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Managing alcohol withdrawal in the hospitalized patient
Symptom-triggered therapy has multiple benefits
Case
A 57-year-old man with a history of alcohol abuse (no history of seizures) presents to the ED “feeling awful.” He claims his last drink was 1 day prior. Initial vital signs are: T = 99.1°F, HR 102 bpm, BP 162/85 mm Hg, respirations 18/minute, and 99% oxygen saturation. He is tremulous, diaphoretic, and has an unsteady gait. What is the best way to manage his symptoms while hospitalized?
Brief overview of the issue
With over 15 million people with alcohol use disorder (AUD) in the United States alone, alcohol dependence and misuse remain significant issues among hospitalized patients.1 It is estimated that over 20% of admitted patients meet DSM-5 criteria for AUD and that over 2 million will withdraw each year.2,3 Acute withdrawal includes a spectrum of symptoms ranging from mild anxiety and diaphoresis to hallucinations, seizures, and delirium tremens. Onset of these symptoms ranges from 24 hours up to 5 days.
Severe alcohol withdrawal syndrome (SAWS) attributable to abrupt discontinuation of alcohol leads to increased morbidity and mortality; therefore, early detection and prevention in the acute care setting is critical. Several factors can help predict who may withdraw, and once detected, pharmacological treatment is necessary.4 Thorough evaluation and treatment can help reduce mortality from the most severe forms of alcohol withdrawal including delirium tremens, which has up to 40% mortality if left untreated.5
Overview of the data
How do we use benzodiazepines to treat alcohol withdrawal?
Benzodiazepines are the mainstay of alcohol withdrawal treatment. Benzodiazepines work by stimulating the gamma-aminobutyric acid (GABA) receptor resulting in a reduction of neuronal activity. This leads to a sedative effect and thus slows the progression of withdrawal symptoms.
Long-acting benzodiazepines, such as chlordiazepoxide and diazepam, are the preferred choices for most patients. Their active metabolites have a rapid onset of action and their long half-lives allow for a lower incidence of breakthrough symptoms and rebound phenomena such as seizures.6 Benzodiazepines with shorter half-lives, such as lorazepam and oxazepam, are preferred in patients with liver dysfunction and those prone to respiratory depression.
Intravenous administration has a rapid onset of action and is the standard administration route of choice in patients with acute severe withdrawal, delirium tremens, and seizure activity. In patients with mild withdrawal symptoms or those in the outpatient setting, oral administration is generally effective.6
The Clinical Institute Withdrawal Assessment (CIWA) is one commonly used titration model that requires calculation of a symptom-based withdrawal score. Data have consistently demonstrated that a symptom-triggered method results in administration of less total benzodiazepines over a significantly shorter duration, thereby reducing cost and duration of treatment and minimizing side effects. This regimen may also reduce the risk of undermedicating or overmedicating a patient since the dosing is based upon an individual’s symptoms.7,8
The efficacy of symptom-triggered regimens however, depends on the reliability and accuracy of the patient assessment. A fixed-interval benzodiazepine-dosing approach where benzodiazepines are administered regardless of symptoms is useful when frequent monitoring and reassessment are not feasible or are unreliable.
What about phenobarbital?
Phenobarbital has similar pharmacokinetics to the benzodiazepines frequently used for alcohol withdrawal, including simultaneous effects on gamma-aminobutyric acid (GABA) and N-methyl-D-aspartate (NMDA) receptors, and has been proposed as a treatment option for delirium tremens.
In 2019, as reported in the American Journal of Emergency Medicine, Nelson et al. found that incorporating phenobarbital into a benzodiazepine-based protocol or as sole agent led to similar rates of ICU admission, length of stay, and need for mechanical ventilation in patients treated for alcohol withdrawal in the emergency department.9 The authors concluded that “phenobarbital (was) a safe and effective treatment alternative for alcohol withdrawal.” The systematic review by Hammond et al. in 2017 found that phenobarbital, either as monotherapy or in conjunction with benzodiazepines, could have comparable or superior results in comparison to other treatments, including benzodiazepines monotherapy.10 Further studies are needed to determine dosing and the most effective way to incorporate the use of phenobarbital in treatment of Alcohol Withdrawal Syndrome (AWS).
Should gabapentin or any other medications be added to his treatment regimen?
Chronic alcohol use induces a reduction in GABA activity (the major inhibitory neurotransmitter in the brain) and alcohol cessation results in decreased inhibitory tone. This physiologic imbalance contributes to the syndrome of alcohol withdrawal. As such, gabapentin has emerged as a promising treatment option in AWS and may help reduce the need for benzodiazepines.
Gabapentin has few drug-drug interactions and is safe for use in patients with impaired liver function; however, dosage adjustment is required for renal dysfunction (CrCl less than 60 mL/min). Gabapentin’s neuroprotective effects may also help decrease the neurotoxic effects associated with AWS. Common side effects of gabapentin include dizziness, drowsiness, ataxia, diarrhea, nausea, and vomiting. The potential for misuse has been reported.
In several small studies, gabapentin monotherapy was found to be comparable to benzodiazepines in the treatment of mild to moderate AWS. Gabapentin is efficacious in reducing cravings as well as improving mood, anxiety, and sleep, and showed an advantage over benzodiazepines in preventing relapse with no difference in length of hospital stay.6,11 Given the small sample sizes of these studies and the differing methods, settings, and inclusion/ exclusion criteria used, the generalizability of these findings to patients with significant medical and/or psychiatric comorbidities remains limited. Additional studies are needed to standardize dosing protocols and treatment strategies for both inpatients and outpatients.
Alternative agents such as antipsychotics (e.g., haloperidol), centrally acting alpha-2 agonists (e.g., clonidine), beta-blockers, and an agonist of the GABA-B receptor (e.g., baclofen) may also attenuate the symptoms of withdrawal. Since these all have limited evidence of their efficacy and have potential for harm, such as masking symptoms of progressive withdrawal and lowering seizure threshold, these agents are not routinely recommended for use. Valproic acid/divalproex, levetiracetam, topiramate, and zonisamide have also showed some efficacy in reducing symptoms of alcohol withdrawal in limited studies. The data on prevention of withdrawal seizures or delirium tremens when used as monotherapy is less robust.12
A daily multivitamin and folate are ordered. What about thiamine? Does the route matter?
Alarmingly, 80% of people who chronically abuse alcohol are thiamine deficient.13 This deficiency is attributable to several factors including inadequate oral intake, malabsorption, and decreased cellular utilization. Thiamine is a crucial factor in multiple enzymatic and metabolic pathways. Its deficiency can lead to free radical production, neurotoxicity, impaired glucose metabolism, and ultimately, cell death.14 A clinical concern stemming from thiamine deficiency is the development of Wernicke’s encephalopathy (WE), which is potentially reversible with prompt recognition and treatment, in comparison to its irreversible amnestic sequela, Korsakoff’s syndrome.
Wernicke’s encephalopathy had been defined as a triad of ataxia, ophthalmoplegia, and global confusion. However, Harper et al. discovered that only 16% of patients presented with the classic triad and 19% had none of these signs.15 Diagnosis is clinical since thiamine serology results do not accurately represent brain storage.
Currently, there are no consistent guidelines regarding repletion of thiamine administration in the treatment or prevention of WE attributable to alcohol overuse. Thiamine has a safe toxicity profile as excess thiamine is excreted in the urine. Outside of rare reports of anaphylactoid reactions involving large parenteral doses, there is no concern for overtreatment. As Wernicke-Korsakoff syndrome is associated with significant morbidity and mortality, high doses such as 200 to 500 mg are recommended to ensure blood-brain barrier passage. The intravenous route is optimal over oral administration to bypass concerns of gastrointestinal malabsorption. Thiamine 100 mg by mouth daily for ongoing supplementation can be considered for patients who are at risk for WE. It is also important to recognize that magnesium and thiamine are intertwined in several key enzymatic pathways. To optimize the responsiveness of thiamine repletion, magnesium levels should be tested and repleted if low.
Application of the data to our patient
Nurses are able to frequently monitor the patient so he is started on symptom-triggered treatment with chlordiazepoxide using the CIWA protocol. This strategy will help limit the amount of benzodiazepines he receives and shorten his treatment duration. Given the ataxia, the patient is also started on high-dose IV thiamine three times a day to treat possible Wernicke’s encephalopathy. Gabapentin is added to his regimen to help manage his moderate alcohol withdrawal syndrome.
Bottom line
Long-acting benzodiazepines using symptom-triggered administration when feasible are the mainstay of treating alcohol withdrawal. Other medications such as gabapentin, carbamazepine, and phenobarbital can be considered as adjunctive agents. Given the high rate of thiamine deficiency and the low risk of overreplacement, intravenous thiamine can be considered for inpatients with AWS.
Dr. Agrawal, Dr. Chernyavsky, Dr. Dharapak, Dr. Grabscheid, Dr. Merrill, Dr. Pillay, and Dr. Rizk are hospitalists at Mount Sinai Beth Israel in New York.
References
1. CDC - Fact Sheets: “Alcohol Use And Health – Alcohol.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 3 Jan. 2018.
2. Rawlani V et al. Treatment of the hospitalized alcohol-dependent patient with alcohol withdrawal syndrome. Internet J Intern Med. 2008;8(1).
3. Grant BF et al. Epidemiology of DSM-5 alcohol use disorder: Results from the National Epidemiologic Survey on Alcohol and Related Conditions III. JAMA Psychiatry. 2015;72:757.
4. Wood E et al. Will this hospitalized patient develop severe alcohol withdrawal syndrome?: The Rational Clinical Examination Systematic Review. JAMA. 2018;320:825.
5. Sarkar S et al. Risk factors for the development of delirium in alcohol dependence syndrome: Clinical and neurobiological implications. Indian J Psychiatry. 2017 Jul-Sep;59(3):300-5.
6. Sachdeva A et al. Alcohol withdrawal syndrome: Benzodiazepines and beyond. J Clinical Diagn Res. 2015 Sep 9(9).
7. Sullivan JT et al. Benzodiazepine requirements during alcohol withdrawal syndrome: Clinical implications of using a standardized withdrawal scale. J Clin Psychopharmacol. 1991;11:291-5.
8. Saitz R et al. Individualized treatment for alcohol withdrawal. A randomized double-blind controlled trial. JAMA. 1994;272(7):519.
9. Nelson AC et al. Benzodiazepines vs. barbiturates for alcohol withdrawal: Analysis of 3 different treatment protocols. Am J Emerg Med. 2019 Jan 3.
10. Hammond DA et al. Patient outcomes associated with phenobarbital use with or without benzodiazepines for alcohol withdrawal syndrome: A systematic review. Hosp Pharm. 2017 Oct;52(9):607-16.
11. Mo Y et al. Current practice patterns in the management of alcohol withdrawal syndrome. P T. 2018 Mar;43(3):158-62.
12. Leung JG et al. The role of gabapentin in the management of alcohol withdrawal and dependence. Ann Pharmacother. 2015 Aug;49(8):897-906.
13. Martin P et al. The role of thiamine deficiency in alcoholic brain disease. Alcohol Res Health. 2003:27(2):134-42.
14. Flannery A et al. Unpeeling the evidence for the banana bag: Evidence-based recommendations for the management of alcohol-associated vitamin and electrolyte deficiencies in the ICU. Crit Care Med. 2016 Aug:44(8):1545-52.
15. Harper CG et al. Clinical signs in Wernicke Korsakoff complex: A retrospective analysis of 131 cases diagnosed at autopsy. J Neurol Neurosurg Psychiatry. 1986;49(4):341-5.
Key points
- Alcohol use disorder and alcohol withdrawal are significant problems in hospitalized patients; early detection and treatment are crucial in preventing high morbidity and mortality.
- Long acting benzodiazepines with active metabolites such as chlordiazepoxide and diazepam are the preferred treatment for alcohol withdrawal except for patients with advanced liver disease or those prone to respiratory depression.
- Symptom-triggered therapy decreases the amount of medication, shortens treatment duration, and decreases inpatient length of stay, compared with fixed schedule dosing.
- Gabapentin may be effective in the treatment of mild to moderate AWS but cannot yet be routinely recommended as monotherapy in severe withdrawal, in patients with seizure history, or in patients who are at high risk for progression to delirium tremens.
- Thiamine deficiency is common in chronic alcohol use disorders; thiamine repletion should be considered for patients at risk or when Wernicke’s encephalopathy and Korsakoff’s syndrome are suspected.
Additional reading
1. Perry EC. Inpatient management of acute alcohol withdrawal syndrome. CNS Drugs. 2014;28(5):401-10.
2. Mayo-Smith MF. Pharmacological management of alcohol withdrawal: A meta-analysis and evidence-based practice guideline. JAMA. 1997;278(2):144-51.
3. Michael F. Mayo-Smith, MD, MPH et al. for the Working Group on the Management of Alcohol Withdrawal Delirium, Practice Guidelines Committee, American Society of Addiction Medicine. Management of alcohol withdrawal delirium: An evidence-based practice guideline. Arch Intern Med. 2004;164(13):1405-12.
Quiz
A 51-year-old female with a history of hypertension and continuous alcohol abuse presents to the hospital with fever and cough. She is found to have community-acquired pneumonia and is admitted for treatment. How else would you manage this patient?
A. Start scheduled benzodiazepines and oral thiamine.
B. Start CIWA protocol using a long-acting benzodiazepine and oral thiamine.
C. Start scheduled benzodiazepines and IV thiamine.
D. Start CIWA protocol using a long-acting benzodiazepine and consider IV or oral thiamine.
Answer: D. Symptom-triggered benzodiazepine therapy is favored as is consideration for thiamine repletion in the treatment of AWS.
Symptom-triggered therapy has multiple benefits
Symptom-triggered therapy has multiple benefits
Case
A 57-year-old man with a history of alcohol abuse (no history of seizures) presents to the ED “feeling awful.” He claims his last drink was 1 day prior. Initial vital signs are: T = 99.1°F, HR 102 bpm, BP 162/85 mm Hg, respirations 18/minute, and 99% oxygen saturation. He is tremulous, diaphoretic, and has an unsteady gait. What is the best way to manage his symptoms while hospitalized?
Brief overview of the issue
With over 15 million people with alcohol use disorder (AUD) in the United States alone, alcohol dependence and misuse remain significant issues among hospitalized patients.1 It is estimated that over 20% of admitted patients meet DSM-5 criteria for AUD and that over 2 million will withdraw each year.2,3 Acute withdrawal includes a spectrum of symptoms ranging from mild anxiety and diaphoresis to hallucinations, seizures, and delirium tremens. Onset of these symptoms ranges from 24 hours up to 5 days.
Severe alcohol withdrawal syndrome (SAWS) attributable to abrupt discontinuation of alcohol leads to increased morbidity and mortality; therefore, early detection and prevention in the acute care setting is critical. Several factors can help predict who may withdraw, and once detected, pharmacological treatment is necessary.4 Thorough evaluation and treatment can help reduce mortality from the most severe forms of alcohol withdrawal including delirium tremens, which has up to 40% mortality if left untreated.5
Overview of the data
How do we use benzodiazepines to treat alcohol withdrawal?
Benzodiazepines are the mainstay of alcohol withdrawal treatment. Benzodiazepines work by stimulating the gamma-aminobutyric acid (GABA) receptor resulting in a reduction of neuronal activity. This leads to a sedative effect and thus slows the progression of withdrawal symptoms.
Long-acting benzodiazepines, such as chlordiazepoxide and diazepam, are the preferred choices for most patients. Their active metabolites have a rapid onset of action and their long half-lives allow for a lower incidence of breakthrough symptoms and rebound phenomena such as seizures.6 Benzodiazepines with shorter half-lives, such as lorazepam and oxazepam, are preferred in patients with liver dysfunction and those prone to respiratory depression.
Intravenous administration has a rapid onset of action and is the standard administration route of choice in patients with acute severe withdrawal, delirium tremens, and seizure activity. In patients with mild withdrawal symptoms or those in the outpatient setting, oral administration is generally effective.6
The Clinical Institute Withdrawal Assessment (CIWA) is one commonly used titration model that requires calculation of a symptom-based withdrawal score. Data have consistently demonstrated that a symptom-triggered method results in administration of less total benzodiazepines over a significantly shorter duration, thereby reducing cost and duration of treatment and minimizing side effects. This regimen may also reduce the risk of undermedicating or overmedicating a patient since the dosing is based upon an individual’s symptoms.7,8
The efficacy of symptom-triggered regimens however, depends on the reliability and accuracy of the patient assessment. A fixed-interval benzodiazepine-dosing approach where benzodiazepines are administered regardless of symptoms is useful when frequent monitoring and reassessment are not feasible or are unreliable.
What about phenobarbital?
Phenobarbital has similar pharmacokinetics to the benzodiazepines frequently used for alcohol withdrawal, including simultaneous effects on gamma-aminobutyric acid (GABA) and N-methyl-D-aspartate (NMDA) receptors, and has been proposed as a treatment option for delirium tremens.
In 2019, as reported in the American Journal of Emergency Medicine, Nelson et al. found that incorporating phenobarbital into a benzodiazepine-based protocol or as sole agent led to similar rates of ICU admission, length of stay, and need for mechanical ventilation in patients treated for alcohol withdrawal in the emergency department.9 The authors concluded that “phenobarbital (was) a safe and effective treatment alternative for alcohol withdrawal.” The systematic review by Hammond et al. in 2017 found that phenobarbital, either as monotherapy or in conjunction with benzodiazepines, could have comparable or superior results in comparison to other treatments, including benzodiazepines monotherapy.10 Further studies are needed to determine dosing and the most effective way to incorporate the use of phenobarbital in treatment of Alcohol Withdrawal Syndrome (AWS).
Should gabapentin or any other medications be added to his treatment regimen?
Chronic alcohol use induces a reduction in GABA activity (the major inhibitory neurotransmitter in the brain) and alcohol cessation results in decreased inhibitory tone. This physiologic imbalance contributes to the syndrome of alcohol withdrawal. As such, gabapentin has emerged as a promising treatment option in AWS and may help reduce the need for benzodiazepines.
Gabapentin has few drug-drug interactions and is safe for use in patients with impaired liver function; however, dosage adjustment is required for renal dysfunction (CrCl less than 60 mL/min). Gabapentin’s neuroprotective effects may also help decrease the neurotoxic effects associated with AWS. Common side effects of gabapentin include dizziness, drowsiness, ataxia, diarrhea, nausea, and vomiting. The potential for misuse has been reported.
In several small studies, gabapentin monotherapy was found to be comparable to benzodiazepines in the treatment of mild to moderate AWS. Gabapentin is efficacious in reducing cravings as well as improving mood, anxiety, and sleep, and showed an advantage over benzodiazepines in preventing relapse with no difference in length of hospital stay.6,11 Given the small sample sizes of these studies and the differing methods, settings, and inclusion/ exclusion criteria used, the generalizability of these findings to patients with significant medical and/or psychiatric comorbidities remains limited. Additional studies are needed to standardize dosing protocols and treatment strategies for both inpatients and outpatients.
Alternative agents such as antipsychotics (e.g., haloperidol), centrally acting alpha-2 agonists (e.g., clonidine), beta-blockers, and an agonist of the GABA-B receptor (e.g., baclofen) may also attenuate the symptoms of withdrawal. Since these all have limited evidence of their efficacy and have potential for harm, such as masking symptoms of progressive withdrawal and lowering seizure threshold, these agents are not routinely recommended for use. Valproic acid/divalproex, levetiracetam, topiramate, and zonisamide have also showed some efficacy in reducing symptoms of alcohol withdrawal in limited studies. The data on prevention of withdrawal seizures or delirium tremens when used as monotherapy is less robust.12
A daily multivitamin and folate are ordered. What about thiamine? Does the route matter?
Alarmingly, 80% of people who chronically abuse alcohol are thiamine deficient.13 This deficiency is attributable to several factors including inadequate oral intake, malabsorption, and decreased cellular utilization. Thiamine is a crucial factor in multiple enzymatic and metabolic pathways. Its deficiency can lead to free radical production, neurotoxicity, impaired glucose metabolism, and ultimately, cell death.14 A clinical concern stemming from thiamine deficiency is the development of Wernicke’s encephalopathy (WE), which is potentially reversible with prompt recognition and treatment, in comparison to its irreversible amnestic sequela, Korsakoff’s syndrome.
Wernicke’s encephalopathy had been defined as a triad of ataxia, ophthalmoplegia, and global confusion. However, Harper et al. discovered that only 16% of patients presented with the classic triad and 19% had none of these signs.15 Diagnosis is clinical since thiamine serology results do not accurately represent brain storage.
Currently, there are no consistent guidelines regarding repletion of thiamine administration in the treatment or prevention of WE attributable to alcohol overuse. Thiamine has a safe toxicity profile as excess thiamine is excreted in the urine. Outside of rare reports of anaphylactoid reactions involving large parenteral doses, there is no concern for overtreatment. As Wernicke-Korsakoff syndrome is associated with significant morbidity and mortality, high doses such as 200 to 500 mg are recommended to ensure blood-brain barrier passage. The intravenous route is optimal over oral administration to bypass concerns of gastrointestinal malabsorption. Thiamine 100 mg by mouth daily for ongoing supplementation can be considered for patients who are at risk for WE. It is also important to recognize that magnesium and thiamine are intertwined in several key enzymatic pathways. To optimize the responsiveness of thiamine repletion, magnesium levels should be tested and repleted if low.
Application of the data to our patient
Nurses are able to frequently monitor the patient so he is started on symptom-triggered treatment with chlordiazepoxide using the CIWA protocol. This strategy will help limit the amount of benzodiazepines he receives and shorten his treatment duration. Given the ataxia, the patient is also started on high-dose IV thiamine three times a day to treat possible Wernicke’s encephalopathy. Gabapentin is added to his regimen to help manage his moderate alcohol withdrawal syndrome.
Bottom line
Long-acting benzodiazepines using symptom-triggered administration when feasible are the mainstay of treating alcohol withdrawal. Other medications such as gabapentin, carbamazepine, and phenobarbital can be considered as adjunctive agents. Given the high rate of thiamine deficiency and the low risk of overreplacement, intravenous thiamine can be considered for inpatients with AWS.
Dr. Agrawal, Dr. Chernyavsky, Dr. Dharapak, Dr. Grabscheid, Dr. Merrill, Dr. Pillay, and Dr. Rizk are hospitalists at Mount Sinai Beth Israel in New York.
References
1. CDC - Fact Sheets: “Alcohol Use And Health – Alcohol.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 3 Jan. 2018.
2. Rawlani V et al. Treatment of the hospitalized alcohol-dependent patient with alcohol withdrawal syndrome. Internet J Intern Med. 2008;8(1).
3. Grant BF et al. Epidemiology of DSM-5 alcohol use disorder: Results from the National Epidemiologic Survey on Alcohol and Related Conditions III. JAMA Psychiatry. 2015;72:757.
4. Wood E et al. Will this hospitalized patient develop severe alcohol withdrawal syndrome?: The Rational Clinical Examination Systematic Review. JAMA. 2018;320:825.
5. Sarkar S et al. Risk factors for the development of delirium in alcohol dependence syndrome: Clinical and neurobiological implications. Indian J Psychiatry. 2017 Jul-Sep;59(3):300-5.
6. Sachdeva A et al. Alcohol withdrawal syndrome: Benzodiazepines and beyond. J Clinical Diagn Res. 2015 Sep 9(9).
7. Sullivan JT et al. Benzodiazepine requirements during alcohol withdrawal syndrome: Clinical implications of using a standardized withdrawal scale. J Clin Psychopharmacol. 1991;11:291-5.
8. Saitz R et al. Individualized treatment for alcohol withdrawal. A randomized double-blind controlled trial. JAMA. 1994;272(7):519.
9. Nelson AC et al. Benzodiazepines vs. barbiturates for alcohol withdrawal: Analysis of 3 different treatment protocols. Am J Emerg Med. 2019 Jan 3.
10. Hammond DA et al. Patient outcomes associated with phenobarbital use with or without benzodiazepines for alcohol withdrawal syndrome: A systematic review. Hosp Pharm. 2017 Oct;52(9):607-16.
11. Mo Y et al. Current practice patterns in the management of alcohol withdrawal syndrome. P T. 2018 Mar;43(3):158-62.
12. Leung JG et al. The role of gabapentin in the management of alcohol withdrawal and dependence. Ann Pharmacother. 2015 Aug;49(8):897-906.
13. Martin P et al. The role of thiamine deficiency in alcoholic brain disease. Alcohol Res Health. 2003:27(2):134-42.
14. Flannery A et al. Unpeeling the evidence for the banana bag: Evidence-based recommendations for the management of alcohol-associated vitamin and electrolyte deficiencies in the ICU. Crit Care Med. 2016 Aug:44(8):1545-52.
15. Harper CG et al. Clinical signs in Wernicke Korsakoff complex: A retrospective analysis of 131 cases diagnosed at autopsy. J Neurol Neurosurg Psychiatry. 1986;49(4):341-5.
Key points
- Alcohol use disorder and alcohol withdrawal are significant problems in hospitalized patients; early detection and treatment are crucial in preventing high morbidity and mortality.
- Long acting benzodiazepines with active metabolites such as chlordiazepoxide and diazepam are the preferred treatment for alcohol withdrawal except for patients with advanced liver disease or those prone to respiratory depression.
- Symptom-triggered therapy decreases the amount of medication, shortens treatment duration, and decreases inpatient length of stay, compared with fixed schedule dosing.
- Gabapentin may be effective in the treatment of mild to moderate AWS but cannot yet be routinely recommended as monotherapy in severe withdrawal, in patients with seizure history, or in patients who are at high risk for progression to delirium tremens.
- Thiamine deficiency is common in chronic alcohol use disorders; thiamine repletion should be considered for patients at risk or when Wernicke’s encephalopathy and Korsakoff’s syndrome are suspected.
Additional reading
1. Perry EC. Inpatient management of acute alcohol withdrawal syndrome. CNS Drugs. 2014;28(5):401-10.
2. Mayo-Smith MF. Pharmacological management of alcohol withdrawal: A meta-analysis and evidence-based practice guideline. JAMA. 1997;278(2):144-51.
3. Michael F. Mayo-Smith, MD, MPH et al. for the Working Group on the Management of Alcohol Withdrawal Delirium, Practice Guidelines Committee, American Society of Addiction Medicine. Management of alcohol withdrawal delirium: An evidence-based practice guideline. Arch Intern Med. 2004;164(13):1405-12.
Quiz
A 51-year-old female with a history of hypertension and continuous alcohol abuse presents to the hospital with fever and cough. She is found to have community-acquired pneumonia and is admitted for treatment. How else would you manage this patient?
A. Start scheduled benzodiazepines and oral thiamine.
B. Start CIWA protocol using a long-acting benzodiazepine and oral thiamine.
C. Start scheduled benzodiazepines and IV thiamine.
D. Start CIWA protocol using a long-acting benzodiazepine and consider IV or oral thiamine.
Answer: D. Symptom-triggered benzodiazepine therapy is favored as is consideration for thiamine repletion in the treatment of AWS.
Case
A 57-year-old man with a history of alcohol abuse (no history of seizures) presents to the ED “feeling awful.” He claims his last drink was 1 day prior. Initial vital signs are: T = 99.1°F, HR 102 bpm, BP 162/85 mm Hg, respirations 18/minute, and 99% oxygen saturation. He is tremulous, diaphoretic, and has an unsteady gait. What is the best way to manage his symptoms while hospitalized?
Brief overview of the issue
With over 15 million people with alcohol use disorder (AUD) in the United States alone, alcohol dependence and misuse remain significant issues among hospitalized patients.1 It is estimated that over 20% of admitted patients meet DSM-5 criteria for AUD and that over 2 million will withdraw each year.2,3 Acute withdrawal includes a spectrum of symptoms ranging from mild anxiety and diaphoresis to hallucinations, seizures, and delirium tremens. Onset of these symptoms ranges from 24 hours up to 5 days.
Severe alcohol withdrawal syndrome (SAWS) attributable to abrupt discontinuation of alcohol leads to increased morbidity and mortality; therefore, early detection and prevention in the acute care setting is critical. Several factors can help predict who may withdraw, and once detected, pharmacological treatment is necessary.4 Thorough evaluation and treatment can help reduce mortality from the most severe forms of alcohol withdrawal including delirium tremens, which has up to 40% mortality if left untreated.5
Overview of the data
How do we use benzodiazepines to treat alcohol withdrawal?
Benzodiazepines are the mainstay of alcohol withdrawal treatment. Benzodiazepines work by stimulating the gamma-aminobutyric acid (GABA) receptor resulting in a reduction of neuronal activity. This leads to a sedative effect and thus slows the progression of withdrawal symptoms.
Long-acting benzodiazepines, such as chlordiazepoxide and diazepam, are the preferred choices for most patients. Their active metabolites have a rapid onset of action and their long half-lives allow for a lower incidence of breakthrough symptoms and rebound phenomena such as seizures.6 Benzodiazepines with shorter half-lives, such as lorazepam and oxazepam, are preferred in patients with liver dysfunction and those prone to respiratory depression.
Intravenous administration has a rapid onset of action and is the standard administration route of choice in patients with acute severe withdrawal, delirium tremens, and seizure activity. In patients with mild withdrawal symptoms or those in the outpatient setting, oral administration is generally effective.6
The Clinical Institute Withdrawal Assessment (CIWA) is one commonly used titration model that requires calculation of a symptom-based withdrawal score. Data have consistently demonstrated that a symptom-triggered method results in administration of less total benzodiazepines over a significantly shorter duration, thereby reducing cost and duration of treatment and minimizing side effects. This regimen may also reduce the risk of undermedicating or overmedicating a patient since the dosing is based upon an individual’s symptoms.7,8
The efficacy of symptom-triggered regimens however, depends on the reliability and accuracy of the patient assessment. A fixed-interval benzodiazepine-dosing approach where benzodiazepines are administered regardless of symptoms is useful when frequent monitoring and reassessment are not feasible or are unreliable.
What about phenobarbital?
Phenobarbital has similar pharmacokinetics to the benzodiazepines frequently used for alcohol withdrawal, including simultaneous effects on gamma-aminobutyric acid (GABA) and N-methyl-D-aspartate (NMDA) receptors, and has been proposed as a treatment option for delirium tremens.
In 2019, as reported in the American Journal of Emergency Medicine, Nelson et al. found that incorporating phenobarbital into a benzodiazepine-based protocol or as sole agent led to similar rates of ICU admission, length of stay, and need for mechanical ventilation in patients treated for alcohol withdrawal in the emergency department.9 The authors concluded that “phenobarbital (was) a safe and effective treatment alternative for alcohol withdrawal.” The systematic review by Hammond et al. in 2017 found that phenobarbital, either as monotherapy or in conjunction with benzodiazepines, could have comparable or superior results in comparison to other treatments, including benzodiazepines monotherapy.10 Further studies are needed to determine dosing and the most effective way to incorporate the use of phenobarbital in treatment of Alcohol Withdrawal Syndrome (AWS).
Should gabapentin or any other medications be added to his treatment regimen?
Chronic alcohol use induces a reduction in GABA activity (the major inhibitory neurotransmitter in the brain) and alcohol cessation results in decreased inhibitory tone. This physiologic imbalance contributes to the syndrome of alcohol withdrawal. As such, gabapentin has emerged as a promising treatment option in AWS and may help reduce the need for benzodiazepines.
Gabapentin has few drug-drug interactions and is safe for use in patients with impaired liver function; however, dosage adjustment is required for renal dysfunction (CrCl less than 60 mL/min). Gabapentin’s neuroprotective effects may also help decrease the neurotoxic effects associated with AWS. Common side effects of gabapentin include dizziness, drowsiness, ataxia, diarrhea, nausea, and vomiting. The potential for misuse has been reported.
In several small studies, gabapentin monotherapy was found to be comparable to benzodiazepines in the treatment of mild to moderate AWS. Gabapentin is efficacious in reducing cravings as well as improving mood, anxiety, and sleep, and showed an advantage over benzodiazepines in preventing relapse with no difference in length of hospital stay.6,11 Given the small sample sizes of these studies and the differing methods, settings, and inclusion/ exclusion criteria used, the generalizability of these findings to patients with significant medical and/or psychiatric comorbidities remains limited. Additional studies are needed to standardize dosing protocols and treatment strategies for both inpatients and outpatients.
Alternative agents such as antipsychotics (e.g., haloperidol), centrally acting alpha-2 agonists (e.g., clonidine), beta-blockers, and an agonist of the GABA-B receptor (e.g., baclofen) may also attenuate the symptoms of withdrawal. Since these all have limited evidence of their efficacy and have potential for harm, such as masking symptoms of progressive withdrawal and lowering seizure threshold, these agents are not routinely recommended for use. Valproic acid/divalproex, levetiracetam, topiramate, and zonisamide have also showed some efficacy in reducing symptoms of alcohol withdrawal in limited studies. The data on prevention of withdrawal seizures or delirium tremens when used as monotherapy is less robust.12
A daily multivitamin and folate are ordered. What about thiamine? Does the route matter?
Alarmingly, 80% of people who chronically abuse alcohol are thiamine deficient.13 This deficiency is attributable to several factors including inadequate oral intake, malabsorption, and decreased cellular utilization. Thiamine is a crucial factor in multiple enzymatic and metabolic pathways. Its deficiency can lead to free radical production, neurotoxicity, impaired glucose metabolism, and ultimately, cell death.14 A clinical concern stemming from thiamine deficiency is the development of Wernicke’s encephalopathy (WE), which is potentially reversible with prompt recognition and treatment, in comparison to its irreversible amnestic sequela, Korsakoff’s syndrome.
Wernicke’s encephalopathy had been defined as a triad of ataxia, ophthalmoplegia, and global confusion. However, Harper et al. discovered that only 16% of patients presented with the classic triad and 19% had none of these signs.15 Diagnosis is clinical since thiamine serology results do not accurately represent brain storage.
Currently, there are no consistent guidelines regarding repletion of thiamine administration in the treatment or prevention of WE attributable to alcohol overuse. Thiamine has a safe toxicity profile as excess thiamine is excreted in the urine. Outside of rare reports of anaphylactoid reactions involving large parenteral doses, there is no concern for overtreatment. As Wernicke-Korsakoff syndrome is associated with significant morbidity and mortality, high doses such as 200 to 500 mg are recommended to ensure blood-brain barrier passage. The intravenous route is optimal over oral administration to bypass concerns of gastrointestinal malabsorption. Thiamine 100 mg by mouth daily for ongoing supplementation can be considered for patients who are at risk for WE. It is also important to recognize that magnesium and thiamine are intertwined in several key enzymatic pathways. To optimize the responsiveness of thiamine repletion, magnesium levels should be tested and repleted if low.
Application of the data to our patient
Nurses are able to frequently monitor the patient so he is started on symptom-triggered treatment with chlordiazepoxide using the CIWA protocol. This strategy will help limit the amount of benzodiazepines he receives and shorten his treatment duration. Given the ataxia, the patient is also started on high-dose IV thiamine three times a day to treat possible Wernicke’s encephalopathy. Gabapentin is added to his regimen to help manage his moderate alcohol withdrawal syndrome.
Bottom line
Long-acting benzodiazepines using symptom-triggered administration when feasible are the mainstay of treating alcohol withdrawal. Other medications such as gabapentin, carbamazepine, and phenobarbital can be considered as adjunctive agents. Given the high rate of thiamine deficiency and the low risk of overreplacement, intravenous thiamine can be considered for inpatients with AWS.
Dr. Agrawal, Dr. Chernyavsky, Dr. Dharapak, Dr. Grabscheid, Dr. Merrill, Dr. Pillay, and Dr. Rizk are hospitalists at Mount Sinai Beth Israel in New York.
References
1. CDC - Fact Sheets: “Alcohol Use And Health – Alcohol.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 3 Jan. 2018.
2. Rawlani V et al. Treatment of the hospitalized alcohol-dependent patient with alcohol withdrawal syndrome. Internet J Intern Med. 2008;8(1).
3. Grant BF et al. Epidemiology of DSM-5 alcohol use disorder: Results from the National Epidemiologic Survey on Alcohol and Related Conditions III. JAMA Psychiatry. 2015;72:757.
4. Wood E et al. Will this hospitalized patient develop severe alcohol withdrawal syndrome?: The Rational Clinical Examination Systematic Review. JAMA. 2018;320:825.
5. Sarkar S et al. Risk factors for the development of delirium in alcohol dependence syndrome: Clinical and neurobiological implications. Indian J Psychiatry. 2017 Jul-Sep;59(3):300-5.
6. Sachdeva A et al. Alcohol withdrawal syndrome: Benzodiazepines and beyond. J Clinical Diagn Res. 2015 Sep 9(9).
7. Sullivan JT et al. Benzodiazepine requirements during alcohol withdrawal syndrome: Clinical implications of using a standardized withdrawal scale. J Clin Psychopharmacol. 1991;11:291-5.
8. Saitz R et al. Individualized treatment for alcohol withdrawal. A randomized double-blind controlled trial. JAMA. 1994;272(7):519.
9. Nelson AC et al. Benzodiazepines vs. barbiturates for alcohol withdrawal: Analysis of 3 different treatment protocols. Am J Emerg Med. 2019 Jan 3.
10. Hammond DA et al. Patient outcomes associated with phenobarbital use with or without benzodiazepines for alcohol withdrawal syndrome: A systematic review. Hosp Pharm. 2017 Oct;52(9):607-16.
11. Mo Y et al. Current practice patterns in the management of alcohol withdrawal syndrome. P T. 2018 Mar;43(3):158-62.
12. Leung JG et al. The role of gabapentin in the management of alcohol withdrawal and dependence. Ann Pharmacother. 2015 Aug;49(8):897-906.
13. Martin P et al. The role of thiamine deficiency in alcoholic brain disease. Alcohol Res Health. 2003:27(2):134-42.
14. Flannery A et al. Unpeeling the evidence for the banana bag: Evidence-based recommendations for the management of alcohol-associated vitamin and electrolyte deficiencies in the ICU. Crit Care Med. 2016 Aug:44(8):1545-52.
15. Harper CG et al. Clinical signs in Wernicke Korsakoff complex: A retrospective analysis of 131 cases diagnosed at autopsy. J Neurol Neurosurg Psychiatry. 1986;49(4):341-5.
Key points
- Alcohol use disorder and alcohol withdrawal are significant problems in hospitalized patients; early detection and treatment are crucial in preventing high morbidity and mortality.
- Long acting benzodiazepines with active metabolites such as chlordiazepoxide and diazepam are the preferred treatment for alcohol withdrawal except for patients with advanced liver disease or those prone to respiratory depression.
- Symptom-triggered therapy decreases the amount of medication, shortens treatment duration, and decreases inpatient length of stay, compared with fixed schedule dosing.
- Gabapentin may be effective in the treatment of mild to moderate AWS but cannot yet be routinely recommended as monotherapy in severe withdrawal, in patients with seizure history, or in patients who are at high risk for progression to delirium tremens.
- Thiamine deficiency is common in chronic alcohol use disorders; thiamine repletion should be considered for patients at risk or when Wernicke’s encephalopathy and Korsakoff’s syndrome are suspected.
Additional reading
1. Perry EC. Inpatient management of acute alcohol withdrawal syndrome. CNS Drugs. 2014;28(5):401-10.
2. Mayo-Smith MF. Pharmacological management of alcohol withdrawal: A meta-analysis and evidence-based practice guideline. JAMA. 1997;278(2):144-51.
3. Michael F. Mayo-Smith, MD, MPH et al. for the Working Group on the Management of Alcohol Withdrawal Delirium, Practice Guidelines Committee, American Society of Addiction Medicine. Management of alcohol withdrawal delirium: An evidence-based practice guideline. Arch Intern Med. 2004;164(13):1405-12.
Quiz
A 51-year-old female with a history of hypertension and continuous alcohol abuse presents to the hospital with fever and cough. She is found to have community-acquired pneumonia and is admitted for treatment. How else would you manage this patient?
A. Start scheduled benzodiazepines and oral thiamine.
B. Start CIWA protocol using a long-acting benzodiazepine and oral thiamine.
C. Start scheduled benzodiazepines and IV thiamine.
D. Start CIWA protocol using a long-acting benzodiazepine and consider IV or oral thiamine.
Answer: D. Symptom-triggered benzodiazepine therapy is favored as is consideration for thiamine repletion in the treatment of AWS.
Hospital-acquired C. diff. tied to four ‘high-risk’ antibiotic classes
The use of four antibiotic classes designated “high risk” was found to be an independent predictor of hospital-acquired Clostridioides difficile (CDI), based upon an analysis of microbiologic and pharmacy data from 171 hospitals in the United States.
The high-risk antibiotic classes were second-, third-, and fourth-generation cephalosporins, fluoroquinolones, carbapenems, and lincosamides, according to a report by Ying P. Tabak, PhD, of Becton Dickinson in Franklin Lakes, N.J., and colleagues published in Infection Control & Hospital Epidemiology.
Of the 171 study sites studied, 66 (39%) were teaching hospitals and 105 (61%) were nonteaching hospitals. The high-risk antibiotics most frequently used were cephalosporins (47.9%), fluoroquinolones (31.6%), carbapenems (13.0%), and lincosamides (7.6%). The sites were distributed across various regions of the United States. The hospital-level antibiotic use was measured as days of therapy (DOT) per 1,000 days present (DP).
The study was not able to determine specific links to individual antibiotic classes but to the use of high-risk antibiotics as a whole, except for cephalosporins, which were significantly correlated with hospital-acquired CDI (r = 0.23; P less than .01).
The overall correlation of high-risk antibiotic use and hospital-acquired CDI was 0.22 (P = .003). Higher correlation was observed in teaching hospitals (r = 0.38; P = .002) versus nonteaching hospitals (r = 0.19; P = .055), according to the researchers. The authors attributed this to the possibility of teaching hospitals dealing with more elderly and sicker patients.
After adjusting for significant confounders, the use of high-risk antibiotics was still independently associated with significant risk for hospital-acquired CDI. “For every 100-day increase of DOT per 1,000 DP in high-risk antibiotic use, there was a 12% increase in [hospital-acquired] CDI (RR, 1.12; 95% [confidence interval], 1.04-1.21; P = .002),” according to the authors. This translated to four additional hospital-acquired CDI cases with every 100 DOT increase per 1,000 DP.
“Using a large and current dataset, we found an independent impact of hospital-level high-risk antibiotic use on [hospital-acquired] CDI even after adjusting for confounding factors such as community CDI pressure, proportion of patients aged 65 years or older, average length of stay, and hospital teaching status,” the researchers concluded.
Funding was provided by Nabriva Therapeutics, an antibiotic development company. Four of the authors are full-time employees of Becton Dickinson, which sells diagnostics for infectious diseases, including CDI, and one author was an employee of Nabriva Therapeutics.
SOURCE: Tabak YP et al. Infect Control Hosp Epidemiol. 2019 Sep 16. doi: 10.1017/ice.2019.236.
The use of four antibiotic classes designated “high risk” was found to be an independent predictor of hospital-acquired Clostridioides difficile (CDI), based upon an analysis of microbiologic and pharmacy data from 171 hospitals in the United States.
The high-risk antibiotic classes were second-, third-, and fourth-generation cephalosporins, fluoroquinolones, carbapenems, and lincosamides, according to a report by Ying P. Tabak, PhD, of Becton Dickinson in Franklin Lakes, N.J., and colleagues published in Infection Control & Hospital Epidemiology.
Of the 171 study sites studied, 66 (39%) were teaching hospitals and 105 (61%) were nonteaching hospitals. The high-risk antibiotics most frequently used were cephalosporins (47.9%), fluoroquinolones (31.6%), carbapenems (13.0%), and lincosamides (7.6%). The sites were distributed across various regions of the United States. The hospital-level antibiotic use was measured as days of therapy (DOT) per 1,000 days present (DP).
The study was not able to determine specific links to individual antibiotic classes but to the use of high-risk antibiotics as a whole, except for cephalosporins, which were significantly correlated with hospital-acquired CDI (r = 0.23; P less than .01).
The overall correlation of high-risk antibiotic use and hospital-acquired CDI was 0.22 (P = .003). Higher correlation was observed in teaching hospitals (r = 0.38; P = .002) versus nonteaching hospitals (r = 0.19; P = .055), according to the researchers. The authors attributed this to the possibility of teaching hospitals dealing with more elderly and sicker patients.
After adjusting for significant confounders, the use of high-risk antibiotics was still independently associated with significant risk for hospital-acquired CDI. “For every 100-day increase of DOT per 1,000 DP in high-risk antibiotic use, there was a 12% increase in [hospital-acquired] CDI (RR, 1.12; 95% [confidence interval], 1.04-1.21; P = .002),” according to the authors. This translated to four additional hospital-acquired CDI cases with every 100 DOT increase per 1,000 DP.
“Using a large and current dataset, we found an independent impact of hospital-level high-risk antibiotic use on [hospital-acquired] CDI even after adjusting for confounding factors such as community CDI pressure, proportion of patients aged 65 years or older, average length of stay, and hospital teaching status,” the researchers concluded.
Funding was provided by Nabriva Therapeutics, an antibiotic development company. Four of the authors are full-time employees of Becton Dickinson, which sells diagnostics for infectious diseases, including CDI, and one author was an employee of Nabriva Therapeutics.
SOURCE: Tabak YP et al. Infect Control Hosp Epidemiol. 2019 Sep 16. doi: 10.1017/ice.2019.236.
The use of four antibiotic classes designated “high risk” was found to be an independent predictor of hospital-acquired Clostridioides difficile (CDI), based upon an analysis of microbiologic and pharmacy data from 171 hospitals in the United States.
The high-risk antibiotic classes were second-, third-, and fourth-generation cephalosporins, fluoroquinolones, carbapenems, and lincosamides, according to a report by Ying P. Tabak, PhD, of Becton Dickinson in Franklin Lakes, N.J., and colleagues published in Infection Control & Hospital Epidemiology.
Of the 171 study sites studied, 66 (39%) were teaching hospitals and 105 (61%) were nonteaching hospitals. The high-risk antibiotics most frequently used were cephalosporins (47.9%), fluoroquinolones (31.6%), carbapenems (13.0%), and lincosamides (7.6%). The sites were distributed across various regions of the United States. The hospital-level antibiotic use was measured as days of therapy (DOT) per 1,000 days present (DP).
The study was not able to determine specific links to individual antibiotic classes but to the use of high-risk antibiotics as a whole, except for cephalosporins, which were significantly correlated with hospital-acquired CDI (r = 0.23; P less than .01).
The overall correlation of high-risk antibiotic use and hospital-acquired CDI was 0.22 (P = .003). Higher correlation was observed in teaching hospitals (r = 0.38; P = .002) versus nonteaching hospitals (r = 0.19; P = .055), according to the researchers. The authors attributed this to the possibility of teaching hospitals dealing with more elderly and sicker patients.
After adjusting for significant confounders, the use of high-risk antibiotics was still independently associated with significant risk for hospital-acquired CDI. “For every 100-day increase of DOT per 1,000 DP in high-risk antibiotic use, there was a 12% increase in [hospital-acquired] CDI (RR, 1.12; 95% [confidence interval], 1.04-1.21; P = .002),” according to the authors. This translated to four additional hospital-acquired CDI cases with every 100 DOT increase per 1,000 DP.
“Using a large and current dataset, we found an independent impact of hospital-level high-risk antibiotic use on [hospital-acquired] CDI even after adjusting for confounding factors such as community CDI pressure, proportion of patients aged 65 years or older, average length of stay, and hospital teaching status,” the researchers concluded.
Funding was provided by Nabriva Therapeutics, an antibiotic development company. Four of the authors are full-time employees of Becton Dickinson, which sells diagnostics for infectious diseases, including CDI, and one author was an employee of Nabriva Therapeutics.
SOURCE: Tabak YP et al. Infect Control Hosp Epidemiol. 2019 Sep 16. doi: 10.1017/ice.2019.236.
FROM INFECTION CONTROL & HOSPITAL EPIDEMIOLOGY
Key clinical point:
Major finding: For every 100-day increase in high-risk antibiotic therapy, there was a 12% increase in hospital-acquired C. difficile.
Study details: Microbiological and pharmacy data from 171 hospitals comparing hospitalwide use of four antibiotics classes on hospital-acquired C. difficile.
Disclosures: Funding was provided Nabriva Therapeutics, an antibiotic development company. Four of the authors are full-time employees of Becton Dickinson, which sells diagnostics for infectious diseases, including C. difficile, and one author was an employee of Nabriva Therapeutics.
Source: Tabak YP et al. Infect Control Hosp Epidemiol. 2019 Sep 16. doi: 10.1017/ice.2019.236.
Short Takes
Pharmacist-led intervention reduced inappropriate medication prescriptions
An outpatient pharmacy-led intervention of notifying prescribing physicians to discontinue inappropriate Beers Criteria medications resulted in a greater discontinuation of inappropriate medications for older adults at 6 months, compared with the control group (43% vs. 12% discontinuation).
Citation: Martin P et al. Effect of a pharmacist-led educational intervention on inappropriate medication prescriptions in older adults: The D-PRESCRIBE randomized clinical trial. JAMA. 2018;320(18):1889-98.
Omadacycline noninferior for community-acquired pneumonia and acute bacterial soft tissue skin infections
Randomized, double-blind, double-dummy trials showed omadacycline is a noninferior alternative to moxifloxacin for the treatment of community-acquired pneumonia and to linezolid for acute bacterial soft-tissue skin infections.
Citation: Nuzyra (omadacycline) [package insert]. Boston, MA: Paratek Pharmaceuticals. 2018.
Lack of evidence to support low-salt diet in adult heart failure patients
Systematic review of multiple databases demonstrated there is limited high-quality evidence to support current guidelines that recommend a low-salt diet to heart failure patients.
Citation: Mahtani KR et al. Reduced salt intake for heart failure: A systematic review. JAMA Int Med. 2018;178(12):1693-700.
Magnesium for rate control in rapid atrial fibrillation
Randomized, controlled trial demonstrated that intravenous magnesium sulfate in combination with atrioventricular (AV) nodal blocking agents resulted in better rate control for atrial fibrillation with rapid ventricular response than did placebo given in combination with AV nodal blocking agents.
Citation: Bouida W et al. Low-dose magnesium sulfate versus high-dose in the early management of rapid atrial fibrillation: Randomized controlled double-blind study (LOMAGHI Study). Acad Emerg Med. 2019 Feb;26(2):183-91.
Low versus intermediate tidal volume strategy on ventilator-free days in ICU patients without ARDS
Randomized, clinical trial of low tidal volume versus intermediate tidal volume strategies in invasively ventilated patients without accute respiratory distress syndrome (ARDS) demonstrated no difference in number of ventilator-free days, ICU length of stay, hospital length of stay, incidence of ventilator-associated adverse events (ARDS, pneumonia, severe atelectasis, pneumothorax), or 28-day mortality.
Citation: Writing Group for the PReVENT Investigators, Simonis FD, Serpa Neto A. Effect of a low vs intermediate tidal volume strategy on ventilator-free days in intensive care unit patients without ARDS: A randomized clinical trial. JAMA. 2018;320(18):1872-80.
Pharmacist-led intervention reduced inappropriate medication prescriptions
An outpatient pharmacy-led intervention of notifying prescribing physicians to discontinue inappropriate Beers Criteria medications resulted in a greater discontinuation of inappropriate medications for older adults at 6 months, compared with the control group (43% vs. 12% discontinuation).
Citation: Martin P et al. Effect of a pharmacist-led educational intervention on inappropriate medication prescriptions in older adults: The D-PRESCRIBE randomized clinical trial. JAMA. 2018;320(18):1889-98.
Omadacycline noninferior for community-acquired pneumonia and acute bacterial soft tissue skin infections
Randomized, double-blind, double-dummy trials showed omadacycline is a noninferior alternative to moxifloxacin for the treatment of community-acquired pneumonia and to linezolid for acute bacterial soft-tissue skin infections.
Citation: Nuzyra (omadacycline) [package insert]. Boston, MA: Paratek Pharmaceuticals. 2018.
Lack of evidence to support low-salt diet in adult heart failure patients
Systematic review of multiple databases demonstrated there is limited high-quality evidence to support current guidelines that recommend a low-salt diet to heart failure patients.
Citation: Mahtani KR et al. Reduced salt intake for heart failure: A systematic review. JAMA Int Med. 2018;178(12):1693-700.
Magnesium for rate control in rapid atrial fibrillation
Randomized, controlled trial demonstrated that intravenous magnesium sulfate in combination with atrioventricular (AV) nodal blocking agents resulted in better rate control for atrial fibrillation with rapid ventricular response than did placebo given in combination with AV nodal blocking agents.
Citation: Bouida W et al. Low-dose magnesium sulfate versus high-dose in the early management of rapid atrial fibrillation: Randomized controlled double-blind study (LOMAGHI Study). Acad Emerg Med. 2019 Feb;26(2):183-91.
Low versus intermediate tidal volume strategy on ventilator-free days in ICU patients without ARDS
Randomized, clinical trial of low tidal volume versus intermediate tidal volume strategies in invasively ventilated patients without accute respiratory distress syndrome (ARDS) demonstrated no difference in number of ventilator-free days, ICU length of stay, hospital length of stay, incidence of ventilator-associated adverse events (ARDS, pneumonia, severe atelectasis, pneumothorax), or 28-day mortality.
Citation: Writing Group for the PReVENT Investigators, Simonis FD, Serpa Neto A. Effect of a low vs intermediate tidal volume strategy on ventilator-free days in intensive care unit patients without ARDS: A randomized clinical trial. JAMA. 2018;320(18):1872-80.
Pharmacist-led intervention reduced inappropriate medication prescriptions
An outpatient pharmacy-led intervention of notifying prescribing physicians to discontinue inappropriate Beers Criteria medications resulted in a greater discontinuation of inappropriate medications for older adults at 6 months, compared with the control group (43% vs. 12% discontinuation).
Citation: Martin P et al. Effect of a pharmacist-led educational intervention on inappropriate medication prescriptions in older adults: The D-PRESCRIBE randomized clinical trial. JAMA. 2018;320(18):1889-98.
Omadacycline noninferior for community-acquired pneumonia and acute bacterial soft tissue skin infections
Randomized, double-blind, double-dummy trials showed omadacycline is a noninferior alternative to moxifloxacin for the treatment of community-acquired pneumonia and to linezolid for acute bacterial soft-tissue skin infections.
Citation: Nuzyra (omadacycline) [package insert]. Boston, MA: Paratek Pharmaceuticals. 2018.
Lack of evidence to support low-salt diet in adult heart failure patients
Systematic review of multiple databases demonstrated there is limited high-quality evidence to support current guidelines that recommend a low-salt diet to heart failure patients.
Citation: Mahtani KR et al. Reduced salt intake for heart failure: A systematic review. JAMA Int Med. 2018;178(12):1693-700.
Magnesium for rate control in rapid atrial fibrillation
Randomized, controlled trial demonstrated that intravenous magnesium sulfate in combination with atrioventricular (AV) nodal blocking agents resulted in better rate control for atrial fibrillation with rapid ventricular response than did placebo given in combination with AV nodal blocking agents.
Citation: Bouida W et al. Low-dose magnesium sulfate versus high-dose in the early management of rapid atrial fibrillation: Randomized controlled double-blind study (LOMAGHI Study). Acad Emerg Med. 2019 Feb;26(2):183-91.
Low versus intermediate tidal volume strategy on ventilator-free days in ICU patients without ARDS
Randomized, clinical trial of low tidal volume versus intermediate tidal volume strategies in invasively ventilated patients without accute respiratory distress syndrome (ARDS) demonstrated no difference in number of ventilator-free days, ICU length of stay, hospital length of stay, incidence of ventilator-associated adverse events (ARDS, pneumonia, severe atelectasis, pneumothorax), or 28-day mortality.
Citation: Writing Group for the PReVENT Investigators, Simonis FD, Serpa Neto A. Effect of a low vs intermediate tidal volume strategy on ventilator-free days in intensive care unit patients without ARDS: A randomized clinical trial. JAMA. 2018;320(18):1872-80.
Drug doses for heart failure could possibly be halved for women
Men and women react differently to common drugs used to treat heart failure with reduced ejection fraction (HFrEF), according to findings from a new European study, and women may be able to safely cut their doses in half and get the same level of relief as that provided by larger doses.
“This study ... brings into question what the true optimal medical therapy is for women versus men,” the study authors, led by Bernadet T. Santema, MD, of the University Medical Center Groningen (the Netherlands), wrote in an article published in the Lancet.
Dr. Santema and colleagues noted that current guidelines for the use of ACE inhibitors or angiotensin-receptor blockers (ARBs) and beta-blockers for men and women with heart failure do not differentiate between the genders, despite findings showing that, “with the same dose, the maximum plasma concentrations of ACE inhibitors, ARBs, and beta-blockers were up to 2.5 times higher in women than in men.”
In addition, the researchers wrote, women are much more likely than men to suffer side effects from medications, and the effects tend to be more severe.
HFrEF accounts for an estimated 50% of the 5.7 million patients with heart failure in the United States (Nat Rev Dis Primers. 2017 Aug 24. doi: 10.1038/nrdp.2017.58; Card Fail Rev. 2017;3[1]:7-11.)
For the new study, researchers launched an ad hoc analysis of the findings of a prospective study of HFrEF patients in 11 European countries (1,308 men and 402 women) who took drugs in the three classes. Patients were receiving suboptimal medication doses at the start of the study, and physicians were encouraged to increase their medication. The median follow-up for the primary endpoint was 21 months.
“In men, the lowest hazards of death or hospitalization for heart failure occurred at 100% of the recommended dose of ACE inhibitors or ARBs and beta-blockers, but women showed about 30% lower risk at only 50% of the recommended doses, with no further decrease in risk at higher dose levels,” the researchers wrote. “These sex differences were still present after adjusting for clinical covariates, including age and body surface area.”
The researchers analyzed an Asian registry (3,539 men, 961 women) as a comparison and found the identical numbers.
“Our study provides evidence supporting the hypothesis that women with HFrEF might have the best outcomes with lower doses of ACE inhibitors or ARBs and beta-blockers than do men, and lower doses than recommended in international guidelines for heart failure,” they wrote. However, they added that it was not likely that sex-specific studies analyzing doses would be performed.
In an accompanying editorial, Heather P. Whitley, PharmD, and Warren D. Smith, PharmD, noted that clinical research has often failed to take gender differences into account. They wrote that the study – the first of its kind – was well executed and raises important questions, but the analysis did not take into account the prevalence of adverse effects or the serum concentrations of the various medications. Although those limitations weaken the findings, the study still offers evidence that gender-based, drug-dose guidelines deserve consideration, wrote Dr. Whitley, of Auburn (Ala.) University, and Dr. Smith, of Baptist Health System, Montgomery, Ala (Lancet. 2019 Aug 22. doi: 10.1016/S0140-6736[19]31812-4).
The study was funded by the European Commission. Several study authors reported various disclosures. Dr. Whitley and Dr. Smith reported no conflicts of interest.
SOURCE: Santema BT et al. Lancet. 2019 Aug 22. doi: 10.1016/S0140-6736(19)31792-1.
Men and women react differently to common drugs used to treat heart failure with reduced ejection fraction (HFrEF), according to findings from a new European study, and women may be able to safely cut their doses in half and get the same level of relief as that provided by larger doses.
“This study ... brings into question what the true optimal medical therapy is for women versus men,” the study authors, led by Bernadet T. Santema, MD, of the University Medical Center Groningen (the Netherlands), wrote in an article published in the Lancet.
Dr. Santema and colleagues noted that current guidelines for the use of ACE inhibitors or angiotensin-receptor blockers (ARBs) and beta-blockers for men and women with heart failure do not differentiate between the genders, despite findings showing that, “with the same dose, the maximum plasma concentrations of ACE inhibitors, ARBs, and beta-blockers were up to 2.5 times higher in women than in men.”
In addition, the researchers wrote, women are much more likely than men to suffer side effects from medications, and the effects tend to be more severe.
HFrEF accounts for an estimated 50% of the 5.7 million patients with heart failure in the United States (Nat Rev Dis Primers. 2017 Aug 24. doi: 10.1038/nrdp.2017.58; Card Fail Rev. 2017;3[1]:7-11.)
For the new study, researchers launched an ad hoc analysis of the findings of a prospective study of HFrEF patients in 11 European countries (1,308 men and 402 women) who took drugs in the three classes. Patients were receiving suboptimal medication doses at the start of the study, and physicians were encouraged to increase their medication. The median follow-up for the primary endpoint was 21 months.
“In men, the lowest hazards of death or hospitalization for heart failure occurred at 100% of the recommended dose of ACE inhibitors or ARBs and beta-blockers, but women showed about 30% lower risk at only 50% of the recommended doses, with no further decrease in risk at higher dose levels,” the researchers wrote. “These sex differences were still present after adjusting for clinical covariates, including age and body surface area.”
The researchers analyzed an Asian registry (3,539 men, 961 women) as a comparison and found the identical numbers.
“Our study provides evidence supporting the hypothesis that women with HFrEF might have the best outcomes with lower doses of ACE inhibitors or ARBs and beta-blockers than do men, and lower doses than recommended in international guidelines for heart failure,” they wrote. However, they added that it was not likely that sex-specific studies analyzing doses would be performed.
In an accompanying editorial, Heather P. Whitley, PharmD, and Warren D. Smith, PharmD, noted that clinical research has often failed to take gender differences into account. They wrote that the study – the first of its kind – was well executed and raises important questions, but the analysis did not take into account the prevalence of adverse effects or the serum concentrations of the various medications. Although those limitations weaken the findings, the study still offers evidence that gender-based, drug-dose guidelines deserve consideration, wrote Dr. Whitley, of Auburn (Ala.) University, and Dr. Smith, of Baptist Health System, Montgomery, Ala (Lancet. 2019 Aug 22. doi: 10.1016/S0140-6736[19]31812-4).
The study was funded by the European Commission. Several study authors reported various disclosures. Dr. Whitley and Dr. Smith reported no conflicts of interest.
SOURCE: Santema BT et al. Lancet. 2019 Aug 22. doi: 10.1016/S0140-6736(19)31792-1.
Men and women react differently to common drugs used to treat heart failure with reduced ejection fraction (HFrEF), according to findings from a new European study, and women may be able to safely cut their doses in half and get the same level of relief as that provided by larger doses.
“This study ... brings into question what the true optimal medical therapy is for women versus men,” the study authors, led by Bernadet T. Santema, MD, of the University Medical Center Groningen (the Netherlands), wrote in an article published in the Lancet.
Dr. Santema and colleagues noted that current guidelines for the use of ACE inhibitors or angiotensin-receptor blockers (ARBs) and beta-blockers for men and women with heart failure do not differentiate between the genders, despite findings showing that, “with the same dose, the maximum plasma concentrations of ACE inhibitors, ARBs, and beta-blockers were up to 2.5 times higher in women than in men.”
In addition, the researchers wrote, women are much more likely than men to suffer side effects from medications, and the effects tend to be more severe.
HFrEF accounts for an estimated 50% of the 5.7 million patients with heart failure in the United States (Nat Rev Dis Primers. 2017 Aug 24. doi: 10.1038/nrdp.2017.58; Card Fail Rev. 2017;3[1]:7-11.)
For the new study, researchers launched an ad hoc analysis of the findings of a prospective study of HFrEF patients in 11 European countries (1,308 men and 402 women) who took drugs in the three classes. Patients were receiving suboptimal medication doses at the start of the study, and physicians were encouraged to increase their medication. The median follow-up for the primary endpoint was 21 months.
“In men, the lowest hazards of death or hospitalization for heart failure occurred at 100% of the recommended dose of ACE inhibitors or ARBs and beta-blockers, but women showed about 30% lower risk at only 50% of the recommended doses, with no further decrease in risk at higher dose levels,” the researchers wrote. “These sex differences were still present after adjusting for clinical covariates, including age and body surface area.”
The researchers analyzed an Asian registry (3,539 men, 961 women) as a comparison and found the identical numbers.
“Our study provides evidence supporting the hypothesis that women with HFrEF might have the best outcomes with lower doses of ACE inhibitors or ARBs and beta-blockers than do men, and lower doses than recommended in international guidelines for heart failure,” they wrote. However, they added that it was not likely that sex-specific studies analyzing doses would be performed.
In an accompanying editorial, Heather P. Whitley, PharmD, and Warren D. Smith, PharmD, noted that clinical research has often failed to take gender differences into account. They wrote that the study – the first of its kind – was well executed and raises important questions, but the analysis did not take into account the prevalence of adverse effects or the serum concentrations of the various medications. Although those limitations weaken the findings, the study still offers evidence that gender-based, drug-dose guidelines deserve consideration, wrote Dr. Whitley, of Auburn (Ala.) University, and Dr. Smith, of Baptist Health System, Montgomery, Ala (Lancet. 2019 Aug 22. doi: 10.1016/S0140-6736[19]31812-4).
The study was funded by the European Commission. Several study authors reported various disclosures. Dr. Whitley and Dr. Smith reported no conflicts of interest.
SOURCE: Santema BT et al. Lancet. 2019 Aug 22. doi: 10.1016/S0140-6736(19)31792-1.
FROM THE LANCET
Consider triple therapy for the management of COPD
Background: The Global Initiative for Obstructive Lung Disease (GOLD) recommends triple therapy with inhaled corticosteroids, long-acting beta2-adrenoceptor agonists (LABA), and long-acting muscarinic receptor antagonists (LAMA) for patients with severe COPD who have frequent exacerbations despite treatment with a LABA and LAMA. Triple therapy has been shown to improve forced expiratory volume in 1 second (FEV1), but its effect on preventing exacerbations has not been well documented in previous meta-analyses.
Study design: Meta-analysis.
Setting: Studies published on PubMed, Embase, Cochrane Library website, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases.
Synopsis: 21 randomized, controlled trials of triple therapy in stable cases of moderate to very severe COPD were included in this meta-analysis. Triple therapy was associated with a significantly greater reduction in the rate of COPD exacerbations, compared with dual therapy of LAMA and LABA (rate ratio, 0.78; 95% confidence interval, 0.70-0.88), inhaled corticosteroid and LABA (rate ratio, 0.77; 95% CI, 0.66-0.91), or LAMA monotherapy (rate ratio, 0.71; 95% CI, 0.60-0.85). Triple therapy was also associated with greater improvement in FEV1.
There was a significantly higher incidence of pneumonia in patients using triple therapy, compared with those using dual therapy (LAMA and LABA), and there also was a trend toward increased pneumonia incidence with triple therapy, compared with LAMA monotherapy. Triple therapy was not shown to improve survival; however, most trials lasted less than 6 months, which limits their analysis of survival outcomes.
Bottom line: In patients with advanced COPD, triple therapy is associated with lower rates of COPD exacerbations and improved lung function, compared with dual therapy or monotherapy.
Citation: Zheng Y et al. Triple therapy in the management of chronic obstructive pulmonary disease: Systemic review and meta-analysis. BMJ. 2018;363:k4388.
Dr. Chace is an associate physician in the division of hospital medicine at the University of California, San Diego.
Background: The Global Initiative for Obstructive Lung Disease (GOLD) recommends triple therapy with inhaled corticosteroids, long-acting beta2-adrenoceptor agonists (LABA), and long-acting muscarinic receptor antagonists (LAMA) for patients with severe COPD who have frequent exacerbations despite treatment with a LABA and LAMA. Triple therapy has been shown to improve forced expiratory volume in 1 second (FEV1), but its effect on preventing exacerbations has not been well documented in previous meta-analyses.
Study design: Meta-analysis.
Setting: Studies published on PubMed, Embase, Cochrane Library website, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases.
Synopsis: 21 randomized, controlled trials of triple therapy in stable cases of moderate to very severe COPD were included in this meta-analysis. Triple therapy was associated with a significantly greater reduction in the rate of COPD exacerbations, compared with dual therapy of LAMA and LABA (rate ratio, 0.78; 95% confidence interval, 0.70-0.88), inhaled corticosteroid and LABA (rate ratio, 0.77; 95% CI, 0.66-0.91), or LAMA monotherapy (rate ratio, 0.71; 95% CI, 0.60-0.85). Triple therapy was also associated with greater improvement in FEV1.
There was a significantly higher incidence of pneumonia in patients using triple therapy, compared with those using dual therapy (LAMA and LABA), and there also was a trend toward increased pneumonia incidence with triple therapy, compared with LAMA monotherapy. Triple therapy was not shown to improve survival; however, most trials lasted less than 6 months, which limits their analysis of survival outcomes.
Bottom line: In patients with advanced COPD, triple therapy is associated with lower rates of COPD exacerbations and improved lung function, compared with dual therapy or monotherapy.
Citation: Zheng Y et al. Triple therapy in the management of chronic obstructive pulmonary disease: Systemic review and meta-analysis. BMJ. 2018;363:k4388.
Dr. Chace is an associate physician in the division of hospital medicine at the University of California, San Diego.
Background: The Global Initiative for Obstructive Lung Disease (GOLD) recommends triple therapy with inhaled corticosteroids, long-acting beta2-adrenoceptor agonists (LABA), and long-acting muscarinic receptor antagonists (LAMA) for patients with severe COPD who have frequent exacerbations despite treatment with a LABA and LAMA. Triple therapy has been shown to improve forced expiratory volume in 1 second (FEV1), but its effect on preventing exacerbations has not been well documented in previous meta-analyses.
Study design: Meta-analysis.
Setting: Studies published on PubMed, Embase, Cochrane Library website, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases.
Synopsis: 21 randomized, controlled trials of triple therapy in stable cases of moderate to very severe COPD were included in this meta-analysis. Triple therapy was associated with a significantly greater reduction in the rate of COPD exacerbations, compared with dual therapy of LAMA and LABA (rate ratio, 0.78; 95% confidence interval, 0.70-0.88), inhaled corticosteroid and LABA (rate ratio, 0.77; 95% CI, 0.66-0.91), or LAMA monotherapy (rate ratio, 0.71; 95% CI, 0.60-0.85). Triple therapy was also associated with greater improvement in FEV1.
There was a significantly higher incidence of pneumonia in patients using triple therapy, compared with those using dual therapy (LAMA and LABA), and there also was a trend toward increased pneumonia incidence with triple therapy, compared with LAMA monotherapy. Triple therapy was not shown to improve survival; however, most trials lasted less than 6 months, which limits their analysis of survival outcomes.
Bottom line: In patients with advanced COPD, triple therapy is associated with lower rates of COPD exacerbations and improved lung function, compared with dual therapy or monotherapy.
Citation: Zheng Y et al. Triple therapy in the management of chronic obstructive pulmonary disease: Systemic review and meta-analysis. BMJ. 2018;363:k4388.
Dr. Chace is an associate physician in the division of hospital medicine at the University of California, San Diego.
Older IBD patients are most at risk of postdischarge VTE
Hospitalized patients with inflammatory bowel diseases (IBD) are most likely to be readmitted for venous thromboembolism (VTE) within 60 days of discharge, according to a new study that analyzed 5 years of U.S. readmissions data.
“Given increased thrombotic risk postdischarge, as well as overall safety of VTE prophylaxis, extending prophylaxis for those at highest risk may have significant benefits,” wrote Adam S. Faye, MD, of Columbia University, and coauthors. The study was published in Clinical Gastroenterology and Hepatology.
To determine which IBD patients would be most in need of postdischarge VTE prophylaxis, as well as when to administer it, the researchers analyzed 2010-2014 data from the Nationwide Readmissions Database (NRD). They found a total of 872,122 index admissions for IBD patients; 4% of those patients had a prior VTE. Of the index admissions, 1,160 led to a VTE readmission within 90 days. Readmitted patients had a relatively equal proportion of ulcerative colitis (n = 522) and Crohn’s disease (n = 638).
More than 90% of VTE readmissions occurred within 60 days of discharge; the risk was highest over the first 10 days and then decreased in each ensuing 10-day period until a slight increase at the 81- to 90-day period. All patients over age 30 had higher rates of readmission than those of patients under age 18, with the highest risk in patients between the ages of 66 and 80 years (risk ratio 4.04; 95% confidence interval, 2.54-6.44, P less than .01). Women were at lower risk (RR 0.82; 95% CI, 0.73-0.92, P less than .01). Higher risks of readmission were also associated with being on Medicare (RR 1.39; 95% CI, 1.23-1.58, P less than .01) compared with being on private insurance and being cared for at a large hospital (RR 1.26; 95% CI, 1.04-1.52, P = .02) compared with a small hospital.
The highest risk of VTE readmission was associated with a prior history of VTE (RR 2.89; 95% CI, 2.40-3.48, P less than .01), having two or more comorbidities (RR 2.57; 95% CI, 2.11-3.12, P less than .01) and having a Clostridioides difficile infection as of index admission (RR 1.90; 95% CI, 1.51-2.38, P less than .01). In addition, increased risk was associated with being discharged to a nursing or care facility (RR 1.85; 95% CI, 1.56-2.20, P less than .01) or home with health services (RR 2.05; 95% CI, 1.78-2.38, P less than .01) compared with a routine discharge.
In their multivariable analysis, similar factors such as a history of VTE (adjusted RR 2.41; 95% CI, 1.99-2.90, P less than .01), two or more comorbidities (aRR 1.78; 95% CI, 1.44-2.20, P less than .01) and C. difficile infection (aRR 1.47; 95% CI, 1.17-1.85, P less than.01) continued to be associated with higher risk of VTE readmission.
Though they emphasized that the use of NRD data offered the impressive ability to “review over 15 million discharges across the U.S. annually,” Dr. Faye and coauthors acknowledged that their study did have limitations. These included the inability to verify via chart review the study’s outcomes and covariates. In addition, they were unable to assess potential contributing risk factors such as medication use, use of VTE prophylaxis during hospitalization, disease severity, and family history. Finally, though unlikely, they admitted the possibility that patients could be counted more than once if they were readmitted with a VTE each year of the study.
The authors reported being supported by grants from the National Institutes of Health and various pharmaceutical companies, as well as receiving honoraria and serving as consultants.
SOURCE: Faye AS et al. Clin Gastroenterol Hepatol. 2019 July 20. doi: 10.1016/j.cgh.2019.07.028.
Hospitalized patients with inflammatory bowel diseases (IBD) are most likely to be readmitted for venous thromboembolism (VTE) within 60 days of discharge, according to a new study that analyzed 5 years of U.S. readmissions data.
“Given increased thrombotic risk postdischarge, as well as overall safety of VTE prophylaxis, extending prophylaxis for those at highest risk may have significant benefits,” wrote Adam S. Faye, MD, of Columbia University, and coauthors. The study was published in Clinical Gastroenterology and Hepatology.
To determine which IBD patients would be most in need of postdischarge VTE prophylaxis, as well as when to administer it, the researchers analyzed 2010-2014 data from the Nationwide Readmissions Database (NRD). They found a total of 872,122 index admissions for IBD patients; 4% of those patients had a prior VTE. Of the index admissions, 1,160 led to a VTE readmission within 90 days. Readmitted patients had a relatively equal proportion of ulcerative colitis (n = 522) and Crohn’s disease (n = 638).
More than 90% of VTE readmissions occurred within 60 days of discharge; the risk was highest over the first 10 days and then decreased in each ensuing 10-day period until a slight increase at the 81- to 90-day period. All patients over age 30 had higher rates of readmission than those of patients under age 18, with the highest risk in patients between the ages of 66 and 80 years (risk ratio 4.04; 95% confidence interval, 2.54-6.44, P less than .01). Women were at lower risk (RR 0.82; 95% CI, 0.73-0.92, P less than .01). Higher risks of readmission were also associated with being on Medicare (RR 1.39; 95% CI, 1.23-1.58, P less than .01) compared with being on private insurance and being cared for at a large hospital (RR 1.26; 95% CI, 1.04-1.52, P = .02) compared with a small hospital.
The highest risk of VTE readmission was associated with a prior history of VTE (RR 2.89; 95% CI, 2.40-3.48, P less than .01), having two or more comorbidities (RR 2.57; 95% CI, 2.11-3.12, P less than .01) and having a Clostridioides difficile infection as of index admission (RR 1.90; 95% CI, 1.51-2.38, P less than .01). In addition, increased risk was associated with being discharged to a nursing or care facility (RR 1.85; 95% CI, 1.56-2.20, P less than .01) or home with health services (RR 2.05; 95% CI, 1.78-2.38, P less than .01) compared with a routine discharge.
In their multivariable analysis, similar factors such as a history of VTE (adjusted RR 2.41; 95% CI, 1.99-2.90, P less than .01), two or more comorbidities (aRR 1.78; 95% CI, 1.44-2.20, P less than .01) and C. difficile infection (aRR 1.47; 95% CI, 1.17-1.85, P less than.01) continued to be associated with higher risk of VTE readmission.
Though they emphasized that the use of NRD data offered the impressive ability to “review over 15 million discharges across the U.S. annually,” Dr. Faye and coauthors acknowledged that their study did have limitations. These included the inability to verify via chart review the study’s outcomes and covariates. In addition, they were unable to assess potential contributing risk factors such as medication use, use of VTE prophylaxis during hospitalization, disease severity, and family history. Finally, though unlikely, they admitted the possibility that patients could be counted more than once if they were readmitted with a VTE each year of the study.
The authors reported being supported by grants from the National Institutes of Health and various pharmaceutical companies, as well as receiving honoraria and serving as consultants.
SOURCE: Faye AS et al. Clin Gastroenterol Hepatol. 2019 July 20. doi: 10.1016/j.cgh.2019.07.028.
Hospitalized patients with inflammatory bowel diseases (IBD) are most likely to be readmitted for venous thromboembolism (VTE) within 60 days of discharge, according to a new study that analyzed 5 years of U.S. readmissions data.
“Given increased thrombotic risk postdischarge, as well as overall safety of VTE prophylaxis, extending prophylaxis for those at highest risk may have significant benefits,” wrote Adam S. Faye, MD, of Columbia University, and coauthors. The study was published in Clinical Gastroenterology and Hepatology.
To determine which IBD patients would be most in need of postdischarge VTE prophylaxis, as well as when to administer it, the researchers analyzed 2010-2014 data from the Nationwide Readmissions Database (NRD). They found a total of 872,122 index admissions for IBD patients; 4% of those patients had a prior VTE. Of the index admissions, 1,160 led to a VTE readmission within 90 days. Readmitted patients had a relatively equal proportion of ulcerative colitis (n = 522) and Crohn’s disease (n = 638).
More than 90% of VTE readmissions occurred within 60 days of discharge; the risk was highest over the first 10 days and then decreased in each ensuing 10-day period until a slight increase at the 81- to 90-day period. All patients over age 30 had higher rates of readmission than those of patients under age 18, with the highest risk in patients between the ages of 66 and 80 years (risk ratio 4.04; 95% confidence interval, 2.54-6.44, P less than .01). Women were at lower risk (RR 0.82; 95% CI, 0.73-0.92, P less than .01). Higher risks of readmission were also associated with being on Medicare (RR 1.39; 95% CI, 1.23-1.58, P less than .01) compared with being on private insurance and being cared for at a large hospital (RR 1.26; 95% CI, 1.04-1.52, P = .02) compared with a small hospital.
The highest risk of VTE readmission was associated with a prior history of VTE (RR 2.89; 95% CI, 2.40-3.48, P less than .01), having two or more comorbidities (RR 2.57; 95% CI, 2.11-3.12, P less than .01) and having a Clostridioides difficile infection as of index admission (RR 1.90; 95% CI, 1.51-2.38, P less than .01). In addition, increased risk was associated with being discharged to a nursing or care facility (RR 1.85; 95% CI, 1.56-2.20, P less than .01) or home with health services (RR 2.05; 95% CI, 1.78-2.38, P less than .01) compared with a routine discharge.
In their multivariable analysis, similar factors such as a history of VTE (adjusted RR 2.41; 95% CI, 1.99-2.90, P less than .01), two or more comorbidities (aRR 1.78; 95% CI, 1.44-2.20, P less than .01) and C. difficile infection (aRR 1.47; 95% CI, 1.17-1.85, P less than.01) continued to be associated with higher risk of VTE readmission.
Though they emphasized that the use of NRD data offered the impressive ability to “review over 15 million discharges across the U.S. annually,” Dr. Faye and coauthors acknowledged that their study did have limitations. These included the inability to verify via chart review the study’s outcomes and covariates. In addition, they were unable to assess potential contributing risk factors such as medication use, use of VTE prophylaxis during hospitalization, disease severity, and family history. Finally, though unlikely, they admitted the possibility that patients could be counted more than once if they were readmitted with a VTE each year of the study.
The authors reported being supported by grants from the National Institutes of Health and various pharmaceutical companies, as well as receiving honoraria and serving as consultants.
SOURCE: Faye AS et al. Clin Gastroenterol Hepatol. 2019 July 20. doi: 10.1016/j.cgh.2019.07.028.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Readmission for VTE in patients with inflammatory bowel diseases most often occurs within 60 days of discharge.
Major finding: The highest readmission risk was in patients between the ages of 66 and 80 (risk ratio 4.04; 95% confidence interval, 2.54-6.44, P less than .01).
Study details: A retrospective cohort study of 1,160 IBD patients who had VTE readmissions via 2010-2014 data from the Nationwide Readmissions Database.
Disclosures: The authors reported being supported by grants from the National Institutes of Health and various pharmaceutical companies, as well as receiving honoraria and serving as consultants.
Source: Faye AS et al. Clin Gastroenterol Hepatol. 2019 July 20. doi: 10.1016/j.cgh.2019.07.028.
Statins may do double duty as antidepressants
COPENHAGEN – The tantalizing prospect that statins could be repurposed as adjunctive antidepressant drugs in a defined subgroup of patients with major depression is finally about to undergo rigorous testing.
Several lines of preliminary evidence, including large observational cohort studies as well as three small, short-duration randomized trials, suggest that this might indeed be the case. It’s an extremely attractive possibility, since patients and physicians wish that antidepressant therapy were more effective, statins are among the most widely prescribed drugs worldwide, and their safety profile is thoroughly established. The expectation is that a definitive answer as to whether repurposing of statins as antidepressants is worthwhile will be provided by the SIMCODE trial, recently approved for funding by the German Federal Ministry of Education and Research, Christian Otte, MD, announced at the annual congress of the European College of Neuropsychopharmacology.
SIMCODE is a multicenter, double-blind, placebo-controlled randomized trial to be conducted at eight German academic medical centers. Participants, all of whom must have major depressive disorder and comorbid obesity, will be randomized to simvastatin or placebo on top of standard antidepressant therapy with escitalopram, an SSRI which, like simvastatin, is available as a relatively inexpensive generic, explained Dr. Otte, professor and vice director of the department of psychiatry and psychotherapy at Charite University in Berlin.
For Dr. Otte, SIMCODE will close a circle he helped open with his 2012 report from the Heart and Soul Study, a prospective longitudinal study of nearly 1,000 San Francisco Bay Area patients with coronary heart disease who were assessed annually for depressive symptoms for 6 years. The 65% of patients who were on statin therapy, albeit in nonrandomized fashion, had an adjusted 38% lower risk of developing depression (J Clin Psychiatry. 2012 May;73[5]:610-5).
His was one of seven observational studies involving more than 9,000 patients included in a subsequent meta-analysis showing that statin users were 37% less likely to develop depression than were nonusers (J Affect Disord. 2014 May;160:62-7).
All agreed that the verdict isn’t in yet as to statins’ effectiveness as adjunctive antidepressants, and that the subgroup of patients with major depression who are most likely to gain added antidepressive effect from a statin are those with what the speakers variously described as comorbid cardiometabolic disease, immunometabolic disease, or simply, as in SIMCODE, obesity. These are patients with a high degree of systemic inflammation, which often makes their depression less responsive to standard antidepressant therapies. The working hypothesis is that the pleiotropic anti-inflammatory effects of statins will result in a greater response to conventional antidepressants.
Animal studies point to multiple potential mechanisms by which statins might have antidepressant efficacy in clinical practice, according to Dr. Otte. Beyond their anti-inflammatory effects, these include the drugs’ documented effects on glutamatergic N-methyl-D-aspartate (NMDA) receptors, dopamine receptors, brain-derived neurotrophic factor, glucocorticoid receptors, and hippocampal serotonin 2A receptors.
Ole Kohler, MD, a psychiatrist at Aarhus (Denmark) University, presented highlights of his eye-popping population-based study of more than 872,000 Danes on an SSRI in 1997-2012, more than 113,000 of whom were on a concomitant statin. The key finding: During roughly 3 years of follow-up, the risk of contact with a psychiatric hospital for depression was 36% lower in the group on concomitant SSRI/statin therapy than in those not on a statin (Am J Psychiatry. 2016 Aug 1;173[8]:807-15).
He was quick to observe that a study such as this is vulnerable to various forms of confounding. This risk can be mitigated to a considerable extent by careful propensity score matching. Of note, however, none of the three studies that have been conducted with propensity score matching, including his own recent study of nearly 194,000 statin users and an equal number of matched nonusers, showed a difference in risk of depression between statin users and nonusers. All three studies were performed in general populations without known depression, leading Dr. Kohler to conclude that it’s unlikely that statins have a role in preventing depression in nondepressed individuals.
The focus should instead be on the possible role of statins in reducing the risk of depression in patients with cardiometabolic disease – that is, heart disease, metabolic syndrome, or type 2 diabetes – where more than a half-dozen cohort studies, including the Heart and Soul Study, have found that statins have a favorable impact, he added.
Estela Salagre, MD, a psychiatrist at the University of Barcelona, has carried out a meta-analysis of the three randomized, double-blind, placebo-controlled trials of add-on statin therapy in patients on standard therapies for moderate to severe depression published to date. She found that statin therapy was associated with a 27% greater reduction in scores on the Hamilton Depression Rating Scale, compared with placebo (J Affect Disord. 2016 Aug;200:235-42). Those findings recently were confirmed in a separate meta-analysis by other investigators using different methodologies (J Affect Disord. 2019 Oct 1;257:55-63).
Femke Lamers, PhD, presented evidence based on the nearly 3,000-subject longitudinal Netherlands Study of Depression and Anxiety that roughly one-quarter of individuals with major depressive disorder have a distinct subtype of nonmelancholic depression characterized by a clustering of obesity, inflammation, increased appetite, fatigue, hypersomnia, and increased levels of insulin and leptin. She calls it immunometabolic depression. She and her coinvestigators in the international Psychiatric Genomics Consortium have demonstrated that this phenotypic clustering is associated with a shared genetic vulnerability between major depression and obesity (JAMA Psychiatry. 2017 Dec 1;74[12]:1214-25).
“Major depressive disorder is not a one-size-fits-all disorder. There is an immunometabolic form of depression,” declared Dr. Lamers, an epidemiologist at the University of Amsterdam.
All speakers reported having no financial conflicts of interest.
COPENHAGEN – The tantalizing prospect that statins could be repurposed as adjunctive antidepressant drugs in a defined subgroup of patients with major depression is finally about to undergo rigorous testing.
Several lines of preliminary evidence, including large observational cohort studies as well as three small, short-duration randomized trials, suggest that this might indeed be the case. It’s an extremely attractive possibility, since patients and physicians wish that antidepressant therapy were more effective, statins are among the most widely prescribed drugs worldwide, and their safety profile is thoroughly established. The expectation is that a definitive answer as to whether repurposing of statins as antidepressants is worthwhile will be provided by the SIMCODE trial, recently approved for funding by the German Federal Ministry of Education and Research, Christian Otte, MD, announced at the annual congress of the European College of Neuropsychopharmacology.
SIMCODE is a multicenter, double-blind, placebo-controlled randomized trial to be conducted at eight German academic medical centers. Participants, all of whom must have major depressive disorder and comorbid obesity, will be randomized to simvastatin or placebo on top of standard antidepressant therapy with escitalopram, an SSRI which, like simvastatin, is available as a relatively inexpensive generic, explained Dr. Otte, professor and vice director of the department of psychiatry and psychotherapy at Charite University in Berlin.
For Dr. Otte, SIMCODE will close a circle he helped open with his 2012 report from the Heart and Soul Study, a prospective longitudinal study of nearly 1,000 San Francisco Bay Area patients with coronary heart disease who were assessed annually for depressive symptoms for 6 years. The 65% of patients who were on statin therapy, albeit in nonrandomized fashion, had an adjusted 38% lower risk of developing depression (J Clin Psychiatry. 2012 May;73[5]:610-5).
His was one of seven observational studies involving more than 9,000 patients included in a subsequent meta-analysis showing that statin users were 37% less likely to develop depression than were nonusers (J Affect Disord. 2014 May;160:62-7).
All agreed that the verdict isn’t in yet as to statins’ effectiveness as adjunctive antidepressants, and that the subgroup of patients with major depression who are most likely to gain added antidepressive effect from a statin are those with what the speakers variously described as comorbid cardiometabolic disease, immunometabolic disease, or simply, as in SIMCODE, obesity. These are patients with a high degree of systemic inflammation, which often makes their depression less responsive to standard antidepressant therapies. The working hypothesis is that the pleiotropic anti-inflammatory effects of statins will result in a greater response to conventional antidepressants.
Animal studies point to multiple potential mechanisms by which statins might have antidepressant efficacy in clinical practice, according to Dr. Otte. Beyond their anti-inflammatory effects, these include the drugs’ documented effects on glutamatergic N-methyl-D-aspartate (NMDA) receptors, dopamine receptors, brain-derived neurotrophic factor, glucocorticoid receptors, and hippocampal serotonin 2A receptors.
Ole Kohler, MD, a psychiatrist at Aarhus (Denmark) University, presented highlights of his eye-popping population-based study of more than 872,000 Danes on an SSRI in 1997-2012, more than 113,000 of whom were on a concomitant statin. The key finding: During roughly 3 years of follow-up, the risk of contact with a psychiatric hospital for depression was 36% lower in the group on concomitant SSRI/statin therapy than in those not on a statin (Am J Psychiatry. 2016 Aug 1;173[8]:807-15).
He was quick to observe that a study such as this is vulnerable to various forms of confounding. This risk can be mitigated to a considerable extent by careful propensity score matching. Of note, however, none of the three studies that have been conducted with propensity score matching, including his own recent study of nearly 194,000 statin users and an equal number of matched nonusers, showed a difference in risk of depression between statin users and nonusers. All three studies were performed in general populations without known depression, leading Dr. Kohler to conclude that it’s unlikely that statins have a role in preventing depression in nondepressed individuals.
The focus should instead be on the possible role of statins in reducing the risk of depression in patients with cardiometabolic disease – that is, heart disease, metabolic syndrome, or type 2 diabetes – where more than a half-dozen cohort studies, including the Heart and Soul Study, have found that statins have a favorable impact, he added.
Estela Salagre, MD, a psychiatrist at the University of Barcelona, has carried out a meta-analysis of the three randomized, double-blind, placebo-controlled trials of add-on statin therapy in patients on standard therapies for moderate to severe depression published to date. She found that statin therapy was associated with a 27% greater reduction in scores on the Hamilton Depression Rating Scale, compared with placebo (J Affect Disord. 2016 Aug;200:235-42). Those findings recently were confirmed in a separate meta-analysis by other investigators using different methodologies (J Affect Disord. 2019 Oct 1;257:55-63).
Femke Lamers, PhD, presented evidence based on the nearly 3,000-subject longitudinal Netherlands Study of Depression and Anxiety that roughly one-quarter of individuals with major depressive disorder have a distinct subtype of nonmelancholic depression characterized by a clustering of obesity, inflammation, increased appetite, fatigue, hypersomnia, and increased levels of insulin and leptin. She calls it immunometabolic depression. She and her coinvestigators in the international Psychiatric Genomics Consortium have demonstrated that this phenotypic clustering is associated with a shared genetic vulnerability between major depression and obesity (JAMA Psychiatry. 2017 Dec 1;74[12]:1214-25).
“Major depressive disorder is not a one-size-fits-all disorder. There is an immunometabolic form of depression,” declared Dr. Lamers, an epidemiologist at the University of Amsterdam.
All speakers reported having no financial conflicts of interest.
COPENHAGEN – The tantalizing prospect that statins could be repurposed as adjunctive antidepressant drugs in a defined subgroup of patients with major depression is finally about to undergo rigorous testing.
Several lines of preliminary evidence, including large observational cohort studies as well as three small, short-duration randomized trials, suggest that this might indeed be the case. It’s an extremely attractive possibility, since patients and physicians wish that antidepressant therapy were more effective, statins are among the most widely prescribed drugs worldwide, and their safety profile is thoroughly established. The expectation is that a definitive answer as to whether repurposing of statins as antidepressants is worthwhile will be provided by the SIMCODE trial, recently approved for funding by the German Federal Ministry of Education and Research, Christian Otte, MD, announced at the annual congress of the European College of Neuropsychopharmacology.
SIMCODE is a multicenter, double-blind, placebo-controlled randomized trial to be conducted at eight German academic medical centers. Participants, all of whom must have major depressive disorder and comorbid obesity, will be randomized to simvastatin or placebo on top of standard antidepressant therapy with escitalopram, an SSRI which, like simvastatin, is available as a relatively inexpensive generic, explained Dr. Otte, professor and vice director of the department of psychiatry and psychotherapy at Charite University in Berlin.
For Dr. Otte, SIMCODE will close a circle he helped open with his 2012 report from the Heart and Soul Study, a prospective longitudinal study of nearly 1,000 San Francisco Bay Area patients with coronary heart disease who were assessed annually for depressive symptoms for 6 years. The 65% of patients who were on statin therapy, albeit in nonrandomized fashion, had an adjusted 38% lower risk of developing depression (J Clin Psychiatry. 2012 May;73[5]:610-5).
His was one of seven observational studies involving more than 9,000 patients included in a subsequent meta-analysis showing that statin users were 37% less likely to develop depression than were nonusers (J Affect Disord. 2014 May;160:62-7).
All agreed that the verdict isn’t in yet as to statins’ effectiveness as adjunctive antidepressants, and that the subgroup of patients with major depression who are most likely to gain added antidepressive effect from a statin are those with what the speakers variously described as comorbid cardiometabolic disease, immunometabolic disease, or simply, as in SIMCODE, obesity. These are patients with a high degree of systemic inflammation, which often makes their depression less responsive to standard antidepressant therapies. The working hypothesis is that the pleiotropic anti-inflammatory effects of statins will result in a greater response to conventional antidepressants.
Animal studies point to multiple potential mechanisms by which statins might have antidepressant efficacy in clinical practice, according to Dr. Otte. Beyond their anti-inflammatory effects, these include the drugs’ documented effects on glutamatergic N-methyl-D-aspartate (NMDA) receptors, dopamine receptors, brain-derived neurotrophic factor, glucocorticoid receptors, and hippocampal serotonin 2A receptors.
Ole Kohler, MD, a psychiatrist at Aarhus (Denmark) University, presented highlights of his eye-popping population-based study of more than 872,000 Danes on an SSRI in 1997-2012, more than 113,000 of whom were on a concomitant statin. The key finding: During roughly 3 years of follow-up, the risk of contact with a psychiatric hospital for depression was 36% lower in the group on concomitant SSRI/statin therapy than in those not on a statin (Am J Psychiatry. 2016 Aug 1;173[8]:807-15).
He was quick to observe that a study such as this is vulnerable to various forms of confounding. This risk can be mitigated to a considerable extent by careful propensity score matching. Of note, however, none of the three studies that have been conducted with propensity score matching, including his own recent study of nearly 194,000 statin users and an equal number of matched nonusers, showed a difference in risk of depression between statin users and nonusers. All three studies were performed in general populations without known depression, leading Dr. Kohler to conclude that it’s unlikely that statins have a role in preventing depression in nondepressed individuals.
The focus should instead be on the possible role of statins in reducing the risk of depression in patients with cardiometabolic disease – that is, heart disease, metabolic syndrome, or type 2 diabetes – where more than a half-dozen cohort studies, including the Heart and Soul Study, have found that statins have a favorable impact, he added.
Estela Salagre, MD, a psychiatrist at the University of Barcelona, has carried out a meta-analysis of the three randomized, double-blind, placebo-controlled trials of add-on statin therapy in patients on standard therapies for moderate to severe depression published to date. She found that statin therapy was associated with a 27% greater reduction in scores on the Hamilton Depression Rating Scale, compared with placebo (J Affect Disord. 2016 Aug;200:235-42). Those findings recently were confirmed in a separate meta-analysis by other investigators using different methodologies (J Affect Disord. 2019 Oct 1;257:55-63).
Femke Lamers, PhD, presented evidence based on the nearly 3,000-subject longitudinal Netherlands Study of Depression and Anxiety that roughly one-quarter of individuals with major depressive disorder have a distinct subtype of nonmelancholic depression characterized by a clustering of obesity, inflammation, increased appetite, fatigue, hypersomnia, and increased levels of insulin and leptin. She calls it immunometabolic depression. She and her coinvestigators in the international Psychiatric Genomics Consortium have demonstrated that this phenotypic clustering is associated with a shared genetic vulnerability between major depression and obesity (JAMA Psychiatry. 2017 Dec 1;74[12]:1214-25).
“Major depressive disorder is not a one-size-fits-all disorder. There is an immunometabolic form of depression,” declared Dr. Lamers, an epidemiologist at the University of Amsterdam.
All speakers reported having no financial conflicts of interest.
REPORTING FROM ECNP 2019
Exercise intervention reverses functional decline in elderly patients during acute hospitalization
Background: Acute hospitalization has been associated with functional and cognitive decline, particularly in elderly adults. This decline is associated with increased morbidity and mortality.
Study design: Single-center, single-blind, randomized clinical trial.
Setting: Acute care unit in a tertiary public hospital in Navarra, Spain.
Synopsis: 370 patients aged 75 years or older who were hospitalized in an acute care unit received either individualized moderate intensity exercise regimens (focusing on resistance, balance, and walking) or standard hospital care (with physical rehabilitation as appropriate). Patients who received standard care had a decrease in functional capacity at discharge when compared with their baseline function (mean change of –5.0 points on the Barthel Index of Independence; 95% confidence interval, –6.8 to –3.2 points), while those who received the exercise intervention had no functional decline from baseline on discharge (mean change of 1.9 points; 95% CI, 0.2-3.7 points).
Patients who received the exercise intervention had significantly higher scores on functional and cognitive assessments at discharge, compared with patients who received standard hospital care alone. Specifically, the study demonstrated a mean increase of 2.2 points (95% CI, 1.7-2.6 points) on the Short Physical Performance Battery, 6.9 points (95% CI, 4.4-9.5 points) on the Barthel Index, and 1.8 points (95% CI, 1.3-2.3 points) on a cognitive assessment, compared with those who received standard hospital care.
Bottom line: An individualized, multicomponent exercise intervention can help reverse functional and cognitive decline associated with acute hospitalization in elderly patients.
Citation: Martinez-Velilla N et al. Effect of exercise intervention on functional decline in very elderly adults during acute hospitalization. JAMA Intern Med. 2019;179(1):28-36.
Dr. Chace is an associate physician in the division of hospital medicine at the University of California, San Diego.
Background: Acute hospitalization has been associated with functional and cognitive decline, particularly in elderly adults. This decline is associated with increased morbidity and mortality.
Study design: Single-center, single-blind, randomized clinical trial.
Setting: Acute care unit in a tertiary public hospital in Navarra, Spain.
Synopsis: 370 patients aged 75 years or older who were hospitalized in an acute care unit received either individualized moderate intensity exercise regimens (focusing on resistance, balance, and walking) or standard hospital care (with physical rehabilitation as appropriate). Patients who received standard care had a decrease in functional capacity at discharge when compared with their baseline function (mean change of –5.0 points on the Barthel Index of Independence; 95% confidence interval, –6.8 to –3.2 points), while those who received the exercise intervention had no functional decline from baseline on discharge (mean change of 1.9 points; 95% CI, 0.2-3.7 points).
Patients who received the exercise intervention had significantly higher scores on functional and cognitive assessments at discharge, compared with patients who received standard hospital care alone. Specifically, the study demonstrated a mean increase of 2.2 points (95% CI, 1.7-2.6 points) on the Short Physical Performance Battery, 6.9 points (95% CI, 4.4-9.5 points) on the Barthel Index, and 1.8 points (95% CI, 1.3-2.3 points) on a cognitive assessment, compared with those who received standard hospital care.
Bottom line: An individualized, multicomponent exercise intervention can help reverse functional and cognitive decline associated with acute hospitalization in elderly patients.
Citation: Martinez-Velilla N et al. Effect of exercise intervention on functional decline in very elderly adults during acute hospitalization. JAMA Intern Med. 2019;179(1):28-36.
Dr. Chace is an associate physician in the division of hospital medicine at the University of California, San Diego.
Background: Acute hospitalization has been associated with functional and cognitive decline, particularly in elderly adults. This decline is associated with increased morbidity and mortality.
Study design: Single-center, single-blind, randomized clinical trial.
Setting: Acute care unit in a tertiary public hospital in Navarra, Spain.
Synopsis: 370 patients aged 75 years or older who were hospitalized in an acute care unit received either individualized moderate intensity exercise regimens (focusing on resistance, balance, and walking) or standard hospital care (with physical rehabilitation as appropriate). Patients who received standard care had a decrease in functional capacity at discharge when compared with their baseline function (mean change of –5.0 points on the Barthel Index of Independence; 95% confidence interval, –6.8 to –3.2 points), while those who received the exercise intervention had no functional decline from baseline on discharge (mean change of 1.9 points; 95% CI, 0.2-3.7 points).
Patients who received the exercise intervention had significantly higher scores on functional and cognitive assessments at discharge, compared with patients who received standard hospital care alone. Specifically, the study demonstrated a mean increase of 2.2 points (95% CI, 1.7-2.6 points) on the Short Physical Performance Battery, 6.9 points (95% CI, 4.4-9.5 points) on the Barthel Index, and 1.8 points (95% CI, 1.3-2.3 points) on a cognitive assessment, compared with those who received standard hospital care.
Bottom line: An individualized, multicomponent exercise intervention can help reverse functional and cognitive decline associated with acute hospitalization in elderly patients.
Citation: Martinez-Velilla N et al. Effect of exercise intervention on functional decline in very elderly adults during acute hospitalization. JAMA Intern Med. 2019;179(1):28-36.
Dr. Chace is an associate physician in the division of hospital medicine at the University of California, San Diego.
ARNIs effective for acute decompensated heart failure
Background: The PARADIGM-HF trial demonstrated that patients with chronic HFrEF treated with an ARNI (sacubitril/valsartan) had significantly reduced cardiovascular mortality and hospitalizations when compared with enalapril. Patients with acute decompensated heart failure were excluded from this trial. The PIONEER-HF trial was designed to determine whether initiation of an ARNI in patients with acute decompensated heart failure is effective.
Study design: Multicenter, randomized, double-blind, active-controlled trial.
Setting: A total of 129 centers in the United States.
Synopsis: Of 881 patients with acute HFrEF, 440 were randomized to receive sacubitril/valsartan and 441 were randomized to receive enalapril. The majority of patients were men; mean age was 61 years. The primary outcome was the mean reduction in NT-proBNP concentration at weeks 4 and 8 as compared with baseline. In the sacubitril/valsartan group, there was a 46.7% reduction from baseline, and in the enalapril group, there was a 25.3% reduction from baseline. With regard to drug safety, there was no difference between groups in worsening renal function, symptomatic hypotension, or hyperkalemia.
A limitation of this study is that 20% of patients in each group discontinued treatment by 8 weeks secondary to an adverse event. Additionally, a clinical measure such as cardiovascular mortality, all-cause mortality, or rehospitalization for heart failure was not included in the primary outcome.
Bottom line: In patients with acute decompensated HFrEF, ARNIs are more effective at reducing NT-proBNP levels than enalapril, while maintaining a similar safety profile. Further investigation to evaluate clinical outcomes needs to be completed.
Citation: Velazquez EJ et al. Angiotensin–neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2018 Nov 11. doi: 10.1056/NEJMoa1812851.
Dr. McIntyre is an associate physician in the division of hospital medicine at the University of California, San Diego.
Background: The PARADIGM-HF trial demonstrated that patients with chronic HFrEF treated with an ARNI (sacubitril/valsartan) had significantly reduced cardiovascular mortality and hospitalizations when compared with enalapril. Patients with acute decompensated heart failure were excluded from this trial. The PIONEER-HF trial was designed to determine whether initiation of an ARNI in patients with acute decompensated heart failure is effective.
Study design: Multicenter, randomized, double-blind, active-controlled trial.
Setting: A total of 129 centers in the United States.
Synopsis: Of 881 patients with acute HFrEF, 440 were randomized to receive sacubitril/valsartan and 441 were randomized to receive enalapril. The majority of patients were men; mean age was 61 years. The primary outcome was the mean reduction in NT-proBNP concentration at weeks 4 and 8 as compared with baseline. In the sacubitril/valsartan group, there was a 46.7% reduction from baseline, and in the enalapril group, there was a 25.3% reduction from baseline. With regard to drug safety, there was no difference between groups in worsening renal function, symptomatic hypotension, or hyperkalemia.
A limitation of this study is that 20% of patients in each group discontinued treatment by 8 weeks secondary to an adverse event. Additionally, a clinical measure such as cardiovascular mortality, all-cause mortality, or rehospitalization for heart failure was not included in the primary outcome.
Bottom line: In patients with acute decompensated HFrEF, ARNIs are more effective at reducing NT-proBNP levels than enalapril, while maintaining a similar safety profile. Further investigation to evaluate clinical outcomes needs to be completed.
Citation: Velazquez EJ et al. Angiotensin–neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2018 Nov 11. doi: 10.1056/NEJMoa1812851.
Dr. McIntyre is an associate physician in the division of hospital medicine at the University of California, San Diego.
Background: The PARADIGM-HF trial demonstrated that patients with chronic HFrEF treated with an ARNI (sacubitril/valsartan) had significantly reduced cardiovascular mortality and hospitalizations when compared with enalapril. Patients with acute decompensated heart failure were excluded from this trial. The PIONEER-HF trial was designed to determine whether initiation of an ARNI in patients with acute decompensated heart failure is effective.
Study design: Multicenter, randomized, double-blind, active-controlled trial.
Setting: A total of 129 centers in the United States.
Synopsis: Of 881 patients with acute HFrEF, 440 were randomized to receive sacubitril/valsartan and 441 were randomized to receive enalapril. The majority of patients were men; mean age was 61 years. The primary outcome was the mean reduction in NT-proBNP concentration at weeks 4 and 8 as compared with baseline. In the sacubitril/valsartan group, there was a 46.7% reduction from baseline, and in the enalapril group, there was a 25.3% reduction from baseline. With regard to drug safety, there was no difference between groups in worsening renal function, symptomatic hypotension, or hyperkalemia.
A limitation of this study is that 20% of patients in each group discontinued treatment by 8 weeks secondary to an adverse event. Additionally, a clinical measure such as cardiovascular mortality, all-cause mortality, or rehospitalization for heart failure was not included in the primary outcome.
Bottom line: In patients with acute decompensated HFrEF, ARNIs are more effective at reducing NT-proBNP levels than enalapril, while maintaining a similar safety profile. Further investigation to evaluate clinical outcomes needs to be completed.
Citation: Velazquez EJ et al. Angiotensin–neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2018 Nov 11. doi: 10.1056/NEJMoa1812851.
Dr. McIntyre is an associate physician in the division of hospital medicine at the University of California, San Diego.
Wrong cuff size throws off pediatric BP by 5 mm Hg
NEW ORLEANS – according to investigators from Columbia University in New York.
There are five cuff sizes in pediatrics, depending on a child’s arm circumference. Ideally, it’s measured beforehand so the right cuff size is used, but that doesn’t always happen in everyday practice.
Sometimes, clinicians just estimate arm size before choosing a cuff or opt for the medium-sized cuff in most kids; other times, the correct size has gone missing, said lead investigator Ruchi Gupta Mahajan, MD, a pediatric nephrology fellow at Columbia.
For those situations, she and her colleagues wanted to quantify how much the wrong cuff size throws off blood pressure readings in children, something that’s been done before in adult medicine, but not in pediatrics.
The idea was to give clinicians a decent estimate of true blood pressure even when the cuff isn’t quite right, something that’s particularly important with an increasing emphasis on catching hypertension as early as possible in children, she said.
After her subjects sat quietly for 10 minutes, Dr. Mahajan took automated blood pressure readings on 137 children; once with the right cuff size, once with a cuff one size too small, and once with a cuff one size too big, with a minute apart between readings.
The children were aged 4-12 years old and were in the office for wellness visits. None of them had heart or kidney disease, and none were on steroids or any other medications that affect blood pressure. There were a few more boys than girls, and almost all the children were Hispanic.
Overall, systolic blood pressure was an average of 5 mm Hg less with the larger cuff and 5 mm Hg more with the smaller cuff. The finding was the same in both girls and boys, and it held across age groups and in under, over, and normal weight children.
“I was really surprised there was no difference between ages, 4-12 years of age, its just a single number: 5. [Even] if [you] don’t have the appropriate cuff size,” the finding means that it’s still possible to have a good estimate of blood pressure, Dr. Mahajan said at the joint scientific sessions of the American Heart Association (AHA) Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
Meanwhile, cuff size didn’t have any statistically significant effect on diastolic pressure.
There was no outside funding for the study and Dr. Mahajan reported having no disclosures.
SOURCE: Mahajan RG et al. Joint Hypertension 2019, Abstract P182.
NEW ORLEANS – according to investigators from Columbia University in New York.
There are five cuff sizes in pediatrics, depending on a child’s arm circumference. Ideally, it’s measured beforehand so the right cuff size is used, but that doesn’t always happen in everyday practice.
Sometimes, clinicians just estimate arm size before choosing a cuff or opt for the medium-sized cuff in most kids; other times, the correct size has gone missing, said lead investigator Ruchi Gupta Mahajan, MD, a pediatric nephrology fellow at Columbia.
For those situations, she and her colleagues wanted to quantify how much the wrong cuff size throws off blood pressure readings in children, something that’s been done before in adult medicine, but not in pediatrics.
The idea was to give clinicians a decent estimate of true blood pressure even when the cuff isn’t quite right, something that’s particularly important with an increasing emphasis on catching hypertension as early as possible in children, she said.
After her subjects sat quietly for 10 minutes, Dr. Mahajan took automated blood pressure readings on 137 children; once with the right cuff size, once with a cuff one size too small, and once with a cuff one size too big, with a minute apart between readings.
The children were aged 4-12 years old and were in the office for wellness visits. None of them had heart or kidney disease, and none were on steroids or any other medications that affect blood pressure. There were a few more boys than girls, and almost all the children were Hispanic.
Overall, systolic blood pressure was an average of 5 mm Hg less with the larger cuff and 5 mm Hg more with the smaller cuff. The finding was the same in both girls and boys, and it held across age groups and in under, over, and normal weight children.
“I was really surprised there was no difference between ages, 4-12 years of age, its just a single number: 5. [Even] if [you] don’t have the appropriate cuff size,” the finding means that it’s still possible to have a good estimate of blood pressure, Dr. Mahajan said at the joint scientific sessions of the American Heart Association (AHA) Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
Meanwhile, cuff size didn’t have any statistically significant effect on diastolic pressure.
There was no outside funding for the study and Dr. Mahajan reported having no disclosures.
SOURCE: Mahajan RG et al. Joint Hypertension 2019, Abstract P182.
NEW ORLEANS – according to investigators from Columbia University in New York.
There are five cuff sizes in pediatrics, depending on a child’s arm circumference. Ideally, it’s measured beforehand so the right cuff size is used, but that doesn’t always happen in everyday practice.
Sometimes, clinicians just estimate arm size before choosing a cuff or opt for the medium-sized cuff in most kids; other times, the correct size has gone missing, said lead investigator Ruchi Gupta Mahajan, MD, a pediatric nephrology fellow at Columbia.
For those situations, she and her colleagues wanted to quantify how much the wrong cuff size throws off blood pressure readings in children, something that’s been done before in adult medicine, but not in pediatrics.
The idea was to give clinicians a decent estimate of true blood pressure even when the cuff isn’t quite right, something that’s particularly important with an increasing emphasis on catching hypertension as early as possible in children, she said.
After her subjects sat quietly for 10 minutes, Dr. Mahajan took automated blood pressure readings on 137 children; once with the right cuff size, once with a cuff one size too small, and once with a cuff one size too big, with a minute apart between readings.
The children were aged 4-12 years old and were in the office for wellness visits. None of them had heart or kidney disease, and none were on steroids or any other medications that affect blood pressure. There were a few more boys than girls, and almost all the children were Hispanic.
Overall, systolic blood pressure was an average of 5 mm Hg less with the larger cuff and 5 mm Hg more with the smaller cuff. The finding was the same in both girls and boys, and it held across age groups and in under, over, and normal weight children.
“I was really surprised there was no difference between ages, 4-12 years of age, its just a single number: 5. [Even] if [you] don’t have the appropriate cuff size,” the finding means that it’s still possible to have a good estimate of blood pressure, Dr. Mahajan said at the joint scientific sessions of the American Heart Association (AHA) Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
Meanwhile, cuff size didn’t have any statistically significant effect on diastolic pressure.
There was no outside funding for the study and Dr. Mahajan reported having no disclosures.
SOURCE: Mahajan RG et al. Joint Hypertension 2019, Abstract P182.
REPORTING FROM JOINT HYPERTENSION 2019