 5 had relapsed MM following prior HSCT.

The patients received Evomela at 200 mg/m², given as 2 doses on day -3 and day -2 prior to autologous HSCT (day 0).

All 61 patients achieved myeloablation at a median of 5 days post-HSCT. And all patients had successful neutrophil and platelet engraftment at a median of 12 days and 13 days post-HSCT, respectively.

Efficacy was assessed by clinical response at day 100. According to investigator assessment, the overall response rate was 95%, and the complete response (CR) rate was 31%.

According to independent pathology review, the overall response rate was 100%, and the CR rate was 21%. The lower rate of confirmed CRs in the independent review was due to missing data.

Treatment-related mortality was 0%, and non-hematologic adverse events were mostly grade 1 and 2 in severity. The incidence of grade 3 mucositis and grade 3 stomatitis were 10% and 5%, respectively, with no grade 4 mucositis or stomatitis reported.

Twenty percent of patients experienced treatment-emergent serious adverse events, most of which were grade 3 and consisted of events commonly reported in patients undergoing myeloablative chemotherapy. No new safety signals were identified.

Micrograph showing HSCs

in the bone marrow

A 2-drug combination can be more effective than granulocyte colony-stimulating factor (G-CSF) for mobilizing hematopoietic stem cells (HSCs), according to preclinical research published in Nature Communications.

The combination consists of the dual α9β1/α4β1 antagonist BOP and the CXCR4 antagonist AMD3100, also known as plerixafor.

In experiments with mice, researchers found that treatment with BOP and AMD3100 directly impacts HSCs so they can be seen in the blood stream within an hour.

And when these HSCs are transplanted into recipient mice, they can replenish the entire hematopoietic system.

“Current treatment requires [a transplant donor] to have growth factor injections for several days leading up to the [harvesting] procedure,” said study author Susie Nilsson, PhD, of Monash University in Clayton, Victoria, Australia.

“Using the [2-drug combination] eliminates the need for this, meaning a procedure that once took days can be reduced to around an hour.”

Combination vs monotherapy

Dr Nilsson and her colleagues found that, when given alone, AMD3100 and BOP produced similar increases in white blood cell (WBC) counts and the proportion of progenitors (LSK cells) in the peripheral blood (PB) of mice.

However, BOP produced a significantly greater increase in the proportion of HSCs (LSKSLAM cells) in the PB. The researchers said this suggests that AMD3100 predominantly mobilizes progenitors, and BOP predominantly mobilizes HSCs.

The team also found that, in combination, BOP and AMD3100 mobilized WBCs, progenitors, and HSCs more effectively than either agent alone.

To determine if these drugs could mobilize HSCs and progenitors with long-term multi-lineage engraftment potential, the researchers performed limiting dilution transplant analysis using BOP, AMD3100, or both drugs.

The team observed superior survival in mice that received 30 ml of PB mobilized using the combination, when compared to either drug alone.

In addition, PB mobilized with the combination resulted in a greater repopulation frequency (1 HSC in 23 ml PB) than PB mobilized with BOP (1 HSC in 327 ml) or AMD3100 (1 HSC in 351 ml).

The researchers said this was a more than 10-fold improvement with the combination, as compared to monotherapy.

Comparisons with G-CSF

Treating mice with a single dose of BOP following 4 days of G-CSF treatment resulted in significant synergistic increases in HSCs (LSKSLAM cells) and progenitors (LSK cells), when compared to G-CSF alone.

BOP and AMD3100 in combination produced equivalent numbers of HSCs and progenitors as G-CSF alone.

And the combination of G-CSF and AMD3100 mobilized significantly more HSCs and progenitors than G-CSF alone.

But the greatest number of HSCs and progenitors were mobilized with the combination of G-CSF, AMD3100, and BOP. This combination produced a significant increase in cells when compared with G-CSF alone or the combination of AMD3100 and BOP.

The researchers also compared the hematopoietic potential of PB mobilized with multiple doses of G-CSF to PB mobilized with a single dose of BOP and AMD3100 in combination.

Although equivalent numbers of HSCs were mobilized, BOP and AMD3100 significantly enhanced short-term and long-term multi-lineage engraftment, when compared to G-CSF.

To determine whether the HSC mobilization observed in these experiments is equivalent in humans, the researchers tested the mobilizing agents in humanized NSG mice.

They found that a single dose of BOP or AMD3100 alone, or multiple doses of G-CSF for 4 days, did not significantly increase human WBCs or human CD34+ stem and progenitor cells.

However, a single dose of BOP and AMD3100 in combination produced a significant increase in both WBCs and stem and progenitor cells.

The researchers said the next step is a phase 1 trial assessing the combination of BOP with G-CSF before they can test the combination of BOP and AMD3100 in humans.

Micrograph showing HSCs

in the bone marrow

A 2-drug combination can be more effective than granulocyte colony-stimulating factor (G-CSF) for mobilizing hematopoietic stem cells (HSCs), according to preclinical research published in Nature Communications.

The combination consists of the dual α9β1/α4β1 antagonist BOP and the CXCR4 antagonist AMD3100, also known as plerixafor.

In experiments with mice, researchers found that treatment with BOP and AMD3100 directly impacts HSCs so they can be seen in the blood stream within an hour.

And when these HSCs are transplanted into recipient mice, they can replenish the entire hematopoietic system.

“Current treatment requires [a transplant donor] to have growth factor injections for several days leading up to the [harvesting] procedure,” said study author Susie Nilsson, PhD, of Monash University in Clayton, Victoria, Australia.

“Using the [2-drug combination] eliminates the need for this, meaning a procedure that once took days can be reduced to around an hour.”

Combination vs monotherapy

Dr Nilsson and her colleagues found that, when given alone, AMD3100 and BOP produced similar increases in white blood cell (WBC) counts and the proportion of progenitors (LSK cells) in the peripheral blood (PB) of mice.

However, BOP produced a significantly greater increase in the proportion of HSCs (LSKSLAM cells) in the PB. The researchers said this suggests that AMD3100 predominantly mobilizes progenitors, and BOP predominantly mobilizes HSCs.

The team also found that, in combination, BOP and AMD3100 mobilized WBCs, progenitors, and HSCs more effectively than either agent alone.

To determine if these drugs could mobilize HSCs and progenitors with long-term multi-lineage engraftment potential, the researchers performed limiting dilution transplant analysis using BOP, AMD3100, or both drugs.

The team observed superior survival in mice that received 30 ml of PB mobilized using the combination, when compared to either drug alone.

In addition, PB mobilized with the combination resulted in a greater repopulation frequency (1 HSC in 23 ml PB) than PB mobilized with BOP (1 HSC in 327 ml) or AMD3100 (1 HSC in 351 ml).

The researchers said this was a more than 10-fold improvement with the combination, as compared to monotherapy.

Comparisons with G-CSF

Treating mice with a single dose of BOP following 4 days of G-CSF treatment resulted in significant synergistic increases in HSCs (LSKSLAM cells) and progenitors (LSK cells), when compared to G-CSF alone.

BOP and AMD3100 in combination produced equivalent numbers of HSCs and progenitors as G-CSF alone.

And the combination of G-CSF and AMD3100 mobilized significantly more HSCs and progenitors than G-CSF alone.

But the greatest number of HSCs and progenitors were mobilized with the combination of G-CSF, AMD3100, and BOP. This combination produced a significant increase in cells when compared with G-CSF alone or the combination of AMD3100 and BOP.

The researchers also compared the hematopoietic potential of PB mobilized with multiple doses of G-CSF to PB mobilized with a single dose of BOP and AMD3100 in combination.

Although equivalent numbers of HSCs were mobilized, BOP and AMD3100 significantly enhanced short-term and long-term multi-lineage engraftment, when compared to G-CSF.

To determine whether the HSC mobilization observed in these experiments is equivalent in humans, the researchers tested the mobilizing agents in humanized NSG mice.

They found that a single dose of BOP or AMD3100 alone, or multiple doses of G-CSF for 4 days, did not significantly increase human WBCs or human CD34+ stem and progenitor cells.

However, a single dose of BOP and AMD3100 in combination produced a significant increase in both WBCs and stem and progenitor cells.

The researchers said the next step is a phase 1 trial assessing the combination of BOP with G-CSF before they can test the combination of BOP and AMD3100 in humans.

Micrograph showing HSCs

in the bone marrow

A 2-drug combination can be more effective than granulocyte colony-stimulating factor (G-CSF) for mobilizing hematopoietic stem cells (HSCs), according to preclinical research published in Nature Communications.

The combination consists of the dual α9β1/α4β1 antagonist BOP and the CXCR4 antagonist AMD3100, also known as plerixafor.

In experiments with mice, researchers found that treatment with BOP and AMD3100 directly impacts HSCs so they can be seen in the blood stream within an hour.

And when these HSCs are transplanted into recipient mice, they can replenish the entire hematopoietic system.

“Current treatment requires [a transplant donor] to have growth factor injections for several days leading up to the [harvesting] procedure,” said study author Susie Nilsson, PhD, of Monash University in Clayton, Victoria, Australia.

“Using the [2-drug combination] eliminates the need for this, meaning a procedure that once took days can be reduced to around an hour.”

Combination vs monotherapy

Dr Nilsson and her colleagues found that, when given alone, AMD3100 and BOP produced similar increases in white blood cell (WBC) counts and the proportion of progenitors (LSK cells) in the peripheral blood (PB) of mice.

However, BOP produced a significantly greater increase in the proportion of HSCs (LSKSLAM cells) in the PB. The researchers said this suggests that AMD3100 predominantly mobilizes progenitors, and BOP predominantly mobilizes HSCs.

The team also found that, in combination, BOP and AMD3100 mobilized WBCs, progenitors, and HSCs more effectively than either agent alone.

To determine if these drugs could mobilize HSCs and progenitors with long-term multi-lineage engraftment potential, the researchers performed limiting dilution transplant analysis using BOP, AMD3100, or both drugs.

The team observed superior survival in mice that received 30 ml of PB mobilized using the combination, when compared to either drug alone.

In addition, PB mobilized with the combination resulted in a greater repopulation frequency (1 HSC in 23 ml PB) than PB mobilized with BOP (1 HSC in 327 ml) or AMD3100 (1 HSC in 351 ml).

The researchers said this was a more than 10-fold improvement with the combination, as compared to monotherapy.

Comparisons with G-CSF

Treating mice with a single dose of BOP following 4 days of G-CSF treatment resulted in significant synergistic increases in HSCs (LSKSLAM cells) and progenitors (LSK cells), when compared to G-CSF alone.

BOP and AMD3100 in combination produced equivalent numbers of HSCs and progenitors as G-CSF alone.

And the combination of G-CSF and AMD3100 mobilized significantly more HSCs and progenitors than G-CSF alone.

But the greatest number of HSCs and progenitors were mobilized with the combination of G-CSF, AMD3100, and BOP. This combination produced a significant increase in cells when compared with G-CSF alone or the combination of AMD3100 and BOP.

The researchers also compared the hematopoietic potential of PB mobilized with multiple doses of G-CSF to PB mobilized with a single dose of BOP and AMD3100 in combination.

Although equivalent numbers of HSCs were mobilized, BOP and AMD3100 significantly enhanced short-term and long-term multi-lineage engraftment, when compared to G-CSF.

To determine whether the HSC mobilization observed in these experiments is equivalent in humans, the researchers tested the mobilizing agents in humanized NSG mice.

They found that a single dose of BOP or AMD3100 alone, or multiple doses of G-CSF for 4 days, did not significantly increase human WBCs or human CD34+ stem and progenitor cells.

However, a single dose of BOP and AMD3100 in combination produced a significant increase in both WBCs and stem and progenitor cells.

The researchers said the next step is a phase 1 trial assessing the combination of BOP with G-CSF before they can test the combination of BOP and AMD3100 in humans.

Prescription medications

Photo courtesy of the CDC

New research suggests that starting all patients with chronic myeloid leukemia (CML) on the generic form of Gleevec, imatinib, could result in substantial savings for patients and insurance companies in the US.

Researchers found that starting treatment with generic imatinib and then switching patients to the second-generation tyrosine kinase inhibitors (TKIs) dasatinib (Sprycel) and nilotinib (Tasigna) if necessary would be more cost-effective than the current standard of care, which allows physicians to start patients on any of the aforementioned TKIs.

In fact, the data suggest that starting all CML patients on generic imatinib could reduce the cost of treatment per patient over 5 years by nearly $90,000.

“If we start all patients on the generic form of Gleevec, and it works, then they are on a generic for the rest of their lives,” said study author William V. Padula, PhD, of Johns Hopkins University in Baltimore, Maryland.

“This amounts to a huge cost savings for them and their insurers.”

Dr Padula and his colleagues described these potential savings in the Journal of the National Cancer Institute.

The researchers compared the cost-effectiveness of the different TKIs by analyzing Truven Health Analytics MarketScan data from newly diagnosed CML patients between January 1, 2011, and December 31, 2012.

The team constructed Markov models to compare the 5-year cost-effectiveness of imatinib-first vs physician’s choice. The main outcome of the models was cost per quality-adjusted life-year (QALY).

The researchers interpreted outcomes based on a willingness-to-pay threshold of $100,000/QALY. They found that both imatinib-first and physician’s choice met that threshold.

However, imatinib-first cost less over 5 years and conferred only slightly fewer QALYs than physician’s choice—$277,401 and 3.87 QALYs for imatinib-first and $365,744 and 3.97 QALYs for physician’s choice.

So that’s a 0.10 decrement in QALYs and a savings of $88,343 over 5 years with imatinib-first. The imatinib-first incremental cost-effectiveness ratio was about $883,730/QALY.

“There is minimal risk to starting all patients on imatinib first,” Dr Padula said. “If the patient can’t tolerate the medication or it seems to be ineffective in that patient, then we can switch the patient to a more expensive drug.”

“Insurance companies have the ability to dictate which drugs physicians prescribe first, and they regularly do. Doing so here would mean very little risk to health and a lot of cost savings.”

Prescription medications

Photo courtesy of the CDC

New research suggests that starting all patients with chronic myeloid leukemia (CML) on the generic form of Gleevec, imatinib, could result in substantial savings for patients and insurance companies in the US.

Researchers found that starting treatment with generic imatinib and then switching patients to the second-generation tyrosine kinase inhibitors (TKIs) dasatinib (Sprycel) and nilotinib (Tasigna) if necessary would be more cost-effective than the current standard of care, which allows physicians to start patients on any of the aforementioned TKIs.

In fact, the data suggest that starting all CML patients on generic imatinib could reduce the cost of treatment per patient over 5 years by nearly $90,000.

“If we start all patients on the generic form of Gleevec, and it works, then they are on a generic for the rest of their lives,” said study author William V. Padula, PhD, of Johns Hopkins University in Baltimore, Maryland.

“This amounts to a huge cost savings for them and their insurers.”

Dr Padula and his colleagues described these potential savings in the Journal of the National Cancer Institute.

The researchers compared the cost-effectiveness of the different TKIs by analyzing Truven Health Analytics MarketScan data from newly diagnosed CML patients between January 1, 2011, and December 31, 2012.

The team constructed Markov models to compare the 5-year cost-effectiveness of imatinib-first vs physician’s choice. The main outcome of the models was cost per quality-adjusted life-year (QALY).

The researchers interpreted outcomes based on a willingness-to-pay threshold of $100,000/QALY. They found that both imatinib-first and physician’s choice met that threshold.

However, imatinib-first cost less over 5 years and conferred only slightly fewer QALYs than physician’s choice—$277,401 and 3.87 QALYs for imatinib-first and $365,744 and 3.97 QALYs for physician’s choice.

So that’s a 0.10 decrement in QALYs and a savings of $88,343 over 5 years with imatinib-first. The imatinib-first incremental cost-effectiveness ratio was about $883,730/QALY.

“There is minimal risk to starting all patients on imatinib first,” Dr Padula said. “If the patient can’t tolerate the medication or it seems to be ineffective in that patient, then we can switch the patient to a more expensive drug.”

“Insurance companies have the ability to dictate which drugs physicians prescribe first, and they regularly do. Doing so here would mean very little risk to health and a lot of cost savings.”

Prescription medications

Photo courtesy of the CDC

New research suggests that starting all patients with chronic myeloid leukemia (CML) on the generic form of Gleevec, imatinib, could result in substantial savings for patients and insurance companies in the US.

Researchers found that starting treatment with generic imatinib and then switching patients to the second-generation tyrosine kinase inhibitors (TKIs) dasatinib (Sprycel) and nilotinib (Tasigna) if necessary would be more cost-effective than the current standard of care, which allows physicians to start patients on any of the aforementioned TKIs.

In fact, the data suggest that starting all CML patients on generic imatinib could reduce the cost of treatment per patient over 5 years by nearly $90,000.

“If we start all patients on the generic form of Gleevec, and it works, then they are on a generic for the rest of their lives,” said study author William V. Padula, PhD, of Johns Hopkins University in Baltimore, Maryland.

“This amounts to a huge cost savings for them and their insurers.”

Dr Padula and his colleagues described these potential savings in the Journal of the National Cancer Institute.

The researchers compared the cost-effectiveness of the different TKIs by analyzing Truven Health Analytics MarketScan data from newly diagnosed CML patients between January 1, 2011, and December 31, 2012.

The team constructed Markov models to compare the 5-year cost-effectiveness of imatinib-first vs physician’s choice. The main outcome of the models was cost per quality-adjusted life-year (QALY).

The researchers interpreted outcomes based on a willingness-to-pay threshold of $100,000/QALY. They found that both imatinib-first and physician’s choice met that threshold.

However, imatinib-first cost less over 5 years and conferred only slightly fewer QALYs than physician’s choice—$277,401 and 3.87 QALYs for imatinib-first and $365,744 and 3.97 QALYs for physician’s choice.

So that’s a 0.10 decrement in QALYs and a savings of $88,343 over 5 years with imatinib-first. The imatinib-first incremental cost-effectiveness ratio was about $883,730/QALY.

“There is minimal risk to starting all patients on imatinib first,” Dr Padula said. “If the patient can’t tolerate the medication or it seems to be ineffective in that patient, then we can switch the patient to a more expensive drug.”

“Insurance companies have the ability to dictate which drugs physicians prescribe first, and they regularly do. Doing so here would mean very little risk to health and a lot of cost savings.”

Researchers in the lab

Photo by Rhoda Baer

A review of the biomedical literature indicates an increase in the use of P values in recent years, but researchers say this technique can provide misleading results.

“It’s usually a suboptimal technique, and then it’s used in a biased way, so it can become very misleading,” said John Ioannidis, MD, of Stanford University in California.

He and his colleagues reviewed the use of P values and recounted their findings in JAMA.

The team used automated text-mining analysis to extract data on P values reported in 12,821,790 MEDLINE abstracts and 843,884 abstracts and full-text articles in PubMed Central from 1990 to 2015.

The researchers also assessed the reporting of P values in 151 English-language core clinical journals and specific article types as classified by PubMed.

They manually evaluated a random sample of 1000 MEDLINE abstracts for reporting of P values and other types of statistical information. And of those abstracts reporting empirical data, 100 articles were assessed in their entirety.

The data showed that reporting of P values more than doubled from 1990 to 2014—increasing from 7.3% to 15.6%.

In abstracts from core medical journals, 33% reported P values in 2014. And in the subset of randomized, controlled clinical trials, nearly 55% reported P values in 2014.

Dr Ioannidis noted that some researchers mistakenly think a P value is an estimate of how likely it is that a result is true.

“The P value does not tell you whether something is true,” he explained. “If you get a P value of 0.01, it doesn’t mean you have a 1% chance of something not being true.”

“A P value of 0.01 could mean the result is 20% likely to be true, 80% likely to be true, or 0.1% likely to be true—all with the same P value. The P value alone doesn’t tell you how true your result is.”

For an actual estimate of how likely a result is to be true or false, Dr Ioannidis said, researchers should instead use false-discovery rates or Bayes factor calculations.

He and his colleagues assessed the use of false-discovery rates, Bayes factor calculations, effect sizes, and confidence intervals in the 796 papers in their review that contained empirical data.

They found that 111 of these papers reported effect sizes, and 18 reported confidence intervals. None of the papers reported Bayes factors or false-discovery rates.

Fewer than 2% of the abstracts the team reviewed reported both an effect size and a confidence interval.

In a manual review of 99 randomly selected full-text articles, the researchers found that 55 articles reported at least 1 P value. But only 4 articles reported confidence intervals for all effect sizes, none used Bayesian methods, and 1 used false-discovery rates.

In light of these findings, Dr Ioannidis advocates more stringent approaches to analyzing data.

“The way to move forward is that P values need to be used more selectively,” he said. “When used, they need to be complemented by effect sizes and uncertainty [confidence intervals]. And it would often be a good idea to use a Bayesian approach or a false-discovery rate to answer the question, ‘How likely is this result to be true?’”

Researchers in the lab

Photo by Rhoda Baer

A review of the biomedical literature indicates an increase in the use of P values in recent years, but researchers say this technique can provide misleading results.

“It’s usually a suboptimal technique, and then it’s used in a biased way, so it can become very misleading,” said John Ioannidis, MD, of Stanford University in California.

He and his colleagues reviewed the use of P values and recounted their findings in JAMA.

The team used automated text-mining analysis to extract data on P values reported in 12,821,790 MEDLINE abstracts and 843,884 abstracts and full-text articles in PubMed Central from 1990 to 2015.

The researchers also assessed the reporting of P values in 151 English-language core clinical journals and specific article types as classified by PubMed.

They manually evaluated a random sample of 1000 MEDLINE abstracts for reporting of P values and other types of statistical information. And of those abstracts reporting empirical data, 100 articles were assessed in their entirety.

The data showed that reporting of P values more than doubled from 1990 to 2014—increasing from 7.3% to 15.6%.

In abstracts from core medical journals, 33% reported P values in 2014. And in the subset of randomized, controlled clinical trials, nearly 55% reported P values in 2014.

Dr Ioannidis noted that some researchers mistakenly think a P value is an estimate of how likely it is that a result is true.

“The P value does not tell you whether something is true,” he explained. “If you get a P value of 0.01, it doesn’t mean you have a 1% chance of something not being true.”

“A P value of 0.01 could mean the result is 20% likely to be true, 80% likely to be true, or 0.1% likely to be true—all with the same P value. The P value alone doesn’t tell you how true your result is.”

For an actual estimate of how likely a result is to be true or false, Dr Ioannidis said, researchers should instead use false-discovery rates or Bayes factor calculations.

He and his colleagues assessed the use of false-discovery rates, Bayes factor calculations, effect sizes, and confidence intervals in the 796 papers in their review that contained empirical data.

They found that 111 of these papers reported effect sizes, and 18 reported confidence intervals. None of the papers reported Bayes factors or false-discovery rates.

Fewer than 2% of the abstracts the team reviewed reported both an effect size and a confidence interval.

In a manual review of 99 randomly selected full-text articles, the researchers found that 55 articles reported at least 1 P value. But only 4 articles reported confidence intervals for all effect sizes, none used Bayesian methods, and 1 used false-discovery rates.

In light of these findings, Dr Ioannidis advocates more stringent approaches to analyzing data.

“The way to move forward is that P values need to be used more selectively,” he said. “When used, they need to be complemented by effect sizes and uncertainty [confidence intervals]. And it would often be a good idea to use a Bayesian approach or a false-discovery rate to answer the question, ‘How likely is this result to be true?’”

Researchers in the lab

Photo by Rhoda Baer

A review of the biomedical literature indicates an increase in the use of P values in recent years, but researchers say this technique can provide misleading results.

“It’s usually a suboptimal technique, and then it’s used in a biased way, so it can become very misleading,” said John Ioannidis, MD, of Stanford University in California.

He and his colleagues reviewed the use of P values and recounted their findings in JAMA.

The team used automated text-mining analysis to extract data on P values reported in 12,821,790 MEDLINE abstracts and 843,884 abstracts and full-text articles in PubMed Central from 1990 to 2015.

The researchers also assessed the reporting of P values in 151 English-language core clinical journals and specific article types as classified by PubMed.

They manually evaluated a random sample of 1000 MEDLINE abstracts for reporting of P values and other types of statistical information. And of those abstracts reporting empirical data, 100 articles were assessed in their entirety.

The data showed that reporting of P values more than doubled from 1990 to 2014—increasing from 7.3% to 15.6%.

In abstracts from core medical journals, 33% reported P values in 2014. And in the subset of randomized, controlled clinical trials, nearly 55% reported P values in 2014.

Dr Ioannidis noted that some researchers mistakenly think a P value is an estimate of how likely it is that a result is true.

“The P value does not tell you whether something is true,” he explained. “If you get a P value of 0.01, it doesn’t mean you have a 1% chance of something not being true.”

“A P value of 0.01 could mean the result is 20% likely to be true, 80% likely to be true, or 0.1% likely to be true—all with the same P value. The P value alone doesn’t tell you how true your result is.”

For an actual estimate of how likely a result is to be true or false, Dr Ioannidis said, researchers should instead use false-discovery rates or Bayes factor calculations.

He and his colleagues assessed the use of false-discovery rates, Bayes factor calculations, effect sizes, and confidence intervals in the 796 papers in their review that contained empirical data.

They found that 111 of these papers reported effect sizes, and 18 reported confidence intervals. None of the papers reported Bayes factors or false-discovery rates.

Fewer than 2% of the abstracts the team reviewed reported both an effect size and a confidence interval.

In a manual review of 99 randomly selected full-text articles, the researchers found that 55 articles reported at least 1 P value. But only 4 articles reported confidence intervals for all effect sizes, none used Bayesian methods, and 1 used false-discovery rates.

In light of these findings, Dr Ioannidis advocates more stringent approaches to analyzing data.

“The way to move forward is that P values need to be used more selectively,” he said. “When used, they need to be complemented by effect sizes and uncertainty [confidence intervals]. And it would often be a good idea to use a Bayesian approach or a false-discovery rate to answer the question, ‘How likely is this result to be true?’”

The Food and Drug Administration has approved a new propylene glycol–free formulation of melphalan hydrochloride as a high-dose conditioning treatment for autologous stem cell transplantation, and as a palliative therapy for multiple myeloma.

Evomela (Spectrum Pharmaceuticals) is intended to be reconstituted with normal saline at the time of intravenous administration. The solution is stable for 4 hours using Captisol, a proprietary agent containing modified cyclodextrin. It is also stable for 1 hour after reconstitution.

Extended stability without the need for propylene glycol is its major advantage over the other formulations of melphalan, a chemotherapy agent originally approved in 1964, according to a statement by Spectrum.

Evomela was approved on the basis of a phase IIa pharmacokinetic trial comprising 24 patients undergoing autologous stem cell transplantation. Evomela was bioequivalent with Alkeran, with a 10% higher maximum plasma concentration and area under the plasma concentration-time curve (Bone Marrow Transplant. 2014 Aug;49[8]:1042-5).

According to that, and other studies, adverse reactions included decreased neutrophil count (100%), decreased white blood cell count (100%), decreased lymphocyte count (98%), decreased platelet count (98%), diarrhea (93%), nausea (90%), fatigue (77%), hypokalemia (74%), anemia (66%), and vomiting (64%). About 2% of patients have experienced hypersensitivity reactions.

For palliative treatment, the recommended does is 16 mg/m² infused over 15-20 minutes at 2-week intervals for four doses, and then, after adequate recovery from toxicity, at 4-week intervals.

For conditioning treatment, the recommended does is 100 mg/m² per day infused over 30 minutes for 2 consecutive days before stem cell transplant.

[email protected]

The Food and Drug Administration has approved a new propylene glycol–free formulation of melphalan hydrochloride as a high-dose conditioning treatment for autologous stem cell transplantation, and as a palliative therapy for multiple myeloma.

Evomela (Spectrum Pharmaceuticals) is intended to be reconstituted with normal saline at the time of intravenous administration. The solution is stable for 4 hours using Captisol, a proprietary agent containing modified cyclodextrin. It is also stable for 1 hour after reconstitution.

Extended stability without the need for propylene glycol is its major advantage over the other formulations of melphalan, a chemotherapy agent originally approved in 1964, according to a statement by Spectrum.

Evomela was approved on the basis of a phase IIa pharmacokinetic trial comprising 24 patients undergoing autologous stem cell transplantation. Evomela was bioequivalent with Alkeran, with a 10% higher maximum plasma concentration and area under the plasma concentration-time curve (Bone Marrow Transplant. 2014 Aug;49[8]:1042-5).

According to that, and other studies, adverse reactions included decreased neutrophil count (100%), decreased white blood cell count (100%), decreased lymphocyte count (98%), decreased platelet count (98%), diarrhea (93%), nausea (90%), fatigue (77%), hypokalemia (74%), anemia (66%), and vomiting (64%). About 2% of patients have experienced hypersensitivity reactions.

For palliative treatment, the recommended does is 16 mg/m² infused over 15-20 minutes at 2-week intervals for four doses, and then, after adequate recovery from toxicity, at 4-week intervals.

For conditioning treatment, the recommended does is 100 mg/m² per day infused over 30 minutes for 2 consecutive days before stem cell transplant.

[email protected]

The Food and Drug Administration has approved a new propylene glycol–free formulation of melphalan hydrochloride as a high-dose conditioning treatment for autologous stem cell transplantation, and as a palliative therapy for multiple myeloma.

Evomela (Spectrum Pharmaceuticals) is intended to be reconstituted with normal saline at the time of intravenous administration. The solution is stable for 4 hours using Captisol, a proprietary agent containing modified cyclodextrin. It is also stable for 1 hour after reconstitution.

Extended stability without the need for propylene glycol is its major advantage over the other formulations of melphalan, a chemotherapy agent originally approved in 1964, according to a statement by Spectrum.

Evomela was approved on the basis of a phase IIa pharmacokinetic trial comprising 24 patients undergoing autologous stem cell transplantation. Evomela was bioequivalent with Alkeran, with a 10% higher maximum plasma concentration and area under the plasma concentration-time curve (Bone Marrow Transplant. 2014 Aug;49[8]:1042-5).

According to that, and other studies, adverse reactions included decreased neutrophil count (100%), decreased white blood cell count (100%), decreased lymphocyte count (98%), decreased platelet count (98%), diarrhea (93%), nausea (90%), fatigue (77%), hypokalemia (74%), anemia (66%), and vomiting (64%). About 2% of patients have experienced hypersensitivity reactions.

For palliative treatment, the recommended does is 16 mg/m² infused over 15-20 minutes at 2-week intervals for four doses, and then, after adequate recovery from toxicity, at 4-week intervals.

For conditioning treatment, the recommended does is 100 mg/m² per day infused over 30 minutes for 2 consecutive days before stem cell transplant.

[email protected]

Nonopioid therapy is the preferred approach for managing chronic pain outside of active cancer, palliative, and end-of-life care, according to a new guideline released today by the Centers for Disease Control and Prevention.

The 12 recommendations included in the guideline center around this principle and two others: using the lowest possible effective dosage when opioids are used, and exercising caution and monitoring patients closely when prescribing opioids.

Specifically, the guideline states that “clinicians should consider opioid therapy only if expected benefits for both pain and function are anticipated to outweigh risks to the patient,” and that “treatment should be combined with nonpharmacologic and nonopioid therapy, as appropriate.”

The guideline also addresses steps to take before starting or continuing opioid therapy, and drug selection, dosage, duration, follow-up, and discontinuation. Recommendations for assessing risk and addressing harms of opioid use are also included.

The CDC developed the guideline as part of the U.S. government’s urgent response to the epidemic of overdose deaths, which has been fueled by a quadrupling of the prescribing and sales of opioids since 1999, according to a CDC press statement. The guideline’s purpose is to help prevent opioid misuse and overdose.

“The CDC Guideline for Prescribing Opioids for Chronic Pain, United States, 2016 will help primary care providers ensure the safest and most effective treatment for their patients,” according to the statement. The CDC’s director, Dr. Tom Frieden, noted that “overprescribing opioids – largely for chronic pain – is a key driver of America’s drug-overdose epidemic.”

In a CDC teleconference marking the release of the guideline, Dr. Frieden said it has become increasingly clear that opioids “carry substantial risks but only uncertain benefits, especially compared with other treatments for chronic pain.

“Beginning treatment with an opioid is a momentous decision, and it should only be done with full understanding by both the clinician and the patient of the substantial risks and uncertain benefits involved,” Dr. Frieden said. He added that he knows of no other medication “that’s routinely used for a nonfatal condition [and] that kills patients so frequently.

“With more than 250 million prescriptions written each year, it’s so important that doctors understand that any one of those prescriptions could potentially end a patient’s life,” he cautioned.

A 2015 study showed that 1 of every 550 patients treated with opioids for noncancer pain – and 1 of 32 who received the highest doses (more than 200 morphine milligram equivalents per day) – died within 2.5 years of the first prescription.

Dr. Frieden noted that opioids do have a place when the potential benefits outweigh the potential harms. “But for most patients – the vast majority of patients – the risks will outweigh the benefits,” he said.

The opioid epidemic is one of the most pressing public health issues in the United States today, said Sylvia M. Burwell, secretary of the Department of Health & Human Services. A year ago, she announced an HHS initiative to reduce prescription opioid and heroin-related drug overdose, death, and dependence.

“Last year, more Americans died from drug overdoses than car crashes,” Ms. Burwell said during the teleconference, noting that families across the nation and from all walks of life have been affected.

Combating the opioid epidemic is a national priority, she said, and the CDC guideline will help in that effort.

“We believe this guideline will help health care professionals provide safer and more effective care for patients dealing with chronic pain, and we also believe it will help these providers drive down the rates of opioid use disorder, overdose, and ... death,” she said.

The American Medical Association greeted the guideline with cautious support.

“While we are largely supportive of the guidelines, we remain concerned about the evidence base informing some of the recommendations,” noted Dr. Patrice A. Harris, chair-elect of the AMA board and chair of the AMA Task Force to Reduce Opioid Abuse, in a statement.

The AMA also cited potential conflicts between the guideline and product labeling and state laws, as well as obstacles such as insurance coverage limits on nonpharmacologic treatments.

“If these guidelines help reduce the deaths resulting from opioids, they will prove to be valuable,” Dr. Harris said in the statement. “If they produce unintended consequences, we will need to mitigate them.”

Of note, the guideline stresses the right of patients with chronic pain to receive safe and effective pain management, and focuses on giving primary care providers – who account for about half of all opioid prescriptions – a road map for providing such pain management by increasing the use of effective nonopioid and nonpharmacologic therapies.

It was developed through a “rigorous scientific process using the best available scientific evidence, consulting with experts, and listening to comments from the public and partner organizations,” according to the CDC statement. The organization “is dedicated to working with partners to improve the evidence base and will refine the recommendations as new research becomes available.

”In conjunction with the release of the guideline, the CDC has provided a checklist for prescribing opioids for chronic pain, and a website with additional tools for implementing the recommendations within the guideline.

The CDC's opioid recommendations

The Centers for Disease Control and Prevention’s new opioid prescription guideline includes 12 recommendations. Here they are, modified slightly for style:

1. Nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain. Providers should only consider adding opioid therapy if expected benefits for both pain and function are anticipated to outweigh risks.

2. Before starting opioid therapy for chronic pain, providers should establish treatment goals with all patients, including realistic goals for pain and function. Providers should not initiate opioid therapy without consideration of how therapy will be discontinued if unsuccessful. Providers should continue opioid therapy only if there is clinically meaningful improvement in pain and function.

3. Before starting and periodically during opioid therapy, providers should discuss with patients known risks and realistic benefits of opioid therapy, and patient and provider responsibilities for managing therapy.

4. When starting opioid therapy for chronic pain, providers should prescribe immediate-release opioids instead of extended-release/long-acting opioids.

5. When opioids are started, providers should prescribe the lowest effective dosage. Providers should use caution when prescribing opioids at any dosage, should implement additional precautions when increasing dosage to 50 or more morphine milligram equivalents (MME) per day, and generally should avoid increasing dosage to 90 or more MME per day.

6. When opioids are used for acute pain, providers should prescribe the lowest effective dose of immediate-release opioids. Three or fewer days often will be sufficient.

7. Providers should evaluate the benefits and harms with patients within 1-4 weeks of starting opioid therapy for chronic pain or of dose escalation. They should reevaluate continued therapy’s benefits and harms every 3 months or more frequently. If continued therapy’s benefits do not outweigh harms, providers should work with patients to reduce dosages or discontinue opioids.

8. During therapy, providers should evaluate risk factors for opioid-related harm. Providers should incorporate into the management plan strategies to mitigate risk, including considering offering naloxone when factors that increase risk for opioid overdose – such as history of overdose, history of substance use disorder, or higher opioid dosage (50 MME or more) – are present.

9. Providers should review the patient’s history of controlled substance prescriptions using state prescription drug monitoring program (PDMP) data to determine whether the patient is receiving high opioid dosages or dangerous combinations that put him or her at high risk for overdose. Providers should review PDMP data when starting opioid therapy for chronic pain and periodically during opioid therapy for chronic pain, ranging from every prescription to every 3 months.

10. When prescribing opioids for chronic pain, providers should use urine drug testing before starting opioid therapy and consider urine drug testing at least annually to assess for prescribed medications, as well as other controlled prescription drugs and illicit drugs.

11. Providers should avoid concurrent prescriptions of opioid pain medication and benzodiazepines whenever possible.

12. Providers should offer or arrange evidence-based treatment (usually medication-assisted treatment with buprenorphine or methadone in combination with behavioral therapies) for patients with opioid use disorder.

M. Alexander Otto contributed to this article.

[email protected]

Nonopioid therapy is the preferred approach for managing chronic pain outside of active cancer, palliative, and end-of-life care, according to a new guideline released today by the Centers for Disease Control and Prevention.

The 12 recommendations included in the guideline center around this principle and two others: using the lowest possible effective dosage when opioids are used, and exercising caution and monitoring patients closely when prescribing opioids.

Specifically, the guideline states that “clinicians should consider opioid therapy only if expected benefits for both pain and function are anticipated to outweigh risks to the patient,” and that “treatment should be combined with nonpharmacologic and nonopioid therapy, as appropriate.”

The guideline also addresses steps to take before starting or continuing opioid therapy, and drug selection, dosage, duration, follow-up, and discontinuation. Recommendations for assessing risk and addressing harms of opioid use are also included.

The CDC developed the guideline as part of the U.S. government’s urgent response to the epidemic of overdose deaths, which has been fueled by a quadrupling of the prescribing and sales of opioids since 1999, according to a CDC press statement. The guideline’s purpose is to help prevent opioid misuse and overdose.

“The CDC Guideline for Prescribing Opioids for Chronic Pain, United States, 2016 will help primary care providers ensure the safest and most effective treatment for their patients,” according to the statement. The CDC’s director, Dr. Tom Frieden, noted that “overprescribing opioids – largely for chronic pain – is a key driver of America’s drug-overdose epidemic.”

In a CDC teleconference marking the release of the guideline, Dr. Frieden said it has become increasingly clear that opioids “carry substantial risks but only uncertain benefits, especially compared with other treatments for chronic pain.

“Beginning treatment with an opioid is a momentous decision, and it should only be done with full understanding by both the clinician and the patient of the substantial risks and uncertain benefits involved,” Dr. Frieden said. He added that he knows of no other medication “that’s routinely used for a nonfatal condition [and] that kills patients so frequently.

“With more than 250 million prescriptions written each year, it’s so important that doctors understand that any one of those prescriptions could potentially end a patient’s life,” he cautioned.

A 2015 study showed that 1 of every 550 patients treated with opioids for noncancer pain – and 1 of 32 who received the highest doses (more than 200 morphine milligram equivalents per day) – died within 2.5 years of the first prescription.

Dr. Frieden noted that opioids do have a place when the potential benefits outweigh the potential harms. “But for most patients – the vast majority of patients – the risks will outweigh the benefits,” he said.

The opioid epidemic is one of the most pressing public health issues in the United States today, said Sylvia M. Burwell, secretary of the Department of Health & Human Services. A year ago, she announced an HHS initiative to reduce prescription opioid and heroin-related drug overdose, death, and dependence.

“Last year, more Americans died from drug overdoses than car crashes,” Ms. Burwell said during the teleconference, noting that families across the nation and from all walks of life have been affected.

Combating the opioid epidemic is a national priority, she said, and the CDC guideline will help in that effort.

“We believe this guideline will help health care professionals provide safer and more effective care for patients dealing with chronic pain, and we also believe it will help these providers drive down the rates of opioid use disorder, overdose, and ... death,” she said.

The American Medical Association greeted the guideline with cautious support.

“While we are largely supportive of the guidelines, we remain concerned about the evidence base informing some of the recommendations,” noted Dr. Patrice A. Harris, chair-elect of the AMA board and chair of the AMA Task Force to Reduce Opioid Abuse, in a statement.

The AMA also cited potential conflicts between the guideline and product labeling and state laws, as well as obstacles such as insurance coverage limits on nonpharmacologic treatments.

“If these guidelines help reduce the deaths resulting from opioids, they will prove to be valuable,” Dr. Harris said in the statement. “If they produce unintended consequences, we will need to mitigate them.”

Of note, the guideline stresses the right of patients with chronic pain to receive safe and effective pain management, and focuses on giving primary care providers – who account for about half of all opioid prescriptions – a road map for providing such pain management by increasing the use of effective nonopioid and nonpharmacologic therapies.

It was developed through a “rigorous scientific process using the best available scientific evidence, consulting with experts, and listening to comments from the public and partner organizations,” according to the CDC statement. The organization “is dedicated to working with partners to improve the evidence base and will refine the recommendations as new research becomes available.

”In conjunction with the release of the guideline, the CDC has provided a checklist for prescribing opioids for chronic pain, and a website with additional tools for implementing the recommendations within the guideline.

The CDC's opioid recommendations

The Centers for Disease Control and Prevention’s new opioid prescription guideline includes 12 recommendations. Here they are, modified slightly for style:

1. Nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain. Providers should only consider adding opioid therapy if expected benefits for both pain and function are anticipated to outweigh risks.

2. Before starting opioid therapy for chronic pain, providers should establish treatment goals with all patients, including realistic goals for pain and function. Providers should not initiate opioid therapy without consideration of how therapy will be discontinued if unsuccessful. Providers should continue opioid therapy only if there is clinically meaningful improvement in pain and function.

3. Before starting and periodically during opioid therapy, providers should discuss with patients known risks and realistic benefits of opioid therapy, and patient and provider responsibilities for managing therapy.

4. When starting opioid therapy for chronic pain, providers should prescribe immediate-release opioids instead of extended-release/long-acting opioids.

5. When opioids are started, providers should prescribe the lowest effective dosage. Providers should use caution when prescribing opioids at any dosage, should implement additional precautions when increasing dosage to 50 or more morphine milligram equivalents (MME) per day, and generally should avoid increasing dosage to 90 or more MME per day.

6. When opioids are used for acute pain, providers should prescribe the lowest effective dose of immediate-release opioids. Three or fewer days often will be sufficient.

7. Providers should evaluate the benefits and harms with patients within 1-4 weeks of starting opioid therapy for chronic pain or of dose escalation. They should reevaluate continued therapy’s benefits and harms every 3 months or more frequently. If continued therapy’s benefits do not outweigh harms, providers should work with patients to reduce dosages or discontinue opioids.

8. During therapy, providers should evaluate risk factors for opioid-related harm. Providers should incorporate into the management plan strategies to mitigate risk, including considering offering naloxone when factors that increase risk for opioid overdose – such as history of overdose, history of substance use disorder, or higher opioid dosage (50 MME or more) – are present.

9. Providers should review the patient’s history of controlled substance prescriptions using state prescription drug monitoring program (PDMP) data to determine whether the patient is receiving high opioid dosages or dangerous combinations that put him or her at high risk for overdose. Providers should review PDMP data when starting opioid therapy for chronic pain and periodically during opioid therapy for chronic pain, ranging from every prescription to every 3 months.

10. When prescribing opioids for chronic pain, providers should use urine drug testing before starting opioid therapy and consider urine drug testing at least annually to assess for prescribed medications, as well as other controlled prescription drugs and illicit drugs.

11. Providers should avoid concurrent prescriptions of opioid pain medication and benzodiazepines whenever possible.

12. Providers should offer or arrange evidence-based treatment (usually medication-assisted treatment with buprenorphine or methadone in combination with behavioral therapies) for patients with opioid use disorder.

M. Alexander Otto contributed to this article.

[email protected]

Nonopioid therapy is the preferred approach for managing chronic pain outside of active cancer, palliative, and end-of-life care, according to a new guideline released today by the Centers for Disease Control and Prevention.

The 12 recommendations included in the guideline center around this principle and two others: using the lowest possible effective dosage when opioids are used, and exercising caution and monitoring patients closely when prescribing opioids.

Specifically, the guideline states that “clinicians should consider opioid therapy only if expected benefits for both pain and function are anticipated to outweigh risks to the patient,” and that “treatment should be combined with nonpharmacologic and nonopioid therapy, as appropriate.”

The guideline also addresses steps to take before starting or continuing opioid therapy, and drug selection, dosage, duration, follow-up, and discontinuation. Recommendations for assessing risk and addressing harms of opioid use are also included.

The CDC developed the guideline as part of the U.S. government’s urgent response to the epidemic of overdose deaths, which has been fueled by a quadrupling of the prescribing and sales of opioids since 1999, according to a CDC press statement. The guideline’s purpose is to help prevent opioid misuse and overdose.

“The CDC Guideline for Prescribing Opioids for Chronic Pain, United States, 2016 will help primary care providers ensure the safest and most effective treatment for their patients,” according to the statement. The CDC’s director, Dr. Tom Frieden, noted that “overprescribing opioids – largely for chronic pain – is a key driver of America’s drug-overdose epidemic.”

In a CDC teleconference marking the release of the guideline, Dr. Frieden said it has become increasingly clear that opioids “carry substantial risks but only uncertain benefits, especially compared with other treatments for chronic pain.

“Beginning treatment with an opioid is a momentous decision, and it should only be done with full understanding by both the clinician and the patient of the substantial risks and uncertain benefits involved,” Dr. Frieden said. He added that he knows of no other medication “that’s routinely used for a nonfatal condition [and] that kills patients so frequently.

“With more than 250 million prescriptions written each year, it’s so important that doctors understand that any one of those prescriptions could potentially end a patient’s life,” he cautioned.

A 2015 study showed that 1 of every 550 patients treated with opioids for noncancer pain – and 1 of 32 who received the highest doses (more than 200 morphine milligram equivalents per day) – died within 2.5 years of the first prescription.

Dr. Frieden noted that opioids do have a place when the potential benefits outweigh the potential harms. “But for most patients – the vast majority of patients – the risks will outweigh the benefits,” he said.

The opioid epidemic is one of the most pressing public health issues in the United States today, said Sylvia M. Burwell, secretary of the Department of Health & Human Services. A year ago, she announced an HHS initiative to reduce prescription opioid and heroin-related drug overdose, death, and dependence.

“Last year, more Americans died from drug overdoses than car crashes,” Ms. Burwell said during the teleconference, noting that families across the nation and from all walks of life have been affected.

Combating the opioid epidemic is a national priority, she said, and the CDC guideline will help in that effort.

“We believe this guideline will help health care professionals provide safer and more effective care for patients dealing with chronic pain, and we also believe it will help these providers drive down the rates of opioid use disorder, overdose, and ... death,” she said.

The American Medical Association greeted the guideline with cautious support.

“While we are largely supportive of the guidelines, we remain concerned about the evidence base informing some of the recommendations,” noted Dr. Patrice A. Harris, chair-elect of the AMA board and chair of the AMA Task Force to Reduce Opioid Abuse, in a statement.

The AMA also cited potential conflicts between the guideline and product labeling and state laws, as well as obstacles such as insurance coverage limits on nonpharmacologic treatments.

“If these guidelines help reduce the deaths resulting from opioids, they will prove to be valuable,” Dr. Harris said in the statement. “If they produce unintended consequences, we will need to mitigate them.”

Of note, the guideline stresses the right of patients with chronic pain to receive safe and effective pain management, and focuses on giving primary care providers – who account for about half of all opioid prescriptions – a road map for providing such pain management by increasing the use of effective nonopioid and nonpharmacologic therapies.

It was developed through a “rigorous scientific process using the best available scientific evidence, consulting with experts, and listening to comments from the public and partner organizations,” according to the CDC statement. The organization “is dedicated to working with partners to improve the evidence base and will refine the recommendations as new research becomes available.

”In conjunction with the release of the guideline, the CDC has provided a checklist for prescribing opioids for chronic pain, and a website with additional tools for implementing the recommendations within the guideline.

The CDC's opioid recommendations

The Centers for Disease Control and Prevention’s new opioid prescription guideline includes 12 recommendations. Here they are, modified slightly for style:

1. Nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain. Providers should only consider adding opioid therapy if expected benefits for both pain and function are anticipated to outweigh risks.

2. Before starting opioid therapy for chronic pain, providers should establish treatment goals with all patients, including realistic goals for pain and function. Providers should not initiate opioid therapy without consideration of how therapy will be discontinued if unsuccessful. Providers should continue opioid therapy only if there is clinically meaningful improvement in pain and function.

3. Before starting and periodically during opioid therapy, providers should discuss with patients known risks and realistic benefits of opioid therapy, and patient and provider responsibilities for managing therapy.

4. When starting opioid therapy for chronic pain, providers should prescribe immediate-release opioids instead of extended-release/long-acting opioids.

5. When opioids are started, providers should prescribe the lowest effective dosage. Providers should use caution when prescribing opioids at any dosage, should implement additional precautions when increasing dosage to 50 or more morphine milligram equivalents (MME) per day, and generally should avoid increasing dosage to 90 or more MME per day.

6. When opioids are used for acute pain, providers should prescribe the lowest effective dose of immediate-release opioids. Three or fewer days often will be sufficient.

7. Providers should evaluate the benefits and harms with patients within 1-4 weeks of starting opioid therapy for chronic pain or of dose escalation. They should reevaluate continued therapy’s benefits and harms every 3 months or more frequently. If continued therapy’s benefits do not outweigh harms, providers should work with patients to reduce dosages or discontinue opioids.

8. During therapy, providers should evaluate risk factors for opioid-related harm. Providers should incorporate into the management plan strategies to mitigate risk, including considering offering naloxone when factors that increase risk for opioid overdose – such as history of overdose, history of substance use disorder, or higher opioid dosage (50 MME or more) – are present.

9. Providers should review the patient’s history of controlled substance prescriptions using state prescription drug monitoring program (PDMP) data to determine whether the patient is receiving high opioid dosages or dangerous combinations that put him or her at high risk for overdose. Providers should review PDMP data when starting opioid therapy for chronic pain and periodically during opioid therapy for chronic pain, ranging from every prescription to every 3 months.

10. When prescribing opioids for chronic pain, providers should use urine drug testing before starting opioid therapy and consider urine drug testing at least annually to assess for prescribed medications, as well as other controlled prescription drugs and illicit drugs.

11. Providers should avoid concurrent prescriptions of opioid pain medication and benzodiazepines whenever possible.

12. Providers should offer or arrange evidence-based treatment (usually medication-assisted treatment with buprenorphine or methadone in combination with behavioral therapies) for patients with opioid use disorder.

M. Alexander Otto contributed to this article.

[email protected]

I hear it at least 6 times a month: “How can I get involved? How do I get on an AAD committee?” The quick answer is to pick a committee where you have some expertise, and get others (including other organizations where you have done committee work) to write supporting letters to the American Academy of Dermatology president-elect (this year Henry Lim). In October, the president-elect fills the empty committee spots, and whoever has the most expertise and support usually gets the spot. The support of the existing committee chair is most helpful as well.

The focus of the question above, however, is too limited. AAD committee work is important, but there are many other venues in which you can develop your skills and make an impact. The best spot to start is probably your local and state dermatology or county and state medical societies. They are always looking for new enthusiastic members. You will learn about parliamentary order and how to write and defend a resolution, and you may advance quickly – perhaps right up to a state leadership position or the state American Medical Association delegation. In the state and local societies, you will also learn about challenges practitioners face outside of dermatology. The skills you will develop are useful in any physician organization, including the AAD. The state medical societies are always interested in members who will travel to testify at the state legislature. This can be a valuable experience as well.

There are many state dermatology societies that need you for advocacy, service, and leadership. These are superb places to learn leadership skills and state advocacy.

The AAD “sister” societies – including the American Society for Dermatologic Surgery (ASDS), the American College of Mohs Surgery (ACMS), the American Society for Mohs Surgery ASMS, and the Women’s Dermatologic Society (WDS) – also have multiple committees, boards, and officer positions, which do advocacy and develop policy, and are arenas in which you can learn and contribute.

You should attend a meeting of the advisory board to the AAD. This is full-throttle democracy. State and local dermatology organizations are allowed to send delegates and alternate delegates to the advisory board, and these spots often go empty. The advisory board’s resolutions go directly to the AAD board of directors to be acted on. In addition, the advisory board also appoints one of the directors to the AAD board of directors. This opportunity is underappreciated.

Involvement in SkinPAC would be most welcome (and earns you an asterisk by your name on the committee nomination roster!). The importance of legislative efforts cannot be overemphasized. Attending the legislative conference should be high on your list of things to do when you ask how to get involved.

You should also consider community involvement, regardless of your other activities. This will help your larger community in ways you could never imagine. I have served on the local health department for many years and find it rewarding and interesting. They are always keen to have more medical doctors on the board.

You can get appointed by writing the local officials (the county judge executive or mayor of the city) and expressing an interest, or to the medical director of the health department.

State medical boards are a large time commitment and a lot of work, but can be most important. We need more dermatologists on state medical boards since we are a unique specialty, and other physicians have no idea what you do in your office. Medical boards often make policy, and can have a huge impact. These positions are competitive in larger states and may require some political support from the governor in order for you to be appointed.

Charitable work is also important. Most of us volunteer to do skin cancer screenings, but there are also opportunities to provide dermatology services overseas. Dermatologists are rare in most of the world, and you will find the service most gratifying. There are opportunities closer to home in the free clinics almost anywhere.

Engagement and service by as many as possible is crucial for a specialty as small as ours, and your efforts will be noted and appreciated. There are thousands of ways to get involved, and I encourage you to get in there and do it.

Dr. Coldiron is a past president of the American Academy of Dermatology. He is currently in private practice, but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics.

I hear it at least 6 times a month: “How can I get involved? How do I get on an AAD committee?” The quick answer is to pick a committee where you have some expertise, and get others (including other organizations where you have done committee work) to write supporting letters to the American Academy of Dermatology president-elect (this year Henry Lim). In October, the president-elect fills the empty committee spots, and whoever has the most expertise and support usually gets the spot. The support of the existing committee chair is most helpful as well.

The focus of the question above, however, is too limited. AAD committee work is important, but there are many other venues in which you can develop your skills and make an impact. The best spot to start is probably your local and state dermatology or county and state medical societies. They are always looking for new enthusiastic members. You will learn about parliamentary order and how to write and defend a resolution, and you may advance quickly – perhaps right up to a state leadership position or the state American Medical Association delegation. In the state and local societies, you will also learn about challenges practitioners face outside of dermatology. The skills you will develop are useful in any physician organization, including the AAD. The state medical societies are always interested in members who will travel to testify at the state legislature. This can be a valuable experience as well.

There are many state dermatology societies that need you for advocacy, service, and leadership. These are superb places to learn leadership skills and state advocacy.

The AAD “sister” societies – including the American Society for Dermatologic Surgery (ASDS), the American College of Mohs Surgery (ACMS), the American Society for Mohs Surgery ASMS, and the Women’s Dermatologic Society (WDS) – also have multiple committees, boards, and officer positions, which do advocacy and develop policy, and are arenas in which you can learn and contribute.

You should attend a meeting of the advisory board to the AAD. This is full-throttle democracy. State and local dermatology organizations are allowed to send delegates and alternate delegates to the advisory board, and these spots often go empty. The advisory board’s resolutions go directly to the AAD board of directors to be acted on. In addition, the advisory board also appoints one of the directors to the AAD board of directors. This opportunity is underappreciated.

Involvement in SkinPAC would be most welcome (and earns you an asterisk by your name on the committee nomination roster!). The importance of legislative efforts cannot be overemphasized. Attending the legislative conference should be high on your list of things to do when you ask how to get involved.

You should also consider community involvement, regardless of your other activities. This will help your larger community in ways you could never imagine. I have served on the local health department for many years and find it rewarding and interesting. They are always keen to have more medical doctors on the board.

You can get appointed by writing the local officials (the county judge executive or mayor of the city) and expressing an interest, or to the medical director of the health department.

State medical boards are a large time commitment and a lot of work, but can be most important. We need more dermatologists on state medical boards since we are a unique specialty, and other physicians have no idea what you do in your office. Medical boards often make policy, and can have a huge impact. These positions are competitive in larger states and may require some political support from the governor in order for you to be appointed.

Charitable work is also important. Most of us volunteer to do skin cancer screenings, but there are also opportunities to provide dermatology services overseas. Dermatologists are rare in most of the world, and you will find the service most gratifying. There are opportunities closer to home in the free clinics almost anywhere.

Engagement and service by as many as possible is crucial for a specialty as small as ours, and your efforts will be noted and appreciated. There are thousands of ways to get involved, and I encourage you to get in there and do it.

Dr. Coldiron is a past president of the American Academy of Dermatology. He is currently in private practice, but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics.

I hear it at least 6 times a month: “How can I get involved? How do I get on an AAD committee?” The quick answer is to pick a committee where you have some expertise, and get others (including other organizations where you have done committee work) to write supporting letters to the American Academy of Dermatology president-elect (this year Henry Lim). In October, the president-elect fills the empty committee spots, and whoever has the most expertise and support usually gets the spot. The support of the existing committee chair is most helpful as well.

The focus of the question above, however, is too limited. AAD committee work is important, but there are many other venues in which you can develop your skills and make an impact. The best spot to start is probably your local and state dermatology or county and state medical societies. They are always looking for new enthusiastic members. You will learn about parliamentary order and how to write and defend a resolution, and you may advance quickly – perhaps right up to a state leadership position or the state American Medical Association delegation. In the state and local societies, you will also learn about challenges practitioners face outside of dermatology. The skills you will develop are useful in any physician organization, including the AAD. The state medical societies are always interested in members who will travel to testify at the state legislature. This can be a valuable experience as well.

There are many state dermatology societies that need you for advocacy, service, and leadership. These are superb places to learn leadership skills and state advocacy.

The AAD “sister” societies – including the American Society for Dermatologic Surgery (ASDS), the American College of Mohs Surgery (ACMS), the American Society for Mohs Surgery ASMS, and the Women’s Dermatologic Society (WDS) – also have multiple committees, boards, and officer positions, which do advocacy and develop policy, and are arenas in which you can learn and contribute.

You should attend a meeting of the advisory board to the AAD. This is full-throttle democracy. State and local dermatology organizations are allowed to send delegates and alternate delegates to the advisory board, and these spots often go empty. The advisory board’s resolutions go directly to the AAD board of directors to be acted on. In addition, the advisory board also appoints one of the directors to the AAD board of directors. This opportunity is underappreciated.

Involvement in SkinPAC would be most welcome (and earns you an asterisk by your name on the committee nomination roster!). The importance of legislative efforts cannot be overemphasized. Attending the legislative conference should be high on your list of things to do when you ask how to get involved.

You should also consider community involvement, regardless of your other activities. This will help your larger community in ways you could never imagine. I have served on the local health department for many years and find it rewarding and interesting. They are always keen to have more medical doctors on the board.

You can get appointed by writing the local officials (the county judge executive or mayor of the city) and expressing an interest, or to the medical director of the health department.

State medical boards are a large time commitment and a lot of work, but can be most important. We need more dermatologists on state medical boards since we are a unique specialty, and other physicians have no idea what you do in your office. Medical boards often make policy, and can have a huge impact. These positions are competitive in larger states and may require some political support from the governor in order for you to be appointed.

Charitable work is also important. Most of us volunteer to do skin cancer screenings, but there are also opportunities to provide dermatology services overseas. Dermatologists are rare in most of the world, and you will find the service most gratifying. There are opportunities closer to home in the free clinics almost anywhere.

Engagement and service by as many as possible is crucial for a specialty as small as ours, and your efforts will be noted and appreciated. There are thousands of ways to get involved, and I encourage you to get in there and do it.

Dr. Coldiron is a past president of the American Academy of Dermatology. He is currently in private practice, but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics.

An increased rate of adverse events, including deaths, have been reported in clinical trials with idelalisib (Zydelig) in combination with other cancer medicines, the U.S. Food and Drug Administration announced.

Gilead Sciences, Inc. has confirmed that they are stopping six clinical trials in patients with chronic lymphocytic leukemia, small lymphocytic lymphoma and indolent non-Hodgkin lymphomas. The FDA is reviewing the findings of the clinical trials and will communicate new information as necessary, according to the FDA press release.

Idelalisib is not approved for previously untreated chronic lymphocytic leukemia. It is approved by the FDA for the treatment of:

• Relapsed chronic lymphocytic leukemia, in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities.

• Relapsed follicular B-cell non-Hodgkin lymphoma in patients who have received at least two prior systemic therapies.

• Relapsed small lymphocytic lymphoma in patients who have received at least two prior systemic therapies.

Adverse events involving idelalisib should be reported to the FDA MedWatch program, the release advised.

[email protected]

On Twitter @maryjodales

An increased rate of adverse events, including deaths, have been reported in clinical trials with idelalisib (Zydelig) in combination with other cancer medicines, the U.S. Food and Drug Administration announced.

Gilead Sciences, Inc. has confirmed that they are stopping six clinical trials in patients with chronic lymphocytic leukemia, small lymphocytic lymphoma and indolent non-Hodgkin lymphomas. The FDA is reviewing the findings of the clinical trials and will communicate new information as necessary, according to the FDA press release.

Idelalisib is not approved for previously untreated chronic lymphocytic leukemia. It is approved by the FDA for the treatment of:

• Relapsed chronic lymphocytic leukemia, in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities.

• Relapsed follicular B-cell non-Hodgkin lymphoma in patients who have received at least two prior systemic therapies.

• Relapsed small lymphocytic lymphoma in patients who have received at least two prior systemic therapies.

Adverse events involving idelalisib should be reported to the FDA MedWatch program, the release advised.

[email protected]

On Twitter @maryjodales

An increased rate of adverse events, including deaths, have been reported in clinical trials with idelalisib (Zydelig) in combination with other cancer medicines, the U.S. Food and Drug Administration announced.

Gilead Sciences, Inc. has confirmed that they are stopping six clinical trials in patients with chronic lymphocytic leukemia, small lymphocytic lymphoma and indolent non-Hodgkin lymphomas. The FDA is reviewing the findings of the clinical trials and will communicate new information as necessary, according to the FDA press release.

Idelalisib is not approved for previously untreated chronic lymphocytic leukemia. It is approved by the FDA for the treatment of:

• Relapsed chronic lymphocytic leukemia, in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities.

• Relapsed follicular B-cell non-Hodgkin lymphoma in patients who have received at least two prior systemic therapies.

• Relapsed small lymphocytic lymphoma in patients who have received at least two prior systemic therapies.

Adverse events involving idelalisib should be reported to the FDA MedWatch program, the release advised.

[email protected]

On Twitter @maryjodales

I’m happier doing patient messages these days. That’s because of a little feature that we turned on in EPIC, our electronic medical record. The change doesn’t make me any faster or smarter. It doesn’t make me any more money. It merely adds a sprinkle of meaning to the work I do, and that has made all the difference.

In contrast to the usually glamorous portrayal of physicians’ work, most of our days are mundane. On a typical clinic day I’ll get up to a dozen requests from patients asking for something. Usually it’s just a refill, but several are from patients asking for a earlier appointment, when there are none. Or asking for a stronger treatment, when there aren’t any. Most of these requests are from patients who do not have interesting diagnoses or require sophisticated treatments. They are the itchy, and they remain itchy despite my advice. After a long day of seeing patients, the long list of messages that requires action feels endless, burdensome. Optimizing extenders has made me more efficient, but the work that remains isn’t fulfilling. A subtle change in our EMR has helped, though.

What is different? Our EPIC now includes a photo of each patient. That’s it. Ostensibly, having a photo is a security feature: it allows us to positively identify a patient, thereby reducing the risk that we treat an imposter posing as that patient (a small but real problem with drug seekers).

Why might this matter for physician satisfaction? Because seeing a patient photo brings an actual person to the top of mind. This changes our emotional connection to the work: how we interpret work is all that matters when it comes to job satisfaction. This is why volunteer work is so rewarding, despite having no monetary incentive, and why highly compensated professions, like those of many Wall Street traders, can ultimately fail to be fulfilling.

Tonight, long after the sun has set, I’m still working through messages. The next one, however, is not from any patient with nummular eczema. I see it’s from Mrs. Morales (not her real name), a sweet older woman with a warm smile and rich accent. She teaches water aerobics and she spent 5 minutes describing a typical Puerto Rican dinner (lots of stews) during her last appointment with me. Seeing her smiling face in the top left corner of the chart reminds me that the work I’m doing is for someone I know, someone I care for.

Radiologists have actually studied this phenomenon. Like much of medicine, radiology can be tedious. Researchers devised a simple test to see if making radiology work more human could improve not only the experience for, but also the effectiveness of, doctors. With patients’ consent, they took photos of 300 participants before their films were sent for reading. Radiologists who saw a patient’s photo along with their radiographic studies reported feeling more empathy for their patients. They also reported reading cases with photos more meticulously than those cases without photos. But that’s not all. When the radiologists were later shown the same films but without the patient photos, the doctors were less likely to notice incidental findings in the radiographs. The authors concluded that seeing patient photos made radiologists both more effective and more empathic (ScienceDaily 2008 Dec 14).

So consider adding photos of your patients to your EMR. Then remember to take a second or two to look at them before engaging in the task to be done. You, and your patients, will be better off because of it.

Dr. Benabio is a partner physician in the department of dermatology of the Southern California Permanente Group in San Diego, and a volunteer clinical assistant professor at the University of California, San Diego. He is @dermdoc on Twitter. He has no conflicts related to the topic of this column.

I’m happier doing patient messages these days. That’s because of a little feature that we turned on in EPIC, our electronic medical record. The change doesn’t make me any faster or smarter. It doesn’t make me any more money. It merely adds a sprinkle of meaning to the work I do, and that has made all the difference.

In contrast to the usually glamorous portrayal of physicians’ work, most of our days are mundane. On a typical clinic day I’ll get up to a dozen requests from patients asking for something. Usually it’s just a refill, but several are from patients asking for a earlier appointment, when there are none. Or asking for a stronger treatment, when there aren’t any. Most of these requests are from patients who do not have interesting diagnoses or require sophisticated treatments. They are the itchy, and they remain itchy despite my advice. After a long day of seeing patients, the long list of messages that requires action feels endless, burdensome. Optimizing extenders has made me more efficient, but the work that remains isn’t fulfilling. A subtle change in our EMR has helped, though.

What is different? Our EPIC now includes a photo of each patient. That’s it. Ostensibly, having a photo is a security feature: it allows us to positively identify a patient, thereby reducing the risk that we treat an imposter posing as that patient (a small but real problem with drug seekers).

Why might this matter for physician satisfaction? Because seeing a patient photo brings an actual person to the top of mind. This changes our emotional connection to the work: how we interpret work is all that matters when it comes to job satisfaction. This is why volunteer work is so rewarding, despite having no monetary incentive, and why highly compensated professions, like those of many Wall Street traders, can ultimately fail to be fulfilling.

Tonight, long after the sun has set, I’m still working through messages. The next one, however, is not from any patient with nummular eczema. I see it’s from Mrs. Morales (not her real name), a sweet older woman with a warm smile and rich accent. She teaches water aerobics and she spent 5 minutes describing a typical Puerto Rican dinner (lots of stews) during her last appointment with me. Seeing her smiling face in the top left corner of the chart reminds me that the work I’m doing is for someone I know, someone I care for.

Radiologists have actually studied this phenomenon. Like much of medicine, radiology can be tedious. Researchers devised a simple test to see if making radiology work more human could improve not only the experience for, but also the effectiveness of, doctors. With patients’ consent, they took photos of 300 participants before their films were sent for reading. Radiologists who saw a patient’s photo along with their radiographic studies reported feeling more empathy for their patients. They also reported reading cases with photos more meticulously than those cases without photos. But that’s not all. When the radiologists were later shown the same films but without the patient photos, the doctors were less likely to notice incidental findings in the radiographs. The authors concluded that seeing patient photos made radiologists both more effective and more empathic (ScienceDaily 2008 Dec 14).

So consider adding photos of your patients to your EMR. Then remember to take a second or two to look at them before engaging in the task to be done. You, and your patients, will be better off because of it.

Dr. Benabio is a partner physician in the department of dermatology of the Southern California Permanente Group in San Diego, and a volunteer clinical assistant professor at the University of California, San Diego. He is @dermdoc on Twitter. He has no conflicts related to the topic of this column.

I’m happier doing patient messages these days. That’s because of a little feature that we turned on in EPIC, our electronic medical record. The change doesn’t make me any faster or smarter. It doesn’t make me any more money. It merely adds a sprinkle of meaning to the work I do, and that has made all the difference.

In contrast to the usually glamorous portrayal of physicians’ work, most of our days are mundane. On a typical clinic day I’ll get up to a dozen requests from patients asking for something. Usually it’s just a refill, but several are from patients asking for a earlier appointment, when there are none. Or asking for a stronger treatment, when there aren’t any. Most of these requests are from patients who do not have interesting diagnoses or require sophisticated treatments. They are the itchy, and they remain itchy despite my advice. After a long day of seeing patients, the long list of messages that requires action feels endless, burdensome. Optimizing extenders has made me more efficient, but the work that remains isn’t fulfilling. A subtle change in our EMR has helped, though.

What is different? Our EPIC now includes a photo of each patient. That’s it. Ostensibly, having a photo is a security feature: it allows us to positively identify a patient, thereby reducing the risk that we treat an imposter posing as that patient (a small but real problem with drug seekers).

Why might this matter for physician satisfaction? Because seeing a patient photo brings an actual person to the top of mind. This changes our emotional connection to the work: how we interpret work is all that matters when it comes to job satisfaction. This is why volunteer work is so rewarding, despite having no monetary incentive, and why highly compensated professions, like those of many Wall Street traders, can ultimately fail to be fulfilling.

Tonight, long after the sun has set, I’m still working through messages. The next one, however, is not from any patient with nummular eczema. I see it’s from Mrs. Morales (not her real name), a sweet older woman with a warm smile and rich accent. She teaches water aerobics and she spent 5 minutes describing a typical Puerto Rican dinner (lots of stews) during her last appointment with me. Seeing her smiling face in the top left corner of the chart reminds me that the work I’m doing is for someone I know, someone I care for.

Radiologists have actually studied this phenomenon. Like much of medicine, radiology can be tedious. Researchers devised a simple test to see if making radiology work more human could improve not only the experience for, but also the effectiveness of, doctors. With patients’ consent, they took photos of 300 participants before their films were sent for reading. Radiologists who saw a patient’s photo along with their radiographic studies reported feeling more empathy for their patients. They also reported reading cases with photos more meticulously than those cases without photos. But that’s not all. When the radiologists were later shown the same films but without the patient photos, the doctors were less likely to notice incidental findings in the radiographs. The authors concluded that seeing patient photos made radiologists both more effective and more empathic (ScienceDaily 2008 Dec 14).

So consider adding photos of your patients to your EMR. Then remember to take a second or two to look at them before engaging in the task to be done. You, and your patients, will be better off because of it.

Dr. Benabio is a partner physician in the department of dermatology of the Southern California Permanente Group in San Diego, and a volunteer clinical assistant professor at the University of California, San Diego. He is @dermdoc on Twitter. He has no conflicts related to the topic of this column.